Early Life Stress and Depression: Molecular and Functional Imaging

Severe childhood adversity accounts for a large portion of psychiatric illness, and an increased risk for major depressive disorder (MDD). For some individuals, childhood adversity has negative psychological and medical consequences; others preserve mental and physical health despite such experiences (they are resilient). In spite of this, little is known about the neurobiological mechanisms related to childhood adversity, especially oxidative stress abnormalities in the brain. To fill this gap, this study combines functional, structural, and molecular imaging approaches to examine the role of oxidative stress abnormalities related to childhood adversity.

Epidemiological studies have shown that severe childhood adversity explains 32-44% of psychiatric disorders, and is associated with 4.6-fold risk for MDD later in life. In spite of these epidemiological data, the neurobiological underpinnings associated with maladaptive sequelae of severe childhood adversity as well as resilience remain largely unknown. Preclinical research suggests that early adversity leads to (1) structural abnormalities in brain regions critically implicated in stress regulation; (2) increased oxidative stress; and (3) glutamatergic abnormalities. The current research protocol is designed to prospectively test the contributions of these abnormalities in individuals exposed to severe childhood adversity. Improving our understanding of neurobiological mechanisms associated with different childhood adversity outcomes is of paramount importance in order to (1) identify individuals at risk for psychopathology and maladaptive behavior, (2) prevent re-victimization, and (3) develop more targeted therapeutic interventions.