Schizophrenia#Cognitive symptoms

Schizophrenia is a mental disorder characterized by significant alterations in perception, thoughts, mood, and behavior. Symptoms are described in terms of positive, negative, and cognitive symptoms.{{cite journal |vauthors=Stępnicki P, Kondej M, Kaczor AA |title=Current Concepts and Treatments of Schizophrenia |journal= Molecules|volume=23 |issue=8 |date=20 August 2018 |pmid=30127324|doi=10.3390/molecules23082087 |pmc=6222385 |page=2087|doi-access=free }} The positive symptoms of schizophrenia are the same for any psychosis and are sometimes referred to as psychotic symptoms. These may be present in any of the different psychoses and are often transient, making early diagnosis of schizophrenia problematic. Psychosis noted for the first time in a person who is later diagnosed with schizophrenia is referred to as a first-episode psychosis (FEP).{{cite web |title=RAISE Questions and Answers |url=https://www.nimh.nih.gov/health/topics/schizophrenia/raise/raise-questions-and-answers.shtml#4 |publisher= US National Institute of Mental Health|access-date=29 December 2019}}{{cite journal | vauthors = Marshall M | title = Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review | journal = Archives of General Psychiatry | date = September 2005 | volume = 62 | issue = 9 | pages = 975–983 | doi = 10.1001/archpsyc.62.9.975 | pmid = 16143729| s2cid = 13504781 | doi-access = }}

Positive symptoms are those symptoms that are not normally experienced, but are present in people during a psychotic episode in schizophrenia, including delusions, hallucinations, and disorganized thoughts, speech and behavior or inappropriate affect, typically regarded as manifestations of psychosis. Hallucinations occur at some point in the lifetimes of 80% of those with schizophrenia{{cite journal |vauthors=Montagnese M, Leptourgos P, Fernyhough C, et al |title=A Review of Multimodal Hallucinations: Categorization, Assessment, Theoretical Perspectives, and Clinical Recommendations |journal=Schizophr Bull |volume=47 |issue=1 |pages=237–248 |date=January 2021 |pmid=32772114 |pmc=7825001 |doi=10.1093/schbul/sbaa101 }} and most commonly involve the sense of hearing (most often hearing voices), but can sometimes involve any of the other senses such as taste, sight, smell, and touch.{{cite journal |vauthors=Császár N, Kapócs G, Bókkon I |s2cid=52813070 |title=A possible key role of vision in the development of schizophrenia |journal=Reviews in the Neurosciences |volume=30 |issue=4 |pages=359–379 |date=27 May 2019 |pmid=30244235 |doi=10.1515/revneuro-2018-0022}} The frequency of hallucinations involving multiple senses is double the rate of those involving only one sense. They are also typically related to the content of the delusional theme.{{cite book | author = American Psychiatric Association. Task Force on DSM-IV. | year = 2000 | title = Diagnostic and statistical manual of mental disorders: DSM-IV-TR. | publisher = American Psychiatric Pub. | isbn = 978-0-89042-025-6 | pages = 299–304 }} Delusions are bizarre or persecutory in nature. Distortions of self-experience such as feeling that others can hear one's thoughts (thought broadcasting delusion) or that thoughts are being inserted into one's mind, sometimes termed passivity phenomena, are also common.{{cite journal | vauthors = Heinz A, Voss M, Lawrie SM, Mishara A, Bauer M, Gallinat J, Juckel G, Lang U, Rapp M, Falkai P, Strik W, Krystal J, Abi-Dargham A, Galderisi S | title = Shall we really say goodbye to first rank symptoms? | journal = European Psychiatry | volume = 37 | pages = 8–13 | date = September 2016 | pmid = 27429167 | doi = 10.1016/j.eurpsy.2016.04.010 | s2cid = 13761854 }} Positive symptoms generally respond well to medication and become reduced over the course of the illness, perhaps linked to the age-related decline in dopamine activity.

Negative symptoms are deficits of normal emotional responses, or of other thought processes. The five recognized domains of negative symptoms are: blunted affect – showing flat expressions (monotone) or little emotion; alogia – a poverty of speech; anhedonia – an inability to feel pleasure; asociality – the lack of desire to form relationships, and avolition – a lack of motivation and apathy.{{cite journal |vauthors=Adida M, Azorin JM, Belzeaux R, Fakra E |title=[Negative Symptoms: Clinical and Psychometric Aspects] |journal=L'Encephale |volume=41 |issue=6 Suppl 1 |pages=6S15–17 |date=December 2015 |pmid=26776385 |doi=10.1016/S0013-7006(16)30004-5}}{{cite journal |vauthors=Mach C, Dollfus S |title=[Scale for Assessing Negative Symptoms in Schizophrenia: A Systematic Review] |journal=L'Encephale |volume=42 |issue=2 |pages=165–171 |date=April 2016 |pmid=26923997 |doi=10.1016/j.encep.2015.12.020}} Avolition and anhedonia are seen as motivational deficits resulting from impaired reward processing.{{cite book |vauthors=Waltz JA, Gold JM |title=Behavioral Neuroscience of Motivation |chapter=Motivational Deficits in Schizophrenia and the Representation of Expected Value | series = Current Topics in Behavioral Neurosciences|volume=27 |pages=375–410 |date=2016 |pmid=26370946 |doi=10.1007/7854_2015_385 |pmc=4792780 |isbn=978-3-319-26933-7 }}{{cite journal |vauthors=Husain M, Roiser JP |s2cid=49428707 |title=Neuroscience of apathy and anhedonia: a transdiagnostic approach. |journal=Nature Reviews. Neuroscience|volume=19 |issue=8 |pages=470–484 |date=August 2018 |pmid=29946157 |doi=10.1038/s41583-018-0029-9|url=https://ora.ox.ac.uk/objects/uuid:3e481f87-0ede-47dd-bdd8-2db78dfd3694 }} Reward is the main driver of motivation and this is mostly mediated by dopamine. It has been suggested that negative symptoms are multidimensional and they have been categorised into two subdomains of apathy or lack of motivation, and diminished expression.{{cite journal |vauthors=Galderisi S, Mucci A, Buchanan RW, Arango C |title=Negative symptoms of schizophrenia: new developments and unanswered research questions |journal=The Lancet. Psychiatry |volume=5 |issue=8 |pages=664–677 |date=August 2018 |pmid=29602739 |doi=10.1016/S2215-0366(18)30050-6 |s2cid=4483198 }} Apathy includes avolition, anhedonia, and social withdrawal; diminished expression includes blunt affect and alogia.{{cite journal |vauthors=Klaus F, Dorsaz O, Kaiser S |title=[Negative symptoms in schizophrenia – overview and practical implications] |journal=Revue médicale suisse |volume=14 |issue=619 |pages=1660–1664 |date=19 September 2018 |doi=10.53738/REVMED.2018.14.619.1660 |pmid=30230774|s2cid=246764656 }} Sometimes diminished expression is treated as both verbal and non-verbal.{{cite journal |vauthors=Batinic B |title=Cognitive Models of Positive and Negative Symptoms of Schizophrenia and Implications for Treatment. |journal=Psychiatria Danubina |volume=31 |issue=Suppl 2 |pages=181–184 |date=June 2019 |pmid=31158119}}

Apathy accounts for around 50% of the most often found negative symptoms and affects functional outcome and subsequent quality of life. Apathy is related to disrupted cognitive processing affecting memory and planning, including goal-directed behaviour.{{cite journal |vauthors=Bortolon C, Macgregor A, Capdevielle D, Raffard S |s2cid=13411386 |title=Apathy in schizophrenia: A review of neuropsychological and neuroanatomical studies. |journal=Neuropsychologia |volume=118 |issue=Pt B |pages=22–33 |date=September 2018 |pmid=28966139 |doi=10.1016/j.neuropsychologia.2017.09.033}} The two subdomains have suggested a need for separate treatment approaches.{{cite journal |vauthors=Marder SR, Kirkpatrick B |s2cid=5172022 |title=Defining and measuring negative symptoms of schizophrenia in clinical trials |journal=European Neuropsychopharmacology|volume=24 |issue=5 |pages=737–743 |date=May 2014 |pmid=24275698 |doi=10.1016/j.euroneuro.2013.10.016}} A lack of distress is another noted negative symptom.{{cite journal |vauthors=Tatsumi K, Kirkpatrick B, Strauss GP, Opler M |s2cid=211141678 |title=The brief negative symptom scale in translation: A review of psychometric properties and beyond |journal=European Neuropsychopharmacology |date=April 2020 |volume=33 |pages=36–44 |doi=10.1016/j.euroneuro.2020.01.018 |pmid=32081498}} A distinction is often made between those negative symptoms that are inherent to schizophrenia, termed primary; and those that result from positive symptoms, from the side effects of antipsychotics, substance use disorder, and social deprivation, termed secondary negative symptoms.{{cite journal |vauthors=Klaus F, Kaiser S, Kirschner M |title=[Negative Symptoms in Schizophrenia – an Overview]. |journal=Therapeutische Umschau |volume=75 |issue=1 |pages=51–56 |date=June 2018 |pmid=29909762 |doi=10.1024/0040-5930/a000966|s2cid=196502392 }} Negative symptoms are less responsive to medication and the most difficult to treat. However, if properly assessed, secondary negative symptoms are amenable to treatment. There is some evidence that the negative symptoms of schizophrenia are amenable to psychostimulant medication, although such drugs have varying degrees of risk for causing positive psychotic symptoms.{{Cite journal |last1=Lindenmayer |first1=Jean-Pierre |last2=Nasrallah |first2=Henry |last3=Pucci |first3=Michael |last4=James |first4=Steven |last5=Citrome |first5=Leslie |date=2013-07-01 |title=A systematic review of psychostimulant treatment of negative symptoms of schizophrenia: Challenges and therapeutic opportunities |url=https://www.sciencedirect.com/science/article/abs/pii/S0920996413001655 |journal=Schizophrenia Research |volume=147 |issue=2 |pages=241–252 |doi=10.1016/j.schres.2013.03.019 |pmid=23619055 |issn=0920-9964}}

Scales for specifically assessing the presence of negative symptoms, and for measuring their severity, and their changes have been introduced since the earlier scales such as the PANNS that deals with all types of symptoms. These scales are the Clinical Assessment Interview for Negative Symptoms (CAINS), and the Brief Negative Symptom Scale (BNSS) also known as second-generation scales.{{cite journal |vauthors=Wójciak P, Rybakowski J |title=Clinical picture, pathogenesis and psychometric assessment of negative symptoms of schizophrenia. |journal=Psychiatria Polska |volume=52 |issue=2 |pages=185–197 |date=30 April 2018 |pmid=29975360 |doi=10.12740/PP/70610|doi-access=free }} In 2020, ten years after its introduction, a cross-cultural study of the use of BNSS found valid and reliable psychometric evidence for its five-domain structure cross-culturally. The BNSS can assess both the presence and severity of negative symptoms of the five recognized domains and an additional item of reduced normal distress. It has been used to measure changes in negative symptoms in trials of psychosocial and pharmacological interventions.

{{See also |Visual processing abnormalities in schizophrenia}}

File:SchizophreniaBrain.jpg throughout the human brain in a patient with schizophrenia. The most deficient areas are magenta, while the least deficient areas are blue.]]

An estimated 70% of those with schizophrenia have cognitive deficits, and these are most pronounced in early-onset and late-onset illness.{{cite journal |vauthors=Kar SK, Jain M |title=Current understandings about cognition and the neurobiological correlates in schizophrenia |journal=Journal of Neurosciences in Rural Practice |volume=7 |issue=3 |pages=412–418 |date=July 2016 |pmid=27365960 |doi=10.4103/0976-3147.176185 |pmc=4898111 |doi-access=free }} These are often evident long before the onset of illness in the prodromal stage, and may be present in childhood or early adolescence.{{cite journal | vauthors = Shah JN, Qureshi SU, Jawaid A, Schulz PE | s2cid = 10970088 | title = Is there evidence for late cognitive decline in chronic schizophrenia? | journal = The Psychiatric Quarterly | volume = 83 | issue = 2 | pages = 127–144 | date = June 2012 | pmid = 21863346 | doi = 10.1007/s11126-011-9189-8 }} They are a core feature but not considered to be core symptoms, as are positive and negative symptoms.{{cite journal |vauthors = Biedermann F, Fleischhacker WW | title = Psychotic disorders in DSM-5 and ICD-11 | journal = CNS Spectrums | date = August 2016 | volume = 21 | issue = 4 | pages = 349–354 | doi = 10.1017/S1092852916000316 | pmid = 27418328| s2cid = 24728447 }} However, their presence and degree of dysfunction is taken as a better indicator of functionality than the presentation of core symptoms.{{cite journal | vauthors = Bozikas VP, Andreou C | s2cid = 26135485 | title = Longitudinal studies of cognition in first episode psychosis: a systematic review of the literature | journal = The Australian and New Zealand Journal of Psychiatry | volume = 45 | issue = 2 | pages = 93–108 | date = February 2011 | pmid = 21320033 | doi = 10.3109/00048674.2010.541418 }} Cognitive deficits become worse at first episode psychosis but then return to baseline, and remain fairly stable over the course of the illness.

The deficits in cognition are seen to drive the negative psychosocial outcome in schizophrenia, and are claimed{{By whom|date=March 2024}} to equate to a possible reduction in IQ from the norm of 100 to 70–85.{{cite journal | vauthors=Javitt DC, Sweet RA |title=Auditory dysfunction in schizophrenia: integrating clinical and basic features. |journal=Nature Reviews. Neuroscience|volume=16 |issue=9 |pages=535–550 |date=September 2015|pmid=26289573|doi=10.1038/nrn4002|pmc=4692466 }}{{cite journal |vauthors=Megreya AM |s2cid=26125559 |title=Face perception in schizophrenia: a specific deficit |journal=Cognitive Neuropsychiatry |volume=21 |issue=1 |pages=60–72 |date=2016 |pmid=26816133|doi=10.1080/13546805.2015.1133407}}{{failed verification|date=January 2025}} Cognitive deficits may be of neurocognition (nonsocial) or of social cognition.{{cite journal |vauthors=Murante T, Cohen CI |title=Cognitive Functioning in Older Adults With Schizophrenia |journal=Focus (American Psychiatric Publishing) |volume=15 |issue=1 |pages=26–34 |date=January 2017 |pmid=31975837 |doi=10.1176/appi.focus.20160032|pmc=6519630 }} Neurocognition is the ability to receive and remember information, and includes verbal fluency, memory, reasoning, problem solving, speed of processing, and auditory and visual perception. Verbal memory and attention are seen to be the most affected.{{cite journal |vauthors=Eack SM |title=Cognitive remediation: a new generation of psychosocial interventions for people with schizophrenia |journal=Social Work |volume=57 |issue=3 |pages=235–246 |date=July 2012 |pmid=23252315 |doi=10.1093/sw/sws008|pmc=3683242 }} Verbal memory impairment is associated with a decreased level of semantic processing (relating meaning to words).{{cite journal

|vauthors=Pomarol-Clotet E, Oh M, Laws KR, McKenna PJ | title=Semantic priming in schizophrenia: systematic review and meta-analysis |journal=The British Journal of Psychiatry |volume=192 |issue=2 | pages=92–97 |date=February 2008 |pmid=18245021 |doi=10.1192/bjp.bp.106.032102 | hdl=2299/2735 |doi-access=free |hdl-access=free }} Another memory impairment is that of episodic memory.{{cite journal | vauthors = Goldberg TE, Keefe RS, Goldman RS, Robinson DG, Harvey PD | title = Circumstances under which practice does not make perfect: a review of the practice effect literature in schizophrenia and its relevance to clinical treatment studies | journal = Neuropsychopharmacology | volume = 35 | issue = 5 | pages = 1053–1062 | date = April 2010 | pmid = 20090669 | pmc = 3055399 | doi = 10.1038/npp.2009.211 | df = dmy-all }} An impairment in visual perception that is consistently found in schizophrenia is that of visual backward masking. Visual processing impairments include an inability to perceive complex visual illusions.{{cite journal |vauthors=King DJ, Hodgekins J, Chouinard PA, Chouinard VA, Sperandio I |title=A review of abnormalities in the perception of visual illusions in schizophrenia. |journal=Psychonomic Bulletin and Review |volume=24 |issue=3 |pages=734–751 |date=June 2017 |pmid=27730532 |doi=10.3758/s13423-016-1168-5 |pmc = 5486866}} Social cognition is concerned with the mental operations needed to interpret, and understand the self and others in the social world.{{cite journal |vauthors=Green MF, Horan WP, Lee J |title=Nonsocial and social cognition in schizophrenia: current evidence and future directions |journal=World Psychiatry|volume=18 |issue=2 |pages=146–161 |date=June 2019 |pmid=31059632 |doi=10.1002/wps.20624|pmc=6502429 }} This is also an associated impairment, and facial emotion perception is often found to be difficult.{{cite journal | vauthors = Kohler CG, Walker JB, Martin EA, Healey KM, Moberg PJ | title = Facial emotion perception in schizophrenia: a meta-analytic review | journal = Schizophrenia Bulletin | volume = 36 | issue = 5 | pages = 1009–1019 | date = September 2010 | pmid = 19329561 | pmc = 2930336 | doi = 10.1093/schbul/sbn192 | df = dmy-all }}{{cite journal | vauthors = Le Gall E, Iakimova G | title = [Social cognition in schizophrenia and autism spectrum disorder: Points of convergence and functional differences] | journal = L'Encéphale | volume = 44 | issue = 6 | pages = 523–537 | date = December 2018 | pmid = 30122298 | doi = 10.1016/j.encep.2018.03.004 | s2cid = 150099236 }} Facial perception is critical for ordinary social interaction.{{cite journal | vauthors = Grill-Spector K, Weiner KS, Kay K, Gomez J | title = The Functional Neuroanatomy of Human Face Perception | journal = Annual Review of Vision Science | volume = 3 | pages = 167–196 | date = September 2017 | pmid = 28715955 | pmc = 6345578 | doi = 10.1146/annurev-vision-102016-061214 }} Cognitive impairments do not usually respond to antipsychotics, and there are a number of interventions that are used to try to improve them; cognitive remediation therapy is of particular help.

Neurological soft signs of clumsiness and loss of fine motor movement are often found in schizophrenia, which may resolve with effective treatment of FEP.{{cite journal |vauthors=Fountoulakis KN, Panagiotidis P, Kimiskidis V, Nimatoudis I, Gonda X |s2cid=56476015 |title=Neurological soft signs in familial and sporadic schizophrenia |journal=Psychiatry Research |volume=272 |pages=222–229 |date=February 2019 |pmid=30590276 |doi=10.1016/j.psychres.2018.12.105 }}

{{Further|Basic symptoms of schizophrenia}}

{{See also|Childhood schizophrenia|Adolescence#Changes in the brain}}

Onset typically occurs between the late teens and early 30s, with the peak incidence occurring in males in the early to mid-twenties, and in females in the late twenties. Onset before the age of 17 is known as early-onset,{{cite journal |vauthors=Bourgou Gaha S, Halayem Dhouib S, Amado I, Bouden A |title=[Neurological soft signs in early onset schizophrenia] |journal=L'Encephale |volume=41 |issue=3 |pages=209–214 |date=June 2015 |pmid=24854724 |doi=10.1016/j.encep.2014.01.005}} and before the age of 13, as can sometimes occur, is known as childhood schizophrenia or very early-onset.{{cite journal |vauthors=Da Fonseca D, Fourneret P |title=[Very early onset schizophrenia] |journal=L'Encephale |volume=44 |issue=6S |pages=S8–S11 |date=December 2018 |pmid=30935493 |doi=10.1016/S0013-7006(19)30071-5|s2cid=150798223 }} Onset can occur between the ages of 40 and 60, known as late-onset schizophrenia. Onset over the age of 60, which may be difficult to differentiate as schizophrenia, is known as very-late-onset schizophrenia-like psychosis. Late onset has shown that a higher rate of females are affected; they have less severe symptoms and need lower doses of antipsychotics. The tendency for earlier onset in males is later seen to be balanced by a post-menopausal increase in the development in females. Estrogen produced pre-menopause has a dampening effect on dopamine receptors but its protection can be overridden by a genetic overload.{{cite journal |vauthors=Häfner H |title=From Onset and Prodromal Stage to a Life-Long Course of Schizophrenia and Its Symptom Dimensions: How Sex, Age, and Other Risk Factors Influence Incidence and Course of Illness |journal=Psychiatry Journal |volume=2019 |page=9804836 |date=2019 |pmid=31139639 |doi=10.1155/2019/9804836 |pmc=6500669 |doi-access=free }} There has been a dramatic increase in the numbers of older adults with schizophrenia.{{cite journal | vauthors = Cohen CI, Freeman K, Ghoneim D, Vengassery A, Ghezelaiagh B, Reinhardt MM | title = Advances in the Conceptualization and Study of Schizophrenia in Later Life | journal = The Psychiatric Clinics of North America | volume = 41 | issue = 1 | pages = 39–53 | date = March 2018 | pmid = 29412847 | doi = 10.1016/j.psc.2017.10.004 }}

Onset may happen suddenly or may occur after the slow and gradual development of a number of signs and symptoms, a period known as the prodromal stage. Up to 75% of those with schizophrenia go through a prodromal stage.{{cite journal |vauthors=George M, Maheshwari S, Chandran S, Manohar JS, Sathyanarayana Rao TS |title=Understanding the schizophrenia prodrome |journal=Indian Journal of Psychiatry |volume=59 |issue=4 |pages=505–509 |date=October 2017 |pmid=29497198 |doi=10.4103/psychiatry.IndianJPsychiatry_464_17|doi-broken-date=1 November 2024 |doi-access=free|pmc=5806335 }} The negative and cognitive symptoms in the prodrome stage can precede FEP (first episode psychosis) by many months and up to five years.{{cite journal |vauthors=Hashimoto K |s2cid=195814019 |title=Recent Advances in the Early Intervention in Schizophrenia: Future Direction from Preclinical Findings |journal=Current Psychiatry Reports |volume=21 |issue=8 |page=75 |date=5 July 2019 |pmid=31278495 |doi=10.1007/s11920-019-1063-7}}{{cite journal |vauthors=Conroy S, Francis M, Hulvershorn LA |title=Identifying and treating the prodromal phases of bipolar disorder and schizophrenia |journal=Current Treatment Options in Psychiatry |volume=5 |issue=1 |pages=113–128 |date=March 2018 |pmid=30364516 |doi=10.1007/s40501-018-0138-0|pmc=6196741 }} The period from FEP and treatment is known as the duration of untreated psychosis (DUP) which is seen to be a factor in functional outcome. The prodromal stage is the high-risk stage for the development of psychosis. Since the progression to first episode psychosis is not inevitable, an alternative term is often preferred of at risk mental state. Cognitive dysfunction at an early age impacts a young person's usual cognitive development.{{cite journal |vauthors=Lecardeur L, Meunier-Cussac S, Dollfus S |title=[Cognitive deficits in first episode psychosis patients and people at risk for psychosis: from diagnosis to treatment] |journal=L'Encephale |volume=39 |pages=S64-71 |date=May 2013 |issue=Suppl 1 |pmid=23528322 |doi=10.1016/j.encep.2012.10.011}} Recognition and early intervention at the prodromal stage would minimize the associated disruption to educational and social development and has been the focus of many studies.

{{Main|Risk factors of schizophrenia}}

Schizophrenia is described as a neurodevelopmental disorder with no precise boundary, or single cause, and is thought to develop from gene–environment interactions with involved vulnerability factors.{{cite journal | vauthors = Mullin AP, Gokhale A, Moreno-De-Luca A, Sanyal S, Waddington JL, Faundez V | title = Neurodevelopmental disorders: mechanisms and boundary definitions from genomes, interactomes and proteomes | journal = Translational Psychiatry | volume = 3 | issue = 12 | pages = e329 | date = December 2013 | pmid = 24301647 | pmc = 4030327 | doi = 10.1038/tp.2013.108 }} The interactions of these risk factors are complex, as numerous and diverse insults from conception to adulthood can be involved.{{cite journal | vauthors = Davis J, Eyre H, Jacka FN, Dodd S, Dean O, McEwen S, Debnath M, McGrath J, Maes M, Amminger P, McGorry PD, Pantelis C, Berk M | title = A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis | journal = Neuroscience and Biobehavioral Reviews | volume = 65 | pages = 185–194 | date = June 2016 | pmid = 27073049 | pmc = 4876729 | doi = 10.1016/j.neubiorev.2016.03.017 }} A genetic predisposition on its own, without interacting environmental factors, will not give rise to the development of schizophrenia.{{cite journal | vauthors = Perkovic MN, Erjavec GN, Strac DS, Uzun S, Kozumplik O, Pivac N | title = Theranostic Biomarkers for Schizophrenia | journal = International Journal of Molecular Sciences | volume = 18 | issue = 4 | page = 733 | date = March 2017 | pmid = 28358316 | pmc = 5412319 | doi = 10.3390/ijms18040733 | doi-access = free }} The genetic component means that prenatal brain development is disturbed, and environmental influence affects the postnatal development of the brain.{{cite journal | vauthors = Suvisaari J | title = [Risk factors of schizophrenia] | language = Finnish | journal = Duodecim; Laaketieteellinen Aikakauskirja | volume = 126 | issue = 8 | pages = 869–876 | date = 2010 | pmid = 20597333 }} Evidence suggests that genetically susceptible children are more likely to be vulnerable to the effects of environmental risk factors.

Estimates of the heritability of schizophrenia are between 70% and 80%, which implies that 70% to 80% of the individual differences in risk of schizophrenia are associated with genetics. These estimates vary because of the difficulty in separating genetic and environmental influences, and their accuracy has been queried.{{cite journal | vauthors = O'Donovan MC, Williams NM, Owen MJ | title = Recent advances in the genetics of schizophrenia | journal = Human Molecular Genetics | volume = 12 Spec No 2 | pages = R125–133 | date = October 2003 | pmid = 12952866 | doi = 10.1093/hmg/ddg302 | doi-access = free }}{{Cite journal |vauthors=Torrey EF, Yolken RH |s2cid=173991937 |date=August 2019 |title=Schizophrenia as a pseudogenetic disease: A call for more gene-environmental studies |journal=Psychiatry Research |volume=278 |pages=146–150 |doi=10.1016/j.psychres.2019.06.006|pmid=31200193 }} The greatest risk factor for developing schizophrenia is having a first-degree relative with the disease (risk is 6.5%); more than 40% of identical twins of those with schizophrenia are also affected.{{cite journal | vauthors = Picchioni MM, Murray RM | title = Schizophrenia | journal = BMJ | volume = 335 | issue = 7610 | pages = 91–95 | date = July 2007 | pmid = 17626963 | pmc = 1914490 | doi = 10.1136/bmj.39227.616447.BE }} If one parent is affected the risk is about 13% and if both are affected the risk is nearly 50%.{{cite book|title=Adult psychopathology and diagnosis |year=2011 |publisher=John Wiley & Sons |isbn=978-1-118-13884-7 |chapter-url= https://books.google.com/books?id=iJtzm1KfU5oC&pg=PT282 |chapter= Chapter 8: Schizophrenia: Etiological considerations| veditors = Hersen M, Beidel DC |edition=6th| vauthors = Combs DR, Mueser KT, Gutierrez MM }} However, the DSM-5 indicates that most people with schizophrenia have no family history of psychosis. Results of candidate gene studies of schizophrenia have generally failed to find consistent associations,{{cite journal | vauthors = Farrell MS, Werge T, Sklar P, Owen MJ, Ophoff RA, O'Donovan MC, Corvin A, Cichon S, Sullivan PF | title = Evaluating historical candidate genes for schizophrenia | journal = Molecular Psychiatry | volume = 20 | issue = 5 | pages = 555–562 | date = May 2015 | pmid = 25754081 | pmc = 4414705 | doi = 10.1038/mp.2015.16 }} and the genetic loci identified by genome-wide association studies explain only a small fraction of the variation in the disease.{{Cite book |url= https://books.google.com/books?id=7ukmDAAAQBAJ |title=Schizophrenia and Psychotic Spectrum Disorders | vauthors = Schulz SC, Green MF, Nelson KJ |date=2016 |publisher=Oxford University Press |isbn=9780199378067 |pages=124–125 }}

Many genes are known to be involved in schizophrenia, each with small effects and unknown transmission and expression.{{cite journal | vauthors = Schork AJ, Wang Y, Thompson WK, Dale AM, Andreassen OA | title = New statistical approaches exploit the polygenic architecture of schizophrenia—implications for the underlying neurobiology | journal = Current Opinion in Neurobiology | volume = 36 | pages = 89–98 | date = February 2016 | pmid = 26555806 | pmc = 5380793 | doi = 10.1016/j.conb.2015.10.008 }}{{cite journal|vauthors= Coelewij L, Curtis D|title=Mini-review: Update on the genetics of schizophrenia|journal=Annals of Human Genetics|volume=82|issue=5|year= 2018|pages=239–243|issn=0003-4800|doi=10.1111/ahg.12259|pmid= 29923609|s2cid=49311660|url=https://discovery.ucl.ac.uk/id/eprint/10064654/ |doi-access=free}} The summation of these effect sizes into a polygenic risk score can explain at least 7% of the variability in liability for schizophrenia.{{cite journal | vauthors = Kendler KS | title = The Schizophrenia Polygenic Risk Score: To What Does It Predispose in Adolescence? | journal = JAMA Psychiatry | volume = 73 | issue = 3 | pages = 193–194 | date = March 2016 | pmid = 26817666 | doi = 10.1001/jamapsychiatry.2015.2964 }} Around 5% of cases of schizophrenia are understood to be at least partially attributable to rare copy number variations (CNVs); these structural variations are associated with known genomic disorders involving deletions at 22q11.2 (DiGeorge syndrome) and 17q12 (17q12 microdeletion syndrome), duplications at 16p11.2 (most frequently found) and deletions at 15q11.2 (Burnside–Butler syndrome).{{cite journal | vauthors = Lowther C, Costain G, Baribeau DA, Bassett AS | s2cid = 4776174 | title = Genomic Disorders in Psychiatry—What Does the Clinician Need to Know? | journal = Current Psychiatry Reports | volume = 19 | issue = 11 | page = 82 | date = September 2017 | doi = 10.1007/s11920-017-0831-5 | pmid = 28929285 }} Some of these CNVs increase the risk of developing schizophrenia by as much as 20-fold, and are frequently comorbid with autism and intellectual disabilities.

The genes CRHR1 and CRHBP are associated with the severity of suicidal behavior. These genes code for stress response proteins needed in the control of the HPA axis, and their interaction can affect this axis. Response to stress can cause lasting changes in the function of the HPA axis possibly disrupting the negative feedback mechanism, homeostasis, and the regulation of emotion leading to altered behaviors.

The question of how schizophrenia could be primarily genetically influenced, given that people with schizophrenia have lower fertility rates, is a paradox. It is expected that genetic variants that increase the risk of schizophrenia would be selected against, due to their negative effects on reproductive fitness. A number of potential explanations have been proposed, including that alleles associated with schizophrenia risk confers a fitness advantage in unaffected individuals.{{Cite journal |vauthors= Bundy H, Stahl D, MacCabe JH |date=February 2011 |title=A systematic review and meta-analysis of the fertility of patients with schizophrenia and their unaffected relatives: Fertility in schizophrenia |journal=Acta Psychiatrica Scandinavica |volume=123 |issue=2 |pages=98–106 |doi= 10.1111/j.1600-0447.2010.01623.x|pmid=20958271 |s2cid=45179016 }}{{Cite journal |vauthors= van Dongen J, Boomsma DI |date=March 2013 |title=The evolutionary paradox and the missing heritability of schizophrenia |journal=American Journal of Medical Genetics Part B: Neuropsychiatric Genetics |volume=162 |issue=2 |pages=122–136 |doi= 10.1002/ajmg.b.32135|pmid=23355297 |s2cid=9648115 }} While some evidence has not supported this idea, others propose that a large number of alleles each contributing a small amount can persist.{{cite journal |vauthors= Owen MJ, Sawa A, Mortensen PB |title=Schizophrenia |journal=Lancet |date=2 July 2016 |volume=388 |issue=10039 |pages=86–97 |doi=10.1016/S0140-6736(15)01121-6 |pmid= 26777917|pmc=4940219}}

A meta-analysis found that oxidative DNA damage was significantly increased in schizophrenia.{{cite journal |vauthors=Goh XX, Tang PY, Tee SF |title= 8-Hydroxy-2'-Deoxyguanosine and Reactive Oxygen Species as Biomarkers of Oxidative Stress in Mental Illnesses: A Meta-Analysis |journal= Psychiatry Investig |volume=18 |issue=7 |pages=603–618 |date=July 2021 |pmid=34340273 |pmc=8328836 |doi=10.30773/pi.2020.0417 |type= Meta-analysis}}

{{Further|Prenatal nutrition|Prenatal stress|Neuroplastic effects of pollution}}

Environmental factors, each associated with a slight risk of developing schizophrenia in later life include oxygen deprivation, infection, prenatal maternal stress, and malnutrition in the mother during prenatal development.{{cite journal |vauthors=Stilo SA, Murray RM |title=Non-Genetic Factors in Schizophrenia |journal=Current Psychiatry Reports |volume=21 |issue=10 |page=100 |date=14 September 2019 |pmid=31522306 |doi=10.1007/s11920-019-1091-3 |pmc=6745031 }} A risk is associated with maternal obesity, in increasing oxidative stress, and dysregulating the dopamine and serotonin pathways.{{cite journal |vauthors=Cirulli F, Musillo C, Berry A |s2cid=211029692 |title=Maternal Obesity as a Risk Factor for Brain Development and Mental Health in the Offspring |journal=Neuroscience|date= 5 February 2020 |volume=447 |pages=122–135 |pmid=32032668|doi= 10.1016/j.neuroscience.2020.01.023|hdl=11573/1387747 |hdl-access=free }} Both maternal stress and infection have been demonstrated to alter fetal neurodevelopment through an increase of pro-inflammatory cytokines.{{cite book |vauthors=Upthegrove R, Khandaker GM |title=Neuroinflammation and Schizophrenia |chapter=Cytokines, Oxidative Stress and Cellular Markers of Inflammation in Schizophrenia | series = Current Topics in Behavioral Neurosciences|volume=44 |pages=49–66 |date=2020 |pmid=31115797 |doi= 10.1007/7854_2018_88|isbn=978-3-030-39140-9 |s2cid=162169817 |chapter-url= http://pure-oai.bham.ac.uk/ws/files/74984176/Upthegrove_Khandaker_Cytokines_oxidative_stress_and_cellular_markers_of_inflammation_in_schizophrenia_Current_Topics_in_Behavioral_Neurosciences_2019.pdf }} There is a slighter risk associated with being born in the winter or spring possibly due to vitamin D deficiency{{cite journal |vauthors=Chiang M, Natarajan R, Fan X |s2cid= 206926835 |title=Vitamin D in schizophrenia: a clinical review |journal= Evidence-Based Mental Health |volume=19 |issue=1 |pages=6–9 |date= February 2016 |pmid=26767392 |doi=10.1136/eb-2015-102117 |pmc=10699337 }} or a prenatal viral infection. Other infections during pregnancy or around the time of birth that have been linked to an increased risk include infections by Toxoplasma gondii and Chlamydia.{{cite journal | vauthors = Arias I, Sorlozano A, Villegas E, de Dios Luna J, McKenney K, Cervilla J, Gutierrez B, Gutierrez J | title = Infectious agents associated with schizophrenia: a meta-analysis | journal = Schizophrenia Research | volume = 136 | issue = 1–3 | pages = 128–136 | date = April 2012 | pmid = 22104141 | doi = 10.1016/j.schres.2011.10.026 | hdl-access = free | s2cid = 2687441 | hdl = 10481/90076 }} The increased risk is about five to eight percent.{{cite journal | vauthors = Yolken R | title = Viruses and schizophrenia: a focus on herpes simplex virus | journal = Herpes | volume = 11 | issue = Suppl 2 | pages = 83A–88A | date = June 2004 | pmid = 15319094 }} Viral infections of the brain during childhood are also linked to a risk of schizophrenia during adulthood.{{cite journal | vauthors = Khandaker GM | title = Childhood infection and adult schizophrenia: a meta-analysis of population-based studies. | journal = Schizophr. Res. | volume = 139 | issue = 1–3 | pages = 161–168 |date = August 2012 | pmid = 22704639 | pmc = 3485564 | doi = 10.1016/j.schres.2012.05.023}} Cat exposure is also associated with an increased risk of broadly defined schizophrenia-related disorders, with an odds ratio of 2.4.{{cite journal | title = Cat Ownership and Schizophrenia-Related Disorders and Psychotic-Like Experiences: A Systematic Review and Meta-Analysis | journal = Schizophrenia Bulletin | volume = 50 | issue = 3 | pages = 489–495 | date = May 2024 | pmid = 38491934 | pmc = 11059805 | doi = 10.1093/schbul/sbad168 | vauthors = McGrath JJ, Lim CC, Saha S }}

Adverse childhood experiences (ACEs), severe forms of which are classed as childhood trauma, range from being bullied or abused, to the death of a parent.{{cite journal |vauthors=Pearce J, Murray C, Larkin W |title=Childhood adversity and trauma:experiences of professionals trained to routinely enquire about childhood adversity |journal=Heliyon |volume=5 |issue=7 |page=e01900 |date=July 2019 |pmid=31372522 |doi=10.1016/j.heliyon.2019.e01900|doi-access=free |pmc=6658729 |bibcode=2019Heliy...501900P }} Many adverse childhood experiences can cause toxic stress and increase the risk of psychosis.{{cite journal | vauthors = Dvir Y, Denietolis B, Frazier JA | title = Childhood trauma and psychosis | journal = Child and Adolescent Psychiatric Clinics of North America | volume = 22 | issue = 4 | pages = 629–641 | date = October 2013 | pmid = 24012077 | doi = 10.1016/j.chc.2013.04.006 | s2cid = 40053289 }}{{cite journal | vauthors = Misiak B, Krefft M, Bielawski T, Moustafa AA, Sąsiadek MM, Frydecka D | s2cid = 21614845 | title = Toward a unified theory of childhood trauma and psychosis: A comprehensive review of epidemiological, clinical, neuropsychological and biological findings | journal = Neuroscience and Biobehavioral Reviews | volume = 75 | pages = 393–406 | date = April 2017 | pmid = 28216171 | doi = 10.1016/j.neubiorev.2017.02.015 }} Chronic trauma, including ACEs, can promote lasting inflammatory dysregulation throughout the nervous system.{{cite book | vauthors = Nettis MA, Pariante CM, Mondelli V | title = Neuroinflammation and Schizophrenia | chapter = Early-Life Adversity, Systemic Inflammation and Comorbid Physical and Psychiatric Illnesses of Adult Life | series = Current Topics in Behavioral Neurosciences| volume = 44 | pages = 207–225 | date = 2020 | pmid = 30895531 | doi = 10.1007/7854_2019_89 | isbn = 978-3-030-39140-9 | s2cid = 84842249 | chapter-url = https://kclpure.kcl.ac.uk/portal/en/publications/earlylife-adversity-systemic-inflammation-and-comorbid-physical-and-psychiatric-illnesses-of-adult-life(d2cdfc38-19e7-4918-80f1-5525e6ff45bf).html}} It is suggested that early stress may contribute to the development of schizophrenia through these alterations in the immune system. Schizophrenia was the last diagnosis to benefit from the link made between ACEs and adult mental health outcomes.{{cite journal |vauthors=Guloksuz S, van Os J |title=The slow death of the concept of schizophrenia and the painful birth of the psychosis spectrum |journal=Psychological Medicine |volume=48 |issue=2 |pages=229–244 |date=January 2018 |pmid=28689498 |doi=10.1017/S0033291717001775|doi-access=free }}

Living in an urban environment during childhood or as an adult has consistently been found to increase the risk of schizophrenia by a factor of two,{{cite journal |vauthors= Costa E, Silva JA, Steffen RE |title=Urban environment and psychiatric disorders: a review of the neuroscience and biology |journal=Metabolism: Clinical and Experimental |volume=100S |page=153940 |date=November 2019 |pmid=31610855|doi=10.1016/j.metabol.2019.07.004|s2cid=204704312 }} even after taking into account drug use, ethnic group, and size of social group.{{cite journal | vauthors = van Os J | title = Does the urban environment cause psychosis? | journal = The British Journal of Psychiatry | volume = 184 | issue = 4 | pages = 287–8 | date = April 2004 | pmid = 15056569 | doi = 10.1192/bjp.184.4.287 | doi-access = free }} A possible link between the urban environment and pollution has been suggested to be the cause of the elevated risk of schizophrenia.{{cite journal |vauthors=Attademo L, Bernardini F, Garinella R, Compton MT |s2cid=25505446 |title= Environmental pollution and risk of psychotic disorders: A review of the science to date |journal=Schizophrenia Research |volume=181 |pages=55–59 |date=March 2017 |pmid=27720315 |doi=10.1016/j.schres.2016.10.003}} Other risk factors include social isolation, immigration related to social adversity and racial discrimination, family dysfunction, unemployment, and poor housing conditions.{{cite journal | vauthors = Selten JP, Cantor-Graae E, Kahn RS | s2cid = 21391349 | title = Migration and schizophrenia | journal = Current Opinion in Psychiatry | volume = 20 | issue = 2 | pages = 111–115 | date = March 2007 | pmid = 17278906 | doi = 10.1097/YCO.0b013e328017f68e }} Having a father older than 40 years, or parents younger than 20 years are also associated with schizophrenia.{{cite journal | vauthors = Sharma R, Agarwal A, Rohra VK, Assidi M, Abu-Elmagd M, Turki RF | title = Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring | journal = Reproductive Biology and Endocrinology | volume = 13 | pages = 35 | date = April 2015 | pmid = 25928123 | pmc = 4455614 | doi = 10.1186/s12958-015-0028-x | doi-access = free }}

{{Further|Risk factors of schizophrenia#Substance use|Substance-induced psychosis}}

About half of those with schizophrenia use recreational drugs including alcohol, tobacco, and cannabis excessively.{{cite journal | vauthors = Sagud M, Mihaljević-Peles A, Mück-Seler D, Pivac N, Vuksan-Cusa B, Brataljenović T, Jakovljević M | title = Smoking and schizophrenia | journal = Psychiatria Danubina | volume = 21 | issue = 3 | pages = 371–375 | date = September 2009 | pmid = 19794359 }} Use of stimulants such as amphetamine and cocaine can lead to a temporary stimulant psychosis, which presents very similarly to schizophrenia. Rarely, alcohol use can also result in a similar alcohol-related psychosis.{{Cite journal |url= http://www.emedicine.com/med/topic3113.htm |title=Alcohol-Related Psychosis |access-date=27 September 2006 | vauthors = Larson M |date=30 March 2006 |journal=EMedicine |url-status=live |archive-url= https://web.archive.org/web/20081109011819/http://www.emedicine.com/MED/topic3113.htm |archive-date=9 November 2008}} Drugs may also be used as coping mechanisms by people who have schizophrenia, to deal with depression, anxiety, boredom, and loneliness.{{cite journal | vauthors = Gregg L, Barrowclough C, Haddock G | title = Reasons for increased substance use in psychosis | journal = Clinical Psychology Review | volume = 27 | issue = 4 | pages = 494–510 | date = May 2007 | pmid = 17240501 | doi = 10.1016/j.cpr.2006.09.004 }}{{cite journal | vauthors = Leweke FM, Koethe D | title = Cannabis and psychiatric disorders: it is not only addiction | journal = Addiction Biology | volume = 13 | issue = 2 | pages = 264–75 | date = June 2008 | pmid = 18482435 | doi = 10.1111/j.1369-1600.2008.00106.x | s2cid = 205400285 }} The use of cannabis and tobacco are not associated with the development of cognitive deficits, and sometimes a reverse relationship is found where their use improves these symptoms.{{cite journal | vauthors = Vidailhet P | title = [First-episode psychosis, cognitive difficulties and remediation]. | journal = L'Encéphale | date = September 2013 | volume = 39 | issue = Suppl 2 | language= fr| pages = S83-92 | doi = 10.1016/S0013-7006(13)70101-5 | pmid=24084427}} However, substance use disorders are associated with an increased risk of suicide, and a poor response to treatment.{{cite book |vauthors=Khokhar JY, Henricks AM, Sullivan ED, Green AI |title=Apprentices to Genius: A tribute to Solomon H. Snyder |chapter=Unique Effects of Clozapine: A Pharmacological Perspective |series=Advances in Pharmacology |volume=82 |pages=137–162 |date=2018 |pmid=29413518|doi=10.1016/bs.apha.2017.09.009|pmc=7197512 |isbn=978-0128140871 }}{{cite journal |vauthors=Bighelli I, Rodolico A, García-Mieres H, et al |title=Psychosocial and psychological interventions for relapse prevention in schizophrenia: a systematic review and network meta-analysis |journal=Lancet Psychiatry |volume=8 |issue=11 |pages=969–980 |date=November 2021 |pmid=34653393 |doi=10.1016/S2215-0366(21)00243-1 |s2cid=239003358 |doi-access=free |url=https://boris.unibe.ch/160225/8/Bighelli_LancetPsychiatry_2021.pdf }}

Cannabis use may be a contributory factor in the development of schizophrenia, potentially increasing the risk of the disease in those who are already at risk.{{cite journal |vauthors=Patel S, Khan S, M S, Hamid P |title=The Association Between Cannabis Use and Schizophrenia: Causative or Curative? A Systematic Review |journal= Cureus |volume=12 |issue=7 |pages=e9309 |date=July 2020 |pmid=32839678 |pmc=7442038 |doi=10.7759/cureus.9309 |doi-access=free |url=}}{{cite journal |vauthors=Hasan A, von Keller R, Friemel CM, Hall W, Schneider M, Koethe D, Leweke FM, Strube W, Hoch E |title=Cannabis use and psychosis: a review of reviews |journal=Eur Arch Psychiatry Clin Neurosci |volume=270 |issue=4 |pages= 403–412 |date=June 2020 |pmid=31563981 |doi=10.1007/s00406-019-01068-z |s2cid=203567900 |url=}}{{cite web |title=Causes — Schizophrenia | url= https://www.nhs.uk/mental-health/conditions/schizophrenia/causes/ |publisher= UK National Health Service |date=11 November 2019 |access-date= 8 December 2021}} The increased risk may require the presence of certain genes within an individual.{{cite journal | vauthors = Parakh P, Basu D | title = Cannabis and psychosis: have we found the missing links? | journal = Asian Journal of Psychiatry | volume = 6 | issue = 4 | pages = 281–287 | date = August 2013 | pmid = 23810133 | doi = 10.1016/j.ajp.2013.03.012 | type = Review | quote = Cannabis acts as a component cause of psychosis, that is, it increases the risk of psychosis in people with certain genetic or environmental vulnerabilities, though by itself, it is neither a sufficient nor a necessary cause of psychosis. }} Its use is associated with doubling the rate.{{cite journal | vauthors = Ortiz-Medina MB, Perea M, Torales J, Ventriglio A, Vitrani G, Aguilar L, Roncero C | title = Cannabis consumption and psychosis or schizophrenia development | journal = The International Journal of Social Psychiatry | volume = 64 | issue = 7 | pages = 690–704 | date = November 2018 | pmid = 30442059 | doi = 10.1177/0020764018801690 | s2cid = 53563635 }}

{{Main|Causes of schizophrenia}}{{See also|Aberrant salience}}

The causes of schizophrenia are still unknown. Several models have been put forward to explain the link between altered brain function and schizophrenia. The prevailing model of schizophrenia is that of a neurodevelopmental disorder, and the underlying changes that occur before symptoms become evident are seen as arising from the interaction between genes and the environment.{{cite journal |vauthors=Hayes D, Kyriakopoulos M |title=Dilemmas in the treatment of early-onset first-episode psychosis |journal=Therapeutic Advances in Psychopharmacology |volume=8 |issue=8 |pages=231–239 |date=August 2018 |pmid=30065814 |doi=10.1177/2045125318765725|pmc=6058451 |doi-access= free }} Extensive studies support this model. Maternal infections, malnutrition and complications during pregnancy and childbirth are known risk factors for the development of schizophrenia, which usually emerges between the ages of 18 and 25, a period that overlaps with certain stages of neurodevelopment.{{cite journal |vauthors=Cannon TD |title=How Schizophrenia Develops: Cognitive and Brain Mechanisms Underlying Onset of Psychosis |journal=Trends Cogn Sci |volume=19 |issue=12 |pages=744–756 |date= December 2015 |pmid=26493362 |pmc=4673025 |doi=10.1016/j.tics.2015.09.009 }} Gene-environment interactions lead to deficits in the neural circuitry that affect sensory and cognitive functions.

The common dopamine and glutamate models proposed are not mutually exclusive; each is seen to have a role in the neurobiology of schizophrenia.{{cite journal |vauthors=Correll CU, Schooler NR |title=Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment |journal= Neuropsychiatric Disease and Treatment |volume=16 |pages=519–534 |date=2020 |pmid=32110026 |doi=10.2147/NDT.S225643 |pmc=7041437 |doi-access=free }} The most common model put forward was the dopamine hypothesis of schizophrenia, which attributes psychosis to the mind's faulty interpretation of the misfiring of dopaminergic neurons.{{cite journal | vauthors = Howes OD | title = The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia | journal = Biological Psychiatry | date = 1 January 2017 | volume = 81 | issue = 1 | pages = 9–20 | doi = 10.1016/j.biopsych.2016.07.014 | pmid = 27720198| pmc = 5675052 }} This has been directly related to the symptoms of delusions and hallucinations.{{cite journal|vauthors=Broyd A, Balzan RP, Woodward TS, Allen P|date=June 2017|title=Dopamine, cognitive biases and assessment of certainty: A neurocognitive model of delusions| url= https://kclpure.kcl.ac.uk/portal/en/publications/dopamine-cognitive-biases-and-assessment-of-certainty-a-neurocognitive-model-of-delusions(138513dd-3a44-4deb-bac1-be45767ef51b).html|journal=Clinical Psychology Review|volume=54|pages=96–106|doi= 10.1016/j.cpr.2017.04.006 |pmid= 28448827|s2cid=3729566 }}{{cite journal | vauthors = Howes OD, Murray RM | title = Schizophrenia: an integrated sociodevelopmental-cognitive model | journal = Lancet | volume = 383 | issue = 9929 | pages = 1677–1687 | date = May 2014 | pmid = 24315522 | pmc = 4127444 | doi = 10.1016/S0140-6736(13)62036-X }}{{cite journal | vauthors = Grace AA | title = Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression | journal = Nature Reviews. Neuroscience | volume = 17 | issue = 8 | pages = 524–532 | date = August 2016 | pmid = 27256556 | pmc = 5166560 | doi = 10.1038/nrn.2016.57 }} Abnormal dopamine signaling has been implicated in schizophrenia based on the usefulness of medications that affect the dopamine receptor and the observation that dopamine levels are increased during acute psychosis.{{cite journal | vauthors = Fusar-Poli P, Meyer-Lindenberg A | title = Striatal presynaptic dopamine in schizophrenia, part II: meta-analysis of [(18)F/(11)C]-DOPA PET studies | journal = Schizophrenia Bulletin | volume = 39 | issue = 1 | pages = 33–42 | date = January 2013 | pmid = 22282454 | pmc = 3523905 | doi = 10.1093/schbul/sbr180 }}{{cite journal | vauthors = Howes OD, Kambeitz J, Kim E, Stahl D, Slifstein M, Abi-Dargham A, Kapur S | title = The nature of dopamine dysfunction in schizophrenia and what this means for treatment | journal = Archives of General Psychiatry | volume = 69 | issue = 8 | pages = 776–786 | date = August 2012 | pmid = 22474070 | pmc = 3730746 | doi = 10.1001/archgenpsychiatry.2012.169 }} A decrease in D₁ receptors in the dorsolateral prefrontal cortex may also be responsible for deficits in working memory.{{cite journal | vauthors = Arnsten AF, Girgis RR, Gray DL, Mailman RB | title = Novel Dopamine Therapeutics for Cognitive Deficits in Schizophrenia | journal = Biological Psychiatry | volume = 81 | issue = 1 | pages = 67–77 | date = January 2017 | pmid = 26946382 | pmc = 4949134 | doi = 10.1016/j.biopsych.2015.12.028 }}{{cite journal | vauthors = Maia TV, Frank MJ | title = An Integrative Perspective on the Role of Dopamine in Schizophrenia | journal = Biological Psychiatry | volume = 81 | issue = 1 | pages = 52–66 | date = January 2017 | pmid = 27452791 | pmc = 5486232 | doi = 10.1016/j.biopsych.2016.05.021 }}

The glutamate hypothesis of schizophrenia links alterations between glutamatergic neurotransmission and the neural oscillations that affect connections between the thalamus and the cortex. Studies have shown that a reduced expression of a glutamate receptor – NMDA receptor, and glutamate blocking drugs such as phencyclidine and ketamine can mimic the symptoms and cognitive problems associated with schizophrenia.{{cite journal | vauthors = Pratt J, Dawson N, Morris BJ, Grent-'t-Jong T, Roux F, Uhlhaas PJ | title = Thalamo-cortical communication, glutamatergic neurotransmission and neural oscillations: A unique window into the origins of ScZ? | journal = Schizophrenia Research | volume = 180 | pages = 4–12 | date = February 2017 | pmid = 27317361 | doi = 10.1016/j.schres.2016.05.013 | s2cid = 205075178 | url = https://eprints.gla.ac.uk/132874/1/132874.pdf }}{{cite journal | vauthors = Catts VS, Lai YL, Weickert CS, Weickert TW, Catts SV | title = A quantitative review of the post-mortem evidence for decreased cortical N-methyl-D-aspartate receptor expression levels in schizophrenia: How can we link molecular abnormalities to mismatch negativity deficits? | journal = Biological Psychology | volume = 116 | pages = 57–67 | date = April 2016 | pmid = 26549579 | doi = 10.1016/j.biopsycho.2015.10.013 | doi-access = free }}{{cite journal | vauthors = Michie PT, Malmierca MS, Harms L, Todd J | s2cid = 41179430 | title = The neurobiology of MMN and implications for schizophrenia | journal = Biological Psychology | volume = 116 | pages = 90–97 | date = April 2016 | pmid = 26826620 | doi = 10.1016/j.biopsycho.2016.01.011 }} Post-mortem studies consistently find that a subset of these neurons fail to express GAD67 (GAD1),{{cite journal | vauthors = Marín O | s2cid = 205507186 | title = Interneuron dysfunction in psychiatric disorders | journal = Nature Reviews. Neuroscience | volume = 13 | issue = 2 | pages = 107–120 | date = January 2012 | pmid = 22251963 | doi = 10.1038/nrn3155 }} in addition to abnormalities in brain morphometry. The subsets of interneurons that are abnormal in schizophrenia are responsible for the synchronizing of neural ensembles needed during working memory tasks. These give the neural oscillations produced as gamma waves that have a frequency of between 30 and 80 hertz. Both working memory tasks and gamma waves are impaired in schizophrenia, which may reflect abnormal interneuron functionality.{{cite journal | vauthors = Lewis DA, Hashimoto T, Volk DW | s2cid = 3335493 | title = Cortical inhibitory neurons and schizophrenia | journal = Nature Reviews. Neuroscience | volume = 6 | issue = 4 | pages = 312–324 | date = April 2005 | pmid = 15803162 | doi = 10.1038/nrn1648 }}{{cite journal | vauthors = Senkowski D, Gallinat J | s2cid = 206104940 | title = Dysfunctional prefrontal gamma-band oscillations reflect working memory and other cognitive deficits in schizophrenia | journal = Biological Psychiatry | volume = 77 | issue = 12 | pages = 1010–1019 | date = June 2015 | pmid = 25847179 | doi = 10.1016/j.biopsych.2015.02.034 |quote=Several studies that investigated perceptual processes found impaired GBR in ScZ patients over sensory areas, such as the auditory and visual cortex. Moreover, studies examining steady-state auditory-evoked potentials showed deficits in the gen- eration of oscillations in the gamma band.}}{{cite journal | vauthors = Reilly TJ, Nottage JF, Studerus E, Rutigliano G, Micheli AI, Fusar-Poli P, McGuire P | title = Gamma band oscillations in the early phase of psychosis: A systematic review | journal = Neuroscience and Biobehavioral Reviews | volume = 90 | pages = 381–399 | date = July 2018 | pmid = 29656029 | doi = 10.1016/j.neubiorev.2018.04.006 | quote = Decreased gamma power in response to a task was a relatively consistent finding, with 5 out of 6 studies reported reduced evoked or induced power. | s2cid = 4891072 | url = https://kclpure.kcl.ac.uk/portal/en/publications/e2f500b7-f358-433d-9f9c-7f6b9c52bb2f }} An important process that may be disrupted in neurodevelopment is astrogenesis – the formation of astrocytes. Astrocytes are crucial in contributing to the formation and maintenance of neural circuits and it is believed that disruption in this role can result in a number of neurodevelopmental disorders including schizophrenia.{{cite journal |vauthors=Sloan SA, Barres BA |title=Mechanisms of astrocyte development and their contributions to neurodevelopmental disorders |journal=Curr Opin Neurobiol |volume=27 |pages=75–81 |date=August 2014 |pmid=24694749 |pmc=4433289 |doi=10.1016/j.conb.2014.03.005 }} Evidence suggests that reduced numbers of astrocytes in deeper cortical layers are assocociated with a diminished expression of EAAT2, a glutamate transporter in astrocytes; supporting the glutamate hypothesis.

Deficits in executive functions, such as planning, inhibition, and working memory, are pervasive in schizophrenia. Although these functions are separable, their dysfunction in schizophrenia may reflect an underlying deficit in the ability to represent goal related information in working memory, and to use this to direct cognition and behavior.{{cite journal | vauthors = Lesh TA, Niendam TA, Minzenberg MJ, Carter CS | title = Cognitive control deficits in schizophrenia: mechanisms and meaning |journal=Neuropsychopharmacology | volume = 36 | issue = 1 | pages = 316–338 | date = January 2011 | pmid = 20844478 |pmc = 3052853 |doi =10.1038/npp.2010.156 }}{{cite journal | vauthors = Barch DM, Ceaser A | title = Cognition in schizophrenia: core psychological and neural mechanisms | journal = Trends in Cognitive Sciences | volume = 16 | issue = 1 | pages = 27–34 | date = January 2012 | pmid = 22169777 | pmc = 3860986 | doi = 10.1016/j.tics.2011.11.015 }} These impairments have been linked to a number of neuroimaging and neuropathological abnormalities. For example, functional neuroimaging studies report evidence of reduced neural processing efficiency, whereby the dorsolateral prefrontal cortex is activated to a greater degree to achieve a certain level of performance relative to controls on working memory tasks. These abnormalities may be linked to the consistent post-mortem finding of reduced neuropil, evidenced by increased pyramidal cell density and reduced dendritic spine density. These cellular and functional abnormalities may also be reflected in structural neuroimaging studies that find reduced grey matter volume in association with deficits in working memory tasks.{{cite journal | vauthors = Eisenberg DP, Berman KF | title = Executive function, neural circuitry, and genetic mechanisms in schizophrenia | journal = Neuropsychopharmacology | volume = 35 |issue = 1 | pages = 258–277 | date = January 2010 | pmid = 19693005 | pmc = 2794926 | doi = 10.1038/npp.2009.111}}

Positive symptoms have been linked to cortical thinning in the superior temporal gyrus.{{cite journal | vauthors = Walton E, Hibar DP, van Erp TG, Potkin SG, Roiz-Santiañez R, Crespo-Facorro B, Suarez-Pinilla P, Van Haren NE, de Zwarte SM, Kahn RS, Cahn W, Doan NT, Jørgensen KN, Gurholt TP, Agartz I, Andreassen OA, Westlye LT, Melle I, Berg AO, Mørch-Johnsen L, Faerden A, Flyckt L, Fatouros-Bergman H, Jönsson EG, Hashimoto R, Yamamori H, Fukunaga M, Preda A, De Rossi P, Piras F, Banaj N, Ciullo V, Spalletta G, Gur RE, Gur RC, Wolf DH, Satterthwaite TD, Beard LM, Sommer IE, Koops S, Gruber O, Richter A, Krämer B, Kelly S, Donohoe G, McDonald C, Cannon DM, Corvin A, Gill M, Di Giorgio A, Bertolino A, Lawrie S, Nickson T, Whalley HC, Neilson E, Calhoun VD, Thompson PM, Turner JA, Ehrlich S | title = Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium | journal = Acta Psychiatrica Scandinavica | volume = 135 | issue = 5 | pages = 439–447 | date = May 2017 | pmid = 28369804 | pmc = 5399182 | doi = 10.1111/acps.12718 }} The severity of negative symptoms has been linked to reduced thickness in the left medial orbitofrontal cortex.{{cite journal | vauthors = Walton E, Hibar DP, van Erp TG, Potkin SG, Roiz-Santiañez R, Crespo-Facorro B, Suarez-Pinilla P, van Haren NE, de Zwarte SM, Kahn RS, Cahn W, Doan NT, Jørgensen KN, Gurholt TP, Agartz I, Andreassen OA, Westlye LT, Melle I, Berg AO, Morch-Johnsen L, Færden A, Flyckt L, Fatouros-Bergman H, Jönsson EG, Hashimoto R, Yamamori H, Fukunaga M, Jahanshad N, De Rossi P, Piras F, Banaj N, Spalletta G, Gur RE, Gur RC, Wolf DH, Satterthwaite TD, Beard LM, Sommer IE, Koops S, Gruber O, Richter A, Krämer B, Kelly S, Donohoe G, McDonald C, Cannon DM, Corvin A, Gill M, Di Giorgio A, Bertolino A, Lawrie S, Nickson T, Whalley HC, Neilson E, Calhoun VD, Thompson PM, Turner JA, Ehrlich S | title = Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium | journal = Psychological Medicine | volume = 48 | issue = 1 | pages = 82–94 | date = January 2018 | pmid = 28545597 | pmc = 5826665 | doi = 10.1017/S0033291717001283 | collaboration = Karolinska Schizophrenia Project Consortium (KaSP) }} Anhedonia, traditionally defined as a reduced capacity to experience pleasure, is frequently reported in schizophrenia. However, a large body of evidence suggests that hedonic responses are intact in schizophrenia,{{cite journal | vauthors = Cohen AS, Minor KS | title = Emotional experience in patients with schizophrenia revisited: meta-analysis of laboratory studies | journal = Schizophrenia Bulletin | volume = 36 | issue = 1 | pages = 143–150 | date = January 2010 | pmid = 18562345 | pmc = 2800132 | doi = 10.1093/schbul/sbn061 }} and that what is reported to be anhedonia is a reflection of dysfunction in other processes related to reward.{{cite journal | vauthors = Strauss GP, Gold JM | title = A new perspective on anhedonia in schizophrenia | journal = The American Journal of Psychiatry | volume = 169 | issue = 4 | pages = 364–373 | date = April 2012 | pmid = 22407079 | pmc = 3732829 | doi = 10.1176/appi.ajp.2011.11030447 }} Overall, a failure of reward prediction is thought to lead to impairment in the generation of cognition and behavior required to obtain rewards, despite normal hedonic responses.{{cite book | vauthors = Young J, Anticevic A, Barch D | veditors = Charney D, Buxbaum J, Sklar P, Nestler E |title=Charney & Nestler's Neurobiology of Mental Illness |date=2018 |publisher=Oxford University Press. |location=New York |isbn=9780190681425 |pages=215, 217 |edition=5th |chapter=Cognitive and Motivational Neuroscience of Psychotic Disorders |quote=Several recent reviews (e.g., Cohen and Minor, 2010) have found that individuals with schizophrenia show relatively intact self-reported emotional responses to affect-eliciting stimuli as well as other indicators of intact response(215)...Taken together, the literature increasingly suggests that there may be a deficit in putatively DA-mediated reward learning and/ or reward prediction functions in schizophrenia. Such findings suggest that impairment in striatal reward prediction mechanisms may influence "wanting" in schizophrenia in a way that reduces the ability of individuals with schizophrenia to use anticipated rewards to drive motivated behavior.(217)}}

Another theory links abnormal brain lateralization to the development of being left-handed which is significantly more common in those with schizophrenia.{{cite journal | vauthors = Wiberg A, Ng M, Al Omran Y, Alfaro-Almagro F, McCarthy P, Marchini J, Bennett DL, Smith S, Douaud G, Furniss D | title = Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics | journal = Brain | volume = 142 | issue = 10 | pages = 2938–2947 | date = October 2019 | pmid = 31504236 | pmc = 6763735 | doi = 10.1093/brain/awz257 }} This abnormal development of hemispheric asymmetry is noted in schizophrenia.{{cite book |vauthors=Tzourio-Mazoyer N, Kennedy H, Van Essen DC, Christen Y |title=Micro-, Meso- and Macro-Connectomics of the Brain |chapter=Intra- and Inter-hemispheric Connectivity Supporting Hemispheric Specialization |series=Research and Perspectives in Neurosciences |date=2016 |pages=129–146 |doi=10.1007/978-3-319-27777-6_9 |pmid=28590670|isbn=978-3-319-27776-9 |s2cid=147813648 }} Studies have concluded that the link is a true and verifiable effect that may reflect a genetic link between lateralization and schizophrenia.{{cite journal | vauthors = Ocklenburg S, Güntürkün O, Hugdahl K, Hirnstein M | title = Laterality and mental disorders in the postgenomic age—A closer look at schizophrenia and language lateralization | journal = Neuroscience and Biobehavioral Reviews | volume = 59 | pages = 100–110 | date = December 2015 | pmid = 26598216 | doi = 10.1016/j.neubiorev.2015.08.019 | s2cid = 15983622 }}

Bayesian models of brain functioning have been used to link abnormalities in cellular functioning to symptoms.{{cite journal | vauthors = Friston KJ, Stephan KE, Montague R, Dolan RJ | title = Computational psychiatry: the brain as a phantastic organ | journal = The Lancet. Psychiatry | volume = 1 | issue = 2 | pages = 148–158 | date = July 2014 | pmid = 26360579 | doi = 10.1016/S2215-0366(14)70275-5 | s2cid = 15504512 }}{{cite journal | vauthors = Griffin JD, Fletcher PC | title = Predictive Processing, Source Monitoring, and Psychosis | journal = Annual Review of Clinical Psychology | volume = 13 | pages = 265–289 | date = May 2017 | pmid = 28375719 | pmc = 5424073 | doi = 10.1146/annurev-clinpsy-032816-045145}} Both hallucinations and delusions have been suggested to reflect improper encoding of prior expectations, thereby causing expectation to excessively influence sensory perception and the formation of beliefs. In approved models of circuits that mediate predictive coding, reduced NMDA receptor activation, could in theory result in the positive symptoms of delusions and hallucinations.{{cite journal | vauthors = Fletcher PC, Frith CD | s2cid = 6219485 | title = Perceiving is believing: a Bayesian approach to explaining the positive symptoms of schizophrenia | journal = Nature Reviews. Neuroscience | volume = 10 | issue = 1 | pages = 48–58 | date = January 2009 | pmid = 19050712 | doi = 10.1038/nrn2536 | url = https://pure.au.dk/ws/files/48560345/fletcher_frithNRN.pdf }}{{cite journal | vauthors = Corlett PR, Taylor JR, Wang XJ, Fletcher PC, Krystal JH | title = Toward a neurobiology of delusions | journal = Progress in Neurobiology | volume = 92 | issue = 3 | pages = 345–369 | date = November 2010 | pmid = 20558235 | pmc = 3676875 | doi = 10.1016/j.pneurobio.2010.06.007 }}{{cite journal | vauthors = Bastos AM, Usrey WM, Adams RA, Mangun GR, Fries P, Friston KJ | title = Canonical microcircuits for predictive coding | journal = Neuron | volume = 76 | issue = 4 | pages = 695–711 | date = November 2012 | pmid = 23177956 | pmc = 3777738 | doi = 10.1016/j.neuron.2012.10.038 }}

{{Main|Diagnosis of schizophrenia}}

Schizophrenia is diagnosed based on criteria in either the Diagnostic and Statistical Manual of Mental Disorders (DSM) published by the American Psychiatric Association or the International Statistical Classification of Diseases and Related Health Problems (ICD) published by the World Health Organization (WHO). These criteria use the self-reported experiences of the person and reported abnormalities in behavior, followed by a psychiatric assessment. The mental status examination is an important part of the assessment.{{cite journal | vauthors = Soltan M, Girguis J | title = How to approach the mental state examination | url = https://www.bmj.com/content/357/sbmj.j1821 | journal = BMJ | volume = 357 | page = j1821 | access-date = 9 January 2020 | doi = 10.1136/sbmj.j1821 | pmid = 31055448 | date = 8 May 2017| s2cid = 145820368 }} An established tool for assessing the severity of positive and negative symptoms is the Positive and Negative Syndrome Scale (PANSS).{{cite journal | vauthors = Lindenmayer JP | title = Are Shorter Versions of the Positive and Negative Syndrome Scale (PANSS) Doable? A Critical Review. | journal = Innovations in Clinical Neuroscience | date = 1 December 2017 | volume = 14 | issue = 11–12 |pages=73–76 | pmid = 29410940| pmc = 5788254 }} This has been seen to have shortcomings relating to negative symptoms, and other scales – the Clinical Assessment Interview for Negative Symptoms (CAINS), and the Brief Negative Symptoms Scale (BNSS) have been introduced. The DSM-5, published in 2013, gives a Scale to Assess the Severity of Symptom Dimensions outlining eight dimensions of symptoms.

DSM-5 states that to be diagnosed with schizophrenia, two diagnostic criteria have to be met over the period of one month, with a significant impact on social or occupational functioning for at least six months. One of the symptoms needs to be either delusions, hallucinations, or disorganized speech. A second symptom could be one of the negative symptoms, or severely disorganized or catatonic behaviour. A different diagnosis of schizophreniform disorder can be made before the six months needed for the diagnosis of schizophrenia.

In Australia, the guideline for diagnosis is for six months or more with symptoms severe enough to affect ordinary functioning.{{cite web |title=Diagnosis of schizophrenia |url=https://www.healthdirect.gov.au/diagnosis-of-schizophrenia |publisher= Australian Department of Health |access-date=28 January 2020 |date=10 January 2019}} In the UK diagnosis is based on having the symptoms for most of the time for one month, with symptoms that significantly affect the ability to work, study, or carry on ordinary daily living, and with other similar conditions ruled out.{{cite web |title=Schizophrenia – Diagnosis |url=https://www.nhs.uk/conditions/schizophrenia/diagnosis/ |publisher= UK National Health Service |access-date=28 January 2020 |date=23 October 2017}}

The ICD criteria are typically used in European countries; the DSM criteria are used predominantly in the United States and Canada, and are prevailing in research studies. In practice, agreement between the two systems is high.{{cite journal | vauthors = Jakobsen KD, Frederiksen JN, Hansen T, Jansson LB, Parnas J, Werge T | title = Reliability of clinical ICD-10 schizophrenia diagnoses | journal = Nordic Journal of Psychiatry | volume = 59 | issue = 3 | pages = 209–212 | year = 2005 | pmid = 16195122 | doi = 10.1080/08039480510027698 | s2cid = 24590483 }} The current proposal for the ICD-11 criteria for schizophrenia recommends adding self-disorder as a symptom.

A major unresolved difference between the two diagnostic systems is that of the requirement in DSM of an impaired functional outcome. WHO for ICD argues that not all people with schizophrenia have functional deficits and so these are not specific for the diagnosis.

Functional magnetic resonance imaging (fMRI) has become a tool in understanding brain activity and connectivity differences in individuals with schizophrenia. Through resting-state fMRI, researchers have observed altered connectivity patterns within several key brain networks, such as the default mode network (DMN),{{Cite journal |last1=Whitfield-Gabrieli |first1=Susan |last2=Ford |first2=Judith M. |date=2012-04-27 |title=Default Mode Network Activity and Connectivity in Psychopathology |url=https://www.annualreviews.org/doi/10.1146/annurev-clinpsy-032511-143049 |journal=Annual Review of Clinical Psychology |language=en |volume=8 |issue=1 |pages=49–76 |doi=10.1146/annurev-clinpsy-032511-143049 |pmid=22224834 |issn=1548-5943}} salience network (SN),{{Cite journal |last=Menon |first=Vinod |date=October 2011 |title=Large-scale brain networks and psychopathology: a unifying triple network model |url=https://linkinghub.elsevier.com/retrieve/pii/S1364661311001719 |journal=Trends in Cognitive Sciences |language=en |volume=15 |issue=10 |pages=483–506 |doi=10.1016/j.tics.2011.08.003|pmid=21908230 }} and central executive network (CEN).{{Cite journal |last1=Baker |first1=Justin T. |last2=Holmes |first2=Avram J. |last3=Masters |first3=Grace A. |last4=Yeo |first4=B. T. Thomas |last5=Krienen |first5=Fenna |last6=Buckner |first6=Randy L. |last7=Öngür |first7=Dost |date=2014-02-01 |title=Disruption of Cortical Association Networks in Schizophrenia and Psychotic Bipolar Disorder |journal=JAMA Psychiatry |language=en |volume=71 |issue=2 |pages=109–118 |doi=10.1001/jamapsychiatry.2013.3469 |issn=2168-622X |pmc=4435541 |pmid=24306091}} Alterations may underlie cognitive and emotional symptoms in schizophrenia, such as disorganized thinking, impaired attention, and emotional dysregulation.

File:Overlapping clinical phenotypes in genes associated with monogenic forms of autism spectrum disorder (ASD), dystonia, epilepsy and schizophrenia.svg showing overlapping clinical phenotypes in genes associated with monogenic forms of autism spectrum disorder (ASD), dystonia, epilepsy and schizophrenia:

{{legend|#007fff|Genes associated with epilepsy}}

{{legend|#007f7f|Genes associated with schizophrenia}}

{{legend|#d4aaff|Genes associated with autism spectrum disorder}}

{{legend|#ff0000|Genes associated with dystonia}}]]

Many people with schizophrenia may have one or more other mental disorders, such as anxiety disorders, obsessive–compulsive disorder, or substance use disorder. These are separate disorders that require treatment. When comorbid with schizophrenia, substance use disorder and antisocial personality disorder both increase the risk for violence. Comorbid substance use disorder also increases the risk of suicide.

Sleep disorders often co-occur with schizophrenia, and may be an early sign of relapse. Sleep disorders are linked with positive symptoms such as disorganized thinking and can adversely affect cortical plasticity and cognition.{{cite journal |vauthors=Staedt J, Hauser M, Gudlowski Y, Stoppe G |title=Sleep disorders in schizophrenia |journal=Fortschritte der Neurologie-Psychiatrie |volume=78 |issue=2 |pages=70–80 |date=February 2010 |pmid=20066610 |doi=10.1055/s-0028-1109967|s2cid=260137215 }} The consolidation of memories is disrupted in sleep disorders. They are associated with severity of illness, a poor prognosis, and poor quality of life.{{cite journal |vauthors=Faulkner SM, Bee PE, Meyer N, Dijk DJ, Drake RJ |title=Light therapies to improve sleep in intrinsic circadian rhythm sleep disorders and neuro-psychiatric illness: A systematic review and meta-analysis |journal=Sleep Medicine Reviews |volume=46 |pages=108–123 |date=August 2019 |pmid=31108433|doi=10.1016/j.smrv.2019.04.012|doi-access=free }} Sleep onset and maintenance insomnia is a common symptom, regardless of whether treatment has been received or not.{{cite journal | vauthors = Monti JM, BaHammam AS, Pandi-Perumal SR, Bromundt V, Spence DW, Cardinali DP, Brown GM | title = Sleep and circadian rhythm dysregulation in schizophrenia | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 43 | pages = 209–216 | date = June 2013 | pmid = 23318689 | doi = 10.1016/j.pnpbp.2012.12.021 | hdl-access = free | s2cid = 19626589 | hdl = 11336/3858 }} Genetic variations have been found associated with these conditions involving the circadian rhythm, dopamine and histamine metabolism, and signal transduction.{{cite journal | vauthors = Assimakopoulos K, Karaivazoglou K, Skokou M, Kalogeropoulou M, Kolios P, Gourzis P, Patrinos GP, Tsermpini EE | title = Genetic Variations Associated with Sleep Disorders in Patients with Schizophrenia: A Systematic Review | journal = Medicines | volume = 5 | issue = 2 | page = 27 | date = March 2018 | pmid = 29587340 | pmc = 6023503 | doi = 10.3390/medicines5020027 | doi-access = free }}

Schizophrenia is also associated with a number of somatic comorbidities including diabetes mellitus type 2, autoimmune diseases, and cardiovascular diseases. The association of these with schizophrenia may be partially due to medications (e.g. dyslipidemia from antipsychotics), environmental factors (e.g. complications from an increased rate of cigarette smoking), or associated with the disorder itself (e.g. diabetes mellitus type 2 and some cardiovascular diseases are thought to be genetically linked). These somatic comorbidities contribute to reduced life expectancy among persons with the disorder.{{cite journal |vauthors=Dieset I, Andreassen O, Haukvik U|title=Somatic Comorbidity in Schizophrenia: Some Possible Biological Mechanisms Across the Life Span |journal= Schizophrenia Bulletin|volume=42 |issue=6 |date=2016 |pages=1316–1319 | pmid=27033328|doi=10.1093/schbul/sbw028 |pmc=5049521 |doi-access=free }}

{{see also|Dual diagnosis|Comparison of bipolar disorder and schizophrenia}}

To make a diagnosis of schizophrenia other possible causes of psychosis need to be excluded.{{cite journal |vauthors=Schrimpf LA, Aggarwal A, Lauriello J |title=Psychosis |journal=Continuum (Minneap Minn) |volume=24 |issue=3 |pages=845–860 |date=June 2018 |pmid=29851881 |doi=10.1212/CON.0000000000000602|s2cid=243933980 }}{{Rp|page=858|quote=Psychosis as a primary mental health disorder is a diagnosis of exclusion. Many different manifestations of psychotic symptoms are directly related to an underlying medical or neurologic disorder. Delirium and dementia are the two most important disorders to rule out and can present in a very subtle fashion.}} Psychotic symptoms lasting less than a month may be diagnosed as brief psychotic disorder, or as schizophreniform disorder. Psychosis is noted in Other specified schizophrenia spectrum and other psychotic disorders as a DSM-5 category. Schizoaffective disorder is diagnosed if symptoms of mood disorder are substantially present alongside psychotic symptoms. Psychosis that results from a general medical condition or substance is termed secondary psychosis.

Psychotic symptoms may be present in several other conditions, including bipolar disorder, borderline personality disorder,{{cite journal | vauthors = Paris J | title = Differential Diagnosis of Borderline Personality Disorder | journal = The Psychiatric Clinics of North America | date = December 2018 | volume = 41 | issue = 4 | pages=575–582 | doi = 10.1016/j.psc.2018.07.001 | pmid = 30447725| s2cid = 53951650 }} substance intoxication, substance-induced psychosis, and a number of drug withdrawal syndromes. Non-bizarre delusions are also present in delusional disorder, and social withdrawal in social anxiety disorder, avoidant personality disorder and schizotypal personality disorder. Schizotypal personality disorder has symptoms that are similar but less severe than those of schizophrenia. Schizophrenia occurs along with obsessive–compulsive disorder (OCD) considerably more often than could be explained by chance, although it can be difficult to distinguish obsessions that occur in OCD from the delusions of schizophrenia.{{cite journal | vauthors = Bottas A |title=Comorbidity: Schizophrenia With Obsessive-Compulsive Disorder |journal=Psychiatric Times |volume=26 |issue=4 |date=15 April 2009 |url=http://www.psychiatrictimes.com/display/article/10168/1402540 |url-status=live |archive-url=https://web.archive.org/web/20130403064649/http://www.psychiatrictimes.com/display/article/10168/1402540 |archive-date=3 April 2013}} There can be considerable overlap with the symptoms of post-traumatic stress disorder.{{cite journal |vauthors=OConghaile A, DeLisi LE |title=Distinguishing schizophrenia from posttraumatic stress disorder with psychosis |journal=Curr Opin Psychiatry |volume=28 |issue=3 |pages=249–255 |date=May 2015 |pmid=25785709 |doi=10.1097/YCO.0000000000000158 |s2cid=12523516 }}

A more general medical and neurological examination may be needed to rule out medical illnesses which may rarely produce psychotic schizophrenia-like symptoms, such as metabolic disturbance, systemic infection, syphilis, HIV-associated neurocognitive disorder, epilepsy, limbic encephalitis, and brain lesions. Stroke, multiple sclerosis, hyperthyroidism, hypothyroidism, and dementias such as Alzheimer's disease, Huntington's disease, frontotemporal dementia, and the Lewy body dementias may also be associated with schizophrenia-like psychotic symptoms.{{cite book|title=Bradley's neurology in clinical practice|year=2012|publisher=Elsevier/Saunders|location=Philadelphia, PA|isbn=978-1-4377-0434-1| vauthors= Murray ED, Buttner N, Price BH | volume = 1 | edition=6th|pages=92–111| veditors = Bradley WG, Daroff RB, Fenichel GM, Jankovic J |chapter=Depression and Psychosis in Neurological Practice}} It may be necessary to rule out a delirium, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, and indicates an underlying medical illness. Investigations are not generally repeated for relapse unless there is a specific medical indication or possible adverse effects from antipsychotic medication.{{cite journal |vauthors=Leucht S, Bauer S, Siafis S, Hamza T, Wu H, Schneider-Thoma J, Salanti G, Davis JM |title=Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia: A Meta-analysis |journal=JAMA Psychiatry |volume=78 |issue=11 |pages=1238–1248 |date=November 2021 |pmid=34406325 |pmc=8374744 |doi=10.1001/jamapsychiatry.2021.2130}} In children hallucinations must be separated from typical childhood fantasies. It is difficult to distinguish childhood schizophrenia from autism.

Prevention of schizophrenia is difficult as there are no reliable markers for the later development of the disorder.{{cite journal | vauthors = Cannon TD, Cornblatt B, McGorry P | title = The empirical status of the ultra high-risk (prodromal) research paradigm | journal = Schizophrenia Bulletin | volume = 33 | issue = 3 | pages = 661–664 | date = May 2007 | pmid = 17470445 | pmc = 2526144 | doi = 10.1093/schbul/sbm031 }}

Early intervention programs diagnose and treat patients in the prodromal phase of the illness. There is some evidence that these programs reduce symptoms. Patients tend to prefer early treatment programs to ordinary treatment and are less likely to disengage from them. As of 2020, it is unclear whether the benefits of early treatment persist once the treatment is terminated.{{cite journal |vauthors=Puntis S, Minichino A, De Crescenzo F, Cipriani A, Lennox B, Harrison R |title=Specialised early intervention teams for recent-onset psychosis |journal=Cochrane Database Syst Rev |volume=11 |issue=11 |pages=CD013288 |date=November 2020 |pmid=33135811 |doi=10.1002/14651858.CD013288.pub2 |pmc=8092671 | quote=p. 22: There is low-certainty evidence for the use of SEl services in comparison to TAU for a small reduction in psychiatric hospitalisation, and moderate-certainty evidence of a large effect of reduction in disengagement from mental health services. There is moderate-certainty evidence that SEI results in a small reduction of positive (hallucinations, delusions and disordered thinking) and negative symptoms (social withdrawal, flat or blunted affect, and poverty of speech) and low-certainty evidence that it greatly increases satisfaction in care, while there is low-certainty evidence that it improves general functioning and the likelihood of recovery. These effects were only observed during treatment and there was no evidence that outcomes are improved after the treatment has finished, although these were based on only one trial.}}

Cognitive behavioral therapy may reduce the risk of psychosis in those at high risk after a year{{cite journal | vauthors = Stafford MR, Jackson H, Mayo-Wilson E, Morrison AP, Kendall T | title = Early interventions to prevent psychosis: systematic review and meta-analysis | journal = BMJ | volume = 346 | page = f185 | date = January 2013 | pmid = 23335473 | pmc = 3548617 | doi = 10.1136/bmj.f185 }} and is recommended in this group, by the National Institute for Health and Care Excellence (NICE).{{cite web|title=Psychosis and schizophrenia in adults: treatment and management |url=http://www.nice.org.uk/nicemedia/live/14382/66534/66534.pdf |publisher = National Institute for Health and Care Excellence (NICE) |access-date=19 April 2014 |pages=4–34|date=March 2014 |archive-url=https://web.archive.org/web/20140420070946/http://www.nice.org.uk/nicemedia/live/14382/66534/66534.pdf |archive-date=20 April 2014 }} Another preventive measure is to avoid drugs that have been associated with development of the disorder, including cannabis, cocaine, and amphetamines.

Antipsychotics are prescribed following a first-episode psychosis, and following remission, a preventive maintenance use is continued to avoid relapse. However, it is recognized that some people do recover following a single episode and that long-term use of antipsychotics will not be needed but there is no way of identifying this group.{{cite journal |vauthors=Taylor M, Jauhar S |title=Are we getting any better at staying better? The long view on relapse and recovery in first episode nonaffective psychosis and schizophrenia |journal=Therapeutic Advances in Psychopharmacology |volume=9 |date=September 2019|page=204512531987003 |pmid=31523418|doi=10.1177/2045125319870033 |pmc=6732843 }}

{{Main|Management of schizophrenia}}

The primary treatment of schizophrenia is the use of antipsychotic medications, often in combination with psychosocial interventions and social supports.{{cite journal | vauthors = Weiden PJ |title=Beyond Psychopharmacology: Emerging Psychosocial Interventions for Core Symptoms of Schizophrenia. |journal=Focus (American Psychiatric Publishing) |volume=14 |issue=3 |pages=315–327 |date=July 2016 |pmid=31975812|doi=10.1176/appi.focus.20160014|pmc=6526802 }} Community support services including drop-in centers, visits by members of a community mental health team, supported employment,{{cite journal | vauthors = McGurk SR, Mueser KT, Feldman K, Wolfe R, Pascaris A | title = Cognitive training for supported employment: 2–3 year outcomes of a randomized controlled trial | journal = The American Journal of Psychiatry | volume = 164 | issue = 3 | pages = 437–441 | date = March 2007 | pmid = 17329468 | doi = 10.1176/appi.ajp.164.3.437 }} and support groups are common. The time between the onset of psychotic symptoms to being given treatment – the duration of untreated psychosis (DUP) – is associated with a poorer outcome in both the short term and the long term.{{cite journal | vauthors = Souaiby L, Gaillard R, Krebs MO |title=[Duration of untreated psychosis: A state-of-the-art review and critical analysis] |journal=Encephale |volume=42 |issue=4 |pages=361–366 |date=August 2016|pmid=27161262 |doi=10.1016/j.encep.2015.09.007 }}

Voluntary or involuntary admission to hospital may be imposed by doctors and courts who deem a person to be having a severe episode. In the UK, large mental hospitals termed asylums began to be closed down in the 1950s with the advent of antipsychotics, and with an awareness of the negative impact of long-term hospital stays on recovery.{{cite journal |vauthors=Killaspy H|title= Contemporary mental health rehabilitation|journal=East Asian Archives of Psychiatry|volume=24 | issue=3|pages=89–94|date=September 2014|pmid = 25316799}} This process was known as deinstitutionalization, and community and supportive services were developed to support this change. Many other countries followed suit with the US starting in the 60s.{{cite journal | vauthors = Fuller Torrey E | title = Deinstitutionalization and the rise of violence. | journal = CNS Spectrums | date = June 2015 | volume = 20 | issue = 3 | pages = 207–214 | doi = 10.1017/S1092852914000753 | pmid = 25683467| s2cid = 22210482 }} There still remain a smaller group of people who do not improve enough to be discharged. In some countries that lack the necessary supportive and social services, long-term hospital stays are more usual.

File:Risperdal tablets.jpg (trade name Risperdal) is a common atypical antipsychotic medication.]]

The first-line treatment for schizophrenia is an antipsychotic. The first-generation antipsychotics, now called typical antipsychotics, like haloperidol, are dopamine antagonists that block D₂ receptors, and affect the neurotransmission of dopamine. Those brought out later, the second-generation antipsychotics known as atypical antipsychotics, including olanzapine and risperidone, can also have an effect on another neurotransmitter, serotonin. Antipsychotics can reduce the symptoms of anxiety within hours of their use, but, for other symptoms, they may take several days or weeks to reach their full effect. They have little effect on negative and cognitive symptoms, which may be helped by additional psychotherapies and medications.{{cite journal | vauthors = Ortiz-Orendain J, Covarrubias-Castillo SA, Vazquez-Alvarez AO, Castiello-de Obeso S, Arias Quiñones GE, Seegers M, Colunga-Lozano LE | title = Modafinil for people with schizophrenia or related disorders | journal = The Cochrane Database of Systematic Reviews | volume = 12 | page = CD008661 | date = December 2019 | issue = 12 | pmid = 31828767 | pmc = 6906203 | doi = 10.1002/14651858.CD008661.pub2 }} There is no single antipsychotic suitable for first-line treatment for everyone, as responses and tolerances vary between people.{{cite journal | vauthors = Lally J, MacCabe JH | title = Antipsychotic medication in schizophrenia: a review | journal = British Medical Bulletin | volume = 114 | issue = 1 | pages = 169–179 | date = June 2015 | pmid = 25957394 | doi = 10.1093/bmb/ldv017 | doi-access = }} Stopping medication may be considered after a single psychotic episode where there has been a full recovery with no symptoms for twelve months. Repeated relapses worsen the long-term outlook and the risk of relapse following a second episode is high, and long-term treatment is usually recommended.{{cite journal | vauthors = Keks N, Schwartz D, Hope J | title = Stopping and switching antipsychotic drugs | journal = Australian Prescriber | volume = 42 | issue = 5 | pages = 152–157 | date = October 2019 | pmid = 31631928 | pmc = 6787301 | doi = 10.18773/austprescr.2019.052 }}{{cite journal | vauthors = Harrow M, Jobe TH | title = Does long-term treatment of schizophrenia with antipsychotic medications facilitate recovery? | journal = Schizophrenia Bulletin | volume = 39 | issue = 5 | pages = 962–5 | date = September 2013 | pmid = 23512950 | pmc = 3756791 | doi = 10.1093/schbul/sbt034 }}

About half of those with schizophrenia will respond favourably to antipsychotics, and have a good return of functioning.{{cite journal |vauthors=Elkis H, Buckley PF |title=Treatment-Resistant Schizophrenia |journal=The Psychiatric Clinics of North America |volume=39 |issue=2 |pages=239–65 |date=June 2016 |pmid=27216902|doi=10.1016/j.psc.2016.01.006}} However, positive symptoms persist in up to a third of people. Following two trials of different antipsychotics over six weeks, that also prove ineffective, they will be classed as having treatment-resistant schizophrenia (TRS), and clozapine will be offered.{{cite journal |vauthors=Gillespie AL, Samanaite R, Mill J, Egerton A, MacCabe JH |title=Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review |journal=BMC Psychiatry |volume=17 |issue=1 |page=12 |date=13 January 2017 |pmid=28086761 |doi=10.1186/s12888-016-1177-y|pmc=5237235 |doi-access=free }} Clozapine is of benefit to around half of this group although it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.{{cite journal | vauthors = Essali A, Al-Haj Haasan N, Li C, Rathbone J | title = Clozapine versus typical neuroleptic medication for schizophrenia | journal = The Cochrane Database of Systematic Reviews | issue = 1 | page = CD000059 | date = January 2009 | volume = 2009 | pmid = 19160174 | doi = 10.1002/14651858.CD000059.pub2 | pmc = 7065592 }}

About 30 to 50 percent of people with schizophrenia do not accept that they have an illness or comply with their recommended treatment.{{cite journal | vauthors = Baier M | title = Insight in schizophrenia: a review | journal = Current Psychiatry Reports | volume = 12 | issue = 4 | pages = 356–361 | date = August 2010 | pmid = 20526897 | doi = 10.1007/s11920-010-0125-7 | s2cid = 29323212 }} For those who are unwilling or unable to take medication regularly, long-acting injections of antipsychotics may be used,{{cite journal | vauthors = Peters L, Krogmann A, von Hardenberg L, Bödeker K, Nöhles VB, Correll CU | title = Long-Acting Injections in Schizophrenia: a 3-Year Update on Randomized Controlled Trials Published January 2016 – March 2019 | journal = Current Psychiatry Reports | volume = 21 | issue = 12 | pages = 124 | date = November 2019 | pmid = 31745659 | doi = 10.1007/s11920-019-1114-0 | s2cid = 208144438 }} which reduce the risk of relapse to a greater degree than oral medications.{{cite journal | vauthors = Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, Davis JM | title = Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis | journal = Lancet | volume = 379 | issue = 9831 | pages = 2063–2071 | date = June 2012 | pmid = 22560607 | doi = 10.1016/S0140-6736(12)60239-6 | s2cid = 2018124 }} When used in combination with psychosocial interventions, they may improve long-term adherence to treatment.{{cite journal | vauthors = McEvoy JP | title = Risks versus benefits of different types of long-acting injectable antipsychotics | journal = The Journal of Clinical Psychiatry | volume = 67 | issue = Suppl 5 | pages = 15–18 | year = 2006 | pmid = 16822092 }}

The fixed-dose combination medication xanomeline/trospium chloride (Cobenfy) was approved for medical use in the United States in September 2024.{{cite press release | title=FDA Approves Drug with New Mechanism of Action for Treatment of Schizophrenia | website=U.S. Food and Drug Administration (FDA) | date=26 September 2024 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-drug-new-mechanism-action-treatment-schizophrenia | access-date=27 September 2024 | archive-date=27 September 2024 | archive-url=https://web.archive.org/web/20240927004824/https://www.fda.gov/news-events/press-announcements/fda-approves-drug-new-mechanism-action-treatment-schizophrenia | url-status=live }} {{PD-notice}}{{cite press release | title=U.S. Food and Drug Administration Approves Bristol Myers Squibb's Cobenfy (xanomeline and trospium chloride), a First-In-Class Muscarinic Agonist for the Treatment of Schizophrenia in Adults | publisher=Bristol Myers Squibb | via=Business Wire | date=27 September 2024 | url=https://www.businesswire.com/news/home/20240925382351/en/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibb%E2%80%99s-COBENFY%E2%84%A2-xanomeline-and-trospium-chloride-a-First-In-Class-Muscarinic-Agonist-for-the-Treatment-of-Schizophrenia-in-Adults | access-date=27 September 2024}} It is the first cholinergic agonist approved by the US Food and Drug Administration (FDA) to treat schizophrenia.

Negative and cognitive symptoms are an unmet clinical need in antipsychotic-based treatment approaches. Psychostimulant drugs have been found effective in the treatment of negative symptoms, but are rarely prescribed due to concerns about the excacerbation of positive symptoms. It is possible that low-dose psychedelic therapies could be of benefit in schizophrenia through their prosocial and procognitive effects, although there is a serious risk that high dose psychedelic therapies could lead to worsening of positive symptoms.{{Cite journal |last1=Sapienza |first1=Jacopo |last2=Martini |first2=Francesca |last3=Comai |first3=Stefano |last4=Cavallaro |first4=Roberto |last5=Spangaro |first5=Marco |last6=De Gregorio |first6=Danilo |last7=Bosia |first7=Marta |date=2024-09-18 |title=Psychedelics and schizophrenia: a double-edged sword |url=https://www.nature.com/articles/s41380-024-02743-x |journal=Molecular Psychiatry |volume=30 |issue=2 |language=en |pages=679–692 |doi=10.1038/s41380-024-02743-x |pmid=39294303 |issn=1476-5578}}

{{Further information|Antipsychotic#Adverse effects}}

Extrapyramidal symptoms, including akathisia, are associated with all commercially available antipsychotic to varying degrees.{{cite journal |vauthors=Chow CL, Kadouh NK, Bostwick JR, VandenBerg AM |date=June 2020 |title=Akathisia and Newer Second-Generation Antipsychotic Drugs: A Review of Current Evidence |url= |journal=Pharmacotherapy |volume=40 |issue=6 |pages=565–574 |doi=10.1002/phar.2404 |pmid=32342999|hdl=2027.42/155998 |s2cid=216596357 |hdl-access=free }}{{Rp|page=566|quote=However, EPS, particularly akathisia, occurs, to some degree, with all commercially available SGAs.}} There is little evidence that second generation antipsychotics have reduced levels of extrapyramidical symptoms compared to typical antipsychotics.{{Rp|page=566|quote=Furthermore, previous meta-analyses and systematic reviews comparing the safety and tolerability of FGAs and SGAs have found little evidence to support the notion that as a class, SGAs pose a reduced risk for EPS com- pared with FGAs. However, high-potency FGAs do tend to pose the greatest risk for EPS.}} Tardive dyskinesia can occur due to long-term use of antipsychotics, developing after months or years of use.{{cite journal |vauthors=Carbon M, Kane JM, Leucht S, Correll CU |date=October 2018 |title=Tardive dyskinesia risk with first- and second-generation antipsychotics in comparative randomized controlled trials: a meta-analysis |journal=World Psychiatry |volume=17 |issue=3 |pages=330–340 |doi=10.1002/wps.20579 |pmc=6127753 |pmid=30192088}} The antipsychotic clozapine is also associated with thromboembolism (including pulmonary embolism), myocarditis, and cardiomyopathy.

{{Further|Management of schizophrenia#Psychosocial}}

A number of psychosocial interventions that include several types of psychotherapy may be useful in the treatment of schizophrenia such as: family therapy,{{cite journal | vauthors = Pharoah F, Mari J, Rathbone J, Wong W | title = Family intervention for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 12 | issue = 12 | pages = CD000088 | date = December 2010 | pmid = 21154340 | pmc = 4204509 | doi = 10.1002/14651858.CD000088.pub2 | veditors = Pharoah F }} group therapy, cognitive remediation therapy (CRT),{{cite journal | vauthors = Bellani M, Ricciardi C, Rossetti MG, Zovetti N, Perlini C, Brambilla P | title = Cognitive remediation in schizophrenia: the earlier the better? | journal = Epidemiology and Psychiatric Sciences | volume = 29 | issue = | pages = e57 | date = September 2019 | pmid = 31556864 | pmc = 8061237 | doi = 10.1017/S2045796019000532 }} cognitive behavioral therapy (CBT), and metacognitive training.{{cite journal | vauthors = Philipp R, Kriston L, Lanio J, Kühne F, Härter M, Moritz S, Meister R | title = Effectiveness of metacognitive interventions for mental disorders in adults-A systematic review and meta-analysis (METACOG) | journal = Clinical Psychology & Psychotherapy | volume = 26 | issue = 2 | pages = 227–240 | date = March 2019 | pmid = 30456821 | doi = 10.1002/cpp.2345 | s2cid = 53872643 }}{{cite journal | vauthors = Rouy M, Saliou P, Nalborczyk L, Pereira M, Roux P, Faivre N | title = Systematic review and meta-analysis of metacognitive abilities in individuals with schizophrenia spectrum disorders | journal = Neuroscience and Biobehavioral Reviews | volume = 126 | issue = | pages = 329–337 | date = July 2021 | pmid = 33757817 | doi = 10.1016/j.neubiorev.2021.03.017 | s2cid = 232288918 | url = https://hal.archives-ouvertes.fr/hal-03178486/file/2020.12.03.20243113v1.full.pdf }} Skills training, help with substance use, and weight management – often needed as a side effect of an antipsychotic – are also offered.{{cite journal | vauthors = Dixon LB, Dickerson F, Bellack AS, Bennett M, Dickinson D, Goldberg RW, Lehman A, Tenhula WN, Calmes C, Pasillas RM, Peer J, Kreyenbuhl J | title = The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements | journal = Schizophrenia Bulletin | volume = 36 | issue = 1 | pages = 48–70 | date = January 2010 | pmid = 19955389 | pmc = 2800143 | doi = 10.1093/schbul/sbp115 }} In the US, interventions for first episode psychosis have been brought together in an overall approach known as coordinated speciality care (CSC) and also includes support for education. In the UK care across all phases is a similar approach that covers many of the treatment guidelines recommended. The aim is to reduce the number of relapses and stays in the hospital.

Other support services for education, employment, and housing are usually offered. For people with severe schizophrenia, who are discharged from a stay in the hospital, these services are often brought together in an integrated approach to offer support in the community away from the hospital setting. In addition to medicine management, housing, and finances, assistance is given for more routine matters such as help with shopping and using public transport. This approach is known as assertive community treatment (ACT) and has been shown to achieve positive results in symptoms, social functioning and quality of life.{{cite journal | vauthors = Bond GR, Drake RE | title = The critical ingredients of assertive community treatment. | journal = World Psychiatry | date = June 2015 | volume = 14 | issue = 2 | pages = 240–242 | doi = 10.1002/wps.20234 | pmid = 26043344| pmc = 4471983 }}{{cite journal | vauthors = Smeerdijk M | title = [Using resource groups in assertive community treatment; literature review and recommendation]. | journal = Tijdschrift voor Psychiatrie | date = 2017 | volume = 59 | issue = 8 | pages = 466–473 | pmid = 28880347}} Another more intense approach is known as intensive care management (ICM). ICM is a stage further than ACT and emphasises support of high intensity in smaller caseloads, (less than twenty). This approach is to provide long-term care in the community. Studies show that ICM improves many of the relevant outcomes including social functioning.{{cite journal | vauthors = Dieterich M | title = Intensive case management for severe mental illness | journal=The Cochrane Database of Systematic Reviews | date = 6 January 2017 | volume = 1 | issue = 1 | page = CD007906 | doi = 10.1002/14651858.CD007906.pub3 | pmid = 28067944| pmc = 6472672 }}

Some studies have shown little evidence for the effectiveness of CBT in either reducing symptoms or preventing relapse.{{cite journal | vauthors = Jauhar S, McKenna PJ, Radua J, Fung E, Salvador R, Laws KR | title = Cognitive-behavioural therapy for the symptoms of schizophrenia: systematic review and meta-analysis with examination of potential bias | journal = The British Journal of Psychiatry | volume = 204 | issue = 1 | pages = 20–29 | date = January 2014 | pmid = 24385461 | doi = 10.1192/bjp.bp.112.116285 | type = Review | doi-access = free }}{{cite journal | vauthors = Jones C, Hacker D, Meaden A, Cormac I, Irving CB, Xia J, Zhao S, Shi C, Chen J | title = Cognitive behavioural therapy plus standard care versus standard care plus other psychosocial treatments for people with schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD008712 | date = November 2018 | pmid = 30480760 | pmc = 6516879 | doi = 10.1002/14651858.CD008712.pub3 }} However, other studies have found that CBT does improve overall psychotic symptoms (when in use with medication) and it has been recommended in Canada, but has been seen to have no effect on social function, relapse, or quality of life.{{cite journal | title = Cognitive Behavioural Therapy for Psychosis: A Health Technology Assessment| journal = Ontario Health Technology Assessment Series | date = 2018 |volume = 18 | issue = 5 |pages = 1–141 | pmid = 30443277 | pmc = 6235075 | author = Health Quality Ontario }} In the UK it is recommended as an add-on therapy in the treatment of schizophrenia. Arts therapies are seen to improve negative symptoms in some people, and are recommended by NICE in the UK.{{cite web | title = Schizophrenia – Treatment | url = https://www.nhs.uk/conditions/schizophrenia/treatment/ | publisher= UK National Health Service | access-date = 8 January 2020 | date = 23 October 2017}} This approach is criticised as having not been well-researched,{{cite journal | vauthors = Ruddy R, Milnes D | title = Art therapy for schizophrenia or schizophrenia-like illnesses | journal = The Cochrane Database of Systematic Reviews | issue = 4 | page = CD003728 | date = October 2005 | pmid = 16235338 | doi = 10.1002/14651858.CD003728.pub2 | url = http://www.cochrane.org/reviews/en/ab003728.html | archive-url = https://web.archive.org/web/20111027132811/http://www2.cochrane.org/reviews/en/ab003728.html | df = dmy-all | url-status=live | archive-date = 27 October 2011 }}{{cite journal | vauthors = Ruddy RA, Dent-Brown K | title = Drama therapy for schizophrenia or schizophrenia-like illnesses | journal = The Cochrane Database of Systematic Reviews | issue = 1 | page = CD005378 | date = January 2007 | pmid = 17253555 | doi = 10.1002/14651858.CD005378.pub2 | url = http://www.cochrane.org/reviews/en/ab005378.html | archive-url = https://web.archive.org/web/20110825024045/http://www2.cochrane.org/reviews/en/ab005378.html | df = dmy-all | url-status=live | archive-date = 25 August 2011 }} and arts therapies are not recommended in Australian guidelines for example.{{cite journal |vauthors=Galletly C, Castle D, Dark F, et al |title=Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders |journal=Aust N Z J Psychiatry |volume=50 |issue=5 |pages=410–472 |date=May 2016 |pmid=27106681 |doi=10.1177/0004867416641195 |s2cid=6536743 |url=|doi-access=free }} Peer support, in which people with personal experience of schizophrenia, provide help to each other, is of unclear benefit.{{cite journal |vauthors= Chien WT, Clifton AV, Zhao S, Lui S |title=Peer support for people with schizophrenia or other serious mental illness. |journal=The Cochrane Database of Systematic Reviews |date=4 April 2019 |volume=4 |issue=6 |page=CD010880 |doi=10.1002/14651858.CD010880.pub2 |pmid=30946482|pmc=6448529 }}

Exercise including aerobic exercise has been shown to improve positive and negative symptoms, cognition, working memory, and improve quality of life.{{cite journal | vauthors =Girdler SJ, Confino JE, Woesner ME | title = Exercise as a Treatment for Schizophrenia: A Review. |journal= Psychopharmacology Bulletin | date = 15 February 2019 | volume = 49 | issue = 1 | pages=56–69 | pmid=30858639| pmc = 6386427 }}{{cite journal | vauthors = Firth J | title = Aerobic Exercise Improves Cognitive Functioning in People With Schizophrenia: A Systematic Review and Meta-Analysis | journal = Schizophrenia Bulletin | date = 1 May 2017 | volume = 43 | issue = 3 | pages = 546–556 | doi = 10.1093/schbul/sbw115 | pmid = 27521348| pmc = 5464163 }} Exercise has also been shown to increase the volume of the hippocampus in those with schizophrenia. A decrease in hippocampal volume is one of the factors linked to the development of the disease. However, there still remains the problem of increasing motivation for, and maintaining participation in physical activity.{{cite journal | vauthors = Tréhout M, Dollfus S |title = [Physical activity in patients with schizophrenia: From neurobiology to clinical benefits]. | journal = L'Encéphale | date = December 2018 | volume = 44 | issue = 6 | pages = 538–547 | doi=10.1016/j.encep.2018.05.005 | pmid = 29983176|s2cid = 150334210 }} Supervised sessions are recommended. In the UK healthy eating advice is offered alongside exercise programs.{{cite web |title=Quality statement 7: Promoting healthy eating, physical activity and smoking cessation {{!}} Psychosis and schizophrenia in adults |date=12 February 2015 |url=https://www.nice.org.uk/guidance/qs80/chapter/Quality-statement-7-Promoting-healthy-eating-physical-activity-and-smoking-cessation |publisher= UK National Institute for Health and Care Excellence}}

An inadequate diet is often found in schizophrenia, and associated vitamin deficiencies including those of folate, and vitamin D are linked to the risk factors for the development of schizophrenia and for early death including heart disease.{{cite journal | vauthors = Firth J, Carney R, Stubbs B, Teasdale SB, Vancampfort D, Ward PB, Berk M, Sarris J | title = Nutritional Deficiencies and Clinical Correlates in First-Episode Psychosis: A Systematic Review and Meta-analysis | journal = Schizophrenia Bulletin | volume = 44 | issue = 6 | pages = 1275–1292 | date = October 2018 | pmid = 29206972 | pmc = 6192507 | doi = 10.1093/schbul/sbx162 }}{{cite journal | vauthors = Rastogi A, Viani-Walsh D, Akbari S, Gall N, Gaughran F, Lally J | title = Pathogenesis and management of Brugada syndrome in schizophrenia: A scoping review | journal = General Hospital Psychiatry | volume = 67 | pages = 83–91 | date = October 2020 | pmid = 33065406 | pmc = 7537626 | doi = 10.1016/j.genhosppsych.2020.09.003 }} Those with schizophrenia possibly have the worst diet of all the mental disorders. Lower levels of folate and vitamin D have been noted as significantly lower in first episode psychosis. The use of supplemental folate is recommended.{{cite journal | vauthors = Martone G | title = Enhancement of recovery from mental illness with l-methylfolate supplementation | journal = Perspectives in Psychiatric Care | volume = 54 | issue = 2 | pages = 331–334 | date = April 2018 | pmid = 28597528 | doi = 10.1111/ppc.12227 | doi-access = free }} A zinc deficiency has also been noted.{{cite journal | vauthors = Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, Veronese N, Schuch F, Smith L, Solmi M, Carvalho AF, Vancampfort D, Berk M, Stubbs B, Sarris J | title = The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials | journal = World Psychiatry | volume = 18 | issue = 3 | pages = 308–324 | date = October 2019 | pmid = 31496103 | pmc = 6732706 | doi = 10.1002/wps.20672 }} Vitamin B₁₂ is also often deficient and this is linked to worse symptoms. Supplementation with B vitamins has been shown to significantly improve symptoms, and to put in reverse some of the cognitive deficits. It is also suggested that the noted dysfunction in gut microbiota might benefit from the use of probiotics.

{{Main|Prognosis of schizophrenia}}{{See also|Physical health in schizophrenia}}

File:Schizophrenia world map - DALY - WHO2004.svgs lost due to schizophrenia per 100,000 inhabitants in 2004

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Schizophrenia has great human and economic costs. It decreases life expectancy by between 10 and 28 years. This is primarily because of its association with heart disease,{{cite journal |vauthors=Kritharides L, Chow V, Lambert TJ |date=6 February 2017 |title=Cardiovascular disease in patients with schizophrenia |journal=The Medical Journal of Australia |volume=206 |issue=2 |pages=91–95 |doi=10.5694/mja16.00650 |pmid=28152356 |s2cid=5388097}} diabetes, obesity, poor diet, a sedentary lifestyle, and smoking, with an increased rate of suicide playing a lesser role.{{cite journal | vauthors = Erlangsen A, Eaton WW, Mortensen PB, Conwell Y | title = Schizophrenia—a predictor of suicide during the second half of life? | journal = Schizophrenia Research | volume = 134 | issue = 2–3 | pages = 111–117 | date = February 2012 | pmid = 22018943 | pmc = 3266451 | doi = 10.1016/j.schres.2011.09.032 }} Side effects of antipsychotics may also increase the risk.

Almost 40% of those with schizophrenia die from complications of cardiovascular disease which is seen to be increasingly associated. An underlying factor of sudden cardiac death may be Brugada syndrome (BrS) – BrS mutations that overlap with those linked with schizophrenia are the calcium channel mutations. BrS may also be drug-induced from certain antipsychotics and antidepressants. Primary polydipsia, or excessive fluid intake, is relatively common in people with chronic schizophrenia.{{cite book| vauthors = Goroll AH, Mulley AG |title=Primary Care Medicine: Office Evaluation and Management of The Adult Patient |edition=Sixth|date=2011|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-2159-9|page=Chapter 101|url=https://books.google.com/books?id=fXpKo1afC2YC&pg=PT1766}}{{cite journal | vauthors = Rizvi S, Gold J, Khan AM | title = Role of Naltrexone in Improving Compulsive Drinking in Psychogenic Polydipsia. | journal = Cureus | date = 5 August 2019 | volume = 11 | issue = 8 | page =e5320 | doi = 10.7759/cureus.5320 | doi-access = free | pmid = 31598428| pmc = 6777931 }} This may lead to hyponatremia which can be life-threatening. Antipsychotics can lead to a dry mouth, but there are several other factors that may contribute to the disorder; it may reduce life expectancy by 13 percent. Barriers to improving the mortality rate in schizophrenia are poverty, overlooking the symptoms of other illnesses, stress, stigma, and medication side effects.{{cite journal |vauthors=Seeman MV |s2cid=170078453 |title=Schizophrenia Mortality: Barriers to Progress |journal=The Psychiatric Quarterly |volume=90 |issue=3 |pages=553–563 |date=September 2019 |pmid=31147816 |doi=10.1007/s11126-019-09645-0}}{{Cite book |last=Farrell |first=Michael |title=Controversies in schizophrenia: issues, causes, and treatment |date=2024 |publisher=Routledge, Taylor & Francis Group |isbn=978-1-003-41355-4 |location=New York, NY}}{{Cite book |last1=Assis |first1=Jorge Cândido de |url=https://link.springer.com/10.1007/978-3-031-24556-5 |title=Between Reason and Illusion: Demystifying Schizophrenia |last2=Villares |first2=Cecília Cruz |last3=Bressan |first3=Rodrigo Affonseca |date=2023 |publisher=Springer Nature Switzerland |isbn=978-3-031-24555-8 |series=Copernicus Books |location=Cham |language=en |doi=10.1007/978-3-031-24556-5}}

Schizophrenia is a major cause of disability. In 2016, it was classed as the 12th most disabling condition.{{cite journal | vauthors = Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, McGrath JJ, Whiteford HA | title = Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016 | journal = Schizophrenia Bulletin | volume = 44 | issue = 6 | pages = 1195–1203 | date = October 2018 | pmid = 29762765 | pmc = 6192504 | doi = 10.1093/schbul/sby058 }} Approximately 75% of people with schizophrenia have ongoing disability with relapses.{{cite journal | vauthors = Smith T, Weston C, Lieberman J | title = Schizophrenia (maintenance treatment) | journal = American Family Physician | volume = 82 | issue = 4 | pages = 338–339 | date = August 2010 | pmid = 20704164}} Some people do recover completely and others function well in society.{{cite journal | vauthors = Warner R | s2cid = 26666000 | title = Recovery from schizophrenia and the recovery model | journal = Current Opinion in Psychiatry | volume = 22 | issue = 4 | pages = 374–380 | date = July 2009 | pmid = 19417668 | doi = 10.1097/YCO.0b013e32832c920b }} Most people with schizophrenia live independently with community support. About 85% are unemployed. In people with a first episode of psychosis in schizophrenia a good long-term outcome occurs in 31%, an intermediate outcome in 42% and a poor outcome in 31%.{{cite journal | vauthors = Menezes NM, Arenovich T, Zipursky RB | s2cid = 23475454 | title = A systematic review of longitudinal outcome studies of first-episode psychosis | journal = Psychological Medicine | volume = 36 | issue = 10 | pages = 1349–62 | date = October 2006 | pmid = 16756689 | doi = 10.1017/S0033291706007951 | url = https://pdfs.semanticscholar.org/8539/923c1b4f6bacb128d478b9ec7f6e95559210.pdf | archive-url = https://web.archive.org/web/20200922015257/https://pdfs.semanticscholar.org/8539/923c1b4f6bacb128d478b9ec7f6e95559210.pdf | archive-date = 22 September 2020}} Males are affected more often than females, and have a worse outcome.{{cite book |vauthors=Coyle JT |title=Neurodegenerative Diseases |chapter=Schizophrenia: Basic and Clinical |series=Advances in Neurobiology |volume=15 |pages=255–280 |date=2017 |pmid=28674984 |doi=10.1007/978-3-319-57193-5_9|isbn=978-3-319-57191-1 }} Studies showing that outcomes for schizophrenia appear better in the developing than the developed world{{cite journal | vauthors = Isaac M, Chand P, Murthy P | title = Schizophrenia outcome measures in the wider international community | journal = The British Journal of Psychiatry. Supplement | volume = 50 | pages = s71–77 | date = August 2007 | pmid = 18019048 | doi = 10.1192/bjp.191.50.s71 | doi-access = free }} have been questioned.{{cite journal | vauthors = Cohen A, Patel V, Thara R, Gureje O | title = Questioning an axiom: better prognosis for schizophrenia in the developing world? | journal = Schizophrenia Bulletin | volume = 34 | issue = 2 | pages = 229–244 | date = March 2008 | pmid = 17905787 | pmc = 2632419 | doi = 10.1093/schbul/sbm105 }} Social problems, such as long-term unemployment, poverty, homelessness, exploitation, stigmatization and victimization are common consequences, and lead to social exclusion.

There is a higher than average suicide rate associated with schizophrenia estimated at 5% to 6%, most often occurring in the period following onset or first hospital admission.{{cite book |title=Ferri's clinical advisor 2019: 5 books in 1 |pages=1225–1226|date=2019 |isbn=9780323530422 | vauthors = Ferri FF |publisher=Elsevier }} Several times more (20 to 40%) attempt suicide at least once. There are a variety of risk factors, including male sex, depression, a high IQ,{{cite journal | vauthors = Carlborg A, Winnerbäck K, Jönsson EG, Jokinen J, Nordström P | s2cid = 204385719 | title = Suicide in schizophrenia | journal = Expert Review of Neurotherapeutics | volume = 10 | issue = 7 | pages = 1153–1164 | date = July 2010 | pmid = 20586695 | doi = 10.1586/ern.10.82 | doi-access = free }} heavy smoking,{{cite journal |vauthors=Tsoi DT, Porwal M, Webster AC |title=Interventions for smoking cessation and reduction in individuals with schizophrenia |journal=The Cochrane Database of Systematic Reviews |issue=2 |page=CD007253 |date=28 February 2013 |volume=2013 |pmid=23450574|doi=10.1002/14651858.CD007253.pub3|pmc=6486303 }} and substance use. Repeated relapse is linked to an increased risk of suicidal behavior. The use of clozapine can reduce the risk of suicide, and of aggression.{{cite journal |vauthors=Sriretnakumar V, Huang E, Müller DJ |date=2015 |title=Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update |journal=Expert Opinion on Drug Metabolism & Toxicology |volume=11 |issue=11 |pages=1709–1731 |doi=10.1517/17425255.2015.1075003 |pmid=26364648 |s2cid=207492339}}

A strong association between schizophrenia and tobacco smoking has been shown in worldwide studies.{{cite journal | vauthors = de Leon J, Diaz FJ | s2cid = 32975940 | title = A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors | journal = Schizophrenia Research | volume = 76 | issue = 2–3 | pages = 135–157 | date = July 2005 | pmid = 15949648 | doi = 10.1016/j.schres.2005.02.010 }}{{cite journal | vauthors = Keltner NL, Grant JS | title = Smoke, smoke, smoke that cigarette | journal = Perspectives in Psychiatric Care | volume = 42 | issue = 4 | pages = 256–261 | date = November 2006 | pmid = 17107571 | doi = 10.1111/j.1744-6163.2006.00085.x }} Smoking is especially high in those diagnosed with schizophrenia, with estimates ranging from 80 to 90% being regular smokers, as compared to 20% of the general population. Those who smoke tend to smoke heavily, and additionally smoke cigarettes with high nicotine content. Some propose that this is in an effort to improve symptoms.{{cite journal | vauthors = Kumari V, Postma P | s2cid = 15581894 | title = Nicotine use in schizophrenia: the self medication hypotheses | journal = Neuroscience and Biobehavioral Reviews | volume = 29 | issue = 6 | pages = 1021–1034 | date = January 2005 | pmid = 15964073 | doi = 10.1016/j.neubiorev.2005.02.006 }} Among people with schizophrenia use of cannabis is also common.

Schizophrenia leads to an increased risk of dementia.{{cite journal |vauthors=Cai L, Huang J |title=Schizophrenia and risk of dementia: a meta-analysis study |journal=Neuropsychiatr Dis Treat |volume=14 |issue= |pages=2047–2055 |date=2018 |pmid=30147318 |pmc=6095111 |doi=10.2147/NDT.S172933 |doi-access=free }}

Most people with schizophrenia are not aggressive, and are more likely to be victims of violence rather than perpetrators. People with schizophrenia are commonly exploited and victimized by violent crime as part of a broader dynamic of social exclusion. People diagnosed with schizophrenia are also subject to forced drug injections, seclusion, and restraint at high rates.

The risk of violence by people with schizophrenia is small. There are minor subgroups where the risk is high.{{cite journal |vauthors=Richard-Devantoy S, Olie JP, Gourevitch R |title=[Risk of homicide and major mental disorders: a critical review] |journal=L'Encephale |volume=35 |issue=6 |pages=521–530 |date=December 2009 |pmid=20004282 |doi=10.1016/j.encep.2008.10.009}} This risk is usually associated with a comorbid disorder such as a substance use disorder – in particular alcohol, or with antisocial personality disorder. Substance use disorder is strongly linked, and other risk factors are linked to deficits in cognition and social cognition including facial perception and insight that are in part included in theory of mind impairments.{{cite journal |vauthors=Ng R, Fish S, Granholm E |title=Insight and theory of mind in schizophrenia. |journal=Psychiatry Research |volume=225 |issue=1–2 |pages=169–174 |date=30 January 2015 |pmid=25467703 |doi=10.1016/j.psychres.2014.11.010|pmc=4269286 }}{{cite journal |vauthors=Bora E |title=Relationship between insight and theory of mind in schizophrenia: A meta-analysis |journal=Schizophrenia Research |volume=190 |pages=11–17 |date=December 2017 |pmid=28302393 |doi=10.1016/j.schres.2017.03.029|s2cid=36263370 }} Poor cognitive functioning, decision-making, and facial perception may contribute to making a wrong judgement of a situation that could result in an inappropriate response such as violence.{{cite journal |vauthors=Darmedru C, Demily C, Franck N |title=[Preventing violence in schizophrenia with cognitive remediation] |journal=L'Encephale |volume=44 |issue=2 |pages=158–167 |date=April 2018 |pmid=28641817 |doi=10.1016/j.encep.2017.05.001}} These associated risk factors are also present in antisocial personality disorder which when present as a comorbid disorder greatly increases the risk of violence.{{cite journal | vauthors = Richard-Devantoy S, Bouyer-Richard AI, Jollant F, Mondoloni A, Voyer M, Senon JL | title = [Homicide, schizophrenia and substance abuse: a complex interaction] | journal = Revue d'Épidemiologie et de Santé Publique | volume = 61 | issue = 4 | pages = 339–350 | date = August 2013 | pmid = 23816066 | doi = 10.1016/j.respe.2013.01.096 }}{{cite journal | vauthors = Sedgwick O, Young S, Baumeister D, Greer B, Das M, Kumari V | title = Neuropsychology and emotion processing in violent individuals with antisocial personality disorder or schizophrenia: The same or different? A systematic review and meta-analysis | journal = The Australian and New Zealand Journal of Psychiatry | volume = 51 | issue = 12 | pages = 1178–1197 | date = December 2017 | pmid = 28992741 | doi = 10.1177/0004867417731525 | s2cid = 206401875 | doi-access = free }}

{{Main|Epidemiology of schizophrenia}}

[[File:Schizophrenia world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.3|Deaths per million persons due to schizophrenia in 2012

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In 2017,{{update after|2022|8|22}} the Global Burden of Disease Study estimated there were 1.1 million new cases; in 2022 the World Health Organization (WHO) reported a total of 24 million cases globally. Schizophrenia affects around 0.3–0.7% of people at some point in their life.{{cite web|title=Schizophrenia |url= http://www.nimh.nih.gov/health/statistics/prevalence/schizophrenia.shtml |date= 22 April 2022 |access-date= 23 August 2022 |publisher= US National Institute of Mental Health (NIMH)|work= Statistics}} In areas of conflict this figure can rise to between 4.0 and 6.5%.{{cite journal | vauthors = Charlson F, van Ommeren M, Flaxman A, Cornett J, Whiteford H, Saxena S | title = New WHO prevalence estimates of mental disorders in conflict settings: a systematic review and meta-analysis | journal = Lancet | volume = 394 | issue = 10194 | pages = 240–248 | date = July 2019 | pmid = 31200992 | pmc = 6657025 | doi = 10.1016/S0140-6736(19)30934-1 }} It occurs 1.4 times more frequently in males than females and typically appears earlier in men.

Worldwide, schizophrenia is the most common psychotic disorder. The frequency of schizophrenia varies across the world, within countries,{{cite journal | vauthors = Kirkbride JB, Fearon P, Morgan C, Dazzan P, Morgan K, Tarrant J, Lloyd T, Holloway J, Hutchinson G, Leff JP, Mallett RM, Harrison GL, Murray RM, Jones PB | title = Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study | journal = Archives of General Psychiatry | volume = 63 | issue = 3 | pages = 250–258 | date = March 2006 | pmid = 16520429 | doi = 10.1001/archpsyc.63.3.250 | doi-access = free }} and at the local and neighborhood level;{{cite journal | vauthors = Kirkbride JB, Fearon P, Morgan C, Dazzan P, Morgan K, Murray RM, Jones PB | title = Neighbourhood variation in the incidence of psychotic disorders in Southeast London | journal = Social Psychiatry and Psychiatric Epidemiology | volume = 42 | issue = 6 | pages = 438–445 | date = June 2007 | pmid = 17473901 | doi = 10.1007/s00127-007-0193-0 | s2cid = 19655724 }} this variation in prevalence between studies over time, across geographical locations, and by gender is as high as fivefold.

Schizophrenia causes approximately one percent of worldwide disability adjusted life years{{update after|2022|8|24}} and resulted in 17,000 deaths in 2015.

In 2000,{{update after|2022|8|22}} WHO found the percentage of people affected and the number of new cases that develop each year is roughly similar around the world, with age-standardized prevalence per 100,000 ranging from 343 in Africa to 544 in Japan and Oceania for men, and from 378 in Africa to 527 in Southeastern Europe for women.{{update after|2022|8|22}} {{cite web|title=Global burden of schizophrenia in the year 2000|date= 15 August 2006| url=https://www.who.int/healthinfo/statistics/bod_schizophrenia.pdf|publisher=World Health Organization | vauthors = Ayuso-Mateos JL |access-date=27 February 2013|url-status=live|archive-url=https://web.archive.org/web/20160304075113/http://www.who.int/healthinfo/statistics/bod_schizophrenia.pdf|archive-date=4 March 2016}}

{{Main|History of schizophrenia}}

{{Main|History of schizophrenia#Conceptual development}}

{{Further|Dementia praecox}}

File:Eugen bleuler.jpg.]]

Accounts of a schizophrenia-like syndrome are rare in records before the 19th century; the earliest case reports were in 1797 and 1809.{{cite journal | vauthors = Heinrichs RW | title = Historical origins of schizophrenia: two early madmen and their illness | journal = Journal of the History of the Behavioral Sciences | volume = 39 | issue = 4 | pages = 349–363 | year = 2003 | pmid = 14601041 | doi = 10.1002/jhbs.10152 | doi-access = free }} The term dementia praecox ("premature dementia") was used by German psychiatrist Heinrich Schüle in 1886 and then in 1891 by Arnold Pick in a case report of hebephrenia. In 1893 Emil Kraepelin used the term in making a distinction, known as the Kraepelinian dichotomy, between the two psychoses: dementia praecox and manic depression (now called bipolar disorder). When it became evident that the disorder was not a degenerative dementia, it was renamed schizophrenia by Eugen Bleuler in 1908.{{cite journal | vauthors = Kuhn R, Cahn CH | title = Eugen Bleuler's concepts of psychopathology | journal = History of Psychiatry | volume = 15 | issue = 59 Pt 3 | pages = 361–366 | date = September 2004 | pmid = 15386868 | doi = 10.1177/0957154X04044603 | s2cid = 5317716 }}

The word schizophrenia ("splitting of the mind") is Modern Latin, derived from the Greek schizein ({{Langx|grc|σχίζειν|lit=to split}}) and phrēn ({{langx|grc|φρήν|lit=mind}}).{{cite web |title=Schizophrenia {{!}} Definition of Schizophrenia by Lexico |url=https://www.lexico.com/en/definition/schizophrenia |archive-url=https://web.archive.org/web/20200310144713/https://www.lexico.com/en/definition/schizophrenia |archive-date=10 March 2020 |publisher=Lexico Dictionaries {{!}} English }} Its use was intended to describe the separation of function between personality, thinking, memory, and perception.

In the early 20th century, the psychiatrist Kurt Schneider categorized the psychotic symptoms of schizophrenia into two groups: hallucinations and delusions. The hallucinations were listed as specific to auditory and the delusions included thought disorders. These were seen as important symptoms, termed first-rank. The most common first-rank symptom was found to belong to thought disorders.{{page needed|date=August 2022}}{{page needed|date=August 2022}} {{cite book| vauthors = Schneider K |author-link1=Kurt Schneider |title=Clinical Psychopathology |edition=5th |year=1959 |publisher=Grune & Stratton |location=New York }}{{page needed|date=August 2022}}{{page needed|date=August 2022}} {{cite book | vauthors = Moore D |title=Textbook of Clinical Neuropsychiatry |edition=Second |publisher=CRC Press |date=25 April 2008|isbn=9781444109740 }} In 2013 the first-rank symptoms were excluded from the DSM-5 criteria;{{cite journal | vauthors = Tandon R, Gaebel W, Barch DM, Bustillo J, Gur RE, Heckers S, Malaspina D, Owen MJ, Schultz S, Tsuang M, Van Os J, Carpenter W | title = Definition and description of schizophrenia in the DSM-5 | journal = Schizophrenia Research | volume = 150 | issue = 1 | pages = 3–10 | date = October 2013 | pmid = 23800613 | doi = 10.1016/j.schres.2013.05.028 | s2cid = 17314600 }} while they may not be useful in diagnosing schizophrenia, they can assist in differential diagnosis.{{cite journal | vauthors = Picardi A | title = The Two Faces of First-Rank Symptoms | journal = Psychopathology | volume = 52 | issue = 4 | pages = 221–231 | date = 2019 | pmid = 31610542 | doi = 10.1159/000503152 | s2cid = 204702486 | doi-access = free }}

Subtypes of schizophrenia—classified as paranoid, disorganized, catatonic, undifferentiated, and residual—were difficult to distinguish and are no longer recognized as separate conditions by DSM-5 (2013) or ICD-11.{{cite journal | vauthors = Reed GM, First MB, Kogan CS, Hyman SE, Gureje O, Gaebel W, Maj M, Stein DJ, Maercker A, Tyrer P, Claudino A, Garralda E, Salvador-Carulla L, Ray R, Saunders JB, Dua T, Poznyak V, Medina-Mora ME, Pike KM, Ayuso-Mateos JL, Kanba S, Keeley JW, Khoury B, Krasnov VN, Kulygina M, Lovell AM, de Jesus Mari J, Maruta T, Matsumoto C, Rebello TJ, Roberts MC, Robles R, Sharan P, Zhao M, Jablensky A, Udomratn P, Rahimi-Movaghar A, Rydelius PA, Bährer-Kohler S, Watts AD, Saxena S | title = Innovations and changes in the ICD-11 classification of mental, behavioural and neurodevelopmental disorders | journal = World Psychiatry | volume = 18 | issue = 1 | pages = 3–19 | date = February 2019 | pmid = 30600616 | pmc = 6313247 | doi = 10.1002/wps.20611 }}{{Cite web |title=Updates to DSM-5 Criteria & Text |url=https://www.psychiatry.org/psychiatrists/practice/dsm/updates-to-dsm-5/updates-to-dsm-5-criteria-text |access-date=21 February 2019 |publisher=www.psychiatry.org}}{{cite journal | vauthors = Tandon R | title = Schizophrenia and Other Psychotic Disorders in Diagnostic and Statistical Manual of Mental Disorders (DSM)-5: Clinical Implications of Revisions from DSM-IV | journal = Indian Journal of Psychological Medicine | volume = 36 | issue = 3 | pages = 223–225 | date = July 2014 | pmid = 25035542 | pmc = 4100404 | doi = 10.4103/0253-7176.135365 | doi-access = free }}

Before the 1960s, nonviolent petty criminals and women were sometimes diagnosed with schizophrenia, categorizing the latter as ill for not performing their duties as wives and mothers. In the mid- to late 1960s, black men were categorized as "hostile and aggressive" and diagnosed as schizophrenic at much higher rates, their civil rights and Black Power activism labeled as delusions.{{Cite web |vauthors= Lane C |date= 5 May 2010|title=How Schizophrenia Became a Black Disease: An Interview With Jonathan Metzl|url=http://www.psychologytoday.com/blog/side-effects/201005/how-schizophrenia-became-black-disease-interview-jonathan-metzl|access-date=5 April 2021|work=Psychology Today}}{{page needed|date=August 2022}} {{Cite book|vauthors=Metz J|title=The Protest Psychosis|year=2010|isbn=978-0-8070-8592-9| publisher = Beacon Press}}

In the early 1970s in the United States, the diagnostic model for schizophrenia was broad and clinically based using DSM II. Schizophrenia was diagnosed far more in the United States than in Europe, where the ICD-9 criteria were followed. The US model was criticised for failing to demarcate clearly those people with a mental illness. In 1980 DSM III was published and showed a shift in focus from the clinically based biopsychosocial model to a reason-based medical model.{{clarify|date=December 2024}}{{cite journal |vauthors=Wilson M |date=March 1993 |title=DSM-III and the transformation of American psychiatry: a history |journal=The American Journal of Psychiatry |volume=150 |issue=3 |pages=399–410 |doi=10.1176/ajp.150.3.399 |pmid=8434655}} DSM IV brought an increased focus on an evidence-based medical model.{{cite journal |vauthors=Fischer BA |date=December 2012 |title=A review of American psychiatry through its diagnoses: the history and development of the Diagnostic and Statistical Manual of Mental Disorders. |journal=The Journal of Nervous and Mental Disease |volume=200 |issue=12 |pages=1022–1030 |doi=10.1097/NMD.0b013e318275cf19 |pmid=23197117 |s2cid=41939669}}

{{Main|History of schizophrenia#Development of treatments in the 20th century}}

File:Chlorpromazine-3D-vdW.png, the first antipsychotic developed in the 1950s]]

In the 1930s a number of shock procedures which induced seizures (convulsions) or comas were used to treat schizophrenia.{{cite journal |vauthors=Jones K |date=March 2000 |title=Insulin coma therapy in schizophrenia |journal=Journal of the Royal Society of Medicine |volume=93 |issue=3 |pages=147–149 |doi=10.1177/014107680009300313 |pmc=1297956 |pmid=10741319}} Insulin shock involved injecting large doses of insulin to induce comas, which in turn produced hypoglycemia and convulsions.{{cite journal |vauthors=Jobes DA, Chalker SA |date=26 September 2019 |title=One Size Does Not Fit All: A Comprehensive Clinical Approach to Reducing Suicidal Ideation, Attempts, and Deaths. |journal=International Journal of Environmental Research and Public Health |volume=16 |issue=19 |page=3606 |doi=10.3390/ijerph16193606 |pmc=6801408 |pmid=31561488 |doi-access=free}} The use of electricity to induce seizures was in use as electroconvulsive therapy (ECT) by 1938.{{cite journal |vauthors=Ali SA, Mathur N, Malhotra AK, Braga RJ |date=April 2019 |title=Electroconvulsive Therapy and Schizophrenia: A Systematic Review |journal=Molecular Neuropsychiatry |volume=5 |issue=2 |pages=75–83 |doi=10.1159/000497376 |pmc=6528094 |pmid=31192220}}

Carried out from the 1930s until the 1970s in the United States and until the 1980s in France, psychosurgery, including such modalities as the lobotomy, is recognized as a human rights abuse.{{cite journal |vauthors=Mashour GA, Walker EE, Martuza RL |date=June 2005 |title=Psychosurgery: past, present, and future |journal=Brain Research. Brain Research Reviews |volume=48 |issue=3 |pages=409–419 |doi=10.1016/j.brainresrev.2004.09.002 |pmid=15914249 |s2cid=10303872}}{{Cite web |vauthors=Mendez J |date=1 February 2013|title=Report of the Special Rapporteur on torture and other cruel, inhuman or degrading treatment or punishment |url= https://www.ohchr.org/sites/default/files/Documents/HRBodies/HRCouncil/RegularSession/Session22/A.HRC.22.53_English.pdf |access-date= 22 August 2022 |publisher=Office of the High Commissioner for Human Rights}} In the mid-1950s, chlorpromazine, the first typical antipsychotic, was introduced,{{cite journal |vauthors=Turner T |date=January 2007 |title=Chlorpromazine: unlocking psychosis |journal=BMJ |volume=334 Suppl 1 |issue=suppl |page=s7 |doi=10.1136/bmj.39034.609074.94 |pmid=17204765 |s2cid=33739419}} followed in the 1970s by clozapine, the first atypical antipsychotic.{{cite journal |vauthors=Aringhieri S |date=December 2018 |title=Molecular targets of atypical antipsychotics: From mechanism of action to clinical differences. |journal=Pharmacology & Therapeutics |volume=192 |pages=20–41 |doi=10.1016/j.pharmthera.2018.06.012 |pmid=29953902 |s2cid=49602956}}

{{Further information|Political abuse of psychiatry}}

From the 1960s until 1989, psychiatrists in the USSR and Eastern Bloc diagnosed thousands of people with sluggish schizophrenia,{{Cite journal|vauthors=Park YS, Sang M, Jun JY, Kim SJ|date=2014|title=Psychiatry in former socialist countries: implications for north korean psychiatry|journal=Psychiatry Investigation|volume=11|issue=4|pages=363–370|doi=10.4306/pi.2014.11.4.363|issn=1738-3684|pmc=4225199|pmid=25395966}}{{page needed|date=August 2022}} {{Cite book|vauthors=Gosden R|title=Punishing the patient: how psychiatrists misunderstand and mistreat schizophrenia|date=2001|publisher=Scribe Publications|isbn=0-908011-52-0|location=Melbourne|oclc=47177633}} without signs of psychosis, based on "the assumption that symptoms would later appear".{{cite journal | vauthors = Sfera A | title = Can Psychiatry be Misused Again? | journal = Frontiers in Psychiatry | volume = 4 | pages = 101 | date = September 2013 | pmid = 24058348 | pmc = 3766833 | doi = 10.3389/fpsyt.2013.00101 | doi-access = free }} Now discredited, the diagnosis provided a convenient way to confine political dissidents.{{Cite journal| vauthors = Merskey H |date=15 October 1988|title=IPPNW: Forum for Soviet anti-American propaganda?|journal=CMAJ: Canadian Medical Association Journal|volume=139|issue=8|pages=699–700|issn=0820-3946|pmc=1268271}}

{{See also|List of people with schizophrenia|Religion and schizophrenia|}}In the United States, the annual cost of schizophrenia – including direct costs (outpatient, inpatient, drugs, and long-term care) and non-healthcare costs (law enforcement, reduced workplace productivity, and unemployment) – was estimated at $62.7 billion for the year 2002.{{cite journal | vauthors = Wu EQ, Birnbaum HG, Shi L, Ball DE, Kessler RC, Moulis M, Aggarwal J | title = The economic burden of schizophrenia in the United States in 2002 | journal = The Journal of Clinical Psychiatry | volume = 66 | issue = 9 | pages = 1122–1129 | date = September 2005 | pmid = 16187769 | doi = 10.4088/jcp.v66n0906 }}{{efn|A 2007 review stated that the 2002 estimate was still the best available,{{cite journal | vauthors = McEvoy JP | title = The costs of schizophrenia | journal = The Journal of Clinical Psychiatry | volume = 68 | issue = Suppl 14 | pages = 4–7 | date = 2007 | pmid = 18284271 | doi = }} and a 2018 review cited the same $62.7 billion.

{{cite journal |vauthors=Zhang W, Amos TB, Gutkin SW, et al |title=A systematic literature review of the clinical and health economic burden of schizophrenia in privately insured patients in the United States |journal=Clinicoecon Outcomes Res |volume=10 |issue= |pages=309–320 |date=2018 |pmid=29922078 |pmc=5997131 |doi=10.2147/CEOR.S156308 |doi-access=free }}}} In the UK the cost in 2016 was put at £11.8 billion per year with a third of that figure directly attributable to the cost of hospital, social care and treatment.

File:John Forbes Nash, Jr. by Peter Badge.jpg, an American mathematician and joint recipient of the 1994 Nobel Memorial Prize in Economic Sciences, had schizophrenia. His life was the subject of the 1998 book, A Beautiful Mind, by Sylvia Nasar.]]

In 2002, the term for schizophrenia in Japan was changed from {{nihongo||精神分裂病|seishin-bunretsu-byō|lit. 'mind-split disease'}} to {{nihongo||統合失調症|tōgō-shitchō-shō|lit. 'integration–dysregulation syndrome'}} to reduce stigma and confusion with "multiple personalities".{{cite journal | vauthors = Yamaguchi S, Mizuno M, Ojio Y, Sawada U, Matsunaga A, Ando S, Koike S | title = Associations between renaming schizophrenia and stigma-related outcomes: A systematic review | journal = Psychiatry and Clinical Neurosciences | volume = 71 | issue = 6 | pages = 347–362 | date = June 2017 | pmid = 28177184 | doi = 10.1111/pcn.12510 | doi-access = free }} The new name, also interpreted as "integration disorder", was inspired by the biopsychosocial model.{{cite journal | vauthors = Sato M | title = Renaming schizophrenia: a Japanese perspective | journal = World Psychiatry | volume = 5 | issue = 1 | pages = 53–55 | date = February 2006 | pmid = 16757998 | pmc = 1472254 }} A similar change was made in South Korea in 2012 to attunement disorder.{{cite journal | vauthors = Park SC, Park YC | title = Korea in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition | journal = Journal of Korean Medical Science | volume = 35 | issue = 2 | pages = e6 | date = January 2020 | pmid = 31920014 | pmc = 6955430 | doi = 10.3346/jkms.2020.35.e6 | edition = Fifth }}

Stigma may prevent further research and treatment as in history treated some in the past invariably worse to recovery.

Media coverage, especially movies, reinforce the public perception of an association between schizophrenia and violence.{{cite journal | vauthors = Fazel S, Gulati G, Linsell L, Geddes JR, Grann M | title = Schizophrenia and violence: systematic review and meta-analysis | journal = PLOS Medicine | volume = 6 | issue = 8 | pages = e1000120 | date = August 2009 | pmid = 19668362 | pmc = 2718581 | doi = 10.1371/journal.pmed.1000120 | doi-access = free }} A majority of movies have historically depicted characters with schizophrenia as criminal, dangerous, violent, unpredictable and homicidal, and depicted delusions and hallucinations as the main symptoms of schizophrenic characters, ignoring other common symptoms,{{cite journal |vauthors=Owen PR |title=Portrayals of schizophrenia by entertainment media: a content analysis of contemporary movies |journal=Psychiatr Serv |volume=63 |issue=7 |pages=655–9 |date=July 2012 |pmid=22555313 |doi=10.1176/appi.ps.201100371}} furthering stereotypes of schizophrenia including the idea of a split personality.{{cite journal |vauthors=Katschnig H |title=Psychiatry's contribution to the public stereotype of schizophrenia: Historical considerations |journal=J Eval Clin Pract |volume=24 |issue=5 |pages=1093–1100 |date=October 2018 |pmid=30112785 |pmc=6174929 |doi=10.1111/jep.13011 }}

The book A Beautiful Mind chronicled the life of John Forbes Nash who had been diagnosed with schizophrenia and won the Nobel Memorial Prize in Economic Sciences. The book was made into a film with the same name; an earlier documentary film was A Brilliant Madness.

In the UK, guidelines for reporting conditions and award campaigns have shown a reduction in negative reporting since 2013.{{cite journal |vauthors=Chen M, Lawrie S |title=Newspaper depictions of mental and physical health. |journal=BJPsych Bulletin |volume=41 |issue=6 |pages=308–313 |date=December 2017 |pmid=29234506 |doi=10.1192/pb.bp.116.054775|pmc=5709678 }}

In 1964 a case study of three males diagnosed with schizophrenia who each had the delusional belief that they were Jesus Christ was published as The Three Christs of Ypsilanti; a film with the title Three Christs was released in 2020.{{cite journal | vauthors = Dyga K, Stupak R | title = Ways of understanding of religious delusions associated with a change of identity on the example of identification with Jesus Christ. | journal=Psychiatria Polska | date = 28 February 2018 | volume = 52 | issue = 1 | pages = 69–80 | doi=10.12740/PP/64378 | pmid=29704415| doi-access = free }}{{cite journal | vauthors = Dein S, Littlewood R | title = Religion and psychosis: a common evolutionary trajectory? | journal = Transcultural Psychiatry | date = July 2011 | volume = 48 | issue = 3 | pages =318–335 | doi = 10.1177/1363461511402723 | pmid = 21742955| s2cid = 12991391 }}

{{See also|Animal models of schizophrenia}}

A 2015 Cochrane review found unclear evidence of benefit from brain stimulation techniques to treat the positive symptoms of schizophrenia, in particular auditory verbal hallucinations (AVHs).{{cite journal |vauthors =Dougall N, Maayan N, Soares-Weiser K, McDermott LM, McIntosh A |title=Transcranial magnetic stimulation (TMS) for schizophrenia. |journal=The Cochrane Database of Systematic Reviews |volume=2015 |date=20 August 2015 |issue=8 |pages=CD006081 |doi=10.1002/14651858.CD006081.pub2 |pmid=26289586|pmc=9395125 |hdl=1893/22520 |hdl-access=free }} Most studies focus on transcranial direct-current stimulation (tDCM), and repetitive transcranial magnetic stimulation (rTMS).{{cite journal |vauthors=Nathou C, Etard O, Dollfus S |date=2019 |title=Auditory verbal hallucinations in schizophrenia: current perspectives in brain stimulation treatments. |journal=Neuropsychiatric Disease and Treatment|volume=15 |pages=2105–2117 |pmid=31413576 |pmc=6662171 |doi=10.2147/NDT.S168801 |doi-access=free }} Techniques based on focused ultrasound for deep brain stimulation could provide insight for the treatment of AVHs.

The study of potential biomarkers that would help in diagnosis and treatment of schizophrenia is an active area of research as of 2020. Possible biomarkers include markers of inflammation, neuroimaging,{{cite journal |vauthors=Kraguljac NV, McDonald WM, Widge AS, Rodriguez CI, Tohen M, Nemeroff CB |title=Neuroimaging Biomarkers in Schizophrenia |journal=Am J Psychiatry |pages=509–521 |date=January 2021 |volume=178 |issue=6 |pmid=33397140 |doi=10.1176/appi.ajp.2020.20030340|pmc=8222104 }} brain-derived neurotrophic factor (BDNF),{{cite journal |vauthors=Khavari B, Cairns MJ |title=Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers |journal=Cells |volume=9 |issue=8 |date=August 2020 |page=1837 |pmid=32764320 |doi=10.3390/cells9081837|pmc=7463953 |doi-access=free }} and speech analysis. Some markers such as C-reactive protein are useful in detecting levels of inflammation implicated in some psychiatric disorders but they are not disorder-specific. Other inflammatory cytokines are found to be elevated in first episode psychosis and acute relapse that are normalized after treatment with antipsychotics, and these may be considered as state markers.{{cite journal |vauthors=Goldsmith DR, Crooks CL, Walker EF, Cotes RO |title=An Update on Promising Biomarkers in Schizophrenia |journal=Focus (American Psychiatric Publishing)|volume=16 |issue=2 |pages=153–163 |date=April 2018 |doi=10.1176/appi.focus.20170046 |pmid=31975910|pmc=6526854 }} Deficits in sleep spindles in schizophrenia may serve as a marker of an impaired thalamocortical circuit, and a mechanism for memory impairment.{{cite journal |vauthors=Pocivavsek A, Rowland LM |title=Basic Neuroscience Illuminates Causal Relationship Between Sleep and Memory: Translating to Schizophrenia |journal=Schizophrenia Bulletin |volume=44 |issue=1 |pages=7–14 |date=13 January 2018 |pmid=29136236|doi=10.1093/schbul/sbx151|pmc=5768044 |doi-access=free }} MicroRNAs are highly influential in early neuronal development, and their disruption is implicated in several CNS disorders; circulating microRNAs (cimiRNAs) are found in body fluids such as blood and cerebrospinal fluid, and changes in their levels are seen to relate to changes in microRNA levels in specific regions of brain tissue. These studies suggest that cimiRNAs have the potential to be early and accurate biomarkers in a number of disorders including schizophrenia.{{cite journal |vauthors=Kumar S, Reddy PH |title=Are circulating microRNAs peripheral biomarkers for Alzheimer's disease? |journal=Biochim Biophys Acta |volume=1862 |issue=9 |pages=1617–1627 |date=September 2016 |pmid=27264337 |pmc=5343750 |doi=10.1016/j.bbadis.2016.06.001 |url=}}{{cite journal |vauthors=van den Berg MM, Krauskopf J, Ramaekers JG, et al. |title=Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders |journal=Prog Neurobiol |volume=185 |pages=101732 |date=February 2020 |pmid=31816349 |doi=10.1016/j.pneurobio.2019.101732 |s2cid=208790466|doi-access=free }}

Ongoing fMRI research aims to identify biomarkers within these brain networks,{{Cite journal |last1=Palaniyappan |first1=Lena |last2=Liddle |first2=Peter F. |date=2013-04-24 |title=Diagnostic Discontinuity in Psychosis: A Combined Study of Cortical Gyrification and Functional Connectivity |url=https://academic.oup.com/schizophreniabulletin/article-abstract/40/3/675/1903745?redirectedFrom=fulltext |journal=Schizophrenia Bulletin |volume=40 |issue=3 |pages=675–684 |doi=10.1093/schbul/sbt050 |issn=1745-1701 |pmc=3984507 |pmid=23615812}} potentially aiding in earlier diagnosis and better tracking of treatment responses in schizophrenia.

{{Notelist}}

{{Reflist}}

• [https://direct.mit.edu/books/oa-edited-volume/5036/SchizophreniaEvolution-and-Synthesis Schizophrenia: Evolution and Synthesis]

{{Medical condition classification and resources

| DiseasesDB = 11890

| ICD11 = {{ICD11|6A20}}

| ICD10 = {{ICD10|F|20||f|20}}

| ICD9 = {{ICD9|295}}

| ICDO =

| OMIM = 181500

| MedlinePlus = 000928

| eMedicineSubj = med

| eMedicineTopic = 2072

| eMedicine_mult = {{eMedicine2|emerg|520}}

| MeshName = Schizophrenia

| MeshNumber = F03.700.750

| Scholia = Q41112

}}

{{Schizophrenia}}

{{Mental and behavioural disorders|selected = schizophrenia}}

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| d = yes

| n = yes

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|Psychiatry|Psychology}}

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Category:1900s neologisms

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