General Hospital Psychiatry xxx (2014) xxx–xxx

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Mediterranean diet is associated on symptoms of depression and anxiety in patients with bronchiectasis☆,☆☆,★,★★,☆☆☆ Casilda Olveira, M.D., Ph.D. a,⁎, Gabriel Olveira, M.D., Ph.D. b, c, Francisco Espildora, M.D. d, Rosa-María Girón, M.D. e, Montserrat Vendrell, M.D., Ph.D. f, Antonio Dorado, M.D., Ph.D. g, Miguel-Ángel Martínez-García, M.D., Ph.D. h a

Pneumology, Malaga Regional University Hospital, Instituto de Biomedicina de Málaga (IBIMA), Universidad de Málaga, Spain Endocrinology and Nutrition, Malaga Regional University Hospital, Instituto de Biomedicina de Málaga (IBIMA), Universidad de Málaga, Spain c CIBERDEM, CIBER of Diabetes and Associated Metabolic Diseases (Instituto de Salud Carlos III: CB07/08/0019) d Pneumology, Malaga Regional University Hospital, Málaga, Spain e Pneumology, Instituto de Investigación la Princesa Hospital, Madrid, Spain f Pneumology, Girona Biomedical Research Institute (IDIBGI), Dr. Trueta University Hospital, CIBERes (CIBER respiratory diseases), Girona, Spain g Pneumology, Malaga Regional University Hospital, Malaga, Spain h Pneumology, Polytechnic and University La Fe Hospital, CIBERes (CIBER respiratory diseases), Valencia, Spain b

a r t i c l e

i n f o

Article history: Received 14 August 2013 Revised 4 December 2013 Accepted 24 January 2014 Available online xxxx Keywords: Bronchiectasis Mediterranean diet PREDIMED score Symptoms of anxiety Symptoms of depression

a b s t r a c t Background: The aim was to measure symptoms of depression and anxiety in patients with bronchiectasis and evaluate their relationship with a Mediterranean diet. Methods: This cross-sectional study recruited patients with bronchiectasis at four Spanish centers. Patients completed the hospital anxiety and depression scale (HADS) and the Mediterranean diet questionnaire (PREDIMED). Demographic, health and outcome data were recorded from medical charts. Logistic regression was used to determine the predictors of elevated symptoms of depression and anxiety (HADS≥11). Results: Of the 205 participants recruited, 37 (18.0%) had elevated anxiety-related scores and 26 (12.7%) had elevated depression-related scores (HADS≥11). Increased symptoms of depression were significantly associated with being unemployed, a lower education, older age, comorbidity, major dyspnea, worse quality of life (QOL) and a lower PREDIMED score. Increased symptoms of anxiety were significantly associated with more exacerbations, worse QOL and a lower PREDIMED score. Regression analyses indicated that, after adjustment, QOL and the PREDIMED score predicted elevated symptoms of depression and QOL predicted elevated symptoms of anxiety. Conclusions: The prevalence of elevated symptoms of depression and anxiety is high in patients with bronchiectasis and greater adherence to a Mediterranean diet is associated with a lower likelihood of having these symptoms, particularly for depression. © 2014 Elsevier Inc. All rights reserved.

1. Introduction Bronchiectasis is the end result of several different diseases, managed in similar ways, but that lead to pulmonary infections, chronic

inflammation, loss of lung function and worsening of health-related quality of life. Care should be supervised by specialized units, at least in cases of chronic infection, recurrent exacerbations or bronchiectasis with an etiology susceptible to specific therapy. The prevalence is unknown

☆ The work was performed at Malaga Regional University Hospital, Málaga; Instituto de Investigación la Princesa Hospital, Madrid; Dr. Trueta University Hospital, Girona; and Polytechnic and University La Fe Hospital, Valencia, Spain. ☆☆ This study is included in the PII of Bronchiectasis of SEPAR (Spanish Society of Pulmonology and Thoracic Surgery). ★ Funding: This study was supported by a grant from SEPAR (31/2011). ★★ Contributions of authors: C. Olveira and G. Olveira contributed to the conception and design of the study; acquisition, analysis and interpretation of the data; and statistical analysis and drafting of the manuscript. Both authors are the guarantor of the paper, taking responsibility for the integrity of the word as a whole from inception to published article. Francisco Espíldora, Rosa-María Girón, Montserrat Vendrell, Antonio Dorado and Miguel-Ángel Martínez-García contributed to acquisition of the data and critical revision of the manuscript. ☆☆☆ Other contributions: Gerard Muñoz [Girona Biomedical Research Institute (IDIBGI), Dr. Trueta University Hospital, Girona, Spain] and Nuria Porras (Endocrinology and Nutrition Service, Málaga Regional University Hospital, Málaga, Spain) have also participated in this study. ⁎ Corresponding author. Tel.: +34-952286704; fax: +34-661210876. E-mail addresses: [email protected] (C. Olveira), [email protected] (G. Olveira), [email protected] (F. Espildora), [email protected] (R.-M. Girón), [email protected] (M. Vendrell), [email protected] (A. Dorado), [email protected] (M.-Á. Martínez-García). 0163-8343/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.genhosppsych.2014.01.010

Please cite this article as: Olveira C., et al, Mediterranean diet is associated on symptoms of depression and anxiety in patients with bronchiectasis, Gen Hosp Psychiatry (2014), http://dx.doi.org/10.1016/j.genhosppsych.2014.01.010

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C. Olveira et al. / General Hospital Psychiatry xxx (2014) xxx–xxx

and probably varies by population [1,2]; in the Unites States, the estimated prevalence of bronchiectasis is 53 cases per 100,000 adults [3]. Several studies have found that patients with bronchiectasis report worse health-related quality of life than the general population, particularly those with poor lung function, more frequent exacerbations, daily bronchorrhea, chronic infection with Pseudomonas aeruginosa [4–8] and symptoms of depression and anxiety [9]. Furthermore, patients who have both a chronic medical condition and either depression or anxiety exhibit more medical symptoms [10], physical disability [11], worse adherence to prescribed treatments and increased health care utilization and costs, compared to patients without significant psychological symptoms [10,12,13]. These psychiatric disorders are often under-diagnosed [14]. Though a high prevalence of these symptoms has been reported in patients with bronchiectasis [4,9,15], studies have so far focused mainly on patients with cystic fibrosis (CF) [16], with small sample sizes, in highly selected populations and, in some cases, applying evaluation tests that overlap the symptoms of the chronic disease itself with those of depression and/or anxiety [15]. A previous study by our group, involving 93 patients with bronchiectasis (including 43 with CF), showed that symptoms of depression and anxiety were increased and predicted a worse health-related quality of life [9]. The Mediterranean diet is considered to represent a healthy dietary pattern, and it has been characterized by the United Nations as an intangible cultural heritage of humanity [17]. The protective role of the Mediterranean diet could be multidimensional [18,19], encompassing anti-inflammatory functions [20], protection from oxidative stress [21] and atherothrombosis [22]. Greater adherence to a Mediterranean diet is associated with a marked improvement in health status [18,19], a significant reduction in overall mortality [18], mortality from cardiovascular diseases [23], incidence of mortality from cancer [24], incidence of Parkinson's disease [25], dementia and cognitive impairment [26,27] and particularly Alzheimer's disease [28,29]. High or moderate adherence to a Mediterranean diet was also consistently associated with a reduced risk for depression [27,30–32]. Conversely, the intake of trans fatty acids or the consumption of foods rich in this kind of fat, like those found in fast food or commercial bakery products, have been reported to be contributors to a higher risk for depression [33]. Diet might affect brain functions that are involved in the etiology of depression, including the synthesis and regulation of neurotransmitters, synaptic plasticity, membrane fluidity and neuroinflammation [27]. Depression is associated with a low-grade inflammatory status and beneficial effects are reported for lipids with anti-inflammatory properties, such as omega-3 fatty acids or virgin olive oil [32,34,35]. Adherence to a Mediterranean diet has also been suggested to be protective against respiratory disorders [36,37] and a high consumption of fruit, greens and fish has been associated with a lower risk of developing chronic obstructive pulmonary disease [38]. In patients with bronchiectasis, high plasma levels of inflammatory cytokines have been described, and these increases may be associated with nutritional status [39,40]. The protective role of the Mediterranean diet could be a result of its anti-inflammatory functions [18–21]. No studies have yet addressed the relationship of dietary patterns and depression among bronchiectasis patients. The hypothesis of this study was that a Mediterranean diet could modulate the prevalence of symptoms of depression and anxiety in this population. Accordingly, the aim of this multicenter study was to measure symptoms of depression and anxiety in a large sample of patients with bronchiectasis and evaluate their relationship to the Mediterranean diet. 2. Patients and methods This cross-sectional multicenter study included patients aged 16 years or older who met the diagnostic criteria for bronchiectasis [1,2]

and attended a specific bronchiectasis unit at one of four Spanish university hospitals for routine monitoring and treatment, over a recruitment period of 8 months. In all cases, bronchiectasis was diagnosed by high-resolution computed tomography of the chest, with the use of a 1- to 1.5-mm window every 10 mm and acquisition times of 1 s during full inspiration, following the criteria of Naidich et al. [41]. All the patients had undergone a full etiological study following the diagnostic algorithm for bronchiectasis of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) [1]. A full clinical history, from diagnosis to study participation, was recorded following the SEPAR protocol [1]. At each visit (every 2–3 months), demographic and clinical variables were collected prospectively. Patients performed spirometry, were weighed and measured, and a sputum sample was collected and cultured for the usual bronchiectasis pathogens [1]. Data were gathered on anthropometric (body mass index, BMI) and clinical aspects of bronchiectasis. The degree of dyspnea was recorded using the Medical Research Council (MRC) scale [42] and comorbidity with the Charlson index [43]. Assessment of the mean amount of sputum produced daily (in millilitres) was evaluated by instructing the patients to collect sputum during the 3 days prior to the visit in three graded sterile containers (one per day), marking the amount reached each day on the container. Instructions were given to ensure that sputum was collected correctly, with low percentages of saliva recorded [6]. We analyzed chronic colonisation by P. aeruginosa, considering its appearance in sputum (at least 3 positive), regardless of its persistence at the time of the study [1]. Exacerbations in the year prior to the evaluation were assessed prospectively using the SEPAR criteria [1]. Demographic variables recorded included age, gender, the educational level (no education or just primary studies/more than primary studies), employment status (unemployed/not studying or employed/studying), marital/partner status (with/without) and smoking history (current smokers/exsmokers or nonsmokers). Spirometry was also performed, with the forced expiratory volume in 1 s (FEV1) expressed in absolute terms (ml) and as a percentage, using a reference population [44]. 2.1. Questionnaires The questionnaires were completed after a clinical examination to confirm that the patients were in a stable phase and before completing the clinical measures (including spirometry) performing the various elective medical procedures in order not to bias responses. If at this time the patients had a respiratory exacerbation or a recent hospital admission, their participation was postponed for at least 60 days, until any acute illness was resolved. The St. George's Respiratory Questionnaire (SGRQ) is a self-report health-status measure, consisting of 50 items distributed across three domain scores (Symptoms, Activity and Impact) and a total score. The items in the dimension Symptoms concern the frequency and severity of the respiratory symptoms. The dimension Activity contains items concerning the limitation in activity due to dyspnea. The dimension Impact has items about psychological and social disorders as well as work-related problems produced by the respiratory disease. Scores range from 0 to 100, with higher scores representing worse health status [45]. The Spanish version has been validated for use in patients with bronchiectasis [7,46]. 2.1.1. Hospital anxiety and depression scale (HADS) [47] The HADS is a brief, 14-item screening tool to measure symptoms of depression and anxiety. It has been well validated for use in a Spanish population [9,48] and excludes somatic symptoms. The Spanish version of the HADS had good internal consistency and external validity, with favorable sensitivity and specificity in identifying cases of psychiatric disorder as defined by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The psychometric properties of the HADS and its

Please cite this article as: Olveira C., et al, Mediterranean diet is associated on symptoms of depression and anxiety in patients with bronchiectasis, Gen Hosp Psychiatry (2014), http://dx.doi.org/10.1016/j.genhosppsych.2014.01.010

C. Olveira et al. / General Hospital Psychiatry xxx (2014) xxx–xxx

brevity make it useful for screening for psychiatric disorders in the medically ill [9,48]. A score less than 8 is considered a negative result on the screening, and from 8 to 10 indicates mild symptoms. In this study, a positive screening to define clear symptoms of depression or anxiety was considered to be represented by a score ≥ 11 [47,48]. 2.1.2. PREDIMED A 14-item dietary screening questionnaire was used to assess adherence to the Mediterranean diet. This is a self-administered validated dietary questionnaire used in the PREDIMED trial (Prevención con Dieta Mediterránea) [23,49–51] with questions about the consumption of olive oil, vegetables or garden produce, fruit, red meat, hamburgers, sausages, carbonated or sweetened drinks, wine, legumes, fish or sea food, confectionary, nuts, chicken, turkey or rabbit and stir-fry. The score ranges from 0 to 14, with higher scores representing greater adherence to a Mediterranean diet. Patients were excluded if they had CF [52], if they had difficulty understanding the questionnaires (e.g., were unable to read or comprehend the questions due, for example, to advanced age), or if they refused to participate or sign the consent form. The study was approved by the Malaga Northeast Ethics and Research Committee, and all the participants provided written informed consent. 2.2. Data analysis Data were analyzed with SPSS version 12 (SPSS Inc., Chicago, IL). Continuous variables were expressed as mean±standard deviation, with 95% confidence intervals. The normality of distributions was verified using the Kolmogorov–Smirnov test. Categorical variables were compared using Chi-square tests, with Fisher's Exact Test when necessary. Continuous variables were compared using t tests or the Mann–Whitney test. Step-wise logistic regression was then used to determine the predictors of having symptom scores of depression or anxiety ≥ 11. The variables analyzed for potential predictors of depression or anxiety included those reaching statistical significance in the univariate study [exacerbations, dyspnea (MRC), PREDIMED score, quality of life — St. George total score] adjusting for age, gender, Charlson index, work status and educational level. For all variables, significance was set at Pb .05 for two tails. 3. Results A total of 218 patients with bronchiectasis were approached for the study and 205 agreed to participate. Of the 13 patients who were excluded, 3 had problems understanding the questionnaires and 10 declined participation. The mean age of the participants was 57.2 years (range, 17–86) and 62.8% were women. The mean FEV1% was 68.3±22.2% (range, 15–123%). Table 1 shows the main characteristics of the participants. Antidepressants were being taken by 19 (9.2%), and anxiolytics, by 28 (13.6%) patients; no other medication, such as hypnotics or other psychotropic drugs, was being used. No gender differences were found for any demographic or clinical variables. Clinically elevated depression-related scores (≥11) were found in 26 (12.68%) patients. Similarly, high rates of anxiety were reported, with 37 (18.05%) scoring above the clinical cut-off score (≥ 11). The patients with an elevated score for depressive symptoms were significantly older and had significantly higher Charlson comorbidity scores and degrees of dyspnea, as measured according to the MRC, than those with scores b 11. The patients with an elevated score for anxiety symptoms had significantly more exacerbations during the previous year (Tables 2 and 3). Symptoms of depression and anxiety were not significantly related to gender, FEV1%, FVC%, BMI, bronchorrhea or Pseudomonas infection (Table 2). Patients who were unemployed and those with less education had a significantly higher prevalence of elevated symptoms of depression, but not anxiety, than

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Table 1 Demographic and clinical characteristics Characteristics

Mean

S.D.

Age Males BMI (kg/m2) Smoking history Current smokers Ex-smokers/Nonsmokers Etiology Idiopathic Post-infection Immunodeficiency Collagen disease Ciliary dyskinesia Other FEV1% of predicted Chronic P. aeruginosa Exacerbations in the last year Sputum production (ml/day) PREDIMED

57.2

18.1

25.0

4.4

68.3

22.2

1.7

1.6 21.8 2.1

7.9

n

(%) 77

37.2

9 198

4.3 95,7

58 80 12 7 22 28

28.0 38.6 5.8 3.4 10.6 13.5

68

32.9

25.6

FEV1: forced expiratory volume in the first second. PREDIMED: a 14-item dietary screener used to assess adherence to the Mediterranean diet.

those who were employed or those with more education. Symptoms of depression and anxiety were not significantly related to whether the patient had a partner or not (Table 3). The patients with a score ≥ 11 for depressive symptoms and for anxiety symptoms had significantly higher total and subscale scores on the SGRQ (worse quality of life) (Table 2). The overall score for the Mediterranean diet in the whole group was 7.95±2.1. The patients with elevated symptoms of anxiety and depression (≥11) had significantly lower scores on the PREDIMED than those who scored b11. After adjusting for confounders, only dyspnea (MRC) and the Mediterranean diet score were significant predictors of elevated symptoms of anxiety (Table 4). However, when the total St. George score (SGTotal) was added to the model, the significance of the MRC and the Mediterranean diet score disappeared, with just SGTotal remaining significant (Table 4). After adjustment for confounders, only dyspnea (MRC) and the Mediterranean diet score were significant predictors of elevated symptoms of depression. However, when the total St. George score (SGTotal) was added to the model, the significance of the MRC disappeared, with just the Mediterranean diet score and SGTotal remaining significant (Table 4). 4. Discussion The results of this study indicate that the prevalence of elevated symptoms of depression and anxiety was high in patients with bronchiectasis in comparison with the data reported for the general population [12,14,53–56], and Mediterranean diet was associated with a lower likelihood of having these symptoms, particularly depression. As expected, patients with bronchiectasis reported higher rates of elevated symptoms (HADS≥11) of depression (12.68%) and anxiety (18%) than those published for the general population in Spain [53–55] and other countries [12,14,56]. In the general Spanish population, Haro et al. [54] found prevalence rates of 4.3 of depressive disorders and 6.2% for anxiety disorders. These results are consistent with prior studies in which higher rates of depression and anxiety have been reported by patients with chronic illnesses [10,12,56], including patients with a variety of respiratory diseases [11,16,57–61] and bronchiectasis [4,9,15]. Differences in rates of elevated symptoms of depression were found in relation to age, with older patients reporting more symptoms, although no differences were seen in rates of anxiety. A previous study by our group also detected greater symptoms of depression and anxiety related with age in a group of bronchiectasis patients (including some with CF) [9]. O'Leary et al. [4], in non-CF

Please cite this article as: Olveira C., et al, Mediterranean diet is associated on symptoms of depression and anxiety in patients with bronchiectasis, Gen Hosp Psychiatry (2014), http://dx.doi.org/10.1016/j.genhosppsych.2014.01.010

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C. Olveira et al. / General Hospital Psychiatry xxx (2014) xxx–xxx

Table 2 Clinical variables according to the presence of elevated symptoms of depression and anxiety Dimension

HADS-A

FVC% FEV1% BMI Chronic Pseudomonas infection Yes No No. of exacerbations per year Dyspnea (MRC) Sputum production (ml/day) Quality of life (St. George) Symptoms Activity Impact Total Charlson comorbidity index PREDIMED score

HADS-D

b11

≥11

b11

n=168

≥11

n=37

n=179

n=26

81.95%

18.05%

87.32%

12.68%

76.00±18.5 68.20±22.1 25.13±4.2

79.78±19.1 69.21±23.5 24.59±5.1

0.152 0.760 0.322

77.00±18.7 69.33±21.4 24.94±4.3

74.50±18.8 61.88±27.4 25.65±5.0

0.403 0.100 0.583

55 (32.7) 113 (67.3) 1.63±1.7 0.93±0.9 20.11±23.04

13 (35.1) 24 (64.9) 2.29±0.3 1.27±1.0 27.30±33.11

0.779

12 (46.2) 14 (53.8) 2.11±1.3 1.54±1.1 28.65±29.07

0.132

0.011 0.088 0.21

56 (31.3) 123 (68.7) 1.70±1.7 0.92±0.9 20.36±24.52

38.88±19.2 38.01±25.7 24.85±18.7 31.27±17.9 2.28±1.7 8.08±2.0

50.25±22.7 54.68±22.1 40.76±20.8 47.00±19.7 2.35±1.7 7.35±2.1

0.004 0.000 0.000 0.000 0.777 0.049

39.66±20.2 38.94±25.2 25.51±18.9 32.10±18.1 2.17±1.6 8.11±2.0

50.12±18.7 56.01±26.0 43.67±20.7 48.70±20.3 3.11±2.4 6.84±1.9

0.024 0.006 0.000 0.000 0.030 0.005

P

P

0.069 0.008 0.11

The values are presented as the ±S.D. or n (%). PREDIMED: a 14-item dietary screener used to assess adherence to the Mediterranean diet. FVC%: forced vital capacity. FEV1%: forced expiratory volume in the first second.

bronchiectasis, found no differences according to age or gender. Likewise, in our study, symptoms of depression and anxiety were not significantly related with gender. Patients who had less education and were not employed had a greater prevalence of elevated symptoms of depression than those with more education or who were employed. These results are similar to those found in a previous study by our group that evaluated patients with bronchiectasis of different etiologies, including CF [9]. In the general population and in patients with other chronic diseases, being unemployed is also related with more depressive symptoms [53,54,57,58,62]. In terms of clinical variables, only the Charlson comorbidity index, dyspnea and frequency of exacerbations were related with a greater Table 3 Demographic data according to the presence of elevated symptoms of depression and anxiety Dimension

HADS-A

HADS-D

b11

≥11

168 (81.9)

37 (18.0)

Age 57.22±18.9 Gender Male 67 (39.9) Female 101 (60.1) Educational level No or just 93 (55.4) primary studies 75 (44.6) More than primary Work status Studies or 66 (39.5) works 101 (60.5) Does not study or work Partner status With 111 (66.1) a partner Without 57 (33.9) a partner

prevalence of psychological symptoms, with a higher prevalence of elevated symptoms of depression associated with greater comorbidity and worse degrees of dyspnea and a higher prevalence of elevated symptoms of anxiety associated with more frequent exacerbations. In the logistic regression models, dyspnea was a predictive variable for the risk of elevated symptoms of depression and anxiety, after adjusting for confounding variables. However, when the quality-oflife score was included in the model, this association was lost. The total score on the St. George quality-of-life questionnaire may reflect better than other clinical variables (including dyspnea), how the patient functions, feels or survives in relation to his/her chronic illness. It thus helps to assess the patient's perception of severity in a single variable. O'Leary et al. [4] also found in patients with bronchiectasis that dyspnea was correlated with depression scores but anxiety was not. Other studies have also shown that those patients with more

P

b11

≥11

179 (87.3)

26 (12.68)

P

56.64±14.9 0.549 56.05±18.3 64.46±16.0 0.021 10 (27.0) 27 (73.0)

20 (54.1)

17 (45.9)

16 (43.2) 21 (56.8)

29 (78.4) 8 (21.6)

0.189 69 (38.5) 110 (61.5)

1.000 93 (52.0)

86 (48)

0.713 77 (43.3) 101 (56.7)

0.174 123 (68.7) 56 (31.3)

The values are presented as the mean±S.D. or n (%).

8 (30.8) 18 (69.2)

20 (76.9)

0.020

0.020

21 (80.8)

17 (65.4) 9 (34.6)

B

Odds ratio

0.520

6 (23.1)

5 (19.2)

Table 4 Logistic regression analysis: adjusted risk of presenting elevated symptoms (HADS≥11) of depression and anxiety

0.822

Elevated symptoms of anxiety Model 1 MRC 0.502 PREDIMED score −0.195 Model 2 MRC −0.162 PREDIMED score −0.167 TotalSG 0.058 Elevated symptoms of depression Model 1 MRC 0.506 PREDIMED score −0.434 Model 2 MRC 0.073 PREDIMED score −0.167 TotalSG 0.058

95% Confidence interval

P

Lower

Upper

1.652 0.823

1.077 0.680

2.532 0.995

0.021 0.044

0.851 0.846 1.060

0.499 0.695 1.030

1.45 1.030 1.090

0.552 0.096 0.000

1.659 0.648

1.001 0.502

2.75 0.83

0.049 0.001

1.075 0.663 1.038

0.572 0.512 1.004

2.02 0.85 1.07

0.821 0.002 0.027

Adjusted for age, educational level, work status and Charlson comorbidity index. TotalSG: total score on the St. George quality-of-life test. MRC: degree of dyspnea recorded using the MRC scale. PREDIMED: a 14-item dietary screener used to assess adherence to the Mediterranean diet.

Please cite this article as: Olveira C., et al, Mediterranean diet is associated on symptoms of depression and anxiety in patients with bronchiectasis, Gen Hosp Psychiatry (2014), http://dx.doi.org/10.1016/j.genhosppsych.2014.01.010

C. Olveira et al. / General Hospital Psychiatry xxx (2014) xxx–xxx

comorbidities have more symptoms of depression and anxiety [10,12,56]. No associations were found between spirometric parameters and elevated symptoms of depression and anxiety. Prior literature addressing this question has produced mixed results [9,16,59–61]. Patients who have elevated symptoms of depression and anxiety also reported a worse quality of life across all SGRQ scales. This is consistent with previous studies of adults with CF [9,16,63] and nonCF bronchiectasis [4,9]. As mentioned above, after adjusting for sociodemographic and clinical factors, the quality-of-life score was found to have an independent association with the risk of having elevated symptoms of depression and anxiety. A previous study by our group, in a cohort that included patients with CF and non-CF bronchiectasis, also found that symptoms of depression and anxiety predicted a worse quality of life, independently of demographic variables, diagnosis and respiratory disease markers [9]. The Mediterranean diet is characterized by a high intake of vegetables, fruits, cereals, pulses, nuts and seed; moderate consumption of dairy products, fish, poultry and eggs and unsaturated fats, such as olive oil as the primary source of mono-unsaturated fat for cooking and dressing; a low to moderate intake of wine during meals; and a low intake of red, processed meats and saturated fats [64]. In our study, we assessed adherence to the Mediterranean diet using a brief 14-item questionnaire. This tool is a key element in the intervention conducted in the PREDIMED trial. It has been previously validated and its application has been proposed for other settings [23,49–51]. In our sample, the patients with bronchiectasis had a mean score of 7.95± 2.1, which was slightly lower than the 8.6±2.0 reported for the PREDIMED cohort, which included 7447 persons with a high cardiovascular risk in Spain [23]. The persons with elevated symptoms of depression and anxiety (HADS≥11) had lower PREDIMED scores. Furthermore, the logistic regression models showed that the risk of having elevated symptoms of depression was significantly associated with the Mediterranean diet score after adjustment for confounders, even after including the quality-of-life score in the model. Thus, a higher PREDIMED score (better adherence to a Mediterranean diet) reflected a lower likelihood for elevated symptoms of depression. On the other hand, their likelihood of having high symptoms of anxiety was significantly associated with the Mediterranean diet score after adjustment for confounders, though it disappeared after including the quality-of-life score in the model. Persons with a worse socioeconomic level and those with more symptoms of depression or anxiety have been reported to have worse dietary habits [12,13,18], which could influence the results of this study given its cross-sectional nature. Although no studies have yet been done in patients with bronchiectasis, the mechanisms by which a Mediterranean diet can affect the presence of symptoms of depression or anxiety in these patients may be similar to those found in other groups [18]. As mentioned earlier, patients with bronchiectasis have been found to have high plasma levels of inflammatory cytokines and these increases may be associated with nutritional status [39,40]. The protective role of the Mediterranean diet could therefore be due to its anti-inflammatory functions [18–21]. In another prospective study of Spanish graduates, increasing adherence to a Mediterranean dietary pattern (scored on a high intake of fruits, vegetables and fish; moderate alcohol consumption; and a low intake of meat and dairy products) was prospectively associated with a lower risk of clinically diagnosed depression [31]. It has also been shown that the risk of depression increased with the consumption of fast-food items (hamburgers, sausages and pizza) [33]. Rienks et al. [65] also found that consumption of a “Mediterranean-style” dietary pattern by middle-aged women may have a protective influence against the onset of depressive symptoms. In elderly men and women [66], the consumption of fish, vegetables, olive oil and cereal correlated negatively with the severity of

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depressive symptoms. The benefits from fish and olive oil intake remained significant even when adjusted for confounders such as age, gender, education status, BMI and physical activity status, as well as the presence of a number of medical conditions [66]. In a study by Jacka et al. [67], consuming a “traditional” diet comprising vegetables, fruit, meat, fish and whole grains was also associated with a reduced risk of depression or dysthymia. Research into the diet of adolescents [68] and of low socioeconomic status, community dwelling, elderly people [69] has also provided evidence for an association between diet quality and depression. Depressive symptoms are also positively associated with the consumption of sweets [70]. A number of plausible biological mechanisms have been suggested for the association between diet and depression, including some that are consistent with a preventive role for a Mediterranean diet [27,30– 32,34,35,65]. Diet might affect brain functions that are involved in the etiology of depression, including the synthesis and regulation of neurotransmitters [65,71], synaptic plasticity [71–73], membrane fluidity and neuroinflammation [73,74]. It has been shown that, in people with depression, inflammation is increased [73] and brainderived neurotrophic factor is reduced [72]. Depression has been associated with low levels of the neurotransmitter serotonin; tryptophan is the only precursor for serotonin, which is an essential amino acid whose dietary sources include fish, legumes, whole grains and nuts [72,75]. Another plausible mechanism relates to the ratio of omega-6 to omega-3 fatty acids in western diets [34,73,76]. Omega-6 fatty acids are associated with an increase in proinflammatory eicosanoids, a decrease in brain-derived neurotrophic factor and a decrease in membrane fluidity [74,77]. The omega-3 fatty acid docosahexaenoic acid, which is most abundant in the brain, can inhibit the release of proinflammatory cytokines [73,74,76] and increase the levels of the brain-derived neurotrophic factor, which in turn enhances neurotransmission and synaptic plasticity [71–73]. Furthermore, increased homocysteine levels have been associated with depression, and folate deficiency could be one of the causes [78,79]. Folate is present in dark-green leafy vegetables, legumes, citrus fruits and many types of bread and other cereals. As a consequence of low folate levels, the synthesis of homocysteine to methionine and S-adenosyl-methionine is impaired. S-Adenosylmethionine is a methyl donor and is involved in the synthesis and metabolism of neurotransmitters [78].

5. Strengths and weaknesses The strengths of this study lie in the use of a large sample of patients with bronchiectasis and the use of validated measures to assess the Mediterranean diet, psychological symptoms and quality of life, as well as the ability to adjust for a wide range of sociodemographic and clinical factors. Nevertheless, the study is not exempt from limitations. First, the study used a cross-sectional design, which precluded our ability to examine causal relationships between a Mediterranean diet and psychological symptoms in patients with bronchiectasis. Large-scale, longitudinal studies are needed to address these questions. Second, no measurement was made of dietary biomarkers, total energy intake or other dietary data, which could have enhanced the value of the study. Third, although adjustment for potential confounders had little effect on the association between a Mediterranean diet and the reporting of depressive symptoms, residual confounding could still be present as there may be unmeasured variables (such as a family history of depression and personality traits, physical activity or the socioeconomic status of the study subjects). Based on the results of this study and given the high prevalence detected of symptoms of depression and anxiety in patients with bronchiectasis, we suggest that a program for annual screening of depression and anxiety could be effective in this particular population.

Please cite this article as: Olveira C., et al, Mediterranean diet is associated on symptoms of depression and anxiety in patients with bronchiectasis, Gen Hosp Psychiatry (2014), http://dx.doi.org/10.1016/j.genhosppsych.2014.01.010

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C. Olveira et al. / General Hospital Psychiatry xxx (2014) xxx–xxx

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Please cite this article as: Olveira C., et al, Mediterranean diet is associated on symptoms of depression and anxiety in patients with bronchiectasis, Gen Hosp Psychiatry (2014), http://dx.doi.org/10.1016/j.genhosppsych.2014.01.010