Late-life depression: Managing mood in patients with vascular disease

Post-stroke depression (PSD) occurs within 12 to 24 months after a cerebrovascular accident.¹³ DSM-IV-TR categorizes PSD as a “mood disorder due to a general medical condition with the specifiers of (a) depressive features, (b) major depressive-like episodes, or (c) mixed features.”

Although important in depression’s pathophysiology, the location of stroke lesions is not the exclusive etiologic factor. Personal diathesis for depression, psychosocial factors, and physical and social impairment related to post-stroke neurologic deficits also may contribute to PSD.¹⁶

PSD patients with right-sided lesions often have family histories of depressive illness.¹⁷ Different serotonergic mechanisms might be responsible for depressive illness associated with right-sided vs left-sided lesions. This notion is supported by observed lateralized changes in serotonin type-2 (5-HT2) receptors¹⁸ and the influence of lateralized lesions on prolactin responsivity to d-fenfluramine challenge in PSD.¹⁹ Damage closer to the frontal lobes is likely to affect catecholamine-mediated brain activity.

The 8-year Framingham study²⁰ examined the risk of developing cerebrovascular events in persons age ≤65 vs those age >65. Subjects age ≤65 with significant depressive symptoms—Center for Epidemiologic Studies Depression scale score >16²¹—were 4 times more likely to develop stroke or transient ischemic attack compared with the same age group without depression. Another study found a link between depression and stroke risk across the adult age range.²² Mechanisms by which depressive symptoms may predispose to stroke are not fully known, but depression has been shown to affect autonomic function and platelet activation.²³

CHD and depression. In the United States, approximately 20% of coronary heart disease (CHD) patients have clinically significant depressive symptoms.²⁴ A history of depression also has been shown to increase the relative risk of developing CHD by >80%.²⁵

The association between depression and CHD is unclear but likely includes:

• direct biological mechanisms such as autonomic dysfunction and dysregulated inflammation
• behavioral factors such as smoking or poor self-care (Table 1).

A recent analysis of 13 cross-sectional studies²⁶ suggests that reduced heart rate variability (HRV) related to autonomic dysfunction may be the link between depression and CHD risk. The studies’ effect sizes were small, however, and their methodologies varied considerably.

C-reactive protein (CRP), interleukin-6, tumor necrosis factor-α (TNF-α), and fibrinogen are inflammatory markers. In a 2-year follow-up study, Frasure-Smith et al²⁷ investigated the relationship between depression and inflammatory markers in 741 patients (602 male) with acute coronary syndrome. Two months after an acute coronary event, depressive symptoms and elevated CRP levels were overlapping risk factors for future cardiac events in men.

Carney et al²⁸ showed that fibrinogen was most associated with altered heart rate variability in depressed CHD patients and proposed deficits in parasympathetic modulation of immunity and coagulation as the cause. In contrast, Whooley et al²⁹ found no association between major depression and inflammatory markers—including CRP, fibrinogen, and interleukin-6—in 984 outpatients with CHD. Differences in assessment scales and sample heterogeneity may have contributed to these disparate findings.

Diabetes and depression. As with CHD, a bidirectional relationship exists between depression and diabetes mellitus, although depression is only a modest risk factor for diabetes.³⁰ Possible explanations include hypercortisolemia and increased inflammation resulting in increased insulin resistance and metabolic syndrome.

Table 1

Shared risk factors for depression and heart disease

Diagnosis of vascular depression

Vascular depression is characterized by a clinical diagnosis of DSM-IV-TR-defined MDD, dysthymia, or depression not-otherwise-specified, accompanied by:

• evidence of CVD or
• known vascular risk factors (hypertension, diabetes, hyperlipidemia, stroke, heart failure, etc.).

In performing thorough neurologic, neuropsychiatric, and neuropsychological examinations, look for soft neurologic signs with regional weakness, apathy, and executive dysfunction. Useful bedside scales include the clock-drawing test, word list generation, brief dementia screens, and the Apathy Evaluation Scale.³¹

CT or MRI can provide supportive evidence by demonstrating signs of subcortical or cortical stroke. Neuroimaging studies may not be necessary, however, when depression onset is temporally associated with strong physical evidence of a stroke (such as falling, peripheral muscle weakness, or incontinence).

Treating depression symptoms

When treating vascular depression, clinical goals are to ameliorate affective symptoms, improve quality of life, and help patients perform activities of daily living (Table 2).

Psychosocial interventions. When depression is less than severe, consider psychosocial interventions as first-line treatment. Investigate environmental factors such as financial and marital problems or loneliness in patients’ depressive symptoms, and develop corresponding interventions—such as education, nutrition, exercise, socialization, or pain and stress management. Cognitive rehabilitation training and cognitive-behavioral therapy can reduce cognitive impairment and associated depression.