Many studies have demonstrated an increased risk for depression among the children of mothers with depression.  Exactly how this vulnerability to depression is transmitted to the child is not precisely understood.  Genetic factors clearly play an important role, but there are other important factors which contribute to the intergenerational transmission of depression.  For example, many studies have shown that postpartum depression may contribute to parenting styles which increase a child’s likelihood of developing depression later on.   While the child appears to be particularly sensitive to the effects of maternal depression during the first year of life, it appears that older children are also affected by maternal depression and are more likely to suffer from depression and other psychiatric symptoms than children with non-depressed mothers.

There is also evidence that what happens in utero, while the fetus is developing, may predispose a child to certain illnesses later on in life.  This concept of fetal programming is gaining traction and has been used to explain susceptibility to cardiovascular disease, obesity, and diabetes.  There is less information regarding fetal programming when it comes to risk for psychiatric illness; however, it has been hypothesized that alterations of the maternal hypothalamic-pituitary-adrenal (HPA) axis may influence the development of the fetal HPA axis.  When dysregulation of the maternal HPA axis occurs — as a result of exposure to stressful life events or the experience of anxiety or depressive symptoms during pregnancy – this may lead to long-standing alterations in the fetal HPA axis, making the child more susceptible to depression or anxiety as an adult.

Impact of Antenatal Anxiety

In 2008, van den Bergh and colleagues tested this hypothesis, exploring the connection between anxiety in mothers during pregnancy and disturbances in HPA axis regulation and subsequent vulnerability to depression in their children at adolescence.  Maternal anxiety was assessed at 12–22, 23–32, and 32–40 weeks of gestation using the State Trait Anxiety Inventory (STAI).  A total of 56 children were assessed at 14 to 15 years of age; the researchers found that higher anxiety levels at weeks 12-22 were associated with higher cortisol levels in the children at 15 years of age.  And in the female adolescents, antenatal exposure to maternal anxiety at 12–22 weeks was associated with an increased risk of depressive symptoms.

Impact of Antenatal Depression

A recent study demonstrates that antenatal exposure to maternal depression may also increase the risk of adolescent depression.  This study included participants of the Avon Longitudinal Study of Parents and Children (ALSPAC), a large prospective study enrolling mothers during pregnancy and following their children from birth onward.  Symptoms of maternal depression were measured using the Edinburgh Postnatal Depression Scale (EPDS).  Depression in the offspring was measured at 18 years of age using the computerized version of the Clinical Interview Schedule–Revised (CIS-R).

A total of 3374 children were included in the analysis.  The proportion of women with EPDS scores suggestive of major depression (mean scores of >12 at 2 time points) was 11.6% antenatally and 7.4% postnatally.  There was a strong correlation between antenatal and postnatal depressive symptoms.

For women with antenatal depression, the odds ratio (OR) of having a child with depression at age 18 was 1.47 (95% CI, 1.0-2.2; P=.047).  For women with postpartum depression, the OR was 1.67 (95% CI, 1.1-2.6; P=.03).  These effects were independent of exposure to maternal depression later on in the child’s life.

Because so many women with antenatal depression during also have postnatal depression, it is more difficult to determine which exposure – antenatal or postpartum — is responsible for increasing the child’s risk of depression.  Using various statistical models, the researchers were able to demonstrate that antenatal depression was an independent risk factor for offspring depression at age 18.

There appeared to be a dose effect, where higher scores of both antenatal and postpartum depression were associated with a higher risk of depression in the child.  Interestingly, maternal education appeared to modulate this risk for children exposed to postnatal but not antenatal depression.  In women with higher levels of education, antenatal depression was much more strongly associated with adolescent depression than postpartum depression.

While this study did not specifically test how maternal depression is transmitted to the adolescent child, the study provides indirect evidence that while antenatal and postnatal depression both increase the risk of depression in the adolescent offspring, their pathways appear to be different.  The authors speculate that because education is associated with various important environmental factors and moderates the negative effects of postpartum depression, postnatal depression increases the risk of adolescent depression through an environmental mechanism. Higher maternal education is typically associated with multiple sources of psychosocial support which, in turn, are likely to be protective in the context of depression.

In contrast, education does not appear to moderate the risk in women with antenatal depression.  Thus, the authors conclude that the effects of antenatal depression on the operating occur as a result of the biological consequences of depression in utero, which are unlikely to be mitigated by education and other environmental advantages.  They hypothesize that dysregulation of the HPA axis (similar to that observed in the van den Bergh study described above) may play an important role in modulating the negative effects of depression.

Opportunities for Intervention

These studies underline the importance of early detection and treatment of perinatal mood and anxiety disorders.  Over the last decade, there has been a push to identify and treat postpartum depression in order to minimize the impact of maternal depression on the family.  While this approach may help, these studies indicate that intervening after the baby is born may be too late and may not be able to significantly modulate the risks in children who are exposed to depression and anxiety antenatally.

Studies indicate that about 10%-15% of women suffer from depression during pregnancy.   Most women with antenatal depression receive no treatment, and even in those who do get some sort of treatment, it has been shown that the treatment is inadequate or less aggressive than would be required to fully treat the depression.  In this context, antenatal depression may predispose women to postpartum depression.  But most importantly, we may be missing an opportunity to reduce the long-term effects of maternal depression on the child, where treatment of depression during pregnancy, either with medication or non-pharmacologic strategies, may help to reduce the risk of depression and other psychiatric disorders in the children of depressed mothers.

Ruta Nonacs, MD PhD

Pearson RM, Evans J, Kounali D, et al. Maternal Depression During Pregnancy and the Postnatal Period: Risks and Possible Mechanisms for Offspring Depression at Age 18 Years.  JAMA Psychiatry. 2013 Oct 9.

Van den Bergh BR, Van Calster B, Smits T, Van Huffel S, Lagae L.  Antenatal Maternal Anxiety is Related to HPA-Axis Dysregulation and Self-Reported Depressive Symptoms in Adolescence: A Prospective Study on the Fetal Origins of Depressed Mood.  Neuropsychopharmacology. 2008 Feb;33(3):536-45.