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Author Spotlight: Understanding Adolescent Social Adversity Effects on Neurodevelopment in Mice
Published on: March 15, 2024
Shared neurogenetic architecture links adolescent neurodevelopmental deviations to adult psychopathological
Yuanyuan Hu1,2, Yancheng Tang3, Wei Li3
1State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China.
Abstract:
While general procrastination is common, psychopathological procrastination, a debilitating phenotype often indicative of subclinical psychiatric conditions, remains poorly understood in terms of its neurobiological underpinning. Challenging its traditional conceptualization as a mere behavioral deficit, we investigated the neurogenetic architecture of psychopathological procrastination. Leveraging a prospective adolescent twin cohort (N = 71 twin pairs) with neuroanatomical imaging (baseline) and psychopathological procrastination phenotyping in young adulthood (8-year follow-up), we first established moderate heritability for psychopathological procrastination (h² = 0.47, 95% CI: 0.14 - 0.71). Employing normative modeling of brain morphology, we found that adolescent neurodevelopmental deviations, specifically within the nucleus accumbens (NAcc), predicted adult psychopathological procrastination. Crucially, these predictive adolescent NAcc deviations exhibited a strong shared genetic basis with adult psychopathological procrastination (rg = 0.89, 95% CI: 0.89 - 1.00). Beyond regional effects, psychopathological-procrastination-specific whole-brain deviation patterns were identified, which showed neurobiological enrichment with cortical functional gradient and key dopaminergic (DAT/D1) and serotonergic (5-HT receptors) neurotransmitter systems. Both cross-sectional and longitudinal transcriptomic integration of these neuroimaging signatures with human brain gene expression data pinpointed significant associations with molecular transport, neuroimmune responses, and neuroinflammation, further implicating dysregulation within serotonergic and dopaminergic pathways. Collectively, our findings delineate a multisystem neurogenetic architecture of psychopathological procrastination, providing supportive evidence that recontextualizes this debilitating phenotype from a simple behavioral issue to a condition with neurodevelopmental antecedents, potentially suggesting its conceptualization as a subclinical brain disorder.
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