Early life adversities are associated with lower expected value signaling in the adult brain.

BACKGROUND: Early adverse experiences are assumed to affect fundamental processes of reward learning and decision-making. However, computational neuroimaging studies investigating these circuits in the context of adversity are sparse and limited to studies conducted in adolescent samples, leaving the long-term effects unexplored. METHODS: Using data from a longitudinal birth cohort study (n=156, 87 females), we investigated associations between adversities and computational markers of reward learning (i.e., expected value (EV), prediction errors). At the age of 33 years, all participants completed an fMRI-based passive avoidance task. Psychopathology measures were collected at the time of fMRI investigation and during the COVID-19 pandemic. We applied a principal component analysis to capture common variation across seven adversity measures. The resulting adversity factors (factor-1: postnatal psychosocial adversities and prenatal maternal smoking, factor-2: prenatal maternal stress and obstetric adversity, and factor-3: lower maternal stimulation) were linked with psychopathology and neural responses in the core reward network using multiple regression analysis. RESULTS: We found that the adversity dimension primarily informed by lower maternal stimulation was linked to lower EV representation in the right putamen, right nucleus accumbens (NAcc), and anterior cingulate cortex. EV encoding in the right NAcc further mediated the relationship between this adversity dimension and psychopathology and predicted higher withdrawn symptoms during the COVID-19 pandemic. CONCLUSIONS: Our results suggested that early adverse experiences in caregiver context might have a long-term disruptive effect on reward learning in reward-related brain regions, which can be associated with suboptimal decision-making and thereby may increase the vulnerability of developing psychopathology.

Randomized controlled trial of individualized arousal-biofeedback for children and adolescents with disruptive behavior disorders (DBD).

Disruptive behavior disorders [including conduct disorder (CD) and oppositional defiant disorder (ODD)] are common childhood and adolescent psychiatric conditions often linked to altered arousal. The recommended first-line treatment is multi-modal therapy and includes psychosocial and behavioral interventions. Their modest effect sizes along with clinically and biologically heterogeneous phenotypes emphasize the need for innovative personalized treatment targeting impaired functions such as arousal dysregulation. A total of 37 children aged 8-14 years diagnosed with ODD/CD were randomized to 20 sessions of individualized arousal biofeedback using skin conductance levels (SCL-BF) or active treatment as usual (TAU) including psychoeducation and cognitive-behavioral elements. The primary outcome was the change in parents´ ratings of aggressive behavior measured by the Modified Overt Aggression Scale. Secondary outcome measures were subscales from the Child Behavior Checklist, the Inventory of Callous-Unemotional traits, and the Reactive-Proactive Aggression Questionnaire. The SCL-BF treatment was neither superior nor inferior to the active TAU. Both groups showed reduced aggression after treatment with small effects for the primary outcome and large effects for some secondary outcomes. Importantly, successful learning of SCL self-regulation was related to reduced aggression at post-assessment. Individualized SCL-BF was not inferior to active TAU for any treatment outcome with improvements in aggression. Further, participants were on average able to self-regulate their SCL, and those who best learned self-regulation showed the highest clinical improvement, pointing to specificity of SCL-BF regulation for improving aggression. Further studies with larger samples and improved methods, for example by developing BF for mobile use in ecologically more valid settings are warranted.

Lifespan adversities affect neural correlates of behavioral inhibition in adults.

Introduction: Growing evidence suggests that adverse experiences have long-term effects on executive functioning and underlying neural circuits. Previous work has identified functional abnormalities during inhibitory control in frontal brain regions in individuals exposed to adversities. However, these findings were mostly limited to specific adversity types such as maltreatment and prenatal substance abuse. Methods: We used data from a longitudinal birth cohort study (n = 121, 70 females) to investigate the association between adversities and brain responses during inhibitory control. At the age of 33 years, all participants completed a stop-signal task during fMRI and an Adult Self-Report scale. We collected seven prenatal and postnatal adversity measures across development and performed a principal component analysis to capture common variations across those adversities, which resulted in a three-factor solution. Multiple regression analysis was performed to identify links between adversities and brain responses during inhibitory control using the identified adversity factors to show the common effect and single adversity measures to show the specific contribution of each adversity. To find neural correlates of current psychopathology during inhibitory control, we performed additional regression analyses using Adult Self-Report subscales. Results: The first adversity factor reflecting prenatal maternal smoking and postnatal psychosocial adversities was related to higher activation during inhibitory control in bilateral inferior frontal gyri, insula, anterior cingulate cortex, and middle temporal gyri. Similar results were found for the specific contribution of the adversities linked to the first adversity factor. In contrast, we did not identify any significant association between brain responses during inhibitory control and the second adversity factor reflecting prenatal maternal stress and obstetric risk or the third adversity factor reflecting lower maternal sensitivity. Higher current depressive symptoms were associated with higher activation in the bilateral insula and anterior cingulate cortex during inhibitory control. Conclusion: Our findings extended previous work and showed that early adverse experiences have a long-term effect on the neural circuitry of inhibitory control in adulthood. Furthermore, the overlap between neural correlates of adversity and depressive symptomatology suggests that adverse experiences might increase vulnerability via neural alterations, which needs to be investigated by future longitudinal research.

Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors.

BACKGROUND: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities. METHODS: The large sample of children and adolescents aged 8-18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla. RESULTS: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for. CONCLUSIONS: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.

A coordinate-based meta-analysis of human amygdala connectivity alterations related to early life adversities.

By affecting core neurobiological systems early in development, early life adversities (ELAs) might confer latent vulnerability to future psychopathologies. This coordinate-based meta-analysis aims to identify significant convergent alterations in functional connectivity of the amygdala related to ELAs across resting-state and task-based fMRI-studies. Five electronic databases were systematically searched until 22 October 2020, retrieving 49 eligible studies (n = 3162 participants). Convergent alterations in functional connectivity related to ELAs between the amygdala and the anterior cingulate cortex (ACC) and left hippocampus were found. Sub-analyses based on hemisphere and direction showed that connectivity seeded in the right amygdala was affected and, moreover, revealed that connectivity with ACC was decreased. Analyses based on paradigm and age showed that amygdala-ACC coupling was altered during resting state and that amygdala-left hippocampus connectivity was mostly affected during task-based paradigms and in adult participants. While both regions showed altered connectivity during emotion processing and following adverse social postnatal experiences such as maltreatment, amygdala-ACC coupling was mainly affected when ELAs were retrospectively assessed through self-report. We show that ELAs are associated with altered functional connectivity of the amygdala with the ACC and hippocampus. As such, ELAs may embed latent vulnerability to future psychopathologies by systematically affecting important neurocognitive systems.

A stable and replicable neural signature of lifespan adversity in the adult brain.

Environmental adversities constitute potent risk factors for psychiatric disorders. Evidence suggests the brain adapts to adversity, possibly in an adversity-type and region-specific manner. However, the long-term effects of adversity on brain structure and the association of individual neurobiological heterogeneity with behavior have yet to be elucidated. Here we estimated normative models of structural brain development based on a lifespan adversity profile in a longitudinal at-risk cohort aged 25 years (n = 169). This revealed widespread morphometric changes in the brain, with partially adversity-specific features. This pattern was replicated at the age of 33 years (n = 114) and in an independent sample at 22 years (n = 115). At the individual level, greater volume contractions relative to the model were predictive of future anxiety. We show a stable neurobiological signature of adversity that persists into adulthood and emphasize the importance of considering individual-level rather than group-level predictions to explain emerging psychopathology.

The importance of high quality real-life social interactions during the COVID-19 pandemic.

The coronavirus pandemic has brought about dramatic restrictions to real-life social interactions and a shift towards more online social encounters. Positive social interactions have been highlighted as an important protective factor, with previous studies suggesting an involvement of the amygdala in the relationship between social embeddedness and well-being. The present study investigated the effect of the quality of real-life and online social interactions on mood, and explored whether this association is affected by an individual's amygdala activity. Sixty-two participants of a longitudinal study took part in a one-week ecological momentary assessment (EMA) during the first lockdown, reporting their momentary well-being and their engagement in real-life and online social interactions eight times per day (N ~ 3000 observations). Amygdala activity was assessed before the pandemic during an emotion-processing task. Mixed models were calculated to estimate the association between social interactions and well-being, including two-way interactions to test for the moderating effect of amygdala activity. We found a positive relationship between real-life interactions and momentary well-being. In contrast, online interactions had no effect on well-being. Moreover, positive real-life social interactions augmented this social affective benefit, especially in individuals with higher amygdala being more sensitive to the interaction quality. Our findings demonstrate a mood-lifting effect of positive real-life social interactions during the pandemic, which was dependent on amygdala activity before the pandemic. As no corresponding effect was found between online social interactions and well-being, it can be concluded that increased online social interactions may not compensate for the absence of real-life social interactions.

Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: a systematic review.

Neurodevelopmental disorders - including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders - manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence - from two or more studies from independent research groups, with results going into the same direction - of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi-level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost-effectiveness, before they can be implemented in daily clinical practice.

Early Social Adversity, Altered Brain Functional Connectivity, and Mental Health.

Early adverse environmental exposures during brain development are widespread risk factors for the onset of severe mental disorders and strong and consistent predictors of stress-related mental and physical illness and reduced life expectancy. Current evidence suggests that early negative experiences alter plasticity processes during developmentally sensitive time windows and affect the regular functional interaction of cortical and subcortical neural networks. This, in turn, may promote a maladapted development with negative consequences on the mental and physical health of exposed individuals. In this review, we discuss the role of functional magnetic resonance imaging-based functional connectivity phenotypes as potential biomarker candidates for the consequences of early environmental exposures-including but not limited to-childhood maltreatment. We take an expanded concept of developmentally relevant adverse experiences from infancy over childhood to adolescence as our starting point and focus our review of functional connectivity studies on a selected subset of functional magnetic resonance imaging-based phenotypes, including connectivity in the limbic and within the frontoparietal as well as default mode networks, for which we believe there is sufficient converging evidence for a more detailed discussion in a developmental context. Furthermore, we address specific methodological challenges and current knowledge gaps that complicate the interpretation of early stress effects on functional connectivity and deserve particular attention in future studies. Finally, we highlight the forthcoming prospects and challenges of this research area with regard to establishing functional connectivity measures as validated biomarkers for brain developmental processes and individual risk stratification and as target phenotypes for mechanism-based interventions.

Age-related brain deviations and aggression.

BACKGROUND: Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities. METHODS: We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8-18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities. RESULTS: While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample. CONCLUSIONS: Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.

Emotion recognition profiles in clusters of youth based on levels of callous-unemotional traits and reactive and proactive aggression.

Youth with disruptive behavior showing high callous-unemotional (CU) traits and proactive aggression are often assumed to exhibit distinct impairments in emotion recognition from those showing mainly reactive aggression. Yet, reactive and proactive aggression and CU traits may co-occur to varying degrees across individuals. We aimed to investigate emotion recognition in more homogeneous clusters based on these three dimensions. In a sample of 243 youth (149 with disruptive behavior problems and 94 controls) aged 8-18 years, we used model-based clustering on self-report measures of CU traits and reactive and proactive aggression and compared the resulting clusters on emotion recognition (accuracy and response bias) and working memory. In addition to a Low and Low-Moderate symptom cluster, we identified two high CU clusters. The CU-Reactive cluster showed high reactive and low-to-medium proactive aggression; the CU-Mixed cluster showed high reactive and proactive aggression. Both CU clusters showed impaired fear recognition and working memory, whereas the CU-Reactive cluster also showed impaired recognition of disgust and sadness, partly explained by poor working memory, as well as a response bias for anger and happiness. Our results confirm the importance of CU traits as a core dimension along which youth with disruptive behavior may be characterized, yet challenge the view that high CU traits are closely linked to high proactive aggression per se. Notably, distinct neurocognitive processes may play a role in youth with high CU traits and reactive aggression with lower versus higher proactive aggression.

No robust evidence for an interaction between early-life adversity and protective factors on global and regional brain volumes.

Childhood adversity is associated with brain morphology and poor psychological outcomes, and evidence of protective factors counteracting childhood adversity effects on neurobiology is scarce. We examined the interplay of childhood adversity with protective factors in relation to brain morphology in two independent longitudinal cohorts, the Generation R Study (N = 3008) and the Mannheim Study of Children at Risk (MARS) (N = 179). Cumulative exposure to 12 adverse events was assessed across childhood until age 9 years in Generation R and 11 years in MARS. Protective factors (temperament, cognition, self-esteem, maternal sensitivity, friendship quality) were assessed at various time-points during childhood. Global brain volumes and volumes of amygdala, hippocampus, and the anterior cingulate, medial orbitofrontal and rostral middle frontal cortices were assessed with anatomical scans at 10 years in Generation R and at 25 years in MARS. Childhood adversity was related to smaller cortical grey matter, cerebral white matter, and cerebellar volumes in children. Also, no buffering effects of protective factors on the association between adversity and the brain outcomes survived multiple testing correction. We found no robust evidence for an interaction between protective factors and childhood adversity on broad brain structural measures. Small interaction effects observed in one cohort only warrant further investigation.

Exploring psychophysiological indices of disruptive behavior disorders and their subtypes of aggression.

BACKGROUND: Psychophysiological measures of arousal are often considered as potential biomarkers for disruptive behavior disorder (DBD). Nevertheless, the evidence is mixed, possibly reflecting the heterogeneity of DBD and different subtypes of aggression. Additionally, arousal measures of the central nervous system (e.g. electroencephalogram: EEG) are underrepresented compared to peripheral ones (heart rate: HR; skin conductance: SC). METHODS: We recorded HR, SC, and EEG (frequency band power at three electrodes Fz, Cz, Pz) in 49 participants with DBD, and 15 typically developing peers during two resting state and an emotional task condition. Group differences were assessed by a repeated measure ANOVA and regression analyses were applied to evaluate subtype-specific patterns. RESULTS: Our results showed higher mean HR activity in DBD participants, which was however driven by medicated participants and no significant group differences were found for SC. Interestingly, a significant group x frequency band interaction emerged for the EEG. DBD youth showed lower alpha activity. Regression analyses showed that higher theta and lower alpha band activity were related to more general aggression scores and higher delta and lower beta activity predicted proactive aggression. CONCLUSIONS: The lack of robust and significant differences for peripheral measurements (HR and SC) fits with previous mixed findings for externalizing disorders. Our results suggest that EEG measurements might be more sensitive to detect group differences and higher delta and lower beta activity might represent an index of a proactive subtype of aggression.

Neurostructural traces of early life adversities: A meta-analysis exploring age- and adversity-specific effects.

Early life adversities (ELAs) are associated with an increased risk of psychopathology, with studies suggesting a relation to structural brain alterations. Given the recently growing evidence of ELA effects on brain structure, an updated summary is highly warranted. Therefore, anatomical likelihood estimation was used to conduct a coordinate-based meta-analysis of gray matter volume (GMV) alterations associated with ELAs, including sub-analyses for different age groups and maltreatment as specific ELA-type. The analyses uncovered a convergence of pooled ELA-effects on GMV in the right hippocampus and amygdala and the left inferior frontal gyrus, age-specific effects for the right amygdala and hippocampus in children and adolescents, and maltreatment-specific effects for the right perigenual anterior cingulate cortex in adults. These results reveal a possible underlying commonality in the impact of adversity and also point to specific age and maltreatment effects. They suggest neural markers of ELAs in regions involved in socio-emotional functioning and stress regulation, with the potential to be used as targets for interventions designed to buffer or reverse harmful ELA-effects.

A Developmental Perspective on Facets of Impulsivity and Brain Activity Correlates From Adolescence to Adulthood.

BACKGROUND: On a theoretical level, impulsivity represents a multidimensional construct associated with acting without foresight, inefficient inhibitory response control, and alterations in reward processing. On an empirical level, relationships and changes in associations between different measures of impulsivity from adolescence into young adulthood and their relation to neural activity during inhibitory control and reward anticipation have not been fully understood. METHODS: We used data from IMAGEN, a longitudinal multicenter, population-based cohort study in which 2034 healthy adolescents were investigated at age 14, and 1383 were reassessed as young adults at age 19. We measured the construct of trait impulsivity using self-report questionnaires and neurocognitive indices of decisional impulsivity. With functional magnetic resonance imaging, we assessed brain activity during inhibition error processing using the stop signal task and during reward anticipation in the monetary incentive delay task. Correlations were analyzed, and mixed-effect models were fitted to explore developmental and predictive effects. RESULTS: All self-report and neurocognitive measures of impulsivity proved to be correlated during adolescence and young adulthood. Further, pre-supplementary motor area and inferior frontal gyrus activity during inhibition error processing was associated with trait impulsivity in adolescence, whereas in young adulthood, a trend-level association with reward anticipation activity in the ventral striatum was found. For adult delay discounting, a trend-level predictive effect of adolescent neural activity during inhibition error processing emerged. CONCLUSIONS: Our findings help to inform theories of impulsivity about the development of its multidimensional nature and associated brain activity patterns and highlight the need for taking functional brain development into account when evaluating neuromarker candidates.

Real-time individual benefit from social interactions before and during the lockdown: the crucial role of personality, neurobiology and genes.

Social integration is a major resilience factor for staying healthy. However, the COVID-19-pandemic led to unprecedented restrictions in social life. The consequences of these social lockdowns on momentary well-being are yet not fully understood. We investigated the affective benefit from social interactions in a longitudinal birth cohort. We used two real-time, real-life ecological momentary assessments once before and once during the initial lockdown of the pandemic (N = 70 participants; n~6800 observations) capturing the protective role of social interactions on well-being. Moreover, we used a multimethod approach to analyze ecological assessment data with individual risk and resilience factors, which are promising moderators in the relationship of social behavior, stress reactivity, and affective states (i.e., amygdala volume, neuroticism, polygenic risk for schizophrenia). Social contacts were linked to higher positive affect both during normal times and during the COVID-19-pandemic (beta coefficient = 0.1035), highlighting the beneficial role of social embedding. Interestingly, this relationship was differentially moderated by individual risk and resilience factors. In detail, participants with a larger left amygdala volume (beta coefficient = -0.0793) and higher neuroticism (beta coefficient = -0.0958) exhibited an affective benefit from more social interactions prior to the pandemic. This pattern changed during the pandemic with participants with smaller amygdala volumes and lower neurotic traits showing an affective gain during the pandemic. Moreover, participants with low genetic risk for schizophrenia showed an affective benefit (beta coefficient = -0.0528) from social interactions irrespective of the time point. Our results highlight the protective role of social integration on momentary well-being. Thereby, we offer new insights into how this relationship is differently affected by a person's neurobiology, personality, and genes under adverse circumstances.

The effects of callous-unemotional traits and aggression subtypes on amygdala activity in response to negative faces.

BACKGROUND: Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing. METHODS: We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8-18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task. RESULTS: Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression. CONCLUSIONS: Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.

Coping under stress: Prefrontal control predicts stress burden during the COVID-19 crisis.

The coronavirus (COVID-19) pandemic has confronted millions of people around the world with an unprecedented stressor, affecting physical and mental health. Accumulating evidence suggests that emotional and cognitive self-regulation is particularly needed to effectively cope with stress. Therefore, we investigated the predictive value of affective and inhibitory prefrontal control for stress burden during the COVID-19 crisis. Physical and mental health burden were assessed using an online survey, which was administered to 104 participants of an ongoing at-risk birth cohort during the first wave in April 2020. Two follow-ups were carried out during the pandemic, one capturing the relaxation during summer and the other the beginning of the second wave of the crisis. Prefrontal activity during emotion regulation and inhibitory control were assessed prior to the COVID-19 crisis. Increased inferior frontal gyrus activity during emotion regulation predicted lower stress burden at the beginning of the first and the second wave of the crisis. In contrast, inferior and middle frontal gyrus activity during inhibitory control predicted effective coping only during the summer, when infection rates decreased but stress burden remained unchanged. These findings remained significant when controlling for sociodemographic and clinical confounders such as stressful life events prior to the crisis or current psychopathology. We demonstrate that differential stress-buffering effects are predicted by the neural underpinnings of emotion regulation and cognitive regulation at different stages during the pandemic. These findings may inform future prevention strategies to foster stress coping in unforeseen situations.

Actigraphy-Derived Sleep Profiles of Children with and without Attention-Deficit/Hyperactivity Disorder (ADHD) over Two Weeks-Comparison, Precursor Symptoms, and the Chronotype.

Although sleep problems are common in children with ADHD, their extent, preceding risk factors, and the association between neurocognitive performance and neurobiological processes in sleep and ADHD, are still largely unknown. We examined sleep variables in school-aged children with ADHD, addressing their intra-individual variability (IIV) and considering potential precursor symptoms as well as the chronotype. Additionally, in a subgroup of our sample, we investigated associations with neurobehavioral functioning (n = 44). A total of 57 children (6-12 years) with (n = 24) and without ADHD (n = 33) were recruited in one center of the large ESCAlife study to wear actigraphs for two weeks. Actigraphy-derived dependent variables, including IIV, were analyzed using linear mixed models in order to find differences between the groups. A stepwise regression model was used to investigate neuropsychological function. Overall, children with ADHD showed longer sleep onset latency (SOL), higher IIV in SOL, more movements during sleep, lower sleep efficiency, and a slightly larger sleep deficit on school days compared with free days. No group differences were observed for chronotype or sleep onset time. Sleep problems in infancy predicted later SOL and the total number of movements during sleep in children with and without ADHD. No additional effect of sleep problems, beyond ADHD symptom severity, on neuropsychological functioning was found. This study highlights the importance of screening children with ADHD for current and early childhood sleep disturbances in order to prevent long-term sleep problems and offer individualized treatments. Future studies with larger sample sizes should examine possible biological markers to improve our understanding of the underlying mechanisms.