This study looks at the association of depression and serum ferritin level.
Two hundred and five female medical students of Free University of Medical Sciences in Tehran were selected for the study (mean age; 24.5±1.6 years). Of these, 13 subjects were excluded and finally 192 subjects took part in the study.
A questionnaire was filled in by each participant for the diagnosis of depression to be made. Based on the Beck score, the students were grouped as depressed and healthy (67 depressed students and 125 healthy controls). The participants were evaluated in terms of hemoglobin (Hgb) level, serum ferritin, ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), folic acid, vitamin B12 and Hgb simultaneously.
The prevalence of depression in the study population was 34.7%. The mean ferritin level in students with depression was significantly lower than the healthy ones (P<0.001). By changing the status from normal ferritin level to low ferritin level, odds of depression was increased by 1.92 (P<0.05).
The study implies a possible association between depression and decreased ferritin level before the occurrence of anemia.
Free University of Medical Sciences.
Depression is among the commonest psychological disorders. The rate has been estimated between 8 and 20% in the US (Kaplan et al., 2003). Some causes of depression (genetic) are not liable to change, whereas some others are modifiable (Benton and Donohoe, 1999). Nutrition can play an important role in preventing depression. In fact, nutrient deficiencies can affect mental and cerebral mechanisms resulting in mood disorders such as depression (Benton and Donohoe, 1999). The association of depression with some vitamin deficiencies (folic acid, vitamin B12, niacin and vitamin C) has been established (Kaplan et al, 2003). Data from the Third National Health and Nutrition Examination Survey (NHANES III; 1988–1994) indicated that iron deficiency without anemia occurred in up to 11% of women (most often premenopausal) and 4% of men (Looker et al., 1997). The patients affected by iron deficiency anemia show many mood and behavioral signs and symptoms similar to the depressed individuals. Of note, many of these signs and symptoms occur in the initial stage of iron deficiency (dropped serum ferritin level) before the establishment of frank anemia (Beard et al., 1993). Many of the symptoms of depression in patients with iron deficiency anemia can be treated with iron supplementation therapy even before any improvement in RBC counts or indices. It seems that this phenomenon is due to the recovery of neurotransmitters and enzyme levels dependent on iron, unrelated to hemoglobin (Hgb) concentration (Kathlen and Escott-Stump, 2004). Whereas these results concur with some previous series (Lozell et al., 2000; Mansson et al., 2002; Beard et al., 2005), there are some studies that have shown different results (Mansson et al., 2002).
As there was no precedent to this study in Iran, we looked at the association of ferritin with depression.
Patients and methods
The present study was a case–control study, which was carried out during 2004–2005 at Free University of Medical Science in Tehran. A hundred and ninety-two female medical students, who were on their clinical rotation in the psychiatry department of Shahid Doctor Lavasani Hospital, were recruited. The study protocol was endorsed by the responsible ethics committee and written informed consent was obtained from each participant.
The students completed preliminary questionnaires inquiring into demographic characteristics, medical history and history of receiving any medication including iron or multivitamin supplements.
Given the difficulty of measuring leukocyte levels of vitamin C and niacin metabolites in urine in our country, each participant received one vitamin C tablet (250 mg) and one vitamin B complex tablet (containing 20 mg niacin, without iron) daily for 1 month before study.
Based on the Beck score, they were divided into two groups (67 depressed students and 125 healthy controls). Controls were matched to cases. At the same time, fasting blood sample (0800 hours) in sitting position was taken from each participant. The samples were used to check for serum ferritin levels (ELISA; Boeti, Italy), erythrocyte sedimentation rate (ESR) (Westergreen, Parsazmoon), C-reactive protein (CRP) (quantitative agglutination), B12, folic acid of serum (Radioimmunoassay, Parsazmoon) and Hgb, and the analyses were performed immediately after drawing the blood. Normal range for serum ferritin level is 15–200 μg/l and levels below 15 indicated iron deficiency (Kasper et al., 2005).
Students who had Hgb level lower than 12 g/dl or a history of physical disease that is accompanied with mood disorders such as multiple sclerosis, Parkinson's disease and hypothyroidism (Kasper et al., 2005) were not eligible for this study.
Students who were consuming drugs that could affect mood such as β blockers, calcium channel blockers and anticonvulsants (Kasper et al., 2005), were excluded from the study.
As ferritin is one of the acute phase reactants and as inflammatory processes are accompanied with raised levels of these reactants, people with inflammatory disorders were excluded from the study. Disqualified for study were also the subjects who had high ESR, positive CRP, serum folic acid level <4 ng/ml or B12<300 pg/ml.
Several studies have proposed a linkage between depression and folic acid and vitamin B12 deficiencies (Kaplan et al., 2003). Students with serum folic acid levels lower than 4 ng/ml and serum vitamin B12 levels lower than 300 pg/ml were excluded from the study. Finally, seven people who were consuming iron supplements, one receiving corticosteroid, one with minor thalassemia, one with positive CRP, two with folic acid deficiency and one with vitamin B12 deficiency, were excluded from the study.
SPSS software version 12 was used to analyze data. Student's t-test was used to compare mean serum ferritin levels between the two groups. Spearman correlation analysis was employed to examine the relationship between depression and serum ferritin level. In order to determine the degree of relationship between the two variables of depression and serum ferritin level, logistic regression was used. P-values less than 0.05 were considered as significant.
All study participants were in their reproductive years with a mean age of 24.5±1.6 years. Mean serum ferritin levels were 26.95±11.3 and 38.36±17.1 in depressed and healthy participants, respectively (Table 1).
In depressed individuals it ranged between 2 and 103, and in healthy ones between 2 and 197.9 μg/l. Student's t-test showed that serum ferritin levels of the two groups were significantly different (P<0.001).
Spearman correlation coefficient for ferritin and depression was −0.167 and statistically significant (P=0.01). It showed little and negative relation.
To measure odds ratio, serum ferritin level was transformed into a dummy variable (ferritin levels 15 or >15) and its relation with depression was examined using logistic regression analysis. The equation (Logit (π)=−0.827+0.625X, Exp 0.625=1.92) showed that changing the status from normal ferritin level to low ferritin level increases the odds of depression by 1.92 (P<0/05).
Total prevalence of iron deficiency (serum ferritin15 ng/l) in the study population was 29.5%, higher than what was reported in NHANES III (11%) (Looker et al., 1997).
The frequency of iron deficiency was significantly higher in depressed participants compared to the healthy ones (40.3 vs 23.8%; P<0.05).
The prevalence of depression in married students was 31.7%, which was not significantly different from the single students (35.5%; P>0.05).
The current study evaluated the relation between serum ferritin level and depression. It has been shown that mean ferritin levels were within normal range in both groups. However, it was 11 μg/l lower in depressed students than in healthy students.
Iron deficiency was observed in 29.5% of the participants, which seems rather high. In addition, the frequency of iron deficiency was 15% higher in depressed participants than healthy ones. A clinical trial recently conducted in Sweden showed that iron supplementation could diminish depressive symptoms in students compared to the control group (Mansson et al., 2002). In another study in the US, prescription of iron led to decreased depression in mothers with iron deficiency anemia compared to the controls (Beard et al., 2005). In a study in the US, infants with severe iron deficiency anemia were followed up for a 10-year period. The study revealed that these infants later had lower psychomotor scores. Depressed mood, anxiety and difficulty in concentration were more common in these children (Lozell et al., 2000).
A study in the US, based on the MMPI questionnaire, reported that serum iron, ferritin and Hgb level were not associated with depression (Hunt and Peland, 1999). It is notable that the participants of that study were not evaluated with regards to inflammatory diseases, thalassemia, use of iron or multivitamin supplements and some other drugs that could affect serum ferritin level. Neither were the indicators of inflammatory process examined (ESR and CRP). Any of the mentioned disorders and/or positive ESR or CRP tests could increase or be accompanied with increased ferritin level (Kasper et al., 2005).
The fact that mean serum ferritin level was lower in depressed students than in healthy ones can indicate the possible role of iron in brain function and the establishment of depressive mood. Iron plays an important role in the oxygenation of brain parenchyma and the synthesis of many neurotransmitters and enzymes of the nervous system (Beard et al., 1993). Iron acts on the molecular level and its effect on depression may be multifactorial with positive and negative effects. For example, as a negative effect on depression, a sufficient amount of iron is particularly needed for the synthesis of dopamine, a neurotransmitter that plays a significant role in mood disorders (Paul et al., 2002). In depression, we face depressed levels of blood dopamine (Kaplan et al., 2003).
In our study, the correlation coefficient was low; however, the amount or the direction is important. It showed an inverse correlation between serum ferritin level and depression that seems important. The figure is low because the role of iron on depression is due to the sum of its positive and negative effects with resultant to the negative effects.
It seems necessary that iron supplementation, in treating symptoms of depressive patients, should be evaluated in a clinical trial.
We are grateful to the Free Islamic University of Medical Sciences, the health deputy of Social Security Organization, Shahid Doctor Lavasani Hospital and all those who contributed to this study for their valuable help and support.