Relationship of depression to bilateral
121 Relationship of depression to bilateral hemisphere brain injury
greater than 3 months) (depending on relative lucency of the lesion and mass effect).
Patients were grouped according to whether or not they had a left anterior lesion. We hypothesized that there would no longer be an increased frequency of major depression among patients with left anterior lesions and that the existence of bilateral brain injury would be manifested by indifference or apathy rather than depression. In other words, the effect of the right hemisphere lesion could amelio-rate the depressive effects of the left frontal lesion. An anterior lesion was defined, as in previous studies, as any lesion whose anterior border was rostral to 40% of the anterior–posterior distance.
Background characteristics such as age (62 8 SD years left anterior (n 8) versus 59 20 SD years no left anterior (n 6)), gender distribution (55% male left anterior versus 67% male non-left anterior), social class family or personal prior psychiatric history (none for either left anterior or non-left group), or other background characteristics showed no statistically significant intergroup differ-ences. Of the 15 patients in this study, eight had a single lesion in each hemisphere, five had one lesion of the left hemisphere and two lesions of the right hemisphere, one had two left and one right hemisphere lesions, and one patient had two left and two right hemisphere lesions.
There were no significant differences in neurological findings between patients with and without left anterior brain lesions. Among patients with left anterior lesions, 89% had unilateral motor impairment compared to 100% of patients without left anterior brain lesions. Similarly, 38% of patients with left anterior lesions and 50% of those with no such lesions had aphasia.
Patients with left anterior lesions, however, had significantly more severe symptoms of depression than those without left anterior lesions on the Hamilton depression scale (p 0.05, Fig. 12.1). There were no intergroup differences, however, in terms of the severity of impairment in activities of daily living (Johns Hopkins functioning inventory (JHFI)) or cognitive function (mini-mental state examination) (Fig. 12.1). Furthermore, correlational analysis showed a statistically significant inverse correlation (r 0.64, p 0.05) between Hamilton depression score and the distance between the anterior border of the lesion and the frontal pole only in the left hemisphere (Fig. 12.2). In the two patients who had more than one left hemisphere lesion, the most anterior lesion was chosen for measurement of the distance from the frontal pole. There was no significant cor-relation, however, between Hamilton depression score and the distance between the lesion and the frontal pole for right-sided lesions. Similarly, there were no sig-nificant correlations between Hamilton depression scores and either cognitive impairment (mini-mental state examination) or impairment in activities of daily living (JHFI).
122 Poststroke depression
We next examined whether these findings may have been influenced by the age of the lesions. There was no significant difference between patients with left ante-rior lesions and those without left anteante-rior lesions in terms of the mean age of their left hemisphere lesions. There was also no significant correlation between the age
0 5 10 15 20 25 30
Hamilton ADL MMSE
Severity
p 0.05
Left anterior lesion No left anterior lesion
Figure 12.1 Severity of depression (Hamilton), impairment in activities of daily living (ADL) and impairment in cognitive function (mini-mental state examination (MMSE)) in patients with bilateral hemispheric strokes divided into those with one lesion whose anterior border is rostral to 40% of the over anterior–posterior (A–P) diameter of the left
hemisphere and those without a left anterior lesion. Patients with left anterior lesions had more severe depressive symptoms than patients without this lesion location but there were no significant differences in the severity of ADL or cognitive impairments.
0 10 20 30
Hamilton depression score
10 20 30 40 50 60 70
Distance of left hemisphere lesion from frontal pole (%) r 0.64; p 0.05
Figure 12.2 Severity of depression as measured by the Hamilton depression scale and proximity of the most anterior left hemisphere lesion to the frontal pole in patients with bilateral strokes.
Severity of depression increased with proximity of the lesion to the left frontal lobe.
Severity of depression, however, was not significantly correlated with right hemisphere lesion location or the age of the most recent stroke.
123 Relationship of depression to bilateral hemisphere brain injury
category (i.e.,3 weeks, 3 weeks, 3 months) of the left hemisphere lesion and the severity of depression. Thus, the increased severity of depression in the left anterior lesion group was not the result of their lesions being more acute than those of the group with no left anterior lesion. Finally, we examined the temporal sequence of the lesions using the lesion age categories. In the group with left ante-rior lesions, this lesion was more recent in three out of nine patients while the right hemisphere lesion was more recent in the six remaining patients. In the group of patients without a left anterior lesion, the left lesion was the most recent in one of six patients while the right lesion was more recent in the remaining five patients.
Thus, a hypothesis of increased frequency of left-sided acute lesions in the left anterior compared with the non-left anterior group was not supported by statisti-cal analysis (p NS). This finding indicates that the greater severity of depression among patients with left anterior lesions was not explained by the location of the most recent infarct. Most of the patients with left anterior lesions (i.e., the group with significantly higher depression scores) actually had an acute right hemisphere infarct as their most recent lesion.
What are the implications of this study for understanding the mechanisms of depression? Firstly, this study of bilateral lesions indicates the predominance of left frontal pathology over other lesion locations in the mechanism of poststroke depres-sion during the acute period following a second stroke. Secondly, neural mechanisms within the left hemisphere probably played a dominant role in the generation of depression since the existence of a concomitant, frequently acute, right hemisphere lesion did not alter the clinical presentation. The left hemisphere did not appear to be
“released” by a right hemisphere lesion and this finding suggests that the mechanism for depression is mediated within the left hemisphere. Thus, the suggestion by Tucker (1981) that contralateral release plays a role in depression is not supported by these findings. These findings are, however, consistent with Davidson’s (1998) suggestion that left frontal hemisphere dysfunction may be manifested by the absence of approach motivation and the inability to experience pleasure. The fact that we did not find an augmentation of depression by a combination of left anterior and right hemi-sphere lesions (i.e., the depression scores were the same as we have previously found in patients with single left anterior lesions) does not lend confirmation (although it also does not disprove) to the suggestion of Kinsbourne and Bemporad (1984) that both right and left hemisphere dysfunction are involved in depression.
In summary, this unusual study of the interaction of the cerebral hemispheres in the etiology of poststroke depression demonstrated that the existence of a left ante-rior brain lesion was significantly associated with more severe depression inde-pendent of the age or temporal sequence of a concomitant right hemisphere lesion.
In addition, the proximity of the left anterior lesion to the frontal pole correlated significantly with severity of depression. It should be emphasized, however, that
dichotomous distinctions between right and left hemisphere functions in the pro-duction of emotion are probably oversimplifications and mediation of emotion using both hemispheres is likely. However, this study of patients with bilateral brain injury is rarely done and does contribute some intriguing findings to our understanding of the role that each cerebral hemisphere plays in the production or maintenance of depression.
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Davidson, J., Pearlstein, T., Londborg, P., et al. Efficacy of sertraline in preventing relapse of post-traumatic stress disorder: results of a 28-week double-blind, placebo-controlled study. Am J Psychiatr (2001) 158(12):1974–1981.
Davidson, R. J. Affective style and affective disorders: perspectives from affective neuroscience.
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Flor-Henry, P. Uncertain aspects of the localization of the cerebral symptoms relating and deter-mining emotion. Biol Psychiatr (1979) 14:677–698.
Kinsbourne, M., and Bemporad, B. Lateralization of emotion: a model and the evidence. In N. A. Fox and R. J. Davidson, eds., The Psychobiology of Affective Development, Hinsdale, N.J.:
Lawrence Erlbaum Associates, 1984.
Lipsey, J. R., Robinson, R. G., Pearlson, G. D., et al. Mood change following bilateral hemisphere brain injury. Br J Psychiatr (1983) 143:266–273.
Tucker, D. M. Lateral brain function, emotion, and conceptualizations. Psychol Bull (1981) 89:19–46.
124 Poststroke depression