White Matter Lesions as a Predictor of Depression in the Elderly: The 3C-Dijon Study

Neuroepidemiology, Institut National de Santé et de Recherche Médicale, Paris, France.
Biological psychiatry (Impact Factor: 10.26). 05/2008; 63(7):663-9. DOI: 10.1016/j.biopsych.2007.09.006
Source: PubMed


There is increasing evidence for a link between cerebrovascular disease and depression in the elderly but the mechanisms are still unknown. This study examines the longitudinal relationship between depression and white matter lesions (WML) in a sample of elderly aged 65 years and older.
Three City (3C)-Dijon is a 4-year follow-up population-based prospective study of 1658 subjects. At baseline, lifetime major depressive episode diagnosis was established using the Mini International Neuropsychiatric Interview. At each study wave, severity of depressive symptoms was assessed using Center for Epidemiological Studies-Depression (CES-D), and antidepressants intake was recorded. At baseline, lifetime major depression (LMD) was defined as lifetime major depressive episode or antidepressant medication intake. At follow-up, subjects were classified "incident depression" if scoring high at CES-D or antidepressant users. At baseline, cerebral magnetic resonance imaging (MRI) was performed to quantify WML volumes using an automated method of detection. At 4-year follow-up, 1214 subjects had a second MRI.
Cross-sectional analysis showed a significantly higher WML volume in subjects with LMD compared with other subjects. Adjusted longitudinal analysis showed that increase in WML load was significantly higher in subjects with baseline LMD (2.1 cm(3) vs. 1.5 cm(3), p = .004). Among subjects free of depression up to baseline (n = 956), the higher the baseline WML volume, the higher the risk of developing depression during follow-up (odds ratio one quartile increase: 1.3; 95% confidence interval: = 1.1-1.7).
Our data show that depression and WML volumes are strongly related. These results are consistent with the hypothesis of a vascular depression in the elderly.

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    • "This hypothesis postulates that cerebral small vessel lesions can lead to depressive symptoms via damage to deep and frontal brain structures that are involved in mood regulation[54,55]. Only few longitudinal studies evaluated the association between early vascular changes and depression, and found a positive association between markers of cerebral small vessel disease and levels of depressive symptoms and/or recurrent depression565758. In addition, higher levels of arterial stiffening, an early phenomenon in the development of cardiovascular disease which is accelerated in type 2 diabetes , were found to be slightly higher in individuals with depression[59,60]. "
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    • "Basically the premutation may be more vulnerable to environmental toxicity including chronic methadone use. Some other factors might also contribute to progression of WMD, such as depression [Fields 2008; Godin et al., 2008], hypertension [Godin et al., 2011; Hamlin et al., 2012], and chronic pain [Buckalew et al., 2013] "
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    • "Late-life major depression has been consistently linked to brain abnormalities. Many neuroimaging studies have found that late-life major depression is associated with decreased medial frontal gray matter volume [10], [11] and an increased number of white matter lesions (WMLs) [12], [13], but the relationship between late-life major depression and limbic system abnormalities remains unclear [14]–[16]. Late-life subsyndromal depression could be related to these brain structures if it shares common neuroanatomical substrates with late-life major depression. "
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