title: Effects of ketamine-induced psychopathological symptoms on continuous overt rhyme fluency.
abstract: The N-methyl-D-aspartate receptor (NMDAR) has been implicated in the pathophysiology of schizophrenia. Administered to healthy individuals, a subanesthetic dose of the noncompetitive NMDAR antagonist ketamine reproduces several psychopathological symptoms commonly observed in patients with schizophrenia. In a counterbalanced, placebo-controlled, double-blind, within-participants study, fifteen healthy subjects were administered a continuous subanesthetic S-ketamine infusion while cortical activation was measured using functional magnetic resonance imaging. While being scanned, subjects performed an overt word generation task. Ketamine-induced psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Ketamine administration elicited effects on psychopathology, including difficulties in abstract thinking, lack of spontaneity and flow of conversation as well as formal thought disorder. On a behavioral level, verbal fluency performance was unaffected. The PANSS score for formal thought disorder positively correlated with activation measures encompassing the left superior temporal gyrus, the right middle and inferior frontal gyrus and the precuneus. Difficulty in abstract thinking was correlated with pronounced activations in prefrontal as well as in anterior cingulate regions, whereas hyperactivations in the left superior temporal gyrus were found in association with a lack of spontaneity and flow of conversation. In the absence of behavioral impairments during verbal fluency, NMDAR blocking evoked psychopathological symptoms and cortical activations in regions previously reported in schizophrenia patients. The results provide further support for the hypothesis of an NMDAR dysfunction in the pathophysiology of schizophrenia.
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany. nagels@med.uni-marburg.de
authors.forename: Arne
authors.initials: A
authors.lastname: Nagels
authors.forename: André
authors.initials: A
authors.lastname: Kirner-Veselinovic
authors.forename: Richard
authors.initials: R
authors.lastname: Wiese
authors.forename: Frieder M
authors.initials: FM
authors.lastname: Paulus
authors.forename: Tilo
authors.initials: T
authors.lastname: Kircher
authors.forename: Sören
authors.initials: S
authors.lastname: Krach
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D001931:Brain Mapping; D003072:Cognition Disorders / Q000139:chemically induced / Q000473:pathology / Q000523:psychology; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects*; D007839:Functional Laterality / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007649:Ketamine / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced / Q000473:pathology / Q000523:psychology; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D011569:Psychiatric Status Rating Scales; D014705:Verbal Behavior / Q000187:drug effects*; D014825:Vocabulary
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D010100:Oxygen