In Case Control Study, Two-Thirds of Patients With Severe Depression Had Underlying Metabolic Abnormalities
A recent study suggests that potentially treatable metabolic abnormalities in the central nervous system may underlie a large proportion of cases of severe, treatment-resistant depression. These abnormalities, such as folate deficiency in the cerebrospinal fluid, are not screened for regularly, as they require a spinal tap to diagnose.
Researchers led by Lisa A. Pan were inspired to assess metabolic function in people with treatment-resistant depression after a young patient with severe, persistent depression who had attempted suicide several times improved dramatically after being diagnosed with a tetrahydrobiopterin deficiency in his cerebrospinal fluid and treated for the deficiency. Tetrahydrobiopterin is critical to the production of monoamine neurotransmitters.
The researchers carried out a case-control study of 33 teen and young adult patients who had had treatment-resistant depression since childhood and 16 healthy control participants. Twenty-one of the 33 patients with severe depression had metabolic abnormalities in their cerebrospinal fluid. Twelve had cerebral folate deficiencies (but no folate deficiency in blood tests). Those who took folinic acid for at least six weeks (1–2 mg/kg/day) in addition to their regular medications showed sometimes dramatic improvement in their depression.
Other metabolic issues identified in the patients with severe depression included abnormal levels of acylcarnitine in five patients, low tetrahydrobiopterin intermediates in one, low guanidinoacetate in another, and unusual creatine/creatinine ratios in three patients. None of the healthy participants had any metabolic abnormality.
While the study, published in the American Journal of Psychiatry in 2017, was small, it suggests that the underlying causes of some severe depression cases are going undiagnosed and untreated. The authors suggest that assessment of metabolic function should be more common in cases of severe treatment-resistant depression.
