Individuals with Bipolar Disorder Have a Higher Level of Homocysteine Than Major Depressive Disorder: A Retrospective Chart Review and Observational Study

Abstract

Purpose Previous studies suggest that homocysteine (Hcy) may be involved in the pathogenesis of bipolar disorder (BD) and major depressive disorder (MDD) by influencing glutamatergic transmission, inflammation, and other mechanisms. There are no established biomarkers to distinguish BD from MDD. This study aims to compare Hcy levels between BD and MDD. Patients and Methods We collected medical records of patients aged 14–75 admitted to the hospital from January 1 to July 1, 2022 with a discharge diagnosis of MDD or BD, including all examinations of patients at admission (acute phase) and discharge (non-acute phase). We measured Hcy levels in healthy controls (HC). Results The analysis included 104 patients with MDD, 103 patients with BD, and 80 HC. Hcy levels were higher in the MDD and BD group than in the HC group and higher in the BD group than in the MDD group, both in the acute and non-acute phases (all P < 0.05). There was no significant difference in Hcy levels between the psychotropic medication users and non-users in the BD or MDD group (all P > 0.05). Multivariate logistic regression analysis only for the MDD and BD group indicated that the likelihood of BD diagnosis was significantly associated with Hcy levels (in the acute phase: OR = 1.052, P = 0.016; in the non-acute phase: OR = 1.101, P < 0.001) after controlling for gender, age, and metabolic indicators. Conclusion Our study suggests that Hcy levels were elevated in MDD and BD patients and were higher in BD patients than in MDD patients, which provides evidence for a possible relationship between one-carbon metabolism and the pathogenesis of BD. Besides, Hcy may be one of the potential biomarkers to distinguish BD from MDD.

Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes

“…For example, distinct gut microbial compositions were identified in MDD patients compared to BD patients ( 30 ). Homocysteine levels were elevated in MDD and BD patients, and were higher in BD patients than in MDD patients ( 31 ). The resting state functional magnetic resonance imaging (fMRI) studies revealed that BD patients had a specific increased amplitude of low frequency fluctuations in the right brain regions and bilateral cerebellum ( 32 , 33 ), while specific abnormalities were found in functional connectivity in the amygdala-ventral PFC in MDD ( 33 , 34 ).…”

Association between elevated homocysteine levels and obstructive sleep apnea hypopnea syndrome: a systematic review and updated meta-analysis

“…In recent years, HCY has gained extensive attention. According to epidemiologic data, HCY is strongly correlated with the prognosis of cardiovascular disease and serves as an independent risk factor for the condition ( 6 ). Further research is required to determine whether elevated HCY levels are associated with an increased risk of major adverse cerebrocardiovascular events (MACCEs) in individuals with OSAHS.…”