Comparison of thalamic nucleus volumes in schizophrenia and schizoaffective disorder patients with a healthy control group and investigation of clinical test correlations

The schizophrenia spectrum disorder group of illnesses, of which schizophrenia and schizoaffective disorder are members, constitutes major psychiatric diseases that affect people at the productive period of their life, leading to significant morbidity and loss of functionality. The diagnosis of these disorders is made according to the DSM-V criteria. DSM-V criteria state that schizoaffective disorder is characterized by the presence of mood disorders during most of the schizophrenic episodes, distinguishing it from schizophrenia. As a result, it is more difficult to diagnose than schizophrenia.Conventionally regarded as mental disorders, newer neurodegenerative and neurodevelopmental theories suggest that these disorders may not be purely psychological problems but have a contribution from morphological changes in the brain parenchyma. The thalamus forms part of the diencephalon and thus occupies the central part as it is the site of somatosensory pathways. Developmental histology has shown that the thalamus is intimately linked to cortical development, and disruption of this relationship could lead to functional and structural abnormalities of both the cortex and the thalamus. Most of the studies in the literature have pointed to the link of these developmental abnormalities with psychotic disorders. The aim of our study was to investigate the possible relationship and differences between the thalamus in schizophrenia and schizoaffective disorder, as well as in healthy controls, and explore the correlation between these potential differences and clinical test outcomes. After local ethical committee approval, our study included 45 patients with schizophrenia or schizoaffective disorder according to the DSM-V criteria, after they fulfilled the inclusion criteria and volunteered to participate in this study, from February 2023 to September 2024, and 26 healthy volunteers, summing up 71 participants altogether. Clinical tests applied to the patient group included the Positive and Negative Syndrome Scale, Clinical Global Impression Scale, and Pittsburgh Sleep Quality Index, while the Young Mania Rating Scale and Hamilton Depression Rating Scale were also administered to schizoaffective disorder patients. All patients and healthy subjects were clinically and radiologically evaluated for eligibility prior to MRI studies. Subsequently, all participants received routine cranial MRI without contrast using 3D sagittal 1mm slice thickness T1-weighted sequences. MRI image data were processed by using FreeSurfer, v7.2.0, software to quantify volumes of the thalamus and its subnuclei. These indeed reflected significant volume reduction of the ventral, intralaminar, medial, and posterior parts of the right thalamus in patients as compared to controls. Other subregions did not exhibit any statistically significant difference. Subnuclei level analysis further disclosed statistically significant volume reductions in medial, (MVRE,MDI,MDm,Pt), intralaminar (Pf, CM), ventral (VM, VPL, VLp), and posterior (PuA) nuclei in the patients relative to controls. The clinical tests further exhibited different associations with the thalamic subnuclei where several subnuclei were found to show significant correlations. Of note, there existed significant differences between schizophrenia and schizoaffective disorder concerning the ventral nuclei, including VM, VPL, and VLp. These differences in the volume of the thalamus and its subnuclei reached statistical significance in schizophrenia, schizoaffective disorder, and healthy subjects. These findings seem to indicate that thalamic abnormalities might provide an important marker that may differentiate schizophrenia spectrum disorders. However, replication in larger studies is necessary to confirm such findings and understand their mechanisms.