Analyses of Pathophysiology and Development of Treatment Strategies in Late-Life Refractory Depression.

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1. We investigated the short-term response rates of ECT in consecutive 16 patients with late-life refractory depression and 6-month relapse rates in 13 patients following response to ECT.Short-term response rate was 81% and 6-month relapse rate was 46%.2. Using ^<99m>Tc-HMPAO SPECT, we examined the changes of rCBF patterns in nine late-life patients with major depressive episodes before and following response to ECT A mean rCBF was significantly decreased in the patients before ECT compared with the control, significantly increased (normalized) in the patients 2 weeks after ECT compared with that before ECT, and still increased in the patients 12 weeks after ECT compared with that before ECT.However, a significant rCBF reduction was found in the bilateral pre- and subcallosal anterior cingulate cortex, the bilateral caudal orbitofrontal cortex, the right insular cortex and the right posterior middle frontal gyrus in patients before ECT compared with the control, and similar rCBF patterns were shown at 2 weeks and 12 weeks after ECT.A mean rCBF reduction may have a state-related property while persistent anterior paralimbic hypoperfusion may have a trait-related property in late-life depression referred for ECT.3. We investigated the effects of acute and chronic ECS on 5-HT transporter mRNA expression in rat raphe nucleus. 5-HTT mRNA expression was decreased 9, 24 hours after acute ECS and 3, 9, 24 hours and 2 weeks after chronic ECS in rat raphe nucleus. We presume that the adaptive change in 5-HTT mRNA expression is possibly related to the therapeutic efficacy of ECT on medication-resistant depression.