Three cortico-striatopallido-thalamo-corti cal (CSPTC) pathways may be relevant to depression.76,77 Damage of the orbitofrontal circuit may lead to disinhibition, irritability, and diminished sensitivity to social cues.76 Damage of the anterior cingulate may result in apathy

and reduced initiative.76 Damage of the dorsolateral circuit may result in difficulties in set shifting, learning, and word list generation.76 These behavioral abnormalities resemble in part the depressive syndrome. Treatment response in vascular depression Several studies suggest that vascular depression may have a poor outcome. Late-onset Inhibitors,research,lifescience,medical depression, an entity that often occurs in the context of vascular disease, is a rather chronic disorder.78 In elderly dépressives, leukoencephalopathy

was found to be associated with low quantitative electroencephalogram (qEEG) coherence79,80; low qEEG coherence predicted failure to recover, residual depressive symptomatology, increased mortality, and disability.79,80 Inhibitors,research,lifescience,medical We studied the relationship of clinical, neuropsychological, and electrophysiological measures Inhibitors,research,lifescience,medical of prefrontal dysfunction with treatment response in elderly patients with major depression.81 Abnormal initiation/perseveration scores of the Dementia Rating Scale, psychomotor retardation, and long P300 latency of the auditory evoked potential predicted 58% of the variance in change of depression scores from baseline to 6 weeks. Depressed patients who remained symptomatic had more abnormal Inhibitors,research,lifescience,medical initiation/perseveration scores and longer P300 latency compared with depressed patients who achieved remission and control subjects. There were no differences between the last two groups. These findings suggest that prefrontal dysfunction is associated with poor or delayed antidepressant response in depressed elderly patients. Although not very specific, abnormal initiation/perseveration

Inhibitors,research,lifescience,medical scores, psychomotor retardation, and long P300 latency are thought to reflect striatofrontal impairment, an abnormality often caused by vascular disease.82 also We are currently conducting a study of average evoked SGC-CBP30 in vivo responses following the Stroop response inhibition test. The Stroop requires integrity of the anterior cingulate and thus is more specific to frontal dysfunction than our earlier tests. Preliminary findings suggest that, compared with controls, depressed elderly patients overrecruit prefrontal neurons during the response inhibition task (Figure 3). Further research will examine whether this abnormality is associated with poor réponse to antidepressants. Figure 3. Increased frontal activation in a 73-year-old patient with major depression (top) compared with a 70-year-old psychiatrically normal subject (bottom). Evoked responses were recorded following the Stroop Color interference task. À total of 162 …