Background Suicidal ideation (SI) is a common symptom of bipolar disorder (BD). Patients with BD and suicidal ideation (BDSI) have been shown to exhibit abnormal spontaneous brain activity and homocysteine (Hcy) levels. Additionally, cognitive deficits are also considered to be a critical symptom in BD. However, the relationship among spontaneous brain activity, Hcy levels, and cognitive deficits in patients with BDSI remains unclear. Methods A total of 74 participants were enrolled, comprising individuals with BDSI (n = 20), BD patients without suicidal ideation (BDNSI) (n = 24), and age-/sex-matched healthy controls (HC) (n = 30). Each participant underwent cognitive performance assessments, and blood samples were collected to measure Hcy levels. We then calculated the amplitude of low-frequency fluctuation (ALFF) from resting-state functional magnetic resonance imaging data. Mediated-effects analysis was conducted to explore the association among these three variables. Results Hcy levels were significantly higher in the BDNSI group than in the BDSI group (t = 2.33, P = 0.024). Specifically, a significant positive correlation was observed between Hcy levels and the fractional amplitude of low-frequency fluctuation (fALFF) signals in the left posterior cingulate gyrus in the BDSI group (r = 0.644, P = 0.005). Mediation analyses revealed that the left posterior cingulate gyrus significantly mediated the negative relationship between Hcy levels and both visual learning /verbal learning performance (95% confidence intervals for the indirect effects ranging from <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="12888_2025_6925_Article_IEq1.gif" Format="GIF" Height="13" Rendition="HTML" Resolution="72" Type="Linedraw" Width="18" /> </InlineMediaObject> <EquationSource Format="TEX">\(\:-\)</EquationSource> </InlineEquation>0.592 to <InlineEquation ID="IEq2"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="12888_2025_6925_Article_IEq1.gif" Format="GIF" Height="13" Rendition="HTML" Resolution="72" Type="Linedraw" Width="18" /> </InlineMediaObject> <EquationSource Format="TEX">\(\:-\)</EquationSource> </InlineEquation>0.069 and <InlineEquation ID="IEq3"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="12888_2025_6925_Article_IEq1.gif" Format="GIF" Height="13" Rendition="HTML" Resolution="72" Type="Linedraw" Width="18" /> </InlineMediaObject> <EquationSource Format="TEX">\(\:-\)</EquationSource> </InlineEquation>0.465 to <InlineEquation ID="IEq4"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="12888_2025_6925_Article_IEq1.gif" Format="GIF" Height="13" Rendition="HTML" Resolution="72" Type="Linedraw" Width="18" /> </InlineMediaObject> <EquationSource Format="TEX">\(\:-\)</EquationSource> </InlineEquation>0.042, respectively) in the BDSI group. Conclusions Our data suggest that patients with BDSI and BDNSI may exhibit distinct Hcy-neurocognitive-brain function profiles, which could be further verified by investigating the underlying pathophysiological mechanism of BDSI.

Differential relationships among homocysteine levels, cognitive deficits, and low-frequency fluctuation in brain activity in bipolar disorder with suicidal ideation

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2025年5月21日

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Yuanyuan Huang,
Sumiao Zhou,
Shixuan Feng,
Hehua Li,
Ziyun Zhang,
Chenyu Liu,
Junhao Li,
Wei Han,
Kai Wu,
Xingbing Huang,
Fengchun Wu

摘要

Background

Suicidal ideation (SI) is a common symptom of bipolar disorder (BD). Patients with BD and suicidal ideation (BDSI) have been shown to exhibit abnormal spontaneous brain activity and homocysteine (Hcy) levels. Additionally, cognitive deficits are also considered to be a critical symptom in BD. However, the relationship among spontaneous brain activity, Hcy levels, and cognitive deficits in patients with BDSI remains unclear.

Methods

A total of 74 participants were enrolled, comprising individuals with BDSI (n = 20), BD patients without suicidal ideation (BDNSI) (n = 24), and age-/sex-matched healthy controls (HC) (n = 30). Each participant underwent cognitive performance assessments, and blood samples were collected to measure Hcy levels. We then calculated the amplitude of low-frequency fluctuation (ALFF) from resting-state functional magnetic resonance imaging data. Mediated-effects analysis was conducted to explore the association among these three variables.

Results

Hcy levels were significantly higher in the BDNSI group than in the BDSI group (t = 2.33, P = 0.024). Specifically, a significant positive correlation was observed between Hcy levels and the fractional amplitude of low-frequency fluctuation (fALFF) signals in the left posterior cingulate gyrus in the BDSI group (r = 0.644, P = 0.005). Mediation analyses revealed that the left posterior cingulate gyrus significantly mediated the negative relationship between Hcy levels and both visual learning /verbal learning performance (95% confidence intervals for the indirect effects ranging from \(\:-\) 0.592 to \(\:-\) 0.069 and \(\:-\) 0.465 to \(\:-\) 0.042, respectively) in the BDSI group.

Conclusions

Our data suggest that patients with BDSI and BDNSI may exhibit distinct Hcy-neurocognitive-brain function profiles, which could be further verified by investigating the underlying pathophysiological mechanism of BDSI.