Family History Affects the Individual Risk of Major Depression


Exposure to maternal, paternal, or full sibling major depression was associated with a two-fold higher risk of major depression for men.

Family History Affects the Individual Risk of Major Depression

Frederikke Hørdam Gronemann, PhD, Msc

A family history of major depression can drastically increase the individual risk of developing major depression.1

A team, led by Frederikke Hørdam Gronemann, PhD, Msc, Center for Clinical Research and Prevention, Copenhagen University Hospital–Bispebjerg and Frederiksberg, identified the association between family history major depression and the risk of major depression, including the association with age, sex, type of kinship, and age of the affected family member.

Major Depression Within Families

Major depression often aggregates within families. However, it is unknown how family history of major depression confers the risk of major pression over the course of an individuals life. This could help shed light on the importance of identifying and preventing possible depressogenic effects of family environment.

In the cohort study, the investigators examined data for all Danish citizens born between 1960-2003 with known parental identity followed up from their 15th birthday until the time of major depression, censoring, or December 31, 2018.

Exposures included family members with first-time major depression using International Classification of Diseases, Eighth Revision codes 296.09, 296.29, 298.09, and 300.49 or 10th Revision codes F32.0-F33.9, family members’ age at MD onset, and individuals’ age at exposure to family major depression.


The investigators sought main outcomes of the estimation of incidence risk ratios (IRR) and 95% confidence intervals (CI) for first-time major depression, calculated by multivariable Poisson regression.

The study included 2.9 million individuals who developed major depression during the follow-up.

The results show exposure to maternal, paternal, or full sibling major depression was associated with a two-fold higher risk of major depression (IRR, 2.10; 95% CI, 2.02-2.19; IRR, 2.04; 95% CI, 1.94-2.14; IRR, 2.08; 95% CI, 1.97-2.19) for men specifically. The investigators found the associated risk increased with the number of affected family members.

There was a similar pattern found in women.

Family members age at the major depression onset for men was not associated with major depression, while maternal onset at 69 years or younger for women was associated with higher IRRs of major depression (age <40 years: IRR, 1.64; 95% CI, 1.28-2.10; age 40-49 years: IRR, 1.62; 95% CI, 1.27-2.07; age 50-59 years: IRR, 1.56; 95% CI, 1.22-2.00; and age 60-69 years: IRR, 1.67; 95% CI, 1.28-2.16) compared with women with maternal MD onset at 70 years or older.

On the other hand, for men, exposure to maternal major depression younger than 30 years (age <1 year: IRR, 1.95; 95% CI, 1.70-2.25; age 1 to <12 years: IRR, 2.31; 95% CI, 2.16-2.47; age 12 to <19 years: IRR, 2.18; 95% CI, 2.03-2.35; age 19 to <30 years: IRR, 1.42; 95% CI, 1.32-1.53) was associated with increased IRRs.

Moreover, exposure to maternal major depression at 30 years or older was linked to a lower IRR of 0.77 (95% CI, 0.70-0.85).

The findings were similar across the types of kindships and for women.

“In this study, risk of [major depression] was associated with increased numbers of affected family members but did not vary by gender or type of kinship. Exposure to family [major depression] during childhood and adolescence was associated with increased risk,” the authors wrote.


Gronemann FH, Jacobsen RK, Wium-Andersen MK, Jørgensen MB, Osler M, Jørgensen TSH. Association of Familial Aggregation of Major Depression With Risk of Major Depression. JAMA Psychiatry. Published online February 08, 2023. doi:10.1001/jamapsychiatry.2022.4965

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