Neurochemical abnormalities in unmedicated bipolar depression and mania: A 2D 1H MRS investigation

https://doi.org/10.1016/j.pscychresns.2013.02.008Get rights and content

Abstract

The neurobiology and neurochemistry of bipolar disorder and its different phases are poorly understood. This study investigated metabolite abnormalities in both unmedicated bipolar depression as well as mania using 2D 1H magnetic resonance spectroscopy imaging (MRSI). MRSI data were obtained from 24 unmedicated bipolar disorder (BP) subjects (12 (hypo)manic (BPM)) and 12 depressed (BPD), and 20 closely matched healthy controls. 2D 1H MRSI data were collected from a 15-mm axial slice placed along the anterior commissure-posterior commissure (AC-PC) line to measure brain metabolites bilaterally in the thalamus and also the anterior and posterior cingulate cortex (ACC and PCC). Brain Lac/Cr levels were significantly increased in the BP group as a whole compared to healthy controls. Glutamate abnormalities varied across bipolar state as well as brain region: significantly increased Glx/Cr values were found in the left thalamus in BPD, but BPM had decreased Glu/Cr and Glx/Cr levels in the PCC when compared to healthy controls and decreased Glu/Cr levels even when compared to the BPD subjects group. The findings of the study point to state-related abnormalities of oxidative and glutamate metabolism in bipolar disorder.

Section snippets

Background

Bipolar disorder (BP) is a debilitating mood disorder with unpredictable cycles of depression (BPD) and manic episodes (BPM) interspersed with variable lengths of euthymia. The etiology of bipolar disorder is not clear, although a strong biological basis is suspected due to its hereditary nature. The occurrence of the diametrically opposite mood states of mania and depression is the most striking and perplexing aspect of the illness; therefore, investigating the similarities and differences in

Subjects

Medication-free bipolar depressed (BPD) (N=12, age: 37+10 years; 6 F) and bipolar manic (BPM) (N=12, age: 31+13 years, 9 F) outpatients were recruited from the outpatient clinic at University Hospital, Indiana University School of Medicine and by advertisement from the community. Healthy controls matched for age and gender (N=20, age: 31±9 years; 13 F) were recruited via advertisement. All subjects took part in the study after signing an informed consent form approved by the Investigational

Results

No differences were found between the three groups by either age (p=0.25) or gender (p=0.45). As expected, the YMRS score was significantly higher in the BPM group when compared to the BPD patients (p<0.001), while the HDRS score was significantly higher in the BPD group when compared to the BPM group (p<0.001) (Table 1). Bipolar subjects reported an early age of onset. This is consistent with recent reports which have shown that a majority of bipolar patients have onset of illness in late

Discussion

The results of this study show a significantly increased Lac/Cr in the BP group as a whole regardless of region. Lactate is important in brain bioenergetics and can be increased in states of brain injury, hypoxia or increased metabolism which are accompanied with a redox shift towards anaerobic metabolism (Dager et al., 2008). As reviewed in the introduction, a number of studies point to abnormalities of the brain energy metabolism in BP disorder. Decreased frontal lobe pH observed in BP

Acknowledgments

This project was funded by the NIMH to AA (R01MH075025). The following does not pertain to the conduct of this study but is provided in the spirit of full disclosure. In the past 2 years Dr. Anand has served on the advisory board of AstraZeneca, Pfizer Pharmaceuticals, Merck Pharmaceuticals and Dey Pharmaceuticals. Dr. Anand has been a speaker for Merck Pharmaceuticals. Dr. Anand has received Grant support from Astra-Zeneca and Lilly Pharmaceuticals.

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