TY - JOUR
T1 - Atlas of type 2 dopamine receptors in the human brain: Age and sex dependent variability in a large PET cohort
AU - Malén, Tuulia
AU - Karjalainen, Tomi
AU - Isojärvi, Janne
AU - Vehtari, Aki
AU - Bürkner, Paul Christian
AU - Putkinen, Vesa
AU - Kaasinen, Valtteri
AU - Hietala, Jarmo
AU - Nuutila, Pirjo
AU - Rinne, Juha
AU - Nummenmaa, Lauri
N1 - Funding Information:
This study was supported by the Academy of Finland (grants #294897 and #332225 to L.N.), the Sigrid Jus?lius Foundation (grant to L.N.), the P?ivikki and Sakari Sohlberg Foundation (personal grant to T.M.) and the State research funding for expert responsibility area (ERVA) of the Tyks Turku University Hospital (personal grants to T.M. and L.N.), as well as Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy (personal grant EXC 2075 ? 390740016 to P.B.). We thank senior researchers Marco Bucci and Semi Helin, as well as Professor Kari Auranen for sharing their expertise on kinetic modeling, radiochemistry and Bayesian data analysis, respectively. We also thank Post-Doctoral researcher Jouni Tuisku for his consultance and help with image preprocessing and data management, as well as hospital physicists Tuula Tolvanen and Jukka Ihalainen for sharing their knowledge on the physical properties of the scanners. Authors have nothing to disclose.
PY - 2022/7/15
Y1 - 2022/7/15
N2 - Background: The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. Methods: In this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. Results: Striatal D2R availability decreased through age for both sexes (2-5 % in striatal ROIs per 10 years) and was higher in females versus males throughout age (7-8% in putamen). BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). Conclusions: D2R availability is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.
AB - Background: The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. Methods: In this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. Results: Striatal D2R availability decreased through age for both sexes (2-5 % in striatal ROIs per 10 years) and was higher in females versus males throughout age (7-8% in putamen). BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). Conclusions: D2R availability is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.
KW - Ageing
KW - Bayesian data-analysis
KW - Positron emission tomography
KW - Sex-difference
KW - Type 2 dopamine receptors
KW - [11C]raclopride
UR - http://www.scopus.com/inward/record.url?scp=85129477217&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2022.119149
DO - 10.1016/j.neuroimage.2022.119149
M3 - Article
C2 - 35367652
AN - SCOPUS:85129477217
SN - 1053-8119
VL - 255
SP - 1
EP - 9
JO - NeuroImage
JF - NeuroImage
M1 - 119149
ER -