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Psychiatry Practice Research Review

Released: September 29, 2021
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Multigenerational Family History of Depression: Association with Lifetime Depressive and Other Psychiatric Disorders in Children; Results From the Adolescent Brain Cognitive Development (ABCD) Study

Van Dijk MT, et al. JAMA Psychiatry. 2021;78:778-787.

This study evaluated whether having multiple generations affected by depression increases risk of psychopathology in children and if this can be reliably measured in large, diverse samples using informant-reported family history. Previous studies established heightened risk of psychopathology for offspring in families with 2 previous generations affected with depression compared with those with one or none. Consequently, the 3-generation family risk paradigm established in family studies can be a critical neuropsychiatric tool if similar transmission patterns are reliably demonstrated with the family history method to examine the association of multigenerational family history of depression with lifetime depressive disorders and other psychopathology in children.

In this analysis of the Adolescent Brain Cognitive Development (ABCD) study data, retrospective, cross-sectional reports on psychiatric functioning among 11 200 children (generation 3 [G3]) and parent reports on parents’ (G2) and grandparents’ (G1) depression histories were analyzed. The ABCD study sampling weights were used for generalized estimating equation models and descriptive analyses. Data were collected from September 2016 to November 2018, and data were analyzed from July to November 2020.

Main outcomes and measures included 4 risk categories reflecting the number of prior generations with a history of depression: (1) neither G1 nor G2 (G1-/G2-), (2) only G1 (G1+/G2-), (3) only G2 (G1-/G2+), and (4) both G1 and G2 (G1+/G2+). Child lifetime prevalence and relative risks of psychiatric disorders were based on child and caregiver reports and grouped according to familial risk category derived from G1 and G2 depression history.

Among 11,200 included children, 5355 (47.8%) were female, and the mean age was 9.9 years. By parent reports, the weighted prevalence of the depressive disorder among children was 3.8% for G1-/G2- children, 5.5% for G1+/G2- children, 10.4% for G1-/G2+ children, and 13.3% for G1+/G2+ children. The weighted suicidal behavior prevalence among children was 5.0% for G1-/G2- children, 7.2% for G1+/G2- children, 12.1% for G1-/G2+ children, and 15.0% for G1+/G2+ children. By child reports, the weighted prevalence of depressive disorder was 4.8% for G1-/G2- children, 4.3% for G1+/G2- children, 6.3% for G1-/G2+ children, and 7.0% for G1+/G2+ children, and the weighted prevalence of suicidal behaviors was 7.4% for G1-/G2- children, 7.0% for G1+/G2- children, 9.8% for G1-/G2+ children, and 13.8% for G1+/G2+ children. Similar patterns were observed for other disorders for both parent and child reports and across sex, socioeconomic status, and race/ethnicity.

In this study, having multiple prior affected generations was associated with an increased risk of childhood psychopathology. Furthermore, these findings were detectable even at prepubertal ages and existed in diverse racial/ethnic and socioeconomic groups. Clinically, they underscore the need for screening for family history of mental illness in pediatric settings and highlight implications for biological research with homogenous subgroups using MRI or genetic analyses.

Clinical Commentary
This study took data from ABCD, the largest long-term study of brain development and child health in the United States. This was a multisite study that assessed neurocognition, physical and mental health, social and emotional functions, and culture and environment and is unique for analyzing how multiple prior affected generations may be associated with increased risk of childhood psychopathology. Based on parent reports, higher prevalence of psychiatric disorders in older generations may be associated with increased risk of childhood psychopathology. A limitation of this study is that it relies on family history reports from one informant instead of direct interviews with family members, which may lead to bias from reporters who themselves have psychopathology. There were anticipated parent–child discrepancies in reporting in line with previous findings. The detectability of mental health issues in prepubertal children based on familial risks observed in this study made these findings particularly remarkable.

Clinical Insights
Based on parental reports

  • Children with both parents and grandparents with depression were 6.0-fold more likely to have major depressive disorder and 2.1-fold more likely to have any psychiatric disorder when compared with children with psychologically healthy parents and grandparents.
  • Having a parent with depression confers a higher risk than having a grandparent with depression, a difference that may become more pronounced as the children grow older.
  • Boys had higher rates of suicidal behavior than girls.
  • Rates of depression in the lower and medium socioeconomic status (SES) increased with family risk whereas risk did not increase in the higher socioeconomic status. This pattern was generally observed across sex, socioeconomic status, and race/ethnic groups.
  • Based on child reports, Black children and those of other races/ethnicities had a greater prevalence of any disorder compared with White children.
  • Biological underpinnings include a difference in microstructure in the dentate gyrus of the hippocampus in offspring with 2 generations of depression vs no prior generations of depression. This is a factor that affects resilience.

In my clinical opinion, this study underscores the importance of documenting comprehensive patient history for prepubertal children who present a challenge when diagnosing psychopathology as one must often differentiate psychopathology from parenting issues. Hence, it is important not only to interview the child and parents but also to derive firsthand information from the grandparents. Often family history of psychiatric illnesses is not communicated to younger generations because of stigma or inadequate information. In current times, telepsychiatry offers an excellent tool to interview parents and grandparents. The assessment of multigenerational family history can help improve diagnosis and treatment outcomes. Despite some discrepancies in parent and child reporting, these findings clearly demonstrate that depressive disorder in parents and grandparents significantly increases an individual’s psychopathology risk. Moreover, this study validates the predictive value of big data and family studies in psychiatric epidemiology.

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