Resting regional brain metabolism in social anxiety disorder and the effect of moclobemide therapy
While there is mounting evidence of abnormal reactivity of several brain regions in social anxiety disorder, and disrupted functional connectivity between these regions at rest, relatively little is known regarding resting regional neural activity in these structures, or how such activity is affected by pharmacotherapy. Using 2-deoxy-2-(F-18)fluoro-D-glucose positron emission tomography, we compared resting regional brain metabolism between SAD and healthy control groups; and in SAD participants before and after moclobemide therapy. Voxel-based analyses were confined to a predefined search volume. A second, exploratory whole-brain analysis was conducted using a more liberal statistical threshold. Fifteen SAD participants and fifteen matched controls were included in the group comparison. A subgroup of SAD participants (n = 11) was included in the therapy effect comparison. No significant clusters were identified in the primary analysis. In the exploratory analysis, the SAD group exhibited increased metabolism in left fusiform gyrus and right temporal pole. After therapy, SAD participants exhibited reductions in regional metabolism in a medial dorsal prefrontal region and increases in right caudate, right insula and left postcentral gyrus. This study adds to the limited existing work on resting regional brain activity in SAD and the effects of therapy. The negative results of our primary analysis suggest that resting regional activity differences in the disorder, and moclobemide effects on regional metabolism, if present, are small. While the outcomes of our secondary analysis should be interpreted with caution, they may contribute to formulating future hypotheses or in pooled analyses.
KeywordsSocial anxiety disorder Moclobemide therapy Positron emission tomography Fluorodeoxyglucose Regional metabolism Resting state
The PhD from which this study emanated was funded by the South African Medical Research Council under the MRC Clinician Researcher Programme. Study costs were funded by the Nuclear Technologies in Medicine and the Biosciences Initiative (NTeMBI), a national technology platform developed and managed by the South African Nuclear Energy Corporation (Necsa) and funded by the department of Science and Technology; and the Harry Crossley Foundation.
Data collection: A Doruyter, L Taljaard, C Lochner.
Data processing and analysis: A Doruyter, P Dupont.
Manuscript: A Doruyter.
Manuscript review: All authors.
Supervisors: JM Warwick, C Lochner.
Compliance with ethical standards
None of the funders played any role in study design; collection, analysis, or interpretation of data; in the writing of this article or in the decision to submit it for publication.
Disclosure of potential conflicts of interest
This study was funded by the South African Medical Research Council under the MRC Clinician Researcher Programme; the Nuclear Technologies in Medicine and the Biosciences Initiative (NTeMBI), a national technology platform developed and managed by the South African Nuclear Energy Corporation (Necsa) and funded by the department of Science and Technology; and the Harry Crossley Foundation.
Profs Stein and Lochner receive funding from the MRC.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- Arnold-Anteraper S, Triantafyllou C, Sawyer AT et al (2014) Hyper-connectivity of subcortical resting-state networks in social anxiety disorder. Brain Connect. https://doi.org/10.1089/brain.2013.0180
- Beck AT, Steer RA, Brown GK, Beck depression inventory—II M (1996) Manual for beck depression inventory-IIGoogle Scholar
- Bonnet U (2003) Moclobemide: therapeutic use and clinical studies. CNS Drug Rev 9:97–140. https://doi.org/10.1111/j.1527-3458.2003.tb00245.x CrossRefPubMedGoogle Scholar
- Caulfield MD, Servatius RJ (2013) Focusing on the possible role of the cerebellum in anxiety disorders. New Insights into Anxiety Disorders. https://doi.org/10.5772/52954.
- Doruyter A, Groenewold NA, Dupont P, Stein DJ, Warwick JM (2017) Resting-state FMRI and social cognition: an opportunity to connect. Hum Psychopharmacol Clin Exp e2627. https://doi.org/10.1002/hup.2627
- First MB, Spitzer RL, Gibbon M, Williams JBW (1996) Structured clinical interview for DSM-IV Axis I disorders — clinician edition. Biometrics Research Department, New York State Research Institute, New YorkGoogle Scholar
- Guideline For Good Clinical Practice: ICH Harmonised Tripartite Guideline. European Medicines Agency (2002) www.edctp.org/fileadmin/documents/EMEA_ICH-GCP_Guidelines_July_2002.pdf Accessed 9 Oct 2017
- Guy W (1976) Clinical global impression (CGI). ECDEU assessment manual for psychopharmacology, revised. US Department of Health, Education, and Welfare, RockvilleGoogle Scholar
- Langer JK, Rodebaugh TL (2014) Comorbidity of social anxiety disorder and depression. https://doi.org/10.1093/oxfordhb/9780199797004.013.030
- Murray RJ, Schaer M, Debbané M (2012) Degrees of separation: a quantitative neuroimaging meta-analysis investigating self-specificity and shared neural activation between self- and other-reflection. Neurosci Biobehav Rev 36:1043–1059. https://doi.org/10.1016/j.neubiorev.2011.12.013 CrossRefPubMedGoogle Scholar
- National Collaborating Centre for Mental Health (UK) (2013) Social anxiety disorder: recognition, Assessment and treatment. British Psychological Society, Leicester (UK)Google Scholar
- Spielberger CD, Gorsuch RL (1983) Manual for the state-trait anxiety inventory (Form Y) (Self-evaluation questionnaire). Consulting Psychologists Press, Palo AltoGoogle Scholar
- van der Linden G, van Heerden B, Warwick J et al (2000) Functional brain imaging and pharmacotherapy in social phobia: single photon emission computed tomography before and after treatment with the selective serotonin reuptake inhibitor citalopram. Prog Neuro-Psychopharmacol Biol Psychiatry 24:419–438CrossRefGoogle Scholar