title: Interaction between serotonin transporter and dopamine D2/D3 receptor radioligand measures is associated with harm avoidant symptoms in anorexia and bulimia nervosa.
abstract: Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have alterations of measures of serotonin (5-HT) and dopamine (DA) function, which persist after long-term recovery and are associated with elevated harm avoidance (HA), a measure of anxiety and behavioral inhibition. Based on theories that 5-HT is an aversive motivational system that may oppose a DA-related appetitive system, we explored interactions of positron emission tomography (PET) radioligand measures that reflect portions of these systems. Twenty-seven individuals recovered (REC) from eating disorders (EDs) (7 AN-BN, 11 AN, 9 BN) and nine control women (CW) were analyzed for correlations between [(11)C]McN5652 and [(11)C]raclopride binding. There was a significant positive correlation between [(11)C]McN5652 binding potential (BP(non displaceable(ND))) and [(11)C]Raclopride BP(ND) for the dorsal caudate, antero-ventral striatum (AVS), middle caudate, and ventral and dorsal putamen. No significant correlations were found in CW. [(11)C]Raclopride BP(ND), but not [(11)C]McN5652 BP(ND), was significantly related to HA in REC EDs. A linear regression analysis showed that the interaction between [(11)C]McN5652 BP(ND) and [(11)C]raclopride BP(ND) in the dorsal putamen significantly predicted HA. This is the first study using PET and the radioligands [(11)C]McN5652 and [(11)C]raclopride to show a direct relationship between 5-HT transporter and striatal DA D2/D3 receptor binding in humans, supporting the possibility that 5-HT and DA interactions contribute to HA behaviors in EDs.
authors.affiliation: University of California San Diego, UCSD Department of Psychiatry, 8950 Villa La Jolla Drive, La Jolla, CA 92037, USA.
authors.forename: Ursula F
authors.initials: UF
authors.lastname: Bailer
authors.forename: Guido K
authors.initials: GK
authors.lastname: Frank
authors.forename: Julie C
authors.initials: JC
authors.lastname: Price
authors.forename: Carolyn C
authors.initials: CC
authors.lastname: Meltzer
authors.forename: Carl
authors.initials: C
authors.lastname: Becker
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: Angela
authors.initials: A
authors.lastname: Wagner
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Barbarich-Marsteller
authors.forename: Cinnamon S
authors.initials: CS
authors.lastname: Bloss
authors.forename: Karen
authors.initials: K
authors.lastname: Putnam
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Anthony
authors.initials: A
authors.lastname: Gamst
authors.forename: Walter H
authors.initials: WH
authors.lastname: Kaye
mesh_terms: D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D052018:Bulimia Nervosa / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D018492:Dopamine Antagonists / Q000032:analysis; D005260:Female; D059907:Functional Neuroimaging; D040261:Harm Reduction; D006801:Humans; D007546:Isoquinolines / Q000032:analysis; D008875:Middle Aged; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000032:analysis; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000032:analysis; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
chemical_list: C581293:DRD2 protein, human; D018492:Dopamine Antagonists; D007546:Isoquinolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D020891:Raclopride; C058079:McN 5652