In every cell, genetic material is contained within the double-stranded molecules of DNA called chromosomes. Every time a cell divides, the chromosomes are copied so that each new cell gets a copy of this genetic material.  However, the process isn’t perfect – a little bit of the end of the chromosome is lost each time so the copy is not a perfect reproduction. To prevent important genetic material from being lost, the cell protects itself with structures called telomeres located at the ends of the chromosomes. Telomeres are repeating DNA sequences and proteins that act like a guard so that when the chromosome is copied, the important material is protected and only the telomere is shortened. Since telomere shortening happens every time the cell divides, telomeres act like biological clocks for the cell. When the chromosome has been copied enough times that the telomere has been completely worn away, any future copies of the chromosome may be missing important genetic material and the cell may cease to function normally.

Researchers have found that other things can shorten telomeres prematurely. Recently, it has been shown that people with major depressive disorder (MDD) have shorter telomeres than people without MDD. Telomere length and MDD have independently been associated with increased stress levels and abnormally high levels of cortisol, the hormone that is released by the body in response to stress. Wolkowitz and colleagues observed an inverse relationship between telomere length and lifetime exposure to depression.  This finding suggests that shortened telomere length is a consequence of the stress associated with experiencing depression. It is also possible, however, that exposure to stressors in childhood brings about shortening of the telomeres, which may later contribute to the onset of depression.

Previous studies have shown that children of mothers with a history of depression are 3 to 5 times more likely to have a depressive episode than the children of mothers with no history of depression. In a recent study, Gotlib and colleagues looked at the relationship between depression, telomere length, and cortisol reactivity in a group of female children at high risk for depression.  The researchers looked at 97 girls between the ages of 10 and 14 whose mothers either had a history of depression during their daughters’ lifetimes (n=50) or girls whose mothers had no history of depression (n=47). The goal of this study was to determine whether the biological aging associated with shorter telomeres is present before the onset of depressive symptoms, and whether cortisol reactivity is related to telomere length.

Depressive symptoms in the girls were measured using the Children’s Depression Inventory (CDI-S). Subjects in the high risk group were found to have significantly higher scores on the CDI than those in the control group, though the difference was very small and both groups had CDI scores much below the range of depression. However, no relationship was found between telomere length and CDI scores. Saliva samples were taken from all subjects to measure telomere length. Cortisol levels were determined before, during, and after a stress test in which subjects performed a stress-inducing task and were asked stressful questions.

The study found that girls in the high risk group had significantly shorter telomeres than their counterparts in the control group (p=0.001), and this relationship was independent of age, pubertal status, or CDI score. Baseline cortisol levels and rate of recovery from the stress test were similar between the two groups and independent of telomere length. However, subjects with shorter telomeres had significantly greater cortisol reactivity in response to a stress test, meaning that their cortisol levels increased faster and reached higher levels than the control group (p=0.046). These findings did not differ significantly when age, pubertal status, CDI score, or time of day when the stress test was performed were taken into account.

These results suggest that girls at familial risk for depression have shorter telomeres prior to onset of any clinical depressive symptoms, and that the length of their telomeres is associated with increased reactivity to stressful situations. We need additional studies, however, to tease apart genetic and environmental factors impacting these relationships. For example, other studies have shown that shorter telomeres may be due to exposure to stress and adversity, and maternal depression may serve as a potent source of adversity in this model. As shorter telomeres are associated with many chronic illnesses such as heart disease, diabetes, osteoporosis, and dementia in addition to MDD, learning more about the causes and effects of telomere shortening is of critical importance.

Abigail Davies, BA

Gotlib IH, LeMoult J, Colich NL, Foland-Ross LC, Hallmayer J, Joormann J, Lin J, Wolkowitz OM.  Telomere length and cortisol reactivity in children of depressed mothers.  Mol Psychiatry. 2014 Sep 30.