Imaging the serotonin transporter during major depressive disorder and antidepressant treatment.
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.
Meyer
Jeffrey H
JH
Neurochemical Imaging Program in Mood Disorders, PET Centre, Centre for Addiction and Mental Health, Toronto, Ont. jeff.meyer@camhpet.ca
D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000188:drug therapy; D006801:Humans; D049268:Positron-Emission Tomography; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon
D000928:Antidepressive Agents; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors