- Email: [email protected]
Nutritional effects on depressive symptoms in Parkinson’s disease patients
e-SPEN Journal 7 (2012) e64ee68
Contents lists available at SciVerse ScienceDirect
e-SPEN Journal journal homepage: http://www.elsevier.com/locate/clnu
Original article
Nutritional effects on depressive symptoms in Parkinson’s disease patients Tetsuhito Fukushima a, *, Xiaodong Tan b, Yunwen Luo c, Puqing Wang c, Jinhui Song c, Hideyuki Kanda a, Takehito Hayakawa a, Takeyasu Kakamu a, Masayoshi Tsuji a a
Department of Hygiene & Preventive Medicine, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima 960-1295, Japan School of Public Health, Wuhan University, Wuhan, China c Xiangfan No.1 Hospital, Xiangfan, China b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 April 2011 Received in revised form 1 February 2012 Accepted 12 February 2012
Background & aims: Factors associated with depression in Parkinson’s disease, especially lifestyle and nutrition, have been poorly studied. Our study was conducted to investigate nutritional factors associated with depression in Parkinson’s disease. Methods: The subjects were 82 Parkinson’s disease patients and the same number of sex and agematched controls recruited from the outpatient clinic of Xiangfan No. 1 People’s Hospital in Hubei, China between 2006 and 2008. The Parkinson’s disease patients were divided into two groups, 24 Parkinson’s disease with depression and 58 Parkinson’s disease without depression. DSM-IV criteria was used for the primary diagnosis of depressive disorders. The severity of depression in patients was assessed by the criteria of the Hamilton Depression Rating Scale (HAMD-17), and a score 14 was defined as “depression”. Information about eating habits and other factors was obtained by subject recall of state prior to diagnosis of Parkinson’s disease and depression Results: Compared with the Parkinson’s disease patients without depression and the controls, the Parkinson’s disease patients with depression had relatively low levels of income and education. Fat and vitamin B1 intake was significantly higher in the Parkinson’s disease patients with depression than in both the Parkinson’s disease patients without depression and the controls. Bean product intake was significantly lower in the Parkinson’s disease patients with depression than in both the Parkinson’s disease patients without depression and the controls. Conclusions: Less fat and vitamin B1 but more bean product intake might be associated with a lower risk for depression in Parkinson’s disease patients from a higher income bracket with better educational background. Ó 2012 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
Keywords: Parkinson’s disease Depression Nutrition survey Fat Vitamin Bean
1. Introduction Depression is common in Parkinson’s disease (PD) and approximately 30e40% of PD patients have significant depressive disorders.1 Some researchers have studied the factors of depression in PD. Dissanayaka et al.2 reported that depression was identified in 66% of the PD patients, and depressed PD patients were more likely to have lower level of education and a history of smoking. JasinskaMyga et al.3 reported that factors associated with depression included longer PD duration, greater impairment in activities of daily living, and a positive family history of motor neuron disease. The determinants of depression in PD, however, are complex and poorly understood. * Corresponding author. Tel.: þ81 245471173; fax: þ81 245471174. E-mail address: [email protected] (T. Fukushima).
The role of certain food intake on depression has been considered epidemiologically. Murakami et al.4 reported that the subjects with depressive symptoms had a lower mean value of vegetable intake in a group of adolescents. In the group of adults, higher dietary intake of folate was associated with a lower prevalence of depressive symptoms in Japanese men, but not women.5 It has been discussed whether polyunsaturated fatty acids (PUFAs) are associated with a risk of depression or not. Serum concentrations of n-6 PUFAs, n6/n3 PUFA ratio, and individual fatty acids were not associated with a risk of severe depression in middle-aged Finnish men.6 To evaluate the association between fatty acid intake, the use of culinary fats, and depression incidence, a prospective cohort study of university graduates (mean age: 37.5 years) was conducted. Inverse associations were found between monounsaturated fatty acids, PUFAs and olive oil intake and depression risk.7 To evaluate factors associated with depression in the elderly,
2212-8263/$36.00 Ó 2012 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clnme.2012.02.002
T. Fukushima et al. / e-SPEN Journal 7 (2012) e64ee68
553 men and 637 women (aged 65e100 years) were recruited.8 Twenty five per cent of men and 35% of women were classified in the highest Geriatric Depression Scale category (score >10), indicating intense depressive symptoms, while 54% of men and 70% of women scored above the depression cut-off (score >5), indicating mild-to-severe depressive symptoms. The consumption of fish, vegetables and cereal was more prevalent among people with low or moderate depression. A “traditional” dietary pattern characterized by consumption of vegetables, fruit, meat, fish, and whole grains might be associated with a lower risk of depression.9 Factors associated with depression in PD, especially those related to lifestyle or nutrition, have been poorly studied. To clarify the association, a case-control study was carried out. 2. Methods The study was carried out in Xiangfan, Hubei, China. The subjects used were the same as those in a previous report10 and were comprised of 82 PD patients (47 men, 35 women; mean age standard deviation (SD) ¼ 64.0 9.4 years) who had been patients for less than 3 years and were recruited from the outpatient clinic of Xiangfan No. 1 People’s Hospital in Hubei, China, between 2006 and 2008, and sex and age-matched (3 years) controls (n ¼ 82; mean age ¼ 63.7 9.4 years) had no PD, but had symptoms such as headaches and dizziness, and were recruited from the same outpatient clinic at the same time. PD was diagnosed according to the criteria of the UK Parkinson’s Disease Society Brain Bank.11 The depressive status was assessed simultaneously with the diagnosis of PD in the first medical examination by the neurologist in Xiangfan No. 1 People’s Hospital. DSM-IV criteria12 was used for the primary diagnosis of a depressive disorder. Major depression and dysthymia were our outcomes of interest. The severity of depression in patients was assessed by the criteria of the Hamilton Depression Rating Scale (HAMD-17),13 and a score 14 was defined as “depression”.14 All the PD patients and all the controls were examined by neurologists from the clinic and underwent computed tomography inspection to exclude secondary causes of parkinsonism and morbidity unsuitable for controls. Informed consent was obtained from all the subjects, and the study protocol was approved by the ethics boards of Xiangfan No. 1 People’s Hospital (Hubei, China) and Fukushima Medical University (Fukushima, Japan). Information was collected according to a structured close-ended questionnaire by trained interviewers in face-to-face interviews with subjects and their family members, if available. Previous eating habits in the period during which the subjects first noticed symptoms of PD were obtained, along with other information. The controls were asked current eating habits. The nutritional intake survey was carried out in accordance with a book by Qu and Yang.15 Food intake, macronutrient and micronutrient were determined by ingestion frequency and amount per week. We calculated intake based on the components of each food. Sex, age, marital status, height, weight, educational background and annual income were obtained, along with details of alcohol consumption and smoking status. The questionnaire consisted of 11 categories: (1) general information (sex, age, marital status, height, weight, educational background, annual income, alcohol consumption, smoking status); (2) dairy product intake (whole milk, milk powder, yogurt, cake, ice cream, other daily products); (3) beverage and liquor intake (orange or other fruit juice, soda “Cola, Sprite, Seven-Up, etc.”, soybean milk, tea (amount of sugar or honey added), coffee (amount of sugar or milk added), beer, wine (red or white), liquor, water, soup, others); (4) dessert, snacks, and nuts (candy, biscuits, pies, peanuts or other nuts or seeds); (5) fruits (apple, pear, banana, orange, tangerine, tangelo, peach, nectarine, plum, pineapple,
e65
grape, grapefruit, kiwifruit, apricot, watermelon, others); (6) staple foods like rice, cereal, bread and noodles, etc. (oatmeal, cooked rice, porridge, steamed bread, baked pancake, fried food, noodles “instant noodles, cut noodles, fried noodles”, rice flour, buns with meat filling, buns with vegetable filling, sticky rice products, corn products, bread, others); (7) meat, poultry, fish, and eggs (lean pork meat only, sausage, chicken, duck, other poultry, beef and beef products, mutton, pork (fat and lean meat), sparerib, shrimp (various), whole crab or crab meat, organ meats (pork liver, chicken liver, intestines, heart, kidney, etc.), fish, boiled egg, duck egg, fried egg, others); (8) vegetables (bean curd, tofu (all kinds: soft, firm, dried, fried), mung bean sprout, soybean sprout, green soybeans, spinach, rape, cabbage, eggplant, celery, chive, cucumber, Chinese wax gourd, bitter melon, sponge gourd, pumpkin, tomato, carrot, green pepper, hot pepper, lettuce, garlic sprouts, garlic, onion, caraway, mushroom, radish, lotus root, potato, sweet potato, taro, sea tangle, laver, edible tree fungus, others); (9) condiments and sauces (catsup, sesame paste, chili, others); (10) vegetable oil used in making dishes (salad oil, bean oil, peanut oil, others); (11) animal oil used in making dishes (lard, butter, others). The SPSS statistical package was used. Differences in sex, marriage, alcohol consumption, smoking and educational background among groups were assessed using the c2 test for bivariate analysis. Means for continuous values (age, height, weight, body mass index and income) were analyzed using analysis of variance (ANOVA). For comparison of food, macronutrient and micronutrient intake among groups, analysis of covariance (ANCOVA) with sex and age as the covariates was used, and means identified differences (P < 0.06) by ANCOVA were compared using t-tests. 3. Results The PD patients were divided into two groups, 24 PD with depression (11 men, 13 women; mean age ¼ 63.0 9.6 years) and 58 PD without depression (36 men, 22 women; mean age ¼ 64.3 9.4 years). After exclusion of one control woman with depressive symptoms, the controls consisted of 47 men and 34 women (mean age ¼ 63.7 9.4 years). General information for subjects is shown in Table 1. Compared with the PD patients without depression and the controls, the PD patients with depression had significantly lower levels of income and education. Food and macronutrient intake in subjects is shown in Table 2. Differences were seen in intake of animal protein (p ¼ 0.012), fat (p ¼ 0.044), bean products (p ¼ 0.053), and vegetables (p ¼ 0.051) among the three groups. Micronutrient intake in subjects is shown in Table 3. Differences were seen in intake of sodium (p ¼ 0.058), retinol (p ¼ 0.011), vitamin B1 (p ¼ 0.001), lysine (p ¼ 0.032), methionine (p ¼ 0.006) and threonine (p ¼ 0.037). Means identified differences (p < 0.06) by ANCOVA were compared in Fig. 1. Fat and vitamin B1 intake was significantly higher in the PD patients with depression than in both the PD patients without depression and the controls. Bean product intake was significantly lower in the PD patients with depression than in both the PD patients without depression and the controls. 4. Discussion Factors associated with depression in PD, especially lifestyle and nutrition, have been poorly studied. As reported by Dissanayaka et al., anxiety disorders contributed to a poor quality of life in PD patients. Age was significantly associated with anxiety, and younger PD patients were more likely to experience anxiety disorders. Other factors, however, such as tea consumption, coffee
e66
T. Fukushima et al. / e-SPEN Journal 7 (2012) e64ee68
Table 1 Subject characteristics.
Table 3 Micronutrient intake.
Characteristics
PD þ depression PD-depression Control (n ¼ 24) (n ¼ 58) (n ¼ 81)
p
Micronutrient
PD þ depression (n ¼ 24)
PD-depression (n ¼ 58)
Control (n ¼ 81)
p
Sex (male/female) Age (years, mean SD) Marriage (n, spouse) Height (cm, mean SD) Weight (kg, mean SD) Body mass index (mean SD) Alcohol (n) Smoke (n, now/past) Income (Yuan/year, mean SD) Educational background (n, illiterate/ primary school/ middle school/ high schoolor skill school/ college, university)
11/13 63.0 9.6
36/22 64.3 9.4
47/34 63.7 9.4
0.398 0.828
14/10 162.3 8.9
39/19 164.4 8.2
53/28 165.3 6.6
0.739 0.245
58.4 9.8
61.9 10.8
63.3 9.9
0.116
22.3 3.3
22.9 2.8
23.2 2.9
0.422
7 2/2 6058 6220
18 7/11 8739 7414
31 0.571 16/12 0.362 11926 8994 0.004
5/7/6/1/5
8/14/19/11/5
2/17/21/22/17 0.020
Calcium Iron Zinc Selenium Copper Manganese Magnesium Sodium Potassium Phosphorus Retinol Vitamin E Vitamin B1 Vitamin B2 Vitamin C Niacin Cholesterol Histidine Tyrosine Lysine Tryptophane Isoleucine Phenylalanine Methionine Aminoisovaleric acid Amidocaproic acid Threonine Dicysteine
615.9 366.3 28.1 19.1 9.1 3.4 32.6 16.7 1.6 1.0 4.7 1.8 288.3 118.8 798.2 507.6 1806.2 937.3 814.6 341.8 731.6 555.4 29.8 17.5 1.5 1.7 1.2 0.8 176.3 121.2 14.9 7.2 372.4 289.6 673.9 452.8 861.9 577.9 1613.5 1029.5 365.1 232.3 1114.4 752.7 1163.5 830.4 539.1 368.4 1290.3 871.9
559.5 345.3 26.0 14.1 9.2 4.4 31.6 13.3 1.4 1.0 4.6 2.2 303.3 150.1 585.5 282.9 1810.8 967.7 934.8 552.0 537.1 375.2 31.2 14.2 0.8 0.5 1.1 0.9 179.7 152.2 14.6 6.7 299.8 180.7 651.0 300.3 768.8 390.3 1409.5 859.6 420.8 224.8 1013.1 505.0 1331.9 1124.8 499.9 261.9 1655.0 1099.7
589.5 284.7 30.0 18.1 9.9 4.9 30.4 14.7 1.6 1.0 4.6 2.7 300.0 151.5 713.6 440.8 2041.6 1114.7 955.0 466.3 847.0 696.8 29.1 13.6 0.9 0.5 1.2 0.7 197.0 152.7 15.1 6.9 333.9 231.4 818.3 533.5 978.6 680.3 1955.1 1490.3 425.5 234.3 1264.5 867.4 1427.7 1021.5 717.7 522.2 1937.1 1396.9
0.765 0.394 0.579 0.676 0.450 0.956 0.971 0.058 0.371 0.532 0.011 0.709 0.001 0.833 0.725 0.922 0.235 0.075 0.095 0.032 0.603 0.129 0.576 0.006 0.082
1896.8 1350.5
2443.4 1530.2
2767.5 1880.8
0.100
1029.1 666.3 432.0 363.0
1434.5 933.1 343.3 152.8
1698.4 1303.6 414.4 238.6
0.037 0.122
Differences in sex, marriage, alcohol drinking, smoking and educational background among groups were assessed using the c2 test for bivariate analysis. Means for continuous values were analyzed using analysis of variance. PD þ depression, Parkinson’s disease patient with depression; PD-depression, Parkinson’s disease patient without depression. Marriage (spouse-) consists of “Single”, “Divorced”, “Separated” and “Widowed”. Educational background was unknown for 1 PDdepression and 2 controls.
consumption, smoking and alcohol consumption were not significantly associated with anxiety in the PD patients.16 The role of fatty acid intake in depression in general has been considered. Several studies have shown that an association exists between u-3 PUFAs and depression. Intake of u-3 PUFAs, especially docosahexaenoic acid and eicosapentaenoic acid, may improve Table 2 Food and macronutrient intake. Food and macronutrient
PDþdepression (n ¼ 24)
PD-depression (n ¼ 58)
Control (n ¼ 81)
p
Daily energy Energy source From protein From fat From carbohydrate
2005.4 872.7
2008.5 568.3
1926.7 566.5
0.667
224.1 87.9 821.2 275.1 840.9 476.7
284.9 167.8 714.2 275.1 835.3 405.5
299.6 161.4 738.5 274.1 763.8 412.7
0.132 0.245 0.491
Protein Animal protein Bean protein Phytoprotein
58.3 24.8 21.0 18.9 4.3 6.8 30.8 13.4
59.8 29.2 22.3 9.8 5.7 17.6 29.8 10.5
65.1 30.4 30.3 21.4 5.9 10.7 28.7 16.6
0.459 0.012 0.851 0.699
Fat Animal fat Vegetable fat
99.8 51.1 20.0 11.4 71.3 30.9
82.1 27.7 20.5 15.4 58.8 26.1
81.6 29.9 17.9 12.7 61.3 29.0
0.044 0.502 0.233
218.5 127.2 10.4 5.2 368.4 150.9 56.3 84.6 554.8 386.4 90.0 140.0 93.1 108.3 49.6 52.3 42.6 89.2
229.0 95.4 10.5 5.7 400.0 168.1 115.2 130.1 393.9 250.0 107.0 122.7 120.5 75.2 42.1 34.6 41.5 63.8
202.2 88.8 11.1 8.2 376.9 172.1 122.4 111.8 506.2 304.2 82.1 104.0 148.9 131.0 39.3 40.5 62.1 105.5
0.262 0.844 0.666 0.053 0.051 0.391 0.082 0.454 0.353
Carbohydrate Dietary fiber Foodstuff Bean Vegetables Fruit Animal meat Egg Milk
Each value is the mean and standard deviation. Analysis of covariance with sex and age as the covariates was used to identify differences among three groups. Units: daily energy and energy source: kcal/day; all others: g/day.
Each value is the mean and standard deviation. Analysis of covariance with sex and age as the covariates was used to identify differences among three groups. Units: Selenium: mg/day; all others: mg/day.
maternal depression.17 To investigate this association in the elderly, a double-blind, randomized, placebo-controlled study was performed. Treatment with u-3 PUFAs was clinically more effective in treating depression in comparison with the placebo. Low-dose u-3 PUFAs may have some efficacy in the treatment of mild-to moderate depression in the elderly.18 Usually u-3 PUFAs are found predominantly in fish and bean products (soybeans, etc.). Vegetable intake may also prevent depression.4,8 Although in the present study, reliable data concerning fish intake was not obtained due to the study being carried out in the inland areas of China where fish intake is not common, bean product intake was significantly lower in the PD patients with depression than in both the PD patients without depression and the controls. Fat and vitamin B1 intake was significantly higher in the PD patients with depression than in both the PD patients without depression and the controls. A prospective cohort study demonstrated an association between fatty acid intake, the use of culinary fats and depression incidence in a Mediterranean population.7 A detrimental relationship was found between trans unsaturated fatty acid intake and depression risk, whereas weak inverse associations were found for monounsaturated fatty acids, PUFAs and olive oil. Cardiovascular disease and depression might share some common nutritional determinants related to subtypes of fat intake. A “traditional” dietary pattern characterized by a balanced dietary pattern, relatively lowfat diet, might be associated with a lower risk of depression,9 as in cardiovascular disease. Because beans usually contain an abundance of u-3 PUFAs, not only a low-fat diet, but also a high intake of bean products might be effective in depression prevention for PD patients. The reason why vitamin B1 intake was high in the PD patients with depression was unknown. No reports suggesting a relationship between vitamin B1 intake and depression were found. Vitamin B1 is a water-soluble vitamin, but is found
T. Fukushima et al. / e-SPEN Journal 7 (2012) e64ee68
e67
Animal protein
Fat
∗∗
60
200
30 20 0
0 PD+depression PD-depression
Bean
∗
Control
PD+depression PD-depression
Vegetables
∗∗
1000
250 150 100 0
600 400
0 PD+depression PD-depression
Control
PD+depression PD-depression
2000
1000
0 Control
PD+depression PD-depression
∗
Control
Lysine
∗∗
∗
4000 mg/day
mg/day
Vitamin B1
3000 2000 1000 0
PD+depression PD-depression
Control
PD+depression PD-depression
PD+depression PD-depression
Control
Threonine
∗∗ mg/day
Methionine
mg/day
∗∗
1500
500
PD+depression PD-depression
1400 1200 1000 800 600 400 200 0
Control
Retinol
∗
mg/day
mg/day
Sodium
3.5 3 2.5 2 1.5 1 0.5 0
∗
200
50
1400 1200 1000 800 600 400 200 0
∗
Control
800
200
g/day
g/day
100 50
10
300
∗
150
40
g/day
g/day
50
∗
Control
3500 3000 2500 2000 1500 1000 500 0
∗
PD+depression PD-depression
Control
Fig. 1. Comparison of food, macronutrient and micronutrient intake among three subject groups. Each value is the mean and standard deviation. Means for values are compared using t-tests to identify differences between groups. *p < 0.05, **p < 0.01.
e68
T. Fukushima et al. / e-SPEN Journal 7 (2012) e64ee68
abundantly in meat, especially pork products. Since PD patients with depression do not ingest much animal protein, high vitamin B1 intake in PD patients with depression may be caused by many factors rather than be an effect of meat intake. To investigate the relationship between some expected risk factors and depression in PD patients, clinical factors were examined. Depression was associated with an increased severity of PD or comorbidities such as anxiety, memory problems, hallucinations, sleep disturbance and postural hypotension. Social status was also examined, and depressed PD patients were more likely to have a lower level of education.2 According to the report by Kummer et al., depression might exacerbate executive dysfunction, especially in the PD patients with a lower level of education.19 There may be a close relationship between aggravation of PD, depression and educational history. In the present study, compared with the PD patients without depression and the controls, the PD patients with depression were less educated and had a lower income. Social status may therefore be an important risk factor of depression in PD patients. It seems that education and annual income affect nutritional quality. Lemke et al.20 reported anxiety and depression were the risk factors for the development of PD and might be present many years before the appearance of motor symptoms. Bower et al.21 studied the association of three personality traits related to neuroticism with the subsequent risk of PD using a historical cohort study. The study suggested that an anxious personality trait might predict an increased risk of PD developing many years later. Sanyal et al.22 also reported that the multivariate analysis revealed that a previous history of depression was associated with increased risk of PD. Further study is needed to verify the meaning of depression in PD. Statement of authorship TF organized the research group, carried out the studies, and drafted the manuscript. XT and HK participated in the design of the study and conducted the nutrition survey. YL, PW and JS performed medical examinations of the subjects. TH, TK and MT participated in the design of the study and carried out the data analyses. All authors read and approved the final manuscript. Conflict of interest statement There are none.
Acknowledgements This research was funded by a Grant-in-Aid for Scientific Research (No. 18590563 and No. 21590657) from the Japanese Society for the Promotion of Science. This study sponsor has had no involvement in this work.
References 1. Barone P. Treatment of depressive symptoms in Parkinson’s disease. Eur J Neurol 2011;18(Suppl. 1):11e5. 2. Dissanayaka NNW, Sellbach A, Silburn PA, O’Sullivan JD, Marsh R, Mellick GD. Factors associated with depression in Parkinson’s disease. J Affect Disord 2011;132:82e8. 3. Jasinska-Myga B, Putzke JD, Wider C, Wszolek ZK, Uitti RJ. Depression in Parkinson’s disease. Can J Neurol Sci 2010;37:61e6. 4. Murakami K, Miyake Y, Sasaki S, Tanaka K, Arakawa M. Fish and n-3 polyunsaturated fatty acid intake and depressive symptoms: Ryukyus Child Health Study. Pediatrics 2010;126:e623e30. 5. Murakami K, Mizoue T, Sasaki S, Ohta M, Sato M, Matsushita Y, et al. Dietary intake of folate, other B vitamins, and omega-3 polyunsaturated fatty acids in relation to depressive symptoms in Japanese adults. Nutrition 2008;24:140e7. 6. Ruusunen A, Virtanen JK, Lehto SM, Tolmunen T, Kauhanen J, Voutilainen S. Serum polyunsaturated fatty acids are not associated with the risk of severe depression in middle-aged Finnish men: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Eur J Nutr 2011;50:89e96. 7. Sánchez-Villegas A, Verberne L, de Irala J, Ruíz-Canela M, Toledo E, SerraMajem L, et al. Dietary fat intake and the risk of depression: The SUN project. PLoS ONE 2011;6(1). Article number e16268. 8. Mamplekou E, Bountziouka V, Psaltopoulou T, Zeimbekis A, Tsakoundakis N, Papaerakleous N, et al. Urban environment, physical inactivity and unhealthy dietary habits correlate to depression among elderly living in eastern Mediterranean islands: The MEDIS (Mediterranean Islands Elderly) study. J Nutr Health Aging 2010;14:449e55. 9. Jacka FN, Pasco JA, Mykletun A, Williams LJ, Hodge AM, O’Reilly SL, et al. Association of Western and traditional diets with depression and anxiety in women. Am J Psychiatry 2010;167:305e11. 10. Fukushima T, Tan X, Luo Y, Kanda H. Relationship between blood levels of heavy metals and Parkinson’s disease in China. Neuroepidemiology 2010;34:18e24. 11. Daniel SE, Lees AJ. Parkinson’s disease society brain bank, London: overview and research. J Neural Transm Suppl 1993;39:165e72. 12. American Psychiatric Association. In: Diagnostic and statistical manual of mental disorders: DSM-IV. 4th ed. Washington DC: American Psychiatric Association; 1994. 13. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psych 1960;23:56e62. 14. Leentjens AF, Verhey FR, Lousberg R, Spitsbergen H, Wilmink FW. The validity of the Hamilton and Montgomery-Asberg depression rating scales as screening and diagnostic tools for depression in Parkinson’s disease. Int J Geriatr Psychiatry 2000;15:644e9. 15. Qu F, Yang X. Nutritional and health survey for Chinese citizen in 2002. Beijing: People’s Health Press; 2006. 16. Dissanayaka NN, Sellbach A, Matheson S, O’Sullivan JD, Silburn PA, Byrne GJ, et al. Anxiety disorders in Parkinson’s disease: prevalence and risk factors. Mov Disord 2010;25:838e45. 17. Ramakrishnan U. Fatty acid status and maternal mental health. Matern Child Nutr 2011;7(Suppl. 2):99e111. 18. Tajalizadekhoob Y, Sharifi F, Fakhrzadeh H, Mirarefin M, Ghaderpanahi M, Badamchizade Z, et al. The effect of low-dose omega 3 fatty acids on the treatment of mild to moderate depression in the elderly: a double-blind, randomized, placebo-controlled study. Eur Arch Psychiatry Clin Neurosci 2011:1e11. 19. Kummer A, Harsányi E, Dias FM, Cardoso F, Caramelli P, Teixeira AL. Depression impairs executive functioning in Parkinson disease patients with low educational level. Cogn Behav Neurol 2009;22:167e72. 20. Lemke MR. Depressive symptoms in Parkinson’s disease. Eur J Neurol 2008;15(Suppl. 1):21e5. 21. Bower JH, Grossardt BR, Maraganore DM, Ahlskog JE, Colligan RC, Geda YE, et al. Anxious personality predicts an increased risk of parkinson’s disease. Mov Disord 2010;25:2105e13. 22. Sanyal J, Chakraborty DP, Sarkar B, Banerjee TK, Mukherjee SC, Ray BC, et al. Environmental and familial risk factors of Parkinsons disease: caseecontrol study. Can J Neurol Sci 2010;37:637e42.
Contents lists available at SciVerse ScienceDirect
e-SPEN Journal journal homepage: http://www.elsevier.com/locate/clnu
Original article
Nutritional effects on depressive symptoms in Parkinson’s disease patients Tetsuhito Fukushima a, *, Xiaodong Tan b, Yunwen Luo c, Puqing Wang c, Jinhui Song c, Hideyuki Kanda a, Takehito Hayakawa a, Takeyasu Kakamu a, Masayoshi Tsuji a a
Department of Hygiene & Preventive Medicine, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima 960-1295, Japan School of Public Health, Wuhan University, Wuhan, China c Xiangfan No.1 Hospital, Xiangfan, China b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 April 2011 Received in revised form 1 February 2012 Accepted 12 February 2012
Background & aims: Factors associated with depression in Parkinson’s disease, especially lifestyle and nutrition, have been poorly studied. Our study was conducted to investigate nutritional factors associated with depression in Parkinson’s disease. Methods: The subjects were 82 Parkinson’s disease patients and the same number of sex and agematched controls recruited from the outpatient clinic of Xiangfan No. 1 People’s Hospital in Hubei, China between 2006 and 2008. The Parkinson’s disease patients were divided into two groups, 24 Parkinson’s disease with depression and 58 Parkinson’s disease without depression. DSM-IV criteria was used for the primary diagnosis of depressive disorders. The severity of depression in patients was assessed by the criteria of the Hamilton Depression Rating Scale (HAMD-17), and a score 14 was defined as “depression”. Information about eating habits and other factors was obtained by subject recall of state prior to diagnosis of Parkinson’s disease and depression Results: Compared with the Parkinson’s disease patients without depression and the controls, the Parkinson’s disease patients with depression had relatively low levels of income and education. Fat and vitamin B1 intake was significantly higher in the Parkinson’s disease patients with depression than in both the Parkinson’s disease patients without depression and the controls. Bean product intake was significantly lower in the Parkinson’s disease patients with depression than in both the Parkinson’s disease patients without depression and the controls. Conclusions: Less fat and vitamin B1 but more bean product intake might be associated with a lower risk for depression in Parkinson’s disease patients from a higher income bracket with better educational background. Ó 2012 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
Keywords: Parkinson’s disease Depression Nutrition survey Fat Vitamin Bean
1. Introduction Depression is common in Parkinson’s disease (PD) and approximately 30e40% of PD patients have significant depressive disorders.1 Some researchers have studied the factors of depression in PD. Dissanayaka et al.2 reported that depression was identified in 66% of the PD patients, and depressed PD patients were more likely to have lower level of education and a history of smoking. JasinskaMyga et al.3 reported that factors associated with depression included longer PD duration, greater impairment in activities of daily living, and a positive family history of motor neuron disease. The determinants of depression in PD, however, are complex and poorly understood. * Corresponding author. Tel.: þ81 245471173; fax: þ81 245471174. E-mail address: [email protected] (T. Fukushima).
The role of certain food intake on depression has been considered epidemiologically. Murakami et al.4 reported that the subjects with depressive symptoms had a lower mean value of vegetable intake in a group of adolescents. In the group of adults, higher dietary intake of folate was associated with a lower prevalence of depressive symptoms in Japanese men, but not women.5 It has been discussed whether polyunsaturated fatty acids (PUFAs) are associated with a risk of depression or not. Serum concentrations of n-6 PUFAs, n6/n3 PUFA ratio, and individual fatty acids were not associated with a risk of severe depression in middle-aged Finnish men.6 To evaluate the association between fatty acid intake, the use of culinary fats, and depression incidence, a prospective cohort study of university graduates (mean age: 37.5 years) was conducted. Inverse associations were found between monounsaturated fatty acids, PUFAs and olive oil intake and depression risk.7 To evaluate factors associated with depression in the elderly,
2212-8263/$36.00 Ó 2012 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clnme.2012.02.002
T. Fukushima et al. / e-SPEN Journal 7 (2012) e64ee68
553 men and 637 women (aged 65e100 years) were recruited.8 Twenty five per cent of men and 35% of women were classified in the highest Geriatric Depression Scale category (score >10), indicating intense depressive symptoms, while 54% of men and 70% of women scored above the depression cut-off (score >5), indicating mild-to-severe depressive symptoms. The consumption of fish, vegetables and cereal was more prevalent among people with low or moderate depression. A “traditional” dietary pattern characterized by consumption of vegetables, fruit, meat, fish, and whole grains might be associated with a lower risk of depression.9 Factors associated with depression in PD, especially those related to lifestyle or nutrition, have been poorly studied. To clarify the association, a case-control study was carried out. 2. Methods The study was carried out in Xiangfan, Hubei, China. The subjects used were the same as those in a previous report10 and were comprised of 82 PD patients (47 men, 35 women; mean age standard deviation (SD) ¼ 64.0 9.4 years) who had been patients for less than 3 years and were recruited from the outpatient clinic of Xiangfan No. 1 People’s Hospital in Hubei, China, between 2006 and 2008, and sex and age-matched (3 years) controls (n ¼ 82; mean age ¼ 63.7 9.4 years) had no PD, but had symptoms such as headaches and dizziness, and were recruited from the same outpatient clinic at the same time. PD was diagnosed according to the criteria of the UK Parkinson’s Disease Society Brain Bank.11 The depressive status was assessed simultaneously with the diagnosis of PD in the first medical examination by the neurologist in Xiangfan No. 1 People’s Hospital. DSM-IV criteria12 was used for the primary diagnosis of a depressive disorder. Major depression and dysthymia were our outcomes of interest. The severity of depression in patients was assessed by the criteria of the Hamilton Depression Rating Scale (HAMD-17),13 and a score 14 was defined as “depression”.14 All the PD patients and all the controls were examined by neurologists from the clinic and underwent computed tomography inspection to exclude secondary causes of parkinsonism and morbidity unsuitable for controls. Informed consent was obtained from all the subjects, and the study protocol was approved by the ethics boards of Xiangfan No. 1 People’s Hospital (Hubei, China) and Fukushima Medical University (Fukushima, Japan). Information was collected according to a structured close-ended questionnaire by trained interviewers in face-to-face interviews with subjects and their family members, if available. Previous eating habits in the period during which the subjects first noticed symptoms of PD were obtained, along with other information. The controls were asked current eating habits. The nutritional intake survey was carried out in accordance with a book by Qu and Yang.15 Food intake, macronutrient and micronutrient were determined by ingestion frequency and amount per week. We calculated intake based on the components of each food. Sex, age, marital status, height, weight, educational background and annual income were obtained, along with details of alcohol consumption and smoking status. The questionnaire consisted of 11 categories: (1) general information (sex, age, marital status, height, weight, educational background, annual income, alcohol consumption, smoking status); (2) dairy product intake (whole milk, milk powder, yogurt, cake, ice cream, other daily products); (3) beverage and liquor intake (orange or other fruit juice, soda “Cola, Sprite, Seven-Up, etc.”, soybean milk, tea (amount of sugar or honey added), coffee (amount of sugar or milk added), beer, wine (red or white), liquor, water, soup, others); (4) dessert, snacks, and nuts (candy, biscuits, pies, peanuts or other nuts or seeds); (5) fruits (apple, pear, banana, orange, tangerine, tangelo, peach, nectarine, plum, pineapple,
e65
grape, grapefruit, kiwifruit, apricot, watermelon, others); (6) staple foods like rice, cereal, bread and noodles, etc. (oatmeal, cooked rice, porridge, steamed bread, baked pancake, fried food, noodles “instant noodles, cut noodles, fried noodles”, rice flour, buns with meat filling, buns with vegetable filling, sticky rice products, corn products, bread, others); (7) meat, poultry, fish, and eggs (lean pork meat only, sausage, chicken, duck, other poultry, beef and beef products, mutton, pork (fat and lean meat), sparerib, shrimp (various), whole crab or crab meat, organ meats (pork liver, chicken liver, intestines, heart, kidney, etc.), fish, boiled egg, duck egg, fried egg, others); (8) vegetables (bean curd, tofu (all kinds: soft, firm, dried, fried), mung bean sprout, soybean sprout, green soybeans, spinach, rape, cabbage, eggplant, celery, chive, cucumber, Chinese wax gourd, bitter melon, sponge gourd, pumpkin, tomato, carrot, green pepper, hot pepper, lettuce, garlic sprouts, garlic, onion, caraway, mushroom, radish, lotus root, potato, sweet potato, taro, sea tangle, laver, edible tree fungus, others); (9) condiments and sauces (catsup, sesame paste, chili, others); (10) vegetable oil used in making dishes (salad oil, bean oil, peanut oil, others); (11) animal oil used in making dishes (lard, butter, others). The SPSS statistical package was used. Differences in sex, marriage, alcohol consumption, smoking and educational background among groups were assessed using the c2 test for bivariate analysis. Means for continuous values (age, height, weight, body mass index and income) were analyzed using analysis of variance (ANOVA). For comparison of food, macronutrient and micronutrient intake among groups, analysis of covariance (ANCOVA) with sex and age as the covariates was used, and means identified differences (P < 0.06) by ANCOVA were compared using t-tests. 3. Results The PD patients were divided into two groups, 24 PD with depression (11 men, 13 women; mean age ¼ 63.0 9.6 years) and 58 PD without depression (36 men, 22 women; mean age ¼ 64.3 9.4 years). After exclusion of one control woman with depressive symptoms, the controls consisted of 47 men and 34 women (mean age ¼ 63.7 9.4 years). General information for subjects is shown in Table 1. Compared with the PD patients without depression and the controls, the PD patients with depression had significantly lower levels of income and education. Food and macronutrient intake in subjects is shown in Table 2. Differences were seen in intake of animal protein (p ¼ 0.012), fat (p ¼ 0.044), bean products (p ¼ 0.053), and vegetables (p ¼ 0.051) among the three groups. Micronutrient intake in subjects is shown in Table 3. Differences were seen in intake of sodium (p ¼ 0.058), retinol (p ¼ 0.011), vitamin B1 (p ¼ 0.001), lysine (p ¼ 0.032), methionine (p ¼ 0.006) and threonine (p ¼ 0.037). Means identified differences (p < 0.06) by ANCOVA were compared in Fig. 1. Fat and vitamin B1 intake was significantly higher in the PD patients with depression than in both the PD patients without depression and the controls. Bean product intake was significantly lower in the PD patients with depression than in both the PD patients without depression and the controls. 4. Discussion Factors associated with depression in PD, especially lifestyle and nutrition, have been poorly studied. As reported by Dissanayaka et al., anxiety disorders contributed to a poor quality of life in PD patients. Age was significantly associated with anxiety, and younger PD patients were more likely to experience anxiety disorders. Other factors, however, such as tea consumption, coffee
e66
T. Fukushima et al. / e-SPEN Journal 7 (2012) e64ee68
Table 1 Subject characteristics.
Table 3 Micronutrient intake.
Characteristics
PD þ depression PD-depression Control (n ¼ 24) (n ¼ 58) (n ¼ 81)
p
Micronutrient
PD þ depression (n ¼ 24)
PD-depression (n ¼ 58)
Control (n ¼ 81)
p
Sex (male/female) Age (years, mean SD) Marriage (n, spouse) Height (cm, mean SD) Weight (kg, mean SD) Body mass index (mean SD) Alcohol (n) Smoke (n, now/past) Income (Yuan/year, mean SD) Educational background (n, illiterate/ primary school/ middle school/ high schoolor skill school/ college, university)
11/13 63.0 9.6
36/22 64.3 9.4
47/34 63.7 9.4
0.398 0.828
14/10 162.3 8.9
39/19 164.4 8.2
53/28 165.3 6.6
0.739 0.245
58.4 9.8
61.9 10.8
63.3 9.9
0.116
22.3 3.3
22.9 2.8
23.2 2.9
0.422
7 2/2 6058 6220
18 7/11 8739 7414
31 0.571 16/12 0.362 11926 8994 0.004
5/7/6/1/5
8/14/19/11/5
2/17/21/22/17 0.020
Calcium Iron Zinc Selenium Copper Manganese Magnesium Sodium Potassium Phosphorus Retinol Vitamin E Vitamin B1 Vitamin B2 Vitamin C Niacin Cholesterol Histidine Tyrosine Lysine Tryptophane Isoleucine Phenylalanine Methionine Aminoisovaleric acid Amidocaproic acid Threonine Dicysteine
615.9 366.3 28.1 19.1 9.1 3.4 32.6 16.7 1.6 1.0 4.7 1.8 288.3 118.8 798.2 507.6 1806.2 937.3 814.6 341.8 731.6 555.4 29.8 17.5 1.5 1.7 1.2 0.8 176.3 121.2 14.9 7.2 372.4 289.6 673.9 452.8 861.9 577.9 1613.5 1029.5 365.1 232.3 1114.4 752.7 1163.5 830.4 539.1 368.4 1290.3 871.9
559.5 345.3 26.0 14.1 9.2 4.4 31.6 13.3 1.4 1.0 4.6 2.2 303.3 150.1 585.5 282.9 1810.8 967.7 934.8 552.0 537.1 375.2 31.2 14.2 0.8 0.5 1.1 0.9 179.7 152.2 14.6 6.7 299.8 180.7 651.0 300.3 768.8 390.3 1409.5 859.6 420.8 224.8 1013.1 505.0 1331.9 1124.8 499.9 261.9 1655.0 1099.7
589.5 284.7 30.0 18.1 9.9 4.9 30.4 14.7 1.6 1.0 4.6 2.7 300.0 151.5 713.6 440.8 2041.6 1114.7 955.0 466.3 847.0 696.8 29.1 13.6 0.9 0.5 1.2 0.7 197.0 152.7 15.1 6.9 333.9 231.4 818.3 533.5 978.6 680.3 1955.1 1490.3 425.5 234.3 1264.5 867.4 1427.7 1021.5 717.7 522.2 1937.1 1396.9
0.765 0.394 0.579 0.676 0.450 0.956 0.971 0.058 0.371 0.532 0.011 0.709 0.001 0.833 0.725 0.922 0.235 0.075 0.095 0.032 0.603 0.129 0.576 0.006 0.082
1896.8 1350.5
2443.4 1530.2
2767.5 1880.8
0.100
1029.1 666.3 432.0 363.0
1434.5 933.1 343.3 152.8
1698.4 1303.6 414.4 238.6
0.037 0.122
Differences in sex, marriage, alcohol drinking, smoking and educational background among groups were assessed using the c2 test for bivariate analysis. Means for continuous values were analyzed using analysis of variance. PD þ depression, Parkinson’s disease patient with depression; PD-depression, Parkinson’s disease patient without depression. Marriage (spouse-) consists of “Single”, “Divorced”, “Separated” and “Widowed”. Educational background was unknown for 1 PDdepression and 2 controls.
consumption, smoking and alcohol consumption were not significantly associated with anxiety in the PD patients.16 The role of fatty acid intake in depression in general has been considered. Several studies have shown that an association exists between u-3 PUFAs and depression. Intake of u-3 PUFAs, especially docosahexaenoic acid and eicosapentaenoic acid, may improve Table 2 Food and macronutrient intake. Food and macronutrient
PDþdepression (n ¼ 24)
PD-depression (n ¼ 58)
Control (n ¼ 81)
p
Daily energy Energy source From protein From fat From carbohydrate
2005.4 872.7
2008.5 568.3
1926.7 566.5
0.667
224.1 87.9 821.2 275.1 840.9 476.7
284.9 167.8 714.2 275.1 835.3 405.5
299.6 161.4 738.5 274.1 763.8 412.7
0.132 0.245 0.491
Protein Animal protein Bean protein Phytoprotein
58.3 24.8 21.0 18.9 4.3 6.8 30.8 13.4
59.8 29.2 22.3 9.8 5.7 17.6 29.8 10.5
65.1 30.4 30.3 21.4 5.9 10.7 28.7 16.6
0.459 0.012 0.851 0.699
Fat Animal fat Vegetable fat
99.8 51.1 20.0 11.4 71.3 30.9
82.1 27.7 20.5 15.4 58.8 26.1
81.6 29.9 17.9 12.7 61.3 29.0
0.044 0.502 0.233
218.5 127.2 10.4 5.2 368.4 150.9 56.3 84.6 554.8 386.4 90.0 140.0 93.1 108.3 49.6 52.3 42.6 89.2
229.0 95.4 10.5 5.7 400.0 168.1 115.2 130.1 393.9 250.0 107.0 122.7 120.5 75.2 42.1 34.6 41.5 63.8
202.2 88.8 11.1 8.2 376.9 172.1 122.4 111.8 506.2 304.2 82.1 104.0 148.9 131.0 39.3 40.5 62.1 105.5
0.262 0.844 0.666 0.053 0.051 0.391 0.082 0.454 0.353
Carbohydrate Dietary fiber Foodstuff Bean Vegetables Fruit Animal meat Egg Milk
Each value is the mean and standard deviation. Analysis of covariance with sex and age as the covariates was used to identify differences among three groups. Units: daily energy and energy source: kcal/day; all others: g/day.
Each value is the mean and standard deviation. Analysis of covariance with sex and age as the covariates was used to identify differences among three groups. Units: Selenium: mg/day; all others: mg/day.
maternal depression.17 To investigate this association in the elderly, a double-blind, randomized, placebo-controlled study was performed. Treatment with u-3 PUFAs was clinically more effective in treating depression in comparison with the placebo. Low-dose u-3 PUFAs may have some efficacy in the treatment of mild-to moderate depression in the elderly.18 Usually u-3 PUFAs are found predominantly in fish and bean products (soybeans, etc.). Vegetable intake may also prevent depression.4,8 Although in the present study, reliable data concerning fish intake was not obtained due to the study being carried out in the inland areas of China where fish intake is not common, bean product intake was significantly lower in the PD patients with depression than in both the PD patients without depression and the controls. Fat and vitamin B1 intake was significantly higher in the PD patients with depression than in both the PD patients without depression and the controls. A prospective cohort study demonstrated an association between fatty acid intake, the use of culinary fats and depression incidence in a Mediterranean population.7 A detrimental relationship was found between trans unsaturated fatty acid intake and depression risk, whereas weak inverse associations were found for monounsaturated fatty acids, PUFAs and olive oil. Cardiovascular disease and depression might share some common nutritional determinants related to subtypes of fat intake. A “traditional” dietary pattern characterized by a balanced dietary pattern, relatively lowfat diet, might be associated with a lower risk of depression,9 as in cardiovascular disease. Because beans usually contain an abundance of u-3 PUFAs, not only a low-fat diet, but also a high intake of bean products might be effective in depression prevention for PD patients. The reason why vitamin B1 intake was high in the PD patients with depression was unknown. No reports suggesting a relationship between vitamin B1 intake and depression were found. Vitamin B1 is a water-soluble vitamin, but is found
T. Fukushima et al. / e-SPEN Journal 7 (2012) e64ee68
e67
Animal protein
Fat
∗∗
60
200
30 20 0
0 PD+depression PD-depression
Bean
∗
Control
PD+depression PD-depression
Vegetables
∗∗
1000
250 150 100 0
600 400
0 PD+depression PD-depression
Control
PD+depression PD-depression
2000
1000
0 Control
PD+depression PD-depression
∗
Control
Lysine
∗∗
∗
4000 mg/day
mg/day
Vitamin B1
3000 2000 1000 0
PD+depression PD-depression
Control
PD+depression PD-depression
PD+depression PD-depression
Control
Threonine
∗∗ mg/day
Methionine
mg/day
∗∗
1500
500
PD+depression PD-depression
1400 1200 1000 800 600 400 200 0
Control
Retinol
∗
mg/day
mg/day
Sodium
3.5 3 2.5 2 1.5 1 0.5 0
∗
200
50
1400 1200 1000 800 600 400 200 0
∗
Control
800
200
g/day
g/day
100 50
10
300
∗
150
40
g/day
g/day
50
∗
Control
3500 3000 2500 2000 1500 1000 500 0
∗
PD+depression PD-depression
Control
Fig. 1. Comparison of food, macronutrient and micronutrient intake among three subject groups. Each value is the mean and standard deviation. Means for values are compared using t-tests to identify differences between groups. *p < 0.05, **p < 0.01.
e68
T. Fukushima et al. / e-SPEN Journal 7 (2012) e64ee68
abundantly in meat, especially pork products. Since PD patients with depression do not ingest much animal protein, high vitamin B1 intake in PD patients with depression may be caused by many factors rather than be an effect of meat intake. To investigate the relationship between some expected risk factors and depression in PD patients, clinical factors were examined. Depression was associated with an increased severity of PD or comorbidities such as anxiety, memory problems, hallucinations, sleep disturbance and postural hypotension. Social status was also examined, and depressed PD patients were more likely to have a lower level of education.2 According to the report by Kummer et al., depression might exacerbate executive dysfunction, especially in the PD patients with a lower level of education.19 There may be a close relationship between aggravation of PD, depression and educational history. In the present study, compared with the PD patients without depression and the controls, the PD patients with depression were less educated and had a lower income. Social status may therefore be an important risk factor of depression in PD patients. It seems that education and annual income affect nutritional quality. Lemke et al.20 reported anxiety and depression were the risk factors for the development of PD and might be present many years before the appearance of motor symptoms. Bower et al.21 studied the association of three personality traits related to neuroticism with the subsequent risk of PD using a historical cohort study. The study suggested that an anxious personality trait might predict an increased risk of PD developing many years later. Sanyal et al.22 also reported that the multivariate analysis revealed that a previous history of depression was associated with increased risk of PD. Further study is needed to verify the meaning of depression in PD. Statement of authorship TF organized the research group, carried out the studies, and drafted the manuscript. XT and HK participated in the design of the study and conducted the nutrition survey. YL, PW and JS performed medical examinations of the subjects. TH, TK and MT participated in the design of the study and carried out the data analyses. All authors read and approved the final manuscript. Conflict of interest statement There are none.
Acknowledgements This research was funded by a Grant-in-Aid for Scientific Research (No. 18590563 and No. 21590657) from the Japanese Society for the Promotion of Science. This study sponsor has had no involvement in this work.
References 1. Barone P. Treatment of depressive symptoms in Parkinson’s disease. Eur J Neurol 2011;18(Suppl. 1):11e5. 2. Dissanayaka NNW, Sellbach A, Silburn PA, O’Sullivan JD, Marsh R, Mellick GD. Factors associated with depression in Parkinson’s disease. J Affect Disord 2011;132:82e8. 3. Jasinska-Myga B, Putzke JD, Wider C, Wszolek ZK, Uitti RJ. Depression in Parkinson’s disease. Can J Neurol Sci 2010;37:61e6. 4. Murakami K, Miyake Y, Sasaki S, Tanaka K, Arakawa M. Fish and n-3 polyunsaturated fatty acid intake and depressive symptoms: Ryukyus Child Health Study. Pediatrics 2010;126:e623e30. 5. Murakami K, Mizoue T, Sasaki S, Ohta M, Sato M, Matsushita Y, et al. Dietary intake of folate, other B vitamins, and omega-3 polyunsaturated fatty acids in relation to depressive symptoms in Japanese adults. Nutrition 2008;24:140e7. 6. Ruusunen A, Virtanen JK, Lehto SM, Tolmunen T, Kauhanen J, Voutilainen S. Serum polyunsaturated fatty acids are not associated with the risk of severe depression in middle-aged Finnish men: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Eur J Nutr 2011;50:89e96. 7. Sánchez-Villegas A, Verberne L, de Irala J, Ruíz-Canela M, Toledo E, SerraMajem L, et al. Dietary fat intake and the risk of depression: The SUN project. PLoS ONE 2011;6(1). Article number e16268. 8. Mamplekou E, Bountziouka V, Psaltopoulou T, Zeimbekis A, Tsakoundakis N, Papaerakleous N, et al. Urban environment, physical inactivity and unhealthy dietary habits correlate to depression among elderly living in eastern Mediterranean islands: The MEDIS (Mediterranean Islands Elderly) study. J Nutr Health Aging 2010;14:449e55. 9. Jacka FN, Pasco JA, Mykletun A, Williams LJ, Hodge AM, O’Reilly SL, et al. Association of Western and traditional diets with depression and anxiety in women. Am J Psychiatry 2010;167:305e11. 10. Fukushima T, Tan X, Luo Y, Kanda H. Relationship between blood levels of heavy metals and Parkinson’s disease in China. Neuroepidemiology 2010;34:18e24. 11. Daniel SE, Lees AJ. Parkinson’s disease society brain bank, London: overview and research. J Neural Transm Suppl 1993;39:165e72. 12. American Psychiatric Association. In: Diagnostic and statistical manual of mental disorders: DSM-IV. 4th ed. Washington DC: American Psychiatric Association; 1994. 13. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psych 1960;23:56e62. 14. Leentjens AF, Verhey FR, Lousberg R, Spitsbergen H, Wilmink FW. The validity of the Hamilton and Montgomery-Asberg depression rating scales as screening and diagnostic tools for depression in Parkinson’s disease. Int J Geriatr Psychiatry 2000;15:644e9. 15. Qu F, Yang X. Nutritional and health survey for Chinese citizen in 2002. Beijing: People’s Health Press; 2006. 16. Dissanayaka NN, Sellbach A, Matheson S, O’Sullivan JD, Silburn PA, Byrne GJ, et al. Anxiety disorders in Parkinson’s disease: prevalence and risk factors. Mov Disord 2010;25:838e45. 17. Ramakrishnan U. Fatty acid status and maternal mental health. Matern Child Nutr 2011;7(Suppl. 2):99e111. 18. Tajalizadekhoob Y, Sharifi F, Fakhrzadeh H, Mirarefin M, Ghaderpanahi M, Badamchizade Z, et al. The effect of low-dose omega 3 fatty acids on the treatment of mild to moderate depression in the elderly: a double-blind, randomized, placebo-controlled study. Eur Arch Psychiatry Clin Neurosci 2011:1e11. 19. Kummer A, Harsányi E, Dias FM, Cardoso F, Caramelli P, Teixeira AL. Depression impairs executive functioning in Parkinson disease patients with low educational level. Cogn Behav Neurol 2009;22:167e72. 20. Lemke MR. Depressive symptoms in Parkinson’s disease. Eur J Neurol 2008;15(Suppl. 1):21e5. 21. Bower JH, Grossardt BR, Maraganore DM, Ahlskog JE, Colligan RC, Geda YE, et al. Anxious personality predicts an increased risk of parkinson’s disease. Mov Disord 2010;25:2105e13. 22. Sanyal J, Chakraborty DP, Sarkar B, Banerjee TK, Mukherjee SC, Ray BC, et al. Environmental and familial risk factors of Parkinsons disease: caseecontrol study. Can J Neurol Sci 2010;37:637e42.