Increased orbitofrontal cortex activation associated with “pro-obsessive” antipsychotic treatment in patients with schizophrenia

• Published in: Journal of psychiatry & neuroscience 2015-03, Vol.40 (2), p.89-99
• Main Authors: Schirmbeck, Frederike, PhD, Esslinger, Christine, MD, Rausch, Franziska, MPsych, Englisch, Susanne, MD, Eifler, Sarah, MPsych, Meyer-Lindenberg, Andreas, MD, Zink, Mathias, MD, Mier, Daniela, PhD, Kirsch, Peter, PhD
• Format: Article
• Language: English
• Subjects: Adult; Antipsychotic Agents - therapeutic use; Antipsychotics; Aripiprazole; Benzodiazepines - therapeutic use; Brain Mapping; Clozapine - therapeutic use; Cognitive ability; Comorbidity; Executive Function - drug effects; Executive Function - physiology; Female; Humans; Inhibition (Psychology); Investigations; Magnetic Resonance Imaging; Male; Medical Education; Medical imaging; Memory; Neuroimaging; Neuropsychological Tests; Obsessive Behavior - drug therapy; Obsessive Behavior - physiopathology; Obsessive compulsive disorder; Pathogenesis; Piperazines - therapeutic use; Prefrontal Cortex - drug effects; Prefrontal Cortex - physiopathology; Psychiatric Status Rating Scales; Psychiatry; Psychomotor Performance - drug effects; Psychomotor Performance - physiology; Psychotropic drugs; Quinolones - therapeutic use; Research Paper; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - physiopathology; Sulpiride - analogs & derivatives; Sulpiride - therapeutic use
• ISSN: 1180-4882; 1488-2434
• DOI: 10.1503/jpn.140021

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. Limitations The main limitation of this study is its cross-sectional design. Conclusion 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.