title: The electroretinogram as a biomarker of central dopamine and serotonin: potential relevance to psychiatric disorders.
abstract: BACKGROUND
  Dysfunctions in brain dopamine and serotonin neurotransmission are believed to be involved in the etiology of psychiatric disorders, and electroretinogram (ERG) anomalies have been reported in psychiatric patients. The goal of this study was to evaluate whether ERG anomalies could result from central dopamine or serotonin dysfunctions or from changes in the retinal bioavailability of these neurotransmitters.
  
  
  METHODS
  Photopic and scotopic ERGs were recorded in R439H tryptophan hydroxylase 2 knockin (Tph2-KI) mice that have an approximately 80% decrease in brain serotonin and dopamine transporter knockout (DAT-KO) mice showing a fivefold increase in brain extracellular dopamine. Dopamine and serotonin retinal and striatal tissue content were also measured. The role of dopamine D1 receptors (D1R) and D2 receptors (D2R) in the ERG responses was evaluated in D1R-KO and D2R-KO mice.
  
  
  RESULTS
  An increase in photopic b-wave implicit time was observed in Tph2-KI mice (wildtype = 24.25 msec, KI = 25.22 msec; p = .011). The DAT-KO mice showed a decrease in rod sensitivity (wildtype =-1.97 log units, KO =-1.81 log units; p = .014). In contrast to remarkable alterations in brain levels, no changes in dopamine and serotonin retinal content were found in DAT-KO and Tph2-KI mice, respectively. The D1R-KO mice showed anomalies in photopic and scotopic maximal amplitude, whereas D2R-KO mice showed higher oscillatory potentials relative contribution to the b-wave amplitude.
  
  
  CONCLUSIONS
  Alterations in central dopamine and serotonin neurotransmission can affect the ERG responses. The ERG anomalies reported in psychiatric disorders might serve as biomarkers of central monoaminergic dysfunction, thus promoting ERG measurements as a useful tool in psychiatric research.
authors.affiliation: Department of Psychiatry and Neurosciences, Quebec City, Quebec, Canada; Department of Ophthalmology and Otorhinolaryngology, Faculty of Medicine, Université Laval, Quebec City, Quebec, Canada; Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Quebec, Canada.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Lavoie
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Placido
authors.initials: P
authors.lastname: Illiano
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Tatyana D
authors.initials: TD
authors.lastname: Sotnikova
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Raul R
authors.initials: RR
authors.lastname: Gainetdinov
authors.affiliation: Department of Psychiatry and Neurosciences, Quebec City, Quebec, Canada; Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Quebec, Canada.
authors.forename: Jean-Martin
authors.initials: JM
authors.lastname: Beaulieu
authors.affiliation: Department of Ophthalmology and Otorhinolaryngology, Faculty of Medicine, Université Laval, Quebec City, Quebec, Canada; Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Quebec, Canada. Electronic address: marc.hebert@fmed.ulaval.ca.
authors.forename: Marc
authors.initials: M
authors.lastname: Hébert
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D059290:Dopaminergic Neurons / Q000378:metabolism*; D004596:Electroretinography; D005260:Female; D055879:Gene Knock-In Techniques; D008297:Male; D001523:Mental Disorders / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000502:physiology; D012160:Retina / Q000378:metabolism; D059326:Serotonergic Neurons / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000502:physiology
chemical_list: D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase; D004298:Dopamine
keywords: Biomarker; dopamine; dopamine transporter; electroretinogram; psychiatric disorders; serotonin