Soc Psychiatry Psychiatr Epidemiol (2015) 50:419–427 DOI 10.1007/s00127-014-0915-z

ORIGINAL PAPER

Gender-specific associations between leisure-time physical activity and symptoms of anxiety: the HUNT study Audun Brunes • Sigridur Lara Gudmundsdottir Liv Berit Augestad

•

Received: 4 July 2013 / Accepted: 22 June 2014 / Published online: 27 June 2014 Ó Springer-Verlag Berlin Heidelberg 2014

Abstract Purpose The underlying goal of the study was to examine gender-specific effects of leisure-time physical activity on the development of symptoms of anxiety. Methods The second wave of a prospective cohort survey (HUNT 2) was conducted during 1995–1997 in the county of Nord-Trøndelag, Norway, with a follow-up in 2006–2008 (HUNT 3). The sample consisted of 12,796 women and 11,195 men with an age range of 19–85 years. A binomial model with a log-link function and generalized linear model analysis with gamma distribution was used to assess the association between physical activity and anxiety symptoms (Hospital Anxiety and Depression Scale anxiety subscale, HADS-A). Results A total of 1,211 (9.5 %) women and 650 (5.8 %) men developed HADS-defined anxiety (C8 on the HADS-A scale). Men who scored in the middle tertile of the calculated physical activity index developed significantly fewer cases of HADS-defined anxiety compared with men in the lowest tertile (p \ 0.05). In the gamma regression analysis for women, having higher scores on the moderate-high physical activity was associated with fewer symptoms of anxiety (p \ 0.01). Conclusions Women developed almost twice as many cases of HADS-defined anxiety compared to men. Significant associations were found between general leisure-time A. Brunes
L. B. Augestad (&) Department of Neuroscience, The Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway e-mail: [email protected] S. L. Gudmundsdottir Center for Sport and Health Sciences, University of Iceland, Reykjavik, Iceland

physical activity and anxiety symptoms among women and men, but the true effect is likely to be different from the observed associations due to several threats to the internal validity in the study. Keywords Anxiety
Epidemiology
Physical activity
Prospective study design

Introduction Anxiety disorders are highly prevalent in the Westernized world [1–3]. Some types of anxiety disorders (e.g., obsessive compulsive disorder) may not only cause severe problems for the individuals’ everyday functioning and quality of life [4], but also have consequences on the society as a whole [5]. The total annual cost of treating anxiety disorders in Europe is substantial due to medical and non-medical expenses [6], but the costs may be even higher than estimated because somatic and mental health co-morbidities occur frequently with anxiety disorders [7]. The pathology of anxiety disorders is likely to be complex and may involve interrelated biological and environmental factors, such as young age, avoidant behavior, family history of mental health problems, personality, and overprotective parenting [8]. In addition, women are found to be twice as likely to suffer from almost all subtypes of anxiety disorders compared to men [1–3, 9, 10] and the higher prevalence in women is found consistently throughout the lifespan [10]. To date, knowledge of gender-specific efforts in preventing the development of anxiety disorders is limited [10]. It has been suggested that physical activity (PA) is beneficial for the prevention and treatment of mental health problems [11]. Meta-analyses of experimental studies have

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found that aerobic fitness training and other exercise programs may reduce symptoms of anxiety in non-clinical samples [12–16] and clinical samples [17, 18]. In recent years, a number of observational studies have been conducted to address this issue on a population level and the results are equivocal [19–29]. However, the studies had some methodological challenges, e.g., most, but not all, used a cross-sectional design [19–25]; some addressed PA as a dichotomous measure [23, 26, 28, 29], some included specific subgroups of the population [26, 27], and considerations of possible confounding factors differed widely across the studies. We are aware of four prospective studies on the subject and all included adults already affected by anxiety at baseline [26–29] or investigated the reverse causality [27]. Therefore, prospective population-based studies are needed that addresses whether baseline PA levels prevent the development of anxiety symptoms in the future. The underlying goal of our study was to evaluate gender-specific effects of physical activity on the occurrence of symptoms of anxiety among healthy adults using data from a prospective, population-based study in Norway.

Materials and methods Design and sample Data were collected from the Health Survey in NordTrøndelag (HUNT), a prospective population-based observational health survey in Norway [30]. All inhabitants of the county of Nord-Trøndelag aged C19 years received an invitation to participate in a health study in 1995–1997 (HUNT 2) and in the follow-up study in 2006–2008 (HUNT 3). Of the 94,149 eligible participants for HUNT 2, a total of 65,220 (70.2 %) returned the health-related questionnaire. In HUNT 3, a total of 50,810 (54.0 %) of those invited participated and answered the questionnaires. Both studies included comprehensive questionnaires designed to assess demographics, health, and lifestyle. Those who had missing responses on all questions regarding PA and/or the Hospital Anxiety and Depression Scale (HADS) anxiety subscale were excluded from the study. In addition, respondents scoring C8 points on HADS anxiety subscale in HUNT 2 were excluded in order to study the preventive effect of physical activity in healthy women and men. Further, we excluded respondents that had previously used or were using anti-depressive medication and tranquilizers at the time of participation in HUNT 2, because use of such medication is strongly associated with anxiety symptoms. Overall, 23,991 respondents aged 19 years or older were included in the study, 12,796 (53.3 %) women and 11,195 (46.7 %) men. The mean

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baseline age was 45.7 years (SD 13.1, range 19–85.1) for women and 47.7 years (SD 12.7, range 19–85.0) for men.

Measures Physical activity In HUNT 2, respondents reported their average weekly hours of low intensity of leisure-time PA (not sweating or being out of breath) and moderate-high intensity of leisuretime PA (sweating or being out of breath) by selecting the applicable option on the following scale: none, \1, 1–2, or 3 or more hours per week. The PA questionnaire has previously been validated among men [31]. The question regarding PA with moderate-high intensity has been found to have an acceptable correlation with maximal oxygen consumption (VO2max) measurements (r = 0.46) and the long version of the International Physical Activity Questionnaire (IPAQ-L) (r = 0.31). The question of PA with low intensity correlated poorly with both VO2max (r = -0.03) and IPAQ-L (r = -0.08) [31]. The test–retest correlation coefficient was found poor for the question of low PA item (r = 0.19) and moderate for the question of moderate-high PA item (r = 0.50) [31]. A summary index of PA was created by scoring each hour of low-intensity activity as 1 and each hour of moderate-high intensity activity as 2.5, and subsequently summarizing the scores. The scores of the PA index ranges from 0 to 10.5. The participants were categorized at the 33.3rd and 66.6th percentiles of the index score, indicating the lowest, middle, and highest tertile of activity. The cutoff for women was 2.0 and 5.25 points, while the cutoff for men was 3.25 and 5.75 points. Among those who had missing answer on either low or moderate-high PA, the index calculations were based merely on the registered answers, based on the assumption that the respondents had left out whichever intensity level they had not experienced during their exercise. The scoring of the PA index has been frequently used in other studies analyzing data from the HUNT surveys [32, 33]. Hospital Anxiety and Depression Scale (HADS) The HADS was designed for use in health surveys with the aim of estimating the occurrence of mental health problems in populations. The anxiety (HADS-A) and depression (HADS-D) subscales each consist of 7 items, giving total of 14 items [34]. Each question has a 4-point Likert scale, ranging from 0 (not present) to 3 (maximally present). The classification of scores on HADS-A and HADS-D subscale is as follows: 0–7 = normal, 8–10 = mild disorder, 11–14 = moderate disorder, and 15–21 = severe disorder.

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In the analyses for the present study, a cutoff point of 8 was used [34]. Results from validation studies show a high sensitivity and specificity of a score C8 for HADS-A for defining possible cases of anxiety [35, 36]. A review study found that the sensitivity and specificity of HADS-A cutoff C8 varied from 0.70 to 0.90 [35]. Confounding variables Due to the large number of potential confounding factors measured in the HUNT studies, a series of univariate regression analyses were performed, where each potential covariate was tested against a model fitting only an intercept term for women and men separately, with HADSdefined anxiety as the dependent variable. Suspected confounders showing an association with a significance level of \0.2 in the analysis for each gender were subsequently included in all the analyses for the gender in question. The following variables, measured at baseline, were included in the final adjusted analyses: age (19–29, 30–39, 40–49, 50–59 60–69, and C70), daily smoking (yes, no), frequency of alcohol consumption per month (teetotaler, 1–2 times, 3–7 times, 8–12 times, [12 times), body mass index (\18.5, 18.5–24.9, 25–29.9, C30 kg/m2), HADS-depression (C8, \8), and chronic somatic disease (yes, no). The chronic somatic disease variable included asthma, struma, and epilepsy among men, and hyperthyroidism, struma, osteoporosis, arthritis, osteoarthritis, asthma, cancer, and fibromyalgia among women. All twoway interactions between PA and other variables included in the models were examined. Statistical methods Descriptive statistical analyses included means, standard deviations (SDs), and percentages of respondents within categories of baseline characteristics that developed HADS-A scores C8 at follow-up. The frequency of HADSdefined anxiety across the subgroups of each baseline characteristic was examined using Pearson’s Chi-squared analyses. A binominal regression model, with a log-link function, was used to assess the prospective probability of developing HADS-defined anxiety measured at follow-up (HADS-A score C8) based on respondents’ PA level at baseline. We obtained 95 % confidence intervals (CIs) for the relative risk (RR) estimates. As a secondary model, generalized linear regression model with a gamma distribution and log-link function was carried out in order to calculate the prospective association between PA and symptoms of anxiety on a continuous scale. The mean score of HADS-A for each PA category was estimated by log-likelihood function (95 % CI).

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Analyses of linear trend in mean values between PA categories were performed by treating PA as a continuous variable in the regression models. Baseline depression scores were included as a covariate in the models in order to investigate the association between PA and anxiety independently of the potential effect on baseline depression. The analyses were computed as either simple (adjusted for age) or multivariable. All analyses were computed separately for women and men and separately for each of the PA variables (PA index, hours of low-intensity PA, and hours of moderate-high intensity PA). The analyses were carried out using the lowest score on PA as a reference category. The total number of respondents differed in the analyses due to missing responses. An alpha level below p = 0.05 was regarded as statistically significant, but in the analysis for trend a significance level below p = 0.01 was used. Statistical analyses were carried out using IBM SPSS Version 19 for Windows. Ethics The study was approved by the Norwegian Regional Committee for Ethics in Medical Research, and the Norwegian Data Inspectorate and each of the respondents gave written informed consent prior to participation.

Results Baseline characteristics and their association with HADSA score at follow-up are shown in Table 1. At baseline, a total of 412 (4.5 %) women and 526 (6.3 %) men reported that they did not engage in any leisure-time PA. Participants excluded from the analyses (n = 37,070) differed on some baseline characteristics compared to those included in the analyses: the excluded women and men had a lower percentage reported good and very good health, higher mean scores of HADS-depression, lower frequency of disability from mental disorders, and lower levels of life satisfaction. Furthermore, the excluded women were slightly older (results not shown). In HUNT 3, a total of 1,211 (9.6 %) women and 650 (5.8 %) men had developed HADS-defined anxiety according to the cutoff of C8 on the HADS-A scale [32]. According to the HADS-A classification [32], 928 (7.3 %) women reported ‘‘mild’’ anxiety, 214 (1.7 %) reported ‘‘moderate’’ anxiety, and 69 (0.5 %) reported ‘‘severe’’ anxiety. Among men, 493 (4.4 %) reported ‘‘mild’’ anxiety, 131 (1.2 %) reported ‘‘moderate’’ anxiety, and 26 (0.2 %) reported ‘‘severe’’ anxiety. We conducted age-adjusted and adjusted for multiple variables analyses for the association between PA variables and anxiety symptoms. The results were adjusted for age,

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Table 1 Mean HADS-A score and percentage of HADS-A score C8 from HUNT 3 among each level of baseline characteristics from HUNT 2 for all included persons, according to gender Variables

HADS anxiety subscale Women (N = 12,796) N

Age (years) 19–29 30–64 C65 Missing Smokes daily Yes No BMI \18.5 18.5–24.9 25–29.9 30–34.9 C35 Missing Marital status Unmarried Married/partnership Widowed Separated/divorced Missing HADS-depression C8 \8 Missing Alcohol (past month) Teetotaler 1–2 times per month 3–7 times per month 8–12 times per month [12 times per month Missing Chronic somatic disease Yes No Missing Hours of low PA None \1 h 1–2 h [3 h Missing Hours of moderate-high PA None

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Mean

Men (N = 11,195) SD

% of cases with HADSA score C8

N

Mean

SD

% of cases with HADSA score C8

1,007 9,694 476 18

3.35 2.97 2.87

2.62 2.56 2.48

* 7.7 5.7 4.9

2,611 8,584

3.18 2.94

2.69 2.51

* 7.0 5.4

18 3,806 5,922 1,270 152 27

2.42 3.08 2.98 2.89 2.51

2.75 2.61 2.53 2.54 2.24

11.1 6.6 5.5 5.0 3.3

2,493 7,914 135 637 16

3.29 2.91 2.69 2.98

2.69 2.49 2.56 2.76

* 7.7 5.1 6.7 6.9

611 10,578 6

4.30 2.92

2.89 2.52

* 12.4 5.4

1,987 3,344 3,957 877 171 859

2.91 3.03 3.04 3.03 3.07

2.60 2.51 2.54 2.63 2.70

5.6 6.1 5.6 5.8 5.3

1,017 10,013 165

3.36 2.95

2.79 2.52

* 7.9 5.5

12.1 9.3 9.1 9.8

711 1,896 3,802 3,704 1,082

2.94 3.05 3.05 2.95

2.60 2.62 2.57 2.50

5.9 6.5 5.9 5.5

10.1

2,648

3.03

2.67

* 7.1

1,621 10,072 1,081 22

3.69 3.51 3.43

2.96 2.86 2.83

10.9 9.2 9.4

3,262 9,534

3.83 3.43

3.04 2.80

104 5,987 4,797 1,432 424 52

3.98 3.55 3.56 3.50 3.10

3.41 2.87 2.86 2.89 2.74

* 11.5 8.8 * 16.3 9.4 9.7 9.6 6.1

2,410 8,786 704 865 31

3.62 3.51 3.29 3.62

2.94 2.84 2.69 3.05

* 10.8 9.2 7.1 10.5

432 12,352 12

4.92 3.48

2.93 2.85

* 19.7 9.1

3,836 3,942 2,876 443 62 1,637

3.47 3.65 3.51 3.16 3.63

2.83 2.93 2.82 2.61 3.24

* 8.9 10.3 9.0 6.3 12.9

2,444 9,356 996

3.66 3.47

2.87 2.86

* 10.5 9.0

547 1,951 5,231 4,419 648

3.59 3.63 3.51 3.53

3.31 2.86 2.80 2.90

3,836

3.60

2.92

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Table 1 continued Variables

HADS anxiety subscale Women (N = 12,796) N

\1 h 1–2 h C3 h Missing PA indexa Lowest tertile Middle tertile Highest tertile

Men (N = 11,195)

Mean

SD

% of cases with HADSA score C8

2,781 2,373 764 3,042

3.57 3.43 3.38

2.82 2.81 3.04

9.5 8.8 9.3

4,305 4,818 3,673

3.56 3.56 3.45

2.91 2.83 2.87

9.9 9.4 9.0

N

Mean

SD

% of cases with HADSA score C8

2,737 2,439 1,550 1,821

3.03 2.96 3.03

2.56 2.45 2.62

5.7 5.0 6.6

4,854 3,164 3,177

3.05 2.89 3.03

2.61 2.48 2.55

6.2 4.9 6.0

HADS-A Hospital Anxiety and Depression Scale anxiety subscale, PA physical activity, HUNT Nord-Trøndelag Health Study, BMI body mass index, SD standard deviation * Sig. p values (\0.05) indicate results of the Pearson’s Chi-squared test between HADS-A (\8, C8) and levels of baseline categorical variables a A sum score of amount of low and moderate-high intensity PA

smoking, chronic somatic disease, and HADS-defined depression for women and men. Additionally, the results for men were adjusted for body mass index. Based on the statistical model, candidate models including alcohol consumption, marital status, and body mass index (for women) was omitted due to substantial higher p values for those particular variables when including the variables in the models. Table 2 shows the outcomes of the adjusted analyses of the association between PA variables and the risk of developing HADS-defined anxiety (a score of C8 points). The results from the log-binomial analyses indicated a significantly lower risk of developing HADS-defined anxiety among men with moderate PA according to the index compared with men categorized as low PA according to the index. These above-mentioned results are partly explained by that men who reported \1 h and 1–2 h per week of moderate-high intensity PA at baseline had lower RR at follow-up compared to those who did not perform any moderate-high intensity PA and those with more such hours. Women who engaged in some low-intensity PA per week at baseline had significantly lower age-adjusted RR of HADS-defined anxiety at follow-up compared with those who did not engage in any low-intensity activity. However, this association was not observed in the multivariable analysis. Supplementary analyses were conducted using gamma regression model. The association between PA variables and HADS-A score was approximately identical to the results from the binomial model (results not shown). Except that, after adjusting for confounding factors in the

analysis for men, scoring\1 h and 1–2 h of moderate-high intensity PA was no longer significantly associated with lower HADS-A score compared with men who did no moderate-high intensity PA (results not shown). For women, scoring 1–2 h of moderate-high intensity PA was associated with lower anxiety symptoms than performing no moderate-high intensity PA in the simple and the multivariable model (B -0.06, p \ 0.05, CI -0.09 to -0.02). In order to examine the linear trend in HADS-A scores across PA categories, PA was included as a continuous variable in the binomial and gamma regression models. A significant negative trend for symptoms of anxiety across the hours of moderate-high intensity PA was observed among women in the gamma regression model: more hours of moderate-high PA was associated with lower scores on the HADS-A in the simple (p = 0.003) and adjusted model (p = 0.008). The association was close to significant in the log-binomial model (p = 0.06). The HADS-A score was insignificantly associated with PA on a continuous scale among men (p [ 0.01). The choice of which respondents to include in the analyses had an impact on the observed association between PA and anxiety symptoms. By including those with missing response on one of the PA questions and assigning them a score of 0 h, less substantial differences in HADS-A score were seen between the PA categories for women and men compared with when treating these cases as missing from the analysis (results not shown). No significant two-way statistical interactions were observed in the log-binominal models or gamma regression models (p [ 0.05).

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Table 2 Adjusted risk ratios from binomial analysis for HADS-defined anxiety (HUNT 3) in relation to physical activity (HUNT 2) according to gender PA variables

HADS anxiety subscale Women RR

a

Men 95 % CI

RR

b

95 % CI

RRa

95 % CI

RRc

95 % CI

Hours of low PA None

Ref

\1 h

0.76*

0.58–0.99

0.83

Ref 0.62–1.10

1.10

Ref 0.79–1.55

1.13

0.81–1.58

1–2 h

0.75*

0.58–0.94

0.83

0.63–1.08

1.02

0.74–1.41

1.06

0.77–1.47

C3 h

0.80

0.63–1.01

0.91

0.70–1.19

0.96

0.69–1.32

0.99

0.72–1.37

N

12,129

11,159

Ref

10,097

9,937

Hours of moderate-high PA None

Ref

\1 h

0.89

0.69–1.13

0.91

Ref 0.78–1.05

0.77*

Ref 0.63–0.95

0.80*

0.65–0.99

1–2 h

0.85

0.72–1.00

0.85

0.72–1.01

0.69*

0.55–0.86

0.72*

0.58–0.90

C3 h

0.91

0.79–1.06

0.90

0.70–1.15

0.90

0.70–1.11

0.96

0.66–1.22

N

9,375

9,101

Ref

9,359

9,226

PA indexd Low Moderate

Ref 0.93

0.82–1.05

High

0.87

0.76–1.00

N

12,774

Ref 0.94

0.83–1.08

0.88

0.76–1.02

11,770

Ref 0.81*

0.67–0.98

0.95

0.80–1.14

11,177

Ref 0.82*

0.68–1.00

0.99

0.83–1.18

10,997

HADS Hospital Anxiety and Depression Scale, HADS-defined anxiety sum score of 8 or higher on HADS anxiety subscale, PA physical activity, RR risk ratio, CI confidence interval a

Age-adjusted

b

Adjusted for age, smoking, chronic somatic disease, and HADS-defined depression

c

Adjusted for age, smoking, chronic somatic disease, body mass index, and HADS-defined depression A sum score of hours of low and moderate-high intensity PA

d

* p value (\0.05) of the binomial regression model analysis with PA run as a fixed factor

Discussion The incidence of symptoms of anxiety was almost double among women compared with men at the time of followup. For men, scoring in the middle tertile of the PA index at baseline was associated with lower HADS-defined anxiety at follow-up compared with those who scored in the lowest tertile of the PA index. For women, more hours of moderate-high intensity PA was associated with lower symptoms of anxiety. Although anxiety is an essential emotion for human existence in order to fight or flight, a large part of the population experiences anxiety that becomes counterproductive or incapacitating. Many population-based studies have been conducted to investigate if being physically active could be associated with fewer anxiety symptoms compared with those being inactive [19–29], but they have found equivocal results. By using a prospective observational study design, we found that increased number of hours of moderate-high intensity PA prevented to some

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extent the development of anxiety symptoms as estimated 11 years later, compared with not doing any moderate-high intensity PA. The associations between PA variables and anxiety symptoms were in some cases dependent on whether the variables were treated as continuous or categorical. This may be, however, an indication of the large variability of psychological data relative to the effect of the exposure [37]. As stated in a systematic review of RCT studies from 2014 [18], that although exercise seems to reduce anxiety symptoms, there has been no consensus on the effects of specific doses or modalities of PA on anxiety disorders. We observed that weekly hours of PA resulting in sweating or becoming out of breath was associated with fewer symptoms of anxiety compared with no hours of moderate-high intensity PA. Therefore, the results from present study support the statement by Salmon [38] that moderate or higher intensity activity may provide adequate physiological responses or psychological rewards to influence the risk of anxiety symptoms. On the other hand, the dual-mode

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model states that cognitive variables related to the interpretation of the PA experience is essential for the mental health outcome [39]. Low-intensity activities could be rewarding for individuals that find these types of activities beneficial. However, it is possible that when answering the question regarding low-intensity PA in the HUNT studies, subjects may associate that term with hours of activities related to transportation and household tasks, and these nonoptional tasks could impact mental health in a different way than more enjoyable, self-selected activities. We acknowledge that the present study design is merely suitable for explaining what level of various PA intensities may prevent the development of anxiety symptoms [37]. To date, the explicit associative mechanisms of the anxiolytic effect of PA are not fully understood [40]. There may be numerous social, psychological, physiological, and neurobiological pathways that may directly or indirectly influence anxiety symptoms. For example, PA can improve psychosocial factors such as self-esteem and self-efficacy [41], which in turn can further increase mastery through finding coping strategies to reduce stress that are more comprehensive with regard to the situation [42]. Biological mechanisms have also been suggested, whereby being physically active could affect the balance of neurotransmitter substances in the brain [43] and reduce inflammatory processes and oxidative stress [44]. The association could also be bi-directional, that anxiety disorder may cause declines in physical activity levels [27]. We tried to rule out the latter possibility by excluding those with possible anxiety disorder at baseline. The study found that women are more prone to symptoms of anxiety compared with men—a finding that is in agreement with other large studies [1–3, 9, 10, 45]. Several genetic [46, 47], neurobiological [46, 48], psychological [10], and bioenvironmental [46] factors and theories have been suggested in explaining the gender-specific difference of mental health problems. However, stereotype gender roles of masculinity impeding men to display weakness, gender differences in substance abuse, cultural gender roles, and the methods used to measure anxiety are claimed to bias the observed higher occurrence of some anxiety disorders among women compared to men [10]. Previous observational studies have not found genderspecific associations between exercise and anxiety disorders [23–26, 29]. However, a recently published crosssectional study observed fewer anxiety symptoms among physically active women compared with inactive respondents, but the association was not so clear among men [22]. The results from present study gave limited support to gender differences in the preventive effect of PA on development of anxiety symptoms among adults. Asztalos et al. [49] have suggested that rather than overall level of PA, the motives of being physically active and the domains

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of sport describes the association between PA and mental distress. A similar principal may apply to the association between PA and risk of developing anxiety levels, i.e., the individual drive and the social surroundings may enhance or dampen the anxiolytic effect of PA. Unfortunately, we did not have information on these potentially interesting factors. The dual-continuum hypothesis states that mental health and mental disorders are located on separate continuums [50]. Therefore, for some individuals, PA may improve well-being and quality of life independently of the effect on mental health problems. However, we only focused on anxiety symptoms in the current study. We observed a considerably higher mean scores on HADS-A among women and men in all categories of PA after adjusting for HADS-defined depression. This may be due to the fact that anxiety and depression are highly co-morbid disorders [3, 7]. The main strength of the study is the prospective observational population-based design, as this made it possible to assess the prospective association between various intensities of PA and symptoms of anxiety over an extended period of time and perform separate analyses, comparing women and men. Although the county of Nord-Trøndelag is mostly a rural area, the HUNT population has been found to be representative of the Norwegian population [30]. There may be some limitations to the study. There may be a risk of selection bias as quite many of the respondents did not answer questions regarding anxiety and PA. Therefore, we cannot exclude the possibility that they differed from the respondents who did answer. As an example, we observed that the association between PA and HADS-A score changed to some extent by including those with missing responses on either one question of the PA questionnaire in the analyses. Individuals with mental health problems may also be more reluctant to participate in a population-based study compared with people without mental health problems. If non-participation at follow-up was jointly associated with PA and anxiety, the results may have been biased. However, we do not have access to data that could enlighten whether non-participation from the population we sampled from could have biased our results. There may also be some information bias related the use of the self-reported questionnaire for assessing PA and anxiety symptoms [51]. Firstly, the participants may have underestimated or overestimated their responses in accordance with the reality. Secondly, that we did not observe association between conducting PA for 3 h or more per week and anxiety symptoms may be explained by the open end of the category. This could result in heterogeneous levels of moderate-high PA included in that category resulting in masking the potential relationship [52]. Thirdly, the question used to estimate low-intensity PA has

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previously been found to have poor validity and reliability [31], hampering interpretation of the results. Fourthly, PA level and anxiety symptoms may have fluctuated during the course of the study and we cannot rule out the possibility that changes that occurred shortly before baseline and during follow-up may have affected the results. Lastly, anxiety was assessed by a self-reported measure and was not verified by other clinical measures. The HADS-A subscale is a measure of particular psychological and behavioral aspects of generalized anxiety disorder and panic disorder [36]. However, HADS-A cannot be used to measure somatic-related anxiety symptoms. Although we identified several possible confounders in the association between PA and symptoms of anxiety, other meaningful variables than those measured in the HUNT study could have biased the association between PA and symptoms of anxiety. Vulnerable personality traits, education, and other socioeconomic variables were not included in the present study. We identified body mass index, alcohol consumption, and marital status as possible confounding factors, but the variables were excluded to prevent overadjustment. Furthermore, some possible confounding variables included in the statistical model may be both confounding and mediating factors, but we observed negligible differences in the association between PA and anxiety symptoms when including the variables in the models. Anxiety is one of the most prevalent mental health problems in the Westernized world and can lead to severe consequences for individuals and societies. PA may represent a possible prevention initiative that is mostly self-managed, safe, inexpensive, and with few side effects. The present study indicates that different intensities of leisure-time PA may have different associations with the risk of anxiety symptoms, and women and men have similar preventive effects of general leisure-time PA on self-reported anxiety. This may be of special interest to health practitioners. Further research is encouraged to study the prospective gender-specific and time-dependent association between PA and anxiety by measuring PA objectively or by using a more comprehensive self-reported questionnaire (e.g., covering mode, frequency, duration, and intensity of activity), using other characteristics or underlying conditions of PA, or evaluating other epidemiological aspects of anxiety (re-occurrence, course of disease, and severity). It may also be worth considering possible genetic, biological, and environmental factors that could confound, mediate, or moderate the relationship between PA and anxiety.

Conclusion HADS-defined anxiety was almost twice as common in women compared to men. Weekly hours of physical

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activity with moderate-high intensity was associated with less likelihood of developing anxiety symptoms in healthy women and men, although the true effect size may be different from the observed associations due to several threats to the internal validity in the study. More research is needed to examine specific characteristics of physical activity that may prevent the development of anxiety symptoms. Conflict of interest

None declared.

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