Nutritional Status in Patients with Major Depressive Disorders: A Pilot Study in Tabriz, Iran

Abstract

Introduction: This study was conducted to assess the nutritional status in Iranian major depres¬sive disorder patients. We also determined the relationship between nutrients intake with depres¬sion severity.

Methods: Seventy major depressive patients were selected randomly from outpatient depressive subjects, referred to Razi Psychiatry Hospital in Tabriz, Iran in 2007. Dietary intakes were rec¬orded and compared with dietary reference intakes (DRIs). Definition of the disease and its se¬verity were according to DSM-IV-TR and Hamilton Depression Rating Scale, respectively. Nu¬tritionist III program, Chi-square, correlation and t-test were used for data analyses. Demo¬graphic, clinical and laboratory data were analyzed using SPSS software for windows (ver¬sion13.0).

Results: According to dietary analysis, 11.4% and 55% of patients had dietary protein and energy deficiency, respectively. 97.1% and 95.7% of patients had less folate and B12 intakes than recom¬mended dietary allowances. The mean (Mean ± SD) for plasma folate and B12 was 5.18±6.11 ng/ml and 389.05±346.9 pg/ml, respectively. Low plasma folate and B12 was observed in 51.4% and 50.0 % of patients, respectively. There was no significant relationship between blood folate and B12 levels with depression severity. Similarly, nutrients intake had no effect on depression se¬verity.

Conclusion: Low plasma concentrations and low dietary intakes of folate and B12 are common among Tabrizian depressive patients. It seems that nutritional intervention for increasing folate and vitamin B12 intake must be considered as health promotive and preventative program for patients suffering from depression disorders.

Introduction

Unipolar major depression is the fourth most important cause of premature mortality and disability [1]. Low dietary intake of folate and vitamin B₁₂ has been implicated as a risk factor for depression [2]. Folic acid and vitamin B₁₂ are important for normal functioning of the nervous system. One central biochemical reaction that unifies folate and vitamin B₁₂ metabolism is the methylation of homocysteine to methionine, catalyzed by methionine synthetase. Folate (5′-methyltetrahydrofolate) provides the methyl group for the conversion of methionine to S-adenosylmethionine, the major methyl donor for most methyltransferase reactions [3].

Studies on the association of folate deficiency with depression extend back to the mid 1960’s [3]. The initial studies were conducted on epileptic patients and showed that anticonvulsant therapy, which led to low serum folate levels, resulted in a higher incidence of mental symptoms including depression and psychosis [3]. The first study of the incidence of folate deficiency in psychiatric patients was described in 1967 by Carney [4],who showed high incidence of folate deficiency occurs in patients with depression (29–30%), organic psychosis (24%), and schizophrenia (20%). In several studies, plasma folate and vitamin B₁₂ levels in depressive patients have been assessed. Low folate and vitamin B₁₂ levels have been reported in some of them [5-17]. Approximately 10-30% of depressed patients may have low plasma folate levels, which may be higher than the general population, so it is postulated that there is relevance between depression and folate and vitamin B₁₂ [18]. Depressed patients have impaired one-carbon metabolism regulation [15,19,20].

In Iran, there are very limited studies on the assessment of nutritional status among patients suffering depression; so the present study was designed to assess the nutritional status, focusing on folate and vitamin B₁₂ deficiency; in patients with major depressive disorder. Moreover, the relationship between dietary folate, vitamin B₁₂ and other nutrients intake with plasma folate and vitamin B₁₂ levels and depression severity were determined.

Materials and Methods

Participants

This cross-sectional was performed among seventy outpatients (54 females and 16 males) referred to Razi Psychiatry Hospital in Tabriz, Iran in 2007. DSM-IV-TR diagnosis criteria for depression and Hamilton test were applied to distinguish depression by psychiatrist Score greater than 20 with Hamilton test were selected randomly.

The inclusion criteria were age of > 18 yr, and new episode of depression. A new episode was defined as the first depressive episode in a period of at least six months pervious to the study. Patients with severe physical or psychological illness such as history of mania, drug or alcohol misuse, use of psychotropic medication and vitamin supplementation for at least 8 weeks prior to the study, depression caused by physical illness or medication, megaloblastic anemia and pregnant or lactating women were excluded.

The study was approved by the Ethical Committee of Tabriz University of Medical Sciences, and also the informed consent was obtained from the patients or their attendants.

Procedures

Fasting blood samples were collected at 8.00 - 9.00 am. Blood samples were centrifuged at 1500 rpm and plasma was isolated and stored at −80 °C until analysis. Plasma folate and vitamin B₁₂ concentrations were measured using radio assay method [Simul-TRAC MP Biomedical USA kit]. Folate and vitamin B₁₂ deficiencies were considered as plasma folate and vitamin B₁₂ less than 3 ng/ml and 200 pg/ml, respectively [21,22]. Depression severity was assessed by the 17-item Hamilton Depression Rating Scale [23]. Dietary intake was assessed using three 24 hours-recalls in three different days (two consecutive no weekend and one weekend day). Dietary assessment was conducted by a nutritionist through face to face interview. Height was recorded to the nearest 0.1 cm with a stadiometer and weight was measured to the nearest 0.1 kg with a Seca scale.

Body mass index (BMI) was computed as weight (kg) divided by height (m²). According to the BMI, patients were divided to underweight (BMI≤18.5), normal weight (18.5<BMI<25), overweight (25≤BMI<30), and obese (30≤BMI) groups. According to the age, patients were divided to three groups 18-30, 30-50, and 50 -70 yr.

Measures

A structured clinical interview for DSM-IV-TR was used for diagnosis of the major depressive disorder. Its scoring was done by using from the 17-item Hamilton Rating Scale. The scale consists of 17 questions. Each question has between 3-5 possible responses. A score of 0-7 is considered to be normal, scores of 20 or higher indicate moderately severe depression [23]. Both of diagnosis and scaling of major depressive disorder were done by a psychiatrist with interview.

Statistical analysis

Dietary data were analyzed by Nutritionist III software. Demographic, clinical and laboratory data were analyzed using SPSS software for windows (version13.0). Chi-square and t-test were used to compare variables. For quantitative values, data were expressed as mean ± standard deviation (SD). Correlations were assessed by Pearson coefficient. Statistical significance was set at P<0.05.

Results

Of the 70 depressed patients (male: 16, female: 54); 10% (7) were illiterate, 25.7 % (18) had elementary education, 45.7% (32) had secondary or high school education, and 18.6 % (13) had higher high school educations. The mean and standard deviation for age, body mass index (BMI), and Hamilton Depression Rating Scale score in studied subjects are presented in Table 1. According to BMI, 1 patient (1.43%), 25 patients (35.71%), and 12 patients (17.14%) were underweight, overweight and obese, respectively.

Table 1. Mean and standard deviation of general characteristics in studied subjects.

	Women (n=54)	Men (n=16)	Total (n=70)
Variables	Mean (SD)	Mean (SD)	Mean (SD)
Age (yr)	35.04 (11.81)	33.56 (12.81)	34.70 (11.97)
Weight (kg)	67.84 (14.35)	73.53 (6.22)	69.14 (13.14)
Height (cm)	160.32 (5.92)*	174.41 (5.08)	163.54 (8.25)
Body Mass Index (kg/m2)	26.20 (4.80)	24.43 (2.83)	25.80 (4.48)
Hamilton depression rate	27.70 (4.51)	26.88 (6.18)	27.51 (4.91)

*. There was a significant difference between men and women’s height (P < 0.05).

Mean± SD for plasma folate and vitamin B₁₂ concentrations in different age and sex groups, are shown in Table 2.

Table 2. Mean and standard deviation of plasma folate and vitamin B₁₂ in studied subjects, in different age, and sex groups .

Variables	Folate (ng/ml)	Vitamin B12(pg/ml)
	Mean (SD)	Mean (SD)
Age (yr)	18-30 (n=29)	4.31(4.73)	384.65 (311.27)
	31-50 (n=33)	6.63 (7.38)	399.29 (401.29)
	51-70 (n=8)	3.56 (4.24)	362.84 (247.29)
Sex	Female (n=54)	5.36 (6.37)	420.43 (374.42)
	Male (n=16)	4.57 (5.33)	283.15 (206.69)

In different age and sex groups, no significant differences were observed for plasma folate and vitamin B₁₂ levels

Mean level of plasma folate and vitamin B₁₂ concentrations of patients suffering depression were 5.18 ± 6.11ng/ml and 389.05 ± 346.9 pg/ml, respectively. No significant differences were found in plasma folate and B₁₂ levels between different age and sex groups.

Prevalence of folate and B₁₂ deficiency in different age and sex groups are shown in Table 3. Totally, 36 patients (51.4%) had low plasma folate levels (≤ 3ng/ml). Low plasma vitamin B₁₂ (≤ 200 pg/ml) was seen in half of the studied subjects (35 patients). There was no significant difference between prevalence of folate or vitamin B₁₂ deficiency in different age and sex groups.

Table 3. Distribution of folate and vitamin B₁₂ status in patients with major depressive disorder, in different age, and sex groups .

Variable	Groups	Folate (ng/ml)		Vitamin B12(pg/ml)
	Deficient n (%)	Normal n (%)	Deficient n(%)	Normal n (%)
Age (yr)	18-30 (n=29)	17(58.6)	12(41.4)	14(48.3)	15(51.7)
	31-50 (n=33)	13(39.4)	20(60.6)	18(54.5)	15(45.5)
	51-70 (n=8)	6(75)	2(25)	3(37.5)	5(62.5)
Sex	Male (n=16)	11(68.8)	5(31.3)	8(50)	8(50)
	Female (n=54)	25(46.3)	29(53.7)	27(50)	27(50)

Plasma folate and B₁₂ deficiency were defined as: plasma folate and B₁₂ less than 3 ng/ml, and 200 pg/ml, respectively.

Results for dietary assessment are shown in Table 4. According to the RDA, deficiencies in folate and vitamin B₁₂ intakes were seen in more than 90% of patients. About 11.4% and 55% of studied subjects had low dietary protein and energy intakes, respectively. The main source of daily energy intake among depressed patients was carbohydrate (60.7%). The remaining was obtained from protein (13.1%) and fat (26.2%).

Table 4. Mean and standard deviation of dietary intakes and distribution of nutrients deficiency in patients with major depressive disorder.

Nutrient	Intake	Deficiency(< RDA)	Normal(≥ RDA)
	Mean(SD)	n (%)	n (%)
Carbohydrate (g)	318.6 (360.49)	-	-
Protein (g)	58.9 (22.84)	8 (11.4)	62 (88.6)
Fat (g)	55.86 (26.68)	-	-
Energy (kcal/day)	1808.5 (675.82)	38 (54.3)	32 (45.7)
B1 (mg/day)	1.56 (0.91)	12 (17.1)	58 (82.9)
B2 (mg/day)	13.20 (11.98)	25(35.7)	45 (64.3)
B3 (mg/day)	15.77 (7.68)	16(22.9)	54 (77.1)
B6 (mg/day)	1.48 (0.99)	23(32.9)	47 (67.1)
Folate (?g/day)	125.61± 182.16	65(92.9)	5 (7.1)
B12 (?g/day)	1.14 ± 0.87	64(91.4)	6 (8.6)

Assessed correlations between dietary macronutrients and micronutrients with plasma folate, B12 and Hamilton score are shown in Table 5. There was a negative but not significant relationship between plasma folate and vitamin B₁₂ with Hamilton Depression Rating Scale score (r=-0.22, r=-0.14, respectively). No association was found between dietary folate and B₁₂ with Hamilton Depression Rating Scale. A positive linear relationship was observed between plasma folate and its dietary intake (r = 0.24, P<0.05). Other nutrients (vitamins B₂ and B₆) did not have any significant relation with plasma folate or B₁₂.

Table 5. Correlation (Pearson's coefficient) between plasma folate and vitaminB₁₂ with dietary variables and Hamilton score in patients with major depressive disorder .

Dietary intake	Plasma Folate	Plasma Vitamin B12	Hamilton Depression Rate
Carbohydrate	0.152	-0.083	0.106
Protein	-0.043	-0.008	0.047
Fat	-0.149	0.000	0.109
Energy	-0.08	-0.063	0.089
Vitamin B2	0.054	0.096	- 0.031
vitamin B6	-0.057	0.005	0.102
Folate	0.238*	0.030	- 0.005
Vitamin B12	0.076	0.075	0.098
Plasma Folate	-	0.09	-0.22
Plasma Vitamin B12	0.05	-	-0.14

P < 0.05

Discussion

To the best of our knowledge, this survey was the first one for assessment of nutritional status in patients with major depressive disorder in Iran. Results of the study showed that 51.4% of patients with major depressive disorder had low plasma folate levels (≤ 3 ng/ml) and 50.0% of them had low plasma vitamin B₁₂ levels (≤ 200 pg/ml). In the present study, prevalence of hypofolatemia was higher than the other studies [10,13,16,24,25].

Fava et al. [10] showed that the prevalence of folate deficiency (defined as plasma folate less than 1.5 ng/ml) in depressive patients was low (2.0%), whereas borderline values (1.5–2.5 ng/ml) were more common (17.0%). Lee et al. in a study in China showed that no patient with major depressive disorder had low plasma folate [13]. In the mentioned study, four patients (3.4%) had low erythrocyte folate. Papakastas et al. [16] in a study on 52 patients with major depressive disorder reported that 26.9% and 10.9% of them had plasma folate and vitamin B₁₂ deficiency, respectively. In this study, low plasma folate and vitamin B₁₂, were considered as: ≤ 2.5 ng/ml and ≤ 200 pg/ml, respectively. In a study on 121 depressive patients only two patients (1.65%) had serum folate ≤ 3 ng/ml [17]. In our study low vitamin B₁₂ levels (≤ 200 pg/ml) were reported in 14 patients (11.57%). In another study [14] 26.3% and 29.9 % of psychiatric patients had serum cobalamin and folate less than 223 pg/ml and 3.1 ng/ml, respectively. Similarly, the prevalence of low plasma folate and vitamin B₁₂ has been reported less than our results [26,27].

In the present study, patients’ plasma folate was 5.18 ± 6.11 ng/ml which is lower than many other studies [12,13,15]. In the USA, mean serum folate in depressive patients has been reported as 10.4 ng/ml [15]. In Hong Kong mean serum folate in depressive patients has been shown 24.6 ± 10.0 ng/ml [13]. In a study on 30 depressive patients plasma folate was 6.4 ± 4.0 ng/ml [12].

It seems that low dietary intakes of folate and vitamin B₁₂ are the most common causes of low plasma levels. High daily intake of leafy green vegetables, in addition to soybean, green tea, meat and animal liver, all of which are rich sources of folate and vitamin B₁₂, can restore body folate and B₁₂ reservoirs [21,22]. Many authors suggested poor appetite and inappropriate food intake as symptoms of depression, which could result in low levels of folate and vitamin B₁₂ [25]. Depression may affect the quality and quantity of food in the diet and so decreases blood levels of nutrients [25]. In the present study, three days dietary intake of folate and vitamin B₁₂ were significantly lower than recommended dietary allowances (RDA) (P < 0.05). More than 90% of patients had deficiency in dietary folate and vitamin B₁₂ intake. Energy intake in 54% of patients was less than recommended daily allowances (Table 4). Furthermore according to Pearson's correlation coefficient, there was a significant association between plasma folate and dietary intake of folate (r = 0.28, P <0.05), while there was no relation between dietary intakes and plasma levels of folate and vitamin B₁₂ with depression severity (Table 5).

About 1.3% and 5.4% of depressive patients had low dietary vitamin B₁₂ and folate intake [27]. In our study, lower prevalence of vitamin B₁₂ and folate deficiencies might be related to high intake of meat and dairy products in Finnish diet [28]. Furthermore, they suggested that low dietary folate intake was related to three-fold increase in depression risk, but there was no relation between vitamin B₁₂ and depression incidence [28].There was a significant relation between folate intake and depression signs while there was no relation between vitamin B₁₂, B₆ or riboflavin and depression [27]. Miyake et al. in 121 outpatients with postpartum depression showed that mean intakes of folate and vitamin B₁₂, were 286.1 and 5.7 μg/day, respectively. In this study, there was no association between intakes of folate, vitamin B₁₂, or pyridoxine and the risk of depression [29]. In another study, there was no significant relationship between red cell folate with depression severity, measured by Montgomery Asberg Depression Rating Scale [30]. Likewise, plasma folate or vitamin B₁₂ levelswere not significantly related to depression [31]. Unlike these studies, Murakami et al. showed that higher dietary intake of folate was associated with a lower prevalence of depressive symptoms in Japanese men but not women [32].In anotherstudy, dietary intakes of vitamin B₁₂ and folate were related to depression [33].In fact, it is not known whether the association between low levels of folate and depression is caused by a low intake, poor absorption or higher requirement of folate or whether it could be considered a result of poor appetite as a symptom of depression.

The main cause(s) for controversy among different studies results and between our study results with others could be due to geographical variations, racial and ethnic differences, genetic causes, different lifestyle, e.g. different cooking methods of vegetables, inadequate intake of B vitamins [34,35] and not implementing fortification of grain products with folic acid.

Our study had some limitations. It was a cross sectional, descriptive study. We used only from one questionnaire for definition of major depression and not considered co morbid psychiatric diseases that may exist with major depression. It may have a selection bias in sampling. It was done only on depressive patients.

Conclusions

In general, comparison of the study’s results with other studies shows higher prevalence of folate and vitamin B₁₂ deficiencies in major depressive disorders patients. It seems that programs such as nutrition education, food fortification with folate and folate supplementation can increase these nutrients intake. Assessment of folate and B₁₂ levels should be included in routine clinical assessment in depressed patients. Other indices of nutrient status (like blood cells folate and vitamin B₁₂ concentrations) have not been measured, so further comprehensive epidemiological and clinical studies with higher sample size are required for assessment of these nutrients status and their relation to depression.