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Lanzenberger R, Baldinger P, Hahn A, Global decrease of serotonin-1A receptor binding after electroconvulsive therapy in major depression measured by PET

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
Molecular Psychiatry (Impact Factor: 15.15). 07/2012; 18(1). DOI: 10.1038/mp.2012.93
Source: PubMed

ABSTRACT Electroconvulsive therapy (ECT) is a potent therapy in severe treatment-refractory depression. Although commonly applied in psychiatric clinical routine since decades, the exact neurobiological mechanism regarding its efficacy remains unclear. Results from preclinical and clinical studies emphasize a crucial involvement of the serotonin-1A receptor (5-HT(1A)) in the mode of action of antidepressant treatment. This includes associations between treatment response and changes in 5-HT(1A) function and density by antidepressants. Further, alterations of the 5-HT(1A) receptor are consistently reported in depression. To elucidate the effect of ECT on 5-HT(1A) receptor binding, 12 subjects with severe treatment-resistant major depression underwent three positron emission tomography (PET) measurements using the highly selective radioligand [carbonyl-(11)C]WAY100635, twice before (test-retest variability) and once after 10.08±2.35 ECT sessions. Ten patients (∼83%) were responders to ECT. The voxel-wise comparison of the 5-HT(1A) receptor binding (BP(ND)) before and after ECT revealed a widespread reduction in cortical and subcortical regions (P<0.05 corrected), except for the occipital cortex and the cerebellum. Strongest reductions were found in regions consistently reported to be altered in major depression and involved in emotion regulation, such as the subgenual part of the anterior cingulate cortex (-27.5%), the orbitofrontal cortex (-30.1%), the amygdala (-31.8%), the hippocampus (-30.6%) and the insula (-28.9%). No significant change was found in the raphe nuclei. There was no significant difference in receptor binding in any region comparing the first two PET scans conducted before ECT. This PET study proposes a global involvement of the postsynaptic 5-HT(1A) receptor binding in the effect of ECT.Molecular Psychiatry advance online publication, 3 July 2012; doi:10.1038/mp.2012.93.

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    • "This is in accordance with investigations in depressed patients similarly exhibiting reduced 5-HT 1A receptor densities compared with healthy subjects (Drevets et al., 1999). Just as shown for SSRIs in anxiety disorders (Spindelegger et al., 2009), electroconvulsive therapy was accompanied by a downregulation of 5-HT 1A receptor binding in depressed patients (Lanzenberger et al., 2013). Additionally, Gray et al. (2013) determined a decrease of 5-HT 1A receptor binding in depressed patients following shortterm treatment with SSRIs. "
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    • "Seminal studies by Mayberg and colleagues have demonstrated evidence for hyperactivity of SGC in treatment-resistant populations of depressed patients [28] and have documented that deep brain stimulation (DBS) of subgenual cingulate white matter results in remission in some previously treatment-resistant patients [29]. Consistently, recent evidence demonstrates that electroconvulsive therapy (ECT) in major depression weakens symptomatology while reducing serotonin-1A receptor binding in the subgenual part of cingulate cortex [30] as well as decreasing left dorsolateral prefrontal connectivity [16]. Transcranial magnetic stimulation over dorsolateral prefrontal cortex (DLPFC) also appears to be effective by indirectly influencing SGC, whose activity is anti-correlated to DLPFC [31]. "
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    • "We previously published an in-loop set-up for the routine production of [carbo- nyl- 11 C]WAY-100635 (Wadsak et al., 2007) which is still in use in our facility in various clinical studies dealing with the (patho-)physiological distribution of serotonin 5HT 1A receptor, e.g. basic neuroscience investigations (Hahn et al., 2012; Savli et al., 2012; Witte et al., 2009), studies of several psychiatric disorders including major depression (MDD) (Lanzenberger et al., 2012), anxiety disorders (Lanzenberger et al., 2007; Spindelegger et al., 2009) and temporal lobe epilepsy (Assem-Hilger et al., 2010). "
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