Korean Journal of Biological Psychiatry

Objectives : Dopamine dysregulation has been regarded as one of the core pathologies in patients with schizophrenia. Since dopamine synthesis capacity has found to be inconsistent in patients with schizophrenia, current classification of patients based on clinical symptoms cannot reflect the neurochemical heterogeneity of the disease. Here we performed new subtyping of patients with first-episode psychosis (FEP) through biotype-based cluster analysis. We specifically suggested basal ganglia structural changes as a biotype, which deeply involves in the dopaminergic circuit.

Methods : Forty FEP and 40 demographically matched healthy participants underwent 3T T1 MRI. Whole brain parcellation was conducted, and volumes of total 6 regions of basal ganglia have been extracted as features for cluster analysis. We used K-means clustering, and external validation was conducted with Positive and Negative Syndrome Scale (PANSS).

Results : K-means clustering divided 40 FEP subjects into 2 clusters. Cluster 1 (n = 25) showed substantial volume decrease in 4 regions of basal ganglia compared to Cluster 2 (n = 15). Cluster 1 showed higher positive scales of PANSS compared with Cluster 2 (F = 2.333, p = 0.025). Compared to healthy controls, Cluster 1 showed smaller volumes in 4 regions, whereas Cluster 2 showed larger volumes in 3 regions.

Conclusions : Two subgroups have been found by cluster analysis, which showed a distinct difference in volume patterns of basal ganglia structures and positive symptom severity. The result possibly reflects the neurobiological heterogeneity of schizophrenia. Thus, the current study supports the importance of paradigm shift toward biotype-based diagnosis, instead of phenotype, for future precision psychiatry.

Keywords Biotype;First-episode psychosis;Schizophrenia;Basal ganglia;Clustering.