Brain Structural Changes in Schizophrenia Patients Compared to the Control: An MRI-based Cavalieri’s Method

Introduction: Schizophrenia is a severe psychotic brain disorder. One of the potential mechanisms underlying this disease may be volumetric changes in some brain regions. The present study aimed to employ magnetic resonance imaging (MRI) to estimate and quantitatively analyze the brain of patients with schizophrenia compared to the controls. Methods: This case-control study was conducted on MRI scans of 20 patients with schizophrenia and 20 healthy controls in Zahedan City, Southeastern Iran. MRIs with 4 mm slice thickness and 5 mm intervals in coronal and sagittal planes were captured. Then, quantitative parameters, including volume and volume density of various brain regions, were estimated in both groups using Cavalieri’s point counting method. Data analyses were performed using the Mann-Whitney U test. Results: The findings of this investigation revealed that volumes of gray matter, hippocampus, and gray/white matter in patients with schizophrenia were significantly lower than the controls (P<0.05). The volumes of lateral ventricles in patients with schizophrenia (36.60±4.32 mm3) were significantly higher than the healthy individuals (30.10±7.98 mm3). However, there were no statistically significant differences between the two groups regarding the changes in the brain’s total volume, cerebral hemispheres, white matter, brain stem, cerebellum, and corpus callosum (P>0.05). Conclusion: Volumetric estimations on brain MRI-based stereological technique can be helpful for elucidation of structural changes, following up the treatment trends, and evaluating the therapeutic situations in schizophrenia patients. Volumetric alternations in specific brain areas might be linked to cognitive impairments and the severity of symptoms in patients with schizophrenia. Further research is needed in this regard. Highlights Volumetric changes occur in certain regions of the brain of schizophrenia patients. Structural changes in the brain of schizophrenia patients are associated with the severity of clinical manifestations. A brain MRI-based stereological technique can clarify neuropathology and assess therapeutic efficiency in patients with schizophrenia. Plain Language Summary Schizophrenia is a severe neuropsychiatric disorder with worldwide prevalence that disrupts a person's social life. It’s characterized by progressive neuroanatomical alterations in both gray and white matter in different brain regions and associated with changes in the structural and functioning of some critical brain circuits. Several factors have been suggested to be involved in the development and progression of the disease including alternations and disconnection in myelin, genetic factors, neurodegenerative process, neuroinflammation, neurodevelopmental deficiencies, the number of dopaminergic neurons and volumetric changes in different areas of the brain. It has shown that quantitative volumetric brain measurements on magnetic resonance imaging (MRI) scans in patients with neurodegenerative disease owing to selective regional atrophy are beneficial for clinicians to ascertain disease progression and to evaluate volume alternations and response to treatment. Thus, we investigated structural changes of the brain in schizophrenia patients on MR images using accurate Cavalieri’s estimation and compared to healthy controls. The findings demonstrated that some structural changes occurs in various brain areas which involved in many critical roles in normal brain’s functionality and connectivity. On the other hand, these changes are associated with cognitive impairments and the severity of clinical symptoms in patients with schizophrenia. It’s appears that elucidation of the different pathways of various structural abnormalities related to schizophrenia is required to recognize and determine the role of discrete pathophysiological phenomena in mental illness development and progress.