A Comparative Study of Frontal and Cerebellar Lobe Volumes Between Patients With First-Episode Schizophrenia and Healthy Controls and Its Association With Psychopathology and Neurological Soft Signs in Patients

Objectives Our study aimed to investigate the fronto-cerebellar volumes in both patients and controls, as well as explore their relationship with symptomatology. Our primary objectives were to compare the frontal and cerebellar lobe volumetric measurements between patients with first-episode schizophrenia (FES) and healthy controls and to assess the relationship of these volumes with psychopathology, cognition, and neurological soft signs in FES patients. The secondary objective was to explore the association of fronto-cerebellar lobe volumes with socio-demographic factors among patients and controls, as well as the duration of untreated illness (DUI) among patients. Materials and methods This was a cross-sectional, case-control study involving 60 participants, including 30 antipsychotic-naïve FES patients and 30 healthy controls. Participants underwent MRI scanning to measure frontal and cerebellar lobe volumes using the volBrain platform. Additionally, FES patients were assessed using the Positive and Negative Syndrome Scale (PANSS), Montreal Cognitive Assessment-Basic (MoCA-B), and Brief Motor Scale (BMS). Pearson's correlation, independent sample t-tests, multivariate linear regression, and binomial logistic regression were used to analyze the relationships between brain volumes, clinical assessments, and socio-demographic factors. Results No significant differences in frontal volumes were found between the two groups, while cerebellar volumes were significantly smaller in FES patients (p=0.004), particularly in younger males (p=0.026). Frontal volumes were negatively correlated with age in both groups (p=0.012), which remained robust in patients even after controlling for their gender, education, and DUI (p=0.012, aR2=0.221). Cerebellar volume reduction was associated with a higher likelihood of being classified as a patient (p=0.029). BMS was significantly correlated with frontal lobe volumes, especially in motor sequencing (MoSe), after adjusting for age, gender, and education (p=0.009). BMS MoSe scores were also significantly positively correlated with the DUI (r=0.415, p=0.023) and PANSS-General Psychopathology (GP) (r=0.494, p=0.005). MoCA-B scores were significantly lower in females than males (p=0.016), while PANSS-GP was significantly negatively correlated with age (r=-0.432, p=0.017). Conclusion Frontal and cerebellar volumes were differentially impacted in FES, with cerebellar atrophy being a significant distinguishing feature of the disorder. Frontal atrophy was associated with motor dysfunction but did not appear to influence psychopathology or cognition significantly in the early stages. The independent effects of frontal and cerebellar volumes, as shown by the lack of correlation between them, may suggest that these brain regions undergo separate pathological processes in schizophrenia, with frontal functional changes impacting motor function and cerebellar structural changes contributing to broader psychiatric symptoms, thereby warranting further exploration involving larger sample size.