Sara Dar1, Einat Liebenthal2, Hong Pan3, Thomas Smith4, Adam Savitz5, Yulia Landa6, David Silbersweig7, Emily Stern8. 1. Brigham & Women's Hospital, Department of Psychiatry, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA. Electronic address: sara_dar@alumni.harvard.edu. 2. Brigham & Women's Hospital, Department of Psychiatry, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA. Electronic address: eliebenthal@mclean.harvard.edu. 3. Brigham & Women's Hospital, Departments of Psychiatry and Radiology, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA. Electronic address: hpan@bwh.harvard.edu. 4. New York State Psychiatric Institute, Columbia University, New York, NY, USA. Electronic address: thomas.Smith@nyspi.columbia.edu. 5. Weill Cornell Medical Center, Department of Psychiatry, New York, NY, USA. Electronic address: ads9002@med.cornell.edu. 6. Weill Cornell Medical Center, Department of Psychiatry, New York, NY, USA. Electronic address: yulia.landa@mssm.edu. 7. Brigham & Women's Hospital, Department of Psychiatry, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA. Electronic address: dsilbersweig@bwh.harvard.edu. 8. Brigham & Women's Hospital, Departments of Psychiatry and Radiology, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA. Electronic address: estern@ceretype.com.
Abstract
BACKGROUND: Schizophrenia (SZ) is associated with devastating emotional, cognitive and language impairments. Understanding the deficits in each domain and their interactions is important for developing novel, targeted psychotherapies. This study tested whether negative-threat word processing is altered in individuals with SZ compared to healthy controls (HC), in relation to SZ symptom severity across domains. METHODS: Thirty-one SZ and seventeen HC subjects were scanned with functional magnetic resonance imaging while silently reading negative-threat and neutral words. Post-scan, subjects rated the valence of each word. The effects of group (SZ, HC), word type (negative, neutral), task period (early, late), and severity of clinical symptoms (positive, negative, excitement/hostility, cognitive, depression/anxiety), on word valence ratings and brain activation, were analyzed. RESULTS: SZ and HC subjects rated negative versus neutral words as more negative. The SZ subgroup with severe versus mild excitement/hostility symptoms rated the negative words as more negative. SZ versus HC subjects hyperactivated left language areas (angular gyrus, middle/inferior temporal gyrus (early period)) and the amygdala (early period) to negative words, and the amygdala (late period) to neutral words. In SZ, activation to negative versus neutral words in left dorsal temporal pole and dorsal anterior cingulate was positively correlated with excitement/hostility scores. CONCLUSIONS: A negatively-biased behavioral response to negative-threat words was seen in SZ with severe versus mild excitement/hostility symptoms. The biased behavioral response was mediated by hyperactivation of brain networks associated with semantic processing of emotion concepts. Thus, word-level semantic processing may be a relevant psychotherapeutic target in SZ.
BACKGROUND: Schizophrenia (SZ) is associated with devastating emotional, cognitive and language impairments. Understanding the deficits in each domain and their interactions is important for developing novel, targeted psychotherapies. This study tested whether negative-threat word processing is altered in individuals with SZ compared to healthy controls (HC), in relation to SZ symptom severity across domains. METHODS: Thirty-one SZ and seventeen HC subjects were scanned with functional magnetic resonance imaging while silently reading negative-threat and neutral words. Post-scan, subjects rated the valence of each word. The effects of group (SZ, HC), word type (negative, neutral), task period (early, late), and severity of clinical symptoms (positive, negative, excitement/hostility, cognitive, depression/anxiety), on word valence ratings and brain activation, were analyzed. RESULTS: SZ and HC subjects rated negative versus neutral words as more negative. The SZ subgroup with severe versus mild excitement/hostility symptoms rated the negative words as more negative. SZ versus HC subjects hyperactivated left language areas (angular gyrus, middle/inferior temporal gyrus (early period)) and the amygdala (early period) to negative words, and the amygdala (late period) to neutral words. In SZ, activation to negative versus neutral words in left dorsal temporal pole and dorsal anterior cingulate was positively correlated with excitement/hostility scores. CONCLUSIONS: A negatively-biased behavioral response to negative-threat words was seen in SZ with severe versus mild excitement/hostility symptoms. The biased behavioral response was mediated by hyperactivation of brain networks associated with semantic processing of emotion concepts. Thus, word-level semantic processing may be a relevant psychotherapeutic target in SZ.
Authors: Martijn P van den Heuvel; René C W Mandl; Cornelis J Stam; René S Kahn; Hilleke E Hulshoff Pol Journal: J Neurosci Date: 2010-11-24 Impact factor: 6.167
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