The D-allele of ACE insertion/deletion polymorphism is associated with regional white matter volume changes and cognitive impairment in remitted geriatric depression.
ABSTRACT Prior studies suggested that angiotensin-converting enzyme (ACE) affected vascular homeostasis and degradation of amyloid beta (Abeta ). It is associated with the therapeutic outcome in major depression. The aim of this study was to investigate the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and structural abnormalities in remitted geriatric depression (RGD), and test the relationship of neuropsychological performances and regional white matter volumes. 31 RGD patients were recruited and neuropsychological tests, magnetic resonance imaging (MRI) and genotype of ACE I/D were examined for each subject. The differences in regional white matter volume were tested between I homozygotes and D-allele carriers (I/D or D/D genotype) by optimized VBM. D-allele carriers exhibited significantly smaller white matter volumes of right superior frontal gyrus (SFG) and right anterior cingulated gyrus (ACG), but had larger volumes of left middle temporal gyrus (MTG) and right middle occipital gyrus (MOG) than I homozygotes (P < 0.001). Meanwhile, there was a significant positive correlation between white matter volume enlargement of left MTG and Symbol Digit Modalities Test (SDMT) (r = 0.456, P = 0.043), and the reduction of right ACG was negatively related to Clock Drawing Test (CDT) performance (r = -0.445, P = 0.050) in D-allele carriers. The finding suggests that ACE can modulates the pathology of RGD, the left MTG and right ACG might be involved in the pathophysiology of cognitive dysfunction in RGD patients.
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ABSTRACT: This paper reviews neuroimaging studies of depressive disorders conducted in Chinese populations since 2000. Both cross-sectional and longitudinal studies using structural and functional imaging techniques have compared different types of depressed individuals, with and without specific genotypes, and the characteristics of depressed individuals before and after treatment with antidepressants. Many of the findings are unstable - probably because most of the studies are underpowered - but there have been some important contributions to the international literature. Future studies in China need to use standardized methods, longitudinal designs, and joint application of both structural and functional MRI.Shanghai archives of psychiatry. 06/2014; 26(3):113-8.
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ABSTRACT: Aging is associated with appearance of white matter hyperintensities (WMH) on MRI scans. Vascular risk and inflammation, which increase with age, may contribute to white matter deterioration and proliferation of WMH. We investigated whether circulating biomarkers and genetic variants associated with elevated vascular risk and inflammation are associated with WMH volume in healthy adults (144 volunteers, 44-77 years of age). We examined association of WMH volume with age, sex, hypertension, circulating levels of total plasma homocysteine (tHcy), cholesterol (low-density lipoprotein), and C-reactive protein (CRP), and four polymorphisms related to vascular risk and inflammation: Apolipoprotein ε (ApoE ε2,3,4), Angiotensin-Converting Enzyme insertion/deletion (ACE I/D), methylenetetrahydrofolate reductase (MTHFR) C677T, C-reactive protein (CRP)-286C>A>T, and interleukin-1β (IL-1β) C-511T. We found that larger WMH volume was associated with advanced age, hypertension, and elevated levels of homocysteine and CRP but not with low-density lipoprotein levels. Homozygotes for IL-1β-511T allele and carriers of CRP-286T allele that are associated with increased inflammatory response had larger WMH than the other allelic combinations. Carriers of the APOE ε2 allele had larger frontal WMH than ε3 homozygotes and ε4 carriers did. Thus, in healthy adults, who are free of neurological and vascular disease, genetic variants that promote inflammation and elevated levels of vascular risk biomarkers can contribute to brain abnormalities. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.Biochimica et Biophysica Acta 08/2011; 1822(3):361-9. · 4.66 Impact Factor
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ABSTRACT: The renin-angiotensin system (RAS) is implicated in the response to physiological and psychosocial stressors, but its role in stress-related psychiatric disorders is poorly understood. We examined if variation in AGTR1, the gene coding for the type 1 angiotensin II receptor (AT(1)R), is associated with a diagnosis of depression and differences in white matter hyperintensities and frontotemporal brain volumes. Participants comprised 257 depressed and 116 nondepressed elderly Caucasian subjects who completed clinical assessments and provided blood samples for genotyping. We used a haplotype-tagging single nucleotide polymorphism (htSNP) analysis to test for variation in AGTR1. For measurement of hyperintense lesions, 1.5 Tesla magnetic resonance imaging (MRI) data were available on 33 subjects. For measurements of the hippocampus and dorsolateral prefrontal cortex (dlPFC), 3 Tesla MRI data were available on 70 subjects. Two htSNPs exhibited statistically significant frequency differences between diagnostic cohorts: rs10935724 and rs12721331. Although hyperintense lesion volume did not significantly differ by any htSNP, dlPFC and hippocampus volume differed significantly for several htSNPs. Intriguingly, for those htSNPs differing significantly for both dlPFC and hippocampus volume, the variant associated with smaller dlPFC volume was associated with larger hippocampal volume. This supports the idea that genetic variation in AGTR1 is associated with depression and differences in frontotemporal morphology.Psychiatry Research 06/2012; 202(2):104-9. · 2.68 Impact Factor