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A higher baseline somatization score at sea level as an independent predictor of acute mountain sickness
A higher baseline somatization score at sea level as an independent predictor of acute mountain sickness Shi-Zhu Bian, Jun Jin, Jun-Qing Dong, Qian-Ning Li, Jie Yu, Cai-Fa Tang, Shi-Yong Yu, Xiao-Hui Zhao, Jun Qin, Lan Huang PII: DOI: Reference:
S0031-9384(16)30812-5 doi: 10.1016/j.physbeh.2016.09.008 PHB 11488
To appear in:
Physiology & Behavior
Received date: Revised date: Accepted date:
15 April 2016 28 August 2016 12 September 2016
Please cite this article as: Bian Shi-Zhu, Jin Jun, Dong Jun-Qing, Li Qian-Ning, Yu Jie, Tang Cai-Fa, Yu Shi-Yong, Zhao Xiao-Hui, Qin Jun, Huang Lan, A higher baseline somatization score at sea level as an independent predictor of acute mountain sickness, Physiology & Behavior (2016), doi: 10.1016/j.physbeh.2016.09.008
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ACCEPTED MANUSCRIPT Title page Title: A higher baseline somatization score at sea level as an independent predictor of
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acute mountain sickness
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Shi-Zhu Bian1,2, Jun Jin1,2, Jun-Qing Dong1,2, Qian-Ning Li3, Jie Yu1,2, Cai-Fa Tang3, Shi-Yong Yu1,2, Xiao-Hui Zhao1,2, Jun Qin1,2 and Lan Huang1,2*. Institute of Cardiovascular Diseases of PLA; 2 Department of Cardiology;
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Department of Neurology, Xinqiao Hospital, Third Military Medical University.
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1
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Corresponding author: Lan Huang MD, PhD, Institute of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, 183 Xinqiao Street, Chongqing
+86-23-68755601.
E-mail:
Lan
Huang:
[email protected];
Tel/Fax:
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China.
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400037,
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This work was conducted by Institute of Cardiovascular Diseases of PLA; Department of Cardiology; Department of Neurology, Xinqiao Hospital, Third
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Military Medical University.
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ACCEPTED MANUSCRIPT A higher baseline somatization score at sea level as an independent predictor of acute mountain sickness
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Shi-Zhu Bian1,2, Jun Jin1,2, Jun-Qing Dong1,2, Qian-Ning Li3, Jie Yu1,2, Cai-Fa Tang3,
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Shi-Yong Yu1,2, Xiao-Hui Zhao1,2, Jun Qin1,2 and Lan Huang1,2*. 1
Institute of Cardiovascular Diseases of PLA; 2 Department of Cardiology;
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Department of Neurology, Xinqiao Hospital, Third Military Medical University.
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Email addresses: Shi-Zhu Bian: [email protected]; Jun Jin: [email protected];
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Jun-Qing Dong: [email protected]; Qian-Ning Li: [email protected]; Jie Yu: [email protected]; Cai-Fa Tang: [email protected]; Shi-Yong Yu:
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[email protected]; Xiao-Hui Zhao: [email protected]; Jun Qin:
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[email protected]; Lan Huang: [email protected].
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Abstract
Objective: The current study aimed to identify the predictive values of psychological
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factors that are evaluated by the Symptoms Checklist-90 (SCL-90) for acute mountain sickness (AMS).
Methods: The subjects (n = 285, non-acclimatized young Chinese men), who were recruited in July 2013, completed a case report questionnaire. In addition, their vital signs (heart rate [HR], blood pressure and pulse oxygen saturation) were measured, and their psychological factors were examined using the SCL-90 at sea level. AMS was diagnosed using the Lake Louise self-assessment scoring system in the morning of the second day after their arrival at 3450 m. Results: Of the nine factors of the SCL-90, the AMS patients (AMS score ≥ 3) were
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ACCEPTED MANUSCRIPT characterized by significantly higher scores for baseline somatization [14.0 (5.0) vs. 13.0 (3.0), p < 0.001], obsession–compulsion, depression, anxiety and hostility
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compared with the non-AMS group (all p values < 0.05). Spearman’s correlation
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analyses revealed associations between AMS scores and somatization (r = 0.316, p < 0.001), depression, anxiety, obsession-compulsion, interpersonal sensitivity, hostility, phobic anxiety, paranoid ideation and psychoticism scores (all p values < 0.001).
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Although all nine factors were associated with AMS in a univariate regression (all p <
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0.05), a further adjusted logistic regression analysis indicated that only baseline somatization score (odds ratio = 1.129, p = 0.001) was an independent predictor of
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AMS. Furthermore, some non-AMS often-occurred symptoms (paresthesia, shortness
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of breath, reduced activity and tinnitus) were also found to be associated with the
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baseline SCL-90 scores.
Conclusion: AMS is correlated with the baseline somatization score at sea level,
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which was measured using the SCL-90. A higher baseline somatization score is also an independent predictor of AMS. Keywords: somatization symptoms, predictor, acute mountain sickness, Symptoms Checklist-90
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ACCEPTED MANUSCRIPT 1. Introduction Acute mountain sickness (AMS) describes a syndrome that occurs after exposure
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to altitudes of 2500 m or higher [1, 2], which is diagnosed by Lake Louise self-score
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system (LLS) [2]. The incidence of AMS has been reported to range from 10 to 85% [1, 3]. AMS is a critical medical issue that threatens tourists, workers and migrants who move from lower altitudes to a high altitude because of its high incidence, the
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resulting discomfort and the deadly risk of high-altitude cerebral edema (HACE).
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Previous researchers have identified many risk factors for AMS[4, 5], including decreased pulse oxygen saturation (SpO2), increased HR, evaluated cerebral
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hemodynamics, faster climbing speeds and higher altitudes [6, 7]. Furthermore,
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vasoconstriction, vasodilatation and increased intracranial pressure or higher
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perfusion pressure may participate in the mechanisms of AMS [2, 8, 9]. Additionally, the physiological or psychological activation of the sympathetic nervous system has
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also been indicated as a consequence of high-altitude exposure and as a risk factor for AMS [1, 2].
Previous studies have paid particular attention to the physiological factors associated with AMS or high-altitude headache [10], but few of them have focused on the psychological aspects [11, 12]. Although a few studies have focused on the effects of high altitude on mental behavior [13] and psychiatric symptoms, the associations between AMS and the associated psychiatric symptoms have not been fully investigated. New onsets of anxiety and depression after high-altitude exposure have been reported. Samuel J. Oliver and colleagues investigated physiological and
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ACCEPTED MANUSCRIPT psychological illness symptoms at high altitude and found that anxiety contributed to the symptom burden when altitude was gained [11]. Furthermore, a relationship
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between changes in negative mood states, including anxiety and cognitive
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performance after hypoxia exposure [14] may account for AMS symptoms. Thus, psychiatric symptoms may be associated with or even predict AMS. In addition, AMS is diagnosed using a subjective self-report questionnaire; thus, psychological factors
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and emotional states are critical in relation to AMS, especially for psychological and
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neurological clinical manifestations, which include headache, dizziness and insomnia [2].
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In addition to the AMS symptoms, many other complaints (non LLS related
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symptoms), such as the symptoms included in the environmental symptoms
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questionnaire (ESQ-III), account for a large proportion of the discomforts of high-altitude exposure. These symptoms may also limit daily work and life at high
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altitudes, although they are not essential for an AMS diagnosis. Therefore, it is critical and urgent to study both the AMS-related problems and the non LLS related symptoms that affect individuals coming to high altitudes from lower altitudes. We postulated that baseline psychological factors would be associated with or predict AMS, and conducted this study with the aim of identifying the relationships between AMS and baseline psychological factors, as assessed using the Symptoms Checklist-90 (SCL-90).
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ACCEPTED MANUSCRIPT 2. Methods 2.1 Participants and procedures
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Participants This prospective observational study was designed to identify the
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predictive values of baseline SCL-90 scores at sea level for AMS after high-altitude exposure. The participants (285 young Chinese soldiers on an altitude-training mission) were recruited in July 2013 at sea level (400 m) in Chongqing and were
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assessed at 3450 m after a four-day bus trip. The inclusion criteria were as follows:
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healthy Chinese men between 16 and 30 years old; subjects did not take medication or receive any intervention before ascending. However, severe headache subjects were
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treated with NSAIDs or Sanlietong (Taiji medicine, Xi’an, China) as necessary at high
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altitude. Subjects with any of the following conditions were excluded:
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cerebrovascular diseases, cardiovascular diseases, neuro-psychosis, respiratory diseases, malignant tumors and disorders of the liver or kidneys.
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The study was thoroughly explained to all of the volunteers, and all of them signed informed consent forms prior to their examinations. This study was reviewed and approved by the Ethics Committee of Xinqiao Hospital at the Second Clinic Medical College of the Third Military Medical University. Procedures The baseline parameters were examined in Chongqing before their trip using structured case report forms [i.e., age, body mass index (BMI), smoking and alcohol consumption]. The physiological measurements were conducted during routine examinations prior their travel. Blood pressure was measured using a sphygmomanometer (HEM-6200, OMRON, China) after a 30-min rest period. The
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ACCEPTED MANUSCRIPT subjects’ HR and SpO2 were also measured using a pulse oximeter (NONIN-9550, Nonin Onyx, USA). Histories of traumatic brain injury, psychiatric disorder/treatment,
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physical injuries, AMS (high-altitude headache) and high-altitude exposure over the
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past 2 years were also recorded on the case report form. The primary version of the SCL-90 was used to measure the subjects’ psychiatric symptoms (Appendix 1) [15-17]. The subjects were questioned using the SCL-90 checklist, which includes 90
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items (9 factor categories). These items were presented out of order and were
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translated into Chinese[18]. Our trained physicians performed the physiological evaluations of HR, blood pressure and SpO2.
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The AMS questionnaires were performed at 3450 m (Xin Duqiao, 8:00-10:00 in
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the morning on the fifth day after one night’s rest, Figure 1A) after the participants
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had completed a four-day trip from sea level (400 m from Chongqing) via bus. AMS-related symptoms (i.e. the LLS symptoms, headache, dizziness, gastrointestinal
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symptoms, difficulty sleeping and fatigue/weakness) and non LLS related symptoms were recorded. AMS was diagnosed based on the LLS scores. Subjects whose LLS score was 3 or higher and who had a headache were identified as having AMS. Furthermore, many other frequently occurring non LLS related symptoms that threaten health and daily life at high altitudes, including lethargy, constipation, dim eyesight, dyspnea and cough, were also queried in the case report form (as present or not present). 2.2 Statistical analysis
Normally distributed variables [i.e., age, BMI, HR, systolic blood pressure (SBP), 7
ACCEPTED MANUSCRIPT diastolic blood pressure (DBP) and SpO2] were expressed as the mean ± standard deviation (SD). Non-normally distributed variables (the nine factors of the SCL-90)
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were expressed as median (quartile range). The AMS+ (with AMS) and AMS-
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(without AMS) groups were compared using independent samples T tests or Mann-Whitney U-tests, as appropriate. The relationships between AMS score and each of the aforementioned parameters were analyzed using Spearman’s correlations.
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Univariate and adjusted logistic regressions were performed to identify the
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independent variables associated with AMS (Figure 1B, the statistical analysis chart).
Figure 1. The process and flowchart of the study
A: Profile of the ascent; B: The statistical analysis flowchart
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ACCEPTED MANUSCRIPT 3. Results Data were excluded if the subjects’ demographic information or other items were
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missing (e.g., lack of demographic information, AMS symptoms or the sub-items of
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the SCL-90); totally 280 valid case report forms and examinations were collected. The mean age and BMI of the subjects in this study were 20.88 ± 2.42 years and 21.28 ± 2.28 kg/m2 respectively. The percentages of participants who smoked or consumed
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alcohol were 26.0% and 4.5% respectively. At sea level, the mean SBP, DBP, HR and
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SpO2 were 112.44 ± 10.94 mmHg, 67.64 ± 8.84 mmHg, 70.20 ± 9.82 beats per min and 97.37 ± 1.15%. The incidences of AMS, headache and dizziness were 24.7%,
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41.9% and 50.2% (Figure 2A). Furthermore, the incidences of non LLS related
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symptoms were shown in figure 2B.
Figure 2. Incidences of AMS-related and non LLS related symptoms A: Incidences of AMS and AMS-related symptoms; B: Incidences of non LLS related symptoms.
The descriptive statistics for the nine factors of the SCL-90 were shown in Figure 3 (a-i). Most of the 280 individuals were characterized by normal or mild scores on the nine factors of the SCL-90 (table 1). More specifically, 186 subjects had
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ACCEPTED MANUSCRIPT a somatization score between 12 and 24, and 135 had an anxiety score between 10 and 20. Mild obsession-compulsion characterized a proportion of the participants (185).
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Regarding depression, 119 participants reported mild depression. The reported
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incidences of positive hostility (130), phobic anxiety (70) and paranoid ideation (111) symptoms were somewhat lower. Furthermore, 95 individuals developed mild
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psychoticism (table 1).
Figure 3. Scatter plots for the nine factors of the SCL-90
Note: The nine factors of the SCL-90 were shown as medians (ranges). a. Somatization; b. Obsession–compulsion; c. Interpersonal sensitivity; d. Depression; e. Anxiety; f. Hostility; g. Phobic anxiety; h. Paranoid ideation; and i. Psychoticism. Table 1. Distribution of baseline SCL-90 factors Without
Mild
Moderate*
Severe
Somatization Cases(AMS)
12 84(11)
12–24 186(53)
24–36 7(3)
≥ 36 3(2)
Obsession–compulsion Cases(AMS)
10 86(12)
10–20 185(52)
20–30 9(5)
≥ 30 0(0)
10
18–27 4(3)
≥ 27 0(0)
13
13–26
26–39
≥ 39
155(31)
119(34)
6(4)
0(0)
10
10–20
20–30
≥ 30
Cases(AMS)
139(25)
135(41)
6(3)
Hostility Cases(AMS)
6 150(30)
6–12 119(32)
12–18 10(6)
≥ 18 1(1)
Phobic anxiety Cases(AMS)
7 205(41)
7–14 72(26)
14–21 3(2)
≥ 21 0(0)
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6–12
12–18
≥ 18
Cases(AMS)
169(36)
106(29)
5(4)
0(0)
Psychoticism Cases(AMS)
10 182(38)
10–20 95(29)
20–30 3(2)
≥ 30 0(0)
90–160
160–200
≥ 200
6(4)
1(1)
Depression Cases(AMS) Anxiety
Paranoid ideation
90
Cases(AMS)
101(16)
* Includes the lower border.
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Total Score
172(48)
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9 125(26)
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Interpersonal sensitivity Cases(AMS)
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9–18 151(40)
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0(0)
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In terms of the demographic data, the age and BMI did not significantly differ
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between the AMS+ and AMS- groups. Furthermore, baseline SBP, DBP, HR and SpO2
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did not differ between two groups (all p values > 0.05). Of the nine factors of the SCL-90, somatization, obsession-compulsion, depression and anxiety scores were
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significantly higher in the AMS+ group than in the AMS- group (p < 0.001). Furthermore, the hostility, phobic anxiety, paranoid ideation and psychoticism scores also showed significant differences between two groups (all p values < 0.001). Most of the nine factors revealed differences between the groups with and without headache and dizziness. The differences in physiological and psychological parameters between the groups are presented in table 2.
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AMS+
p-value
Headache-
Headache+
p-value
13.0 (3.0) 11.0(3.0) 10.0(2.0) 13.0(1.0) 10.0(2.0) 6.0(1.0) 7.0(0.0) 6.0(1.0) 10.0(1.0)
14.0 (5.0) 13.0(4.0) 10.0(3.0) 14.0(3.0) 11.0(2.0) 7.0(3.0) 7.0(1.0) 6.0(2.0) 10.0(3.0)
< 0.001 < 0.001 0.126 0.004 0.009 0.007 0.008 0.020 0.005
13.0(2.25) 11.0(2.0) 10.0(2.0) 13.0(2.0) 10.0(2.0) 6.0(1.0) 7.0(0.0) 6.0(1.0) 10. 0(1.0)
14.0(4.0) 12.0(3.0) 10.0(3.0) 14.0(3.0) 11.0(2.0) 7.0(2.0) 7.0(1.0) 6.0(1.25) 10.0(2.0)
< 0.001 < 0.001 0.110 0.029 0.058 0.003 0.193 0.010 0.002
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SCL-90 Somatization Obsession-compulsion Interpersonal sensitivity Depression Anxiety Hostility Phobic anxiety Paranoid ideation Psychoticism
Dizziness-
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Table 2. Differences of psychological parameters between different groups
13.0(3.0) 11.0(3.0) 10.0(2.0) 13.0(1.0) 10.0(1.0) 6.0(1.0) 7.0(0.5) 6.0(1.0) 10.0(1.0)
Dizziness+
p-value
14.0(5.0) 12.0(4.0) 10.0(3.0) 14.0(3.0) 10.0(2.0) 7.0(2.0) 7.0(1.0) 6.0(1.0) 10.0(2.0)
0.036 0.013 0.098 0.014 0.007 0.009 0.480 0.059 0.081
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Non-normally distributed variables (the nine factors of the SCL-90) were expressed as medians (quartile ranges). AMS: Acute mountain sickness; AMS+: (with AMS); AMS-: (without AMS); BMI: body mass index; DBP: diastolic blood pressure; SBP: systolic blood pressure; SCL-90: Symptoms Checklist-90; SpO2: pulse oxygen saturation.
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ACCEPTED MANUSCRIPT Spearman’s correlation analyses indicated relationships between AMS scores and baseline
BMI,
somatization,
obsession-compulsion,
interpersonal
sensitivity,
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depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism
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scores (all p values < 0.05). Regarding the nervous symptoms of AMS, headache was related to baseline scores for somatization, obsession-compulsion, depression, hostility, phobic anxiety, paranoid ideation and psychoticism (all p values < 0.05).
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Dizziness was associated with somatization, obsession-compulsion, interpersonal
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sensitivity, depression, anxiety, hostility, paranoid ideation and psychoticism (all p-values < 0.05), though not with phobic anxiety (p = 0.164). The associations
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between SCL-90 factors and AMS and its symptoms were shown in table 3.
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Table 3. Relationships between SCL-90 and AMS and its symptoms AMS score
SCL-90
r
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Variables
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Somatization Obsession-compulsion Interpersonal sensitivity Depression Anxiety Hostility Phobic anxiety Paranoid ideation Psychoticism
0.316 0.319 0.215 0.274 0.234 0.242 0.163 0.212 0.248
Headache
Dizziness
p
r
p
r
p
< 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
0.222 0.235 0.104 0.141 0.111 0.173 0.079 0.149 0.181
< 0.001 < 0.001 0.083 0.019 0.064 0.004 0.188 0.013 0.002
0.164 0.203 0.150 0.196 0.201 0.183 0.083 0.141 0.129
0.006 0.001 0.012 0.001 0.001 0.002 0.164 0.019 0.030
Univariate regressions were performed for each single variable. However, the baselines for age, BMI, SBP, DBP, HR and SpO2 were not associated with AMS (all p values > 0.05). We have also indicated that baseline scores for somatization (p < 0.001), obsession-compulsion (p < 0.001), interpersonal sensitivity (p= 0.015), depression (p = 0.002), anxiety (p = 0.027), hostility (p = 0.001), phobic anxiety (p = 0.007), paranoid ideation (p = 0.004) and psychoticism (p = 0.001) were correlated 13
ACCEPTED MANUSCRIPT with AMS in each univariate regression analysis. A further adjusted logistic regression analysis was performed to identify that the factors were independently associated with
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AMS; this analysis indicated that only baseline somatization (β = 0.121; OR: 1.129;
confounding factors (table 4).
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95% CI: 1.053-1.210; p = 0.001) was still a predictor of AMS independent of other
Table 4. Logistic regressions for baseline parameters and AMS β-coefficient
Odds ratio
Univariate regression Age
-0.011
0.990
0.882
1.110
0.857
BMI
-0.032
0.852
1.101
0.625
SBP
-0.006
0.968 0.994
0.969
1.020
0.661
DBP
-0.010
0.990
0.960
1.022
0.548
HR
-0.003
0.997
0.969
1.025
0.815
SpO2
-0.190
0.827
0.657
1.042
0.108
1.129
1.054
1.209
0.001
0.121
Obsession–compulsion Depression Anxiety Hostility
1.177
1.078
1.286
< 0.001
0.138
1.148
1.028
1.283
0.015
0.129
1.138
1.048
1.234
0.002
0.117
1.125
1.014
1.248
0.027
0.220
1.246
1.090
1.423
0.001
0.257
1.293
1.071
1.561
0.007
Paranoid ideation
0.268
1.307
1.091
1.566
0.004
Psychoticism
0.248
1.281
1.103
1.488
0.001
0.121
1.129
1.053
1.210
0.001
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Phobic anxiety
p-value
0.163
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Interpersonal sensitivity
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Somatization
(95% CI)
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SCL-90
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Risk factors
Adjusted regression Somatization
The baseline of somatization was an independent predictor for AMS. Furthermore, we have also examined the SCL-90 characteristics of AMS at altitude. The results showed that only higher somatization score and depression score were independent risk factors for AMS (Appendix 2, table 1A-3A). Regarding the association between the alterations of SCL-90 and AMS, we have also analyzed the differences and regression for AMS in the alterations of the SCL-90.
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ACCEPTED MANUSCRIPT Only the change of somatization score was associated with AMS score (r = 0.188, p <0.001). Furthermore, only change of somatization was still predictor for AMS (β =
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0.132,OR=1.141,95%CI:1.041-1.250, p = 0.05).
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In order to further identify the roles of SCL-90 in AMS, we have performed the analyses between the groups with a cut-off at 4 for the LLS. The baseline SpO2 (β = -0.563, OR = 0.569, 95%CI: 0.409-0.793, p = 0.001), somatization(β = 0.174,OR =
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1.182, 95%CI: 1.046-1.353,p = 0.007) and paranoid ideation(β = 0.181,OR = 1.355,
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95%CI: 1.001-1.835, p = 0.049) scores were still independent predictors for patients whose LLS ≥ 4. Regarding the alterations of the parameters, only changes of
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somatization (β =0.152,OR =1.165, 95%CI: 1.038-1.307, p = 0.010) and depression
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(β = 0.466, OR = 1.593, 95%CI: 1.084-2.343, p = 0.018) were independent predictor
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for people whose LLS ≥ 4 (Appendix 2, table 4A-5A). Additionally, we investigated the incidences of non LLS related symptoms that
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commonly occurred after high-altitude exposure, including paresthesia (24.7%), shortness of breath (26.2%), chest pain (19.5%), tinnitus (21.7%), reduced activity (23.6%), dim eyesight (9.0%), lethargy (14.2%), constipation (13.5%), cough (7.5%) and dyspnea (8.2%; Figure 2B). The differences in SCL-90 factor scores were also tested in relation to the four main symptoms (incidence > 20%). We observed that the somatization, obsession–compulsion, interpersonal sensitivity, depression, anxiety and hostility scores were significantly higher in individuals with paresthesia than in those without
paresthesia.
Moreover,
higher
baseline
scores
for
somatization,
obsession–compulsion and depression scores were accompanied by a greater
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ACCEPTED MANUSCRIPT reduction in activity (table 5). The differences between those with and without
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shortness of breath groups in the SCL-90 factors have been identified (table 5).
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Reduction in
Reduction in
activity-
activity+
13.0 (3.0)
14.0 (6.0)
< 0.001
11.0 (3.0)
13.0 (4.0)
< 0.001
10.0 (2.0)
10.0 (4.0)
14.0 (4.0)
< 0.001
13.0 (1.0)
10.0 (1.25)
11.0 (2.5)
< 0.001
10.0 (1.5)
6.0 (1.0)
7.0 (3.0)
< 0.001
6.0 (1.0)
Phobic anxiety
7.0(0.0)
7.0 (1.0)
0.002
7.0(0.0)
Paranoid ideation
6.0(1.0)
6.0 (2.0)
< 0.001
6.0(1.0)
10.0 (1.0)
10.0(2.0)
0.001
10.0(1.0)
14.0 (5.0)
< 0.001
Obsession-compulsion
11.0 (3.0)
13.0 (5.0)
Interpersonal sensitivity
9.0 (1.0)
11.0(2.5)
Depression
13.0 (1.0)
Anxiety Hostility
Psychoticism
of breath-
breath+
0.011
14.0 (5.0)
< 0.001 0.014
14.0 (3.0)
p
Tinnitus-
Tinnitus+
p
14.0 (6.0)
0.043
13.0 (3.0)
14.0 (4.0)
0.067
12.0 (4.0)
13.0 (4.0)
0.002
11.0 (3.0)
14.0 (4.0)
0.830
10.0 (3.0)
10.0 (4.0)
0.04
10.0 (2.0)
10.0 (2.0)
0.565
< 0.001
14.0 (3.0)
14.0 (3.0)
0.050
13.0 (2.0)
13.0 (3.0)
0.803
11.0 (3.0)
0.001
11.0 (2.0)
11.0 (3.0)
0.008
10.0 (2.0)
11.0 (2.0)
0.236
7.0 (3.0)
0.017
7.0 (2.0)
7.0 (3.0)
0.030
6.0 (2.0)
6.0 (2.0)
0.566
7.0 (1.0)
0.041
7.0(1.0)
7.0 (1.0)
0.743
7.0(1.0)
7.0 (1.0)
0.521
7.0 (2.0)
< 0.001
7.0(2.0)
7.0 (2.0)
0.003
6.0(1.0)
6.0 (1.0)
0.540
11.0 (2.0)
< 0.001
10.0(2.0)
11.0 (2.0)
0.113
10.0(1.0)
10.0 (2.0)
0.526
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13.0 (3.0)
Shortness of
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Somatization
Shortness
p
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p
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Paresthesia+
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Paresthesia-
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Table 5. Differences of SCL-90 in four main non-AMS related symptoms
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6A).
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Furthermore, the non LLS related symptoms’ characteristics of SCL-90 at altitude has also been carried out and attached in Appendix 2 (Table
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ACCEPTED MANUSCRIPT 4. Discussion The main finding of our study was that SCL-90 scores at low altitude were
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associated with risk of AMS. In specific a tendency for somatization was a significant
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predictor of AMS. Given the subjective nature of questionnaires such as the LLS to diagnose AMS, this is noteworthy.
We observed associations between the baselines of harmful psychological
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symptoms as well as AMS and the associated headache, dizziness, and nervous
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symptoms. Additionally, we found that the baseline somatization score is an independent predictor of AMS at 3450 m. Finally, we have also observed the
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differences between the SCL-90 factors and the non LLS related symptoms.
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4.1 AMS was associated with SCL-90 factors at both altitudes
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Previous studies have focused on the associations between high altitude mountaineering and psychological factors [19] and have indicated the partial
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association of AMS with psychological factors through meta-analysis and field trials [20]. AMS symptoms and progression have been also reported in normobaric hypoxia equivalent which was similar to our study[21]. However, the predictive values of the baseline psychological factors for AMS have not been fully investigated. The current study further reveals that individuals with AMS have higher baseline somatization, depression, anxiety and obsession-compulsion scores. Subjects susceptible to AMS have been found to be more anxiou. Additionally, investigators have proposed the term “acute hypoxic physiological anxiety” to describe the anxiety that occurs after the arrival at altitudes and it is associated with AMS [22]. AMS patients showed more
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ACCEPTED MANUSCRIPT baseline somatization symptoms score at sea level prior to high-altitude exposure, a finding that is in accordance with the results of previous studies on AMS
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symptomatology [22]. AMS severity was also positively correlated with the baseline
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scores for somatization, anxiety and depression, highlighting the roles of psychological factors in the AMS diagnosis. It is possible that anxiety and depression reactions to high-altitude exposure lead to self-reported AMS symptoms [14, 23], but
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subjective feelings about symptoms should not be ignored.
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The emotional and behavioral changes resulting from high-altitude exposure have been indicated in previous studies [13].We have also identified the associations
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between AMS and SCL-90 at altitude. The AMS individuals had higher somatization,
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depression, anxiety and obsession-compulsion scores, indicating that anxiety and
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depression may affect the incidence of AMS. Furthermore, the average somatization score was significantly higher in the AMS+ group than in the AMS- group, indicating
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that the AMS patients have more somatization symptoms, which is in accordance with the previous studies on AMS symptomatology[24]. The SCL-90 characteristics of AMS may be useful for the clinical practice in treatment of AMS. However, the associations and predictive values of baseline emotional states prior to high-altitude exposure have not been widely investigated. Thus, the impact of baseline psychological states before high-altitude exposure on AMS should be of great importance. Furthermore, headache and dizziness were the most frequently reported nervous symptoms of AMS; these symptoms may be more likely to be affected by psychological factors than other symptoms. Therefore, we analyzed these two
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ACCEPTED MANUSCRIPT symptoms in particular. The associations between AMS and the psychological states of anxiety and depression may be caused by their relationships with AMS-related
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symptoms, such as headache and dizziness, which is partially in accordance with
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previous reports [14, 23, 25]. A hypobaric chamber simulation study indicated the associations between anxiety and the symptomatology of AMS and the effects of anxiety on performance [14]. Studies at sea level have shown a relationship between
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headache (including episodic headache, chronic cluster headache and tension-type
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headache) and anxiety or depression [26, 27]. Further studies have demonstrated that headaches at high altitude present with the clinical characteristics of migraine, cluster
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or episodic headaches [28, 29]. The relationship between anxiety (panic attacks) and
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headache has also been indicated [30], which is in accordance with our finding that
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headache patients had a higher baseline anxiety level. Our previous study also showed that somatic symptoms were associated with anxiety severity after high-altitude
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exposure [25, 31].
Dizziness is another nervous complaint of AMS that may be affected by psychological risk factors and may result in somatic symptoms. However, fewer studies have indicated a relationship between dizziness and anxiety, although depression-induced dizziness has been reported [32, 33]. In this study, we have also observed the association between dizziness and the basic psychological parameters on the SCL-90. Although AMS is not characterized by higher scores for interpersonal sensitivity, the distribution was more varied in AMS+ individuals than in AMSindividuals.
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ACCEPTED MANUSCRIPT 4.2 Associations between SCL-90 and non LLS related symptoms Many symptoms that frequently occur after high-altitude exposure were not used
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for the AMS diagnosis. We further analyzed the associations between the SCL-90
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factors and the non-AMS symptoms with an incidence greater than 20%, including paresthesia, reduced activity, shortness of breath and tinnitus. Similar to the AMS-related symptoms, paresthesia, reduced activity and shortness of breath were
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associated with significantly higher scores on most of the SCL-90 factors at baseline
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level, especially somatization, depression and anxiety. It is not difficult to understand that baseline psychological factors result in paresthesia and reduced activities as a
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result of fear, anxiety and depression. Shortness of breath may be caused by
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somatization and anxiety about addressing hypoxia, or it may be caused by hypoxia
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per se [34, 35]. Although paresthesia, shortness of breath and tinnitus were not included in the diagnostic criteria, the diagnostic value of these symptoms should be
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given proper attention.
Based on the discussion above, the non-AMS related symptoms with a high incidence may be potential symptoms, and they should receive proper attention. The non-AMS symptomatology should also been prevented and treated promptly. 4.3 Baseline somatization score as an independent predictor of AMS After adjusting for other parameters, only the baseline somatization score remained an independent predictor of AMS. The sub-items of somatization include headache, cardiovascular, gastrointestinal and respiratory symptoms. In the past several decades, most studies have given greater attention to physiological and genetic
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ACCEPTED MANUSCRIPT risk factors and have identified some valuable factors that contribute to AMS [9, 36-38]. Though anxiety has a widely demonstrated association with AMS or
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high-altitude exposure, the baseline anxiety score was not an independent predictor of
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AMS in the adjusted regression. However, the baseline somatization score predicted AMS in the adjusted analysis that excluded the effects of the confounding factors. Combined with the current results, somatization symptoms, emotional disorders and
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psychiatric symptoms may be considered risk factors, predictors or even clinical
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manifestation of AMS that need to be investigated in further studies.
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ACCEPTED MANUSCRIPT 4.5 Limitations The participants in our study were all young Chinese men, which could have
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generated an age or gender bias; our future studies will address these possible biases.
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Another limitation of the current study is that further detailed examinations of the mechanisms and other methods for measuring anxiety and depression were not
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performed; such examinations should be performed in future studies.
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ACCEPTED MANUSCRIPT 5. Conclusion AMS is associated with the baseline somatization and other symptom scores
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measured by SCL-90. However, only the somatization score at baseline was a
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predictor of AMS independent of other confounding factors; thus, further studies of
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the AMS mechanisms and possible clinical applications are warranted.
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ACCEPTED MANUSCRIPT Abbreviation AMS: Acute mountain sickness;
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AMS+: (with AMS);
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AMS-: (without AMS); BMI: body mass index;
LLS: Lake Louise self-score system;
SCL-90: Symptoms Checklist-90;
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OR: odds ratio.
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SpO2: pulse oxygen saturation;
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SBP: systolic blood pressure;
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DBP: diastolic blood pressure;
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ACCEPTED MANUSCRIPT Acknowledgements This work is supported by the Ministry of Health of P. R. China [grant No. 201002012]
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and the People's Liberation Army P. R. China [grant No. BWS14J040]. We would like
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to thank all of the individuals who participated in this study for their support. We are grateful to Mr. Can Chen, Mr. Bai-Da Xu and Miss Shuang-Fei Li for their help. We also thank Mr. Ru-Fu Xu for his suggestions about statistics. Finally, I would like to
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thank Miss Meng Zhou for her help and support in preparation of this manuscript.
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ACCEPTED MANUSCRIPT Conflict of Interest Statement:
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The authors declare that there is no conflict of interests.
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ACCEPTED MANUSCRIPT Figure legend
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1A: Profile of the ascent; 1B: The statistical analysis flowchart
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Figure 1. The process and flowchart of the study
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Figure 2. Incidences of AMS-related and non LLS related symptoms 2A. Incidences of AMS and AMS-related symptoms 2B. Incidences of non LLS related symptoms
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Figure 3. Scatter plots for the nine factors of the SCL-90
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Note: The nine factors of the SCL-90 are shown as median (range). a. Somatization; b. Obsession–compulsion; c. Interpersonal sensitivity; d. Depression;
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e. Anxiety; f. Hostility; g. Phobic anxiety; h. Paranoid ideation; i. Psychoticism.
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ACCEPTED MANUSCRIPT Highlights
Described novel epidemiology and characteristics of SCL-90 pre- and post
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high-altitude exposure
Identified the associations between SCL-90 factors and AMS
Identified the predictive role of baseline somatization score for AMS
Found associations between non-AMS-related symptoms and SCL-90 items
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S0031-9384(16)30812-5 doi: 10.1016/j.physbeh.2016.09.008 PHB 11488
To appear in:
Physiology & Behavior
Received date: Revised date: Accepted date:
15 April 2016 28 August 2016 12 September 2016
Please cite this article as: Bian Shi-Zhu, Jin Jun, Dong Jun-Qing, Li Qian-Ning, Yu Jie, Tang Cai-Fa, Yu Shi-Yong, Zhao Xiao-Hui, Qin Jun, Huang Lan, A higher baseline somatization score at sea level as an independent predictor of acute mountain sickness, Physiology & Behavior (2016), doi: 10.1016/j.physbeh.2016.09.008
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ACCEPTED MANUSCRIPT Title page Title: A higher baseline somatization score at sea level as an independent predictor of
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acute mountain sickness
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Shi-Zhu Bian1,2, Jun Jin1,2, Jun-Qing Dong1,2, Qian-Ning Li3, Jie Yu1,2, Cai-Fa Tang3, Shi-Yong Yu1,2, Xiao-Hui Zhao1,2, Jun Qin1,2 and Lan Huang1,2*. Institute of Cardiovascular Diseases of PLA; 2 Department of Cardiology;
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Department of Neurology, Xinqiao Hospital, Third Military Medical University.
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1
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Corresponding author: Lan Huang MD, PhD, Institute of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, 183 Xinqiao Street, Chongqing
+86-23-68755601.
E-mail:
Lan
Huang:
[email protected];
Tel/Fax:
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China.
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400037,
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This work was conducted by Institute of Cardiovascular Diseases of PLA; Department of Cardiology; Department of Neurology, Xinqiao Hospital, Third
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Military Medical University.
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ACCEPTED MANUSCRIPT A higher baseline somatization score at sea level as an independent predictor of acute mountain sickness
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Shi-Zhu Bian1,2, Jun Jin1,2, Jun-Qing Dong1,2, Qian-Ning Li3, Jie Yu1,2, Cai-Fa Tang3,
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Shi-Yong Yu1,2, Xiao-Hui Zhao1,2, Jun Qin1,2 and Lan Huang1,2*. 1
Institute of Cardiovascular Diseases of PLA; 2 Department of Cardiology;
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Department of Neurology, Xinqiao Hospital, Third Military Medical University.
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Email addresses: Shi-Zhu Bian: [email protected]; Jun Jin: [email protected];
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Jun-Qing Dong: [email protected]; Qian-Ning Li: [email protected]; Jie Yu: [email protected]; Cai-Fa Tang: [email protected]; Shi-Yong Yu:
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[email protected]; Xiao-Hui Zhao: [email protected]; Jun Qin:
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[email protected]; Lan Huang: [email protected].
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Abstract
Objective: The current study aimed to identify the predictive values of psychological
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factors that are evaluated by the Symptoms Checklist-90 (SCL-90) for acute mountain sickness (AMS).
Methods: The subjects (n = 285, non-acclimatized young Chinese men), who were recruited in July 2013, completed a case report questionnaire. In addition, their vital signs (heart rate [HR], blood pressure and pulse oxygen saturation) were measured, and their psychological factors were examined using the SCL-90 at sea level. AMS was diagnosed using the Lake Louise self-assessment scoring system in the morning of the second day after their arrival at 3450 m. Results: Of the nine factors of the SCL-90, the AMS patients (AMS score ≥ 3) were
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ACCEPTED MANUSCRIPT characterized by significantly higher scores for baseline somatization [14.0 (5.0) vs. 13.0 (3.0), p < 0.001], obsession–compulsion, depression, anxiety and hostility
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compared with the non-AMS group (all p values < 0.05). Spearman’s correlation
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analyses revealed associations between AMS scores and somatization (r = 0.316, p < 0.001), depression, anxiety, obsession-compulsion, interpersonal sensitivity, hostility, phobic anxiety, paranoid ideation and psychoticism scores (all p values < 0.001).
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Although all nine factors were associated with AMS in a univariate regression (all p <
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0.05), a further adjusted logistic regression analysis indicated that only baseline somatization score (odds ratio = 1.129, p = 0.001) was an independent predictor of
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AMS. Furthermore, some non-AMS often-occurred symptoms (paresthesia, shortness
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of breath, reduced activity and tinnitus) were also found to be associated with the
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baseline SCL-90 scores.
Conclusion: AMS is correlated with the baseline somatization score at sea level,
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which was measured using the SCL-90. A higher baseline somatization score is also an independent predictor of AMS. Keywords: somatization symptoms, predictor, acute mountain sickness, Symptoms Checklist-90
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ACCEPTED MANUSCRIPT 1. Introduction Acute mountain sickness (AMS) describes a syndrome that occurs after exposure
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to altitudes of 2500 m or higher [1, 2], which is diagnosed by Lake Louise self-score
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system (LLS) [2]. The incidence of AMS has been reported to range from 10 to 85% [1, 3]. AMS is a critical medical issue that threatens tourists, workers and migrants who move from lower altitudes to a high altitude because of its high incidence, the
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resulting discomfort and the deadly risk of high-altitude cerebral edema (HACE).
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Previous researchers have identified many risk factors for AMS[4, 5], including decreased pulse oxygen saturation (SpO2), increased HR, evaluated cerebral
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hemodynamics, faster climbing speeds and higher altitudes [6, 7]. Furthermore,
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vasoconstriction, vasodilatation and increased intracranial pressure or higher
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perfusion pressure may participate in the mechanisms of AMS [2, 8, 9]. Additionally, the physiological or psychological activation of the sympathetic nervous system has
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also been indicated as a consequence of high-altitude exposure and as a risk factor for AMS [1, 2].
Previous studies have paid particular attention to the physiological factors associated with AMS or high-altitude headache [10], but few of them have focused on the psychological aspects [11, 12]. Although a few studies have focused on the effects of high altitude on mental behavior [13] and psychiatric symptoms, the associations between AMS and the associated psychiatric symptoms have not been fully investigated. New onsets of anxiety and depression after high-altitude exposure have been reported. Samuel J. Oliver and colleagues investigated physiological and
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ACCEPTED MANUSCRIPT psychological illness symptoms at high altitude and found that anxiety contributed to the symptom burden when altitude was gained [11]. Furthermore, a relationship
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between changes in negative mood states, including anxiety and cognitive
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performance after hypoxia exposure [14] may account for AMS symptoms. Thus, psychiatric symptoms may be associated with or even predict AMS. In addition, AMS is diagnosed using a subjective self-report questionnaire; thus, psychological factors
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and emotional states are critical in relation to AMS, especially for psychological and
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neurological clinical manifestations, which include headache, dizziness and insomnia [2].
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In addition to the AMS symptoms, many other complaints (non LLS related
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symptoms), such as the symptoms included in the environmental symptoms
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questionnaire (ESQ-III), account for a large proportion of the discomforts of high-altitude exposure. These symptoms may also limit daily work and life at high
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altitudes, although they are not essential for an AMS diagnosis. Therefore, it is critical and urgent to study both the AMS-related problems and the non LLS related symptoms that affect individuals coming to high altitudes from lower altitudes. We postulated that baseline psychological factors would be associated with or predict AMS, and conducted this study with the aim of identifying the relationships between AMS and baseline psychological factors, as assessed using the Symptoms Checklist-90 (SCL-90).
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ACCEPTED MANUSCRIPT 2. Methods 2.1 Participants and procedures
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Participants This prospective observational study was designed to identify the
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predictive values of baseline SCL-90 scores at sea level for AMS after high-altitude exposure. The participants (285 young Chinese soldiers on an altitude-training mission) were recruited in July 2013 at sea level (400 m) in Chongqing and were
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assessed at 3450 m after a four-day bus trip. The inclusion criteria were as follows:
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healthy Chinese men between 16 and 30 years old; subjects did not take medication or receive any intervention before ascending. However, severe headache subjects were
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treated with NSAIDs or Sanlietong (Taiji medicine, Xi’an, China) as necessary at high
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altitude. Subjects with any of the following conditions were excluded:
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cerebrovascular diseases, cardiovascular diseases, neuro-psychosis, respiratory diseases, malignant tumors and disorders of the liver or kidneys.
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The study was thoroughly explained to all of the volunteers, and all of them signed informed consent forms prior to their examinations. This study was reviewed and approved by the Ethics Committee of Xinqiao Hospital at the Second Clinic Medical College of the Third Military Medical University. Procedures The baseline parameters were examined in Chongqing before their trip using structured case report forms [i.e., age, body mass index (BMI), smoking and alcohol consumption]. The physiological measurements were conducted during routine examinations prior their travel. Blood pressure was measured using a sphygmomanometer (HEM-6200, OMRON, China) after a 30-min rest period. The
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ACCEPTED MANUSCRIPT subjects’ HR and SpO2 were also measured using a pulse oximeter (NONIN-9550, Nonin Onyx, USA). Histories of traumatic brain injury, psychiatric disorder/treatment,
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physical injuries, AMS (high-altitude headache) and high-altitude exposure over the
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past 2 years were also recorded on the case report form. The primary version of the SCL-90 was used to measure the subjects’ psychiatric symptoms (Appendix 1) [15-17]. The subjects were questioned using the SCL-90 checklist, which includes 90
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items (9 factor categories). These items were presented out of order and were
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translated into Chinese[18]. Our trained physicians performed the physiological evaluations of HR, blood pressure and SpO2.
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The AMS questionnaires were performed at 3450 m (Xin Duqiao, 8:00-10:00 in
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the morning on the fifth day after one night’s rest, Figure 1A) after the participants
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had completed a four-day trip from sea level (400 m from Chongqing) via bus. AMS-related symptoms (i.e. the LLS symptoms, headache, dizziness, gastrointestinal
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symptoms, difficulty sleeping and fatigue/weakness) and non LLS related symptoms were recorded. AMS was diagnosed based on the LLS scores. Subjects whose LLS score was 3 or higher and who had a headache were identified as having AMS. Furthermore, many other frequently occurring non LLS related symptoms that threaten health and daily life at high altitudes, including lethargy, constipation, dim eyesight, dyspnea and cough, were also queried in the case report form (as present or not present). 2.2 Statistical analysis
Normally distributed variables [i.e., age, BMI, HR, systolic blood pressure (SBP), 7
ACCEPTED MANUSCRIPT diastolic blood pressure (DBP) and SpO2] were expressed as the mean ± standard deviation (SD). Non-normally distributed variables (the nine factors of the SCL-90)
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were expressed as median (quartile range). The AMS+ (with AMS) and AMS-
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(without AMS) groups were compared using independent samples T tests or Mann-Whitney U-tests, as appropriate. The relationships between AMS score and each of the aforementioned parameters were analyzed using Spearman’s correlations.
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Univariate and adjusted logistic regressions were performed to identify the
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independent variables associated with AMS (Figure 1B, the statistical analysis chart).
Figure 1. The process and flowchart of the study
A: Profile of the ascent; B: The statistical analysis flowchart
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ACCEPTED MANUSCRIPT 3. Results Data were excluded if the subjects’ demographic information or other items were
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missing (e.g., lack of demographic information, AMS symptoms or the sub-items of
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the SCL-90); totally 280 valid case report forms and examinations were collected. The mean age and BMI of the subjects in this study were 20.88 ± 2.42 years and 21.28 ± 2.28 kg/m2 respectively. The percentages of participants who smoked or consumed
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alcohol were 26.0% and 4.5% respectively. At sea level, the mean SBP, DBP, HR and
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SpO2 were 112.44 ± 10.94 mmHg, 67.64 ± 8.84 mmHg, 70.20 ± 9.82 beats per min and 97.37 ± 1.15%. The incidences of AMS, headache and dizziness were 24.7%,
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41.9% and 50.2% (Figure 2A). Furthermore, the incidences of non LLS related
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symptoms were shown in figure 2B.
Figure 2. Incidences of AMS-related and non LLS related symptoms A: Incidences of AMS and AMS-related symptoms; B: Incidences of non LLS related symptoms.
The descriptive statistics for the nine factors of the SCL-90 were shown in Figure 3 (a-i). Most of the 280 individuals were characterized by normal or mild scores on the nine factors of the SCL-90 (table 1). More specifically, 186 subjects had
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ACCEPTED MANUSCRIPT a somatization score between 12 and 24, and 135 had an anxiety score between 10 and 20. Mild obsession-compulsion characterized a proportion of the participants (185).
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Regarding depression, 119 participants reported mild depression. The reported
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incidences of positive hostility (130), phobic anxiety (70) and paranoid ideation (111) symptoms were somewhat lower. Furthermore, 95 individuals developed mild
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psychoticism (table 1).
Figure 3. Scatter plots for the nine factors of the SCL-90
Note: The nine factors of the SCL-90 were shown as medians (ranges). a. Somatization; b. Obsession–compulsion; c. Interpersonal sensitivity; d. Depression; e. Anxiety; f. Hostility; g. Phobic anxiety; h. Paranoid ideation; and i. Psychoticism. Table 1. Distribution of baseline SCL-90 factors Without
Mild
Moderate*
Severe
Somatization Cases(AMS)
12 84(11)
12–24 186(53)
24–36 7(3)
≥ 36 3(2)
Obsession–compulsion Cases(AMS)
10 86(12)
10–20 185(52)
20–30 9(5)
≥ 30 0(0)
10
18–27 4(3)
≥ 27 0(0)
13
13–26
26–39
≥ 39
155(31)
119(34)
6(4)
0(0)
10
10–20
20–30
≥ 30
Cases(AMS)
139(25)
135(41)
6(3)
Hostility Cases(AMS)
6 150(30)
6–12 119(32)
12–18 10(6)
≥ 18 1(1)
Phobic anxiety Cases(AMS)
7 205(41)
7–14 72(26)
14–21 3(2)
≥ 21 0(0)
6
6–12
12–18
≥ 18
Cases(AMS)
169(36)
106(29)
5(4)
0(0)
Psychoticism Cases(AMS)
10 182(38)
10–20 95(29)
20–30 3(2)
≥ 30 0(0)
90–160
160–200
≥ 200
6(4)
1(1)
Depression Cases(AMS) Anxiety
Paranoid ideation
90
Cases(AMS)
101(16)
* Includes the lower border.
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Total Score
172(48)
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9 125(26)
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Interpersonal sensitivity Cases(AMS)
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9–18 151(40)
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0(0)
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In terms of the demographic data, the age and BMI did not significantly differ
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between the AMS+ and AMS- groups. Furthermore, baseline SBP, DBP, HR and SpO2
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did not differ between two groups (all p values > 0.05). Of the nine factors of the SCL-90, somatization, obsession-compulsion, depression and anxiety scores were
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significantly higher in the AMS+ group than in the AMS- group (p < 0.001). Furthermore, the hostility, phobic anxiety, paranoid ideation and psychoticism scores also showed significant differences between two groups (all p values < 0.001). Most of the nine factors revealed differences between the groups with and without headache and dizziness. The differences in physiological and psychological parameters between the groups are presented in table 2.
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AMS+
p-value
Headache-
Headache+
p-value
13.0 (3.0) 11.0(3.0) 10.0(2.0) 13.0(1.0) 10.0(2.0) 6.0(1.0) 7.0(0.0) 6.0(1.0) 10.0(1.0)
14.0 (5.0) 13.0(4.0) 10.0(3.0) 14.0(3.0) 11.0(2.0) 7.0(3.0) 7.0(1.0) 6.0(2.0) 10.0(3.0)
< 0.001 < 0.001 0.126 0.004 0.009 0.007 0.008 0.020 0.005
13.0(2.25) 11.0(2.0) 10.0(2.0) 13.0(2.0) 10.0(2.0) 6.0(1.0) 7.0(0.0) 6.0(1.0) 10. 0(1.0)
14.0(4.0) 12.0(3.0) 10.0(3.0) 14.0(3.0) 11.0(2.0) 7.0(2.0) 7.0(1.0) 6.0(1.25) 10.0(2.0)
< 0.001 < 0.001 0.110 0.029 0.058 0.003 0.193 0.010 0.002
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SCL-90 Somatization Obsession-compulsion Interpersonal sensitivity Depression Anxiety Hostility Phobic anxiety Paranoid ideation Psychoticism
Dizziness-
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AMS-
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Table 2. Differences of psychological parameters between different groups
13.0(3.0) 11.0(3.0) 10.0(2.0) 13.0(1.0) 10.0(1.0) 6.0(1.0) 7.0(0.5) 6.0(1.0) 10.0(1.0)
Dizziness+
p-value
14.0(5.0) 12.0(4.0) 10.0(3.0) 14.0(3.0) 10.0(2.0) 7.0(2.0) 7.0(1.0) 6.0(1.0) 10.0(2.0)
0.036 0.013 0.098 0.014 0.007 0.009 0.480 0.059 0.081
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Non-normally distributed variables (the nine factors of the SCL-90) were expressed as medians (quartile ranges). AMS: Acute mountain sickness; AMS+: (with AMS); AMS-: (without AMS); BMI: body mass index; DBP: diastolic blood pressure; SBP: systolic blood pressure; SCL-90: Symptoms Checklist-90; SpO2: pulse oxygen saturation.
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ACCEPTED MANUSCRIPT Spearman’s correlation analyses indicated relationships between AMS scores and baseline
BMI,
somatization,
obsession-compulsion,
interpersonal
sensitivity,
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depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism
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scores (all p values < 0.05). Regarding the nervous symptoms of AMS, headache was related to baseline scores for somatization, obsession-compulsion, depression, hostility, phobic anxiety, paranoid ideation and psychoticism (all p values < 0.05).
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Dizziness was associated with somatization, obsession-compulsion, interpersonal
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sensitivity, depression, anxiety, hostility, paranoid ideation and psychoticism (all p-values < 0.05), though not with phobic anxiety (p = 0.164). The associations
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between SCL-90 factors and AMS and its symptoms were shown in table 3.
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Table 3. Relationships between SCL-90 and AMS and its symptoms AMS score
SCL-90
r
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Variables
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Somatization Obsession-compulsion Interpersonal sensitivity Depression Anxiety Hostility Phobic anxiety Paranoid ideation Psychoticism
0.316 0.319 0.215 0.274 0.234 0.242 0.163 0.212 0.248
Headache
Dizziness
p
r
p
r
p
< 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
0.222 0.235 0.104 0.141 0.111 0.173 0.079 0.149 0.181
< 0.001 < 0.001 0.083 0.019 0.064 0.004 0.188 0.013 0.002
0.164 0.203 0.150 0.196 0.201 0.183 0.083 0.141 0.129
0.006 0.001 0.012 0.001 0.001 0.002 0.164 0.019 0.030
Univariate regressions were performed for each single variable. However, the baselines for age, BMI, SBP, DBP, HR and SpO2 were not associated with AMS (all p values > 0.05). We have also indicated that baseline scores for somatization (p < 0.001), obsession-compulsion (p < 0.001), interpersonal sensitivity (p= 0.015), depression (p = 0.002), anxiety (p = 0.027), hostility (p = 0.001), phobic anxiety (p = 0.007), paranoid ideation (p = 0.004) and psychoticism (p = 0.001) were correlated 13
ACCEPTED MANUSCRIPT with AMS in each univariate regression analysis. A further adjusted logistic regression analysis was performed to identify that the factors were independently associated with
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AMS; this analysis indicated that only baseline somatization (β = 0.121; OR: 1.129;
confounding factors (table 4).
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95% CI: 1.053-1.210; p = 0.001) was still a predictor of AMS independent of other
Table 4. Logistic regressions for baseline parameters and AMS β-coefficient
Odds ratio
Univariate regression Age
-0.011
0.990
0.882
1.110
0.857
BMI
-0.032
0.852
1.101
0.625
SBP
-0.006
0.968 0.994
0.969
1.020
0.661
DBP
-0.010
0.990
0.960
1.022
0.548
HR
-0.003
0.997
0.969
1.025
0.815
SpO2
-0.190
0.827
0.657
1.042
0.108
1.129
1.054
1.209
0.001
0.121
Obsession–compulsion Depression Anxiety Hostility
1.177
1.078
1.286
< 0.001
0.138
1.148
1.028
1.283
0.015
0.129
1.138
1.048
1.234
0.002
0.117
1.125
1.014
1.248
0.027
0.220
1.246
1.090
1.423
0.001
0.257
1.293
1.071
1.561
0.007
Paranoid ideation
0.268
1.307
1.091
1.566
0.004
Psychoticism
0.248
1.281
1.103
1.488
0.001
0.121
1.129
1.053
1.210
0.001
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Phobic anxiety
p-value
0.163
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Interpersonal sensitivity
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Somatization
(95% CI)
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SCL-90
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Risk factors
Adjusted regression Somatization
The baseline of somatization was an independent predictor for AMS. Furthermore, we have also examined the SCL-90 characteristics of AMS at altitude. The results showed that only higher somatization score and depression score were independent risk factors for AMS (Appendix 2, table 1A-3A). Regarding the association between the alterations of SCL-90 and AMS, we have also analyzed the differences and regression for AMS in the alterations of the SCL-90.
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ACCEPTED MANUSCRIPT Only the change of somatization score was associated with AMS score (r = 0.188, p <0.001). Furthermore, only change of somatization was still predictor for AMS (β =
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0.132,OR=1.141,95%CI:1.041-1.250, p = 0.05).
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In order to further identify the roles of SCL-90 in AMS, we have performed the analyses between the groups with a cut-off at 4 for the LLS. The baseline SpO2 (β = -0.563, OR = 0.569, 95%CI: 0.409-0.793, p = 0.001), somatization(β = 0.174,OR =
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1.182, 95%CI: 1.046-1.353,p = 0.007) and paranoid ideation(β = 0.181,OR = 1.355,
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95%CI: 1.001-1.835, p = 0.049) scores were still independent predictors for patients whose LLS ≥ 4. Regarding the alterations of the parameters, only changes of
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somatization (β =0.152,OR =1.165, 95%CI: 1.038-1.307, p = 0.010) and depression
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(β = 0.466, OR = 1.593, 95%CI: 1.084-2.343, p = 0.018) were independent predictor
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for people whose LLS ≥ 4 (Appendix 2, table 4A-5A). Additionally, we investigated the incidences of non LLS related symptoms that
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commonly occurred after high-altitude exposure, including paresthesia (24.7%), shortness of breath (26.2%), chest pain (19.5%), tinnitus (21.7%), reduced activity (23.6%), dim eyesight (9.0%), lethargy (14.2%), constipation (13.5%), cough (7.5%) and dyspnea (8.2%; Figure 2B). The differences in SCL-90 factor scores were also tested in relation to the four main symptoms (incidence > 20%). We observed that the somatization, obsession–compulsion, interpersonal sensitivity, depression, anxiety and hostility scores were significantly higher in individuals with paresthesia than in those without
paresthesia.
Moreover,
higher
baseline
scores
for
somatization,
obsession–compulsion and depression scores were accompanied by a greater
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ACCEPTED MANUSCRIPT reduction in activity (table 5). The differences between those with and without
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shortness of breath groups in the SCL-90 factors have been identified (table 5).
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Reduction in
Reduction in
activity-
activity+
13.0 (3.0)
14.0 (6.0)
< 0.001
11.0 (3.0)
13.0 (4.0)
< 0.001
10.0 (2.0)
10.0 (4.0)
14.0 (4.0)
< 0.001
13.0 (1.0)
10.0 (1.25)
11.0 (2.5)
< 0.001
10.0 (1.5)
6.0 (1.0)
7.0 (3.0)
< 0.001
6.0 (1.0)
Phobic anxiety
7.0(0.0)
7.0 (1.0)
0.002
7.0(0.0)
Paranoid ideation
6.0(1.0)
6.0 (2.0)
< 0.001
6.0(1.0)
10.0 (1.0)
10.0(2.0)
0.001
10.0(1.0)
14.0 (5.0)
< 0.001
Obsession-compulsion
11.0 (3.0)
13.0 (5.0)
Interpersonal sensitivity
9.0 (1.0)
11.0(2.5)
Depression
13.0 (1.0)
Anxiety Hostility
Psychoticism
of breath-
breath+
0.011
14.0 (5.0)
< 0.001 0.014
14.0 (3.0)
p
Tinnitus-
Tinnitus+
p
14.0 (6.0)
0.043
13.0 (3.0)
14.0 (4.0)
0.067
12.0 (4.0)
13.0 (4.0)
0.002
11.0 (3.0)
14.0 (4.0)
0.830
10.0 (3.0)
10.0 (4.0)
0.04
10.0 (2.0)
10.0 (2.0)
0.565
< 0.001
14.0 (3.0)
14.0 (3.0)
0.050
13.0 (2.0)
13.0 (3.0)
0.803
11.0 (3.0)
0.001
11.0 (2.0)
11.0 (3.0)
0.008
10.0 (2.0)
11.0 (2.0)
0.236
7.0 (3.0)
0.017
7.0 (2.0)
7.0 (3.0)
0.030
6.0 (2.0)
6.0 (2.0)
0.566
7.0 (1.0)
0.041
7.0(1.0)
7.0 (1.0)
0.743
7.0(1.0)
7.0 (1.0)
0.521
7.0 (2.0)
< 0.001
7.0(2.0)
7.0 (2.0)
0.003
6.0(1.0)
6.0 (1.0)
0.540
11.0 (2.0)
< 0.001
10.0(2.0)
11.0 (2.0)
0.113
10.0(1.0)
10.0 (2.0)
0.526
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13.0 (3.0)
Shortness of
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Somatization
Shortness
p
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p
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Paresthesia+
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Paresthesia-
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Table 5. Differences of SCL-90 in four main non-AMS related symptoms
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6A).
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Furthermore, the non LLS related symptoms’ characteristics of SCL-90 at altitude has also been carried out and attached in Appendix 2 (Table
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ACCEPTED MANUSCRIPT 4. Discussion The main finding of our study was that SCL-90 scores at low altitude were
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associated with risk of AMS. In specific a tendency for somatization was a significant
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predictor of AMS. Given the subjective nature of questionnaires such as the LLS to diagnose AMS, this is noteworthy.
We observed associations between the baselines of harmful psychological
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symptoms as well as AMS and the associated headache, dizziness, and nervous
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symptoms. Additionally, we found that the baseline somatization score is an independent predictor of AMS at 3450 m. Finally, we have also observed the
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differences between the SCL-90 factors and the non LLS related symptoms.
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4.1 AMS was associated with SCL-90 factors at both altitudes
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Previous studies have focused on the associations between high altitude mountaineering and psychological factors [19] and have indicated the partial
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association of AMS with psychological factors through meta-analysis and field trials [20]. AMS symptoms and progression have been also reported in normobaric hypoxia equivalent which was similar to our study[21]. However, the predictive values of the baseline psychological factors for AMS have not been fully investigated. The current study further reveals that individuals with AMS have higher baseline somatization, depression, anxiety and obsession-compulsion scores. Subjects susceptible to AMS have been found to be more anxiou. Additionally, investigators have proposed the term “acute hypoxic physiological anxiety” to describe the anxiety that occurs after the arrival at altitudes and it is associated with AMS [22]. AMS patients showed more
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ACCEPTED MANUSCRIPT baseline somatization symptoms score at sea level prior to high-altitude exposure, a finding that is in accordance with the results of previous studies on AMS
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symptomatology [22]. AMS severity was also positively correlated with the baseline
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scores for somatization, anxiety and depression, highlighting the roles of psychological factors in the AMS diagnosis. It is possible that anxiety and depression reactions to high-altitude exposure lead to self-reported AMS symptoms [14, 23], but
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subjective feelings about symptoms should not be ignored.
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The emotional and behavioral changes resulting from high-altitude exposure have been indicated in previous studies [13].We have also identified the associations
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between AMS and SCL-90 at altitude. The AMS individuals had higher somatization,
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depression, anxiety and obsession-compulsion scores, indicating that anxiety and
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depression may affect the incidence of AMS. Furthermore, the average somatization score was significantly higher in the AMS+ group than in the AMS- group, indicating
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that the AMS patients have more somatization symptoms, which is in accordance with the previous studies on AMS symptomatology[24]. The SCL-90 characteristics of AMS may be useful for the clinical practice in treatment of AMS. However, the associations and predictive values of baseline emotional states prior to high-altitude exposure have not been widely investigated. Thus, the impact of baseline psychological states before high-altitude exposure on AMS should be of great importance. Furthermore, headache and dizziness were the most frequently reported nervous symptoms of AMS; these symptoms may be more likely to be affected by psychological factors than other symptoms. Therefore, we analyzed these two
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ACCEPTED MANUSCRIPT symptoms in particular. The associations between AMS and the psychological states of anxiety and depression may be caused by their relationships with AMS-related
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symptoms, such as headache and dizziness, which is partially in accordance with
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previous reports [14, 23, 25]. A hypobaric chamber simulation study indicated the associations between anxiety and the symptomatology of AMS and the effects of anxiety on performance [14]. Studies at sea level have shown a relationship between
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headache (including episodic headache, chronic cluster headache and tension-type
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headache) and anxiety or depression [26, 27]. Further studies have demonstrated that headaches at high altitude present with the clinical characteristics of migraine, cluster
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or episodic headaches [28, 29]. The relationship between anxiety (panic attacks) and
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headache has also been indicated [30], which is in accordance with our finding that
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headache patients had a higher baseline anxiety level. Our previous study also showed that somatic symptoms were associated with anxiety severity after high-altitude
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exposure [25, 31].
Dizziness is another nervous complaint of AMS that may be affected by psychological risk factors and may result in somatic symptoms. However, fewer studies have indicated a relationship between dizziness and anxiety, although depression-induced dizziness has been reported [32, 33]. In this study, we have also observed the association between dizziness and the basic psychological parameters on the SCL-90. Although AMS is not characterized by higher scores for interpersonal sensitivity, the distribution was more varied in AMS+ individuals than in AMSindividuals.
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ACCEPTED MANUSCRIPT 4.2 Associations between SCL-90 and non LLS related symptoms Many symptoms that frequently occur after high-altitude exposure were not used
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for the AMS diagnosis. We further analyzed the associations between the SCL-90
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factors and the non-AMS symptoms with an incidence greater than 20%, including paresthesia, reduced activity, shortness of breath and tinnitus. Similar to the AMS-related symptoms, paresthesia, reduced activity and shortness of breath were
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associated with significantly higher scores on most of the SCL-90 factors at baseline
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level, especially somatization, depression and anxiety. It is not difficult to understand that baseline psychological factors result in paresthesia and reduced activities as a
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result of fear, anxiety and depression. Shortness of breath may be caused by
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somatization and anxiety about addressing hypoxia, or it may be caused by hypoxia
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per se [34, 35]. Although paresthesia, shortness of breath and tinnitus were not included in the diagnostic criteria, the diagnostic value of these symptoms should be
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given proper attention.
Based on the discussion above, the non-AMS related symptoms with a high incidence may be potential symptoms, and they should receive proper attention. The non-AMS symptomatology should also been prevented and treated promptly. 4.3 Baseline somatization score as an independent predictor of AMS After adjusting for other parameters, only the baseline somatization score remained an independent predictor of AMS. The sub-items of somatization include headache, cardiovascular, gastrointestinal and respiratory symptoms. In the past several decades, most studies have given greater attention to physiological and genetic
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ACCEPTED MANUSCRIPT risk factors and have identified some valuable factors that contribute to AMS [9, 36-38]. Though anxiety has a widely demonstrated association with AMS or
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high-altitude exposure, the baseline anxiety score was not an independent predictor of
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AMS in the adjusted regression. However, the baseline somatization score predicted AMS in the adjusted analysis that excluded the effects of the confounding factors. Combined with the current results, somatization symptoms, emotional disorders and
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psychiatric symptoms may be considered risk factors, predictors or even clinical
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manifestation of AMS that need to be investigated in further studies.
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ACCEPTED MANUSCRIPT 4.5 Limitations The participants in our study were all young Chinese men, which could have
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generated an age or gender bias; our future studies will address these possible biases.
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Another limitation of the current study is that further detailed examinations of the mechanisms and other methods for measuring anxiety and depression were not
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performed; such examinations should be performed in future studies.
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ACCEPTED MANUSCRIPT 5. Conclusion AMS is associated with the baseline somatization and other symptom scores
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measured by SCL-90. However, only the somatization score at baseline was a
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predictor of AMS independent of other confounding factors; thus, further studies of
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the AMS mechanisms and possible clinical applications are warranted.
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ACCEPTED MANUSCRIPT Abbreviation AMS: Acute mountain sickness;
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AMS+: (with AMS);
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AMS-: (without AMS); BMI: body mass index;
LLS: Lake Louise self-score system;
SCL-90: Symptoms Checklist-90;
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OR: odds ratio.
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SpO2: pulse oxygen saturation;
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SBP: systolic blood pressure;
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DBP: diastolic blood pressure;
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ACCEPTED MANUSCRIPT Acknowledgements This work is supported by the Ministry of Health of P. R. China [grant No. 201002012]
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and the People's Liberation Army P. R. China [grant No. BWS14J040]. We would like
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to thank all of the individuals who participated in this study for their support. We are grateful to Mr. Can Chen, Mr. Bai-Da Xu and Miss Shuang-Fei Li for their help. We also thank Mr. Ru-Fu Xu for his suggestions about statistics. Finally, I would like to
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thank Miss Meng Zhou for her help and support in preparation of this manuscript.
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ACCEPTED MANUSCRIPT Conflict of Interest Statement:
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The authors declare that there is no conflict of interests.
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ACCEPTED MANUSCRIPT Figure legend
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1A: Profile of the ascent; 1B: The statistical analysis flowchart
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Figure 1. The process and flowchart of the study
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Figure 2. Incidences of AMS-related and non LLS related symptoms 2A. Incidences of AMS and AMS-related symptoms 2B. Incidences of non LLS related symptoms
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Figure 3. Scatter plots for the nine factors of the SCL-90
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Note: The nine factors of the SCL-90 are shown as median (range). a. Somatization; b. Obsession–compulsion; c. Interpersonal sensitivity; d. Depression;
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e. Anxiety; f. Hostility; g. Phobic anxiety; h. Paranoid ideation; i. Psychoticism.
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ACCEPTED MANUSCRIPT [37] Richalet, J.-P., Larmignat, P., Poitrine, E., Letournel, M., Canoui-Poitrine, F. Physiological risk factors for severe high-altitude illness: a prospective cohort study. American journal of respiratory and critical care medicine. 2012,185:192-8. [38] Ding, H., Liu, Q., Hua, M., Ding, M., Du, H., Zhang, W., et al. Polymorphisms of hypoxia-related
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diseases. 2011,81:236-41.
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ACCEPTED MANUSCRIPT Highlights
Described novel epidemiology and characteristics of SCL-90 pre- and post
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high-altitude exposure
Identified the associations between SCL-90 factors and AMS
Identified the predictive role of baseline somatization score for AMS
Found associations between non-AMS-related symptoms and SCL-90 items
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