Multimodal white matter alterations in adolescent obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) emerging during adolescence coincides with a critical period of white matter maturation, yet the structural, functional, and molecular characteristics of white matter abnormalities remain incompletely understood. We acquired multimodal magnetic resonance imaging data from 40 adolescents with OCD and 40 healthy controls and quantified fractional anisotropy (FA) and fractional amplitude of low-frequency fluctuations (fALFF) along white matter tracts using Automated Fiber Quantification. Group comparisons, clinical correlation analyses, support vector machine classification, and molecular association analyses were performed. Adolescents with OCD exhibited increased FA in the bilateral anterior thalamic radiation (ATR) and left corticospinal tract, together with increased fALFF in the right ATR and right cingulum bundle (cingulate segment). Greater functional activity within the cingulum bundle was associated with lower symptom severity. A multimodal model integrating FA and fALFF achieved better classification performance than either modality alone. Molecular analyses linked white matter structural alterations to dopaminergic and cholinergic neurotransmitter systems, while transcriptomic analyses implicated neurodevelopmental and synaptic processes as well as excitatory and inhibitory neuronal cell types. These findings demonstrate convergent structural and functional alterations of white matter in adolescent OCD and suggest that their associated molecular signatures may provide insights into the biological context of these imaging abnormalities.