Effect of electroconvulsive therapy on brain 5-HT₂ receptors in major depression

<jats:sec><jats:title>Background</jats:title><jats:p>Brain serotonin<jats:sub>2</jats:sub> (5-hydroxytryptamine<jats:sub>2</jats:sub>; 5-HT<jats:sub>2</jats:sub>) receptors were considered potential targets for therapeutic efficacy of electroconvulsive therapy (ECT), but pre-clinical studies showed that electroconvulsive shock up-regulates 5-HT<jats:sub>2</jats:sub> receptors in contrast to antidepressant medications, which down-regulate brain 5-HT<jats:sub>2</jats:sub> receptors. Positron emission tomography (PET) studies in individuals with depression confirmed that antidepressant medications reduce brain 5-HT<jats:sub>2</jats:sub> receptors, but the effects of ECT on these receptors in individuals with depression are unknown.</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>To determine if a course of ECT alters brain 5-HT<jats:sub>2</jats:sub> receptors in individuals with depression and whether such changes correlate with improvement in symptoms.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Fifteen people with major depression, refractory to antidepressant therapy and referred for a course of ECT, had an [<jats:sup>18</jats:sup>F]setoperone scan during baseline drug-free washout period and another after a course of ECT. We assessed changes in brain 5-HT<jats:sub>2</jats:sub> receptors with ECT and their relationship to therapeutic outcome.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Widespread reduction in brain 5-HT<jats:sub>2</jats:sub> 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-HT<jats:sub>2</jats:sub> receptors in right parahippocampal gyrus, right lingual gyrus and right medial frontal gyrus, and improvement in depressive symptoms.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Unlike in rodents, and similar to antidepressants, ECT reduces brain 5-HT<jats:sub>2</jats:sub> receptors in individuals with depression. The ability of ECT to further down-regulate brain 5-HT<jats:sub>2</jats:sub> receptors in antidepressant non-responsive individuals may explain its efficacy in those people with antidepressant refractory depression.</jats:p></jats:sec>