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Background: Psychosocial stressors characterized by social threat, such as interpersonal loss and social rejection, are associated with depression in adolescents. Few studies, however, have examined whether social threat affects fronto-cingulate-limbic systems implicated in adolescent depression. Methods: We assessed lifetime stressor severity across several domains using the Stress and Adversity Inventory (STRAIN) in 57 depressed adolescents (16.15 ± 1.32 years, 34 females), and examined whether the severity of social threat and non-social threat stressors was associated with gray matter volumes (GMVs) in the anterior cingulate cortex (ACC), amygdala, hippocampus, and nucleus accumbens (NAcc). We also examined how lifetime social threat severity and GMVs in these regions related to depressive symptoms at baseline and over 9 months. Results: General stressor severity was related to greater depression severity at baseline and over 9 months. Moreover, greater severity of social threat (but not non-social threat) stressors was associated with smaller bilateral amygdala and NAcc GMVs, and smaller bilateral surface areas of caudal and rostral ACC (all p FDR ⩽ 0.048). However, neither social threat nor non-social threat stressor severity was related to hippocampal GMVs (all p FDR ⩾ 0.318). All fronto-cingulate-limbic structures that were associated with the severity of social threat were negatively associated with greater depression severity over 9 months (all p FDR ⩽ 0.014). Post-hoc analyses suggested that gray matter morphometry of bilateral amygdala, NAcc, and rostral and caudal ACC mediated the association between social threat and depression severity in adolescents over 9 months (all p FDR < 0.048). Conclusions: Social threat specifically affects fronto-cingulate-limbic pathways that contribute to the maintenance of depression in adolescents. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is a unique period of stress, uncertainty, and adversity that will have significant implications for adolescent mental health. Nevertheless, stress and adversity related to COVID-19 may be more consequential for some adolescents' mental health than for others. We examined whether heart rate variability (HRV) indicated differential susceptibility to mental health difficulties associated with COVID-19 stress and COVID-19 family adversity. Approximately 4 years prior to the pandemic, we assessed resting HRV and HRV reactivity to a well-validated stress paradigm in 87 adolescents. During the pandemic, these adolescents (ages 13–19) reported on their health-related stress and concerns about COVID-19, family adversity related to COVID-19, and their recent emotional problems. The association between COVID-19 stress and emotional problems was significantly stronger for adolescents who previously exhibited higher resting HRV or higher HRV reactivity. For adolescents who exhibited lower resting HRV or HRV augmentation, COVID-19 stress was not associated with emotional problems. Conversely, lower resting HRV indicated vulnerability to the effect of COVID-19 family adversity on emotional problems. Different patterns of parasympathetic functioning may reflect differential susceptibility to the effects of COVID-19 stress versus vulnerability to the effects of COVID-19 family adversity on mental health during the pandemic. [ABSTRACT FROM AUTHOR]

Social anxiety disorder (SAD) is commonly diagnosed during adolescence and is associated with psychological stress reactivity and heightened physiological arousal. No study, however, has systematically examined which aspects of autonomic nervous system function mediate likely links between stress sensitivity and social anxiety symptoms in adolescents. Here, we assessed 163 adolescents (90 females; 12.29 ± 1.39 years) with respect to life stress and social anxiety symptoms, and measured respiratory sinus arrhythmia (RSA) and skin conductance levels (SCL) during a psychosocial stress paradigm. We operationalized stress sensitivity as the residual variance in subjective stress severity after accounting for objective severity and changes in autonomic regulation using standardized change scores in RSA and SCL. In females only, stress sensitivity and social anxiety symptoms were significantly correlated with each other (p <.001) and with autonomic regulation during both reactivity and recovery (all ps < 0.04). Further, sympathetic nervous system dominance during recovery specifically mediated associations between stress sensitivity and social anxiety symptoms (B = 1.06, 95% CI: 0.02–2.64). In contrast, in males, stress sensitivity, autonomic regulation during reactivity or recovery, and social anxiety symptoms were not significantly associated (all ps > 0.1). We interpret these results in the context of psychobiological models of SAD and discuss implications for interventions targeting autonomic processes. [ABSTRACT FROM AUTHOR]

Early life stress (ELS) is a risk factor for the development of depression in adolescence; the mediating neurobiological mechanisms, however, are unknown. In this study, we examined in early pubertal youth the associations among ELS, cortisol stress responsivity, and white matter microstructure of the uncinate fasciculus and the fornix, two key frontolimbic tracts; we also tested whether and how these variables predicted depressive symptoms in later puberty. A total of 208 participants (117 females; M age = 11.37 years; M Tanner stage = 2.03) provided data across two or more assessment modalities: ELS; salivary cortisol levels during a psychosocial stress task; diffusion magnetic resonance imaging; and depressive symptoms. In early puberty there were significant associations between higher ELS and decreased cortisol production, and between decreased cortisol production and increased fractional anisotropy in the uncinate fasciculus. Further, increased fractional anisotropy in the uncinate fasciculus predicted higher depressive symptoms in later puberty, above and beyond earlier symptoms. In post hoc analyses, we found that sex moderated several additional associations. We discuss these findings within a broader conceptual model linking ELS, emotion dysregulation, and depression across the transition through puberty, and contend that brain circuits implicated in the control of hypothalamic–pituitary–adrenal axis function should be a focus of continued research. [ABSTRACT FROM AUTHOR]

Early life stress (ELS) is a significant risk factor for the emergence of internalizing problems in adolescence. Beginning in adolescence, females are twice as likely as males to experience internalizing disorders. The present study was designed to examine 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. Fifty-nine early pubertal males and 78 early pubertal females, ages 9-13 years (all Tanner Stage 3 or below) underwent functional magnetic resonance imaging as they performed an emotion label task that robustly interrogates corticolimbic function. Participants were also interviewed about their experience of ELS. 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 the ventrolateral prefrontal cortex during implicit emotion regulation, males showed no such association. Activation in these regions was positively associated with internalizing problems in females but not males; however, activation in these regions did not mediate the association between ELS and internalizing problems. Finally, both boys and girls exhibited an association between ELS and increased negative connectivity between the right ventrolateral prefrontal cortex and bilateral amygdala. Using a carefully characterized sample of early pubertal adolescents, the current study highlights important sex differences in the development of corticolimbic circuitry during a critical period of brain development. These sex differences may play a significant role in subsequent risk for internalizing problems. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is a unique period of stress, uncertainty, and adversity that will have significant implications for adolescent mental health. Nevertheless, stress and adversity related to COVID-19 may be more consequential for some adolescents' mental health than for others. We examined whether heart rate variability (HRV) indicated differential susceptibility to mental health difficulties associated with COVID-19 stress and COVID-19 family adversity. Approximately 4 years prior to the pandemic, we assessed resting HRV and HRV reactivity to a well-validated stress paradigm in 87 adolescents. During the pandemic, these adolescents (ages 13-19) reported on their health-related stress and concerns about COVID-19, family adversity related to COVID-19, and their recent emotional problems. The association between COVID-19 stress and emotional problems was significantly stronger for adolescents who previously exhibited higher resting HRV or higher HRV reactivity. For adolescents who exhibited lower resting HRV or HRV augmentation, COVID-19 stress was not associated with emotional problems. Conversely, lower resting HRV indicated vulnerability to the effect of COVID-19 family adversity on emotional problems. Different patterns of parasympathetic functioning may reflect differential susceptibility to the effects of COVID-19 stress versus vulnerability to the effects of COVID-19 family adversity on mental health during the pandemic.

Background: Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age., Methods: Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer., Results: CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions., Conclusions: Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.