Identifying the pathophysiology of depression and its permeability across the lifespan
Major depressive disorder (MDD) and risk for its development are characterized by reduced reactivity and flexibility to environmental demands. Frontal alpha asymmetry (FAA), heart rate variability (HRV), and salivary cortisol reactivity are each well-established indicators of regulation across neural, autonomic, and hypothalamic-pituitary-adrenal (HPA) physiological systems, respectively. Growing literature suggests that each of these processes is dysregulated in individuals with a history of MDD. However, patterns of dysregulation across these physiological systems and relative MDD risk are unknown. Moreover, these physiological regulatory patterns may extent beyond markers of MDD risk in adulthood to also capture the transmission of risk for MDD from parent to offspring. The following series of five studies investigated the pathophysiology of MDD and the permeability of risk across the lifespan. First, the pattern of dysregulation across physiological indices—representing neural, autonomic, and HPA functioning—in adults was examined with regard to depressive symptoms. Second, the associations amongst infant FAA, HRV, and cortisol reactivity and maternal depressive symptoms were assessed as potential early markers of depression risk. Third, mother-infant associations across physiological indices were investigated to assess direct intergenerational transmission of depression risk. Studies 4 and 5 further investigated pathophysiological functioning in mothers and infants within the context of comorbid anxiety and current depressive symptomatology versus lifetime MDD illness. Mothers and their 12-month-old infants (n = 35 dyads) completed resting- state and stressor tasks to assess regulatory patterns across neural, autonomic, and HPA systems, associations with MDD, and intergenerational transmission. In adults, results suggest that lifetime history of MDD is significantly associated with blunted cortisol reactivity; FAA and high- frequency HRV also demonstrated the same direction of associations. In infants, results demonstrated that maternal depressive symptoms, particularly current symptoms, relate to blunted physiological regulation in infants specifically for FAA and HRV indices. For mothers and infants, there was support for the direct intergenerational transmission of FAA and HRV indices. These intergenerational associations did not fully account for intergenerational risk of depression, as maternal physiological regulation and maternal depression were found to each significantly predict infant regulation as simultaneous predictors. Accounting for comorbid anxiety and examining current symptoms versus lifetime illness were essential to investigating associations amongst physiological functioning and depression. These patterns in conjunction with the literature suggest a developmental model to MDD pathophysiology that encompasses multiple theoretical frameworks. Future research is necessary to clarify regulatory patterns across physiological systems within individuals and across time with regard to MDD risk, onset, and course.