Imaging the serotonin transporter during major depressive disorder and antidepressant treatment

• Published in: Journal of psychiatry & neuroscience Vol. 32; no. 2; pp. 86 - 102
• Main Author: Meyer, Jeffrey H., MD
• Format: Journal Article
• Language: French; English
• Published: Ottawa, ON Canadian Medical Association 01.03.2007; CMA Impact Inc; CMA Impact, Inc
• Subjects: Adult and adolescent clinical studies; Antidepressants; Antidepressive Agents - therapeutic use; Biological and medical sciences; Brain - diagnostic imaging; Brain - drug effects; Brain Mapping; Depression; Depression, Mental; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - drug therapy; Drug therapy; Fundamental and applied biological sciences. Psychology; Humans; Medical Education; Medical sciences; Mental depression; Mood disorders; Neurotransmitters; Positron-Emission Tomography; Psychiatric research; Psychiatry; Psychoanalysis; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Review Paper; Sensitivity and Specificity; Serotonin; Serotonin - metabolism; Serotonin Plasma Membrane Transport Proteins - drug effects; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin Uptake Inhibitors - therapeutic use; Studies; Tomography; Tomography, Emission-Computed, Single-Photon; Canada; Mood disorder; Serotonin; Psychotropic; Psychology; Neurotransmitter; Antidepressant agent; Depression; Medical imagery; Psychopathology; Severe; Psychiatry
• ISSN: 1180-4882; 1488-2434
• DOI: 10.1016/S1180-4882(07)50013-2

This paper focuses on serotonin transporter 5-HTT imaging to investigate major depressive disorder (MDD) and antidepressant occupancy. Such investigations have only recently been possible as a result of major advances in ligand development. The state of the art method is [11C]DASB PET or [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) positron emission tomography. [11C]DASB is a breakthrough for brain imaging 5-HTT. Compared with previous radioligands, [11C]DASB offers both high selectivity and a favourable ratio of specific binding relative to free and nonspecific binding. These characteristics contribute to valid, reliable quantitation of the 5-HTT binding potential (BP). The 5-HTT BP can be viewed as an index of 5-HTT density in a medication free state, or unblocked 5-HTT density in a medication-treated state. During major depressive episodes with no other axis I comorbidity, either no difference in regional 5-HTT BP or a trend toward elevated 5-HTT BP is typically found. During major depressive episodes (of MDD) with more severe symptoms of pessimism (dysfunctional attitudes), regional 5-HTT BP is elevated. In subjects with major depressive episodes and comorbid axis I psychiatric illnesses, decreased regional 5-HTT BP is often reported. With selective serotonin reuptake inhibitor (SSRI) treatment at doses that distinguish from placebo in the treatment of major depressive episodes, 5-HTT occupancy is approximately 80%, and there is a strong relation between plasma level and occupancy that is not predictable based on affinity alone. Implications of 5-HTT imaging findings for understanding major depressive disorder and antidepressant treatment will be discussed.