title: Reduced cortical thickness is associated with the glutamatergic regulatory gene risk variant DAOA Arg30Lys in schizophrenia.
abstract: In light of current etiological concepts the glutamatergic system plays an essential role for the pathophysiology of the disorder, offering multiple options for new treatment strategies. The D-amino oxidase activator (DAOA) gene is closely connected to the glutamatergic system and its therapeutic and pathophysiological relevance for schizophrenia is therefore intensively debated. In a further step to shed light on the role of DAOA in schizophrenia, we aimed to investigate the association of the functional DAOA Arg30Lys (rs2391191) variant and cortical thickness in schizophrenia. Cortical thickness was computed by an automated surface-based technique (FreeSurfer) in 52 genotyped patients with schizophrenia and 42 healthy controls. Cortical thickness of the entire cortex was compared between risk carriers and non-risk carriers regarding the Arg30Lys polymorphism in patients and healthy controls on the basis of a node-by-node procedure and an automated clustering approach. Risk carriers with schizophrenia show significantly thinner cortex in two almost inversely arranged clusters on the left and right hemisphere comprising middle temporal, inferior parietal, and lateral occipital cortical areas. The clusters encompass an area of 1174 mm(2) (left) and 1156 mm(2) (right). No significant effect was observed in healthy controls.The finding of our study that the Arg30Lys risk variant is associated with a distinct cortical thinning provides new evidence for the pathophysiological impact of DAOA in schizophrenia. The affected areas are mostly confined to cortical regions with a crucial role in the ToM network and visual processing, which both can be influenced by glutamatergic modulation. Our finding thus underlines the importance of DAOA and related glutamatergic processes as a putative target for therapeutic interventions in schizophrenia.
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Schiller-University Jena, Jena, Germany. christoph.schultz@med.uni-jena.de
authors.forename: C Christoph
authors.initials: CC
authors.lastname: Schultz
authors.forename: Igor
authors.initials: I
authors.lastname: Nenadic
authors.forename: Kathrin
authors.initials: K
authors.lastname: Koch
authors.forename: Gerd
authors.initials: G
authors.lastname: Wagner
authors.forename: Martin
authors.initials: M
authors.lastname: Roebel
authors.forename: Claudia
authors.initials: C
authors.lastname: Schachtzabel
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Mühleisen
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Thomas
authors.initials: T
authors.lastname: Deufel
authors.forename: Michael
authors.initials: M
authors.lastname: Kiehntopf
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Reichenbach
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sauer
authors.forename: Ralf G M
authors.initials: RG
authors.lastname: Schlösser
mesh_terms: D000328:Adult; D001120:Arginine / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018698:Glutamic Acid; D001120:Arginine; D008239:Lysine