Telomere length and its associations with mental disorders, age and genetic risk for mental disorders

Abstract Background Mental disorders are associated with substantially increased morbidity and reduced life expectancy. Accelerated biological ageing might contribute to excess mortality of individuals with mental disorders. The aim of this study was to characterise telomere length, a biological hallmark of ageing, in individuals with mental disorders, and to examine associations between telomere length, age and genetic risk for mental disorders. Methods The UK Biobank is a multicentre, community-based observational study that recruited >500,000 middle-aged and older adults across England, Scotland and Wales. Average leukocyte telomere length (T/S ratio) was measured using quantitative polymerase chain reaction. Polygenic risk scores (PRS) were calculated for individuals of European ancestry. We estimated differences in T/S ratio and age-related changes in T/S ratio between individuals with anxiety disorder, depression or bipolar disorder and people without mental disorders. We also estimated associations between T/S ratio and PRS for these three disorders. Results The analyses included up to 308,725 participants. Individuals with depression had shorter telomeres than people without mental disorders (adjusted β = -0.011, 95% CI -0.019 to -0.004, p Bonf. = 0.027). There was only limited evidence of case-control differences in telomere length for anxiety disorders or bipolar disorders. Age-related changes in telomere length did not differ between individuals with and without mental disorders. PRS for depression were associated with shorter telomeres ( β = -0.006, 95% CI -0.010 to -0.003, p Bonf. = 0.001). There was no evidence that PRS for anxiety disorder or bipolar disorder were associated with telomere length. Conclusion Although telomere length is a biological hallmark of ageing, we observed limited evidence that leukocyte telomere length is a clinically useful marker to quantify accelerated biological ageing in middle-aged and older adults with a lifetime history of anxiety disorder, depression or bipolar disorder.