Clinical Practice & Epidemiology in Mental Health




ISSN: 1745-0179 ― Volume 15, 2019

Quality of Life in Carotid Atherosclerosis: The Role of Co-morbid Mood Disorders



Maria Lecca1, Luca Saba2, Roberto Sanfilippo3, Elisa Pintus1, Michela Cadoni1, Federica Sancassiani1, Maria Francesca Moro1, Davide Craboledda3, Chiara Lo Giudice3, Roberto Montisci3, *
1 Department of Public Health and Clinical and Molecular Medicine and Center for Liaison Psychiatry and Psychoso-mathics, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari, Italy
2 Department of Radiology, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari, Italy
3 Department of Surgical Sciences, Università di Cagliari, Italy

Abstract

Introduction/Objective:

To study in severe carotid atherosclerosis (CA): the frequency of mood disorders (MD); the impairment of quality of life (QoL); the role of co-morbid MD in such impairment.

Methods:

Case-control study. Cases: consecutive in-patients with CA (stenosis ≥ 50%). Controls: subjects with no diagnosis of CA randomized from a database of a community survey. Psychiatric diagnosis according to DSM-IV made by clinicians and semi-structured interview, QoL measured by the Short Form Health Survey (SF-12).

Results:

This is the first study on comorbidity on CA disease and MD in which psychiatric diagnoses are conducted by clinicians according to DSM-IV diagnostic criteria. Major Depressive Disorder (MDD) (17.4% vs 2.72%, P <0.0001) but not Bipolar Disorders (BD) (4.3% vs 0.5%, P = 0.99) was higher in cases (N=46) than in controls (N= 184). SF-12 scores in cases were lower than in controls (30.56±8.12 vs 36.81±6:40; p <0.001) with QoL comparable to serious chronic diseases of the central nervous system. The burden of a concomitant MDD or BD amplifies QoL impairment.

Conclusion:

Comorbid MD aggravates the impairment of QoL in CA. Unlike autoimmune diseases or degenerative diseases of the Central Nervous System, CA shows a strong risk of MDD than BD.

Keywords: Bipolar disorder, carotid atherosclerosis, major depressive disorder, mood disorders, quality of life.


Article Information


Identifiers and Pagination:

Year: 2016
Volume: 12
First Page: 1
Last Page: 8
Publisher Id: CPEMH-12-1
DOI: 10.2174/1745017901612010001

Article History:

Received Date: 7/5/2015
Revision Received Date: 20/5/2015
Acceptance Date: 20/5/2015
Electronic publication date: 8/3/2016
Collection year: 2016

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© Lecca et al.; Licensee Bentham Open.

open-access license: This is an open access articles licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided that the work is properly cited.


* Address correspondence to this author at the Department of Surgical Sciences, Università di Cagliari, SS554, Bivio Sestu, 09142 Monserrato CA, Italy; Tel: +39 0706753161; E-mail: roberto.montisci@iol.it




INTRODUCTION

Carotid atherosclerosis is a leading public health issue. The atherosclerotic disease has been the first cause of death and morbidity in developed countries for the past decades, while recently the traditional risk factors for atherosclerotic and cardiovascular diseases have increased also in some developing countries like China and India. It is estimated that by 2020 cardiovascular diseases will be the major causes of morbidity and mortality also in most developing nations around the world [1Celermajer DS, Chow CK, Marijon E, Anstey NM, Woo KS. Cardiovascular Disease in the Developing World Prevalences, Patterns, and the Potential of Early Disease Detection. J Am Coll Cardiol 2012; 60(14): 1207-16.
[http://dx.doi.org/10.1016/j.jacc.2012.03.074]
]. Carotid atherosclerosis is a determinant of acute cerebrovascular events - e.g. stroke - and of early cognitive impairment [2Lloyd-Jones D, Adams RJ, Brown TM, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 2010; 121(7): 948-54.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.192666]
]. The incidence of stroke in the US is about 800,000 identified events each year [3Carta MG, Pala AN, Finco G, Musu M, Moro MF. Depression and cerebrovascular disease: could vortioxetine represent a valid treatment option? Clin Pract Epidemol Ment Health 2015; 11: 144-9.
[http://dx.doi.org/10.2174/1745017901511010144]
, 4Brott TG, Halperin JL, Abbara S, et al. ASA/ACCF/ AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/ SVS guideline on the management of patients with extracranial carotid and vertebral artery disease. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. Circulation 2011; 124(4): e54-e130.].

Approximately one out of 10 subjects over 70 years of age in the community presents with Carotid Stenosis. Many of them are apparently asymptomatic, in the sense that these cases were not diagnosed for cardiovascular disease or acute vascular events [5de Weerd M, Greving JP, Hedblad B, et al. Prediction of asymptomatic carotid artery stenosis in the general population: identification of high-risk groups. Stroke 2014; 45(8): 2366-71.
[http://dx.doi.org/10.1161/STROKEAHA.114.005145]
]; prevalence is twofold in subjects at risk [6Vallina-Victorero M, Vaquero F, Alvarez A, Ramos MJ, Vicente M, Alvarez J. Carotid bifurcation atherosclerosis in the over-65s: a prevalence study. J Cardiovasc Surg (Torino) 2008; 49(2): 207-11.]. Elderly age, male sex, history of vascular disease, hypertension, hypercholesterolemia, metabolic diseases and diabetes mellitus, and history of smoking have been identified as predictors of atherosclerosis [7de Weerd M, Greving JP, Hedblad B, et al. Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant datameta-analysis. Stroke 2010; 41(6): 1294-7.
[http://dx.doi.org/10.1161/STROKEAHA.110.581058]
]. This means that adequate preventive measures could be implemented and, in the caseof already manifested and identified significative stenosis, an appropriate intervention could prevent cerebral vascular attacks and stroke. In fact there are now standardized and safe enough methods to treat carotid stenosis: for many years the gold standard has been a surgical treatment with carotid endarterectomy (CEA), sided in the past two decades by endovascular stenting of carotid lesions (CAS), a valid alternative [8Morr S, Lin N, Siddiqui AH. Carotid artery stenting: current and emerging options. Med Devices (Auckl) 2014; 7: 343-55. [Published online 2014 October 20]., 9Gargiulo G, Tortora F, Cirillo M, et al. Unexpected preserved brain perfusion imaging despite severe and diffuse atherosclerosis of supra-aortic trunks. Cardiovasc J Afr 2013; 23(3): 214-14.]. Both treatments have shown similar effectiveness [10Brott TG, Hobson RW II, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010; 363(1): 11-23.
[http://dx.doi.org/10.1056/NEJMoa0912321]
].

Prevention programs have encountered implementation difficulties and the appropriate surgical intervention is not well accepted by patients yet [11Constantinou J, Jayia P, Hamilton G. Best evidence for medical therapy for carotid artery stenosis. J Vasc Surg 2013; 58(4): 1129-39.
[http://dx.doi.org/10.1016/j.jvs.2013.06.085]
]. A better assessment of the damage caused by carotid atherosclerosis to the quality of life of people suffering from it could be useful to estimate the weight and the importance of appropriate prevention programs.

Another remarkable aspect requiring clarification is the role of comorbid depressive and mood disorders in treatment compliance and in the impairment of quality of life. Around 20% of patients with stroke were found comorbid with depression [12Hadidi N, Treat-Jacobson DJ, Lindquist R. Poststroke depression and functional outcome: a critical review of literature. Heart Lung 2009; 38: 151-62.
[http://dx.doi.org/10.1016/j.hrtlng.2008.05.002]
]. However all research on comorbidity of vascular (and cerebrovascular) diseases and depressive disorders published to date for the identification of cases of depression have adopted a questionnaire like the Center for Epidemiologic Studies Depression Scale (CES-D) [13Roberts RE. Reliability of the CES-D Scale in different ethnic contexts. Psychiatry Res 1980; 2(2): 125-34.
[http://dx.doi.org/10.1016/0165-1781(80)90069-4]
] and not a structured clinical interview. The latter is considered the best method by the international standards of research in psychiatry [14Tiemeier H, van Dijck W, Hofman A, Witteman JC, Stijnen T, Breteler MM. Relationship between atherosclerosis and late-life depression: the Rotterdam Study. Arch Gen Psychiatry 2004; 61(4): 369-76.
[http://dx.doi.org/10.1001/archpsyc.61.4.369]
-20Lee YH, Shin MH, Choi JS, et al. Gender Differences in the Association between Depressive Symptoms and Carotid Atherosclerosis among Middle-Aged and Older Koreans: The Namwon Study. J Korean Med Sci 2014; 29(11): 1507-13.
[http://dx.doi.org/10.3346/jkms.2014.29.11.1507]
].

A correct estimate of such comorbidity is a critical issue, because some researchers have found that concomitant depression is a determinant of poorer clinical outcomes, mortality, and risk of functional disabilities [21Whooley MA, De JP, Vittinghoff E, et al. Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease. JAMA 2008; 300: 2379-88.
[http://dx.doi.org/10.1001/jama.2008.711]
]. Coherently an effective treatment of depression was found to be associated with a better course of coronary heart disease, patient’s adherence to interventions, and a decrease in acute events [22Vieweg WV, Julius DA, Fernandez A, et al. Treatment of depression in patients with coronary heart disease. Am J Med 2006; 119(7): 567-73.
[http://dx.doi.org/10.1016/j.amjmed.2006.02.037]
].

Evidence shows that the co-morbidity between depression and atherosclerosis can occur because people with depression have a high risk of developing atherosclerosis and, vice versa, because people with atherosclerosis - and with neuro-vascular diseases in particular - are at risk of depression [23Sneed JR, Culang-Reinlieb ME. The vascular depression hypothesis: An update. Am J Geriatr Psychiatry 2011; 19(2): 99-103.
[http://dx.doi.org/10.1097/JGP.0b013e318202fc8a]
]. A specific subtype of depression - called vascular depression - is characterized by: 1) onset in late life; 2) hyperintensities at brain Magnetic Resonance Imaging (MRI); 3) great neuropsychological impairment; 4) poor response to antidepressants especially when brain damage is associated with deficits in executive functioning [23Sneed JR, Culang-Reinlieb ME. The vascular depression hypothesis: An update. Am J Geriatr Psychiatry 2011; 19(2): 99-103.
[http://dx.doi.org/10.1097/JGP.0b013e318202fc8a]
, 24Alexopoulos GS, Kiosses DN, Choi SJ, et al. Frontal white matter microstructure and treatment response of late-life depression: a preliminary study. Am J Psychiatry 2002; 159: 1929-32.
[http://dx.doi.org/10.1176/appi.ajp.159.11.1929]
]. Despite the lively debate stimulated by this new diagnosis, so far researchers have not made an agreement on the diagnostic criteria of Vascular Depression. This concept is nevertheless an indicator of how the two disorders may be influencing their respective evolutionary paths [23Sneed JR, Culang-Reinlieb ME. The vascular depression hypothesis: An update. Am J Geriatr Psychiatry 2011; 19(2): 99-103.
[http://dx.doi.org/10.1097/JGP.0b013e318202fc8a]
].

The purpose of this work is to study the items listed below through standardized psychiatric diagnosis conducted by means of semi-structured interviews carried out by clinicians and a case control design:

  1. The frequency of major depressive disorder and other mood disorders in severe carotid atherosclerosis and the risk compared to healthy controls;
  2. The impairment of quality of life in people with carotid atherosclerosis;
  3. The role played by mood disorders in the impairment of quality of life in people with carotid atherosclerosis.

METHODS

Design: Case-control Study

Subjects

Cases (Table 1) were inpatients with Carotid Atherosclerosis of the Thoracic and Vascular Surgery Clinic of the University Hospital of Cagliari, Italy, from July 2013 to May 2014.

The controls included subjects with no diagnosis of Carotid Atherosclerosis who were selected from a database used for an epidemiological survey in Italy [25Carta MG, Aguglia E, Bocchetta A, et al. The use of antidepressant drugs and the lifetime prevalence of major depressive disorders in Italy. Clin Pract Epidemol Ment Health 2010; 6: 94-100.
[http://dx.doi.org/10.2174/1745017901006010094]
]. The selection of sex- age- and residence-matched controls from the 3498-subject database followed a randomized block design. A block was created for each case that included all eligible ages (± 2 years) and sex-matched controls drawn from the database. Four individuals per block were extracted for each case and were automatically excluded from the remaining blocks.

Psychiatric Diagnosis

The “Advanced Neuropsychiatric Tools and Assessment Schedule” (ANTAS) is a semi-structured clinical interview derived from the Structured Clinical Interview for DSM Disorders, non-patient version (SCID/NP-DSM-IV). It allows detecting and diagnosing psychiatric disorders [26First M, Spitzer R, Gibbon M, Williams J. Structured clinical interview for DSM-IV axis I disorders, research version, non-patient edition (SCID-I/ NP). New York: Biometrics Research, New York State Psychiatric Institute 1997.]. The validity and reliability of the diagnoses derived from the ANTAS were tested against SCID. Agreement with SCID was found with mean Cohen’s K = 0.85 [25Carta MG, Aguglia E, Bocchetta A, et al. The use of antidepressant drugs and the lifetime prevalence of major depressive disorders in Italy. Clin Pract Epidemol Ment Health 2010; 6: 94-100.
[http://dx.doi.org/10.2174/1745017901006010094]
]. The interviews were carried out by clinicians with at least of experience in psychiatry. Bipolar Spectrum Diosrders were screened by means of the Mood Disorder Questionnaire, Italian version [27Hardoy MC, Cadeddu M, Murru A, et al. Validation of the Italian version of the “Mood Disorder Questionnaire” for the screening of bipolar disorders. Clin Pract Epidemol Ment Health 2005; 1: 8.
[http://dx.doi.org/10.1186/1745-0179-1-8]
].

Table 1

Demographic characteristics of the study sample.




Diagnosis of Carotid Atherosclerosis

The diagnosis of carotid stenosis in the selected cases was performed through clinical examination, including Duplex ultrasound scanning of the epi-aortic trunks and Contrast Enhancement Computed Tomography (CECT) of the neck [28Saba L, Anzidei M, Sanfilippo R, et al. Imaging of the carotid artery. Atherosclerosis 2012; 220(2): 294-309.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.08.048]
]. We included subjects with documented stenosis ≥ 50%, using ECST criteria. In controls, the presence of Carotid Atherosclerosis was excluded after a clinical interview and anamnesis, subjects with history of severe vascular disease, severe hypertension and diabetes mellitus were also excluded from controls.

Measure of Quality of Life

In both cases and controls the subject’s perception of their quality of life was measured by means of the Short Form Health Survey (SF-12) [29Ware J Jr, Kosinski M, Keller SD. 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996; 34(3): 220-33.
[http://dx.doi.org/10.1097/00005650-199603000-00003]
]. The SF-12 is widely used tool internationally; it measures the perception of quality of life according to specific dimensions: physical activity, health problems inducing limitation of physical activities and roles, emotional status, pain, general health, vitality, effectiveness of the social network, and mental health. The period of reference for the scoring is one month prior to evaluation. Higher scores on the SF-12 are associated with a higher quality of life.

Table 2

Quality of life and mood disorders in cases and controls.




Analysis of Data and Measure of Attributable Burden in Worsening QoL

Comparison between means and standard deviations of SF-12 scores and other numerical data in the sample was carried out by means of ANOVA one-way statistics. According to previous published papers [30Carta MG, Preti A, Moro MF, et al. Eating disorders as a public health issue: Prevalence and attributable impairment of quality of life in an Italian community sample. Int Rev Psychiatry 2014; 26(4): 486-92.
[http://dx.doi.org/10.3109/09540261.2014.927753]
, 31Carta MG, Moro MF, Lorefice L, et al. Multiple sclerosis and bipolar disorders: The burden of comorbidity and its consequences on quality of life. J Affect Disord 2014; 167C: 192-7.
[http://dx.doi.org/10.1016/j.jad.2014.05.024]
] “Attributable Burden in Worsening QoL” means the difference between the SF-12 score of cases with Carotid Atherosclerosis and the SF-12 score of an age- and sex-matched sample without the disorder and drawn from the Italian database community survey [25Carta MG, Aguglia E, Bocchetta A, et al. The use of antidepressant drugs and the lifetime prevalence of major depressive disorders in Italy. Clin Pract Epidemol Ment Health 2010; 6: 94-100.
[http://dx.doi.org/10.2174/1745017901006010094]
]. A comparison on “Attributable Burden in Worsening QoL” was carried out comparing Carotid Athrosclerosis scores with other impairing health condition measures in studies that had drawn their controls from the same data base used in the preset study for controls, and where all cases were consecutive cases referring to units of the same University Hospital in the same city [30Carta MG, Preti A, Moro MF, et al. Eating disorders as a public health issue: Prevalence and attributable impairment of quality of life in an Italian community sample. Int Rev Psychiatry 2014; 26(4): 486-92.
[http://dx.doi.org/10.3109/09540261.2014.927753]
-34Carta MG, Aguglia E, Caraci F, et al. Quality of life and urban / rural living: preliminary results of a community survey in Italy. Clin Pract Epidemol Ment Health 2012; 8: 169-74.
[http://dx.doi.org/10.2174/1745017901208010169]
].

Ethical Aspects

The community survey and the program of a series of case controls on databank-based studies for controls were approved by the ethical committee of the Italian National Health Institute (Rome). This study protocol was approved by the independent ethical committee of the Azienda Ospedaliero Universitaria of Cagliari, Italy. An informed consent form was signed by each candidate. The study did not imply any change of the scheduled treatment for patients, which is defined according to the clinical judgment and international guidelines and by the patients’ decision to accept the treatment or not.

RESULTS

The sample of this research (see Table 1) consisted of 46 patients with carotid stenosis; it was composed of 30 men (65.2%) and 16 women (34.8%). It included 8 (17.39%) patients with Transitory Ischemic Attack, 4 (8.70%) with slight Stroke, 3 (6.52%) with a history of "drop-attack", and 31 (67.39%) with asymptomatic carotid disease.

The control group consisted of 184 subjects without a diagnosis of carotid stenosis, selected with the above-described matching technique. This technique creates a sample of controls that is perfectly homogeneous with the study cases in terms of gender and age variables.

Table 3

Burden Attributable to Carotid Atherosclerosis in worsening quality of life and comparison with other disease (studies were carried out with controls drawn from the same community study data bank, and cases were consecutive ones in wards of the same University Hospital).




Cases show a lifetime prevalence of manic/hypomanic episodes measured as positive at the screening (MDQ score> 7) and higher than in controls (13.0% vs 2.76% P = 0.003). Regarding the prevalence of Bipolar Disorder (BP 1/BP 2 according to DSM-IV) the difference between cases and controls did not reach statistical significance (4.3% vs 0.5%, P = 0.99) (Table 2).

The lifetime prevalence of Major Depressive Disorder, diagnosed according to DSM-IV criteria, was higher in cases than in controls (17.4% vs 2.72%, P <0.0001). Among cases, out of the six patients with co-morbid major depressive disorder four had had onset after the age of 60 (8.7%) as against one in the control group (0.5%).

The mean scores of SF12 in patients with carotid atherosclerosis (cases) were significantly lower than those of healthy controls (30.56 ± 8:12 vs 36.81 ± 6:40; p <0.001) (see Table 2).

The burden attributable to carotid atherosclerosis in worsening quality of life is comparable to that of serious chronic diseases of the central nervous system such as Wilson’s disease and Multiple Sclerosis, and with severe psychiatric disorders like Major Depressive Disorder (Table 3). The burden of a concomitant major mood disorder (MDD or BD) amplifies quality of life impairment, patients with carotid atherosclerosis in comorbidity with a major mood disorder have a greater impairment than those who have major depression (DF 1,293,294; F=9.16 P=0.003) end ever than those with Wilson's disease (DF 1,31,32; F=8.49 p=0.003 (Table 3).

DISCUSSION

Our study found that carotid atherosclerosis is comorbid (lifetime) with Major Depressive Disorder in about 1 case out 5 with an approximate risk is about 6 times higher than the standardized sample without atherosclerosis disease. This result is consistent with the prevalence of depression among patients with cerebrovascular disease or stroke, which oscillates between 15 and 25% [12Hadidi N, Treat-Jacobson DJ, Lindquist R. Poststroke depression and functional outcome: a critical review of literature. Heart Lung 2009; 38: 151-62.
[http://dx.doi.org/10.1016/j.hrtlng.2008.05.002]
]. As underlined in the introduction of this study we must consider that the research works carried out so far have adopted a questionnaire as the CES-D for the identification of cases of depression; they did not use structured clinical interviews carried out by clinicians. The latter is considered the best method available for psychiatric diagnosis in clinical patients ad in community epidemiological samples [35Carta MG, Carpiniello B, Kovess V, Porcedda R, Zedda A, Rudas N. Lifetime prevalence of major depression and dystymia. Eur Neuropsychopharmacol 1995; 5(Suppl.): 103-7.
[http://dx.doi.org/10.1016/0924-977X(95)00036-O]
, 36Hardoy MC, Carta MG, Marci AR, et al. Exposure to aircraft noise and risk of psychiatric disorder: the Elmas survey. Soc Psychiatry Psychiatr Epidemiol 2005; 40(1): 24-6.
[http://dx.doi.org/10.1007/s00127-005-0837-x]
]. The use of this method in addition to screening questionnaires allows identifying “cases” according to international classification systems as DSM-IV. The use of CES-D was common of those studies that have found an association between carotid disease and depressive symptoms [15Haas DC, Davidson KW, Schwartz DJ, et al. Depressive symptoms are independently predictive of carotid atherosclerosis. Am J Cardiol 2005; 95(4): 547-50.
[http://dx.doi.org/10.1016/j.amjcard.2004.10.032]
-20Lee YH, Shin MH, Choi JS, et al. Gender Differences in the Association between Depressive Symptoms and Carotid Atherosclerosis among Middle-Aged and Older Koreans: The Namwon Study. J Korean Med Sci 2014; 29(11): 1507-13.
[http://dx.doi.org/10.3346/jkms.2014.29.11.1507]
] as well as in the famous "Rotterdam Study" that did not find this association [14Tiemeier H, van Dijck W, Hofman A, Witteman JC, Stijnen T, Breteler MM. Relationship between atherosclerosis and late-life depression: the Rotterdam Study. Arch Gen Psychiatry 2004; 61(4): 369-76.
[http://dx.doi.org/10.1001/archpsyc.61.4.369]
]. This is therefore the first study on comorbidity between mood disorders and carotid vascular disease in which psychiatric diagnoses are conducted by clinicians, through a semi-structured interview and in accordance with international diagnostic criteria. It is also the first study that allows a better approximation of the risk by means of a case-control model.

Our sample did not show a risk of DSM-IV Bipolar I or II Disorder that would be similar to the risk found for DSM-IV MDD, although patients with hypomanic episodes attributable to the bipolar spectrum - as measured with an instrument like the MDQ – tend to have a greater risk in the presence of carotid atherosclerosis. A vast literature on the association between vascular heart disease and bipolar disorder is available, often with a positive association ([37Fiedorowicz JG, Solomon DA, Endicott J, et al. Manic/hypomanic symptom burden and cardiovascular mortality in bipolar disorder. Psychosom Med 2009; 71: 598-606.
[http://dx.doi.org/10.1097/PSY.0b013e3181acee26]
-39Fiedorowicz JG, Coryell WH, Rice JP, Warren LL, Haynes WG. Vasculopathy related to manic/hypomanic symptom burden and first-generation antipsychotics in a sub-sample from the collaborative depression study. Psychother Psychosom 2012; 81: 235-43.
[http://dx.doi.org/10.1159/000334779]
], and sometimes with no association at all [40Chiarani F, Tramontina JF, Ceresér KM, et al. Homocysteine and other markers of cardiovascular risk during a manic episode in patients with bipolar disorder. Rev Bras Psiquiatr 2013; 35(2): 157-60.
[http://dx.doi.org/10.1590/1516-4446-2012-0797]
]. Data in the literature related to vascular brain diseases are rare, but an association was proved by one study at least [41Subramaniam H, Dennis MS, Byrne EJ. The role of vascular risk factors in late onset bipolar disorder. Int J Geriatr Psychiatry 2007; 22(8): 733-7.
[http://dx.doi.org/10.1002/gps.1730]
]. However the most important determinants of vascular disease such as diabetes, alcohol abuse and smoking were found more frequently in bipolar patients than in healthy controls [42Schoepf D, Heun R. Bipolar disorder and comorbidity: increased prevalence and increased relevance of comorbidity for hospital-based mortality during a 12.5-year observation period in general hospital admissions. J Affect Disord 2014; 169: 170-8.
[http://dx.doi.org/10.1016/j.jad.2014.08.025]
]. The lack of homogeneity among the results and the fact that an association between atherosclerotic disease and bipolar disorder was not always found despite an increased presence of hypothetical risk factors in the studies, as in our case, could be explained by bipolar disorders’ developing only belatedly vascular lesions [39Fiedorowicz JG, Coryell WH, Rice JP, Warren LL, Haynes WG. Vasculopathy related to manic/hypomanic symptom burden and first-generation antipsychotics in a sub-sample from the collaborative depression study. Psychother Psychosom 2012; 81: 235-43.
[http://dx.doi.org/10.1159/000334779]
]. Moreover the association between vascular and cerebrovascular disease and bipolar disorder would drastically shorten life expectancy, generating a bias in cross-sectional studies [41Subramaniam H, Dennis MS, Byrne EJ. The role of vascular risk factors in late onset bipolar disorder. Int J Geriatr Psychiatry 2007; 22(8): 733-7.
[http://dx.doi.org/10.1002/gps.1730]
]. An alternative hypothesis is that the Bipolar Spectrum Disorders associated with vascular disease can present with unusual symptoms. Our study found an association with the broad area of the bipolar spectrum defined by positivity to MDQ, and not with the diagnosis of bipolar disorder according to DSM-IV. This might be supportive of the second hypothesis.

The finding that carotid disease has a higher risk of major depression than the risk of bipolar disorders is opposite to the finding on autoimmune diseases of the central nervous system like Multiple Sclerosis [43Carta MG, Moro MF, Lorefice L, et al. The risk of Bipolar Disorders in Multiple Sclerosis. J Affect Disord 2014; 155: 255-60. c
[http://dx.doi.org/10.1016/j.jad.2013.11.008]
], or degenerative diseases with a genetic basis like Wilson's disease [32Carta MG, Sorbello O, Moro MF, et al. Bipolar disorders and Wilson's disease. BMC Psychiatry 2012; 12(1): 52.
[http://dx.doi.org/10.1186/1471-244X-12-52]
].

The measure of the subjective perception of quality of life in a done disorder is a construct of relevance in todays clinical practice and for public health issues, the subjective quality of life is adopted as a measure of outcome in diseases having a strong impact on the daily life of patients [44Mantovani G, Astara G, Lampis B, et al. Evaluation by multidimensional instruments of health related quality of life of elderly cancer patients. Support Cancer Care 1996; 4: 129-40.
[http://dx.doi.org/10.1007/BF01845762]
, 45Mantovani G, Astara G, Lampis B, et al. Impact of psychosocial interventions on quality of life of elderly cancer patients. Psychooncology 1996; 5: 127-35.
[http://dx.doi.org/10.1002/(SICI)1099-1611(199606)5:2<127::AID-PON220>3.0.CO;2-L]
]. Our study has detected that carotid atherosclerosis compromises quality of life when compared to people who do not have it, and its burden is comparable to that of serious chronic diseases of the central nervous system such as the aforementioned Wilson’s disease and Multiple Sclerosis, and with severe psychiatric disorders like Major Depressive Disorder (Table 3). The burden of a concomitant major mood disorder (MDD or BD) amplifies quality of life impairment to the extent that people with carotid atherosclerosis in comorbidity with a major mood disorder have a greater impairment, at a statistically significant level, than those who have major depression only or a severe degenerative disease such as Wilson's disease. Only against Multiple Sclerosis does the difference reach the limits of statistical significance, although carotid atherosclerosis shows a greater impairment of quality of life still.

LIMITATIONS

The diagnosis of Carotid Atherosclerosis in the selected cases was made by clinicians by means of Doppler ultrasound scanning and CECT scan. In contrast, community controls reported to the interviewing clinicians a diagnosis of Carotid Atherosclerosis if they were aware of such a problem even if subjects with history of severe vascular disease, severe hypertension and diabetes mellitus were also excluded from controls

The risk of false negatives in the group of controls thus quite exists, although the hypothetical false negatives among the control group would reinforce the null hypothesis of no association between Mood Disorders and Carotid Atherosclerosis, and decrease the Attributable Burden to Carotid Atheroscleris in impairing quality of life. This limitation therefore does not invalidate the results of the study, but we may only speculate that the association found may be rounded downward.

On the other hand the case-control design does not allow excluding the effect of Berkson’s bias.

CONCLUSION

Mood Disorders are associated with the carotid vascular disease with a tight fit. Unlike autoimmune diseases or degenerative diseases of the Central Nervous System, carotid atherosclerosis shows a higher risk of MDD than of BD.

The combination with a mood disorder aggravates the impairment of quality of life to the extent that the attributable burden to these diseases in comorbidity is higher than the impairment caused by major depression or Wilsons’s disease only.

CONFLICT OF INTEREST

The authors confirm that this article content has no conflict of interest.

ACKNOWLEDGEMENTS

We are grateful to all the patients of the University Hospital of Cagliari for participating in the research. The research was supported by the University of Cagliari.

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