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NMR metabonomics of post mortem brain chemistry reveals that sufferers of bipolar disorder (often referred to as manic depression) have a distinct chemical signature linked to this mental illness. A collaboration between researchers in the UK and US also suggests a possible mode of action for the mood stabilisers used to treat the disorder and how they counteract changes in brain chemistry. Bipolar disorder is a debilitating psychiatric condition that affects around one percent of the population. It is a chronic disorder characterised by alternating extremes of elevated mood, or mania, and bouts of severe depression that can last days or months. Onset usually occurs in late adolescence but can occur as late as middle age. The disorder is a complex of conditions and is difficult to diagnose and treat with only limited mood-stabilising drugs including lithium and valproic acid available to treat it. Researchers do not yet fully understand how and why these treatments work and finding new drugs without the side-effects of these treatments are a focus of research. Now, researchers at the University of Cambridge led by Sabine Bahn, Imperial College London, and the National Institutes of Mental Health in the US are using NMR to better understand the condition and how it can be treated. vImperial's Tsz Tsang from the Department of Biomolecular Medicine and colleagues compared post mortem brain tissue samples of people with manic depression with those of age and gender matched controls. The samples were taken from a region of the brain known as the dorsolateral prefrontal cortex. This brain region is thought to control the processes involved in higher cognitive functioning. NMR spectroscopy was used to glean the metabolic fingerprint of the samples and revealed that people with manic depression had different concentrations of chemicals in this area of the brain than those without the disorder. Tsang and colleagues have also investigated the effects of lithium and valproic acid on a rat model to see what effects these drugs have on the metabolic makeup of non-bipolar brain tissue. The NMR revealed that these drugs caused the opposite chemical changes to those seen in the bipolar brain tissue samples. Chemicals that were increased in the bipolar brain tissue were decreased in those rats given the mood stabilising drugs. The converse was also shown to hold. The findings suggest that in manic depression the balance of excitatory and inhibitory neurotransmitters is disturbed and that it is this imbalance that may be central to the disorder. The researchers also conclude that lithium and valproic acid work by somehow restoring the balance of these neurotransmitters in the brain. More specifically, the team found that levels of the neurotransmitter glutamate, an amino acid, found in the central nervous system, were increased in post mortem bipolar brain but following valproic acid treatment the glutamate to glutamine ratio was decreased. Levels of another neurotransmitter, gamma-aminobutyric acid (GABA), were also shown to be increased following lithium treatment but are lower in the bipolar brain. Both creatine and myo-inositol were increased in the post-mortem brain but depleted following medication. "By identifying a distinct biochemical profile in patients with bipolar disorder, our new research provides a valuable insight into the origins and causes of the disease," explains Tsang, "Moreover, the changes we see in people's metabolic signatures may give a target for drug therapy, allowing us to see how effective a drug is at correcting these changes." "In this instance, we have already shown that the biochemical changes which valproic acid and lithium bring about in mammalian models represent almost a mirror image of the perturbations in bipolar disorder," Tsang adds, "This may provide a useful insight to the actions of these treatments and a basis for which to improve therapy in the future." Related links: The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
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 NMR reveals manic spectroscopy
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