Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development

Influence of Maternal and Paternal History of Mental Health in Clinical, Social Cognition and Metacognitive Variables in People with First-Episode Psychosis

This study investigates, for the first time, clinical, cognitive, social cognitive and metacognitive differences in people diagnosed with first-episode of psychosis (FEP) with and without a family history of mental disorder split by maternal and paternal antecedents. A total of 186 individuals with FEP between 18 and 45 years old were recruited in community mental-health services. A transversal, descriptive, observational design was chosen for this study. Results suggest that there is a higher prevalence of maternal history of psychosis rather than paternal, and furthermore, these individuals exhibit a specific clinical, social and metacognitive profile. Individuals with a maternal history of mental disorder scored higher in delusional experiences, inhibition of the response to a stimulus and higher emotional irresponsibility while presenting a poorer overall functioning as compared to individuals without maternal history. Individuals with paternal history of mental disorder score higher in externalizing attributional bias, irrational beliefs of need for external validation and high expectations. This study elucidates different profiles of persons with FEP and the influence of the maternal and paternal family history on clinical, cognitive, social and metacognitive variables, which should be taken into account when offering individualized early treatment