Depression and Cerebrovascular Disease
Depression and Cerebrovascular Disease
Abstract & commentary
Source: Ramasubbu R. Relationship between depression and cerebrovascular disease: Conceptual issues. J Affect Disord 2000;57:1-11.
Depression and cerebrovascular disease (cvd) commonly co-occur. Depressive disorders may be a direct consequence of ischemic brain damage. Depression may also influence vascular risk factors, stroke recovery, and the risk of CVD via factors such as hypertension. Finally, the two conditions may be a state of co-occurrence without an etiological link. Naturally, the relationship between the disorders has important treatment implications (e.g., treating the vascular problem and/or the depression as the primary cause).
Hierarchical Relationship(s). The concepts of vascular depression1 and post-stroke depression2 (PSD) imply that ischemic brain damage is the (sole) cause of depression, almost to the exclusion of potentially concurrent genetic, nonvascular biological, and psychosocial factors. Vascular depression was hypothesized as an etiology in patients with onset of depression after 60 years of age1 and attempts have been made to validate its nosologic status. Geriatric vascular depression (GVD) patients have been shown by MRI to have vascular lesions and their depression was associated with more apathy and a lower rate of familial depression than nonvascular depression. Vascular depression is a broad heterogeneous entity, though, for which Hugen and colleagues offer subtyping analogous to categorization of vascular dementia: Type I (PSD) depression after a single infarct, which is commonly associated with a history of depression; Type II (GVD) depression associated with subcortical white matter lesions, which may also occur in nongeriatric patients; Type III depression associated with multiple silent cerebral infarcts, and/or a combination of Types I and II.
Interactive Aspects. Studies have examined the unidirectional relationship between depression and CVD, but the bidirectional relationship has largely been overlooked. Decreases in global perfusion in elderly patients with depression have been suggested to result from occlusive CVD (i.e., a trait phenomenon). Another view is that the perfusion deficits result from decreased output from subcortical nuclei associated with depression (i.e., a state phenomenon); interestingly, increased sympathetic activity with a coexisting anxiety disorder may also reduce cerebral perfusion. Vascular challenge tests would allow us to measure cerebral vasomotor reactivity or cerebrovascular reserve without altering the neuronal or metabolic activity of the brain. Such tests during and after remission of depression may help to elucidate the vascular mechanisms in depression. Depression scores in noninstitutionalized elderly patients predicted a greater incidence of stroke; the significance was not maintained with control of variables of age, sex, hypertension, diabetes, and smoking.3 However, the "negative" result does not preclude the interactive effect of depression and risk factors on stroke incidence.
In addition to the etiological considerations of depression on CVD, the effect of antidepressants and psychosocial treatments on the cerebrovasculature needs to be addressed. The most obvious example is the host of deleterious cardiovascular and cerebrovascular side effects of tricyclic antidepressants (i.e., arrhythmia, hypotension, and potentially reduction in cerebral metabolism). The effects of cognitive therapy, social support, and other psychosocial treatments need to be evaluated more fully for their direct benefits with regard to depression, prevention of CVD, or both.
Comorbid Aspects. The concept of comorbidity has heuristic value, but no clear conceptualization or comprehensive theoretical framework. The term is used in different ways too; some define comorbidity as the relative risk of a person with one disorder to acquire another disorder, while others define it as the presence of one specific disorder in a person with another disorder in a defined period. In any event, comorbidity may first reflect the overlap in diagnostic categories (e.g., depression and general anxiety disorder). Patients with depression and CVD may experience mood changes and mood-independent vegetative symptoms like anergia and changes in appetite, sleep, and sexual interest. Second, comorbidity reflects the coexistence of well-defined disorders, though subthreshold mood disorders may be clinically relevant in CVD patients. Third, the comorbidity of depression and CVD may be an artifact of chance (i.e., depression and white matter intensities are completely unrelated). Finally, are these diseases separate or the same entity (i.e., false comorbidity)?
Ramasubbu concludes with several recommendations including: 1) development of a depression and CVD database analogous to those of depression and cardiovascular disease; 2) vascular challenge tests to study the cerebrovascular reactivity, depression, and the effects of treatments; 3) comparative trials of antidepressants; 4) studies to evaluate the subclassification of vascular depression; 5) common etiological factors that may contribute to co-occurrence of depression and CVD (e.g., alcohol, anxiety); 6) the relationship of psychosocial factors and treatments; and 7) longitudinal studies to understand how one disorder influences the predisposition, progression, or outcome of the other disorder.
Comment by Donald M. Hilty, MD
This is an excellent review of a complex topic. Depression most likely increases the risk for CVD through several indirect mechanisms that include: increasing platelet aggregation, elevating cholesterol and high-density lipoprotein levels, enhancing hypertension, worsening diabetes, and inducing poor adherence to treatment. In addition, there is a cascade of chemical and hormonal factors via "stress" that have yet to be fully explored (e.g., how neurotransmitters and hormones influence one another and/or work together). Carefully designed, prospective studies with enormous funding, multiple sites, and sizable populations will be necessary to analyze the relationship.
Interestingly, despite the apparent side effect limitations of tricyclic antidepressants, they have equal (and, in some studies, better) efficacy than SSRIs, at least in short-term, controlled efficacy trials.
A new vein of research, however, will evaluate the potential beneficial vascular effects of SSRIs (e.g., decreased platelet reactivity as manifested by lower levels of platelet factor and B-thromboglobulin, which may eventually make them a preferable choice. It is unclear whether short-term trials are sufficient to show the benefits of such changes in platelet reactivity, and once again, longitudinal trials may be indicated. v
References
1. Miller MD, et al. Rating chronic medical illness burden in geropsychiatric practice and research: Application of the Cumulative Illness Rating Scale. Psychiatry Res 1992;41:237-248.
2. Robinson RG, et al. Mood disorders in stroke patients. Importance of location of lesion. Brain 1984;107:81-93.
3. Colantonio A, et al. Depressive symptoms and other psychosocial factors as predictors of stroke in the elderly. Am J Epidemiol 1992;136:884-894.
The indirect mechanisms by which depression may increase the risk for CVD include:
a. increasing platelet aggregation.
b. elevating cholesterol and high-density lipoprotein levels.
c. enhancing hypertension.
d. inducing poor adherence to treatment.
e. All of the above
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