Cerebrovascular Risk Factors and Later-Life Major Depression: Testing a Small-Vessel Brain Disease Model

Lyness, Jeffrey M.; Caine, Eric D.; Cox, Christopher; King, Deborah A.; Conwell, Yeates; Olivares, Telva

doi:10.1097/00019442-199802000-00002

Cited by 39 publications

(38 citation statements)

References 50 publications

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“…There was no significant correlation between Hgb A1c levels and frontal white matter myo-inositol levels suggesting that the medical co-morbidities associated with diabetes are a more important factor than the degree of glycemic control in our study subjects. This is consistent with a study by Lyness et al (1998) where they showed an association between diabetes and late-life depression that lost statistical significance when medical disability was controlled for.…”

Section: Discussionsupporting

confidence: 91%

Measurement of Brain Metabolites in Patients with type 2 Diabetes and Major Depression Using Proton Magnetic Resonance Spectroscopy

Ajilore¹,

Haroon²,

Kumaran³

et al. 2006

Neuropsychopharmacol

109

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Type 2 diabetes and major depression are disorders that are mutual risk factors and may share similar pathophysiological mechanisms. To further understand these shared mechanisms, the purpose of our study was to examine the biochemical basis of depression in patients with type 2 diabetes using proton MRS. Patients with type 2 diabetes and major depression (n ¼ 20) were scanned along with patients with diabetes alone (n ¼ 24) and healthy controls (n ¼ 21) on a 1.5 T MRI/MRS scanner. Voxels were placed bilaterally in dorsolateral white matter and the subcortical nuclei region, both areas important in the circuitry of late-life depression. Absolute values of myoinositol, creatine, N-acetyl aspartate, glutamate, glutamine, and choline corrected for CSF were measured using the LC-Model algorithm. Glutamine and glutamate concentrations in depressed diabetic patients were significantly lower (po0.001) in the subcortical regions as compared to healthy and diabetic control subjects. Myo-inositol concentrations were significantly increased (po0.05) in diabetic control subjects and depressed diabetic patients in frontal white matter as compared to healthy controls. These findings have broad implications and suggest that alterations in glutamate and glutamine levels in subcortical regions along with white matter changes in myo-inositol provide important neurobiological substrates of mood disorders.

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Section: Discussionsupporting

confidence: 91%

Measurement of Brain Metabolites in Patients with type 2 Diabetes and Major Depression Using Proton Magnetic Resonance Spectroscopy

Ajilore¹,

Haroon²,

Kumaran³

et al. 2006

Neuropsychopharmacol

109

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“…We found that patients who were exposed to CVRFs for more than 20 years were significantly more likely to develop depression with age at onset between 50 and 69 years than patients without CVRFs. In the context of the proposed model of Lyness et al (1998Lyness et al ( , 1999, this suggests that a long-term exposure to CVRFs is required before they contribute via the development of small-vessel brain disease to the occurrence of depression in later life. It should be noted that our measure of exposure duration to CVRFs weighted each individual CVRF (hypertension, diabetes, cardiovascular disease) equally and also did not take into account treatment of CVRFs.…”

Section: Discussionmentioning

confidence: 99%

“…An implication of this hypothesis is the existence of an association between cerebrovascular risk factors (CVRFs), such as hypertension, diabetes mellitus and cardiac disease, and depression in later life. More specifically, Lyness et al (1998Lyness et al ( , 1999 have suggested that the increase in prevalence of CVRFs with age contributes over time to the development of small-vessel brain disease, which, in turn, disrupts neurobiological functioning resulting in depression.…”

Section: Introductionmentioning

confidence: 99%

“…These reports have yielded mixed results Baldwin and Tomenson, 1995;Greenwald et al, 1996;Hickie et al, 2001;Lyness et al, 1998Lyness et al, , 1999Krishnan et al, 1995;Mast et al, 2004a;Stewart et al, 2001;Taylor et al, 2004). A major limitation of these studies is their transversal design.…”

Section: Introductionmentioning

confidence: 99%

“…Since the theoretical model by Lyness et al (1998Lyness et al ( , 1999 postulates that CVRFs produce depression through the development of small-vessel brain disease over time, exposure duration to CVRFs is an essential factor to be taken into consideration. In addition, age at depression onset may modify the relationship between CVRFs and the subsequent development of depression.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cerebrovascular risk factors and subsequent depression in older general practice patients

Nuyen

Spreeuwenberg

Beekman

et al. 2007

Journal of Affective Disorders

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Is depression associated with microvascular disease in patients with type 2 diabetes?

et al. 2008

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We hypothesize that late-life depression is a manifestation of microvascular disease in patients with type 2 diabetes. We conducted a clinic-based cross-sectional study, comparing retinal vascular caliber, a marker of microvascular disease, in participants with type 2 diabetes with major depression (n=34), without depression (n=27) and healthy non-diabetic controls (n=38). Retinal vascular caliber was measured from digital retinal photographs using a validated computer-assisted method. After adjusting for age and gender, there was a trend of increasing retinal arteriolar caliber from healthy controls (132.6 microm), to diabetic patients without depression (139.2 microm), and diabetic patients with major depression (145.3 microm, P=0.008). The trend in retinal arteriolar caliber remains significant after adjusting for duration of diabetes, but not after further adjusting for vascular risk factors. Our findings suggest that there is variation in the retinal vascular caliber between type 2 diabetic patients with and without major depression and non-diabetic controls. This variation was largely related to poorer diabetes control and a higher frequency of vascular risk factors in diabetic patients, particularly those with depression. Studies with larger sample size may provide further insights into this association.

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Cerebrovascular Risk Factors and Later-Life Major Depression: Testing a Small-Vessel Brain Disease Model

Cited by 39 publications

References 50 publications

Measurement of Brain Metabolites in Patients with type 2 Diabetes and Major Depression Using Proton Magnetic Resonance Spectroscopy

Measurement of Brain Metabolites in Patients with type 2 Diabetes and Major Depression Using Proton Magnetic Resonance Spectroscopy

Cerebrovascular risk factors and subsequent depression in older general practice patients

Is depression associated with microvascular disease in patients with type 2 diabetes?

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