Changes over time in lesion locations associated with depression

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We examined the effect of time since stroke on the relationship between lesion location and depression (Shimoda and Robinson 1999). Using the same population of stroke patients with 2-year follow-up (i.e., 142 patients), we identified patients who had a single stroke lesion involving either the right or left middle cerebral artery (MCA) distribution that was visible on CT scan and who had a follow-up evaluation either at 3 or 6 months (short-term follow-up) or at 12 or 24 months (long-term follow-up). Of 60 patients who met these qualifications, 41 were seen at short-term follow-up and 46 were seen at long-term follow-up. There were no statistically significant differences between the short- and long-term follow-up groups in terms of age, gender, race, marital status, education, socioeconomic status, frequency of family or personal psychiatric history or prevalence of major or minor depression (39% of the short-term follow-up patients and 43% of the long-term follow-up patients had in-hospital major or minor depression). The frequency of depression in patients with right and left hemisphere lesions during the initial evaluation and at the short- and long-term follow-up is shown in Fig. 10.2. During the initial evaluation, patients with left hemisphere stroke had a significantly higher prevalence of both major and minor depression (as defined by DSM-IV criteria) than patients with right hemisphere stroke (p = 0.0006) (Fig. 10.2). At short- and long-term follow-up, however, there were no significant differences between right and left hemisphere lesion groups in terms of the frequency of major or minor depression. Thus, failure by other investigators to find a lateralized effect of hemispheric lesion location as summarized by Carson et al. (2000) was probably the result of including studies that were conducted after the first 2 months following stroke.

Depression and hemispheric lesion location

Depression and hemispheric lesion location

Initial 3-6 months 12-24 months

Initial 3-6 months 12-24 months

□ Minor depression □ Major depression *p = 0.006

Figure 10.2 The frequency of major and minor depression defined by DSM-IV criteria associated with single lesions of the right or left hemisphere during the acute stroke period and at follow-up. The lateralized effect of left hemisphere lesions on both major and minor depression was found only during the acute stroke period. At 3-6- and 12-24-month follow-up, there were no hemispheric lesion effects on the frequency of depression.

To test the hypothesis that depressive disorders are more frequent in patients with left frontal or left basal ganglia lesions over the first 2 months following stroke, we conducted our own meta-analysis (Robinson 2003). The results of the meta-analysis are shown in Table 10.2. All studies which examined patients within 8 weeks following acute stroke and compared the relative risk of major depression following left anterior versus left posterior stroke or left anterior versus right anterior stroke were included. Meta-analyses utilizing 126 patients, based on the fixed model effect found a relative risk of 2.29 (95% confidence interval, 1.55-3.33) and using the random model, found a relative risk of 2.29 (95% confident interval, 1.55-3.37) (Table 10.2). The random model is a more conservative statistic which assumes that there are random variations in the inter study variance. The fixed model does not make this assumption. When the effect of left anterior versus right anterior lesion location on the risk of major depression was compared, the odds ratio was 2.18 using the fixed model (95% confidence interval 1.44-3.30) and using the random model was 2.16 (95% confidence interval 1.28-3.64). Thus, by defining the parameters of the analysis, the statement by Carson et al. at the beginning of this chapter appears to be at least overstated. On the other hand, the Carson et al. (2000) analysis helped to define the parameters of the lesion location hypothesis. I stated in the first edition of this text that lesion location and depression were phenomenon of the first few months following stroke. Although we do not know why this phenomenon of asymmetry in association with depression is a temporally related phenomenon, it suggests that pathophysiological changes provoked by the acute stroke are occurring within a 2-month period which initially promotes depressive disorder associated with left anterior hemisphere lesions and then changes in some way to allow both right and left hemisphere lesions to lead to depression. In fact, our data as well as other investigators (Finset et al. 1989; Sharpe et al. 1994; Shimoda and Robinson 1999) suggest that by 2 or more years poststroke, depressive disorders may be more common following right posterior lesions than any other lesion location.

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