Childhood maltreatment influences adult brain structure through its effects on immune, metabolic, and psychosocial factors.

Childhood maltreatment (CM) leads to a lifelong susceptibility to mental ill-health which might be reflected by its effects on adult brain structure, perhaps indirectly mediated by its effects on adult metabolic, immune, and psychosocial systems. Indexing these systemic factors via body mass index (BMI), C-reactive protein (CRP), and rates of adult trauma (AT), respectively, we tested three hypotheses: (H1) CM has direct or indirect effects on adult trauma, BMI, and CRP; (H2) adult trauma, BMI, and CRP are all independently related to adult brain structure; and (H3) childhood maltreatment has indirect effects on adult brain structure mediated in parallel by BMI, CRP, and AT. Using path analysis and data from N = 116,887 participants in UK Biobank, we find that CM is related to greater BMI and AT levels, and that these two variables mediate CM's effects on CRP [H1]. Regression analyses on the UKB MRI subsample (N = 21,738) revealed that greater CRP and BMI were both independently related to a spatially convergent pattern of cortical effects (Spearman's ρ = 0.87) characterized by fronto-occipital increases and temporo-parietal reductions in thickness. Subcortically, BMI was associated with greater volume, AT with lower volume and CPR with effects in both directions [H2]. Finally, path models indicated that CM has indirect effects in a subset of brain regions mediated through its direct effects on BMI and AT and indirect effects on CRP [H3]. Results provide evidence that childhood maltreatment can influence brain structure decades after exposure by increasing individual risk toward adult trauma, obesity, and inflammation.

Affect and mental health across the lifespan during a year of the COVID-19 pandemic: The role of emotion regulation strategies and mental flexibility.

During the COVID-19 pandemic, there has been a rise in common mental health problems compared to prepandemic levels, especially in young people. Understanding the factors that place young people at risk is critical to guide the response to increased mental health problems. Here we examine whether age-related differences in mental flexibility and frequency of use of emotion regulation strategies partially account for the poorer affect and increased mental health problems reported by younger people during the pandemic. Participants (N = 2,367; 11-100 years) from Australia, the UK, and US were surveyed thrice at 3-month intervals between May 2020 and April 2021. Participants completed measures of emotion regulation, mental flexibility, affect, and mental health. Younger age was associated with less positive (b = 0.008, p < .001) and more negative (b = -0.015, p < .001) affect across the first year of the pandemic. Maladaptive emotion regulation partially accounted for age-related variance in negative affect (ß = -0.013, p = .020), whereby younger age was associated with more frequent use of maladaptive emotion regulation strategies, which, in turn, was associated with more negative affect at our third assessment point. More frequent use of adaptive emotion regulation strategies, and in turn, changes in negative affect from our first to our third assessment, partially accounted for age-related variance in mental health problems (ß = 0.007, p = .023). Our findings add to the growing literature demonstrating the vulnerability of younger people during the COVID-19 pandemic and suggest that emotion regulation may be a promising target for intervention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The stress-buffering role of friendships in young people with childhood threat experiences: a preliminary report.

Background: High-quality friendships have a positive impact on the mental health of young people with childhood adversity (CA). Social stress buffering, the phenomenon of a social partner attenuating acute stress responses, is a potential yet unexplored mechanism that may underlie this relationship.Objective: This study examined whether perceived friendship quality was related to better mental health and lower neural stress response in young people with CA.Method: A total of N = 102 young people (aged 16-26) with low to moderate CA were included in the study. We first investigated associations between friendship quality, mental health, and CA. In a representative subset (n = 62), we assessed neural stress responses using the Montreal Imaging Stress Task. In our sample, CA was best described along two dimensions resembling threat or deprivation like experiences. Hence, we investigated both cumulative and dimensional effects of CA.Results: We found no support for social thinning after CA, meaning that the severity of CA (cumulative or dimensional) did not differentially impact friendship quality. High-quality friendships, on the other hand, were strongly associated with better mental health. Furthermore, acute stress increased state anxiety and enhanced neural activity in five frontolimbic brain regions, including the left hippocampus. We found weak support that threat experiences interacted with friendship quality to predict left hippocampal reactivity to stress. However, this effect did not survive multiple comparison correction.Conclusion: The absence of social thinning in our sample may suggest that the risk of developing impoverished social networks is low for rather well-functioning young people with low to moderate CA. Regardless, our findings align with prior research, consistently showing a strong association between high-quality friendships and better mental health in young people with CA. Future research is needed to examine whether friendships aid neural stress responses in young people with childhood threat experiences.

Young people with childhood adversity underwent acute stress induction, eliciting frontolimbic reactivity.High-quality friendships were strongly associated with better mental health.Weak support for friendship stress buffering did not survive multiple comparison correction.

Child maltreatment and victimization.

It is estimated that up to 25% of all children growing up worldwide experience child maltreatment, making it a global emergency with substantial individual and public health consequences. This chapter addresses one of the most societally pervasive consequences of child maltreatment which is known as the "cycle of victimization." This concept depicts the increased risk of maltreated individuals to victimize others later in life, both within and outside the family environment. To understand the architecture of this victimization cycle, the chapter further sheds light on neurocognitive mechanisms aiding different forms of victimization and the buffering role of social support that could help break the cycle of victimization. Advancing our understanding of these complex and interrelated mechanisms will ultimately facilitate the design and implementation of more targeted early treatments and (preventive) interventions and support a move toward a safer society.

Resilient functioning is associated with altered structural brain network topology in adolescents exposed to childhood adversity.

Childhood adversity is one of the strongest predictors of adolescent mental illness. Therefore, it is critical that the mechanisms that aid resilient functioning in individuals exposed to childhood adversity are better understood. Here, we examined whether resilient functioning was related to structural brain network topology. We quantified resilient functioning at the individual level as psychosocial functioning adjusted for the severity of childhood adversity in a large sample of adolescents (N = 2406, aged 14-24). Next, we examined nodal degree (the number of connections that brain regions have in a network) using brain-wide cortical thickness measures in a representative subset (N = 275) using a sliding window approach. We found that higher resilient functioning was associated with lower nodal degree of multiple regions including the dorsolateral prefrontal cortex, the medial prefrontal cortex, and the posterior superior temporal sulcus (z > 1.645). During adolescence, decreases in nodal degree are thought to reflect a normative developmental process that is part of the extensive remodeling of structural brain network topology. Prior findings in this sample showed that decreased nodal degree was associated with age, as such our findings of negative associations between nodal degree and resilient functioning may therefore potentially resemble a more mature structural network configuration in individuals with higher resilient functioning.

The effect of intolerance of uncertainty on anxiety and depression, and their symptom networks, during the COVID-19 pandemic.

Individuals vary in their ability to tolerate uncertainty. High intolerance of uncertainty (the tendency to react negatively to uncertain situations) is a known risk factor for mental health problems. In the current study we examined the degree to which intolerance of uncertainty predicted depression and anxiety symptoms and their interrelations across the first year of the COVID-19 pandemic. We examined these associations across three time points (May 2020 - April 2021) in an international sample of adults (N = 2087, Mean age = 41.13) from three countries (UK, USA, Australia) with varying degrees of COVID-19 risk. We found that individuals with high and moderate levels of intolerance of uncertainty reported reductions in depression and anxiety symptoms over time. However, symptom levels remained significantly elevated compared to individuals with low intolerance of uncertainty. Individuals with low intolerance of uncertainty had low and stable levels of depression and anxiety across the course of the study. Network analyses further revealed that the relationships between depression and anxiety symptoms became stronger over time among individuals with high intolerance of uncertainty and identified that feeling afraid showed the strongest association with intolerance of uncertainty. Our findings are consistent with previous work identifying intolerance of uncertainty as an important risk factor for mental health problems, especially in times marked by actual health, economic and social uncertainty. The results highlight the need to explore ways to foster resilience among individuals who struggle to tolerate uncertainty, as ongoing and future geopolitical, climate and health threats will likely lead to continued exposure to significant uncertainty.

Social and cognitive vulnerability to COVID-19-related stress in pregnancy: A case-matched-control study of antenatal mental health.

Emerging evidence shows that compared to pre-pandemic norms pregnant women report significant increases in clinical levels of depressive and anxiety symptoms during COVID-19. This pre-registered study examined cognitive and social vulnerability factors for poor mental health in pregnancy during COVID-19. Understanding vulnerability profiles is key to identifying women at risk for deteriorating peripartum mental health. N = 742 pregnant women and N = 742 age and country-matched controls from the COVID-19 Risks Across the Lifespan Study were included. Using a case-match control design allowed us to explore whether the cognitive vulnerability profiles would differ between pregnant and non-pregnant women. The findings showed that COVID-19-related stress was associated with heightened levels of depression and anxiety during pregnancy. Its impact was greatest in women with cognitive (i.e., higher intolerance of uncertainty and tendency to worry) and social (i.e., higher level of self-reported loneliness) vulnerabilities. Importantly, our data show that the mental health impacts of the pandemic were greater in pregnant women compared to women who were not pregnant, especially those with cognitive and social vulnerabilities. The results highlight the urgent need to prioritize mental health care for pregnant women to mitigate the impact of COVID-19-related stress on women's postpartum mental health and their infants' well-being.

Social determinants of mental health during a year of the COVID-19 pandemic.

Belonging is a basic human need, with social isolation signaling a threat to biological fitness. Sensitivity to ostracism varies across individuals and the lifespan, peaking in adolescence. Government-imposed restrictions upon social interactions during COVID-19 may therefore be particularly detrimental to young people and those most sensitive to ostracism. Participants (N = 2367; 89.95% female, 11-100 years) from three countries with differing levels of government restrictions (Australia, UK, and USA) were surveyed thrice at three-month intervals (May 2020 - April 2021). Young people, and those living under the tightest government restrictions, reported the worst mental health, with these inequalities in mental health remaining constant throughout the study period. Further dissection of these results revealed that young people high on social rejection sensitivity reported the most mental health problems at the final assessment. These findings help account for the greater impact of enforced social isolation on young people's mental health, and open novel avenues for intervention.

Elevated cognitive rumination and adverse life events are associated with lower cortical surface area and suicidal ideation in adolescents with major depressive disorder.

INTRODUCTION: Suicide is the second most common cause of death among young people. Structural brain alterations, rumination, and recent stressful experiences contribute to suicidal thoughts and behaviors (STBs). METHODS: Here, we employed structural equation modeling (SEM) to examine the unique and combined relationships of these risk factors with STBs in a sample of young people with major depressive disorder (MDD) from the Magnetic Resonance-Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT) study (N = 67, mean age = 15.90; standard deviation ± 1.32). RESULTS: Whereas increased rumination and lower surface area of brain regions, that have been previously reported to be involved in both STBs and rumination, were associated with each other (Beta = -0.268, standard error (SE) = 0.114, Z = -2.346, p = 0.019), only increased rumination was related to greater severity of suicidal ideation (Beta = 0.281, SE = 0.132, Z = 2.134, p = 0.033). In addition, we observed that recent stress was associated with lower surface area in the suicidal ideation model without covariate only (Beta = -0.312, SE = 0.149, Z = -2.089, p = 0.037). For the attempt models, no associations were found between any of the risk factors and suicide attempts. LIMITATIONS: We emphasize that these findings from this secondary analysis are hypothesis-forming and preliminary in nature given the small sample size for SEM analyses. CONCLUSION: Our findings suggest that neither lower surface area nor recent stress are directly associated with youth suicidal ideation or attempt. However, lower surface area is related to recent stress and increased rumination, which predicted greater severity of suicidal ideation in young people with MDD.

Tracking Mental Wellbeing of Dutch Adolescents During the First Year of the COVID-19 Lockdown: A Longitudinal Study.

PURPOSE: Adolescents might be susceptible to the effects of the COVID-19 lockdown. We assessed changes in mental wellbeing throughout the first year of the pandemic and compared these with prepandemic levels. METHODS: This five-wave prospective study among Dutch adolescents aged 12-17 years used data collected before the pandemic (n = 224) (T0), in May (T1), July (T2), and October 2020 (T3), and in February 2021 (T4). Generalized estimating equations were used to assess the association between stringency of the lockdown with mental wellbeing. RESULTS: Adolescents had a lower life satisfaction during the first full lockdown (T1) [adjusted ß: -0.36, 95% confidence interval (CI): -0.58 to -0.13], during the partial lockdown (T3) (adjusted ß: -0.37, 95% CI: -0.63 to -0.12), and during the second full lockdown (T4) (adjusted ß: -0.79, 95% CI: -1.07 to -0.52) compared to before the pandemic (T0). Adolescents reported more internalizing symptoms during only the second full lockdown (T4) (adjusted ß: 2.58, 95% CI: 0.41-4.75). During the pandemic [at T1 (adjusted ß: 0.29, 95% CI: 0.20-0.38), T2 (adjusted ß: 0.36, 95% CI: 0.26-0.46), T3 (adjusted ß: 0.33, 95% CI: 0.22-0.45), and T4 (adjusted ß: 0.20, 95% CI: 0.07-0.34)], adolescents reported a better psychosomatic health, partly attributable to less trouble falling asleep (p < .01). DISCUSSION: The COVID-19 lockdown measures have had both a negative and positive impact on mental wellbeing of Dutch adolescents. However, mental wellbeing was most impacted during the second full lockdown compared to before the pandemic.

The importance of friendships in reducing brain responses to stress in adolescents exposed to childhood adversity: a preregistered systematic review.

Up to 50% of all children and adolescents growing up worldwide are exposed to at least one form of childhood adversity (CA), which is one of the strongest predictors for later life psychopathology. One way through which CA confers such vulnerability in later life is through increased sensitivity to and likelihood of social stress. A growing body of research demonstrates the positive impact of adolescent friendship support on mental well-being after CA; however, the mechanisms that may underlie this relationship are unknown. Neurobiological models of social buffering suggest that social support can reduce perceptions, reactions, and physiological responses to and after stress. Therefore, this preregistered, systematic literature search examined whether friendships reduce neural stress responses in adolescents with CA.

Brain grey and white matter structural associations with future suicidal ideation and behaviors in adolescent and young adult females with mood disorders.

Background: To reduce suicide in females with mood disorders, it is critical to understand brain substrates underlying their vulnerability to future suicidal ideation and behaviors (SIBs) in adolescence and young adulthood. In an international collaboration, grey and white matter structure was investigated in adolescent and young adult females with future suicidal behaviors (fSB) and ideation (fSI), and without SIBs (fnonSIB). Methods: Structural (n = 91) and diffusion-weighted (n = 88) magnetic resonance imaging scans at baseline and SIB measures at follow-up on average two years later (standard deviation, SD = 1 year) were assessed in 92 females [age(SD) = 16.1(2.6) years] with bipolar disorder (BD, 28.3%) or major depressive disorder (MDD, 71.7%). One-way analyses of covariance comparing baseline regional grey matter cortical surface area, thickness, subcortical grey volumes, or white matter tensor-based fractional anisotropy across fSB (n = 40, 43.5%), fSI (n = 33, 35.9%) and fnonSIB (n = 19, 20.6%) groups were followed by pairwise comparisons in significant regions (p < 0.05). Results: Compared to fnonSIBs, fSIs and fSBs showed significant decreases in cortical thickness of right inferior frontal gyrus pars orbitalis and middle temporal gyrus, fSIs of left inferior frontal gyrus, pars orbitalis. FSIs and fSBs showed lower fractional anisotropy in left uncinate fasciculus and corona radiata, and fSBs in right uncinate and superior fronto-occipital fasciculi. Conclusions: The study provides preliminary evidence of grey and white matter alterations in brain regions subserving emotional and behavioral regulation and perceptual processing in adolescent and young adult females with mood disorders with, versus without, future SIBs. Findings suggest potential targets to prevent SIBs in female adolescents and young adults.

Wealth Inequality and Intimate Partner Violence: An Individual and Ecological Level Analysis Across 20 Countries.

Intimate Partner Violence (IPV) has been linked to poor health. Economic position may be an important risk factor for IPV. We examined the association between economic position and IPV at country and individual levels. We analyzed Demographic and Health Surveys data of 187,716 ever-partnered women between ages 10 and 59 from 20 low- and middle-income countries. We calculated direct age-standardized 12-month prevalence of physical IPV and performed ecological analysis using Gini coefficients and Concentration indexes to assess correlation with 12-month prevalence of physical IPV. We conducted multivariable logistic regression for each country to assess the association between wealth status and physical IPV and a meta-analysis of the regression model to present results across countries. Compared to the Poorest quintile, odds of IPV among wealthier quintiles varied by country. In the Middle quintile, India had significantly reduced IPV (OR 0.75, 95%CI: 0.68-0.83). In the Richer and Richest quintiles, 4 and 6 countries had significant reductions in IPV, respectively. Only Mozambique was found to have significant increased IPV in the wealthiest quintile (OR 2.51, 95%CI: 1.45-4.38). Gini coefficient and physical IPV had a correlation coefficient of 0.502 (p value 0.033), while Concentration index had -0.276 (p value .253). Standardized prevalence for physical IPV ranged from 1.58% to 18.91%. Findings suggest that the relationship between wealth and IPV vary considerably in the included low- and middle-income countries, and that risk of IPV may not necessarily be higher among women in lower wealth brackets. Mozambique was the only country with increased odds of IPV among the Richest group as compared to the Poorest group. This study provides evidence IPV may transcend economic boundaries, and that studies looking at the link between inequality and IPV are paramount for designing adequate preventative policies.

Prospective Pathways From Impulsivity to Non-Suicidal Self-Injury Among Youth.

Non-suicidal self-injury (NSSI) is a common behavior, particularly among adolescents and young adults. Impulsivity has been implicated as an important factor associated with NSSI, however prospective longitudinal research is lacking. Moreover, the relationship between impulsivity and other risk factors for NSSI is unclear. By examining longitudinal models including impulsivity, attachment, and distress we hope to elucidate the nature of the association between impulsivity and NSSI. 1,686 community-recruited young people (ages 14-25) with no NSSI in the past year were followed up for one year, completing self-report measures of the above factors. Impulsivity independently predicted new onset of NSSI over and above other risk factors, indicating heightened impulsivity is a prospective risk factor for NSSI. Psychological distress mediated the parenting-NSSI association.

Psychological Network Analysis of General Self-Efficacy in High vs. Low Resilient Functioning Healthy Adults.

Resilience to stress has gained increasing interest by researchers from the field of mental health and illness and some recent studies have investigated resilience from a network perspective. General self-efficacy constitutes an important resilience factor. High levels of self-efficacy have shown to promote resilience by serving as a stress buffer. However, little is known about the role of network connectivity of self-efficacy in the context of stress resilience. The present study aims at filling this gap by using psychological network analysis to study self-efficacy and resilience. Based on individual resilient functioning scores, we divided a sample of 875 mentally healthy adults into a high and low resilient functioning group. To compute these scores, we applied a novel approach based on Partial Least Squares Regression on self-reported stress and mental health measures. Separately for both groups, we then estimated regularized partial correlation networks of a ten-item self-efficacy questionnaire. We compared three different global connectivity measures-strength, expected influence, and shortest path length-as well as absolute levels of self-efficacy between the groups. Our results supported our hypothesis that stronger network connectivity of self-efficacy would be present in the highly resilient functioning group compared to the low resilient functioning group. In addition, the former showed higher absolute levels of general self-efficacy. Future research could consider using partial least squares regression to quantify resilient functioning to stress and to study the association between network connectivity and resilient functioning in other resilience factors.

Gender-Specific Changes in Life Satisfaction After the COVID-19-Related Lockdown in Dutch Adolescents: A Longitudinal Study.

PURPOSE: The purposes of this study were to assess whether mental well-being has changed after introduction of the lockdown measures compared with that before, whether this change differs between boys and girls, and whether this change is associated with COVID-19-related concerns. METHODS: This is a two-wave prospective study among Dutch adolescents using data collected up to one year before the COVID-19 pandemic (n = 224) and 5-8 weeks after the first introduction of lockdown measures (n = 158). Mental well-being was assessed by three indicators: life satisfaction, internalizing symptoms, and psychosomatic health. General linear model repeated-measures analysis of variance was used to assess whether mental well-being has changed and if this differed by sex. Univariate linear regressions were used to assess associations between COVID-19-related concerns and a change in mental well-being. RESULTS: Life satisfaction decreased (η2p = .079, p < .001), but no change in internalizing symptoms was observed (η2p = .014, p = .14), and psychosomatic health increased (η2p = .194, p < .001) after the introduction of lockdown measures. Boys scored significantly better on all mental health indicators compared with girls at baseline and follow-up. However, boys' life satisfaction significantly decreased at the follow-up (η2p = .038, p = .015), whereas girls' life satisfaction did not change. Concerns about COVID-19 were significantly associated with a lower life satisfaction and more internalizing symptoms. CONCLUSIONS: Adolescents', especially boys', life satisfaction decreased during the lockdown. They reported no change in internalizing symptoms and an improved psychosomatic health. Adolescents' mental well-being is expected to vary during the COVID-19 pandemic and should continue to be monitored.

Tracking Stress, Mental Health, and Resilience Factors in Medical Students Before, During, and After a Stress-Inducing Exam Period: Protocol and Proof-of-Principle Analyses for the RESIST Cohort Study.

BACKGROUND: Knowledge of mental distress and resilience factors over the time span from before to after a stressor is important to be able to leverage the most promising resilience factors and promote mental health at the right time. To shed light on this topic, we designed the RESIST (Resilience Study) study, in which we assessed medical students before, during, and after their yearly exam period. Exam time is generally a period of notable stress among medical students, and it has been suggested that exam time triggers mental distress. OBJECTIVE: In this paper, we aim to describe the study protocol and to examine whether the exam period indeed induces higher perceived stress and mental distress. We also aim to explore whether perceived stress and mental distress coevolve in response to exams. METHODS: RESIST is a cohort study in which exam stress functions as a within-subject natural stress manipulation. In this paper, we outline the sample (N=451), procedure, assessed measures (including demographics, perceived stress, mental distress, 13 resilience factors, and adversity), and ethical considerations. Moreover, we conducted a series of latent growth models and bivariate latent change score models to analyze perceived stress and mental distress changes over the 3 time points. RESULTS: We found that perceived stress and mental distress increased from the time before the exams to the exam period and decreased after the exams to a lower level than before the exams. Our findings further suggest that higher mental distress before exams increased the risk of developing more perceived stress during exams. Higher perceived stress during exams, in turn, increased the risk of experiencing a less successful (or quick) recovery of mental distress after exams. CONCLUSIONS: As expected, the exam period caused a temporary increase in perceived stress and mental distress. Therefore, the RESIST study lends itself well to exploring resilience factors in response to naturally occurring exam stress. Such knowledge will eventually help researchers to find out which resilience factors lend themselves best as prevention targets and which lend themselves best as treatment targets for the mitigation of mental health problems that are triggered or accelerated by natural exam stress. The findings from the RESIST study may therefore inform student support services, mental health services, and resilience theory.

How biopsychosocial depressive risk shapes behavioral and neural responses to social evaluation in adolescence.

INTRODUCTION: Understanding the emotional responsivity style and neurocognitive profiles of depression-related processes in at-risk youth may be helpful in revealing those most likely to develop affective disorders. However, the multiplicity of biopsychosocial risk factors makes it difficult to disentangle unique and combined effects at a neurobiological level. METHODS: In a population-derived sample of 56 older adolescents (aged 17-20), we adopted partial least squares regression and correlation models to explore the relationships between multivariate biopsychosocial risks for later depression, emotional response style, and fMRI activity, to rejecting and inclusive social feedback. RESULTS: Behaviorally, higher depressive risk was associated with both reduced negative affect following negative social feedback and reduced positive affect following positive social feedback. In response to both cues of rejection and inclusion, we observed a general neural pattern of increased cingulate, temporal, and striatal activity in the brain. Secondly, in response to rejection only, we observed a pattern of activity in ostensibly executive control- and emotion regulation-related brain regions encompassing fronto-parietal brain networks including the angular gyrus. CONCLUSION: The results suggest that risk for depression is associated with a pervasive emotional insensitivity in the face of positive and negative social feedback.

Childhood Trauma in Adult Depressive and Anxiety Disorders: An Integrated Review on Psychological and Biological Mechanisms in the NESDA Cohort.

BACKGROUND: Childhood trauma (CT) has adverse consequences on mental health across the lifespan. The understanding of how CT increases vulnerability for psychiatric disorders is growing. However, lack of an integrative approach to psychological and biological mechanisms of CT hampers further advancement. This review integrates CT findings across explanatory levels from a longitudinal adult cohort - the Netherlands Study of Depression and Anxiety (NESDA). METHODS: We reviewed all studies (k = 37) from the NESDA cohort (n = 2981) published from 2009 to 2020 containing CT findings related to psychopathology and potential psychological and biological mechanisms of CT. RESULTS: CT was associated with a higher risk of anxiety and depressive disorders with the strongest associations in the comorbid group. CT predicted the onset of these disorders, recurrence, and poorer outcomes (more comorbidity and chronicity). CT was associated with maladaptive personality characteristics and cognitions (e.g., higher neuroticism and negative self-associations), mild stress systems dysregulations (heightened levels of cortisol and inflammation), advanced biological aging (increased epigenetic aging and telomere attrition), poorer lifestyle (higher smoking rate and body mass index), somatic health decline (e.g., increased metabolic syndrome dysregulations), and brain alterations (e.g., reduced mPFC volume and increased amygdala reactivity). LIMITATIONS: Literature review of one cohort using mixed analytical approaches. CONCLUSION: CT impacts the functioning of the brain, mind, and body, which together may contribute to a higher vulnerability for affective disorders. It is essential to employ an integrative approach combining different sources of data to understand the mechanisms of CT better.

REACT study protocol: resilience after the COVID-19 threat (REACT) in adolescents.

INTRODUCTION: COVID-19-related social isolation and stress may have significant mental health effects, including post-traumatic stress, anxiety and depression. These factors are thought to disproportionately affect populations at risk of psychopathology, such as adolescents with a history of childhood adversity (CA). Therefore, examining which factors may buffer the impact of COVID-19-related stress and isolation in vulnerable adolescents is critical. The Resilience After the COVID-19 Threat (REACT) study assesses whether emotion regulation capacity, inflammation and neuroimmune responses to stress induced in the laboratory prior to the pandemic predict responses to COVID-19-related social isolation and stress in adolescents with CA. We aim to elucidate the mechanisms that enable vulnerable adolescents to maintain or regain good mental health when confronted with COVID-19. METHODS AND ANALYSIS: We recruited 79 adolescents aged 16-26 with CA experiences from the Resilience After Individual Stress Exposure study in which we assessed emotion regulation, neural and immune stress responses to an acute stress task. Our sample completed questionnaires at the start of the UK lockdown ('baseline'; April 2020) and three (July 2020) and 6 months later (October 2020) providing crucial longitudinal information across phases of the pandemic progression and government response. The questionnaires assess (1) mental health, (2) number and severity of life events, (3) physical health, (4) stress perception and (5) loneliness and friendship support. We will use multilevel modelling to examine whether individual differences at baseline are associated with responses to COVID-19-related social isolation and stress. ETHICS AND DISSEMINATION: This study has been approved by the Cambridge Psychology Research Ethics Committee (PRE.2020.037). Results of the REACT study will be disseminated in publications in scientific peer-reviewed journals, presentations at scientific conferences and meetings, publications and presentations for the general public, and through social media.