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.

The mechanism by which rapid tryptophan depletion (RTD) paradigm induces depressive relapse in recently remitted patients with depression is unknown.

To determine the effects of RTD on brain 5-HT2 receptors using positron emission tomography (PET) and 18F-labelled setoperone.

Ten healthy women underwent two PET scans. Each scan was done 5 h after the ingestion of either a balanced or a tryptophan-deficient amino acid mixture, and the two test sessions were separated by at least 5 days.

The RTD decreased plasma free tryptophan levels significantly but it had no significant effects on mood. Subjects showed a significant decrease in brain 5-HT2 receptor binding in various cortical regions following the RTD session.

When taken with the evidence that antidepressant treatment is associated with a decrease in brain 5-HT2 receptors, these findings suggest that a decrease in 5-HT2 binding following RTD might be an adaptive response that provides protection against depressive symptoms.