Microglial markers in the frontal cortex are related to cognitive dysfunctions in major depressive disorder.

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 [F]-FEPPA positron emission tomography (PET) to examine translocator protein total distribution volume (TSPO V), 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 V 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 V 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 [F]-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.