Abnormal default-mode network in angiotensin converting enzyme D allele carriers with remitted geriatric depression

Using a cross-sectional case–control study of remitted geriatric depression (RGD), we characterised the relationships among cognitive function, whole-brain functional connectivity of the posterior cingulate cortex (PCC), and the angiotensin-converting enzyme (ACE) insertion or deletion (I/D) polymorphism during resting state. A total of 26 RGD patients and 24 matched controls were recruited, and neuropsychological tests, functional magnetic resonance imaging (fMRI) and ACE I/D genotype were examined for each subject. A 2 × 2 factorial analysis of variance (ANOVA) model (presence/absence of depression and presence/absence of ACE-D) was used to detect the interaction effect. Subsequent analyses were restricted to the significant interaction regions. There were significant interactions between disease and genotype at two clusters: left superior temporal gyrus/middle temporal gyrus and left cerebellum. And the ACE I/D polymorphism has disease-specific effects on the left superior temporal gyrus/middle temporal gyrus and cerebellum crus I. Furthermore, there was a significant positive correlation between the functional connection of PCC-left cerebellum crus I and the CFT-delayed recall test scores (r = 0.668, P = 0.003) in RGD group ACE-D allele carriers. These results suggest that the ACE I/D polymorphism can modulate the pathology of RGD, and the status of geriatric depression and the ACE-D allele may synergistically induce altered resting state network activity, which could influence the cognitive function and increase the mortality risk for cognitive impairment.

► Remitted geriatric depression (RGD) patients and healthy controls were recruited.
► Angiotensin-converting enzyme (ACE) polymorphism was analyzed in each subject.
► Whole-brain functional connectivity of the posterior cingulate cortex was conducted.
► Disease by genotype interactions were driven by genetic differences in RGD patients.
► RGD-specific clusters located on the left lateral temporal lobe and cerebellum.