Amygdala reactivity during socioemotional processing and cortisol reactivity to a psychosocial stressor.

Threat-related amygdala reactivity and the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis have been linked to negative psychiatric outcomes. The amygdala and HPA axis have bidirectional connections, suggesting that functional variation in one system may influence the other. However, research on the functional associations between these systems has demonstrated mixed findings, potentially due to small sample sizes and cortisol sampling and data analytic procedures that investigate only pre-post differences in cortisol rather than the specific phases of the cortisol stress response. Further, previous research has primarily utilized samples of adults of mostly European descent, limiting generalizability to those of other ethnoracial identities and ages. Therefore, studies addressing these limitations are needed in order to investigate the functional relations between amygdala reactivity to threat and HPA axis stress responsivity. Using a sample of 159 adolescents from a diverse cohort (75% African American, ages 15-17 years), the present study evaluated associations between amygdala reactivity during socioemotional processing using fMRI and HPA axis reactivity to a socially-evaluative cold pressor task. Greater amygdala activation to fearful and neutral faces was associated with greater cortisol peak values and steeper activation slope. As cortisol peak values and cortisol activation slope capture the intensity of the cortisol stress response, these data suggest that greater activation of the amygdala in response to social distress and ambiguity among adolescents may be related to hyper-reactivity of the HPA axis.

DHEA Moderates the Impact of Childhood Trauma on the HPA Axis in Adolescence.

BACKGROUND: Trauma can lead to long-term downregulation of the hypothalamic pituitary adrenal (HPA) axis. However, dehydroepiandrosterone (DHEA) has neuroprotective effects that may reduce the need for downregulation of the axis in response to stress. Furthermore, high DHEA/cortisol ratios are often conceptualized as better markers of DHEA's availability than DHEA alone, as ratios account for the coupling of DHEA and cortisol in response to stress. OBJECTIVES: In this study, we explored if DHEA and DHEA/cortisol ratios moderated the association between childhood maltreatment and the HPA axis stress response. METHODS: The sample consisted of 101 adolescents (ages 12-16) who completed the Child Trauma Questionnaire (CTQ) and the Trier Social Stress Test (TSST). Cortisol was modeled using saliva samples at 8 time points throughout the TSST. Cortisol and DHEA ratios were examined at baseline and 35 min after stress initiation. RESULTS: Childhood maltreatment was associated with less steep cortisol activation slope and peak cortisol levels, but DHEA and DHEA/cortisol ratios moderated this effect. At high levels of DHEA, the impact of childhood maltreatment on cortisol peak levels was no longer significant. In contrast, high DHEA/cortisol ratios were associated with an intensification of the impact of childhood maltreatment on peak levels. CONCLUSIONS: Results suggest that DHEA can limit the blunting of the HPA axis in response to childhood maltreatment. However, this protective effect was not reflected in high DHEA/cortisol ratios as predicted. Therefore, high DHEA and high DHEA/cortisol ratios may reflect different, and potentially opposite, processes.

Violence exposure and social deprivation is associated with cortisol reactivity in urban adolescents.

The present study tested how two different dimensions of childhood adversity, violence exposure and social deprivation, were associated with the cortisol response to the Socially Evaluated Cold-Pressor task in a sample of 222 adolescents (n = 117 girls, n = 167 African American). Participants were part of the Fragile Families and Child Wellbeing Study, a probability sample of births in large US cities (>200,000) between 1998 and 2000. Our subsample includes births in three cities: Detroit, Toledo, and Chicago. The study design called for an oversampling of births to unmarried parents (3:1) which led to a large number of minority and economically disadvantaged adolescents. When children were ages 3, 5, and 9, mothers reported on exposures to violence and social deprivation that occurred in the past year. Exposures from the three waves were averaged to reflect violence exposure and social deprivation during childhood. Greater levels of violence exposure from ages 3 to 9 were associated with a blunted cortisol response to stress at age 15, even after controlling for social deprivation and other factors known to influence cortisol reactivity. Social deprivation from ages 3 to 9 was not associated with the cortisol response to stress; though in an exploratory analysis, social deprivation moderated the association between violence exposure and cortisol peak activation. In line with the Dimensional Model of Adversity and Psychopathology, these findings suggest that experiences of violence, but not social deprivation, during childhood may contribute to cortisol blunting that has been previously reported in samples with high levels of social deprivation. Findings from the present longitudinal study on a relatively large sample of under-represented minority youth provide insight into the ways two different dimensions of childhood adversity impact the cortisol response to stress.

Early trauma moderates the link between familial risk for depression and post-stress DHEA/cortisol ratios in adolescents.

BACKGROUND: One proposed mechanism for familial transmission of depression risk is impaired ability to regulate stress. While much of this work has focused on the stress hormone cortisol, there is evidence that the neuroprotective hormone dehydroepiandrosterone (DHEA) may play a critical role in stress regulation and that the ratios of DHEA to cortisol may provide meaningful information about individual differences in stress processing. In this study, we examined DHEA and DHEA/cortisol ratios among teens at low and high risk for depression. METHODS: Participants included 101 youth (12-16-year-old; 50 female) including 53 with a family history of depression (High Risk for depression). Adolescents and their parents completed diagnostic interviews, the Childhood Trauma Questionnaire and the Childhood Depression Inventory. Saliva samples were collected at multiple time points before and after adolescents underwent the Trier Social Stress Test. Cortisol and DHEA ratios were examined at baseline and 35 min post-stress initiation. RESULTS: High risk (HR) and low risk (LR) participants did not differ on DHEA/cortisol ratios. However, childhood trauma moderated the relationship between risk group and DHEA/cortisol ratios, where at high levels of trauma, HR participants had significantly higher ratios than LR participants. CONCLUSION: Our findings suggest that higher DHEA/cortisol ratios may not be indicative of greater protection against risk for depression as previously conceptualized. In the context of early trauma, higher DHEA/cortisol ratios may reflect a blunting of the HPA-axis that is not observed when examining cortisol levels alone. This study has implications for our conceptualization of DHEA/cortisol ratios as an indicator of risk for psychopathology.

Developmental influences on stress response systems: Implications for psychopathology vulnerability in adolescence.

The adolescent transition is marked by increases in stress exposure and significant maturation of neural and hormonal stress processing systems. Variability in the development of these systems during adolescence may influence the risk for stress-related psychopathology. This paper aims to review the developmental maturation of the HPA axis and related stress regulation systems, and demonstrate how interference in this adaptive developmental process may increase the risk for negative outcomes. We argue that the developmental maturation of the HPA axis aims to improve the regulatory capacity of the axis in order to more adaptively respond to these increases in stress reactivity. Additionally, we review evidence that sex differences in the development of the HPA and related axes may contribute to sex differences in the risk for stress-related psychopathology. Finally, we discuss how contextual factors, such as early trauma and obesity may alter the development of HPA axis during the adolescence transition and how alterations of normative development increase the risk for stress-related disorders.

Virtual reality job interview training and 6-month employment outcomes for individuals with schizophrenia seeking employment.

BACKGROUND: Individuals with schizophrenia have low employment rates and the job interview presents a critical barrier for them to obtain employment. Virtual reality training has demonstrated efficacy at improving interview skills and employment outcomes among multiple clinical populations. However, the effects of this training on individuals with schizophrenia are unknown. This study evaluated the efficacy of virtual reality job interview training (VR-JIT) at improving job interview skills and employment outcomes among individuals with schizophrenia in a small randomized controlled trial (n=21 VR-JIT trainees, n=11 waitlist controls). METHODS: Trainees completed up to 10h of virtual interviews using VR-JIT, while controls received services as usual. Primary outcome measures included two pre-test and two post-test video-recorded role-play interviews scored by blinded raters with expertise in human resources and self-reported interviewing self-confidence. Six-month follow-up data on employment outcomes were collected. RESULTS: Trainees reported that the intervention was easy-to-use, helpful, and prepared them for future interviews. Trainees demonstrated increased role-play scores between pre-test and post-test while controls did not (p=0.001). After accounting for neurocognition and months since prior employment, trainees had greater odds of receiving a job offer by 6month follow-up compared to controls (OR: 8.73, p=0.04) and more training was associated with fewer weeks until receiving a job offer (r=-0.63, p<0.001). CONCLUSIONS: Results suggest that VR-JIT is acceptable to trainees and may be efficacious for improving job interview skills in individuals with schizophrenia. Moreover, trainees had greater odds of receiving a job offer by 6-month follow-up. Future studies could evaluate the effectiveness of VR-JIT within community-based services.

Cannabis-related episodic memory deficits and hippocampal morphological differences in healthy individuals and schizophrenia subjects.

Cannabis use has been associated with episodic memory (EM) impairments and abnormal hippocampus morphology among both healthy individuals and schizophrenia subjects. Considering the hippocampus' role in EM, research is needed to evaluate the relationship between cannabis-related hippocampal morphology and EM among healthy and clinical groups. We examined differences in hippocampus morphology between control and schizophrenia subjects with and without a past (not current) cannabis use disorder (CUD). Subjects group-matched on demographics included 44 healthy controls (CON), 10 subjects with a CUD history (CON-CUD), 28 schizophrenia subjects with no history of substance use disorders (SCZ), and 15 schizophrenia subjects with a CUD history (SCZ-CUD). Large-deformation, high-dimensional brain mapping with MRI produced surface-based representations of the hippocampus that were compared across all four groups and correlated with EM and CUD history. Surface maps of the hippocampus were generated to visualize morphological differences. CON-CUD and SCZ-CUD were characterized by distinct cannabis-related hippocampal shape differences and parametric deficits in EM performance. Shape differences observed in CON-CUD were associated with poorer EM performance, while shape differences observed in SCZ-CUD were associated with a longer duration of CUD and shorter duration of CUD remission. A past history of CUD may be associated with notable differences in hippocampal morphology and EM impairments among adults with and without schizophrenia. Although the results may be compatible with a causal hypothesis, we must consider that the observed cannabis-related shape differences in the hippocampus could also be explained as biomarkers of a neurobiological susceptibility to poor memory or the effects of cannabis.