Age-associated alterations in thalamocortical structural connectivity in youths with a psychosis-spectrum disorder.

Psychotic symptoms typically emerge in adolescence. Age-associated thalamocortical connectivity differences in psychosis remain unclear. We analyzed diffusion-weighted imaging data from 1254 participants 8-23 years old (typically developing (TD):N = 626, psychosis-spectrum (PS): N = 329, other psychopathology (OP): N = 299) from the Philadelphia Neurodevelopmental Cohort. We modeled thalamocortical tracts using deterministic fiber tractography, extracted Q-Space Diffeomorphic Reconstruction (QSDR) and diffusion tensor imaging (DTI) measures, and then used generalized additive models to determine group and age-associated thalamocortical connectivity differences. Compared to other groups, PS exhibited thalamocortical reductions in QSDR global fractional anisotropy (GFA, p-values range = 3.0 × 10-6-0.05) and DTI fractional anisotropy (FA, p-values range = 4.2 × 10-4-0.03). Compared to TD, PS exhibited shallower thalamus-prefrontal age-associated increases in GFA and FA during mid-childhood, but steeper age-associated increases during adolescence. TD and OP exhibited decreases in thalamus-frontal mean and radial diffusivities during adolescence; PS did not. Altered developmental trajectories of thalamocortical connectivity may contribute to the disruptions observed in adults with psychosis.

Defining data-driven subgroups of obsessive-compulsive disorder with different treatment responses based on resting-state functional connectivity.

Characterization of obsessive-compulsive disorder (OCD), like other psychiatric disorders, suffers from heterogeneities in its symptoms and therapeutic responses, and identification of more homogeneous subgroups may help to resolve the heterogeneity. We aimed to identify the OCD subgroups based on resting-state functional connectivity (rsFC) and to explore their differences in treatment responses via a multivariate approach. From the resting-state functional MRI data of 107 medication-free OCD patients and 110 healthy controls (HCs), we selected rsFC features, which discriminated OCD patients from HCs via support vector machine (SVM) analyses. With the selected brain features, we subdivided OCD patients into subgroups using hierarchical clustering analyses. We identified 35 rsFC features that achieved a high sensitivity (82.74%) and specificity (76.29%) in SVM analyses. The OCD patients were subdivided into two subgroups, which did not show significant differences in their demographic and clinical backgrounds. However, one of the OCD subgroups demonstrated more impaired rsFC that was involved either within the default mode network (DMN) or between DMN brain regions and other network regions. This subgroup also showed both lower improvements in symptom severity in the 16-week follow-up visit and lower responder percentage than the other subgroup. Our results highlight that not only abnormalities within the DMN but also aberrant rsFC between the DMN and other networks may contribute to the treatment response and support the importance of these neurobiological alterations in OCD patients. We suggest that abnormalities in these connectivity may play predictive biomarkers of treatment response, and aid to build more optimal treatment strategies.