Prof. Dr. Dr. Tobias Banaschewski

Neurodevelopmental conditions, such as autism, are highly heterogeneous at both the mechanistic and phenotypic levels. Therefore, parsing heterogeneity is vital for uncovering underlying processes that could inform the development of targeted, personalized support. We aimed to parse heterogeneity in autism by identifying subgroups that converge at both the phenotypic and molecular levels. An imaging transcriptomics approach was used to link neuroanatomical imaging-derived phenotypes in autism to whole-brain gene expression signatures provided by the Allen Human Brain Atlas. Neuroimaging and clinical data of 359 autistic participants ages 6 to 30 years were provided by EU-AIMS (European Autism Interventions) LEAP (Longitudinal European Autism Project). Individuals were stratified using data-driven clustering techniques based on the correlation between brain phenotypes and transcriptomic profiles. The resulting subgroups were characterized on the clinical, neuroanatomical, and molecular levels. We identified 3 subgroups of autistic individuals based on the correlation between imaging-derived phenotypes and transcriptomic profiles that showed different clinical phenotypes. The individuals with the strongest transcriptomic associations with imaging-derived phenotypes showed the lowest level of symptom severity. The gene sets most characteristic for each subgroup were significantly enriched for genes previously implicated in autism etiology, including processes such as synaptic transmission and neuronal communication, and mapped onto different gene ontology categories. Autistic individuals can be subgrouped based on the transcriptomic signatures associated with their neuroanatomical fingerprints, which reveal subgroups that show differences in clinical measures. The study presents an analytical framework for linking neurodevelopmental and clinical diversity in autism to underlying molecular mechanisms, thus highlighting the need for personalized support strategies.

Early life stress is associated with alterations in brain function and connectivity during affective processing, especially in the fronto-limbic pathway. However, most of the previous studies were limited to a small set of priori-selected regions and did not address the impact of stress timing on functional connectivity. Using data from a longitudinal birth cohort study (n = 161, 87 females, mean age (SD) = 32.2(0.3)), we investigated the associations between different time points of stress exposure and functional connectivity. We measured stressful life events across development using a modified version of Munich Event List and grouped into four developmental stages: prenatal/newborn (prenatal-3 months), infancy and toddlerhood (3 months-4.5 years), childhood (4.5–11 years), and adolescence (11–19 years). All participants completed an fMRI-based emotion regulation task at the age of 33 years. Task-dependent directed functional connectivity was calculated using whole-brain generalized psychophysiological interactions. The association between life stress and connectivity was investigated within a multiple regression framework. Our findings revealed distinct associations between stress exposure and task-specific functional connectivity, depending on the developmental timing of stress exposure. While prenatal and childhood stress were associated with lower connectivity between subcortex and cognitive networks, stress exposure unique to adolescence was related to higher connectivity from the salience network to the cognitive networks. These results suggest that early life stress alters the connectivity of cognitive and limbic networks, which are important for emotion processing and regulation. Future research should replicate and extend the findings regarding sensitive periods by utilizing diverse paradigms in cognitive, social, and emotional domains.

Heidelberg University is Germany’s oldest university, founded in 1386. Renowned for its research excellence and strong emphasis on the humanities, natural sciences, and medicine, it consistently ranks among Europe’s top universities. The university fosters a rich academic tradition and an international outlook, attracting students and scholars from around the world.

The Central Institute of Mental Health (Zentralinstitut für Seelische Gesundheit) in Mannheim, Germany, is a leading psychiatric research institution affiliated with Heidelberg University. It specializes in research, treatment, and education related to mental health disorders, neuroscience, and psychosocial factors influencing mental well-being. The institute plays a crucial role in advancing psychiatric knowledge and developing innovative therapies through interdisciplinary collaboration and state-of-the-art facilities.