Table 3.
Study characteristics, clinical and epidemiological data analysis of anxiety disorders impacts on telomere lenght.
| Date of Publication | Country | Study Design | Patients | Age, Years, Mean (SD) | Sex, n (%) Male | Main Comorbidities/ Lifestyle Factors Associated | Race/Ethnicity | Other Associated Psychiatric Diseases in This Study | Medication | Telomere Measurement and Tissue | Measurement of Psychiatric Disorder | Level of Anxiety | Telomere Lenght | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Verhoeven et al. [68] | January 2018 | The Netherlands | Case control study | Control | 582 | 41.7 (14.8) | 230 (39.5%) | Obesity (13.2%), former smoker (35.6%), current smoker (26.8%), moderate drinker (78.2%), heavy drinker (11.5). Years of education, mean (SD): 12.9 (3.2) | NA | Agoraphobia, panic disorder, socialphobia, generalised anxiety disorder | Antidepressant use, % Tricyclic antidepressant (0.2) Selective serotonin reuptake inhibitor (0.5), other antidepressant (0.2). Benzodiazepine use, %: (0.5) |
mTL, qPCR, Leukocytes | BAI | BAI, mean (SD): 2.9 (2.9) | Patients with current—but not remitted—anxiety disorder had shorter telomere length, suggesting a process of accelerated cellular ageing, which in part may be reversible after remission. |
| Case 1—Remitted anxiety | 459 | 43.6 (12.7) | 131 (28.5%) | Obesity (17%), former smoker (39.8%), current smoker (33.8%), moderate drinker (73.2%), heavy drinker (11.8%). Years of education, mean (SD): 12.4 (3.4) | Antidepressant use, % Tricyclic antidepressant (2.4) Selective serotonin reuptake inhibitor (16.3), other antidepressant (3.5). Benzodiazepine use, %: (3.9) |
BAI, mean (SD): 8.9 (7.3) | |||||||||
| Case 2—Current anxiety group | 1283 | 41.3 (12.4) | 412(32.1%) | Obesity (18.4%), former smoker (29.6%), current smoker (45.6%), moderate drinker (65%), heavy drinker (13.1%). Years of education, mean (SD): 11.6 (3.3) | Antidepressant use, % Tricyclic antidepressant (4.4) Selective serotonin reuptake inhibitor (26.8), other antidepressant (9.1). Benzodiazepine use, %: (13.1) |
BAI, mean (SD): 18.5 (10.8) | |||||||||
| Groer M et al. [69] | December 2019 | USA | Cross-sectional | 97 | 29.6 (6.3) | 0 | Smoking (n = 2), more than an hour of exercise per week (n = 5), BMI: 28.8 (5.9). Completed completion or postgraduate education preparation (54%) | The sample was 76% Caucasian (39% of whom were of Hispanic origin) and 15% African American. The remaining 9% were Asian or other racial categories |
Depression | NA | RTL, qPCR, DNA was extracted from PBMCs with DNeasy Blood and Tissue Ki | POMS, PSS | NA | There were no statistically significant relationships between TL and demographic factors, stress, depression, or TPO status. There were significant negative correlations between TL and anxiety and a trend for a relationship between TL and IL-6 levels. IL-6 levels were significantly, positively associated with negative moods.Higher anxiety scores and inflammation were associated with shorter TL. Inflammation was related to anxiety and other dysphoric moods and was marginally associated with shorter TLs. | |
| Schaakxs et al. [71] | April 2015 | The Netherlands | cross-sectional study | Control | 128 | 70.1 (7.2) | 49 (38.3) | Cigarette years, median: 170.00 (598.75); moderate drinker, n (%): 99 (77.3); heavy drinker, n (%): 12 (9.4);years of education, mean (SD): 12.5 (3.5); Obesity, n (%): 26 (20.3%); physical activity, median (IQR): 2.61 (2.96) | NA | MDD, n (%): 249 (70.1); dysthymia, n (%): 6 (1.7); Co-morbid MDD and dysthymia, n (%): 92 (25.9%) | - | mTL, qPCR, Leukocyte | CIDI, IDS, BAI, AS, CTI | NA | Mean TL did not differ between depressed persons (bp (SD): 5035 (431)) and never-depressed (bp (SD): 5057 (729)) comparisons. Further, TL was not associated with severity, duration, and age at onset of depression; comorbid anxiety disorders; anxiety symptoms; apathy severity; antidepressant use; benzodiazepine use; cognitive functioning; and childhood trauma |
| Case | 355 | 70.6 (7.4) | 120 (33.8) | Cigarette years, median (IQR): 100.00 (435.00); moderate drinker, n (%): 200 (56.3); heavy drinker, n (%): 15 (4.2); years of education, mean (SD): 10.3 (3.4); Obesity, n (%): 60 (16.9%); physical activity, median (IQR): 1.60 (2.96) | TCA, n (%): 78 (22.0); SSRI, n (%): 94 (26.6); Other antidepressants, n (%): 101 (28.5); Benzodiazepine use, n (%): 141 (39.7) |
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| Wang et al. [34] | April 2017 | Sweden | Case-control study | Control | 320 | 44.6 (12.5) | 197 (61.5%) | Smokers—NA | NA | Depression and stress and adjustment disorders | mTL, qRT-PCR, Leukocyte | PHQ-9, HADS-A/HADS-D, MADRS-S | Telomere length, as compared with healthy controls, is shortened in patients with depression, anxiety and stress and adjustment disorders |
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| Case | 181 | 41.9 (11.1) | 22 (12.15%) | Smokers (n = 27, 15%) | Antidepressant use (n = 63, 35%) | Baselines—Median score (IQR): MADRS-S: 20 (14–25); HAD-D: 8 (6–11); HAD-A: 12 (9–15); PHQ-9: 13 (9–17) | |||||||||
| Tyrka et al. [18] | January 2016 | USA | Case-Control study | Control | 113 | 28.5 (9.2) | 50 (44.2%) | Smokers (8.3%) | White (82.3%) | Adversities, depression, PTSD | NA | mTL, qPCR,, Leukocytes | SCID, STAI, PSS, CD-RISC | Significantly higher mtDNA copy numbers and shorter telomeres were seen in individuals with major depression, depressive disorders, and anxiety disorders, as well as those with parental loss and childhood maltreatment. | |
| Case 1—Adverity with no psychiatric disorder | 66 | 31.3 (11.1) | 26 (39.4%) | Smokers (7.8%) | White (80.3%) | ||||||||||
| Case 2—Psichyatric disorder with no adversity | 39 | 30.7 (10.4) | 15 (38.5%) | Smokers (7.7%) | White (92.3%) | MDD (n = 6), depressive (n = 7) | |||||||||
| Case 3—Adversity and psychiatric disorder | 72 | 34.8 (12.0) | 22 (30.6%) | Smokers (17.1%) | White (81.9%) | MDD (n = 7), depressive (n = 18) | |||||||||
| Prelog M et al. [70] | June 2016 | Germany | Case-control study | Control | 129 | Female (n = 85): 36.8 (10.9) Male (n = 44): 34.1(10.8) | 44 (34.1%) | Not documented | NA | Depression (n = 46) | RTL, RT-qPCR, Leukocytes | SCID-I | Panic disorder (n = 129) | Relative telomere lengths (RTLs) were not different between patients and HC. However, within the patient group, smokers had significantly shorter telomeres (0.91 ± 0.30) compared to non-smokers (1.07 ± 0.37) (p = 0.018) and females (0.96 ± 0.34) had shorter telomeres than males (1.10 ± 0.32) | |
| Case | 129 | Female (n = 85): 36.9 (10.8) Male (n = 44): 34.1(11.7) | 44 (34.1%) | Smokers (n = 39) | Antidepressants, yes, n (%): 52 (40.3%) | ||||||||||
| B L Needham et al. [11] | September 2014 | USA | Cross-sectional study | Control—No anxiety | 952 | 29.3(5.8) | 413 (43.4%) | NA | Non-Hispanic white 485 (51%); African american 184 (19.3%); Mexican American 283 (29.7%) | - | Antidepressant use, n (%): 27 (2.8%) | mTL, qPCR, Leukocytes | CIDI | - | The primary finding from this study is that depressive and anxious symptomatology, overall, have no direct relationship with TL in young adulthood. Although associations did not vary by race/ethnicity, among women (but not men) past-year GAD/PD was associated with shorter TL. There was no direct effect of antidepressant medication use on TL, but among current users of antidepressants, those with past-year MD had shorter TL than those with no depression. To our knowledge, this is the first study to examine relationships between antidepressant medication use and depressive and anxious symptomology, as well as the first to examine variation in these relationships by race/ethnicity, in a nationally representative sample. |
| Case 2—GAD/PD or anxious affect | 212 | 30.0(6.0) | 94 (44.3%) | Non-Hispanic white 101 (47.6%); African american 43 (20.3%); Mexican American 68 (32.1%) | Antidepressant use, n(%): 25 (11.8%) | ||||||||||
| Hoen et al. [21] | August 2012 | Netherlands | Longitudinal study | Control | 980 | 53.7 (11.3) | F: 551 (56.22%) M: 465 (43.78%) | Smoking (n = 225; 77%), Alcohol consumption (n = 788; 80%), Sedentarism (n = 50; 52%) | NA | Depression | mTL, PCR, Leukocytes | CIDI | NA | No association was found between depressive disorders and shorter telomeres at follow-up. Anxiety disorders predicted shorter telomere length at follow-up in a general population cohort. |
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| Case | 97 | 51.3 (10.7) | F: 62 M: 36 | Smokers (n = 32; 65%); Alcohol consumption (n = 78; 80%), Sedentarism (n = 505; 52%) | Antidepressant use (n = 14; 15%) | ||||||||||
| Verhoeven et al. [26] | June 2016 | USA and The Netherlands | Longitudinal study | Baseline | 2936 | 41.8 (13.1) | 986 (33.6%) | Former Smokers (n = 975), Current Smokers (n = 1.136); Mild-moderate drinker (n = 2064), Heavy drinker (n = 373) | NA | Current Depressive diagnosis disorder (n = 389, 23.3%), Control (n = 644, 21.9%), Remitted (n = 620, 21.1%) | Tricyclic antidepressants (n = 79, 2.7%); Selective serotonin reuptake inhibitor (n = 502, 17.1), Other antidepressants (n = 164, 5.6%) | RTL, qPCR, Leukocytes | CIDI | Current anxiety disorder (n = 535, 32.0%) | Robust associations of depressive and anxiety disorders with shorter telomeres, but interestingly, it did not demonstrate that depressive and anxiety disorders and LTL change together over time, suggesting the absence of a direct within-person relationship. Short LTL is suggested to be either a long-term consequence or an underlying vulnerability factor for depressive or anxiety disorders |
| Year 6 | 1883 | 48.6 (12.9) | 641 (34.6%) | Former Smokers (n = 797), Current Smokers (n = 531); Mild-moderate drinker (n = 1367), Heavy drinker (n = 186) | Current Depressive diagnosis disorder (n = 159, 30.1%), Control (n = 440, 23.4%), Remitted (n = 915, 48.6%) | Tricyclic antidepressants (n = 56, 3.0%); Selective serotonin reuptake inhibitor (n = 224, 11.9), Other antidepressants (n = 104, 5.5%) | Current anxiety disorder (n = 190, 36.0%) | ||||||||
| Chae et al. [31] | September 2015 | USA | Cross-sectional study | 92 | 43.86 (5.73) | 92 (100%) | Education, n (%): high school or less 38 (41.3), some college or more 54 (58.7). Work status, n (%): working 42 (45.7), unemployed 50 (54.4). Smoking status, n (%): noncurrent 41 (44.6), current 51 (55.4) Health conditions, mean (SD): 1.73 (1.89) |
African American | - | Current doctor-prescribed medication use—Yes n (%): 29 (31.5) | mTL, qPCR, Leukocytes | CES-D, HADS | Anxiety, mean (SD): 5.02 (3.86) | Controlling for sociodemographic factors, greater anxiety symptoms were associated with shorter LTL | |
| Starnino et al. [42] | October 2016 | Canada | Cohort study | 132 | 45.34 (11.16) | 54 (40,9%) | Glasses of alcohol/week, mean (SD): 3.84 (5.38); Smoker n (%): 19(14%), BMI: 25.35 (5.00) | NA | Depression | - | RTL, qPCR, Leukocyte | BDI-II, BAI, CRP, MCSD, CMHo | Beck Depression Inventory-II, mean (SD): 7.64 (8.21) | Shorter TL was observed among individuals high in defensiveness and depressive symptoms, as well as in those with less hostility and anxiety. Telomere length is associated with psychological burden though the direction of effect differs depending on the psychological variables under study |
List of Abbreviations: bp—base pair; TCA—tricyclic antidepressants; mtDNA—mitochondrial DNA; BMI—Body Mass Index; F—female; M—male; IQR—interquartile range; GAD—Generalized Anxiety Disorder; MDD—major depression disorder; TPO—Thyroid Peroxidase; IL—interleukin; HC—healthy controls; USA—United States of America; SD—Standard Deviation; LTL—Leucocyte Telomere Length.