Neurophysiology, Estrogen, and Stress Exposure in the Emergence of Depression in Adolescent Girls
Neurophysiology, Estrogen, and Stress Exposure in the Emergence of Depression in Adolescent Girls
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.
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.
Inclusion Criteria:

 -  Female, 11 to 14 years of age

 -  Meet Tanner developmental stage criteria (as indicated by self-report and pictorial
 scales of breast and pubic hair development) for pubertal stages 3 or 4

 -  Must be undergoing a healthy pubertal transition, pre-or-post menarche (within 15
 months of menarche, with cycle irregularity)

 -  Girls must be able to read at a 4th-grade reading level

 Exclusion Criteria:

 -  Current suicidal intent (based off Columbia-Suicide Severity rating scale)

 -  A history or current diagnosis of bipolar disorder or psychosis

 -  Currently on any prescription medications