Recent Advances in Poststroke Depression
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Recent Advances in Poststroke Depression Haresh M. Tharwani, MD, Pavan Yerramsetty, MD, Paolo Mannelli, MD, Ashwin Patkar, MD, and Prakash Masand, MD Corresponding author Much of the literature on PSD notes a significantly Haresh M. Tharwani, MD increased mortality associated with PSD (in comparison to Duke Psychiatry Specialty Clinic, 2000 Regency Parkway, those poststroke patients without depression) [2,3,4•,5,6]. Suite 280, Cary, NC 27518, USA. E-mail: [email protected] PSD seems to be associated with an increase in inpatient Current Psychiatry Reports 2007, 9:225–231 and outpatient medical utilization over the long term Current Medicine Group LLC ISSN 1523-3812 [2]. PSD has been studied for more than 100 years, but Copyright © 2007 by Current Medicine Group LLC we still face several challenges to understand its precise pathophysiology and effective pharmacotherapy. Depression is the most common psychiatric complication after stroke. Its prevalence varies from 20% to 80%, and Epidemiology it is underdiagnosed and undertreated. It has significant Over the past several years, various researchers have impact on rehabilitation, motor recovery, activities of attempted, with very little agreement, to quantify the daily living, social and interpersonal life, and mortality. prevalence of PSD. The prevalence across these varied Several studies have shown that biological and psycho- studies ranges from 20% to 80% [7,8], depending greatly social factors play significant roles in the development upon the tools of assessment, the size and diversity of the of this disabling disease. Recent research shows that population studied, prior personal history of depression, neurochemical processes also may play some role in and the evaluation time after stroke, as well as varying the pathophysiology of this condition. Several trials have diagnostic criteria of depression itself. Conservative esti- shown evidence that the older, as well as newer anti- mates tended to be very specific in usingDSM IV criteria depressants and psychostimulants may reduce/prevent for major and minor depressive disorders, often excluding depressive symptoms after stroke. At this point there are severely disabled (yet potentially depressed) patients with no clear guidelines available to choose safe and effective aphasia, anosognosia, cognitive impairment, or delirium treatments. Drugs are selected based on their efficacy [9–11]. These studies also often focused on depression and side effect profile in these patients. More research is diagnoses at only one specific time period poststroke. On needed to understand the pathophysiology of depression the other hand, studies with higher levels of prevalence after stroke. There also is a need for more randomized tried to assess depression in a wide range of patients, clinical trials to better treat patients with this condition. in effect including some patients unable to verbally describe their depression [2,8,9]. Instead, these studies often focused on such global depressive behaviors as cry- Introduction ing, included a disproportionate number of hospitalized Depression (major and minor) is the most common patients (who have greater disability), and did not correct psychiatric complication after an individual sustains for past depressive history of the stroke patients [3,7,12]. a clinically apparent stroke (as evidenced by neu- Given that there are approximately 600,000 strokes per roimaging) [1]. Even with its high prevalence, it is year in the United States, this means a sizeable number of underdiagnosed and undertreated. Poststroke depres- Americans (not even considering even larger population sion (PSD) has been associated with increased distress, counts around the world) are suffering with PSD each disability, poor rehabilitation, morbidity, mortality, year [1]. In any epidemiologic study of a disease, it also and suicidal thoughts [1]. Do the negative outcomes is important to examine the risk factors that predispose a associated with stroke lead to the development of stroke patient to PSD. Ouimet et al. [12], in a meta-analy- PSD in these patients, or does the depression in the sis of 25 articles describing the psychosocial risk factors poststroke period cause these negative outcomes? The for PSD, noted that a history of depression, personal psy- authors note that studying this disease may in fact give chiatric history, dysphasia, functional impairment, living us significant insight into the pathophysiology of all alone, and poststroke social isolation all correlated with a forms of depression in general. higher probability of a PSD diagnosis. 226 Medicopsychiatric Disorders Pathophysiology of PSD between PSD and lesion location. They noted that “a Biological hypothesis patient’s risk of depression is not related to where the Stroke is one of the few diseases considered by DSM IV cerebral lesion is located” [17]. to directly cause depression [13]. Searching for such a A unique argument for the psychological basis of PSD biological cause has been a primary driving force in PSD put forth by these researchers relates to the similarity of research. One group of researchers, led by Robinson et al. symptoms and treatment response profiles between func- [4•,14], has proposed a primary biological mechanism tional depression and PSD. Their argument is that if PSD causing PSD whereby ischemic insults directly affect neu- is caused by specific brain lesions and the subsequent dis- ral circuits involved in mood regulation. More specifically, ruption of neural circuitry, it should have a significantly one researcher noted that the disruption of frontal-sub- different symptom and treatment profile than functional cortical circuits after stroke led to a depletion in cortical depression. This is further strengthened by their claim biogenic amines [8]. This biological mechanism has been that the symptom profile of PSD is also significantly dif- supported by a number of findings. First, as early as 1977, ferent than that of vascular depression, a condition that scientists had noticed that stroke survivors had a higher the biological camp had linked etiologically with PSD [1]. prevalence of major depression compared with physically These researchers have noted that many of the risk ill patients with a similar disability level [1]. This seemed factors for PSD are also risk factors for more traditional to suggest that some biological effect of the stroke itself functional depression. As described earlier in this paper, was causing the depression, rather than the level of dis- severity of disability (regardless of whether that disability tress/disability being caused by the particular illness. is a stroke) is one of the most important predictors for Over the past 20 years, a plethora of studies have also the development of depression. Summarizing the middle supported or challenged the specific lesion hypothesis ground position held by many present-day PSD research- first posited by Robinson et al. [14] in 1981, which has ers, Whyte and Mulsant [1] state that, “Any particular sought to find specific stroke-related lesions that cause stroke survivor may have a poststroke depression that PSD [14–17]. Initial support for this argument came from is purely biological in origin, or purely psychosocial, or several small studies noting a correlation between PSD truly multifactorial. Overall, most poststroke depressions and left anterior cortical and left basal ganglia lesions. appear to be multifactorial in origin and consistent with More specifically, notes this group, PSD severity was cor- the biopsychosocial model of psychiatric illness.” related with the “proximity of the anterior border of the Lastly, there is some discussion of potential psychoso- lesion on computed tomography scan (CT) to the frontal cial or even genetic vulnerabilities in certain populations pole in the left hemisphere but not in the right hemi- that might predispose them to depression after a stroke. sphere” [18]. However, these bold claims have not come without significant criticism, particularly from Carson et al. [17] (described subsequently). Another piece of sup- Current and Future Research Directions portive evidence for the biological understanding of PSD Much of the PSD research in the last year has focused centers around the presence of depression in the context on the composition of the neurochemical environment of anosognosia or silent infarcts. If PSD is a result of a after stroke. One study by Craft and DeVries [21••] has psychological response to the stroke itself, the main argu- hypothesized that pathophysiologic processes happening ment of the advocates of psychological hypothesis, then acutely after stroke significantly contribute to the etiology how can we explain the presence of clinical depression of PSD. Noting that stroke is associated with a dysregu- in patients who, due to their stroke, are not cognitively lation of the hypothalamic-pituitary-adrenal axis and aware of their disability? In the case of patients developing neuroinflammation, they sought to flesh out the implica- depression after a silent infarct (not symptomatic, but ver- tions of this unique chemical environment on a patient’s ified by MRI), a condition known as vascular depression, psychological health through the use of animal models of there is a similar issue of the patient’s lack of awareness of stroke progression. Although rats do not express “depres- his or her own condition. Although it is outside the scope sion” in any observable way, researchers have for a long of this