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A metabolic "double hit" in prefrontal gray and white matter shapes microbiota-related visual learning memory
Xiaodong Song1, Dong Huang1, Shilin Liu1
1Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
Background:
Visual learning memory deficits are key issues in major depressive disorder (MDD), but the specific gut microbiota involved are not well understood. While gut dysbiosis and metabolic alterations in the frontolimbic region are linked to MDD, the influence of regional neurochemistry on the microbiota-cognition relationship remains unknown.
Methods:
Visual learning memory was assessed in 38 MDD patients and 41 healthy controls (HC) using the Brief Visuospatial Memory Test-Revised. Gut microbiota were analyzed via 16S rRNA gene sequencing of fecal samples, and neurochemical ratios N-acetylaspartate/Creatine (NAA/Cr) and Choline/Creatine (Cho/Cr) in anterior cingulate cortex (ACC) and prefrontal white matter (PWM) were quantified using proton magnetic resonance spectroscopy.
Results:
MDD exhibited visual learning memory deficits, elevated NAA/Cr in the right ACC, reduced NAA/Cr in the right PWM compared to HC. Ruminococcus abundance was increased in MDD and negatively correlated with visual learning memory. The relationship between Ruminococcus abundance and visual learning memory was moderated by NAA/Cr ratios in the ACC and PWM in a configuration-dependent manner. Specifically, the most pronounced negative association emerged when the ACC NAA/Cr ratio was high and the PWM NAA/Cr ratio was low.
Conclusions:
The study indicates that simultaneous metabolic dysregulation in gray and white matter, shown by elevated ACC NAA/Cr and decreased PWM NAA/Cr, constitutes a "double hit" that exacerbated visual learning memory impairment associated with Ruminococcus in MDD. This dual impact underscores distinct yet interconnected vulnerabilities in gray and white matter, where microbiota-cognition associations are critically shaped by the broader neurochemical environment.
Insights
Major depressive disorder (MDD) involves visual memory deficits linked to gut bacteria like Ruminococcus. Brain metabolism in gray and white matter, influenced by Ruminococcus, exacerbates these memory issues in MDD patients.
Area of Science:
- Neuroscience
- Microbiology
- Psychiatry
Background:
- Visual learning memory deficits are a core issue in major depressive disorder (MDD).
- The specific gut microbiota contributing to these deficits and their interaction with brain neurochemistry are not fully understood.
- Gut dysbiosis and frontolimbic metabolic alterations are associated with MDD, but the role of regional neurochemistry in the gut-brain-cognition axis is unclear.
Purpose of the Study:
- To investigate the relationship between gut microbiota, neurochemical changes in the anterior cingulate cortex (ACC) and prefrontal white matter (PWM), and visual learning memory deficits in MDD patients.
- To explore how neurochemical ratios (NAA/Cr, Cho/Cr) in the ACC and PWM modulate the association between gut microbiota and cognitive function in MDD.
Main Methods:
- Assessed visual learning memory using the Brief Visuospatial Memory Test-Revised in 38 MDD patients and 41 healthy controls (HC).
- Analyzed fecal gut microbiota composition using 16S rRNA gene sequencing.
- Quantified neurochemical ratios (N-acetylaspartate/Creatine [NAA/Cr] and Choline/Creatine [Cho/Cr]) in the ACC and PWM via proton magnetic resonance spectroscopy.
Main Results:
- MDD patients showed visual learning memory deficits, with elevated right ACC NAA/Cr and reduced right PWM NAA/Cr compared to HC.
- Ruminococcus abundance was higher in MDD patients and negatively correlated with visual learning memory.
- The negative association between Ruminococcus and memory was moderated by ACC and PWM NAA/Cr ratios, particularly when ACC NAA/Cr was high and PWM NAA/Cr was low.
Conclusions:
- A "double hit" of simultaneous gray matter (ACC) and white matter (PWM) metabolic dysregulation exacerbates Ruminococcus-associated visual learning memory impairment in MDD.
- Distinct yet interconnected vulnerabilities in gray and white matter neurochemistry critically shape microbiota-cognition associations within the MDD context.
- These findings highlight the complex interplay between gut microbiota, brain metabolism, and cognitive function in major depressive disorder.
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