Mood disorders following stroke: new findings and future directions

Previous investigations by our group and others have demonstrated that poststroke depressions are not fully explained by the severity of associated impairment. We have consistently found, however, a strong association between development of major depression and left anterior brain injury. Recent studies have demonstrated that either left anterior cortical or subcortical lesions may lead to the development of major depression and that preexisting subcortical atrophy may play an important permissive role in the development of major depression. Patients with a mild degree of ventricular enlargement perhaps related to perinatal damage may be more likely to develop poststroke major depression following a lesion of the left frontal cortex or left basal ganglia than a patient without preexisting atrophy. Poststroke mania, on the other hand, is strongly associated with right hemisphere lesions as well as a preexisting subcortical atrophy and sometimes a family history of affective disorder. Thus, mania following brain injury may require the convergence of two factors: a right hemisphere brain injury and either a preexisting subcortical atrophy or a genetic vulnerability. PET scan findings have suggested that the biochemical response of the two hemispheres to stroke may be different. Right hemisphere stroke produces an increase in serotonin receptor binding, which is not found following comparable left hemisphere strokes. Within the left hemisphere, the lower the serotonin binding, the more severe the depression. This suggests that the right but not the left hemisphere may have an ability to increase serotonin binding in noninjured regions, producing a biochemical "compensation" for damage. This differential biochemical response to injury between the right and left hemisphere may partially explain why left hemisphere injury leads to depression and right hemisphere injury (in special circumstances) lead to mania. There remain, however, numerous unanswered questions and many important areas for future research. Although this area of neuropsychiatry is just beginning to develop, it is hoped that insights gained from studying mood disorders in brain-injured patients may also help to illuminate mechanisms involved in affective disorder in patients without brain injury.