Plasma homocysteine concentrations and depression: A twin study

J Affect Disord Rep. 2021 Apr:4:100087. doi: 10.1016/j.jadr.2021.100087. Epub 2021 Jan 16.

Abstract

Background: Homocysteine is an amino acid formed during metabolism of the essential amino acid methionine that plays an important role in energy metabolism and neurotransmitter synthesis. High levels of homocysteine have been linked to both depression and cardiovascular disease, however studies of depression have not always been consistent, possibly related to differences in methodology among studies. The study of twins in clinical research can be useful in controlling for confounding factors. The purpose of this study was to assess the relationship between depression and plasma homocysteine in a study of twins.

Methods: Homocysteine concentration was assessed in twins (N = 202) from the Vietnam Era Twin Registry, including twin pairs discordant for the diagnosis of Major Depressive Disorder (MDD) and twin pairs without MDD. Self reported depressive symptom levels were also measured as a continous variable using the Beck Depression Inventory (BDI).

Results: The average homocysteine concentration was 7.9 μmol/L (2.1 μmol/L SD, range of 2.0-17.1 μmol/L). There were no within twin pair differences in homocysteine concentration within twin pairs discordant for MDD and within twin pairs that differed for BDI score. There was a significant pair-level relationship between depressive symptoms as measured by mean BDI score and homocysteine concentration, such that the higher the mean BDI score of the twin pair, the higher the mean homocystein of the pair (p < .001). Every 10 point increase in BDI score was associated with an 0.8 μmol/L increase in homocysteine concentration at the pair level.

Conclusions: These findings are not consistent with a causal role for elevated homocysteine in the development of depression, but rather point to familial confounding or other factors that are shared by twin brothers and that contribute to both depression and homocysteine levels.

Keywords: Depression; Homocysteine; Stress.