August 1, 2016

expert reaction to genetic associations for major depressive disorder

A group of researchers have attempted to find genetic markers of major depressive disorder by using samples from patients with self-reported diagnosis. Publishing in the journal Nature Genetics the team report a number of markers which they say are associated with self-reporting of clinical diagnosis or treatment for depression.

The SMC also produced a Factsheet on depression. All our previous output on this subject can be seen here.

Prof. Jonathan Flint, Professor in Center for Neurobehavioral Genetics, University of California, Los Angeles, said:

“Making headway with the genetic basis of depression has proven to be a hard problem, and this paper is welcome for reporting genetic association results using a robust design: a large sample size with replication. Significant findings could provide a starting point for understanding the biology of the condition and thus help in the development of new treatments.

“However, the association findings may have nothing to do with major depressive disorder. Diagnosis is based on a single self-report item: ‘Have you ever been diagnosed with clinical depression?’ There are many reasons why people might reply ‘yes’ to this question, not all of which reflect the presence of major depressive disorder.  For instance a study of 5,639 subjects diagnosed with depression by a clinician found that only 38% met criteria for major depressive disorder (DOI:10.1159/000345968 – 2013). Conversely, up to half of people with depression are never diagnosed as such.  So what does a comparison between people who answer yes or no to the 23AndMe question mean?  The answer might represent differences in help-seeking behaviour, not depression at all. So before we can confidently claim that the genetics of depression can be tackled using a minimal approach to diagnosis, we need to understand much more about the trait that is being mapped.”

Dr Elisabeth Binder, Associate Professor in Psychiatry, Max-Planck Institute of Psychiatry, and member of the European College of Neuropsychopharmacology (ECNP) Executive Committee, said:

“This manuscript is an important breakthrough in the genetics of major depression and is a valuable step forward for a better understanding of its underlying biology.

“For a long time, genetic studies in major depression have not been successful, even though it was clear that genes contribute to the risk for depression. Several reasons had been brought forward, the impact of adverse life events that are not well accounted for in depression or the fact that there may not be one depression, but many different subtypes that are not accounted for. Another hypothesis was that very large samples will be needed to uncover the small, cumulative effects. This strategy has panned out for other psychiatric disorders. Given the complexity of depression, it was however estimated that samples with well over 100,000 patients will be necessary, and these were still in the far future using classical recruitment strategy.

“This study has proven that sample size is key, as it now identifies over 15 genetic loci with well over 100,000 patients and 300,000 controls. It is also the first study to show that this can be achieved repurposing large commercial databases for science, in this case from 23andme. Without this collaboration such samples sizes could not have been achieved.

“This is a great leap forward for depression researchers and a first glimpse of light on the horizon for clinicians and patients, that in the future, we may be able base diagnoses and treatment on biology.”

‘Identification of 15 genetic loci associated with risk of major depression in individuals of European descent’ by Hyde et al. published in Nature Genetics UK time on Monday 1^st  August. 

Declared interests

Prof. Flint: “Nothing to declare”

Dr Binder: “I do not have any relevant declarations of interest”