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Brain serotonin2 (5-hydroxytryptamine2; 5-HT2) receptors were considered potential targets for therapeutic efficacy of electroconvulsive therapy (ECT), but pre-clinical studies showed that electroconvulsive shock up-regulates 5-HT2 receptors in contrast to antidepressant medications, which down-regulate brain 5-HT2 receptors. Positron emission tomography (PET) studies in individuals with depression confirmed that antidepressant medications reduce brain 5-HT2 receptors, but the effects of ECT on these receptors in individuals with depression are unknown.
To determine if a course of ECT alters brain 5-HT2 receptors in individuals with depression and whether such changes correlate with improvement in symptoms.
Fifteen people with major depression, refractory to antidepressant therapy and referred for a course of ECT, had an [18F]setoperone scan during baseline drug-free washout period and another after a course of ECT. We assessed changes in brain 5-HT2 receptors with ECT and their relationship to therapeutic outcome.
Widespread reduction in brain 5-HT2 receptors was observed in all cortical areas with changes slightly more prominent in the right hemisphere. There was a trend for correlation between reduction in brain 5-HT2 receptors in right parahippocampal gyrus, right lingual gyrus and right medial frontal gyrus, and improvement in depressive symptoms.
Unlike in rodents, and similar to antidepressants, ECT reduces brain 5-HT2 receptors in individuals with depression. The ability of ECT to further down-regulate brain 5-HT2 receptors in antidepressant non-responsive individuals may explain its efficacy in those people with antidepressant refractory depression.
Although 5-hydroxytryptamine (5-HT) has been implicated in mania, the precise alterations in the 5-HT system remain elusive.
To assess brain 5-HT2 receptors in drug-free individuals experiencing a manic episode in comparison with healthy volunteers using positron emission tomography (PET).
Participants (n = 10) with DSM–IV bipolar I disorder – manic episode and healthy controls (n = 10) underwent [18F]- setoperone scans. The differences in 5-HT2 receptor binding potential between the two groups were determined using statistical parametric mapping (SPM) analysis.
Age was a significant correlate with 5-HT2 receptor binding potential with a similar magnitude of correlation in both groups. The SPM analysis with age as a covariate showed that the individuals with current mania had significantly lower 5-HT2 receptor binding potential in frontal, temporal, parietal and occipital cortical regions, with changes more prominent in the right cortical regions compared with controls.
This study suggests that brain 5-HT∗2 receptors are decreased in people with acute mania.
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