title: Increased orbitofrontal cortex activation associated with "pro-obsessive" antipsychotic treatment in patients with schizophrenia.
abstract: BACKGROUND
  Patients with schizophrenia have an approximately 10-fold higher risk for obsessive-compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms.
  
  
  METHODS
  To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory.
  
  
  RESULTS
  We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level.
  
  
  CONCLUSIONS
  The main limitation of this study is its cross-sectional design.
  
  
  CONCLUSIONS
  To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations.
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany and the Department of Psychiatry, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Frederike
authors.initials: F
authors.lastname: Schirmbeck
authors.affiliation: Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mier
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Esslinger
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Rausch
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Englisch
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Eifler
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
authors.affiliation: Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kirsch
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Zink
mesh_terms: D000328:Adult; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000627:therapeutic use; D001931:Brain Mapping; D003024:Clozapine / Q000627:therapeutic use; D056344:Executive Function / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009770:Obsessive Behavior / Q000188:drug therapy / Q000503:physiopathology; D000077152:Olanzapine; D010879:Piperazines / Q000627:therapeutic use; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D015363:Quinolones / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology*; D013469:Sulpiride / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D001569:Benzodiazepines; D013469:Sulpiride; D000077582:Amisulpride; D000068180:Aripiprazole; D003024:Clozapine; D000077152:Olanzapine