Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics, and anesthetics. Integrating eQTL data implicated 15 genes robustly linked to BD via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of BD subtypes indicated high but imperfect genetic correlation between BD type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of BD, identify novel therapeutic leads, and prioritize genes for functional follow-up studies.

Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic and calcium signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers and antiepileptics. Integrating eQTL data implicated 15 genes robustly linked to BD via gene expression, including druggable genes such as HTR6, MCHR1, DCLK3 and FURIN. This GWAS provides the best-powered BD polygenic scores to date, when applied in both European and diverse ancestry samples. Together, these results advance our understanding of the biological etiology of BD, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

BackgroundAlexithymia, the difficulty in describing or recognizing emotions, has been associated with various psychosomatic pathologies including psoriasis. The aim of this study was to examine the prevalence of alexithymia and its association with anxiety and depression in patients with psoriasis compared with healthy participants, while taking into consideration demographic and clinical variables.MethodsOne hundred and eight psoriatic patients and 100 healthy participants from the general population completed the Toronto Alexithymia Scale (TAS-20) and the Hospital Anxiety and Depression Scale (HADS). The severity of patients’ psoriasis was clinically assessed using the Psoriasis Area and Severity Index (PASI).ResultsPsoriatic patients had higher levels of alexithymia compared with healthy participants. While a rather high rate of psoriatic patients presented anxiety and depression as defined by the HADS, the differences that were found in comparison with the control group were not significant. Neither alexithymia nor its dimensions, difficulty in identifying feelings (DIF), difficulty in describing feelings (DDF) and externally oriented thinking (EOT), were associated with gender or psoriasis severity. Age was associated only with EOT, which was independent of depression and anxiety. Higher anxiety and depression were connected with higher alexithymia and DIF, while higher anxiety with higher DDF as well.ConclusionsThe alexithymia prevalence was higher in psoriatic patients than that in healthy participants, while it was positively correlated with anxiety and depression. Difficulty in identifying feelings was connected with both anxiety and depression, whereas difficulty in describing them was only with anxiety. Finally, externally oriented thinking was predicted only from age.

Objectives The Mental Health Continuum‐Short Form (MHC‐SF), measuring emotional, social, and psychological well‐being, has scarcely been validated in clinical populations. We evaluated MHC‐SF in 203 patients with affective disorders and 163 nonclinical participants. Method Traditional confirmatory factor analysis (CFA), bifactor CFA, three‐factor exploratory structural equation modeling (ESEM), and bifactor ESEM models were compared. Convergent/discriminant validity was tested against classic well‐being validators and current mood state. Results All three subscales were significantly lower in patients. Test‐retest reliability in patients was moderate. Bifactor ESEM fitted data best and displayed full scalar gender and partial scalar invariance across groups. Factor strength indices suggested that MHC‐SF is primarily unidimensional, especially in patients. However, subscales differed considerably on size, internal consistency, distinctness, discriminant validity, and temporal stability. Conclusions MHC‐SF was valid and reliable for monitoring well‐being in both clinical and nonclinical samples, but further research is needed before safely concluding on its dimensionality.