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. Currently, there are five different types of schizophrenia listed in the DSM-IV-TR titled: catatonic, residual, disorganized, undifferentiated, and paranoid. Current 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. "Current research into schizophrenia has remained highly fragmented, much like the clinical presentation of the disease itself".
Although no common cause of schizophrenia has been identified in all individuals diagnosed with the condition, currently most researchers and clinicians believe it results from a combination of both brain vulnerabilities (either inherited or acquired) and life events. This widely adopted approach is known as the 'stress-vulnerability' model, and much scientific debate now focuses on how much each of these factors contributes to the development and maintenance of schizophrenia.
Schizophrenia is most commonly first diagnosed during late adolescence or early adulthood, suggesting it is often the end process of childhood and adolescent development. There is on average a somewhat earlier onset for men than women, with the possible influence of the female hormone estrogen being one hypothesis and sociocultural influences another.
Evidence suggests that genetic vulnerability and environmental factors can act in combination to result in diagnosis of schizophrenia. Research suggests that genetic vulnerability to schizophrenia is multifactorial, caused by interactions of several genes.
Reelin is a crucial factor for long term potentiation. Within the hippocampus of schizophrenic patients, levels of mRNA expressing this were found to be over %50 less than controls. Deficits are also observed in bipolar and autistic people. However, antipsychotics also effect reelin expression, so this data may be of some question. Regardless, how these drugs affect this signalling cascade is the mechanism of their long term effects upon the brain.
Both individual twin studies and meta-analyses of twin studies estimate 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). Concordance rates between monozygotic twins was close to 50%; whereas dizygotic twins was 17%. Adoption studies have also indicated a somewhat increased risk in those with a parent with schizophrenia even when raised apart. Studies suggest that the phenotype is genetically influenced but not genetically determined; that the variants in genes are generally within the range of normal human variation and have low risk associated with them each individually; and that some interact with each other and with environmental risk factors; and that they may not be specific to schizophrenia.
Some twin studies have found rates as low as 11.0%–13.8% among monozygotic twins, and 1.8%–4.1% among dizygotic twins, however. Tyronne Cannon reviewed the situation, stating: "Previous twin studies have reported estimates of broad heritability ranging from 0.41 to 0.87" Yet, in the "Pairs of Veteran Twins" study, for example, 338 pairs were schizophrenic with only 26 pairs concordant, and it was concluded in one report: "the role of the suggested genetic factor appears to be a limited one; 85 percent of the affected monozygotic pairs in the sample were discordant for schizophrenia". In addition, some scientists criticize the methodology of the twin studies, and have argued that the genetic basis of schizophrenia is still largely unknown or open to different interpretations.
For example, although the concordance of schizophrenia occurrence in monozygotic twins has traditionally been used to estimate a genetic component to the illness, the results could be skewed because of environmental factors like a shared placenta
In fact, researchers, have used the phenomenon of 'fetal programming' to account for familial patterns in epidemiological studies. "Intra-uterine growth is a complex outcome that is influenced by a wide range of factors including fetal genotype, maternal physiology and behaviour as well as the function of that crucial interface—the placenta," said one journal.
After reviewing techniques like: Genome Wide Association Studies; Single Nucleotide Polymorphisms and Copy Number Variations; the journal Nature journal reports: the basic observation is that, "You have this clear tangible phenomenon in which children resemble their parents"...."Despite what children get told in elementary school science we just don't know how that works," as Professor of ecology and evolutionary biology at Princeton, Leonid Kruglyak, says (in reviewing heretability in general). It cites schizophrenia as a trait in which the genes have gone missing.
A great deal of effort has been put into molecular genetic studies of schizophrenia, which attempt to identify specific genes which may increase risk. A 2003 review of linkage studies listed seven genes as likely to increase risk for a later diagnosis of the disorder. Two recent reviews 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. Variations near the gene FXYD6 have also been associated with schizophrenia in the UK but not in Japan. In 2008, rs7341475 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. Still another review found evidence that the protein phosphatase 2B (calcineurin) might be involved in susceptibility to schizophrenia.
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.
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.
Other research has suggested that a greater than average number of rare deletions or duplications of tiny DNA sequences within genes (known as copy number variants) are linked to increased risk for schizophrenia, especially in those "sporadic" cases not linked to family history of schizophrenia, and that the genetic factors and developmental pathways can thus be different in different individuals. 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.
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. Epigenetics may also play a role in schizophrenia, with the expression of Protocadherin 11 X/Protocadherin Y playing a possible role in schizophrenia.
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.
A 2009 study was able to create mice matching schizophrenic symptoms 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. 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 autistics some genome locations have only single copies and in schizophrenics extra copies are present at the same locations." "Source"
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.
Another evolutionary explanations 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.
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.
One epidemiological finding is that people diagnosed with schizophrenia are more likely to have been born in winter or spring (at least in the northern hemisphere). However, the effect is not large. 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.
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. Studies of Finnish mothers who were pregnant when they found out that their husbands had been killed during the Winter War of 1939–1940 have shown that their children were significantly more likely to develop schizophrenia when compared with mothers who found out about their husbands' death after pregnancy, suggesting that maternal stress may have an effect.
Lower than average birth weight has been one of the most consistent findings, indicating slowed fetal growth possibly mediated by genetic effects. Almost any factor adversely affecting the fetus will affect growth rate, however, so the association has been described as not particularly informative regarding causation. 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.
Animal models have suggested links between intrauterine growth restriction and specific neurological abnormalities similar to those that may be involved in the development of schizophrenia, including ventricular enlargement and reduced hippocampal volume in guinea pigs.
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.
Hypoxia is now being demonstrated as relevant to schizophrenia in animal models, molecular biology and epidemiology studies. One study in Molecular Psychiatry was able to differentiate 90% of schizophrenics from controls based on hypoxia and metabolism. Hypoxia has been recently 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. 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.
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 and/or vascular expression" even though only 3.5% of all genes were estimated to be involved in hypoxia/ischemia or the vasculature.
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. 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. 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.
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. 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.
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".
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. One paper restated that cerebellum neurological disorders were frequently found in schizophrenics and speculated hypoxia may cause the subsequent cognitive dysmetria
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 Neurological 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 schizophrenic cases; the study revealed increasing odds of schizophrenia according to graded increase in severity of hypoxia.
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." 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. References for many of these environmental risk factors have been collected in an online database.
There may be an association between celiac disease (gluten intolerance) and schizophrenia in a small proportion of patients, 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 schizophrenic patients.
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.
Numerous viral infections, in utero or in childhood, have been associated with an increased risk of later developing schizophrenia. Schizophrenia is somewhat more common in those born in winter to early spring, when infections are more common.
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. This result was corroborated by a later British study of the same pandemic, but not by a 1994 study of the pandemic in Croatia. A Japanese study also found no support for a link between schizophrenia and birth after an influenza epidemic.
Polio, measles, varicella-zoster, rubella, herpes simplex virus type 2, maternal genital infections, Borna disease virus, and more recently Toxoplasma gondii, have been correlated with the later development of schizophrenia. 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.
In a meta-analysis of several studies, they found moderately higher levels of Toxoplasma antibodies in those with schizophrenia 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.
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 and direct studies have linked dysfunctional immune status to some of the clinical features of schizophrenia.
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). 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.
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.
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.
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. The early subtle motor signs persisted to some extent, showing a small link to later school performance in adolescence. 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). (Patients in this age group with these symptoms were significantly less likely to progress to high school, despite academic ability.)
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. 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.
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. 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.
Some small studies on offspring of individuals with schizophrenia have identified various neurobehavioral deficits, a poorer family environment and disruptive school behaviour, poor peer engagement, immaturity or unpopularity or poorer social competence and increasing schizophrenic symptomology emerging during adolescence.
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.
There is evidence that childhood experiences of abuse or trauma are risk factors for a diagnosis of schizophrenia later in life. 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. 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.
The relationship between schizophrenia and drug use is complex, meaning that a clear causal connection between drug use and schizophrenia has been difficult to tease apart. There is strong evidence that using certain drugs can trigger either the onset or relapse of schizophrenia in some people. It may also be the case, however, that people with schizophrenia use drugs to overcome negative feelings associated with both the commonly prescribed antipsychotic medication and the condition itself, where negative emotion, paranoia and anhedonia are all considered to be core features.
The rate of substance use is known to be particularly high in this group. In a recent study, 60% of people with schizophrenia were found to use substances and 37% would be diagnosable with a substance use disorder.
There is some evidence that cannabis use can contribute to schizophrenia. Some studies suggest that cannabis is neither a sufficient nor necessary factor in developing schizophrenia, but that cannabis may significantly increase the risk of developing schizophrenia and may be, among other things, a significant causal factor. Nevertheless, some previous research in this area has been criticised as it has often not been clear whether cannabis use is a cause or effect of schizophrenia. To address this issue, a recent review of studies from which a causal contribution to schizophrenia can be assessed has suggested that cannabis statistically doubles the risk of developing schizophrenia on the individual level, and may, assuming a causal relationship, be responsible for up to 8% of cases in the population.
An older longitudinal study, published in 1987, suggested a sixfold increase of schizophrenia risks for high consumers of cannabis (use on more than fifty occasions) in Sweden.
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. Also, Sweden and Japan, where self-reported marijuana use is very low, do not have lower rates of psychosis than the U.S. and Canada do. Thus, there remains controversy over whether or not the apparent association between cannabis and schizophrenia is a causal relationship.
Amphetamines and other 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. 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.
Drugs such as ketamine, PCP, and LSD have been used to mimic schizophrenia for research purposes. Using LSD and other psychedelics as a model has now fallen out of favor with the scientific research community, as the differences between the drug induced states and the typical presentation of schizophrenia have become clear. The dissociatives ketamine and PCP, 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.
People with schizophrenia tend to smoke significantly more tobacco than the general population. The rates are exceptionally high amongst institutionalized patients and homeless people. In a UK census from 1993, 74% of people with schizophrenia living in institutions were found to be smokers. A 1999 study that covered all people with schizophrenia in Nithsdale, Scotland found a 58% prevalence rate of cigarette smoking, to compare with 28% in the general population. An older study found that as much as 88% of outpatients with schizophrenia were smokers.
Despite the higher prevalence of tobacco smoking, people diagnosed with schizophrenia have a much lower than average chance of developing and dying from lung cancer. While the reason for this is unknown, it may be because of a genetic resistance to the cancer, a side effect of drugs being taken, or a statistical effect of increased likelihood of dying from causes other than lung cancer.
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. 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.
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.
The increased rate of smoking in schizophrenia may be due to a desire to self-medicate with nicotine. One possible reason is that smoking produces a short term effect to improve alertness and cognitive functioning in persons who suffer this illness. It has been postulated that the mechanism of this effect is that people with schizophrenia have a disturbance of nicotinic receptor functioning which is temporarily abated by tobacco use. However, some researchers have questioned whether self-medication is really the best explanation for the association.
A study from 1989 and a 2004 case study 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. This gives credence to the idea tobacco could be used to self medicate by limiting effects of the illness, the medication, or both.
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. Stressful life events generally precede the onset of schizophrenia. 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. Unemployment and early separation from parents are some important factors which are responsible for the higher rates of schizophrenia among British African Caribbean, in comparison to native African Caribbean. This is an example which shows that social disadvantage plays an equally major hand in onset schizophrenia as genetics.
Childhood experiences of abuse or trauma are risk factors for a diagnosis of schizophrenia later in life. Recent large-scale general population studies indicate the relationship is a causal one, with an increasing risk with additional experiences of maltreatment, although a critical review suggests conceptual and methodological issues require further research. There is some evidence that adversities may lead to cognitive biases and/or altered dopamine neurotransmission, a process that has been termed "sensitization".
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.
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. A recent 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.
The effect does not appear to be due to a higher incidence of obstetric complications in urban environments. 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.
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.
Evidence is consistent that 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). 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. The risk of developing schizophrenia can also be increased by an individual developing a very low sense of self, in which ones boundaries become confused with that of the mother and/ or father. Firm psychological boundaries should be established between ones self and ones identity and ones parents. Pushing the role of parents into the background and developing a healthy sense of self can be a method for recovery. Social support systems are very important for schizophrenics and the people with whom they are in relationships.
Other proposed etiologies
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.
In 1956, Gregory Bateson and his colleagues Paul Watzlawick, Donald Jackson, and Jay Haley 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. 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. Researchers into shamanism have speculated that in some cultures schizophrenia or related conditions may predispose an individual to becoming a shaman; the experience of having access to multiple realities is not uncommon in schizophrenia, and is a core experience in many shamanic traditions. Equally, the shaman may have the skill to bring on and direct some of the altered states of consciousness psychiatrists label as illness. 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. Commentators such as Paul Kurtz and others have endorsed the idea that major religious figures experienced psychosis, heard voices and displayed delusions of grandeur.
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. However, the findings regarding cognitive difficulties in schizophrenia are reliable and consistent enough for some researchers to argue that they are diagnostic.
Impaired capacity to appreciate one's own and others' mental states has been reported to be the single-best predictor of poor social competence in schizophrenia, and similar cognitive features have been identified in close relatives of people diagnosed with schizophrenia.
A number of emotional factors have been implicated in schizophrenia, with some models putting them at the core of the disorder. It was thought that the appearance of blunted affect meant that sufferers did not experience strong emotions, but more recent studies indicate there is often a normal or even heightened level of emotionality, particularly in response to negative events or stressful social situations. Some theories suggest positive symptoms of schizophrenia can result from or be worsened by negative emotions, including depressed feelings and low self-esteem and feelings of vulnerability, inferiority or loneliness. Chronic negative feelings and maladaptive coping skills may explain some of the association between psychosocial stressors and symptomology. Critical and controlling behaviour by significant others (high expressed emotion) causes increased emotional arousal and lowered self-esteem and a subsequent increase in positive symptoms such as unusual thoughts. Countries or cultures where schizotypal personalities or schizophrenia symptoms are more accepted or valued appear to be associated with reduced onset of, or increased recovery from, schizophrenia.
Related studies suggest that the content of delusional and psychotic beliefs in schizophrenia can be meaningful and play a causal or mediating role in reflecting the life history, or social circumstances of the individual. Holding minority 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.
Some experts think autonomy vs intimacy is a motivation for schizophrenic symptoms.
Other lines of work relating to the self in schizophrenia have linked it to psychological dissociation or abnormal states of awareness and identity as understood from phenomenological and other perspectives.
Psychiatrist Tim Crow has argued that schizophrenia may be the evolutionary price we pay for a left brain hemisphere specialization for language. 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. 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. However, it is not entirely clear how many (if any) patients initially diagnosed with schizophrenia these alternative explanations may account for.
- ^ Carlson, N. R. (2010). Psychology, the science of behaviour. (4 ed.). Upper Saddle River, New Jersey: Pearson Education, Inc.
- ^ http://www.schizophreniaforum.org/for/int//Murray/murray.asp as at 12-8-10
- ^ http://www.nature.com/nature/journal/v468/n7321/full/nature09552.html
- ^ a b Manji, Hk; Gottesman, Ii; Gould, Td (November 2003). "Signal transduction and genes-to-behaviors pathways in psychiatric diseases". Science's STKE: signal transduction knowledge environment 2003 (207): pe49. doi:10.1126/stke.2003.207.pe49. PMID 14600293.
- ^ Marcotte ER, Pearson DM, Srivastava LK (November 2001). "Animal models of schizophrenia: a critical review". J Psychiatry Neurosci 26 (5): 395–410. PMC 167198. PMID 11762207. //www.ncbi.nlm.nih.gov/pmc/articles/PMC167198/.
- ^ Zubin J, Spring B (April 1977). "Vulnerability--a new view of schizophrenia". J Abnorm Psychol 86 (2): 103–26. doi:10.1037/0021-843X.86.2.103. PMID 858828.
- ^ Age of menarche and schizophrenia onset in women Schizophrenia Research, Volume 69, Issues 2-3, 1 August 2004, Pages 183-188 Karen M. Hochman, Richard R. Lewine
- ^ a b Harrison PJ, Owen MJ (February 2003). "Genes for schizophrenia? Recent findings and their pathophysiological implications". Lancet 361 (9355): 417–9. doi:10.1016/S0140-6736(03)12379-3. PMID 12573388.
- ^ a b Owen MJ, Craddock N, O'Donovan MC (September 2005). "Schizophrenia: genes at last?". Trends Genet 21 (9): 518–25. doi:10.1016/j.tig.2005.06.011. PMID 16009449.
- ^ a b c Riley B, Kendler KS (June 2006). "Molecular genetic studies of schizophrenia". Eur J Hum Genet 14 (6): 669–80. doi:10.1038/sj.ejhg.5201571. PMID 16721403.
- ^ Koskenvuo M, Langinvainio H, Kaprio J, Lönnqvist J, Tienari P (1984). "Psychiatric hospitalization in twins". Acta Genet Med Gemellol (Roma) 33 (2): 321–32. PMID 6540965.
- ^ Hoeffer A, Pollin W (November 1970). "Schizophrenia in the NAS-NRC panel of 15,909 veteran twin pairs". Arch Gen Psychiatry 23 (5): 469–77. PMID 5478575.
- ^ The Genetic Epidemiology of Schizophrenia in a Finnish Twin Cohort A Population-Based Modeling Study Tyrone D. Cannon, PhD; Jaakko Kaprio, MD, PhD; Jouko Lönnqvist, MD; Matti. Huttunen, MD; Markku Koskenvuo, MD Arch Gen Psychiatry. 1998;55:67.-74..
- ^ WILLIAM POLLIN M.D., MARTIN G. ALLEN M.D., AXEL HOFFER M.D., JAMES R. STABENAU M.D., , and ZDENEK HRUBEC D.SC.Psychopathology in 15,909 Pairs of Veteran Twins: Evidence for a Genetic Factor in the Pathogenesis of Schizophrenia and Its Relative Absence in Psychoneurosis Am J Psychiatry 126:597-610, November 1969 doi:10.1176/appi.ajp.126.5.597
- ^ Pearce B D (2001). "Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms". Molecular Psychiatry 6 (6): 634–646.
- ^ http://en.wikipedia.org/wiki/Twin#Monochorionic
- ^ Schizophr Bull. 1995;21(3):357-66. Prenatal development of monozygotic twins and concordance for schizophrenia. Davis JO, Phelps JA, Bracha HS. Erratum in: Schizophr Bull 1995;21(4):539. PMID 7481567. (The erratum was needed to substantiate the percentages quoted)
- ^ . http://ije.oxfordjournals.org/cgi/content/full/30/1/96. as at 12-08-10 - note one of the authors of the referenced schizophrenia study was Robin Murray
- ^ Maher, Brendan; "The case of the missing hereditability"; NEWS FEATURE PERSONAL GENOMES NATURE|Vol 456|6 November 2008 p21
- ^ Shao, Lisha; YC Shuai, J Wang, SX Feng, BY Lu, Z Li, YK Zhao, LZ Wang, Y Zhong (October 2011). "Schizophrenia susceptibility gene dysbindin regulates glutamatergic and dopaminergic functions via distinctive mechanisms in Drosophila". PNAS 108 (46): 18831–18836. doi:10.1073/pnas.1114569108.
- ^ "Getting crowded on chromosome 11q22—make way for phosphohippolin". Schizophrenia Research Forum. 14 March 2007. http://www.schizophreniaforum.org/new/detail.asp?id=1326. Retrieved 2007-05-16.
- ^ Choudhury K, McQuillin A, Puri V et al. (April 2007). "A Genetic Association Study of Chromosome 11q22-24 in Two Different Samples Implicates the FXYD6 Gene, Encoding Phosphohippolin, in Susceptibility to Schizophrenia". Am J Hum Genet 80 (4): 664–72. doi:10.1086/513475. PMC 1852702. PMID 17357072. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1852702/.
- ^ Ito Y, Nakamura Y, Takahashi N et al. (June 2008). "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". Neurosci. Lett. 438 (1): 70–5. doi:10.1016/j.neulet.2008.04.010. PMID 18455306.
- ^ Shifman S, Johannesson M, Bronstein M, Chen SX, Collier DA, Craddock NJ, Kendler KS, Li T, O'Donovan M, O'Neill FA, Owen MJ, Walsh D, Weinberger DR, Sun C, Flint J, Darvasi A (2008). "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. doi:10.1371/journal.pgen.0040028. PMC 2242812. PMID 18282107. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2242812/.
- ^ Allen NC, Bagade S, McQueen MB, Ioannidis JPA, Kawoura FK, Khoury MJ, Tanzi RE, Bertram L (July 2008). "Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database". Nature Genetics 40 (7): 827–824. doi:10.1038/ng.171. PMID 18583979.
- ^ Walsh T; McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, Nord AS, Kusenda M, Malhotra D, Bhandari A, Stray SM, Rippey CF, Roccanova P, Makarov V, Lakshmi B, Findling RL, Sikich L, Stromberg T, Merriman B, Gogtay N, Butler P, Eckstrand K, Noory L, Gochman P, Long R, Chen Z, Davis S, Baker C, Eichler EE, Meltzer PS, Nelson SF, Singleton AB, Lee MK, Rapoport JL, King MC, Sebat J (April 2008). "Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia". Science 320 (5875): 539–43. doi:10.1126/science.1155174. PMID 18369103. http://www.sciencemag.org/cgi/content/abstract/320/5875/539.
- ^ Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M (July 2008). "Strong association of de novo copy number mutations with sporadic schizophrenia". Nat Genet 40 (7): 880–5. doi:10.1038/ng.162. PMID 18511947.
- ^ The International Schizophrenia Consortium (11 September 2008). "Rare chromosomal deletions and duplications increase risk of schizophrenia". Nature 455 (7210): 237–41. doi:10.1038/nature07239. PMID 18668038.
- ^ Lee JA, Lupski JR (2006). "Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders". Neuron 52 (1): 103–121. doi:10.1016/j.neuron.2006.09.027. PMID 17015230.
- ^ Kalmady, Sunil V; 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.
- ^ Rujescu, Dan; Andres Ingason, Sven Cichon, Olli P.H. Pietiläinen, Michael R. Barnes, Timothea Toulopoulou, Marco Picchioni, Evangelos Vassos, Ulrich Ettinger, Elvira Bramon, Robin Murray, Mirella Ruggeri, Sarah Tosato, Chiara Bonetto, Stacy Steinberg, Engilbert Sigurdsson, Thordur Sigmundsson, Hannes Petursson, Arnaldur Gylfason, Pall I. Olason, Gudmundur Hardarsson, Gudrun A. Jonsdottir, Omar Gustafsson, Ragnheidur Fossdal, Ina Giegling, Hans-Jürgen Möller, Annette M. Hartmann, Per Hoffmann, Caroline Crombie, Gillian Fraser, Nicholas Walker, Jouko Lonnqvist, Jaana Suvisaari, Annamari Tuulio-Henriksson, Srdjan Djurovic, Ingrid Melle, Ole A. Andreassen, Thomas Hansen, Thomas Werge, Lambertus A. Kiemeney, Barbara Franke, Joris Veltman, Jacobine E. Buizer-Voskamp, GROUP Investigators, Chiara Sabatti, Roel A. Ophoff, Marcella Rietschel, Markus M. No ¨ then, Kari Stefansson, Leena Peltonen, David St Clair, Hreinn Stefansson and David A. Collier (2009). "Disruption of the neurexin 1 gene is associated with schizophrenia". Human Molecular Genetics 18 (5): 988–996. doi:10.1093/hmg/ddn351. http://hmg.oxfordjournals.org/content/18/5/988.full.
- ^ Barros CS, Calabrese B, Chamero P, Roberts AJ, Korzus E, Lloyd K, Stowers L, Mayford M, Halpain S, Müller U (17 March 2009). "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. doi:10.1073/pnas.0900355106. PMC 2657442. PMID 19240213. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2657442/. Lay summary.
- ^ Del Giudice, M. (2010). Gilbert, M. Thomas P. ed. "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. PMC 3012205. PMID 21253008. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3012205/.
- ^ Schlomer, G. L.; Del Giudice, M.; Ellis, B. 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.
- ^ a b c Clarke MC, Harley M, Cannon M (January 2006). "The Role of Obstetric Events in Schizophrenia". Schizophr Bull 32 (1): 3–8. doi:10.1093/schbul/sbj028. PMC 2632192. PMID 16306181. http://schizophreniabulletin.oxfordjournals.org/cgi/content/full/32/1/3.
- ^ Davies G, Welham J, Chant D, Torrey EF, McGrath J (2003). "A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia". Schizophr Bull 29 (3): 587–93. PMID 14609251. http://schizophreniabulletin.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=14609251.
- ^ Gobet F; Chassy P (March 2008). "Season of birth and chess expertise" (PDF). J Biosoc Sci 40 (2): 313–6. doi:10.1017/S0021932007002222. PMID 18335581. http://bura.brunel.ac.uk/bitstream/2438/736/1/Seasonality+and+chess.pdf. PDF (65.8 KiB)
- ^ Susser E, Neugebauer R, Hoek HW et al. (January 1996). "Schizophrenia after prenatal famine. Further evidence". Arch. Gen. Psychiatry 53 (1): 25–31. PMID 8540774.
- ^ Huttunen MO, Niskanen P (April 1978). "Prenatal loss of father and psychiatric disorders". Arch. Gen. Psychiatry 35 (4): 429–31. PMID 727894.
- ^ a b Welham J, Isohanni M, Jones P, McGrath J (July 2008). "The Antecedents of Schizophrenia: A Review of Birth Cohort Studies". Schizophr Bull 35 (3): 603–23. doi:10.1093/schbul/sbn084. PMC 2669575. PMID 18658128. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2669575/.
- ^ Mallard EC, Rehn A, Rees S, Tolcos M, Copolov D (November 1999). "Ventriculomegaly and reduced hippocampal volume following intrauterine growth-restriction: implications for the aetiology of schizophrenia". Schizophr. Res. 40 (1): 11–21. doi:10.1016/S0920-9964(99)00041-9. PMID 10541002. http://linkinghub.elsevier.com/retrieve/pii/S0920-9964(99)00041-9.
- ^ Handford HA (February 1975). "Brain hypoxia, minimal brain dysfunction, and schizophrenia". Am J Psychiatry 132 (2): 192–4. PMID 1111324. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=1111324.
- ^ The above 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)."Disorganized Children : A Guide for Parents and Professionals Jessica Kingsley Publishers Ltd. Stein, Samuel M.p135
- ^ Prabakaran, S., Swatton, J. E., Ryan, M. M., Huffaker, S. J., Huang, J. T., Griffin, J. L., Wayland, M., Freeman, T., Dudbridge, F., Lilley, K. S., Karp, N. A., Hester, S., Tkachev, D., Mimmack, M. L., Yolken, R. H., Webster, M. J., Torrey, E. F. and Bahn, S. (2004). "Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress," Molecular Psychiatry, 9, 684-697. This study has a lot of rigor as the results were reproduced: "Almost half the altered proteins identified by proteomics were associated with mitochondrial function and oxidative stress responses. This was mirrored by transcriptional and metabolite perturbations;" says the abstract
- ^ Br J Psychiatry. 2005 Feb;186:93-5. Origins of cognitive dysfunction in schizophrenia: clues from age at onset. Joyce E. Comment on: Br J Psychiatry. 2004 Sep;185:215-9.
- ^ Van Erp TG, Saleh PA, Rosso IM et al. (September 2002). "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. doi:10.1176/appi.ajp.159.9.1514. PMID 12202271. http://ajp.psychiatryonline.org/cgi/content/full/159/9/1514.
- ^ Schmidt-Kastner R, van Os J, W M Steinbusch H, Schmitz C (June 2006). "Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia". Schizophrenia research 84 (2–3): 253–71. doi:10.1016/j.schres.2006.02.022. PMID 16632332. http://linkinghub.elsevier.com/retrieve/pii/S0920996406001113.
- ^ a b Cannon M, Caspi A, Moffitt TE et al. (May 2002). "Evidence for early-childhood, pan-developmental impairment specific to schizophreniform disorder: results from a longitudinal birth cohort". Arch. Gen. Psychiatry 59 (5): 449–56. doi:10.1001/archpsyc.59.5.449. PMID 11982449. http://archpsyc.ama-assn.org/cgi/content/full/59/5/449.
- ^ a b Rosso IM, Bearden CE, Hollister JM et al. (2000). "Childhood neuromotor dysfunction in schizophrenia patients and their unaffected siblings: a prospective cohort study". Schizophr Bull 26 (2): 367–78. PMID 10885637. http://schizophreniabulletin.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=10885637.
- ^ Kunugi H, Urushibara T, Murray RM, Nanko S, Hirose T (June 2003). "Prenatal underdevelopment and schizophrenia: a case report of monozygotic twins". Psychiatry Clin. Neurosci. 57 (3): 271–4. doi:10.1046/j.1440-1819.2003.01116.x. PMID 12753566. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=1323-1316&date=2003&volume=57&issue=3&spage=271.
- ^ Murray RM, Fearon P (1999). "The developmental 'risk factor' model of schizophrenia". J Psychiatr Res 33 (6): 497–9. doi:10.1016/S0022-3956(99)00032-1. PMID 10628525. http://linkinghub.elsevier.com/retrieve/pii/S0022-3956(99)00032-1.
- ^ Cannon M, Murray RM (January 1998). "Neonatal origins of schizophrenia". Arch. Dis. Child. 78 (1): 1–3. doi:10.1136/adc.78.1.1. PMC 1717442. PMID 9534666. http://adc.bmj.com/cgi/pmidlookup?view=long&pmid=9534666.
- ^ Golan H, Huleihel M (July 2006). "The effect of prenatal hypoxia on brain development: short- and long-term consequences demonstrated in rodent models". Developmental science 9 (4): 338–49. doi:10.1111/j.1467-7687.2006.00498.x. PMID 16764607. http://www3.interscience.wiley.com/journal/118633736/abstract?CRETRY=1&SRETRY=0.
- ^ Golan H, Kashtutsky I, Hallak M, Sorokin Y, Huleihel M (2004). "Maternal hypoxia during pregnancy delays the development of motor reflexes in newborn mice". Developmental neuroscience 26 (1): 24–9. doi:10.1159/000080708. PMID 15509895.
- ^ Ellman, LM and Cannon TD, "Chapter 7. Environmental pre- and preinatal influences in etiology" in Clinical Handbook of Schizophrenia by Kim T. Mueser, Dilip V. Jeste New York : Guilford Press, ©2008 p69
- ^ Loss of synaptic but not cytoskeletal proteins in the cerebellum of chronic schizophrenics Neuroscience Letters, Volume 317, Issue 3, 14 January 2002, Pages 161-165 E. B. Mukaetova-Ladinska, J. Hurt, W. G. Honer, C. R. Harrington, C. M. Wischik
- ^ Zornberg GL, Buka SL, Tsuang MT (February 2000). "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. doi:10.1176/appi.ajp.157.2.196. PMID 10671387. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=10671387.
- ^ Torrey EF, Buka S, Cannon TD, Goldstein JM, Seidman LJ, Liu T, Hadley T, Rosso IM, Bearden C, Yolken RH (2009). "Paternal age as a risk factor for schizophrenia: how important is it?". Schizophr Res 114 (1–3): 1–5. doi:10.1016/j.schres.2009.06.017. PMID 19683417. http://www.schres-journal.com/article/S0920-9964%2809%2900290-4/abstract.
- ^ Environmental risk factors and comorbid medical conditions in schizophrenia
- ^ Kalaydjian, A. E.; Eaton, W.; Cascella, N.; Fasano, A. (2006). "The gluten connection: the association between schizophrenia and celiac disease". Acta Psychiatrica Scandinavica 113 (2): 82. doi:10.1111/j.1600-0447.2005.00687.x. PMID 16423158.
- ^ a b 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. PMC 1241919. PMID 15064159. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1241919/.
- ^ Brown AS (January 2008). "The risk for schizophrenia from childhood and adult infections". The American Journal of Psychiatry 165 (1): 7–10. doi:10.1176/appi.ajp.2007.07101637. PMID 18178749. http://ajp.psychiatryonline.org/cgi/content/full/ajp;165/1/7.
- ^ Torrey EF, Miller J, Rawlings R, Yolken RH (November 1997). "Seasonality of births in schizophrenia and bipolar disorder: a review of the literature". Schizophrenia research 28 (1): 1–38. doi:10.1016/S0920-9964(97)00092-3. PMID 9428062. http://linkinghub.elsevier.com/retrieve/pii/S0920-9964(97)00092-3.
- ^ Mednick SA, Machon RA, Huttunen MO, Bonett D (February 1988). "Adult schizophrenia following prenatal exposure to an influenza epidemic". Archives of General Psychiatry 45 (2): 189–92. PMID 3337616.
- ^ Cooper SJ (September 1992). "Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic". The British journal of psychiatry 161 (3): 394–6. doi:10.1192/bjp.161.3.394. PMID 1393310.
- ^ Erlenmeyer-Kimling L, Folnegović Z, Hrabak-Zerjavić V, Borcić B, Folnegović-Smalc V, Susser E (October 1994). "Schizophrenia and prenatal exposure to the 1957 A2 influenza epidemic in Croatia". The American Journal of Psychiatry 151 (10): 1496–8. PMID 8092342. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=8092342.
- ^ Mino Y, Oshima I, Tsuda T, Okagami K (2000). "No relationship between schizophrenic birth and influenza epidemics in Japan". J Psychiatr Res 34 (2): 133–8. doi:10.1016/S0022-3956(00)00003-0. PMID 10758255. http://linkinghub.elsevier.com/retrieve/pii/S0022-3956(00)00003-0.
- ^ Mortensen PB, Nørgaard-Pedersen B, Waltoft BL, Sørensen TL, Hougaard D, Yolken RH (May 2007). "Early Infections of Toxoplasma gondii and the Later Development of Schizophrenia". Schizophr Bull 33 (3): 741–4. doi:10.1093/schbul/sbm009. PMC 2526131. PMID 17329231. http://schizophreniabulletin.oxfordjournals.org/cgi/content/full/33/3/741.
- ^ Torrey EF, Yolken RH (November 2003). "Toxoplasma gondii and Schizophrenia". Emerging Infect. Dis. 9 (11): 1375–80. PMC 3035534. PMID 14725265. http://www.cdc.gov/ncidod/EID/vol9no11/03-0143.htm.
- ^ Torrey EF, Bartko JJ, Lun ZR, Yolken RH (May 2007). "Antibodies to Toxoplasma gondii in Patients With Schizophrenia: A Meta-Analysis". Schizophr Bull 33 (3): 729–36. doi:10.1093/schbul/sbl050. PMC 2526143. PMID 17085743. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2526143/.
- ^ Wang HL, Wang GH, Li QY, Shu C, Jiang MS, Guo Y (July 2006). "Prevalence of Toxoplasma infection in first-episode schizophrenia and comparison between Toxoplasma-seropositive and Toxoplasma-seronegative schizophrenia". Acta Psychiatr Scand 114 (1): 40–8. doi:10.1111/j.1600-0447.2006.00780.x. PMID 16774660.
- ^ Conejero-Goldberg C, Torrey EF, Yolken RH (March 2003). "Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric patients". Schizophr. Res. 60 (1): 65–9. doi:10.1016/S0920-9964(02)00160-3. PMID 12505139. http://linkinghub.elsevier.com/retrieve/pii/S0920996402001603.
- ^ Eaton WW, Byrne M, Ewald H et al. (March 2006). "Association of schizophrenia and autoimmune diseases: linkage of Danish national registers". Am J Psychiatry 163 (3): 521–8. doi:10.1176/appi.ajp.163.3.521. PMID 16513876.
- ^ Jones AL, Mowry BJ, Pender MP, Greer JM (February 2005). "Immune dysregulation and self-reactivity in schizophrenia: do some cases of schizophrenia have an autoimmune basis?". Immunol. Cell Biol. 83 (1): 9–17. doi:10.1111/j.1440-1711.2005.01305.x. PMID 15661036.
- ^ Strous RD, Shoenfeld Y (September 2006). "Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited". J. Autoimmun. 27 (2): 71–80. doi:10.1016/j.jaut.2006.07.006. PMID 16997531.
- ^ Brown, AS; Hooton, J, Schaefer, CA, Zhang, H, Petkova, E, Babulas, V, Perrin, M, Gorman, JM, Susser, ES (2004 May). "Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring". The American Journal of Psychiatry 161 (5): 889–95. doi:10.1176/appi.ajp.161.5.889. PMID 15121655.
- ^ Brown, AS (2006 Apr). "Prenatal Infection as a Risk Factor for Schizophrenia". Schizophrenia bulletin 32 (2): 200–2. doi:10.1093/schbul/sbj052. PMC 2632220. PMID 16469941. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2632220/.
- ^ Jones P, Rodgers B, Murray R, Marmot M (November 1994). "Child development risk factors for adult schizophrenia in the British 1946 birth cohort". Lancet 344 (8934): 1398–402. doi:10.1016/S0140-6736(94)90569-X. PMID 7968076.
- ^ Isohanni M, Jones PB, Moilanen K et al. (October 2001). "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. doi:10.1016/S0920-9964(00)00179-1. PMID 11595387. http://linkinghub.elsevier.com/retrieve/pii/S0920996400001791.
- ^ Isohanni M, Murray GK, Jokelainen J, Croudace T, Jones PB (December 2004). "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. doi:10.1016/j.schres.2004.03.008. PMID 15474893. http://linkinghub.elsevier.com/retrieve/pii/S0920996404001045.
- ^ Cannon M, Jones P, Huttunen MO, Tanskanen A, Murray R (1999). "Motor Co-ordination Deficits as Predictors of Schizophrenia Among Finnish School Children". Hum. Psychopharmacol. Clin. Exp. 14 (7): 491–7. doi:10.1002/(SICI)1099-1077(199910)14:7<491::AID-HUP134>3.0.CO;2-V. http://www3.interscience.wiley.com/journal/66002277/abstract.
- ^ School Performance in Finnish Children and Later Development of Schizophrenia A Population-Based Longitudinal Study Mary Cannon, MD, MSc; Peter Jones, MD, PhD; Matti O. Huttunen, MD, PhD; Antti Tanskanen, BSc; Tiia Huttunen, MSc; Sophia Rabe-Hesketh, PhD; Robin M. Murray, MD, DSc Arch Gen Psychiatry. 1999;56:457-463. http://archpsyc.ama-assn.org/cgi/content/abstract/56/5/457
- ^ 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. http://archpsyc.ama-assn.org/cgi/content/full/57/8/813.
- ^ I. Helling, A. Öhman, C. M. Hultman School achievements and schizophrenia: a case–control study Acta Psychiatrica Scandinavica Volume 108 Issue 5, Pages 381 - 386
- ^ Hans SL, Marcus J, Nuechterlein KH, Asarnow RF, Styr B, Auerbach JG (August 1999). "Neurobehavioral deficits at adolescence in children at risk for schizophrenia: The Jerusalem Infant Development Study". Arch. Gen. Psychiatry 56 (8): 741–8. doi:10.1001/archpsyc.56.8.741. PMID 10435609. http://archpsyc.ama-assn.org/cgi/pmidlookup?view=long&pmid=10435609.
- ^ Carter JW, Schulsinger F, Parnas J, Cannon T, Mednick SA (2002). "A multivariate prediction model of schizophrenia". Schizophr Bull 28 (4): 649–82. PMID 12795497. http://schizophreniabulletin.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12795497.
- ^ Hans SL, Auerbach JG, Asarnow JR, Styr B, Marcus J (November 2000). "Social adjustment of adolescents at risk for schizophrenia: the Jerusalem Infant Development Study". J Am Acad Child Adolesc Psychiatry 39 (11): 1406–14. doi:10.1097/00004583-200011000-00015. PMID 11068896. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0890-8567&volume=39&issue=11&spage=1406.
- ^ Dworkin RH, Bernstein G, Kaplansky LM et al. (September 1991). "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): 1182–8. PMID 1882996. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=1882996.
- ^ Galderisi S, Maj M, Mucci A, Cassano GB, Invernizzi G, Rossi A, Vita A, Dell'Osso L, Daneluzzo E, Pini S. (2002) Historical, psychopathological, neurological, and neuropsychological aspects of deficit schizophrenia: a multicenter study Am J Psychiatry. 2002 Jun;159(6):983-90.
- ^ Larkin, W; Read, J (2008). "Childhood trauma and psychosis: evidence, pathways, and implications". Journal of Postgraduate Medicine 54 (4): 287–293. PMID 18953148. http://www.jpgmonline.com/text.asp?2008/54/4/287/41437. Retrieved 5 April 2012.
- ^ a b 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. http://healingattention.org/documents/doc_litreviewpsychosis.pdf. Retrieved 5 April 2012.
- ^ Swartz MS, Wagner HR, Swanson JW et al. (March 2006). "Substance use in persons with schizophrenia: baseline prevalence and correlates from the NIMH CATIE study". J. Nerv. Ment. Dis. 194 (3): 164–72. doi:10.1097/01.nmd.0000202575.79453.6e. PMID 16534433.
- ^ Arseneault L, Cannon M, Witton J, Murray RM (February 2004). "Causal association between cannabis and psychosis: examination of the evidence". Br J Psychiatry 184 (2): 110–7. doi:10.1192/bjp.184.2.110. PMID 14754822. http://bjp.rcpsych.org/cgi/content/full/184/2/110.
- ^ Andréasson S, Allebeck P, Engström A, Rydberg U (December 1987). "Cannabis and schizophrenia. A longitudinal study of Swedish conscripts". Lancet 2 (8574): 1483–6. doi:10.1016/S0140-6736(87)92620-1. PMID 2892048. http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(87)92620-1.
- ^ Degenhardt L, Hall W, Lynskey M (2001) (PDF). Comorbidity between cannabis use and psychosis: Modelling some possible relationships. Technical Report No. 121.. Sydney: National Drug and Alcohol Research Centre.. http://ndarc.med.unsw.edu.au/NDARCWeb.nsf/resources/TR_18/$file/TR.121.PDF. Retrieved 2006-08-19.
- ^ Martin Frisher, Ilana Crome, Orsolina Martino, and Peter Croft. (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.
- ^ http://www.nhsconfed.org/Publications/Documents/MHN_factsheet_August_2009_FINAL_2.pdf Key facts and trends in mental health, National Health Service, 2009
- ^ "Interpreting hazy warnings about pot and mental illness". Huffington Post. 2007-08-07. http://www.huffingtonpost.com/paul-armentano-and-mitch-earleywine/interpreting-hazy-warning_b_59543.html. Retrieved 2009-01-23.
- ^ Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9235-40.Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects.Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB.
- ^ McNeill, Ann (2001) (PDF). Smoking and mental health — a review of the literature. SmokeFree London Programme. Archived from the original on 2006-09-24. http://web.archive.org/web/20060924194321/http://www.ash.org.uk/html/policy/menlitrev.pdf. Retrieved 2006-12-14.
- ^ Meltzer H, Gill B, Petticrew M, Hinds K. (1995). OPCS Surveys of Psychiatric Morbidity Report 3: Economic Activity and Social Functioning of Adults With Psychiatric Disorders. London, Her Majesty’s Stationery Office. Available for fee.
- ^ Kelly, C; McCreadie RG (1 November 1999). "Smoking Habits, Current Symptoms, and Premorbid Characteristics of Schizophrenic Patients in Nithsdale, Scotland". The American Journal of Psychiatry (American Psychiatric Association) 156 (11): 1751–1757. PMID 10553739. http://ajp.psychiatryonline.org/cgi/content/abstract/156/11/1751. Retrieved 2006-12-14.
- ^ Hughes, JR; Hatsukami DK, Mitchell JE, Dahlgren LA (1 August 1986). "Prevalence of smoking among psychiatric outpatients". The American Journal of Psychiatry (American Psychiatric Association) 143 (8): 993–997. PMID 3487983. http://ajp.psychiatryonline.org/cgi/content/abstract/143/8/993. Retrieved 2006-12-14.
- ^ "Conditions in Occupational Therapy: effect on occupational performance." ed. Ruth A. Hansen and Ben Atchison (Baltimore: Lippincott Williams & Williams, 2000), 54–74. ISBN 0-683-30417-8
- ^ Zammit S, Allebeck P, Dalman C, Lundberg I, Hemmingsson T, Lewis G (December 2003). "Investigating the association between cigarette smoking and schizophrenia in a cohort study". Am J Psychiatry 160 (12): 2216–21. doi:10.1176/appi.ajp.160.12.2216. PMID 14638593. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=14638593.
- ^ Mark Weiser, M.D., Abraham Reichenberg, Ph.D., Itamar Grotto, M.D., Ross Yasvitzky, B.Sc., Jonathan Rabinowitz, Ph.D., Gad Lubin, M.D., Daniella Nahon, M.A., Haim Y. Knobler, M.D., and Michael Davidson, M.D. (July 20034). "Higher Rates of Cigarette Smoking in Male Adolescents Before the Onset of Schizophrenia: A Historical-Prospective Cohort Study". Am J Psychiatry 161 (12): 1219–1223. doi:10.1176/appi.ajp.161.7.1219. PMID 15229054. http://ajp.psychiatryonline.org/cgi/content/abstract/161/7/1219.
- ^ a b 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.
- ^ http://www.informaworld.com/smpp/content~db=all~content=a910940707 Chambers, R.A. A Nicotine Challenge to the Self-Medication Hypothesis in a Neurodevelopmental Animal Model of Schizophrenia Journal of Dual Diagnosis Volume 5, Issue 2, 2009, Pages 139 - 148
- ^ Prasad C, Spahn SA, Ikegami H (February 1989). "Chronic nicotine use blocks haloperidol-induced increase in striatal D2-dopamine receptor density". Biochem. Biophys. Res. Commun. 159 (1): 48–52. doi:10.1016/0006-291X(89)92402-9. PMID 2522303. http://linkinghub.elsevier.com/retrieve/pii/0006-291X(89)92402-9.
- ^ Silvestri S, Negrete JC, Seeman MV, Shammi CM, Seeman P (April 2004). "Does nicotine affect D2 receptor upregulation? A case-control study". Acta Psychiatr Scand 109 (4): 313–7; discussion 317–8. doi:10.1111/j.1600-0447.2004.00293.x. PMID 15008806. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0001-690X&date=2004&volume=109&issue=4&spage=313.
- ^ Anfang MK, Pope HG (November 1997). "Treatment of neuroleptic-induced akathisia with nicotine patches". Psychopharmacology (Berl.) 134 (2): 153–6. doi:10.1007/s002130050436. PMID 9399378. http://link.springer.de/link/service/journals/00213/bibs/7134002/71340153.htm.
- ^ Wicks S, Hjern A, Gunnell D, Lewis G, Dalman C (September 2005). "Social adversity in childhood and the risk of developing psychosis: a national cohort study". The American Journal of Psychiatry 162 (9): 1652–7. doi:10.1176/appi.ajp.162.9.1652. PMID 16135624. http://ajp.psychiatryonline.org/cgi/content/full/162/9/1652.
- ^ Mueser KT, McGurk SR (2004). "Schizophrenia". The Lancet 363 (9426): 2063–72. doi:10.1016/S0140-6736(04)16458-1. PMID 15207959.
- ^ Day R, Nielsen JA, Korten A et al. (June 1987). "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. doi:10.1007/BF00122563. PMID 3595169.
- ^ Selten JP, Cantor-Graae E, Kahn RS (March 2007). "Migration and schizophrenia". Current Opinion in Psychiatry 20 (2): 111–115. doi:10.1097/YCO.0b013e328017f68e. PMID 17278906. http://www.co-psychiatry.com/pt/re/copsych/abstract.00001504-200703000-00003.htm. Retrieved 2008-07-06.
- ^ Cantor-Graae E, Selten JP (January 2005). "Schizophrenia and migration: a meta-analysis and review". Am J Psychiatry 162 (1): 12–24. doi:10.1176/appi.ajp.162.1.12. PMID 15625195. http://ajp.psychiatryonline.org/cgi/content/full/162/1/12.
- ^ "Social factors 'cause ethnic schizophrenia'". BBC News. 2002-06-22. http://news.bbc.co.uk/2/hi/health/2057205.stm.
- ^ MacMillan HL, Fleming JE, Streiner DL et al. (November 2001). "Childhood abuse and lifetime psychopathology in a community sample". Am J Psychiatry 158 (11): 1878–83. doi:10.1176/appi.ajp.158.11.1878. PMID 11691695. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=11691695.
- ^ Schenkel LS, Spaulding WD, DiLillo D, Silverstein SM (July 2005). "Histories of childhood maltreatment in schizophrenia: relationships with premorbid functioning, symptomatology, and cognitive deficits". Schizophr. Res. 76 (2–3): 273–86. doi:10.1016/j.schres.2005.03.003. PMID 15949659. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TC2-4FWT420-3&_user=10&_coverDate=04%2F08%2F2005&_rdoc=1&_fmt=summary&_orig=browse&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=a75a0204ebb590104747e8115cddd64a.
- ^ Janssen I, Krabbendam L, Bak M et al. (January 2004). "Childhood abuse as a risk factor for psychotic experiences". Acta Psychiatr Scand 109 (1): 38–45. doi:10.1046/j.0001-690X.2003.00217.x. PMID 14674957. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0001-690X&date=2004&volume=109&issue=1&spage=38.
- ^ Read J, Perry BD, Moskowitz A, Connolly J (2001). "The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurodevelopmental model" (PDF). Psychiatry 64 (4): 319–45. doi:10.1521/psyc.64.4.319.18602. PMID 11822210. http://www.childtrauma.org/CTAMATERIALS/Psychiatry_02.pdf.
- ^ 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): 330–50. doi:10.1111/j.1600-0447.2005.00634.x. PMID 16223421. http://www3.interscience.wiley.com/journal/118641029/abstract.
- ^ Morgan C, Fisher H (January 2007). "Environment and Schizophrenia: Environmental Factors in Schizophrenia: Childhood Trauma—A Critical Review". Schizophrenia bulletin 33 (1): 3–10. doi:10.1093/schbul/sbl053. PMC 2632300. PMID 17105965. http://schizophreniabulletin.oxfordjournals.org/cgi/content/full/33/1/3.
- ^ Collip D, Myin-Germeys I, Van Os J (March 2008). "Does the Concept of "Sensitization" Provide a Plausible Mechanism for the Putative Link Between the Environment and Schizophrenia?". Schizophr Bull 34 (2): 220–5. doi:10.1093/schbul/sbm163. PMC 2632409. PMID 18203757. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2632409/.
- ^ Bentall RP, Fernyhough C (August 2008). "Social Predictors of Psychotic Experiences: Specificity and Psychological Mechanisms". Schizophr Bull 34 (6): 1012–20. doi:10.1093/schbul/sbn103. PMC 2632492. PMID 18703667. http://schizophreniabulletin.oxfordjournals.org/cgi/content/abstract/sbn103v1.
- ^ van Os J (April 2004). "Does the urban environment cause psychosis?". Br J Psychiatry 184 (4): 287–8. doi:10.1192/bjp.184.4.287. PMID 15056569. http://bjp.rcpsych.org/cgi/pmidlookup?view=long&pmid=15056569.
- ^ Sundquist K, Frank G, Sundquist J (April 2004). "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. doi:10.1192/bjp.184.4.293. PMID 15056572. http://bjp.rcpsych.org/cgi/pmidlookup?view=long&pmid=15056572.
- ^ Eaton WW, Mortensen PB, Frydenberg M (June 2000). "Obstetric factors, urbanization and psychosis". Schizophr. Res. 43 (2–3): 117–23. doi:10.1016/S0920-9964(99)00152-8. PMID 10858630. http://linkinghub.elsevier.com/retrieve/pii/S0920-9964(99)00152-8.
- ^ Pedersen CB, Mortensen PB (November 2001). "Evidence of a dose-response relationship between urbanicity during upbringing and schizophrenia risk". Arch. Gen. Psychiatry 58 (11): 1039–46. doi:10.1001/archpsyc.58.11.1039. PMID 11695950. http://archpsyc.ama-assn.org/cgi/pmidlookup?view=long&pmid=11695950.
- ^ Krabbendam L, van Os J (October 2005). "Schizophrenia and urbanicity: a major environmental influence—conditional on genetic risk". Schizophr Bull 31 (4): 795–9. doi:10.1093/schbul/sbi060. PMID 16150958. http://schizophreniabulletin.oxfordjournals.org/cgi/content/full/31/4/795#BIB37.
- ^ Bebbington P, Kuipers L (August 1994). "The predictive utility of expressed emotion in schizophrenia: an aggregate analysis". Psychol Med 24 (3): 707–18. doi:10.1017/S0033291700027860. PMID 7991753.
- ^ Bentall RP; Fernyhough C, Morrison AP, Lewis S, Corcoran R (2007). "Prospects for a cognitive-developmental account of psychotic experiences". Br J Clin Psychol 46 (Pt 2): 155–73. doi:10.1348/014466506X123011. PMID 17524210.
- ^ Subotnik, KL; Goldstein, MJ, Nuechterlein, KH, Woo, SM and Mintz, J (2002). "Are Communication Deviance and Expressed Emotion Related to Family History of Psychiatric Disorders in Schizophrenia?". Schizophrenia Bulletin 28 (4): 719–29. PMID 12795501.
- ^ MacPherson M (PDF). "Psychological Causes of Schizophrenia". http://www-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/pmc/articles/PMC2659314/pdf/sbn179.pdf.
- ^ Brichford, Connie. "Schizophrenia and Relationships". Article. Everyday health. http://www.everydayhealth.com/schizophrenia/schizophrenia-and-relationships.aspx. Retrieved 26 November 2011.
- ^ R.D. Laing's and Aaron Esterson. Sanity, Madness and the Family (1964)
- ^ Bateson G, Jackson DD, Haley J, Weakland JH (1956). "Toward a theory of schizophrenia". Behavioral Science 1 (4): 251–264. doi:10.1002/bs.3830010402.
- ^ Jaynes J (1976). The origin of consciousness in the breakdown of the bicameral mind. Boston: Houghton Mifflin. ISBN 0-395-20729-0.
- ^ Polimeni J, Reiss JP (March 2002). "How shamanism and group selection may reveal the origins of schizophrenia". Med. Hypotheses 58 (3): 244–8. doi:10.1054/mehy.2001.1504. PMID 12018978. http://linkinghub.elsevier.com/retrieve/pii/S030698770191504X. Retrieved 2008-07-07.
- ^ DeMause L (2002). "The seven stages of historical personality". Emotional Life of Nations. Other Press (NY). ISBN 1-892746-98-0. http://primal-page.com/ps2.htm. Retrieved 2008-07-07.
- ^ Kurtz P (1991). The transcendental temptation: a critique of religion and the paranormal. Buffalo, N.Y: Prometheus Books. ISBN 0-87975-645-4.
- ^ Broome MR, Woolley JB, Tabraham P et al. (November 2005). "What causes the onset of psychosis?". Schizophr. Res. 79 (1): 23–34. doi:10.1016/j.schres.2005.02.007. PMID 16198238.
- ^ Lewis R (March 2004). "Should cognitive deficit be a diagnostic criterion for schizophrenia?" (PDF). J Psychiatry Neurosci 29 (2): 102–13. PMC 383342. PMID 15069464. http://www.cma.ca/multimedia/staticContent/HTML/N0/l2/jpn/vol-29/issue-2/pdf/pg102.pdf.
- ^ Brüne M, Abdel-Hamid M, Lehmkämper C, Sonntag C (May 2007). "Mental state attribution, neurocognitive functioning, and psychopathology: what predicts poor social competence in schizophrenia best?". Schizophr Res 92 (1–3): 151–9. doi:10.1016/j.schres.2007.01.006. PMID 17346931.
- ^ Sitskoorn MM, Aleman A, Ebisch SJ, Appels MC, Kahn RS (December 2004). "Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis". Schizophr Res 71 (2–3): 285–95. doi:10.1016/j.schres.2004.03.007. PMID 15474899.
- ^ Cohen AS, Docherty NM (July 2004). "Affective reactivity of speech and emotional experience in patients with schizophrenia". Schizophr Res 69 (1): 7–14. doi:10.1016/S0920-9964(03)00069-0. PMID 15145465.
- ^ Smith B, Fowler DG, Freeman D et al. (September 2006). "Emotion and psychosis: links between depression, self-esteem, negative schematic beliefs and delusions and hallucinations". Schizophr Res 86 (1–3): 181–8. doi:10.1016/j.schres.2006.06.018. PMID 16857346.
- ^ Beck AT (2004). "A cognitive model of schizophrenia". Journal of Cognitive Psychotherapy 18 (3): 281–8. doi:10.1891/jcop.18.3.281.65649. http://www.atypon-link.com/SPC/doi/abs/10.1891/jcop.18.3.281.65649?cookieSet=1&journalCode=jcop.
- ^ Horan WP, Blanchard JJ (April 2003). "Emotional responses to psychosocial stress in schizophrenia: the role of individual differences in affective traits and coping". Schizophr Res 60 (2–3): 271–83. doi:10.1016/S0920-9964(02)00227-X. PMID 12591589.
- ^ Tarrier N, Turpin G (July 1992). "Psychosocial factors, arousal and schizophrenic relapse. The psychophysiological data". Br J Psychiatry 161: 3–11. doi:10.1192/bjp.161.1.3. PMID 1638327.
- ^ Barrowclough C, Tarrier N, Humphreys L, Ward J, Gregg L, Andrews B (February 2003). "Self-esteem in schizophrenia: relationships between self-evaluation, family attitudes, and symptomatology". J Abnorm Psychol 112 (1): 92–9. doi:10.1037/0021-843X.112.1.92. PMID 12653417.
- ^ Birchwood M, Meaden A, Trower P, Gilbert P, Plaistow J (March 2000). "The power and omnipotence of voices: subordination and entrapment by voices and significant others". Psychol Med 30 (2): 337–44. doi:10.1017/S0033291799001828. PMID 10824654.
- ^ Honig A, Romme MA, Ensink BJ, Escher SD, Pennings MH, deVries MW (October 1998). "Auditory hallucinations: a comparison between patients and nonpatients". J Nerv Ment Dis 186 (10): 646–51. doi:10.1097/00005053-199810000-00009. PMID 9788642. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0022-3018&volume=186&issue=10&spage=646.
- ^ Cognitive therapy for delusions, voices and paranoia / Paul Chadwick, Max Birchwood, Peter Trower. Chadwick, Paul (Paul D.) Chichester, England ; New York ; Brisbane : John Wiley & Sons, 1996.
- ^ Colin R (2004). Schizophrenia: Innovations in Diagnosis and Treatment. Haworth Press. ISBN 0-7890-2269-9.
- ^ Sass LA, Parnas J (2003). "Schizophrenia, consciousness, and the self". Schizophr Bull 29 (3): 427–44. PMID 14609238. http://schizophreniabulletin.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=14609238.
- ^ Lysaker PH, Lysaker JT (September 2008). "Schizophrenia and Alterations in Self-experience: A Comparison of 6 Perspectives". Schizophr Bull 36 (2): 331–40. doi:10.1093/schbul/sbn077. PMC 2833111. PMID 18635676. http://schizophreniabulletin.oxfordjournals.org/cgi/content/abstract/sbn077v3.
- ^ Crow TJ (August 1997). "Schizophrenia as failure of hemispheric dominance for language". Trends Neurosci. 20 (8): 339–43. doi:10.1016/S0166-2236(97)01071-0. PMID 9246721. http://linkinghub.elsevier.com/retrieve/pii/S0166223697010710. Retrieved 2008-07-07.
- ^ http://www.alternativementalhealth.com/articles/causesofschizophrenia.htm Twenty-Nine Medical Causes of "Schizophrenia" Excerpted from Nutrition and Mental Illness by the late Carl C. Pfeiffer, Ph.D., M.D. Accessed 06-22-2011
- ^ Bowman, M. B.; Lewis, M. S. (1982). "The copper hypothesis of schizophrenia: A review". Neuroscience and biobehavioral reviews 6 (3): 321–328. PMID 7177508.
- ^ Mackay-Sim, A.; Féron, F. O.; Eyles, D.; Burne, T.; McGrath, J. (2004). Schizophrenia, vitamin D, and brain development. "Disorders of Synaptic Plasticity and Schizophrenia". International review of neurobiology. International Review of Neurobiology 59: 351–380. doi:10.1016/S0074-7742(04)59014-1. ISBN 9780123668608. PMID 15006495.