TY  - JOUR
PY  - 2022//
TI  - Serotonin transporter binding in major depressive disorder: impact of serotonin system anatomy
JO  - Molecular psychiatry
A1  - Bartlett, Elizabeth A.
A1  - Zanderigo, Francesca
A1  - Shieh, Denise
A1  - Miller, Jeffrey
A1  - Hurley, Patrick
A1  - Rubin-Falcone, Harry
A1  - Oquendo, Maria A.
A1  - Sublette, M. Elizabeth
A1  - Ogden, R. Todd
A1  - Mann, J. John
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - Serotonin transporter (5-HTT) binding deficits are reported in major depressive disorder (MDD). However, most studies have not considered serotonin system anatomy when parcellating brain regions of interest (ROIs). We now investigate 5-HTT binding in MDD in two novel ways: (1) use of a 5-HTT tract-based analysis examining binding along serotonergic axons; and (2) using the Copenhagen University Hospital Neurobiology Research Unit (NRU) 5-HT Atlas, based on brain-wide binding patterns of multiple serotonin receptor types. [(11)C]DASB 5-HTT PET scans were obtained in 60 unmedicated participants with MDD in a current depressive episode and 31 healthy volunteers (HVs). Binding potential (BP(P)) was quantified with empirical Bayesian estimation in graphical analysis (EBEGA). Within the [(11)C]DASB tract, the MDD group showed significantly lower BP(P) compared with HVs (p = 0.02). This BP(P) diagnosis difference also significantly varied by tract location (p = 0.02), with the strongest MDD binding deficit most proximal to brainstem raphe nuclei. NRU 5-HT Atlas ROIs showed a BP(P) diagnosis difference that varied by region (p < 0.001). BP(P) was lower in MDD in 3/10 regions (p-values < 0.05). Neither [(11)C]DASB tract or NRU 5-HT Atlas BP(P) correlated with depression severity, suicidal ideation, suicide attempt history, or antidepressant medication exposure. Future studies are needed to determine the causes of this deficit in 5-HTT binding being more pronounced in proximal axon segments and in only a subset of ROIs for the pathogenesis of MDD. Such regional specificity may have implications for targeting antidepressant treatment, and may extend to other serotonin-related disorders.<p />  <p>Language: en</p>
LA  - en
SN  - 1359-4184
UR  - http://dx.doi.org/10.1038/s41380-022-01578-8
ID  - ref1
ER  -