To examine any association of birth decade, sex and exposure to alcohol and/or substance use disorders (ASUD) with age at onset (AAO) of bipolar I disorder (BD-I).

Using data from a representative clinical sample of 3896 BD-I cases recruited from 14 European countries, we examined AAO distributions in individuals born in consecutive birth decades. Cumulative probabilities with Mantel-Cox log-rank tests, pairwise comparisons and Odds Ratios (OR) with 95% confidence intervals (95% CI) were employed to analyze AAO according to birth decade, sex, and presence or absence of an ASUD.

In the total sample, median AAO of BD-I decreased from about 41 years for those born in the 1930s to about 26 years for those born in the 1960s. In a sub-sample of 1247 individuals (selected to minimize confounding), AAO significantly decreased for males and females born in each consecutive decade between 1930 and 50 (OR: 0.65; 95% CI: 0.51, 0.81), and for cases with an ASUD as compared to without (OR: 0.77, 95% CI: 0.69, 0.87). The best fitting regression model identified an independent effect for each birth decade and an interaction between ASUD status and sex, with a consistently earlier AAO in males with an ASUD (OR: 0.79: 95% CI: 0.70, 0.91).

In BD-I cases diagnosed according to internationally recognized criteria and recruited to pan-European clinical observational studies, the AAO distributions are compatible with a birth cohort effect. A potentially modifiable risk factor, namely ASUD status, was associated with the observed reduction in AAO, especially in males.

Given the rapid increase in prescription and illicit drug poisoning deaths in the 50+ age group, we examined precipitating/risk factors and toxicology results associated with poisoning deaths classified as suicides compared to intent-undetermined death (UnD) among decedents aged 50+.

Data were from the 2005–2015 US National Violent Death Reporting System (N = 15,453). χ2 tests and multinomial logistic regression models were used to compare three groups of decedents: suicide decedent who left a suicide note, suicide decedent who did not leave a note, and UnD cases.

Compared to suicide decedents without a note (37.7% of the sample), those with a note (29.4%) were more likely to have been depressed and had physical health problems and other life stressors, while UnD cases (32.9%) were less likely to have had mental health problems and other life stressors but more likely to have had substance use and health problems. UnD cases were also more likely to be opioid (RRR = 2.65, 95% CI = 2.42–2.90) and cocaine (RRR = 2.59, 95% CI = 2.09–3.21) positive but less likely to be antidepressant positive. Blacks were more than twice as likely as non-Hispanic Whites to be UnDs. Results from separate regression models in the highest UnD states (Maryland and Utah) and in states other than Maryland/Utah were similar.

Many UnDs may be more correctly classified as unintentional overdose deaths. Along with more accurate determination processes for intent/manner of death, substance use treatment and approaches to curbing opioid and other drug use problems are needed to prevent intentional and unintentional poisoning deaths.