Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31P-MRS chemical shift imaging at 4 Tesla

Jensen, J. Eric; Miller, Jodi; Williamson, Peter C.; Neufeld, Richard W. J.; Menon, Ravi S.; Malla, Ashok; Manchanda, Rahul; Schaefer, Betsy; Densmore, Maria; Drost, Dick J.

doi:10.1016/j.pscychresns.2005.11.004

Cited by 61 publications

(41 citation statements)

References 23 publications

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“…However, more recent studies have not found this to be a consistent finding (Yacubian et al 2002;Jensen et al 2006;Smesny et al 2007). No consistent patterns of abnormalities in brain creatine, choline, or myo-inositol have been observed in schizophrenia (Deicken et al 2000;Kim et al 2005;Steen et al 2005).…”

Section: Other Metabolitesmentioning

confidence: 94%

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

Maddock

Buonocore

2011

Current Topics in Behavioral Neurosciences

225

196

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The measurement of brain metabolites with magnetic resonance spectroscopy (MRS) provides a unique perspective on the brain bases of neuropsychiatric disorders. As a context for interpreting MRS studies of neuropsychiatric disorders, we review the characteristic MRS signals, the metabolic dynamics,and the neurobiological significance of the major brain metabolites that can be measured using clinical MRS systems. These metabolites include N-acetylaspartate(NAA), creatine, choline-containing compounds, myo-inositol, glutamate and glutamine, lactate, and gamma-amino butyric acid (GABA). For the major adult neuropsychiatric disorders (schizophrenia, bipolar disorder, major depression, and the anxiety disorders), we highlight the most consistent MRS findings, with an emphasis on those with potential clinical or translational significance. Reduced NAA in specific brain regions in schizophrenia, bipolar disorder, post-traumatic stress disorder, and obsessive–compulsive disorder corroborate findings of reduced brain volumes in the same regions. Future MRS studies may help determine the extent to which the neuronal dysfunction suggested by these findings is reversible in these disorders. Elevated glutamate and glutamine (Glx) in patients with bipolar disorder and reduced Glx in patients with unipolar major depression support models of increased and decreased glutamatergic function, respectively, in those conditions. Reduced phosphomonoesters and intracellular pH in bipolar disorder and elevated dynamic lactate responses in panic disorder are consistent with metabolic models of pathogenesis in those disorders. Preliminary findings of an increased glutamine/glutamate ratio and decreased GABA in patients with schizophrenia are consistent with a model of NMDA hypofunction in that disorder. As MRS methods continue to improve, future studies may further advance our understanding of the natural history of psychiatric illnesses, improve our ability to test translational models of pathogenesis, clarify therapeutic mechanisms of action,and allow clinical monitoring of the effects of interventions on brain metabolicmarkers

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Section: Other Metabolitesmentioning

confidence: 94%

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

Maddock

Buonocore

2011

Current Topics in Behavioral Neurosciences

225

196

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“…Studies varied in the clinical characteristics of patients, field strengths used to acquire data, regions of interest, data processing methods, and metabolites measured. Eight studies included patients reported as medication-naïve first episode (Pettegrew et al, 1991;Keshavan et al, 1993;Fukuzako et al, 1999;Jayakumar et al, 2003;Gangadhar et al, 2004Gangadhar et al, , 2006Jayakumar et al, 2006;Jayakumar et al 2010), 2 studies included separate analyses for medication-naïve and other patients Yacubian et al, 2002) and 4 additional studies included first episode patients (some were taking medication) (Jensen et al, , 2006Miller et al, 2009;Miller et al 2012). 7 studies acquired data at 4T and the rest used 1.5 or 2T scanners.…”

Section: Resultsmentioning

confidence: 99%

“…For the location of data acquisition 14 studies used chemical shift imaging (CSI) whereas the rest used a-priori defined regions of interest, either single or multiple voxels. There were overlaps in subjects and/or 31 P MRS data between several studies: 13/16 of patient and control scans in Miller et al, 2012were included in Miller et al, 2009subjects in Theberge et al, 2004, Jensen et al, 2006, Volz et al, 1997aand Volz 1998b were subsets of cohorts in Jensen et al, 2002, Volz et al, 1997band Volz et al, 1998astudies, respectively. Also, sample in Volz et al, 1997b study consisted of 10 MF patients in addition to the medicated patients in Volz et al, 1998a, and included separate analysis for MF and medicated patients.…”

Section: Resultsmentioning

confidence: 99%

“…Another research group published four studies which included only FE patients some using medications. Three of these found increased GroPCho in ACC with no change in any other phospholipids Miller et al, 2009Miller et al, , 2012, and one reported no differences for any phospholipid metabolites in the FL (Jensen et al, 2006). However, GroPCho returned to the control levels in Miller 2009, and studies at 30 months and 52 months, respectively.…”

Section: Frontal Lobementioning

confidence: 93%

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Phosphorus magnetic resonance spectroscopy studies in schizophrenia

Yüksel

Tegin

O’Connor

et al. 2015

Journal of Psychiatric Research

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“…The hg J has been proposed to harbor mt-DNA missense mutations that partially uncouple the mitochondrial oxidative phosphorylation system (OXPHOS) and thus reduce ATP production [Ruiz-Pesini et al, 2004]. Furthermore, reduced ATP levels have been reported to occur in some defined areas of the brain in schizophrenia patients [Fukuzako et al, 1996;Kegeles et al, 1998;Jensen et al, 2006]. Bridging together these two indications, it may be reasonable to hypothesize that a partially uncoupled mt-OXPHOS associated with hg J could anticipate the appearance of schizophrenia, exacerbating an otherwise underlying sub-threshold ATP deficit.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA haplogroups and age at onset of schizophrenia

Magri

Gardella

Barlati

et al. 2007

American J of Med Genetics Pt B

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A number of studies support a possible link between mitochondrial dysfunction and schizophrenia. To test the hypothesis of a direct contribution of mitochondrial DNA (mt-DNA) in susceptibility to DSM-IV-TR-schizophrenia, we looked for differences in the frequency distribution of the major European haplogroups (hgs) in 142 patients and 190 controls both of Italian origin. A subgroup of patients (N = 37) and healthy counterparts (N = 41) was also analyzed for possible differences in the relative amount of mt-DNA versus nuclear-DNA in blood cells. Patients and controls were comparable for hg frequency distribution and the relative levels of mt-DNA even after stratification by gender and schizophrenia subtype. However, patients harboring the hg J-T showed an anticipated onset of the disorder. These results indicate that the J-T hg of mt-DNA may have a modulator effect on deeper determinants of schizophrenia.

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Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31P-MRS chemical shift imaging at 4 Tesla

Cited by 61 publications

References 23 publications

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

Phosphorus magnetic resonance spectroscopy studies in schizophrenia

Mitochondrial DNA haplogroups and age at onset of schizophrenia

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