Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10⁻⁴ in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10⁻⁸) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

Brainstorming diseases: Consistent classification of neuropsychiatric diseases is problematic because it can lead to misunderstanding of etiology. The Brainstorm Consortium examined multiple genome-wide association studies drawn from more than 200,000 patients for 25 brain-associated disorders and 17 phenotypes. Broadly, it appears that psychiatric and neurologic disorders share relatively little common genetic risk. However, different and independent pathways can result in similar clinical manifestations (e.g., psychosis, which occurs in both schizophrenia and Alzheimer's disease). Schizophrenia correlated with many psychiatric disorders, whereas the immunopathological affliction Crohn's disease did not, and posttraumatic stress syndrome was also largely independent of underlying traits. Essentially, the earlier the onset of a disorder, the more inheritable it appeared to be. Science , this issue p. eaap8757

Background: The public health emergency of coronavirus disease (COVID-19) is rapidly evolving worldwide; some countries, including Spain, have implemented restrictive measures. Populations that are vulnerable to this outbreak and its physical and mental health effects include community-dwelling older adults with mild cognitive impairment or mild dementia. Telehealth is a potential tool to deliver health care and decrease exposure risk. Objective: The aims of this study were to explore the impact of confinement on the health and well-being of community-dwelling older adults with mild cognitive impairment or mild dementia, to provide television-based and telephone-based health and social support, and to study the effects of a television-based assistive integrated technology, TV-AssistDem (TeleVision-based ASSistive Integrated Service to supporT European adults living with mild DEMentia or mild cognitive impairment). Methods: A telephone-based survey was administered in Spain to 93 participants in the TV-AssistDem clinical trial from March 25 to April 6, 2020. Results: Of the respondents, 60/93 (65%) were women. The mean age was 73.34 (SD 6.07), and 69/93 (74%) lived accompanied. Lockdown measures forced 17/93 respondents (18%) to change their living arrangements. Health status was found to be optimal in 89/93 respondents (96%), with no COVID-19 symptoms. Grocery and pharmacy outings were performed by family members of 68/93 participants (73%); 57 (61%) reported overall well-being, and 65 (70%) maintained their sleep quality. However, participants living alone reported greater negative feelings and more sleeping problems. Regarding leisure activities, 53/93 respondents (57%) took walks, 32 (35%) played memory games, 55 (60%) watched television, and 91 (98%) telephoned relatives. 58/93 (64%) respondents reported accessing moderate or too much COVID-19 information, 89 (97%) received it from television, and 56 (62%) stated that their understanding of the information was extreme. 39/93 (39%) respondents had contacted health and social services, while 29 (31%) requested information regarding these services during the telephone call. There were no significant differences in health and well-being between the intervention and control groups. Respondents with TV-AssistDem performed more memory exercises (24/93, 52% vs 8/93, 17.4%; P<.001) than control respondents. Conclusions: Our findings suggest that during COVID-19 confinement, the physical and mental health and well-being was optimal for the majority of our vulnerable population. However, those living alone reported greater negative psychological effects and sleeping problems. Measures adopted to address the negative experiences of confinement included keeping informed about the situation, accessing health and social services, having a support network that prevents risk of exposure to COVID-19 and guarantees food and medical supplies, a daily routine with maintained sleeping habits and leisure activities, staying physically and mentally active with cognitive stimulation exercises, and ensuring social connectedness using technology. Television sets were preferred technological devices to access COVID-19 information, watch television as a recreational activity, and perform memory exercises as an intellectual activity. Television-based telehealth support using TV-AssistDem demonstrated potential for cognitive stimulation. Trial Registration: ClinicalTrials.gov NCT03653234; https://clinicaltrials.gov/ct2/show/NCT03653234