Macro- and Microstructural Alterations in the Midbrain in Early Psychosis Associates with Clinical Symptom Scores

Early psychosis (EP) is a critical period for psychotic disorders during which the brain undergoes rapid and significant functional and structural changes ( Shinn et al., 2017). The Human Connectome Project (HCP) is a global effort to map the human brain's connectivity in health and disease. Here we focus on HCP-EP subjects (i.e., those within 5 years of the initial psychotic episode) to determine macro- and microstructural alterations in EP (HCP-EP sample, <i>n</i> = 179: EP, <i>n</i> = 123, controls, <i>n</i> = 56) and their association with clinical outcomes (i.e., symptoms severity) in HCP-EP. We carried out analyses of deformation-based morphometry (DBM), scalar indices from the diffusion tensor imaging (DTI), and tract-based spatial statistics (TBSS). Lastly, we conducted correlation analyses focused on the midbrain (DBM and DTI) to examine associations between its structure and clinical symptoms. Our results show that the midbrain displays robust alteration in its structure (DBM and DTI) in the voxel-based analysis. Complimentary alterations were also observed for the hippocampus and putamen. A seed-based analysis centered around the midbrain confirms the voxel-based analysis of DBM and DTI. TBSS displays structural differences within the midbrain and complementary alterations in the corticospinal tract and cingulum. Correlations between the midbrain structures and behavior showed that the quantified features correlate with cognition and clinical scores. Our findings contribute to understanding the midbrain-focused circuitry involvement in EP and provide a path for future investigations to inform specific brain-based biomarkers of EP.