Bipolar-Disorder Marker Found

People with manic depression, or bipolar disorder, have a distinct chemical signature in their brains, according to results of a new study. The research involved using nuclear magnetic resonance (NMR) spectroscopy to analyze post-mortem-patient samples from the dorsolateral prefrontal cortex, which controls processes involved in higher cognitive functioning .

The researchers -- from Imperial College London, the University of Cambridge, and the National Institutes of Mental Health in the US -- found that people with manic depression had different concentrations of chemicals in this area of the brain than those without.

The findings, published in the journal Molecular Psychiatry, may also indicate how the mood stabilizers used to treat the disorder counteract the changes in the brain that it appears to cause.

Bipolar disorder is a debilitating psychiatric condition characterized by alternating mania and depression, affecting about one in every hundred people worldwide. Although it is known that the condition can be treated relatively effectively using the mood-stabilizing drugs lithium and valproic acid, the reasons why these treatments work are poorly understood. The authors hope that their research will enable a better understanding of the condition and of how it can be treated.

The team also used rat models to see the effects of lithium and valproic acid on the metabolite makeup of nonbipolar brain tissue. They found 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 rats given the mood stabilizing drugs, and vice versa. The findings lead them to believe that an upset in the balance of different neurotransmitters known as excitatory and inhibitory neurotransmitters, which are involved in sending signals in the brain, may be central to the disorder. The study also suggests that lithium and valproic acid work by restoring the balance of these neurotransmitters in the brain.

Levels of glutamate, an amino acid which acts as a neurotransmitter in the central nervous system, were increased in post-mortem bipolar brain tissue, but glutamate/glutamine ratios were decreased following valproate treatment. Levels of another neurotransmitter, gamma-aminobutyric acid, were increased after lithium treatment and decreased in the bipolar brain. Both creatine and myo-inositol were increased in the post-mortem brain but depleted with the medications.

Tsz Tsang, a researcher at Imperial College London's biomolecular medicine department and an author of the study, said: “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. 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. This may provide a useful insight to the actions of these treatments and a basis for which to improve therapy in the future,” he said.

For more information, visit: www.imperial.ac.uk