Association of serum homocysteine and methionine levels with cognition and functioning in bipolar disorder

Abstract

The relationship between homocysteine (HCY) levels and cognitive impairments, particularly executive functions in bipolar disorder (BD), has recently been investigated. However, conflicting results were reported. The aim of the present study is to investigate changes in serum HCY, methionine, vitamine B12 and levels in BD patients are relative to controls and to investigate the relationship between HCY, methionine, vitamin B12, and folate levels and clinical features, cognitive functions and psychosocial functioning in euthymic BD patients and controls. Methods: Sixty BD type I euthymic patients and twenty controls were assessed with Global Assessment of Functioning and a battery of neuropsychological tests including the Wisconsin card sorting test, the Rey's auditory verbal learning test, the Cancellation test, Trail making test A, Trail making test B, and the Stroop test. HCY, vitamin B12, methionine and folate levels were measured together after collecting blood samples from both patient and controls. Results: Mean serum methionine concentration was different between groups. Low serum methionine was found to be a predictor of BD. However, a statistically significant difference was not detected between groups for mean serum values of HCY, folate, or vitamin B12. HCY levels showed a positive correlation with illness duration, the number of total episodes, and the number of manic episodes. A significant correlation was not found between HCY, methionine, folate, B12 levels with cognitive functions and functioning in the BD group. Conclusion: Low serum methionine was found to be a predictor of BD, a condition which can lead to a decrease in SAM synthesis and thus to a variety of complications in methylation reactions. Additional studies are needed to clarify the impact of single carbon metabolism on BD.

Homocysteine as a peripheral biomarker in bipolar disorder: A meta-analysis

“…Since no response was provided, this article was also excluded [104]. In total, we identified 10 studies fulfilling our inclusion criteria, of which two studies measured Hcy levels in mania (227 persons with BD and 268 healthy controls) [105,106], eight in euthymia (436 persons with BD and 616 healthy controls) [44,106–112] and one in depression [60] (Fig. 1).…”

“…In six of the nine studies, the control group was matched by sex and age [90,106–108,111,112]. All subjects with BD were on psychopharmacological treatment.…”

“…All subjects with BD were on psychopharmacological treatment. Seven studies provided details on the medications used [105,107–112], the most common being mood stabilizers, antidepressants, and first and second generation antipsychotics. All studies excluded subjects with either long-term somatic conditions or substance use disorders.…”

“…We included two studies in the meta-analysis of Hcy levels in subjects with BD in manic state compared with healthy controls [105,106] and eight studies in the meta-analysis that compared subjects with BD in euthymic state compared with healthy controls [44,106–112]. Random-effects meta-analysis showed that serum and plasma levels of Hcy were increased in subjects with BD either in mania or in euthymia when compared to healthy controls, with a large effect in the mania group ( g = 0.98, 95% CI: 0.80–1.17, P < 0.001, 2 between-group comparisons, n = 495) and a small effect in the euthymia group ( g = 0.30, 95% CI: 0.11–0.48, P = 0.002, 8 between-group comparisons, n = 1052) (Fig.…”

Serum folate levels in bipolar disorder: a systematic review and meta-analysis

“…None of the included studies compared peripheral folate levels in plasma or whole blood. Of these six studies, two [29, 50] measured folate levels in patients with mania, two [49, 51] in patients with euthymia, and two [47, 48] did not specify the mood state. Of these six studies, two [47, 48] consisted of patients on medication, and the other four studies did not mention information about medication.…”