Macro- and Micro-Structural Alterations in the Midbrain in Early Psychosis associates with clinical symptom scores.

Abstract

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 five years of the initial psychotic episode) to determine macro- and micro-structural alterations in EP (HCP-EP sample, n=179: EP, n=123, Controls, n=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.Significance statement Psychotic disorders are preceded by a critical period known as early psychosis (EP), where detection and effective interventions could substantially improve symptoms and have the potential to modify the subsequent disease course. However, early biomarkers of the disease are not established, and the current clinical MRI practices do not contribute to diagnosis or treatment. Therefore, identifying critical and comprehensive features of brain alteration (e.g., via multimodal MRI approaches) for EP is a high priority for the field to determine future impactful biomarkers. The HCP-EP provides a refined, high-quality, and specific dataset focusing on the EP period (i.e., those within five years of the initial psychotic episode), which we focus on to provide insights into putative early targets of EP.