Depression gene has a silver lining

Some people have a gene which magnifies the psychological impact of life events — for better or for worse.

A recent study challenges our traditional thinking about depression as it shows what might be considered a risk for depression on one hand — and a beneficial outcome on the other. Researchers at the University of Melbourne, Australia were interested in why some adults who were sexually or physically abused as children develop long-term depression — while others do not.

The research, published in British Journal of Psychiatry Open focussed on a particular gene, SERT, which transports the mood-regulating chemical called serotonin. Everybody has one of three types of SERT genes: — long-long l/l — short-long s/l — or short-short s/s.

SERT is one type of protein that transports serotonin from the point of synapse to the neuron. "Short or Long" refers to the length of repeat variations seen in a particular SERT gene. "Short" repeats can partly account for increased anxiety-related personality traits and gut dysfunction.

Researchers tested DNA in 333 middle-aged Australians of Northern and Western European ancestry, this is important to note as there are substantial differences in the s/s gene prevalence in different populations. They then recorded the depressive symptoms of each over five-years.

Those people with the s/s genotype (23% of the 333) who had experienced sexual or physical abuse as a child were more likely to experience ongoing severe depressive symptoms in middle age. However, those with this same genotype and NO history of abuse were happier than the rest of the population. These findings challenge traditional thinking about depression.

Though the gene could signal a person's susceptibility to depression, it would significantly assist in identifying people with a history of child abuse as needing extra assistance to recover from depression.

Lead investigator Dr Chad Bousman added that while the relationship between the SERT gene and depression has been studied before, it was never examined over any length of time. Tracking this relationship over five years provided new knowledge on how depressive symptoms are exacerbated by one's own life experiences. Dr Bousman believes this could offer hope to people who experience ongoing clinical depression.

"Our results suggest some people have a genetic makeup that makes them more susceptible to negative environments. But, if put in a supportive environment these same people are likely to thrive.You can't change your genotype or go back and change your childhood, but you can take steps to modify your current environment.

"It also means that it's not as clear-cut as telling a person that because they have a risk gene, they're doomed. This research is showing that's not the case at all.

"A person's genes alone are not enough to determine how they might experience depression. This research tells us what may be considered a risk gene in one context, may actually be beneficial in another. So this directly opposes the notion of genetic determinism, the idea that your genes define your fate."

Chad A. Bousman MD, PhD, head of Gene-Environment Neuropsychiatry research, Melbourne Neuropsychiatry Centre, Adjunct Research Fellow, the Centre of Human Psychopharmacology at Swinburne University of Technology, Honorary Research Fellow the University of Melbourne Department of General Practice as well as the Florey Institute of Neuroscience and Mental Health.

Dr. Bousman believes this is good news for people experiencing depression and the health professionals treating them. University of Melbourne researchers are now exploring ways to identify which people are more sensitive to life experiences by examining multiple genes in each.

Background Cross-sectional studies suggest that the serotonin transporter promoter region polymorphism (5-HTT gene-linked polymorphic region, 5HTTLPR) moderates the relationship between childhood abuse and major depressive disorder.

Aims To examine whether the 5HTTLPR polymorphism moderates the effect childhood abuse has on 5-year depressive symptom severity trajectories in adulthood.

Method At 5-year follow-up, DNA from 333 adult primary care attendees was obtained and genotyped for the 5HTTLPR polymorphism. Linear mixed models were used to test for a genotype × childhood abuse interaction effect on 5-year depressive symptom severity trajectories.

Results After covariate adjustment, homozygous s allele carriers with a history of severe childhood abuse had significantly greater depressive symptom severity at baseline compared with those without a history of severe childhood abuse and this effect persisted throughout the 5-year period of observation.

Conclusions The 5HTTLPR s/s genotype robustly moderates the effects of severe childhood abuse on depressive symptom severity trajectories in adulthood.

Declaration of interest None.

Copyright and usage © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

About the research

The research was conducted in collaboration between Department of Psychiatry and the Department of General Practice at the University of Melbourne.

Participants were recruited from the Diagnosis, Management and Outcomes of Depression in Primary Care (diamond) study, an ongoing prospective cohort of primary care attendees, led by Professor Jane Gunn. The project started in 2005 and works with 30 randomly recruited rural and metropolitan general practices in Victoria, Australia.

The study was supported by the National Health and Medical Research Council and the L.E.W. Carty Charitable Fund.

*It is important to note that the participants in this study were of Northern and Western European descent, as there are substantial differences in prevalence of the s/s genotype in different populations.

Depression symptom severity was measured each year over five years using the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (PHQ-9).

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