A Prospective Study of the Offspring of Depressed Parents: An Extension of the Barker Hypothesis?

P. Martinez

Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, U.S.A.

Background: Individuals with major depression have an attenuated ACTH response to exogenous CRH infusion, compared to normal controls. A similar response has been found in severely depressed children. Animal studies have demonstrated the long-term effects of rearing practices on the HPA axis function in the offspring. To date similar studies have not been carried out in humans. It has been shown that the genetic and behavioral contributions of parents with affective disorders, increase the vulnerability of the offspring to psychopathology. However, little is known about the development of the HPA axis function in offspring of mothers with mood disorders.

Methods: We performed a CRH infusion test in 63 offspring (ages 9 to 18 years) participating in a longitudinal study of mothers with major depression, bipolar illness or no psychiatric illness. Psychiatric and observational assessments of these families were done over the course of 15 years.

Results: Adolescents in late puberty (Tanner 4 and 5) had lower ACTH and cortisol responses to CRH infusion than those in early puberty (p < 0.02) (Fig. [1]). Offspring who experienced major depression subsequent to the CRH challenge, had an attenuated ACTH response during the CRH challenge (p < 0.03) (Fig. [2]). Offspring of mothers with avoidant personality disorders had an exaggerated ACTH but normal cortisol response (p < 0.001) (Fig. [3]). Chronic high family stress was associated with reduced cortisol responses (p < 0.02).

Fig. 1 a

Fig. 1 b

Fig. 2 a

Fig. 2 b

Fig. 3

Conclusions: Our findings suggest mechanisms through which maternal psychopathology can be transmitted to her offspring. The present study highlights the relationship between early childhood experiences and differential HPA axis responses. Maternal characteristics and environmental factors may contribute to specific HPA axis patterns. Post CRH infusion patterns displayed by adults with depression appear to develop with repeated depressive episodes and may be mediated by puberty. Attenuated ACTH response to the CRH infusion could be an early indicator of susceptibility to the development of depression later in life.