THE IMMUNOMODULATORY POTENTIAL: ANTIPSYCHOTICS WITH VITAMIN D AND E INTERPLAY ON INTERFERON GAMMA AND TUMOUR NECROTIC FACTOR ALPHA
Keywords:
Vitamin E, vitamin D, Antipsychotics, Tumour Necrosis Factor Alpha, interferonAbstract
Background: Interferon-gamma (IFN-?) and Tumour Necrotic Factor-alpha (TNF-?) are important immunomodulators raised in psychiatric illnesses. This study is aimed to determine the effects of antipsychotic drugs alone and in combination with vitamin D and E on inflammatory cytokines IFN-? and TNF-? level in psychotic patients. Methods: An ERB-approved (NCT 06200584), randomized control trial was carried out from Jan to Jun 2021 at the Baluchistan Institute of Psychiatry and Behavioural Sciences, Quetta, Pakistan. With non-probability purposive sampling, a total of 260 were enrolled. Group-1 had healthy controls while group-2, 3 and 4 had psychotic patients on olanzapine (10 mg/day), risperidone (2 mg/day) or quetiapine (100 mg/day) respectively. Patients in groups 5, 6 and 7 were kept on recommended risperidone, olanzapine or quetiapine respectively with added vitamin D (200,000 IU once weekly) and Vitamin E (400 mg daily). After two months, the blood samples were analysed for IFN-? and TNF-?. The results were tabulated with SPSS-26 for 35 patients in each group who completed the study. Results: The groups treated with antipsychotics had statistically higher IFN-? and TNF-? expression than the control group (p<0.001). The combination of antipsychotics with added Vitamin D and Vitamin E led to a significant reduction in IFN-? and TNF-? (p<0.001) with maximum decrease with quetiapine in combination with Vitamin D and E. Conclusion: Antipsychotics increase IFN-? and TNF-? expression. The combination therapy across various antipsychotic treatment groups with added Vitamin D and E resulted in lower IFN-? and TNF-?.
Pak J Physiol 2024;20(3):8?12 DOI: https://doi.org/10.69656/pjp.v20i3.1691
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References
Miller AH. Beyond depression: the expanding role of inflammation in psychiatric disorders. World Psychiatry 2020;19(1):108–9.
Kivimäki M, Shipley MJ, Batty GD, Hamer M, Akbaraly TN, Kumari M, et al. Long-term inflammation increases risk of common mental disorder: a cohort study. Mol Psychiatry 2014;19(2)149–50.
Berk M, Williams LJ, Jacka FN, O’Neil A, Pasco JA, Moylan S, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med 2013;11:200.
Dantzer R. Depression and inflammation: an intricate relationship. Biol Psychiatry 2012;71(1):4–5.
Tayab MA, Islam MN, Chowdhury KA, Tasnim FM. Targeting neuroinflammation by polyphenols: A promising therapeutic approach against inflammation-associated depression. Biomed Pharmacother 2022;147:112668.
Berk M, Köhler?Forsberg O, Turner M, Penninx BW, Wrobel A, Firth J, et al. Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management. World Psychiatry 2023;22:366–87.
De Giorgi R, Rizzo Pesci N, Quinton A, De Crescenzo F, Cowen PJ, Harmer CJ. Statins in depression: an evidence-based overview of mechanisms and clinical studies. Front Psychiatry 2021;12:702617.
Grudet C, Wolkowitz OM, Mellon SH, Malm J, Reus VI, Brundin L, et al. Vitamin D and inflammation in major depressive disorder. J Affect Disord 2020;267:33–41.
Singh U, Devaraj S, Jialal I. Vitamin E, Oxidative Stress, and inflammation. Annu Rev Nutr 2005;25:151–74.
Dogan-Sander E, Mergl R, Willenberg A, Baber R, Wirkner K, Riedel-Heller SG, et al. Inflammation and the association of vitamin D and depressive symptomatology. Nutrients 2021;13:1972.
Zhao W, Zhu DM, Li S, Cui S, Jiang P, Wang R, et al. The reduction of vitamin D in females with major depressive disorder is associated with worse cognition mediated by abnormal brain functional connectivity. Prog Neuro-Psychopharmacol Biol Psychiatry 2022;118:110577.
Nisar M, Mohammad RM, Fatima S, Shaikh PR, Rehman M. Perceptions pertaining to clinical depression in Karachi, Pakistan. Cureus 2019;11(7):e5094.
Wu F, Xiong ZQ, Mao SH, Hu JM, Wang JQ, Jiang HW, et al. Aldosterone induces inflammatory cytokines in penile corpus cavernosum by activating the NF-?B pathway. Asian J Androl 2018;20(1):24–9.
Harris DP, Goodrich S, Gerth AJ, Peng SL, Lund FE. Regulation of IFN-? production by B effector 1 cells: essential roles for T-bet and the IFN-? receptor. J Immunol 2005;174(11):6781–90.
Kim YK, Myint AM, Lee BH, Han CS, Lee HJ, Kim DJ, et al. Th1, Th2, and Th3 cytokine alteration in schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 2004;28:1129–34.
Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. A meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 2011;70:663–71.
Baptista T, Sandia I, Lacruz A, Rangel N, de Mendoza S, Beaulieu S, et al. Insulin counter-regulatory factors, fibrinogen and C-reactive protein during olanzapine administration: Effects of the antidiabetic metformin. Int Clin Psychopharmacol 2007;22:69–76.
Lü LX, Guo SQ, Chen W, Li Q, Cheng J, Guo JH. Effect of clozapine and risperidone on serum cytokine levels in patients with first-episode paranoid schizophrenia. Di Yi Jun Yi Da Xue Xue Bao 2004;24:1251–4.
Kim YK, Myint AM, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Cytokine changes and tryptophan metabolites in medication-naïve and medication-free schizophrenic patients. Neuropsychobiology 2009;59(2):123–9.
Capuzzi E, Bartoli F, Crocamo C, Clerici M, Carrà G. Acute variations of cytokine levels after antipsychotic treatment in drug-naïve subjects with a first-episode psychosis: A meta-analysis, Neurosci Biobehav Rev 2017;77:122–8.
Vakilian A, Razavi-Nasab SM, Ravari A, Mirzaei T, Moghadam-Ahmadi A, Jalali N, et al. Vitamin B12 in association with antipsychotic drugs can modulate the expression of pro-/anti-inflammatory cytokines in Alzheimer disease patients. Neuroimmunomodulation 2017;24(6):310–9.
Pandurangi AK, Buckley PF. Inflammation, antipsychotic drugs, and evidence for effectiveness of anti-inflammatory agents in schizophrenia. In: Khandaker G, Meyer U, Jones P. (Eds). Neuroinflammation and Schizophrenia 2019. Curr Top Behav Neurosci, Vol. 44. Springer, Cham; 2019.p. 227–44.
Saboori S, Shab-Bidar S, Speakman JR, Yousefi Rad E, Djafarian K. Effect of vitamin E supplementation on serum C-reactive protein level: a meta-analysis of randomized controlled trials. Eur J Clin Nutr 2015;69(8):867–73.
Asbaghi O, Sadeghian M, Nazarian B, Sarreshtedari M, Mozaffari-Khosravi H, Maleki V, et al. The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials. Sci Rep 2020;10(1):17234.
Gaughran F, Stringer D, Wojewodka G, Landau S, Smith S, Gardner-Sood P, et al. Effect of vitamin D supplementation on outcomes in people with early psychosis: The DFEND randomized clinical trial. JAMA Netw Open 2021;4(12):e2140858.
Jamilian H, Amirani E, Milajerdi A, Kolahdooz F, Mirzaei H, Zaroudi M, et al. The effects of vitamin D supplementation on mental health, and biomarkers of inflammation and oxidative stress in patients with psychiatric disorders: a systematic review and meta-analysis of randomized controlled trials. Prog Neuro-Psychopharmacol Biol Psychiatry 2019;94:109651.
Di Nicola M, Dattoli L, Moccia L, Pepe M, Janiri D, Fiorillo A, et al. Serum 25-hydroxyvitamin D levels and psychological distress symptoms in patients with affective disorders during the COVID-19 pandemic. Psychoneuroendocrinology 2020;122:104869.
Moslemi E, Musazadeh V, Kavyani Z, Naghsh N, Shoura SMS, Dehghan P. Efficacy of vitamin D supplementation as an adjunct therapy for improving inflammatory and oxidative stress biomarkers: An umbrella meta-analysis. Pharmacol Res 2022;186:106484.
Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, et al. IFN-?-and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol 2007;178(11):7190–8.
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