Brain monoamine oxidase A binding in major depressive disorder: relationship to selective serotonin reuptake inhibitor treatment, recovery, and recurrence.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
Case-control study.


METHODS
Tertiary care psychiatric hospital.


METHODS
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.


METHODS
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.
Meyer
Jeffrey H
JH
Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario M5T 1R8, Canada. jeff.meyer@camhpet.ca
Wilson
Alan A
AA
Sagrati
Sandra
S
Miler
Laura
L
Rusjan
Pablo
P
Bloomfield
Peter M
PM
Clark
Michael
M
Sacher
Julia
J
Voineskos
Aristotle N
AN
Houle
Sylvain
S
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology*; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000378:metabolism; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology; D006247:Harmine / Q000378:metabolism; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology; D012008:Recurrence; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014018:Tissue Distribution; D016896:Treatment Outcome
D002250:Carbon Radioisotopes; D006247:Harmine; D008995:Monoamine Oxidase; D017367:Selective Serotonin Reuptake Inhibitors