Biology subjects

Rakesh, D.

Publications and source records attributed to Rakesh, D..

5 recordsLinked to original sources

bioRxiv2026

Psychotic-like experiences in children born very preterm: evidence from clinical and population-based cohorts

Background and aimVery preterm birth (VPT; [≤]32 weeks gestation) is associated with an increased risk of later psychiatric disorders, including psychosis. Although psychosis typically emerges in adulthood, subclinical early signs along the psychosis continuum, such as psychotic-like experiences (PLEs), can be observed much earlier. We therefore aimed to study PLEs in childhood in VPT individuals recruited from a clinical cohort compared with full-term (FT) controls. We subsequently investigated whether findings could be replicated in an independent population-based cohort. MethodsPrimary analyses were conducted in the Brain, Immunity and Psychopathology (BIPP) study, including 197 children born VPT recruited through Neonatal Intensive Care Units and 72 FT controls assessed at a mean age of 10.50{+/-}1.77 years. Between-group differences in PLEs were then examined in the Adolescent Brain Cognitive Development (ABCD) study, including 149 children born VPT and 9519 FT controls assessed at a mean age of 9.94 {+/-} 0.63 years. PLEs were assessed using the Prodromal Questionnaire-Brief Child Version (PQ-BC), yielding frequency and distress-related scores for both the total scale and three specific domains (unusual thought content, perceptual abnormalities, disorganised speech). Regression models tested associations between birth status (VPT and control) and PQ-BC scores adjusting for age, sex, and socio-economic status, with secondary models additionally adjusting for cognitive ability and broader psychopathology. Pooled analyses examined cohort effects (BIPP and ABCD) and cohort-by-group status (VPT and control) interactions. ResultsIn BIPP, VPT birth was associated with higher PQ-BC total ({beta}=1.61, p=0.004) and distress scores ({beta}=0.78, p=0.039), with the strongest and most consistent associations observed for perceptual abnormalities across total score (sum of endorsed items), distressing items, and distress severity scores (all p[≤]0.01). These associations were attenuated but largely persisted after adjustment for cognitive ability and broader psychopathology, particularly for perceptual abnormalities. In ABCD, VPT birth was not significantly associated with global or domain-specific PQ-BC outcomes. DiscussionVPT birth is associated with increased vulnerability to PLEs in childhood, particularly in the domain of perceptual abnormalities. The lack of clear replication in the population-based ABCD cohort may reflect differences in the composition of its VPT subgroup, which may not fully represent VPT individuals typically seen in clinical cohorts.

developmental biology↗

bioRxiv2026

Adversity and adolescent brain development: differential associations with grey and white matter across two longitudinal cohorts

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.

neuroscience↗

bioRxiv2025

Sex-specific brain structural predictors and outcomes of adolescent depression trajectories

ObjectivesDepressive symptoms often emerge and increase during adolescence, yet the neural predictors and long-term brain outcomes associated with depressive trajectories remain poorly understood. This study adopts a trajectory-based approach to explore the temporal relationship between brain structure and dynamic changes in depressive symptoms across adolescence. MethodsWe used a large longitudinal adolescent neuroimaging sample across five annual waves (n = 11,862; mean age = 9.91 at baseline) from the ABCD study. First, growth mixture models were applied separately for males and females to identify distinct developmental trajectories of depressive symptoms. We then used linear mixed-effects models to identify which baseline brain structural features differentiated trajectory classes, and how these trajectories influenced subsequent brain structure. ResultsWe identified high-decreasing, stable-low, and low-increasing trajectories in females, and relatively stable high, moderate, and low trajectories in males. No baseline brain regions were found to be associated with female trajectories, whereas smaller global brain measures (total subcortical volume, cortical volume, and surface area) predicted the high trajectory in males. Regarding brain outcomes, a low-increasing trajectory in females was associated with smaller global subcortical and cortical volumes, while high and moderate trajectories in males predicted thinner global cortices. Additional trajectory-related regional brain alterations were observed in both sexes. ConclusionsThese findings highlight distinct neurodevelopmental patterns linked to depressive symptom trajectories in males and females, underscoring the importance of a sex-specific and longitudinal approach to identifying neural risk and outcomes in adolescent depression.

neuroscience↗

bioRxiv2025

Neuroanatomical signatures of depression and anxiety in at-risk adolescents: A symptom-oriented perspective

BackgroundMajor depressive disorder (MDD) and generalized anxiety disorder (GAD) often emerge in adolescence. Identifying their symptom structures and neural biomarkers in youth with elevated risk is critical for early detection and developing interventions. This study investigated the central symptoms of MDD and GAD and identified the key brain regions ("brain bridges") linking structural neuroanatomy to symptoms in at-risk adolescents. MethodsA total of 1,568 adolescents at high risk for MDD and 413 adolescents at high risk for GAD were identified from the Adolescent Brain Cognitive Development (ABCD) study. Participants completed MDD and GAD symptom assessments and underwent Magnetic Resonance Imaging scanning. We constructed 10 psychological network models incorporating symptoms and brain structural indices to identify central symptoms and brain bridges. ResultsConcentration difficulties emerged as the shared core symptom, while self-hatred and irritability were the unique central symptoms for MDD and GAD, respectively. Left- and right-pallidum volumes exhibited the highest bridge centrality for MDD symptoms, whereas left-nucleus accumbens volume showed the highest bridge centrality for GAD symptoms. ConclusionOur findings highlight the pallidum and nucleus accumbens as key brain regions linking structural anatomy to symptom networks in high-risk youth. These results provide novel insights into early neurobiological markers of MDD and GAD from a symptom-oriented perspective and may inform targeted interventions.

neuroscience↗

bioRxiv2025

Shared Neural Signatures of Socioeconomic Status, Scarcity, and Neighborhood Threat in Youth

Early life adversity is a known risk factor for psychopathology, yet the neurodevelopmental impacts of distinct types of adversity remain unclear. Using machine learning, we examined how adversity (physical and sexual abuse, neighborhood threat, scarcity, household dysfunction, prenatal substance exposure, parental psychopathology) and socioeconomic status are associated with cortical thickness in youth. We used data from the Adolescent Brain Cognitive Development Study at three time points: baseline (N=6,908, ages 9-10), two-year follow-up (N=5,808), and four-year follow-up (N=2,245). Cortical thickness was linked to socioeconomic status and neighborhood threat at all time points, and scarcity at baseline. The strongest negative associations were in medial temporal and occipital regions. Our analyses revealed neural effects of socioeconomic status, neighborhood threat, and scarcity, converging on regions involved in memory, visual processing, and higher-order cognition. These findings suggest consistent neural signatures linked to socioeconomic disadvantage, highlighting the importance of addressing inequality to promote neurodevelopmental health.

neuroscience↗