Although bipolar disorder (BPD) usually presents in adolescence or young adulthood, most patients with BPD follow a life-long recurrent course, with ongoing psychosocial and functional deficits and high utilization of health services that persist into later life. Currently, there is a lack of data in geriatric BPD overall and in geriatrc bipolar depression in particular. Bipolar depression, both in adulthood and later life, represents the predominant and least successfully treated phase of this devastating illness and is associated with an elevated risk of suicide. The disease mechanisms that underlie bipolar depression remain unclear and resistance to current treatments is high. N-Acetyl Cysteine (NAC) appears to be a promising therapeutic target and provides a window of treatment opportunity in a field where current treatments are limited or have remained suboptimal. At this point, the mechanism of action of NAC is not entirely understood. While it's been hypothesized that NAC may alter brain glutathione (GSH), main antioxidant important for the maintenance of oxidative balance, this has not been studied in humans or in the context of bipolar depression. The research plans of this proposal aim at identifying the underlying mechanism by which NAC works and include three specific aims.
The first aim i s to use improved quantitative magnetic resonance spectroscopy methods to determine whether brain GSH levels are altered in older adults with BPD compared to matched controls. A secondary aim is determine whether NAC supplementation will increase GSH levels dose-dependently in the BPD group.
A third aim i s to determine whether there is an association between the NAC intervention, brain GSH/neurotransmitter levels and depression symptom severity. It is hypothesized that GSH levels will be lower in patients with BPD compared to healthy controls and NAC supplementation will elevate brain GSH reducing oxidative stress and depression symptoms in aging individuals with BPD.

Public Health Relevance

Easily accessible N-acetylcysteine (NAC) has been shown to be well-tolerated agent with low side effect profile and promising therapeutic roles in the treatment of depression. This proposal will employ improved quantitative magnetic resonance spectroscopy methods to shed light on its mechanism of action and better define its usefulness in geriatric bipolar depression.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Adult Psychopathology and Disorders of Aging Study Section (APDA)
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Evans, Jovier D
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Mclean Hospital
United States
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