Elsevier

Biological Psychiatry

Volume 60, Issue 3, 1 August 2006, Pages 265-269
Biological Psychiatry

Original article
Homocysteine-Reducing Strategies Improve Symptoms in Chronic Schizophrenic Patients with Hyperhomocysteinemia

https://doi.org/10.1016/j.biopsych.2005.10.009Get rights and content

Background

An elevated homocysteine level is reported to be a risk factor for several diseases, including Alzheimer’s and cerebrovascular disease. Recently, several studies have reported that homocysteine levels are elevated in many schizophrenic patients. Homocysteine levels can be lowered by oral folic acid, B-12, and pyridoxine.

Methods

Forty-two schizophrenic patients with plasma homocysteine levels >15 μmol/L were treated with these vitamins for 3 months and placebo for 3 months in a study with a randomized, double-blind, placebo-controlled, crossover design.

Results

Homocysteine levels declined with vitamin therapy compared with placebo in all patients except for one noncompliant subject. Clinical symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale declined significantly with active treatment compared with placebo. Neuropsychological test results overall, and Wisconsin Card Sort (Categories Completed) test results in particular, were significantly better after vitamin treatment than after placebo.

Conclusions

A subgroup of schizophrenic patients with hyperhomocysteinemia might benefit from the simple addition of B vitamins.

Section snippets

Methods and Materials

The study was approved by the Helsinki Committee (institutional review board) of Ben Gurion University. Chronic schizophrenia patients from the Beersheva Mental Center Inpatient Service and affiliated inpatient hostels were screened for plasma homocysteine (Applebaum et al 2004, Levine et al 2002). Patients with levels >15 μmol/L (the standard upper limit of plasma homocysteine in clinical laboratories) who had been continuously ill for at least 1 year were accepted for study after providing

Results

Figure 1 illustrates PANSS scores during the two-period crossover-design treatment. Effects of treatment (vitamins vs. placebo) and time showed a significant interaction [F(3,120) = 3.77, p < .013]. There were no significant differences at baseline (LSD post hoc test, p = 0.4). Significant differences between vitamins and placebo in reduction of PANSS score appeared at month 3 (LSD post hoc test, p < .02). There was a three-way interaction between treatment, time, and treatment order [F(3,120)

Discussion

Godfrey et al (1990) reported that 6 months of folate administration as an adjunct to pharmacotherapy in schizophrenic patients demonstrating borderline or deficient plasma folate levels led to symptomatic improvement that grew with length of treatment. The present study suggests that specific vitamins in a specific clinical population defined by hyperhomocysteinemia might yield measurable clinical benefit.

From our study, it is not clear whether hyperhomocysteinemia is necessary for the

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