Background
Methods
Identification and selection of studies
Eligibility criteria
Data extraction
Statistical analyses
Results
Literature search
Characteristics of eligible articles
Study | N | Country | Trauma type | Controls | Female | Mean Age | PTSD Assessment | Collection time | Assayed Methods | Interassay variation | Intra-assay variation | Sensitivity | T-frozen |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Carrion 2001 [43] | 51 | USA | Mixed trauma | NTC | 21 | 10.7 | DSM-IV Reaction Index | AM,PM | RIA | 12% | NR | NR | -20 °C |
Coupland 2003 [44] | 66 | Canada | Abuse | NTC | 66 | 38 ± 11 | DSM-IV CAPS-1 | AM,PM | ELISA | 2% | 8% | 0.05 mg/dl. | −80 °C |
Feldman 2013 [45] | 232 | Israeli | Combat | TC,NTC | 110 | 1.5–5.0 | Clinicians diagnose | AM | ELISA | 10.5% | 13.4% | NR | −20 °C |
Gill 2008 [46] | 71 | USA | Civilian trauma | TC,NTC | 71 | 42.9 ± 7.82 | DSM-IV CAPS | PM | ELISA | 9% | 9% | NR | −80 °C |
Kloet 2006 [47] | 83 | Netherland | Combat | TC,NTC | 0 | 34.1 ± 5.8 | DSM-IV CAPS | AM,PM | RIA | 4% | 5.5–9% | NR | −80 °C |
Kobayashi 2014 [48] | 39 | USA | Injury | TC | 7 | 40.3 ± 10.7 | DSM-IV CAPS | AM,PM | RIA | NR | NR | NR | −20 °C |
Lindauer 2006 [49] | 24 | Netherland | Mixed trauma | TC | 10 | 35.1 ± 11.4 | DSM-IV CAPS | AM,PM | RIA | 10% | 10% | NR | −20 °C |
Lipschitz, DS 2003 [50] | 48 | USA | Mixed trauma | TC,NTC | 37 | 16.4 ± 2.6 | DSM-IV CTQ | AM | RIA | 8.00% | 9.00% | NR | −80 °C |
Mcfarlane 2011 [51] | 48 | Australia | Traumatic accident | TC | 12 | 34 ± 12.7 | DSM-IV CAPS | AM,PM | RIA | NR | NR | NR | − 20 °C |
Neylan 2009 [52] | 22 | USA | Combat | TC | 0 | 51.1 ± 2.5 | DSM-IV SCID | AM | NR | NR | NR | NR | NR |
Tucker 2010 [53] | 100 | USA | Bombing registry | TC,NTC | 54 | 47.0 ± 10.0 | DSM-IV DIS | AM | RIA | NR | NR | NR | −20 °C |
Roth 2007 [54] | 218 | Sweden | Combat | TC | 122 | NR | DSM-IV HTQ | AM | RIA | 10% | 10% | 0.8 nmol/l | −70 °C |
Shalev 2007 [55] | 155 | Israel | Road traffic accidents | TC | 64 | 31.2 ± 11.6 | DSM-IV CAPS | AM | NR | NR | NR | NR | −40 °C |
Su, T 2009 [56] | 27 | China | Mixed trauma | NTC | 2 | 43.15 ± 12.8 | DSM-IV CAPS | AM | RIA | 3% | 6% | 10 pg/tube | −80 °C |
Wahbeh 2013 [57] | 71 | USA | Combat | TC | 0 | 55.5 ± 8.9 | DSM-IV CAPS | AM,PM | ELISA | 4.74% | 3.03% | NR | NR |
Witteveen, AB 2010 [58] | 1880 | Netherlands | Mixed trauma | TC | 141 | 47.0 ± 8.0 | DSM-IV CAPS | AM,PM | RIA | NR | NR | NR | −20 °C |
Yehuda 2005 [59] | 63 | USA | Holocaust | TC,NTC | 36 | 69.7 ± 5.0 | DSM-IV CAPS | AM,PM | RIA | 3.90% | 12.00% | 10 ng/dl | NR |
Yehuda, R 2005 [60] | 67 | USA | Holocaust | TC,NTC | 34 | 68.5 ± 5.9 | DSM-IV CAPS | AM,PM | RIA | 3.90% | 12.00% | 10 ng/dl | NR |
Young, EA 2004 [61] | 516 | USA | Mixed trauma | TC,NTC | 457 | 36.8 ± 2.2 | DSM-III | AM,PM | NR | 6.50% | 5.00% | 1 ng/mL | −20 °C |
Young 2004 [62] | 171 | USA | Mixed trauma | TC,NTC | 171 | 18–54 | DSM-III | AM,PM | NR | 10% | NR | 2 μg/dL | −20 °C |
Steven 2004 [63] | 34 | USA | Childhood trauma | NTC | 30 | 40.3 ± 3.3 | DSM-IV CAPS | AM | ELISA | 5.70% | 6.90% | 7 μg/dL | NR |
Neylan 2003 [64] | 32 | USA | Combat | TC | 0 | 49.4 ± 5.7 | DSM-IV CAPS | AM | NR | NR | NR | NR | NR |
Salivary cortisol levels in PTSD as compared with controls
Participants with PTSD, n | controls n | SMD (95% CI) | p value | Heterogeneity | Begg’S test Kendall’s tau statistic (p value) | |||
---|---|---|---|---|---|---|---|---|
Q statistic (DF; p value) | τ2 | I2 | ||||||
all | 1064 | 2322 | −0.28 (−0.53; −0.04) | 0.022 | 236.00(33 < 0.0001) | 0.427 | 86.00% | −0.1907, p = 0.117 |
am | 628 | 1316 | −0.39 (− 0.70; − 0.09) | 0.012 | 132.68(20 < 0.0001) | 0.412 | 84.90% | −0.2000, p = 0.219 |
pm | 436 | 1006 | −0.11 (− 0.52; 0.30) | 0.598 | 96.40(12 < 0.0001) | 0.476 | 87.60% | −0.1795, p = 0.435 |
<2007 | 659 | 734 | −0.13 (− 0.50; 0.23) | 0.479 | 163.59(18 < 0.0001) | 0.568 | 89.00% | −0.2281, p = 0.186 |
≥2007 | 405 | 1588 | −0.48 (− 0.75; − 0.20) | 0.001 | 52.71(14 < 0.0001) | 0.199 | 73.40% | −0.2952, p = 0.140 |
Meta-regression analyses
Estimate | se | zval | pval | ci.lb | ci.ub | |
---|---|---|---|---|---|---|
Collection time | − 0.306 | 0.362 | − 0.844 | 0.399 | −1.015 | 0.404 |
Country | −0.085 | 0.362 | −0.236 | 0.814 | −0.795 | 0.624 |
Publication year | −0.352 | 0.351 | −1.002 | 0.316 | −1.041 | 0.337 |
PTSD assessment | −0.812 | 0.371 | −2.187 | 0.029 | −1.540 | −0.084 |
Assayed methods | −0.344 | 0.384 | −0.896 | 0.370 | −1.097 | 0.409 |
Inter-assay variation | −0.090 | 0.391 | −0.229 | 0.819 | −0.857 | 0.677 |
Frozen | 0.686 | 0.390 | 1.762 | 0.078 | −0.077 | 1.450 |
Heterogeneity and bias analysis
Discussion
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① Saliva collection time should be unified. Considering the preceding cortisol awakening response hypothesis, it could be suggested that the ideal time for morning saliva sampling is after awakening. We suggest that researchers control for waking when saliva samples are to be collected in the morning in practical investigation (by getting people to wake at the same time, e.g. 8.00 am). Besides, the guidelines for assessment of the salivary cortisol must be strictly followed and these include: objective control of sampling adherence, participant instructions, sampling protocols and quantification strategies, as well as reporting and interpreting of salivary cortisol data [40].
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② Storage methods of saliva must be unified. That is, the collected saliva sample should be stored at − 20 °C~ − 80 °C until assayed. Assay methods of saliva must be unified. We recommend using enzyme-linked immunoassay and radioimmunoassay; and inter-assay and intra-assay coefficients of variation of lower than 10%.
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③ The meta-regression analysis had 8 variables, of which only one was significant: PTSD assessment method (Table 3). It means this variable can explain the overall heterogeneity. Thus, we recommend using DSM-IVdiagnostic criteria with the clinician-administered PTSD scale (CAPS). This scale has proved to show high degree of reliability and validity, and can provide a better reference for further study of PTSD and salivary cortisol [41]. It is expected that meeting these consensus guidelines in future research could create more powerful research designs that would yield reliable and reproducible data and results. Although no biomarkers have yet demonstrated clinical applicability for PTSD [23, 41], in future, we believe that salivary cortisol could be a quick biomarker assay to assist in screening patients for PTSD hence promising a possibility for screening a lot of people within a short time for PTSD. After screening, clinicians can then assess symptom severity by conducting clinical interviews with those suspected of having PTSD. On the one hand, as we know from natural disasters (like earthquake, hurricane, tsunami and flood) [42]; the affected population is generally large. Especially for developing countries such as China and India, with an enormous population density and limited psychiatrists, millions of people would be at high risk for PTSD after natural disasters. It can save a lot of clinicians and psychological guidance resources to enable the large-scale PTSD screening to become a reality.