Characterizing Psychological Consequences of Childhood Trauma
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Study type: Observational

Summary: 
      This study will characterize the mental health consequences of early-life trauma.
    

Detailed description: 
      This primary goal of this Center is to characterize the neurobiological consequences of
      early-life trauma. The Center comprises 6 projects that include human subjects. Human
      subjects are recruited through Project 6.

      Project 2: Psychoimmunology (PI A.H. Miller) Project 4: A Model of Learned Safety(PI: M.
      Davis) Project 6: Clinical Psychobiology(PI: C. Heim) Project 7: Children of Depressed
      Mothers(PI: Z. Stowe) Project 8: Functional Brain Imaging (PIs: H.S. Mayberg, G. Berns)
      Project 9: Structural & Anatomical Connectivity Studies (PI: C.Kilts, X. Hu).

      Project 2: The study seeks to examine the impact of psychosocial stress on neuroendocrine and
      immune signaling pathways of adult men and women with and without major depression who have
      experienced serious trauma (abuse, loss) during development. Serial blood samples will be
      collected at baseline and after an acute speech/math stressor (see Project 6). Assessments
      include IL-1alpha, and beta, IL-6, TNF alpha as well as DNS binding of relevant
      neuroendocrine-immune transcription factors, i.e. GR, CREB, and NFkB.

      Project 4: This study uses a model of that allows for the independent evaluation of
      excitation and inhibition of fear-conditioning measured with the acoustic startle reflex. In
      addition, a dark-enhanced startle paradigm will be used that tests for anxiety. The effects
      of early-life stress will be evaluated in humans with and without major depressive disorder.

      Project 6: This study assesses neuroendocrine and autonomic responses to stress and
      pharmacological challenge in subjects with and without major depression who have or have nor
      experienced early life stress. We seek to identify causes of variability in
      neuroendocrine-autonomic outcome after early life stress. To achieve this principle aim, we
      study the role of moderating and mediating factors including gender, genotype, type/timing of
      childhood trauma, as well as the role of adulthood trauma, comorbidity and cognitive
      dysfunction. The projects serves as a human subjects core for the other projects.

      Project 7: This project characterizes effects of maternal depression on offspring in a
      longitudinal study. Women with and without depression will be prospectively followed through
      pregnancy and the first 6 months post-partum. Maternal stress and psychopathology, pregnancy
      and birth complications, medications and infants' physiological and behavioral stress
      responses will be assessed.

      Project 8: This study uses PET and fMRI to characterize the impact of early-life stress on
      functional neural pathways mediating mood reactivity, self reference and reward-processing in
      patients with major depression. Cortical-limbic-striatal changes in cases with early stress
      but no psychopathology that define vulnerability to depression are also identified.

      Project 9: This Project uses data obtained in Project 8 as well as diffusion tensor imaging
      to define the influence of early-life trauma on brain anatomical and functional connectivity.
    

Intervention name(s): DEX-CRF stimulation test; Psychosocial stress induction; Brain imaging of sad mood , self-reference, reward; Acoustic startle
Intervention type(s): Drug; Behavioral; Procedure; Behavioral
Intervention description(s): 1 ug/kg body weight of CRF for determining hpa response post dexamethasone ingestion; Laboratory stress induction, no drug administration; Brain imaging; No drugs involved
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        This study will include participants who have experienced early-life trauma.
      
Keywords: Child Abuse; Hypothalamic-Pituitary-Adrenal Axis; Brain Imaging; Depression