Scientists have shown for the first time that a chemical in the brain called galanin is involved in the risk of developing depression.
And the research, undertaken by a European research team, points to a strong reason to develop drugs that modify galanin functioning as a new class of antidepressant drug.
Galanin is a neuropeptide (a small protein) that was discovered and investigated over 30 years ago by various groups including the Swedish scientist Tomas Hokfelt. He is one of the senior authors of the paper published in the journal PNAS.
Hokfelt and others made the fundamental discovery that neurons can release peptides alongside their classical transmitters and that galanin and noradrenaline are one such pair. Both have long been implicated in pain and stress and therefore depression but in the past it had been difficult to study peptides in humans.
The new research by scientists from Sweden, Hungary and the UK demonstrates that galanin is an important stress mechanism in the human brain that influences how sensitive or resilient people are to psychosocial stress.
Lead author Gabriella Juhasz, who is a Research Fellow at the University of Manchester and the Semmelweis University in Budapest, said: "Our research shows that some versions of the gene coding for galanin protect against the risk of depression and anxiety but only in people who have experienced early life neglect or trauma, or recent adverse events.
"Furthermore, the three genes for the three receptors through which galanin acts also influence the risk of depression in people experiencing early or recent life adversity. Crucially, all the galanin related genes are widely separated on different chromosomes and the odds are stacked against four random genes acting in the same way by chance."
Results from the research indicate that although the results are statistically reliable, galanin effects modify the substantial effects of stress by only a few percent. Indeed the moderate overall genetic influence (about 35%) on depression is likely to be mediated by many small genetic effects interacting with each other and with psychosocial factors converging on stress mechanism in brain.
Co-author Professor Bill Deakin, from the University of Manchester, said: "The findings provide a strong reason to develop drugs that modify galanin functioning as a new class of antidepressant drug. And new drugs are badly needed as almost all commonly prescribed antidepressants act on serotonin and they are often not very effective.
"Our research confirms what previous reports have shown about the variation in the serotonin 'transporter' gene and how it influences the risk of depression. We found that the galanin effects are substantially greater than the effects of serotonin."
The research team also say there is increasing evidence suggesting that depression, obesity, diabetes and Alzheimer's disease may be varying manifestations of shared underlying abnormalities of body metabolism.
"Galanin may be part of this general vulnerability since it has a significant role in appetite and obesity," added Professor Deakin.
- G. Juhasz, G. Hullam, N. Eszlari, X. Gonda, P. Antal, I. M. Anderson, T. G. M. Hokfelt, J. F. W. Deakin, G. Bagdy. Brain galanin system genes interact with life stresses in depression-related phenotypes. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1403649111
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