Unmanageable depression poses significant morbidity and mortality, as well as a substantial societal price. In this study young adults (n=33) who were non-responsive to traditional therapy were assessed for abnormalities in their cerebral spinal fluid (CFS) metabolites, plasma and urine. Cerebral folate deficiency was observed to be the most common deficiency (n=12), with these patients exhibiting low levels of 5-MTHF. These subjects were treated with folinic acid, which improved their depression score. This study concluded by stating that an unexpectedly large proportion of the patients had “potentially treatable abnormalities”, which was improved with the folinic acid therapy. It was also noted that none of the healthy controls had a metabolite deviation.
Pan LA, Martin P, Zimmer T, et al. Neurometabolic Disorders: Potentially Treatable Abnormalities in Patients with Treatment-Refractory Depression and Suicidal Behavior. Am J Psychiatry. 2017 174(1):42-50.