Causes of Schizophrenia: Comparison
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The causes of schizophrenia have been the subject of much debate, with various factors proposed and discounted or modified. The language of schizophrenia research under the medical model is scientific. Such studies suggest that genetics, prenatal development, early environment, neurobiology, and psychological and social processes are important contributory factors. Psychiatric research into the development of the disorder is often based on a neurodevelopmental model (proponents of which see schizophrenia as a syndrome.) However, schizophrenia is diagnosed on the basis of symptom profiles. Neural correlates do not provide sufficiently useful criteria. The one thing that researchers can agree on is that schizophrenia is a complicated and variable condition. It is best thought of as a syndrome, a cluster of symptoms that may or may not have related causes, rather than a single disease. It is possible for schizophrenia to develop at any age, but it mostly happens to people within the ages of 16–30 (generally males aged 16–25 years and females 25–30 years); about 75 percent of people living with the illness developed it in these age-ranges. Childhood schizophrenia that develops before the age of 13 is quite rare. There is on average a somewhat earlier onset for men than women, with the possible influence of the female sex hormone estrogen being one hypothesis and socio-cultural influences another. Studies have found that people born during the months of late winter and early spring have a slight risk of developing schizophrenia, a phenomenon known as the seasonality effect. Possible factors implicated include vitamin D deficiency, and prenatal infection.

  • medical model
  • seasonality
  • schizophrenia

1. Genetics

1.1. Heritability

Evidence suggests that genetic vulnerability with environmental factors can act in combination resulting in the development of schizophrenia.[1] Although schizophrenia is very strongly heritable, there is also some evidence that all cases are not caused by heredity. Many people who appear to carry "schizophrenia genes" may not develop the disease.[2] Research suggests that genetic vulnerability to schizophrenia is multifactorial, caused by interactions of several genes.[3]

Individual twin studies and meta-analyses of twin studies have estimated the heritability of risk for schizophrenia to be approximately 80% (this refers to the proportion of variation between individuals in a population that is influenced by genetic factors, not the degree of genetic determination of individual risk), but the heritability estimate varies from 41 to 87%.[4] Concordance rates between monozygotic twins vary in different studies, approximately 50%; whereas dizygotic twins was 17%. Some twin studies[5][6] have found rates as low as 11.0%–13.8% among monozygotic twins, and 1.8%–4.1% among dizygotic twins, however.

Family studies indicate that the closer a person’s genetic relatedness to a person with schizophrenia, the greater the likelihood of developing the disorder. The paternal age is a factor in schizophrenia because of the increased likelihood of mutations in the chromosomes of cells that produce sperms. In contrast, women's oocytes divide twenty-three times before the time of birth and only once after that. The chance of a copying error in DNA replication during cell division increases with the number of cell divisions, and an increase in copying errors may cause an accumulation of mutations that are responsible for an increased incidence of schizophrenia.[2] The average concordance rates are higher for identical twins than for fraternal twins and evidence also suggests that the prenatal and perinatal environments may also affect concordance rates in identical twins.[7]

1.2. Genetic Candidates

Although twin studies and family studies have indicated a large degree of heritability for schizophrenia, the exact genetic causes remain unclear. However, some large-scale studies have begun to unravel the genetic underpinnings for the disease. Important segregation should be made between lower risk, common variants (identified by candidate studies or genome-wide association studies (GWAS)) and high risk, rare variants (which could be caused by de novo mutations) and copy-number variations (CNVs).

Candidate gene studies

An older 2003 review of linkage studies also listed seven genes as likely to increase risk for a later diagnosis of the disorder.[1] Two reviews[3][8] suggested that the evidence was strongest for two genes known as dysbindin (DTNBP1) and neuregulin (NRG1), and that a number of other genes (such as COMT, RGS4, PPP3CC, ZDHHC8, DISC1, and AKT1) showed some early promising results. Knockout studies in Drosophila show that reduced expression of dysbindin reduced glutamatergic synaptic transmission, resulting in impaired memory.[9] Variations near the gene FXYD6 have also been associated with schizophrenia in the UK[10][11] but not in Japan.[12] In 2008, rs7341475 single nucleotide polymorphism (SNP) of the reelin gene was associated with an increased risk of schizophrenia in women, but not in men. This female-specific association was replicated in several populations.[13] Studies have found evidence that the protein phosphatase 3 known as calcineurin might be involved in susceptibility to schizophrenia.[14][15]

The largest most comprehensive genetic study of its kind, involving tests of several hundred single-nucleotide polymorphisms (SNPs) in nearly 1,900 individuals with schizophrenia or schizoaffective disorder and 2,000 comparison subjects, reported in 2008 that there was no evidence of any significant association between the disorders and any of 14 previously identified candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT, and ARVCF). The statistical distributions suggested nothing more than chance variation. The authors concluded that the findings make it unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects could not be ruled out.[16][17]

The perhaps largest analysis of genetic associations in schizophrenia is with the SzGene database at the Schizophrenia Research Forum. One 2008 meta-analysis examined genetic variants in 16 genes and found nominally significant effects.[18]

A 2009 study was able to create mice matching symptoms of schizophrenia by the deletion of only one gene set, those of the neuregulin post-synaptic receptor. The result showed that although the mice mostly developed normally, on further brain development, glutamate receptors broke down. This theory supports the glutamate hypothesis of schizophrenia.[19] Another study in 2009 by Simon Fraser University researchers identifies a link between autism and schizophrenia: "The SFU group found that variations in four sets of genes are related to both autism and schizophrenia. People normally have two copies of each gene, but in those people with autism some genome locations have only single copies, and in those with schizophrenia extra copies are present at the same locations."[20][21]

Genome-wide association studies

To increase sample size for a better powered detection of common variants with small effects, data from genome-wide association studies (GWAS) is continuing to be clustered in large international consortia. The Psychiatric Genomics Consortium (PGC) attempts to aggregate GWAS data on schizophrenia to detect associations of common variants with small effect on disease risk.[22]

In 2011, this collaboration identified by meta-analyse of genome-wide association studies that 129 over 136 single-nucleotide polymorphism (SNP) significantly associated with schizophrenia were located in major histocompatibility complex region of the genome.[23]

In 2013 this dataset was expanded to identify in total 13 candidate loci for the disease, and also implicated calcium signalling as an important factor in the disease.[24]

In 2014 this collaboration expanded to an even larger meta-analysis, the largest to date, on GWAS data (36,989 cases and 113,075 controls) in Nature, indicating 108 schizophrenia-associated genetic loci, of which 83 have not been previously described.[25] Together, these candidate genes pointed to an importance of neurotransmission and immunology as important factors in the disease.

Distinct symptomatic subtypes of schizophrenia groups showed to have a different pattern of SNP variations, reflecting the heterogeneous nature of the disease.[26]

A 2016 study implicated the C4A gene in schizophrenia risk. C4A was found to play a role in synapse pruning, and increased C4A expression leads to reduced dendritic spines and a higher schizophrenia risk.[27]

Copy-number variations

Other research has suggested that a greater than average number of structural variations such as rare deletions or duplications of tiny DNA sequences within genes (known as copy number variations) are linked to increased risk for schizophrenia, especially in "sporadic" cases not linked to family history of schizophrenia, and that the genetic factors and developmental pathways can thus be different in different individuals.[28][29] A genome wide survey of 3,391 individuals with schizophrenia found CNVs in less than 1% of cases. Within them, deletions in regions related to psychosis were observed, as well as deletions on chromosome 15q13.3 and 1q21.1.[30]

CNVs occur due to non-allelic homologous recombination mediated by low copy repeats (sequentially similar regions). This results in deletions and duplications of dosage sensitive genes. It has been speculated that CNVs underlie a significant proportion of normal human variation, including differences in cognitive, behavioral, and psychological features, and that CNVs in at least three loci can result in increased risk for schizophrenia in a few individuals.[31] Epigenetics may also play a role in schizophrenia, with the expression of Protocadherin 11 X-linked/Protocadherin 11 Y-linked playing a possible role in schizophrenia.[32]

A 2008 investigation of 2,977 schizophrenia patients and 33,746 controls from seven European populations examined CNVs in neurexins, and found that exon-affecting deletions in the NRXN1 gene conferred risk of schizophrenia.[33]

An updated meta-analysis on CNVs for schizophrenia published in 2015 expanded the number of CNVs indicated in the disease, which was also the first genetic evidence for the involvement of GABAergic neurotransmission.[34] This study further supported genetic involvement for excitatory neurotransmission.

1.3. Overlap with Other Disorders

Several studies have suggested that genetic overlap exists between schizophrenia and other psychiatric disorders. On 28 February 2013 The Lancet published an article about the possible genetic correlation between autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. They analyzed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33,332 cases and 27,888 controls of European ancestry. This group found four gene areas that all overlapped with the five disorders, two of which regulate calcium balance in the brain.[35]

2. Evolutionary Psychology

Schizophrenia has been considered an evolutionary puzzle due to the combination of high heritability, relatively high prevalence, and reduced reproductive success. One explanation could be increased reproductive success by close relatives without symptoms but this does not seem to be the case. Still, it has been argued that it is possible that a low amount of schizotypy increasing genes may increase reproductive success by increasing such traits such as creativity, verbal ability, and emotional sensitivity.[36]

Another evolutionary explanation is the "imprinted brain theory" which argues that psychosis and autism are contrasting disorders on a number of different variables. This is argued to be caused by an unbalanced genomic imprinting favoring paternal genes in the case of autism and maternal genes in the case of psychosis.[37]

3. Before Birth

It is well established that obstetric complications or events are associated with an increased chance of the child later developing schizophrenia, although overall they constitute a non-specific risk factor with a relatively small effect. Obstetric complications occur in approximately 25 to 30% of the general population and the vast majority do not develop schizophrenia, and likewise the majority of individuals with schizophrenia have not had a detectable obstetric event. Nevertheless, the increased average risk is well-replicated, and such events may moderate the effects of genetic or other environmental risk factors. The specific complications or events most linked to schizophrenia, and the mechanisms of their effects, are still under examination.[38]

One epidemiological finding is that people diagnosed with schizophrenia are more likely to have been born in winter or spring[39] (at least in the northern hemisphere). This has been termed the seasonality effect, however, the effect is not large. Explanations have included a greater prevalence of viral infections at that time, or a greater likelihood of vitamin D deficiency. A similar effect (increased likelihood of being born in winter and spring) has also been found with other, healthy populations, such as chess players.[40]

Women who were pregnant during the Dutch famine of 1944, where many people were close to starvation (experiencing malnutrition) had a higher chance of having a child who would later develop schizophrenia.[41] Studies of Finland 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 significantly more likely to develop schizophrenia when compared with mothers who found out about their husbands' death after pregnancy, suggesting that prenatal stress may have an effect.[42]

3.1. Fetal Growth

Lower than average birth weight has been one of the most consistent findings, indicating slowed fetal growth possibly mediated by genetic effects. In the first and only prospective study of the low birthweight, schizophrenia, and enlargement of brain ventricles suggestive of cerebral atrophy, Leigh Silverton and colleagues found that low birthweight (measured prospectively with regard to psychopathology) was associated with enlarged ventricles on CT scans in a sample at risk for schizophrenia over 30 years later. These signs suggestive of cerebral atrophy were associated with schizophrenia symptoms.[43] In a follow up study, Silverton et al. noted an interaction between genetic risk for schizophrenia and low birthweight. The risk of enlarged ventricles on brain scan (associated with schizophrenia symptoms and biologically suggestive of Emil Kraepelin's dementia praecox type of schizophrenia ) was greatly increased if the subjects had both a higher genetic load for schizophrenia and lower birthweight. The investigators suggested that in utero insults may specifically stress those with a schizophrenia diathesis suggesting to the authors a diathesis stress etiological model for a certain type of schizophrenia (that Kraepelin identified) with early abnormalities suggesting brain atrophy.[44]

Some investigators have noted, however, that any factor adversely affecting the fetus will affect growth rate, however, some believe that this association may not be particularly informative regarding causation.[38] In addition, the majority of birth cohort studies have failed to find a link between schizophrenia and low birth weight or other signs of growth retardation.[45] The majority of studies do not measure the interaction of genetic risk and birthweight as was done in the Silverton et al. studies.

3.2. Hypoxia

It has been hypothesized since the 1970s that brain hypoxia (low oxygen levels) before, at or immediately after birth may be a risk factor for the development of schizophrenia.[46]

Hypoxia is demonstrated as relevant to schizophrenia in animal models, molecular biology and epidemiology studies. One study was able to differentiate 90% of cases of schizophrenia from controls based on hypoxia and metabolism.[47] Hypoxia has been described as one of the most important of the external factors that influence susceptibility, although studies have been mainly epidemiological. Such studies place a high degree of importance on hypoxic influence, but because of familial pattern of the illness in some families, propose a genetic factor also; stopping short of concluding hypoxia to be the sole cause.[48] Fetal hypoxia, in the presence of certain unidentified genes, has been correlated with reduced volume of the hippocampus, which is in turn correlated with schizophrenia.[49]

Although most studies have interpreted hypoxia as causing some form of neuronal dysfunction or even subtle damage, it has been suggested that the physiological hypoxia that prevails in normal embryonic and fetal development, or pathological hypoxia or ischemia, may exert an effect by regulating or dysregulating genes involved in neurodevelopment. A literature review judged that over 50% of the candidate genes for susceptibility to schizophrenia met criteria for "ischemia–hypoxia regulation or vascular expression" even though only 3.5% of all genes were estimated to be involved in hypoxia/ischemia or the vasculature.[clarification needed][50]

A longitudinal study found that obstetric complications involving hypoxia were one factor associated with neurodevelopmental impairments in childhood and with the later development of schizophreniform disorders.[51] Fetal hypoxia has been found to predict unusual movements at age 4 (but not age 7) among children who go on to develop schizophrenia, suggesting that its effects are specific to the stage of neurodevelopment.[52] A Japanese case study of monozygotic twins discordant for schizophrenia (one has the diagnosis while the other does not) draws attention to their different weights at birth and concludes hypoxia may be the differentiating factor.[53]

The unusual functional laterality in speech production (e.g. right hemisphere auditory processing) found in some individuals with schizophrenia could be due to aberrant neural networks established as a compensation for left temporal lobe damage induced by pre- or perinatal hypoxia.[54] Prenatal and perinatal hypoxia appears to be important as one factor in the neurodevelopmental model, with the important implication that some forms of schizophrenia may thus be preventable.[55]

Research on rodents seeking to understand the possible role of prenatal hypoxia in disorders such as schizophrenia has indicated that it can lead to a range of sensorimotor and learning/memory abnormalities. Impairments in motor function and coordination, evident on challenging tasks when the hypoxia was severe enough to cause brain damage, were long-lasting and described as a "hallmark of prenatal hypoxia".[56][57]

Several animal studies have indicated that fetal hypoxia can affect many of the same neural substrates implicated in schizophrenia, depending on the severity and duration of the hypoxic event as well as the period of gestation, and in humans moderate or severe (but not mild) fetal hypoxia has been linked to a series of motor, language and cognitive deficits in children, regardless of genetic liability to schizophrenia.[58] One paper restated that cerebellum neurological disorders were frequently found in those with schizophrenia and speculated hypoxia may cause the subsequent cognitive dysmetria[59]

Whereas most studies find only a modest effect of hypoxia in schizophrenia, a longitudinal study using a combination of indicators to detect possible fetal hypoxia, such as early equivalents of neurologic soft signs or obstetric complications, reported that the risk of schizophrenia and other nonaffective psychoses was "strikingly elevated" (5.75% versus 0.39%). Although objective estimates of hypoxia did not account for all cases of schizophrenia; the study revealed increasing odds of schizophrenia according to graded increase in severity of hypoxia.[60]

3.3. Other Factors

There is an emerging literature on a wide range of prenatal risk factors, such as prenatal stress, intrauterine (in the womb) malnutrition, and prenatal infection. Increased paternal age has been linked to schizophrenia, possibly due to "chromosomal aberrations and mutations of the aging germline."[61] Maternal-fetal rhesus or genotype incompatibility has also been linked, via increasing the risk of an adverse prenatal environment. Also, in mothers with schizophrenia, an increased risk has been identified via a complex interaction between maternal genotype, maternal behavior, prenatal environment and possibly medication and socioeconomic factors.[38] References for many of these environmental risk factors have been collected in an online database.[62]

There may be an association between celiac disease (gluten intolerance) and schizophrenia in a small proportion of people, though large randomized controlled trials and epidemiological studies will be needed before such an association can be confirmed. Withdrawal of gluten from the diet is an inexpensive measure which may improve the symptoms in a small (≤3%) number of people with schizophrenia.[63]

In addition, there is some evidence that exposure to toxins such as lead can also increase the risk of later development of schizophrenia spectrum disorders.[64]

A meta-analysis found that high neuroticism increases the risk of psychosis and schizophrenia.[65]

Several long-term studies found that individuals born with congenital visual impairment do not develop schizophrenia.[66][67]

4. Infections and Immune System

Numerous viral infections, in utero or in childhood, have been associated with an increased risk of later developing schizophrenia.[68] Schizophrenia is somewhat more common in those born in winter to early spring, when infections are more common.[69]

Influenza has long been studied as a possible factor. A 1988 study found that individuals who were exposed to the Asian flu as second trimester fetuses were at increased risk of eventually developing schizophrenia.[70] This result was corroborated by a later British study of the same pandemic,[71] but not by a 1994 study of the pandemic in Croatia.[72] A Japanese study also found no support for a link between schizophrenia and birth after an influenza epidemic.[73]

Polio, measles, varicella-zoster, rubella, herpes simplex virus type 2, maternal genital infections, Borna disease virus, and Toxoplasma gondii[74] have been correlated with the later development of schizophrenia.[75] Psychiatrists E. Fuller Torrey and R.H. Yolken have hypothesized that the latter, a common parasite in humans, contributes to some, if not many, cases of schizophrenia.[76]

In a meta-analysis of several studies, they found moderately higher levels of Toxoplasma antibodies in those with schizophrenia[77][78] and possibly higher rates of prenatal or early postnatal exposure to Toxoplasma gondii, but not acute infection. However, in another study of postmortem brain tissue, the authors have reported equivocal or negative results, including no evidence of herpes virus or T. gondii involvement in schizophrenia.[79]

There is some evidence for the role of autoimmunity in the development of some cases of schizophrenia. A statistical correlation has been reported with various autoimmune diseases[80] and direct studies have linked dysfunctional immune status to some of the clinical features of schizophrenia.[81][82]

This is known as the pathogenic theory of schizophrenia or germ theory of schizophrenia. It is a pathogenic theory of disease in which it is thought that a proximal cause of certain cases of schizophrenia is the interaction of the developing fetus with pathogens such as viruses, or with antibodies from the mother created in response to these pathogens (in particular, Interleukin 8).[83] Substantial research suggests that exposure to certain illnesses (e.g., influenza) in the mother of the neonate (especially at the end of the second trimester) causes defects in neural development which may emerge as a predisposition to schizophrenia around the time of puberty, as the brain grows and develops.[84]

Findings have supported the hypothesis that schizophrenia is associated with alterations of the tryptophane-kynurenine metabolic pathway due to activation of specific sections of the immune system.[85][86]

The relevance of some auto-antibodies that act against the NMDAR and VGKC is being studied.[87][88] Current estimates suggest that between 1.5 [89] - 6.5[88]% of patients have these antibodies in their blood. Preliminary results have shown that these patients can be treated with immunotherapy such as IVIG or Plasma exchange and steroids, on top of anti-psychotic medication, which can lead to a reduction in symptoms.[90]

5. Childhood Antecedents

In general, the antecedents of schizophrenia are subtle and those who will go on to develop schizophrenia do not form a readily identifiable subgroup - which would lead to identification of a specific cause. Average group differences from the norm may be in the direction of superior as well as inferior performance. Overall, birth cohort studies have indicated subtle nonspecific behavioral features, some evidence for psychotic-like experiences (particularly hallucinations), and various cognitive antecedents. There have been some inconsistencies in the particular domains of functioning identified and whether they continue through childhood and whether they are specific to schizophrenia.[45]

A prospective study found average differences across a range of developmental domains, including reaching milestones of motor development at a later age, having more speech problems, lower educational test results, solitary play preferences at ages four and six, and being more socially anxious at age 13. Lower ratings of the mother's skills and understanding of the child at age 4 were also related.[91]

Some of the early developmental differences were identified in the first year of life in a study in Finland, although generally related to psychotic disorders rather than schizophrenia in particular.[92] The early subtle motor signs persisted to some extent, showing a small link to later school performance in adolescence.[93] An earlier Finnish study found that childhood performance of 400 individuals diagnosed with schizophrenia was significantly worse than controls on subjects involving motor co-ordination (sports and handcrafts) between ages 7 and 9, but there were no differences on academic subjects (contrary to some other IQ findings).[94] (Patients in this age group with these symptoms were significantly less likely to progress to high school, despite academic ability.[95])

Symptoms of schizophrenia often appear soon after puberty, when the brain is undergoing significant maturational changes. Some investigators believe that the disease process of schizophrenia begins prenatally, lies dormant until puberty, and then causes a period of neural degeneration that causes the symptoms to emerge.[2] However, reanalysis of the data from the later Finnish study, on older children (14 to 16) in a changed school system, using narrower diagnostic criteria and with less cases but more controls, did not support a significant difference on sports and handicraft performance.[96] However, another study found that unusual motor coordination scores at 7 years of age were associated in adulthood with both those with schizophrenia and their unaffected siblings, while unusual movements at ages 4 and 7 predicted adult schizophrenia but not unaffected sibling status.[52]

A birth cohort study in New Zealand found that children who went on to develop schizophreniform disorder had, as well as emotional problems and interpersonal difficulties linked to all adult psychiatric outcomes measured, significant impairments in neuromotor, receptive language, and cognitive development.[51] A retrospective study found that adults with schizophrenia had performed better than average in artistic subjects at ages 12 and 15, and in linguistic and religious subjects at age 12, but worse than average in gymnastics at age 15.[97]

Some small studies on offspring of individuals with schizophrenia have identified various neurobehavioral deficits,[98] a poorer family environment and disruptive school behaviour,[99] poor peer engagement, immaturity, or unpopularity[100] or poorer social competence and increasing schizophrenic symptomology emerging during adolescence.[101]

A minority "deficit syndrome" subtype of schizophrenia is proposed to be more marked by early poor adjustment and behavioral problems, as compared to non-deficit subtypes.[102]

There is evidence that childhood experiences of abuse or trauma are risk factors for a diagnosis of schizophrenia later in life.[103] Some researchers reported that hallucinations and other symptoms considered characteristic of schizophrenia and psychosis were at least as strongly related to neglect and childhood abuse as many other mental health problems.[104] The researchers concluded that there is a need for staff training in asking patients about abuse, and a need to offer appropriate psychosocial treatments to those who have been neglected and abused as children.[104]

6. Substance Use

The relationship between schizophrenia and drug use is complex, meaning that a clear causal connection between drug use and schizophrenia has been difficult to tease apart. Most substances can induce psychosis. A diagnosis of substance-induced psychosis is made if symptoms persist after drug use or intoxication has ended.[105] There is strong evidence that using substances can trigger either the onset or relapse of schizophrenia in some people.

A 2019 systematic review and meta-analysis by Murrie et al found that the pooled proportion of transition from substance-induced psychosis to schizophrenia was 25% (95% CI 18%–35%), compared with 36% (95% CI 30%–43%) for brief, atypical and not otherwise specified psychoses [106]. Type of substance was the primary predictor of transition from drug-induced psychosis to schizophrenia, with highest rates associated with cannabis (6 studies, 34%, CI 25%–46%), hallucinogens (3 studies, 26%, CI 14%–43%) and amphetamines (5 studies, 22%, CI 14%–34%). Lower rates were reported for opioid (12%), alcohol (10%) and sedative (9%) induced psychoses. Transition rates were slightly lower in older cohorts but were not affected by sex, country of the study, hospital or community location, urban or rural setting, diagnostic methods, or duration of follow-up [107].

The rate of substance use is known to be particularly high in this group. One study found that 60% of people with schizophrenia were found to use substances and 37% would be diagnosable with a substance use disorder.[108]

6.1. Cannabis

There is growing evidence that cannabis use can contribute to schizophrenia.[109][110] Some studies[clarification needed] 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[clarification needed] 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 review of prospective cohort studies has suggested that cannabis[clarification needed] statistically doubles the risk of developing schizophrenia on the individual level, and may, if a causal relationship is assumed, be responsible for up to 8% of cases in the population.[clarification needed][2][14][28][38][45][51][52][61][64][75][111][112][113][114][115][116][117][118]

Cannabis misuse by young people is suspected of causing schizophrenia in later life by interfering with and distorting neurodevelopment particularly of the prefrontal cortex region of the brain.[112] An older longitudinal study, published in 1987, suggested a sixfold increase of schizophrenia risks for high consumers of cannabis (use on more than fifty occasions) in Sweden.[28][119]

Cannabis use is also suspected to contribute to the hyperdopaminergic state that is characteristic of schizophrenia.[2][120] Compounds found in cannabis, such as THC, have been shown to increase the activity of dopamine pathways in the brain,[121] suggesting that cannabis may exacerbate symptoms of psychosis in schizophrenia.

Despite increases in cannabis consumption in the 1960s and 1970s in western society, rates of psychotic disorders such as schizophrenia remained relatively stable over time.[122][123][124]

6.2. Amphetamines and oOther Stimulants

As amphetamines trigger the release of dopamine and excessive dopamine function is believed to be responsible for many symptoms of schizophrenia (known as the dopamine hypothesis of schizophrenia), amphetamines may worsen schizophrenia symptoms.[125] Methamphetamine, a potent neurotoxic amphetamine derivative, induces psychosis in a substantial minority of regular users which resembles paranoid schizophrenia. For most people, this psychosis fades away within a month of abstinence but for a minority the psychosis can become chronic. Individuals who develop a long lasting psychosis, despite abstinence from methamphetamine, more commonly have a family history of schizophrenia.[126]

Concerns have been raised that long-term therapy with stimulants for ADHD might cause paranoia, schizophrenia and behavioral sensitization.[127] Family history of mental illness does not predict the incidence of stimulant toxicosis in ADHD children. High rates of childhood stimulant use have been noted in patients with a diagnosis of schizophrenia and bipolar disorder independent of ADHD. Individuals with a diagnosis of bipolar or schizophrenia who were prescribed stimulants during childhood typically have a significantly earlier onset of the psychotic disorder and suffer a more severe clinical course of psychotic disorder. It has been suggested that this small subgroup of children who develop schizophrenia due to stimulant use during childhood have a genetic vulnerability to developing psychosis.[128] In addition, amphetamines are known to cause a stimulant psychosis in otherwise healthy individuals that superficially resembles schizophrenia, and may be misdiagnosed as such by some healthcare professionals.

6.3. Hallucinogens

Drugs such as ketamine, PCP, and LSD have been used to mimic schizophrenia for research purposes. Using LSD and other psychedelics as a model has fallen out of favor with the scientific research community, as the differences between the drug induced states and the typical presentation of schizophrenia have become clear. The dissociatives ketamine and PCP, however, are still considered to produce states that are remarkably similar, and are considered to be even better models than stimulants since they produce both positive and negative symptoms.

6.4. Alcohol

Approximately three percent of people who are alcohol dependent experience psychosis during acute intoxication or withdrawal. The mechanism of alcohol-related psychosis is due to distortions to neuronal membranes, gene expression, as well as thiamin deficiency. There is evidence that alcohol abuse via a kindling mechanism can occasionally cause the development of a chronic substance induced psychotic disorder, i.e. schizophrenia.[129]

6.5. Tobacco Use

People with schizophrenia tend to smoke significantly more tobacco than the general population. The rates are exceptionally high amongst institutionalized patients and homeless people. In a UK census from 1993, 74% of people with schizophrenia living in institutions were found to be smokers.[130][131] A 1999 study that covered all people with schizophrenia in Nithsdale, Scotland found a 58% prevalence rate of cigarette smoking, to compare with 28% in the general population.[113] An older study found that as much as 88% of outpatients with schizophrenia were smokers.[114]

Despite the higher prevalence of tobacco smoking, people diagnosed with schizophrenia have a much lower than average chance of developing and dying from lung cancer. While the reason for this is unknown, it may be because of a genetic resistance to the cancer, a side effect of drugs being taken, or a statistical effect of increased likelihood of dying from causes other than lung cancer.[132]

A 2003 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.[133] While the authors of the study stressed that the risks of smoking far outweigh these minor benefits, this study provides further evidence for the 'self-medication' theory of smoking in schizophrenia and may give clues as to how schizophrenia might develop at the molecular level. Furthermore, many people with schizophrenia have smoked tobacco products long before they are diagnosed with the illness, and a cohort study of Israeli conscripts found that healthy adolescent smokers were more likely to develop schizophrenia in the future than their nonsmoking peers.[134]

It is of interest that cigarette smoking affects liver function such that the antipsychotic drugs used to treat schizophrenia are broken down in the blood stream more quickly. This means that smokers with schizophrenia need slightly higher doses of antipsychotic drugs in order for them to be effective than do their non-smoking counterparts.[135]

The increased rate of smoking in schizophrenia may be due to a desire to self-medicate with nicotine. One possible reason is that smoking produces a short term effect to improve alertness and cognitive functioning in persons who suffer this illness.[115] It has been postulated that the mechanism of this effect is that people with schizophrenia have a disturbance of nicotinic receptor functioning which is temporarily abated by tobacco use.[115] However, some researchers have questioned whether self-medication is really the best explanation for the association.[136]

A study from 1989[137] and a 2004 case study[138] show that when haloperidol is administered, nicotine limits the extent to which the antipsychotic increases the sensitivity of the dopamine 2 receptor. Dependent on the dopamine system, symptoms of Tardive Dyskinesia are not found in the nicotine administered patients despite a roughly 70% increase in dopamine receptor activity, but the controls have more than 90% and do develop symptoms. A 1997 study showed that akathisia was significantly reduced upon administration of nicotine when the akathisia was induced by antipsychotics.[139] This gives credence to the idea tobacco could be used to self-medicate by limiting effects of the illness, the medication, or both.

7. Life Experiences

7.1. Social Adversity

The chance of developing schizophrenia has been found to increase with the number of adverse social factors (e.g. indicators of socioeconomic disadvantage or social exclusion) present in childhood.[140][141] Stressful life events generally precede the onset of schizophrenia.[142] A personal or recent family history of migration is a considerable risk factor for schizophrenia, which has been linked to psychosocial adversity, social defeat from being an outsider, racial discrimination, family dysfunction, unemployment, and poor housing conditions.[116][143] Unemployment and early separation from parents are some important factors which are responsible for the higher rates of schizophrenia among British African Caribbean populations, in comparison to native African Caribbean populations. This is an example which shows that social disadvantage plays an equally major hand in the onset of schizophrenia as genetics.[144]

Childhood experiences of abuse or trauma are risk factors for a diagnosis of schizophrenia later in life.[145][146][147][148] Large-scale general population studies have indicated that the relationship is a causal one, with an increasing risk with additional experiences of maltreatment,[149] although a critical review suggests conceptual and methodological issues require further research.[150] There is some evidence that adversities may lead to cognitive biases and altered dopamine neurotransmission, a process that has been termed "sensitization".[151] Childhood trauma, and bereavement or separation in families, have been found to be risk factors for schizophrenia and psychosis.[152]

Specific social experiences have been linked to specific psychological mechanisms and psychotic experiences in schizophrenia. In addition, structural neuroimaging studies of victims of sexual abuse and other traumas have sometimes reported findings similar to those sometimes found in psychotic patients, such as thinning of the corpus callosum, loss of volume in the anterior cingulate cortex, and reduced hippocampal volume.[153]

7.2. Urbanicity

A particularly stable and replicable finding has been the association between living in an urban environment and the development of schizophrenia, even after factors such as drug use, ethnic group and size of social group have been controlled for.[154] A study of 4.4 million men and women in Sweden found a 68%–77% increased risk of diagnosed psychosis for people living in the most urbanized environments, a significant proportion of which is likely to be described as schizophrenia.[155]

The effect does not appear to be due to a higher incidence of obstetric complications in urban environments.[156] The risk increases with the number of years and degree of urban living in childhood and adolescence, suggesting that constant, cumulative, or repeated exposures during upbringing occurring more frequently in urbanized areas are responsible for the association.[157] The cumulative effects of pollution associated with the urban environment have been suggested as the link between urbanicity and the higher risk of developing schizophrenia.[158]

Various possible explanations for the effect have been judged unlikely based on the nature of the findings, including infectious causes or a generic stress effect. It is thought to interact with genetic dispositions and, since there appears to be nonrandom variation even across different neighborhoods, and an independent association with social isolation, it has been proposed that the degree of "social capital" (e.g. degree of mutual trust, bonding and safety in neighborhoods) can exert a developmental impact on children growing up in these environments.[159]

Negative attitudes from others increase the risk of schizophrenia relapse, in particular critical comments, hostility, authoritarian, and intrusive or controlling attitudes (termed high expressed emotion by researchers).[160] Although family members and significant others are not held responsible for schizophrenia - the attitudes, behaviors and interactions of all parties are addressed - unsupportive dysfunctional relationships may also contribute to an increased risk of developing schizophrenia.[117][161] The risk of developing schizophrenia can also be increased by an individual developing a very low sense of self, in which one's boundaries become confused with that of the mother and/ or father. Firm psychological boundaries should be established between one's self and one's identity and one's parents. Pushing the role of parents into the background and developing a healthy sense of self can be a method for recovery.[162] Social support systems are very important for those with schizophrenia and the people with whom they are in relationships.[163] Recovery from schizophrenia is possible when one develops a healthy self and establishes firm psychological boundaries with each of their parents.[162]

8. Synergistic Effects

Experiments on mice have provided evidence that several stressors can act together to increase the risk of schizophrenia. In particular, the combination of a maternal infection during pregnancy followed by heightened stress at the onset of sexual maturity markedly increases the probability that a mouse develops symptoms of schizophrenia, whereas the occurrence of one of these factors without the other does not.[164]

9. Other Views

Schizophrenia is suggested to be a brain disorder rather than a mental illness. It is labeled as a mental illness because the symptoms align as such and the causes of the disorder are not completely known and understood.[165] Psychiatrists R. D. Laing, Silvano Arieti, Theodore Lidz and others have argued that the symptoms of what is called mental illness are comprehensible reactions to impossible demands that society and particularly family life places on some sensitive individuals. Laing, Arieti and Lidz were notable in valuing the content of psychotic experience as worthy of interpretation, rather than considering it simply as a secondary and essentially meaningless marker of underlying psychological or neurological distress. Laing 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.[166]

In 1956, Gregory Bateson and his colleagues Paul Watzlawick, Donald Jackson, and Jay Haley[167] articulated a theory of schizophrenia, related to Laing's work, as stemming from double bind situations where a person receives different or contradictory messages. Madness was therefore an expression of this distress and should be valued as a cathartic and transformative experience. In the books Schizophrenia and the Family and The Origin and Treatment of Schizophrenic Disorders Lidz and his colleagues explain their belief that parental behaviour can result in mental illness in children. Arieti's Interpretation of Schizophrenia won the 1975 scientific National Book Award in the United States.

The concept of schizophrenia as a result of civilization has been developed further by psychologist Julian Jaynes in his 1976 book The Origin of Consciousness in the Breakdown of the Bicameral Mind; he proposed that until the beginning of historic times, schizophrenia or a similar condition was the normal state of human consciousness.[118] 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. Psychohistorians, on the other hand, accept the psychiatric diagnoses. However, unlike the current medical model of mental disorders they may argue that poor parenting in tribal societies causes the shaman's schizoid personalities.[168] Commentators such as Paul Kurtz and others have endorsed the idea that major religious figures experienced psychosis, heard voices and displayed delusions of grandeur.[169]

Modern clinical psychological research has indicated a number of processes which may cause or bring on episodes of schizophrenia.

A number of cognitive biases and deficits have been identified. These include attribution biases in social situations, difficulty distinguishing inner speech from speech from an external source (source monitoring), difficulty in adjusting speech to the needs of the hearer, difficulties in the very earliest stages of processing visual information (including reduced latent inhibition), and an attentional bias towards threats.

Some of these tendencies have been shown to worsen or appear when under emotional stress or in confusing situations. As with related neurological findings, they are not shown by all individuals with a diagnosis of schizophrenia, and it is not clear how specific they are to schizophrenia.[170] However, the findings regarding cognitive difficulties in schizophrenia are reliable and consistent enough for some researchers to argue that they are diagnostic.[171]

Impaired capacity to appreciate one's own and others' mental states has been reported to be the single-best predictor of poor social competence in schizophrenia,[172] and similar cognitive features have been identified in close relatives of people diagnosed with schizophrenia.[173]

A number of emotional factors have been implicated in schizophrenia, with some models putting them at the core of the disorder. It was thought that the appearance of blunted affect meant that sufferers did not experience strong emotions, however, other studies have indicated that there is often a normal or even heightened level of emotionality, particularly in response to negative events or stressful social situations.[174] Some theories suggest positive symptoms of schizophrenia can result from or be worsened by negative emotions, including depressed feelings and low self-esteem[175] and feelings of vulnerability, inferiority or loneliness.[176] Chronic negative feelings and maladaptive coping skills may explain some of the association between psychosocial stressors and symptomology.[177] Critical and controlling behaviour by significant others (high expressed emotion) causes increased emotional arousal[178] and lowered self-esteem[179] and a subsequent increase in positive symptoms such as unusual thoughts. Countries or cultures where schizotypal personalities or schizophrenia symptoms are more accepted or valued appear to be associated with reduced onset of, or increased recovery from, schizophrenia.

Related studies suggest that the content of delusional and psychotic beliefs in schizophrenia can be meaningful and play a causal or mediating role in reflecting the life history, or social circumstances of the individual.[180] Holding minority socio-cultural beliefs, for example due to ethnic background, has been linked to increased diagnosis of schizophrenia. The way an individual interprets his or her delusions and hallucinations (e.g. as threatening or as potentially positive) has also been found to influence functioning and recovery.[181]

Some experts think autonomy vs. intimacy is a motivation for schizophrenic symptoms.[182]

Other lines of work relating to the self in schizophrenia have linked it to psychological dissociation[183] or abnormal states of awareness and identity as understood from phenomenological, such as in self-disorders, and other perspectives.[184][185]

Psychiatrist Tim Crow has argued that schizophrenia may be the evolutionary price we pay for a left brain hemisphere specialization for language.[186] 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.

In alternative medicine, some practitioners believe that there are a vast number of physical causes of what ends up being diagnosed as schizophrenia.[187] While some of these explanations may stretch credulity, others (such as heavy metal poisoning and nutritional imbalances) have been supported at least somewhat by research.[64][188][189] However, it is not entirely clear how many (if any) patients initially diagnosed with schizophrenia these alternative explanations may account for.

Psychological stress may worsen schizophrenia.[190]

References

  1. "Genes for schizophrenia? Recent findings and their pathophysiological implications". Lancet 361 (9355): 417–9. February 2003. doi:10.1016/S0140-6736(03)12379-3. PMID 12573388.  https://dx.doi.org/10.1016%2FS0140-6736%2803%2912379-3
  2. Carlson, Neil R. (2013). Physiology of Behavior (11th ed.). p. 568. https://archive.org/details/physiologybehavi00carl_811. 
  3. "Schizophrenia: Genes at last?". Trends Genet 21 (9): 518–25. September 2005. doi:10.1016/j.tig.2005.06.011. PMID 16009449.  https://dx.doi.org/10.1016%2Fj.tig.2005.06.011
  4. Tyrone D. Cannon; Jaakko Kaprio; Jouko Lönnqvist; Matti Huttunen; Markku Koskenvuo (1998). "The genetic epidemiology of schizophrenia in a Finnish twin cohort A population-based modeling study". Archives of General Psychiatry 55 (1): 67–74. doi:10.1001/archpsyc.55.1.67. PMID 9435762.  https://dx.doi.org/10.1001%2Farchpsyc.55.1.67
  5. "Psychiatric hospitalization in twins". Acta Genet Med Gemellol (Roma) 33 (2): 321–332. 1984. doi:10.1017/S0001566000007364. PMID 6540965.  https://dx.doi.org/10.1017%2FS0001566000007364
  6. "Schizophrenia in the NAS-NRC panel of 15,909 veteran twin pairs". Archives of General Psychiatry 23 (5): 469–77. November 1970. doi:10.1001/archpsyc.1970.01750050085012. PMID 5478575.  https://dx.doi.org/10.1001%2Farchpsyc.1970.01750050085012
  7. Schacter, Daniel L.; Gilbert, Daniel T.; Wegner, Daniel M. (2010). Psychology. Macmillan. ISBN 9781429237192. https://books.google.com/books?id=emAyzTNy1cUC&pg=PR7#v=snippet. 
  8. "Molecular genetic studies of schizophrenia". European Journal of Human Genetics 14 (6): 669–80. June 2006. doi:10.1038/sj.ejhg.5201571. PMID 16721403.  https://dx.doi.org/10.1038%2Fsj.ejhg.5201571
  9. Shao, Lisha; Shuai, YC; Wang, J; Feng, S.X.; Lu B.Y.; Li, Z et al. (October 2011). "Schizophrenia susceptibility gene dysbindin regulates glutamatergic and dopaminergic functions via distinctive mechanisms in Drosophila". Proceedings of the National Academy of Sciences 108 (46): 18831–18836. doi:10.1073/pnas.1114569108. PMID 22049342. Bibcode: 2011PNAS..10818831S.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3219129
  10. "Getting crowded on chromosome 11q22 – make way for phosphohippolin". Schizophrenia Research Forum. 14 March 2007. http://www.schizophreniaforum.org/new/detail.asp?id=1326. 
  11. "A Genetic Association Study of Chromosome 11q22-24 in Two Different Samples Implicates the FXYD6 Gene, Encoding Phosphohippolin, in Susceptibility to Schizophrenia". American Journal of Human Genetics 80 (4): 664–72. April 2007. doi:10.1086/513475. PMID 17357072.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1852702
  12. "A genetic association study of the FXYD domain containing ion transport regulator 6 (FXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population". Neuroscience Letters 438 (1): 70–5. June 2008. doi:10.1016/j.neulet.2008.04.010. PMID 18455306.  https://dx.doi.org/10.1016%2Fj.neulet.2008.04.010
  13. "Genome-wide association identifies a common variant in the Reelin gene that increases the risk of schizophrenia only in women". PLOS Genetics 4 (2): e28. 2008. doi:10.1371/journal.pgen.0040028. PMID 18282107.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2242812
  14. Manji, H.K.; Gottesman, I.I.; Gould, T.D. (November 2003). "Signal transduction and genes-to-behaviors pathways in psychiatric diseases". Science's STKE 2003 (207): pe49. doi:10.1126/stke.2003.207.pe49. PMID 14600293.  https://dx.doi.org/10.1126%2Fstke.2003.207.pe49
  15. Wada, A; Kunii, Y; Matsumoto, J; Hino, M; Yang, Q; Niwa, SI; Yabe, H (January 2017). "Prominent increased calcineurin immunoreactivity in the superior temporal gyrus in schizophrenia: A postmortem study". Psychiatry Research 247: 79-83. doi:10.1016/j.psychres.2016.11.018. PMID 27871031.  https://dx.doi.org/10.1016%2Fj.psychres.2016.11.018
  16. "No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: Implications for psychiatric genetics". American Journal of Psychiatry 165 (4): 497–506. 2008. doi:10.1176/appi.ajp.2007.07101573. PMID 18198266.  https://dx.doi.org/10.1176%2Fappi.ajp.2007.07101573
  17. Hamilton, S. P. (2008). "Schizophrenia candidate genes: Are we really coming up blank?". American Journal of Psychiatry 165 (4): 420–423. doi:10.1176/appi.ajp.2008.08020218. PMID 18381911.  https://dx.doi.org/10.1176%2Fappi.ajp.2008.08020218
  18. "Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: The SzGene database". Nature Genetics 40 (7): 827–834. July 2008. doi:10.1038/ng.171. PMID 18583979.  https://dx.doi.org/10.1038%2Fng.171
  19. "Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system". Proc Natl Acad Sci U S A 106 (11): 4507–12. 17 March 2009. doi:10.1073/pnas.0900355106. PMID 19240213. Bibcode: 2009PNAS..106.4507B.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2657442
  20. Randy Shore (December 2, 2009). "Researchers find link between autism and schizophrenia". Vancouver Sun. https://vancouversun.com/health/researchers+find+link+between+autism+schizophrenia/2295674/story.html. 
  21. Crespi (2010). "Comparative genomics of autism and schizophrenia". PNAS 107: 1736–1741. doi:10.1073/pnas.0906080106. PMID 19955444. Bibcode: 2010PNAS..107.1736C.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2868282
  22. The Psychiatric GWAS Consortium Steering Committee (2009). "A framework for interpreting genome-wide association studies of psychiatric disorders". Molecular Psychiatry 14 (1): 10–17. doi:10.1038/mp.2008.126. PMID 19002139. http://www.tweelingenregister.org/nederlands/verslaggeving/NTR-publicaties_2009/GWAS_MP_2009.pdf. 
  23. Ripke, Stephan (October 2011). "Genome-wide association study identifies five new schizophrenia loci". Nat. Genet. 43 (10): 969–76. doi:10.1038/ng.940. PMID 21926974.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3303194
  24. "Genome-wide association analysis identifies 13 new risk loci for schizophrenia". Nature Genetics 45 (10): 1150–1159. 2013. doi:10.1038/ng.2742. PMID 23974872. PMC 3827979. https://dash.harvard.edu/bitstream/handle/1/12152923/3827979.pdf?sequence=1. 
  25. Schizophrenia Working Group of the Psychiatric Genomics Consortium; Neale, Benjamin M.; Corvin, Aiden; Walters, James T. R.; Farh, Kai-How; Holmans, Peter A. et al. (2014). "Biological insights from 108 schizophrenia-associated genetic loci". Nature 511 (7510): 421–7. doi:10.1038/nature13595. PMID 25056061. PMC 4112379. Bibcode: 2014Natur.511..421S. https://www.duo.uio.no/bitstream/10852/43574/1/Biological%2binsights%2bfrom%2b108%2bschizophrenia-associated%2bgenetic%2bloci.pdf. 
  26. "Uncovering the Hidden Risk Architecture of the Schizophrenias: Confirmation in Three Independent Genome-Wide- Association Studies". American Journal of Psychiatry 172 (AJP in Advance): 139–153. 2014. doi:10.1176/appi.ajp.2014.14040435. PMID 25219520.  https://dx.doi.org/10.1176%2Fappi.ajp.2014.14040435
  27. "Schizophrenia's strongest known genetic risk deconstructed". National Institutes of Health. http://www.nih.gov/news-events/news-releases/schizophrenias-strongest-known-genetic-risk-deconstructed. 
  28. "Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia". Science 320 (5875): 539–43. April 2008. doi:10.1126/science.1155174. PMID 18369103. Bibcode: 2008Sci...320..539W.  https://dx.doi.org/10.1126%2Fscience.1155174
  29. "Strong association of de novo copy number mutations with sporadic schizophrenia". Nat Genet 40 (7): 880–5. July 2008. doi:10.1038/ng.162. PMID 18511947.  https://dx.doi.org/10.1038%2Fng.162
  30. The International Schizophrenia Consortium; O'Donovan; Gurling; Kirov; Blackwood; Corvin et al. (11 September 2008). "Rare chromosomal deletions and duplications increase risk of schizophrenia". Nature 455 (7210): 237–41. doi:10.1038/nature07239. PMID 18668038. Bibcode: 2008Natur.455..237S.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3912847
  31. "Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders". Neuron 52 (1): 103–121. 2006. doi:10.1016/j.neuron.2006.09.027. PMID 17015230.  https://dx.doi.org/10.1016%2Fj.neuron.2006.09.027
  32. Sunil V. Kalmady; Ganesan Venkatasubramanian (2009). "Evidence for positive selection on Protocadherin Y gene in Homo sapiens: Implications for schizophrenia". Schizophrenia Research 108 (1–3): 299–300. doi:10.1016/j.schres.2008.09.015. PMID 18938061.  https://dx.doi.org/10.1016%2Fj.schres.2008.09.015
  33. Dan Rujescu; Andres Ingason; Sven Cichon; Olli P.H. Pietiläinen; Michael R. Barnes; Timothea Toulopoulou et al. (2009). "Disruption of the neurexin 1 gene is associated with schizophrenia". Human Molecular Genetics 18 (5): 988–996. doi:10.1093/hmg/ddn351. PMID 18945720.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2695245
  34. Pocklington, A. J.; Rees, E.; Walters, J. T.; Han, J.; Kavanagh, D. H.; Chambert, K. D. et al. (2015). "Novel Findings from CNVs Implicate Inhibitory and Excitatory Signaling Complexes in Schizophrenia". Neuron 86 (5): 1203–1214. doi:10.1016/j.neuron.2015.04.022. PMID 26050040.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4460187
  35. Cross-Disorder Group of the Psychiatric Genomics Consortium (2013). "Identification of risk loci with shared effects on five major psychiatric disorders: A genome-wide analysis". The Lancet 381 (9875): 1371–1379. doi:10.1016/S0140-6736(12)62129-1. PMID 23453885.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3714010
  36. Del Giudice, Marco (2010). "Reduced Fertility in Patients' Families is Consistent with the Sexual Selection Model of Schizophrenia and Schizotypy". PLOS ONE 5 (12): e16040. doi:10.1371/journal.pone.0016040. PMID 21253008. Bibcode: 2010PLoSO...516040D.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3012205
  37. Schlomer, Gabriel L.; Del Giudice, Marco; Ellis, Bruce J. (2011). "Parent–offspring conflict theory: An evolutionary framework for understanding conflict within human families". Psychological Review 118 (3): 496–521. doi:10.1037/a0024043. PMID 21604906.  https://dx.doi.org/10.1037%2Fa0024043
  38. "The Role of Obstetric Events in Schizophrenia". Schizophr Bull 32 (1): 3–8. January 2006. doi:10.1093/schbul/sbj028. PMID 16306181.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2632192
  39. "A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia". Schizophr Bull 29 (3): 587–593. 2003. doi:10.1093/oxfordjournals.schbul.a007030. PMID 14609251.  https://dx.doi.org/10.1093%2Foxfordjournals.schbul.a007030
  40. Gobet, F; Chassy, P (March 2008). "Season of birth and chess expertise". J Biosoc Sci 40 (2): 313–6. doi:10.1017/S0021932007002222. PMID 18335581. http://bura.brunel.ac.uk/bitstream/2438/736/1/Seasonality%20and%20chess.pdf. 
  41. "Schizophrenia after prenatal famine: Further evidence". Arch. Gen. Psychiatry 53 (1): 25–31. January 1996. doi:10.1001/archpsyc.1996.01830010027005. PMID 8540774.  https://dx.doi.org/10.1001%2Farchpsyc.1996.01830010027005
  42. "Prenatal loss of father and psychiatric disorders". Arch. Gen. Psychiatry 35 (4): 429–31. April 1978. doi:10.1001/archpsyc.1978.01770280039004. PMID 727894.  https://dx.doi.org/10.1001%2Farchpsyc.1978.01770280039004
  43. Silverton, Leigh; Finello; Schulsinger; Mednick (1984). "Low birth weight and ventricular enlargement in a high-risk sample". Journal of Abnormal Psychology. 3 94 (3): 405–9. doi:10.1037/0021-843X.94.3.405. PMID 4031237.  https://dx.doi.org/10.1037%2F0021-843X.94.3.405
  44. Silverton, Leigh; Mednick; Schulsinger; Parnas; Harrington (Nov 1988). "Gentic risk for schizophrenia, birthweight, and cerebral ventricular enlargement". Journal of Abnormal Psychology. 97 97 (3): 496–498. doi:10.1037/0021-843X.97.4.496.  https://dx.doi.org/10.1037%2F0021-843X.97.4.496
  45. "The Antecedents of Schizophrenia: A Review of Birth Cohort Studies". Schizophr Bull 35 (3): 603–23. July 2008. doi:10.1093/schbul/sbn084. PMID 18658128.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2669575
  46. "Brain hypoxia, minimal brain dysfunction, and schizophrenia". Am J Psychiatry 132 (2): 192–4. February 1975. doi:10.1176/ajp.132.2.192. PMID 1111324. "This reference is cited in a 2006 work, in giving a history of minimal brain dysfunction saying: "It was also noted that individuals who experienced perinatal brain hypoxia constituted a population at risk for minimal brain dysfunction, and that children attending psychiatric clinics often presented with illnesses or perinatal complications of a sort known to be associated with neurological brain damage (Handford 1975). Stein, Samuel M. Disorganized Children: A Guide for Parents and Professionals, p 135. Jessica Kingsley Publishers Ltd.".  https://dx.doi.org/10.1176%2Fajp.132.2.192
  47. Prabakaran, S; Swatton, J E; Ryan, M M; Huffaker, S J; Huang, JT-J; Griffin, J L et al. (2004). "Mitochondrial dysfunction in Schizophrenia: Evidence for compromised brain metabolism and oxidative stress". Molecular Psychiatry 9 (7): 684–97, 643. doi:10.1038/sj.mp.4001511. PMID 15098003.  https://dx.doi.org/10.1038%2Fsj.mp.4001511
  48. Joyce, E. (2005). "Origins of cognitive dysfunction in schizophrenia: Clues from age at onset". The British Journal of Psychiatry 186 (2): 93–95. doi:10.1192/bjp.186.2.93. PMID 15684229.  https://dx.doi.org/10.1192%2Fbjp.186.2.93
  49. "Contributions of genetic risk and fetal hypoxia to hippocampal volume in patients with schizophrenia or schizoaffective disorder, their unaffected siblings, and healthy unrelated volunteers". The American Journal of Psychiatry 159 (9): 1514–20. September 2002. doi:10.1176/appi.ajp.159.9.1514. PMID 12202271.  https://dx.doi.org/10.1176%2Fappi.ajp.159.9.1514
  50. "Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia". Schizophrenia Research 84 (2–3): 253–271. June 2006. doi:10.1016/j.schres.2006.02.022. PMID 16632332.  https://dx.doi.org/10.1016%2Fj.schres.2006.02.022
  51. "Evidence for early-childhood, pan-developmental impairment specific to schizophreniform disorder: Results from a longitudinal birth cohort". Arch. Gen. Psychiatry 59 (5): 449–456. May 2002. doi:10.1001/archpsyc.59.5.449. PMID 11982449.  https://dx.doi.org/10.1001%2Farchpsyc.59.5.449
  52. "Childhood neuromotor dysfunction in schizophrenia patients and their unaffected siblings: a prospective cohort study". Schizophr Bull 26 (2): 367–378. 2000. doi:10.1093/oxfordjournals.schbul.a033459. PMID 10885637.  https://dx.doi.org/10.1093%2Foxfordjournals.schbul.a033459
  53. "Prenatal underdevelopment and schizophrenia: A case report of monozygotic twins". Psychiatry and Clinical Neurosciences 57 (3): 271–274. June 2003. doi:10.1046/j.1440-1819.2003.01116.x. PMID 12753566.  https://dx.doi.org/10.1046%2Fj.1440-1819.2003.01116.x
  54. "The developmental 'risk factor' model of schizophrenia". Journal of Psychiatric Research 33 (6): 497–9. 1999. doi:10.1016/S0022-3956(99)00032-1. PMID 10628525.  https://dx.doi.org/10.1016%2FS0022-3956%2899%2900032-1
  55. "Neonatal origins of schizophrenia". Arch. Dis. Child. 78 (1): 1–3. January 1998. doi:10.1136/adc.78.1.1. PMID 9534666.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1717442
  56. "The effect of prenatal hypoxia on brain development: Short- and long-term consequences demonstrated in rodent models". Developmental Science 9 (4): 338–49. July 2006. doi:10.1111/j.1467-7687.2006.00498.x. PMID 16764607.  https://dx.doi.org/10.1111%2Fj.1467-7687.2006.00498.x
  57. "Maternal hypoxia during pregnancy delays the development of motor reflexes in newborn mice". Developmental Neuroscience 26 (1): 24–29. 2004. doi:10.1159/000080708. PMID 15509895.  https://dx.doi.org/10.1159%2F000080708
  58. Clinical Handbook of Schizophrenia. New York: Guilford Press. 2008. p. 69. ISBN 9781606237663. https://books.google.com/books?id=jAx9HFFaLGIC&pg=PA69&dq=fetal+hypoxia+schizophrenia+motor. 
  59. "Loss of synaptic but not cytoskeletal proteins in the cerebellum of chronic schizophrenics". Neuroscience Letters 317 (3): 161–165. 2002. doi:10.1016/S0304-3940(01)02458-2. PMID 11755264.  https://dx.doi.org/10.1016%2FS0304-3940%2801%2902458-2
  60. "Hypoxic-ischemia-related fetal/neonatal complications and risk of schizophrenia and other nonaffective psychoses: A 19 year longitudinal study". The American Journal of Psychiatry 157 (2): 196–202. February 2000. doi:10.1176/appi.ajp.157.2.196. PMID 10671387.  https://dx.doi.org/10.1176%2Fappi.ajp.157.2.196
  61. "Paternal age as a risk factor for schizophrenia: how important is it?". Schizophrenia Research 114 (1–3): 1–5. 2009. doi:10.1016/j.schres.2009.06.017. PMID 19683417.  https://dx.doi.org/10.1016%2Fj.schres.2009.06.017
  62. "Environmental risk factors and comorbid medical conditions in schizophrenia". http://www.polygenicpathways.co.uk/schizrisk.html. 
  63. "The gluten connection: The association between schizophrenia and celiac disease". Acta Psychiatrica Scandinavica 113 (2): 82–90. 2006. doi:10.1111/j.1600-0447.2005.00687.x. PMID 16423158.  https://dx.doi.org/10.1111%2Fj.1600-0447.2005.00687.x
  64. Opler, M. G.; Brown, A. S.; Graziano, J.; Desai, M.; Zheng, W.; Schaefer, C.; Factor-Litvak, P.; Susser, E. S. (2004). "Prenatal lead exposure, delta-aminolevulinic acid, and schizophrenia". Environmental Health Perspectives 112 (5): 548–552. doi:10.1289/ehp.6777. PMID 15064159.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1241919
  65. Jeronimus, B.F.; Kotov, R.; Riese, H.; Ormel, J. (2016). "Neuroticism's prospective association with mental disorders halves after adjustment for baseline symptoms and psychiatric history, but the adjusted association hardly decays with time: a meta-analysis on 59 longitudinal / prospective studies with 443 313 participants". Psychological Medicine 46 (14): 2883–2906. doi:10.1017/S0033291716001653. PMID 27523506. https://zenodo.org/record/895885. 
  66. "Is Congenital Blindness A Safeguard For Schizophrenia?" (in en-US). 2020-02-20. https://truththeory.com/2020/02/20/people-who-are-born-blind-appear-to-somehow-be-protected-from-getting-schizophrenia/. 
  67. "Why Early Blindness Prevents Schizophrenia" (in en-US). http://www.psychologytoday.com/blog/the-imprinted-brain/201302/why-early-blindness-prevents-schizophrenia. 
  68. "The risk for schizophrenia from childhood and adult infections". The American Journal of Psychiatry 165 (1): 7–10. January 2008. doi:10.1176/appi.ajp.2007.07101637. PMID 18178749.  https://dx.doi.org/10.1176%2Fappi.ajp.2007.07101637
  69. "Seasonality of births in schizophrenia and bipolar disorder: a review of the literature". Schizophrenia Research 28 (1): 1–38. November 1997. doi:10.1016/S0920-9964(97)00092-3. PMID 9428062. https://zenodo.org/record/1260133. 
  70. "Adult schizophrenia following prenatal exposure to an influenza epidemic". Archives of General Psychiatry 45 (2): 189–92. February 1988. doi:10.1001/archpsyc.1988.01800260109013. PMID 3337616.  https://dx.doi.org/10.1001%2Farchpsyc.1988.01800260109013
  71. "Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic". The British Journal of Psychiatry 161 (3): 394–396. September 1992. doi:10.1192/bjp.161.3.394. PMID 1393310.  https://dx.doi.org/10.1192%2Fbjp.161.3.394
  72. "Schizophrenia and prenatal exposure to the 1957 A2 influenza epidemic in Croatia". The American Journal of Psychiatry 151 (10): 1496–8. October 1994. doi:10.1176/ajp.151.10.1496. PMID 8092342.  https://dx.doi.org/10.1176%2Fajp.151.10.1496
  73. "No relationship between schizophrenic birth and influenza epidemics in Japan". J Psychiatr Res 34 (2): 133–8. 2000. doi:10.1016/S0022-3956(00)00003-0. PMID 10758255.  https://dx.doi.org/10.1016%2FS0022-3956%2800%2900003-0
  74. Flegr, J (2013). "Influence of latent Toxoplasma infection on human personality, physiology and morphology: Pros and cons of the Toxoplasma-human model in studying the manipulation hypothesis". The Journal of Experimental Biology 216 (Pt 1): 127–133. doi:10.1242/jeb.073635. PMID 23225875.  https://dx.doi.org/10.1242%2Fjeb.073635
  75. "Early Infections of Toxoplasma gondii and the Later Development of Schizophrenia". Schizophr Bull 33 (3): 741–4. May 2007. doi:10.1093/schbul/sbm009. PMID 17329231.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2526131
  76. "Toxoplasma gondii and Schizophrenia". Emerging Infect. Dis. 9 (11): 1375–80. November 2003. doi:10.3201/eid0911.030143. PMID 14725265.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3035534
  77. "Antibodies to Toxoplasma gondii in Patients With Schizophrenia: A Meta-Analysis". Schizophr Bull 33 (3): 729–36. May 2007. doi:10.1093/schbul/sbl050. PMID 17085743.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2526143
  78. "Prevalence of Toxoplasma infection in first-episode schizophrenia and comparison between Toxoplasma-seropositive and Toxoplasma-seronegative schizophrenia". Acta Psychiatr Scand 114 (1): 40–8. July 2006. doi:10.1111/j.1600-0447.2006.00780.x. PMID 16774660.  https://dx.doi.org/10.1111%2Fj.1600-0447.2006.00780.x
  79. "Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric patients". Schizophr. Res. 60 (1): 65–9. March 2003. doi:10.1016/S0920-9964(02)00160-3. PMID 12505139.  https://dx.doi.org/10.1016%2FS0920-9964%2802%2900160-3
  80. "Association of schizophrenia and autoimmune diseases: linkage of Danish national registers". Am J Psychiatry 163 (3): 521–8. March 2006. doi:10.1176/appi.ajp.163.3.521. PMID 16513876.  https://dx.doi.org/10.1176%2Fappi.ajp.163.3.521
  81. "Immune dysregulation and self-reactivity in schizophrenia: Do some cases of schizophrenia have an autoimmune basis?". Immunol. Cell Biol. 83 (1): 9–17. February 2005. doi:10.1111/j.1440-1711.2005.01305.x. PMID 15661036. http://espace.library.uq.edu.au/view/UQ:9934/mp_icb_83_05.pdf. 
  82. "Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited". J. Autoimmun. 27 (2): 71–80. September 2006. doi:10.1016/j.jaut.2006.07.006. PMID 16997531.  https://dx.doi.org/10.1016%2Fj.jaut.2006.07.006
  83. Brown, AS; Hooton, J; Schaefer, CA; Zhang, H; Petkova, E; Babulas, V et al. (May 2004). "Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring". The American Journal of Psychiatry 161 (5): 889–895. doi:10.1176/appi.ajp.161.5.889. PMID 15121655.  https://dx.doi.org/10.1176%2Fappi.ajp.161.5.889
  84. Brown, AS (April 2006). "Prenatal Infection as a Risk Factor for Schizophrenia". Schizophrenia Bulletin 32 (2): 200–2. doi:10.1093/schbul/sbj052. PMID 16469941.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2632220
  85. "Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in Schizophrenia and genetic association with wchizophrenia endophenotypes". Arch Gen Psychiatry 68 (7): 665–674. 2011. doi:10.1001/archgenpsychiatry.2011.71. PMID 21727251.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3855543
  86. Müller, Norbert; Schwarz, Markus J. (2010). "Immune System and Schizophrenia". Curr Immunol Rev 6 (3): 213–220. doi:10.2174/157339510791823673. PMID 21057585.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2971548
  87. Lennox, Belinda R.; Coles, Alasdair J.; Vincent, Angela (2012-02-01). "Antibody-mediated encephalitis: a treatable cause of schizophrenia". The British Journal of Psychiatry 200 (2): 92–94. doi:10.1192/bjp.bp.111.095042. ISSN 0007-1250. PMID 22297586.  https://dx.doi.org/10.1192%2Fbjp.bp.111.095042
  88. Zandi, Michael S.; Irani, Sarosh R.; Lang, Bethan; Waters, Patrick; Jones, Peter B.; McKenna, Peter et al. (2010-10-26). "Disease-relevant autoantibodies in first episode schizophrenia". Journal of Neurology 258 (4): 686–688. doi:10.1007/s00415-010-5788-9. ISSN 0340-5354. PMID 20972895.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3065649
  89. Pollak, T. A.; McCormack, R.; Peakman, M.; Nicholson, T. R.; David, A. S. (2014-09-01). "Prevalence of anti-N-methyl-d-aspartate (NMDA) receptor antibodies in patients with schizophrenia and related psychoses: A systematic review and meta-analysis". Psychological Medicine 44 (12): 2475–2487. doi:10.1017/S003329171300295X. ISSN 1469-8978. PMID 24330811.  https://dx.doi.org/10.1017%2FS003329171300295X
  90. Zandi, Michael S.; Deakin, Julia B.; Morris, Katrina; Buckley, Camilla; Jacobson, Leslie; Scoriels, Linda et al. (2014). "Immunotherapy for patients with acute psychosis and serum N-Methyl d-Aspartate receptor (NMDAR) antibodies: A description of a treated case series". Schizophrenia Research 160 (1–3): 193–195. doi:10.1016/j.schres.2014.11.001. PMID 25468187.  https://dx.doi.org/10.1016%2Fj.schres.2014.11.001
  91. "Child development risk factors for adult schizophrenia in the British 1946 birth cohort". Lancet 344 (8934): 1398–1402. November 1994. doi:10.1016/S0140-6736(94)90569-X. PMID 7968076.  https://dx.doi.org/10.1016%2FS0140-6736%2894%2990569-X
  92. "Early developmental milestones in adult schizophrenia and other psychoses. A 31-year follow-up of the Northern Finland 1966 Birth Cohort". Schizophr. Res. 52 (1–2): 1–19. October 2001. doi:10.1016/S0920-9964(00)00179-1. PMID 11595387.  https://dx.doi.org/10.1016%2FS0920-9964%2800%2900179-1
  93. "The persistence of developmental markers in childhood and adolescence and risk for schizophrenic psychoses in adult life. A 34 year follow-up of the Northern Finland 1966 birth cohort". Schizophr. Res. 71 (2–3): 213–25. December 2004. doi:10.1016/j.schres.2004.03.008. PMID 15474893. http://urn.fi/urn:nbn:fi-fe201709258729. 
  94. "Motor co-ordination deficits as predictors of schizophrenia among Finnish school children". Hum. Psychopharmacol. Clin. Exp. 14 (7): 491–497. 1999. doi:10.1002/(SICI)1099-1077(199910)14:7<491::AID-HUP134>3.0.CO;2-V.  https://dx.doi.org/10.1002%2F%28SICI%291099-1077%28199910%2914%3A7%3C491%3A%3AAID-HUP134%3E3.0.CO%3B2-V
  95. Cannon, Mary; Jones, Peter; Huttunen, Matti O.; Tanskanen, Antti; Huttunen, Tiia; Rabe-Hesketh, Sophia; Murray, Robin M. (1999). "School Performance in Finnish Children and Later Development of Schizophrenia". Archives of General Psychiatry 56 (5): 457–63. doi:10.1001/archpsyc.56.5.457. PMID 10232301.  https://dx.doi.org/10.1001%2Farchpsyc.56.5.457
  96. Isohanni, M.; Isohanni, I.; Nieminen, P.; Jokelainen, J.; Järvelin, M.-R. (2000). "School predictors of schizophrenia. Letter to the editor". Arch. Gen. Psychiatry 57 (8): 813. doi:10.1001/archpsyc.57.8.813. PMID 10920472.  https://dx.doi.org/10.1001%2Farchpsyc.57.8.813
  97. Helling, I.; Ohman, A.; Hultman, C. M. (2003). "School achievements and schizophrenia: A case-control study". Acta Psychiatrica Scandinavica 108 (5): 381–386. doi:10.1034/j.1600-0447.2003.00151.x. PMID 14531759.  https://dx.doi.org/10.1034%2Fj.1600-0447.2003.00151.x
  98. "Neurobehavioral deficits at adolescence in children at risk for schizophrenia: The Jerusalem Infant Development Study". Arch. Gen. Psychiatry 56 (8): 741–748. August 1999. doi:10.1001/archpsyc.56.8.741. PMID 10435609.  https://dx.doi.org/10.1001%2Farchpsyc.56.8.741
  99. "A multivariate prediction model of schizophrenia". Schizophrenia Bulletin 28 (4): 649–82. 2002. doi:10.1093/oxfordjournals.schbul.a006971. PMID 12795497.  https://dx.doi.org/10.1093%2Foxfordjournals.schbul.a006971
  100. "Social adjustment of adolescents at risk for schizophrenia: The Jerusalem infant development study". J Am Acad Child Adolesc Psychiatry 39 (11): 1406–1414. November 2000. doi:10.1097/00004583-200011000-00015. PMID 11068896.  https://dx.doi.org/10.1097%2F00004583-200011000-00015
  101. "Social competence and positive and negative symptoms: a longitudinal study of children and adolescents at risk for schizophrenia and affective disorder". Am J Psychiatry 148 (9): 1182–1188. September 1991. doi:10.1176/ajp.148.9.1182. PMID 1882996.  https://dx.doi.org/10.1176%2Fajp.148.9.1182
  102. Galderisi, S.; Maj, M; Mucci, A; Cassano, GB; Invernizzi, G; Rossi, A et al. (2002). "Historical, Psychopathological, Neurological, and Neuropsychological Aspects of Deficit Schizophrenia: A Multicenter Study". American Journal of Psychiatry 159 (6): 983–990. doi:10.1176/appi.ajp.159.6.983. PMID 12042187.  https://dx.doi.org/10.1176%2Fappi.ajp.159.6.983
  103. Larkin, W; Larkin, J (2008). "Childhood trauma and psychosis: evidence, pathways, and implications". Journal of Postgraduate Medicine 54 (4): 287–293. doi:10.4103/0022-3859.41437. PMID 18953148.  https://dx.doi.org/10.4103%2F0022-3859.41437
  104. Read, J; van Os, J; Morrison, AP; Ross, CA (November 2005). "Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications". Acta Psychiatrica Scandinavica 112 (5): 330–350. doi:10.1111/j.1600-0447.2005.00634.x. PMID 16223421.  https://dx.doi.org/10.1111%2Fj.1600-0447.2005.00634.x
  105. Lieberman, Jeffrey; First, Michael (20 Jan 2007). "Renaming schizophrenia". British Medical Journal 334 (7585): 108. doi:10.1136/bmj.39057.662373.80. PMID 17235058.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1779873
  106. Murrie, Benjamin; Lappin, Julia; Large, Matthew; Sara, Grant (16 October 2019). "Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis". Schizophrenia Bulletin 46 (3): 505–516. doi:10.1093/schbul/sbz102. PMID 31618428.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7147575
  107. Murrie, Benjamin; Lappin, Julia; Large, Matthew; Sara, Grant (16 October 2019). "Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis". Schizophrenia Bulletin 46 (3): 505–516. doi:10.1093/schbul/sbz102. PMID 31618428.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7147575
  108. "Substance use in persons with schizophrenia: Baseline prevalence and correlates from the NIMH CATIE study". J. Nerv. Ment. Dis. 194 (3): 164–172. March 2006. doi:10.1097/01.nmd.0000202575.79453.6e. PMID 16534433.  https://dx.doi.org/10.1097%2F01.nmd.0000202575.79453.6e
  109. Murrie, Benjamin; Lappin, Julia; Large, Matthew; Sara, Grant (16 October 2019). "Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis". Schizophrenia Bulletin 46 (3): 505–516. doi:10.1093/schbul/sbz102. PMID 31618428.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7147575
  110. Agius, Mark; Grech, Anton; Zammit, Stanley (1 March 2010). "Cannabis and psychosis : the Maltese contribution". Malta Medical Journal 22 (1): 6–8. https://www.um.edu.mt/library/oar/bitstream/123456789/958/1/2010.Vol22.Issue1.A1.pdf. 
  111. "Causal association between cannabis and psychosis: Examination of the evidence". Br J Psychiatry 184 (2): 110–117. February 2004. doi:10.1192/bjp.184.2.110. PMID 14754822.  https://dx.doi.org/10.1192%2Fbjp.184.2.110
  112. Bossong, MG.; Niesink, RJ. (Nov 2010). "Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia". Prog Neurobiol 92 (3): 370–385. doi:10.1016/j.pneurobio.2010.06.010. PMID 20624444.  https://dx.doi.org/10.1016%2Fj.pneurobio.2010.06.010
  113. "Smoking habits, current symptoms, and premorbid characteristics of schizophrenic patients in Nithsdale, Scotland". American Journal of Psychiatry 156 (11): 1751–1757. 1 November 1999. doi:10.1176/ajp.156.11.1751. PMID 10553739. http://ajp.psychiatryonline.org/cgi/content/abstract/156/11/1751. Retrieved 2006-12-14. 
  114. "Prevalence of smoking among psychiatric outpatients". American Journal of Psychiatry 143 (8): 993–997. 1 August 1986. doi:10.1176/ajp.143.8.993. PMID 3487983.  https://dx.doi.org/10.1176%2Fajp.143.8.993
  115. Compton, Michael T. (2005-11-16). "Cigarette Smoking in Individuals with Schizophrenia". Medscape Psychiatry & Mental Health. http://www.medscape.com/viewarticle/516304_print. Retrieved 2007-05-17. 
  116. "Migration and schizophrenia". Current Opinion in Psychiatry 20 (2): 111–115. March 2007. doi:10.1097/YCO.0b013e328017f68e. PMID 17278906. http://www.co-psychiatry.com/pt/re/copsych/abstract.00001504-200703000-00003.htm. Retrieved 2008-07-06. 
  117. "Prospects for a cognitive-developmental account of psychotic experiences". British Journal of Clinical Psychology 46 (2): 155–73. 2007. doi:10.1348/014466506X123011. PMID 17524210.  https://dx.doi.org/10.1348%2F014466506X123011
  118. Jaynes, Julian (1976). The origin of consciousness in the breakdown of the bicameral mind. Boston: Houghton Mifflin. ISBN 978-0-395-20729-1. https://archive.org/details/originofconsciou00jaynrich. 
  119. "Cannabis and schizophrenia: A longitudinal study of Swedish conscripts". Lancet 2 (8574): 1483–1486. December 1987. doi:10.1016/S0140-6736(87)92620-1. PMID 2892048.  https://dx.doi.org/10.1016%2FS0140-6736%2887%2992620-1
  120. "Cannabis and schizophrenia: Towards a cannabinoid hypothesis of schizophrenia". Expert Review of Neurotherapeutics 8 (7): 1037–48. June 2008. doi:10.1586/14737175.8.7.1037. PMID 18590475.  https://dx.doi.org/10.1586%2F14737175.8.7.1037
  121. "The effects of cannabinoids on the brain". Prog. Neurobiol. 58 (4): 315–348. July 1999. doi:10.1016/s0301-0082(98)00087-2. PMID 10368032.  https://dx.doi.org/10.1016%2Fs0301-0082%2898%2900087-2
  122. Comorbidity between cannabis use and psychosis: Modelling some possible relationships. Sydney: National Drug and Alcohol Research Centre. 2001. Technical Report No. 121. Archived from the original on 2006-05-24. https://web.archive.org/web/20060524165747/http://ndarc.med.unsw.edu.au/NDARCWeb.nsf/resources/TR_18/%24file/TR.121.PDF. Retrieved 2006-08-19. 
  123. Frisher, Martin; Crome, Ilana; Martino, Orsolina; Croft, Peter (2009). "Assessing the impact of cannabis use on trends in diagnosed schizophrenia in the United Kingdom from 1996 to 2005". Schizophrenia Research 113 (2–3): 123–128. doi:10.1016/j.schres.2009.05.031. PMID 19560900. http://www.ukcia.org/research/keele_study/Assessing-the-impact-of-cannabis-use-on-trend-in-diagnosed-schizophrenia.pdf. 
  124. "Key facts and trends in mental health". National Health Service. 2009. Archived from the original on 2010-09-22. https://web.archive.org/web/20100922115831/http://www.nhsconfed.org/Publications/Documents/MHN_factsheet_August_2009_FINAL_2.pdf. Retrieved 2010-07-05. 
  125. "Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects". Proceedings of the National Academy of Sciences 93 (17): 9235–9240. 1996-08-20. doi:10.1073/pnas.93.17.9235. PMID 8799184. Bibcode: 1996PNAS...93.9235L.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=38625
  126. "Methamphetamine-associated psychosis". J Neuroimmune Pharmacol 7 (1): 113–139. March 2012. doi:10.1007/s11481-011-9288-1. PMID 21728034. PMC 3280383. http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1562&context=psychfacpub. 
  127. "The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: A review of its locomotor effects". Brain Research Bulletin 68 (6): 393–405. 15 February 2006. doi:10.1016/j.brainresbull.2005.10.005. PMID 16459193.  https://dx.doi.org/10.1016%2Fj.brainresbull.2005.10.005
  128. "Psychotic and manic-like symptoms during stimulant treatment of attention deficit hyperactivity disorder". Am J Psychiatry 163 (7): 1149–1152. July 2006. doi:10.1176/appi.ajp.163.7.1149. PMID 16816217.  https://dx.doi.org/10.1176%2Fappi.ajp.163.7.1149
  129. Alcohol-Related Psychosis at eMedicine http://www.emedicine.com/med/topic3113.htm#
  130. McNeill, Ann (2001). Smoking and mental health: A review of the literature. SmokeFree London Programme. Archived from the original on 2006-09-24. https://web.archive.org/web/20060924194321/http://www.ash.org.uk/html/policy/menlitrev.pdf. Retrieved 2006-12-14. 
  131. Economic Activity and Social Functioning of Adults With Psychiatric Disorders. OPCS Surveys of Psychiatric Morbidity. Report 3. London, UK: Her Majesty’s Stationery Office. 1995. http://www.statistics.gov.uk/STATBASE/Product.asp?vlnk=7993&More=Y. 
  132. Hansen, Ruth A.; Atchison, Ben, eds (2000). Conditions in Occupational Therapy: Effect on occupational performance. Baltimore, MD: Lippincott, Williams, & Wilkins. pp. 54–74. ISBN 978-0-683-30417-6. https://archive.org/details/conditionsinoccu0000unse_y0e2/page/54. 
  133. "Investigating the association between cigarette smoking and schizophrenia in a cohort study". Am J Psychiatry 160 (12): 2216–2221. December 2003. doi:10.1176/appi.ajp.160.12.2216. PMID 14638593.  https://dx.doi.org/10.1176%2Fappi.ajp.160.12.2216
  134. Mark Weiser, M.D.; Abraham Reichenberg; Itamar Grotto, M.D.; Ross Yasvitzky, B.Sc. et al. (1 July 2004). "Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: A historical-prospective cohort study". American Journal of Psychiatry 161 (12): 1219–1223. doi:10.1176/appi.ajp.161.7.1219. PMID 15229054.  https://dx.doi.org/10.1176%2Fappi.ajp.161.7.1219
  135. Sagud, Marina; Mihaljević-Peles, Alma; Mück-Seler, Dorotea; Pivac, Nela et al. (September 2009). "Smoking and schizophrenia". Psychiatria Danubina 21 (3): 371–375. ISSN 0353-5053. PMID 19794359.  http://www.worldcat.org/issn/0353-5053
  136. Chambers, R. Andrew (2009). "A nicotine challenge to the self-medication hypothesis in a neurodevelopmental animal model of schizophrenia". Journal of Dual Diagnosis 5 (2): 139–148. doi:10.1080/15504260902869808. PMID 20556221.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2885739
  137. "Chronic nicotine use blocks haloperidol-induced increase in striatal D2-dopamine receptor density". Biochem. Biophys. Res. Commun. 159 (1): 48–52. February 1989. doi:10.1016/0006-291X(89)92402-9. PMID 2522303.  https://dx.doi.org/10.1016%2F0006-291X%2889%2992402-9
  138. "Does nicotine affect D2 receptor upregulation? A case-control study". Acta Psychiatr Scand 109 (4): 313–7; discussion 317–8. April 2004. doi:10.1111/j.1600-0447.2004.00293.x. PMID 15008806.  https://dx.doi.org/10.1111%2Fj.1600-0447.2004.00293.x
  139. "Treatment of neuroleptic-induced akathisia with nicotine patches". Psychopharmacology 134 (2): 153–6. November 1997. doi:10.1007/s002130050436. PMID 9399378.  https://dx.doi.org/10.1007%2Fs002130050436
  140. "Social adversity in childhood and the risk of developing psychosis: A national cohort study". The American Journal of Psychiatry 162 (9): 1652–7. September 2005. doi:10.1176/appi.ajp.162.9.1652. PMID 16135624.  https://dx.doi.org/10.1176%2Fappi.ajp.162.9.1652
  141. "Schizophrenia". The Lancet 363 (9426): 2063–72. 2004. doi:10.1016/S0140-6736(04)16458-1. PMID 15207959.  https://dx.doi.org/10.1016%2FS0140-6736%2804%2916458-1
  142. "Stressful life events preceding the acute onset of schizophrenia: A cross-national study from the World Health Organization". Cult Med Psychiatry 11 (2): 123–205. June 1987. doi:10.1007/BF00122563. PMID 3595169.  https://dx.doi.org/10.1007%2FBF00122563
  143. "Schizophrenia and migration: a meta-analysis and review". Am J Psychiatry 162 (1): 12–24. January 2005. doi:10.1176/appi.ajp.162.1.12. PMID 15625195.  https://dx.doi.org/10.1176%2Fappi.ajp.162.1.12
  144. "Social factors 'cause ethnic schizophrenia'". BBC News. 2002-06-22. http://news.bbc.co.uk/2/hi/health/2057205.stm. 
  145. "Childhood abuse and lifetime psychopathology in a community sample". Am J Psychiatry 158 (11): 1878–83. November 2001. doi:10.1176/appi.ajp.158.11.1878. PMID 11691695.  https://dx.doi.org/10.1176%2Fappi.ajp.158.11.1878
  146. "Histories of childhood maltreatment in schizophrenia: relationships with premorbid functioning, symptomatology, and cognitive deficits". Schizophr. Res. 76 (2–3): 273–86. July 2005. doi:10.1016/j.schres.2005.03.003. PMID 15949659. http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1116&context=psychfacpub. 
  147. "Childhood abuse as a risk factor for psychotic experiences". Acta Psychiatr Scand 109 (1): 38–45. January 2004. doi:10.1046/j.0001-690X.2003.00217.x. PMID 14674957.  https://dx.doi.org/10.1046%2Fj.0001-690X.2003.00217.x
  148. "The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurodevelopmental model". Psychiatry 64 (4): 319–45. 2001. doi:10.1521/psyc.64.4.319.18602. PMID 11822210. Archived from the original on 2007-07-08. https://web.archive.org/web/20070708032809/http://www.childtrauma.org/CTAMATERIALS/Psychiatry_02.pdf. 
  149. "Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications". Acta Psychiatrica Scandinavica 112 (5): 330–50. November 2005. doi:10.1111/j.1600-0447.2005.00634.x. PMID 16223421.  https://dx.doi.org/10.1111%2Fj.1600-0447.2005.00634.x
  150. "Environment and schizophrenia: Childhood trauma – a critical review". Schizophrenia Bulletin 33 (1): 3–10. January 2007. doi:10.1093/schbul/sbl053. PMID 17105965. PMC 2632300. http://schizophreniabulletin.oxfordjournals.org/cgi/content/full/33/1/3. 
  151. "Does the Concept of "Sensitization" Provide a Plausible Mechanism for the Putative Link Between the Environment and Schizophrenia?". Schizophr Bull 34 (2): 220–5. March 2008. doi:10.1093/schbul/sbm163. PMID 18203757.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2632409
  152. "The Report". The Schizophrenia Commission. 2012-11-13. Archived from the original on 2013-04-05. https://web.archive.org/web/20130405104051/http://www.schizophreniacommission.org.uk/the-report/. Retrieved 2013-04-23. 
  153. "Social Predictors of Psychotic Experiences: Specificity and Psychological Mechanisms". Schizophr Bull 34 (6): 1012–1020. August 2008. doi:10.1093/schbul/sbn103. PMID 18703667. PMC 2632492. http://schizophreniabulletin.oxfordjournals.org/cgi/content/abstract/sbn103v1. 
  154. "Does the urban environment cause psychosis?". Br J Psychiatry 184 (4): 287–8. April 2004. doi:10.1192/bjp.184.4.287. PMID 15056569.  https://dx.doi.org/10.1192%2Fbjp.184.4.287
  155. "Urbanisation and incidence of psychosis and depression: follow-up study of 4.4 million women and men in Sweden". Br J Psychiatry 184 (4): 293–8. April 2004. doi:10.1192/bjp.184.4.293. PMID 15056572.  https://dx.doi.org/10.1192%2Fbjp.184.4.293
  156. "Obstetric factors, urbanization and psychosis". Schizophr. Res. 43 (2–3): 117–23. June 2000. doi:10.1016/S0920-9964(99)00152-8. PMID 10858630.  https://dx.doi.org/10.1016%2FS0920-9964%2899%2900152-8
  157. "Evidence of a dose-response relationship between urbanicity during upbringing and schizophrenia risk". Arch. Gen. Psychiatry 58 (11): 1039–46. November 2001. doi:10.1001/archpsyc.58.11.1039. PMID 11695950. http://archpsyc.ama-assn.org/cgi/pmidlookup?view=long&pmid=11695950. 
  158. "Environmental pollution and risk of psychotic disorders: A review of the science to date". Schizophrenia Research 181: 55–59. March 2017. doi:10.1016/j.schres.2016.10.003. PMID 27720315.  https://dx.doi.org/10.1016%2Fj.schres.2016.10.003
  159. "Schizophrenia and urbanicity: A major environmental influence, conditional on genetic risk". Schizophrenia Bulletin 31 (4): 795–9. October 2005. doi:10.1093/schbul/sbi060. PMID 16150958. http://schizophreniabulletin.oxfordjournals.org/cgi/content/full/31/4/795#BIB37. 
  160. "The predictive utility of expressed emotion in schizophrenia: An aggregate analysis". Psychol Med 24 (3): 707–718. August 1994. doi:10.1017/S0033291700027860. PMID 7991753.  https://dx.doi.org/10.1017%2FS0033291700027860
  161. "Are Communication Deviance and Expressed Emotion Related to Family History of Psychiatric Disorders in Schizophrenia?". Schizophrenia Bulletin 28 (4): 719–29. 2002. doi:10.1093/oxfordjournals.schbul.a006975. PMID 12795501.  https://dx.doi.org/10.1093%2Foxfordjournals.schbul.a006975
  162. MacPherson, M. (2009). "Psychological Causes of Schizophrenia". Schizophrenia Bulletin 35 (2): 284–6. doi:10.1093/schbul/sbn179. PMID 19176473.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2659314
  163. Brichford, Connie. "Schizophrenia and relationships". http://www.everydayhealth.com/schizophrenia/schizophrenia-and-relationships.aspx. Retrieved 26 November 2011. 
  164. Giovanoli, Sandra; Engler, Harald; Engler, Andrea; Richetto, Juliet; Voget, Mareike; Willi, Roman et al. (2013). "Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice". Science 339 (6123): 1095–1099. doi:10.1126/science.1228261. PMID 23449593. Bibcode: 2013Sci...339.1095G. https://air.unimi.it/bitstream/2434/219638/4/science1095.full.pdf (28 February 2013). 
  165. "Renaming schizophrenia". British Medical Journal 334 (7585): 108. 2007. doi:10.1136/bmj.39057.662373.80. PMID 17235058.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1779873
  166. Laing, R.D.; Esterson, Aaron (1964). Sanity, Madness, and the Family. 
  167. "Toward a theory of schizophrenia". Behavioral Science 1 (4): 251–264. 1956. doi:10.1002/bs.3830010402.  https://dx.doi.org/10.1002%2Fbs.3830010402
  168. "The seven stages of historical personality". Emotional Life of Nations. Other Press (NY). 2002. ISBN 978-1-892746-98-6. http://primal-page.com/ps2.htm. 
  169. Kurtz, Paul (1991). The transcendental temptation: A critique of religion and the paranormal. Buffalo, NY: Prometheus Books. ISBN 978-0-87975-645-1. 
  170. "What causes the onset of psychosis?". Schizophr. Res. 79 (1): 23–34. November 2005. doi:10.1016/j.schres.2005.02.007. PMID 16198238.  https://dx.doi.org/10.1016%2Fj.schres.2005.02.007
  171. Lewis R (March 2004). "Should cognitive deficit be a diagnostic criterion for schizophrenia?". J Psychiatry Neurosci 29 (2): 102–13. PMID 15069464. PMC 383342. http://www.cma.ca/multimedia/staticContent/HTML/N0/l2/jpn/vol-29/issue-2/pdf/pg102.pdf. Retrieved 2011-02-18. 
  172. "Mental state attribution, neurocognitive functioning, and psychopathology: what predicts poor social competence in schizophrenia best?". Schizophr Res 92 (1–3): 151–9. May 2007. doi:10.1016/j.schres.2007.01.006. PMID 17346931.  https://dx.doi.org/10.1016%2Fj.schres.2007.01.006
  173. "Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis". Schizophr Res 71 (2–3): 285–95. December 2004. doi:10.1016/j.schres.2004.03.007. PMID 15474899.  https://dx.doi.org/10.1016%2Fj.schres.2004.03.007
  174. "Affective reactivity of speech and emotional experience in patients with schizophrenia". Schizophr Res 69 (1): 7–14. July 2004. doi:10.1016/S0920-9964(03)00069-0. PMID 15145465.  https://dx.doi.org/10.1016%2FS0920-9964%2803%2900069-0
  175. "Emotion and psychosis: Links between depression, self-esteem, negative schematic beliefs, and delusions and hallucinations". Schizophr Res 86 (1–3): 181–8. September 2006. doi:10.1016/j.schres.2006.06.018. PMID 16857346. http://discovery.ucl.ac.uk/2182/1/Microsoft_Word_-_Schiz_Res_02_04_2006__2_.pdf. 
  176. "A cognitive model of schizophrenia". Journal of Cognitive Psychotherapy 18 (3): 281–8. 2004. doi:10.1891/jcop.18.3.281.65649.  https://dx.doi.org/10.1891%2Fjcop.18.3.281.65649
  177. "Emotional responses to psychosocial stress in schizophrenia: the role of individual differences in affective traits and coping". Schizophr Res 60 (2–3): 271–283. April 2003. doi:10.1016/S0920-9964(02)00227-X. PMID 12591589.  https://dx.doi.org/10.1016%2FS0920-9964%2802%2900227-X
  178. "Psychosocial factors, arousal and schizophrenic relapse. The psychophysiological data". British Journal of Psychiatry 161 (1): 3–11. July 1992. doi:10.1192/bjp.161.1.3. PMID 1638327.  https://dx.doi.org/10.1192%2Fbjp.161.1.3
  179. "Self-esteem in schizophrenia: Relationships between self-evaluation, family attitudes, and symptomatology". Journal of Abnormal Psychology 112 (1): 92–9. February 2003. doi:10.1037/0021-843X.112.1.92. PMID 12653417.  https://dx.doi.org/10.1037%2F0021-843X.112.1.92
  180. "The power and omnipotence of voices: subordination and entrapment by voices and significant others". Psychol Med 30 (2): 337–44. March 2000. doi:10.1017/S0033291799001828. PMID 10824654.  https://dx.doi.org/10.1017%2FS0033291799001828
  181. "Auditory hallucinations: A comparison between patients and nonpatients". J Nerv Ment Dis 186 (10): 646–651. October 1998. doi:10.1097/00005053-199810000-00009. PMID 9788642.  https://dx.doi.org/10.1097%2F00005053-199810000-00009
  182. Paul Chadwick; Max Birchwood; Peter Trower (1996). Cognitive therapy for delusions, voices, and paranoia. Chichester, UK; New York; Brisbane: John Wiley & Sons. 
  183. Schizophrenia: Innovations in Diagnosis and Treatment. Haworth Press. 2004. ISBN 978-0-7890-2269-1. 
  184. "Schizophrenia, consciousness, and the self". Schizophr Bull 29 (3): 427–44. 2003. doi:10.1093/oxfordjournals.schbul.a007017. PMID 14609238.  https://dx.doi.org/10.1093%2Foxfordjournals.schbul.a007017
  185. "Schizophrenia and Alterations in Self-experience: A Comparison of 6 Perspectives". Schizophr Bull 36 (2): 331–340. September 2008. doi:10.1093/schbul/sbn077. PMID 18635676.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2833111
  186. "Schizophrenia as failure of hemispheric dominance for language". Trends Neurosci. 20 (8): 339–43. August 1997. doi:10.1016/S0166-2236(97)01071-0. PMID 9246721.  https://dx.doi.org/10.1016%2FS0166-2236%2897%2901071-0
  187. Pfeiffer, Carl C.. "Twenty-nine medical causes of "schizophrenia"". http://www.alternativementalhealth.com/articles/causesofschizophrenia.htm. 
  188. Bowman, M B; Lewis, M S (1982). "The copper hypothesis of schizophrenia: A review". Neuroscience and Biobehavioral Reviews 6 (3): 321–8. doi:10.1016/0149-7634(82)90044-6. PMID 7177508.  https://dx.doi.org/10.1016%2F0149-7634%2882%2990044-6
  189. Mackay-Sim, A; Féron, F; Eyles, D; Burne, T; McGrath, J (2004). Schizophrenia, vitamin D, and brain development. International Review of Neurobiology. 59. pp. 351–380. doi:10.1016/S0074-7742(04)59014-1. ISBN 9780123668608.  https://dx.doi.org/10.1016%2FS0074-7742%2804%2959014-1
  190. Arnsten, A F (June 2009). "Stress signalling pathways that impair prefrontal cortex structure and function". Nature Reviews Neuroscience 10 (6): 410–422. doi:10.1038/nrn2648. PMID 19455173.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2907136
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