Effectiveness of a Multimodal Therapeutic Approach for Disorganization Symptoms in Hebephrenic Schizophrenia: A Case Report
DOI:
https://doi.org/10.61978/psychosocia.v4i1.1160Keywords:
Hebephrenic Schizophrenia, Disorganization Symptoms, Multimodal Therapy, Aripiprazole, Cognitive Behavioral Therapy, Case ReportAbstract
Hebephrenic schizophrenia, or disorganized-type schizophrenia, represents one of the most disabling and treatment-resistant subtypes of psychotic disorders, marked by disorganized thinking, affect, and behavior. These symptoms often persist despite standard pharmacological treatment and are associated with poor cognitive and social functioning. This case report explores the effectiveness of an integrated multimodal therapeutic approach that combines pharmacological, cognitive-behavioral, and metabolic strategies in managing a young woman with chronic hebephrenic schizophrenia. The patient, a 23-year-old female with a six-year illness duration and history of medication nonadherence, was treated with aripiprazole 15 mg/day (dopamine D2 partial agonist), trifluoperazine 5 mg/day (full D2 antagonist), folic acid 1 mg/day, and vitamin B6 100 mg/day. Cognitive Behavioral Therapy (CBT) and family psychoeducation were conducted twice weekly for three weeks. After treatment, she demonstrated measurable improvement, including a 1-point reduction in conceptual disorganization and a 2-point improvement in blunted affect (PANSS-R), alongside qualitative gains in coping with auditory hallucinations and affective responsiveness. These results suggest that synergistic modulation of dopaminergic circuits, cognitive restructuring, and metabolic support may yield short-term benefits for patients with treatment-resistant disorganization symptoms. Further longitudinal studies are warranted to evaluate long-term outcomes and neurobiological mechanisms.
References
Ahmed, A., El-Gharieb, M., & Salama, R. (2022). Vitamin B6 supplementation and cognition in psychotic disorders: A randomized controlled trial. Nutrients, 14(9), 1853. https://doi.org/10.3390/nu14091853 DOI: https://doi.org/10.3390/nu14091853
Bliźniewska-Kowalska, K., & Gałecki, P. (2024). Dopaminergic system dysfunction and novel pharmacological targets in schizophrenia treatment. Pharmacological Reports, 76(1), 1–12. https://doi.org/10.1007/s43440-023-00497-w
Cezar, R., Lopes, R. T., Oliveira, I. R., & Rangé, B. P. (2022). Cognitive Behavioral Therapy for psychotic symptoms: A case study and literature review. Revista Brasileira de Terapias Cognitivas, 18(1), 1–10. https://doi.org/10.5935/1678-5568.20220001
Charlson, F. J., Ferrari, A. J., & Santomauro, D. F. (2018). Global epidemiology and burden of schizophrenia: Findings from the Global Burden of Disease Study. Psychological Medicine, 48(3), 1–12. https://doi.org/10.1017/S003329171700324X
Cheng, P., Liu, Y., & Ning, L. (2022). Homocysteine-lowering vitamins for cognitive deficits and negative symptoms in schizophrenia: Systematic review and meta-analysis. Schizophrenia Research, 243, 84–92. https://doi.org/10.1016/j.schres.2022.04.014
Cookson, J., Pimm, J., & Brentnall, A. (2023). Partial agonists of dopamine receptors: Clinical effects and receptor interactions when combining aripiprazole with full antagonists. BJPsych Advances, 29(2), 106–115. https://doi.org/10.1192/bja.2022.61 DOI: https://doi.org/10.1192/bja.2022.86
Correll, C. U. (2020). From receptor pharmacology to improved outcomes: Individualizing antipsychotic treatment. Journal of Clinical Psychiatry, 81(3), 19 12980. https://doi.org/10.4088/JCP.19rp12980
Ebrahimi, A., & Asmundson, G. J. G. (2024). Multidisciplinary approaches in psychiatric treatment: Improving adherence and patient outcomes. Journal of Psychiatric Research, 170, 113–121. https://doi.org/10.1016/j.jpsychires.2023.12.006 DOI: https://doi.org/10.1016/j.jpsychires.2023.12.006
Giordano, F., Granata, G., & Manuli, A. (2022). Polypharmacy and schizophrenia: The challenge of antipsychotic treatment adherence. Journal of Clinical Medicine, 11(18), 5285. https://doi.org/10.3390/jcm11185285 DOI: https://doi.org/10.3390/jcm11185285
González-Pablos, E., Torre-Luque, A., Iruretagoyena, B., & González-Torres, M. A. (2023). Language disorganization in schizophrenia and its relation to social functioning. International Journal of Environmental Research and Public Health, 20(3), 2307. https://doi.org/10.3390/ijerph20032307 DOI: https://doi.org/10.3390/ijerph20032307
Harvey, P. D., & Strassnig, M. (2019). Cognitive impairment and functional decline in schizophrenia. Schizophrenia Research: Cognition, 16, 1–6. https://doi.org/10.1016/j.scog.2018.11.003
Hasan, A. (2023). Family-based psychosocial interventions in schizophrenia: An updated systematic review. Schizophrenia Bulletin, 49(2), 331–344. https://doi.org/10.1093/schbul/sbac137 DOI: https://doi.org/10.1093/schbul/sbac137
Koutsouleris, N., Kambeitz, J., Schmidt, A., Wood, S. J., & Borgwardt, S. (2023). Multimodal neuroimaging markers of disorganization in schizophrenia: A network-based approach. Nature Communications, 14, 2104. https://doi.org/10.1038/s41467-023-37913-3
Kronenberg, G., Harms, C., Sobol, A., & Gertz, K. (2009). Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking methylenetetrahydrofolate reductase. Journal of Neuroscience Research, 87(7), 1605–1615. https://doi.org/10.1002/jnr.21979 DOI: https://doi.org/10.1002/jnr.21979
Laursen, T. M., Fink-Jensen, A., & Gasse, C. (2021). Excess mortality in schizophrenia: 30-year population-based study. Acta Psychiatrica Scandinavica, 144(6), 550–560. https://doi.org/10.1111/acps.13355 DOI: https://doi.org/10.1111/acps.13355
Li, X., & Wang, Q. (2021). Combined pharmacological and cognitive intervention in chronic schizophrenia: A translational perspective. Translational Psychiatry, 11(1), 545. https://doi.org/10.1038/s41398-021-01699-x
Linden, D. (2023). Neuroplastic effects of cognitive behavioral therapy in psychosis: Meta-analytic review. Neuroscience & Biobehavioral Reviews, 148, 105146. https://doi.org/10.1016/j.neubiorev.2023.105146 DOI: https://doi.org/10.1016/j.neubiorev.2023.105146
Marone, A., Dagani, J., & Girolamo, G. (2022). The role of psychosocial interventions in recovery-oriented care for schizophrenia: A systematic review. European Psychiatry, 65(1), 35. https://doi.org/10.1192/j.eurpsy.2022.35 DOI: https://doi.org/10.1192/j.eurpsy.2022.35
Meis, L. A., Griffin, J. M., Greer, N., & MacDonald, R. (2022). Family-involved psychosocial interventions for adults with schizophrenia: A systematic review. Psychiatric Services, 73(7), 801–809. https://doi.org/10.1176/appi.ps.202100541
Mervis, J. E., Capizzi, R. J., Borodkin, K., & Johnson, J. M. (2017). Targeting the DLPFC with noninvasive brain stimulation in schizophrenia: A meta-analysis. Schizophrenia Research, 191, 38–45. https://doi.org/10.1016/j.schres.2017.04.044 DOI: https://doi.org/10.1016/j.schres.2017.04.044
Misiak, B., Stańczykiewicz, B., & Łaczmański, Ł. (2014). The role of homocysteine and B vitamins in the etiopathogenesis of schizophrenia. Psychiatria Polska, 48(6), 1181–1193. https://doi.org/10.12740/PP/27414
Najmi, E., & Akhondzadeh, S. (2022). Early-onset schizophrenia and cognitive decline: A narrative review. Journal of Clinical Neuroscience, 100, 1–9. https://doi.org/10.1016/j.jocn.2022.03.015 DOI: https://doi.org/10.1016/j.jocn.2022.03.015
Nibbio, G., Vita, A., & Comandini, A. (2020). Cognitive and functional trajectories in schizophrenia and their association over six years. Psychological Medicine, 50(11), 1805–1812. https://doi.org/10.1017/S0033291719002016
Nielsen, J., Leucht, S., & Kane, J. M. (2022). Aripiprazole mechanisms of action: Insights into dopamine partial agonism and clinical implications. CNS Drugs, 36(1), 1–12. https://doi.org/10.1007/s40263-021-00869-4
Ochi, R., Nakamura, T., & Hashimoto, K. (2022). Structural subdivisions of the anterior cingulate cortex in treatment-resistant schizophrenia: A neuroimaging perspective. Journal of Psychiatry & Neuroscience, 47(4), 255– 264. https://doi.org/10.1503/jpn.210113 DOI: https://doi.org/10.1503/jpn.210113
O’Connor, K., Rossell, S., & Thomas, N. (2021). Cognitive behavioural therapy for hallucinations: Mechanisms and outcomes. Frontiers in Psychiatry, 12, 658307. https://doi.org/10.3389/fpsyt.2021.658307
Olaso-Gonzalez, G., Pérez-Martínez, A., & Navarro-González, I. (2021). Homocysteine and cognitive impairment: Role of folate and vitamin B6 in neurological function. Nutrients, 13(5), 1633. https://doi.org/10.3390/nu13051633 DOI: https://doi.org/10.3390/nu13051633
Organization, W. H. (2023). Schizophrenia fact sheet. https://doi.org/10.46981/sfjhv2n1-004 DOI: https://doi.org/10.46981/sfjhv2n1-004
Patel, K. R. (2024). Integrated approaches for treatment-resistant schizophrenia. World Journal of Psychiatry, 14(3), 215–229. https://doi.org/10.5498/wjp.v14.i3.215
Penn, D. L., Meyer, P. S., Evans, E., Wasan, A., Bucci, W., & Silverstein, S. M. (2010). A cognitive-behavioral therapy-based intervention for persistent auditory hallucinations: A preliminary study. Cognitive and Behavioral Practice, 17(2), 148–155. https://doi.org/10.1016/j.cbpra.2009.08.003 DOI: https://doi.org/10.1016/j.cbpra.2009.08.003
Perkovic, M. N. (2023). Disorganization symptoms and cognitive impairment in schizophrenia: A meta-analysis. Schizophrenia Research, 253, 28–37. https://doi.org/10.1016/j.schres.2022.11.021 DOI: https://doi.org/10.1016/j.schres.2022.11.021
Porter, A., Fei, S., & Damme, K. S. F. (2023). A meta-analysis of multimodal neuroimaging in psychosis classification. Molecular Psychiatry, 28(8), 3278–3292. https://doi.org/10.1038/s41380-023-02195-9 DOI: https://doi.org/10.1038/s41380-023-02195-9
Reynolds, G. P. (2021). Receptor mechanisms in the treatment of schizophrenia. In D. J. Heal & G. P. Reynolds (Eds.), New Approaches to Psychiatric Drug Development (pp. 41–56). Springer. https://doi.org/10.1007/978-3-030-79647-3_3
Roffman, J. L., Lamberti, J. S., & Achilles, J. (2013). A randomized, double-blind, placebo-controlled trial of folate plus vitamin B12 for cognitive deficits in schizophrenia. American Journal of Psychiatry, 170(11), 1326–1334. https://doi.org/10.1176/appi.ajp.2013.13020220
Selvaraj, S., & Fatemi, S. H. (2022). Pathophysiology of schizophrenia: Beyond dopamine. Molecular Psychiatry, 27, 270–286. https://doi.org/10.1038/s41380-021-01337-5
Sitko, K., Bewick, B. M., Owens, D., & Masterson, C. (2020). Metaregression of CBT for psychosis across time. Schizophrenia Bulletin Open, 1(1), 23. https://doi.org/10.1093/schizbullopen/sgaa023 DOI: https://doi.org/10.1093/schizbullopen/sgaa023
Sousa, T., Fernandes, H. M., Firmino, H., Silva, C. F., Marques-Teixeira, J., & Barbosa, F. (2019). Poor emotion recognition is associated with disorganized symptoms in schizophrenia. Schizophrenia Research, 210, 188–194. https://doi.org/10.1016/j.schres.2019.05.034 DOI: https://doi.org/10.1016/j.schres.2019.05.034
Tandon, R., Belmaker, R. H., & Gattaz, W. F. (2008). World Psychiatric Association statement on comparative effectiveness of antipsychotics. Schizophrenia Research, 100(1–3), 20–38. https://doi.org/10.1016/j.schres.2007.12.477 DOI: https://doi.org/10.1016/j.schres.2007.11.033
Trifu, S., Vladuti, A., & Tudor, R. (2020). Disorganized behavior and self-neglect in schizophrenia: An integrative view. Journal of Medicine and Life, 13(2), 248–251. https://doi.org/10.25122/jml-2020-1009
Tuplin, E. W., & Holahan, M. R. (2017). Aripiprazole as a partial agonist with functional selectivity: A review and update. CNS Drugs, 31(5), 411–417. https://doi.org/10.1007/s40263-017-0439-4
Vita, A., & Barlati, S. (2021). Recovery in schizophrenia: Toward functional outcomes. World Psychiatry, 20(3), 267–284. https://doi.org/10.1002/wps.20874 DOI: https://doi.org/10.1002/wps.20874
Yildiz, M. (2021). Cognitive-behavioral therapy in schizophrenia: Updates and clinical applications. Frontiers in Psychiatry, 12, 690301. https://doi.org/10.3389/fpsyt.2021.690301
