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BMC Psychiatry
Published in: BMC Psychiatry 1/2016

Open Access 01-12-2016 | Research article

Metabolic syndrome and adverse clinical outcomes in patients with bipolar disorder

Authors: Ya-Mei Bai, Cheng-Ta Li, Shih-Jen Tsai, Pei-Chi Tu, Mu-Hong Chen, Tung-Ping Su

Published in: BMC Psychiatry | Issue 1/2016

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Abstract

Background

Metabolic syndrome (MetS) is highly prevalent among patients with bipolar disorder. MetS may cause complications in the brain, but studies investigating MetS-associated clinical psychiatric outcomes remain scant.

Methods

We enrolled clinically stable outpatients with bipolar disorder aged 18–65 years and performed anthropometric and fasting biochemical assessments to investigate MetS prevalence. We then performed clinical assessments by using the Young Mania Rating Scale for manic symptoms, the Montgomery–Åsberg Depression Rating Scale for depressive symptoms, the Positive and Negative Symptom Scale for psychotic symptoms, the Involuntary Movement Scale for tardive dyskinesia, the Barnes Akathisia Rating Scale for akathisia, the Udvalg for Kliniske Undersogelser for general side effects, the Schedule for Assessment of Insight for insight, the Global Assessment of Functioning scale for global functioning, and the Wisconsin Card Sorting Test (WCST) for cognitive executive function.

Results

In total, 143 patients were enrolled and had a MetS prevalence of 29.4%. The patients treated with atypical antipsychotics plus mood stabilizers (36.3%) and atypical antipsychotics alone (36.0%) had a significantly higher prevalence of MetS than did those treated with mood stabilizers alone (10.5%; p = 0.012). According to multivariate regression analyses adjusted for age, sex, smoking status, bipolar disorder subtype (I or II), pharmacological treatment duration, and psychiatric medication, compared with patients without MetS, those with MetS had significantly more previous hospitalizations (p = 0.036), severer tardive dyskinesia (p = 0.030), poorer insight (p = 0.036), poorer global function (p = 0.046), and more impaired executive function (conceptual level response on the WCST; p = 0.042).

Conclusions

Our results indicated that patients with comorbid bipolar disorder and MetS have more adverse clinical outcomes than those without, with more hospitalizations, severer tardive dyskinesia, poorer insight, poorer global function, and more impaired executive function. Monitoring MetS is crucial for assessing not only physical burden, but also psychiatric outcomes.
Literature
1.
McIntyre RS, Danilewitz M, Liauw SS, Kemp DE, Nguyen HT, Kahn LS, Kucyi A, Soczynska JK, Woldeyohannes HO, Lachowski A, et al. Bipolar disorder and metabolic syndrome: an international perspective. J Affect Disord. 2010;126(3):366–87.CrossRefPubMed
2.
3.
Vancampfort D, Vansteelandt K, Correll CU, Mitchell AJ, De Herdt A, Sienaert P, Probst M, De Hert M. Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. Am J Psychiatry. 2013;170(3):265–74.CrossRefPubMed
4.
McElroy SL, Keck Jr PE. Metabolic syndrome in bipolar disorder: a review with a focus on bipolar depression. J Clin Psychiatry. 2014;75(1):46–61.CrossRefPubMed
5.
Fagiolini A, Chengappa KN, Soreca I, Chang J. Bipolar disorder and the metabolic syndrome: causal factors, psychiatric outcomes and economic burden. CNS Drugs. 2008;22(8):655–69.CrossRefPubMed
6.
Loffler D, Landgraf K, Korner A, Kratzsch J, Kirkby KC, Himmerich H. Modulation of triglyceride accumulation in adipocytes by psychopharmacological agents in vitro. J Psychiatr Res. 2016;72:37–42.CrossRefPubMed
7.
Zuo S, Fries BE, Szafara K, Regal R. Valproic Acid as a potentiator of metabolic syndrome in institutionalized residents on concomitant antipsychotics: fat chance, or slim to none? P & T : a peer-reviewed journal for formulary management. 2015;40(2):126–32.
8.
Sylvia LG, Shelton RC, Kemp DE, Bernstein EE, Friedman ES, Brody BD, McElroy SL, Singh V, Tohen M, Bowden CL, et al. Medical burden in bipolar disorder: findings from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE). Bipolar Disord. 2015;17(2):212–23.
9.
Laursen TM, Wahlbeck K, Hallgren J, Westman J, Osby U, Alinaghizadeh H, Gissler M, Nordentoft M. Life expectancy and death by diseases of the circulatory system in patients with bipolar disorder or schizophrenia in the Nordic countries. PLoS One. 2013;8(6), e67133.CrossRefPubMedPubMedCentral
10.
Crump C, Sundquist K, Winkleby MA, Sundquist J. Comorbidities and mortality in bipolar disorder: a Swedish national cohort study. JAMA Psychiat. 2013;70(9):931–9.CrossRef
11.
Fagiolini A, Kupfer DJ, Houck PR, Novick DM, Frank E. Obesity as a correlate of outcome in patients with bipolar I disorder. Am J Psychiatry. 2003;160(1):112–7.CrossRefPubMed
12.
Calkin C, van de Velde C, Ruzickova M, Slaney C, Garnham J, Hajek T, O'Donovan C, Alda M. Can body mass index help predict outcome in patients with bipolar disorder? Bipolar Disord. 2009;11(6):650–6.CrossRefPubMedPubMedCentral
13.
Goldstein BI, Liu SM, Zivkovic N, Schaffer A, Chien LC, Blanco C. The burden of obesity among adults with bipolar disorder in the United States. Bipolar Disord. 2011;13(4):387–95.CrossRefPubMedPubMedCentral
14.
Goldstein BI, Liu SM, Schaffer A, Sala R, Blanco C. Obesity and the three-year longitudinal course of bipolar disorder. Bipolar Disord. 2013;15(3):284–93.CrossRefPubMedPubMedCentral
15.
Kemp DE, Gao K, Chan PK, Ganocy SJ, Findling RL, Calabrese JR. Medical comorbidity in bipolar disorder: relationship between illnesses of the endocrine/metabolic system and treatment outcome. Bipolar Disord. 2010;12(4):404–13.CrossRefPubMedPubMedCentral
16.
Galvez JF, Bauer IE, Sanches M, Wu HE, Hamilton JE, Mwangi B, Kapczinski FP, Zunta-Soares G, Soares JC. Shared clinical associations between obesity and impulsivity in rapid cycling bipolar disorder: a systematic review. J Affect Disord. 2014;168:306–13.CrossRefPubMed
17.
Yim CY, Soczynska JK, Kennedy SH, Woldeyohannes HO, Brietzke E, McIntyre RS. The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder. Eur Psychiatry. 2012;27(3):223–8.CrossRefPubMed
18.
Depp CA, Strassnig M, Mausbach BT, Bowie CR, Wolyniec P, Thornquist MH, Luke JR, McGrath JA, Pulver AE, Patterson TL, et al. Association of obesity and treated hypertension and diabetes with cognitive ability in bipolar disorder and schizophrenia. Bipolar Disord. 2014;16(4):422–31.CrossRefPubMedPubMedCentral
19.
Lackner N, Bengesser SA, Birner A, Painold A, Fellendorf FT, Platzer M, Reininghaus B, Weiss EM, Mangge H, McIntyre RS et al. Abdominal obesity is associated with impaired cognitive function in euthymic bipolar individuals. World J Biol Psychiatry. 2016;17(7):535–46.
20.
Calkin CV, Ruzickova M, Uher R, Hajek T, Slaney CM, Garnham JS, O'Donovan MC, Alda M. Insulin resistance and outcome in bipolar disorder. Br J Psychiatry. 2015;206(1):52–7.CrossRefPubMed
21.
Ruzickova M, Slaney C, Garnham J, Alda M. Clinical features of bipolar disorder with and without comorbid diabetes mellitus. Can J Psychiatry. 2003;48(7):458–61.CrossRefPubMed
22.
McIntyre RS, Muzina DJ, Kemp DE, Blank D, Woldeyohannes HO, Lofchy J, Soczynska JK, Banik S, Konarski JZ. Bipolar disorder and suicide: research synthesis and clinical translation. Curr Psychiatry Rep. 2008;10(1):66–72.CrossRefPubMed
23.
Trevino S, Aguilar-Alonso P, Flores Hernandez JA, Brambila E, Guevara J, Flores G, Lopez-Lopez G, Munoz-Arenas G, Morales-Medina JC, Toxqui V, et al. A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats. Synapse. 2015;69(9):421–33.CrossRefPubMed
24.
Song SW, Chung JH, Rho JS, Lee YA, Lim HK, Kang SG, Kim HN, Kim JE, Kim SH. Regional cortical thickness and subcortical volume changes in patients with metabolic syndrome. Brain Imaging Behav. 2015;9(3):588–96.CrossRefPubMed
25.
Gabriel A. Adjunctive topiramate treatment in refractory obese bipolar patients: a descriptive open label study. Eating and weight disorders : EWD. 2007;12(1):48–53.CrossRefPubMed
26.
McIntyre RS, Riccardelli R, Binder C, Kusumakar V. Open-label adjunctive topiramate in the treatment of unstable bipolar disorder. Can J Psychiatry. 2005;50(7):415–22.CrossRefPubMed
27.
Tramontina S, Zeni CP, Pheula G, Rohde LA. Topiramate in adolescents with juvenile bipolar disorder presenting weight gain due to atypical antipsychotics or mood stabilizers: an open clinical trial. J Child Adolesc Psychopharmacol. 2007;17(1):129–34.CrossRefPubMed
28.
Vieta E, Torrent C, Garcia-Ribas G, Gilabert A, Garcia-Pares G, Rodriguez A, Cadevall J, Garcia-Castrillon J, Lusilla P, Arrufat F. Use of topiramate in treatment-resistant bipolar spectrum disorders. J Clin Psychopharmacol. 2002;22(4):431–5.CrossRefPubMed
29.
Lopresti AL, Drummond PD. Obesity and psychiatric disorders: Commonalities in dysregulated biological pathways and their implications for treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2013;45:92–9.CrossRefPubMed
30.
Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl. 1970;212:11–9.CrossRefPubMed
31.
Munetz MR, Schulz SC. Screening for tardive dyskinesia. J Clin Psychiatry. 1986;47(2):75–7.PubMed
32.
33.
Lingjaerde O, Ahlfors UG, Bech P, Dencker SJ, Elgen K. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl. 1987;334:1–100.CrossRefPubMed
34.
David A, Buchanan A, Reed A, Almeida O. The assessment of insight in psychosis. Br J Psychiatry. 1992;161:599–602.CrossRefPubMed
35.
Szulinska M, Piorunek T, Suliburska J, Pupek-Musialik D, Kupsz J, Drzymala-Czyz S, Bogdanski P. Evaluation of insulin resistance, tumor necrosis factor alpha, and total antioxidant status in obese patients smoking cigarettes. Eur Rev Med Pharmacol Sci. 2013;17(14):1916–22.PubMed
36.
Szlagatys-Sidorkiewicz A, Wos E, Aleksandrowicz E, Luczak G, Zagierski M, Martysiak-Zurowska D, Marek K, Kaminska B. Cytokine profile of mature milk from smoking and nonsmoking mothers. J Pediatr Gastroenterol Nutr. 2013;56(4):382–4.CrossRefPubMed
37.
Bai YM, Su TP, Tsai SJ, Wen-Fei C, Li CT, Pei-Chi T, Mu-Hong C. Comparison of inflammatory cytokine levels among type I/type II and manic/hypomanic/euthymic/depressive states of bipolar disorder. J Affect Disord. 2014;166:187–92.CrossRefPubMed
38.
Barbosa IG, Huguet RB, Mendonca VA, Sousa LP, Neves FS, Bauer ME, Teixeira AL. Increased plasma levels of soluble TNF receptor I in patients with bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 2011;261(2):139–43.CrossRefPubMed
39.
Guloksuz S, Cetin EA, Cetin T, Deniz G, Oral ET, Nutt DJ. Cytokine levels in euthymic bipolar patients. J Affect Disord. 2010;126(3):458–62.CrossRefPubMed
40.
Bai YM, Chang CJ, Tsai SY, Chen YC, Hsiao MC, Li CT, Tu P, Chang SW, Shen WW, Su TP. Taiwan consensus of pharmacological treatment for bipolar disorder. Journal of the Chinese Medical Association : JCMA. 2013;76(10):547–56.CrossRefPubMed
41.
Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, Macqueen G, McIntyre RS, Sharma V, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 2013;15(1):1–44.CrossRefPubMed
42.
Chang HH, Chou CH, Chen PS, Gean PW, Huang HC, Lin CY, Yang YK, Lu RB. High prevalence of metabolic disturbances in patients with bipolar disorder in Taiwan. J Affect Disord. 2009;117(1–2):124–9.CrossRefPubMed
43.
Cerit C, Vural M, Bos Gelmez SU, Ozten E, Aker AT, Yildiz M. Metabolic syndrome with different antipsychotics: a multicentre cross-sectional study. Psychopharmacol Bull. 2010;43(4):22–36.PubMed
44.
Galling B, Garcia MA, Osuchukwu U, Hagi K, Correll CU. Safety and tolerability of antipsychotic-mood stabilizer co-treatment in the management of acute bipolar disorder: results from a systematic review and exploratory meta-analysis. Expert Opin Drug Saf. 2015;14(8):1181–99.CrossRefPubMed
45.
Liu YT, Chau YL, Hsu SC, Chu CL, Chen CY. Factors influencing weight gain in an Asian population of psychiatric inpatients: a retrospective study in Taiwan. Asia-Pacific psychiatry. 2014;6(2):226–34.CrossRefPubMed
46.
Correll CU, Sheridan EM, DelBello MP. Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo-controlled trials. Bipolar Disord. 2010;12(2):116–41.CrossRefPubMed
47.
Baker RW, Brown E, Akiskal HS, Calabrese JR, Ketter TA, Schuh LM, Trzepacz PT, Watkin JG, Tohen M. Efficacy of olanzapine combined with valproate or lithium in the treatment of dysphoric mania. Br J Psychiatry. 2004;185:472–8.CrossRefPubMed
48.
Carlson BX, Ketter TA, Sun W, Timko K, McQuade RD, Sanchez R, Vester-Blokland E, Marcus R. Aripiprazole in combination with lamotrigine for the long-term treatment of patients with bipolar I disorder (manic or mixed): a randomized, multicenter, double-blind study (CN138-392). Bipolar Disord. 2012;14(1):41–53.CrossRefPubMed
49.
Ketter TA, Nasrallah HA, Fagiolini A. Mood stabilizers and atypical antipsychotics: bimodal treatments for bipolar disorder. Psychopharmacol Bull. 2006;39(1):120–46.PubMed
50.
Abraham KM. Animal models of obesity and metabolic syndrome: potential tools for Alzheimer's disease research. Curr Alzheimer Res. 2007;4(2):145–6.CrossRefPubMed
51.
Choi J, Chandrasekaran K, Demarest TG, Kristian T, Xu S, Vijaykumar K, Dsouza KG, Qi NR, Yarowsky PJ, Gallipoli R, et al. Brain diabetic neurodegeneration segregates with low intrinsic aerobic capacity. Annals of clinical and translational neurology. 2014;1(8):589–604.CrossRefPubMedPubMedCentral
52.
Dyck PJ, Giannini C. Pathologic alterations in the diabetic neuropathies of humans: a review. J Neuropathol Exp Neurol. 1996;55(12):1181–93.CrossRefPubMed
53.
Yates KF, Sweat V, Yau PL, Turchiano MM, Convit A. Impact of metabolic syndrome on cognition and brain: a selected review of the literature. Arterioscler Thromb Vasc Biol. 2012;32(9):2060–7.CrossRefPubMedPubMedCentral
54.
Segura B, Jurado MA, Freixenet N, Bargallo N, Junque C, Arboix A. White matter fractional anisotropy is related to processing speed in metabolic syndrome patients: a case–control study. BMC Neurol. 2010;10:64.CrossRefPubMedPubMedCentral
55.
Thompson WK, Kupfer DJ, Fagiolini A, Scott JA, Frank E. Prevalence and clinical correlates of medical comorbidities in patients with bipolar I disorder: analysis of acute-phase data from a randomized controlled trial. J Clin Psychiatry. 2006;67(5):783–8.CrossRefPubMed
56.
McIntyre RS, Konarski JZ, Soczynska JK, Wilkins K, Panjwani G, Bouffard B, Bottas A, Kennedy SH. Medical comorbidity in bipolar disorder: implications for functional outcomes and health service utilization. Psychiatr Serv. 2006;57(8):1140–4.CrossRefPubMed
57.
Castanon N, Lasselin J, Capuron L. Neuropsychiatric comorbidity in obesity: role of inflammatory processes. Front Endocrinol. 2014;5:74.CrossRef
58.
Kane JM. Tardive dyskinesia rates with atypical antipsychotics in adults: prevalence and incidence. J Clin Psychiatry. 2004;65 Suppl 9:16–20.PubMed
59.
Zhang XY, Tan YL, Zhou DF, Cao LY, Wu GY, Haile CN, Kosten TA, Kosten TR. Disrupted antioxidant enzyme activity and elevated lipid peroxidation products in schizophrenic patients with tardive dyskinesia. J Clin Psychiatry. 2007;68(5):754–60.CrossRefPubMed
60.
Bishnoi M, Boparai RK. An animal model to study the molecular basis of tardive dyskinesia. Methods Mol Biol. 2012;829:193–201.CrossRefPubMed
61.
Lane EL, Soulet D, Vercammen L, Cenci MA, Brundin P. Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson's disease. Neurobiol Dis. 2008;32(2):220–8.CrossRefPubMed
62.
Lerner V, Miodownik C, Kaptsan A, Bersudsky Y, Libov I, Sela BA, Witztum E. Vitamin B6 treatment for tardive dyskinesia: a randomized, double-blind, placebo-controlled, crossover study. J Clin Psychiatry. 2007;68(11):1648–54.CrossRefPubMed
63.
Libov I, Miodownik C, Bersudsky Y, Dwolatzky T, Lerner V. Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study. J Clin Psychiatry. 2007;68(7):1031–7.CrossRefPubMed
64.
Telfer S, Shivashankar S, Krishnadas R, McCreadie RG, Kirkpatrick B. Tardive dyskinesia and deficit schizophrenia. Acta Psychiatr Scand. 2011;124(5):357–62.CrossRefPubMed
65.
Ascher-Svanum H, Zhu B, Faries D, Peng X, Kinon BJ, Tohen M. Tardive dyskinesia and the 3-year course of schizophrenia: results from a large, prospective, naturalistic study. J Clin Psychiatry. 2008;69(10):1580–8.CrossRefPubMed
66.
Berry K, Drake R, Stewart C, Aitkin LM, Byrne J, Barrowclough C, Purandare N. Orofacial dyskinesia, frontal lobe dysfunction, and coping in older people with psychosis. Am J Geriatr Psychiatry. 2007;15(9):800–6.CrossRefPubMed
67.
Li CT, Chou KH, Su TP, Huang CC, Chen MH, Bai YM, Lin CP. Gray matter abnormalities in schizophrenia patients with tardive dyskinesia: a magnetic resonance imaging voxel-based morphometry study. PLoS One. 2013;8(8), e71034.CrossRefPubMedPubMedCentral
68.
Bai YM, Chou KH, Lin CP, Chen IY, Li CT, Yang KC, Chou YH, Su TP. White matter abnormalities in schizophrenia patients with tardive dyskinesia: a diffusion tensor image study. Schizophr Res. 2009;109(1–3):167–81.CrossRefPubMed
Metadata
Title
Metabolic syndrome and adverse clinical outcomes in patients with bipolar disorder
Authors
Ya-Mei Bai
Cheng-Ta Li
Shih-Jen Tsai
Pei-Chi Tu
Mu-Hong Chen
Tung-Ping Su
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2016
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-016-1143-8

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