The overarching aim of the study is to determine the role of insulin signaling on the
neurobiological substrates subserving anhedonia within individuals with mood disorders (i.e.,
Bipolar Disorder (BD) and Major Depressive Disorder (MDD)).
Specific aims include:
1. Molecular: Assessment of components of the insulin cascade, as well as of anhedonia and
reward-related processes, using a proteomics and gene expression approach;
2. Physiology: Measurement of peripheral sensitivity to insulin and metabolic correlates,
including body mass index and dyslipidemia;
3. Neural Circuits: Evaluation of the insulin sensitivity of prefrontal (e.g. prefrontal
cortex) and striatal (e.g. nucleus accumbens, ventral tegmental area) networks in the
resting-state and during an effort-based decision making test, using acutely
administered intranasal insulin and functional magnetic resonance imaging (fMRI);
4. Behavioral: Measurement of willingness to make effort for rewards, as well as of other
components of reward response and anhedonia, using validated behavioral tasks and
clinical scales (e.g. Snaith-Hamilton Pleasure Scale - SHPS).
This initiative represents a proof-of-concept study that insulin is important to anhedonia,
neurocognitive functioning, and behavioural deficits in MDD, representing a novel and safe
therapeutic avenue.