A longitudinal proton magnetic resonance spectroscopy study investigating oxidative stress as a result of alcohol and tobacco use in youth with bipolar disorder

Abstract

Alcohol and tobacco have been suggested to be "aggravating factors" for neuroprogression in bipolar disorder (BD), however the impact of these substances on the underlying neurobiology is limited. Oxidative stress is a key target for research into neuroprogression in BD and in accordance with this model, our previous cross-sectional studies have found that risky alcohol and tobacco use in BD is associated with increased oxidative stress, investigated via in vivo glutathione (GSH) measured by proton magnetic resonance spectroscopy( 1 H-MRS) in the anterior cingulate cortex (ACC). What remains unknown is whether the negative impact on GSH levels can be modified as a result of limiting alcohol and tobacco use.Thirty BD patients were included in the study. 1 H-MRS and tobacco and alcohol measures were conducted at baseline and follow-up assessments (15.5 +/-4.6 months apart).Pearson's correlations were performed between percentage change in ACC-GSH and changes in alcohol/tobacco use. Regression analyses were then conducted to further explore the significant correlations. An increase in GSH was associated with a decrease in alcohol consumption (r = -0.381, p < 0.05) and frequency of tobacco use (-0.367, p = 0.05). Change in alcohol consumption, tobacco use and age were significant predictors of change in ACC-GSH (F (3, 26) = 3.69, p < 0.05). Due to the high comorbidity of alcohol and tobacco use in the sample, the individual effects of these substances on GSH levels could not be determined.This study offers longitudinal evidence that changing risky drinking patterns and tobacco use early in the course of BD is associated with improvements in antioxidant capacity, and therefore may be specific targets for early intervention and prevention of neuroprogression in BD.3

Alcohol use in bipolar disorder: A neurobiological model to help predict susceptibility, select treatments and attenuate cortical insult

“…We concluded that this highlights that people with BD are be more susceptible to the oxidative effects of alcohol. Our longitudinal data demonstrates that patients who decreased their drinking after 18 months had an associated increase in GSH, which was supported by the regression model, showing that decrease in alcohol consumption was a significant predictor of increased GSH at follow-up (Chitty et al, 2015a). Importantly these findings suggest that the oxidative effects of alcohol in youth with BD are potentially reversible with a reduction in drinking.…”

“…It is important to re-state here, that in our follow-up study an increase of GSH was found with a decrease in drinking and smoking in BD (Chitty et al, 2015a), suggesting that in the context of the BD-alcohol comorbidity the first line treatment in reducing oxidative stress should be to reduce alcohol consumption and tobacco use.…”

“…Our studies have several limitations, which we refer the reader to the individual papers (Chitty et al, 2014a;Chitty et al, 2013a;2014b;2015a;. Briefly, as with most clinical psychiatry, our studies assess indirect measures of our neurobiological lines of enquiry.…”

“…Furthermore they are both systems that can be probed clinically via electroencephalography (EEG) and magnetic resonance imaging (MRI). Through a number of studies we have investigated the neurobiology associated with alcohol use in BD using these measures (Chitty et al, 2014a;Chitty et al, 2013a;2014b;Chitty et al, 2015a;2015b).…”

Dual diagnosis: Mental disorders vs. substances abuse

“…Promena u potrošnji alkohola, zatim duvana, kao i godine starosti, bili su značajni prediktori promena u koncentraciji GSH. Ova studija pruža dokaz da je korekcija rizičnih obrazaca za piće i duvan u ranoj fazi BP, povezana sa poboljšanjima u sferi antioksidativnog kapaciteta, a samim tim to mogu da budu specifični ciljevi za ranu intervenciju i prevenciju neuroprogresije u bipolarnom poremećaju [31].…”