Failure To Deactivate Medial Prefrontal Cortex Associated With Clinical Not Genetic Risk For Psychosis

Presentation First Author: 
Paul Allen

Background: Dysfunction of the prefrontal cortex (PFC) is consistently reported in patients with schizophrenia. Three types of dysfunction have been described: (1) hypofrontality, (2) hyperfrontality and (3) failure to deactivate the medial PFC (mPFC). The latter finding may be associated with dysfunction of the default mode network (DMN), which is relatively deactivated during goal-oriented activity in healthy subjects. However, it is unclear if DMN-dysfunction is present before the onset of psychosis, and, if dysfunction is mediated genetically or related to early symptom manifestation. Method: 17 clinical high risk (CHR) subjects, 10 non-affected siblings of patients with schizophrenia (genetic high risk; GHR), 10 patients with a first episode of psychosis (FEP), and 14 healthy controls (CTRL) were scanned using functional Magnetic Resonance Imaging during an N-back working memory task. Results: FEP and CHR groups showed task related activation in the left precuneus, right superior lingual gyrus and bilateral mPFC whereas CTRL and GHR groups showed task related deactivation in these regions. Conversely, CTRL and GHR groups showed task related activation in the bilateral PFC that was not seen in FEP and UHR groups. In FEP and CHR groups there were significant correlations between negative symptom scores and activity in the right superior lingual gyrus (r = .25, p = .046) and the left precuneus (r =.32, p = .01). Discussion: These findings suggest that DMN dysfunction might be more related to presence or absence of symptoms, i.e. the clinical manifestation of vulnerability, than to genetic vulnerability.

Conference Name: 
Presentation Date: 
January, 2013
Additional Authors: 
Paul Allen, Irina Falkenberg, Christopher Chaddock, Gemma Modinos, Philip McGuire
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