Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: A sex-stratified analysis in a population-based study

BACKGROUND Depression and anxiety are two common mood disorders that are both linked to systemic inflammation. Increased white blood cell (WBC) count and red cell distribution width (RDW) are associated with negative clinical outcomes in a wide variety of pathological conditions. WBC is a non-specific inflammatory marker and RDW is also strongly related to other inflammatory markers. Therefore, we proposed that there might be an association between these hematological inflammatory markers and depression/anxiety symptoms. OBJECTIVE The primary objective of this study was to examine the association between depression/anxiety symptoms and hematological inflammatory markers including WBC and RDW in a large population-based study. METHODS Symptoms of depression and anxiety and a complete blood count (CBC) were measured in 9274 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventories. RESULTS The mean WBC count increased with increasing severity of symptoms of depression and anxiety among men. Male participants with severe depression had significantly higher values of RDW (p<0.001); however, this relationship was less marked among women (p=0.004). In addition, men (but not women) with severe anxiety symptoms had significantly higher values of RDW (p<0.001). Moreover, there was a negative association between red blood cell (RBC) and mean corpuscular hemoglobin (MCH) and symptoms of depression/anxiety. CONCLUSION Our results suggest that higher depression and anxiety scores are associated with an enhanced inflammatory state, as assessed by higher hematological inflammatory markers including WBC and RDW, even after adjusting for potential confounders.

[1]  C.,et al.  PSYCHOLOGICAL MEDICINE , 1913 .

[2]  B. Penninx,et al.  Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: Findings from the Netherlands Study of Depression and Anxiety (NESDA) , 2010, Psychoneuroendocrinology.

[3]  J. Gillin,et al.  Neutrophilia and lymphopenia in major mood disorders , 1988, Psychiatry Research.

[4]  P. Cosyns,et al.  Leukocytosis, monocytosis and neutrophilia: hallmarks of severe depression. , 1992, Journal of psychiatric research.

[5]  G. Lippi,et al.  The role of red blood cell distribution width in cardiovascular and thrombotic disorders , 2012, Clinical chemistry and laboratory medicine.

[6]  C. Murray,et al.  Burden of disease--implications for future research. , 2001, JAMA.

[7]  M. Bozbay,et al.  Increased Neutrophil/Lymphocyte Ratio in Patients with Depression is Correlated with the Severity of Depression and Cardiovascular Risk Factors , 2015, Psychiatry investigation.

[8]  N. Day,et al.  Association of depression with peripheral leukocyte counts in EPIC-Norfolk--role of sex and cigarette smoking. , 2003, Journal of psychosomatic research.

[9]  B. Leonard,et al.  Association of high-sensitivity C-reactive protein with de novo major depression , 2010, British Journal of Psychiatry.

[10]  C. Nemeroff,et al.  The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. , 1998, Archives of general psychiatry.

[11]  Michael Maes.  Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression , 2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[12]  L. Ferrucci,et al.  Red blood cell distribution width and the risk of death in middle-aged and older adults. , 2009, Archives of internal medicine.

[13]  R. Stewart,et al.  Relationship Between Depressive Symptoms, Anemia, and Iron Status in Older Residents From a National Survey Population , 2012, Psychosomatic medicine.

[14]  M. Ghayour-Mobarhan,et al.  Depression and anxiety both associate with serum level of hs-CRP: A gender-stratified analysis in a population-based study , 2017, Psychoneuroendocrinology.

[15]  V. Arolt,et al.  Major depressive disorder is associated with elevated monocyte counts , 1996, Acta psychiatrica Scandinavica.

[16]  A. Renshaw.  Henry??s Clinical Diagnosis and Management by Laboratory Methods , 2007 .

[17]  Yesheng Wei,et al.  Evaluation of red blood cell distribution width and neutrophil to lymphocyte ratio in patients with major depressive disorder , 2016 .

[18]  Maryam Tayefi,et al.  Association of hematocrit with blood pressure and hypertension , 2017, Journal of clinical laboratory analysis.

[19]  J. Samet,et al.  White blood cell count and risk for all-cause, cardiovascular, and cancer mortality in a cohort of Koreans. , 2005, American journal of epidemiology.

[20]  Ali Taghipour,et al.  hs-CRP is strongly associated with coronary heart disease (CHD): A data mining approach using decision tree algorithm , 2017, Comput. Methods Programs Biomed..

[21]  A. Zonderman,et al.  White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults , 2016, Translational psychiatry.

[22]  C. Meyer.  Depressive disorders were the fourth leading cause of global disease burden in the year 2000 , 2004, Evidence-based mental health.

[23]  V. Chopra,et al.  Relation between red blood cell distribution width (RDW) and all-cause mortality at two years in an unselected population referred for coronary angiography. , 2010, International journal of cardiology.

[24]  D. Panagiotakos,et al.  Anxiety in relation to inflammation and coagulation markers, among healthy adults: the ATTICA study. , 2006, Atherosclerosis.

[25]  T. Hoffmann,et al.  Cost effectiveness of patient education for the prevention of falls in hospital: economic evaluation from a randomized controlled trial , 2013, BMC Medicine.

[26]  E. Bosmans,et al.  Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining , 1992, Psychological Medicine.

[27]  M. Azarpazhooh,et al.  Mashhad stroke and heart atherosclerotic disorder (MASHAD) study: design, baseline characteristics and 10-year cardiovascular risk estimation , 2015, International Journal of Public Health.

[28]  M. Maes,et al.  So depression is an inflammatory disease, but where does the inflammation come from? , 2013, BMC Medicine.

[29]  Mahmoud Ebrahimi,et al.  C-reactive protein associated with coronary artery disease in Iranian patients with angiographically defined coronary artery disease. , 2008, Clinical laboratory.

[30]  H. Neels,et al.  Alterations in iron metabolism and the erythron in major depression: further evidence for a chronic inflammatory process. , 1996, Journal of affective disorders.

[31]  F. Scorza,et al.  Progress in neuro-psychopharmacology and biological psychiatry Re.: Omega-3 fatty acids and sudden unexpected death in epilepsy: What does the evidence tell us? , 2007, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[32]  L. Beutler,et al.  Reliability and validity of the short form Beck Depression Inventory with older adults. , 1988, Journal of clinical psychology.

[33]  J. Januzzi,et al.  Association between C-reactive protein and generalized anxiety disorder in stable coronary heart disease patients. , 2008, European heart journal.

[34]  K. Suzuki,et al.  White blood-cell count and the risk of impaired fasting glucose or Type II diabetes in middle-aged Japanese men , 2002, Diabetologia.

[35]  J. Rottenberg.  Mood and Emotion in Major Depression , 2005 .

[36]  T. Wadden,et al.  Gender differences in the relationship between symptoms of depression and high-sensitivity CRP , 2013, International Journal of Obesity.

[37]  S. Fosså,et al.  Is there an association between haemoglobin, depression, and anxiety in cancer patients? , 2005, Journal of psychosomatic research.

[38]  M. Pfeffer,et al.  Red cell distribution width as a novel prognostic marker in heart failure: data from the CHARM Program and the Duke Databank. , 2007, Journal of the American College of Cardiology.

[39]  W. Bahk,et al.  Associations between immune activation and the current severity of the "with anxious distress" specifier in patients with depressive disorders. , 2016, General hospital psychiatry.

[40]  G. Ferns,et al.  The prevalence of metabolic syndrome increases with serum high sensitivity C-reactive protein concentration in individuals without a history of cardiovascular disease: a report from a large Persian cohort , 2016, Annals of clinical biochemistry.

[41]  A. Beck,et al.  An inventory for measuring clinical anxiety: psychometric properties. , 1988, Journal of consulting and clinical psychology.

[42]  F. Limosin,et al.  Smoking and the Association Between Depressive Symptoms and Absolute Neutrophil Count in the Investigations Préventives et Cliniques Cohort Study , 2015, Psychosomatic medicine.

[43]  J. Whitworth.  Relationship between white blood cell count and incident hypertension. , 2004, American journal of hypertension.

[44]  J. Blumenthal.  Depression and coronary heart disease: association and implications for treatment. , 2008, Cleveland Clinic journal of medicine.

[45]  R. Ulu,et al.  The Impact of Red Blood Cell Distribution Width and Neutrophil/Lymphocyte Ratio on the Diagnosis of Major Depressive Disorder , 2015, Neurology and Therapy.

[46]  B. Olatunji,et al.  Quality of life in the anxiety disorders: a meta-analytic review. , 2007, Clinical psychology review.

[47]  T. Lehtimäki,et al.  Blood leukocyte count is a risk factor for intima-media thickening and subclinical carotid atherosclerosis in middle-aged men. , 2006, Atherosclerosis.

[48]  B. Penninx,et al.  Depressive symptoms and white blood cell count in coronary heart disease patients: Prospective findings from the Heart and Soul Study , 2013, Psychoneuroendocrinology.

[49]  David J. A. Dozois,et al.  A psychometric evaluation of the Beck Depression inventory-II , 1998 .

[50]  T. B. Üstün,et al.  Global burden of depressive disorders in the year 2000 , 2004, British Journal of Psychiatry.

[51]  A. Fietta,et al.  Assessment of lymphocyte subsets and neutrophil leukocyte function in chronic psychiatric patients on long-term drug therapy , 1996, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[52]  A. Mousavi,et al.  PSYCHOMETRIC PROPERTIES OF THE PERSIAN VERSION OF BECK ANXIETY INVENTORY (BAI) , 2008 .

[53]  J. Viikari,et al.  Depressive symptoms and C-reactive protein: The Cardiovascular Risk in Young Finns Study , 2006, Psychological Medicine.

[54]  J. Cohn,et al.  Definition and Classification of Hypertension: An Update , 2009, Journal of clinical hypertension.

[55]  J. Mckenney,et al.  Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). , 2001, JAMA.

[56]  Habibollah Ghassemzadeh,et al.  Psychometric properties of a Persian‐language version of the Beck Depression Inventory ‐ Second edition: BDI‐II‐PERSIAN , 2005, Depression and anxiety.

[57]  M G Marmot,et al.  Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study , 2008, Psychological Medicine.

[58]  W. Kraus,et al.  Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population. , 2011, Clinica chimica acta; international journal of clinical chemistry.

[59]  A. Glaus,et al.  [Hemoglobin and fatigue in cancer patients: inseparable twins?]. , 2000, Schweizerische medizinische Wochenschrift.

[60]  E. van Wijngaarden,et al.  Associations between immunologic, inflammatory, and oxidative stress markers with severity of depressive symptoms: an analysis of the 2005-2006 National Health and Nutrition Examination Survey. , 2010, Neurotoxicology.

[61]  M. Kaya,et al.  The relationship between inflammation and slow coronary flow: increased red cell distribution width and serum uric acid levels. , 2011, Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir.

[62]  Viola Vaccarino,et al.  Association Between Depression and Elevated C-Reactive Protein , 2003, Psychosomatic medicine.

[63]  T. Vos,et al.  prevalence of anxiety disorders : a systematic review and meta regression , 2013 .

[64]  B. Kirkpatrick,et al.  Abnormal glucose tolerance, white blood cell count, and telomere length in newly diagnosed, antidepressant-naïve patients with depression , 2013, Brain, Behavior, and Immunity.

[65]  P. Ridker,et al.  C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. , 2000, The New England journal of medicine.

[66]  Imran Awan,et al.  Leukocyte count and coronary heart disease: implications for risk assessment. , 2004, Journal of the American College of Cardiology.

[67]  P. Sachdev,et al.  Inflammatory biomarkers predict depressive, but not anxiety symptoms during aging: The prospective Sydney Memory and Aging Study , 2012, Psychoneuroendocrinology.

[68]  Sigmund Freud,et al.  The Problem Of Anxiety , 1936 .

[69]  Cooper Jc.  Health and Nutrition Examination Survey of 1971-75: Part I. Ear and race effects in hearing. , 1994 .

[70]  G. Lippi,et al.  Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. , 2009, Archives of pathology & laboratory medicine.