Brain Volume Varies Depending on Symptom Severity and Treatment Response in Schizophrenia

Year 2025, Volume: 8 Issue: 4, 337 - 349

Gülnihal Deniz , Nurgül Karakurt , Halil Özcan , Niyazi Acer

https://doi.org/10.33438/ijdshs.1745223

Abstract

Schizophrenia is a complex psychiatric disorder with varying treatment responses. This study hypothesizes that treatment-resistant schizophrenia patients exhibit distinct structural brain abnormalities compared to treatment-responsive patients and healthy controls. Identifying these differences may provide insight into the neurobiological basis of treatment resistance and guide personalized interventions. A cross-sectional study was conducted with 24 schizophrenia patients and 24 healthy controls. Schizophrenia patients were categorized into treatment responders (≥30% clinical improvement) and treatment-resistant (<30% improvement) based on clinical assessments, including standardized scales and expert evaluation. Among the scales, Positive and Negative Syndrome Scale (PANSS), The Clinical Global Impression Scale (CGI-S), The Global Assessment Scale (GAS), The Brief Psychiatric Rating Scale (BPRS) were used. Brain volumetric data were acquired using MRI and analyzed through the VolBrain platform, focusing on the frontal, temporal, and parietal lobes, cerebellum, and thalamic nuclei. Treatment-resistant demonstrated significantly reduced brain volumes in the frontal, temporal, and parietal lobes, cerebellum, and thalamic nuclei compared to responders and healthy controls (p<0.05). Additionally, treatment-resistant had higher scores on the PANSS negative symptom scale and the BPRS, indicating more severe clinical symptoms (p<0.05). Responders showed less pronounced volumetric reductions and more favorable clinical profiles. This study reveals that treatment-resistant schizophrenia is associated with marked structural brain abnormalities, particularly in regions critical for cognitive and emotional processing. These findings underscore the potential role of neuroanatomical biomarkers in predicting treatment response and highlight the necessity for targeted therapeutic strategies for treatment-resistant patients.

Keywords

Schizophrenia , PANNS , BPRS , Brain Volume , Treatment

Ethical Statement

This study was conducted with the approval of the Atatürk University, Faculty of Medicine Clinical Research Ethics Committee, under the ethics committee decision numbered B.30.2.ATA.0.01.00/805, dated October 26, 2023.

References

• Arathil, P., Bansal, R., & Kuruppath, A. (2024). Predicting the Outcome of First Episode Psychosis Subjects by Assessing Dorsolateral Prefrontal Cortex Volume. Archives of Psychiatry Research: An International Journal of Psychiatry and Related Sciences, 60(1.), 31-38. . [CrossRef]
• Cheng, Y., Wang, T., Zhang, T., Yi, S., Zhao, S., Li, N., Yang, Y., Zhang, F., Xu, L., & Shan, B. (2022). Increased blood-brain barrier permeability of the thalamus correlated with symptom severity and brain volume alterations in patients with schizophrenia. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 7(10), 1025-1034. [CrossRef] [PubMed]
• Correll, C. U., & Schooler, N. R. (2020). Negative symptoms in schizophrenia: a review and clinical guide for recognition, assessment, and treatment. Neuropsychiatric Disease and Treatment, 519-534. [CrossRef] [PubMed]
• Deniz, G., Karakurt, N., Özcan, H., & Acer, N. (2023). Comparison of brain volume measurements in methamphetamine use disorder with healthy individuals using volbrain method. Journal of Health Sciences of Adıyaman University, 9(3), 188-198. [CrossRef]
• Deniz, G., Karakurt, N., Özcan, H., & Acer, N. (2024). Comparison of detailed brain volume measurements in schizophrenia with healthy individuals. Kastamonu Medical Journal, 4(2), 52-61. [CrossRef]
• Deniz, G., Yalçın, A., Yıldırım, E., & Tan, H. (2024). Evaluation of Lesion Burden in Pediatric Patients with Multiple Sclerosis by Computer Aided Algorithm and Comparison with Standard Detection Methods. Journal of Harran University Medical Faculty, 21(2), 159-165. [CrossRef]
• Dönmezler, S., Sönmez, D., Yılbaş, B., Öztürk, H. İ., İskender, G., & Kurt, İ. (2024). Thalamic nuclei volume differences in schizophrenia patients and healthy controls using probabilistic mapping: A comparative analysis. Schizophrenia Research, 264, 266-271. [CrossRef] [PubMed]
• Endicott, J., Spitzer, R. L., Fleiss, J. L., & Cohen, J. (1976). The Global Assessment Scale: A procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry, 33(6), 766-771. [CrossRef] [PubMed]
• Guy, W. (1976). ECDEU assessment manual for psychopharmacology. US Department of Health, Education, and Welfare, Public Health Service. [CrossRef]
• He, H., Luo, C., Luo, Y., Duan, M., Yi, Q., Biswal, B. B., & Yao, D. (2019). Reduction in gray matter of cerebellum in schizophrenia and its influence on static and dynamic connectivity. Human Brain Mapping, 40(2), 517-528. [CrossRef] [PubMed]
• Iasevoli, F., D'Ambrosio, L., Francesco, D. N., Razzino, E., Buonaguro, E. F., Giordano, S., Patterson, T. L., & de Bartolomeis, A. (2018). Clinical evaluation of functional capacity in treatment resistant schizophrenia patients: comparison and differences with non-resistant schizophrenia patients. Schizophrenia Research, 202, 217-225. [CrossRef] [PubMed]
• Kanahara, N., Yamanaka, H., Shiko, Y., Kawasaki, Y., & Iyo, M. (2022). The effects of cumulative antipsychotic dose on brain structures in patients with schizophrenia: Observational study of multiple CT scans over a long-term clinical course. Psychiatry Research: Neuroimaging, 319, 111422. [CrossRef] [PubMed]
• Kay, S. R., Fiszbein, A., & Opler, L. A. (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13(2), 261-276. [CrossRef] [PubMed]
• Kim, J., Plitman, E., Iwata, Y., Nakajima, S., Mar, W., Patel, R., Chavez, S., Chung, J. K., Caravaggio, F., & Chakravarty, M. M. (2020). Neuroanatomical profiles of treatment-resistance in patients with schizophrenia spectrum disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 99, 109839. [CrossRef] [PubMed]
• Kirpinar, M. M., & Demirel, O. F. (2024). The Relationship Between Depressive Symptoms and Psychological Variables in Patients With Schizophrenia. Journal of Psychiatric Practice®, 30(1), 13-22. [CrossRef] [PubMed]
• McCutcheon, R. A., Marques, T. R., & Howes, O. D. (2020). Schizophrenia—an overview. JAMA psychiatry, 77(2), 201-210. [CrossRef] [PubMed]
• Melzer-Ribeiro, D., Napolitano, I., Leite, S., De Souza, J. A., Vizzotto, A., Di Sarno, E., Fortes, M., Gomes, M., De Oliveira, G., & Avrichir, B. (2024). Randomized, double-blind, sham-controlled trial to evaluate the efficacy and tolerability of electroconvulsive therapy in patients with clozapine-resistant schizophrenia. Schizophrenia Research, 268, 252-260. [CrossRef][PubMed]
• Nakajima, S., Takeuchi, H., Plitman, E., Fervaha, G., Gerretsen, P., Caravaggio, F., Chung, J. K., Iwata, Y., Remington, G., & Graff-Guerrero, A. (2015). Neuroimaging findings in treatment-resistant schizophrenia: a systematic review: lack of neuroimaging correlates of treatment-resistant schizophrenia. Schizophrenia Research, 164(1-3), 164-175. [CrossRef] [PubMed]
• Ogyu, K., Noda, Y., Yoshida, K., Kurose, S., Masuda, F., Mimura, Y., Nishida, H., Plitman, E., Tarumi, R., & Tsugawa, S. (2020). Early improvements of individual symptoms as a predictor of treatment response to asenapine in patients with schizophrenia. Neuropsychopharmacology Reports, 40(2), 138-149. [CrossRef] [PubMed]
• Orlovska-Waast, S., Köhler-Forsberg, O., Brix, S. W., Nordentoft, M., Kondziella, D., Krogh, J., & Benros, M. E. (2019). Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis. Molecular Psychiatry, 24(6), 869-887 [CrossRef] [PubMed].
• Roiz-Santiañez, R., Suarez-Pinilla, P., & Crespo-Facorro, B. (2015). Brain structural effects of antipsychotic treatment in schizophrenia: a systematic review. Current Neuropharmacology, 13(4), 422-434 [CrossRef] [PubMed].
• Schmahmann, J. D. (2019). The cerebellum and cognition. Neuroscience Letters, 688, 62-75. [CrossRef] [PubMed]
• Sen, M., Yuzbasıoglu, N., PENÇE, K., & Karamustafalioglu, N. (2023). An Egg & Chicken Paradox: Are changes in the Basal ganglia volume the reason for or the result of Schizophrenia? Authorea Preprints. [CrossRef]
• Tandon, R., Nasrallah, H., Akbarian, S., Carpenter Jr, W. T., DeLisi, L. E., Gaebel, W., Green, M. F., Gur, R. E., Heckers, S., & Kane, J. M. (2024). The schizophrenia syndrome, circa 2024: What we know and how that informs its nature. Schizophrenia Research, 264, 1-28. [CrossRef] [PubMed]
• Tronchin, G., Akudjedu, T. N., Ahmed, M., Holleran, L., Hallahan, B., Cannon, D. M., & McDonald, C. (2020). Progressive subcortical volume loss in treatment-resistant schizophrenia patients after commencing clozapine treatment. Neuropsychopharmacology, 45(8), 1353-1361. [CrossRef] [PubMed]
• van der Velde, J., Gromann, P. M., Swart, M., de Haan, L., Wiersma, D., Bruggeman, R., Krabbendam, L., & Aleman, A. (2015). Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia. Journal of Psychiatry & Neuroscience: JPN, 40(3), 207. [CrossRef] [PubMed]
• Yamazaki, R., Matsumoto, J., Ito, S., Nemoto, K., Fukunaga, M., Hashimoto, N., Kodaka, F., Takano, H., Hasegawa, N., & Yasuda, Y. (2024). Longitudinal reduction in brain volume in patients with schizophrenia and its association with cognitive function. Neuropsychopharmacology reports, 44(1), 206-215. [CrossRef] [Pubmed]