Hemoglobin levels in persons with depressive and/or anxiety disorders

doi:10.1016/j.jpsychores.2014.01.004

Journal of Psychosomatic Research

Volume 76, Issue 4, April 2014, Pages 317-321

https://doi.org/10.1016/j.jpsychores.2014.01.004 Get rights and content

Abstract

Objective

Both low and high hemoglobin levels lead to more physical diseases, and both are linked to mortality. Low hemoglobin, often classified as anemia, has also been linked to more depressive symptoms, but whether both hemoglobin extremes are associated with depressive disorder and potentially also with anxiety disorder has not been examined before. This study examines to which extent hemoglobin levels are associated with depression and anxiety disorders in a large cohort.

Methods

The study sample consisted of 2920 persons from the Netherlands Study of Depression and Anxiety. Hemoglobin levels were determined after venipuncture. Depressive and anxiety disorders were determined according to a DSM-IV-based psychiatric interview. Clinical psychiatric characteristics included the severity of depression and anxiety, the duration of symptoms, the age of onset and the antidepressant use.

Results

Higher hemoglobin levels were found in those with current depressive and/or anxiety disorders after sociodemographic adjustment and both higher, and lower hemoglobin levels were found in persons with higher depression and anxiety severity. However, after full adjustment for sociodemographics, disease indicators and lifestyle, associations were no longer significant.

Conclusions

This cohort study showed that there is no independent association between depressive and/or anxiety disorders and hemoglobin levels or anemia status.

Introduction

Extreme hemoglobin levels (Hb), both low and high levels, lead to deteriorated quality of life [1], [2], have been associated with greater mortality in elderly persons [2], [3] and have been linked to the development of diseases, such as heart failure or cardiovascular diseases (for low hemoglobin levels) [4], [5] and hypertension or thrombosis (for high hemoglobin levels) [6].

Beyond these physical health problems, previous research has shown that low hemoglobin level (anemia) is associated with more depressive symptoms [7], [8], [9], [10], [11]. Such an association could be expected since symptoms of low hemoglobin level (paleness, fatigue, dizziness, shortness of breath during physical activity, higher heart beat in resting state and heart fluttering) also often occur when having depressive (or anxiety) symptoms. This association between low hemoglobin level and depression could potentially be explained by underlying poorer physical health status such as fatigue [12], [13], [14], reduced levels of brain oxygen [15], vitamin B12 deficiency [16], [17], [18] or higher inflammatory levels [19], [20], [21]. Earlier studies on anemia and depression included elderly or diseased persons only and did generally not consider the presence of psychiatric disorders but used self-report measures of depressive symptomatology. Consequently, whether low hemoglobin levels are associated with psychiatric depression in a younger adult sample needs to be clarified. In addition, whether an association between anemia and mental health extends to anxiety disorders, a highly comorbid condition to depression with partly shared pathophysiology, needs to be established as well. Furthermore, whether high hemoglobin levels are also associated with depressive and anxiety disorders has not been examined before. Such an association could be expected since both high hemoglobin and depressive and anxiety disorders are associated with vascular disease [6], [22], [23] and smoking [24], [25] probably due to increased blood viscosity [26].

This cohort study examines the association between hemoglobin levels and the presence of depressive and anxiety disorders in an adult population. Both the low end and the high end of the hemoglobin spectrum will be distinguished, considering the fact that both ends have been associated with poorer health. We also examined whether an association between low or high hemoglobin levels and psychiatric disorders is dependent on clinical psychiatric characteristics, such as severity, duration, age of onset of the depressive or anxiety disorder and antidepressant use.

Section snippets

Study sample

The Netherlands Study of Depression and Anxiety (NESDA) is an ongoing longitudinal cohort study that investigates the long-term course and consequences of depressive and anxiety disorders. During a 4-hour measurement, a wide range of data were collected, including the assessment of demographics, a diagnostic psychiatric interview and a medical examination including blood collection. All respondents signed an informed consent. The NESDA protocol was approved by the ethical review board of all

Results

The mean age of the study sample was 41.9 ± 13.1 years, 66.3% was women and the mean years of education was 12.2 ± 3.3 years. The mean hemoglobin level was 13.9 g/dl (SD = 1.3 g/dl), 7.3% had anemia according to the WHO cutoff and 7.9% had high hemoglobin levels (Hb ≥ 3.1 g/dl above anemia cutoff). Table 1 shows characteristics of the study sample across the different hemoglobin categories. The hemoglobin groups differed from each other: those with anemia were younger, were more often women, had more years

Discussion

This large cohort study comprehensively examined the role of hemoglobin levels in depression and anxiety. The current study provides no clear evidence for an association between depression/anxiety and hemoglobin levels. Higher hemoglobin levels were found in those with current depressive and/or anxiety disorders after sociodemographic adjustment, and both higher and lower hemoglobin levels were found in persons with higher depression and anxiety severity. However, after full adjustment for

Conflict of interest

All authors declare that they have no competing interests to report.

Acknowledgements

The infrastructure for the NESDA study is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-MW, grant no. 10-000-1002) and is supported participating universities and mental health care organizations (VU University Medical Center, GGZinGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, IQ Healthcare, Netherlands Institute for Health Services

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Meanwhile, one study on the relationship between anemia and depression in premenopausal women did not show a significant association (Hunt and Penland, 1999). Another study also reported that the association between anemia and depression was not significant after adjusting for potential confounders (Lever-van Milligen et al., 2014). To our best knowledge, studies investigating the association between anemia and depression in a large national sample population are scarce.
Several studies have reported an association between anemia and depression. However, whether anemia is independently associated with depression remains controversial. The current study aimed to investigate the association between anemia and depression according to sex in a large national sample population.
Data from the 2014, 2016, and 2018 Korean National Health and Nutrition Examination Survey were analyzed, and 15,472 participants were included in this study. Anemia was defined as a hemoglobin level <13 g/dL in men and <12 g/dL in women. We defined a Patient Health Questionnaire-9 score ≥10 as depression and ≥5 as mild depressive symptoms.
The prevalence of depression was significantly higher in women with anemia than in women without anemia (8.9 % vs. 7.0 %, P = 0.036). In women, anemia was significantly associated with depression after adjusting all covariates in multilevel logistic regression analysis (odds ratio, 1.37; 95 % confidence interval, 1.08–1.75; P = 0.011). However, no significant association was observed in men.
There is a limit to explaining the causal direction, and several factors may not have been considered as confounders. Also, patients with severe diseases were excluded from data acquisition. A structured diagnostic interview, other than the self-report method, was not conducted.
The findings of this study suggest that anemia is associated with depression in women but not in men. A decrease in tissue oxygenation, deterioration of physical performance due to anemia, and altered monoamine synthesis due to malnutrition may have an effect on depression.
Prediction of depression among medical check-ups of 433,190 patients: A nationwide population-based study
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Several studies have reported that each hematological factor is associated with depression. Low hemoglobin may increase the risk of depression in the elderly and is an indicator of poor health status and nutrition intake (Chen et al., 2012; Lever-van Milligen et al., 2014; Trevisan et al., 2016). This can be interpreted as related to the main symptoms of depression, such as fatigue and loss of energy; however, it is necessary to be careful in interpreting the relationship between the results of variables importance and depression in only one direction.
Depression is a mental illness that causes significant disturbances in daily life. Depression is commonly associated with low mood, severe health problems, and substantial socioeconomic burden; hence, it is necessary to be able to detect depression earlier. We utilized the medical check-up cohort database of the National Health Insurance Sharing Service in Korea. We split the total dataset into training (70%) and test (30%) sets. Subsequently, five-fold cross validation was performed in the training set. The holdout test set was only used in the last step to evaluate the performance of the predictive model. Random forest algorithm was used for the predictive model. The analysis included 433,190 individuals who had a national medical check-up from 2009–2015, which included 10,824 (2.56%) patients in the depression group. The area under the receiver-operating curve was 0.849. Other performance metrics included a sensitivity of 0.737, specificity of 0.824, positive predictive value of 0.097, negative predictive value of 0.992, and accuracy of 0.780. Our predictive model could contribute to proactively reducing depression prevalence by administering interventions to prevent depression in patients receiving medical check-up. Future studies are needed to prospectively validate the predictability of this model.
Depression, antidepressants and low hemoglobin level in the Paris Prospective Study III: A cross-sectional analysis
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As regards chronic diseases, the participants were required to indicate whether they had a history of hypertension, peripheral artery disease, stroke, myocardial infarction, angina, heart murmur, any other cardiac disease, hepatitis, peptic ulcer, cholelithiasis, intestinal polyp, thyrosis, kidney disease or cancer. In line with previous studies, participants were excluded from the present study if they had high hemoglobin level (>15.0 g/dl (9.30 mmol/l) in women and > 16.0 g/dl (9.90 mmol/l) in men) (Ren et al., 2014; Lever-Van Milligen et al., 2014) as they may be at high risk for depressive symptoms (Lever-Van Milligen et al., 2014). The PPS3 was registered in the World Health Organisation (WHO) International Clinical Trial Registry Platform (NCT00741728) in 25 August 2008.
Anemia is known to be associated with depression both in community and clinical populations. However, it is still unknown if this association depends or not on antidepressant intake. We investigated the respective association of depression and antidepressant intake with low hemoglobin level in a large community-based cohort. In 8640 volunteers aged 50 to 75 recruited between June 2008 and June 2012 in Paris (France), we assessed hemoglobin levels (g/dl), depressive symptoms and antidepressant intake. We examined the association of both depression and antidepressant intake with hemoglobin level, adjusting for numerous socio-demographic and health variables. We also assessed the association with specific antidepressant classes. Depression and antidepressant intake were independently associated with lower hemoglobin level (β = −0.074; p = .05 and β = −0.100; p = .02 respectively in the fully-adjusted model). Regarding antidepressant classes, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) intake were associated with lower hemoglobin level (β = −0.11; p = .01). To conclude, both depression and antidepressant intake were associated with lower hemoglobin level. In particular, as SSRI or SNRIs intake was also related to lower hemoglobin level, these classes should be used with caution in depressed individuals at risk for anemia.
Hemoglobin-derived peptides and mood regulation
2020, Peptides
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However, the use of Hb as a mark of mood is insufficient. A comprehensive cohort study which examined the role of Hb levels in depression and anxiety found that those with current depressive and/or anxiety disorders had increased Hb levels after adjusting for sociodemographic factors, whereas those with more severe depression and anxiety disorders had both increased and decreased Hb levels [15]. Hence, Hb is not always a reliable gauge of the state of mood, thereby raising the question that other molecules may better indicate the mood status.
Evidence accumulated over the past decades has revealed that red blood cells and hemoglobin (Hb) in the blood play important roles in modulating moods and emotions. The number of red blood cells affects the mood. Hb is the principal content in the red blood cells besides water. Denatured Hb is hydrolyzed to produce bioactive peptides. RVD-hemopressin α (RVD-Hpα), which is a fragment of α-chain (95–103) in Hb, functions as a negative allosteric modulator of cannabinoid receptor 1 and a positive allosteric modulator of cannabinoid receptor 2. Hemorphins, which are fragments of β-chain in Hb, exert their effects on opioid receptors. Two hemorphins, namely, LVV-hemorphin-6 and LVV-hemorphin-7, could induce anxiolytic-like effects. The use of Hb-derived bioactive peptides for the treatment of mood disorders is desirable due to cannabinoid–opioid cross modulation and the critical roles of the two systems in physiological processes, such as memory, mood and emotion.
Study of anxiety trait and anxiety state in anemic children: Region of Chefchaouen in northern Morocco
2020, Neuropsychiatrie de l'Enfance et de l'Adolescence
Une anémie peut contribuer à la détérioration de la qualité de vie et avoir un impact physique important entraînant une augmentation de la morbidité, mais son impact psychique n’est pas bien clarifié surtout chez les enfants d’âge scolaire. Notre objectif était d’évaluer le niveau d’anxiété dans un groupe d’enfants anémiques et le comparer à un autre avec hémoglobine normale. Notre population était constituée de 170 élèves âgés entre 8 et 14 ans, dont 51 anémiques et 119 avec hémoglobine normale, l’anxiété est évaluée grâce à l’échelle d’inventaire d’anxiété STAI de Spielberger, selon ses deux concepts ; état et trait. Nos résultats montrent une médiane d’hémoglobine de 10,7 [9,9,9,10] chez les élèves anémiques et de 14,3 [2–13,13–15] chez les non anémiques (p = 0,000). Les moyennes de l’anxiété état et trait sont respectivement de 31,88 ± 7,25 et 34,82 ± 6,84 chez les élèves anémiques et de 32,55 ± 6,37 et 34,89 ± 5,7 chez les non anémiques sans différence significative entre les deux groupes. En conclusion, notre étude n’a pas rapporté de niveaux élevés d’anxiété chez les enfants anémiques ; les moyennes sont comparables à celles retrouvées dans des études cliniques chez des enfants d’âge similaire.
Anemia can contribute to the deterioration of quality of life and have a significant physical impact leading to an increase in morbidity, but its psychological impact remains underestimated and is not well clarified, especially in school-age children. Our objective was to assess the level of anxiety in a group of anemic children and compare it to a group of children with normal hemoglobin. Our population consisted of 170 students aged between 8 and 14 years old, including 51 anemic and 119 with normal hemoglobin. Anxiety is assessed using Spielberger's STAI anxiety inventory scale, according to its two concepts: state and trait. Our results show a median hemoglobin of 10,7 [9,9,9,10] in anemic students and 14,3 [2–13,13–15] in non-anemic students (P = 0,000). The mean state and trait anxiety scores are respectively 31,88 ± 7,25 and 34,82 ± 6,84 in anemic students and 2,55 ± 6,37 and 34,89 ± 5,7 in not anemic, without significant difference between the two groups. In conclusion, our study did not report high levels of anxiety in anemic children; the means are comparable to those found in clinical studies in children of similar age.

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Hemoglobin levels in persons with depressive and/or anxiety disorders

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study sample

Results

Discussion

Conflict of interest

Acknowledgements

Blood Rev

Semin Hematol

Biol Psychiatry

J Am Coll Cardiol

Drug Alcohol Depend

Soc Sci Med

J Psychiatr Res

J Nutr

A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study

Arch Intern Med

What constitutes normal hemoglobin concentration in community-dwelling disabled older women?

J Am Geriatr Soc

Anemia in heart failure

Anadolu Kardiyol Derg

Effects of anaemia on cardiovascular status

Nephrol Dial Transplant

What should the optimal target hemoglobin be?

Kidney Int Suppl

Effect of anemia and comorbidity on functional status and mortality in old age: results from the Leiden 85-plus Study

CMAJ

Cross-sectional and longitudinal associations between anemia and depressive symptoms in the English Longitudinal Study of Ageing

J Am Geriatr Soc

Anemia is associated with depression in older adults: results from the InCHIANTI study

J Gerontol A Biol Sci Med Sci

Anaemia and the development of depressive symptoms following acute coronary syndrome: longitudinal clinical observational study

BMJ Open

Relationship between depressive symptoms, anemia, and iron status in older residents from a national survey population

Psychosom Med

Hemoglobin levels and skeletal muscle: results from the InCHIANTI study

J Gerontol A Biol Sci Med Sci