Cortical glutathione levels in young people with bipolar disorder: a pilot study using magnetic resonance spectroscopy
Glutathione (GSH) is a key scavenger for cellular free radicals, and patients with bipolar disorder may have lowered GSH levels in plasma and in post-mortem brain tissue.
The objective of the current study was to use magnetic resonance spectroscopy (MRS) to measure cortical GSH levels in young people with bipolar disorder to determine if lowered GSH might be a useful biomarker of vulnerability to the illness.
We studied 13 patients with DSM-IV bipolar disorder and 11 healthy age-matched controls using proton MRS in conjunction with the SPECIAL acquisition technique. Voxels were placed in prefrontal and occipital cortex. All patients were clinically euthymic at the time of study and unmedicated. GSH and other relevant neurometabolites were measured relative to creatinine.
There was no difference in GSH levels between bipolar participants and controls in either prefrontal or occipital cortex. Similarly, participants showed no difference from controls in other measured cortical metabolites including γ-aminobutyric acid, glutamate and N-acetylaspartate.
This pilot study suggests that levels of cortical GSH are unlikely to be a useful trait biomarker of bipolar disorder in young people with a history of relatively mild mood instability at an early stage of illness. Lowered GSH levels may be relevant to bipolar pathophysiology in more severely ill patients, particular those with significant current mood disturbance.
KeywordsBipolar disorder Oxidative stress Glutathione Magnetic resonance spectroscopy (MRS)
Conflicts of interest
This study was funded by the Medical Research Council. Philip J. Cowen has been a paid advisor of Lundbeck and Servier and has been a paid lecturer for Lundbeck, Servier and Glaxo Smith Kline. Guy M. Goodwin has held grants from Servier, received honoraria for speaking or chairing educational meeting from AstraZeneca, BMS, Eisai, Lundbeck, Servier and advised AstraZeneca, Boehringer Ingelheim, BMS, Cephalon/Teva Janssen Cilag, Lilly, Lundbeck, Otsuka, P1Vital, Servier, Shire, Takeda and Pfizer. He holds shares in P1vital and acted as expert witness for Lilly. Beata R. Godlewska, Sarah W. Yip and Jamie Near have no conflict of interest to declare.
- Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, Yücel M, Gama CS, Dodd S, Dean B, Magalhães PV, Amminger P, McGorry P, Malhi GS (2011a) Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev 35:804–817. doi: 10.1016/j.neubiorev.2010.10.001 PubMedCrossRefGoogle Scholar
- Berk M, Dean O, Cotton SM, Gama CS, Kapczinski F, Fernandes BS, Kohlmann K, Jeavons S, Hewitt K, Allwang C, Cobb H, Bush AI, Schapkaitz I, Dodd S, Malhi GS (2011b) The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. J Affect Disord 135:389–394. doi: 10.1016/j.jad.2011.06.005 PubMedCrossRefGoogle Scholar
- Hirschfeld RM, Williams JB, Spitzer RL, Calabrese JR, Flynn L, Keck PE Jr, Lewis L, McElroy SL, Post RM, Rapport DJ, Russell JM, Sachs GS, Zajecka J (2000) Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psych 157:1873–1875CrossRefGoogle Scholar
- Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59(Suppl 20):22–33PubMedGoogle Scholar
- Spielberger CD, Gorsuch RL, Lushene PR, Vagg PR, Jacobs GA (1983) Manual for the State-Trait Anxiety Inventory. Consulting Psychologists Press, Inc., Palo Alto, CaGoogle Scholar
- Yildiz-Yesiloglu A, Ankerst DP (2006) Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings. Prog Neuropsychopharmacol Biol Psychiatry 30:969–995PubMedCrossRefGoogle Scholar