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Microglial markers in the frontal cortex are related to cognitive dysfunctions in major depressive disorder
Hua Li1, Aadi P Sagar1, Szabolcs Kéri2
1Nyírő Gyula National Institute of Psychiatry and Addictions, Budapest, Hungary.
Background:
Evidence suggests that microglia-mediated processes are implicated in the pathophysiology of major depressive disorder (MDD). The relationship between these processes and cognitive dysfunctions has not been explored.
Methods:
We recruited 50 never-medicated patients with MDD and 30 healthy control subjects. We used [18F]-FEPPA positron emission tomography (PET) to examine translocator protein total distribution volume (TSPO VT), a marker of microglia. Cognitive functions were evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (attention, immediate and delyed memory, language, and visuospatial functions).
Results:
Patients with MDD showed elevated TSPO VT in all regions of interest (white matter, grey matter, frontal cortex, temporal cortex, and hippocampus) and were impaired on the attention and delayed memory domains of the RBANS. In the frontal cortex, increased TSPO VT was associated with lower scores on the RBANS attention domain when the analysis was corrected for age, gender, education, and depressive symptoms.
Limitations:
Affective functions were not investigated, the specificity of [18F]-FEPPA binding is limited, TSPO may reflect microglia/macrophage density rather than activation, and the sample was not balanced (more patients were included than controls).
Conclusions:
Attentional dysfunctions may be associated with microglial pathology in the frontal cortex of untreated patients with MDD.
Insights
Cognitive impairments in major depressive disorder (MDD) may stem from microglial changes. This study found elevated microglia markers in the frontal cortex linked to attention deficits in untreated MDD patients.
Area of Science:
- Neuroscience
- Psychiatry
- Immunology
Background:
- Microglia-mediated processes are increasingly linked to major depressive disorder (MDD) pathophysiology.
- The specific role of these microglial processes in cognitive dysfunction within MDD remains largely unexplored.
Purpose of the Study:
- To investigate the relationship between microglial activation markers and cognitive functions in never-medicated patients with MDD.
- To explore potential links between neuroinflammation and cognitive deficits in early-stage MDD.
Main Methods:
- Recruited 50 never-medicated MDD patients and 30 healthy controls.
- Utilized [18F]-FEPPA positron emission tomography (PET) to measure translocator protein total distribution volume (TSPO VT) as a marker of microglia.
- Assessed cognitive functions using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), focusing on attention and memory.
Main Results:
- MDD patients exhibited elevated TSPO VT across all brain regions, including the frontal cortex.
- Patients with MDD showed significant impairments in attention and delayed memory domains of the RBANS.
- Increased TSPO VT in the frontal cortex correlated with poorer attention scores in MDD patients, even after controlling for confounding factors.
Conclusions:
- Attentional deficits in untreated MDD patients may be associated with microglial pathology in the frontal cortex.
- These findings suggest a potential neuroinflammatory basis for cognitive dysfunction in MDD.
- Further research is needed to clarify the precise role of microglia in MDD-related cognitive impairments.
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