1 research outputs found
Neural basis of genetic vulnerability to bipolar disorder
Abnormalities of reward processing, decision-making and emotion processing are core
features of bipolar I disorder (BD). These processes are closely linked with fronto-striatal
and midbrain circuitry. I sought to test whether dysfunctions of these pathways were
present in BD and whether they related to genetic vulnerability to illness or resilience.
I recruited twenty-five BD I patients each with their unaffected sibling, and compared them
to 24 healthy age- and gender-matched controls. In chapter 1, I provide a research
background and literature review. Chapter 2 describes the neuropsychological
assessments which demonstrated trait-related deficits in working memory with slower
processing speed representing an endophenotype.
Chapter 3 describes the implicit/ explicit facial emotion processing task performed during
event-related functional MRI (erfMRI). Pairwise comparisons demonstrated implicit
processing was associated with increases in lingual gyrus and insula activations and
explicit processing elicited reduced fusiform activations in patients compared with
controls. Increased posterior cingulate activations and reductions in putamen and
cerebellar activity were found in siblings compared to controls, and reductions in parietal
activations were noted in siblings compared to their ill relatives. These findings suggest
over-activations in regions involved in facial expression recognition and attentional
shifting (lingual and insula respectively) and deactivations in a region important for the
perception and recognition of faces (fusiform) represent correlates of disease expression.
Additionally regional deactivations associated with category learning and attentional
processing (parietal, putamen and cerebellar) and increased activations in a region
involved in emotional salience (posterior cingulate) may represent adaptive responses
associated with resilience.
Chapter 4 describes an instrumental reward-learning task performed during erfMRI. Data
were analysed at whole brain level and using a priori region of interest analyses in ventral
striatum/midbrain and prefrontal cortex (PFC). Results included increased ventral
striatum activation in association with the difference between observed and expected
rewarding outcomes (the prediction error (PE)) in patients compared to controls.
Decreased prefrontal activations were seen in the patient and sibling groups compared
to controls in association with the learning of the value of the conditioned stimulus. These
findings suggest that i) PE associated circuitry (striatal) overactivation, and ii) prefrontal
deactivations underlie the genetic vulnerability to BD