OBJECTIVES: The association of bipolar disorder with early and excessive cardiovascular disease was identified over a century ago. Nonetheless, the vascular-bipolar link remains underrecognized, particularly with regard to how this link can contribute to our understanding of pathogenesis and treatment. METHODS: An international group of experts completed a selective review of the literature, distilling core themes, identifying limitations and gaps in the literature, and highlighting future directions to bridge these gaps. RESULTS: The association between bipolar disorder and vascular disease is large in magnitude, consistent across studies, and independent of confounding variables where assessed. The vascular-bipolar link is multifactorial and is difficult to study given the latency between the onset of bipolar disorder, often in adolescence or early adulthood, and subsequent vascular disease, which usually occurs decades later. As a result, studies have often focused on risk factors for vascular disease or intermediate phenotypes, such as structural and functional vascular imaging measures. There is interest in identifying the most relevant mediators of this relationship, including lifestyle (eg, smoking, diet, exercise), medications, and systemic biological mediators (eg, inflammation). Nonetheless, there is a paucity of treatment studies that deliberately engage these mediators, and thus far no treatment studies have focused on engaging vascular imaging targets. CONCLUSIONS: Further research focused on the vascular-bipolar link holds promise for gleaning insights regarding the underlying causes of bipolar disorder, identifying novel treatment approaches, and mitigating disparities in cardiovascular outcomes for people with bipolar disorder.

Centre for Youth Bipolar Disorder Sunnybrook Health Sciences Centre Toronto ON Canada

Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine Cincinnati OH USA

Department of Psychiatry and Behavioral Science University of Minnesota Medical School Minneapolis MN USA

Department of Psychiatry and Psychology Mayo Clinic College of Medicine and Science Rochester MN USA

Department of Psychiatry and Psychotherapy University of Münster Münster Germany

Department of Psychiatry Dalhousie University Halifax NS Canada

Department of Psychiatry Faculty of Medicine Universidad de los Andes Santiago Chile

Department of Psychiatry Harvard Medical School Cambridge MA USA

Department of Psychiatry Massachusetts General Hospital Boston MA USA

Department of Psychiatry Melbourne Medical School The University of Melbourne Melbourne VIC Australia

Department of Psychiatry Queen's University School of Medicine Kingston ON Canada

Department of Psychiatry School of Medicine College of Medicine Taipei Medical University Taipei Taiwan

Department of Psychiatry Taipei Medical University Hospital Taipei Taiwan

Department of Psychiatry University of California San Diego San Diego CA USA

Department of Psychiatry University of Siena Siena Italy

Departments of Psychiatry and Pharmacology Faculty of Medicine University of Toronto Toronto ON Canada

Departments of Psychiatry Internal Medicine and Epidemiology Carver College of Medicine University of Iowa Iowa City IA USA

Hope Me Mood Disorders Association of Ontario Toronto ON Canada

Lindner Center of HOPE Mason OH USA

Mental Health Service Clínica Universidad de los Andes Santiago Chile

Mood Disorders Psychopharmacology Unit University Health Network Toronto ON Canada

National Institute of Mental Health Klecany Czech Republic

The Florey Institute of Neuroscience and Mental Health The University of Melbourne Parkville VIC Australia

Zobrazit více v PubMed

Osby U, Brandt L, Correia N, Ekbom A, Sparen P. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58:844‐850. PubMed

Laursen TM, Munk‐Olsen T, Nordentoft M, Mortensen PB. Increased mortality among patients admitted with major psychiatric disorders: a register‐based study comparing mortality in unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia. J Clin Psychiatry. 2007;68:899‐907. PubMed

Weiner M, Warren L, Fiedorowicz JG. Cardiovascular morbidity and mortality in bipolar disorder. Ann Clin Psychiatry. 2011;23:40‐47. PubMed PMC

Westman J, Hallgren J, Wahlbeck K, Erlinge D, Alfredsson L, Ösby U . Cardiovascular mortality in bipolar disorder: a population‐based cohort study in Sweden. BMJ Open. 2013;3:e002373. PubMed PMC

Hayes JF, Marston L, Walters K, King MB, Osborn DPJ. Mortality gap for people with bipolar disorder and schizophrenia: UK‐based cohort study 2000–2014. Br J Psychiatry. 2017;211:175‐181. PubMed PMC

Crump C, Sundquist K, Winkleby MA, Sundquist J. Comorbidities and mortality in bipolar disorder: a Swedish national cohort study. JAMA Psychiatry. 2013;70:931‐939. PubMed

Laursen TM, Mortensen PB, MacCabe JH, Cohen D, Gasse C. Cardiovascular drug use and mortality in patients with schizophrenia or bipolar disorder: a Danish population‐based study. Psychol Med. 2014;44:1625‐1637. PubMed

Laursen TM, Wahlbeck K, Hallgren J, et al. 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:e67133. PubMed PMC

Castagnini A, Foldager L, Bertelsen A. Excess mortality of acute and transient psychotic disorders: comparison with bipolar affective disorder and schizophrenia. Acta Psychiatr Scand. 2013;128:370‐375. PubMed

Boden R, Molin E, Jernberg T, Kieler H, Lindahl B, Sundstrom J. Higher mortality after myocardial infarction in patients with severe mental illness: a nationwide cohort study. J Intern Med. 2015;277:727‐736. PubMed

Almeida OP, Hankey GJ, Yeap BB, Golledge J, Norman PE, Flicker L. Mortality among people with severe mental disorders who reach old age: a longitudinal study of a community‐representative sample of 37,892 men. PLoS ONE. 2014;9:e111882. PubMed PMC

Angst J, Hengartner MP, Gamma A, von Zerssen D, Angst F. Mortality of 403 patients with mood disorders 48 to 52 years after their psychiatric hospitalisation. Eur Arch Psychiatry Clin Neurosci. 2013;263:425‐434. PubMed

Osby U, Westman J, Hallgren J, Gissler M. Mortality trends in cardiovascular causes in schizophrenia, bipolar and unipolar mood disorder in Sweden 1987–2010. Eur J Public Health. 2016;26:867‐871. PubMed PMC

Goldstein BI, Schaffer A, Wang S, Blanco C. Excessive and premature new‐onset cardiovascular disease among adults with bipolar disorder in the US NESARC cohort. J Clin Psychiatry. 2015;76:163‐169. PubMed

Tsuang MT, Woolson RF, Fleming JA. Causes of death in schizophrenia and manic‐depression. Br J Psychiatry. 1980;136:239‐242. PubMed

Ahrens B, Grof P, Moller HJ, Muller‐Oerlinghausen B, Wolf T. Extended survival of patients on long‐term lithium treatment. Can J Psychiatry. 1995;40:241‐246. PubMed

Fiedorowicz JG, Solomon DA, Endicott J, et al. Manic/hypomanic symptom burden and cardiovascular mortality in bipolar disorder. Psychosom Med. 2009;71:598‐606. PubMed PMC

Fiedorowicz JG, Jancic D, Potash JB, Butcher B, Coryell WH. Vascular mortality in participants of a bipolar genomics study. Psychosomatics. 2014;55:485‐490. PubMed PMC

Coryell W, Turvey C, Leon A, et al. Persistence of depressive symptoms and cardiovascular death among patients with affective disorder. Psychosom Med. 1999;61:755‐761. PubMed

Prieto ML, Schenck LA, Kruse JL, et al. Long‐term risk of myocardial infarction and stroke in bipolar I disorder: a population‐based Cohort Study. J Affect Disord. 2016;194:120‐127. PubMed PMC

Coello K, Kjærstad HL, Stanislaus S, et al. Thirty‐year cardiovascular risk score in patients with newly diagnosed bipolar disorder and their unaffected first‐degree relatives. Austr NZ J Psychiatry. 2019;53:651‐662. PubMed

Tsao W‐Y, Hsu J‐W, Huang K‐L, et al. Risk of cardiometabolic diseases among siblings of patients with bipolar disorder. J Affect Disord. 2019;253:171‐175. PubMed

Zhao Z, Okusaga OO, Quevedo J, Soares JC, Teixeira AL. The potential association between obesity and bipolar disorder: a meta‐analysis. J Affect Disord. 2016;202:120‐123. PubMed

Ayerbe L, Forgnone I, Addo J, Siguero A, Gelati S, Ayis S. Hypertension risk and clinical care in patients with bipolar disorder or schizophrenia; a systematic review and meta‐analysis. J Affect Disord. 2018;225:665‐670. PubMed

Vancampfort D, Correll CU, Galling B, et al. Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta‐analysis. World Psychiatry. 2016;15:166‐174. PubMed PMC

Heffner JL, Strawn JR, DelBello MP, Strakowski SM, Anthenelli RM. The co‐occurrence of cigarette smoking and bipolar disorder: phenomenology and treatment considerations. Bipolar Disord. 2011;13:439‐453. PubMed PMC

McElroy SL, Frye MA, Suppes T, et al. Correlates of overweight and obesity in 644 patients with bipolar disorder. J Clin Psychiatry. 2002;63:207‐213. PubMed

Goldstein BI, Fagiolini A, Houck P, Kupfer DJ. Cardiovascular disease and hypertension among adults with bipolar I disorder in the United States. Bipolar Disord. 2009;11:657‐662. PubMed PMC

Fagiolini A, Frank E, Houck PR, et al. Prevalence of obesity and weight change during treatment in patients with bipolar I disorder. J Clin Psychiatry. 2002;63:528‐533. PubMed

McIntyre RS, Woldeyohannes HO, Soczynska JK, et al. The rate of metabolic syndrome in euthymic Canadian individuals with bipolar I/II disorder. Adv Ther. 2010;27:828‐836. PubMed

Fagiolini A, Kupfer DJ, Rucci P, Scott JA, Novick DM, Frank E. Suicide attempts and ideation in patients with bipolar I disorder. J Clin Psychiatry. 2004;65:509‐514. PubMed

Fagiolini A, Frank E, Scott JA, Turkin S, Kupfer DJ. Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians. Bipolar Disord. 2005;7:424‐430. PubMed

Shapiro J, Mindra S, Timmins V, et al. Controlled study of obesity among adolescents with bipolar disorder. J Child Adolesc Psychopharmacol. 2017;27:95‐100. PubMed

Goldstein BI, Blanco C, He JP, Merikangas K. Correlates of overweight and obesity among adolescents with bipolar disorder in the National Comorbidity Survey‐Adolescent Supplement (NCS‐A). J Am Acad Child Adolesc Psychiatry. 2016;55:1020‐1026. PubMed

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;13:387‐395. PubMed PMC

Gomes FA, Kauer‐Sant’Anna M, Magalhães PV, et al. Obesity is associated with previous suicide attempts in bipolar disorder. Acta Neuropsychiatr. 2010;22:63‐67. PubMed

Hu C, Torres IJ, Qian H, et al. Trajectories of body mass index change in first episode of mania: 3‐year data from the Systematic Treatment Optimization Program for Early Mania (STOP‐EM). J Affect Disord. 2017;208:291‐297. PubMed

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;160:112‐117. PubMed

McIntyre RSMF. Pappadopulos E Baseline metabolic status is a moderator of outcome in bipolar disorder patients: analysis of pooled data from ziprasidone monotherapy clinical trials. 164th Annual Meeting of the American Psychiatric Association. Honolulu, HI: American Psychiatric Association; 2011.

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;12:404‐413. PubMed PMC

Peters AT, Shesler LW, Sylvia L, et al. Medical burden, body mass index and the outcome of psychosocial interventions for bipolar depression. Aust NZ J Psychiatry. 2016;50:667‐677. PubMed

Ruzickova M, Slaney C, Garnham J, Alda M. Clinical features of bipolar disorder with and without comorbid diabetes mellitus. Can J Psychiatry. 2003;48:458‐461. PubMed

Calkin CV, Ruzickova M, Uher R, et al. Insulin resistance and outcome in bipolar disorder. Br J Psychiatry. 2015;206:52‐57. PubMed

Slomka JM, Piette JD, Post EP, et al. Mood disorder symptoms and elevated cardiovascular disease risk in patients with bipolar disorder. J Affect Disord. 2012;138:405‐408. PubMed PMC

Icick R, Gard S, Barde M, et al. Physical and mental health burden in cases of bipolar disorder classified as current, former, or non‐tobacco smokers. J Affect Disord. 2017;208:406‐413. PubMed

Vanable PA, Carey MP, Carey KB, Maisto SA. Smoking among psychiatric outpatients: relationship to substance use, diagnosis, and illness severity. Psychol Addict Behav. 2003;17:259‐265. PubMed PMC

Waxmonsky JA, Thomas MR, Miklowitz DJ, et al. Prevalence and correlates of tobacco use in bipolar disorder: data from the first 2000 participants in the Systematic Treatment Enhancement Program. Gen Hosp Psychiatry. 2005;27:321‐328. PubMed

Ostacher MJ, Nierenberg AA, Perlis RH, et al. The relationship between smoking and suicidal behavior, comorbidity, and course of illness in bipolar disorder. J Clin Psychiatry. 2006;67:1907‐1911. PubMed

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;27:223‐228. PubMed

Depp CA, Strassnig M, Mausbach BT, et al. Association of obesity and treated hypertension and diabetes with cognitive ability in bipolar disorder and schizophrenia. Bipolar Disord. 2014;16:422‐431. PubMed PMC

Lackner N, Bengesser SA, Birner A, et al. Abdominal obesity is associated with impaired cognitive function in euthymic bipolar individuals. World J Biol Psychiatry. 2016;17:535‐546. PubMed

Bai YM, Li CT, Tsai SJ, Tu PC, Chen MH, Su TP. Metabolic syndrome and adverse clinical outcomes in patients with bipolar disorder. BMC Psychiatry. 2016;16:448. PubMed PMC

Mora E, Portella MJ, Martinez‐Alonso M, et al. The impact of obesity on cognitive functioning in euthymic bipolar patients: a cross‐sectional and longitudinal study. J Clin Psychiatry. 2017;78:e924‐e932. PubMed

Hubenak J, Tuma I, Bazant J. Association of arterial hypertension and cognitive impairment in euthymic bipolar disorder. Neuro Endocrinol Lett. 2015;36:294‐300. PubMed

Bora E, McIntyre RS, Ozerdem A. Neurococognitive and neuroimaging correlates of obesity and components of metabolic syndrome in bipolar disorder: a systematic review. Psychol Med. 2019;49:738–749. PubMed

Naiberg MR, Newton DF, Collins JE, Bowie CR, Goldstein BI. Impulsivity is associated with blood pressure and waist circumference among adolescents with bipolar disorder. J Psychiatr Res. 2016;83:230‐239. PubMed

Naiberg MR, Newton DF, Collins JE, Dickstein DP, Bowie CR, Goldstein BI. Elevated triglycerides are associated with decreased executive function among adolescents with bipolar disorder. Acta Psychiatr Scand. 2016;134:241‐248. PubMed

Silveira LE, Kozicky JM, Muralidharan K, et al. Neurocognitive functioning in overweight and obese patients with bipolar disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP‐EM). Can J Psychiatry. 2014;59:639‐648. PubMed PMC

Bond DJ, Torres IJ, Lee SS, et al. Lower cognitive functioning as a predictor of weight gain in bipolar disorder: a 12‐month study. Acta Psychiatr Scand. 2017;135:239‐249. PubMed

Depp CA, Bowie CR, Mausbach BT, et al. Current smoking is associated with worse cognitive and adaptive functioning in serious mental illness. Acta Psychiatr Scand. 2015;131:333‐341. PubMed PMC

Law CW, Soczynska JK, Woldeyohannes HO, Miranda A, Brooks JO 3rd, McIntyre RS. Relation between cigarette smoking and cognitive function in euthymic individuals with bipolar disorder. Pharmacol Biochem Behav. 2009;92:12‐16. PubMed

Morisano D, Wing VC, Sacco KA, Arenovich T, George TP. Effects of tobacco smoking on neuropsychological function in schizophrenia in comparison to other psychiatric disorders and non‐psychiatric controls. Am J Addict. 2013;22:46‐53. PubMed

Kolotkin RL, Corey‐Lisle PK, Crosby RD, et al. Impact of obesity on health‐related quality of life in schizophrenia and bipolar disorder. Obesity. 2008;16:749‐754. PubMed

Calkin C, van de Velde C, Ruzickova M, et al. Can body mass index help predict outcome in patients with bipolar disorder? Bipolar Disord. 2009;11:650‐656. PubMed PMC

Malhotra N, Kulhara P, Chakrabarti S, Grover S. Lifestyle related factors & impact of metabolic syndrome on quality of life, level of functioning & self‐esteem in patients with bipolar disorder & schizophrenia. Indian J Med Res. 2016;143:434‐442. PubMed PMC

Bond DJ, Kunz M, Torres IJ, Lam RW, Yatham LN. The association of weight gain with mood symptoms and functional outcomes following a first manic episode: prospective 12‐month data from the Systematic Treatment Optimization Program for Early Mania (STOP‐EM). Bipolar Disord. 2010;12:616‐626. PubMed

McElroy SL, Kemp DE, Friedman ES, et al. Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder. Acta Psychiatr Scand. 2016;133:144‐153. PubMed PMC

Miller S, Ittasakul P, Wang PW, et al. Enhanced ziprasidone combination therapy effectiveness in obese compared to nonobese patients with bipolar disorder. J Clin Psychopharmacol. 2012;32:814‐819. PubMed

Jackson JG, Diaz FJ, Lopez L, de Leon J. A combined analysis of worldwide studies demonstrates an association between bipolar disorder and tobacco smoking behaviors in adults. Bipolar Disord. 2015;17:575‐597. PubMed

Vermeulen JM, Wootton RE, Treur JL, et al. Smoking and the risk for bipolar disorder: evidence from a bidirectional Mendelian randomisation study. Br J Psychiatry. 2019;1–7. [Epub ahead of print]. 10.1192/bjp.2019.202 PubMed DOI

Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double‐blind, randomised, placebo‐controlled clinical trial. Lancet. 2016;387:2507‐2520. PubMed

Thorndike AN, Achtyes ED, Cather C, et al. Weight gain and 10‐year cardiovascular risk with sustained tobacco abstinence in smokers with serious mental illness: a subgroup analysis of a randomized trial. J Clin Psychiatry. 2016;77:e320‐e326. PubMed

Harvey AG, Schmidt DA, Scarna A, Semler CN, Goodwin GM. Sleep‐related functioning in euthymic patients with bipolar disorder, patients with insomnia, and subjects without sleep problems. Am J Psychiatry. 2005;162:50‐57. PubMed

Cooper CB, Neufeld EV, Dolezal BA, Martin JL. Sleep deprivation and obesity in adults: a brief narrative review. BMJ Open Sport Exerc Med. 2018;4:e000392. PubMed PMC

Sylvia LG, Chang WC, Kamali M, et al. Sleep disturbance may impact treatment outcome in bipolar disorder: a preliminary investigation in the context of a large comparative effectiveness trial. J Affect Disord. 2018;225:563‐568. PubMed

Norris ER, Karen B, Correll JR, et al. A double‐blind, randomized, placebo‐controlled trial of adjunctive ramelteon for the treatment of insomnia and mood stability in patients with euthymic bipolar disorder. J Affect Disord. 2013;144:141‐147. PubMed

Wang HR, Woo YS, Bahk WM. The role of melatonin and melatonin agonists in counteracting antipsychotic‐induced metabolic side effects: a systematic review. Int Clin Psychopharmacol. 2016;31:301‐306. PubMed

Elmslie JL, Mann JI, Silverstone JT, Williams SM, Romans SE. Determinants of overweight and obesity in patients with bipolar disorder. J Clin Psychiatry. 2001;62:486‐491. PubMed

Kilbourne AM, Rofey DL, McCarthy JF, Post EP, Welsh D, Blow FC. Nutrition and exercise behavior among patients with bipolar disorder. Bipolar Disord. 2007;9:443‐452. PubMed

Cuellar‐Barboza AB, Winham SJ, Biernacka JM, Frye MA, McElroy SL. Clinical phenotype and genetic risk factors for bipolar disorder with binge eating: an update. Expert Rev Neurother. 2019;19:867‐879. PubMed

Yaramala SR, McElroy SL, Geske J, et al. The impact of binge eating behavior on lithium‐ and quetiapine‐associated changes in body weight, body mass index, and waist circumference during 6 months of treatment: findings from the bipolar CHOICE study. J Affect Disord. 2020;266:772‐781. PubMed

Brown S, Birtwistle J, Roe L, Thompson C. The unhealthy lifestyle of people with schizophrenia. Psychol Med. 1999;29:697‐701. PubMed

Ryan M, Collins P, Thakore J. Impaired fasting glucose tolerance in first‐episode, drug‐naive patients with schizophrenia. Am J Psychiatry Res. 2003;160:284‐289. PubMed

Elmslie JL, Silverstone JT, Mann JI, Williams SM, Romans SE. Prevalence of overweight and obesity in bipolar patients. J Clin Psychiatry. 2000;61:179‐184. PubMed

Davidson S, Judd F, Jolley D, Hocking B, Thompson S, Hyland B. Cardiovascular risk factors for people with mental illness. Aust N Z J Psychiatry. 2001;35:196‐202. PubMed

Bly MJ, Taylor SF, Dalack G, et al. Metabolic syndrome in bipolar disorder and schizophrenia: dietary and lifestyle factors compared to the general population. Bipolar Disord. 2014;16:277‐288. PubMed PMC

Romo‐Nava F, Blom TJ, Guerdjikova A, et al. Evening chronotype, disordered eating behavior, and poor dietary habits in bipolar disorder. Acta Psychiatr Scand. 2020. [Epub ahead of print]. 10.1111/acps.13179 PubMed DOI

Melo MC, Daher Ede F, Albuquerque SG, de Bruin VM. Exercise in bipolar patients: a systematic review. J Affect Disord. 2016;198:32‐38. PubMed

Vancampfort D, Firth J, Schuch F, et al. Physical activity and sedentary behavior in people with bipolar disorder: a systematic review and meta‐analysis. J Affect Disord. 2016;201:145‐152. PubMed

Vancampfort D, Wyckaert S, Sienaert P, et al. The functional exercise capacity in patients with bipolar disorder versus healthy controls: a pilot study. Psychiatry Res. 2015;229:194‐199. PubMed

Sylvia LG, Friedman ES, Kocsis JH, et al. Association of exercise with quality of life and mood symptoms in a comparative effectiveness study of bipolar disorder. J Affect Disord. 2013;151:722‐727. PubMed

Lawlor DA, Hopker SW. The effectiveness of exercise as an intervention in the management of depression: systematic review and meta‐regression analysis of randomised controlled trials. BMJ. 2001;322:763‐767. PubMed PMC

Stathopoulou G, Powers MB, Berry AC, Smits JAJ, Otto MW. Exercise interventions for mental health: a quantitative and qualitative review. Clin Psychol Sci Pract. 2006;13:179‐193.

Babyak M, Blumenthal JA, Herman S, et al. Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months. Psychosom Med. 2000;62:633‐638. PubMed

Blumenthal JA, Babyak MA, Moore KA, et al. Effects of exercise training on older patients with major depression. Arch Intern Med. 1999;159:2349‐2356. PubMed

Ng F, Dodd S, Berk M. The effects of physical activity in the acute treatment of bipolar disorder: a pilot study. J Affect Disord. 2007;101:259‐262. PubMed

Schuch FB, da Silveira LE, de Zeni TC, et al. Effects of a single bout of maximal aerobic exercise on BDNF in bipolar disorder: a gender‐based response. Psychiatry Res. 2015;229:57‐62. PubMed

Sylvia LG, Ametrano RM, Nierenberg AA. Exercise treatment for bipolar disorder: potential mechanisms of action mediated through increased neurogenesis and decreased allostatic load. Psychother Psychosom. 2010;79:87‐96. PubMed

Fagiolini A, Frank E, Soreca I, Houck PR, Kupfer DJ. Integrating medical and psychiatric care in patients with bipolar disorder. J Clin Psychopharmacol. 2008;28:257‐258. PubMed

Daumit GL, Dickerson FB, Wang NY, et al. A behavioral weight‐loss intervention in persons with serious mental illness. N Engl J Med. 2013;368:1594‐1602. PubMed PMC

Sylvia LG, Nierenberg AA, Stange JP, Peckham AD, Deckersbach T. Development of an integrated psychosocial treatment to address the medical burden associated with bipolar disorder. J Psychiatr Pract. 2011;17:224‐232. PubMed PMC

Sylvia LG, Salcedo S, Bernstein EE, Baek JH, Nierenberg AA, Deckersbach T. Nutrition, exercise, and wellness treatment in bipolar disorder: proof of concept for a consolidated intervention. Int J Bipolar Disord. 2013;1:24. PubMed PMC

Abosi O, Lopes S, Schmitz S, Fiedorowicz JG. Cardiometabolic effects of psychotropic medications. Horm Mol Biol Clin Investig. 2018;36:1‐15. PubMed PMC

Marano G, Traversi G, Romagnoli E, et al. Cardiologic side effects of psychotropic drugs. J Geriatr Cardiol. 2011;8:243‐253. PubMed PMC

Bowden CL, Mosolov S, Hranov L, et al. Efficacy of valproate versus lithium in mania or mixed mania: a randomized, open 12‐week trial. Int Clin Psychopharmacol. 2010;25:60‐67. PubMed

Calabrese JR, Bowden CL, Sachs G, et al. A placebo‐controlled 18‐month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry. 2003;64:1013‐1024. PubMed

Chengappa KNR, Chalasani L, Brar JS, Parepally H, Houck P, Levine J. Changes in body weight and body mass index among psychiatric patients receiving lithium, valproate, or topiramate: an open‐label, nonrandomized chart review. Clin Ther. 2002;24:1576‐1584. PubMed

Keck PE, Orsulak PJ, Cutler AJ, et al. Aripiprazole monotherapy in the treatment of acute bipolar I mania: a randomized, double‐blind, placebo‐ and lithium‐controlled study. J Affect Disord. 2009;112:36‐49. PubMed

Almandil NB, Liu Y, Murray ML, Besag FM, Aitchison KJ, Wong IC. Weight gain and other metabolic adverse effects associated with atypical antipsychotic treatment of children and adolescents: a systematic review and meta‐analysis. Paediatr Drugs. 2013;15:139‐150. PubMed

Osborn DPJ, Hardoon S, Omar RZ, et al. Cardiovascular risk prediction models for people with severe mental illness: results from the prediction and management of cardiovascular risk in people with severe mental illnesses (PRIMROSE) research program. JAMA Psychiatry. 2015;72:143‐151. PubMed PMC

Wimberley T, MacCabe JH, Laursen TM, et al. Mortality and self‐harm in Association with clozapine in treatment‐resistant schizophrenia. Am J Psychiatry. 2017;174:990‐998. PubMed

Taipale H, Tanskanen A, Mehtälä J, Vattulainen P, Correll CU, Tiihonen J. 20‐year follow‐up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20). World Psychiatry. 2020;19:61‐68. PubMed PMC

Al‐Amin MM, Nasir Uddin MM, Mahmud RH. Effects of antipsychotics on the inflammatory response system of patients with schizophrenia in peripheral blood mononuclear cell cultures. Clin Psychopharmacol Neurosci. 2013;11:144‐151. PubMed PMC

Grossini E, Gramaglia C, Farruggio S, et al. Asenapine increases nitric oxide release and protects porcine coronary artery endothelial cells against peroxidation. Vascul Pharmacol. 2014;60:127‐141. PubMed

Grossini E, Gramaglia C, Farruggio S, et al. Asenapine modulates nitric oxide release and calcium movements in cardiomyoblasts. J Pharmacol Pharmacother. 2016;7:6‐14. PubMed PMC

Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ. 2013;346:f2610. PubMed PMC

Rotella F, Cassioli E, Calderani E, et al. Long‐term metabolic and cardiovascular effects of antipsychotic drugs. A meta‐analysis of randomized controlled trials. Eur Neuropsychopharmacol. 2020;32:56–65. PubMed

McIntyre RS. A vision for drug discovery and development: novel targets and multilateral partnerships. Adv Ther. 2014;31:245‐246. PubMed PMC

Redlich C, Berk M, Williams LJ, Sundquist J, Sundquist K, Li X. Statin use and risk of depression: a Swedish national cohort study. BMC Psychiatry. 2014;14:348. PubMed PMC

Kim SW, Kang HJ, Bae KY, et al. Interactions between pro‐inflammatory cytokines and statins on depression in patients with acute coronary syndrome. Prog Neuropsychopharmacol Biol Psychiatry. 2018;80:250‐254. PubMed

Persons JE, Robinson JG, Payne ME, Fiedorowicz JG. Serum lipid changes following the onset of depressive symptoms in postmenopausal women. Psychiatry Res. 2017;247:282‐287. PubMed PMC

Williams LJ, Pasco JA, Mohebbi M, et al. Statin and aspirin use and the risk of mood disorders among men. Int J Neuropsychopharmacol. 2016;19(6):pii:pyw008. PubMed PMC

Stafford L, Berk M. The use of statins after a cardiac intervention is associated with reduced risk of subsequent depression: proof of concept for the inflammatory and oxidative hypotheses of depression? J Clin Psychiatry. 2011;72:1229‐1235. PubMed

Salagre E, Fernandes BS, Dodd S, Brownstein DJ, Berk M. Statins for the treatment of depression: a meta‐analysis of randomized, double‐blind, placebo‐controlled trials. J Affect Disord. 2016;200:235‐242. PubMed

O'Neil A, Sanna L, Redlich C, et al. The impact of statins on psychological wellbeing: a systematic review and meta‐analysis. BMC Med. 2012;10:154. PubMed PMC

Sung K‐C, Huh JH, Ryu S, et al. Low levels of low‐density lipoprotein cholesterol and mortality outcomes in non‐statin users. J Clin Med. 2019;8:1571. PubMed PMC

Tomson‐Johanson K, Harro J. Low cholesterol, impulsivity and violence revisited. Curr Opin Endocrinol Diabetes Obes. 2018;25:103‐107. PubMed

Messaoud A, Mensi R, Mrad A, et al. Is low total cholesterol levels associated with suicide attempt in depressive patients? Ann Gen Psychiatry. 2017;16:20. PubMed PMC

Huang Y‐J, Tsai S‐Y, Chung K‐H, Chen P‐H, Huang S‐H, Kuo C‐J. State‐dependent alterations of lipid profiles in patients with bipolar disorder. Int J Psychiatry Med. 2018;53:273‐281. PubMed

Cipriani A, Saunders K, Attenburrow MJ, et al. A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development. Mol Psychiatry. 2016;21:1324‐1332. PubMed PMC

Kucukali CI, Aydin M, Ozkok E, et al. Angiotensin‐converting enzyme polymorphism in schizophrenia, bipolar disorders, and their first‐degree relatives. Psychiatr Genet. 2010;20:14‐19. PubMed

Meira‐Lima IV, Pereira AC, Mota GF, Krieger JE, Vallada H. Angiotensinogen and angiotensin converting enzyme gene polymorphisms and the risk of bipolar affective disorder in humans. Neurosci Lett. 2000;293:103‐106. PubMed

Boal AH, Smith DJ, McCallum L, et al. Monotherapy with major antihypertensive drug classes and risk of hospital admissions for mood disorders. Hypertension. 2016;68:1132‐1138. PubMed PMC

Brownstein DJ, Salagre E, Kohler C, et al. Blockade of the angiotensin system improves mental health domain of quality of life: a meta‐analysis of randomized clinical trials. Aust N Z J Psychiatry. 2018;52:24‐38. PubMed

Frey BN, Andreazza AC, Houenou J, et al. Biomarkers in bipolar disorder: a positional paper from the International Society for Bipolar Disorders Biomarkers Task Force. Aust N Z J Psychiatry. 2013;47:321‐332. PubMed

Berk M, Kapczinski F, Andreazza AC, et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. 2011;35:804‐817. PubMed

Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15:6184‐6223. PubMed PMC

Ntaios G, Gatselis NK, Makaritsis K, Dalekos GN. Adipokines as mediators of endothelial function and atherosclerosis. Atherosclerosis. 2013;227:216‐221. PubMed

Fernandes BS, Dash S, Jacka F, et al. Leptin in bipolar disorder: a systematic review and meta‐analysis. Eur Psychiatry. 2016;35:1‐7. PubMed

Goldstein BI, Carnethon MR, Matthews KA, et al. Major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2015;132:965‐986. PubMed

Gergerlioglu HS, Savas HA, Bulbul F, Selek S, Uz E, Yumru M. Changes in nitric oxide level and superoxide dismutase activity during antimanic treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:697‐702. PubMed

Buckley DI, Fu R, Freeman M, Rogers K, Helfand M. C‐reactive protein as a risk factor for coronary heart disease: a systematic review and meta‐analyses for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151:483‐495. PubMed

Glowinska‐Olszewska B, Tolwinska J, Urban M. Relationship between endothelial dysfunction, carotid artery intima media thickness and circulating markers of vascular inflammation in obese hypertensive children and adolescents. J Pediatr Endocrinol Metab. 2007;20:1125‐1136. PubMed

Liu M, Wang F, Wang Y, Jin R. Atorvastatin improves endothelial function and cardiac performance in patients with dilated cardiomyopathy: the role of inflammation. Cardiovasc Drugs Ther. 2009;23:369‐376. PubMed

Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease application to clinical and public health practice: a statement for healthcare professionals from the centers for disease control and prevention and the American Heart Association. Circulation. 2003;107:499‐511. PubMed

Goldstein BI, Young LT. Toward clinically applicable biomarkers in bipolar disorder: focus on BDNF, inflammatory markers, and endothelial function. Curr Psychiatry Rep. 2013;15:425. PubMed PMC

Rao JS, Harry GJ, Rapoport SI, Kim HW. Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients. Mol Psychiatry. 2010;15:384‐392. PubMed PMC

Goldstein BI, Kemp DE, Soczynska JK, McIntyre RS. Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature. J Clin Psychiatry. 2009;70:1078‐1090. PubMed

Brietzke E, Stertz L, Fernandes BS, et al. Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J Affect Disord. 2009;116:214‐217. PubMed

Munkholm K, Vinberg M, Vedel KL. Cytokines in bipolar disorder: a systematic review and meta‐analysis. J Affect Disord. 2013;144:16‐27. PubMed

Kattoor AJ, Pothineni NVK, Palagiri D, Mehta JL. Oxidative stress in atherosclerosis. Curr Atheroscler Rep. 2017;19:42. PubMed

Forstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res. 2017;120:713‐735. PubMed

Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87:840‐844. PubMed

Incalza MA, D'Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vasc Pharmacol. 2018;100:1‐19. PubMed

Huggins GS. Genetic susceptibility to oxidative stress and cardiovascular disease. EBioMedicine. 2015;2:1864‐1865. PubMed PMC

Rocha M, Apostolova N, Hernandez‐Mijares A, Herance R, Victor VM. Oxidative stress and endothelial dysfunction in cardiovascular disease: mitochondria‐targeted therapeutics. Curr Med Chem. 2010;17:3827‐3841. PubMed

Andreazza AC, Shao L, Wang J‐F, Young LT. Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disordermitochondrial dysfunction and oxidative stress. Arch Gen Psychiatry. 2010;67:360‐368. PubMed

Wang J‐F, Shao L, Sun X, Young LT. Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia. Bipolar Disord. 2009;11:523‐529. PubMed

Pius‐Sadowska E, Machaliński B. BDNF – a key player in cardiovascular system. J Mol Cell Cardiol. 2017;110:54‐60. PubMed

Manni L, Nikolova V, Vyagova D, Chaldakov GN, Aloe L. Reduced plasma levels of NGF and BDNF in patients with acute coronary syndromes. Int J Cardiol. 2005;102:169‐171. PubMed

Kaess BM, Preis SR, Lieb W, et al. Circulating brain‐derived neurotrophic factor concentrations and the risk of cardiovascular disease in the community. J Am Heart Assoc. 2015;4:e001544. PubMed PMC

Alomari MA, Khabour OF, Maikano A, Alawneh K. Vascular function and brain‐derived neurotrophic factor: the functional capacity factor. Vasc Med. 2015;20:518‐526. PubMed

Donovan MJ, Lin MI, Wiegn P, et al. Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization. Development. 2000;127:4531‐4540. PubMed

Tang J, Xiao L, Shu C, et al. Association of the brain‐derived neurotrophic factor gene and bipolar disorder with early age of onset in mainland China. Neurosci Lett. 2008;433:98‐102. PubMed

Matsuo K, Walss‐Bass C, Nery FG, et al. Neuronal correlates of brain‐derived neurotrophic factor Val66Met polymorphism and morphometric abnormalities in bipolar disorder. Neuropsychopharmacology. 2009;34:1904‐1913. PubMed

Fernandes BS, Gama CS, Cereser KM, et al. Brain‐derived neurotrophic factor as a state‐marker of mood episodes in bipolar disorders: a systematic review and meta‐regression analysis. J Psychiatr Res. 2011;45:995‐1004. PubMed

Hallahan B, Newell J, Soares JC, et al. Structural magnetic resonance imaging in bipolar disorder: an international collaborative mega‐analysis of individual adult patient data. Biol Psychiat. 2011;69:326‐335. PubMed

Kempton MJ, Geddes JR, Ettinger U, Williams SC, Grasby PM. Meta‐analysis, database, and meta‐regression of 98 structural imaging studies in bipolar disorder. Arch Gen Psychiatry. 2008;65:1017‐1032. PubMed

Smith EE. Leukoaraiosis and stroke. Stroke. 2010;41:S139‐S143. PubMed PMC

Beyer JL, Young R, Kuchibhatla M, Krishnan KRR. Hyperintense MRI lesions in bipolar disorder: a meta‐analysis and review. Int Rev Psychiatry. 2009;21:394‐409. PubMed PMC

Tighe SK, Reading SA, Rivkin P, et al. Total white matter hyperintensity volume in bipolar disorder patients and their healthy relatives. Bipolar Disord. 2012;14:888‐893. PubMed PMC

Gunde E, Novak T, Kopecek M, et al. White matter hyperintensities in affected and unaffected late teenage and early adulthood offspring of bipolar parents: a two‐center high‐risk study. J Psychiatr Res. 2011;45:76‐82. PubMed

Gunde E, Blagdon R, Hajek T. White matter hyperintensities: from medical comorbidities to bipolar disorders and back. Ann Med. 2011;43:571‐580. PubMed PMC

Ward MA, Carlsson CM, Trivedi MA, Sager MA, Johnson SC. The effect of body mass index on global brain volume in middle‐aged adults: a cross sectional study. BMC Neurol. 2005;5:23. PubMed PMC

Taki Y, Kinomura S, Sato K, et al. Relationship between body mass index and gray matter volume in 1,428 healthy individuals. Obesity. 2008;16:119‐124. PubMed

Gunstad J, Paul RH, Cohen RA, et al. Relationship between body mass index and brain volume in healthy adults. Int J Neurosci. 2008;118:1582‐1593. PubMed

Soreca I, Rosano C, Jennings JR, et al. Gain in adiposity across 15 years is associated with reduced gray matter volume in healthy women. Psychosom Med. 2009;71:485‐490. PubMed PMC

Walther K, Birdsill AC, Glisky EL, Ryan L. Structural brain differences and cognitive functioning related to body mass index in older females. Hum Brain Mapp. 2010;31:1052‐1064. PubMed PMC

Ho AJ, Stein JL, Hua X, et al. A commonly carried allele of the obesity‐related FTO gene is associated with reduced brain volume in the healthy elderly. Proc Natl Acad Sci USA. 2010;107:8404‐8409. PubMed PMC

Enzinger C, Fazekas F, Matthews PM, et al. Risk factors for progression of brain atrophy in aging: six‐year follow‐up of normal subjects. Neurology. 2005;64:1704‐1711. PubMed

Bond DJ, Lang DJ, Noronha MM, et al. The association of elevated body mass index with reduced brain volumes in first‐episode mania. Biol Psychiat. 2011;70:381‐387. PubMed

Bond DJ, Ha TH, Lang DJ, et al. Body mass index‐related regional gray and white matter volume reductions in first‐episode mania patients. Biol Psychiat. 2014;76:138‐145. PubMed

Kuswanto CN, Sum MY, Yang GL, Nowinski WL, McIntyre RS, Sim K. Increased body mass index makes an impact on brain white‐matter integrity in adults with remitted first‐episode mania. Psychol Med. 2014;44:533‐541. PubMed

Islam AH, Metcalfe AWS, MacIntosh BJ, Korczak DJ, Goldstein BI. Greater body mass index is associated with reduced frontal cortical volumes among adolescents with bipolar disorder. J Psychiatry Neurosci. 2018;43:120‐130. PubMed PMC

Bond DJ, da Silveira LE, MacMillan EL, et al. Relationship between body mass index and hippocampal glutamate/glutamine in bipolar disorder. Br J Psychiatry. 2016;208:146‐152. PubMed

Bond DJ, Silveira LE, MacMillan EL, et al. Diagnosis and body mass index effects on hippocampal volumes and neurochemistry in bipolar disorder. Transl Psychiat. 2017;7:e1071. PubMed PMC

Viana‐Sulzbach M, Pedrini M, Bucker J, Brietzke E, Gama CS. Hippocampus size does not correlate with body mass index in bipolar disorder. Rev Bras Psiquiatr. 1999;2016:86‐87. PubMed PMC

Bond DJ, Su W, Honer WG, et al. Weight gain as a predictor of frontal and temporal lobe volume loss in bipolar disorder: a prospective MRI study. Bipolar Disord. 2019;21:50‐60. PubMed

Melhorn SJ, Askren MK, Chung WK, et al. FTO genotype impacts food intake and corticolimbic activation. Am J Clin Nutr. 2018;107:145–154. PubMed PMC

Olivo G, Latini F, Wiemerslage L, Larsson EM, Schiöth HB. Disruption of accumbens and thalamic white matter connectivity revealed by diffusion tensor tractography in young men with genetic risk for obesity. Front Hum Neurosci. 2018;12:75. PubMed PMC

Lancaster TM, Ihssen I, Brindley LM, Linden DE. Preliminary evidence for genetic overlap between body mass index and striatal reward response. Transl Psychiatry. 2018;8:19. PubMed PMC

Hajek T, Calkin C, Blagdon R, Slaney C, Uher R, Alda M. Insulin resistance, diabetes mellitus, and brain structure in bipolar disorders. Neuropsychopharmacology. 2014;39:2910‐2918. PubMed PMC

Hajek T, Calkin C, Blagdon R, Slaney C, Alda M. Type 2 diabetes mellitus: a potentially modifiable risk factor for neurochemical brain changes in bipolar disorders. Biol Psychiat. 2015;77:295‐303. PubMed

Jørgensen KN, Skjærvø I, Mørch‐Johnsen L, et al. Cigarette smoking is associated with thinner cingulate and insular cortices in patients with severe mental illness. J Psychiatry Neurosci. 2015;40:241–249. PubMed PMC

Phillips ML, Swartz HA. A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and a road map for future research. Am J Psychiatry. 2014;171:829‐843. PubMed PMC

Peterson EC, Wang Z, Britz G. Regulation of cerebral blood flow. Int J Vasc Med. 2011;2011:823525. PubMed PMC

Jennings JR, Heim AF, Kuan DC, Gianaros PJ, Muldoon MF, Manuck SB. Use of total cerebral blood flow as an imaging biomarker of known cardiovascular risks. Stroke. 2013;44:2480‐2485. PubMed PMC

Shi Y, Thrippleton MJ, Makin SD, et al. Cerebral blood flow in small vessel disease: a systematic review and meta‐analysis. J Cereb Blood Flow Metab. 2016;36:1653‐1667. PubMed PMC

Toma S, MacIntosh BJ, Swardfager W, Goldstein BI. Cerebral blood flow in bipolar disorder: a systematic review. J Affect Disord. 2018;241:505‐513. PubMed

Bhardwaj R, Chakrabarti S, Mittal BR, Sharan P. A single photon emission computerized tomography (SPECT) study of regional cerebral blood flow in bipolar disorder. World J Biol Psychiatry. 2010;11:334‐343. PubMed

Ito H, Kawashima R, Awata S, et al. Hypoperfusion in the limbic system and prefrontal cortex in depression: SPECT with anatomic standardization technique. J Nucl Med. 1996;37:410‐414. PubMed

Drevets WC, Price JL, Simpson JR, et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature. 1997;386:824‐827. PubMed

Rubin E, Sackeim HA, Prohovnik I, Moeller JR, Schnur DB, Mukherjee S. Regional cerebral blood flow in mood disorders: IV. Comparison of mania and depression. Psychiatry Res. 1995;61:1‐10. PubMed

Tutus A, Simsek A, Sofuoglu S, et al. Changes in regional cerebral blood flow demonstrated by single photon emission computed tomography in depressive disorders: comparison of unipolar vs. bipolar subtypes. Psychiatry Res. 1998;83:169‐177. PubMed

Zhao L, Wang Y, Jia Y, et al. Microstructural abnormalities of basal ganglia and thalamus in bipolar and unipolar disorders: a diffusion kurtosis and perfusion imaging study. Psychiatry Investig. 2017;14:471‐482. PubMed PMC

Dev SI, McKenna BS, Sutherland AN, et al. Increased cerebral blood flow associated with better response inhibition in bipolar disorder. J Int Neuropsychol Soc. 2015;21:105‐115. PubMed PMC

Krüger S, Alda M, Young LT, Goldapple K, Parikh S, Mayberg HS. Risk and resilience markers in bipolar disorder: brain responses to emotional challenge in bipolar patients and their healthy siblings. Am J Psychiatry. 2006;163:257‐264. PubMed

Almeida JR, Mourao‐Miranda J, Aizenstein HJ, et al. Pattern recognition analysis of anterior cingulate cortex blood flow to classify depression polarity. Br J Psychiatry. 2013;203:310‐311. PubMed PMC

Goodwin GM, Cavanagh JTO, Glabus MF, Kehoe RF, O'Carroll RE, Ebmeier KP. Uptake of 99mTc‐exametazime shown by single photon emission computed tomography before and after lithium withdrawal in bipolar patients: associations with mania. Br J Psychiatry. 1997;170:426‐430. PubMed

Murray DP, Metz NS, Haynes WG, Fiedorowicz JG. Vascular function is not impaired early in the course of bipolar disorder. J Psychosom Res. 2012;72:195‐198. PubMed PMC

Tong B, Abosi O, Schmitz S, Myers J, Pierce GL, Fiedorowicz JG. Bipolar disorder and related mood states are not associated with endothelial function of small arteries in adults without heart disease. Gen Hosp Psychiatry. 2018;51:36‐40. PubMed PMC

Rybakowski JK, Wykretowicz A, Heymann‐Szlachcinska A, Wysocki H. Impairment of endothelial function in unipolar and bipolar depression. Biol Psychiat. 2006;60:889‐891. PubMed

Sodhi SK, Linder J, Chenard CA, del Miller D, Haynes WG, Fiedorowicz JG. Evidence for accelerated vascular aging in bipolar disorder. J Psychosom Res. 2012;73:175‐179. PubMed PMC

Fiedorowicz 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;81:235‐243. PubMed PMC

Naiberg MR, Hatch JK, Selkirk B, et al. Retinal photography: a window into the cardiovascular‐brain link in adolescent bipolar disorder. J Affect Disord. 2017;218:227‐237. PubMed

Appaji A, Nagendra B, Chako DM, et al. Retinal vascular abnormalities in schizophrenia and bipolar disorder: a window to the brain. Bipolar Disord. 2019;21:634‐641. PubMed

Appaji A, Nagendra B, Chako DM, et al. Retinal vascular fractal dimension in bipolar disorder and schizophrenia. J Affect Disord. 2019;259:98‐103. PubMed

Appaji A, Nagendra B, Chako DM, et al. Examination of retinal vascular trajectory in schizophrenia and bipolar disorder. Psychiatry Clin Neurosci. 2019;73:738‐744. PubMed

Appaji A, Nagendra B, Chako DM, et al. Retinal vascular tortuosity in schizophrenia and bipolar disorder. Schizophr Res. 2019;212:26‐32. PubMed

Ikram MK, Ong YT, Cheung CY, Wong TY. Retinal vascular caliber measurements: clinical significance, current knowledge and future perspectives. Ophthalmologica. 2013;229:125‐136. PubMed

Goldstein BI, Birmaher B, Axelson DA, et al. Preliminary findings regarding overweight and obesity in pediatric bipolar disorder. J Clin Psychiatry. 2008;69:1953‐1959. PubMed PMC

Li C, Birmaher B, Rooks B, et al. High prevalence of metabolic syndrome among adolescents and young adults with bipolar disorder. J Clin Psychiatry. 2019;80:pii:18m12422. PubMed PMC

Toma S, Fiksenbaum L, Omrin D, Goldstein BI. Elevated familial cardiovascular burden among adolescents with familial bipolar disorder. Front Psychiatry. 2019;10:8. PubMed PMC

Goldstein BI, Birmaher B, Axelson DA, et al. Significance of cigarette smoking among youths with bipolar disorder. Am J Addict. 2008;17:364‐371. PubMed PMC

Martin K, Woo J, Timmins V, et al. Binge eating and emotional eating behaviors among adolescents and young adults with bipolar disorder. J Affect Disord. 2016;195:88‐95. PubMed

Jewell L, Abtan R, Scavone A, Timmins V, Swampillai B, Goldstein BI. Preliminary evidence of disparities in physical activity among adolescents with bipolar disorder. Ment Health Phys Act. 2015;8:62‐67.

Hatch JK, Scola G, Olowoyeye O, et al. Inflammatory markers and brain‐derived neurotrophic factor as potential bridges linking bipolar disorder and cardiovascular risk among adolescents. J Clin Psychiatry. 2017;78:e286‐e293. PubMed

Pandey GN, Rizavi HS, Dwivedi Y, Pavuluri MN. Brain‐derived neurotrophic factor gene expression in pediatric bipolar disorder: effects of treatment and clinical response. J Am Acad Child Adolesc Psychiatry. 2008;47:1077‐1085. PubMed

Goldstein BI, Collinger KA, Lotrich F, et al. Preliminary findings regarding proinflammatory markers and brain‐derived neurotrophic factor among adolescents with bipolar spectrum disorders. J Child Adolesc Psychopharmacol. 2011;21:479‐484. PubMed PMC

Hatch J, Andreazza A, Olowoyeye O, Rezin GT, Moody A, Goldstein BI. Cardiovascular and psychiatric characteristics associated with oxidative stress markers among adolescents with bipolar disorder. J Psychosom Res. 2015;79:222‐227. PubMed

Goldstein BI, Lotrich F, Axelson DA, et al. Inflammatory markers among adolescents and young adults with bipolar spectrum disorders. J Clin Psychiatry. 2015;76:1556‐1563. PubMed PMC

Urback AL, Metcalfe AW, Korczak DJ, MacIntosh BJ, Goldstein BI. Reduced cerebrovascular reactivity among adolescents with bipolar disorder. Bipolar Disord. 2019;21:124‐131. PubMed

Sajatovic M, Strejilevich SA, Gildengers AG, et al. A report on older‐age bipolar disorder from the International Society for Bipolar Disorders Task Force. Bipolar Disord. 2015;17:689‐704. PubMed PMC

Dols A, Rhebergen D, Beekman A, Kupka R, Sajatovic M, Stek ML. Psychiatric and medical comorbidities: results from a bipolar elderly cohort study. Am J Geriat Psychiatry. 2014;22:1066‐1074. PubMed

Gildengers AG, Whyte EM, Drayer RA, et al. Medical burden in late‐life bipolar and major depressive disorders. Am J Geriatr Psychiatry. 2008;16:194‐200. PubMed PMC

Lala SV, Sajatovic M. Medical and psychiatric comorbidities among elderly individuals with bipolar disorder: a literature review. J Geriatr Psychiatry Neurol. 2012;25:20‐25. PubMed

Tsai SY, Kuo CJ, Chung KH, Huang YL, Lee HC, Chen CC. Cognitive dysfunction and medical morbidity in elderly outpatients with bipolar disorder. Am J Geriatr Psychiatry. 2009;17:1004‐1011. PubMed

Chen PH, Gildengers AG, Lee CH, Chen ML, Kuo CJ, Tsai SY. High serum sodium level in affective episode associated with coronary heart disease in old adults with bipolar disorder. Int J Psychiatry Med. 2015;50:422‐433. PubMed

Lee H‐C, Hsu J‐L, Chen P‐H, Chung K‐H, Huang Y‐J, Tsai S‐Y. High risk of silent stroke in older bipolar patients with typical‐onset age. Psychogeriatrics. 2019;19:355‐362. PubMed

Huang S‐H, Chung K‐H, Hsu J‐L, Wu J‐Y, Huang Y‐L, Tsai S‐Y. The risk factors for elderly patients with bipolar disorder having cerebral infarction. J Geriatr Psychiatry Neurol. 2012;25:15‐19. PubMed

Liao PC, Chung KH, Chen PH, Kuo CJ, Huang YJ, Tsai SY. Differences in outcomes between older community‐dwelling patients with bipolar disorder and schizophrenia with illness onset at young age. Psychogeriatrics. 2020. 10.1111/psyg.12514 PubMed DOI

Wu SI, Chen SC, Liu SI, et al. Relative risk of acute myocardial infarction in people with schizophrenia and bipolar disorder: a Population‐Based Cohort Study. PLoS ONE. 2015;10:e0134763. PubMed PMC

Jackson CA, Kerssens J, Fleetwood K, Smith DJ, Mercer SW, Wild SH. Incidence of ischaemic heart disease and stroke among people with psychiatric disorders: retrospective cohort study. Br J Psychiatry. 2019;1–8. 10.1192/bjp.2019.250. PubMed DOI PMC

Vance MC, Wiitala WL, Sussman JB, Pfeiffer P, Hayward RA. Increased cardiovascular disease risk in veterans with mental illness. Circ Cardiovasc Qual Outcomes. 2019;12:e005563. PubMed

Roger VL, Go AS, Lloyd‐Jones DM, et al. Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation. 2011;123:e18‐e209. PubMed PMC

Lin HC, Tsai SY, Lee HC. Increased risk of developing stroke among patients with bipolar disorder after an acute mood episode: a six‐year follow‐up study. J Affect Disord. 2007;100:49‐54. PubMed

Simon M, Boutouyrie P, Narayanan K, et al. Sex disparities in ideal cardiovascular health. Heart. 2017;103:1595‐1601. PubMed

Baskaran A, Cha DS, Powell AM, Jalil D, McIntyre RS. Sex differences in rates of obesity in bipolar disorder: postulated mechanisms. Bipolar Disord. 2014;16:83‐92. PubMed

Reininghaus B, Riedrich K, Dalkner N, et al. Physical health in individuals with psychiatric disorders in Austria. J Affect Disord. 2019;257:38–44. PubMed

Lee HC, Lin HC. Maternal bipolar disorder increased low birthweight and preterm births: a nationwide population‐based study. J Affect Disord. 2010;121:100‐105. PubMed

Auger N, Potter BJ, Healy‐Profitós J, He S, Schnitzer ME, Paradis G. Mood disorders in pregnant women and future cardiovascular risk. J Affect Disord. 2020;266:128–134. PubMed

Hippisley‐Cox J, Parker C, Coupland C, et al. Inequalities in the primary care of patients with coronary heart disease and serious mental health problems: a cross‐sectional study. Heart. 2007;93:1256‐1262. PubMed PMC

Vinogradova Y, Coupland C, Hippisley‐Cox J, Whyte S, Penny C. Effects of severe mental illness on survival of people with diabetes. Br J Psychiatry. 2010;197:272‐277. PubMed

Laursen T, Munk‐Olsen T, Agerbo E, Gasse C, Mortensen P. Somatic hospital contacts, invasive cardiac procedures, and mortality from heart disease in patients with severe mental disorder. Arch Gen Psychiatry. 2009;66:713‐720. PubMed

Atzema CL, Schull MJ, Tu JV. The effect of a charted history of depression on emergency department triage and outcomes in patients with acute myocardial infarction. Can Med Assoc J. 2011;183:663‐669. PubMed PMC

Druss BG, Bradford DW, Rosenheck RA, Radford MJ, Krumholz HM. Mental disorders and use of cardiovascular procedures after myocardial infarction. JAMA. 2000;283:506‐511. PubMed

Frayne SM, Halanych JH, Miller DR, et al. Disparities in diabetes care: impact of mental illness. Arch Intern Med. 2005;165:2631‐2638. PubMed

Wu SI, Chen SC, Juang JJ, et al. Diagnostic procedures, revascularization, and inpatient mortality after acute myocardial infarction in patients with schizophrenia and bipolar disorder. Psychosom Med. 2013;75:52‐59. PubMed

Druss BG, Bradford WD, Rosenheck RA, Radford MJ, Krumholz HM. Quality of medical care and excess mortality in older patients with mental disorders. Arch Gen Psychiatry. 2001;58:565‐572. PubMed

Fagiolini A, Frank E, Soreca I, et al. Integrating medical and psychiatric care in patients with bipolar disorder. J Clin Psychopharmacol. 2008;28:257‐258. PubMed

Kilbourne AM, Goodrich DE, Lai Z, et al. Randomized controlled trial to reduce cardiovascular disease risk for patients with bipolar disorder: the Self‐Management Addressing Heart Risk Trial (SMAHRT). J Clin psychiatry. 2013;74:e655‐e662. PubMed PMC

Druss BG, von Esenwein SA, Compton MT, Rask KJ, Zhao L, Parker RM. A randomized trial of medical care management for community mental health settings: the Primary Care Access, Referral, and Evaluation (PCARE) study. Am J Psychiatry. 2010;167(2):151‐159. PubMed PMC

Katon WJ, Lin EHB, Von Korff M, et al. Collaborative care for patients with depression and chronic illnesses. N Engl J Med. 2010;363:2611‐2620. PubMed PMC

Whyte S, Penny C, Phelan M, Hippisley‐Cox J, Majeed A. Quality of diabetes care in patients with schizophrenia and bipolar disorder: cross‐sectional study. Diabet Med. 2007;24:1442‐1448. PubMed

White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals

Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants

The clinical characterization of the adult patient with bipolar disorder aimed at personalization of management

Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals

Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals

Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals

Obesity as a Risk Factor for Accelerated Brain Ageing in First-Episode Psychosis-A Longitudinal Study