Table 2.
Summary of the description of cortisol parameters in the included studies.
| Parameters | Definition or Calculation for these parameters |
|---|---|
| Morning cortisol (n = 11) | Morning cortisol is defined as the cortisol level measured after waking up. When data was collected over multiple days, some studies specified averaging the results across days, while others did not. The exact wake-up times varied across studies, and not all studies reported this information. Studies that used the cortisol awakening response (CAR) as an indicator often described their morning cortisol collection methods. However, because these studies did not focus on morning cortisol as an independent indicator, their references are not included in detail here. (Basson et al., 2019; Ho et al., 2020a, Ho et al., 2020b, Ho et al., 2020c; Holmqvist-Jamsen et al., 2017; Huynh et al., 2016; Keefe et al., 2019; Landau et al., 2021; Pace et al., 2020; Sampedro-Piquero et al., 2020; Starr et al., 2017; Tada, A., 2018; Wong and Shobo, 2017 |
| Afternoon cortisol (n = 4) | Afternoon cortisol is defined as cortisol collected during the afternoon. The exact collection times varied across studies, and not all studies specified the precise timing. [1–5 pm (Boss et al., 2016); 12 pm and 4 pm (Keefe et al., 2019; Pace et al., 2020; Sampedro-Piquero et al., 2020)] |
| Evening cortisol (n = 7) | Evening cortisol is defined as being collected in the evening or at bedtime. However, the exact collection times varied across studies, and not all studies specified the time. [Basson et al., (2019); Chiang et al., (2016); bedtime at 21:30 or late afternoon at 19:30 (Ho et al., 2020c, Ho et al., 2020b, Ho et al., 2020a); 8:00 pm (Keefe et al., 2019; Huynh et al., 2016; Landau et al., 2021; Sampedro-Piquero et al., 2020] |
| Peak cortisol (n = 2) | Peak cortisol is defined as highest cortisol level of each day or 30 min after waking. (Huang et al., 2020; Rosnick et al., 2016) |
| Cortisol Awake Response (CAR) (n = 30) |
CAR is defined differently across studies. Included studies primarily used the following approaches: 1) Change in cortisol concentration: The difference in cortisol levels between the waking sample and the second and/or third sample taken 30 min after waking, sometimes adjusted by dividing the difference by the time interval between the two measures (Fuentecilla et al., 2019; Huynh et al., 2016; Otto et al., 2018; Urizar et al., 2021; Anderson et al., 2021; Ayala-Grosso et al., 2021; Chiang et al., 2016; Darabos et al., 2019; Goldstein et al., 2017; Kristiansen et al., 2020). 2) Morning cortisol output (AUCi): Measurement of the area under the curve with respect to the increase (AUCi) (Abshire et al., 2018; Basson et al., 2019; Benz et al., 2019; Chian et al., 2016; Corominas-Roso et al., 2017; Herane-Vives et al., 2018; Jakuszkowiak-Wojten, 2016; Labad et al., 2018; Laures-Gore et al., 2018; Ramos-Quiroga et al., 2016; Schuler et al., 2017; Sin et al., 2017; Starr et al., 2017; Yu et al., 2016, 2019). 3) Modeling using statistical techniques: a. Piecewise spline models, specifically linear splines, to represent the CAR (Charles et al., 2020). b. Mixed models (Garcia et al., 2017). c. CAR was assessed by calculating the area under the curve (AUC), peak, reactivity, and parameters of a regression line fitted through morning cortisol measurements (T0, T30, T60) (Doolin et al., 2017). 4) CAR increase threshold: Defined as present when cortisol levels 30 or 45 min after awakening increased by 50% above the basal level at awakening (Ramos-Quiroga et al., 2016). 5) Delta measure: The difference in cortisol concentration at the time of waking and 30 min post-awakening, calculated using the formula developed by Clow et al. and Kunz-Ebrecht et al. (Herane-Vives et al., 2018). |
| Total daily cortisol output | Total daily cortisol output is commonly defined as the area under the curve with respect to ground (AUCg) or AUC calculated over a specific test period, varies in calculation methods across studies. 1) Pruessner formula: AUCG with ti denoting the individual time distance between measurements, mi the individual measurement, and n the total amount of measures. Above formula is independent of the total number of measurements and can be used with any number of repetitions. This approach is independent of the total number of measurements and can accommodate any number of repetitions. For detailed information, refer to Pruessner's paper (2003). (Ayala-Grosso et al., 2021; Charles et al., 2020; Chiang et al., 2016; Darabos et al., 2019; Engert et al., 2018; Fuentecilla et al., 2019; Garcia, M.A. et al., 2021; Herane-Vives et al., 2018; Huynh et al., 2016; Johnson et al., 2020; Liu et al., 2017; Otto et al., 2018; Sampedro-Piquero et al., 2020; Schreier and Chen, 2017; Schuler et al., 2017; Seidenfaden et al., 2017; Urizar et al., 2021; Chin et al., 2017; Goldstein et al., 2017). 2)Fekedulegn (2007)formula: The area under the regression line (AUR) was computed by using the estimated equation and integrating the resulting function as follows: where is the time interval in minutes from the baseline measurement to the last measurement,x is the time from baseline (predictor variable), a is the intercept, and b is the slope of the fitted regression line. Used in some studies for calculating AUC. (D'Cunha et al., 2019; Walls et al., 2020). 3) Indexed by AUC with respect to ground (AUCg): Used in studies for assessing total daily cortisol output. (Sin et al., 2017). 4) AUC for morning cortisol: Focused on cortisol levels during the morning period.(Huang et al., 2020). |
| Mean cortisol over the day (n = 6) | Mean cortisol level is used 1) AUC (Ho et al., 2020a, Ho et al., 2020b, Ho et al., 2020c; Ho et al., 2020a, Ho et al., 2020b, Ho et al., 2020c; Ho, Fong, Chan et al., 2020) 2) average score (Hooper, 2019; Huang et al., 2020; Morgan et al., 2017) |
| Change in cortisol (slope-DCS, Diurnal rhythm (DR) A type of slope, like DCS1, DCS2; Change any time point within a day, Change between days) (n = 28) |
The diurnal slope is defined in various ways across studies, including the following: 1) Modeling approaches: Regression models are commonly used, with variations in the number of sampling time points and repeated days (Armer et al., 2018; Charles et al., 2020; Chin et al., 2017; Ho, Lo et al., 2020; Ho, Fong, Yau et al., 2020; Ho, Fong, Chan et al., 2020; Huang et al., 2020; Johnson et al., 2020; Mitchell et al., 2020; Schreier and Chen, 2017). 2) Simple subtraction methods: a. Diurnal rhythm dysregulation (Bitsika et al., 2017). b. Change scores: Calculated as the difference between: Wake to bedtime cortisol levels; 30 min after waking to bedtime levels; Waking to evening levels; Peak saliva levels to evening levels. (Chiang et al., 2016; Cuneo et al., 2017; Darabos et al., 2019; Engert et al., 2018; Fuentecilla et al., 2019; Huynh et al., 2016; Keefe et al., 2019; Labad et al., 2018; Landau et al., 2021; Otto et al., 2018; Pace et al., 2020; Schuler et al., 2017; Urizar et al., 2021; Walls et al., 2020). 3) Cortisol Day Range (CDR): Calculated as the difference between the day's highest and lowest log-transformed cortisol levels (Charles et al., 2020). 4) Linear and quadratic slope: Models fitted to represent the diurnal cortisol decline (Sin et al., 2017). |
| Cortisol amplitude, as a type of slope (n = 1) | Cortisol amplitude is calculated as the difference between the highest value of the two morning samples and the evening cortisol(Kristiansen et al., 2020) |
| CAP and correlated Parameters (Benz et al., 2019) (n = 1) |
CAP is calculated as the area under the curve with respect to the increase (AUCi), based on the total number of cortisol samples representing the first pulse after awakening for each individual. Since the duration of the CAP varies between individuals, this measure includes all cortisol samples from waking to the first trough. For each following pulse, the AUCi uses all cortisol samples from one trough to the next. The second measure, amplitude, is the difference between the peak value of the current pulse and the (detrended) mesor. The third measure, peak-to-valley value, is the difference between the peak value of an individual pulse and its successive trough (detrended). Finally, the duration of each pulse, in minutes, is the time from one trough to the next. For the first pulse, the duration is measured from waking to the first trough. |
| Cortisol related ratios (n = 5) | Cortisol-related ratios were calculated based on specific research aims. These included ratios of cortisol levels at different time points or comparisons of cortisol with other hormones: 1) Cortisol ratio (Basson et al., 2019). 2) Ratios of cortisol at specific time points:
4) Cortisol suppression ratio in the dexamethasone suppression test (DSTR): Defined as the ratio of cortisol at 10:00 a.m. before dexamethasone (DEX) administration to cortisol at 10:00 a.m. after DEX administration (Labad et al., 2018). 5) Average cortisol levels:
|
| Raw cortisol at each sampling point (n = 4) | Four studies used raw cortisol values for subsequent analysis:
|