Does schizophrenia run in families?
Irving Gottesman
Family studies on schizophrenia were reviewed. That the disorder runs in families did not suggest it was genetically inherited, since cultural transmission occurs from parents to children. Twin and adoption studies were presented as the standard methods to disentangle contributions from genes and the environment. Gottesman used a computer-based method for calculating the odds of becoming schizophrenic based on the many causes. The book examines the problems caused by schizophrenia for relatives of patients and for society at large, larger-scale ones exemplified by the eugenics policies of states such as Nazi Germany. Two final chapters cover molecular biology and neuroanatomy briefly. Newer methods of behavioral genetics being researched at the time of publication, such as linkage analysis which used the likelihood of neighboring genes being inherited together, were not covered.
Social construction of schizophrenia
Other genetic analysis examines the role of alleles. One study ascribes links between schizophrenia and bipolar disorder by studying a total group of 6909 Europeans, both diagnosed and undiagnosed. Another study suggests that Genetic markers may be very dissimilar among different lineages of DNA in people of different cultures, making an international commonality in genetics as a precipitating factor in schizophrenia difficult to identify.>
Causes of schizophrenia
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.
Pamela Sklar
Sklar’s research and clinical work focused on characterizing the biology underlying mental illnesses, in particular schizophrenia and bipolar disorder. Her studies of DNA variation have identified both common and rare genetic changes associated with these disorders. While working at the Broad Institute, Sklar co-founded the Stanley Center for Psychiatric Research and served as its genetics director. By studying thousands of affected individuals and comparing them with thousands of healthy people, she was the first to associate recurrent large deletions of DNA with the onset of schizophrenia and also found the first broadly reproducible genetic variants in schizophrenia as well as bipolar disorder using genome-wide association studies. Sklar and her colleagues discovered a molecular basis for polygenicity in schizophrenia among both rare and common DNA alterations and that schizophrenia and bipolar disorder are genetically linked through DNA variants that contribute to both illnesses. In 2011, Sklar joined the Icahn School of Medicine at Mount Sinai and became founding chief of the Division of Psychiatric Genomics there. The division’s scope includes stem cell biology, neurocognition, statistical genetics, and imaging approaches to elucidate the biological variation causing mental illness. While at Mount Sinai, Sklar published papers demonstrating that schizophrenia is linked to many ultra-rare genetic variants. Sklar served as a principal investigator for the Psychiatric Genomics Consortium, the largest international collaboration in the psychiatric community. She helped lead the consortium’s working group on bipolar disorder. She also co-founded the International Schizophrenia Consortium. After she died, Icahn School of Medicine renamed their Division of Psychiatric Genomics in her honor.
Factor H
Alterations in the immune response are involved in pathogenesis of many neuropsychiatric disorders including schizophrenia. Recent studies indicated alterations in the complement system, including hyperactivation of the alternative complement pathway in patients with schizophrenia. It was investigated functional single nucleotide polymorphisms (SNPs) of gene encoding factor H (CFH), and found CFH rs424535 (2783-526T >A) SNP was positively associated with schizophrenia, so rs424535*A minor allele of the CFH gene may represent a risk factor for schizophrenia.
Cognitive epidemiology
Schizophrenia is chronic and disabling mental illness that is characterized by abnormal behavior, psychotic episodes and inability to recognize between reality and fantasy. Even though schizophrenia can severely handicap its sufferers, there has been a great interest in the relationship of this disorder and intelligence. Interest in the association of intelligence and schizophrenia has been widespread partly stems from the perceived connection between schizophrenia and creativity, and posthumous research of famous intellectuals that have been insinuated to have suffered from the illness. Hollywood played a pivotal role popularizing the myth of the schizophrenic genius with the movie A Beautiful Mind that depicted the life story of Nobel Laureate, John Nash and his struggle with the illness.
Childhood schizophrenia
In the DSM-III-R (1987), DSM-IV (1994), DSM-IV-TR (2000), DSM-5 (2013) there are no "childhood schizophrenia". The rationale for this approach was that since the clinical picture of adult schizophrenia and childhood schizophrenia is identical, childhood schizophrenia should not be a separate disorder.
National Alliance on Mental Illness
The Family-to-Family program provides general information about mental illness and how it is currently treated. The programs cover mental illnesses including schizophrenia, depression, bipolar disorder, etc.), as well as the benefits and side effects of medications. Family-to-Family, like the rest of NAMI programs, takes a biologically-based approach to explaining mental illness and its treatments.
Social construction of schizophrenia
Links between autism and schizophrenia have been studied (as above). The implications are both conditions are part of the same spectrum. From clinical observation, both conditions cause a disruption in normative social functioning which may be mild or severe depending on the individual's position within the spectrum. Simon Fraser University researcher Crespi has examined how social cognition is under developed in autism and highly developed in Psychoses and outlines how the relationship between autism and schizophrenic spectrum is not one that has been explored in detail in the latter part of the 20th century. His research hypothesises that the genetic marker for both conditions may lie in the same location. His team have identified four loci that are diametrically opposed in terms of diagnoses of autism and schizophrenia with corresponding deletions for one condition or duplications for the other:
Professor Timothy Crow, from the University Department of Psychiatry at Oxford University, has long argued that schizophrenia as a condition came about as a result of natural selection. He has argued that schizophrenia is a by-product of the development of language, resulting from an evolutionary change approximately 150,000 years ago, that persisted due to sexual selection. However, conversely to study in polygenes or multiple allele combinations, he maintains that the answer lies in:
Mechanisms of schizophrenia
Another hypothesis postulates that inflammation and immune system abnormalities could play a central role in the disease. Abnormal immune system development may help explain roles of environmental effect such as prenatal hazards, post-pubertal onset, stress, climate, and infections, in addition to genetic effects. The immune hypotheses is supported by findings of high levels of immune markers in the blood of schizophrenia patients. High levels of immune markers have also been associated with having more severe psychotic symptoms. Furthermore, a meta-analysis of genome-wide association studies discovered that 129 out of 136 single-nucleotide polymorphisms (SNP) significantly associated with schizophrenia were located in the major histocompatibility complex region of the genome.
DISC1
Besides large familial-based studies in which the pedigrees of various family members are examined, twin studies have also been a source of support for researchers in the investigation of DISC1. In a meta-analysis of twin studies, twelve out of fourteen were found to support the fact that from a genetic perspective, schizophrenia is a complex trait that depends on both genetic and environmental factors. Such findings have encouraged researchers to continue with both macro-analysis of the disorders afflicting individuals with the mutation, as well as explore the micro-level.
Epigenetics of schizophrenia
There is a great deal of evidence to show that schizophrenia is a heritable disease. One key piece of evidence is a twin study that showed that the likelihood of developing the disease is 53% for one member of monozygotic twins (twins with same genetic code), compared to the 15% for dizygotic twins, who don't share the exact DNA. Others question the evidence of heritability due to different definitions of schizophrenia and the similar environment for both twins.
Schizophrenia
Schizophrenia is diagnosed based on criteria in either the American Psychiatric Association's (APA) fifth edition of the "Diagnostic and Statistical Manual of Mental Disorders" (DSM 5), or the World Health Organization's International Statistical Classification of Diseases and Related Health Problems (ICD-10). These criteria use the self-reported experiences of the person and reported abnormalities in behavior, followed by a clinical assessment by a mental health professional. Symptoms associated with schizophrenia occur along a continuum in the population and must reach a certain severity and level of impairment, before a diagnosis is made. As of 2013 there is no objective test.
Interpretation of Schizophrenia
Arieti maintains that in every case of schizophrenia that he studied serious family disturbance was found. When the patient idealizes the parent the idealized image of the parent is maintained in the patient's mind at the expense of an unbearable self-image. He speculates that psychosis starts only when the malevolent image of the parent is transformed "into a distressing other". The parent or parents alters enter the mind accusing the patient of "bad child" or other equivalent accusations in voices that the adult patient hears.
Paranoid schizophrenia
It has a strong hereditary component with a first degree parent or sibling. There is some possibility that there are environmental influences including "prenatal exposure to a viral infection, low oxygen levels during birth (from prolonged labor or premature birth), exposure to a virus during infancy, early parental loss or separation, and verbal, physical or sexual abuse in childhood". Eliminating any of these factors could help reduce an individual's future risk of developing paranoid schizophrenia.
Michael C. O'Donovan
Michael C. O'Donovan is a Scottish psychiatric geneticist who researches the genetics of schizophrenia. He is a clinical professor in the Division of Psychological Medicine and Clinical Neurosciences and the deputy director of the MRC Centre for Neuropsychiatric Genetics and Genomics at the Cardiff University School of Medicine in Cardiff, Wales. He also leads the Schizophrenia Group of the Psychiatric Genomics Consortium. Educated at Glasgow University, he also serves as Academic Psychiatry Lead for the Royal College of Psychiatrists in Wales. He was lead author of a 2014 study in "Nature" which identified over 100 genetic loci associated with an increased risk of schizophrenia. The study, the largest of its kind undertaken at the time, was covered extensively in the media. It was also praised by Thomas Insel, the then-director of the National Institute of Mental Health, who described the study as "a big step forward".
History of schizophrenia
In 1933 Dr. Ernest Rüdin, who was in-charge of the Genealogical-Demographic Department of the German Institute for Psychiatric Research in Munich, expressed his interest in schizophrenia and with the help of Feanz Kallmann, supported the idea that schizophrenia was a Mendelian inherited disease. Kallmann believed that the disorder was transmitted by a regressive gene.
Epigenetics of schizophrenia
The fact that even monozygotic twins don't share a 100% concordance rate suggests environmental factors play a role in the vulnerability and development of the disorder. There are various environmental factors that have been suggested, including the use of marijuana, complications during pregnancy, socioeconomic status and environment, and maternal malnutrition. As the field of epigenetics advances, these and other external risk factors are likely to be considered in epidemiological studies.
Races and creatures in His Dark Materials
When the effects of a Spectre attack on a human are explained to Will, he hypothesises that they, or similar creatures, may also exist in our universe and may cause mental illness. This opinion is formed by the case of his mother, who seems to be suffering from paranoia and other symptoms of a disorder similar to schizophrenia.
Murray Bowen
From 1954 to 1959, Bowen worked at the National Institute of Mental Health, Bethesda, Maryland, where he continued to develop the theory that would be named after him: "Bowen Theory." At that time, family therapy was still only a by-product of theory. Bowen did his initial research on parents who lived with one adult schizophrenic child, which he thought could provide a paradigm for all children. After defining the field of "family therapy" he started integrating new concepts with the theory, noting that none of this had previously been addressed in the psychological literature. His approach gained national attention within two years of its introduction.
Olfactory reference syndrome
The importance of a family history of mental illness or other conditions in ORS is unclear, because most reported cases have lacked this information. In some cases, there has been reported psychiatric and medical conditions in first degree relatives such as schizophrenia, psychosis, alcoholism, suicide, affective disorders, obsessive compulsive disorder, anxiety, paranoia, neurosis, sociopathy, and epilepsy. Sometimes more than one family member had a noteworthy condition.
Causes of schizophrenia
Although twin studies and family studies have indicated a large degree of heritability for schizophrenia, the exact genetic causes remain unclear. Recently however, quite some large-scale studies have now 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).
Hypochondriasis
Family studies of hypochondriasis do not show a genetic transmission of the disorder. Among relatives of people suffering from hypochondriasis only somatization disorder and generalized anxiety disorder were more common than in average families. Other studies have shown that the first degree relatives of patients with OCD have a higher than expected frequency of a somatoform disorder (either hypochondriasis or body dysmorphic disorder).
Epigenetics of schizophrenia
While there haven't been many studies linking environmental factors to schizophrenia-related epigenetics mechanisms at this point in the field, a few studies have shown interesting results.
Advanced paternal age is one of the risk factors for schizophrenia, according to recent research. This is through mutagenesis, which cause further spontaneous changes, or through genomic imprinting. As the parent ages, more and more errors may occur in the epigenetic process. There is also evidence of the association between the inhalation of benzene through the burning of wood and schizophrenic development. This might occur through epigenetic changes. Methamphetamine has also been linked to schizophrenia or similar psychotic symptoms. A recent study found that methamphetamine users had altered DNMT1 levels, similar to how patients with schizophrenia have shown abnormal levels of DNMT1 in GABAergic neurons.
Genain quadruplets
The Genain quadruplets (born in 1930) are a set of identical quadruplet sisters. All four developed schizophrenia, suggesting a large genetic component to the cause of the disease. The pseudonym "Genain", used to protect the identity of the family, comes from the Greek, meaning "dire "(αἶνος)" birth "(γεν-). The sisters were given the pseudonyms Nora, Iris, Myra and Hester, to represent each of the four letters in NIMH, the acronym for the United States National Institute of Mental Health. Nora, Iris, and Hester were hospitalized for their schizophrenia at least once each. As of 2011, Iris and Hester have died.
Causes of schizophrenia
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.
Causes of schizophrenia
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 variants) 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. 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.
John Falloon
Falloon's cousin, Ian Falloon, was one of the first psychiatrists to have family involved in the treatment of schizophrenia.
Paternal age effect
Schizophrenia is thought by some to be associated with advanced paternal age but it is not proven. Some studies examining autism spectrum disorder (ASD) and advanced paternal age have demonstrated an association between the two, although there also appears to be an increase with maternal age.
Prognosis of schizophrenia
Several factors are associated with a better prognosis: female gender, acute (vs. insidious) onset of symptoms, older age of first episode, predominantly positive (rather than negative) symptoms, presence of mood symptoms and good premorbid functioning. Most studies done on this subject, however, are correlational in nature, and a clear cause-and-effect relationship is difficult to establish. Evidence is also consistent that negative attitudes towards individuals with schizophrenia can have a significant adverse impact, especially within the individual's family. Family members' critical comments, hostility, authoritarian and intrusive or controlling attitudes (termed high 'expressed emotion' or 'EE' by researchers) have been found to correlate with a higher risk of relapse in schizophrenia across cultures.
DISC1
Family studies continue to provide an important approach towards deepening understanding of the biological nature of the gene and its clinical implications. While the original Scottish family in which DISC1 was discovered is still being considered, other familial populations in different countries have also become the focus of research in the past decade. In 2005, an American family was found to also possess a frameshift mutation in the DISC1 gene, which again co-segregated with schizophrenia and schizoaffective disorder. Characterized by a deletion of four base-pairs, the mutation was found in two siblings, one with schizophrenia and the other with schizoaffective disorder. Similar studies have also been done with Taiwanese and Finnish families.
DISC1
Schizophrenia affects 1% of the general population and is highly heritable, providing an indication of a genetic basis. DISC1 has been associated with neurological abnormalities such as delusions, deficits in long term and working memory, diminution of gray matter volume in hippocampal and prefrontal regions. These abnormalities are also seen as symptoms of schizophrenia. As DISC1 function is involved in neurogenesis and neuroplasticity, vulnerability to schizophrenia may involve dysfunction in the hippocampus, a brain region in which adult neurogenesis occurs.
Schizoaffective disorder
The historical clinical observation that schizoaffective disorder is an overlap of schizophrenia and mood disorders is explained by genes for both illnesses being present in individuals with schizoaffective disorder; specifically, recent research shows that schizophrenia and mood disorders share common genes "and" polygenic variations.
Schizoaffective disorder was included as a subtype of schizophrenia in DSM-I and DSM-II, though research showed a schizophrenic cluster of symptoms in individuals with a family history of mood disorders whose illness course, other symptoms and treatment outcome were otherwise more akin to bipolar disorder than to schizophrenia. DSM-III placed schizoaffective disorder in "Psychotic Disorders Not Otherwise Specified" before being formally recognized in DSM-III-R. DSM-III-R included its own diagnostic criteria as well as the subtypes, bipolar and depressive. In DSM-IV, published in 1994, schizoaffective disorders belonged to the category "Other Psychotic Disorders" and included almost the same criteria and the same subtypes of illness as DSM-III-R, with the addition of mixed bipolar symptomatology.
Social construction of schizophrenia
Whilst the definitive cause(s) of schizophrenia remain unknown, research has indicated strong links between genetic make-up, social predisposing factors or stressors and environmental conditions in relation to the development and onset of schizophrenia and other conditions. International geneticists are working towards identifying a gene for Schizophrenia, combined efforts are at the SzGene database. In the course of this research geneticists have identified specific genes or copy number variants or alleles that may explain the comorbidity of various conditions.
Causes of schizophrenia
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 altered dopamine neurotransmission, a process that has been termed "sensitization". Childhood trauma, and bereavement or separation in families, have been found to be risk factors for schizophrenia and psychosis.
Interpretation of Schizophrenia
Arieti then describes the psychogenic factors that lead to the disorder. The family environment and psychodynamics in the etiology of psychosis comes under scrutiny. Arieti describes the building of neurotic and psychotic defense mechanisms; the emerging schizoid personality, and fully developed schizophrenia understood as an injury to the inner self. Arieti believes that a state of extreme anxiety originating in early childhood produces vulnerability for the whole life of the individual.
Neurogenomics
Twin studies have revealed that schizophrenia, bipolar disorder, autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) are highly heritable, genetically complex psychiatric disorders. However, linkage studies have largely failed at identifying causative variants for psychiatric disorders such as these, primarily because of their complex genetic architecture. Multiple low penetrance risk variants can be aggregated in affected individuals and families, and sets of causative variants could vary across families. Studies along these lines have determined a polygenic basis for several psychiatric disorders. Several independently occurring "de novo" mutations in patients Alzheimer's Disease have been found to disrupt a shared set of functional pathways involved with neuronal signalling, for example. The quest to understand the causative biology of psychiatric disorders is hence greatly assisted by the ability to analyse entire genomes of affected and unaffected individuals in an unbiased manner.
Epigenetics of schizophrenia
Historically, schizophrenia has been studied and examined through different paradigms, or schools of thought. In the late 1870s, Emil Kraepelin started the idea of studying it as an illness. Another paradigm, introduced by Zubin and Spring in 1977, was the stress-vulnerability model where the individual has unique characteristics that give him or her strengths or vulnerabilities to deal with stress, a predisposition for schizophrenia. More recently, with the decoding of the human genome, there had been a focus on identifying specific genes to study the disease. However, the genetics paradigm faced problems with inconsistent, inconclusive, and variable results. The most recent school of thought is studying schizophrenia through epigenetics.
Imprinted brain theory
However, an extreme genomic imprinting in favor of maternal genes is argued to cause psychosis such as in schizophrenia spectrum disorders while an extreme genomic imprinting in favor of paternal genes is argued to cause autism spectrum disorders. Thus, people with schizophrenia empathize and read too much into situations and see hidden intentions everywhere, causing delusions and paranoia, while people with autism seem to be blind to the intentions of others. This could be confirmed by a recent neuroimaging study.
Schizophrenia
Schizophrenia is a mental disorder characterized by abnormal behavior, strange speech and a decreased ability to understand reality. Other symptoms include false beliefs, unclear or confused thinking, hearing voices that do not exist, reduced social engagement and emotional expression and lack of motivation. People with schizophrenia often have additional mental health problems such as anxiety, depressive or substance-use disorders. Symptoms typically come on gradually, begin in young adulthood and in many cases never resolve.
The causes of schizophrenia include environmental and genetic factors. Possible environmental factors include being raised in a city, cannabis use during adolescence, certain infections, the age of a person's parents, and poor nutrition during pregnancy. Genetic factors include a variety of common and rare genetic variants. Diagnosis is based on observed behavior, the person's reported experiences and reports of others familiar with the person. During diagnosis, a person's culture must also be taken into account. As of 2013, there is no objective test. Schizophrenia does not imply a "split personality" or dissociative identity disorder, conditions with which it is often confused in public perception.
The mainstay of treatment is antipsychotic medication, along with counselling, job training and social rehabilitation. It is unclear whether typical or atypical antipsychotics are better. In those who do not improve with other antipsychotics, clozapine may be tried. In more serious situations where there is risk to self or others, involuntary hospitalization may be necessary, although hospital stays are now shorter and less frequent than they once were.
About 0.3% to 0.7% of people are affected by schizophrenia during their lifetimes. In 2013, there were an estimated 23.6 million cases globally. Males are more often affected and on average experience more severe symptoms. About 20% of people eventually do well, and a few recover completely; about 50% have lifelong impairment. Social problems, such as long-term unemployment, poverty and homelessness, are common. The average life expectancy of people with the disorder is 10–25 years less than that of the general population. This is the result of increased physical health problems and a higher suicide rate (about 5%). In 2015, an estimated 17,000 people worldwide died from behavior related to, or caused by, schizophrenia.
E. Fuller Torrey
In the 1950s, it was commonly thought that schizophrenia was caused by 'bad parenting'. Torrey has argued that this theory had a toxic effect on parents. His sister had severe schizophrenia and spent most of five decades in hospitals and nursing homes until her death.
Endophenotype
The four primary criteria for an endophenotype are that it is present in probands with the disorder, that it is not state-related (that is, it does not occur only during clinical episodes) but instead is present early in the disease course and during periods of remission, that it is observed in unaffected family members at a higher rate than in the general population, and that it is heritable. 
Some distinct genes that could underlie certain endophenotypic traits in schizophrenia include:
Childhood schizophrenia
The grey matter in the cerebral cortex of the brain shrinks over time in people with schizophrenia; the question of whether antipsychotic medication exacerbates or causes this has been controversial. A 2015 meta-analysis found that there is a positive correlation between the cumulative amount of first generation antipsychotics taken by people with schizophrenia and the amount of grey matter loss, and a negative correlation with the cumulative amount of second-generation antipsychotics taken.
Schizophrenia disorders in children are rare. Boys are twice as likely to be diagnosed with childhood schizophrenia. There is often an disproportionately large number of males with childhood schizophrenia, because the age of onset of the disorder is earlier in males than females by about 5 years. People have been and still are reluctant to diagnose schizophrenia early on, primarily due to the stigma attached to it.
Schizophrenia Research Forum
Schizophrenia Research Forum is a web knowledge environment dedicated to news, information resources, and discussion about research on schizophrenia.
It hosts a number of resources such as What We Know About Schizophrenia, Animal Models and Drugs in Trials.
It also hosts the "SzGene" database, an unbiased field synopsis of genetic association studies performed in schizophrenia,
though this database is no longer updated.
Causes of schizophrenia
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 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.
Theodore Lidz
Lidz noted that schizophrenogenic mothers manage to be impervious to the needs and wishes of other family members. “As her psychotic or very strange concepts remain unchallenged by the husband, they create reality within the family”. Dr. Lidz calls this phenomenon "folie à deux" (dual madness), a shared delusion between two parents. And if the delusional ideas of the dominant parent are shared by all family members, the result is a "folie en famille" (family madness).
Interpretation of Schizophrenia
A characteristic of "Homo sapiens" is a prolonged childhood with a consequently extended dependency on adults. This, according to Arieti, "is the basis of the psychodynamics of schizophrenia", a claim that also appears in later writers on child abuse such as Alice Miller and Colin Ross. Arieti reviews the paper by Frieda Fromm-Reichmann about the "schizophrenogenic" mother and reaches the tentative conclusion that only 25 percent of the mothers of people with schizophrenia in his clinical experience fit that image. However, he adds that only in a minority of schizophrenia cases "the child is able to retain the good maternal image". Arieti also mentions the work of Theodore Lidz, another trauma model author of schizophrenia. Like Lidz, Arieti emphasizes the weakness of the father of the patient with schizophrenia in the paternal role. In Arieti's own words:
Pleiotropy
A 2013 study also genetically linked five psychiatric disorders, including schizophrenia and autism. The link was a single nucleotide polymorphism of two genes involved in calcium channel signaling with neurons. One of these genes, CACNA1C, has been found to influence cognition. It has been associated with autism, as well as linked in studies to schizophrenia and bipolar disorder. These particular studies show clustering of these diseases within patients themselves or families. The estimated heritability of schizophrenia is 70% to 90%, therefore the pleiotropy of genes is crucial since it causes an increased risk for certain psychotic disorders and can aid psychiatric diagnosis.
Epidemiology of schizophrenia
However, the impact of schizophrenia tends to be highest in Oceania, the Middle East, and East Asia, while the nations of Australia, Japan, the United States, and most of Europe typically have low impact. Despite relative geographical proximity, the DALY rate of schizophrenia in Indonesia nearly doubles that of Australia (the nations with the highest and lowest respective DALY rates). Discrepancies between DALY rates and prevalence may arise from differences in availability of medical treatment: years lived with mental disorders carry significantly higher DALY values when unmedicated than when medicated.
Causes of schizophrenia
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.
Heritability of autism
A 2005 report examined the family psychiatric history of 58 subjects with Asperger syndrome (AS) diagnosed according to DSM-IV criteria. Three (5%) had first-degree relatives with AS. Nine (19%) had a family history of schizophrenia. Thirty five (60%) had a family history of depression. Out of 64 siblings, 4 (6.25%) were diagnosed with AS.
Childhood schizophrenia
Childhood schizophrenia onset is usually after a period of normal, or near normal, child development. Before the first psychosis there has been described in which strange interests, beliefs and social impairment occur, which could be confused with the deficits of the autism spectrum disorder. Hallucinations and delusions are typical for schizophrenia, but not features of autism spectrum disorder.
Psychotic depression
The families of those who have experienced psychotic depression are at increased risk for both psychotic depression and schizophrenia.
Epidemiology of schizophrenia
Schizophrenia affects around 0.3–0.7% of people at some point in their life, or 21 million people worldwide as of 2011 (about one of every 285). By using precise methods in its diagnosis and a large, representative population, schizophrenia seems to occur with relative consistency over time during the last half-century.
Schizophrenia
Despite the prior belief that schizophrenia occurs at similar rates worldwide, its frequency varies across the world, within countries, and at the local and neighborhood level. This variation has been estimated to be fivefold. It causes approximately one percent of worldwide disability adjusted life years and resulted in 20,000 deaths in 2010. The rate of schizophrenia varies up to threefold depending on how it is defined.
Drift hypothesis
A study by E. M. Goldberg and S. L. Morrison looked at the relationship between schizophrenia and social class. They wanted to find out if men, before they had been admitted to a mental hospital, drifted down the occupational scale to unskilled jobs because of their developing illness, or if it was because they were born into families with a lower social class attainment, that they developed their mental illness. They looked at men who had their first admission in a mental hospital between the ages of 25–34. They also looked at their fathers' occupation, in order to see if the social class they grew up in played a role in the development of schizophrenia. They found the men had grown up in families whose social class was similar to the general population. So the social class they grew up in did not seem to be a contributor to the development of their schizophrenia.
Childhood schizophrenia
Childhood schizophrenia (also known as childhood-onset schizophrenia, and very early-onset schizophrenia) is a schizophrenia spectrum disorder that is characterized by hallucinations, disorganized speech, delusions, catatonic behavior and "negative symptoms", such as inappropriate or blunted affect and avolition with onset before 13 years of age. The term "childhood-onset schizophrenia" and "very early-onset schizophrenia" are used to identify patients in whom the disorder manifests before the age of 13.
Anhedonia
L.J. and J.P. Chapman were the first to discuss the possibility that social anhedonia may stem from a genetic vulnerability. The Disrupted in Schizophrenia 1 (DISC1) gene has been consistently associated with risk for, and cause of, schizophrenia-spectrum disorders and other mental illnesses. More recently, DISC1 has been associated with social anhedonia within the general population. Tomppo (2009) identified a specific DISC1 allele that is associated with an increase in characteristics of social anhedonia. They also identified a DISC1 allele associated with decreased characteristics of social anhedonia, that was found to be preferentially expressed in women. More research needs to be conducted, but social anhedonia may be an important intermediate phenotype (endophenotype) between genes associated with risk for schizophrenia and phenotype of the disorder. Continued study of social anhedonia and its genetic components will help researchers and clinicians learn more about the cause of schizophrenia-spectrum disorders.
Evolutionary approaches to schizophrenia
Contrary to the previous view, there are models rooted in theories that view schizophrenia as granting beneficial powers to patients, their kin, or their social groups. This view is tries to explain the prevalence and persistence of schizophrenia over time and across cultures. Researchers using these models argue that the existence of schizophrenia in humans is not random, basing this argument on the fact that the 1% prevalence rate is higher than gene mutation rates. This view sees benefits that promote the fitness of individuals, kins, or groups and thus enhance chance of survival. The benefits of schizophrenia are likely to buffer the deficits of the disorder and thus balance the selective pressures.
Trauma model of mental disorders
From the 1940s to the 1970s prominent mental health professionals proposed trauma models as a means of understanding schizophrenia, including Harry Stack Sullivan, Frieda Fromm-Reichmann, Theodore Lidz, Gregory Bateson, Silvano Arieti and R.D. Laing. Based on their clinical work they theorised that schizophrenia appears to be induced by children's experiences in profoundly disturbed families and reflect victims attempts to cope with such families and live in societies that are inherently damaging to people's psychological well-being. In the 1950s Sullivan's theory that schizophrenia is related to interpersonal relationships was widely accepted in the United States. Silvano Arieti's book "Interpretation of Schizophrenia" won the American National Book Award in the field of science in 1975. The book advances a psychological model for understanding all the regressive types of the disorder.
Schizophrenia
A combination of genetic and environmental factors play a role in the development of schizophrenia. People with a family history of schizophrenia who have a transient psychosis have a 20–40% chance of being diagnosed one year later.
Social construction of schizophrenia
A strand of research into schizophrenia is to investigate the links between viruses that attack the immune system such as herpes and the onset of schizophrenia. Researchers in this field are hopeful that this connection may provide a cure for schizophrenia within the next 20 years.
Muller proposes that the vulnerability-stress model of analysis of schizophrenia should become the vulnerability-stress-inflammation model:
Research shows that viral infections of the immune system can dramatically increase the frequency of the onset of schizophrenia.
Causes of schizophrenia
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.
Mechanisms of schizophrenia
The exact pathophysiology of schizophrenia remains poorly understood. The most commonly supported theories are the dopamine hypothesis and the glutamate hypothesis. More recent theories center around specific dysfunction of interneurons, abnormalities in the immune system, abnormalities in myelination, and oxidative stress.
Schizoaffective disorder
Viewed broadly then, biological and environmental factors interact with a person's genes in ways which may increase or decrease the risk for developing schizoaffective disorder; exactly how this happens (the biological mechanism) is not yet known. Schizophrenia spectrum disorders, of which schizoaffective disorder is a part, have been increasingly linked to advanced paternal age at the time of conception, a known cause of genetic mutations. The physiology of people diagnosed with schizoaffective disorder appears to be similar, but not identical, to that of those diagnosed with schizophrenia and bipolar disorder; however, human neurophysiological function in normal brain and mental disorder syndromes is not fully understood.
Double bind
Bateson's double bind theory was never followed up by research into whether family systems imposing systematic double binds might be a cause of schizophrenia. This complex theory has been only partly tested, and there are gaps in the current psychological and experimental evidence required to establish causation [citation?]. The current understanding of schizophrenia emphasizes the robust scientific evidence for a genetic predisposition to the disorder, with psychosocial stressors, including dysfunctional family interaction patterns, as secondary causative factors in some instances.
Causes of schizophrenia
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.
Causes of mental disorders
Family-linkage and twin studies have indicated that genetic factors often play an important role in the development of mental disorders. The reliable identification of specific genetic susceptibility to particular disorders, through linkage or association studies, has proven difficult. This has been reported to be likely due to the complexity of interactions between genes, environmental events, and early development or to the need for new research strategies. The heritability of behavioral traits associated with mental disorder may be greater in permissive than in restrictive environments, and susceptibility genes probably work through both "within-the-skin" (physiological) pathways and "outside-the-skin" (behavioral and social) pathways. Investigations increasingly focus on links between genes and endophenotypes—more specific traits (including neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological)—rather than disease categories. With regard to a prominent mental disorder, schizophrenia, for a long time consensus among scientists was that certain alleles (forms of genes) were responsible for schizophrenia, but some research has indicated only multiple, rare mutations thought to alter neurodevelopmental pathways that can ultimately contribute to schizophrenia; virtually every rare structural mutation was different in each individual.
Evolution of schizophrenia
This hypothesis purports that schizophrenia is a vestigial behaviour that was once adaptive to hunting and gathering tribes. Psychosis prompts shamans to communicate with the spirit world, which results in the formation of religious myths. The shamanistic theory posits that the universal presence of shamanism in all hunting and gathering societies is likely due to heritable factors – the same heritable factors that support the worldwide distribution of schizophrenia. One modern version of the theory has invoked the evolutionary mechanism of group selection in order to explain the apparent genetic-based task specialization of shamanism.
Irving Gottesman
"Schizophrenia Genesis" starts with the history of schizophrenia. Gottesman takes the view that schizophrenia is a disease of the industrial world. because it is not mentioned in the Bible, by the ancient Greeks, the ancient physicians, or authors including Shakespeare. He saw it first mentioned by physicians in 1809 and by Balzac in a short story in 1832, showing minimally the disorder had by then been recognized as such. In 1896, Kraepelin defined its symptoms, and his student Ernst Rüdin began a genetic study of its transmission in 1916.} The book noted that schizophrenia existed across cultures and its rates had stayed steady for fifty years.
Hypofrontality
Schizophrenia is a mental disorder that most commonly affects social and emotional functioning. Besides emotional and psychological influences, it is believed that genetics and early development play a role in the onset of schizophrenia. The physical aspects of the disease are actual differences in the brain of the affected. Mostly in the frontal cortex, these differences often stem from a smaller brain volume, and the decreased blood flow that results influences the hypofrontality. It has not been determined if the reduction of the frontal cortex is the ultimate cause of the symptoms, or if the condition worsens as the symptoms develop.
Childhood schizophrenia
Schizophrenia has no definite cause; however, certain risk factors such as family history seem to correlate. There is no known cure, but childhood schizophrenia is controllable with the help of behavioral therapies and medications.
Sarnoff A. Mednick
At the time the High-Risk-for-Schizophrenia study began, in 1962, the offspring of the women with schizophrenia were average age 15 and had not come into the risk period for schizophrenia. (See a review by Cannon and Mednick, 1993.) By the early eighties, many of the study's subjects had fallen ill with schizophrenia. Colleagues and students of Mednick began to examine the association between schizophrenia outcomes and earlier risk factors. Perhaps the first study to support Kraepelin's notion of dementia praecox (that persons with schizophrenia had early dementia), was a study that showed that offspring of those with schizophrenia who had the most serious symptomatology had enlarged ventricles on CT scans suggestive of brain atrophy. In a study by Silverton et al. those with the most severe schizophrenia symptoms on outcome had low birthweights decades before. Their hypothesis that low birthweight might be associated with insults in utero was corroborated. In a follow-up study, the authors tested the notion that schizophrenia is the result of a genetic by environmental interaction, that is that insults in utero may be specifically stressful to persons with a brain vulnerability to schizophrenia. In a follow-up study, Leigh Silverton and Sarnoff Mednick at the University of Southern California hypothesized an interaction between genetic risk for schizophrenia might be most vulnerable to insults in utero. This would be considered a gene X environment interaction, a model for the pathogenesis of schizophrenia that Silverton and Mednick began working on in the early eighties. The authors conducted another study in which they separated subjects into high-risk and "super-high risk" and measured the interaction between genetic risk and birthweight in its effect on ventricular-brain ratio. They found that those most vulnerable to low birthweight, a variable representing subtle birth difficulties in utero, were most likely to have early cerebral ventricular enlargement on CT-scans. At the time, the idea both that schizophrenia was a brain disease and that it could represent a gene x environment interaction was novel. This was possibly the first study to support the notion that earlier findings of brain abnormalities in schizophrenia were not only etiologically significant but related to early environmental factors (such as pregnancy and birth complications or in utero insults), and that pathogenesis was related to factors that could be prevented. A study by Cannon, Mednick, and Parnas (1989) also showed an interaction between perinatal insults (an environmental factor) and very high genetic risk for schizophrenia in determining brain deficits in schizophrenia.
Irving Gottesman
Results of studies comprise another third of the core of "Schizophrenia and Genetics". The data showed that genes made a person likely to develop schizophrenia under environmental pressures. The study was not designed to find the genes responsible, but the authors hypothesized there would be several acting in tandem.Contextual elements responsible could not be identified, though some, such as an overly protective mother, birth order, natal weight, and social and economic elements were ruled out. Gottesman and Shields found roughly half of identical twins had a shared schizophrenic or non-schizophrenic status, but only one-eleventh of fraternal twins had such a shared diagnosis. MMPI scales coincided among identical twin pairs but not among fraternal twin pairs. The Object Sorting Test showed no useful relations. Those meeker than their twins were more liable to develop schizophrenia where their genes already put them at risk.
Icahn Institute for Genomics and Multiscale Biology
In January 2014, scientists from the institute’s Division of Psychiatric Genomics including Pamela Sklar published two papers in the journal Nature that explored the genetic complexity of schizophrenia. The exome sequencing studies of populations in Bulgaria and Sweden revealed that the disorder is likely caused by a lot of rare genetic mutations rather than a few common mutations. The projects also established the world’s largest database on schizophrenia.
The Little Man (comics)
The strip is an anti-psychiatric tract that takes the stance that schizophrenia is not a disease, but a way to label people "-- not by looking for signs of disease but by looking for socially unacceptable beliefs and behaviour." Brown's mother doesn't actually appear in the strip, nor is she directly talked about except briefly in the footnotes, although she appears in "" and "I Never Liked You". In "I Never Liked You" she passes away in the hospital.
Animal model of schizophrenia
Studies involving twins have shown that schizophrenia is a heritable disease. While no one gene is responsible for the disease, a large number of possible genes have been identified. Genetic animal models of schizophrenia often involve knockout mice, genetically modified mice where one or more of these genes is removed or disrupted.
History of schizophrenia
Both Rüdin's and Kallmann’s theories coincided with the growing interest in the idea of Rassenhygiene or “race hygiene”. The eugenics movement had gained great strength in the United States and Britain. Following suit, in 1933 Rüdin became a guiding force in the passage of Germany’s first compulsory sterilization laws known as “the law for the prevention of progeny with hereditary defects” which would target individuals with mental retardation, schizophrenia, manic-depressive disorder, epilepsy, Huntington chorea, hereditary blindness and deafness, hereditary alcoholism and “grave bodily malformation.” It is suggested by the limited data available that of the 400,000 (1% of the entire population) that were sterilized, 132 000 were sterilized for schizophrenia.
Schizophrenia
Schizophrenia has great human and economic costs. It results in a decreased life expectancy by 10–25 years. This is primarily because of its association with obesity, poor diet, sedentary lifestyles, and smoking, with an increased rate of suicide playing a lesser role. Antipsychotic medications may also increase the risk. These differences in life expectancy increased between the 1970s and 1990s.
Schizophrenia is a major cause of disability, with active psychosis ranked as the third-most-disabling condition after quadriplegia and dementia and ahead of paraplegia and blindness. Approximately three-fourths of people with schizophrenia have ongoing disability with relapses and 16.7 million people globally are deemed to have moderate or severe disability from the condition. Some people do recover completely and others function well in society. Most people with schizophrenia live independently with community support. About 85% are unemployed. Some evidence suggests that paranoid schizophrenia may have a better prospect than other types of schizophrenia for independent living and occupational functioning. In people with a first episode of psychosis a good long-term outcome occurs in 42%, an intermediate outcome in 35% and a poor outcome in 27%. Outcomes for schizophrenia appear better in the developing than the developed world. These conclusions have been questioned.
There is a higher than average suicide rate associated with schizophrenia. This has been cited at 10%, but a more recent analysis revises the estimate to 4.9%, most often occurring in the period following onset or first hospital admission. Several times more (20 to 40%) attempt suicide at least once. There are a variety of risk factors, including male gender, depression, and a high intelligence quotient.
Schizophrenia and smoking have shown a strong association in studies worldwide. Use of cigarettes is especially high in those diagnosed with schizophrenia, with estimates ranging from 80 to 90% being regular smokers, as compared to 20% of the general population. Those who smoke tend to smoke heavily, and additionally smoke cigarettes with high nicotine content. Some propose that this is in an effort to improve symptoms. Among people with schizophrenia use of cannabis is also common.
Causes of schizophrenia
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 (such as schizotypal personality disorder) 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.
Cognitive slippage
Meehl (1962) also noted that cognitive slippage occurred in some typically developed relatives of individuals with schizophrenia. Though the findings were preliminary, he noted that among a group of ten individuals with schizophrenia, they were able to detect mild thought disorder in at least one parent of each individual. He thus suggested that future research into this discovery should be a priority of schizophrenia researchers. Meehl also sought to understand where the cognitive dysfunctions associated with schizophrenia stemmed from, yet he found cognitive slippage a difficult symptom to parse out. He considered that, on some level, "everybody has to learn how to think straight," and supposed there could be a social learning component to the development of organized, rational thought and speech.
Gene set enrichment analysis
GSEA can be used to help understand the molecular mechanisms of complex disorders. Schizophrenia is a largely heritable disorder, but is also very complex, and the onset of the disease involves many genes interacting within multiple pathways, as well the interaction of those genes with environmental factors. For instance, epigenetic changes, like DNA methylation, are affected by the environment, but are also inherently dependent on the DNA itself. DNA methylation is the most well-studied epigenetic change, and was recently analyzed using GSEA in relation to schizophrenia-related intermediate phenotypes. Researchers ranked genes for their correlation between methylation patterns and each of the phenotypes. They then used GSEA to look for an enrichment of genes that are predicted to be targeted by microRNAs in the progression of the disease.
Family nexus
Laing was particularly interested in schizophrenia, which he believed could be understood if seen from the viewpoint of the person concerned. He saw how a powerful family nexus could victimise one member, usually a child, who found themselves in the position of not being able to speak or even think the truth without being chastised by the group, who often had vested interests in perpetuating the family myth and excluding reality. In Laing's opinion, "what is called a psychotic episode "in" one person, can often be understood as a crisis of a peculiar kind in the "inter-experience" of the nexus."
Psychiatric genetics
Most psychiatric disorders are highly heritable; the estimated heritability for bipolar disorder, schizophrenia, and autism (80% or higher) is much higher than that of diseases like breast cancer and Parkinson disease. Having a close family member affected by a mental illness is the largest known risk factor, to date. However, linkage analysis and genome-wide association studies have found few reproducible risk factors.
Irving Gottesman
The authors investigated autism and psychiatric disorders among children, but found little relation to adult schizophrenia or genetic influence. They also covered the social implications of the disease, concluding that most schizophrenics were poor because the disorder eroded their resources and abilities. A chapter was devoted to social issues, violence, illnesses, death rates, sexual aspects, and the ability to father or bear children affecting schizophrenics. The authors provided data on the chance of relapse after an episode of the disorder. The book covered new methods and new models for studying schizophrenia. Because the disorder had no unanimously accepted diagnostic criteria, the researchers asked six clinicians and three colleagues to provide their analyses on the reports on 120 twins, and found an agreement of 86% among the clinicians. Averaging the criteria of the clinicians produced a set close to that of Manfred Bleuler, who had adapted it from Emil Kraepelin.
Paranoid personality disorder
A genetic contribution to paranoid traits and a possible genetic link between this personality disorder and schizophrenia exist. A large long-term Norwegian twin study found paranoid personality disorder to be modestly heritable and to share a portion of its genetic and environmental risk factors with the other cluster A personality disorders, schizoid and schizotypal.
Hippocampus
The hippocampus has been seen as central to the pathology of schizophrenia, both in the neural and physiological effects. It has been generally accepted that there is an abnormal synaptic connectivity underlying schizophrenia. Several lines of evidence implicate changes in the synaptic organization and connectivity, in and from the hippocampus Many studies have found dysfunction in the synaptic circuitry within the hippocampus and its activity on the prefrontal cortex. The glutamatergic pathways have been seen to be largely affected. The subfield CA1 is seen to be the least involved of the other subfields, and CA4 and the subiculum have been reported elsewhere as being the most implicated areas. The review concluded that the pathology could be due to genetics, faulty neurodevelopment or abnormal neural plasticity. It was further concluded that schizophrenia is not due to any known neurodegenerative disorder. Oxidative DNA damage is substantially increased in the hippocampus of elderly patients with chronic schizophrenia.
Causes of schizophrenia
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.
Childhood schizophrenia
Schizophrenia is a mental disorder that is expressed in abnormal mental functions and disturbed behavior.
Irving Gottesman
A native of Ohio, Gottesman studied psychology for his undergraduate and graduate degrees, became a faculty member at various universities, and spent most of his career at the University of Virginia and the University of Minnesota. He is known for researching schizophrenia in identical twins to document the contributions of genetics and the family, social, cultural, and economic environment to the onset, progress, and inter-generational transmission of the disorder. Gottesman has worked with researchers to analyze hospital records and conduct follow-up interviews of twins where one or both were schizophrenic. He has also researched the effects of genetics and the environment on human violence and variations in human intelligence. Gottesman and co-researcher James Shields introduced the word epigenetics—the control of genes by biochemical signals modified by the environment from other parts of the genome—to the field of psychiatric genetics.
Emil Kraepelin
Kraepelin also demonstrated specific patterns in the genetics of these disorders and specific and characteristic patterns in their course and outcome. Generally speaking, there tend to be more schizophrenics among the relatives of schizophrenic patients than in the general population, while manic depression is more frequent in the relatives of manic depressives. Though, of course, this does not demonstrate genetic linkage, as this might be a socio-environmental factor as well.
Schizophrenia
Many genes are known to be involved in schizophrenia, each of small effect and unknown transmission and expression. The summation of these effect sizes into a polygenic risk score can explain at least 7% of the variability in liability for schizophrenia. Around 5% of cases of schizophrenia are understood to be at least partially attributable to rare copy number variants (CNVs), including 22q11, 1q21 and 16p11. These rare CNVs increase the risk of someone developing the disorder by as much as 20-fold, and are frequently comorbid with autism and intellectual disabilities. There is a genetic relation between the common variants which cause schizophrenia and bipolar disorder, an inverse genetic correlation with intelligence and no genetic correlation with immune disorders.
Mechanisms of schizophrenia
A novel hypothesis concerning the pathophysiology of schizophrenia, one that closely relates to the glutamate hypothesis, is one that evolves around dysfunction of interneurons in the brain. Interneurons in the brain are GABAergic and local, and function mainly through the inhibition of other cells. One type of interneuron, the fast-spiking, parvalbumin-positive interneuron, has been suggested to play a key role in schizophrenia pathophysiology.
Causes of schizophrenia
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 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. Social support systems are very important for schizophrenics and the people with whom they are in relationships. Recovery from schizophrenia is possible when one develops a healthy self and establishes firm psychological
boundaries with each of their parents.
Glutamate hypothesis of schizophrenia
Frontal cortex activity will be impaired, when combined with excess DA activity: the basis for the advancement of schizophrenia, but it is also the neurologic mechanism behind many other psychotic diseases as well.. Heredation of schizophrenia may even be a result of conspecific "refrigerator parenting" techniques passed on though generations. However, the genetic component is the primary source of the neurological abnormalities which leave one prone to psychological disorders. Specifically, there is much overlap between bipolar disorder and schizophrenia, and other psychotic disorders.
Causes of schizophrenia
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. 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.
Schizophrenia
People with severe mental illness, including schizophrenia, are at a significantly greater risk of being victims of both violent and non-violent crime. Schizophrenia has been associated with a higher rate of violent acts, but most appear to be related to associated substance abuse. Rates of homicide linked to psychosis are similar to those linked to substance misuse, and parallel the overall rate in a region. What role schizophrenia has on violence independent of drug misuse is controversial, but certain aspects of individual histories or mental states may be factors. About 11% of people in prison for homicide have schizophrenia and 21% have mood disorders. Another study found about 8-10% of people with schizophrenia had committed a violent act in the past year compared to 2% of the general population.
P50 (neuroscience)
In a family that has a child with schizophrenia, at least one of the parents tends to show higher rates of abnormal P50 gating compared to normal controls even when the parents themselves do not have schizophrenia.
Causes of schizophrenia
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.
Schizophrenia
The primary treatment of schizophrenia is antipsychotic medications, often in combination with psychological and social supports. Hospitalization may occur for severe episodes either voluntarily or (if mental health legislation allows it) involuntarily. Long-term hospitalization is uncommon since deinstitutionalization beginning in the 1950s, although it still occurs. Community support services including drop-in centers, visits by members of a community mental health team, supported employment and support groups are common. Some evidence indicates that regular exercise has a positive effect on the physical and mental health of those with schizophrenia. As of 2015 it is unclear if transcranial magnetic stimulation (TMS) is useful for schizophrenia.
Schizoid personality disorder
Some evidence suggests the Cluster A personality disorders have shared genetic and environmental risk factors, and there is an increased prevalence of schizoid personality disorder in relatives of people with schizophrenia and schizotypal personality disorder. Twin studies with schizoid personality disorder traits (e.g. low sociability and low warmth) suggest these are inherited. Besides this indirect evidence, the direct heritability estimates of SPD range from 50 to 59%. To Sula Wolff, who did extensive research and clinical work with children and teenagers with schizoid symptoms, "schizoid personality has a constitutional, probably genetic, basis." The link between SPD and being underweight may also point to the involvement of biological factors.