title: Delay discounting of reward and caudate nucleus volume in individuals with α-synuclein gene duplication before and after the development of Parkinson's disease.
abstract: OBJECTIVE
  α-Synuclein (SNCA) may be a key factor in dopaminergic neurotransmission, reward processing, and neurodegeneration in Parkinson's disease (PD). We investigated delay discounting of reward and caudate volume in SNCA gene duplication carriers before and after the development of PD.
  
  
  METHODS
  Participants were 7 presymptomatic SNCA duplication carriers who later developed PD (follow-up period: 5.4 years) and 10 matched non-carrier controls. At the follow-up assessment, patients received levodopa (L-DOPA) therapy. Delay discounting of reward was assessed with the Kirby discounting questionnaire. We measured the volume of the caudate nucleus and cerebral cortex using structural MRI and FreeSurfer software.
  
  
  RESULTS
  In the presymptomatic stage, carriers showed similar delay discounting and caudate volume to that of non-carrier controls. However, after the development of PD, we observed a significant elevation in delay discounting (impulsive decisions) and reduced caudate volume. There was no cortical atrophy.
  
  
  CONCLUSIONS
  Impaired reward-related decision making and caudate volume loss are not detectable in the presymptomatic stage in SNCA duplication carriers. These behavioral and neuroanatomical alterations are observed after the development of clinical symptoms when there is extensive neurodegeneration. Study limitations include a small sample size as well as the potential confounding effect of general cognitive decline.
authors.affiliation: National Psychiatry Center, Semmelweis University, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Szamosi
authors.forename: Helga
authors.initials: H
authors.lastname: Nagy
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Kéri
mesh_terms: D000328:Adult; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002421:Caudate Nucleus / Q000473:pathology* / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology / Q000502:physiology; D003657:Decision Making / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D020440:Gene Duplication / Q000235:genetics*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000502:physiology; D012201:Reward; D011795:Surveys and Questionnaires; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D000978:Antiparkinson Agents; C497604:SNCA protein, human; D051844:alpha-Synuclein; D007980:Levodopa; D004298:Dopamine