Normative database of the serotonergic system in healthy subjects using multi-tracer PET.
The highly diverse serotonergic system with at least 16 different receptor subtypes is implicated in the pathophysiology of most neuropsychiatric disorders including affective and anxiety disorders, obsessive compulsive disorder, post-traumatic stress disorder, eating disorders, sleep disturbance, attention deficit/hyperactivity disorder, drug addiction, suicidal behavior, schizophrenia, Alzheimer, etc. Alterations of the interplay between various pre- and postsynaptic receptor subtypes might be involved in the pathogenesis of these disorders. However, there is a lack of comprehensive in vivo values using standardized procedures. In the current PET study we quantified 3 receptor subtypes, including the major inhibitory (5-HT(1A) and 5-HT(1B)) and excitatory (5-HT(2A)) receptors, and the transporter (5-HTT) in the brain of healthy human subjects to provide a database of standard values. PET scans were performed on 95 healthy subjects (age=28.0 ± 6.9 years; 59% males) using the selective radioligands [carbonyl-(11)C]WAY-100635, [(11)C]P943, [(18)F]altanserin and [(11)C]DASB, respectively. A standard template in MNI stereotactic space served for region of interest delineation. This template follows two anatomical parcellation schemes: 1) Brodmann areas including 41 regions and 2) AAL (automated anatomical labeling) including 52 regions. Standard values (mean, SD, and range) for each receptor and region are presented. Mean cortical and subcortical binding potential (BP) values were in good agreement with previously published human in vivo and post-mortem data. By means of linear equations, PET binding potentials were translated to post-mortem binding (provided in pmol/g), yielding 5.89 pmol/g (5-HT(1A)), 23.5 pmol/g (5-HT(1B)), 31.44 pmol/g (5-HT(2A)), and 11.33 pmol/g (5-HTT) being equivalent to the BP of 1, respectively. Furthermore, we computed individual voxel-wise maps with BP values and generated average tracer-specific whole-brain binding maps. This knowledge might improve our interpretation of the alterations taking place in the serotonergic system during neuropsychiatric disorders.
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
Markus
M
Savli
Andreas
A
Bauer
Markus
M
Mitterhauser
Yu-Shin
YS
Ding
Andreas
A
Hahn
Tina
T
Kroll
Alexander
A
Neumeister
Daniela
D
Haeusler
Johanna
J
Ungersboeck
Shannan
S
Henry
Sanaz Attaripour
SA
Isfahani
Frank
F
Rattay
Wolfgang
W
Wadsak
Siegfried
S
Kasper
Rupert
R
Lanzenberger
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016208:Databases, Factual / Q000592:standards*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods* / Q000592:standards*; D011985:Receptors, Serotonin / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D059326:Serotonergic Neurons / Q000000981:diagnostic imaging* / Q000378:metabolism*; D055815:Young Adult
D011985:Receptors, Serotonin