1. Brain lithium,N-acetyl aspartate andmyo-inositol levels in older adults with bipolar disorder treated with lithium: a lithium-7 and proton magnetic resonance spectroscopy study
- Author
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Constance M. Moore, Chelsea T. Finn, Yosef A. Berlow, Perry F. Renshaw, Megan Wardrop, and Brent P. Forester
- Subjects
Male ,medicine.medical_specialty ,Bipolar Disorder ,Magnetic Resonance Spectroscopy ,Lithium (medication) ,Inositol monophosphatase ,Article ,Treatment of bipolar disorder ,chemistry.chemical_compound ,Lithium Carbonate ,Antimanic Agents ,Internal medicine ,medicine ,Humans ,Inositol ,Bipolar disorder ,Prefrontal cortex ,Biological Psychiatry ,Anterior cingulate cortex ,Aged ,Aged, 80 and over ,Aspartic Acid ,biology ,Brain ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,Cross-Sectional Studies ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Frontal lobe ,Linear Models ,biology.protein ,Female ,Protons ,Psychology ,Neuroscience ,medicine.drug - Abstract
Lithium has been used for over 35 years for the treatment of bipolar disorder (BD), yet the precise neurobiological mechanisms through which lithium exerts its clinical effects are not clear. Concerns regarding neurotoxic side effects of lithium in older adults, including a more prolonged recovery from lithium-induced delirium (1) and the risk of lithium-induced renal insufficiency, have led to both declining rates of lithium use in older adults (2) and questions about the most effective clinical approach to utilizing lithium safely in older adults with BD. Lithium magnetic resonance spectroscopy (7Li MRS) measures in vivo brain lithium levels. In a recent study at McLean Hospital’s Geriatric Psychiatry Research Program and Brain Imaging Center, Belmont, MA, USA, we demonstrated that elevations in brain lithium levels were associated with frontal lobe dysfunction and higher Hamilton Depression Rating Scale (HDRS) (3) scores in older adults with BD (4). The higher HDRS scores were associated with somatic symptoms of depression, such as fatigue. Proton magnetic resonance spectroscopy (1H MRS) measures in vivo levels of brain metabolites, including N-acetyl aspartate (NAA), a putative marker of neuronal viability, and myo-inositol containing compounds (myo-Ino). More than half of the studies of adults with BD compared with healthy comparison subjects (HCS) (5–11) report decreased NAA in subjects with BD compared with HCS (5, 6, 10, 11). Lithium has been shown (after four weeks of treatment) to increase brain NAA levels acutely in subjects with BD and in healthy controls (12). Similarly, Silverstone et al. (13) measured increased NAA/Cr levels in the frontal and temporal lobes of BD subjects chronically treated with lithium compared with healthy controls. NAA, which is synthesized in mitochondria, also helps to maintain myelin and is involved with neuron-to-glia signaling (14, 15). Proton magnetic resonance spectroscopy can also measure myo-Ino levels. The inositol depletion hypothesis suggests that lithium’s efficacy in BD may be related to an inhibition of inositol monophosphatase (IMPase), leading to a reduction in brain myo-Ino and an increase in inositol-1-phosphate (I-1-P) (16). Given our recent findings of frontal lobe dysfunction associated with higher brain lithium levels, the purpose of this study was to establish whether there was an association between brain lithium levels and NAA levels in the anterior cingulate cortex (ACC) of older adults with BD. Regional neuroanatomical abnormalities in the prefrontal cortex (PFC) and ACC have been consistently implicated in BD (17). We also wished to further explore the effects of lithium on myo-Ino in older adults with BD. We hypothesized that elevations in brain lithium would be associated with an increase in NAA and a decrease in myo-Ino, reflecting alterations in cellular signaling required for the therapeutic efficacy of lithium.
- Published
- 2008
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