Neurophysiological Correlates Linking Testosterone Flux and Affective Symptoms in Peripubertal Females

• In Event: Stress and Adversity in Adolescents: The Roles of Stress Physiology

Abstract

Background: The pubertal transition (peripuberty) is characterized by profound changes in the reproductive endocrine environment, refinement of frontal-limbic affective circuitry involved with stress and emotion regulation, and a substantially increased risk of affective illness in females. Experimental studies demonstrate that a differential sensitivity to abrupt hormone changes can precipitate affective symptoms in susceptible females. Additional risk accompanies reproductive transition events characterized by dramatic sex hormone fluctuation, including the pubertal and menopausal transitions. Sex hormones, including testosterone, exert significant modulatory effects on frontal and limbic neural networks and have been associated with affective dysregulation and severity of depressive symptoms. Further, it has been previously reported that weekly changes in testosterone, even more so than estrone, are a strong predictor of affective symptom severity in peripubertal females, especially in the context of stress; however, the neurophysiological mechanisms linking testosterone flux with affective symptoms are poorly understood and thus, was the objective of the present study.

Methods: 42 peripubertal females (ages 11-14, pre- or within 1-year post-menarche) collected 8-weekly salivary testosterone samples (pg/mL, assayed via LC-MS/MS) and mood assessments to evaluate hormone sensitivity (i.e., depressive symptoms tied to weekly change in testosterone). After 8 weeks of hormone collections and mood assessments, participants completed a neurophysiological testing session involving an EEG recording during an emotional go/no-go task, and cortisol (ln ug/dL) during a psychosocial stress manipulation (Trier Social Stress Test for Children). Within-person correlations between weekly change in testosterone and corresponding mood ratings were performed to determine individual differences in mood sensitivity to testosterone flux. Theta oscillatory activity (4-8 Hz) was extracted from frontal channels to index frontal cognitive control. Linear mixed models predicted cortisol stress reactivity and task-evoked frontal theta oscillations from testosterone-sensitivity.

Results: A stronger testosterone-mood relationship predicted decreased cortisol reactivity (F(5,190) = 3.02, p=.012) during the psychosocial stress task. Further, participants who were mood-sensitive to testosterone change exhibited increased event-related frontal theta oscillations indexing aberrant cognitive control (F(1,40) = 8.162, p=0.007) in response to emotional face stimuli and greater behavioral disinhibition (no-go errors), particularly for fear no-go distractor trials (F(1,39) = 5.71, p=0.02).

Conclusion: Results indicated that participants who were mood sensitive to testosterone flux demonstrated a distinct disruption in neurophysiological correlates of frontal control, blunted stress reactivity, and impulsive behavioral tendencies. Thus, aberrant frontal-limbic mediated stress and emotion regulation may increase mood sensitivity to normal peripubertal hormone flux. Ultimately, this research has important implications for identifying early risk factors and potential treatment targets for adolescent psychopathology during a critical window for intervention efforts.

Authors

• Elizabeth Andersen, University of North Carolina at Chapel Hill
  Presenting Author

• Crystal Schiller, University of North Carolina at Chapel Hill

• Alana Campbell, University of North Carolina at Chapel Hill

• Susan Girdler, University of North Carolina at Chapel Hill