Biological, Psychosocial, and Microbial Determinants of Childhood-Onset Obsessive-Compulsive Disorder: A Narrative Review.

The etiology of obsessive-compulsive disorder (OCD) remains incompletely understood, but it is widely recognized as the result of a complex interplay among multiple contributing mechanisms, often emerging during childhood. This narrative review synthesizes current evidence on the etiology of childhood-onset OCD, with particular focus on whether GM alterations are involved in the pathophysiological mechanisms underlying the disorder. Specifically, the review first examines both biological and psychosocial determinants of OCD, and then explores the role of the gut microbiome (GM), including the potential of psychobiotics as a novel therapeutic approach. OCD has a strong hereditary component, involving both common polygenic variants and rare mutations. Epigenetic mechanisms such as DNA methylation and microRNA play a role in mediating gene-environment interactions and influencing OCD risk. Dysfunction and hyperactivity within cortico-striato-thalamo-cortical circuits underlie one of the neurobiological bases of OCD. Infections and autoimmune reactions can trigger or exacerbate OCD, particularly in pediatric populations. A range of psychosocial factors have been implicated in the onset of OCD, often in interaction with underlying neurobiological vulnerabilities. Current evidence indicates that GM alterations may also contribute to OCD pathophysiology through immune-mediated neuroinflammation, disrupted gut-brain signaling, and neurotransmitter imbalance. Individuals with OCD present reduced microbial diversity and lower abundance of butyrate-producing taxa, as well as altered IgA levels and increased infection susceptibility. These shifts may affect dopaminergic, glutamatergic, and serotonergic pathways, particularly via tryptophan metabolism and compromised gut integrity. Thus, the GM plays a pivotal role in OCD, constituting a promising approach for understanding its etiology and highlighting the significant clinical potential of microbial-based treatments such as psychobiotics. Nevertheless, despite progress, gaps remain in understanding childhood-onset OCD determinants, including limited longitudinal studies, incomplete characterization of the GM, scarce psychobiotic trials, and a need for integrated multidisciplinary approaches. Moreover, epidemiological evidence is compromised by reliance on lay diagnoses, questionable assessment validity, and insufficient distinction from related disorders.