Abstract
This study aims to report the correlation of MTHFR gene mutation with the genesis of depression and antidepressants non-response in a patient, highlighting the importance of genetic investigation and indicating the replacement of L-methylfolate as an effective treatment adjuvant. This is a case report of a patient diagnosed with major depressive disorder, refractory to pharmacological therapies, in monotherapy or combination therapy, and psychotherapy. After 1 year and 4 months of persistent residual symptoms, genetic testing of the MTHFR gene was requested with confirmation of a heterozygous double mutation of MTHFR. This gene polymorphism can result in deficiency of L-methylfolate, which is related to psychiatric diseases and refractoriness to antidepressant therapy. With the introduction of l-methylfolate 15mg, the patient reported remission of depressive symptoms in 4 months of follow-up. MTHFR gene mutations influence the action of folate, favoring depression and leading to refractory response to conventional treatment.
Keywords
References
- Jiang, W., Xu, J., Lu, X. J., & Sun, Y. (2016). Association between MTHFR C677T polymorphism and depression: a meta-analysis in the Chinese population. Psychology, health & medicine, 21(6), 675–685. https://doi.org/10.1080/13548506.2015.1120327DOI ↗Google Scholar ↗
- Jha, S., Kumar, P., Kumar, R., & Das, A. (2016). Effectiveness of add-on l-methylfolate therapy in a complex psychiatric illness with MTHFR C677 T genetic polymorphism. Asian journal of psychiatry, 22, 74–75. https://doi.org/10.1016/j.ajp.2016.05.007DOI ↗Google Scholar ↗
- Do Prado CM, Dieckmann LHJ, Dieckmann PM. Farmacogenética na psiquiatria: entendendo os princípios e a aplicabilidade clínica. Rio de Janeiro: DOC Content; 2018.Google Scholar ↗
- Oberg, E., Givant, C., Fisk, B., Parikh, C., & Bradley, R. (2015). Epigenetics in Clinical Practice: Characterizing Patient and Provider Experiences with MTHFR Polymorphisms and Methylfolate. Journal of nutrigenetics and nutrigenomics, 8(3), 137–150. https://doi.org/10.1159/000440700DOI ↗Google Scholar ↗
- Mech, A. W., & Farah, A. (2016). Correlation of clinical response with homocysteine reduction during therapy with reduced B vitamins in patients with MDD who are positive for MTHFR C677T or A1298C polymorphism: a randomized, double-blind, placebo-controlled study. The Journal of clinical psychiatry, 77(5), 668–671. https://doi.org/10.4088/JCP.15m10166DOI ↗Google Scholar ↗
- Bjelland, I., Tell, G. S., Vollset, S. E., Refsum, H., & Ueland, P. M. (2003). Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Archives of general psychiatry, 60(6), 618–626. https://doi.org/10.1001/archpsyc.60.6.618DOI ↗Google Scholar ↗
- Wan, L., Li, Y., Zhang, Z. et al. Methylenetetrahydrofolate reductase and psychiatric diseases. Transl Psychiatry 8, 242 (2018). https://doi.org/10.1038/s41398-018-0276-6DOI ↗Google Scholar ↗
- Gabriela Nielsen, M., Congiu, C., Bortolomasi, M., Bonvicini, C., Bignotti, S., Abate, M., Milanesi, E., Conca, A., Cattane, N., Tessari, E., Gennarelli, M., & Minelli, A. (2015). MTHFR: Genetic variants, expression analysis and COMT interaction in major depressive disorder. Journal of affective disorders, 183, 179–186. https://doi.org/10.1016/j.jad.2015.05.003DOI ↗Google Scholar ↗
- Papakostas, G. I., Shelton, R. C., Zajecka, J. M., Etemad, B., Rickels, K., Clain, A., Baer, L., Dalton, E. D., Sacco, G. R., Schoenfeld, D., Pencina, M., Meisner, A., Bottiglieri, T., Nelson, E., Mischoulon, D., Alpert, J. E., Barbee, J. G., Zisook, S., & Fava, M. (2012). L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. The American journal of psychiatry, 169(12), 1267–1274. https://doi.org/10.1176/appi.ajp.2012.11071114DOI ↗Google Scholar ↗