Article

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: 14.5). 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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    ABSTRACT: Recently, Silexan, a patented active substance comprised of an essential oil produced from Lavandula angustifolia flowers, has been authorized in Germany as a medicinal product for the treatment of states of restlessness related to anxious mood. Its efficacy has been shown in several forms of anxiety disorders. Findings from preclinical and clinical studies attribute a major role in the pathogenesis and treatment of anxiety to the serotonin-1A receptor (5-HT1A). To elucidate the effect of Silexan on 5-HT1A receptor binding, 17 healthy men underwent two positron emission tomography measurements using the radioligand [carbonyl-(11)C]WAY-100635 following the daily intake of 160 mg Silexan or placebo over a minimum of eight weeks, respectively (randomized, double-blind, cross-over design). Additionally, structural magnetic resonance imaging and voxel-based morphometry analysis was performed to determine potential effects on gray matter microstructure. 5-HT1A receptor binding potential was shown to be significantly reduced following the intake of Silexan compared to placebo in two large clusters encompassing the temporal gyrus, the fusiform gyrus, the hippocampus on one hand as well as the insula and the anterior cingulate cortex on the other hand. No effects of Silexan on gray matter volume could be detected in this investigation. This PET study proposes an involvement of the serotonin-1A receptor in the anxiolytic effects of Silexan. © The Author 2014. Published by Oxford University Press on behalf of CINP.
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    • "A possible interpretation would be that the change in BP ND might have been a nonspecific effect of the given intervention but did not mediate the treatment response. In this regard, we have to bear in mind the difficulties in earlier studies in finding associations between symptom ratings of depression and PET data, even with highly effective treatments against depression such as electroconvulsive therapy (Lanzenberger et al., 2013). It is worth noting that the group of patients examined in our study was small and unexpectedly homogenous regarding treatment response, which diminishes the possibility of finding a correlation between PET data and symptom ratings. "
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    ABSTRACT: Major depression is a significant contributor to the global burden of disease, and its pathophysiology is largely unknown. The serotonin hypothesis is, however, the model with most supporting data, although the details are only worked out to some extent. Recent clinical imaging measurements indeed imply a role in major depressive disorder (MDD) for the inhibitory serotonin autoreceptor 5-hydroxytryptamine1B (5-HT1B). The aim of the current study was to examine 5-HT1B receptor binding in the brain of MDD patients before and after psychotherapy. Ten patients with an ongoing untreated moderate depressive episode were examined with positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [11C]AZ10419369, before and after treatment with internet-based cognitive behavioural therapy. All of the patients examined responded to treatment, and 70% were in remission by the time of the second PET measurement. A statistically significant 33% reduction of binding potential (BPND) was found in the dorsal brain stem (DBS) after treatment). No other significant changes in BPND were found. The DBS contains the raphe nuclei, which regulate the serotonin system. This study gives support for the importance of serotonin and the 5-HT1B receptor in the biological response to psychological treatment of MDD.
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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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    ABSTRACT: Alterations of social cognition and dysfunctional interpersonal expectations are thought to play an important role in the etiology of depression and have, thus, become a key target of psychotherapeutic interventions. The underlying neurobiology, however, remains elusive. Based upon the idea of a close link between affective and introspective processes relevant for social interactions and alterations thereof in states of depression, we used a meta-analytically informed network analysis to investigate resting-state functional connectivity in an introspective socio-affective (ISA) network in individuals with and without depression. Results of our analysis demonstrate significant differences between the groups with depressed individuals showing hyperconnectivity of the ISA network. These findings demonstrate that neurofunctional alterations exist in individuals with depression in a neural network relevant for introspection and socio-affective processing, which may contribute to the interpersonal difficulties that are linked to depressive symptomatology.
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