Relationship between severity of depression symptoms and iron deficiency anemia in women with major depressive disorder

© 2015 The Authors; Tabriz University of Medical Sciences This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Relationship between severity of depression symptoms and iron deficiency anemia in women with major depressive disorder

functions and developments. 4,5Iron is required for proper myelination of the spinal cord and brain white matter of cerebellar folds, and it is a cofactor for a number of enzymes involved in neurotransmitter synthesis, such as tryptophan hydroxylase (serotonin) and tyrosine hydroxylase (norepinephrine and dopamine). 6,7he major cell types that comprise iron in human brains are oligodendrocytes, which responsible for the production of myelin.Therefore, alterations in the functioning of these cells are associated with hypomyelination.In ID, oligodendrocytes appear immature.The failure to deliver iron to these cells could be causally related to delay motor maturation and perhaps behavioral alterations during particular periods of early brain development.Iron has different roles in brain metabolism like incorporation into enzymes of oxidation-reduction or electron transport; synthesis and packaging of neurotransmitters; and uptake and degradation of the neurotransmitters into other ironcontaining proteins that may directly or indirectly alter brain function through peroxide reduction, amino acid metabolism, fat desaturation, and altering membrane function. 8epression is the most common mental disorder. 9The overall prevalence of mood disorders was reported 25% [25-10% for major depressive disorder (MDD) in women and 12.5% in men]. 10Prevalence of women's depression in reproductive ages is two times more than men. 11,12Current estimates suggest that 16% of the population will experience a type of depression during their life. 13pproximately, 121 million people suffer from depression worldwide, and it will be the third cause of disability up to 2020. 14ome causes of depression such as genetics couldn't be changed, but others can be modified.Nutrition may play an important role in preventing depression.In fact, nutritional deficiencies can affect the psychological state and brain mechanisms that can lead to mood disorders such as depression. 15The association of depression with some vitamin deficiencies (folic acid, vitamin B12, niacin and vitamin C) has been established. 11Patients, who are suffering from IDA, show signs and symptoms of mood disorders like depression.
Many of depressive symptoms in patients with IDA can be resolved by iron supplementation even before any improvement in red blood cell count or other indicators improvement. 2It seems that this phenomenon is due to improved levels of neurotransmitters, and iron-dependent enzyme that is not related to hemoglobin (Hb) concentration. 16,17DA can cause depression, irritability, fatigue, sleepiness, and it effects on quality of life, the symptoms of depression and anemia can cause a range of similar symptoms, and each has its own special treatment, but simultaneous therapy is useful and alone treatment of them sometimes is not enough.Therefore, such a study to understand the relationship of depression with anemia and the effect of anemia on the severity of symptoms should be required.This cross-sectional study was conducted in 2010-2011 on 100 women diagnosed with MDD, according to psychiatric diagnosis and Hamilton depression rating scale (HDRS) and also HDRS was used for evaluation of depression severity.Convenience sampling was used to select patients from clinics of Tabriz University of Medical Sciences, Iran.Inclusion criteria of the study were psychiatric diagnosis of major depression according to Diagnostic and Statistical Manual of Mental Disorders, 4 th Edition, Text Revision (DSM-IV-TR) criteria, Age over 18 years, being female and exclusion criteria were history of mania, depression due to other physical illnesses, Specific drug intake (or provide 2-week washout period for patients who received the drug), Alcohol consumption during the past 6 months, other severe illnesses such as liver disorders, Pregnancy, lactation, vegetarian diet and vitamins or iron supplementation during 6 months.
After diagnosis by a psychiatrist, all participants were taken tests of thyroid and liver function test.Beta human chorionic gonadotropin (Beta-hCG) test was evaluated in women with they don't know "are they pregnant or not" and enrolled if there was not an impairment in performed tests.In the remained 100 patients, to assess the severity of depression HDRS was used to determine the severity of depression.
Demographic features as age, education level, occupation, marital status, and a number of children were assessed at baseline, and informed consent was obtained.7 ml blood samples were collected from all patients included in 2 ml citrated and 5 ml clot in two separate glasses and delivered in maximum two hours.The clot samples were centrifuged immediately after clotting for serum separation, and maintained in -20 °C.In this study, Hb < 12 g/dl considered as anemia.If the Hb is < 12 g/dl, Fe and total iron binding capacity (TIBC) were also tested.TIBC levels > 360 μg/dl and Fe < 30 μg/dl were considered as IDA.Because levels of mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC) have changed in the early stages of ID, these indicators were also evaluated.
The data were analyzed by SPSS software (version 16, SPSS Inc., Chicago, IL, USA).Statistical significance level was considered P < 0.05.Frequency, percentage, Student's t-test, one-way ANOVA, and Pearson correlation test were used.
Table 1 shows the relationship between blood sample indicators with HDRS scores, and there were not any significant association.The lowest and highest Hb level was 9.40 and 15.90 mg/dl, respectively.Hb levels in 18 patients (18%) were low and in 82 cases (82%) were normal.The mean hematocrit level was 40.73 ± 4.54, and the median was 41.The minimum and maximum rates were 24 and 49, respectively.
MCV levels in 72 cases (72%) were between 90 and 60 and this is a sign of IDA.In 28 cases (28%) MCV was normal.MCH levels in 82 cases normal and in 18 were decreased.MCHC level in 90 cases normal and in 10 was reduced.

HDRS compare scores among different variables
HDRS scores were 31.08 ± 4.23 in householder patients and 33.40 ± 3.32 in employed patients and the difference between the two groups was not statistically significant (P = 0.08).Figure 1 shows the patient's HDRS scores based on marital status.HDRS scores were the higher in unmarried patients compared with married patients and in married patients was higher compared with divorced or widowed patients.However, the difference between groups Were not statistically significant (P = 0.70).
HDRS scores in patients with and without anemia were 33.37 ± 1.99 and 32.09 ± 4.19, respectively.It was observed that patients with IDA had higher scores than the normal group.However, the difference between groups was not statistically significant (P = 0.39).Figure 2 shows HDRS scores between patients with and without anemia.It is observed that the mean HDRS is higher in patients with anemia.However, the difference between groups was not statistically significant (P = 0.70).HDRS scores in patients with normal and low Hb were 32.50 ± 3.38 and 32.13 ± 4.22, respectively.However, the difference between groups was not statistically significant (P = 0.73).
The probable relationships between different levels of scores HDRS using Pearson correlation across all participants were examined, and a significant negative correlation was found between Hb levels and HDRS scores (Pearson correlation = 0.21, P = 0.03).The probable relationships between different levels of HDRS scores using Pearson correlation were studied in patients with IDA and also found a significant negative correlation between Hb levels and HDRS scores (Pearson correlation = 0.77, P = 0.02).The possible relationships between different levels of HDRS scores using Pearson correlation was studied in patients with anemia and also found a significant negative correlation between Hb levels and HDRS Scores (Pearson correlation = 0.48, P = 0.03) and there was no significant correlation between serum ferritin and TIBC level with HDRS scores (Pearson correlation = 0.22, P = 0.39), (Pearson correlation = 0.01, P = 0.96).
ID is one of the most common nutritional problems in the world both in developed and developing countries.
Relationship of iron and brain function, cognition, and behavior (including emotional behavior) has been the subject of interest for researchers over the past decade. 4Changes in iron metabolism has been suggested as potential pathological markers in patients with depression.Ferritin as an intracellular iron storage plays an important role, and this issue has become the subject of extensive investigation. 18Bartalena et al. 19 shows that ferritin level was significantly lower in nonanemic women with untreated major depression compared to healthy control group.Furthermore, increasing in serum ferritin levels was associated with an improvement in depressive symptoms in treatment-resistant depression in chronic hemodialysis patients with major depression. 20n the current study, 19% of women with depression were anemic and about 8% were suffering from IDA.The study of Onder et al. 21shows that 15% of people with depression were anemic.In the study of Kolahi et al. prevalence of anemia in women living in the North West of Tabriz was reported 9.7% and 75.3% of anemic patients had IDA. 22Furthermore in our study, it was found that anemia was significantly higher in patients with depression and HDRS significantly increased with decreased Hb levels, however, Lever-van Milligen et al. 23 showed that there is no association between depressive and/or anxiety disorders and Hb levels or anemia status.Benton and Donohoe 15 showed that depression significantly associated with early fatigue and apathy and the symptoms were exacerbated by IDA.
In the present study, there is no significant association between depressive symptoms and serum ferritin levels.The results of this research are consistent with the study of Yi et al. 20 The findings of these researchers showed that there is not significant relationship between serum ferritin levels and depression in women, however, in men significantly increased depression severity with reduced serum ferritin levels.But Vahdat et al. 17 determined that the mean serum ferritin was significantly lower in patients with depression.

Limitations
We did not have control group but as mentioned above in the North West of Tabriz anemia was reported 9.7% that 75.3% of anemic patients had IDA. 23ere is negative correlation between Hb level and HDRS score in total patients, anemic patients, and IDA group, and it demonstrate the effect of Hb decrease and anemia on depression severity, however, it needs more studies.
Authors have no conflict of interest.Special thanks from staff of Tabriz Razi therapeutic and Educational center and Bozorgmehr specialized and subspecialized clinic of psychiatry.

Figure 1 .Figure 2 .
Figure 1.Hamilton depression rating scale (HDRS) scores based on the marital status of patients

Table 1 .
Comparison experimental variables based on