February 11th, 2019

// Aging-related effects of psychiatric disease associated with antidepressant use

King’s College London study published in Frontiers in Genetics
Aging-related effects of psychiatric disease associated with antidepressant use

The increased risk of shorter telomeres in individuals with depression, bipolar disorder and schizophrenia does not seem to be genetic, but instead is likely mediated by environmental factors – and possibly the use of antidepressantsPeople suffering from depression, bipolar disorder and schizophrenia often have a higher rate of age-related diseases as well as ‘older’ DNA, as measured by shorter chromosome “caps” or telomeres. This suggests that psychiatric disorders may be associated with faster biological aging – but is this due to a genetic predisposition to shorter telomeres in these individuals or instead a consequence of living with a psychiatric disorder? A study in Frontiers in Genetics suggests the latter, finding for the first time that antidepressant use is associated with both shorter telomere length and a higher risk for age-related disease, independent of being diagnosed with depression. While the study could not infer whether there was a causal relationship between antidepressant use, telomere length and age-related disease, the findings nevertheless highlight a need to further study the long-term impact of antidepressant use on aging-related conditions.“Our study shows that susceptibility for shorter telomeres amongst psychiatric disorder patients may not be carried by our genes; in most cases, it’s probably moderated by the environment,” says Dr Tim Powell from King’s College London, UK, and one of the study’s authors.“The good news is, we can change this! Previous research suggests that engaging in behaviours known to protect telomeres from shortening — such as exercise, avoiding fatty foods, soft drinks and cigarettes, as well as stress management — may have a positive impact on overall health, and could prove to be a fundamental way of improving the health of those with a psychiatric disorder.”Major depressive disorder, bipolar disorder and schizophrenia have been linked to an increased risk of severe medical conditions – with age-related conditions like cardiovascular disease and stroke showing the highest prevalence. People suffering from the three psychiatric disorders have also been shown to have shorter telomeres compared to the general population. These special structures at the ends of chromosomes get shorter with each cell division, which is thought to represent a ‘molecular clock’ that underlies cell aging.Teasing apart the relationship between these psychiatric disorders, their associated medical conditions and telomere length is difficult.“By the time blood is drawn for research, patients have often taken some form of medication already, are generally more likely to have smoked, or to have been exposed to stressful life events — all of which constitute environmental factors which may influence cell aging,” explains Powell.To overcome this, Powell and colleagues first analysed DNA in blood samples taken from 290 healthy individuals who did not have a psychiatric disorder diagnosis, measuring both telomere length and the presence of genetic markers for major depressive disorder, bipolar disorder and schizophrenia. The results showed no association between genetic risk for these disorders and telomere length.“This suggests that the risk for premature cell aging in people with a psychiatric disorder more likely stems from environmental factors than from a genetic predisposition,” says Powell.Next, in an expanded cohort of 351 individuals, the researchers compared telomere length, or ‘cell age’, in individuals either taking antidepressants or not. They found those taking medication had shorter telomeres – even if they had not been diagnosed with depression but were taking antidepressants for other reasons.Moreover, the individuals taking antidepressants also reported a higher number of age-related diseases – namely type-2 diabetes, arthritis, cardiovascular disease, stroke, high blood pressure and cancer. This association was also independent of a depression diagnosis.The authors provide two possible explanations. One is that antidepressants directly increase telomere shortening and risk for age-related disease. The other, which they believe more likely, is that antidepressant use is more commonly prescribed in those who suffer from depression or related conditions such as sleep problems, and who also suffer from chronic, debilitating age-related disease.The authors say “Antidepressants remain one of the best treatments for psychiatric illness. We now need to perform larger prospective studies to better understand how its use relates to age-related mechanisms and disease.”The study suggests the relationship between antidepressant use and cell aging should be studied further. While the reduction in telomere length associated with antidepressant use is small, approximately 2%, as estimated by the authors, the impact on public health may be substantial. Mind UK estimates that up to 25% of people will experience depression at one point in their life – and from 2006-2016, prescriptions issued for antidepressants in England, where the study was conducted, more than doubled.

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