Mental health problems run in families, likely due to complex transmission mechanisms. Using nationwide Swedish registers following millions of parents and their children over decades, we investigated how and why mental health problems are transmitted across generations and whether modifiable factors can mitigate these intergenerational risks.Study I examined associations between six parental psychiatric diagnoses and 32 offspring outcomes using a matched cohort design. Most children exposed to parental psychiatric diagnoses were not diagnosed with specialist-assigned disorders by age 44. Nevertheless, these children demonstrated increased risks of all psychiatric, behavioral, and psychosocial outcomes, indicating largely transdiagnostic transmission.Study II explored whether intergenerational transmission was driven by parental psychiatric comorbidity (i.e., captured by a general factor of psychopathology) or by specific dimension- related effects not accounted for by this general factor (i.e., specific internalizing, externalizing, and psychotic factors), using multivariate modeling. We observed that parental general factor of psychopathology significantly predicted all offspring outcomes, while specific factors were primarily associated with corresponding dimensional outcomes. These findings indicate that the transdiagnostic intergenerational transmission of psychiatric risk appeared largely attributable to parental general psychopathology rather than to disorder-specific pathways.Study III explored the intergenerational transmission after controlling for unmeasured familial factors using the largest children-of-identical-twins design to date. Parent-offspring associations attenuated substantially and most (20 of 27) became non-significant when comparing differentially exposed cousins whose parents were identical twins, suggesting that the associations largely reflected unmeasured familial confounding. However, associations between broad psychiatric spectra persisted, suggesting either non-shared confounders or causal environmental effects.Study IV investigated the quasi-experimental effect of parental education on offspring psychiatric, behavioral, and suicidal outcomes using a fuzzy regression discontinuity design. Children of parents exposed to the Swedish education reform (extended compulsory schooling from 7 to 9 years) showed no significant improvement in these offspring outcomes. This indicates that among those parents who would have left school after completing the compulsory schooling (i.e., compliers), additional schooling did not improve their offspring mental health.Study V investigated the quasi-experimental effect of an enriched childhood environment (i.e., proxied by adoption) on broad psychiatric comorbidity using a home-reared versus adopted- away sibling comparison design. Adopted-away siblings scored lower on both the general factor of psychopathology and the externalizing factor, compared to their siblings who remained home-reared by biological parents with psychiatric and behavioral problems. These findings indicate that enriching rearing environments might reduce the transdiagnostic liability toward psychiatric comorbidity among at-risk individuals.In conclusion, the intergenerational transmission of mental health problems appeared largely transdiagnostic (but not deterministic) and driven by parental psychiatric comorbidity. The transmission was largely explained by shared familial factors but also plausibly shaped by environmental effects. While extending parental compulsory schooling showed no causal mental health benefits, enriched childhood rearing environments reduced broad psychopathology vulnerability. These findings support comprehensive and transdiagnostic prevention strategies that improve parental mental health, caregiving quality, and early-life environments, particularly for high-risk families.List of scientific papersI. Mengping Zhou, Christine Takami Lageborn, Arvid Sjölander, Henrik Larsson, Brian D'Onofrio, Mikael Landén, Paul Lichtenstein, Erik Pettersson. Psychiatric Diagnoses in Parents and Psychiatric, Behavioral, and Psychosocial Outcomes in Their Offspring: A Swedish Population-Based Register Study. American Journal of Psychiatry. 2024;181(8):761-773. https://doi.org/10.1176/appi.ajp.20230353II. Mengping Zhou, Henrik Larsson, Brian D'Onofrio, Mikael Landen, Paul Lichtenstein, Erik Pettersson. Intergenerational Transmission of Psychiatric Conditions and Psychiatric, Behavioral, and Psychosocial Outcomes in Offspring. JAMA Network Open. 2023;6(12):e2348439. https://doi.org/10.1001/jamanetworkopen.2023.48439III. Mengping Zhou, Henrik Larsson, Brian D'Onofrio, Mikael Landen, Ralf Kuja- Halkola, Zheng Chang, Isabell Brikell, Paul Lichtenstein, Erik Pettersson. Intergenerational Transmission between Parental Psychiatric Conditions and Offspring Psychiatric, Behavioral, and Psychosocial Outcomes: A Swedish Population-Based Children-of-Monozygotic Twins Study. SubmittedIV. Mengping Zhou, Henrik Larsson, Brian D'Onofrio, Mikael Landen, Paul Lichtenstein, Erik Pettersson. Association between parental education and offspring psychiatric diagnoses, violent crimes, and suicidal behavior: A nationwide Swedish quasi- experimental study. SubmittedV. Mengping Zhou, Henrik Larsson, Brian D'Onofrio, Mikael Landen, Paul Lichtenstein, Erik Pettersson. Association between the Childhood Rearing Environment and General and Specific Psychopathology Factors in Middle Adulthood: A Swedish National High- Risk Home-Reared versus Adopted-Away Sibling Comparison Study. Molecular Psychiatry. 2025;30(9):4023-4028. https://doi.org/10.1038/s41380-025-02979-1
Mengping Zhou (Mon,) studied this question.
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