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.

The aim of this study was to identify factors associated with distress experienced by physicians during their first coronavirus disease 2019 (COVID-19) triage decisions.

An online survey was administered to physicians licensed in New York State.

Of the 164 physicians studied, 20.7% experienced severe distress during their first COVID-19 triage decisions. The mean distress score was not significantly different between physicians who received just-in-time training and those who did not (6.0 ± 2.7 vs 6.2 ± 2.8; P = 0.550) and between physicians who received clinical guidelines and those who did not (6.0 ± 2.9 vs 6.2 ± 2.7; P = 0.820). Substantially increased odds of severe distress were found in physicians who reported that their first COVID-19 triage decisions were inconsistent with their core values (adjusted odds ratio, 6.33; 95% confidence interval, 2.03-19.76) and who reported having insufficient skills and expertise (adjusted odds ratio 2.99, 95% confidence interval 0.91-9.87).

Approximately 1 in 5 physicians in New York experienced severe distress during their first COVID-19 triage decisions. Physicians with insufficient skills and expertise, and core values misaligned to triage decisions are at heightened risk of experiencing severe distress. Just-in-time training and clinical guidelines do not appear to alleviate distress experienced by physicians during their first COVID-19 triage decisions.

Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.

We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.

In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).

AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.

The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.

The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.

The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.

Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.

We sought to investigate the relationship between neuroticism and depression in an elderly cohort. In this paper, we describe the methods of an National Institute of Mental Health—NIMH-supported study and present findings among the cohort enrolled to date.

We used the NEO Personality Inventory to assess neuroticism, and we employed several cognitive neuroscience-based measures to examine emotional control.

Compared with a group of 27 non-depressed older control subjects, 33 older depressed subjects scored higher on measures of state and trait anxiety and neuroticism. On our experimental neuroscience-based measures, depressed subjects endorsed more negative words compared with controls on an emotional characterization test. In addition, we found a significant group-by-congruency effect on an emotional interference test where subjects were asked to identify the face's emotional expression while ignoring the words “fear” or “happy” labeled across the face.

Thus, in this preliminary work, we found significant differences in measures of neuroticism and emotional controls among older adults with and without depression.