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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.
To investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls.
Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls.
Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest.
Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.
Declaration of interest
R.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.
Copy number variants (CNVs) are established risk factors for neurodevelopmental disorders. To date the study of CNVs in psychiatric illness has focused on single disorder populations. The role of CNVs in individuals with intellectual disabilities and psychiatric comorbidities are less well characterised.
To determine the type and frequency of CNVs in adults with intellectual disabilities and comorbid psychiatric disorders.
A chromosomal microarray analysis of 599 adults recruited from intellectual disabilities psychiatry services at three European sites.
The yield of pathogenic CNVs was high – 13%. Focusing on established neurodevelopmental disorder risk loci we find a significantly higher frequency in individuals with intellectual disabilities and comorbid psychiatric disorder (10%) compared with healthy controls (1.2%, P<0.0001), schizophrenia (3.1%, P<0.0001) and intellectual disability/autism spectrum disorder (6.5%, P < 0.00084) populations.
In the largest sample of adults with intellectual disabilities and comorbid psychiatric disorders to date, we find a high rate of pathogenic CNVs. This has clinical implications for the use of genetic investigations in intellectual disability psychiatry.
This chapter reviews the evidence for genetic and environmental influences, both specified and unspecified in antisocial behavior. It discusses heritability of both adult and child mental disorders in DSM-IV-TR, for which antisocial behavior is central to their diagnosis. The chapter also reviews heritability of the related externalizing disorders. It highlights some of the most exciting new directions in this field, which aim to unpack the genetic and environmental black boxes in antisocial behavior, and provides the complexities of the gene-environment interplay in antisocial development. Evidence of genetic influences on antisocial behavior does not implicate that individuals exhibiting antisocial behavior are immune or resistant to interventions. Future research with combined approaches from behavior genetics and neuroscience will lead to better understanding of specific genes that result in structural and functional brain impairments that in turn give rise to antisocial, violent, and psychopathic behavior.
To investigate the effect of the 2004 tsunami on suicide rates in Sri Lanka. the number of suicides in the 2 years prior to and 1 year after the tsunami were considered for the study. Data from districts affected by the tsunami were compared with those from unaffected districts.
No significant differences were found between the number of suicides before and following the disaster or between areas affected and unaffected by the tsunami.
Worldwise, the impact of disasters upon suicide rates is variable. It is possible that the tsunami failed to have any profound effect on societal forces affecting suicide rates in Sri Lanka.
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