Neuroanatomical subtypes of schizophrenia and relationship with illness duration and deficit status

Background

The heterogeneity of schizophrenia (SCZ) regarding psychopathology, illness trajectory and their inter-relationships with underlying neural substrates remain incompletely understood. In a bid to reduce illness heterogeneity using neural substrates, our study aimed to replicate the findings of an earlier study by Chand et al. (2020). We employed brain structural measures for subtyping SCZ patients, and evaluate each subtype’s relationship with clinical features such as illness duration, psychotic psychopathology, and additionally deficit status.

Methods

Overall, 240 subjects (160 SCZ patients, 80 healthy controls) were recruited for this study. The participants underwent brain structural magnetic resonance imaging scans and clinical rating using the Positive and Negative Syndrome Scale. Neuroanatomical subtypes of SCZ were identified using “Heterogeneity through discriminative analysis” (HYDRA), a clustering technique which accounted for relevant covariates and the inter-group normalized percentage changes in brain volume were also calculated.

Results

As replicated, two neuroanatomical subtypes (SG-1 and SG-2) were found amongst our patients with SCZ. The subtype SG-1 was associated with enlargements in the third and lateral ventricles, volume increase in the basal ganglia (putamen, caudate, pallidum), longer illness duration, and deficit status. The subtype SG-2 was associated with reductions of cortical and subcortical structures (hippocampus, thalamus, basal ganglia).

Conclusions

These replicated findings have clinical implications in the early intervention, response monitoring, and prognostication of SCZ. Future studies may adopt a multi-modal neuroimaging approach to enhance insights into the neurobiological composition of relevant subtypes.