The effect of 12-wk ω-3 fatty acid supplementation on in vivo thalamus glutathione concentration in patients "at risk" for major depression.
OBJECTIVE
As life expectancy increases, the need to prevent major health disorders is clear. Depressive symptoms are common in older adults and are associated with cognitive decline and greater risk for transitioning to major depression. Oxidative stress may be implicated in the pathophysiology of major depression and can be measured in vivo using proton magnetic resonance spectroscopy via the neurometabolite glutathione (GSH). Evidence suggests ω-3 fatty acid (FA) supplementation may prevent depression and directly affect GSH concentration. The aim of this study was to examine the effect of ω-3 FA supplementation on in vivo GSH concentration in older adults at risk for depression.


METHODS
Fifty-one older adults at risk for depression were randomized to receive either four 1000-mg ω-3 FA supplements daily (containing eicosapentaenoic acid 1200 mg plus docosahexaenoic acid 800 mg) or placebo (four 1000-mg paraffin oil placebo capsules daily) for 12 wk. Participants underwent magnetic resonance spectroscopy, as well as medical, neuropsychological, and self-report assessments at baseline and after 12 wk of supplementation. GSH was measured in the thalamus and calculated as a ratio to creatine. Depressive symptoms were measured using the Patient Health Questionnaire.


RESULTS
Compared with the group given the ω-3 FA supplements, the placebo group had greater change in the GSH-to-creatine ratio in the thalamus (t = 2.00; P = 0.049) after the 12 wk intervention. This increase was in turn associated with a worsening of depressive symptoms (r = 0.43; P = 0.043).


CONCLUSIONS
Depressive symptom severity in older adults appears to be associated with increased brain levels of GSH, a key marker of oxidative stress. Importantly, ω-3 FA supplementation may attenuate oxidative stress mechanisms, thereby offering benefits for depression prevention.
Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia; Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia. Electronic address: shantel.duffy@sydney.edu.au.
Shantel L
SL
Duffy
Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia.
Jim
J
Lagopoulos
Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia; Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia.
Nicole
N
Cockayne
Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia; Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia.
Simon J G
SJ
Lewis
Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia; Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia.
Ian B
IB
Hickie
Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia.
Daniel F
DF
Hermens
Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia; Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, New South Wales, Australia.
Sharon L
SL
Naismith
D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000150:complications; D003401:Creatine / Q000378:metabolism; D003865:Major Depressive Disorder / Q000209:etiology / Q000517:prevention & control*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D013788:Thalamus / Q000378:metabolism*
D015525:Fatty Acids, Omega-3; D005978:Glutathione; D003401:Creatine
Glutathione; Magnetic resonance spectroscopy; Major depression; Thalamus; ω-3 fatty acid