Bridging Mechanistic Insights Across Autism, Schizophrenia, and Bipolar Disorder: Convergence, Divergence, and Clinical Implications

Autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BD) are complex brain disorders that manifest across different stages of development but share striking overlaps in genetic risk factors. While traditionally categorized as distinct neurodevelopmental or neuropsychiatric disorders, emerging evidence suggests that these diagnoses may reflect a continuum of brain dysfunction rooted in shared molecular and cellular mechanisms. Large-scale genomic studies have identified common susceptibility genes, implicating synaptic, transcriptional, and neurodevelopmental pathways that contribute to all three conditions.Despite these shared genetic foundations, ASD, SCZ, and BD exhibit markedly different clinical profiles, ranging from early-onset social and communication deficits in ASD to adolescent or adult-onset psychosis and mood dysregulation in SCZ and BD. This clinical divergence raises important questions about how common genetic risk converges with disorder-specific developmental trajectories, brain region vulnerabilities, and environmental exposures to produce distinct outcomes. Understanding both the convergence and divergence among these conditions is essential for disentangling the complex biology of psychiatric and neurodevelopmental disorders and for informing more precise approaches to diagnosis and treatment. Recent advances in multi-omics, single-cell transcriptomics, circuit mapping, and neuroimaging are beginning to uncover the intricate interplay between genes, cells, circuits, and environmental context in shaping disorder-specific phenotypes. However, key gaps remain in identifying causal mechanisms, linking molecular alterations to clinical symptoms, and establishing biomarkers that can guide early intervention strategiesThis Research Topic aims to advance our understanding of the molecular, cellular, and circuit-level mechanisms that underlie autism spectrum disorder, schizophrenia, and bipolar disorder, with a focus on elucidating shared biological mechanisms as well as disorder-specific features. We invite contributions that leverage genetic, developmental, and systems-level perspectives to uncover the mechanistic bases of these conditions and to explore why overlapping genetic risk leads to divergent clinical outcomes. Areas of particular interest include, but are not limited to:· Molecular and Genetic Mechanisms: Define shared and distinct risk genes and pathways across ASD, SCZ, and BD; map polygenic risk to specific biological processes; investigate rare variants or copy number variations with pleiotropic effects.· Cellular and Circuit Pathophysiology: Characterize how synaptic function, neural connectivity, glial involvement, or neuroimmune interactions differ or align among the three disorders.· Developmental Trajectories: Investigate how developmental timing, critical windows, and region-specific vulnerabilities influence the expression and progression of ASD, SCZ, and BD.· Gene-Environment Interactions: Examine how environmental exposures (e.g., perinatal stress, inflammation, substance use) interact with genetic susceptibility to shape disorder onset and course.· Biomarkers: Identifying and validating molecular, neuroimaging, electrophysiological, and/or behavioral markers for early detection, diagnostic stratification, monitoring disease progression, and predicting treatment response.· Sources of Clinical Heterogeneity: Analyze factors driving symptom variability, sex differences, and comorbidities, especially within the context of shared biology.By focusing on ASD, SCZ, and BD, this Research Topic seeks to foster interdisciplinary collaboration aimed at clarifying the biological underpinnings of neuropsychiatric disorders that are distinct yet increasingly recognized to overlap. We hope to accelerate translational efforts that will ultimately inform personalized diagnostic and therapeutic strategies. Topic editors: Francesco Longo, Emanuela Santini, Sameer Aryal Source: https://www.frontiersin.org/research-topics/72936/bridging-mechanistic-insights-across-autism-schizophrenia-and-bipolar-disorder-convergence-divergence-and-clinical-implications