Table 2.
Study characteristics, clinical and epidemiological data analysis of PTSD impacts on telomere lenght.
| Authors | 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 | Telomere Lenght | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Zhang et al. [57] | April 2019 | USA | Cross-sectional | Low hostility | 135 | 31.3 ± 8.7 | 127 (29.8%) |
n (%) <12th grade 3 (2.2), High school diploma or G.E.D 33 (24.6), Some college/technical school 57 (42.5), Bachelor’s degree 24 (17.9), Graduate degree 17 (12.7) |
364 Whites, 61 Blacks, 25 Asian or Pacific Islanders, 11 American Indian or Alaskan Natives, and 13 unknown |
Depression (28%) and suicide ideation (24%) of the PTSD subjects |
NA | RTL, qPCR, Leukocytes | BSI, PCL | Among the participants with PTSD, those with medium or high level of hostility had shorter LTL than those with low level hostility (p < 0.01). Stepwise regression indicated that hostility level and age, but not gender and PTSD, were negatively correlated with LTL. |
| Medium hostility | 267 | 28.5 ± 7.1 | 237 (55.6%) | <12th grade 1 (1.1), High school diploma or G.E.D 73 (27.2), Some college/technical school 133 (49.6), Bachelor’s degree 46 (17.2), Graduate degree 13 (4.8) | ||||||||||
| High hostility | 72 | 26.5 ± 5.9 | 62 (14.6%) | <12th grade 3 (1.4), High school diploma or G.E.D 37 (51.4), Some college/technical school 29 (40.3), Bachelor’s degree 5 (6.9), Graduate degree 0 (0.0) | ||||||||||
| Bersani et al. [22] | October 2015 | USA | Cross-sectional | Control | 41 | 34.64 (9.17) | 41 (100%) | Years of education (mean ± SD): 14.79 ± 2.44, current smokers (n): 11 | 35 hispanic and 42 non-hispanic | Depression | Statins (n = 2), NSAIDs (n = 5), antidepressants (n = 13), antibiotics (n = 1), hormone drugs for prostate cancer (n = 1), analgesics (n = 1) |
RTL, PCR, Granulocytes | CAPS, BDI-II, ETI, SCL-90-GSI, PSS, PANAS | TL was negatively correlated with early trauma (p < 0.001),global psycho-pathological severity (p = 0.044) and perceived stress (p = 0.019), positively correlated with positive affect (p = 0.026), not significantly correlated with symptom severity of PTSD, depression or negative affect. |
| Case | 35 (17 also w/ MDD) | 35 (100%) | ||||||||||||
| O’Donovan et al. [58] | September 2011 | USA | Cross-sectional | Control | 47 | 30.68 ± 8.19 | 21 (44.68%) | Female: Education: 15.4 (2.0), BMI: 25.2 (4.2), Current smoker n (%): 5 (20), Alcohol use n (%): 0 (0), Substance use n (%): 1 (4) Past abuse. | 6 African americans, 9 ssian americans, 57 whites, 1 hispanic, 2 hawaiians, 4 pacific islanders and 9 multi-ethnics | 23 past MDD, 8 current MDD | - | qPCR | CAPS, DSM-IV | Participants with PTSD had shorter age-adjusted LTL than controls. Exposure to childhood trauma was also associated with short LTL. In fact, childhood trauma appeared to account for the PTSD group difference in LTL; only participants with PTSD and exposure to multiple categories of childhood trauma had significantly shorter LTL than controls. |
| Male: Education: 15.5 (2.1), BMI: 23.6 (3.1), Current smoker n (%): 3 (14), Alcohol use n (%): 1 (5) Past abuse, Substance use n (%): 0 (0). | ||||||||||||||
| Case | 43 | 30.60 ± 6.63 | 23 (53.48%) | Female: Education: 15.2 (2.1), BMI: 23.9 (2.0), Current smoker n (%): 6 (30), Alcohol use n (%): 4 (20 Past abuse and 4 (20) past dependence, Substance use n (%): 1 (5) past abuse and 2(10) past dependence | ||||||||||
| Male: Education: 14.4 (2.3), BMI: 29.5 (4.3), Current smoker n (%): 4 (18), Alcohol use n (%): 4 (18) Past abuse and 4 (18) past dependence, Substance use n (%): 0 (0) Past abuse and 4 (18) past dependence | ||||||||||||||
| Kang et al. [59] | July 2020 | USA | Cross-sectional | Control 1: low combat exposure | 59 | 33.17 (8.69) | 83 (100%) | Education, Years: 15.01 ± 2.09, Body Mass Index, kg/m2: 28.19 ± 4.14, Waist Circumference, cm: 93.47 ± 11.14, Smoker, Yes/No, n: 17/94, Alcohol Abuse, Yes/No, n: 8/103, Substance Use, Yes/No, n: 2/109, MDD Diagnosis by SCID, Yes/No, n: 0/111, Time Since Severe Combat Event, Months: 65.85 ± 35.15 | 31 Hispanic, 80 others | - | 3 Antidepressant, 6 benzodiazepines and hypnotics and 1 anticonvulsants | RTL, qPCR, Leukocytes | DSM-IV, CAPS, PSS, PANAS | Subjects with PTSD showed shorter telomere length and larger amygdala volume than those without PTSD among veterans exposed to high trauma, while there was no significant group difference in these parameters among those exposed to low trauma. |
| Control 2: high combat exposure | 24 | |||||||||||||
| Case 1: low combat exposure | 12 | 33.66 (8.17) | 65 (100%) | Education, Years: 13.93 ± 1.90, Body Mass Index, kg/m2: 29.79 ± 5.58, Waist Circumference, cm: 98.61 ± 14.72, Smoker, Yes/No, n: 33/69, Alcohol Abuse, Yes/No, n: 13/89, Substance Use Yes/No, n: 6/96, MDD Diagnosis by SCID, Yes/No, n: 50/52, Time Since Severe Combat Event, Months: 77.67 ± 30.95 | 46 Hispanic, 56 others | 50 MDD | 21 Antidepressant, 8 benzodiazepines and hypnotics, 2 antipsychotics and 5 anticonvulsants | |||||||
| Case 2: high combat exposure | 53 | |||||||||||||
| Malan et al. [60] | August 2011 | South Africa | Cohort | Control | 53 | 22.3 | 0 (0) | High school education (Grade 8 and higher) (59 (92%)), primary school education (5 (7.81%)) |
12 (19%) black, 1 (1%) white, and 51 (80%) individuals of mixed ancestry. |
23 (36%) diagnosed with MDD at baseline and 31 (48%) diagnosed with MDD at the 3-month follow-up. | NA | RTL, qPCR, Leukocytes | DSM-IV, CD-RISC, BDI, CES-D, MADRS, ETI | A marginally significant association was evident between relative LTL and PTSD status. |
| Case | 9 | 0 (0) | NA | |||||||||||
| Boks et al. [61] | January 2015 | Netherlands | Cross-sectional | Control: low trauma | 0 | 25.1 (8.1) | 128 (100%) | Smokers = 19, Increase alcohol use = 15, Decrease alcohol use = 10, Unchanged alcohol use = 31 | Dutch ethinicity | - | antibiotics in 4 cases, antihistamines in 3 cases and one case of a benzodiazepine prescription. Stopped medication included: antibiotics in one case, antihistaminic in two cases and one case of oral isotretinoïn. | mTL, qPCR, blood sample | SRIP, ETI | Development of post traumatic stress disorder (PTSD) symptoms was significantly associated with increased telomere length and decreased DNAm ageing. |
| Case: low trauma | 64 | |||||||||||||
| Control: high trauma | 32 | 27.4 (9.3) | ||||||||||||
| Case: high trauma | 32 | |||||||||||||
| Roberts et al. [62] | May 2017 | USA | Cross-sectional | Control | 25 | 45.5 (3.6) | 0 (0) | BMI, blood draw, kg/m2 (Mean (SD)): 25.1 (4.0), Past-month smoking, blood draw, any %(N): 14.3 (4), Past-month alcohol consumption, blood draw, none %(N): 32.1 (9), Diet, least healthy quintile, 1995 %(N): 12.0 (3), Past-month physical activity, blood draw, <1/week %(N): 32.1 (9), High cholesterol, 1995 %(N): 7.1 (1), High blood pressure, 1995 %(N): 3.6 (1) | NA | Depression | Antidepressant 10.7% | RTL, RT-qPCR, Leukocytes | DSM-IV, PHQ-9, PCL-C | Relative to not having PTSD, women with a PTSD diagnosis had shorter log-transformed TL. Adjustment for health behaviors and medical conditions did not attenuate this association. Trauma type was not associated with TL and did not account for the association of PTSD with TL. |
| Case | 66 subclinical PTSD | 46.6 (3.7) | 0 (0) | BMI, blood draw, kg/m2 (Mean (SD)): 26.0 (7.3), Past-month smoking, blood draw, any %(N): 9.0 (6), Past-month alcohol consumption, blood draw, none %(N): 43.9 (29), Diet, least healthy quintile, 1995 %(N): 15.2 (10), Past-month physical activity, blood draw, <1/week %(N): 39.4 (26), High cholesterol, 1995 %(N): 7.6 (5), High blood pressure, 1995 %(N): 3.0 (2) | Antidepressant 9.1% | |||||||||
| 25 PTSD diagnosis | 46.6 (3.9) | 0 (0) | BMI, blood draw, kg/m2 (Mean (SD)): 28.4 (7.6), Past-month smoking, blood draw, any %(N): 16.0 (4), Past-month alcohol consumption, blood draw, none %(N): 56.0 (14), Diet, least healthy quintile, 1995 %(N): 28.0 (7), Past-month physical activity, blood draw, <1/week %(N): 32.0 (8), High cholesterol, 1995 %(N): 12.0 (3), High blood pressure, 1995 %(N): 8.0 (2) | Antidepressant 52% | ||||||||||
| Ladwig et al. [63] | July 2013 | Germany | Cross-sectional | Control | 2687 | 56.5 | 1330 (49.5%) | Means (SD) Low educational level (%) 59.0; Living alone (%) 24.1; BMI (kg/m2) 27.6 (4.8); Current smoking (%) 17.8; Alcohol consumption: No 30.1, Moderate 52.7, High 17.2; Physical inactivity (%) 45.7; Actual hypertension (%) 31.7; TC/HDL-C 4.09 (1.18); History of chronic diseases 16.8 |
NA | Depression (PHQ-9) (%)* 3.9, Depressed mood/exhaustion (DEEX) (%)* 18.4 | NA | mTL, qPCR, Leukocytes | PDS, PHQ-9, DEEX | The multiple model revealed a significant association between partial PTSD and TL as well as between full PTSD and shorter TL indicating shorter TL on average for partial and full PTSD. An additional adjustment for depression and depressed mood/exhaustion gave comparable beta estimations. |
| Case | 262 partial PTSD | 52.5 | 100 (38.2%) | Low educational level (%) 57.6; Living alone (%) 29.4; BMI (kg/m2) 27.4 (5.1); Current smoking (%) 21.4; Alcohol consumption: No 30.2, Moderate 49.6, High 20.2; Physical inactivity (%) 42.7; Actual hypertension (%) 24.4; TC/HDL-C 4.04 (1.20); History of chronic diseases 22.9 | Depression (PHQ-9) (%)* 13.0, Depressed mood/exhaustion (DEEX) (%)* 55.0 | |||||||||
| 51 full PTSD | 54.5 | 19 (37.3%) | Low educational level (%) 64.7; Living alone (%) 35.3; BMI (kg/m2) 28.1 (5.7); Current smoking (%) 9.8; Alcohol consumption (%): No 35.3, Moderate 41.2, High 23.5; Physical inactivity (%) 47.1; Actual hypertension (%) 27.5; TC/HDL-C 4.02 (1.21); History of chronic diseases 19.6 | Depression (PHQ-9) (%)* 5.9, Depressed mood/exhaustion (DEEX) (%)* 56.9 | ||||||||||
| Jergović et al. [64] | June 2014 | Croatia | Case-control study | Control | 17 age-matched | 47.2 (1.71) | 17 (100%) | Body mass index 27.13 ± 4; Education: Elementary/high 29 (96.4), University 1 (3.4) Work status: Employed 1 (3.4); Unemployed/retired 29 (96.4); Tobacco use: Yes 17 (58.6); No 12 (41.4); Alcohol use: Yes 5 (20); No 24 (80); Daily physical exercise 1 (3.33) |
NA | - | NA | RTL, RT-PCR, PBMCs | CAPS, STAI, BDI | Middle-aged war veterans with current PTSD had shorter PBMC telomere length than their age-matched healthy controls while the elderly had the shortest telomeres. |
| 15 elderly | 80 or older | 2 (13.33%) | NA | NA | - | NA | ||||||||
| Case | 30 | 45.9 (1.12) | 30 (100%) | mean ± SD Body mass index 27.3 ± 2.62; Education: Elementary/high 29 (96.4), University 6 (35.3); Work status: Employed 15 (88.2), Unemployed/retired 2 (11.8); Tobacco use: Yes 9 (52.9), No 8 (47.1); Alcohol use: Yes 11 (64.7), No 6 (35.3); Daily physical exercise 1 (5.88) |
NA | 24 (80%) MDD, 13 (43%) panic disorder, 9 (30%) obsessive compulsive disorder, 7 (23%) social phobia | Analgesics (non-steroidal anti-inflammatory drugs, N = 18, 60%; opioid analgesics, N = 3, 10%), hypolipidemics (N = 3, 10%), antihypertensives (N = 3, 10%), proton pump inhibitor (N = 1, 3%), (N = 28, 93%) were treated with psychotropic medication: antidepressants (N = 27, 90%), mood stabilizers (N = 7, 23%), anxiolytics (N = 26, 87%), hypnotics (N = 22, 73%), and antipsychotics (N =14, 47%). |
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| Avetyan et al. [65] | April 2019 | Armenia | Case-control study | Control | 49 | 43.5 (9.4) | 49 (100%) | NA | NA | - | NA | RLT, qPCR, Leukocytes | SCID-I, CAPS | Comparison of LTL in diseased and healthy subjects showed that PTSD patients had 1.5 times shorter average LTL than controls. |
| Case | 41 | 46.4 (7.63) | 41 (100%) | NA | ||||||||||
| Kim et al. [66] | June 2017 | South Korea | Cross-sectional | Control —High combat exposure | 11 | 62.82 (5.74) | 11 (100%) | Education (years) 9.45 (4.28) Socioeconomic status: High/Medium/Low, n 2/5/4 AUDIT score 6.73 (7.56) Heavy smoker: Yes/No, n 8/3 |
NA | - | 20.8% psychoactive medications | RLT, qPCR, Leukocytes | CAPS, CES, AUDIT | As a whole, no significant difference in telomere length was found between PTSD and non-PTSD groups. In linear regression analysis stratified by trauma levels, among veterans exposed to severe combat, PTSD status, antidepressant use, and education level affected telomere length. |
| light-to-moderate combat exposure | 109 | 62.95 (4.23) | 109 (100%) | Education (years) 10.56 (3.03) Socioeconomic status: High/Medium/Low, n 18/50/41 AUDIT score 6.71 (7.67) Heavy smoker: Yes/No, n 65/44 |
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| Case—High combat exposure | 34 | 63.38 (3.13) | 34 (100%) | Education (years) 10.35 (3.28) Socioeconomic status: High/Medium/Low, n 7/14/13 AUDIT score 13.09 (10.77) Heavy smoker: Yes/No, n 20/14 |
71.3% psychoactive medications | |||||||||
| light-to-moderate combat exposure | 88 | 62.84 (3.50) | 88 (100%) | Education (years) 10.38 (2.63) Socioeconomic status: High/Medium/Low, n 18/41/29 AUDIT score 11.01 (10.97) Heavy smoker: Yes/No, n 41/47 |
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| Solomon et al. [54] | July 2017 | Israel | Cohort | Control: Resilient | 47 | 63.6 (3.7) | NA | Years of education (M, SD): 14, 3.7, Physical exercising regularly: 62 (62.6%) Smoking on a regular basis: 21 (21.2%) |
NA | Depression | NA | mTL, Southern blot, Leukocytes | PTSD-I, DSM-IV | PTSD trajectories were not implicated in telomere length. |
| Case 1: chronic PTSD | 5 | |||||||||||||
| Case 2: delayed PTSD | 46 | |||||||||||||
| Case 3: recovered PTSD | 1 | |||||||||||||
| Zhang et al. [67] | November 2013 | USA | Cross-sectional | Control | 566 | 29.2 ± 7.3 | 412 (72.79%) | NA | 65.3% were White, 13.9% were Black, 7.8% were Asian or Pacific Islander, and 12.9% were American Indian or Alaskan Native | - | NA | RTL, RT-PCR, Leukocytes | PCL, DSMI-IV, SLE | Participants with PTSD had a lower relative T/S ratio than non-PTSD control subjects. This remained true when PTSD subjects were compared with age-matched non-PTSD controls. |
| Case | 84 | 76 (90.47%) | NA | 75.0% were White, 10.2% were Black, 4.5% were Asian or Pacific Islander, and 10.2% were American Indian or Alaskan Native |
List of abbreviations: mTL—mean telomere length; RTL—relative telomere length; PCR—Polymerase Chain Reaction; qPCR—Quantitative PCR; RT-PCR—real-time PCR; rQ-PCR or RT-qPCR—real-time quantitative PCR; TL—telomere length; LTL—leukocyte telomere length; PBMC—peripheral blood mononuclear cell; BMI—body mass index, mean (SD); TC/HDL-C—total cholesterol/ high-density lipoprotein-cholesterol; NSAID—nonsteroidal anti-inflammatory drug; MDD—major depressive disorder; G.E.D—General Educational Development.