CONTEXT: Highly significant elevations in regional brain monoamine oxidase A (MAO-A) binding were recently reported during major depressive episodes (MDEs) of major depressive disorder (MDD). The relationship between MAO-A levels and selective serotonin reuptake inhibitor (SSRI) treatment, recovery, and recurrence in MDD is unknown. OBJECTIVES: To determine whether brain MAO-A binding changes after SSRI treatment, whether brain MAO-A binding normalizes in subjects with MDD in recovery, and whether there is a relationship between prefrontal and anterior cingulate cortex MAO-A binding in recovery and subsequent recurrence of MDE. DESIGN: Case-control study. SETTING: Tertiary care psychiatric hospital. PARTICIPANTS: Twenty-eight healthy subjects, 16 subjects with an MDE secondary to MDD, and 18 subjects with MDD in recovery underwent carbon 11-labeled harmine positron emission tomography scans. Subjects with MDE were scanned before and after 6 weeks of SSRI treatment. All were otherwise healthy, nonsmoking, and medication free. Subjects with MDD in recovery were followed up for 6 months after MAO-A binding measurement. MAIN OUTCOME MEASURE: Monoamine oxidase A V(T), an index of MAO-A density, was measured in the prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, dorsal putamen, ventral striatum, thalamus, anterior temporal cortex, midbrain, and hippocampus. RESULTS: Monoamine oxidase A V(T) was significantly elevated in each brain region both during MDE and after SSRI treatment as compared with healthy controls. During recovery, MAO-A V(T) was significantly elevated in each brain region; however, those who went on to recurrence had significantly higher MAO-A V(T) in the prefrontal and anterior cingulate cortex than those who did not. CONCLUSIONS: Elevated MAO-A binding after SSRI treatment indicates persistence of a monoamine-lowering process not present in health. This provides a strong conceptual rationale for continuing SSRI treatment during early remission. Greater MAO-A binding in the prefrontal and anterior cingulate cortex in subjects with MDD in recovery and its association with subsequent recurrence argue that deficient monoamine neuromodulation may persist into recovery and contribute to recurrence.
CONTEXT: Highly significant elevations in regional brain monoamine oxidase A (MAO-A) binding were recently reported during major depressive episodes (MDEs) of major depressive disorder (MDD). The relationship between MAO-A levels and selective serotonin reuptake inhibitor (SSRI) treatment, recovery, and recurrence in MDD is unknown. OBJECTIVES: To determine whether brain MAO-A binding changes after SSRI treatment, whether brain MAO-A binding normalizes in subjects with MDD in recovery, and whether there is a relationship between prefrontal and anterior cingulate cortex MAO-A binding in recovery and subsequent recurrence of MDE. DESIGN: Case-control study. SETTING: Tertiary care psychiatric hospital. PARTICIPANTS: Twenty-eight healthy subjects, 16 subjects with an MDE secondary to MDD, and 18 subjects with MDD in recovery underwent carbon 11-labeled harmine positron emission tomography scans. Subjects with MDE were scanned before and after 6 weeks of SSRI treatment. All were otherwise healthy, nonsmoking, and medication free. Subjects with MDD in recovery were followed up for 6 months after MAO-A binding measurement. MAIN OUTCOME MEASURE: Monoamine oxidase A V(T), an index of MAO-A density, was measured in the prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, dorsal putamen, ventral striatum, thalamus, anterior temporal cortex, midbrain, and hippocampus. RESULTS:Monoamine oxidase A V(T) was significantly elevated in each brain region both during MDE and after SSRI treatment as compared with healthy controls. During recovery, MAO-A V(T) was significantly elevated in each brain region; however, those who went on to recurrence had significantly higher MAO-A V(T) in the prefrontal and anterior cingulate cortex than those who did not. CONCLUSIONS: Elevated MAO-A binding after SSRI treatment indicates persistence of a monoamine-lowering process not present in health. This provides a strong conceptual rationale for continuing SSRI treatment during early remission. Greater MAO-A binding in the prefrontal and anterior cingulate cortex in subjects with MDD in recovery and its association with subsequent recurrence argue that deficient monoamine neuromodulation may persist into recovery and contribute to recurrence.
Authors: Renata L de Oliveira; Guilherme T Voss; Jaini J Paltian; Mikaela P Pinz; Marina Laura C P Torres; Michele P Moreira; Marina C Dilelio; Claudio C Silveira; Ethel A Wilhelm; Cristiane Luchese Journal: Metab Brain Dis Date: 2019-06-08 Impact factor: 3.584
Authors: S J Harrison; A E Tyrer; R D Levitan; X Xu; S Houle; A A Wilson; J N Nobrega; P M Rusjan; J H Meyer Journal: Acta Psychiatr Scand Date: 2015-04-17 Impact factor: 6.392
Authors: Matthew Grunewald; Shakevia Johnson; Deyin Lu; Zhe Wang; Gwen Lomberk; Paul R Albert; Craig A Stockmeier; Jeffrey H Meyer; Raul Urrutia; Klaus A Miczek; Mark C Austin; Junming Wang; Ian A Paul; William L Woolverton; Seungmae Seo; Donald B Sittman; Xiao-Ming Ou Journal: J Biol Chem Date: 2012-05-24 Impact factor: 5.157
Authors: Francesca Zanderigo; Alexandra E D'Agostino; Nandita Joshi; Martin Schain; Dileep Kumar; Ramin V Parsey; Christine DeLorenzo; J John Mann Journal: Mol Imaging Biol Date: 2018-08 Impact factor: 3.488
Authors: Yekta Dowlati; Arun V Ravindran; Zindel V Segal; Donna E Stewart; Meir Steiner; Jeffrey H Meyer Journal: Proc Natl Acad Sci U S A Date: 2017-03-13 Impact factor: 11.205
Authors: Shakevia Johnson; Craig A Stockmeier; Jeffrey H Meyer; Mark C Austin; Paul R Albert; Junming Wang; Warren L May; Grazyna Rajkowska; James C Overholser; George Jurjus; Lesa Dieter; Chandra Johnson; Donald B Sittman; Xiao-Ming Ou Journal: Neuropsychopharmacology Date: 2011-06-08 Impact factor: 7.853