2.1. Study population
The SUN Project (Seguimiento Universidad de Navarra) is a Mediterranean prospective multipurpose dynamic cohort formed by Spanish graduates. The objectives, design and methods have been previously described [21]. Briefly the recruitment started in December 1999 and it is permanently open. The objectives are to identify dietary and lifestyle determinants of metabolic diseases, CVD, mental diseases, cancer and other chronic conditions. Data collection and follow up is carried out through mailed or web-based biennial self-reported questionnaires. More information and cohort profile can be found in the web page: www.medpreventiva.es/xZd6Hh
The baseline questionnaire (QO) collects information on participants’ socio-demographics, anthropometrics, diet and eating behaviors, lifestyles and clinical data. Every two years, shorter follow-up questionnaires (Q2-Q16) track changes in diet, lifestyle and medical aspects and ascertain the incidence of new diseases.
22,473 participants were recruited before September 2015. Appropriate exclusions for prevalent depression and other factors are shown in the flow chart in figure 1. We excluded participants with sedative and hypnotic medication, participants with energy intake values outside the Willet limits and participants with prevalent cardiovascular disease or obesity at baseline, which might affect the capacity to perform PA. After exclusions, 15,488 participants were included with a mean follow-up period of 10.5 years (SD: 4.4).
The written completion of the baseline questionnaire or Q0, once participants understood the specific information needed, the methods used to deliver their data and the future feedback from the research team, was considered to imply informed consent. Information explaining this was included in the Q0. We specifically asked for written permission before follow-up of personal medical records. We informed the potential candidates of their right to refuse to participate in the SUN study or to withdraw their consent to participate at any time without reprisal, according to the principles of the Declaration of Helsinki. The Institutional Review Board of the University of Navarra approved this survey and methods.
2.2. Assessment of leisure time physical activity
LTPA has been defined by WHO as the physical activity realized by an individual not required as an essential activity of the daily routine, excluding therefore sports participation, exercise conditioning, or other recreational activities [17].
The time spent and type of LTPA used in this analysis was derived from a 17-item questionnaire included in the Q0, collecting information about 17 different sports or leisure time activities (walking, jogging, athletics, cycling, stationary cycling, swimming, tennis, soccer, basketball, dancing, hiking, gymnastics, gardening, skiing, martial arts and sailing,) and information about the time spent on each LTPA. This questionnaire was previously validated using triaxial accelerometers (Spearman's ρ 0.51 (95%CI: 0.23- 0.70)). [22]
To calculate the energy expenditure in LTPA, we multiplied the weekly hours dedicated to each activity (Time spent in LTPA) by its typical intensity expressed in metabolic equivalents (METs) [21] to obtain METs-h / wk. Then, we divided the total sum of METs-h / wk by the weekly hours of LTPA to generate an average of METs (intensity in LTPA).
We classified LTPA energy expenditure in three groups, according to the WHO “Global recommendation on Physical Activity for Health” for adults aged 18-64 [17]: a) below the WHO recommendation (<10 MET-h/wk) equivalent < 150 min/wk of moderate-intensity aerobic PA or <75 min/wk of vigorous-intensity aerobic PA throughout the week or an equivalent combination; b) amount suggested by the WHO (10 to 20 METs-h/wk; equivalent to between 150-300 min/wk of moderate-intensity aerobic PA or 75-150 min/wk of vigorous-intensity aerobic PA or an equivalent combination; c) above the WHO recommendation (>20 MET-h/wk) equivalent to > 300 min/wk of moderate-intensity or more than 150 min/wk of vigorous-intensity PA per week or an equivalent combination.
2.3. Outcome assessment: Depression
All follow-up questionnaires included the question: Has a physician diagnosed you of depression in the last 2 years? Participants, who self-reported the diagnosis of depression or the use of antidepressants were considered as incident cases of depression. This procedure for the ascertainment and adjudication of medically diagnosed depression cases in the SUN Project has been previously validated using structured clinical interviews. The validation study in a subsample of the cohort used the Structured Clinical Interview for DSM-IV (SCID-I) administered by a senior psychiatrist as Gold Standard blinded to the responses of the questionnaire. The percentages of depression cases and confirmed non-depression cases both by a psychiatrist were 74.2% (95% CI 63·3-85·1) and 81.1% (95% 69·1,92·9) respectively. [23]
2.4. Assessment of covariates
At baseline (Q0), information of potential confounding factors such as personality traits, health-related habits (sleeping, smoking, alcohol intake, use of nap and time watching TV), prevalent chronic disease (hypertension, diabetes mellitus and cancer), dietary factors (adherence to Mediterranean diet, special diets and total energy intake), validated self-reported anthropometric data (weight and height) and socio-demographic characteristics (sex, age and educational level), were collected. To assess personality traits, validated specific self-reported questions, rated 0-10 regarding competitiveness, level of tension, and dependency, were used, using psychometric Likert-type scales. [23] For measuring dietary factors, we used a 136-item semi-quantitative food frequency questionnaire, previously validated. [24] We classified participants according to their baseline adherence to Mediterranean diet according to the validated 14-item PREDIMED questionnaire. [25]
2.5. Statistical analysis
To analyze the contribution of each type of PA to the total energy expenditure in LTPA, we calculated the percentage of total variability (R2) in the amount of MET-h/wk accounted for, by each type of PA.
Person-years of follow-up was calculated from the date baseline questionnaire was completed to the date of depression diagnosis, death, or return of the last follow-up questionnaire, whichever occurred first. To analyze depression risk according to LTPA categories proposed by the WHO we estimated hazard ratios (HR) and their 95% confidence intervals (CI) using Cox regression models with age as the underlying time variable. We used the lowest LTPA category (<10 MET-h/wk) as the reference category and adjusted for multiple confounding factors (sex, baseline body mass index, time sleeping, time of siesta, time spent watching television, total energy intake, adherence to the Mediterranean Diet, alcohol intake, smoking, educational level, and history of hypertension, diabetes mellitus and cancer). To asses possible changes during follow up in participants PA levels, the specific question: Has your level of PA increased, remained the same or decreased in the last two years? was included in the follow-up questionnaires. This information was taken into account in the multivariable analysis. We used categories of age (decades of age) and calendar year of entering the cohort as stratification variables. Linear trend was analyzed by assigning to each category of energy expenditure the median of that category in METs-h/wk and including this continuous variable in the multivariable models. We repeated these analyses, adjusting for multiple comparisons, for each of the 17 different types of LTPA.
The same analyses were conducted for the time spent in LTPA per week and for LTPA -intensity, using <75 min/wk and inactive, respectively, as reference categories.
Nelson-Aalen curves were used to describe the incidence of depression in different categories of LTPA and applied to these curves inverse probability weighting methods to control for confounding. To build these weights we used multinomial logistic regression models with LTPA (3 categories) as the outcome and derived the conditional probabilities for each subject to be in each category according to potential confounders. Subsequently we calculated stabilized weights as the quotient between the marginal probability of being in that category of LTPA over the conditional probability derived from the multinomial logistic model.To ensure the chronological sequence, and confirm that LTPA temporally preceded depression incidence, supplementary analysis have been done eliminating participants with a diagnosis of depression not only at baseline(Q0) but also in the first follow up questionnaire (Q2). Stratified analyses and tests for interactions with sex, age and adherence to the Mediterranean diet were performed to ensure the robustness of the results in different scenarios. All p values presented are two-tailed; p < 0.05 was considered statistically significant. Analyses were performed using STATA 12.0.