Distinct neurometabolic profiles are evident in the anterior cingulate of young people with major psychiatric disorders

Hermens, Daniel F.; Lagopoulos, Jim; Naismith, Sharon L.; Tobias-Webb, Juliette; Hickie, Ian B.

doi:10.1038/tp.2012.35

Cited by 43 publications

(35 citation statements)

References 64 publications

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“…Recent developments in MRS spectra have enabled in vivo quantification of GSH from specific brain regions [81]. Only a small handful of studies have assessed in vivo brain GSH levels by MRS in patients with CNS conditions-epilepsy [83,84], schizophrenia [85][86][87], multiple sclerosis [88,89], bipolar disorder [90,91], and mood depressive disorder [91,92]. Recent work has added to this body of work by assessing GSH levels in brains of MCI and AD patients [68,69].…”

Section: Potential Of Gsh Quantitation With Mrs As a Biomarkermentioning

confidence: 99%

The Emerging Role of Glutathione in Alzheimer's Disease

Saharan

Mandal

2014

JAD

150

100

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With millions of older individuals presently suffering from Alzheimer's disease (AD) worldwide, AD is an unduly common form of dementia that exacts a heavy toll on affected individuals and their families. One of the emerging causative factors associated with AD pathology is oxidative stress. This AD-related increase in oxidative stress has been attributed to decreased levels of the brain antioxidant, glutathione (GSH). In this article, we review the role of GSH in AD from a pathological as well as a diagnostic point of view. We recapitulate the literature that has assessed the role of GSH in AD onset and progression. We discuss the various methodologies through which alterations in GSH levels might be monitored, and highlight the yet uncharted potential of assaying GSH levels in vivo with magnetic resonance spectroscopy in AD therapeutics and prognostics. Finally, the present manuscript integrates findings from various studies to elucidate the possible molecular mechanisms through which disruptions in GSH homeostasis may contribute to AD pathology.

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Section: Potential Of Gsh Quantitation With Mrs As a Biomarkermentioning

confidence: 99%

The Emerging Role of Glutathione in Alzheimer's Disease

Saharan

Mandal

2014

JAD

150

100

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“…As per previously published protocols (Hermens et al, 2012, participants were scanned on a 3Tesla GE Discovery MR750 MRI (GE Medical Systems, Milwaukee, WI). Firstly, a 3D sagittal whole-brain scout was undertaken for orientation and positioning of scans (TR=50ms; TE=4ms; 256matrix; no averaging, z=5mm thickness).…”

Section: H-mrs Data Acquisition and Processingmentioning

confidence: 99%

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

Chitty

Lagopoulos

Hickie

et al. 2015

Journal of Affective Disorders

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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

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“…Accordingly, neuropsychological deficits have been proposed as endophenotypes that cut across traditional diagnostic boundaries [9]. This idea of intermediate traits spanning the major psychiatric disorders is not new, and is buttressed by findings of neurometabolic [10], neuroanatomical [11], and neurophysiological [12] factors common to major depression, bipolar disorder and psychosis. The overarching premise is that affective and psychotic disorders may exist along a continuum [13], and exploring shared dimensional features is likely to be more informative prognostically, and for the understanding of pathophysiology (e.g.…”

Section: Introductionmentioning

confidence: 99%

Neuropsychological and Socio-Occupational Functioning in Young Psychiatric Outpatients: A Longitudinal Investigation

et al. 2013

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BackgroundClinical symptoms and neuropsychological deficits are longitudinally associated with functional outcome in chronic psychiatric cohorts. The current study extended these findings to young and early-course psychiatric outpatients, with the aim of identifying cognitive markers that predict later socio-occupational functioning.MethodsAt baseline, 183 young psychiatric outpatients were assessed. Ninety-three returned for follow-up (M = 21.6 years old; SD = 4.5) with an average re-assessment interval of 21.6 months (SD = 7.0), and primary diagnoses of major depressive disorder (n = 34), bipolar disorder (n = 29), or psychosis (n = 30). The primary outcome measure was cross-validated with various other functional measures and structural equation modelling was used to map out the interrelationships between predictors and later functional outcome.ResultsGood socio-occupational functioning at follow-up was associated with better quality of life, less disability, current employment and being in a romantic relationship. The final structural equation model explained 47.5% of the variability in functional outcome at follow-up, with baseline neuropsychological functioning (a composite of memory, working memory and attentional switching) the best independent predictor of later functional outcome. Notably, depressive and negative symptoms were only associated with functioning cross-sectionally. Diagnosis at follow-up was not associated with functional outcome.ConclusionsNeuropsychological functioning was the single best predictor of later socio-occupational outcome among young psychiatric outpatients. Therefore, framing psychiatric disorders along a neuropsychological continuum is likely to be more useful in predicting functional trajectory than traditional symptom-based classification systems. The current findings also have implications for early intervention utilising cognitive remediation approaches.

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Distinct neurometabolic profiles are evident in the anterior cingulate of young people with major psychiatric disorders

Cited by 43 publications

References 64 publications

The Emerging Role of Glutathione in Alzheimer's Disease

The Emerging Role of Glutathione in Alzheimer's Disease

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

Neuropsychological and Socio-Occupational Functioning in Young Psychiatric Outpatients: A Longitudinal Investigation

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