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Concentrations of the key "biomarkers" were directly linked to the severity of the disorder.
The researchers are hoping the breakthrough may lead to simple blood tests and a much faster way to assess the impact of medication.
The research, by Indiana University School of Medicine, features online in the journal Molecular Psychiatry.
There are currently no objective clinical laboratory blood tests for mood disorders. Instead, doctors must largely rely on their own judgement to assess a patient's state of mind.
Lead researcher Dr Alexander Niculescu said: "This discovery is a major step towards bringing psychiatry on par with other medical specialties that have diagnostic tools to measure disease states and the effectiveness of treatments.
"Although psychiatrists have been aware that bipolar illness and other psychiatric conditions produced molecular changes in the brain, there was no way to measure those changes while the patient was living.
"Blood now can be used as a surrogate tissue to diagnose and assess the severity of the illness."
Samples at different times
The findings are based on genetic analysis of blood samples from 96 patients with bipolar disorder, formerly known as manic depression.
Some were in a manic phase when the sample was taken, others in a depressive phase.
The research was further bolstered by data obtained from work on mice.
Among the markers identified by the study were five genes involved in the formation of the myelin sheath that protects the nerves, and six involved in controlling growth in the body.
The researchers plan a large study examining how the biomarkers respond when patients are given medication.
Professor David Kendall, an expert in pharmacology at the University of Nottingham, said any correlation between a patient's psychiatric condition and expression of particular genes could potentially give doctors more of an insight into the development of disease.
However, he said a full understanding of how the proteins manufactured by such genes impacted on behaviour was still a long way off.
He said: "It is unlikely that GPs and psychiatrists in the UK are going to be taking blood samples in the near future to aid diagnosis."
(BBC)
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