Severe Mood Lability and Depression in an Adolescent Girl with a Methylenetetrahydrofolate Reductase Gene Mutation

Abstract

Methylenetetrahydrofolate reductase (MTHFR), an enzyme that controls the rate of production of N-methyltetrahydrofolate (a molecule which is necessary for the N-methyltetrahydrofolate-homocysteine methyltransferase reaction), is vital for many of the human body’s biological processes, including DNA and RNA synthesis. Mutations in the MTHFR gene, which have far reaching effects on the negative feedback systems that regulate nucleic acid synthesis (via thymidylate synthesis) and homocysteine levels, are believed to be of clinical significance and have been widely studied.  The neurological and neuro-psychiatric consequences of these changes have been long suspected but have only recently begun to be characterized. In this case report we discuss M., a fourteen-year-old Caucasian girl with a past diagnosis of major depressive disorder, and a recent history of suicide attempt by overdose, who presented for inpatient hospitalization after attempting to drown herself in a bathtub. A psychiatric history revealed that the patient developed severe depression and mood lability after her fourteenth birthday, which rapidly progressed to suicidal thoughts and two suicide attempts, and it was discovered upon taking a medical history and ordering genetic testing that she carried two MTHFR mutations, in locations where polymorphisms are suspected to correlate to mental illness generally and to mood disorders specifically.