title: Increased release of dopamine in the striata of young adults with hearing impairment and its relevance for the social defeat hypothesis of schizophrenia.
abstract: OBJECTIVE
  An increased risk for psychosis is observed in people with hearing impairment. According to the social defeat hypothesis, the long-term experience of exclusion leads to enhanced baseline activity and/or sensitization of the dopamine system and puts the individual at increased risk for psychosis.
  
  
  OBJECTIVE
  To investigate whether young adults with severe hearing impairment (SHI) experience more feelings of social defeat, show greater dopamine release in response to dexamphetamine, and report a stronger subjective reaction to this substance than normal-hearing young adults and to examine whether dopamine release is associated with both self-reported social exclusion and dexamphetamine-induced psychotic experiences.
  
  
  METHODS
  A sample of 19 participants with SHI and 19 smoking-, age-, and sex-matched healthy controls underwent single-photon emission computed tomography with iodine 123-labeled iodobenzamide as a radiotracer before and after an amphetamine challenge at an academic hospital.
  
  
  METHODS
  Dexamphetamine sulfate (0.3 mg/kg) administered intravenously.
  
  
  METHODS
  Baseline D2/3 receptor binding and endogenous dopamine release.
  
  
  RESULTS
  The participants with SHI reported experiencing more feelings of social defeat (U=109, z=-2.09, P=.04) and loneliness (U=87.5, z=-2.72, P=<.001) than did healthy controls, but they did not differ from healthy controls with regard to baseline psychotic symptoms (U=156.5, z=-0.70, P=.48). There were no significant group differences in baseline D2/3 receptor binding. However, repeated-measures multivariate analysis of covariance with age (in months) and tobacco smoking (in pack-years) as covariates showed that there was a greater amphetamine-induced striatal dopamine release among the participants with SHI than among the healthy controls (F1,34=4.55, P=.04). After amphetamine administration, the participants with SHI reported more changes in affect than the healthy controls, but not a greater increase in psychotic symptoms. Likewise, reports of social exclusion and an increase in psychotic symptoms were not associated with dopamine release.
  
  
  CONCLUSIONS
  Our study presents preliminary evidence of dopamine sensitization in a socially excluded group of people with hearing impairment. If replicated by future studies in other excluded groups, this finding may have major implications for our understanding of the underlying mechanism and for prevention of psychotic disorders.
authors.affiliation: Academic Medical Center, Department of Nuclear Medicine, University of Amsterdam, Amsterdam, the Netherlands2Rivierduinen Institute for Mental Health Care, Leiden, the Netherlands3Department of Psychiatry and Psychology, South Limburg Mental Health Resear.
authors.forename: Martin
authors.initials: M
authors.lastname: Gevonden
authors.affiliation: Academic Medical Center, Department of Nuclear Medicine, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
authors.affiliation: Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.affiliation: Academic Medical Center, Department of Radiology, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: Heijtel
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, the Netherlands.
authors.forename: Jim
authors.initials: J
authors.lastname: van Os
authors.affiliation: Rivierduinen Institute for Mental Health Care, Leiden, the Netherlands3Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, the Netherlands.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Selten
mesh_terms: D000328:Adult; D000661:Amphetamine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D059333:Central Nervous System Sensitization; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D059907:Functional Neuroimaging; D034381:Hearing Loss / Q000150:complications / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007462:Iodobenzenes; D008297:Male; D012929:Psychological Distance; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D012463:Saliva / Q000378:metabolism; D012559:Schizophrenia / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D012565:Schizophrenic Psychology; D063189:Symptom Assessment; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
chemical_list: D018765:Dopamine Uptake Inhibitors; D007462:Iodobenzenes; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C426805:idobenzamide; D000661:Amphetamine; D004298:Dopamine; D006854:Hydrocortisone