Functional disconnection and social cognition in schizophrenia
Introduction Social and emotional functions play a key role in schizophrenia. Both positive symptoms, such as hallucinations and persecutory delusions, as well as negative symptoms such as social withdrawal, and flattened affect impact socioemotional function. These functions involve distributed brain networks. The ‘Disconnection Hypothesis’, a plausible unifying theory of schizophrenia, proposes connectivity within such networks as a core pathological feature of schizophrenia. Connectivity is also related to specific genetic risk factors. Therefore the present project addresses the hypothesis that individuals with schizophrenia might show disconnection within socio-emotional brain networks, and examines the effects of a functional polymorphism of the BDNF gene on connectivity within these networks. Methods Here I examined the brain activation and connectivity for implicit emotional reaction and social judgment in schizophrenia, as well as with variation in the val66met polymorphism of BDNF. Brain activation was examined with functional magnetic resonance imaging, and effective connectivity was estimated using psycho-physiological interactions, from the bilateral amygdala to the whole brain (using a facial image paradigm for explicit approachability judgement and implicit fear response respectively). Results Individuals with schizophrenia showed reduced activation in the right lingual gyrus, right superior temporal gyrus and left amygdala during fear processing, as well as reduced connectivity from the left amygdala to the right temporo-parietal junction and precuneus. During approachability judgments, patients overactivated the right inferior frontal gyrus and right precuneus and showed reduced connectivity from the bilateral amygdala to the right inferior frontal gyrus. Met allele carriers of the BDNF val66met polymorphism showed overactivation in the medial anterior cingulate cortex, and bilateral insula, as well as reduced connectivity between the anterior cingulate cortex and hippocampus. For approachability judgment, met carriers overactivated the middle occipital gyrus, and showed reduced connectivity from the left amygdala to the right parahippocampal gyrus and medial frontal gyrus, as well as the left posterior cingulate gyrus, pre and post central gyrus, middle temporal gyrus and cerebellum. Conclusion In conclusion, connectivity between the amygdala and brain regions associated with a range of socially relevant functions were found to be reduced in both patients, and met allele carriers of the BDNF val66met SNP. Given the key role of the amygdala in affective processing this diffuse disconnection in networks for socio-emotional functions might mediate the aberrant emotional and social behavior seen in individuals with schizophrenia.