Understanding risk for depression in adolescence [electronic resource] : the roles of puberty and stress

Adolescence is a period of heightened vulnerability for multiple forms of psychopathology, including major depressive disorder (MDD). Furthermore, a significant sex difference in incidence of MDD emerges in early adolescence, during and after which females are twice as likely as males to develop the disorder (Avenevoli, Swendsen, He, Burstein, & Merikangas, 2015; Breslau et al., 2017). Importantly, the age at which this sex divergence arises corresponds to the complex developmental stage of puberty. Indeed, pubertal development involves a host of biological, psychological, and social changes that researchers posit contribute to the increase in rates of MDD in adolescent females. The research presented in this dissertation was designed to investigate adolescence, and more specifically, puberty, as a period of vulnerability for the development of MDD, particularly for adolescent girls. In this work, we begin to elucidate the puberty-related changes in psychobiological responses to stress that increase adolescent girls' risk for the development of MDD. To do this, we examined HPA axis function and corticolimbic function in two samples of adolescents at high risk for the development of MDD -- a sample of female adolescents with familial history of depression, and a sample of males and females exposed to varying levels of early life stress (ELS). In Study 1, we examined whether pubertal stage moderates the influence of cortisol responses to stress on the subsequent development of MDD in a sample of adolescent females at high familial risk for the development of MDD. We found that the onset of MDD is predicted by cortisol hyporeactivity in girls who are earlier in pubertal development, but by cortisol hyperreactivity in girls who are later in pubertal development. These findings demonstrate that girls' cortisol stress reactivity predicts the subsequent onset of MDD, but that the nature of this effect depends on the girls' level of pubertal development. In Study 2, we extended this work by exploring sex differences in the association between ELS and internalizing problems in early pubertal adolescents, and whether and how corticolimbic function and connectivity may underlie these associations. We found that females exhibited a positive association between ELS and internalizing problems, whereas males exhibited no such association. Whole-brain and amygdala region-of-interest analyses indicated that whereas females exhibited a positive association between ELS and ventrolateral prefrontal cortex (vlPFC) during implicit emotion regulation, males showed no such association. Activation in these regions was positively associated with internalizing problems in females but not males. These sex differences in the effect of ELS on corticolimbic function may play a significant role in subsequent risk for internalizing problems. Finally, in Study 3, we used preliminary longitudinal data from this same sample of pubertal adolescents to explore associations among sex steroids (specifically estradiol and testosterone), corticolimbic function and connectivity, and depressive symptoms. We provided preliminary evidence for a protective effect of testosterone on the association between ELS and depressive symptoms, and an association between higher levels of testosterone and decreased right amygdala activation for negative emotional images. These findings elucidate a potential neurobiological mechanism underlying the emergence of sex differences in rates of depression documented in adolescence. We also found preliminary associations between both testosterone and estradiol levels and greater negative connectivity between amygdala and vlPFC, suggesting that sex steroids drive the adolescent-typical development of negative connectivity between the amygdala and PFC. Together, these findings contribute to a growing body of literature examining the psychobiological effects of pubertal development, and highlight the role that puberty-related psychobiological changes in the stress response system may play a role in the etiology of depression in adolescence.

Keywords: Psychology.
Advisor: Gotlib Ian H.
Gweon Hyowon
Singh Manpreet
Zaki Jamil