Seeking to clarify the parent-offspring transmission of Major Depression (MD) and type I Bipolar Disorder (BD), we examined offspring MD and BD risk in five informative parental pairs: Unaffected x MD, Unaffected x BD, MDxMD, MDxBD and BDxBD.

We identified 289,637 individuals born in Sweden 1970-1990, followed through 2018, from parents with MD and/or BD identified from Swedish medical registers. We quantified the MD→MD, BD→BD, MD→BD and BD→MD parent-offspring transmission and explored effects of parental illness on MD→BD conversions.

The risk for MD was modestly and similarly increased in offspring of Unaffected x MD (HR=1.64) and Unaffected x BD parents (HR=1.53), higher in MDxMD and MDxBD pairings (HRs=2.39 and 2.47) and slightly lower in BDxBD matings (HR=2.29). By contrast, risk for BD was much higher in Unaffected x BD versus Unaffected x MD matings (HRs = 5.59 vs. 1.70), further elevated modestly in MDxBD matings (HR=6.26) and very high in BDxBD matings (HR=13.61). The rate of offspring MD→BD conversions was substantially increased by parental BD but not parental MD. Offspring BD was equally predicted by paternal and maternal affective illness while offspring MD was more strongly predicted by maternal than paternal affective illness.

Examining risk for MD and BD in offspring of different parental mating types of MD and BD is an informative strategy for further clarifying the cross-generational transmission of these two partially related and partially distinct mood disorders.

Adults with intellectual disability (ID) experience marked mental health inequities, yet population-wide estimates that capture both primary- and specialist-care diagnoses remain scarce.

Using nationwide Swedish registries, including primary care, specialist, inpatient, prescription drug, criminal, and suspicion registers, we included all individuals born in Sweden between 1958 and 1997 (N = 3,970,600), including 38,818 individuals with ID diagnoses (0.98%; 49.1% mild, 13.3% moderate, and 9.6% severe/profound). Hazard ratios (HR) were calculated using Cox proportional hazards regression to estimate the relative risk of lifetime diagnoses of major depression, anxiety disorders (ANX), obsessive-compulsive disorder (OCD), bipolar disorder (BD), attention-deficit/hyperactivity disorder (ADHD), drug use disorder, alcohol use disorder, schizophrenia, and other nonaffective psychosis. Additionally, cohort effects on psychiatric diagnosis risks in adults with intellectual disabilities versus the general population were evaluated.

People with ID were at higher risk for all psychiatric and substance use disorders, with HRs ranging from 1.7–2.0 for major depression and anxiety, drug and alcohol use disorders, 3.5–5.8 for BD, OCD and ADHD, and 10.9–12.7 for schizophrenia and other nonaffective psychosis. Higher prevalence was consistently seen among those with mild versus moderate or severe/profound intellectual disability. Relative risks narrowed modestly in successive birth cohorts, although absolute differences remained substantial.

Across six decades of follow-up, adults with ID faced markedly higher psychiatric and substance-use morbidity – most pronounced for psychotic disorders – than the general population. Whole-system mental-health screening and tailored interventions are required to address this persistent disparity.

We utilize a novel contrastive genetic-epidemiological method, the Maternal Half-Sibling Families with Discordant Fathers (MHSFDF) design, to examine cross-generational genetic transmission of posttraumatic stress disorder (PTSD) and related internalizing major depression (MD), and externalizing disorders: alcohol use disorder (AUD) and drug use disorder (DUD).

Using Swedish national registries, we identified 72,467 maternal half-sibling pairs reared together whose biological fathers were discordant for the diagnoses of PTSD, MD, AUD, and DUD. Offspring selected had to have less than 1 year of contact with their affected fathers. We examined the differences in outcome for within- and cross-disorder risk of diagnosis in the half-siblings with an affected versus unaffected father.

Paternal PTSD increased the risk of PTSD (HR: 1.43, 95% CI: 1.05–1.96) and MD (HR: 1.55, CI: 1.28–1.88) in offspring. It did not, however, elevate the risk of externalizing disorders (AUD or DUD). Offspring of fathers with AUD, DUD, or MD had increased risk of PTSD, suggesting sharing of vertically transmitted genetic risk between these disorders. No sex effects were found for any studied diagnosis.

This study is the first to show cross-generation genetic transmission for PTSD using the MHSFDF design. The pattern of cross-disorder genetic risk broadly supported an internalizing versus externalizing disorder split.

We seek to clarify how changes in the prevalence of drug use disorder (DUD) in Sweden in the 1950–1990 birth cohort impact the aggregation and co-aggregation in siblings of DUD and alcohol use disorder (AUD).

We examined risk for DUD and AUD in siblings of 102,624 DUD cases and matched control probands and 123,837 AUD case and matched control probands identified using Swedish registries. Flexible parametric survival models assessed the difference in disorder risk in siblings of case versus control probands.

Over birthyears 1950–1990, rates of DUD increased substantially in the Swedish population. In siblings of DUD cases versus controls, the risk for DUD increased dramatically starting in birthyear 1965 while their risk for AUD fell moderately. A similar, but less pronounced pattern, was seen in the siblings of AUD versus control probands. These differences were much larger in male than in female siblings.

The factors that drove upward population rates of DUD in Sweden (e.g. increased availability, reduced stigma) produced much stronger effects in high-risk subjects (siblings of DUD and AUD probands) than in normal risk groups (siblings of controls), thereby increasing familial aggregation of DUD. However, parallel declines in AUD rates in high-risk versus normal-risk siblings were observed, likely due to ‘competitive effects’ reducing coaggregation of DUD and AUD. Results of genetic studies of substance use disorders can be substantially impacted by changes in availability and stigma of psychoactive substance use and indirectly by ‘competition’ as predicted by behavioral economic models, between abusable substances.

Among individuals with alcohol use disorder (AUD) and drug use disorder (DUD), is their genetic liability and its specificity moderated by substance availability?

Offspring (born 1960–1995) and their biological parents from three family types [not-lived-with (NLW) biological father, mother and adoptive] and their AUD and DUD diagnoses were ascertained from Swedish national registers. Parent–offspring resemblance was calculated by tetrachoric correlation.

In Swedes born from 1960 to 1995, prevalence rates of AUD were stable while DUD rates increased substantially. Best-estimate tetrachoric correlations (±95% confidence intervals) between AUD in biological parents and AUD and DUD in their offspring were, respectively, +0.19 (0.18–0.20) and +0.18 (0.17–0.20). Parallel results from DUD in parents to AUD and DUD in children were +0.12 (0.10–0.13) and +0.27 (0.26–0.28). When divided into older and younger cohorts, the specificity of DUD transmission increased substantially over time, while the genetic correlation between AUD and DUD significantly decreased.

Raised when alcohol was the preferred substance of abuse and illicit drugs highly stigmatized, AUD in parents reflected a general liability to substance use disorders, as they transmitted similar genetic risk for AUD and DUD to their children raised when both substances were widely available and relatively acceptable. DUD in parents, by contrast, reflected a more specific liability to DUD and, when transmitted to offspring, produced a considerably stronger risk for DUD than for AUD that increased over time. The magnitude and specificity of the genetic liability to psychoactive substances can be influenced by the availability of that substance.