FELLOW:CROWLEY, S Sleep Dysregulation and Neuroendocrine Stress Reactivity: Towards a Biopsychosocial Model of Vulnerability to Postpartum Depression

Research project


The proposed pilot research is intended to lay the groundwork for developing a model of prediction and underlying neurobiological basis for postpartum depression (PPD). PPD has been defined as an episode of major depressive disorder which occurs within six months of delivery.1 PPD is estimated to affect 10% to 15% of mothers of childbearing age,2-4 and has been consistently associated with long-term adverse effects on child cognitive and behavioral development,5,6 paternal affect,7,8 and family functioning.9-11 Although a history of depression and clinically significant sleep disturbances during pregnancy are each strong predictors of PPD, the mechanisms by which these factors predict PPD are unknown.

Based on the evidence that both a history of depression and clinically relevant sleep disturbances are linked to chronic stress,12-15 a central hypothesis underlying the proposed research is that these predictors share a common stress-responsive biological mechanism(s), the identification of which would inform preventative interventions not only for PPD, but potentially for depressions across the lifespan.

Indeed, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) stress axis is a robust finding in the insomnia and depression literatures.16-18 Evidence suggests that a particular biological stress reactivity profile, characterized by heightened activity of the HPA axis and reduced allopregnanolone (ALLO) stress reactivity -a metabolite of progesterone that buffers the HPA stress response and also has sedative/hypnotic properties - persists in women with a history of depression even after remission. It is possible that those women predisposed to heightened physiological reactivity to even mild stressors might exhibit more profoundly disturbed sleep during early pregnancy as a result of the increased physiological and psychosocial challenges of pregnancy,19,20 though it must also be acknowledged that disturbed sleep may also drive HPA axis hyper-activity.16,21,22 Consequently, based on the evidence that dysregulation in neurobiological mechanisms which may render certain individuals vulnerable to PPD 23,24 might also confer vulnerability to clinically significant sleep disturbances; 25,26 the biological profile of exaggerated HPA axis and blunted ALLO reactivity that has been observed in women with histories of depression may be one fundamental mechanism which explains the association between sleep dysregulation in pregnancy and the development of PPD symptomatology.
Effective start/end date7/1/146/30/17


  • Foundation of Hope for Research and Treatment of Mental Illness


Postpartum Depression
Physiological Stress
Major Depressive Disorder
Sleep Initiation and Maintenance Disorders
Hypnotics and Sedatives