Luise Poustka

Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups.

Exposure to early life adversity is associated with elevated risk for psychopathology, including internalising disorders, that often endure into adulthood, yet the neurodevelopmental processes linking adversity to symptom emergence remain unclear. Longitudinal analyses of brain development may clarify whether adversity-related structural alterations contribute to this vulnerability. Structural MRI data were analysed from 2,021 participants in the IMAGEN cohort assessed at approximately ages 14, 19, and 22 years. Higher-order mixed-effects modelling examined associations between adversity and volumetric trajectories of 88 brain regions. Regions showing significant adversity effects were further analysed to test whether related brain changes explained or modified later symptom risk and to examine temporal dynamics. Early life adversity was associated with variations in 19 regional volumes, spanning prefrontal (rostral anterior cingulate, orbitofrontal, caudal middle frontal), parietal (superior and supramarginal), and subcortical (thalamus, ventral diencephalon) systems, reflected in both stable differences and adversity-by-age interactions. Greater adversity exposure predicted higher total and emotional symptoms in early adulthood. Regional brain volume change did not mediate the association between adversity and later symptoms. However, moderation analyses indicated that developmental change in select regions amplified vulnerability to symptom emergence, suggesting that brain structure influenced individual susceptibility rather than explaining symptom risk. Adversity-related brain differences do not explain later psychopathology through simple mediation. Instead, findings support a dynamic, bidirectional framework in which adversity, brain maturation, and symptoms interact dynamically across adolescence, highlighting the need for network-level and multivariate approaches sensitive to developmental timing.

Early detection and prevention of psychiatric disorders, particularly depression, remain as major global health challenges, yet reliable tools for identifying individuals before symptom onset are lacking. Here, we combine functional neuroimaging with computational modeling to identify a mechanistic biomarker of depression risk. In a population-based adolescent cohort (IMAGEN, N = 1332), we found that weakened neural representations of emotional signals were linked to depressive symptoms. Perturbation experiments in a brain-aligned deep learning model showed that this deficit reflects overregularized emotion perception, producing a negative perceptual bias. A neurocomputational signature of this mechanism predicted depression symptom onset up to 4 years later at the IMAGEN follow-up ( N = 725), was associated with both a genetic-risk variant and polygenic risk for depression, and improved depression classification in a patient cohort (STRATIFY, N = 411). These findings suggest a possible mechanism linking genetic vulnerability to altered emotion perception and future depression, and propose a predictive computational marker with potential for early detection and prevention.

Introduction: Anhedonia is a transdiagnostic psychiatric symptom linked to increased functional connectivity between the prefrontal cortex and striatum. Here, we examined how dimensions of early adversity contribute to this profile of connectivity. Methods: In a European community sample of young adults (IMAGEN), we examined cross-sectional (n=613) and longitudinal (n=332) associations of adversity dimensions with resting-state fMRI-derived connectivity. We selected 10 ROIs from anhedonia literature, defined in the functional images as 4mm-radius spheres. We then used network-based regression models to identify clusters of ROI-ROI connections associated with threat and deprivation scores, using interaction terms to examine sex and age-specific associations. We also examined associations between adversity and anhedonia, operationalized using factor analysis of six items from self-report surveys. Results: At age 18-22, we identified sex-specific associations between deprivation and connectivity for a cluster of 9 ROI-ROI connections ( p-FWE =0.038), primarily involving the nucleus accumbens. Specifically, we observed positive associations between deprivation and connectivity in males, and negative associations in females. In the longitudinal analysis, negative deprivation associations in females attenuated with age for a cluster of 14 connections ( p-FWE =0.009). A cluster of 17 connections also had initial positive associations with threat in females that attenuated with age ( p-FWE =0.008). No such longitudinal changes were observed in males. Higher deprivation was linked to increased later anhedonia in males but not females ( p =0.026). Conclusion: Compared to females, young adult males may be more vulnerable to developing anhedonia after experiencing deprivation in childhood. Dimensions of early adversity are linked to distinct pathways of frontostriatal development.

Inhibitory control matures progressively from childhood to early adulthood, yet the neural mechanisms driving this development and their relevance to psychiatric risk remain poorly understood. Guided by the Dual Cognitive Control model, we leveraged longitudinal fMRI from two independent cohorts in the US (ABCD, ages 9–12) and Europe (IMAGEN, ages 14–22) to map the spatiotemporal dynamics of reactive and proactive control using novel single-trial modeling and representational similarity analysis. We found both reactive and proactive stopping networks stabilize after mid-adolescence, tracking the developmental patterns of inhibitory control and behavioral stability. By decoding trial-by-trial fluctuations along a speed-caution continuum, we demonstrate that brain-behavior coupling to a proactive “Safe state” tightens progressively with age. Furthermore, network-level representational coherence of this Safe state emerged as a scanner-invariant, trait-like biomarker that robustly predicted inhibitory control, behavioral stability, and transdiagnostic psychopathology across multiple developmental windows, providing a validated neural phenotype for precision psychiatry.

Globally, 60% of the population has experienced at least one type of adversity (e.g., emotional abuse, bullying) across infancy, childhood, and adolescence. Such experiences have been linked to an increased risk for mental health disorders. Changes in brain structure following experiences of childhood adversity have been hypothesised to be a mechanistic pathway explaining later mental health issues. However, to understand how changes in brain structure might mediate the effects of adversity, it is essential to identify which underlying neuronal processes may be affected by different types of adverse experiences. A key open question is whether grey or white matter is more vulnerable to adversity, as these two structures reflect distinct neurobiological mechanisms. This study investigated whether differences in trajectories of grey and white matter development during adolescence can be explained by exposure to different types of adversity. We applied the Adverse Adolescent Experiences Framework (Pollmann et al., 2025) categorising adversity into four levels: Intrapersonal (e.g., accidents), Caregiver (e.g., emotional neglect), Peer (e.g., bullying), and Community (e.g., neighbourhood safety). Exposure to each of the four factors was estimated through principal components analyses. We analysed two large longitudinal datasets: the Adolescent Brain Cognitive Development study (∼12,000 adolescents measured at ages 10, 12, and 14) and the IMAGEN study (∼1,400 adolescents measured at ages 14, 19, and 22). Using latent growth curve models, we captured individual differences in brain development by estimating baseline levels (intercepts) and rates of change (slopes) for total grey matter volume and mean white matter fractional anisotropy. In both cohorts, we found significant interindividual variability in baseline levels and rates of change for both grey matter volume and fractional anisotropy. Caregiver, Peer, and Community adversities were negatively associated only with the intercepts of grey matter volume and white matter fractional anisotropy. Importantly, associations differed between grey and white matter. In ABCD, Peer and Community adversities were more strongly associated with grey matter volume intercepts. In contrast, in IMAGEN, Caregiver, Peer and Community adversities were more strongly linked to white matter fractional anisotropy intercepts. This suggests that adversity has unique associations with grey and white matter, rather than exerting a uniform influence on brain structure. By demonstrating that different environments generate distinct biological associations with brain maturation, this work underscores the need to consider both grey and white matter when assessing the neurodevelopmental pathways to outcomes across the lifespan.

As developmental science expands globally, its theories and methods must rise to the challenge. Children worldwide develop within caregiving ecologies that often differ from traditional family models. Understanding how infants adapt within these contexts reveals general principles of human development. Achieving this requires structural change: consensus-building, open methods, and theories grounded in the environments where most children actually grow up.

Parent training and assisted self-help have proven effective in preschool-age children with attention-deficit/hyperactivity disorder (ADHD). This study analysed a stepped-care approach combining these interventions. Participants were children (3-6 years) with either ADHD or oppositional defiant disorder (ODD) plus substantial ADHD symptoms. Study Step 1 (three months) comprised a randomised, waitlist-controlled trial on the efficacy of parent-directed telephone-assisted self-help (TASH). Based on the response to TASH, in Step 2 (six months), participants either received TASH booster sessions (full responders) or participated in another randomized controlled trial (partial/non-responders) comparing parent management and preschool teacher training (PMPTT) with treatment as usual (TAU). The primary outcome was change in blinded-clinician-rated ADHD and ODD symptoms. The primary analyses were by intention-to-treat. 189 children (79.9% boys, mean age = 5.1 years) were randomised. A univariate analysis of covariance did not yield a significant difference in the primary outcome for Step 1 (n_TASH=58, n_Waitlist=54; mean difference -0.13 ± 0.07, 95%-CI -0.26-0.01; p = 0.06; d= -0.30). Following TASH, 67 children (40.9%) showed a full response and 97 a partial/non-response. In Step 2, PMPTT was superior to TAU (n_PMPTT=23, n_TAU=37; mean difference -0.23 ± 0.11, 95%-CI -0.44-[-0.01]; p = 0.040; d=-0.52, 95%-CI -1.02-[-0.03]). Furthermore, TASH showed effects on parent-rated externalizing symptoms, negative parenting, and parental self-efficacy, and PMPTT on semi-blinded-clinician- and parent-rated impairment. Stepwise adaptive treatment may be beneficial for preschoolers with ADHD. Initial TASH is associated with full responses in a subgroup. Consecutive PMPTT should be offered to children with residual symptoms. (German Clinical Trials Register; DRKS00008971; registered on 01 October 2015).

Spontaneous general movements provide a natural neuromotor baseline for quantifying context-related kinematic modulation as infants transition toward active social engagement. In this longitudinal prospective study, we analyzed 47 infants recorded at 4, 8, 12, and 16 weeks post-term age using 3D markerless motion tracking. Kinematics were compared across three consecutive segments: the final 30 s of solitary baseline, caregiver approach, and the first 30 s after the caregiver’s face appeared above the cot (social context). Motion space, posture, and movement speed were quantified to index age-specific changes in body control and orientation across contexts. Across development, motion space expanded from a predominantly horizontal distribution at 4 weeks to greater vertical and midline occupancy by 16 weeks. Context-related postural modulation emerged with age, shifting from initially minimal differences to sustained head and upper-body orientation toward the caregiver by 12 weeks. Remarkably, speed showed a nonlinear trajectory: infants exhibited a brief reduction in movement speed around caregiver arrival at 4 weeks, a more sustained reduction at 8 weeks, and a reversal to post-arrival acceleration beginning at 12 weeks. These findings highlight continuous ontogenetic adaptation from the outset, in which context-sensitive motor modulation is tuned across development to the infant’s current repertoire and environmental demands, in service of increasingly active social engagement. Our study offers a new framework for detecting potential divergence that may lie less in specific early social behaviors than in cross-domain coordination and context-sensitive modulation.