Changes: Schizophrenia

**Schizophrenia**
ICD-10	F20
ICD-9	295
OMIM	{{{OMIM}}}
DiseasesDB	{{{DiseasesDB}}}
MedlinePlus	{{{MedlinePlus}}}
eMedicine	{{{eMedicineSubj}}}/{{{eMedicineTopic}}}
MeSH	{{{MeshNumber}}}

Revision as of 01:06, 10 February 2006

Clinical: Approaches · Group therapy · Techniques · Types of problem · Areas of specialism · Taxonomies · Therapeutic issues · Modes of delivery · Model translation project · Personal experiences ·

Schizophrenia is a mental disorder characterized by persistent defects in the perception or expression of reality. A person experiencing untreated schizophrenia typically demonstrates disorganized thinking, and may also experience delusions or auditory hallucinations. Although the disorder primarily affects cognition, it can also contribute to chronic problems with behavior or emotions. Due to the many possible combinations of symptoms, it is difficult to say whether it is in fact a single psychiatric disorder; and Eugen Bleuler deliberately called the disease "the schizophrenias" (plural) when he coined the present name.

Diagnosis is based on the self-reported experiences of the patient, in combination with secondary signs observed by a psychiatrist or other competent clinician such as a doctor of psychology. There is no objective biological test for schizophrenia, though studies suggest that genetics and biochemistry are important contributing factors. Current 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 objective laboratory tests to confirm the diagnosis, some question the legitimacy of schizophrenia's status as a disease.

The term "schizophrenia" translates roughly as "shattered mind," and comes from the Greek σχίζω (schizo, "to split" or "to divide") and φρήν (phrēn, "mind"). Despite its etymology, schizophrenia is not synonymous with dissociative identity disorder, also known as multiple personality disorder or "split personality"; in popular culture the two are often confused. Although schizophrenia often leads to social or occupational dysfunction, there is little association of the illness with a predisposition toward aggressive behavior.

Overview

Schizophrenia is often described in terms of "positive" and "negative" symptoms. Positive symptoms include delusions, auditory hallucinations and thought disorder and are typically regarded as manifestations of psychosis. Negative symptoms are so named because they are considered to be the loss or absence of normal traits or abilities, and include features such as flat, blunted or constricted affect and emotion, poverty of speech and lack of motivation. Some models of schizophrenia include formal thought disorder and planning difficulties in a third group, a "disorganization syndrome."

Additionally, neurocognitive deficits may be present. These may take the form of reduced or impaired psychological functions such as memory, attention, problem-solving, executive function or social cognition.

Onset of schizophrenia typically occurs in late adolescence or early adulthood, with males tending to show symptoms earlier than females.

Psychiatrist Emil Kraepelin was the first to draw a distinction between what he termed dementia praecox ("premature dementia") and other psychotic illnesses. In 1911, "dementia praecox" was renamed "schizophrenia" by psychiatrist Eugen Bleuler, who found Kraepelin's term to be misleading, as the disorder is not a form of dementia, premature or otherwise.

The diagnostic approach to schizophrenia has been opposed, most notably by the anti-psychiatry movement, who argue that classifying specific thoughts and behaviors as illness allows social control of people who society finds undesirable but who have committed no crime.

More recently, it has been argued that schizophrenia is just one end of a spectrum of experience and behavior, and everybody in society may have some such experiences in their life. This is known as the 'continuum model of psychosis' or the 'dimensional approach' and is most notably argued for by psychologist Richard Bentall and psychiatrist Jim van Os.

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 and 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, particular 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 many patients due to significant side-effects, and have little effect on some individuals.

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.

History

Accounts that may relate to symptoms of schizophrenia date back as far as 2000 BC in the Book of Hearts, part of the ancient Ebers papyrus. However, a recent study¹ into the ancient Greek and Roman literature showed that, while the general population probably had an awareness of psychotic disorders, there was no recorded condition that would meet the modern diagnostic criteria for schizophrenia in these societies.

This nonspecific concept of "madness" has been around for many thousands of years, but schizophrenia was only classified as a distinct mental disorder by Kraepelin in 1887. He was the first to make a distinction between schizophrenia and manic depression.

The term schizophrenia is derived from the Greek words 'schizo' (split) and 'phren' (mind) and was coined by Eugene Bleuler to refer to the lack of interaction between thought processes and perception. "The patients that I have observed do not respond to situations as they should; they are frightened by what is not there, yet they remain indifferent to what is. It is as if they have a split mind." He was also the first to describe the symptoms as "positive" or "negative."²

Bleuler suggested the name schizophrenia, as it was obvious that Kraepelin's name was misleading. The word "praecox" implied precocious or early onset, hence premature dementia, as opposed to senile dementia from old age. Bleuler realized the illness was not a dementia, as it did not lead to mental deterioration. Rather, schizophrenia led to a sharpening of the senses and a greater awareness of memories and experiences.

With the name 'schizophrenia' Bleuler intended to capture the separation of function between personality, thinking, memory, and perception, however it is commonly misunderstood to mean that affected persons have a 'split personality' (something akin to the character in Robert Louis Stevenson's The Strange Case of Dr Jekyll and Mr Hyde). 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 perhaps arises in part due to the meaning of Bleuler's term 'schizophrenia' (literally 'split mind'). Interestingly, the first known misuse of this word schizophrenia to mean 'split personality' (in the Jekyll and Hyde sense) was in an article by the poet T. S. Eliot in 1933. ³

In the first half of the twentieth century schizophrenia was considered by many to be a "hereditary defect", and individuals affected by schizophrenia became 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. Many people diagnosed with schizophrenia, together with other people labeled "mentally unfit", were murdered in the Nazi "Operation T-4" programme.

Diagnosis

Criteria (signs and symptoms)

Like many mental illnesses, the diagnosis of schizophrenia is based upon the behavior of the person being assessed. There is a list of criteria that must be met for someone to be so diagnosed. These depend on both the presence and duration of certain signs and symptoms.

The most commonly used criteria for diagnosing schizophrenia are from the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM) and the World Health Organization’s International Statistical Classification of Diseases and Related Health Problems (ICD). The most recent versions are ICD-10 and DSM-IV-TR.

Below is an abbreviated version of the diagnostic criteria from the DSM-IV-TR; the full version is available here. (DSM cautionary statement)

To be diagnosed as having schizophrenia, a person must display:

A) Characteristic symptoms: Two or more of the following, each present for a significant portion of time during a one-month period (or less, if successfully treated)
- delusions
- hallucinations
- disorganized speech (e.g., frequent derailment or incoherence; speaking in abstracts). See thought disorder.
- grossly disorganized behavior (e.g. dressing inappropriately, crying frequently) or catatonic behavior
- negative symptoms, i.e., affective flattening (lack or decline in emotional response), alogia (lack or decline in speech), or avolition (lack or decline in motivation).

Note: Only one Criterion A symptom is required if 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.

B) 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 or interpersonal relations are markedly below the level achieved prior to the onset.

C) Duration: Continuous signs of the disturbance persist for at least six months. This six-month period must include at least one month of symptoms that meet Criterion A.

Additional criteria (D, E and F) are also given that exclude a diagnosis of schizophrenia if symptoms of mood disorder or pervasive developmental disorder are present. Additionally a diagnosis of schizophrenia is excluded if the symptoms are the direct result of a substance (e.g., abuse of a drug, medication) or a general medical condition.

Subtypes

Historically, schizophrenia in the West was classified into catatonic, hebephrenic, and paranoid. The DSM now contains five sub-classifications of schizophrenia:

(295.2/F20.2) catatonic type (where marked absences or peculiarities of movement are present),
(295.1/F20.1) disorganized type (where thought disorder and flat affect are present together),
(295.3/F20.0) paranoid type (where delusions and vivid, often horrifying, hallucinations are present but thought disorder, disorganized behavior, and affective flattening is absent),
(295.6/F20.5) residual type (where positive symptoms are present at a low intensity only) and
(295.9/F20.3) undifferentiated type (psychotic symptoms are present but the criteria for paranoid, disorganized, or catatonic types has not been met).

NB: Brackets indicate codes for DSM and ICD-10 diagnostic manuals, respectively. Some older classifications still use "Hebephrenic schizophrenia" instead of "Disorganized schizophrenia".

Presentation

Symptoms may also be described as 'positive symptoms' (those additional to normal experience and behavior) and negative symptoms (the lack or decline in normal experience or behavior). 'Positive symptoms' describe psychosis and typically include delusions, hallucinations and thought disorder. 'Negative symptoms' describe inappropriate or nonpresent emotion, poverty of speech, and lack of motivation. In three-factor models of schizophrenia, a third symptom grouping, the so-called 'disorganization syndrome', is also given. This considers thought disorder and related disorganized behavior to be in a separate symptom cluster from delusions and hallucinations.

Some symptoms, such as social isolation, may be caused by a number of factors. One possible factor is impairment in social cognition, which is associated with schizophrenia, but isolation may also result from an individual reacting to psychotic symptoms (such as paranoia) or avoiding potentially stressful social situations which may exacerbate mental distress in some people.

It is worth noting that many of the positive or psychotic symptoms may occur in a variety of disorders and not only in schizophrenia. The psychiatrist Kurt Schneider tried to list the particular forms of psychotic symptoms that he thought were particularly useful in distinguishing between schizophrenia and other disorders that could produce psychosis. These are called first rank symptoms or Schneiderian first rank symptoms and include delusions of being controlled by an external force, the belief that thoughts are being inserted or withdrawn from your conscious mind, the belief that your thoughts are being broadcast to other people and hearing hallucinated voices which comment on your thoughts or actions, or may have a conversation with other hallucinated voices. As with other diagnostic methods, the reliability of 'first rank symptoms' has been questioned⁴, although they remain in use as diagnostic criteria in many countries.

Diagnostic issues and controversies

It has been argued that the diagnostic approach to schizophrenia is flawed, as it relies on an assumption of a clear dividing line between what is considered to be mental illness (fulfilling the diagnostic criteria) and mental health (not fulfilling the criteria). Recently it has been argued, notably by psychiatrist Jim van Os and psychologist Richard Bentall, that this makes little sense, as studies have shown that psychotic symptoms are present in many people who never become 'ill' in the sense of feeling distressed, becoming disabled in some way or needing medical assistance.⁵

Of particular concern is that the decision as to whether a symptom is present is a subjective decision by the person making the diagnosis or relies on an incoherent definition (for example, see the entries on delusions and thought disorder for a discussion of this issue). More recently, it has been argued that psychotic symptoms are not a good basis for making a diagnosis of schizophrenia as "psychosis is the 'fever' of mental illness — a serious but nonspecific indicator".⁶

Perhaps because of these factors, studies examining the diagnosis of schizophrenia have typically shown relatively low or inconsistent levels of diagnostic reliability. Most famously, David Rosenhan's 1972 study, published as On being sane in insane places, demonstrated that the diagnosis of schizophrenia was (at least at the time) often subjective and unreliable. More recent studies have found agreement between any two psychiatrists when diagnosing schizophrenia tends to reach about 65% at best⁷. This, and the results of earlier studies of diagnostic reliability (which typically reported even lower levels of agreement) have led some critics to argue that the diagnosis of schizophrenia should be abandoned.⁸

Proponents have argued for a new approach that would use the presence of specific neurocognitive deficits to make a diagnosis. These often accompany schizophrenia and take the form of a reduction or impairment in basic psychological functions such as memory, attention, executive function and problem solving. It is these sorts of difficulties, rather than the psychotic symptoms (which can in many cases be controlled by antipsychotic medication), which seem to be the cause of most disability in schizophrenia. However, this argument is relatively new and it is unlikely that the method of diagnosing schizophrenia will change radically in the near future.

The diagnostic approach to schizophrenia has also been opposed by the anti-psychiatry movement, who argue that classifying specific thoughts and behaviors as an illness allows social control of people that society finds undesirable but who have committed no crime. They argue that this is a way of unjustly classifying a social problem as a medical one to allow the forcible detention and treatment of people displaying these behaviors, which is something which can be done under mental health legislation in most western countries.

An example of this can be seen in the Soviet Union, where an additional sub-classification of sluggishly progressing schizophrenia was created. Particularly in the RSFSR (Russian Soviet Federated Socialist Republic), this diagnosis was used for the purpose of silencing political dissidents or forcing them to recant their ideas by the use of forcible confinement and treatment. In 2000 similar concerns about the abuse of psychiatry to unjustly silence and detain practitioners of the Falun Gong movement by the Chinese government led the American Psychiatric Association's Committee on the Abuse of Psychiatry and Psychiatrists to pass a resolution to urge the World Psychiatric Association to investigate the situation in China.

Western psychiatric medicine tends to favor a definition of symptoms that depends on form rather than content (an innovation first argued for by psychiatrists Karl Jaspers and Kurt Schneider). Therefore, you should be able to believe anything, however unusual or socially unacceptable, without being diagnosed delusional, unless your belief is held in a particular way. In principle, this would stop people being forcibly detained or treated simply for what they believe. However, the distinction between form and content is not easy, or always possible, to make in practice (see delusion). This had led to accusations by anti-psychiatry, surrealist and mental health system survivor groups that psychiatric abuses exist to some extent in the West as well.

Causes

Genetic and environmental influences

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), there is evidence to suggest that genetic vulnerability and environmental stressors can act in combination to cause 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 disorder of complex inheritance (analogous to diabetes or high blood pressure). Thus, it is likely that several genes interact to generate risk for schizophrenia. 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.

Genetic

Some researchers estimate schizophrenia to be highly heritable (some estimates are as high as 70%). However, genetic evidence for the role of the environment comes from the observation that one identical twin does not universally develop schizophrenia if the other one does. A recent review of the genetic evidence has suggested a 28% chance of one identical twin developing schizophrenia if the other already has it⁹ (see twin study).

However, the estimates of heritability of schizophrenia from twin studies varies a great deal, with some notable studies¹⁰ ¹¹ showing rates as low as 11.0%–13.8% among monozygotic twins, and 1.8%–4.1% among dizygotic twins.

A recent review of linkage studies listed seven genes as likely to be involved in the inheritance of schizophrenia or the risk of developing the disease¹². Evidence comes from research suggesting multiple chromosomal regions are transmitted to people who are later diagnosed as having schizophrenia. Some genetic association studies have demonstrated a relationship to a gene known as COMT that is involved in encoding the dopamine catabolic enzyme catechol-O-methyl transferase¹³. This is particularly interesting because of the known link between dopamine function, psychosis, and schizophrenia.

Environmental

There is also considerable evidence indicating that stress may trigger episodes of schizophrenia psychosis. For example, emotionally turbulent families¹⁴ and stressful life events¹⁵ have been shown to be risk factors for relapses or triggers for episodes of schizophrenia. In common with other forms of mental illness, abuse as a child and early traumatic experience have also been suggested to be a risk factor for developing schizophrenia later in life¹⁶ ¹⁷ ¹⁸, although the "bad parenting" theory of causation is now largely held in disrepute on the grounds that it overlooks the likelihood that the parental incompetences may have been a result of schizophrenia in the parents, and the disorder itself in the offspring was actually transmitted genetically from the parents.

Factors such as poverty and discrimination may also be involved in increasing the risk of having a schizophrenic episode due to the high levels of stress that these lifestyles harbor. This may explain why minority communities have much higher rates of schizophrenia than when members of the same ethnic groups are resident in their home country. On the other hand, the "social drift hypothesis" suggests that people affected by schizophrenia may be less able to hold steady or demanding, higher-paying jobs, consigning them to lower incomes thereby increasing stress levels and leaving them susceptible to lapsing into a schizophrenic episode.

One particularly stable and replicable finding has been the association between living in an urban environment and risk of developing schizophrenia, even after factors such as drug use, ethnic group and size of social group have been controlled for¹⁹. A recent study of 4.4 million men and women in Sweden found a 68%–77% increased risk of psychosis for people living in the most urbanized environments, a significant proportion of which is likely to be accounted for by schizophrenia²⁰.

One curious finding is that people diagnosed with schizophrenia are more likely to have been born in winter or spring²¹ (at least in the northern hemisphere). However, the effect is not large and it is still not clear why this may occur.

Neurobiological influences

Early neurodevelopment

It is also thought that processes in early neurodevelopment are important, particularly during pregnancy. For example, women who were pregnant during the Dutch famine of 1944, where many people were close to starvation, had a higher chance of having a child who would later develop schizophrenia²². Similarly, studies of Finnish mothers who were pregnant when they found out that their husbands had been killed during the Winter War of 1939–1940 have shown that their children were much more likely to develop schizophrenia when compared with mothers who found out about their husbands' death after pregnancy²³, suggesting that even psychological trauma in the mother may have an effect.

Some researchers have proposed that environmental influences during childhood also interact with neurobiological risk factors to influence the likelihood of developing schizophrenia later in life. The neurological development of children is considered sensitive to features of dysfunctional social settings, such as trauma, violence, lack of warmth in personal relationships and hostility. These have all been found to be risk factors for the later development of schizophrenia. It is thought that the effects of the childhood environment, favorable or unfavorable, interact with genetics and the processes of neurodevelopment, with long-term consequences for brain function. This is thought to influence the underlying vulnerability for psychosis later in life, particularly during the adult years.²⁴

Schizophrenia PET scan — Data from a PET study²⁵ suggests the less the frontal lobes activated (red) during a working memory task, the greater the increase in abnormal dopamine activity in the striatum (green), thought to be related to the neurocognitive deficits in schizophrenia.

Role of dopamine

In adult life, particular 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. These drugs have now been developed further and antipsychotic medication is commonly used as a first line treatment.

However, this theory is now thought to be overly simplistic as a complete explanation, partly because newer antipsychotic medication (called atypical antipsychotic medication) is equally effective as older medication (called typical antipsychotic medication), but also affects serotonin function and may have slightly less of a dopamine blocking effect. Psychiatrist David Healy has also argued that pharmaceutical companies have promoted certain oversimplified biological theories of mental illness to promote their own sales of biological treatments.²⁶

Role of glutamate and the NMDA receptor

Interest has also focused on the neurotransmitter glutamate and the reduced function of the NMDA glutamate receptor in the development of schizophrenia. This theory has largely been suggested by abnormally low levels of glutamate receptors found in postmortem brains of people previously diagnosed with schizophrenia²⁷ and the discovery that the glumatate blocking drugs such as phencyclidine and ketamine can mimic the symptoms and cognitive problems of associated with the condition.⁵⁹ The fact that reduced glutamate function is linked to poor performance on tests requiring frontal lobe and hippocampal function and that glutamate can effect dopamine function, all of which have been implicated in schizophrenia, have suggested the glutamate hypothesis of schizophrenia as an increasingly popular explanation.²⁸ Further support of this theory has come from trials showing the efficacy of molecules, which are coagonists at the NMDA receptor complex, in reducing schizophrenic symptoms. The precurosrs D-serine, glycine, and D-cycloserine all enhance NMDA function through the glycine modulatory site. Several placebo controlled trials have shown a reduction mainly in negative symptoms with high dose therapy.⁶⁰ Currently type 1 glycine transporter inhibitors are in late-state preclinical for the treatment of schizophrenia. They increase glycine concentrations in the brain thus causing increased NMDA receptor activation and a reduction in symptoms.⁶¹

Anatomy and Physiology of the brain

Much recent research has focused on differences in structure or function in certain brain areas in people diagnosed with schizophrenia.

Early evidence for differences in the neural structure came from the discovery of ventricular enlargement in people diagnosed with schizophrenia, for whom negative symptoms were most prominent²⁹. However, this finding has not proved particularly reliable on the level of the individual person, with considerable variation between patients.

More recent studies have shown a large number of differences in brain structure between people with and without diagnoses of schizophrenia.³⁰ However, as with earlier studies, many of these differences are only reliably detected when comparing groups of people, and are unlikely to predict any differences in brain structure of an individual person with schizophrenia.

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 lobes³¹. These differences are heavily linked to the neurocognitive deficits which often occur with schizophrenia, particularly in areas of memory, attention, problem solving, executive function and social cognition.

Electroencephalograph (EEG) recordings of persons with schizophrenia performing perception oriented tasks showed an absence of gamma band activity in the brain, indicating weak integration of critical neural networks in the brain.³² Those who experienced intense hallucinations, delusions and disorganized thinking showed the lowest frequency synchronization. None of the drugs taken by the persons scanned had moved neural synchrony back into the gamma frequency range. Gamma band and working memory alterations may be related to alterations in interneurons that produced the neurotransmitter GABA. Alterations in a subclass of GABAergic interneurons which produce the calcium binding protein parvalbumin have been shown to exist in the DLPFC in schizophrenia. ³³

Incidence and prevalence

Schizophrenia is typically diagnosed in late adolescence or early adulthood. It is found approximately equally in men and women, though the onset tends to be later in women, who also tend to have a better course and outcome.

The lifetime prevalence of schizophrenia is commonly given at 1%; however, a recent review of studies from around the world estimated it to be 0.55%³⁴. The same study also found that prevalence may vary greatly from country to country, despite the received wisdom that schizophrenia occurs at the same rate throughout the world. It is worth noting however, that this may be in part due to differences in the way schizophrenia is diagnosed. The incidence of schizophrenia was given as a range of between 7.5 and 16.3 cases per year per 100,000 population.

Schizophrenia is also a major cause of disability. In a recent 14-country study³⁵, active psychosis was ranked the third most disabling condition after quadriplegia and dementia and before paraplegia and blindness.

Treatment

Medication and hospitalization

The first line treatment for schizophrenia is usually the use of antipsychotic medication. The concept of 'curing' schizophrenia is controversial as there are no clear criteria for what might constitute a cure. Therefore, antipsychotic drugs are only thought to provide symptomatic relief from the postive symptoms of psychosis. The newer atypical antipsychotic medications (such as clozapine, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole) are usually preferred over older typical antipsychotic medications (such as chlorpromazine and haloperidol) due to their favorable side-effect profile. Compared to the typical antipsychotics, the atypicals are associated with a lower incident rate of extrapyramidal side-effects (EPS) and tardive dyskinesia (TD) although they are more likely to induce weight gain and so increase risk for obesity-related diseases⁶². It is still unclear whether newer drugs reduce the chances of developing the rare but potentially life-threatening neuroleptic malignant syndrome (NMS). While the atypical antipsychotics are associated with less EPS and TD than the conventional antipsychotics, some of the agents in this class (especially olanzapine and clozapine) appear to be associated with metabolic side effects such as weight gain, hyperglycemia and hypertriglyceridemia that must be considered when choosing appropriate pharmacotherapy.

Atypical and typical antipsychotics are generally thought to be equivalent for the treatment of the positive symptoms of schizophrenia. It has been suggested by some researchers that the atypicals have some beneficial effects on negative symptoms and cognitive deficits associated with schizophrenia, although the clinical significance of these effects has yet to be established. However, recent reviews have suggested that typical antipsychotics, when dosed conservatively, may have similar effects to atypicals.³⁶

The atypical antipsychotics are much more costly as they are still within patent, whereas the older drugs are available in inexpensive generic forms. Aripiprazole, a drug from a new class of antipsychotic drugs (variously named 'dopamine system stabilizers' or 'partial dopamine agonists'), has recently been developed. Early research suggests that it may be a safe and effective treatment for schizophrenia.³⁷

Hospitalization may occur with severe episodes. This can be voluntary or (if mental health legislation allows it) involuntary (called civil or involuntary commitment). Mental health legislation may also allow people to be treated against their will. However, in many countries such legislation does not exist, or does not have the power to enforce involuntary hospitalization or treatment.

Therapy and community support

Psychotherapy or other forms of talk therapy may be offered, with cognitive behavioral therapy being the most frequently used. This may focus on the direct reduction of the symptoms, or on related aspects, such as issues of self-esteem, social functioning, and insight. Although the results of early trials with cognitive behavioral therapy (CBT) were inconclusive³⁸, more recent reviews suggest that CBT can be an effective treatment for the psychotic symptoms of schizophrenia³⁹.

A relatively new approach has been the use of cognitive remediation therapy, 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.⁴⁰

Electroconvulsive therapy (also known as ECT or 'electroshock therapy') may be used in countries where it is legal. It is not considered a first line treatment but may be prescribed in cases where other treatments have failed. Psychosurgery has now become a rare procedure and is not a recommended treatment for schizophrenia.

Other support services may also be available, such as drop-in centers, visits from members of a 'community mental health team', and patient-led support groups. In recent years the importance of service-user led recovery based movements has grown substantially throughout Europe and America. Groups such as the Hearing Voices Network and more recently, the Paranoia Network, have developed a self-help approach that aims to provide support and assistance outside of 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.

In many non-Western societies, schizophrenia may be treated with more informal, community-led methods. A particularly sobering thought for Western psychiatry is that the outcome for people diagnosed with schizophrenia in non-Western countries may actually be much better⁴¹ than for people in the West. The reasons for this recently discovered fact are still far from clear, although cross-cultural studies are being conducted to find out why.

Prognosis

Prognosis for any particular individual affected by schizophrenia is particularly hard to judge as treatment and access to treatment is continually changing, as new methods become available and medical recommendations change.

A retrospective study has shown that about a third of people make a full recovery, about a third show improvement but not a full recovery, and a third remain ill⁴².

Another study suggests recovery from schizophrenia is much less likely. Where full recovery is defined as concurrent remission of positive and negative symptoms and adequate social/vocational functioning (fulfillment of age-appropriate role expectations, performance of daily living tasks without supervision, and engagement in social interactions) recovery from schizophrenia was put at 13.7%.⁴³.

Generally remission is a less strict standard than is recovery and when a remission standard is used in lieu of a recovery standard the effectiveness of treatments for schizophrenia are greatly overstated.

The World Health Organization conducted two long-term follow-up studies involving more than 2,000 people suffering from schizophrenia in different countries, and discovered these patients have much better long-term outcomes in poor countries (India, Colombia and Nigeria) than in rich countries (USA, UK, Ireland, Denmark, Czechoslovakia, Japan, and Soviet Union)⁴⁴, despite the fact antipsychotic medication is typically not widely available in poorer countries.

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.⁴⁵

There is an extremely 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.⁴⁶ Another study suggested that 10% of persons with schizophrenia die by suicide⁴⁷.

Schizophrenia and drug 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 the commonly prescribed antipsychotic medication, and the disorder itself, where negative emotion, paranoia and anhedonia are all considered to be core features.

Hallucinogens

Schizophrenia can sometimes be triggered by heavy use of stimulant or hallucinogenic 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 Beach Boys songwriter Brian Wilson.

Drugs such as methamphetamine, ketamine, PCP and LSD have been used to mimic schizophrenia for research purposes, although this 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.

Hallucinogenic drugs were also briefly tested as possible treatments for schizophrenia by psychiatrists such as Humphry Osmond and Abram Hoffer in the 1950s. Ironically, 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 increasing evidence that cannabis use can contribute to the onset of 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 doubles the risk of developing schizophrenia on the individual level, and may be responsible for up to 8% of cases in the population.⁴⁸

Tobacco

It has been noted that the majority of people with schizophrenia (estimated between 75% and 90%) smoke tobacco. However, people diagnosed with schizophrenia have a much lower than average chance of getting and dying from lung cancer. While the reason for this is unknown, it may be because of a genetic resistance to the cancer, a side-effect of drugs being taken, or a statistical effect of increased likelihood of dying from causes other than lung cancer⁴⁹.

It is argued that the increased level of smoking in schizophrenia may be due to a desire to self-medicate with nicotine. 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.⁵⁰ Whilst 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.

Schizophrenia and violence

Violence perpetrated by people with schizophrenia

Although schizophrenia is sometimes associated with violence in the media, only a small minority of people with schizophrenia become violent, and only a minority of people who commit criminal violence have been diagnosed with schizophrenia.

Research has suggested that schizophrenia is associated with a slight increase in risk of violence, although this risk is largely due to a small sub-group of individuals for whom violence is associated with concurrent substance abuse, active psychotic symptoms, and ceasing psychiatric drugs⁵¹. For the most serious acts of violence, long-term independent studies of convicted murderers in both New Zealand⁵² and Sweden⁵³ found that 3.7%–8.9% had been given a previous diagnosis of schizophrenia.

There is some evidence to suggest that in some people, the drugs used to treat schizophrenia may produce an increased risk for violence, largely due to agitation induced by akathisia, a side effect sometimes associated with antipsychotic medication.⁵⁴ Similarly, abuse experienced in childhood may contribute both to a slight increase in risk for violence in adulthood, as well as the development of schizophrenia.¹⁶

Violence against people with schizophrenia

Research has shown that a person diagnosed with schizophrenia is more likely to be a victim of violence (4.3% in a one month period) than the perpetrator⁵⁵.

Alternative approaches to schizophrenia

An approach broadly known as the anti-psychiatry movement, notably most active in the 1960s, has opposed the orthodox medical view of schizophrenia as an illness.

Psychiatrist Thomas Szasz has argued that psychiatric patients are not ill but are just individuals with unconventional thoughts and behavior that make society uncomfortable. He argues that society unjustly seeks to control such individuals by classifying their behavior as an illness and forcibly treating them as a method of social control. It is worth noting that Szasz has never considered himself to be "anti-psychiatry" in the sense of being against psychiatric treatment, but simply believes that it should be conducted between consenting adults, rather than imposed upon anyone against their will.

Similarly, psychiatrist R. D. Laing has argued that the symptoms of what is normally called mental illness are comprehensible reactions to impossible demands that society and particularly family life places on some sensitive individuals. Laing was revolutionary in valuing the content of psychotic experience as worthy of interpretation, rather than considering it simply as a secondary but essentially meaningless marker of underlying psychological or neurological distress. His groundbreaking work, co-authored with Aaron Esterson, Sanity, Madness and the Family (1964) described eleven case studies of people diagnosed with schizophrenia and argued that the content of their actions and statements was meaningful and logical in the context of their family and life situations.

In the 1976 book The Origin of Consciousness in the Breakdown of the Bicameral Mind, psychologist Julian Jaynes proposed that until the beginning of historic times, schizophrenia or a similar condition was the normal state of human consciousness. This would take the form of a "bicameral mind" where a normal state of low affect, suitable for routine activities, would be interrupted in moments of crisis by "mysterious voices" giving instructions, which early people characterized as interventions from the gods. This theory was briefly controversial. Continuing research has failed to either further confirm or refute the thesis.

Psychiatrist Tim Crow has argued that schizophrenia may be the evolutionary price we pay for a left brain hemisphere specialization for language.⁵⁶ Since psychosis is associated with greater levels of right brain hemisphere activation and a reduction in the usual left brain hemisphere dominance, our language abilities may have evolved at the cost of causing schizophrenia when this system breaks down.

Researchers into shamanism have speculated that in some cultures schizophrenia or related conditions may predispose an individual to becoming a shaman⁵⁷. Certainly, the experience of having access to multiple realities is not uncommon in schizophrenia, and is a core experience in many shamanic traditions. Equally, the shaman may have the skill to bring on and direct some of the altered states of consciousness psychiatrists label as illness. (See anti-psychiatry.) Speculations regarding primary and important religious figures as having schizophrenia abound. Some commentators have endorsed the idea that major religious figures experienced psychosis, heard voices and displayed delusions of grandeur.

Alternative medicine tends to hold the view that schizophrenia is primarily caused by imbalances in the body's reserves and absorption of dietary minerals, vitamins, fats, and/or the presence of excessive levels of toxic heavy metals. The body's adverse reactions to gluten are also strongly implicated in some alternative theories (see gluten-free, casein-free diet).

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.⁵⁸

An additional approach is suggested by the work of Richard Bandler who argues that "The usual difference between someone who hallucinates and someone who visualizes normally, is that the person who hallucinates doesn't know he's doing it or doesn't have any choice about it." (Time for a Change, p107). He suggests that because visualization is a sophisticated mental capability, schizophrenia is a skill, albeit an involuntary and dysfunctional one that is being used but not controlled. He therefore suggests that a significant route to treating schizophrenia might be to teach the missing skill - how to distinguish created reality from consensus external reality, to reduce its maladaptive impact, and ultimately how to exercise appropriate control over the vizualization or auditory process. Hypnotic approaches have been explored by the physician Milton H. Erickson as a means of facilitating this.

Notable people thought to be affected by schizophrenia

File:ClaraBow23.jpg

Actress Clara Bow was diagnosed with schizophrenia in 1949.

6025 (former rhythm guitarist of the Dead Kennedys)
Adolf Wolfli (artist, in the outsider art tradition)
Antonin Artaud (artist, poet, actor, theater philosopher)
Buddy Bolden (jazz pioneer)
Clara Bow (actress)
Daniel Paul Schreber (German judge)
Eduard Einstein (son of Albert Einstein)
Frederick Frese (Psychologist in Ohio and current Vice President of NAMI)
The Genain quadruplets (a set of four girls who each developed schizophrenia)
Gene Ray (self-proclaimed doctor of cubicism)
H.R. Hudson (affected lightly by schizophrenia, leader of hardcore punk band Bad Brains)
Ingo Schwichtenberg(Original Drummer of Helloween)]
James Tilly Matthews (subject of first book-length psychiatric case study)
Jim Gordon (drummer for the rock group Derek and the Dominos)
John Nash (mathematician, winner of the Nobel Prize in economics and subject of the book and movie A Beautiful Mind)
John Kennedy Toole (author of A Confederacy of Dunces)
Josef Hassid (gifted classical violinist)
Louis Wain (artist)
Ted Kaczynski (terrorist)
Lucia Joyce (dancer, daughter of James Joyce)
Maria Bernoulli (wife of German novelist Hermann Hesse)
Mark Vonnegut (son of the writer Kurt Vonnegut)
Nancy Spungen (girlfriend of Sid Vicious of the punk rock band The Sex Pistols)
Nick Blinko (founder, singer, songwriter, guitarist and artist for Rudimentary Peni)
Peter Green (founder of rock group Fleetwood Mac)
Roky Erickson (founder of 13th Floor Elevators)
Dr Vashishtha Narayan Singh (World renowned mathematician and an ex-NASA scientist from Bihar, India)
Skip Spence (band member of Moby Grape and Jefferson Airplane)
Syd Barrett (founder of Pink Floyd)
Vaslav Nijinsky (ballet dancer and choreographer)
Veronica Lake (actress)
Wesley Willis (musician)
William Chester Minor (army surgeon and major contributor to the Oxford English Dictionary)
Zelda Fitzgerald (painter and wife of F. Scott Fitzgerald)

General reading

Bentall, R. (2003) Madness explained: Psychosis and Human Nature. London: Penguin Books Ltd. ISBN 0713992492
Boyle, Mary,(1993), Schizophrenia: A Scientific Delusion, Routledge, ISBN 0415097002 (Amazon Review).
Green, M.F. (2001) Schizophrenia Revealed: From Neurons to Social Interactions. New York: W.W. Norton. ISBN 0393703347
Jones, S. and Hayward, P. (2004) Coping with Schizophrenia: A Guide for Patients, Families and Caregivers. ISBN 1851683445
Keen, T. M. (1999) Schizophrenia: orthodoxy and heresies. A review of alternative possibilities. Journal of Psychiatric and Mental Health Nursing, 1999, 6, 415-424. PDF. An article reviewing the dominant (orthodox) and alternative (heretical) theories, hypotheses and beliefs about schizophrenia.
Read, J., Mosher, L.R., Bentall, R. (2004) Models of Madness: Psychological, Social and Biological Approaches to Schizophrenia. ISBN 1583919066. A critical approach to biological and genetic theories, and a review of social influences on schizophrenia.
Szasz, T. (1976) Schizophrenia: The Sacred Symbol of Psychiatry. New York: Basic Books. ISBN 0465072224
Torey, E.F., M.D. (2001) Surviving Schizophrenia: A Manual for Families, Consumers, and Providers (4th Edition). Quill (HarperCollins Publishers) ISBN 0060959193
Vonnegut, M. The Eden Express. ISBN 0553027557. A personal account of schizophrenia.

External links

Charities and support groups

SANE UK mental health charity focused on schizophrenia that supports sufferers, runs a helpline and carries out research into mental illness
The Schizophrenia Association of Great Britain

Critical approaches to schizophrenia

The fraud of "schizophrenia" from controversial Scientology based anti-psychiatry group CCHR.
Successfulschizophrenia.org A website critical of Schizophrenia as a disorder, with many links and resources, by Al Siebert, psychologist Ph.D.
Schizophrenia: A Nonexsistent Disease by Lawrence Stevens, J.D

Critical approaches to schizophrenia (from non-Scientologist sources)

Loren Mosher, M.D. (Chief of the Center for Studies of Schizophrenia at the U.S. National Institute of Mental Health 1969-1980) Still Crazy After All These Years
Bola, John R., Ph.D.; & Mosher, Loren R., M.D. (2003). Treatment of Acute Psychosis Without Neuroleptics: Two-Year Outcomes From the Soteria Project. The Journal of Nervous and Mental Disease, (191: 219-229). Available as PDF.
Jonathan Leo, Ph.D. Schizophrenia: Medical students are taught it's all in the genes, but are they hearing the whole story?

News, information and further description

Understanding Schizophrenia - A factsheet from the mental health charity Mind.
DSM-IV-TR Full diagnostic criteria for schizophrenia
World Health Organisation data on schizophrenia from 'The World Health Report 2001. Mental Health: New Understanding, New Hope'
Schizophrenia in history
National Institute of Mental Health (USA) Schizophrenia information
UCLA Laboratory of Neuro Imaging definition
The current World Health Organisation definition of Schizophrenia
A directory of free full-text articles on diagnosis and management of schizophrenia
Symptoms in Schizophrenia Film made in 1940 showing some of the symptoms of Schizophrenia.
Schizophrenia.com A non-profit making information site (pharmaceutical company sponsored)
Schizophrenia and chronic mental illness overview from MayoClinic.com (pharmaceutical company sponsored).
Schizophrenia by WebMD (pharmaceutical company sponsored).
Open The Doors - information on global programme to fight stigma and discrimination because of Schizophrenia. The World Psychiatric Association (WPA)

References

Note 1: Evans, K., McGrath, J., & Milns, R. (2003) Searching for schizophrenia in ancient Greek and Roman literature: a systematic review. Acta Psychiatrica Scandanavica, 107(5), 323–330.
Note 2: Kraepelin, E. (1907) Text book of psychiatry (7th ed) (trans. A.R. Diefendorf). London: Macmillan.
Note 3: Turner, T. (1999) 'Schizophrenia'. In G.E. Berrios and R. Porter (eds) A History of Clinical Psychiatry. London: Athlone Press. ISBN 0485242117
Note 4: Bertelsen, A. (2002) Schizophrenia and Related Disorders: Experience with Current Diagnostic Systems. Psychopathology, 35, 89–93.
Note 5: Verdoux, H., & van Os, J. (2002) Psychotic symptoms in non-clinical populations and the continuum of psychosis. Schizophrenia Research, 54(1–2), 59–65.
Note 6: Tsuang, M. T., Stone, W. S., & Faraone, S. V. (2000) Toward reformulating the diagnosis of schizophrenia. American Journal of Psychiatry, 157(7), 1041–1050.
Note 7: McGorry PD, Mihalopoulos C, Henry L, Dakis J, Jackson HJ, Flaum M, Harrigan S, McKenzie D, Kulkarni J, Karoly R. (1995) Spurious precision: procedural validity of diagnostic assessment in psychotic disorders. American Journal of Psychiatry, 152 (2), 220–3.
Note 8: Read, J. (2004) Does 'schizophrenia' exist ? Reliability and validity. In J. Read, L.R. Mosher, R.P. Bentall (eds) Models of Madness: Psychological, Social and Biological Approaches to Schizophrenia. ISBN 1583919066
Note 9: Torrey, E.F., Bowler, A.E., Taylor, E.H. & Gottesman, I.I (1994) Schizophrenia and manic depressive disorder. New York: Basic books. ISBN 0465072852
Note 10: Koskenvuo M, Langinvainio H, Kaprio J, Lonnqvist J, Tienari P (1984) Psychiatric hospitalization in twins. Acta Genet Med Gemellol (Roma), 33(2),321-32.
Note 11: Hoeffer A, Pollin W. (1970) Schizophrenia in the NAS-NRC panel of 15,909 veteran twin pairs. Archives of General Psychiatry, 1970 Nov; 23(5):469-77.
Note 12: Harrison PJ, Owen MJ. (2003) Genes for schizophrenia? Recent findings and their pathophysiological implications. Lancet, 361(9355), 417–9.
Note 13: Shifman S, Bronstein M, Sternfeld M, Pisante-Shalom A, Lev-Lehman E, Weizman A, Reznik I, Spivak B, Grisaru N, Karp L, Schiffer R, Kotler M, Strous RD, Swartz-Vanetik M, Knobler HY, Shinar E, Beckmann JS, Yakir B, Risch N, Zak NB, Darvasi A (2002) A highly significant association between a COMT haplotype and schizophrenia. American Journal of Human Genetics, 71(6), 1296–302.
Note 14: Bebbington, P., Kuipers, L. (1994) The predictive utility of expressed emotion in schizophrenia: an aggregate analysis. Psychological Medicine, 24 (3),707–18.
Note 15: Day R, Nielsen JA, Korten A, Ernberg G, Dube KC, Gebhart J, Jablensky A, Leon C, Marsella A, Olatawura M et al (1987). Stressful life events preceding the acute onset of schizophrenia: a cross-national study from the World Health Organization. Culture, Medicine and Psychiatry, 11 (2), 123–205
Note 16: Harriet L. MacMillan, Jan E. Fleming, David L. Streiner, Elizabeth Lin, Michael H. Boyle, Ellen Jamieson, Eric K. Duku, Christine A. Walsh, Maria Y.-Y. Wong, William R. Beardslee. (2001) Childhood Abuse and Lifetime Psychopathology in a Community Sample. American Journal of Psychiatry,158, 1878-83.
Note 17: Schenkel, L.S., Spaulding, W.D., Dilillo, D., Silverstein, S.M. (2005) Histories of childhood maltreatment in schizophrenia: Relationships with premorbid functioning, symptomatology, and cognitive deficits. Schizophrenia Research
Note 18: Janssen I., Krabbendam L., Bak M., Hanssen M., Vollebergh W., De Graaf R., Van Os, J. (2004) Childhood abuse as a risk factor for psychotic experiences. Acta Psychiatrica Scandinavica, 109, 38–45.
Note 19: Van Os J. (2004) Does the urban environment cause psychosis? British Journal of Psychiatry, 184 (4), 287–288.
Note 20: Sundquist K, Frank G, Sundquist J. (2004) Urbanisation and incidence of psychosis and depression: Follow-up study of 4.4 million women and men in Sweden. British Journal of Psychiatry, 184 (4), 293–298.
Note 21: Davies G, Welham J, Chant D, Torrey EF, McGrath J. (2003) A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia. Schizophrenia Bulletin, 29 (3), 587–93.
Note 22: Susser E, Neugebauer R, Hoek HW, Brown AS, Lin S, Labovitz D, Gorman JM (1996) Schizophrenia after prenatal famine. Further evidence. Archives of General Psychiatry, 53(1), 25–31.
Note 23: Huttunen MO, Niskanen P. (1978) Prenatal loss of father and psychiatric disorders. Archives of General Psychiatry, 35(4), 429–31.
Note 24: Read J, Perry BD, Moskowitz A, Connolly J (2001) The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurodevelopmental model. Psychiatry, 64, 319-45. (full text)
Note 25: Meyer-Lindenberg A, Miletich RS, Kohn PD, Esposito G, Carson RE, Quarantelli M, Weinberger DR, Berman KF (2002) Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nature Neuroscience, 5, 267-71.
Note 26: Healy, D. (2002) The Creation of Psychopharmacology. Cambridge, MA: Harvard University Press. ISBN 0674006194
Note 27: Konradi C, Heckers S. (2003) Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. Pharmacology and Therapeutics, 97(2), 153-79.
Note 28: Coyle JT, Tsai G, Goff D. (2003) Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia. Annals of the New York Academy of Sciences, 1003, 318-27.
Note 29: Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L. (1976) Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet, 30;2 (7992), 924-6.
Note 30: Flashman LA, Green MF (2004) Review of cognition and brain structure in schizophrenia: profiles, longitudinal course, and effects of treatment. Psychiatric Clinics of North America, 27 (1), 1-18, vii.
Note 31: Green, M.F. (2001) Schizophrenia Revealed: From Neurons to Social Interactions. New York: W.W. Norton. ISBN 0393703347
Note 32: Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, Frumin M, Shenton ME, McCarley (2004) Neural synchrony indexes disordered perception and cognition in schizophrenia. Proceedings of the National Academy of Sciences, 101, 17288-93. (full text)
Note 33: Lewis DA, Hashimoto T, Volk DW (2005) Cortical inhibitory neurons and schizophrenia. Nature Reviews Neuroscience, 6, 312-324.
Note 34: Goldner EM, Hsu L, Waraich P, Somers JM (2002) Prevalence and incidence studies of schizophrenic disorders: a systematic review of the literature. Canadian Journal of Psychiatry, 47(9), 833–43.
Note 35: Ustun TB, Rehm J, Chatterji S, Saxena S, Trotter R, Room R, Bickenbach J, and the WHO/NIH Joint Project CAR Study Group (1999). Multiple-informant ranking of the disabling effects of different health conditions in 14 countries. Lancet, 354(9173), 111–115.
Note 36: Leucht S, Wahlbeck K, Hamann J, Kissling W. (2003) New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet, 361(9369), 1581-9.
Note 37: Potkin SG, Saha AR, Kujawa MJ, Carson WH, Ali M, Stock E, Stringfellow J, Ingenito G, Marder SR (2003) Aripiprazole, an Antipsychotic With a Novel Mechanism of Action, and Risperidone vs Placebo in Patients With Schizophrenia and Schizoaffective Disorder. Archives of General Psychiatry, 60(7), 681–90.
Note 38: Cormac I, Jones C, Campbell C. (2002) Cognitive behaviour therapy for schizophrenia. Cochrane Database of systematic reviews, (1), CD000524.
Note 39: Zimmermann, G., Favrod, J., Trieu, V. H., & Pomini, V. (2005) The effect of cognitive behavioral treatment on the positive symptoms of schizophrenia spectrum disorders: a meta-analysis. Schizophrenia Research, 77, 1-9.
Note 40: Wykes T, Brammer M, Mellers J, Bray P, Reeder C, Williams C, Corner J. (2002) Effects on the brain of a psychological treatment: cognitive remediation therapy: functional magnetic resonance imaging in schizophrenia. British Journal of Psychiatry, 181, 144-52.
Note 41: Kulhara P. (1994) Outcome of schizophrenia: some transcultural observations with particular reference to developing countries. European Archives of Psychiatry and Clinical Neuroscience, 244(5), 227–35.
Note 42: Harding CM, Brooks GW, Ashikaga T, Strauss JS, Breier A. (1987) The Vermont longitudinal study of persons with severe mental illness, II: Long-term outcome of subjects who retrospectively met DSM-III criteria for schizophrenia. American Journal of Psychiatry, 144(6), 727–35.
Note 43: Robinson DG, Woerner MG, McMeniman M, Mendelowitz A, Bilder RM (2004) Symptomatic and functional recovery from a first episode of schizophrenia or schizoaffective disorder. American Journal of Psychiatry, 161, 473-479.
Note 44: Hopper K, Wanderling J (2000) Revisiting the developed versus developing country distinction in course and outcome in schizophrenia: results from ISoS, the WHO collaborative followup project. International Study of Schizophrenia. Schizophrenia Bulletin, 26 (4), 835-46.
Note 45: Hannerz H, Borga P, Borritz M. (2001) Life expectancies for individuals with psychiatric diagnoses. Public Health, 115 (5), 328-37.
Note 46: Radomsky ED, Haas GL, Mann JJ, Sweeney JA (1999) Suicidal behavior in patients with schizophrenia and other psychotic disorders. American Journal of Psychiatry, 156(10), 1590–5.
Note 47: Caldwell CB, Gottesman II. (1990) Schizophrenics kill themselves too: a review of risk factors for suicide. Schizophrenia Bulletin, 16(4), 571–89.
Note 48: Arseneault L, Cannon M, Witton J, Murray RM. (2004) Causal association between cannabis and psychosis: examination of the evidence. British Journal of Psychiatry, 184, 110-7. (full text)
Note 49: "Conditions in Occupational Therapy: effect on occupational performance." ed. Ruth A. Hansen and Ben Atchison (Baltimore: Lippincott Williams & Williams, 2000), 54–74. ISBN 0-683-30417-8
Note 50: Zammit S, Allebeck P, Dalman C, Lundberg I, Hemmingsson T, Lewis (2003) Investigating the association between cigarette smoking and schizophrenia in a cohort study. American Journal of Psychiatry, 160 (12), 2216–21.
Note 51: Walsh E, Gilvarry C, Samele C, Harvey K, Manley C, Tattan T, Tyrer P, Creed F, Murray R, Fahy T (2004) Predicting violence in schizophrenia: a prospective study. Schizophrenia Research, 67(2-3), 247-52.
Note 52: Simpson AI, McKenna B, Moskowitz A, Skipworth J, Barry-Walsh J. (2004) Homicide and mental illness in New Zealand, 1970-2000. British Journal of Psychiatry, 185, 394-8.
Note 53: Fazel S, Grann M. (2004) Psychiatric morbidity among homicide offenders: a Swedish population study. American Journal of Psychiatry, 161(11), 2129-31.
Note 54: Leong GB, Silva JA. (2003) Neuroleptic-induced akathisia and violence: a review. Journal of Forensic Science, 48
Note 55: Fitzgerald PB, de Castella AR, Filia KM, Filia SL, Benitez J, Kulkarni J. (2005) Victimization of patients with schizophrenia and related disorders. Australia and New Zealand Journal of Psychiatry, 39(3), 169-74. (1), 187-9.
Note 56: Crow, T. J. (1997) Schizophrenia as failure of hemispheric dominance for language. Trends in Neurosciences, 20(8), 339–343.
Note 57: Polimeni J, Reiss JP. (2002) How shamanism and group selection may reveal the origins of schizophrenia. Medical Hypothesis, 58(3), 244–8.
Note 58: Torrey EF, Yolken RH. (2003) Toxoplasma gondii and schizophrenia. Emerging Infectious Diseases, 9 (11), 1375-80.
Note 59: Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA. (2001) Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology, 25(4), 455-67.
Note 60: Tuominen HJ, Tiihonen J, Wahlbeck K. (2005) Glutamatergic drugs for schizophrenia: a systematic review and meta-analysis. Schizophr Res, 72:225–34.
Note 61: Kinney GG, Sur C, Burno M, Mallorga PJ, Williams JB, Figueroa DJ, Wittmann M, Lemaire W, Conn PJ. (2003) The Glycine Transporter Type 1 Inhibitor. The Journal of Neuroscience, 23 (20), 7586-7591.
Note 62: Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. The New England Journal of Medicine, 353 (12), 1209-23.

ca:Esquizofrènia cs:Schizofrenie da:Skizofreni de:Schizophrenie es:Esquizofrenia fr:Schizophrénie ko:정신분열증 hr:Shizofrenija io:Skizofrenio id:Skizofrenia he:סכיזופרניה kl:Skizofreni ms:Schizophrenia nl:Schizofrenie no:Schizofreni pt:Esquizofrenia ro:Schizofrenie ru:Шизофрения simple:Schizophrenia sk:Schizofrénia fi:Skitsofrenia sv:Schizofreni zh:精神分裂症

This page uses content from the English-language version of The Psychology Wiki. The original article was at Schizophrenia. The list of authors can be seen in the page history. The text of both The Psychology Wiki and Wikipedia is available under the GNU Free Documentation License.

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 {{DiseaseDisorder infobox |
- Name = Schizophrenia |
  ICD10 = F20 |
  ICD9 = 295 |