How do depression make us older? Molecular Psych.2013. Nov.12.Ahead of print.

13.11.13

Depression is associated with poor physical health.Depression increases the  chances of having aging-related somatic diseases, such as coronary heart disease, type 2 diabetes,obesity, dementia and cancer.It increase the decline in physical and cognitive functioning and increases the overall mortality risk. These are postulated to be part of accelerated biological  ( cellular) aging in the depressed.These are thought to occur in the specialized nucleic acid–protein complexes that cap the ends of linear DNA called telomeres. Telomeres protect DNA from damage. Telomeres become increasingly shorter with cellular divisions and once it reaches a critically short length, cells become susceptible to senescence or apoptosis.Shorter telomere length (TL) has been linked to the development of various aging-related diseases.

Is depression associated with accelerated cellular ageing? Would that mean telomere lengths (TL)  will be shorter in depression? 

First study to show reduced telomere length in depression  was in 2006 ( Simon et al).Though few others replicated these findings, confounders (smoking, alcohol use, BMI and physical activity) remained a problem.

JE Verhoeven, D Révész1, ES Epel, J Lin, OM Wolkowitz and BWJH Penninx  ( Netherlands Study of Depression and Anxiety) report the results of a study large enough to overcome the previous limitations. CIDI was used to make depression diagnosis. Current depression was measured using 30-item Inventory of Depressive Symptoms—Self Report. Depression duration in recent years was assessed by the Life Chart interview. All potential confounders were measured. 2407 individuals participated in this study. 1095 were having current diagnosis of major depression. 800 individuals formed the remitted depression group. Control group had 510 participants.

Results

The Telomere Length (TL)  exhibited a  shortening with advancing age ( shortening rate of 14 bp per year). Females maintained better length.Heavy drinkers, low weight & obese individuals and  smokers had shorter TL.

TL was significantly shorter among remitted MDD patients  and current MDD patients after adjusting for age gender education and life style factors. The remitted MDD group had 83 bp shorter TL (P = 0.036; Cohen’s d = 0.12) and the current MDD group had 84 bp shorter TL (P = 0.027; Cohen’s d = 0.12) compared with controls. Higher current depression and longer duration were associated with  shorter TL.No significant associations were found between TL and age of onset , childhood trauma or psychoactive medication use.

Limitations: Cross-sectional study ( hence causality cannot be proven).”years of aging’ is an estimate only.Aging was studies in leukocytes  (for TL measurement). It would be  worthwhile to examine this in other tissues such as dentate gyrus of the hippocampus that do undergo mitosis.

Conclusion: Currently depressed persons had shorter TL than never-depressed controls.The differences observed indicate 4–6 years of accelerated aging for the current major depression sample as compared to controls.This study clearly show that depression is associated with several years of biological aging, especially among those with the most severe and chronic symptoms.

Comment: Clinicians would instantly agree that severe depression make people  look much older.

Summary of the article:

Major depressive disorder and accelerated cellular agingresults from a large psychiatric cohort study. Verhoeven JE, Révész D, Epel ES, Lin J, Wolkowitz OM, Penninx BW.Mol Psychiatry. 2013 Nov 12. [Epub ahead of print]

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