In a group of 33 young adults with treatment-resistant depression, plasma, urine and cerebral spinal fluid were measured for several metabolites. These were compared to levels of 16 healthy control subjects. Folate deficiency in cerebral spinal fluid was the most common deficiency seen in patients with pharmacological treatment- resistant depression. It is worth noting that serum levels of folate were normal in these same patients. All patients with cerebral spinal folate deficiency showed improvement in depressive symptoms when treated with folinic acid, suggesting that serum measurement of folic acid may be misleading as it does not reflect a functional deficiency. In fact, when folic acid deficiency was confirmed (in this case via cerebral spinal fluid), an unexpectedly large proportion of patients with potentially treatable depression were identified.