Schizophrenia

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Schizophrenia 1

Schizophrenia
Schizophrenia
Classification and external resources

ICD-10 [1]
F 20.

ICD-9 [2]
295

OMIM [3]
181500

DiseasesDB [4]
11890

MedlinePlus 000928 [5]

eMedicine [6]
med/2072 emerg/520
[7]

MeSH [8]
F03.700.750

Schizophrenia (pronounced /ˌskɪtsɵˈfrɛniə/ or English pronunciation: /ˌskɪtsɵˈfriːniə/) is a mental disorder characterized

by abnormalities in the perception or expression of reality. It most commonly manifests as auditory hallucinations,
paranoid or bizarre delusions, or disorganized speech and thinking with significant social or occupational
dysfunction. Onset of symptoms typically occurs in young adulthood,[9] with around 0.4–0.6%[10] [11] of the
population affected. Diagnosis is based on the patient's self-reported experiences and observed behavior. No
laboratory test for schizophrenia currently exists.[12]
Studies suggest that genetics, early environment, neurobiology, psychological and social processes are important
contributory factors; some recreational and prescription drugs appear to cause or worsen symptoms. Current
psychiatric research is focused on the role of neurobiology, but no single organic cause has been found. As a result
of the many possible combinations of symptoms, there is debate about whether the diagnosis represents a single
disorder or a number of discrete syndromes. Despite the etymology of the term from the Greek roots skhizein
(σχίζειν, "to split") and phrēn, phren- (φρήν, φρεν-; "mind"), schizophrenia does not imply a "split mind" and it is
not the same as dissociative identity disorder (previously known as multiple personality disorder or split personality),
a condition with which it is often confused in public perception.[13]
Increased dopamine activity in the mesolimbic pathway of the brain is consistently found in schizophrenic
individuals. The mainstay of treatment is antipsychotic medication; this type of drug primarily works by suppressing
dopamine activity. Dosages of antipsychotics are generally lower than in the early decades of their use.
Psychotherapy, and vocational and social rehabilitation are also important. In more serious cases—where there is
risk to self and others—involuntary hospitalization may be necessary, although hospital stays are less frequent and
for shorter periods than they were in previous times.[14]
The disorder is thought to mainly affect cognition, but it also usually contributes to chronic problems with behavior
and emotion. People with schizophrenia are likely to have additional (comorbid) conditions, including major
depression and anxiety disorders;[15] the lifetime occurrence of substance abuse is around 40%. Social problems,
such as long-term unemployment, poverty and homelessness, are common. Furthermore, the average life expectancy
of people with the disorder is 10 to 12 years less than those without, due to increased physical health problems and a
higher suicide rate ( about 5% ).[16] [17]
Schizophrenia 2

Signs and symptoms

Depending on the individual, a person diagnosed with schizophrenia
may experience hallucinations (most commonly hearing voices),
delusions (often bizarre or persecutory in nature), and disorganized
thinking and speech. The latter may range from loss of train of thought,
to sentences only loosely connected in meaning, to incoherence known
as word salad in severe cases. There is often an observable pattern of
emotional difficulty, for example lack of responsiveness or motivation.
Impairment in social cognition is associated with schizophrenia, as are
symptoms of paranoia, and social isolation commonly occurs. In one
uncommon subtype, the person may be largely mute, remain
motionless in bizarre postures, or exhibit purposeless agitation; these
are signs of catatonia.

Late adolescence and early adulthood are peak years for the onset of
schizophrenia. In 40% of men and 23% of women diagnosed with
schizophrenia, the condition arose before the age of 19.[18] These are The term Schizophrenia was coined by Eugen
Bleuler
critical periods in a young adult's social and vocational development.
To minimize the developmental disruption associated with
schizophrenia, much work has recently been done to identify and treat the prodromal (pre-onset) phase of the illness,
which has been detected up to 30 months before the onset of symptoms, but may be present longer.[19] Those who go
on to develop schizophrenia may experience the non-specific symptoms of social withdrawal, irritability and
dysphoria in the prodromal period,[20] and transient or self-limiting psychotic symptoms in the prodromal phase
before psychosis becomes apparent.[21]

Schneiderian classification
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.[22] Although they have significantly contributed to the current diagnostic criteria, the
specificity of first-rank symptoms has been questioned. A review of the diagnostic studies conducted between 1970
and 2005 found that these studies allow neither a reconfirmation nor a rejection of Schneider's claims, and suggested
that first-rank symptoms be de-emphasized in future revisions of diagnostic systems.[23]

Positive and negative symptoms

Schizophrenia is often described in terms of positive and negative (or deficit) symptoms.[24] The term positive
symptoms refers to symptoms that most individuals do not normally experience but are present in schizophrenia.
They include delusions, auditory hallucinations, and thought disorder, and are typically regarded as manifestations of
psychosis. Negative symptoms are things that are not present in schizophrenic persons but are normally found in
healthy persons, that is, symptoms that reflect the loss or absence of normal traits or abilities. Common negative
symptoms include flat or blunted affect and emotion, poverty of speech (alogia), inability to experience pleasure
(anhedonia), lack of desire to form relationships (asociality), and lack of motivation (avolition). Research suggests
that negative symptoms contribute more to poor quality of life, functional disability, and the burden on others than
Schizophrenia 3

do positive symptoms.[25]
A third symptom grouping, the disorganization syndrome, is sometimes described, and includes chaotic speech,
thought, and behavior. There is evidence for a number of other symptom classifications.[26]

Diagnosis
Schizophrenia is diagnosed on the basis of symptom profiles. Neural correlates do not provide sufficiently useful
criteria.[27] Diagnosis is based on the self-reported experiences of the person, and abnormalities in behavior reported
by family members, friends or co-workers, followed by a clinical assessment by a psychiatrist, social worker, clinical
psychologist or other mental health professional. Psychiatric assessment includes a psychiatric history and some
form of mental status examination.

Standardized criteria
The most widely used standardized criteria for diagnosing schizophrenia come from the American Psychiatric
Association's Diagnostic and Statistical Manual of Mental Disorders, version DSM-IV-TR, and the World Health
Organization's International Statistical Classification of Diseases and Related Health Problems, the ICD-10. The
latter criteria are typically used in European countries, while the DSM criteria are used in the United States and the
rest of the world, as well as prevailing in research studies. The ICD-10 criteria put more emphasis on Schneiderian
first-rank symptoms, although, in practice, agreement between the two systems is high.[28]
According to the revised fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR),
to be diagnosed with schizophrenia, three diagnostic criteria must be met:[12]
1. Characteristic symptoms: Two or more of the following, each present for much of the time during a one-month
period (or less, if symptoms remitted with treatment).
• Delusions
• Hallucinations
• Disorganized speech, which is a manifestation of formal thought disorder
• Grossly disorganized behavior (e.g. dressing inappropriately, crying frequently) or catatonic behavior
• Negative symptoms: Blunted affect (lack or decline in emotional response), alogia (lack or decline in speech),
or avolition (lack or decline in motivation)
If the delusions are judged to be bizarre, or hallucinations consist of hearing one voice participating in a
running commentary of the patient's actions or of hearing two or more voices conversing with each other, only
that symptom is required above. The speech disorganization criterion is only met if it is severe enough to
substantially impair communication.
2. Social/occupational dysfunction: For a significant portion of the time since the onset of the disturbance, one or
more major areas of functioning such as work, interpersonal relations, or self-care, are markedly below the level
achieved prior to the onset.
3. Duration: Continuous signs of the disturbance persist for at least six months. This six-month period must include
at least one month of symptoms (or less, if symptoms remitted with treatment).
If signs of disturbance are present for more than a month but less than six months, the diagnosis of schizophreniform
disorder is applied.[12] Psychotic symptoms lasting less than a month may be diagnosed as brief psychotic disorder,
and various conditions may be classed as psychotic disorder not otherwise specified. Schizophrenia cannot be
diagnosed if symptoms of mood disorder are substantially present (although schizoaffective disorder could be
diagnosed), or if symptoms of pervasive developmental disorder are present unless prominent delusions or
hallucinations are also present, or if the symptoms are the direct physiological result of a general medical condition
or a substance, such as abuse of a drug or medication.
Schizophrenia 4

Confusion with other conditions

There is a spectrum of disorders that share similarities with schizophrenia but which are diagnosed as separate
conditions, including schizophreniform disorder, schizoaffective disorder, schizoid personality disorder and
schizotypal personality disorder (related to the concept of schizotypy). Paranoid personality disorder is also generally
considered to be related.[29]
Psychotic symptoms may be present in several other mental disorders, including bipolar disorder,[30] borderline
personality disorder,[31] , drug intoxication and drug-induced psychosis. Delusions ("non-bizarre") are also present in
delusional disorder, and social withdrawal in social anxiety disorder or avoidant personality disorder. Schizophrenia
is complicated with obsessive-compulsive disorder (OCD) considerably more often than could be explained by pure
chance, although it can be difficult to distinguish compulsions that represent OCD from the delusions of
schizophrenia.[32]
A more general medical and neurological examination may be needed to rule out medical illnesses which may rarely
produce psychotic schizophrenia-like symptoms,[12] such as metabolic disturbance, systemic infection, syphilis, HIV
infection, epilepsy, and brain lesions. 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.
"Schizophrenia" does not mean dissociative identity disorder—formerly and still widely known as "multiple
personalities"—despite the etymology of the word (Greek σχίζω = "I split").

Subtypes
The DSM-IV-TR contains five sub-classifications of schizophrenia (the DSM-5 developers are planning to drop
them[33] ):
• Paranoid type: Where delusions and hallucinations are present but thought disorder, disorganized behavior, and
affective flattening are absent. (DSM code 295.3/ICD code F20.0)
• Disorganized type: Named hebephrenic schizophrenia in the ICD. Where thought disorder and flat affect are
present together. (DSM code 295.1/ICD code F20.1)
• Catatonic type: The subject may be almost immobile or exhibit agitated, purposeless movement. Symptoms can
include catatonic stupor and waxy flexibility. (DSM code 295.2/ICD code F20.2)
• Undifferentiated type: Psychotic symptoms are present but the criteria for paranoid, disorganized, or catatonic
types have not been met. (DSM code 295.9/ICD code F20.3)
• Residual type: Where positive symptoms are present at a low intensity only. (DSM code 295.6/ICD code F20.5)
The ICD-10 defines two additional subtypes.
• Post-schizophrenic depression: A depressive episode arising in the aftermath of a schizophrenic illness where
some low-level schizophrenic symptoms may still be present. (ICD code F20.4)
• Simple schizophrenia: Insidious and progressive development of prominent negative symptoms with no history
of psychotic episodes. (ICD code F20.6)

Controversies and research directions

The scientific validity of schizophrenia, and its defining symptoms such as delusions and hallucinations, have been
criticised.[34] [35] In 2006, a group of consumers and mental health professionals from the UK, under the banner of
Campaign for Abolition of the Schizophrenia Label, argued for a rejection of the diagnosis of schizophrenia based
on its heterogeneity and associated stigma, and called for the adoption of a biopsychosocial model. Other UK
psychiatrists opposed the move arguing that the term schizophrenia is a useful, even if provisional concept.[36] [37]
Schizophrenia 5

Similarly, there is an argument that the underlying issues would be better addressed as a spectrum of conditions[38]
or as individual dimensions along which everyone varies rather than by a diagnostic category based on an arbitrary
cut-off between normal and ill.[39] This approach appears consistent with research on schizotypy, and with a
relatively high prevalence of psychotic experiences, mostly non-distressing delusional beliefs, among the general
public.[40] [41] [42] In concordance with this observation, psychologist Edgar Jones, and psychiatrists Tony David and
Nassir Ghaemi, surveying the existing literature on delusions, pointed out that the consistency and completeness of
the definition of delusion have been found wanting by many; delusions are neither necessarily fixed, nor false, nor
involve the presence of incontrovertible evidence.[43] [44] [45]
Nancy Andreasen, a leading figure in schizophrenia research, has criticized the current DSM-IV and ICD-10 criteria
for sacrificing diagnostic validity for the sake of artificially improving reliability. She argues that overemphasis on
psychosis in the diagnostic criteria, while improving diagnostic reliability, ignores more fundamental cognitive
impairments that are harder to assess due to large variations in presentation.[46] [47] This view is supported by other
psychiatrists.[48] In the same vein, Ming Tsuang and colleagues argue that psychotic symptoms may be a common
end-state in a variety of disorders, including schizophrenia, rather than a reflection of the specific etiology of
schizophrenia, and warn that there is little basis for regarding DSM’s operational definition as the "true" construct of
schizophrenia.[38] Neuropsychologist Michael Foster Green went further in suggesting the presence of specific
neurocognitive deficits may be used to construct phenotypes that are alternatives to those that are purely
symptom-based. These deficits take the form of a reduction or impairment in basic psychological functions such as
memory, attention, executive function and problem solving.[49] [50]
The exclusion of affective components from the criteria for schizophrenia, despite their ubiquity in clinical settings,
has also caused contention. This exclusion in the DSM has resulted in a "rather convoluted" separate
disorder—schizoaffective disorder.[48] Citing poor interrater reliability, some psychiatrists have totally contested the
concept of schizoaffective disorder as a separate entity.[51] [52] The categorical distinction between mood disorders
and schizophrenia, known as the Kraepelinian dichotomy, has also been challenged by data from genetic
epidemiology.[53]
An approach broadly known as the anti-psychiatry movement, most active in the 1960s, opposes the orthodox
medical view of schizophrenia as an illness.[54] Psychiatrist Thomas Szasz argues that psychiatric patients are
individuals with unconventional thoughts and behavior that society diagnoses as a method of social control, and
therefore the diagnosis of "schizophrenia" is merely a form of social construction.[55] The Hearing Voices Movement
argues that many people diagnosed as psychotic need their experiences to be accepted and valued rather than
medicalized.
Schizophrenia 6

Causes
While the reliability of the 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 and environmental factors
can act in combination to result in schizophrenia.[57] Evidence suggests
that the diagnosis of schizophrenia has a significant heritable
component but that onset is significantly influenced by environmental
factors or stressors.[58] The idea of an inherent vulnerability (or
diathesis) in some people, which can be unmasked by biological,
psychological or environmental stressors, is known as the
stress-diathesis model.[59] An alternative idea that biological,
psychological and social factors are all important is known as the
"biopsychosocial" model. [56]
Data from a PET study suggests that the less
the frontal lobes are activated (red) during a
working memory task, the greater the increase in
Genetic
abnormal dopamine activity in the striatum
Twin studies and adoption studies have suggested a high level of (green), thought to be related to the
neurocognitive deficits in schizophrenia.
heritability (the proportion of variation between individuals in a
population that is influenced by genetic factors).[60] It has been
suggested that schizophrenia is a condition of complex inheritance, with many different potential genes each of small
effect, with different pathways for different individuals. Some have suggested that several genetic and other risk
factors need to be present before a person becomes affected but this is still uncertain.[61] Candidate genes linked to
an increased risk of schizophrenia and bipolar disorder as found in recent genome wide association studies appear to
be partly separate and partly overlapping between the two disorders[62] Metaanalyses of genetic linkage studies have
produced evidence of chromosomal regions increasing susceptibility,[63] which interacts directly with the Disrupted
in Schizophrenia 1 (DISC1) gene protein[64] more recently the zinc finger protein 804A.[65] has been implicated as
well as the chromosome 6 HLA region.[66] However, a large and comprehensive genetic study found no evidence of
any significant association with any of 14 previously identified candidate genes.[67] Schizophrenia, in a small
minority of cases, has been associated with rare deletions or duplications of tiny DNA sequences (known as copy
number variants) disproportionately occurring within genes involved in neuronal signaling and brain
development/human cognitive, behavioral, and psychological variation.[68] [69] [70]

Assuming a hereditary genetic basis, one question for evolutionary psychology is why genes that increase the
likelihood of the condition evolved, assuming the condition would have been maladaptive from an
evolutionary/reproductive point of view. One theory implicates genes involved in the evolution of language and
human nature, but so far all theories have been disproved or remain unsubstantiated.[71] [72]

Prenatal
Causal factors are thought to initially come together in early neurodevelopment 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).[73] 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.[74]
Schizophrenia 7

Social
Living in an urban environment has been consistently found to be a risk factor for schizophrenia.[75] [76] Social
disadvantage has been found to be a risk factor, including poverty[77] and migration related to social adversity, racial
discrimination, family dysfunction, unemployment or poor housing conditions.[78] Childhood experiences of abuse
or trauma have also been implicated as risk factors for a diagnosis of schizophrenia later in life.[79] [80] Parenting is
not held responsible for schizophrenia but unsupportive dysfunctional relationships may contribute to an increased
risk.[81] [82]

Substance Abuse
In a recent study of people with schizophrenia and a substance abuse disorder, over a ten year period, "substantial
proportions were above cutoffs selected by dual diagnosis clients as indicators of recovery."[83] Although about half
of all patients with schizophrenia use drugs or alcohol, a clear causal connection between drug use and schizophrenia
has been difficult to prove. The two most often used explanations for this are "substance use causes schizophrenia"
and "substance use is a consequence of schizophrenia", and they both may be correct.[84] A 2007 meta-analysis
estimated that cannabis use is statistically associated with a dose-dependent increase in risk of development of
psychotic disorders, including schizophrenia.[85] There is little evidence to suggest that other drugs including alcohol
cause schizophrenia, or that psychotic individuals choose specific drugs to self-medicate; there is some support for
the hypothesis that they use drugs to cope with unpleasant states such as depression, anxiety, boredom and
loneliness.[86] However, regarding psychosis itself, it is well understood that methamphetamine and cocaine use can
result in methamphetamine- or cocaine-induced psychoses that present very similar symptomatology and may persist
even when users remain abstinent.[87]

Mechanisms

Psychological
A number of psychological mechanisms have been implicated in the development and maintenance of schizophrenia.
Cognitive biases that have been identified in those with a diagnosis or those at risk, especially when under stress or
in confusing situations, include excessive attention to potential threats, jumping to conclusions, making external
attributions, impaired reasoning about social situations and mental states, difficulty distinguishing inner speech from
speech from an external source, and difficulties with early visual processing and maintaining concentration.[88] [89]
[90] [91]
Some cognitive features may reflect global neurocognitive deficits in memory, attention, problem-solving,
executive function or social cognition, while others may be related to particular issues and experiences.[81] [92]
Despite a common appearance of "blunted affect", recent findings indicate that many individuals diagnosed with
schizophrenia are emotionally responsive, particularly to stressful or negative stimuli, and that such sensitivity may
cause vulnerability to symptoms or to the disorder.[93] [94] [95] [93] Some evidence suggests that the content of
delusional beliefs and psychotic experiences can reflect emotional causes of the disorder, and that how a person
interprets such experiences can influence symptomatology.[96] [97] [98] [99] The use of "safety behaviors" to avoid
imagined threats may contribute to the chronicity of delusions.[100] Further evidence for the role of psychological
mechanisms comes from the effects of psychotherapies on symptoms of schizophrenia.[101]
Schizophrenia 8

Neural
Studies using neuropsychological tests and brain imaging technologies such as fMRI and PET to examine functional
differences in brain activity have shown that differences seem to most commonly occur in the frontal lobes,
hippocampus and temporal lobes.[102] These differences have been linked to the neurocognitive deficits often
associated with schizophrenia.[103]
Particular focus has been placed upon the function of dopamine in the
mesolimbic pathway of the brain. This focus largely resulted from the
accidental finding that a drug group which blocks dopamine function,
known as the phenothiazines, could reduce psychotic symptoms. It is
also supported by the fact that amphetamines, which trigger the release
of dopamine, may exacerbate the psychotic symptoms in
schizophrenia.[104] An influential theory, known as the Dopamine
hypothesis of schizophrenia, proposed that excess activation of D2
receptors was the cause of (the positive symptoms of) schizophrenia.
Although postulated for about 20 years based on the D2 blockade effect
Functional magnetic resonance imaging and other
brain imaging technologies allow for the study of
common to all antipsychotics, it was not until the mid-1990s that PET
differences in brain activity among people and SPET imaging studies provided supporting evidence. This
diagnosed with schizophrenia explanation is now thought to be simplistic, partly because newer
antipsychotic medication (called atypical antipsychotic medication)
can be equally effective as older medication (called typical antipsychotic medication), but also affects serotonin
function and may have slightly less of a dopamine blocking effect.[105]

Interest has also focused on the neurotransmitter glutamate and the reduced function of the NMDA glutamate
receptor in schizophrenia. This has largely been suggested by abnormally low levels of glutamate receptors found in
postmortem brains of people previously diagnosed with schizophrenia[106] and the discovery that the glutamate
blocking drugs such as phencyclidine and ketamine can mimic the symptoms and cognitive problems associated with
the condition.[107] The fact that reduced glutamate function is linked to poor performance on tests requiring frontal
lobe and hippocampal function and that glutamate can affect dopamine function, all of which have been implicated
in schizophrenia, have suggested an important mediating (and possibly causal) role of glutamate pathways in
schizophrenia.[108] Positive symptoms fail however to respond to glutamatergic medication.[109]

There have also been findings of differences in the size and structure of certain brain areas in schizophrenia. A 2006
metaanlaysis of MRI studies found that whole brain and hippocampal volume are reduced and that ventricular
volume is increased in patients with a first psychotic episode relative to healthy controls. The average volumetric
changes in these studies are however close to the limit of detection by MRI methods, so it remains to be determined
whether schizophrenia is a neurodegenerative process that begins at about the time of symptom onset, or whether it
is better characterised as a neurodevelopmental process that produces abnormal brain volumes at an early age.[110] In
first episode psychosis typical antipsychotics like haloperidol were associated with significant reductions in gray
matter volume, whereas atypical antipsychotics like olanzapine were not.[111] Studies in non-human primates found
gray and white matter reductions for both typical and atypical antipsychotics.[112]
A 2009 meta-analysis of diffusion tensor imaging studies identified two consistent locations of reduced fractional
anisotropy (roughly the level of organization of neural connections) in schizophrenia. The authors suggest that two
networks of white matter tracts may be affected in schizophrenia, with the potential for "disconnection" of the gray
matter regions which they link.[113] During fMRI studies, greater connectivity in the brain's default network and
task-positive network has been observed in patients diagnosed with schizophrenia, and may reflect excessive
attentional orientation toward introspection and toward extrospection, respectively. The greater anti-correlation
between the two networks suggests excessive rivalry between the networks.[114]
Schizophrenia 9

Screening and prevention

There are no reliable markers for the later development of schizophrenia although research is being conducted into
how well a combination of genetic risk plus non-disabling psychosis-like experience predicts later diagnosis.[115]
People who fulfill the 'ultra high-risk mental state' criteria, that include a family history of schizophrenia plus the
presence of transient or self-limiting psychotic experiences, have a 20–40% chance of being diagnosed with the
condition after one year.[116] The use of psychological treatments and medication has been found effective in
reducing the chances of people who fulfill the 'high-risk' criteria from developing full-blown schizophrenia.[117]
However, the treatment of people who may never develop schizophrenia is controversial,[118] in light of the
side-effects of antipsychotic medication; particularly with respect to the potentially disfiguring tardive dyskinesia
and the rare but potentially lethal neuroleptic malignant syndrome.[119] The most widely used form of preventative
health care for schizophrenia takes the form of public education campaigns that provide information on risk factors
and early symptoms, with the aim to improve detection and provide treatment earlier for those experiencing
delays.[120] The new clinical approach early intervention in psychosis is a secondary prevention strategy to prevent
further episodes and prevent the long term disability associated with schizophrenia.

Management
The concept of a cure as such remains controversial, as there is no
consensus on the definition, although some criteria for the remission of
symptoms have recently been suggested.[121] The effectiveness of
schizophrenia treatment is often assessed using standardized methods,
one of the most common being the Positive and Negative Syndrome
Scale (PANSS).[122] Management of symptoms and improving
function is thought to be more achievable than a cure. Treatment was
revolutionized in the mid-1950s with the development and introduction
of chlorpromazine.[123] A recovery model is increasingly adopted,
emphasizing hope, empowerment and social inclusion.[124]

Hospitalization may occur with severe episodes of schizophrenia. This

can be voluntary or (if mental health legislation allows it) involuntary
Molecule of chlorpromazine, which
(called civil or involuntary commitment). Long-term inpatient stays are revolutionized treatment of schizophrenia in the
now less common due to deinstitutionalization, although can still 1950s
[14]
occur. Following (or in lieu of) a hospital admission, support
services available can include drop-in centers, visits from members of a community mental health team or Assertive
Community Treatment team, supported employment[125] and patient-led support groups.

In many non-Western societies, schizophrenia may only be treated with more informal, community-led methods.
Multiple international surveys by the World Health Organization over several decades have indicated that the
outcome for people diagnosed with schizophrenia in non-Western countries is on average better there than for people
in the West.[126] Many clinicians and researchers suspect the relative levels of social connectedness and acceptance
are the difference,[127] although further cross-cultural studies are seeking to clarify the findings.
Schizophrenia 10

Medication
The first line psychiatric treatment for schizophrenia is antipsychotic medication.[128] These can reduce the positive
symptoms of psychosis. Most antipsychotics take around 7–14 days to have their main effect. Currently available
antipsychotics fail, however, to significantly ameliorate the negative symptoms, and the improvements on cognition
may be attributed to the practice effect.[129] [130] [131] [132]
The newer atypical antipsychotic drugs are usually preferred for initial
treatment over the older typical antipsychotic, although they are
expensive and are more likely to induce weight gain and
obesity-related diseases.[133] In 2008, results from a major randomized
trial sponsored by the US National Institute of Mental Health (Clinical
Antipsychotic Trials of Intervention Effectiveness, or CATIE) found
that a representative first-generation antipsychotic, perphenazine, was
as effective as and more cost-effective than several newer drugs
(olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone)
taken for up to 18 months. The atypical antipsychotic which patients
were willing to continue for the longest, olanzapine, was associated
with considerable weight gain and risk of metabolic syndrome.
Clozapine was most effective for people with a poor response to other
drugs, but it had troublesome side effects. Because the trial excluded
patients with tardive dyskinesia, its relevance to these people is
unclear.[134] Risperidone (trade name Risperdal) is a common
atypical antipsychotic medication
Because of their reportedly lower risk of side effects that affect
mobility, atypical antipsychotics have been first-line treatment for early-onset schizophrenia for many years before
certain drugs in this class were approved by the Food and Drug Administration for use in children and teenagers with
schizophrenia. This advantage comes at the cost of an increased risk of metabolic syndrome and obesity, which is of
concern in the context of long-term use begun at an early age. Especially in the case of children and teenagers who
have schizophrenia, medication should be used in combination with individual therapy and family-based
interventions.[18]

Recent reviews have refuted the claim that atypical antipsychotics have fewer extrapyramidal side effects than
typical antipsychotics, especially when the latter are used in low doses or when low potency antipsychotics are
chosen.[135]
Prolactin elevations have been reported in women with schizophrenia taking atypical antipsychotics.[136] It remains
unclear whether the newer antipsychotics reduce the chances of developing neuroleptic malignant syndrome, a rare
but serious and potentially fatal neurological disorder most often caused by an adverse reaction to neuroleptic or
antipsychotic drugs.[137]
Response of symptoms to medication is variable: treatment-resistant schizophrenia is a term used for the failure of
symptoms to respond satisfactorily to at least two different antipsychotics.[138] Patients in this category may be
prescribed clozapine,[139] a medication of superior effectiveness but several potentially lethal side effects including
agranulocytosis and myocarditis.[140] Clozapine may have the additional benefit of reducing propensity for substance
abuse in schizophrenic patients.[141] For other patients who are unwilling or unable to take medication regularly,
long-acting depot preparations of antipsychotics may be given every two weeks to achieve control. The United States
and Australia are two countries with laws allowing the forced administration of this type of medication on those who
refuse but are otherwise stable and living in the community. At least one study suggested that in the longer-term
some individuals may do better not taking antipsychotics.[142]
Schizophrenia 11

Psychological and social interventions

Psychotherapy is also widely recommended and used in the treatment of schizophrenia, although services may often
be confined to pharmacotherapy because of reimbursement problems or lack of training.[143]
Cognitive behavioral therapy (CBT) is used to target specific symptoms[144] [145] [146] and improve related issues
such as self-esteem, social functioning, and insight. Although the results of early trials were inconclusive[147] as the
therapy advanced from its initial applications in the mid 1990s, more recent reviews clearly show CBT is an
effective treatment for the psychotic symptoms of schizophrenia.[148] [149]
Another approach is cognitive remediation, a technique aimed at remediating the neurocognitive deficits sometimes
present in schizophrenia. Based on techniques of neuropsychological rehabilitation, early evidence has shown it to be
cognitively effective, with some improvements related to measurable changes in brain activation as measured by
fMRI.[150] [151] A similar approach known as cognitive enhancement therapy, which focuses on social cognition as
well as neurocognition, has shown efficacy.[152]
Family therapy or education, which addresses the whole family system of an individual with a diagnosis of
schizophrenia, has been consistently found to be beneficial, at least if the duration of intervention is longer-term.[153]
[154] [155]
Aside from therapy, the effect of schizophrenia on families and the burden on carers has been recognized,
with the increasing availability of self-help books on the subject.[156] [157] There is also some evidence for benefits
from social skills training, although there have also been significant negative findings.[158] [159] Some studies have
explored the possible benefits of music therapy and other creative therapies.[160] [161] [162]
The Soteria model is alternative to inpatient hospital treatment using a minimal medication approach. It is described
as a milieu-therapeutic recovery method, characterized by its founder as "the 24 hour a day application of
interpersonal phenomenologic interventions by a nonprofessional staff, usually without neuroleptic drug treatment,
in the context of a small, homelike, quiet, supportive, protective, and tolerant social environment."[163] Although
research evidence is limited, a 2008 systematic review found the programme equally as effective as treatment with
medication in people diagnosed with first and second episode schizophrenia.[164]

Other
Electroconvulsive therapy is not considered a first line treatment but may be prescribed in cases where other
treatments have failed. It is more effective where symptoms of catatonia are present,[165] and is recommended for use
under NICE guidelines in the UK for catatonia if previously effective, though there is no recommendation for use for
schizophrenia otherwise.[166] Psychosurgery has now become a rare procedure and is not a recommended
treatment.[167]
Service-user led movements have become integral to the recovery process in Europe and the United States; groups
such as the Hearing Voices Network and the Paranoia Network have developed a self-help approach that aims to
provide support and assistance outside the traditional medical model adopted by mainstream psychiatry. By avoiding
framing personal experience in terms of criteria for mental illness or mental health, they aim to destigmatize the
experience and encourage individual responsibility and a positive self-image. Partnerships between hospitals and
consumer-run groups are becoming more common, with services working toward remediating social withdrawal,
building social skills and reducing rehospitalization.[168]
Regular exercise can have healthful effects on both the physical and mental health and well-being of individuals with
schizophrenia.[169]
Schizophrenia 12

Prognosis

Course
Coordinated by the World Health Organization and published in 2001,
The International Study of Schizophrenia (ISoS) was a long-term
follow-up study of 1633 individuals diagnosed with schizophrenia
around the world. Of the 75% who were available for follow-up, half
had a favourable outcome, and 16% had a delayed recovery after an
early unremitting course. More usually, the course in the first two years
predicted the long-term course. Early social intervention was also
related to a better outcome. The findings were held as important in
moving patients, carers and clinicians away from the prevalent belief
of the chronic nature of the condition.[170] A review of major
longitudinal studies in North America noted this variation in outcomes,
although outcome was on average worse than for other psychotic and
psychiatric disorders. A moderate number of patients with
schizophrenia were seen to remit and remain well; the review raised
the question that some may not require maintenance medication.[171]

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.[172] A 5-year community study found that
62% showed overall improvement on a composite measure of clinical
and functional outcomes.[173]
John Nash, a US mathematician, began showing
signs of paranoid schizophrenia during his
college years. Despite having stopped taking his
prescribed medication, Nash continued his studies
and was awarded the Nobel Prize in 1994. His
life was depicted in the 2001 film A Beautiful
Mind.

World Health Organization studies have noted that individuals diagnosed with schizophrenia have much better
long-term outcomes in developing countries (India, Colombia and Nigeria) than in developed countries (United
States, United Kingdom, Ireland, Denmark, Czech Republic, Slovakia, Japan, and Russia),[174] despite antipsychotic
drugs not being widely available.

Defining recovery
Rates are not always comparable across studies because exact definitions of remission and recovery have not been
widely established. A "Remission in Schizophrenia Working Group" has proposed standardized remission criteria
involving "improvements in core signs and symptoms to the extent that any remaining symptoms are of such low
intensity that they no longer interfere significantly with behavior and are below the threshold typically utilized in
justifying an initial diagnosis of schizophrenia".[175] Standardized recovery criteria have also been proposed by a
number of different researchers, with the stated DSM definitions of a "complete return to premorbid levels of
functioning” or "complete return to full functioning" seen as inadequate, impossible to measure, incompatible with
the variability in how society defines normal psychosocial functioning, and contributing to self-fulfilling pessimism
and stigma.[176] Some mental health professionals may have quite different basic perceptions and concepts of
recovery than individuals with the diagnosis, including those in the Consumer/Survivor/Ex-Patient Movement.[177]
One notable limitation of nearly all the research criteria is failure to address the person's own evaluations and
feelings about their life. Schizophrenia and recovery often involve a continuing loss of self-esteem, alienation from
friends and family, interruption of school and career, and social stigma, "experiences that cannot just be reversed or

forgotten".[124] An increasingly influential model defines recovery as a process, similar to being "in recovery" from
drug and alcohol problems, and emphasizes a personal journey involving factors such as hope, choice,
Schizophrenia 13

empowerment, social inclusion and achievement.[124]

Predictors
Several factors have been associated with a better overall prognosis: Being female, rapid (vs. insidious) onset of
symptoms, older age of first episode, predominantly positive (rather than negative) symptoms, presence of mood
symptoms, and good pre-illness functioning.[178] [179] The strengths and internal resources of the individual
concerned, such as determination or psychological resilience, have also been associated with better prognosis.[171]
The attitude and level of support from people in the individual's life can have a significant impact; research framed in
terms of the negative aspects of this—the level of critical comments, hostility, and intrusive or controlling attitudes,
termed high 'Expressed emotion'—has consistently indicated links to relapse.[180] Most research on predictive factors
is correlational in nature, however, and a clear cause-and-effect relationship is often difficult to establish.

Mortality
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 were found to have a
slightly better life expectancy than men, and a diagnosis of schizophrenia was associated with an overall better life
expectancy than substance abuse, personality disorder, heart attack and stroke.[181] Other identified factors include
smoking,[182] poor diet, little exercise and the negative health effects of psychiatric drugs.[16]
There is a higher than average suicide rate associated with schizophrenia. This has been cited at 10%, but a more
recent analysis of studies and statistics revises the estimate at 4.9%, most often occurring in the period following
onset or first hospital admission.[183] Several times more attempt suicide.[184] There are a variety of reasons and risk
factors.[185] [186]

Violence
The relationship between violent acts and schizophrenia is a contentious topic. Current research indicates that the
percentage of people with schizophrenia who commit violent acts is higher than the percentage of people without
any disorder, but lower than is found for disorders such as alcoholism, and the difference is reduced or not found in
same-neighbourhood comparisons when related factors are taken into account, notably sociodemographic variables
and substance misuse.[187] Studies have indicated that 5% to 10% of those charged with murder in Western countries
have a schizophrenia spectrum disorder.[188] [189] [190]
The occurrence of psychosis in schizophrenia has sometimes been linked to a higher risk of violent acts. Findings on
the specific role of delusions or hallucinations have been inconsistent, but have focused on delusional jealousy,
perception of threat and command hallucinations. It has been proposed that a certain type of individual with
schizophrenia may be most likely to offend, characterized by a history of educational difficulties, low IQ, conduct
disorder, early-onset substance misuse and offending prior to diagnosis.[188]
Individuals with a diagnosis of schizophrenia are often the victims of violent crime—at least 14 times more often
than they are perpetrators.[191] [192] Another consistent finding is a link to substance misuse, particularly alcohol,[193]
among the minority who commit violent acts. Violence by or against individuals with schizophrenia typically occurs
in the context of complex social interactions within a family setting,[194] and is also an issue in clinical services[195]
and in the wider community.[196]
Schizophrenia 14

Epidemiology
Schizophrenia occurs equally in males and females, although typically
appears earlier in men—the peak ages of onset are 20–28 years for
males and 26–32 years for females.[9] Onset in childhood is much
rarer,[197] as is onset in middle- or old age.[198] The lifetime prevalence
of schizophrenia—the proportion of individuals expected to experience
the disease at any time in their lives—is commonly given at 1%. Disability-adjusted life year for schizophrenia per
However, a 2002 systematic review of many studies found a lifetime 100,000 inhabitants in 2002.     no data      ≤ 185
[11]
prevalence of 0.55%. Despite the received wisdom that      185–197      197–207      207–218      218–229
     229–240      240–251      251–262      262–273
schizophrenia occurs at similar rates worldwide, its prevalence varies
     273–284      284–295      ≥ 295
across the world,[199] within countries,[200] and at the local and
neighbourhood level.[201] 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.[75] Schizophrenia is known to be a major
cause of disability. In a 1999 study of 14 countries, active psychosis was ranked the third-most-disabling condition
after quadriplegia and dementia and ahead of paraplegia and blindness.[202]

History
Accounts of a schizophrenia-like syndrome are thought to be rare in the historical record before the 1800s, although
reports of irrational, unintelligible, or uncontrolled behavior were common. A detailed case report in 1797
concerning James Tilly Matthews, and accounts by Phillipe Pinel published in 1809, are often regarded as the
earliest cases of the illness in the medical and psychiatric literature.[203] Schizophrenia was first described as a
distinct syndrome affecting teenagers and young adults by Bénédict Morel in 1853, termed démence précoce
(literally 'early dementia'). The term dementia praecox was used in 1891 by Arnold Pick to in a case report of a
psychotic disorder. In 1893 Emil Kraepelin introduced a broad new distinction in the classification of mental
disorders between dementia praecox and mood disorder (termed manic depression and including both unipolar and
bipolar depression). Kraepelin believed that dementia praecox was primarily a disease of the brain,[204] and
particularly a form of dementia, distinguished from other forms of dementia, such as Alzheimer's disease, which
typically occur later in life.[205]
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")[206] —was coined by Eugen Bleuler in 1908
and was intended to describe the separation of function between personality, thinking, memory, and perception.
Bleuler described the main symptoms as 4 A's: flattened Affect, Autism, impaired Association of ideas and
Ambivalence.[207] 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.
In the early 1970s, the diagnostic criteria for schizophrenia was the subject of a number of controversies which
eventually led to the operational criteria used today. It became clear after the 1971 US-UK Diagnostic Study that
schizophrenia was diagnosed to a far greater extent in America than in Europe.[208] This was partly due to looser
diagnostic criteria in the US, which used the DSM-II manual, contrasting with Europe and its ICD-9. David
Rosenhan's 1972 study, published in the journal Science under the title On being sane in insane places, concluded
that the diagnosis of schizophrenia in the US was often subjective and unreliable.[209] These were some 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 in 1980.{subscription required}[210]
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
Schizophrenia 15

personalities, schizophrenia does not involve a person changing among distinct multiple personalities. The confusion
arises in part due to the literal interpretation of Bleuler's term schizophrenia. The first known misuse of the term to
mean "split personality" was in an article by the poet T. S. Eliot in 1933.[211]

Society and culture

Stigma
Social stigma has been identified as a major obstacle in the recovery of patients with schizophrenia.[212] In a large,
representative sample from a 1999 study, 12.8% of Americans believed that individuals with schizophrenia were
"very likely" to do something violent against others, and 48.1% said that they were "somewhat likely" to. Over 74%
said that people with schizophrenia were either "not very able" or "not able at all" to make decisions concerning their
treatment, and 70.2% said the same of money management decisions.[213] The perception of individuals with
psychosis as violent has more than doubled in prevalence since the 1950s, according to one meta-analysis.[214]
In 2002, the Japanese Society of Psychiatry and Neurology changed the term for schizophrenia from
Seishin-Bunretsu-Byo 精神分裂病 (mind-split-disease) to Tōgō-shitchō-shō 統合失調症 (integration disorder) to
reduce stigma,[215] The new name was inspired by the biopsychosocial model, and it increased the percentage of
cases in which patients were informed of the diagnosis from 36.7% to 69.7% over three years.[216]

Iconic cultural depictions

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 Western India, shows the behavior, mentality, and struggle of the patient
as well as his loved-ones. 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,[217] later made into
a movie.
In Bulgakov's The 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 recounts his struggle with schizophrenia and his recovering journey.

See also
• Persecutory delusions
• Catastrophic Schizophrenia
• Schizocaria

Further reading
• Bentall, Richard (2003). Madness explained: psychosis and human nature. London: Allen Lane.
ISBN 0-7139-9249-2.
• Dalby, J. Thomas (1996). Mental disease in history: a selection of translated readings. Bern: Peter Lang.
ISBN 0-8204-3056-0.
• Fallon, James H. (2003). "The Neuroanatomy of Schizophrenia: Circuitry and Neurotransmitter Systems".
Clinical Neuroscience Research 3: 77–107. doi:10.1016/S1566-2772(03)00022-7.
• Fleck, Stephen; Theodore Lidz and Alice Cornelison (1985). Schizophrenia and the family. New York:
International Universities Press. ISBN 0-8236-6001-X.
• Keen TM (December 1999). "Schizophrenia: orthodoxy and heresies. A review of alternative possibilities".
Journal of Psychiatric and Mental Health Nursing 6 (6): 415–24. doi:10.1046/j.1365-2850.1999.00237.x.
Schizophrenia 16

PMID 10818864.
• Laing, Ronald D. (1990). The divided self: an existential study in sanity and madness. New York: Penguin Books.
ISBN 0-14-013537-5.
• Noll, Richard (2006). The Encyclopedia of Schizophrenia And Other Psychotic Disorders (Facts on File Library
of Health and Living). New York: Facts on File. ISBN 0-8160-6405-9.
• Roazen, Paul; Victor Tausk (1991). Sexuality, war, and schizophrenia: collected psychoanalytic papers. New
Brunswick, N.J., U.S.A: Transaction Publishers. ISBN 0-88738-365-3. (On the Origin of the 'Influencing
Machine' in Schizophrenia.)
• Shaner A, Miller G, Mintz J (September 2004). "Schizophrenia as one extreme of a sexually selected fitness
indicator" [218] (PDF). Schizophr. Res. 70 (1): 101–9. doi:10.1016/j.schres.2003.09.014. PMID 15246469.
Retrieved 2008-07-07.
• Szasz, Thomas Stephen (1976). Schizophrenia: the sacred symbol of psychiatry. New York: Basic Books.
ISBN 0-465-07222-4.
• Walker Elaine, et al (2004). "Schizophrenia: Etiology and Course" [219]. Annual Review of Psychology 55:
401-30. doi:10.1146/annurev.psych.55.090902.141950.

External links
• Schizophrenia [220] at the Open Directory Project
• NPR: the sight and sounds of schizophrenia [221]
• The current World Health Organisation definition of Schizophrenia [222]
• Symptoms in Schizophrenia [223] Film made in 1940 showing some of the symptoms of Schizophrenia.

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[219] http:/ / arjournals. annualreviews. org/ doi/ abs/ 10. 1146/ annurev. psych. 55. 090902. 141950
[220] http:/ / www. dmoz. org/ Health/ Mental_Health/ Disorders/ Schizophrenia/ /
[221] http:/ / www. npr. org/ programs/ atc/ features/ 2002/ aug/ schizophrenia/
[222] http:/ / www. who. int/ mental_health/ management/ schizophrenia/ en/
[223] http:/ / www. archive. org/ details/ Symptoms1940
Article Sources and Contributors 26

Article Sources and Contributors

Schizophrenia  Source: http://en.wikipedia.org/w/index.php?oldid=361693013  Contributors: *drew, 0dd1, 100110100, 19.99, 2004-12-29T22:45Z, 204.38.53.xxx, 204.38.55.xxx,
213.253.39.xxx, 213.253.40.xxx, 217.99.105.xxx, 24.58.228.xxx, 24.93.53.xxx, 3x3cut0r, 5.134, 62.253.64.xxx, A bit iffy, A314268, Aaronlg, Academic Challenger, Acnp01, Action potential,
Adashiel, Admiral Roo, Adraeus, Adrian.benko, Aguelff, Aitias, AjitPD, Ajmiller, Akira625, Alangpierce, Alex.tan, AlexLevyOne, AlfieNet, Alg8662, AlistairMcMillan, Alpha3103, Alterrabe,
AmanUwellCant, AmanitaD, Amedrovis, Amelie222, AmishThrasher, Amsterdam360, Andre Engels, Andrewpmk, Andycjp, Angela, Animalresearcher, AnnaFrance, Anom, AnotherSolipsist,
Ans-mo, Antaeus Feldspar, Antandrus, Anthony Appleyard, AntiochCollege, Antonrojo, Apokrif, Appleboy, Aravind4588, Arcadian, Ardric47, ArglebargleIV, Argon233, ArlyneB,
ArmadilloFromHell, Arsene, Aspro, Aurista25, Ausfaller, AussieBoy, AxelBoldt, Axl, B. Pelletier, Banes, Barticus88, Beland, Ben Taylor, Benchik, Benny the wayfarer, Beno1000, Benson85,
Berkeley99, Bernard the Varanid, Bernardlan, Bhadani, Bib, Bibliobaggins, Bioform 1234, Biot, Biruitorul, Blainster, Blend1100, Bluesquareapple, Bobblewik, Bobo192, BorgQueen, Bratsche,
Brendan Moody, Brian0918, Brighterorange, BrokenSegue, Bucketsofg, Bushytails, CDN99, Caesarjbsquitti, CameoAppearance, Can't sleep, clown will eat me, Canadian-Bacon, Cantus, Carlon,
CarolinianJeff, Casliber, Cbrown1023, Cburnett, Ccacsmss, Cenarium, CenozoicEra, Centrx, Ceoil, Cesar Tort, Cestlogique, Charles Matthews, CharlotteWebb, Chris 73, Chris Capoccia, Chris
the speller, Chrislk02, Christian List, Chuck Sirloin, Cimon Avaro, ClaraClayton, ClaudineChionh, Clemmy, CloudSurfer, Cmdrjameson, Cobalt137cc, Codrdan, Colin, Colin Kimbrell, Conch
Shell, Contentmaven, Conversion script, CopperKettle, Coroebus, Cosmic Latte, Cowman109, Crusadeonilliteracy, CryptoDerk, Cubs Fan, Curps, Cushlinkes, Cyclonenim, Cynical, DCDuring,
DPeterson, DVD R W, Dachshund, Dacxjo, Dan Fuhry, Daniel C. Boyer, Danny, Dantheman531, Dar-Ape, Darbus, Dark Charles, Darkhorse82, DashaKat, David Gerard, DavidA, Davril2020,
Dawn Bard, Deb, Delldot, Deltabeignet, DerHexer, Digitalme, Dina, DinoGrawr, Discospinster, Dissolve, Dix d'Épées, Djayjp, Dlmccaslin, Dlohcierekim's sock, Doctorsticky, DonSiano,
Dorftrottel, Dr Archeville, Dr CareBear, Dr.alf, Drgitlow, Dribble101, Drini, DropDeadGorgias, Drorbn, Durova, Dylan Lake, EPM, Earlypsychosis, Eastlaw, Ebbinghaus, Echobeats, Eddycarr,
Edhubbard, Editor182, Eequor, Egcg123, El C, El estremeñu, El3ctr0nika, ElBenevolente, Elb2000, Ema Zee, Emveekay, Eog1916, Epolk, Eric Herboso, ErikStewart, Esap, Esemono, Etaonsh,
Eubulides, Euchiasmus, EverSince, Evercat, Excelsior, Excessivereason, Exir Kamalabadi, Exploding Boy, FETuriousness, FT2, Falconleaf, Fastfission, Faymondo, Feedmecereal, Ferretilicious,
Fibonacci, FilmFemme, Finalnight, Firsfron, Flcelloguy, Florentino floro, Florescent, Fluppy, Fragilewindows, Francesca Allan of MindFreedomBC, FrancisTyers, Franzio, Freakofnurture,
Fred114, Freebiegrabber, Freewilly2009, Frs, Fsoccibpn, FuelWagon, Fuzbaby, Fvasconcellos, Fvw, GDonato, Gaius Cornelius, Garkbit, Garrondo, Garzo, Gdo01, Geb11, Geni, Geoffreygiraffe,
Ghetteaux, Gilgamesh, Gilliam, Gimboid, Ginkgo100, Gladstone, Glen, GngstrMNKY, Gnif global, Go rators, Gogo Dodo, Grace E. Dougle, GraemeL, Graham87, GregAsche, GregorB,
Grooveguru, Grubbmeister, Gurch, Gwernol, H.-P.Haack, HGB, Habj, Hadal, Hagerman, Haham hanuka, Hairy Dude, Hajor, Hall Monitor, Hamburger Hill, HappyInGeneral, Harel, Harryboyles,
Harrymph, Hassocks5489, Haukurth, Hbdragon88, Heah, Heimstern, Helios Entity 2, HenkvD, Hessamnia, Hgurling, Hinges, Hiphats, Hooriaj, HopeMr, Horsten, Horus Greeley, Howdy Doody,
Hu12, Huji, Hypernovic, Iamnotanorange, Ian Pitchford, Icankeepthisupforever, Ideogram, Im.a.lumberjack, Inductionheating, Ingolfson, Inter, Iregretthisname, Irishguy, Isaac, Ivan Tyrrell,
Ixfd64, J-Star, J.delanoy, JForget, JLaTondre, JPK, JSmith60, JTBurman, JackSparrow Ninja, Jagged 85, JakeVortex, Jamesmorrison, Jared Preston, Jaredstein, Jay, Jcw69, Jedsen, Jeekc, Jeffq,
Jeffthejiff, Jengirl1988, Jennydu923, Jerzy, Jfdwolff, Jhp isog, Jiang, Jmak, Jmh649, Jmsanta, JoanneB, Jogers, Johann Gambolputty, Johann Wolfgang, Johnpawl, Johns568, Jojit fb, Jokes
Free4Me, Jon Trist, Jordangordanier, Jose Ramos, JosephO75, Jossi, Joyous!, Jrm2007, Jtotten, Julesd, Jv821, Jweiss11, KJS77, Kafziel, Kaisershatner, KakistocraticLaw, Kanjilearner55,
Karada, Karn, Kate, KayEnigma, Kazak, Kbdank71, Keeno, Keepcalmandcarryon, Kerotan, Kevanbd, Kevin Bielicki, Khoikhoi, Kierensfaroes, Kinda0, Kingfish, Kingturtle, KirkHammett,
Kittybrewster, Knowledge-is-power, KnowledgeOfSelf, Koavf, Kontribuuttori, Koven.rm, Koyaanis Qatsi, KrakatoaKatie, Krash, Kungfuadam, Kusma, Kwamikagami, Kzollman, LFROTA,
Ladlergo, Lalvers, Legit-Anti-Psychiatry101, LeonardoRob0t, Lestrade, Letranova, Levil, LiDaobing, Liftarn, Lightdarkness, Lightmouse, Ligulem, Lilac Soul, Linmhall, Lir, Literaturegeek,
Llnoba, Logologist, Lokiloki, Looie496, Lord Humungus, LordK, LudwigVan, Luna Santin, Lupin, M314abc, MCiura, Majorly, Makeswell, Malcolm Farmer, Malerin, Malo, Mandarax,
Mandark, Mani1, Marc Venot, Mariko, Mark v1.0, MarkWood, Markae, Martian.knight, MartinHarper, Martinezmartinez, Martinl, Marumari, Massimo Macconi, Matt Crypto, Mattisse, Mav,
Maximus Rex, Mbc362, Me eloise, Me2NiK, Megaman en m, Merrypsimon, Metaeducation, Metalhead94, Metaquasi, Mhking, Michael Devore, Michael Hardy, MichaelExe, Mickey436,
Miclick, Midway, Mietchen, Mihai cartoaje, Mike Christie, Mike Rosoft, MikeDawg, Misanthrope00, MisfitToys, Mkamensek, Mmitzelfelt, Mnpeter, Moondoll, Moonlight Mile, Moorlock,
Morgan Leigh, Morwen, Moshe Constantine Hassan Al-Silverburg, Moxy, Mr Rookles, MrDolomite, MrFish, Ms2ger, Muchness, Murmur74, Muscovite99, Muugokszhiion, Muya, Mwanner,
NCurse, Nadavspi, Nathan1134, NathanHurst, NawlinWiki, Nedib1, Nehwyn, Neilbeach, Neitherday, Nepalnt21, Nick Yoder, NickGorton, Nickj, Nickyfann, Nieske, Nigelpm, NightWolf1298,
Nilmerg, Nirajha, Nishkid64, Nixdorf, Nixeagle, Noisy, Nooneknows619, Notpayingthepsychiatrist, NubKnacker, Nufy8, Nuggetboy, Nuno Tavares, Nutriveg, ONEder Boy, Obli, Oblivious,
Obtsu, Od Mishehu, Olaf Stephanos, Olyus, Ombudsman, Omid83, One Salient Oversight, Opelio, Orangutan, Orizon, Ororon, Outriggr, OwenX, Oxico, Palica, Pandawelch, Paranoid, Patrick,
Patrickwilken, Paul gene, Paxsimius, Pearle, Pedro, PeeKay5000, Pele star, Penbat, Peruvianllama, Pgk, Pharos, Phinnaeus, PierreAnoid, Pigsonthewing, Pile-Up, Pippin254, Pissant, Pko, Pohta
ce-am pohtit, Pol098, Polyvios, Prashanthns, Pro translator, Projectc, Prolog, PrometheusX303, Pruneau, Pstarbuck, Psy guy, Psych1212, PsychCat, Psychogerbil, PurrfectPeach, Pyrop, Qooth,
Qtpie16800, Quadzilla99, Quintin3265, RFerreira, RJHall, RNaidu, RPBHANDARI, Rainbird, RalphLender, Ram-Man, Randy Johnston, Raoul NK, Rasmus Faber, Raul654, Rdsmith4,
Rebirtha, Rebrane, Red dwarf, RedRollerskate, RedWolf, Redpijka, Reillyd, Renwick, Returnoftheman, RexNL, Rich Farmbrough, Richard001, Rintrah, Rjwilmsi, Rmky87, Roaster4748,
Roastporkbun, Rob.towers, RobbieRocketPants, Robert Merkel, RobertG, RobinHood70, Rocket000, Roeschter, Rohan Jayasekera, Rorschach567, RoyBoy, Royalguard11, Royboycrashfan,
Rpinz, Runningfridgesrule, Ryulong, S. M. Sullivan, S1lenze, SCB, SDY, ST47, Saenger, Sahafan, SakotGrimshine, SallyForth123, SandyGeorgia, Sango123, Sarafemme, Sarah,
SarahWickedWeasel, Sardaka, Savant1984, Schaefer, ScienceApologist, Scottandrewhutchins, Sderose, Sean Whitton, Seans Potato Business, Secretmessages, Secretsofdiffusion, Serious Sam
Stone, Serrano, Setmyfriendsonfire27, Shadow Android, Shanel, Shanes, Shanew2, Shaxnerd418, ShiftFn, Shimeru, Shoaler, Sietse Snel, Sii, Sir Garland, Sir Nicholas de Mimsy-Porpington,
Sjakkalle, Sjorford, Skagedal, Skinnyweed, Skyfaller, Slakr, Slgordon3, Slunky, Smorty232323, Smurrayinchester, Snake712, SnakeEater1992, Snowolfd4, Snoyes, Solace098, Somegeek,
Someone else, Sophos, Sorenr, Sp0, Spawn Man, Spliffy, Spoon!, Stargelman, Steel, SteveCrook, Stevenfruitsmaak, Stewartadcock, Stizz, SummerWithMorons, Supertask, Supten, Susurrus,
Susvolans, Svetovid, Swartenhouse, SweetNeo85, Swiftly, TVC 15, TaintedMustard, Tanthalas39, Taopman, Tar7arus, Tarek, Tarnas, Tdalby, TeaDrinker, Teamturnz, Teamxdown, Ted
Longstaffe, Teeveegal, Tekkaman, Terbospeed, Terraguy, Tess83, Thaddeusjwhoopie, Thatperson, The Anome, The Geneticist, The Gerg, The Man in Question, The Tom, The-Void-Skull,
TheJC, TheMindsEye, TheProject, TheRanger, TheRealdeal, Thecaucasianasian, Theelf29, ThisGregM, TigerShark, TimVickers, Timwi, Tlogmer, Tom harrison, Tom.k, Tothebarricades.tk,
Tpbradbury, Treisijs, Trilemma, Trilobitealive, Tuncrypt, Tuviya, Tweak279, Twerges, Twotimes, Tylop, Ubiq, UltimateXiphias, Umbralcorax, Unixer, Unyoyega, Urod, Ushionna, VKokielov,
Vague Rant, Valproate, Vaughan, Vegaan, Velvetron, Vilerage, Viridae, W guice, W09110900, WLU, Wakkow, Wapcaplet, Watcher, Wavelength, Wayward, Wclark, Wero, Wesesque, Wgd,
WhatamIdoing, Whig, Wik, Wik! t, WikHead, Wiki alf, WikiCats, WikiDan61, Wikiklrsc, Wikimol, Wikipappy4u, Williams30, Wilsonaljmu, WindAndConfusion, Wisco, Wistungsten,
Wiwaxia, Wk muriithi, Wknight94, Woohookitty, Wouterstomp, Wrathchild, X., XanaX, Xaosflux, Xasodfuih, Xnuala, Xocoyote, Xurich, Yamaguchi先生, Yamamoto Ichiro, Yggdræsil, Yosri,
Yousifnet, Zachorious, Zashaw, Zigger, Ziphon, Ziusudra, 1527 anonymous edits

Image Sources, Licenses and Contributors

File:Eugen Bleuler.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Eugen_Bleuler.jpg  License: Public Domain  Contributors: Clinique du Burghözli
Image:Schizophrenia PET scan.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Schizophrenia_PET_scan.jpg  License: unknown  Contributors: Editor at Large, J.delanoy,
Monkeybait, Skagedal, Was a bee, Ö, 9 anonymous edits
Image:FMRI.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:FMRI.jpg  License: Public Domain  Contributors: Frank C. Müller, Solipsist, Superborsuk, Was a bee, 2 anonymous
edits
Image:Chlorpromazine-3D-vdW.png  Source: http://en.wikipedia.org/w/index.php?title=File:Chlorpromazine-3D-vdW.png  License: Public Domain  Contributors: Ben Mills
Image:Risperdal tablets.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Risperdal_tablets.jpg  License: Creative Commons Attribution-Sharealike 2.5  Contributors: Housed
Image:John f nash 20061102 3.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:John_f_nash_20061102_3.jpg  License: GNU Free Documentation License  Contributors: User:Elya
Image:Schizophrenia world map - DALY - WHO2002.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Schizophrenia_world_map_-_DALY_-_WHO2002.svg  License: Creative
Commons Attribution-Sharealike 2.5  Contributors: User:Lokal_Profil

License
Creative Commons Attribution-Share Alike 3.0 Unported
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