Hyperhomocysteinemia is a result, rather than a cause, of depression under chronic stress.

Shen Chengfeng,Qian Lingjia,Wu Lei,Zhan Rui,Liu Wei,Wang Xinxing,Yong-Hui Dang

doi:10.1371/journal.pone.0106625

Shen Chengfeng, Qian Lingjia + Show 5 more

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https://doi.org/10.1371/journal.pone.0106625

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Abstract

BackgroundAlthough the accumulation of homocysteine (Hcy) has been implicated in the pathogenesis of depression, whether Hcy is directly involved and acts as the primary cause of depressive symptoms remains unclear. The present study was designed to clarify whether increased Hcy plays an important role in stress-induced depression.ResultsWe employed the chronic unpredictable mild stress model (CUMS) of depression for 8 weeks to observe changes in the plasma Hcy level in the development of depression. The results showed that Wistar rats exposed to a series of mild, unpredictable stressors for 4 weeks displayed depression-like symptoms such as anhedonia (decreased sucrose preferences) and a decreased 5-Hydroxy Tryptophan (5-HT) concentration in the hippocampus. At the end of 8 weeks, the plasma Hcy level increased in the CUMS rats. The anti-depressant sertraline could decrease the plasma Hcy level and improve the depression-like symptoms in the CUMS rats. RhBHMT, an Hcy metabolic enzyme, could decrease the plasma Hcy level significantly, although it could not improve the depressive symptoms in the CUMS rats.ConclusionsThe results obtained from the experiments did not support the hypothesis that the increased Hcy concentration mediated the provocation of depression in CUMS rats, and the findings suggested that the increased Hcy concentration in the plasma might be the result of stress-induced depression.

Highlights

The accumulation of homocysteine (Hcy) has been implicated in the pathogenesis of depression, whether Hcy is directly involved and acts as the primary cause of depressive symptoms remains unclear
A comparison of the means in sucrose preference revealed a significant difference between the control and chronic unpredictable mild stress model (CUMS) groups at 4, 6 and 8 weeks (P = 0.049, P = 0.048, P = 0.001, respectively), which indicated that the rats in the CUMS group showed depression-like behavior
The results demonstrated that an increased plasma Hcy level was found at the end of 8 weeks of CUMS exposure; the results did not support the hypothesis that the increased Hcy concentration was one of possible intermediate mechanisms for the provocation of CUMS-induced depression because decreased sucrose preference following CUMS 4 weeks occurred prior to the increase of plasma Hcy concentration

Summary

Introduction

The accumulation of homocysteine (Hcy) has been implicated in the pathogenesis of depression, whether Hcy is directly involved and acts as the primary cause of depressive symptoms remains unclear. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system, associating stress with depression, have been discussed, the pathological mechanisms remain unclear. High concentrations of Hcy in the plasma or serum have been found in depressive patients. It was reported that approximately 20–50% of patients with severe depression had increased total Hcy levels in the plasma [5,6]. The accumulation of Hcy has been implicated in the pathogenesis of depression [9], whether Hcy is directly involved and acts as primary cause of depressive symptoms is unclear [10], and there is little evidence from animal experiments

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