Chronic insomnia in the setting of MTHFR polymorphism.

We present a patient with chronic insomnia resistant to traditional pharmacologic (eg, sedative-hypnotics) and nonpharmacologic (eg, cognitive behavioral therapy for insomnia) therapy. A finding of elevated serum homocysteine triggered a whole-genome sequencing analysis which revealed a homozygous methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T/C677T; dbSNP rs1801133). Interventions targeting her polymorphism-dependent loss of function successfully resolved her insomnia. This case demonstrates a genomic approach for insomnia whereby successful treatment was focused on optimizing the patient's metabolome, which was altered as a result of a missense single-nucleotide polymorphism. CITATION: Kapoor V, Watson NF, Ball L. Chronic insomnia in the setting of MTHFR polymorphism. J Clin Sleep Med. 2022;18(4):1215-1218.