Brain Insulin Resistance in Mood Disorders

• Status: Recruiting
• Trial end date: 2024-10-05
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Health Network, Toronto
• Treatments: Insulin; Insulin, Globin Zinc

Criteria

Inclusion criteria (patients):

1. Age 18-50

2. DSM-5 defined MDD/BD and a total score ≥20 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and no history of dementia or intellectual disability

3. A written, voluntary informed consent prior to study enrollment

Exclusion criteria (patients):

1. Use of insulin and/or oral hypoglycemiants, due to its confounding effects

2. Diagnosis of possible or probable AD, MCI, or any other dementia

3. History of neurological disorder, or evidence of neurologic or other physical illness that could produce cognitive deterioration

4. Substance use disorder within 3 months before screening or a positive baseline toxicology screen

5. Presence of clinically unstable general medical illness

6. Pregnancy or breastfeeding

7. MRI contraindications

Inclusion criteria (healthy controls):

1. Age 18-50

2. A written, voluntary informed consent prior to study enrollment

Exclusion criteria (healthy controls):

1. Use of insulin and/or oral hypoglycemiants, due to its confounding effects

2. Presence of any current or lifetime psychiatric or neurological conditions

3. Substance use disorder within 3 months before screening or a positive baseline toxicology screen

4. Presence of clinically unstable general medical illness

5. Pregnancy or breastfeeding

6. MRI contraindications