The effect of electroconvulsive therapy on cerebral monoamine oxidase A expression in treatment-resistant depression investigated using positron emission tomography

Abstract

a b s t r a c tBackground: Electroconvulsive therapy (ECT) constitutes one of the most effective antidepressant treatment strategies in major depression (MDD). Despite its common use and uncontested efficacy, its mechanism of action is still insufficiently understood. Previously, we showed that ECT is accompanied by a global decrease of serotonin-1A receptors in MDD; however, further studies to investigate the involvement of the serotonergic system in the mechanism of action of ECT are warranted. The monoamine oxidase A (MAO-A) represents an important target for antidepressant treatments and was found to be increased in MDD. Here, we investigated whether ECT impacts on MAO-A levels in treatmentresistant patients (TRD). Methods: 16 TRD patients (12 female, age 45.94 ± 9.68 years, HAMD 25.12 ± 3.16) with unipolar depression according to DSM-IV were scanned twice before (PET1 and PET2, to assess test-retest variability under constant psychopharmacotherapy) and once after (PET3) completing a minimum of eight unilateral ECT sessions using positron emission tomography and the radioligand [ 11 C]harmine to assess cerebral MAO-A distribution volumes (V T ). Age-and sex-matched healthy subjects (HC) were measured once. Results: Response rate to ECT was 87.5%. MAO-A V T was found to be significantly reduced after ECT in TRD patients (À3.8%) when assessed in 27 a priori defined ROIs (p < 0.001). Test-retest variability between PET1 and PET2 was 3.1%. MAO-A V T did not significantly differ between TRD patients and HC at baseline. Conclusions: The small effect size of the significant reduction of MAO-A V T after ECT in the range of testretest variability does not support the hypothesis of a clinically relevant mechanism of action of ECT based on MAO-A. Furthermore, in contrast to studies reporting elevated MAO-A V T in unmedicated depressed patients, MAO-A levels were found to be similar in TRD patients and HC which might be attributed to the continuous antidepressant pharmacotherapy in the present sample.

Treatment‐resistant depression: An overview for psychiatric advanced practice nurses

“…35 The monoamine neurotransmission theory posits that ECT increases neurotransmitter availability and changes receptor sensitivity, enhancing dopaminergic, serotonergic, and adrenergic neurotransmission. 36 There is some evidence that both GABA and glutamate are implicated in ECT, as well. 37 The neuroendocrine theory hypothesizes that ECT induces activation of the hypothalamicpituitary axis and subsequent hormone release, and these hormones mediate antidepressant effects.…”

Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers

“…Because the range of neuroanatomical regions associated with each of these disorders is vast, rarely, if ever, can these therapeutics cover all affected regions of the CNS. Because of this, the medical community has resorted to electrical chemical therapies in the form of deep brain stimulation by transcranial electrode implantation (104), electroconvulsive therapy (ECT) (105), and transmagnetic stimulation (TMS) (106) to treat those patients whose conditions have been resistant to frontline pharmacologic therapies. Although the cellular and molecular mechanisms by which these therapies act is not understood, it does indicate that such approaches have a general effect beyond what is typically seen with any set of pharmacological therapeutics.…”

Correlation of receptor density and mRNA expression patterns in the human cerebral cortex

“…PET) have become commonplace in psychiatric research (Lui et al, 2016), e.g. to investigate possible effects of electroconvulsive therapy in depressed patients (Baldinger-Melich et al, 2019) or the effect of bright light therapy in patients with affective disorders (Spies et al, 2018). However some of the basic hypotheses of modern psychiatry, including the monoamine hypothesis, still stem from decade-old post mortem findings (Cosci and Chouinard, 2019;Horton, 1992).…”