83 The subjects of this study, after remission

of depression, received continuation treatment with nortriptyline at plasma levels 60 to 150 ng/rriL for 16 weeks and were then randomly assigned to cither nortriptyline maintenance therapy or placebo for a period of up to 2 years. Abnormal initiation/perseveration scores, but not memory impairment, were LY335979 purchase associated with relapse (Figure 4) and recurrence (Figure 5) of geriatric depression and with fluctuations of depressive symptomatology in the whole group and in subjects who never met criteria for relapse or recurrence during the follow-up period. Memory impairment, disability, Inhibitors,research,lifescience,medical medical burden, social support, and history of previous episodes did not significantly influence the outcome of depression in this sample. These findings provide the rationale for studies of the role of specific prefrontal pathways in predisposing Inhibitors,research,lifescience,medical or perpetuating depressive syndromes or symptoms in the elderly Abnormal initiation/perseveration scores reflect striatofrontal dysfunction, an abnormality associated with vascular depression. Inhibitors,research,lifescience,medical While direct studies are needed, these findings suggest that vascular depression has a chronic and relapsing course. Figure 4. Cox proportional hazard analysis of 57 elderly patients who

had recovered from major depression and received continuation treatment with nortriptyline at plasma levels of 60 to150 ng/mL Seven patients had a relapse during continuation phase. Fitted survival … Figure 5. Cox proportional hazard analysis of 43 elderly patients who had recovered from major depression, completed

a 16-week continuation treatment with Inhibitors,research,lifescience,medical nortriptyline at plasma levels of 60-150 ng/mL and were randomly assigned to nortriptyline (NT) or placebo … Mechanisms of vascular depression Two broad hypotheses can be tested regarding localization of lesions in vascular depression. The first hypothesis is that small lesions disrupting critical pathways may precipitate vascular depression. This hypothesis is supported by stroke studies showing that lacunar Inhibitors,research,lifescience,medical infarcts of the left caudate head or the left frontal pole often lead to DHFR inhibitor manufacturer depression.26 The direct lesion-depression pathway may account for vascular depression cases that develop after stroke. The second hypothesis is that accumulation of lesions exceeding a threshold predisposes to depression. This hypothesis is most applicable to patients with neurologically silent lesions or an old stroke. The threshold concept is supported by the observation that a total area of WMHs exceeding 10 cm2 may result in impaired attention and executive skills.82 Similar impairments have been noted in late-onset depression with vascular risk factors.84-87 Vascular lesions may damage glutaminergic fibers from cortical areas to the striatum, or the GABAergic neurons of the limbic-basal ganglia circuits and alter the input to cortex.