The Rise of the Creative Class

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.

/pdf/common-schizophrenia-alleles-are-enriched-in-mutation-519f2gf4m7.pdf

Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection

Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

Genome-wide association study identifies 74 loci associated with educational attainment

The term 'Borderline Personality Disorder' (BPD) refers to a psychiatric syndrome that is characterized by emotion dysregulation, impulsivity, risk-taking behavior, irritability, feelings of emptiness, self-injury and fear of abandonment, as well as unstable interpersonal relationships. BPD is not only common in psychiatric populations but also more prevalent in the general community than previously thought, and thus represents an important public health issue. In contrast to most psychiatric disorders, some symptoms associated with BPD may improve over time, even without therapy, though impaired social functioning and interpersonal disturbances in close relationships often persist. Another counterintuitive and insufficiently resolved question is why depressive symptoms and risk-taking behaviors can occur simultaneously in the same individual. Moreover, there is an ongoing debate about the nosological position of BPD, which impacts on research regarding sex differences in clinical presentation and patterns of comorbidity.In this review, it is argued that many features of BPD may be conceptualized within an evolutionary framework, namely behavioral ecology. According to Life History Theory, BPD reflects a pathological extreme or distortion of a behavioral 'strategy' which unconsciously aims at immediate exploitation of resources, both interpersonal and material, based on predictions shaped by early developmental experiences. Such a view is consistent with standard medical conceptualizations of BPD, but goes beyond classic 'deficit'-oriented models, which may have profound implications for therapeutic approaches.

Borderline Personality Disorder Why ‘fast and furious’?

Context It is unknown how genetic variants conferring liability to psychiatric disorders survive in the population despite strong negative selection. However, this is key to understanding their etiology and designing studies to identify risk variants. Objectives To examine the reproductive fitness of patients with schizophrenia and other psychiatric disorders vs their unaffected siblings and to evaluate the level of selection on causal genetic variants. Design We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse and their unaffected siblings compared with the general population. Setting Population databases in Sweden, including the Multi-Generation Register and the Swedish Hospital Discharge Register. Participants In total, 2.3 million individuals among the 1950 to 1970 birth cohort in Sweden. Main Outcome Measures Fertility ratio (FR), reflecting the mean number of children compared with that of the general population, accounting for age, sex, family size, and affected status. Results Except for women with depression, affected patients had significantly fewer children (FR range for those with psychiatric disorder, 0.23-0.93; P  Conclusions Our results suggest that strong selection exists against schizophrenia, autism, and anorexia nervosa and that these variants may be maintained by new mutations or an as-yet unknown mechanism. Bipolar disorder did not seem to be under strong negative selection. Vulnerability to depression, and perhaps substance abuse, may be preserved by balancing selection, suggesting the involvement of common genetic variants in ways that depend on other genes and on environment.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/1390257/yoa120017_22_30.pdf

Fecundity of Patients With Schizophrenia, Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings

Background 

There is a long-standing belief that creativity is coupled with psychopathology.

Aims 

To test this alleged association and to investigate whether any such association is the result of environmental or genetic factors.

Method 

We performed a nested case–control study based on Swedish registries. The likelihood of holding a creative occupation in individuals who had received in-patient treatment for schizophrenia, bipolar disorder or unipolar depression between 1973 and 2003 and their relatives without such a diagnosis was compared with that of controls.

Results 

Individuals with bipolar disorder and healthy siblings of people with schizophrenia or bipolar disorder were overrepresented in creative professions. People with schizophrenia had no increased rate of overall creative professions compared with controls, but an increased rate in the subgroup of artistic occupations. Neither individuals with unipolar depression nor their siblings differed from controls regarding creative professions.

Conclusions 

A familial cosegregation of both schizophrenia and bipolar disorder with creativity is suggested.

/pdf/creativity-and-mental-disorder-family-study-of-300-000-24zak1vorl.pdf

Creativity and mental disorder: family study of 300 000 people with severe mental disorder

https://www.scottbarrykaufman.com/wp-content/uploads/2012/10/Kyaga-et-al.-2012.pdf

Mental illness, suicide and creativity: 40-Year prospective total population study

BackgroundMany studies have addressed the question of whether mental disorder is associated with creativity, but high-quality epidemiological evidence has been lacking.AimsTo test for an association between studying a creative subject at high school or university and later mental disorder.MethodIn a case–control study using linked population-based registries in Sweden (N = 4 454 763), we tested for associations between tertiary education in an artistic field and hospital admission with schizophrenia (N = 20 333), bipolar disorder (N = 28 293) or unipolar depression (N = 148 365).ResultsCompared with the general population, individuals with an artistic education had increased odds of developing schizophrenia (odds ratio = 1.90, 95% CI = [1.69; 2.12]) bipolar disorder (odds ratio = 1.62 [1.50; 1.75]) and unipolar depression (odds ratio = 1.39 [1.34; 1.44]. The results remained after adjustment for IQ and other potential confounders.ConclusionsStudents of artistic subjects at university are at increased risk of developing schizophrenia, bipolar disorder and unipolar depression in adulthood.Declaration of interestNone.

/pdf/artistic-creativity-and-risk-for-schizophrenia-bipolar-2nz0n4snx7.pdf

Artistic creativity and risk for schizophrenia, bipolar disorder and unipolar depression: a Swedish population-based case-control study and sib-pair analysis.

Objective
To investigate whether persons with bipolar disorder and their siblings have leadership traits and are overrepresented in executive professions.

Method
A nested case-control study based on longitudinal Swedish total population registries. Data from officer suitability interviews (n = 1 126 519), and information on occupations were collected. Bipolar patients (n = 68 915) and their healthy siblings were compared with controls.

Results
Bipolar patients without comorbidity (pure; n = 22 980) were overrepresented in both the highest and lowest strata of officer suitability; their healthy siblings in the highest strata only. Patients with pure bipolar disorder were underrepresented in executive professions, whereas their siblings were overrepresented in these professions (particularly political professions). Patients with general bipolar disorder (including those with comorbidities) and their healthy siblings were overrepresented only in the lowest strata of officer suitability ratings. General bipolar patients were underrepresented in executive professions, whereas their siblings had similar rates of executive professions as controls. Adjusting results for IQ slightly attenuated point estimates, but resulted in pure bipolar patients and their siblings no longer being significantly overrepresented in superior strata of officer suitability, and siblings no longer being overrepresented in executive professions.

Conclusion
Results support that traits associated with bipolar disorder are linked to superior leadership qualities.

Simon Kyaga

Papers

Fecundity of Patients With Schizophrenia, Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings

Creativity and mental disorder: family study of 300 000 people with severe mental disorder

Mental illness, suicide and creativity: 40-Year prospective total population study

Artistic creativity and risk for schizophrenia, bipolar disorder and unipolar depression: a Swedish population-based case-control study and sib-pair analysis.

Bipolar disorder and leadership--a total population study.