Imaging serotonergic transmission with [11C]DASB-PET in depressed and non-depressed patients infected with HIV.
BACKGROUND
Site-selective imaging can provide significant insight into the mechanism of HIV-associated neurological disease. The goal of this study was to evaluate the involvement of serotonergic transmission in HIV-associated depression using [(11)C]DASB, a serotonin transporter (5-HTT)-specific radiopharmaceutical for positron emission tomography (PET).


METHODS
Nine depressed HIV+ subjects (HIV-D), 9 non-depressed HIV+ subjects (HIV-ND) and 7 healthy controls (HC) underwent an MRI scan and a [(11)C]DASB-PET scan. The outcome measure was 5-HTT binding potential normalized to non-displaceable tissue radioligand (BP(ND)).


RESULTS
HIV-ND subjects had lower mean regional 5-HTT BP(ND) estimates across regions compared to HC, while HIV-D subjects demonstrated higher mean regional binding values than HIV-ND subjects in most regions. Prior to correction for the false discovery rate, HIV-ND had significantly lower BP(ND) values compared to HC subjects in two regions (insula and anterior cingulate) and all HIV+ patients had significantly lower binding than HC in all regions except for the midbrain, thalamus and pons. After correction for the false discovery rate, only the insula showed significantly lower binding in HIV+ subjects compared to HC (P<0.0045). Despite a significant difference in the duration of illness between the HIV-D and HIV-ND groups, there was no definite correlation between the duration of illness and BP(ND).


CONCLUSIONS
Lower [(11)C]DASB binding in HIV+ patients compared to HC may reflect serotonergic neuronal loss as a component of generalized HIV-associated neurodegeneration. Higher mean regional BP(ND) values in HIV-D compared to HIV-ND subjects could reflect increased density of 5-HTT, leading to increased clearance of serotonin from the synapse, which could account, in part, for symptoms of depression. The lack of correlation between duration of illness and binding argues against these findings being the result of differential neurodegeneration only. Our findings suggest a possible role for dysregulated serotonergic transmission in HIV-associated depression.
Radiology and Imaging Sciences, National Institutes of Health/Clinical Center, Bethesda, MD, USA.
Dima A
DA
Hammoud
Christopher J
CJ
Endres
Edward
E
Hammond
Ovsev
O
Uzuner
Amanda
A
Brown
Avindra
A
Nath
Adam I
AI
Kaplin
Martin G
MG
Pomper
D000328:Adult; D001596:Benzylamines; D002250:Carbon Radioisotopes; D003863:Depression / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic / Q000235:genetics; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D001596:Benzylamines; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins