Examining the neural basis of decision-making using social stimuli, dopamine and oxytocin in schizophrenia

• Main Author: Wigton, Rebekah
• Other Authors: Shergill, Sukhwinder S.
• Published: King's College London (University of London) 2014
• Subjects: 616.89
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677012

Background: Schizophrenia is a devastating disorder, treated with antipsychotics acting via dopaminergic D2 blockade, and significant comorbidity impacting through social dysfunction. The neural mechanisms underlying the processing of socially salient material and the dopaminergic networks posited to be central to this social decision making remain unclear. These mechanisms are explored in this thesis. Methods: fMRI was performed on 20 healthy controls (HC) treated with single dose of a dopamine agonist, ropinirole (0.25mg); dopamine antagonist, amisulpride (400mg), and placebo. fMRI was also performed in 42 patients with schizophrenia (SZ); and a subsample of 20 patients after treatment with oxytocin (40IU) or placebo nasal spray. Participants performed a decision-making task incorporating stochastically rewarded faces of varied social valence during the fMRI. Results: The normal bias towards selecting a happy face was attenuated by all pharmacological agents (ropinirole, amisulpride and oxytocin). In HC, attenuation of bias after ropinirole administration was accompanied by an increase in neural activity within the dorsal anterior cingulate and dorsomedial prefrontal cortex and attenuation in the amygdala. In SZ, attenuation of bias after oxytocin administration was accompanied by attenuation of neural activity in the temporoparietal junction and amygdala. When looking between groups, SZ showed attenuated neural activity in the thalamus, cerebellum and medial prefrontal cortex (mPFC). HC on amisulpride showed similar attenuation in the cerebellum to SZ. Discussion: Modulation of processing of socially salient stimuli was evident during the perturbation of the dopaminergic system, impacting both behaviour and neural processing. The key regions demonstrating change between HC and SZ were the thalamus, cerebellum and mPFC; supporting a deficit in the coordination and integration of decision-making following the cognitive dysmetria model. Oxytocin demonstrated prosocial effects in SZ, through modulation of amygdala activation; and showed some overlap with dopaminergic responsive regions, lending support to a possible action via the dopaminergic system.