# Blood Concentrations of Folic Acid and Homocysteine Are Associated with Treatment-Resistant Depression Among Female Depressed Patients

## TL;DR

Low folic acid and high homocysteine levels are linked to treatment-resistant depression in women with major depressive disorder.

## Contribution

This study identifies blood biomarkers associated with treatment-resistant depression in female patients.

## Key findings

- Folic acid levels were significantly lower in women with treatment-resistant depression.
- Homocysteine levels were significantly higher in women with treatment-resistant depression.
- Lower folic acid levels were associated with higher depression severity.

## Abstract

Treatment-resistant depression (TRD) is a subtype of major depressive disorder (MDD) that fails to respond to first-line pharmacotherapy. This cross-sectional study compared blood concentrations of folic acid, vitamin B12, and homocysteine between female depressed patients with or without TRD, and examined the association of these parameters with the severity of depression. It included 116 female patients treated for MDD, of whom 59 (51%) developed TRD. The diagnosis of MDD was established via a structured clinical interview, while the severity of depression was measured with the Montgomery–Asberg Depression Rating Scale. Blood samples were taken at the initial psychiatric examination to determine the serum levels of folic acid and vitamin B12 and plasma levels of homocysteine. Folic acid levels were significantly lower in the female TRD group (p < 0.001), whereas homocysteine levels were significantly higher in the female TRD group (p < 0.001), compared to the female depressed group without TRD. In the regression analyses, higher levels of homocysteine (p < 0.001) were associated with TRD, while lower levels of folic acid (p = 0.036) were related to higher severity of depression, independently of sociodemographic and clinical parameters. Our findings showed that folate correlated with symptom severity, while homocysteine correlated with the TRD status in female MDD patients.