Neurophysiology, Estrogen, and Stress Exposure in the Emergence of Depression in Adolescent Girls
Condition: Adolescent Development; Stress; Emotional Disturbances
MeSH terms: Affective Symptoms
Study type: Observational

Summary: 
      The prevalence of adolescent depression is steadily rising in the U.S., especially among
      adolescent girls. Currently 20% of adolescent girls experience major depression compared with
      6% of boys (National Institute of Mental Health, 2016). The profound gender disparity in
      depression that emerges at puberty, but not before, implicates a role of ovarian steroid
      hormones in promoting affective (mood) symptoms in adolescent girls. In addition to dramatic
      physical maturation and a rapidly changing reproductive hormone environment at puberty,
      adolescence is also a time of exposure to substantial psychosocial stress, particularly in
      girls. It is well documented that stress interferes with the maturation of neurodevelopmental
      trajectories and is a critical precipitating factor in the pathway to psychopathology.
      However, the neuropathophysiological mechanisms linking stress exposure and sensitivity to
      ovarian hormone fluctuations at puberty to the onset and maintenance of depression symptoms
      in adolescence have yet to be elucidated, and is the purpose of this research.
    

Detailed description: 
      Framed within a diathesis-stress model of disease, the primary objective of this research is
      to determine a pathophysiological role of estradiol (E2) variability in the context of severe
      psychosocial stress exposure in regulating neurophysiological correlates of affective state
      change in girls (ages 11-14) during the pubertal transition (i.e., Tanner developmental
      stages 3 or 4). The rationale for examining E2 variability as a diathesis for mood impairment
      is twofold. First, sensitivity to hormonal flux during specific reproductive events has been
      shown to trigger affective symptoms in susceptible women, and second, E2 is a powerful
      neuroregulator of neural networks implicated in depression.

      55 peripubertal girls undergoing a healthy pubertal transition will be recruited for the
      study. Over an 8-week period, depression symptoms (Center for Epidemiological Studies
      Depression Scale for Children (CES-DC)), anxiety (State Trait Anxiety Inventory (STAI-C)),
      and perceived stress (perceived stress scale (PSS)), and salivary E2 measured by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) will be assessed on a weekly basis. An
      electroencephalogram (EEG) during an emotional go/no-go task will be performed after the
      8-week collection period to probe neurophysiological correlates of maturing fronto-limbic
      circuitry and assess key domains of cognitive and emotional processing impacted by the
      hormonal milieu. At the follow-up visit, an acute psychosocial stressor (Trier Social Stress
      Test) will be administered to examine cortisol and autonomic stress reactivity. The central
      hypothesis of the proposed research is that the amplitude and synchrony of frontal neural
      oscillations evoked during the cognitive-affective processing paradigm, and cortisol
      reactivity to the psychosocial stressor will partially mediate the relationship between
      greater E2 variability and elevated depression symptoms in peripubertal girls, and this
      relationship will be particularly strong in girls who have experienced recent (within six
      months) psychosocial stress.
    

Intervention name(s): Trier Social Stress Test; Emotional go/no-go task
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Participants will perform an acute psychosocial stress manipulation (Trier Social Stress Test) involving a speech task and challenging mental arithmetic.; Participants will perform an emotional go/no-go paradigm to examine electrophysiological (EEG) correlates of cognitive and affective processing.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Study will recruit participants of various racial, ethnic and socioeconomic backgrounds,
        reflective of the local population (60% White, 20% Black or African American, 10% Asian,
        and 10% Hispanic or Latino). Participants will be recruited from medical offices, schools
        and community centers (youth groups, church groups) in Orange and Durham Counties.
      
Biospecimen description: 
      Whole blood and serum samples will be stored to potentially assess neurosteroids and
      additional stress-responsive biomarkers in the future. Samples will be labelled by subject
      ID, without personal identifiers.
    
Keywords: puberty; EEG; estradiol; mood; stress