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Nutrient intakes are correlated with overall psychiatric functioning in adults with mood disorders Davison, Karen M.; Kaplan, Bonnie J. Feb 29, 2012

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CanJPsychiatry 2012;57(2):85-92 Original Research Nutrient Intakes Are Correlated With Overall Psychiatric Functioning in Adults With Mood Disorders Karen M Davison, PhD, RD\ Bonnie J Kaplan, ' Intersections of Mental Health Perspectives in Addictions Research Training (IMPART) Postdoctoral Research Fellow, British Columbia Centre for Excellence in Women's Health, Vancouver, British Columbia. ^ Professor, Faculty of Medicine, University of Calgary, Calgary, Alberta. Correspondence: Department of Paediatrics, Behavioural Research Unit, Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8; Kaplan@ucalgary.ca. Key Words: vitamins, minerals, nutrients, diet, mood disorders. Dietary Reference Intakes Received April 2011, revised, and accepted July 2011. Objective: To evaluate the relation betv\/een nutrient intake and psychiatric functioning in adults with confirmed mood disorders. Method: A cross-sectional study was conducted of the intake of major (that is, carbohydrates, fat, and protein) and minor (that is, vitamins and minerals) nutrients (from 3-day food records and a Food Frequency Questionnaire), Global Assessment of Functioning (GAF) scores, and symptoms of depression and mania (the Hamilton Depression Rating Scale and the Young Mania Rating Scale) in 97 community-based adults with mood disorders whose diagnoses were confirmed with structured interviews. Results: Significant correlations were found between GAF scores and energy (kilocalories), carbohydrates, fibre, total fat, linoleic acid, riboflavin, niacin, folate, vitamin Bg, vitamin B,^ , pantothenic acid, calcium, phosphorus, potassium, and iron (all P values < 0.05), as well as magnesium (r = 0.41, P < 0.001 ) and zinc (r = 0.35, P < 0.001 ). Though modest in magnitude, the pattern of correlations was consistent, indicating higher levels of mental function associated with a higher intake of nutrients. Depression and mania scores, which were generally mild or moderate, did not individually show consistent patterns. When dietary supplement use was added to nutrient intakes from food, GAF scores remained positively correlated (P < 0,05) with all dietary minerals. Conclusion: This detailed analysis in a clinically diagnosed sample was consistent with prior epidemiologic surveys, revealing an association between higher levels of nutrient intakes and better mental health. Nutrient intakes warrant further consideration in the treatment of people with mood disorders. Objectif : Évaluer la relation entre la prise de nutriments et le fonctionnement psychiatrique chez les adultes ayant des troubles de l'humeur confirmés. Méthode : Une étude transversale a été menée sur la prise de nutriments majeurs (c'est-à-dire, glucides, gras, et protéines) et mineurs (c'est-à-dire, vitamines et minéraux) (tirés d'enregistrements alimentaires de 3 jours et du questionnaire de fréquence alimentaire), les scores à l'évaluation globale de fonctionnement (EGF) et les symptômes de dépression et de manie (l'échelle de dépression de Hamilton et l'échelle de manie de Young) chez 97 adultes résidant dans la communauté et souffrant de troubles de l'humeur dont les diagnostics ont été confirmés par des entrevues structurées. Résultats : Des corrélations significatives ont été observées entre les scores à l'EGF et l'énergie (kilocalories), les glucides, les fibres, la matière grasse totale, l'acide linoléique, la riboflavine, la niacine, l'acide folique, la vitamine B6, la vitamine B12, l'acide pantothénique, le calcium, le phosphore, le potassium, et le fer (toutes valeurs de P < 0,05), ainsi que le magnésium (r = 0,41, P < 0,001 ) et le zinc (r = 0,35, P < 0,001 ). Bien que modeste en magnitude, le modèle des corrélations était cohérent, indiquant des niveaux plus élevés de fonction mentale associés à une prise plus élevée de nutriments. Les scores de dépression et de manie, qui étaient généralement bénins ou modérés, ne révélaient pas individuellement de modèles cohérents. Quand l'utilisation de suppléments alimentaires s'ajoutait à la prise de nutriments à partir d'aliments, les scores à l'EFG demeuraient positivement córreles (P < 0,05) avec tous les minéraux alimentaires. www.TheCJP.ca TheCanadian Journalof Psychiatry, Vol 57, No2, February 2012 • 85Original Research Conclusion : Cette analyse détaillée d'un échantillon cliniquement diagnostiqué était conforme à des enquêtes épidémiologiques antérieures, révélant une association entre des niveaux élevés de prises de nutriments et une meilleure santé mentale. La prise de nutriments devrait être prise en considération dans le traitement de personnes souffrant de troubles de l'humeur. Recent epidemiologic investigations have reportedinteresting and consistent associations between dietary patterns and the symptoms of anxiety and depression.'"^ A prospective longitudinal study of 10 094 adults in Spain categorized participants in terms of their adherence to a Mediterranean diet on the basis of a semi-quantitative FFQ.' After several years (median 4.4), 480 participants reported new diagnoses of depression; overall, decreasing levels of adherence to a Mediterranean diet were associated with increased likelihood of receiving such a diagnosis. Similarly, a UK study^ used an FFQ administered to 3486 adults to categorize their dietary patterns as being primarily whole foods, compared with processed foods. In this UK study, rather than self-reported physician diagnosis of depression, mood disorder was evaluated with the 20-item CES-D. The findings supported a protective effect of a relatively healthier diet, in that people with the highest intake of whole foods were the least likely to report high depression scores on the CES-D. In a third such study,' dietary patterns were categorized in 1046 Australian women, whose current major depressive disorder, dysthymia, and anxiety disorders were established with structured interviews. An FFQ was used to categorize dietary patterns as being traditional. Western, or modem. The results were consistent with the previous 2 studies: increasing quality of diet was associated with decreasing symptom severity on a general health checklist. The researchers also found that the traditional dietary pattern appeared to have a protective effect as it was associated with a reduced likelihood of any of the categorical diagnoses. As all 3 of these reports discussed, there is much scientific data on possible mechanisms to explain the way in which relatively healthier diets might exert protective effects on mental health. There is evidence of an anti-inflammatory effect of a Mediterranean diet*; similarly, greater antioxidant Abbreviations CES-D Center for Epidemiologic Studies Depression Scale CNF Canadian Nutrient File FFQ Food Frequency Questionnaire GAF Global Assessment of Functioning HDRS Hamilton Depression Rating Scale MDABC Mood Disorders Association of British Columbia SCID Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition SE standard error YMRS Young Mania Rating Scale Clinical Implications • Some portion of mental dysfunction in patients with mood disorders may be influenced by their nutrient intake. • Clinicians may find it useful to learn about their patients' eating habits and to consider nutritional counselling at times. • These findings combined with others suggest that lower doses of medications may be sufficient in patients who are better nourished. Limitations • Results are based on people with mild or moderate illness, as those with severe symptoms rarely volunteer for research. • Direction of causality cannot be inferred from a cross- sectional study, and may be bidirectional. • The data do not permit drawing any conclusions about specific symptoms of depression or mania, only overall functioning. intake, such as from any diet high in fruits and vegetables, would be protective.' In addition, higher intake of folate and other B vitamins could influence the synthesis of methionine and the metabolism of homocysteine, all of which could contribute to neurotransmitters such as serotonin. Although not yet reported, the logical follow-up to these epidemiologic surveys of dietary patterns is to examine the question of whether there is, in fact, a relation between nutrient consumption and mental health function in people with diagnosed mental health problems. Such an investigation could be more targeted than large population surveys, by carrying out detailed nutrient analyses rather than characterizing general patterns. Our study was developed to fill that important gap by answering the question. Is there a relation between nutrient consumption and mental function in people with diagnosed mood disorders? Nutrients from food and supplement sources were evaluated in adults whose mood disorders were diagnosed first by their physicians and then with a SCID-I/NP (for DSM-IV-TR) Non-patient Edition. Method Sample Adults (aged 18 years and older) were recruited through the MDABC, a nonprofit network that provides support for people with a mood disorder. A letter was mailed to 146 (73 in the summer and 73 in the fall and winter) randomly 86 La Revue canadienne de psychiatrie, vol 57, no 2, février 2012 mfti.LaRCP.caNutrient Intakes Are Correlated With Overall Psychiatric Functioning in Adults With Mood Disorders selected MDABC members, inviting them to participate in a study of food habits. The study staff provided follow-up to the letter by calling recipients, inviting them to participate, and verifying that they had been diagnosed with a mood disorder by a physician. If the person declined participation, an interviewer attempted to complete a nonresponse questionnaire that helped determine if they differed systematically from participants in terms of lifestyle habits. The study was approved by the University of Calgary's Conjoint Health Research Ethics Board. Study Protocol When a person agreed to participate, the research coordinator explained the study and trained the respondent to complete a food record (reporting 2 weekdays and 1 weekend day that were nonconsecutive). When participants came to their appointment at the MDABC office, they first read and signed the consent form. A trained clinical interviewer then administered the SCID-I/NP Axis I Disorders, to confirm the diagnosis of a mood disorder*"; the GAF,' which measured social, occupational, and psychological functioning (scale of 0 to 100); the HDRS**; and the YMRS.' Exclusion criteria, based primarily on the SCID-I/NP diagnosis, were schizophrenia, and other disorders associated with psychotic symptoms, namely, dementia, thyroid dysfunction, or degenerative disorders. If participants were eligible for the study based on the psychiatric measures, they were interviewed by a trained registered dietitian who reviewed their 3-day food record using standard procedures,'" including using food models and household measures to ensure the record was complete and as accurate as possible; administered a semi-quantitative FFQ that focused on fat intake and some foods that are eaten less often or seasonally; and administered a short questionnaire on selected nutrition, health-related, and demographic variables. Information on the type, amount, and frequency (for example, yesterday or monthly) of nutritional supplements was also collected as part of the FFQ. A research assistant (undergraduate nutrition student), trained by the research coordinator, used the nutrient analysis software program by ESHA," which contains the CNF,'^ to record the data from the food records. The CNF is a food composition database containing average values for up to 115 nutrients in 4668 basic foods available in Canada. Input of food record data began with the entry of a key name for a food, followed by the selection of the exact or best match from the options displayed. Existing computerized recipes were used for mixed dishes, with ingredient substitutions or the addition of new recipes entered as required. Amounts consumed were entered in weights or volumes. Quality Control and Data Analysis The interviewer reviewed the forms twice, once at the conclusion of the interview with the participant present and then again within 24 hours. The research coordinator then checked the original forms. All the data were double- entered to ensure accuracy, and automated validations were built in to verify data quality. The nutrient analysis program The Food Processor SQL'-^  was used to record the data from the food records. Nutrient supplement data were entered by name, dose, and nutrient content. Standard conversions for nutrient measures were applied. The research coordinator manually compared the data input for each record with the original forms. The distributions of usual nutrient intakes from food sources of major (that is, carbohydrates, fat, and protein) and minor (that is, folate, niacin, pantothenic acid, ribofiavin, thiamin, vitamin B ,^ vitamin Bj^, vitamin C, calcium, iron, magnesium, phosphorous, zinc, potassium, and sodium) nutrients were determined by averaging the nutrient intakes of the 3-day food records. To determine nutrient intake from food plus supplements, the monthly nutritional supplement use recorded for each participant was expressed as a daily amount and was added to the usual intake obtained from food sources alone. Variables were examined to determine whether they satisfied the assumptions of normality. When skewness occurred, variables were transformed (for example, square root or a log transformation) to attain normality, and analyses were conducted using the transformed variable. Nutrient intakes were assessed according to age, sex, education level, income level, and marital status by an ANOVA or Kruskal-Wallis tests. Before analyzing the effects of these factors, income levels were classified as low income or not low income based on Statistics Canada low-income measures by family type.'-' Education levels were collapsed into 3 groups: high school or less, trade school or some university, and completion of university. Marital status was reclassified into 2 groups: not married (that is, single, widowed, separated, divorced, and never married) and married (that is, married or living common- law). For the analyses, the unadjusted nutrient intakes were initially transformed logarithmically, and the possible effects of education, income, and marital status were then examined using a general linear model procedure. The dependent variable was the nutrient of interest; sex, age, education, and income were entered as fixed effects. Unadjusted energy (kilocalories) intake was entered as a covariate in each model. Both the main effects and the 2-way interactions of these variables were determined. When significant main effects were observed, post hoc analysis, using Bonferroni correction, determined which groups differed significantly from one another. Scores on the GAF, HDRS, and YMRS measurement tools were reported as mean values (standard deviation) or as the median with 25th and 75th percentile, depending on the distribution. The proportion of people experiencing (or not experiencing) manic or depressive symptoms was also reported using standard cut-offs of the respective psychiatric measurement tools. To assess relations between the psychiatric measures and nutrient intakes. Spearman rank correlations were employed because the variables (that is, nutrients) tended wmi.TheCJP.ca The Canadian Journal of Psychiatry, Vol 57, No 2, February 2012 ^ 87Original Research Table 1 Description Variable Diagnosis Bipolar 1 or II Depressive disorder GAF scores GAF, mean (SD) Symptom rating scales Scale (cut-off) YMRS (220 indicates manic episode) HDRS (al7 Indicates depressed phase) of sample by diagnosis, Total (% of total sample) 58 (59,8) 39 (40,2) 62,7(14,7) Total Median = 3 (25th percentile = 1 ; 75th percentile = 5) Range = 1 to 26 Median = 9,6 (25th percentile = 1 ; 75th percentile = 31 ) Range = 1 to 31 GAF, YMRS, and HDRS Males (% of subgroup total) 19(32,8) 11 (28,2) 65,1 (2,9) Males Median = 2 (25th percentile = 1 ; 75th percentile = 4) Range = 1 to 16 Mean = 7,2 (25th percentile = 1 ; 75th percentile = 28) Range = 1 to 28 scores (n = 97) Females (% of subgroup total) 39 (67,2) 28(71,8) 61,1 (1,8) Females Median = 3 (25th percentile = 1 ; 75th percentile = 5) Range = 1 to 26 Mean = 9,8 (25th percentile = 1 ; 75th percentile = 31) Range = 1 to 31 n > cut off 2 Females = 2 14 Females = 9, males = 5 Table 2 Nutrient intakes from food and food plus supplement sources Nutrient Median intakes - food only (25th; 75th percentile) Median intakes - food plus supplements (25th; 75th percentile) 2,3 (1,2; 4,7) 2,8(1,4; 11,4) 27 (14; 45) 6,0 (3,3; 54) 2,9 (1,4; 7,1) Folate 365 (202; 641); Folie acid"= 395 (113; 740) 6,7 (2,6; 27,4) 184 (78; 596) 1212(885; 1627) 370(201; 512) 1189 (863; 1649) 21 (13; 35) 10,6 (6,7; 18,5) Number taking supplements n (% of total sample) 34 (35) 34 (35) 36 (37) 35 (36) 36 (37) 41 (42) 35 (36) 37 (38) 43 (44) 38 (39) 31 (32) 33 (34) 32 (33) Vitamin B, (thiamin), mg Vitamin B^  (riboflavin), mg Vitamin Bj (niacin), NE/d" Vitamin B^  (pantothenic acid), mg Vitamin B^  (pyridoxine), mg Vitamin Bg (folate), DFE" Vitamin B,^  (cobalamin), meg Vitamin C, mg Calcium, mg Magnesium, mg Phosphorous, mg Potassium, mg Sodium, mg Iron, mg Zinc, mg 1.3 (1,0; 2,0) 1,5 (1,1; 2,2) 26 (20; 34) 3,8 (2,6; 5,5) 1,5 (1,1; 2,1) 266 (194; 402) 3.4 (1,9; 3,8) 110 (63; 190) 938(652; 1231) 282 (198; 383) 1083 (836; 1492) 4507 (4235; 5146) 5143 (3907; 6605) 16(11; 22) 8,9(6,1; 12,6) " NE/d = Niacin equivalents (the amount of niacin present in food, including the niacin that can theoretically be made from its precursor, tryptophan, present in the food). To make 1 mg of niacin are required about 60 mg of dietary tryptophan, " DFE = Dietary folate equivalents (values that adjust for the differences in absorption of food folate and synthetic folie acid), 1 meg of DFE = 0,6 meg of folie acid from fortified food or as a supplement taken with a meal = 1 meg food folate = 0,5 meg of folie acid from a supplement taken on an empty stomach, " Folie acid represents the synthetic form of the vitamin (fortified foods and supplements), — = no partieipants reported supplemental sourees of that nutrient 88 LaRevuecanadiennedepsychiatrie, vol 57, no 2, février 2012 wmi.LaRCP.caNutrient Intakes Are Correlated With Overall Psychiatric Functioning in Adults With Mood Disorders Table 3 Correlations for food scores and mood synnptoms Nutrient Energy Protein Carbohydrates Fibre Total fat Linoleic acid alpha-linolenic acid Vitamins Vitamin B, (thiamin) Vitamin B^  (riboflavin) Vitamin B^  (niacin) Vitamin B^  (pantothenic acid) Vitamin B^  (pyridoxine) Vitamin Bg (folate) Vitamin B,^  (cobalamin) Vitamin C Minerals Major minerals Calcium Magnesium Phosphorus Potassium Sodium Trace minerals Iron Zinc = P < 0.05; " P < 0.001 and supplement sources of Food 0.21" 0.19 0.21" 0.26" 0.21" 0.24" 0.16 0.18 0.30" 0.25" 0.28= 0.23" 0.22" 0.22= 0.12 0.25" 0.41" 0.30" 0.26= 0.01 0.31 = 0.35" GAF Food + Supplements — — — — — • — — 0.09 0.17 0.10 0.14 0.11 0.13 0.06 0.19 0.28" 0.24" 0.30= 0.21" -0.03 0.30" 0.22" — = no participants reported supplemental sources of that nutrient macro- and micronutrients Food 0.01 0.04 -0.10 -0.19 0.02 0.08 0.07 -0.05 -0.04 -0.03 0.06 -0.05 -0.08 -0.00 -0.03 -0.06 -0.03 0.09 -0.02 0.16 -0.11 0.07 Scores HDRS Food + Supplements — — — — — — — -0.01 -0.10 -0.07 -0.06 -0.08 -0.05 -0.03 -0.04 -0.07 0.05 -0.04 0.08 0.16 -0.22" 0.13 compared > Food -0.11 -0.01 -0.18 -0.10 -0.03 0.08 0.08 0.03 -0.02 -0.04 -0.09 -0.09 -0.10 0.13 0.25= -0.00 -0.13 -0.07 -0.19 -0.10 -0.09 0.06 with GAF /MRS Food + Supplements — — — — — — — 0.12 -0.10 -0.16 -0.11 -0.12 -0.06 -0.06 -0.05 -0.04 -0.06 -0.01 -0.15 -0.10 -0.14 -0.25= to be non-Gaussian. Three multiple regression models were used to assess nutrition-related factors that predict mood disorder symptoms and functioning. One model assessed dietary predictors (actual nutrient intakes, and sociodemographic and health-related variables) and GAF scores as the dependent variable. Another assessed the same independent variables but the dependent variable was HDRS scores. The final model used YMRS scores as the dependent variable. In these multivariate analyses, the effect of each variable on the psychiatric measures was examined by the appropriate regression coefficient, interpreted, for example, as a change in the depression score for one unit increase in the independent variable (for example, magnesium intake). Significance of the estimates was tested by individual / tests. The adjusted R^ (modification of R^ that adjusts for the number of explanatory terms in a model and calculated as [1 - R^] [n - c]/[n - k]), an estimate of the proportion of the dependent variable (for example, HDRS scores) that is explained by the regression model, was also examined. To assess the plausibility of the multiple linear regression assumptions and overall model fit, various diagnostics were assessed, including plots of the residuals, compared with dependent variable, and measures to examine influential data points. The data were analyzed by the statistical software program Stata, version 7.0.''' Results The overall response rate was 75%. Among the people who declined participation, 44% (11/25) answered the nonresponse questions. Statistical comparisons showed no differences between the respondents and nonrespondents vmN.TheCJP.ca The Canadian Journal of Psychiatry, Vol 57, No 2, February 2012 + 89Original Research based on lifestyle variables (for example, smoking or multivitamin use). The final sample of 97 was more than one-half female (« = 69; 71.1 %), had less than a university degree {n = 76; 78.4%), had low incomes (48.5%), and tended to have excess body weight (« = 65; 67% classified as overweight or obese). On the SCID-I/NP, 58 (59.8%) met criteria for bipolar disorder and 39 (40.2%) for depressive disorder (Table 1). Participants had been diagnosed 1 to 37 years previously (median 9.5 years; 25th percentile = 5; 75th percentile = 19). On the GAF, most people were only mildly or moderately impaired (mean 62.7, SD 14.7). The HDRS scores indicated that 14 people (14.4%) were severely depressed at the time of participation, 14 (14.4%) were experiencing moderate depressive symptoms, 44 (45.4%) were mildly depressed, and the remainder were asymptomatic. Based on YMRS scores, 2.6% (all females) were experiencing symptoms of mania. Over 85% of the participants were taking psychiatric medications, primarily antidepressants (72.9%) and mood stabilizers (52.9%), and about 25% combined medications with herbal remedies. Forty-nine participants (50%) were taking at least one vitamin or mineral supplement, which increased selected nutrient intakes appreciably as shown in Table 2. The effects of education, income, and marital status on nutrient intakes were examined. For education level, significant differences were found only for pantothenic acid intakes (F = 5.54, df= 3,93, P < 0.05). As income levels increased, significantly higher intakes emerged for protein {F = 4.40, df= 3,93, P < 0.05), fibre (F = 3.07, df= 3,93, P < 0.05), vitamin B, (F = 6.41, df= 3,93, P < 0.001), vitamin B^ {F = 5.01, df = 3,93, P < 0.05), vitamin B^ (F = 3.02, df= 3,93, P < 0.05), iron (F = 4.36, df= 3,93, P < 0.05), sodium (F = 4.30, df'= 3,93, P < 0.05), and zinc (F= 3.01, df= 3,93, P < 0.05). For marital status, intakes of the following were significantly lower for those who were considered single (that is, widowed, divorced, separated, or never married): energy (/ = 2.19, df= 95, SE = 195.03, mean difference = -434.39, 95% CI = -815.01 to -40.63, P < 0.05), fibre (t = 2.40, df = 95, SE = 2.87, mean difference = -6.85, 95% Cl = -12.60 to -1.19, P < 0.05), magnesium (/ = 2.58, df= 95, SE = 29.67, mean difference = -79.75,95% CI,= -135.29to-17.51,/'<0.05), phosphorous (t = 2.51, df= 95, SE = 96.83, mean difference = -246.93, 95% CI = -435.51 to -51.04, P < 0.05), and potassium (t = 2.37, df= 95, SE = 255.51, mean difference = -619.32, 95% CI = -1112.03 to -97.54, P < 0.05). Nutrients From Food and Food Plus Supplement Sources (Table 3) Positive, weak correlations (P < 0.05) were found for GAF scores and energy (r = 0.21), carbohydrates (r = 0.21), fibre (r = 0.26), total fat (r = 0.21), and linoleic acid (r = 0.21). HDRS and YMRS scores were not significantly correlated with any of the macronutrients. GAF scores were significantly correlated (P < 0.05) with vitamins B^ (r = 0.30), B3 (r = 0.25), B^ (r = 0.28), B^ (r = 0.23), B,(r = 0.22), and B^^ (r = 0.22). In all cases, higher GAF scores were associated with higher levels of nutrient intake. YMRS scores were weakly and negatively correlated with vitamin C (r = -0.25). Analysis of minerals from food sources showed significant correlations at the 0.05 level between GAF scores and calcium (r = 0.25), phosphorus (r = 0.30), potassium (r = 0.26), and iron (r = 0.31). Two minerals were more strongly correlated with GAF scores: magnesium (r = 0.41, P < 0.001) and zinc (r = 0.35, P < 0.001). When nutrients from food intake were combined with nutrients from supplements, GAF scores were positively correlated (P < 0.05) with 6 of the 7 minerals: calcium (r = 0.28), magnesium (r = 0.24), phosphorus (r = 0.30), potassium (r = 0.21), iron (r = 0.30), and zinc (r = 0.22). HDRS scores correlated with only one nutrient, iron (r = -0.22, P < 0.05), and indicated higher levels of iron associated with fewer symptoms of depression. YMRS scores did not correlate with any vitamin or mineral except zinc, with which it was negatively correlated (r = -0.25, P < 0.05): higher levels of zinc were associated with fewer symptoms of mania. Prediction Models of Psychiatric Symptoms and Functioning Models to predict mood symptoms were analyzed. An example of one model that was analyzed for GAF scores is outlined as follows: GAF scores = Sex (male or female) + Age (years) + Income (<$20 000 or >$20 000) + Energy (kilocalories) + Psychiatric medication (yes or no) + Age X Energy + Sex X Energy Separate models were analyzed as above (for example, with HDRS scores as the dependent variable and the independent variables as indicated) for each nutrient (first nutrients from food sources then models that used nutrients from food plus supplement sources) that was examined in the bivariate analyses. For GAF scores, the only significant predictor was total fat (regression coefficient = 0.39, SE = 0.19, ? = 2.07, df= 90, P = 0.04, 95% CI 0.01 to 0.77). All regression estimates for the models predicting HDRS and YMRS scores were nonsignificant. Conclusions This investigation examined relations between nutrients from food, and food plus supplement sources, with psychiatric symptoms and overall mental functioning in adults with diagnosed mood disorders. Measures of association between nutrient intakes from food and psychiatric functioning showed many weak significant positive correlations, indicating better psychological function associated with higher dietary nutrient intake. When supplement sources were added to food, significant negative correlations were found between mania and zinc as 90 • La Revue canadienne de psychiatrie, vol 57, no 2, février 2012 www.LaRCP.caNutrient lntal<es Are Correlated With Overall Psychiatric Functioning in Adults With Mood Disorders well as depression and iron, both of which were consistent with better mental health being associated with higher dietary nutrient intake. Higher levels of psychological fiinctioning were associated with greater intake of dietary minerals (calcium, magnesium, phosphorus, potassium, iron, and zinc) derived from food plus supplements. The relations between psychiatric measures and nutrient intakes weakened when linear regression analysis was conducted, most likely beeause of the limited sample-to-variable ratio. Regression analyses were signifieant only for total fat intake from food and GAF scores. Perhaps the most notable finding of the study was that all relations that emerged were in the predicted direction: better mental health was consistently associated with higher levels of nutrient intake. The minimal relations between the individual measures of depressive and manic symptoms (HDRS and YMRS) and nutrient intakes may be due to few participants having severe symptoms. This type of self- selection bias among people with mood disorders is not surprising, as volunteering for research is more likely to occur in those who feel well enough to commit to this effort. In contrast, the overall measure of mental health (GAF scores) was correlated consistently with both macronutrients (total fat, carbohydrate, and linoleic acid) and micronutrients (6 vitamins and 6 minerals), indicating better psychological fiinction associated with higher levels of overall nutrient intake from food. These relations were less clear for vitamin intakes when supplements were added. However, when considering food combined with supplement intakes of minerals, significant negative correlations were found between YMRS scores and zinc as well as HDRS scores and iron; positive correlations with GAF scores were found for calcium, magnesium, phosphorus, potassium, iron, and zine. These results suggest that mineral intakes were more closely associated with psychiatric symptoms and functioning than were vitamins. There were several notable limitations of our study. First, the findings from the food intake data were subject to a type of recall bias commonly associated with the process of recording foods, which afl^ ects the way people eat. The lower proportion of males in the sample (about one-third) may limit the generalizability of findings. Because this is a cross- sectional study, one cannot determine the temporal sequence of psychiatric fianctioning and symptoms and nutrient intake. Also, because of the limitations of existing computerized nutrient analysis systems, this investigation could examine only specific nutrients. Finally, the sample size prevented subgroup analyses, such as the effects of individual psychiatric medications in relation to nutrient intakes. One of the strengths of our study includes its use of a reasonably sized sample of people with confirmed mood disorders within a community setting, extensively characterized for sociodemographic variables as well as nutrient intake and psychiatric function. Other key strengths of our study are that it analyzed nutrients from food alone as well as food plus supplements separately in relation to psychiatric symptoms and functioning. The results of our research suggest that supplemental mineral intakes may have affected psychiatric symptoms and functioning by correcting potential deficiencies. In another of our studies,'' which compared nutrient intakes of this sample with the Estimated Average Requirements (nutrient intake value that is estimated to meet the requirements of one-half of the healthy people in a group) of the Dietary Reference Intakes, it was found that a substantial percentage of the sample had inadequate intakes of calcium, magnesium, potassium, iron, phosphorus, and zinc from food sources. In addition, it has also been theorized that coenzyme systems in people with mood disorders require higher levels of selected minerals to function optimally."^ An alternative model for explaining underlying nutrient-related mechanisms and mental function involves energy metabolism. For example, it has been proposed that some mood symptoms represent a mitochondrial disease associated with decreased mitochondrial energy metabolism."~" Treatment benefits from micronutrients would be consistent with this framework as they improve adenosine triphosphate activity. Finally, a recent review^" suggested that a solid foundation for oxidative stress hypotheses in mood disorders and depression has been provided by biochemical, genetic, pharmacological, preclinical therapeutic studies, and one clinical trial. These data suggest that oxidative mechanisms may form unifying pathogenic pathways in psychiatric disorders and may introduce new targets for the development of therapeutic interventions.^" This interpretation would lend support to theories indicating that coenzyme systems in people with mood disorders require higher levels of selected minerals to fiinction optimally.'* Ingesting multiple nutrients simultaneously, as in food sources, may optimize brain health, and may also provide some rationale for the use of multi-nutrient formulas (particularly those with dietary minerals). Several studies of multi-ingredient formulas (for example, vitamins, minerals, fatty acids, and amino acids) indicate they have a greater impact than single-ingredient interventions both in people functioning normally^' and in those with mood and behavioural disturbances,^^" '^ as well as eiïectively augmenting pharmaceutical interventions.^"-^' Our study supports the growing awareness that nutrition is important for mental health, particularly overall functioning. The findings indicate that measures of nutrition-related outeomes in this population should include global indices of mental function, such as the GAF. It is evident that in the treatment of people with mood disorders, factors of importance include the assessment of food and nutrient intakes. Acknowledgements This publication is based on Dr Davison's doctoral work in the Department of Community Health Sciences, Faculty of Medicine, University of Calgary, Calgary, Alberta. \mm.TheCJP.ca TheCanadianJournalofPsychiatry, Vol 57, No 2, February 2012 * 91Original Research Financial support for this project was obtained from The Danone Research Institute, which played no role in carrying out the study, analyzing the results, or influencing publication. The authors thank their funding source. The Danone Research Institute. Dr Kaplan thanks the Alberta Children's Hospital Research Institute for ongoing support. They also acknowledge the assistance of the Mood Disorders Association of British Columbia (including Ed Rogers, Vicki Rogers, Julia Zohab, Johannes Presley, and Rennie Hoffman) for providing support staff, office space, and assistance with recruitment. References 1. Sanchez-Villegas A, Delgado-Rodriguez M, Alonso A, et al. Association of the Mediterranean dietary pattern with the incidence of depression. Arch Gen Psychiatry. 2009;66(t0):1090-l098. 2. Akbaraly TN, Brunner EJ, Ferrie JE, et al. Dietary pattern and depressive symptoms in middle age. Br J Psychiatry. 2009;195:408^l3. 3. Jacka FN, Pasco JA, Mykletun A, et al. Association of Western and traditional diets with depression and anxiety in women. Am J Psychiatry. 2010;167(3):305-31t. 4. Chrysohoou C, Panagiotakos DB, Pitsavos C, et al. Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: the ATTICA Study. J Am Coll Cardiol. 2004;44(l):152-158. 5. Berk M, Conus P, Kapczinski F, et al. From neuroprogression to neuroprotection: implications for clinical care. Med J Aust. 2010;193(4):S36-S40. 6. First MB, Spitzer RL, Gibbon M, et al. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, research edition. Non-patient edition (SCID-I/NP). New York (NY): Biometrics Research, New York State Psychiatric Institute; 2001. 7. Endicott J, Spitzer RL, Fleiss JL, et al. The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry. 1976;33(6):766-771. 8. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-^2. 9. Young RC, Biggs JT, Ziegler VE, et al, A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978; 133:429^35. 10. Melanson C. British Columbia Nutrition Survey—training and resource manual. Victoria (BC): BC Ministry of Health and Ministry Responsible for Seniors; 1999. 11. ESHA Research. The food processor SQL [software]. Salem (OR): ESHA Research; 2006. 12. Health Canada. Canadian nutrient file. Ottawa (ON): Health Canada; 1997. 13. Statistics Canada, Income Statistics Division. Income trends in Canada 1990-1999 before tax. Ottawa (ON): Statistics Canada; 2001. 75-F0002M-01007. 14. Stata Corporation. Stata statistics/data analysis, version 7.0. College Station (TX): Stata Corporation; 2002. 15. Davison KJVl, Kaplan BJ. Vitamin and mineral intakes in adults with mood disorders: comparisons to nutrition standards and associations with sociodemographic and clinical variables. J Am Coll Nutr. Forthcoming. 16. Kaplan BJ, Crawford SG, Field CJ, et al. Vitamins, minerals, and mood. Psychol Bull. 2007;133(5):747-760. 17. Gardner A, Boles RG. Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:730-743. 18. Bjelland I, Tell GS, Vollset SE, et al. Folate, vitamin BI2, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry. 2003;60:618-626. 19. Young LT. Is bipolar disorder a mitochondrial disease? J Psychiatry Neurosci. 2007;32:160-161. 20. Ng F, Berk M, Dean O, et al. Oxidative stress in psychiatric disorders: evidence base arid therapeutic implications. Int J Neuropsychopharmacol. 2008; 11:851-876. 21. Kennedy DO, Veasey R, Watson A, et al. EfTects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacology (Berl). 2010;2ll(l):55-68. 22. Geseh CB, Hammon SM, Hampson SE, et al. Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners. Br J Psychiatry. 2002;l 81:22-28. 23. Frazier EA, Fristad MA, Arnold LE. Multinutrient supplement as treatment: literature review and case report of a 12-year-old boy with bipolar disorder. J Child Adolesc Psychopharmacol. 2009;19(4):453^60. 24. Gately D, Kaplan BJ. Database analysis of adults with bipolar disorder consuming a micronutrient formula. Clin Med Insights Psychiatry. 2009;4:3-l6. 25. Rucklidge JJ, Gately D, Kaplan BJ. Database analysis of children and adolescents with bipolar disorder consuming a micronutrient formula. BMC Psychiatry. 2010; 10:74. 26. Mehl-Madrona L, Leung B, Kennedy C, et al. Mieronutrients versus standard medication management in autism: a naturalistic case-control study. J Child Adolesc Psychopharmacol. 2010;20(2):95-103. 27. Rucklidge J, Taylor M, Whitehead K. Effect of micronutrients on behavior and mood in adults with ADHD: evidence from an 8-week open label trial with natural extension. J Atten Disord. 2O1I;15(1):79-91. 28. Sarris J, Kavanagh DJ, Byrne G. Adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines. J Psychiatr Res. 2010;44(l):32^I. 29. Bell IR, Edman JS, Morrow FD, et al. Brief communication. Vitamin Bl, B2, and B6 augmentation of tricyclic antidcpressant treatment in geriatric depression with cognitive dysfunction. J Am Coll Nutr. 1992; 11 (2): 159-163. 92 ^ LaRevuecanadiennedepsychiatrie, vol 57, no 2, février 2012 www.LaRCP.caCopyright of Canadian Journal of Psychiatry is the property of Canadian Psychiatric Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.

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