Schizophrenia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Irfan Dotani

Schizophrenia the name comes from the Greek roots schizein (σχίζειν, “to split”) and phrēn, phren- (φρήν, φρεν-, “mind“). Studies suggest that genetics, early environment, neurobiology and psychological and social processes are important contributory factors. Historically there was debate as to whether schizophrenia was in fact a single disorder or a combination of separate discrete psychiatric disorders. For this reason, Eugen Bleuler termed the disease the schizophrenias (plural) when he coined the name.

• Descriptions of schizophrenia-like symptoms date to 2000 BC in the Book of Hearts—part of the ancient Ebers papyrus.
  • However, the study of the ancient Greek and Roman literature shows that although the general population probably had an awareness of psychotic disorders, there was no recorded condition that would meet the modern criteria for schizophrenia.^[1]

• Although a broad concept of madness has existed for thousands of years, schizophrenia was only classified as a distinct mental disorder by Emil Kraepelin in 1893.
• He was the first to make a distinction in the psychotic disorders between what he called dementia praecox (early dementia—a term first used by the psychiatrist Bénédict Morel [1809–1873]) and manic depression.
• Kraepelin believed that dementia praecox was primarily a disease of the brain,^[2] and particularly a form of dementia, distinguished from other forms of dementia, such as Alzheimer’s disease, which typically occur later in life.^[3]

• The word schizophrenia—which translates roughly as “splitting of the mind” and comes from the Greek roots schizein (σχίζειν, “to split”) and phrēn, phren- (φρήν, φρεν-, “mind“)—was coined by Eugen Bleuler in 1908 and was intended to describe the separation of function between personality, thinking, memory, and perception.^[4]
• Bleuler described the main symptoms as 4 A’s:^[5]
  • Flattened Affect
  • Autism
  • Impaired Association of ideas
  • Ambivalence
• Bleuler realized that the illness was not a dementia as some of his patients improved rather than deteriorated and hence proposed the term schizophrenia instead.

• The term schizophrenia is commonly misunderstood to mean that affected persons have a “split personality“.
• Although some people diagnosed with schizophrenia may hear voices and may experience the voices as distinct personalities, schizophrenia does not involve a person changing among distinct multiple personalities.
• The confusion arises in part due to the meaning of Bleuler’s term schizophrenia (literally “split” or “shattered mind”).
• The first known misuse of the term to mean “split personality” was in an article by the poet T. S. Eliot in 1933.^[6]

• In the first half of the twentieth-century schizophrenia was considered to be a hereditary defect, and sufferers were subject to eugenics in many countries. *Hundreds of thousands were sterilized, with or without consent—the majority in Nazi Germany, the United States, and Scandinavian countries.^[7][8] Along with other people labeled “mentally unfit”, many diagnosed with schizophrenia were murdered in the Nazi “Action T4” program.^[9]

• The diagnostic description of schizophrenia has changed over time.
  • It became clear after the 1971 US-UK Diagnostic Study that schizophrenia was diagnosed to a far greater extent in America than in Europe.^[10]
• This was partly due to looser diagnostic criteria in the US, which used the DSM-II manual, contrasting with Europe and its ICD-9.
• This was one of the factors in leading to the revision not only of the diagnosis of schizophrenia, but the revision of the whole DSM manual, resulting in the publication of the DSM-III.^[11]

• The psychiatrist Kurt Schneider (1887–1967) listed the forms of psychotic symptoms that he thought distinguished schizophrenia from other psychotic disorders. *These are called first-rank symptoms or Schneider’s first-rank symptoms, and they include delusions of being controlled by an external force; the belief that thoughts are being inserted into or withdrawn from one’s conscious mind; the belief that one’s thoughts are being broadcast to other people; and hearing hallucinatory voices that comment on one’s thoughts or actions or that have a conversation with other hallucinated voices.^[12] The reliability of first-rank symptoms has been questioned,^[13] although they have contributed to the current diagnostic criteria.

• The book and film A Beautiful Mind chronicled the life of John Forbes Nash, a Nobel-Prize-winning mathematician who was diagnosed with schizophrenia. The Marathi film Devrai (Featuring Atul Kulkarni) is a presentation of a patient with schizophrenia. The film, set in the Konkan region of Maharashtra in Western India, shows the behavior, mentality, and struggle of the patient as well as his loved ones’ struggle.
  • It also portrays the treatment of this mental illness using medication, dedication and lots of patience of the close relatives of the patient.
• Other factual books have been written by relatives on family members; Australian journalist Anne Deveson told the story of her son’s battle with schizophrenia in Tell me I’m Here, later made into a movie.^[14]

• In Mikhail Bulgakov’s Master and Margarita the poet Ivan Bezdomnyj is institutionalized and diagnosed with schizophrenia after witnessing the devil (Woland) predict Berlioz’s death.
• The book The Eden Express by Mark Vonnegut accounts his struggle into schizophrenia and his journey back to sanity.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2], Irfan Dotani

• Historically, schizophrenia in the West was classified into simple, catatonic, hebephrenic (now known as disorganized), and paranoid.
• The DSM- IV contains five sub-classifications of schizophrenia: Paranoid, disorganized, catatonic, undifferentiated and residual type, but, this classification has been eliminated due to their limited diagnostic stability, low reliability and poor validity.^[1]

• There is no established system for the classification of schizophrenia as per the diagnostic and statistical manual of mental disorders, Fifth Edition, (DSM-V)

• According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-V, to meet the criteria for diagnosis of schizophrenia, the patient must have experienced at least 2 (or more) of the following symptoms:^[2]
  • Delusions
  • Hallucinations
  • Disorganized speech
  • Disorganized or catatonic behavior
  • Negative symptoms
  • At least 1 of the symptoms must be the presence of delusions, hallucinations, or disorganized speech.

• Continuous signs of the disturbance must persist for at least 6 months, during which the patient must experience at least 1 month of active symptoms (or less if successfully treated), with impairment in social, occupational and other significant areas of functioning. The symptoms are not attributable to any other psychiatric, medical, or substance use disorder.^[3]

• If there is a history of autism spectrum disorder or a communication disorder of childhood onset, diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia, are also present for at least 1 month(or less if successfully treated).^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2], Irfan Dotani

Schizophrenia is a psychiatric diagnosis that describes a mental disorder characterized by impairments in the perception or expression of reality and by significant social or occupational dysfunction.

The causes of schizophrenia have been the subject of much debate over many decades with various factors proposed and discounted. To date none has been fully elucidated, but evidence suggests that genetic vulnerability and environmental stressors act in combination to result in schizophrenia.

Studies suggest that genetics, early environment, neurobiology and psychological and social processes are important contributory factors. Current psychiatric research into the development of the disorder often focuses on the role of neurobiology, although a reliable and identifiable organic cause has not been found. In the absence of a confirmed specific pathology underlying the diagnosis, some question the legitimacy of schizophrenia’s status as a disease. Furthermore, some propose that the perceptions and feelings involved are meaningful and do not necessarily involve impairment. Although no common cause of schizophrenia has been identified in all individuals diagnosed with the condition, currently most researchers and clinicians believe it results from a combination of both brain vulnerabilities (either inherited or acquired) and stressful life-events. This widely-adopted approach is known as the ‘stress-vulnerability’ model, and much scientific debate now focuses on how much each of these factors contributes to the development and maintenance of schizophrenia.

It is also thought that processes in early neurodevelopment are important, particularly prenatal processes. In adult life, importance has been placed upon the function (or malfunction) of dopamine in the mesolimbic pathway in the brain. This theory, known as the dopamine hypothesis of schizophrenia largely resulted from the accidental finding that a drug group which blocks dopamine function, known as the phenothiazines, reduced psychotic symptoms. However, this theory is now thought to be overly simplistic as a complete explanation. These drugs have now been developed further and antipsychotic medication is commonly used as a first-line treatment. Although effective in many cases, these medications are not well tolerated by some patients due to significant side-effects. The positive symptoms are more responsive to medications; negative symptoms being less so.

Differences in brain structure have been found between people with schizophrenia and those without. However, these tend only to be reliable on the group level and, due to the significant variability between individuals, may not be reliably present in any particular individual. Significant brain atrophy and enlarged ventricles are the most conspicuous of such differences.

• While the reliability of the schizophrenia diagnosis introduces difficulties in measuring the relative effect of genes and environment (for example, symptoms overlap to some extent with severe bipolar disorder or major depression), evidence suggests that genetic vulnerability and environmental stressors can act in combination to result in diagnosis of schizophrenia.

• The extent to which these factors influence the likelihood of being diagnosed with schizophrenia is debated widely, and currently, controversial.
• Schizophrenia is likely to be a diagnosis of complex inheritance.
  • Thus, it is likely that several genes interact to generate risk for schizophrenia or for the separate components that can co-occur to lead to a diagnosis.
• This, combined with disagreements over which research methods are best, or how data from genetic research should be interpreted, has led to differing estimates over genetic contribution.

• It is thought that causal factors can initially come together in early neurodevelopment, including during pregnancy, to increase the risk of later developing schizophrenia.
• One curious finding is that people diagnosed with schizophrenia are more likely to have been born in winter or spring (at least in the northern hemisphere).
• However, the effect is not large.
  • Some researchers postulate that the correlation is due to viral infections during the third trimester (4–6 months) of pregnancy.
  • There is now significant evidence that prenatal exposure to infections increases the risk for developing schizophrenia later in life, providing additional evidence for a link between in utero developmental pathology and risk of developing the condition.

• Schizophrenia is most commonly first diagnosed during late adolescence or early adulthood suggesting it is often the end process of childhood and adolescent development.
• Studies have indicated that genetic dispositions can interact with early environment to increase the risk of developing schizophrenia, including through:
  • Global neurobehavioral deficits
  • A poorer family environment and disruptive school behavior
  • Poor peer engagement
  • Immaturity or unpopularity
  • Poorer social competence and increasing schizophrenic symptomology emerging during adolescence
• These developmental problems have also been linked to socioeconomic disadvantage or early experiences of traumatic events.

• There is on average a somewhat earlier onset for men than women, with the possible protective influence of the female hormone oestrogen being one hypothesis made and sociocultural influences another.

Etiology	Description
Genetic	Substantial evidence suggests that the diagnosis of schizophrenia has a heritable component (some estimates are as high as 80%). Current research suggests that environmental factors play a significant role in the expression of any genetic disposition towards schizophrenia (i.e. if someone has the genes that increase risk, this will not automatically result in a diagnosis of schizophrenia later in life). A recent review of the genetic evidence has suggested a more than 28% chance of one identical twin obtaining the diagnosis if the other already has it (see twin studies), but such studies are not noted for pondering the likelihood of similarities of social class and/or other socio-psychological factors between the twins. The estimates of heritability of schizophrenia from twin studies varies a great deal, with some notable studies showing rates as low as 11.0%–13.8% among monozygotic twins, and 1.8%–4.1% among dizygotic twins. However, some scientists criticize the methodology of the twin studies, and have argued that the genetic basis of schizophrenia is still largely unknown or open to different interpretations. The genetic disposition does not always express in twins being the same disorder as cases of one identical twin having schizophrenia and the other having bipolar disorder have been reported. There is currently a great deal of effort being put into molecular genetic studies of schizophrenia, which attempt to identify specific genes which may increase risk. Because of this, the genes that are thought to be most involved can change as new evidence is gathered. A 2003 review of linkage studies listed seven genes as likely to increase risk for a later diagnosis of the disorder.[1] Two more recent reviews[2] have suggested that the evidence is currently strongest for two genes known as dysbindin (DTNBP1) and neuregulin (NRG1), with a number of other genes (such as COMT, RGS4, PPP3CC, ZDHHC8, DISC1, and AKT1) showing some early promising results that have not yet been fully replicated. In 2007, British researchers have identified seven different genetic variations that are associated with schizophrenia and which all lie within or very near a gene FXYD6. A genetic association study of chromosome 11q22-24 in two different samples implicates the FXYD6 gene, encoding phosphohippolin, in susceptibility to schizophrenia. This gene, which lies on the long arm of chromosome 11, plays an important role in regulating Na/K homeostasis. After-conception causes for increase in schizophrenia-rate in a population Lack of sunshine, in the 3rd trimester of gestation ( in the temperate regions a Spring birth, but also El Nino years in Australia, and a particularly overcast 3-month stretch in, IIRC, Brazil, all followed by birth of increased schizophrenia-rate population ). Medical X-Rays, ( IIRC, also in the 3rd trimester of gestation ). Influenza in the mother, during later pregnancy. Older fathers ( poorer-quality genetic contribution ) Therefore, it is likely a genetic activation, rather-than simple-possession of specific genes, that is the true cause of it ( simply having the genes would be Required, but Not Sufficient: having ’em activated might be the sufficient bit ).
Emotional	A number of emotional factors have been implicated in schizophrenia, with some models putting them at the core of the disorder. It was thought that the appearance of blunted affect meant that sufferers did not experience strong emotions, but more recent studies indicate there is often a normal or even heightened level of emotionality, particularly in response to negative events or stressful social situations. Related studies suggest that the content of delusional and psychotic beliefs in schizophrenia can be meaningful and play a causal or mediating role in reflecting the life history or social circumstances of the individual.
Environmental.	Considerable evidence indicates that stressful life events cause or trigger schizophrenia. Childhood experiences of abuse or trauma have also been implicated as risk factors for a diagnosis of schizophrenia later in life. The evidence is also consistent that negative attitudes towards individuals with (or with a risk of developing) schizophrenia can have a significant adverse impact. In particular, critical comments, hostility, authoritarian and intrusive or controlling attitudes (termed ‘high expressed emotion’ by researchers) from family members have been found to correlate with a higher risk of relapse in schizophrenia across cultures. It is not clear whether such attitudes play a causal role in the onset of schizophrenia, although those diagnosed in this way may claim it to be the primary causal factor. The research has focused on family members but also appears to relate to professional staff in regular contact with clients. While initial work addressed those diagnosed as schizophrenic, these attitudes have also been found to play a significant role in other mental health problems. This approach does not blame ‘bad parenting’ or staffing, but addresses the attitudes, behaviors and interactions of all parties. Some go as far as to criticise the whole approach of seeking to localise ‘mental illness’ within one individual — the patient — rather than his/her group and its functionality, citing a scapegoat effect. Factors such as poverty and discrimination also appear to be involved in increasing the risk of schizophrenia or schizophrenia relapse, perhaps due to the high levels of stress they engender, or faults in diagnostic procedure/assumptions. Racism in society, including in diagnostic practices, and/or the stress of living in a different culture, may explain why minority communities have shown higher rates of schizophrenia than members of the same ethnic groups resident in their home country. The “social drift hypothesis” suggests that the functional problems related to schizophrenia, or the stigma and prejudice attached to them, can result in more limited employment and financial opportunities, so that the causal pathway goes from mental health problems to poverty, rather than, or in addition to, the other direction. *Some argue that unemployment and the long-term unemployed and homeless are simply being stigmatised. One particularly stable and replicable finding has been the association between living in an urban environment and schizophrenia diagnosis, even after factors such as drug use, ethnic group and size of social group have been controlled for. A recent study of 4.4 million men and women in Sweden found an alleged 68%–77% increased risk of diagnosed psychosis for people living in the most urbanized environments, a significant proportion of which is likely to be described as schizophrenia. A number of cognitive biases or deficits have been found in people diagnosed with schizophrenia. These include: Jumping to conclusions when faced with limited or contradictory information Specific biases in reasoning about social situations, for example, assuming other people cause things that go wrong (external attribution) Difficulty distinguishing inner speech from speech from an external source (source monitoring) Difficulty in adjusting speech to the needs of the hearer, related to theory of mind difficulties Difficulties in the very earliest stages of processing visual information (including reduced latent inhibition) Difficulty with attention e.g. being more easily distracted, attentional bias towards a threat. Some of these tendencies have been shown to worsen or appear when under emotional stress or in confusing situations. As with the related neurological findings, they are not shown by all individuals with a diagnosis of schizophrenia and it is not clear how specific they are to schizophrenia or to particular symptoms. However, the findings regarding cognitive difficulties in schizophrenia are reliable and consistent enough for some researchers to argue that they are diagnostic. Impaired capacity to appreciate one’s own and others’ mental states has been reported to be the single-best predictor of poor social competence in schizophrenia. Similar cognitive features have been identified in close relatives of people diagnosed with schizophrenia. A number of emotional factors have been implicated in schizophrenia, with some models putting them at the core of the disorder. It was thought that the appearance of blunted affect meant that sufferers did not experience strong emotions, but more recent studies indicate there is often a normal or even heightened level of emotionality, particularly in response to negative events or stressful social situations. Some theories suggest positive symptoms of schizophrenia can result from or be worsened by negative emotions, including depressed feelings and low self-esteem and feelings of vulnerability, inferiority or loneliness. Chronic negative feelings and maladaptive coping skills may explain some of the association between psychosocial stressors and symptomology. Critical and controlling behaviour by significant others (high expressed emotion) causes increased emotional arousal and lowered self-esteem and a subsequent increase in positive symptoms such as unusual thoughts. Countries or cultures where schizotypal personalities or schizophrenia symptoms are more accepted or valued appear to be associated with reduced onset of, or increased recovery from, schizophrenia. Related studies suggest that the content of delusional and psychotic beliefs in schizophrenia can be meaningful and play a causal or mediating role in reflecting the life history or social circumstances of the individual. Holding minority or poorly understood sociocultural beliefs, for example, due to ethnic background, has been linked to increased diagnosis of schizophrenia. The way an individual personally understands and attributes their delusions or hallucinations (e.g. as threatening or as potentially positive) has also been found to influence functioning and recovery.
Infective.	One theory put forward by psychiatrists E. Fuller Torrey and R.H. Yolken is that the parasite Toxoplasma gondii leads to some, if not many, cases of schizophrenia. This is supported by evidence that significantly higher levels of Toxoplasma antibodies in schizophrenia patients compared to the general population.
Substance use	The relationship between schizophrenia and drug use is complex, meaning that a clear causal connection between drug use and schizophrenia has been difficult to tease apart. There is strong evidence that using certain drugs can trigger either the onset or relapse of schizophrenia in some people. It may also be the case, however, that people with schizophrenia use drugs to overcome negative feelings associated with both the commonly prescribed antipsychotic medication and the condition itself, where negative emotion, paranoia and anhedonia are all considered to be core features. The rate of substance use is known to be particularly high in this group. In a recent study, 60% of people with schizophrenia were found to use substances and 37% would be diagnosable with a substance use disorder.
Amphetamines	As amphetamines trigger the release of dopamine and excessive dopamine function is believed to be responsible for many symptoms of schizophrenia (known as the dopamine hypothesis of schizophrenia), amphetamines may worsen schizophrenia symptoms.
Hallucinogens	Schizophrenia can sometimes be triggered by heavy use of hallucinogenic or stimulant drugs, although some claim that a predisposition towards developing schizophrenia is needed for this to occur. There is also some evidence suggesting that people suffering schizophrenia but responding to treatment can have relapse because of subsequent drug use. Some widely known cases where hallucinogens have been suspected of precipitating schizophrenia are Pink Floyd founder-member Syd Barrett and The Beach Boys producer, arranger and songwriter Brian Wilson. Drugs such as ketamine, PCP, and LSD have been used to mimic schizophrenia for research purposes. Using LSD and other psychedelics as a model has now fallen out of favor with the scientific research community, as the differences between the drug induced states and the typical presentation of schizophrenia have become clear. The dissociatives ketamine and PCP are still considered to produce states that are remarkably similar however. Hallucinogenic drugs were also briefly tested as possible treatments for schizophrenia by psychiatrists such as Humphry Osmond and Abram Hoffer in the 1950s. *It was mainly for this experimental treatment of schizophrenia that LSD administration was legal, briefly before its use as a recreational drug led to its criminalization.
Cannabis	There is evidence that cannabis use can contribute to schizophrenia. Some studies suggest that cannabis is neither a sufficient nor necessary factor in developing schizophrenia, but that cannabis may significantly increase the risk of developing schizophrenia and may be, among other things, a significant causal factor. Nevertheless, some previous research in this area has been criticised as it has often not been clear whether cannabis use is a cause or effect of schizophrenia. To address this issue, a recent review of studies from which a causal contribution to schizophrenia can be assessed has suggested that cannabis statistically doubles the risk of developing schizophrenia on the individual level, and may, assuming a causal relationship, be responsible for up to 8% of cases in the population. An older longitudinal study, published in 1987, suggested six-fold increase of schizophrenia risks for high consumers of cannabis (use on more than fifty occasions) in Sweden.
Tobacco	People with schizophrenia tend to smoke significantly more tobacco than the general population. The rates are exceptionally high amongst institutionalized patients and homeless people. In a UK census from 1993, 74% of people with schizophrenia living in institutions were found to be smokers. A 1999 study that covered all people with schizophrenia in Nithsdale, Scotland found a 58% prevalence rate of cigarette smoking, to compare with 28% in the general population. An older study found that as much as 88% of outpatients with schizophrenia were smokers. Despite the higher prevalence of tobacco smoking, people diagnosed with schizophrenia have a much lower than average chance of developing and dying from lung cancer. While the reason for this is unknown, it may be because of a genetic resistance to cancer, a side-effect of drugs being taken, or a statistical effect of increased likelihood of dying from causes other than lung cancer. A recent study of over 50,000 Swedish conscripts found that there was a small but significant protective effect of smoking cigarettes on the risk of developing schizophrenia later in life. While the authors of the study stressed that the risks of smoking far outweigh these minor benefits, this study provides further evidence for the ‘self-medication’ theory of smoking in schizophrenia and may give clues as to how schizophrenia might develop at the molecular level. Furthermore, many people with schizophrenia have smoked tobacco products long before they are diagnosed with the illness, and some groups advocate that the chemicals in tobacco have actually contributed to the onset of the illness and have no benefit of any kind. It is of interest that cigarette smoking affects liver function such that the antipsychotic drugs used to treat schizophrenia are broken down in the bloodstream more quickly. This means that smokers with schizophrenia need slightly higher doses of antipsychotic drugs in order for them to be effective than do their non-smoking counterparts. The increased rate of smoking in schizophrenia may be due to a desire to self-medicate with nicotine. One possible reason is that smoking produces a short term effect to improve alertness and cognitive functioning in persons who suffer this illness. It has been postulated that the mechanism of this effect is that people with schizophrenia have a disturbance of nicotinic receptor functioning which is temporarily abated by tobacco use.[3]
Others	Calcium channel abnormalities are currently being explored as a factor in schizophrenia. Related to this, three small studies have found some improvements on some measures, in schizophrenia with tardive dyskinesia, with the calcium channel blocking agent nilvadipine added to an existing antipsychotic regimen Currently, there is growing evidence of the crucial role of autoimmunity in the etiology and pathogenesis of schizophrenia. This can be seen as a study of the statistical correlation schizophrenia with other autoimmune diseases and the recent work on the direct detailed study immune status of patients with schizophrenia.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2],Vindhya BellamKonda, M.B.B.S [3], Irfan Dotani

Schizophrenia must be differentiated from other diseases such as autism spectrum disorder, bipolar disorder, depressive disorder, and schizoaffective disorder.

Schizophrenia must be differentiated from the following conditions:^[1][2][3][4]

• Autism spectrum disorder or communication disorders
• Major depressive or bipolar disorder with psychotic or catatonic features
• Schizoaffective disorder
• Schizophreniform disorder and brief psychotic disorder
• Delusional disorder
• Schizotypal personality disorder
• Borderline personality disorder
• Obsessive-compulsive disorder and body dysmorphic disorder
• Posttraumatic stress disorder
• Other mental disorders associated with a psychotic episode
• Epilepsy
• Brain lesions
• Chronic disease and metabolic disturbances
• Systemic infection, including HIV and syphilis
• Drug abuse
• Delirium

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2] Irfan Dotani

• The prevalence of schizophrenia is 300 to 700 per 100,000 (0.3%-0.7%) of the overall population.^[1]

• It occurs 1.4 times more frequently in males than females and typically appears earlier in men[14]—the peak ages of onset are 25 years for males and 27 years for females.[174]
• Onset in childhood is much rarer, as is onset in middle or old age.[175][176]

• Despite the prior belief that schizophrenia occurs at similar rates worldwide, its frequency varies across the world, within countries, and at the local and neighborhood level.[5][177][178][179]
• This variation has been estimated to be fivefold.[4]
• It causes approximately one percent of worldwide disability adjusted life years and resulted in 20,000 deaths in 2010.[180]
• The rate of schizophrenia varies up to threefold depending on how it is defined.[9][14]

• In 2000, the World Health Organization 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.[181]
• About 1.1% of adults have schizophrenia in the United States.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2], Irfan Dotani

Risk factors for schizophrenia include the season of birth (late winter, early spring, summer) and genetic predisposition.

The following are associated with increased risk of schizophrenia:^[1]

• Season of birth:

• Early spring
• Summer
• Winter

• Place of growing up:

• Urban areas

• Genetic predisposition to:

• Bipolar disorder
• Depression
• Autism spectrum disorder^[1]

• It is thought that causal factors can initially come together in early neurodevelopment, including during pregnancy, to increase the risk of later developing schizophrenia.
• One curious finding is that people diagnosed with schizophrenia are more likely to have been born in winter or spring, (at least in the northern hemisphere).^[2]
• There is now evidence that prenatal exposure to infections increases the risk for developing schizophrenia later in life, providing additional evidence for a link between in utero developmental pathology and risk of developing the condition.^[3]

• Living in an urban environment has been consistently found to be a risk factor for schizophrenia.^[4]
• Social disadvantage has been found to be a risk factor, including poverty and migration related to social adversity, racial discrimination, family dysfunction, unemployment or poor housing conditions.^[5][6]
• Childhood experiences of abuse or trauma have also been implicated as risk factors for a diagnosis of schizophrenia later in life.^[7][8]
• Parenting is not held responsible for schizophrenia but unsupportive dysfunctional relationships may contribute to an increased risk.^[9]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2] Irfan Dotani

• The disorder is primarily thought to affect cognition, but it also usually contributes to chronic problems with behavior and emotion.
• People diagnosed with schizophrenia are likely to be diagnosed with comorbid conditions, including clinical depression and anxiety disorders; the lifetime prevalence of substance abuse is typically around 40%.
• Social problems, such as long-term unemployment, poverty, and homelessness are common.

• Life expectancy is decreased; the average life expectancy of people with the disorder is 10 to 12 years less than those without, owing to increased physical health problems and a high suicide rate.^[1]
• Numerous international studies have demonstrated favorable long-term outcomes for around half of those diagnosed with schizophrenia, with substantial variation between individuals and regions.^[2]
• One retrospective study found that about a third of people made a full recovery, about a third showed improvement but not a full recovery, and a third remained ill.^[3]
• A clinical study using strict recovery criteria (concurrent remission of positive and negative symptoms and adequate social and vocational functioning continuously for two years) found a recovery rate of 14% within the first five years.^[4]
• A 5-year community study found that 62% showed overall improvement on a composite measure of symptomatic, clinical and functional outcomes.^[5]
• Rates are not always comparable across studies because an exact definition of what constitutes recovery has not been widely accepted, although standardized criteria have been suggested.

• The World Health Organization conducted two long-term follow-up studies involving more than 2,000 people suffering from schizophrenia in different countries.
  • These studies found patients have much better long-term outcomes in developing countries (India, Colombia and Nigeria) than in developed countries (USA, United Kingdom, Ireland, Denmark, Czech Republic, Slovakia, Japan, and Russia), despite the fact antipsychotic drugs are typically not widely available in poorer countries, raising questions about the effectiveness of such drug-based treatments.^[6]

• Several factors are associated with a better prognosis: Being female, acute (vs. insidious) onset of symptoms, older age of the first episode, predominantly positive (rather than negative) symptoms, the presence of mood symptoms and good premorbid functioning.^[7][8]
• Most studies were done on this subject, however, are correlational in nature, and a clear cause-and-effect relationship is difficult to establish.
• The evidence is also consistent that negative attitudes towards individuals with schizophrenia can have a significant adverse impact.
• In particular, critical comments, hostility, authoritarian and intrusive or controlling attitudes (termed high ‘Expressed Emotion’ or ‘EE’ by researchers) from family members have been found to correlate with a higher risk of relapse in schizophrenia across cultures.^[9]

• In a study of over 168,000 Swedish citizens undergoing psychiatric treatment, schizophrenia was associated with an average life expectancy of approximately 80–85% of that of the general population.
• Women with a diagnosis of schizophrenia were found to have a slightly better life expectancy than that of men, and as a whole, a diagnosis of schizophrenia was associated with a better life expectancy than substance abuse, personality disorder, heart attack and stroke.^[10] *There is a high suicide rate associated with schizophrenia; a recent study showed that 30% of patients diagnosed with this condition had attempted suicide at least once during their lifetime.^{[11] [12]}
• Another study suggested that 10% of persons with schizophrenia die by suicide.^[13] Other identified factors include smoking, poor diet, little exercise and the negative health effects of psychiatric drugs.^[1]

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