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Abnormal cellular energy and phospholipid metabolism in the left dorsolateral prefrontal cortex of medication-free individuals with bipolar disorder: an in vivo 1 H MRS study

MOOD-CNS Program, Division of Mood and Anxiety Disorders, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, TX 78229, USA.
Bipolar Disorders (Impact Factor: 4.89). 06/2007; 9(s1):119-127. DOI: 10.1111/j.1399-5618.2007.00454.x
Source: PubMed

ABSTRACT While the pathophysiology of bipolar disorder (BD) remains to be elucidated, postmortem and neuroimaging studies have suggested that abnormalities in the dorsolateral prefrontal cortex (DLPFC) are implicated. We compared the levels of specific brain chemicals of interest measured with proton magnetic resonance spectroscopy ((1)H MRS) in medication-free BD subjects and age- and gender-matched healthy controls. We hypothesized that BD subjects would present abnormal cellular metabolism within the DLPFC, as reflected by lower N-acetyl-aspartate (NAA) and creatine + phosphocreatine (Cr + PCr).
Thirty-two medication-free BD subjects (33.8 +/- 10.2 years) and 32 matched controls (33.8 +/- 9.0 years) underwent a short echo-time (TE = 30 ms) (1)H MRS. An 8-cm(3) single voxel was placed in the left DLPFC, and individual concentrations of NAA, Cr + PCr, choline-containing compounds (GPC + PC), myo-inositol, and glutamate were obtained, using the water signal as an internal reference.
BD subjects had lower Cr + PCr [F((1,62)) = 5.85; p = 0.018; one-way analysis of variance (ANOVA)] and lower GPC + PC [F((1,62)) = 5.79; p = 0.019; one-way ANOVA] levels in the left DLPFC. No significant differences were observed for other brain metabolites.
These findings provide further evidence that the pathophysiology of BD involves impairment in the DLPFC. Our findings can be interpreted as evidence for reduced cellular energy and phospholipid metabolism, consistent with the hypothesis of mitochondrial dysfunction in BD.

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    • "However, there are a few studies that found reduced tCr levels in dorsolateral prefrontal cortex, anterior cingulate cortex, hippocampus and basal ganglia of schizophrenia patients (Ohrmann et al., 2005; Ohrmann et al., 2007; Ongur et al., 2009). In addition, the literature is not conclusive about the concentrations of Cr and Ins for patients with bipolar disorder (Yildiz-Yesiloglu and Ankerst, 2006; Frey et al., 2007; Theberge et al., 2007; Ongur et al., 2009; Silverstone and McGrath, 2009; Kraguljac et al., 2012a; Sikoglu et al., 2013). The decrease in tNAA, tCr and Ins that we observed in patients with bipolar disorder compared to healthy participants may be a region specific disturbance in this disorder, as we investigated an understudied brain area, i.e. the left superior temporal cortex. "
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    • "A number of investigators have utilized neuroimaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to investigate the pathophysiology of the MRC in BP as well as magnetic resonance spectroscopy (MRS) to investigate neurochemical abnormalities within the MRC. This report focuses on MRS abnormalities in BPD and BPM. 1 H MRS studies have reported exciting findings regarding molecular abnormalities in BP (Strakowski et al., 2000; Moore and Galloway, 2002; Yildiz-Yesiloglu and Ankerst, 2006; Dager et al., 2008) such as decreased phosphotidyl inositol (Kim et al., 2005), decreases and increases in choline levels (Moore et al., 2000; Cecil et al., 2002; Frey et al., 2007; Michael et al., 2009; Senaratne et al., 2009), decreased or normal N-acetylaspartate (NAA) (Winsberg et al., 2000; Brambilla et al., 2004; Dager et al., 2004; Gallelli et al., 2005; Frye et al., 2007a), elevated gray matter lactate (Dager et al., 2004; Stork and Renshaw, 2005), decreased or unchanged γ-aminobutyric acid (GABA) (Bhagwagar et al., 2007; Kaufman et al., 2009), and elevated Glx (glutamate+glutamine) concentrations (Dager et al., 2004; Michael et al., 2009; Yüksel and Öngür, 2010). 31 P MRS studies have reported increased phosphomonester (Kato et al., 1991; Volz et al., 1998; Yildiz et al., 2001; Silverstone et al., 2002) levels and decreased phosphocreatinine (Kato et al., 1995; Murashita et al., 2000) levels the BPD phase. "
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