Mediodorsal and pulvinar thalamus reductions across the psychosis spectrum.

BACKGROUND

Abnormalities in thalamic structure and function are a consistent feature of psychosis spectrum disorders including schizophrenia (SZ), schizoaffective (SAD), and bipolar disorder with psychosis (BDP), yet the extent to which specific thalamic nuclei differ across diagnoses, and how these differences relate to cognition and psychopathology, remains unclear. We examined these questions, focusing on two nuclei - the mediodorsal (MD) and pulvinar (Pu), among individuals with psychosis (n = 2160) in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium.

METHODS

Whole thalamus, MD, and Pu were estimated using FreeSurfer. Group comparisons were performed to examine volumetric differences between neurotypical controls (NC) and: (1) traditional diagnostic groups and (2) biologically-defined Biotypes identified through unsupervised clustering of neurophysiological features. Spearman correlations were used to assess the associations between subthalamic nuclei volumes and cognitive performances.

RESULTS

The MD volumes were significantly smaller in individuals with SZ, SAD, BDP and BT1 compared to controls (Cohen's d between -0.17 to -0.37). MD and Pu volumes positively correlated with some cognitive functions, notably in the right MD.

CONCLUSIONS

This is the largest study to date examining thalamic nuclei volumes across both DSM diagnoses and psychosis Biotypes. We demonstrate that MD reductions are transdiagnostic yet most pronounced in BT1, supporting the Biotype framework over traditional nosology. The links between MD volume and cognitive performance suggest that nucleus-specific thalamic markers may help refine mechanistic models and stratify future treatment targets. Multimodal studies integrating electrophysiology and functional imaging are warranted to clarify nuclei-specific contributions to psychosis.