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|Title: ||Functional disconnection and social cognition in schizophrenia|
|Authors: ||Mukherjee, Prerona|
|Supervisor(s): ||Lawrie, Stephen|
|Issue Date: ||25-Nov-2011|
|Publisher: ||The University of Edinburgh|
|Abstract: ||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.|
|Appears in Collections:||Molecular, Genetic and Population Health Sciences thesis and dissertation collection|
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