Multigenerational Depression Boosts Kids' Risk Threefold

Nancy A. Melville

August 11, 2016

The known heightened risk for depression in children of parents with major depressive disorder (MDD) is increased threefold when the family history of depression extends to grandparents, new research shows.

"With the use of data from all three generations, it became clear that embedded within the high-risk sample was a group of children at extremely high risk for MDD, namely, the grandchildren with two previous generations affected with MDD," the authors, led by Myrna Weissman, PhD, of Columbia University and New York State Psychiatric Institute, New York City, report.

This finding, they add, highlights the value of screening for MDD beyond two generations.

The study was published online August 10 in JAMA Psychiatry.

Multigenerational Study

Although it is well established that having a parent with depression is a strong risk factor for depression, until now, no published studies of depression have involved direct interviews spanning three generations of family members.

For the longitudinal, retrospective study spanning 30 years, from January 1982 to June 2015, 251 grandchildren (mean age, 18 years) were interviewed a mean of two times. Their biological parents were interviewed a mean of 4.6 times, and the grandparents were interviewed over a period of up to 30 years. The families were selected from the Yale Depression Research Unit, in New Haven, Connecticut.

There were no significant differences in the groups in terms of age, sex, and educational attainment.

Of the 62 of families participating in the study, biological children of depressed compared to nondepressed parents were found to have a twofold increased risk for MDD (hazard ratio [HR], 2.02; P = .03), which is consistent with previous studies.

For children of parents with depression, the incidence of other disorders was also increased; these included any disruptive disorder (HR, 1.70; P = .03), substance dependence (HR, 2.96; P = .01), any suicidal ideation or gesture (HR, 2.44; P = .007), and poor functioning (P < .001).

Children of parents with depression who also had one or more grandparents with depression were found to have the highest rates of psychiatric disorders, with 27 of 38 (71.1%) having at least one disorder, compared to 63% of those whose parents had depression but whose grandparents did not, and 51.4% in children whose parents and grandparents did not have MDD.

The risk for depression among children with a parent who had MDD was approximately twofold higher when the grandparent also had a history of MDD compared to those whose grandparents did not have MDD.

The risk was nearly three times greater when the parent and grandparent had depression compared to those not having a parent with depression (HR, 2.70; P = .008).

Threefold Increased Risk

"It was a major finding that there was a threefold risk of having depression if two previous generations also had depression," Dr Weissman told Medscape Medical News.

She added that an important strength of the study was the inclusion of direct interviews with the participants.

"The value of this study is that everyone was directly interviewed by clinically trained professionals," she says.

"The subjects didn't just fill out a form; they were directly interviewed, and the data were used blindly by psychiatrists and psychologists to make sure they agreed with the diagnosis. They also didn't know if the subject came from a high- or low-risk family, so we have confidence in the data."

Important limitations of the study were the inability to evaluate sex effects, ethnic diversity, or multiple risk factors due to the sample size, the authors note.

Whereas taking a family history is already standard in the clinical assessment of depression, the findings suggest that inquiring even further into family generations may help identify those most at risk, said Dr Weissman.

"The take-home message from this is that depression is transmitted across generations and grandchildren, and those with two previously affected generations are at the highest risk," she added.

"It's very easy to screen for this using the available family history screens, and it is probably a very useful thing to do. Until we have other biomarkers, this is a very easy and inexpensive one."

The study was supported in part by a grant from the National Institute of Mental Health (NIMH), the Sackler Institute for Developmental Psychobiology, and the Silvio O. Conte Center for Translational Mental Health Research. Dr Weissman has received funding from the NIMH, the National Institute on Drug Abuse, the National Alliance for Research on Schizophrenia and Depression, the Sackler Institute for Developmental Psychobiology, and the John Templeton Foundation and has received royalties from Oxford University Press, Perseus Books Group, American Psychiatric Association Publishing, and Multi-Health Systems (all in the past 3 years).

JAMA Psychiatry. Published online August 10, 2016. Abstract


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