Cardiometabolic risk factors in patients referred to depression nurse case managers HANNU KOPONEN, HANNU KAUTIAINEN, ESA LEPPÄNEN, PEKKA MÄNTYSELKÄ, MAUNO VANHALA
Koponen H, Kautiainen H, Leppänen E, Mäntyselkä P, Vanhala M. Cardiometabolic risk factors in patients referred to depression nurse case managers. Nord J Psychiatry 2015;69:262–267. Background: Disturbances in lipid and glucose metabolism are associated with depressive symptoms, and may increase suicidal behavior. Aims: To investigate the prevalence of cardiometabolic risk factors, severity of depressive symptoms, and suicidal thoughts and previous attempts in patients referred to depression nurse case managers. Methods: Blood cholesterol, triglyceride and glucose levels, depressive symptoms and suicidality were studied in 706 depressed participants and 426 controls. In addition, we compared the Beck Depression Inventory (BDI) with a diagnostic interview. Results: 448 (63%) of the patients scoring ⱖ 10 on BDI had major depression or dysthymic disorder, 258 had an anxiety or alcohol use disorder, 137 (19%) had two or more diagnoses in the Mini-International Neuropsychiatric Interview. Suicidal thoughts (49%) and previous suicide attempts (16%) were more common in patients with depressive disorders. Patients diagnosed with depression had highest BDI scores and higher blood glucose levels measured at baseline and at 2 h in the oral glucose tolerance test (OGTT). Both patient groups also had higher triglyceride levels compared with the controls. In addition, metabolic syndrome and type 2 diabetes were most common among the depressed participants. In the whole study population, levels of low-density lipoprotein-cholesterol as well as baseline and 2-h blood glucose in OGTT were higher among patients with suicidal behavior. Conclusions: Cardiometabolic risk factors and metabolic syndrome are common in patients with depression, and in patients with anxiety and alcohol use disorders. The results imply that disturbance in glucose metabolism may be associated with suicidal thoughts and previous attempts. • Beck Depression Inventory, Cardiometabolic risk factors, Depression, Metabolic syndrome, Suicidal behavior. Hannu Koponen, Professor of Old Age Psychiatry, Department of Psychiatry, Institute of Clinical Medicine, University of Helsinki, PO Box 22, FIN-00014 Helsinki, Finland, E-mail: [email protected]; Accepted 30 September 2014.
D
epression and metabolic syndrome have become increasingly more common in the population over the past 10 years and together they constitute a major health problem (1, 2). Metabolic syndrome is a cluster of type 2 diabetes (T2D) and cardiovascular disease (CVD) risk factors, which can be ascertained for example with the aid of the US National Cholesterol Education Program—Adult Treatment Panel III or International Diabetes Federation criteria (3, 4). Previous crosssectional studies have found metabolic syndrome to be more common among depressive patients compared with general population (5–7). Long-term studies looking at the relationship between depression and metabolic syndrome have revealed a two-way relationship (7–9): depressive patients were found to have about a two-fold risk of metabolic syndrome, whereas metabolic syndrome was associated with about a two-fold risk of depression.
© 2014 Informa Healthcare
Previous studies also suggest that depression may be a risk factor for several components of metabolic syndrome. Depression is associated with a tendency to dyslipidemias and visceral fat accumulation (10). Depressive patients also frequently have insulin resistance, which may resolve after recovery from depression (11, 12). A recent meta-analysis has also shown that the presence of depression increases the risk for diabetes and arterial hypertension (13). Conversely, obesity, T2D, arterial hypertension and dyslipidemias are risk factors for depression (14–19). Biological mechanisms that may explain the association between depression and metabolic syndrome include autonomous nervous system and monoamine neurotransmission dysfunction, cytokine-mediated inflammatory reaction (20–22) and overactivity of the hypothalamic– pituitary–adrenal (HPA) axis (23–25). In more advanced DOI: 10.3109/08039488.2014.972451
CVD RISK
age, focal vascular damage and white matter lesions may also contribute to the development of depression (26). Psychological factors may also play a significant role, as metabolic syndrome is associated with a passive life attitude and negative self-image, both of which may contribute to the development of depression (27, 28). Besides predisposing to depression, disturbances in glucose and lipid metabolism may also be associated with impulsiveness and suicidality (19, 29–31). However, previous studies have reported both low and high cholesterol levels in depressed patients with increased impulsivity and suicidal behavior (30, 32–34). Due to this inconsistency of data, we decided to investigate in a case–control study setting blood glucose and lipid levels and suicidal behavior in patients referred to depression nurse case managers. We also examined the diagnostic accuracy of the Beck Depression Inventory (BDI; 35) in identifying depression subsequently confirmed with diagnostic interview. In order to obtain a representative sample with both mild and more severe depressive participants, self-referred patients were included together with general practitioner referred patients. The lower age limit of 35 years was chosen to obtain a stable study population also facilitating a more prolonged follow-up.
Material and methods New patients ⱖ 35 years of age, who were referred by themselves or by general practitioners to depression nurse case managers in 2008–2009 due to depressive symptoms and scoring ⱖ 10 in the BDI were enrolled in this study. The study was conducted in municipalities belonging to the Central Finland Hospital District (the Finnish Depression and Metabolic Syndrome in Adults study, FDMSA) with a catchment area of 274,000 inhabitants. The number of patients was 706. Enrolment was based on written and oral patient information and a written consent was obtained before any study procedures. The study protocol was approved by the Ethics Committee of Central Finland Hospital District. All participants filled out a standard questionnaire containing questions about previously diagnosed somatic disorders, use of medications including antidepressants and hormone replacement therapy in females. In addition, data were collected on smoking habits, use of alcohol (number of drinks per week) and physical activity (number of ⬎ 30-min exercise sessions per week). The severity of depressive symptoms was measured by the 21-item BDI, which was completed by the participants, and the psychiatric diagnosis was confirmed with a diagnostic interview (Mini-International Neuropsychiatric Interview; M.I.N.I.; 36) delivered by a trained study nurse. A group of 426 middle-aged (ⱖ 35 years) persons was selected as controls among residents in the participating municipalities using random sampling. All NORD J PSYCHIATRY·VOL 69 NO 4·2015
FACTORS AND DEPRESSION
subjects in the control group had a BDI score below 10 and had no psychiatric diagnosis or current depressive symptoms and used no psychoactive medications. Fasting blood samples including the glucose and lipid levels were drawn between 08:00 and 11:00 h after 12 h of fasting, after which an oral glucose tolerance test (OGTT) with 75 g of glucose was carried out. The physical examination included weight, height, waist circumference and blood pressure taken on the same study visit. Height and weight were measured in light clothing to the nearest 0.5 cm and 0.1 kg, respectively. The waist circumference was measured to the nearest 1.0 cm at the midpoint between the lateral iliac crest and lowest rib. Trained nurses measured blood pressure twice with a mercury sphygmomanometer with subjects in sitting position after a 15-min rest. In the evaluation of metabolic syndrome, we used the modified NCEPATPIII criteria with the 100 mg/dl blood glucose cutoff point (37).
Statistical analysis The results are presented using means, standard deviation and frequency distributions. Statistical significance between groups was tested by analysis of variance (ANOVA), Kruskal–Wallis test and chi-square test, and adjusted significance testing with logistic regression analysis.
Results Based on the M.I.N.I. interview used to confirm diagnosis, 448 out of the 706 participants were diagnosed with depression (major depression or dysthymic disorder), 258 patients had an anxiety or alcohol use disorder; 137 (19.4%) of the patients referred to nurse case managers received two or more diagnoses, but were included into the study analyses. The diagnoses based on diagnostic interview for these 706 patients are shown in Table 1. The patients were subdivided according to the M.I.N.I. diagnosis into two groups with either depressive disorder or some other, i.e. some anxiety or alcohol use disorder. In the study population, 309 participants used antidepressive medication, mostly selective serotonin reuptake inhibitors. Table 1. Diagnoses based on diagnostic interview (MiniInternational Neuropsychiatric Interview; M.I.N.I.). Disorder Depression Panic disorder Fear of social situations Obsessive–compulsive disorder Alcohol dependence Harmful alcohol use
Prevalence of the diagnosis in the study population 448 (63.4%) 163 (23.1%) 87 (12.3%) 20 (2.8%) 86 (12.2%) 39 (7.9%)
263
HANNU KOPONEN ET
AL.
The mean age of the participants in different subgroups ranged from 51 to 53 years. The proportion of patients over 65 years was highest in the subgroup with other psychiatric symptomatology (Table 2). Compared with controls and patients with other disorders, patients diagnosed with depression had highest BDI scores and higher blood glucose levels measured at baseline and at 2 h in the OGTT (Table 2). Both patient groups had higher triglyceride levels compared with the controls. In addition, metabolic syndrome and T2D were most common among the depressed participants (Table 2). Figure 1 shows the prevalence of metabolic syndrome in females (P ⬍ 0.001; age-adjusted) and males (P ⬍ 0.025; age-adjusted). According to the M.I.N.I. interview, suicidal thoughts were present in 278 patients, while 98 had a previous suicide attempt; both were most common in the group diagnosed with depression. When subdivided according to the presence or absence of suicidal behavior, patients with suicidal ideation or attempts had higher low-density lipoprotein (LDL)-cholesterol levels (3.20 mmol/l vs. 2.9 mmol/l among controls; P ⫽ 0.013) and higher P-glucose in OGTT (baseline 6.0 mmol/l vs. 5.6 mmol/l among controls; P ⫽ 0.02; the corresponding 2-h values
were 6.2 mmol/l and 5.9 mmol/l; P ⫽ 0.006). In the other cardiometabolic risk factors or body mass index, no differences were found. Alcohol use disorders were also more common among those with suicidal ideation or a previous suicide attempt than among controls (29% vs. 8%, P ⬍ 0.001).
Conclusion In our geographically representative outpatient study population, we observed that overweight and metabolic syndrome were more common among both in patient groups (i.e. with depression or other psychiatric diagnosis) referred to depression case managers, which is in line with previous results in patients with depressive or anxiety disorder (5–7, 38). However, actual CVDs, with the exception of hypertension, were rare in all study groups due to the comparatively low age of the study population as regards to the manifestation of the CVDs. The triglyceride levels were higher in both patient groups, which is in line with the findings of Kinder et al. (5) and Richter et al. (2), and may be linked to the activation of the HPA axis or inflammatory processes in patients with depressive or anxiety disorders (2).
Table 2. Groups taking part in Finnish Depression and Metabolic Syndrome in Adults (FDMSA) study.
Women, n (%) Age, mean⫾s Proportion of participants ⬎ 65 (n, %) BMI, mean⫾s Waist (cm) Men, mean⫾s Women, mean⫾s Blood pressure (mmHg) Systole, mean⫾s Diastole, mean⫾s Total cholesterol (mmol/l) , mean⫾s HDL-cholesterol (mmol/l) , mean⫾s LDL-cholesterol (mmol/l) , mean⫾s Triglyceride (mmol/l) , mean⫾s OGTT, baseline (0 h), P-glucose, mmol/l, mean⫾s OGTT, 2 h, B-glucose, mmol/l, mean⫾s BDI score, mean⫾s Suicidal ideation (M.I.N.I), n (%) Suicide attempt (M.I.N.I.), n (%) Metabolic syndrome (%) Hypertension, n (%) Coronary heart disease, n (%) Previous myocardial infarction, n (%) Previous stroke, n (%) Type 2 diabetes, n (%)
Controls (BDI ⬍ 10), n ⫽ 426
Patients with BDI ⱖ 10, but with other diagnosis than depression on M.I.N.I., n ⫽ 258
Depressive patients with BDI ⱖ 10 and depression on M.I.N.I., n ⫽ 448
P
254 (60) 53 (10) 57 (13) 26.8 (4.6)
191 (74) 53 (11) 44 (17) 27.9 (5.9)
313 (70) 51 (10) 44 (10) 28.1 (5.9)
⬍ 0.001 ⬍ 0.001 0.002 0.001
97 (12) 88 (13)
98 (12) 91 (15)
99 (13) 93 (15)
129 (16) 81 (10) 5.0 (0.9) 1.57 (0.42) 3.10 (0.82) 1.19 (0.65) 5.68 (1.00) 5.83 (1.75) 3.2 (2.7)
130 (16) 81 (10) 5.1 (1,0) 1.57 (0.45) 3.11 (0.84) 1.38 (1.64) 5.65 (0.87) 6.02 (1.82) 17.8 (6.4) 60 (23) 26 (10) 111 (45) 73 (28) 16 (6) 2 (1) 4 (2) 23 (9)
131 (16) 82 (11) 5.1 (1,0) 1.57 (0.48) 3.05 (0.93) 1.38 (0.85) 5.88 (1.45) 6.25 (2.50) 23.4 (8.2) 218 (49) 72 (16) 201 (49) 133 (30) 21 (5) 7 (2) 7 (2) 54 (12)
140 (34) 97 (23) 12 (3) 4 (1) 7 (2) 13 (3)
0.29 0.0037 0.20 0.33 0.58 0.99 0.69 0.016 0.014 0.020 ⬍ 0.001 ⬍ 0.001 0.027 ⬍ 0.001 0.057 0.10 0.56 0.99 ⬍ 0.001
Results in the table shown as means (standard deviation) and numbers (percentage). M.I.N.I., Mini-International Neuropsychiatric Interview; s, standard deviation; BMI, body mass index; HDL, high-density lipoprotein; LDL, low-density lipoprotein; OGTT, oral glucose tolerance test; BDI, Beck Depression Inventory.
264
NORD J PSYCHIATRY·VOL 69 NO 4·2015
CVD RISK 80
70
Female Male
NCEP present, %
60
50
40
30
20
10
0 Controls
Other
Depression
Fig. 1. Age-adjusted prevalence of National Cholesterol Education Program (NCEP)-diagnosed metabolic syndrome in controls and in patients suffering from depression or other psychiatric disorders.
Serum cholesterol has been suggested to reflect central nervous system serotonergic function and to participate in cognitive functioning as well as mood regulation (34). Low cholesterol level has also been linked to impulsiveness and risk of suicide in depressive patients (34). Previous findings have, however, been conflicting, as both low (30) and high cholesterol (32) levels have been associated with suicidal behavior in previous studies. In this study, we found higher LDL-cholesterol level in patients with suicidal behavior, which further suggests inconsistencies in the association between cholesterol levels and suicidal behavior. Some SSRIs, such as sertraline or paroxetine, may have negative effects on total and LDLcholesterol, and thus contribute to the observed higher LDL-cholesterol level. However, the most commonly used SSRI in Finland, citalopram, has neutral effects on the lipid profile (39), and thus the finding is not solely explained by the antidepressant medication. In addition, we found higher P-glucose in OGTT in patients with suicidal ideation and previous suicide attempts, which differ from the results of Batty et al. (19), who reported that diabetes but not raised blood glucose was a risk factor for completed suicide. The mechanism explaining the observed association is, however, obscure. The observed risk to suicidal behavior may at least be related depression itself or explained by the more common alcohol NORD J PSYCHIATRY·VOL 69 NO 4·2015
FACTORS AND DEPRESSION
dependence in the group of patients with suicidal ideation and/or suicide attempts (19, 40–42). The depression nurse case manager system has been implemented in Finland in order to improve the treatment results of depressive disorders. The recognition of depression is still problematic and several different assessment scales have been developed for identifying depressive symptoms. The most commonly used in both clinical work and research is the self-administered BDI. However, a BDI score of ⱖ 10 did not mean a definite diagnosis of depression in our study, as nearly 40% of the patients received another diagnosis, most often an anxiety or alcohol use disorder. This means that the diagnosis of patients scoring above the BDI cut-off of 10 should be confirmed by thorough clinical examination, and in cases of comorbidity, with a structured diagnostic interview. The diagnostic accuracy of BDI was similar in both genders. Suicidal ideation or previous suicide attempts identified by M.I.N.I. were equally frequent as in another Finnish study, i.e. the Vantaa Depression Study (43). The strengths of our study include a geographically representative sample of middle-aged and elderly subjects. In addition, we used a diagnostic interview besides of the self-rating of depressive symptoms. However, due to the cross-sectional design of our study, we cannot make inferences of causality, which is a limitation. In addition, only persons aged 35 or older were enrolled in the study, so the results cannot be generalized to younger age groups. The participants were referred to depression nurse case managers due to depressive symptoms, but we have no data on how long the symptoms have been present, which is also a limitation. An easy-to-use self-administered scale, such as the BDI, may aid in the identification of patients describing depressive symptoms, but in addition to systematic confirmation of clinical diagnosis, assessment of patients scoring above the cut-off must also involve evaluation of suicide risk. Overweight and metabolic syndrome were more common and the triglyceride levels were higher in the both patient groups as compared with the controls. Higher LDL-cholesterol and P-glucose levels were associated with suicidal behavior, suggesting that disturbances in glucose and cholesterol metabolism may be associated with suicidal thoughts and previous attempts. Acknowledgements—The authors would like to thank the depression nurse case managers who took part in the practical implementation of the FDMSA: Mari Alanko, Harri Back, Timo Hannula, Anu Holopainen, Ritva Häkkinen, Katja Johansson, Eija Kinnunen, Kaija Luoma, Hannele Niemi, Hillevi Peura, Inga Pöntiö, Kirsi Rouvinen, Tiina Silvennoinen and Marianne Vihtamäki; the FDMSA study nurses Anne Kirmanen, Reetta Oksanen and Olli Niemi and Pia Jauhiainen, scientific secretary of the study.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
265
HANNU KOPONEN ET
AL.
References 1. Koponen H, Jokelainen J, Keinänen-Kiukaanniemi S, Vanhala M. Depressive symptoms and 10-year risk for cardiovascular morbidity and mortality. World J Biol Psychiatry 2010;11:834–9. 2. Richter N, Juckel G, Assion H-J. Metabolic syndrome: A follow-up study of acute depressive inpatients. Eur Arch Psychiatry Clin Neurosci 2010;260:41–9. 3. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: 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). JAMA 2001;285:2486–97. 4. Alberti KGMM, Zimmet P, Shaw J, for the IDF Epidemiology Task Force Consensus Group. The metabolic syndrome—A new worldwide definition. Lancet 2005;366:1059–62. 5. Kinder LS, Carnethon MR, Palaniappan LP, King AC, Fortman SP. Depression and the metabolic syndrome in young adults: Findings from the third national health and nutrition examination survey. Psychosom Med 2004;66:316–22. 6. Heiskanen TH, Niskanen LK, Hintikka JJ, Koivumaa-Honkanen HT, Honkalampi KM, Haatainen KM et al. Metabolic syndrome and depression: A cross-sectional analysis. J Clin Psychiatry 2006;67:1422–7. 7. Räikkönen K, Matthews KA, Kuller LH. Depressive symptoms and stressful life events predict metabolic syndrome among middle-aged women. A comparison of World Health Organization, Adult Treatment Panel III and International Diabetes Foundation definitions. Diabetes Care 2007;30:872–7. 8. Koponen H, Jokelainen J, Keinänen-Kiukaanniemi S, Kumpusalo E, Vanhala M. Metabolic syndrome predisposes to depression. A population-based 7-year follow-up study. J Clin Psychiatry 2008;69:178–82. 9. Vanhala M, Jokelainen J, Keinänen-Kiukaanniemi S, Kumpusalo E, Koponen H. Depressive symptoms predispose females to metabolic syndrome. A 7-year follow-up study. Acta Psychiatr Scand 2009;119:137–42. 10. Weber-Hamann B, Werner M, Hentschel F, Bindeballe N, Lederbogen F, Deuschle M. Metabolic changes in elderly patients with major depression: Evidence for increased accumulation of visceral fat at follow-up. Psychoneuroendocrinology 2006;31:347–54. 11. Okamura F, Tashiro A, Utumi A, Imai T, Suchi T, Tamura D et al Insulin resistance in patients with depression and its changes during the clinical course of depression: Minimal model analysis. Metabolism 2000;49:1255–60. 12. Kan C, Silva N, Golden SH, Rajala U, Timonen M, Stahl D et al. systematic review and meta-analysis of the association between depression and insulin resistance. Diabetes Care 2013;36:480–9. 13. Knol MJ, Twos JWR, Beekman ATF, Heine RJ, Snoek FJ, Pouwer F. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia 2006;49:837–45. 14. Maes M, Smith R, Christophe A, Vandoolaeghe E, Van Gastel A, Neels H. Low serum high-density cholesterol (HDL-C) in major depression and depressed men with serious suicidal attempts: Relationship with immune-inflammatory markers. Acta Psychiatr Scand 1997;95:212–21. 15. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes. Diabetes Care 2001;24:1069–78. 16. Dixon JB, Dixon ME, O’Brien PE. Depression in association with severe obesity. Changes with weight loss. Arch Intern Med 2003;163:2058–65. 17. Plante GE. Depression and cardiovascular disease: A reciprocal relationship. Metabolism 2005;54 Suppl:45–8. 18. Deisenhammer EA, Lechner-Schoner T, Kemmler G, Ober A, Braidt E, Hinterhuber H. Serum lipids and risk factors for attempted suicide in patients with alcohol dependence. Alcohol Clin Exp Res 2006;30:460–5. 19. Batty GD, Kivimäki M, Park IS, Ha SJ. Diabetes and raised blood glucose as risk factors for future suicide: Cohort study of 1 234 927 Korean men and women. J Epidemiol Community Health 2012;66:650–2.
266
20. Dunn AJ, Swiergiel AH, de Beaurepaire R. Cytokines as mediators of depression: What can we learn from animal studies? Neurosci Biobehav Rev 2005;29:891–909. 21. Ovaskainen Y, Koponen H, Jokelainen J, Keinänen-Kiukaanniemi S, Kumpusalo E, Vanhala M. Depressive symptomatology is associated with decreased interleukin-1 beta and increased interleukin1 receptor antagonist levels in males. Psychiatry Res 2009;167:73–9. 22. Meyer T, Stanske B, Kochen MM, Cordes A, Yuksel I, Wachter R. et al., Serum levels of interleukin-6 and interleukin-10 in relation to depression scores in patients with cardiovascular risk factors. Behav Medicine 2011;37:105–12. 23. Brown ES, Varghese FP, McEwen BS. Association of depression with medical illness: Does cortisol play a role? Biol Psychiatry 2004;55:1–9. 24. Licht CMM, Vreeburg SA, van Reed Dorland AKB, Giltay EJ, Hookendijk WJG, DeRijk RH et al., Increased sympathetic and decreased parasympathetic activity rather than changes in hypothalamic–pituitary–adrenal axis activity is associated with metabolic abnormalities. J Clin Endocrinol Metabolism 2010;95:2458–66. 25. Alexopoulos GS, Morimoto SS. The inflammation hypothesis in geriatric depression. Int J Geriatr Psychiatry 2011;26:1109–18. 26. Taylor WD, Aizenstein HJ, Alexopoulos GS. The vascular depression hypothesis: Mechanisms linking vascular disease with depression. Mol Psychiatry Feb 2013 epub ahead of print (doi: 10.1038/MP.2013.20) 27. Vogelzangs N, Beekman AT, Boelhouwer IG, Bandinelli S, Milaneschi Y, Lerrucci L. Metabolic depression: A chronic depressive subtype? Findings from the InCHIANTI study of older persons. J Clin Psychiatry 2011;72:598–604. 28. Van Reedt Dortland AKB, Vreeburg SA, Giltay EJ, Licht CMM, Vogelzangs N, van Veen T et al impact of stress systems and lifestyle on dyslipidemia and obesity in anxiety and depression. Psychoneuroendocrinology 2013;38:209–18. 29. Golomb BA. Cholesterol and violence: Is there a connection? Ann Intern Med 1998;128:478–87. 30. Plana T, Gracia E, Mendez I, Pintor L, Lazaro L, Castro-Fornieles J. Total serum cholesterol levels and suicide attempts in child and adolescent psychiatric inpatients. Eur Child Adolesc Psychiatry 2010;19:615–9. 31. Löfman S, Hakko H, Mainio A, Timonen M, Räsänen P. Characteristics of suicide among diabetes patients: A population based study of suicide victims in Northern Finland. J Psychosom Res 2012;73:268–71. 32. Tanskanen A, Vartiainen E, Tuomilehto J, Viinamäki H, Lehtonen J, Puska P. High serum cholesterol and risk of suicide. Am J Psychiatry 2000;157:648–50. 33. Tedders SH, Fokong KD, McKenzie LE, Wesley C, Yu L, Zhang J. Low cholesterol is associated with depression among US household population. J Affect Disord 2011;135:115–21. 34. Troisi A. Low cholesterol is a risk factor for attentional impulsivity in patients with mood symptoms. Psychiatry Res 2011;188:83–7. 35. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–71. 36. Sheehan DV, Lecrubier Y. Mini-International Neuropsychiatric Interview (MINI). Tampa, FL, University of South Florida, Institute for Research in Psychiatry; Paris, INSERM-Hopital de la Salpetriere, 1994. 37. Grundy SM, Cleeman JI, Daniel, SR, Donato KA, Eckel RH, Franklin BA et al., Diagnosis and management of the metabolic syndrome: An American Heart Association/National heart, lung, and blood institute scientific statement: Executive summary. Circulation 2005;112:e285–90. 38. Zhao G, Ford ES, Dhringra S, Li C, Strine TW, Mokdad AH. Depression and anxiety among US adults: Associations with body mass index. Int J Obesity 2009;33:257–66. 39. Colotto M, Vinci F, Vo Hong N, Raimo O, Castello A, Carnovale A et al. Effect of treatment with selective serotonin reuptake inhibitors on lipid profile: State of the art. Clin Ter 2012;163:e41–5. 40. Suokas JT, Perälä J, Suominen K, Saari S, Lönnqvist J, Suvisaari JM. Epidemiology of suicide attempts among persons
NORD J PSYCHIATRY·VOL 69 NO 4·2015
CVD RISK with psychotic disorder in the general population. Schizophrenia Res 2010;124:22–8. 41. Mäntyselkä P, Korniloff K, Saaristo T, Koponen H, Eriksson J, Puolijoki H et al Association of depressive symptoms with impaired glucose regulation, screen-detected and previously known type 2 diabetes—Findings from the Finnish D2D survey. Diabetes Care 2011;34:71–6. 42. Ali S, Nathani M, Jabeen S, Yazdani I, Mouton CD, Bailey RK et al. Alcohol: The lubricant to suicidality. Innov Clin Neurosci 2013;10:20–9. 43. Sokero PT, Melartin TK, Rytsälä HJ, Leskelä US, Lestelä-Mielonen PS, Isometsä ET. Suicidal ideation and attempts among psychiatric patients with major depressive disorder. J Clin Psychiatry 2003;64:1094–100. Hannu Koponen, Professor of Old Age Psychiatry, Department of Psychiatry, Institute of Clinical Medicine, University of Helsinki, and
NORD J PSYCHIATRY·VOL 69 NO 4·2015
FACTORS AND DEPRESSION
Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland Hannu Kautiainen, Ph.D., Kuopio University Hospital, Primary Health Care Unit, Central Hospital of Central Finland, Primary Health Care Unit, Jyväskylä, Finland Esa Leppänen, M.D., Ph.D., Chief Physician, Central Finland Hospital District, Public Utility Laboratory KESLAB, Jyväskylä, Finland Pekka Mäntyselkä, Professor, Primary Health Care Unit, Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland; and Primary Health Care Unit, Kuopio University Hospital, Kuopio, Finland Mauno Vanhala, Professor, University of Eastern Finland, Department of Health Sciences, and Kuopio University Hospital, Primary Health Care Unit, Kuopio, and Central Hospital of Central Finland, Primary Health Care Unit, Jyväskylä, Finland
267
Copyright of Nordic Journal of Psychiatry is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Koponen H, Kautiainen H, Leppänen E, Mäntyselkä P, Vanhala M. Cardiometabolic risk factors in patients referred to depression nurse case managers. Nord J Psychiatry 2015;69:262–267. Background: Disturbances in lipid and glucose metabolism are associated with depressive symptoms, and may increase suicidal behavior. Aims: To investigate the prevalence of cardiometabolic risk factors, severity of depressive symptoms, and suicidal thoughts and previous attempts in patients referred to depression nurse case managers. Methods: Blood cholesterol, triglyceride and glucose levels, depressive symptoms and suicidality were studied in 706 depressed participants and 426 controls. In addition, we compared the Beck Depression Inventory (BDI) with a diagnostic interview. Results: 448 (63%) of the patients scoring ⱖ 10 on BDI had major depression or dysthymic disorder, 258 had an anxiety or alcohol use disorder, 137 (19%) had two or more diagnoses in the Mini-International Neuropsychiatric Interview. Suicidal thoughts (49%) and previous suicide attempts (16%) were more common in patients with depressive disorders. Patients diagnosed with depression had highest BDI scores and higher blood glucose levels measured at baseline and at 2 h in the oral glucose tolerance test (OGTT). Both patient groups also had higher triglyceride levels compared with the controls. In addition, metabolic syndrome and type 2 diabetes were most common among the depressed participants. In the whole study population, levels of low-density lipoprotein-cholesterol as well as baseline and 2-h blood glucose in OGTT were higher among patients with suicidal behavior. Conclusions: Cardiometabolic risk factors and metabolic syndrome are common in patients with depression, and in patients with anxiety and alcohol use disorders. The results imply that disturbance in glucose metabolism may be associated with suicidal thoughts and previous attempts. • Beck Depression Inventory, Cardiometabolic risk factors, Depression, Metabolic syndrome, Suicidal behavior. Hannu Koponen, Professor of Old Age Psychiatry, Department of Psychiatry, Institute of Clinical Medicine, University of Helsinki, PO Box 22, FIN-00014 Helsinki, Finland, E-mail: [email protected]; Accepted 30 September 2014.
D
epression and metabolic syndrome have become increasingly more common in the population over the past 10 years and together they constitute a major health problem (1, 2). Metabolic syndrome is a cluster of type 2 diabetes (T2D) and cardiovascular disease (CVD) risk factors, which can be ascertained for example with the aid of the US National Cholesterol Education Program—Adult Treatment Panel III or International Diabetes Federation criteria (3, 4). Previous crosssectional studies have found metabolic syndrome to be more common among depressive patients compared with general population (5–7). Long-term studies looking at the relationship between depression and metabolic syndrome have revealed a two-way relationship (7–9): depressive patients were found to have about a two-fold risk of metabolic syndrome, whereas metabolic syndrome was associated with about a two-fold risk of depression.
© 2014 Informa Healthcare
Previous studies also suggest that depression may be a risk factor for several components of metabolic syndrome. Depression is associated with a tendency to dyslipidemias and visceral fat accumulation (10). Depressive patients also frequently have insulin resistance, which may resolve after recovery from depression (11, 12). A recent meta-analysis has also shown that the presence of depression increases the risk for diabetes and arterial hypertension (13). Conversely, obesity, T2D, arterial hypertension and dyslipidemias are risk factors for depression (14–19). Biological mechanisms that may explain the association between depression and metabolic syndrome include autonomous nervous system and monoamine neurotransmission dysfunction, cytokine-mediated inflammatory reaction (20–22) and overactivity of the hypothalamic– pituitary–adrenal (HPA) axis (23–25). In more advanced DOI: 10.3109/08039488.2014.972451
CVD RISK
age, focal vascular damage and white matter lesions may also contribute to the development of depression (26). Psychological factors may also play a significant role, as metabolic syndrome is associated with a passive life attitude and negative self-image, both of which may contribute to the development of depression (27, 28). Besides predisposing to depression, disturbances in glucose and lipid metabolism may also be associated with impulsiveness and suicidality (19, 29–31). However, previous studies have reported both low and high cholesterol levels in depressed patients with increased impulsivity and suicidal behavior (30, 32–34). Due to this inconsistency of data, we decided to investigate in a case–control study setting blood glucose and lipid levels and suicidal behavior in patients referred to depression nurse case managers. We also examined the diagnostic accuracy of the Beck Depression Inventory (BDI; 35) in identifying depression subsequently confirmed with diagnostic interview. In order to obtain a representative sample with both mild and more severe depressive participants, self-referred patients were included together with general practitioner referred patients. The lower age limit of 35 years was chosen to obtain a stable study population also facilitating a more prolonged follow-up.
Material and methods New patients ⱖ 35 years of age, who were referred by themselves or by general practitioners to depression nurse case managers in 2008–2009 due to depressive symptoms and scoring ⱖ 10 in the BDI were enrolled in this study. The study was conducted in municipalities belonging to the Central Finland Hospital District (the Finnish Depression and Metabolic Syndrome in Adults study, FDMSA) with a catchment area of 274,000 inhabitants. The number of patients was 706. Enrolment was based on written and oral patient information and a written consent was obtained before any study procedures. The study protocol was approved by the Ethics Committee of Central Finland Hospital District. All participants filled out a standard questionnaire containing questions about previously diagnosed somatic disorders, use of medications including antidepressants and hormone replacement therapy in females. In addition, data were collected on smoking habits, use of alcohol (number of drinks per week) and physical activity (number of ⬎ 30-min exercise sessions per week). The severity of depressive symptoms was measured by the 21-item BDI, which was completed by the participants, and the psychiatric diagnosis was confirmed with a diagnostic interview (Mini-International Neuropsychiatric Interview; M.I.N.I.; 36) delivered by a trained study nurse. A group of 426 middle-aged (ⱖ 35 years) persons was selected as controls among residents in the participating municipalities using random sampling. All NORD J PSYCHIATRY·VOL 69 NO 4·2015
FACTORS AND DEPRESSION
subjects in the control group had a BDI score below 10 and had no psychiatric diagnosis or current depressive symptoms and used no psychoactive medications. Fasting blood samples including the glucose and lipid levels were drawn between 08:00 and 11:00 h after 12 h of fasting, after which an oral glucose tolerance test (OGTT) with 75 g of glucose was carried out. The physical examination included weight, height, waist circumference and blood pressure taken on the same study visit. Height and weight were measured in light clothing to the nearest 0.5 cm and 0.1 kg, respectively. The waist circumference was measured to the nearest 1.0 cm at the midpoint between the lateral iliac crest and lowest rib. Trained nurses measured blood pressure twice with a mercury sphygmomanometer with subjects in sitting position after a 15-min rest. In the evaluation of metabolic syndrome, we used the modified NCEPATPIII criteria with the 100 mg/dl blood glucose cutoff point (37).
Statistical analysis The results are presented using means, standard deviation and frequency distributions. Statistical significance between groups was tested by analysis of variance (ANOVA), Kruskal–Wallis test and chi-square test, and adjusted significance testing with logistic regression analysis.
Results Based on the M.I.N.I. interview used to confirm diagnosis, 448 out of the 706 participants were diagnosed with depression (major depression or dysthymic disorder), 258 patients had an anxiety or alcohol use disorder; 137 (19.4%) of the patients referred to nurse case managers received two or more diagnoses, but were included into the study analyses. The diagnoses based on diagnostic interview for these 706 patients are shown in Table 1. The patients were subdivided according to the M.I.N.I. diagnosis into two groups with either depressive disorder or some other, i.e. some anxiety or alcohol use disorder. In the study population, 309 participants used antidepressive medication, mostly selective serotonin reuptake inhibitors. Table 1. Diagnoses based on diagnostic interview (MiniInternational Neuropsychiatric Interview; M.I.N.I.). Disorder Depression Panic disorder Fear of social situations Obsessive–compulsive disorder Alcohol dependence Harmful alcohol use
Prevalence of the diagnosis in the study population 448 (63.4%) 163 (23.1%) 87 (12.3%) 20 (2.8%) 86 (12.2%) 39 (7.9%)
263
HANNU KOPONEN ET
AL.
The mean age of the participants in different subgroups ranged from 51 to 53 years. The proportion of patients over 65 years was highest in the subgroup with other psychiatric symptomatology (Table 2). Compared with controls and patients with other disorders, patients diagnosed with depression had highest BDI scores and higher blood glucose levels measured at baseline and at 2 h in the OGTT (Table 2). Both patient groups had higher triglyceride levels compared with the controls. In addition, metabolic syndrome and T2D were most common among the depressed participants (Table 2). Figure 1 shows the prevalence of metabolic syndrome in females (P ⬍ 0.001; age-adjusted) and males (P ⬍ 0.025; age-adjusted). According to the M.I.N.I. interview, suicidal thoughts were present in 278 patients, while 98 had a previous suicide attempt; both were most common in the group diagnosed with depression. When subdivided according to the presence or absence of suicidal behavior, patients with suicidal ideation or attempts had higher low-density lipoprotein (LDL)-cholesterol levels (3.20 mmol/l vs. 2.9 mmol/l among controls; P ⫽ 0.013) and higher P-glucose in OGTT (baseline 6.0 mmol/l vs. 5.6 mmol/l among controls; P ⫽ 0.02; the corresponding 2-h values
were 6.2 mmol/l and 5.9 mmol/l; P ⫽ 0.006). In the other cardiometabolic risk factors or body mass index, no differences were found. Alcohol use disorders were also more common among those with suicidal ideation or a previous suicide attempt than among controls (29% vs. 8%, P ⬍ 0.001).
Conclusion In our geographically representative outpatient study population, we observed that overweight and metabolic syndrome were more common among both in patient groups (i.e. with depression or other psychiatric diagnosis) referred to depression case managers, which is in line with previous results in patients with depressive or anxiety disorder (5–7, 38). However, actual CVDs, with the exception of hypertension, were rare in all study groups due to the comparatively low age of the study population as regards to the manifestation of the CVDs. The triglyceride levels were higher in both patient groups, which is in line with the findings of Kinder et al. (5) and Richter et al. (2), and may be linked to the activation of the HPA axis or inflammatory processes in patients with depressive or anxiety disorders (2).
Table 2. Groups taking part in Finnish Depression and Metabolic Syndrome in Adults (FDMSA) study.
Women, n (%) Age, mean⫾s Proportion of participants ⬎ 65 (n, %) BMI, mean⫾s Waist (cm) Men, mean⫾s Women, mean⫾s Blood pressure (mmHg) Systole, mean⫾s Diastole, mean⫾s Total cholesterol (mmol/l) , mean⫾s HDL-cholesterol (mmol/l) , mean⫾s LDL-cholesterol (mmol/l) , mean⫾s Triglyceride (mmol/l) , mean⫾s OGTT, baseline (0 h), P-glucose, mmol/l, mean⫾s OGTT, 2 h, B-glucose, mmol/l, mean⫾s BDI score, mean⫾s Suicidal ideation (M.I.N.I), n (%) Suicide attempt (M.I.N.I.), n (%) Metabolic syndrome (%) Hypertension, n (%) Coronary heart disease, n (%) Previous myocardial infarction, n (%) Previous stroke, n (%) Type 2 diabetes, n (%)
Controls (BDI ⬍ 10), n ⫽ 426
Patients with BDI ⱖ 10, but with other diagnosis than depression on M.I.N.I., n ⫽ 258
Depressive patients with BDI ⱖ 10 and depression on M.I.N.I., n ⫽ 448
P
254 (60) 53 (10) 57 (13) 26.8 (4.6)
191 (74) 53 (11) 44 (17) 27.9 (5.9)
313 (70) 51 (10) 44 (10) 28.1 (5.9)
⬍ 0.001 ⬍ 0.001 0.002 0.001
97 (12) 88 (13)
98 (12) 91 (15)
99 (13) 93 (15)
129 (16) 81 (10) 5.0 (0.9) 1.57 (0.42) 3.10 (0.82) 1.19 (0.65) 5.68 (1.00) 5.83 (1.75) 3.2 (2.7)
130 (16) 81 (10) 5.1 (1,0) 1.57 (0.45) 3.11 (0.84) 1.38 (1.64) 5.65 (0.87) 6.02 (1.82) 17.8 (6.4) 60 (23) 26 (10) 111 (45) 73 (28) 16 (6) 2 (1) 4 (2) 23 (9)
131 (16) 82 (11) 5.1 (1,0) 1.57 (0.48) 3.05 (0.93) 1.38 (0.85) 5.88 (1.45) 6.25 (2.50) 23.4 (8.2) 218 (49) 72 (16) 201 (49) 133 (30) 21 (5) 7 (2) 7 (2) 54 (12)
140 (34) 97 (23) 12 (3) 4 (1) 7 (2) 13 (3)
0.29 0.0037 0.20 0.33 0.58 0.99 0.69 0.016 0.014 0.020 ⬍ 0.001 ⬍ 0.001 0.027 ⬍ 0.001 0.057 0.10 0.56 0.99 ⬍ 0.001
Results in the table shown as means (standard deviation) and numbers (percentage). M.I.N.I., Mini-International Neuropsychiatric Interview; s, standard deviation; BMI, body mass index; HDL, high-density lipoprotein; LDL, low-density lipoprotein; OGTT, oral glucose tolerance test; BDI, Beck Depression Inventory.
264
NORD J PSYCHIATRY·VOL 69 NO 4·2015
CVD RISK 80
70
Female Male
NCEP present, %
60
50
40
30
20
10
0 Controls
Other
Depression
Fig. 1. Age-adjusted prevalence of National Cholesterol Education Program (NCEP)-diagnosed metabolic syndrome in controls and in patients suffering from depression or other psychiatric disorders.
Serum cholesterol has been suggested to reflect central nervous system serotonergic function and to participate in cognitive functioning as well as mood regulation (34). Low cholesterol level has also been linked to impulsiveness and risk of suicide in depressive patients (34). Previous findings have, however, been conflicting, as both low (30) and high cholesterol (32) levels have been associated with suicidal behavior in previous studies. In this study, we found higher LDL-cholesterol level in patients with suicidal behavior, which further suggests inconsistencies in the association between cholesterol levels and suicidal behavior. Some SSRIs, such as sertraline or paroxetine, may have negative effects on total and LDLcholesterol, and thus contribute to the observed higher LDL-cholesterol level. However, the most commonly used SSRI in Finland, citalopram, has neutral effects on the lipid profile (39), and thus the finding is not solely explained by the antidepressant medication. In addition, we found higher P-glucose in OGTT in patients with suicidal ideation and previous suicide attempts, which differ from the results of Batty et al. (19), who reported that diabetes but not raised blood glucose was a risk factor for completed suicide. The mechanism explaining the observed association is, however, obscure. The observed risk to suicidal behavior may at least be related depression itself or explained by the more common alcohol NORD J PSYCHIATRY·VOL 69 NO 4·2015
FACTORS AND DEPRESSION
dependence in the group of patients with suicidal ideation and/or suicide attempts (19, 40–42). The depression nurse case manager system has been implemented in Finland in order to improve the treatment results of depressive disorders. The recognition of depression is still problematic and several different assessment scales have been developed for identifying depressive symptoms. The most commonly used in both clinical work and research is the self-administered BDI. However, a BDI score of ⱖ 10 did not mean a definite diagnosis of depression in our study, as nearly 40% of the patients received another diagnosis, most often an anxiety or alcohol use disorder. This means that the diagnosis of patients scoring above the BDI cut-off of 10 should be confirmed by thorough clinical examination, and in cases of comorbidity, with a structured diagnostic interview. The diagnostic accuracy of BDI was similar in both genders. Suicidal ideation or previous suicide attempts identified by M.I.N.I. were equally frequent as in another Finnish study, i.e. the Vantaa Depression Study (43). The strengths of our study include a geographically representative sample of middle-aged and elderly subjects. In addition, we used a diagnostic interview besides of the self-rating of depressive symptoms. However, due to the cross-sectional design of our study, we cannot make inferences of causality, which is a limitation. In addition, only persons aged 35 or older were enrolled in the study, so the results cannot be generalized to younger age groups. The participants were referred to depression nurse case managers due to depressive symptoms, but we have no data on how long the symptoms have been present, which is also a limitation. An easy-to-use self-administered scale, such as the BDI, may aid in the identification of patients describing depressive symptoms, but in addition to systematic confirmation of clinical diagnosis, assessment of patients scoring above the cut-off must also involve evaluation of suicide risk. Overweight and metabolic syndrome were more common and the triglyceride levels were higher in the both patient groups as compared with the controls. Higher LDL-cholesterol and P-glucose levels were associated with suicidal behavior, suggesting that disturbances in glucose and cholesterol metabolism may be associated with suicidal thoughts and previous attempts. Acknowledgements—The authors would like to thank the depression nurse case managers who took part in the practical implementation of the FDMSA: Mari Alanko, Harri Back, Timo Hannula, Anu Holopainen, Ritva Häkkinen, Katja Johansson, Eija Kinnunen, Kaija Luoma, Hannele Niemi, Hillevi Peura, Inga Pöntiö, Kirsi Rouvinen, Tiina Silvennoinen and Marianne Vihtamäki; the FDMSA study nurses Anne Kirmanen, Reetta Oksanen and Olli Niemi and Pia Jauhiainen, scientific secretary of the study.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
265
HANNU KOPONEN ET
AL.
References 1. Koponen H, Jokelainen J, Keinänen-Kiukaanniemi S, Vanhala M. Depressive symptoms and 10-year risk for cardiovascular morbidity and mortality. World J Biol Psychiatry 2010;11:834–9. 2. Richter N, Juckel G, Assion H-J. Metabolic syndrome: A follow-up study of acute depressive inpatients. Eur Arch Psychiatry Clin Neurosci 2010;260:41–9. 3. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: 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). JAMA 2001;285:2486–97. 4. Alberti KGMM, Zimmet P, Shaw J, for the IDF Epidemiology Task Force Consensus Group. The metabolic syndrome—A new worldwide definition. Lancet 2005;366:1059–62. 5. Kinder LS, Carnethon MR, Palaniappan LP, King AC, Fortman SP. Depression and the metabolic syndrome in young adults: Findings from the third national health and nutrition examination survey. Psychosom Med 2004;66:316–22. 6. Heiskanen TH, Niskanen LK, Hintikka JJ, Koivumaa-Honkanen HT, Honkalampi KM, Haatainen KM et al. Metabolic syndrome and depression: A cross-sectional analysis. J Clin Psychiatry 2006;67:1422–7. 7. Räikkönen K, Matthews KA, Kuller LH. Depressive symptoms and stressful life events predict metabolic syndrome among middle-aged women. A comparison of World Health Organization, Adult Treatment Panel III and International Diabetes Foundation definitions. Diabetes Care 2007;30:872–7. 8. Koponen H, Jokelainen J, Keinänen-Kiukaanniemi S, Kumpusalo E, Vanhala M. Metabolic syndrome predisposes to depression. A population-based 7-year follow-up study. J Clin Psychiatry 2008;69:178–82. 9. Vanhala M, Jokelainen J, Keinänen-Kiukaanniemi S, Kumpusalo E, Koponen H. Depressive symptoms predispose females to metabolic syndrome. A 7-year follow-up study. Acta Psychiatr Scand 2009;119:137–42. 10. Weber-Hamann B, Werner M, Hentschel F, Bindeballe N, Lederbogen F, Deuschle M. Metabolic changes in elderly patients with major depression: Evidence for increased accumulation of visceral fat at follow-up. Psychoneuroendocrinology 2006;31:347–54. 11. Okamura F, Tashiro A, Utumi A, Imai T, Suchi T, Tamura D et al Insulin resistance in patients with depression and its changes during the clinical course of depression: Minimal model analysis. Metabolism 2000;49:1255–60. 12. Kan C, Silva N, Golden SH, Rajala U, Timonen M, Stahl D et al. systematic review and meta-analysis of the association between depression and insulin resistance. Diabetes Care 2013;36:480–9. 13. Knol MJ, Twos JWR, Beekman ATF, Heine RJ, Snoek FJ, Pouwer F. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia 2006;49:837–45. 14. Maes M, Smith R, Christophe A, Vandoolaeghe E, Van Gastel A, Neels H. Low serum high-density cholesterol (HDL-C) in major depression and depressed men with serious suicidal attempts: Relationship with immune-inflammatory markers. Acta Psychiatr Scand 1997;95:212–21. 15. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes. Diabetes Care 2001;24:1069–78. 16. Dixon JB, Dixon ME, O’Brien PE. Depression in association with severe obesity. Changes with weight loss. Arch Intern Med 2003;163:2058–65. 17. Plante GE. Depression and cardiovascular disease: A reciprocal relationship. Metabolism 2005;54 Suppl:45–8. 18. Deisenhammer EA, Lechner-Schoner T, Kemmler G, Ober A, Braidt E, Hinterhuber H. Serum lipids and risk factors for attempted suicide in patients with alcohol dependence. Alcohol Clin Exp Res 2006;30:460–5. 19. Batty GD, Kivimäki M, Park IS, Ha SJ. Diabetes and raised blood glucose as risk factors for future suicide: Cohort study of 1 234 927 Korean men and women. J Epidemiol Community Health 2012;66:650–2.
266
20. Dunn AJ, Swiergiel AH, de Beaurepaire R. Cytokines as mediators of depression: What can we learn from animal studies? Neurosci Biobehav Rev 2005;29:891–909. 21. Ovaskainen Y, Koponen H, Jokelainen J, Keinänen-Kiukaanniemi S, Kumpusalo E, Vanhala M. Depressive symptomatology is associated with decreased interleukin-1 beta and increased interleukin1 receptor antagonist levels in males. Psychiatry Res 2009;167:73–9. 22. Meyer T, Stanske B, Kochen MM, Cordes A, Yuksel I, Wachter R. et al., Serum levels of interleukin-6 and interleukin-10 in relation to depression scores in patients with cardiovascular risk factors. Behav Medicine 2011;37:105–12. 23. Brown ES, Varghese FP, McEwen BS. Association of depression with medical illness: Does cortisol play a role? Biol Psychiatry 2004;55:1–9. 24. Licht CMM, Vreeburg SA, van Reed Dorland AKB, Giltay EJ, Hookendijk WJG, DeRijk RH et al., Increased sympathetic and decreased parasympathetic activity rather than changes in hypothalamic–pituitary–adrenal axis activity is associated with metabolic abnormalities. J Clin Endocrinol Metabolism 2010;95:2458–66. 25. Alexopoulos GS, Morimoto SS. The inflammation hypothesis in geriatric depression. Int J Geriatr Psychiatry 2011;26:1109–18. 26. Taylor WD, Aizenstein HJ, Alexopoulos GS. The vascular depression hypothesis: Mechanisms linking vascular disease with depression. Mol Psychiatry Feb 2013 epub ahead of print (doi: 10.1038/MP.2013.20) 27. Vogelzangs N, Beekman AT, Boelhouwer IG, Bandinelli S, Milaneschi Y, Lerrucci L. Metabolic depression: A chronic depressive subtype? Findings from the InCHIANTI study of older persons. J Clin Psychiatry 2011;72:598–604. 28. Van Reedt Dortland AKB, Vreeburg SA, Giltay EJ, Licht CMM, Vogelzangs N, van Veen T et al impact of stress systems and lifestyle on dyslipidemia and obesity in anxiety and depression. Psychoneuroendocrinology 2013;38:209–18. 29. Golomb BA. Cholesterol and violence: Is there a connection? Ann Intern Med 1998;128:478–87. 30. Plana T, Gracia E, Mendez I, Pintor L, Lazaro L, Castro-Fornieles J. Total serum cholesterol levels and suicide attempts in child and adolescent psychiatric inpatients. Eur Child Adolesc Psychiatry 2010;19:615–9. 31. Löfman S, Hakko H, Mainio A, Timonen M, Räsänen P. Characteristics of suicide among diabetes patients: A population based study of suicide victims in Northern Finland. J Psychosom Res 2012;73:268–71. 32. Tanskanen A, Vartiainen E, Tuomilehto J, Viinamäki H, Lehtonen J, Puska P. High serum cholesterol and risk of suicide. Am J Psychiatry 2000;157:648–50. 33. Tedders SH, Fokong KD, McKenzie LE, Wesley C, Yu L, Zhang J. Low cholesterol is associated with depression among US household population. J Affect Disord 2011;135:115–21. 34. Troisi A. Low cholesterol is a risk factor for attentional impulsivity in patients with mood symptoms. Psychiatry Res 2011;188:83–7. 35. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–71. 36. Sheehan DV, Lecrubier Y. Mini-International Neuropsychiatric Interview (MINI). Tampa, FL, University of South Florida, Institute for Research in Psychiatry; Paris, INSERM-Hopital de la Salpetriere, 1994. 37. Grundy SM, Cleeman JI, Daniel, SR, Donato KA, Eckel RH, Franklin BA et al., Diagnosis and management of the metabolic syndrome: An American Heart Association/National heart, lung, and blood institute scientific statement: Executive summary. Circulation 2005;112:e285–90. 38. Zhao G, Ford ES, Dhringra S, Li C, Strine TW, Mokdad AH. Depression and anxiety among US adults: Associations with body mass index. Int J Obesity 2009;33:257–66. 39. Colotto M, Vinci F, Vo Hong N, Raimo O, Castello A, Carnovale A et al. Effect of treatment with selective serotonin reuptake inhibitors on lipid profile: State of the art. Clin Ter 2012;163:e41–5. 40. Suokas JT, Perälä J, Suominen K, Saari S, Lönnqvist J, Suvisaari JM. Epidemiology of suicide attempts among persons
NORD J PSYCHIATRY·VOL 69 NO 4·2015
CVD RISK with psychotic disorder in the general population. Schizophrenia Res 2010;124:22–8. 41. Mäntyselkä P, Korniloff K, Saaristo T, Koponen H, Eriksson J, Puolijoki H et al Association of depressive symptoms with impaired glucose regulation, screen-detected and previously known type 2 diabetes—Findings from the Finnish D2D survey. Diabetes Care 2011;34:71–6. 42. Ali S, Nathani M, Jabeen S, Yazdani I, Mouton CD, Bailey RK et al. Alcohol: The lubricant to suicidality. Innov Clin Neurosci 2013;10:20–9. 43. Sokero PT, Melartin TK, Rytsälä HJ, Leskelä US, Lestelä-Mielonen PS, Isometsä ET. Suicidal ideation and attempts among psychiatric patients with major depressive disorder. J Clin Psychiatry 2003;64:1094–100. Hannu Koponen, Professor of Old Age Psychiatry, Department of Psychiatry, Institute of Clinical Medicine, University of Helsinki, and
NORD J PSYCHIATRY·VOL 69 NO 4·2015
FACTORS AND DEPRESSION
Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland Hannu Kautiainen, Ph.D., Kuopio University Hospital, Primary Health Care Unit, Central Hospital of Central Finland, Primary Health Care Unit, Jyväskylä, Finland Esa Leppänen, M.D., Ph.D., Chief Physician, Central Finland Hospital District, Public Utility Laboratory KESLAB, Jyväskylä, Finland Pekka Mäntyselkä, Professor, Primary Health Care Unit, Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland; and Primary Health Care Unit, Kuopio University Hospital, Kuopio, Finland Mauno Vanhala, Professor, University of Eastern Finland, Department of Health Sciences, and Kuopio University Hospital, Primary Health Care Unit, Kuopio, and Central Hospital of Central Finland, Primary Health Care Unit, Jyväskylä, Finland
267
Copyright of Nordic Journal of Psychiatry is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
