Main Article Content

Najat Rany Kasir
Lisal Sonny Teddy
Idris Irfan
Muis Abdul
Limoa Erlyn
Syamsuddin Saidah


Schizophrenia, Folic acid, Methylcobalamin, Risperidone, Clinical Symptoms, BDNF Serum


Background : Schizophrenia is a mental disorder characterized by delusions, hallucinations, cognitive and affective impairments that impact various aspects of life and society. Schizophrenia patients often have a spectrum of vitamin and mineral deficiencies. Folic acid and methylcobalamin as adjuvant therapy in schizophrenia patients are considered to improve clinical symptoms, maximize the quality of life of schizophrenia patients, and increase BDNF levels, which have been widely studied as a cognitive marker in schizophrenia patients.

Objective: Determine the effect of folic acid and methylcobalamin adjuvant therapy on improving clinical symptoms and BDNF levels in schizophrenic patients receiving risperidone therapy.
Method: We used experimental analysis in our study by measuring pre- and post-tests with non-random group selection. This study was carried out at the Dadi Special Regional Hospital in South Sulawesi Province of Indonesia in February–March 2023, and sample testing was carried out to the HUMRC Research Laboratory of Hasanuddin University. A total of 46 subjects were divided into a treatment group of 23 subjects who received risperidone therapy of 4-6 mg/day plus adjuvant therapy of folic acid and methylcobalamin for 8 weeks and a control group of 23 subjects who only received risperidone therapy of 4-6 mg/day. PANSS was used to assess clinical symptoms, and serum BDNF levels were measured using enzyme-linked immunosorbent assays (ELISA). The Wilcoxon, Mann-Withney, and Spearman correlation tests were carried out to see the significance.

Results: There was a decrease in PANSS both in the treatment group and in the control group after receiving a significant therapeutic dose of antipsychotic risperidone with a p value (< 0,001). The treatment group with risperidone antipsychotic therapy with adjuvants of folic acid and methylcobalamin showed an improvement in clinic symptoms of 63.33 percent, with the clinical interpretation of symptoms showing very much improvement, compared to the control group with a clinical improvement of the symptoms of 46.19 percent, with the clinical manifestation interpretation showing much improvement. There was an increase in the level of BDNF in the treatment group receiving risperidone antipsychotic therapy with adjuvant therapy of folic acid and methylcobalamin, with a significant p value (<0,001) compared to the control group that received only risperidone antipsychotic therapy.

Conclusion: Effects of Folic Acid and Methylcobalamin Adjuvant Therapy and Standard Therapy Risperidone 4-6 mg/day can improve clinical symptoms and increase serum BDNF levels.

Abstract 90 | pdf Downloads 31


1. Abi-Dargham, A. (2007) ‘Alterations of Serotonin Transmission in Schizophrenia’, International Review of Neurobiology, 78(06), pp. 133–164. Available at: https://doi.org/10.1016/S0074-7742(06)78005-9.
2. Abul K. ABBAS, A.H.L. (2016) tahir99-VRG & vip.persianss.ir, Robbins Patologo Básico 9 edição.
3. Azmanova, M., Pitto-Barry, A. and Barry, Nicolas P.E. (2018) ‘Schizophrenia: Synthetic strategies and recent advances in drug design’, MedChemComm, 9(5), pp. 759–782. Available at: https://doi.org/10.1039/c7md00448f.
4. Benjamin J. Sadock, Virginia A. Sadock, P. R. (2014). Synopsis of Psychiatry: Behavioral Sciences / Clinical Psychiatry (P. R. Benjamin J. Sadock, Virginia A. Sadock (ed.); 11th ed). Wolters Kluwer Health. https://www.google.co.id/books/edition/Kaplan_and_Sadock_s_Synopsis_of_Psychiat/IzGYBAAAQBAJ?hl=id’ (no date).
5. Benjamin J. Sadock, Virginia A. Sadock, P.R. (2014) Synopsis of Psychiatry: Behavioral Sciences / Clinical Psychiatry. 11th ed. Edited by P.R. Benjamin J. Sadock, Virginia A. Sadock. USA: Wolters Kluwer Health.
6. Brunzell, D.H. and Mcintosh, J.M. (2011) ‘Alpha7 Nicotinic Acetylcholine Receptors Modulate Motivation to Self-Administer Nicotine : Implications for Smoking and Schizophrenia’, Neuropsychopharmacology, 37(5), pp. 1134–1143. Available at: https://doi.org/10.1038/npp.2011.299.
7. Di Carlo, P., Punzi, G. and Ursini, G. (2019) ‘Brain-derived neurotrophic factor and schizophrenia’, Psychiatric Genetics, 29(5), pp. 200–210. Available at: https://doi.org/10.1097/YPG.0000000000000237.
8. Chien, W.T. and Yip, A.L.K. (2013) ‘Current approaches to treatments for schizophrenia spectrum disorders, part I: An overview and medical treatments’, Neuropsychiatric Disease and Treatment, 9, pp. 1311–1332. Available at: https://doi.org/10.2147/NDT.S37485.
9. Coyle, Donald C. Goff, J.T. (2001) ‘The Emerging Role of Glutamate in the Pathophysiology and Treatment of Schizophrenia Donald’, American Journal of Psychiatry, 75(6), p. 1005. Available at: https://doi.org/10.1176/appi.ajp.158.9.1367.
10. David J. Kupfer, Darrel A. Regier, William E. Narrow, et al. (2013) Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). American Psychiatric Association.
11. Durany, N. et al. (no date) Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses. Available at: www.elsevier.com/locate/schres.
12. Eggers, A.E. (2013) ‘A serotonin hypothesis of schizophrenia’, Medical Hypotheses, 80(6), pp. 791–794. Available at: https://doi.org/10.1016/j.mehy.2013.03.013.
13. Emiliani, F.E., Sedlak, T.W. and Sawa, A. (2014) ‘Oxidative stress and schizophrenia: Recent breakthroughs from an old story’, Current Opinion in Psychiatry, 27(3), pp. 185–190. Available at: https://doi.org/10.1097/YCO.0000000000000054.
14. Fernstrom JD and Fernstrom MH (2011) Nutrition and the Brain. Second, Nutrition and Metabolism. Second. Edited by SA., M.IA., R.H. Lanham. The Atrium, Southern Gate, Chichester, West Sussex, UK: Wiley-Blackwell Publishing was acquired by John Wiley & Sons.
15. Firth, J. et al. (2017) ‘The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis’, Psychological Medicine, 47(9), pp. 1515–1527. Available at: https://doi.org/10.1017/S0033291717000022.
16. Frankenburg, F.R. (2007) ‘The role of one-carbon metabolism in schizophrenia and depression’, Harvard Review of Psychiatry, pp. 146–160. Available at: https://doi.org/10.1080/10673220701551136.
17. García-Miss, M. del R. et al. (2010) ‘Folate, homocysteine, interleukin-6, and tumor necrosis factor alfa levels, but not the methylenetetrahydrofolate reductase C677T polymorphism, are risk factors for schizophrenia’, Journal of Psychiatric Research, 44(7), pp. 441–446. Available at: https://doi.org/10.1016/j.jpsychires.2009.10.011.
18. Goff, D.C. et al. (2004) ‘Folate, Homocysteine, and Negative Symptoms in Schizophrenia’, American Journal of Psychiatry, 161(9), pp. 1705–1708. Available at: https://doi.org/10.1176/appi.ajp.161.9.1705.
19. Hashimoto, T. et al. (2005) ‘Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia’, Journal of Neuroscience, 25(2), pp. 372–383. Available at: https://doi.org/10.1523/JNEUROSCI.4035-04.2005.
21. Howes, O.D. and Kapur, S. (2009) ‘The dopamine hypothesis of schizophrenia: Version III - The final common pathway’, Schizophrenia Bulletin, 35(3), pp. 549–562. Available at: https://doi.org/10.1093/schbul/sbp006.
22. Katzung, B.G. 2010. Farmakologi Dasar dan Klinik. Edisi 10. Jakarta: Penerbit Buku Kedokteran EGC. (no date).
23. Kayser, M.S. and Dalmau, J. (2016) ‘Anti-NMDA receptor encephalitis, autoimmunity, and psychosis’, Schizophrenia Research, 176(1), pp. 36–40. Available at: https://doi.org/10.1016/j.schres.2014.10.007.
24. Kusumawardhani A.A.A.A, Dharmono S, D.H. (2011) Konsensus Penatalaksanaan Gangguan Skizofrenia. Pertama. Jakarta, Indonesia: Perhimpunan Dokter Spesialis Kedokteran Jiwa Indonesia (PDSKJI).
25. Kusumawardhani A.A.A.A, D.S.D.H. (2011) Konsensus Penatalaksanaan Gangguan Skizofrenia. pertama. Jakarta, Indonesia: Perhimpunan Dokter Spesialis Kedokteran Jiwa Indonesia (PDSKJI).
26. Leucht, S. et al. (2005) ‘What does the PANSS mean?’, Schizophrenia Research, 79(2–3), pp. 231–238. Available at: https://doi.org/10.1016/j.schres.2005.04.008.
27. Leucht, S. (2014) ‘Measurements of response, remission, and recovery in schizophrenia and examples for their clinical application’, Journal of Clinical Psychiatry, 75(SUPPL. 1), pp. 8–14. Available at: https://doi.org/10.4088/JCP.13049su1c.02.
28. Li, R. et al. (2016) Why sex differences in schizophrenia? HHS Public Access, J Transl Neurosci (Beijing).
29. Maslim, R. (2003) Pedoman Penggolongan Diagnosis Gangguan Jiwa III. III. Edited by R. Maslim. Jakarta: PT Nuh Jaya Jakarta.
30. Nieto, R, Kukuljan, M. and Silva, H. (2013) ‘BDNF and schizophrenia: from neurodevelopment to neuronal plasticity, learning, and memory.’, Frontiers in psychiatry, 4, p. 45. Available at: https://doi.org/10.3389/fpsyt.2013.00045.
31. Nieto, R., Kukuljan, M. and Silva, H. (2013) ‘BDNF and schizophrenia: From neurodevelopment to neuronal plasticity, learning, and memory’, Frontiers in Psychiatry, 4(JUN), pp. 1–11. Available at: https://doi.org/10.3389/fpsyt.2013.00045.
32. Patel, Krishna R et al. (2014) ‘Schizophrenia: overview and treatment options.’, P & T : a peer-reviewed journal for formulary management, 39(9), pp. 638–45.
33. Patel, Krishna R. et al. (2014) ‘Schizophrenia: Overview and treatment options’, P and T, 39(9), pp. 638–645.
34. Rathod, R., Kale, A. and Joshi, S. (2016) ‘Novel insights into the effect of vitamin B12 and omega-3 fatty acids on brain function’, Journal of Biomedical Science. BioMed Central Ltd. Available at: https://doi.org/10.1186/s12929-016-0241-8.
35. ‘Riset Kesehatan Dasar (Riskesdas) (2018) Persebaran Prevalensi Skizofrenia/Psikosis di Indonesia, Kementrian Kesehatan RI. Available at: https://databoks.katadata.co.id/datapublish/2019/10/08/persebaran-prevalensi-skizofreniapsikosis-di-indonesia.’ (no date).
36. Roffman, J.L. et al. (2013) ‘Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia’, JAMA Psychiatry, 70(5), pp. 481–489. Available at: https://doi.org/10.1001/jamapsychiatry.2013.900.
37. Sable, P.S. et al. (2012) ‘Maternal omega 3 fatty acid supplementation during pregnancy to a micronutrient-imbalanced diet protects postnatal reduction of brain neurotrophins in the rat offspring’, Neuroscience, 217, pp. 46–55. Available at: https://doi.org/10.1016/j.neuroscience.2012.05.001.
38. Song, M., Martinowich, K. and Lee, F.S. (2017) ‘BDNF at the synapse: Why location matters’, Molecular Psychiatry, 22(10), pp. 1370–1375. Available at: https://doi.org/10.1038/mp.2017.144.
39. Stahl, Stephen M. (2013) Stahl’s Essential Psychopharmacology Neuroscientific Basis and Practical Applications. Fourth. Edited by S. M. Stahl. Britania Raya: Cambridge University Press.
40. Stępnicki, P., Kondej, M. and Kaczor, Agnieszka A. (2018) ‘Current concepts and treatments of schizophrenia’, Molecules, 23(8). Available at: https://doi.org/10.3390/molecules23082087.
41. Stępnicki, P., Kondej, M. and Kaczor, Agnieszka A (2018) ‘Current Concepts and Treatments of Schizophrenia.’, Molecules (Basel, Switzerland), 23(8). Available at: https://doi.org/10.3390/molecules23082087.
42. Tso, I.F. et al. (2016) ‘HHS Public Access’, 168(0), pp. 338–344. Available at: https://doi.org/10.1016/j.schres.2015.08.022.Abnormal.
43. Wallace, T.L. and Bertrand, D. (2015) Neuronal α7 Nicotinic Receptors as a Target for the Treatment of Schizophrenia. 1st edn, International Review of Neurobiology. 1st edn. Elsevier Inc. Available at: https://doi.org/10.1016/bs.irn.2015.08.003.
44. Weickert, C.S. et al. (2003) ‘Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia’, Molecular Psychiatry, 8(6), pp. 592–610. Available at: https://doi.org/10.1038/sj.mp.4001308.
45. Wong, A.H.C. and Van Tol, H.H.M. (2003) ‘Schizophrenia: From phenomenology to neurobiology’, Neuroscience and Biobehavioral Reviews, 27(3), pp. 269–306. Available at: https://doi.org/10.1016/S0149-7634(03)00035-6.
46. ‘World Health Organization (2017) Mental health ATLAS 2017 state profile. Geneva: World Health Organization, World Health Organization. WHO. Available at: https://www.who.int/mental_health/evidence/atlas/profiles2017/IDN.pdf?ua=1.’ (no date).
47. Zamanpoor, M. (2020) ‘Schizophrenia in a genomic era: A review from the pathogenesis, genetic and environmental etiology to diagnosis and treatment insights’, Psychiatric Genetics, pp. 1–9. Available at: https://doi.org/10.1097/YPG.0000000000000245.
48. Zanelli, J. et al. (2019) ‘Cognitive change in schizophrenia and other psychoses in the decade following the first episode’, American Journal of Psychiatry, 176(10), pp. 811–819. Available at: https://doi.org/10.1176/appi.ajp.2019.18091088.