Cerebrovascular Disease Cerebrovascular Damage in Late-Life Depression Is Associated With Structural and Functional Abnormalities of Subcutaneous Small Arteries

Late-life depression is increasingly viewed as a vascular illness because of patients exhibiting characteristic white matter brain lesions and in vivo large artery endothelial dysfunction. However, the “vascular depression” hypothesis pertains to the microvasculature, and this circulation has not been studied in this context. Our objective was to examine structure and function of small subcutaneous arteries in patients with late-life depression. Thus, 16 patients aged 71.8±4.0 years with late-life depression were compared with 15 control participants aged 72.1±5.9 years. There were similar cardiovascular profiles between the 2 groups. All of the participants underwent MRI brain scans and subcutaneous gluteal fat biopsy from which small arteries were isolated and studied using pressure myography. Cerebral microvascular damage in depressed patients was confirmed by assessment of basal ganglia Virchow-Robin space scores (depressed patients 3.9±1.7 versus controls: 2.5±1.6; P=0.01). Contractility to norepinephrine was equivalent in both groups, but relaxation of the small arteries to acetylcholine was significantly reduced in depressed patients (84.0±4.0%) compared with control participants (96.0±1.4%; P=0.012). This difference in arterial relaxation was reduced but not entirely eliminated when NO synthase was inhibited. Depressed patients also exhibited hypertrophic wall growth with an increase in medial cross-sectional area (P=0.035, multiple ANOVA and wall thickness; P=0.04, multiple ANOVA). In conclusion, despite similar cardiovascular profiles, depressed patients with cerebral microvascular damage show abnormalities of subcutaneous small artery structure and function.

[1]  Shijing Huang,et al.  Vascular depression , 2010 .

[2]  A. Burns,et al.  Vascular Function in Older Adults with Depressive Disorder , 2010, Biological Psychiatry.

[3]  J. Imig,et al.  Simvastatin and Tempol Protect Against Endothelial Dysfunction and Renal Injury in a Model of Obesity and Hypertension , 2008, American journal of physiology. Renal physiology.

[4]  L. Manzoli,et al.  Effects of Selective Serotonin Reuptake Inhibitor Therapy on Endothelial Function and Inflammatory Markers in Patients With Coronary Heart Disease , 2009, Clinical pharmacology and therapeutics.

[5]  C. de Ciuceis,et al.  Altered structure of small cerebral arteries in patients with essential hypertension , 2009, Journal of hypertension.

[6]  A. Heagerty,et al.  Myogenic tone and small artery remodelling: insight into diabetic nephropathy. , 2008, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[7]  Stavros Stivaros,et al.  Potential surrogate markers of cerebral microvascular angiopathy in asymptomatic subjects at risk of stroke , 2009, European Radiology.

[8]  R. Rouhl,et al.  Virchow-Robin spaces relate to cerebral small vessel disease severity , 2008, Journal of Neurology.

[9]  Mohammed F. Faramawi,et al.  Relation between depressive symptoms and common carotid artery atherosclerosis in American persons > or =65 years of age. , 2007, The American journal of cardiology.

[10]  A. Jackson,et al.  Virchow-Robin space dilatation may predict resistance to antidepressant monotherapy in elderly patients with depression. , 2007, Journal of affective disorders.

[11]  D. Atar,et al.  Platelet and endothelial activity in comorbid major depression and coronary artery disease patients treated with citalopram: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy Trial (CREATE) biomarker sub-study , 2007, Journal of Thrombosis and Thrombolysis.

[12]  G. Alexopoulos.  The Vascular Depression Hypothesis: 10 Years Later , 2006, Biological Psychiatry.

[13]  M. Kähönen,et al.  Increased wall tension in response to vasoconstrictors in isolated mesenteric arterial rings from patients with high blood pressure. , 2006, Basic & clinical pharmacology & toxicology.

[14]  E. Schiffrin,et al.  Angiotensin Receptor Blocker Added to Previous Antihypertensive Agents on Arteries of Diabetic Hypertensive Patients , 2006, Hypertension.

[15]  S. Newman,et al.  Alteration of Decreased Plasma NO Metabolites and Platelet NO Synthase Activity by Paroxetine in Depressed Patients , 2006, Neuropsychopharmacology.

[16]  R. Loutzenhiser,et al.  Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[17]  D. Rizzoni,et al.  Small artery remodeling in hypertension and diabetes , 2006, Current hypertension reports.

[18]  G J Blauw,et al.  Measuring longitudinal white matter changes: comparison of a visual rating scale with a volumetric measurement. , 2006, AJNR. American journal of neuroradiology.

[19]  C. Ko,et al.  Carotid intima‐media thickness in late‐onset major depressive disorder , 2006, International journal of geriatric psychiatry.

[20]  R. Allegri,et al.  A double-blind, randomized clinical trial to assess the augmentation with nimodipine of antidepressant therapy in the treatment of “vascular depression” , 2005, International Psychogeriatrics.

[21]  D. Neary,et al.  Dilatation of the Virchow-Robin space is a sensitive indicator of cerebral microvascular disease: study in elderly patients with dementia. , 2005, AJNR. American journal of neuroradiology.

[22]  C. de Ciuceis,et al.  Effect of Treatment With Candesartan or Enalapril on Subcutaneous Small Artery Structure in Hypertensive Patients With Noninsulin-Dependent Diabetes Mellitus , 2005, Hypertension.

[23]  D. Rizzoni,et al.  Small artery structure and hypertension: adaptive changes and target organ damage. , 2005, Journal of hypertension.

[24]  A. Heagerty,et al.  Effects of Angiotensin Type-1 Receptor Antagonism on Small Artery Function in Patients With Type 2 Diabetes Mellitus , 2005, Hypertension.

[25]  R. Baldwin.  Is vascular depression a distinct sub‐type of depressive disorder? A review of causal evidence , 2005, International journal of geriatric psychiatry.

[26]  M. Bertrand.  Provision of cardiovascular protection by ACE inhibitors:a review of recent trials , 2004, Current medical research and opinion.

[27]  Robert Barber,et al.  Hippocampal volume change in depression: Late- and early-onset illness compared , 2004, British Journal of Psychiatry.

[28]  E. Schiffrin,et al.  Persistent Remodeling of Resistance Arteries in Type 2 Diabetic Patients on Antihypertensive Treatment , 2004, Hypertension.

[29]  C. Sutcliffe,et al.  Treatment response in late-onset depression: relationship to neuropsychological, neuroradiological and vascular risk factors , 2004, Psychological Medicine.

[30]  S. Archer,et al.  Paroxetine-Induced Increase in Metabolic End Products of Nitric Oxide , 2003, Journal of clinical psychopharmacology.

[31]  A. Dominiczak,et al.  Myogenic and structural properties of cerebral arteries from the stroke-prone spontaneously hypertensive rat. , 2003, American journal of physiology. Heart and circulatory physiology.

[32]  A. Hofman,et al.  Late‐Life Depression is Associated with Arterial Stiffness: A Population‐Based Study , 2003, Journal of the American Geriatrics Society.

[33]  E. Schiffrin.  Effect of antihypertensive treatment on small artery remodeling in hypertension. , 2003, Canadian journal of physiology and pharmacology.

[34]  Amir Lerman,et al.  Endothelial Dysfunction: A Marker of Atherosclerotic Risk , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[35]  A. Heagerty,et al.  Vascular Structural and Functional Changes in Type 2 Diabetes Mellitus: Evidence for the Roles of Abnormal Myogenic Responsiveness and Dyslipidemia , 2002, Circulation.

[36]  R. Barber,et al.  Pathologies and Pathological Mechanisms for White Matter Hyperintensities in Depression , 2002, Annals of the New York Academy of Sciences.

[37]  C. Jones,et al.  Arterial endothelial function is impaired in treated depression , 2002, Heart.

[38]  J. O'Brien,et al.  Vascular basis of late-onset depressive disorder , 2002, British Journal of Psychiatry.

[39]  M. Rubenfire,et al.  Abnormal brachial artery flow-mediated vasodilation in young adults with major depression. , 2001, The American journal of cardiology.

[40]  A. Beekman,et al.  Depression in later life: three etiologically different subgroups. , 2001, Journal of affective disorders.

[41]  G. Alexopoulos,et al.  'Vascular depression' hypothesis. , 1997, Archives of general psychiatry.

[42]  W. Katon,et al.  Depressive symptoms and the cost of health services in HMO patients aged 65 years and older. A 4-year prospective study. , 1997, JAMA.

[43]  D. Richens,et al.  Vascular remodelling in intramyocardial resistance vessels in hypertensive human cardiac transplant recipients. , 1997, Heart.

[44]  B. Pollock,et al.  Paroxetine is a novel nitric oxide synthase inhibitor. , 1996, Psychopharmacology bulletin.

[45]  M. Mulvany,et al.  Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. , 1995, Hypertension.

[46]  K. Krishnan,et al.  Arteriosclerotic depression. , 1995, Medical hypotheses.

[47]  M. Åsberg,et al.  A New Depression Scale Designed to be Sensitive to Change , 1979, British Journal of Psychiatry.

[48]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.