Randomized trial reveals unique brain feature differences in early- and late-onset OCD, indicating potential clinical implications.
Background: Obsessive-compulsive disorder (OCD) is heterogeneous, and differences in age at onset may be associated with important feature of distinct subtype. However, no studies have investigated the differences between early- and late-onset OCD using structural and functional multimodal neuroimaging methods that reflect different neurobiological backgrounds. Methods: Structural and resting-state functional magnetic resonance imaging data were obtained from 130 participants (76 medication-free patients with OCD and 54 healthy controls [HCs]). We investigated group differences among early- and late-onset OCD and HCs in the fractional amplitude of low-frequency fluctuation (fALFF) and local gyrification index (LGI). Results: Group differences were detected in the left lateral occipital cortex and bilateral thalamus (a voxel-height threshold of p < 0.001 and a cluster-level threshold of p < 0.05, with a false discovery rate correction). Both patients with early- and late-onset OCD had significantly lower fALFF in the thalamus compared to HCs (Bonferroni corrected p < .01). Patients with early-onset OCD exhibited significantly lower fALFF in the lateral occipital cortex than those with late-onset OCD and HCs (Bonferroni corrected p < .01). No significant differences were observed in the LGI analysis (a nonparametric permutation approach [10,000 iterations]), a cluster-wise threshold of p < 0.05, and a cluster-defining threshold of p < 0.001). Limitations: Our cross-sectional data could limit the interpretation of our results. Conclusions: Our results emphasize the importance of the thalamus in the pathophysiology regardless of the age-of-onset subtype of OCD. In addition, altered fALFF in the lateral occipital cortex, not accompanied by deficits of LGI, could represent a disruption of normal functional developmental processes resulting from the OCD onset at a young age. Future study should examine the relationship between the alteration of fALFF in lateral occipital cortex and clinical and treatment-refractory features of early-onset OCD, potentially improving therapeutic strategies.
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Tomiyama et al. (2026) studied this question.
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