Aberrant static and dynamic functional connectivity within amygdala in type 2 diabetes patients with and without depression associated with neurotransmitter profiles: A multimodal imaging study.

BACKGROUND

Type 2 diabetes mellitus (T2DM) with depression patients exhibit poor treatment adherence and increased social burden. This multimodal neuroimaging study investigated amygdala subregional static/dynamic functional connectivity (sFC/dFC) and the association with neurotransmitter receptor/transporter distributions, to explore the underlying pathophysiological mechanisms of T2DM with depression.

METHODS

Demographic data, clinical characteristics, neuropsychological tests, and resting-state functional magnetic resonance imaging of 191 participants (49 depressed T2DM, 70 non-depressed T2DM, 72 healthy controls) were collected and evaluated. Fourteen amygdala subregions were analyzed for sFC/dFC, followed by correlation and receiver operating characteristic curve analysis. Then, we correlated the aberrant amygdala connectivity with neurotransmitter receptor/transporter maps.

RESULTS

Static analysis revealed abnormal amygdala FC with the middle frontal gyrus (MFG), middle cingulate, and middle occipital gyrus, patterns almost universally presented in dynamic analysis. Notably, the dynamic analysis highlighted more pronounced differences in FC between the left auxiliary basal or basomedial nucleus and the right MFG in the depressed T2DM group, and expanded connections disruptions, including the prefrontal cortex (MFG, medial superior frontal gyrus), ventral visual pathway (middle and inferior occipital gyrus, fusiform gyrus, middle temporal gyrus), anterior cingulate cortex, Crus II, and precuneus. Both sFC and dFC abnormalities exhibited high areas under receiver operating characteristic curve, with dFC being more significant. Moreover, aberrant amygdala connectivity was negatively correlated with spatial distribution of SERT and D2 receptor.

CONCLUSIONS

These findings may provide new insights into the neuropathophysiological mechanisms of depression in T2DM.