Background
Stressful events, such as the COVID‐19 pandemic, are major contributors to anxiety and depression, but only a subset of individuals develop psychopathology. In a population‐based sample ...(N = 174) with a high representation of marginalized individuals, this study examined adolescent functional network connectivity as a marker of susceptibility to anxiety and depression in the context of adverse experiences.
Methods
Data‐driven network‐based subgroups were identified using an unsupervised community detection algorithm within functional neural connectivity. Neuroimaging data collected during emotion processing (age 15) were extracted from a priori regions of interest linked to anxiety and depression. Symptoms were self‐reported at ages 15, 17, and 21 (during COVID‐19). During COVID‐19, participants reported on pandemic‐related economic adversity. Differences across subgroup networks were first examined, then subgroup membership and subgroup–adversity interaction were tested to predict change in symptoms over time.
Results
Two subgroups were identified: Subgroup A, characterized by relatively greater neural network variation (i.e., heterogeneity) and density with more connections involving the amygdala, subgenual cingulate, and ventral striatum; and the more homogenous Subgroup B, with more connections involving the insula and dorsal anterior cingulate. Accounting for initial symptoms, subgroup A individuals had greater increases in symptoms across time (β = .138, p = .042), and this result remained after adjusting for additional covariates (β = .194, p = .023). Furthermore, there was a subgroup–adversity interaction: compared with Subgroup B, Subgroup A reported greater anxiety during the pandemic in response to reported economic adversity (β = .307, p = .006), and this remained after accounting for initial symptoms and many covariates (β = .237, p = .021).
Conclusions
A subgrouping algorithm identified young adults who were susceptible to adversity using their personalized functional network profiles derived from a priori brain regions. These results highlight potential prospective neural signatures involving heterogeneous emotion networks that predict individuals at the greatest risk for anxiety when experiencing adverse events.
There is a critical need for fast, inexpensive, objective, and accurate screening tools for childhood psychopathology. Perhaps most compelling is in the case of internalizing disorders, like anxiety ...and depression, where unobservable symptoms cause children to go unassessed-suffering in silence because they never exhibiting the disruptive behaviors that would lead to a referral for diagnostic assessment. If left untreated these disorders are associated with long-term negative outcomes including substance abuse and increased risk for suicide. This paper presents a new approach for identifying children with internalizing disorders using an instrumented 90-second mood induction task. Participant motion during the task is monitored using a commercially available wearable sensor. We show that machine learning can be used to differentiate children with an internalizing diagnosis from controls with 81% accuracy (67% sensitivity, 88% specificity). We provide a detailed description of the modeling methodology used to arrive at these results and explore further the predictive ability of each temporal phase of the mood induction task. Kinematical measures most discriminative of internalizing diagnosis are analyzed in detail, showing affected children exhibit significantly more avoidance of ambiguous threat. Performance of the proposed approach is compared to clinical thresholds on parent-reported child symptoms which differentiate children with an internalizing diagnosis from controls with slightly lower accuracy (.68-.75 vs. .81), slightly higher specificity (.88-1.00 vs. .88), and lower sensitivity (.00-.42 vs. .67) than the proposed, instrumented method. These results point toward the future use of this approach for screening children for internalizing disorders so that interventions can be deployed when they have the highest chance for long-term success.
•We examined links between chronic stress, hair cortisol and depressive symptoms.•Hair cortisol and depressive responses increased with stressor onset.•However, they were not correlated, following ...distinct trajectories over time.•Links between HPA activity and depression may not be direct and causal.
Stress plays a causal role in depression onset, perhaps via alteration of hypothalamic-pituitary-adrenal (HPA) axis functioning. HPA axis hyperactivity has been reported in depression, though inconsistently, and the nature of this relationship remains unclear, partly because cortisol measurement over time has been challenging. Development of hair cortisol assessment, a method that captures cortisol over prolonged periods of time, creates new possibilities. In this study, hair cortisol was incorporated into a prospective and longitudinal study of medical internship, stress and symptoms of depression. This provided a rare opportunity to 1) prospectively assess hair cortisol responses to stress, and 2) examine whether stress-induced changes in hair cortisol predict depressive symptom development.
Hair cortisol, depressive symptoms, and stress-relevant variables (work hours, sleep, perceived stress, mastery/control) were assessed in interns (n = 74; age 25–33) before and repeatedly throughout medical internship.
Hair cortisol sharply increased with stressor onset, decreased as internship continued, and rose again at year’s end. Depressive symptoms rose significantly during internship, but were not predicted by cortisol levels. Hair cortisol also did not correlate with increased stressor demands (work hours, sleep) or stress perceptions (perceived stress, mastery/control); but these variables did predict depressive symptoms.
Hair cortisol and depressive responses increased with stress, but they were decoupled, following distinct trajectories that likely reflected different aspects of stress reactivity. While depressive symptoms correlated with stressor demands and stress perceptions, the longitudinal pattern of hair cortisol suggested that it responded to contextual features related to anticipation, novelty/familiarity, and social evaluative threat.
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.
•Variability in stress processing systems development during adolescence may influence the risk for psychopathology.•Maturation of the HPA axis during adolescence aims strengthening neural networks regulating negative feedback.•Sex differences in the availability of inhibitory hormones may contribute to greater risk for psychopathology in adolescent females.•Stress exposure may interfere with normative adolescent developmental changes to HPA axis processing, increasing risk for psychopathology.
Summary Research findings on the hypothalamic–pituitary–adrenal (HPA) axis and pediatric depression reflect a variety of methodological approaches that tap different facets of HPA-axis functions. ...Partly owing to the methodological heterogeneity of studies, descriptive reviews of this area have produced inconsistent conclusions. Therefore, we conducted formal meta-analyses of pertinent studies in order to advance our understanding of HPA-axis dysregulation in pediatric depression. We examined: (a) 17 published studies of HPA-axis response to the dexamethasone suppression test (DST) in depressed youth (DST; N = 926) and (b) 17 studies of basal HPA-axis functioning ( N = 1332). We also examined descriptively studies that used corticotropin-releasing hormone (CRH) infusion, and those that used psychological probes of the HPA-axis. The global standardized mean effect size difference in HPA-axis response to the DST between depressed and non-depressed youth was 0.57, z = 4.18, p < 0.01. The global standardized mean difference effect size in basal HPA-axis functioning was 0.20, z = 4.53, p < 0.01. Age, sex, timing of sampling, dexamethasone dosage, or type of control group was not a significant source of variability for the DST or basal studies. In addition, when compared to non-depressed peers, depressed youth have a normative response to CRH infusion but an overactive response to psychological stressors. In conclusion, the HPA-axis system tends to be dysregulated in depressed youth, as evidenced by atypical responses to the DST, higher baseline cortisol values, and an overactive response to psychological stressors. This pattern of dysregulation suggests anomalies within the axis's negative feedback system and CRH production, but intact pituitary and adrenal sensitivity.
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.
•Greater amygdala activation to fear associated with greater cortisol activation slope.•We found coupling of amygdala and HPA axis activation to threat in separate tasks.•Our findings are based on a highly diverse sample of adolescents.
Background: Given the long‐term morbidity of juvenile‐onset major depressive disorder (MDD), it is timely to consider whether more effort should be dedicated to its primary and secondary prevention.
...Methods: We reviewed studies of prodromal symptoms that may herald a first episode pediatric MDD and considered whether that literature has made an impact on secondary prevention (efforts to prevent progression from symptoms to full disorder). We also reviewed studies of children at familial risk for MDD that addressed atypical affectivity and the regulation of sad, dysphoric affect (mood repair) and related physiological systems, and considered whether research in those areas has made an impact on primary prevention of pediatric MDD (efforts to prevent the disorder).
Results: A compelling body of literature indicates that depressive symptoms in youngsters predict subsequent MDD across the juvenile (and early adult) years and that any combination of several symptoms for at least one week is informative in that regard. These findings are echoed in the case selection criteria used by many secondary prevention programs. Convergent findings also indicate that (compared to typical peers) young offspring at familial risk for depression manifest low positive affectivity and compromised mood repair, along with signs of dysfunction in three intertwined physiological systems that contribute to affectivity and mood repair (the hypothalamic–pituitary–adrenal (HPA) axis, cerebral hemispheric asymmetry, and cardiac vagal control). While all these affect‐related parameters are suitable for case selection and as intervention targets, they have not yet made an impact on primary prevention programs.
Conclusions: According to recent meta‐analyses, attempts to prevent pediatric depression have not lived up to expectations. Based on our review, possible reasons for this include: (a) the use of case selection criteria that yield samples heterogeneous with regard to whether the symptoms are truly prodromal to an episode of MDD or are trait‐like (which could affect response to the intervention), (b) failure to fully capitalize on the broad‐ranging literature on vulnerability to pediatric MDD, as evidenced by the infrequent use of family history of depression (a robust index of vulnerability) or combined indices of vulnerability for case selection, and (c) lack of synchrony between dimensions of vulnerability and the content of the prevention program, as indicated by the overwhelming use of cognitive‐behavioral interventions, irrespective of subjects’ age, developmental readiness, and whether or not they evidenced the relevant cognitive vulnerability. Prevention trials of pediatric MDD could benefit from new approaches to case selection that combine various indices of vulnerability, more effective use of existing findings, and new or modified interventions that are developmentally sensitive.
The hypothalamic–pituitary–adrenal axis (HPA axis) is a pathway through which childhood trauma may increase risk for negative health outcomes. The HPA axis is sensitive to stress throughout ...development; however, few studies have examined whether timing of exposure to childhood trauma is related to differences in later HPA axis functioning. Therefore, we examined the association between age of first trauma and HPA axis functioning among adolescents, and whether these associations varied by sex. Parents of 97 youth (aged 9–16 years) completed the Early Trauma Inventory (ETI), and youth completed the Socially‐Evaluated Cold‐Pressor Task (SECPT). We measured salivary cortisol response to the SECPT, the cortisol awakening response, and diurnal regulation at home across 2 consecutive weekdays. Exposure to trauma during infancy related to delayed cortisol recovery from peak responses to acute stress, d = 0.23 to 0.42. Timing of trauma exposure related to diverging patterns of diurnal cortisol regulation for males, d = 0.55, and females, d = 0.57. Therefore, the HPA axis may be susceptible to developing acute stress dysregulation when exposed to trauma during infancy, whereas the consequences within circadian cortisol regulation may occur in the context of later trauma exposure and vary by sex. Further investigations are warranted to characterize HPA axis sensitivity to exposure to childhood trauma across child development.
Resumen
Spanish s by the Asociacion Chilena de Estres Traumatico
El eje hipotalámico‐pituitaria‐adrenal (Eje HPA) es una vía a través de la cual el trauma infantil puede incrementar el riesgo de resultados negativos en salud. El Eje HPA es sensible al estrés durante el desarrollo; sin embargo, pocos estudios han examinado si la temporalidad de la exposición al trauma infantil se relaciona a diferencias en el funcionamiento posterior del Eje HPA. Por consiguiente, examinamos la asociación entre la edad del primer trauma y el funcionamiento del Eje HPA entre adolescentes, y si esa asociación variaba por sexo. Los padres de 97 jóvenes (de edades entre 9 y 16 años) completaron el Early Trauma Inventory (ETI) y los jóvenes completaron el Socially Evaluated Cold‐Pressor Task (SECPT). Medimos la respuesta del cortisol salival al SECPT, la respuesta de cortisol al despertar, y la variación diurna en el hogar entre 2 dias de semana consecutivos. La exposición a trauma durante la infancia se relacionó a recuperación retardada de cortisol desde la respuesta peak a estrés, d = 0.24 a 0.42. La temporalidad de la exposición al trauma se relacionó a patrones divergentes de regulación diurna de cortisol en hombres, d = 0.55 y mujeres, d = 0.57. Por consiguiente, el Eje HPA puede ser susceptible a desarrollar disregulación en estrés agudo cuando se expone a trauma durante la infancia, mientras que las consecuencias en la regulación circadiana del cortisol pueden ocurrir en el contexto de exposición a trauma tardía y varían por sexo. Se requiere mayor investigación para caracterizar la sensibilidad del Eje HPA a la exposición a trauma durante el desarrollo infantil.
抽象
Traditional and Simplified Chinese s by AsianSTSS
標題 : 受創青少年裡首次經歷創傷的年齡與HPA軸調節障礙
撮要: 童年創傷可提升得到負面健康後果的風險༌而「下丘腦‐垂體‐腎上腺軸」(HPA‐axis)是這個關連發展的渠道之一。HPA軸在發育過程裡對壓力敏感༌但少有研究檢視經歷童年創傷的時間點是否跟日後HPA軸的運作差異有關。因此༌我們檢視青少年當中༌首次經歷創傷的年齡與HPA軸運作的關連༌並探查這些關連會否因性別而生異。97名青少年(年齡介乎9 至16歲)完成冷壓性測試社交評估(SECPT)༌他們的家長亦完成早期創傷量表(ETI)。我們測量SECPT中的唾液皮質醇反應、皮質醇覺醒反應和連續兩個工作天在家裡的每日皮質醇調節。研究發現༌從急性壓力而生的最強反應下恢復延遲༌與嬰兒時期經歷創傷有關༌d = 0.23 to 0.42。經歷創傷的時間點跟每日皮質醇調節的不同模式有關༌男性༚d = 0.55༌女性༚d = 0.57。因此༌在嬰兒時期經歷創傷的話༌HPA軸有可能發展出急性壓力調節障礙༛而在較後期經歷創傷可致使晝夜皮質醇調節的問題༌情況因性別而異。研究結果證明༌有需要作進一步研究以找出兒童發育時HPA軸對童年創傷的敏感特點。
标题 : 受创青少年里首次经历创伤的年龄与HPA轴调节障碍
撮要: 童年创伤可提升得到负面健康后果的风险༌而「下丘脑‐垂体‐肾上腺轴」(HPA‐axis)是这个关连发展的渠道之一。HPA轴在发育过程里对压力敏感༌但少有研究检视经历童年创伤的时间点是否跟日后HPA轴的运作差异有关。因此༌我们检视青少年当中༌首次经历创伤的年龄与HPA轴运作的关连༌并探查这些关连会否因性别而生异。97名青少年(年龄介乎9 至16岁)完成冷压性测试社交评估(SECPT)༌他们的家长亦完成早期创伤量表(ETI)。我们测量SECPT中的唾液皮质醇反应、皮质醇觉醒反应和连续两个工作天在家里的每日皮质醇调节。研究发现༌从急性压力而生的最强反应下恢复延迟༌与婴儿时期经历创伤有关༌d = 0.23 to 0.42。经历创伤的时间点跟每日皮质醇调节的不同模式有关༌男性༚d = 0.55༌女性༚d = 0.57。因此༌在婴儿时期经历创伤的话༌HPA轴有可能发展出急性压力调节障碍༛而在较后期经历创伤可致使昼夜皮质醇调节的问题༌情况因性别而异。研究结果证明༌有需要作进一步研究以找出儿童发育时HPA轴对童年创伤的敏感特点。
Highlights • We characterized the relationship between trauma subtypes to HPA-axis functioning. • We examined three common indices of HPA-axis functioning. • Non-intentional trauma predicted elevated ...cortisol at bedtime. • Physical abuse was associated with faster reactivity to acute stress. • Emotional abuse predicted delayed recovery of cortisol following acute stress.
This study examined whether frontal alpha electroencephalographic (EEG) asymmetry moderates the association between stressful life events and depressive symptoms in children at familial risk for ...depression. Participants included 135 children ages 6 to 13, whose mothers had either a history of depression or no history of major psychiatric conditions. Frontal EEG was recorded while participants watched emotion‐eliciting films. Symptoms and stressful life events were obtained via the Child Behavior Check List and a clinical interview, respectively. High‐risk children displayed greater relative right lateral frontal activation (F7/F8) than their low‐risk peers during the films. For high‐risk children, greater relative left lateral frontal activation moderated the association between stressful life events and internalizing symptoms. Specifically, greater relative left lateral frontal activation mitigated the effects of stress in at‐risk children.
PDF
