Insulin Resistance in Schizophrenia

  • Paul C. Guest
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1134)


Schizophrenia and diabetes have been known to be linked disorders for decades. One reason is due to the fact that a major side effect of antipsychotic medication treatment is metabolic syndrome, which increases the risk of the patients developing type 2 diabetes and cardiovascular disorders. However, signs of metabolic syndrome in schizophrenia patients were identified more than 100 years ago, even before the development of antipsychotic drugs. This suggests that schizophrenia itself predisposes towards diabetes and, in turn, insulin resistance may be a risk factor for the development of schizophrenia. This review summarizes the findings surrounding this issue and places them into context with regards to increasing our understanding of the aetiology of schizophrenia and in support of biomarker and drug discovery efforts.


Schizophrenia Psychosis Insulin resistance Antipsychotic Antidiabetic Biomarker 


  1. 1.
    GBD 2016 Disease and Injury Incidence and Prevalence Collaborators (2017) Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390(10100):1211–1259CrossRefGoogle Scholar
  2. 2.
    American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5), 5th edn. American Psychiatric Publishing, Washington, DC. ISBN-10: 8123923791CrossRefGoogle Scholar
  3. 3.
    Zwicker A, Denovan-Wright EM, Uher R (2018) Gene-environment interplay in the etiology of psychosis. Psychol Med 48(12):1925–1936PubMedCrossRefGoogle Scholar
  4. 4.
    Ventriglio A, Gentile A, Stella E, Bellomo A (2015) Metabolic issues in patients affected by schizophrenia: clinical characteristics and medical management. Front Neurosci 9:297. Scholar
  5. 5.
    Stoner SC (2018) Management of serious cardiac adverse effects of antipsychotic medications. Ment Health Clin 7(6):246–254PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Hjorthøj C, Stürup AE, McGrath JJ (2017) Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. Lancet Psychiatry 4:295–301PubMedCrossRefGoogle Scholar
  7. 7.
    Andrade C (2016) Cardiometabolic risks in schizophrenia and directions for intervention, 1: magnitude and moderators of the problem. J Clin Psychiatry 77(7):e844–e847. Scholar
  8. 8.
    Solmi M, Murru A, Pacchiarotti I, Undurraga J, Veronese N, Fornaro M et al (2018) Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag 13:757–777CrossRefGoogle Scholar
  9. 9.
    Harris LW, Guest PC, Wayland MT, Umrania Y, Krishnamurthy D, Rahmoune H et al (2012) Schizophrenia: metabolic aspects of aetiology, diagnosis and future treatment strategies. Psychoneuroendocrinology 38(6):752–766PubMedCrossRefGoogle Scholar
  10. 10.
    Chadda RK, Ramshankar P, Deb KS, Sood M (2013) Metabolic syndrome in schizophrenia: differences between antipsychotic-naïve and treated patients. J Pharmacol Pharmacother 4(3):176–186PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Pillinger T, Beck K, Gobjila C, Donocik JG, Jauhar S, Howes OD (2017) Impaired glucose homeostasis in first-episode schizophrenia: a systematic review and meta-analysis. JAMA Psychiat 74(3):261–269CrossRefGoogle Scholar
  12. 12.
    Kohen D (2004) Diabetes mellitus and schizophrenia: historical perspective. Br J Psychiatry Suppl 47:S64–S66PubMedCrossRefGoogle Scholar
  13. 13.
    Ryan MC, Collins P, Thakore JH (2003) Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry 160(2):284–289PubMedCrossRefGoogle Scholar
  14. 14.
    Spelman LM, Walsh PI, Sharifi N, Collins P, Thakore JH (2007) Impaired glucose tolerance in first-episode drug-naive patients with schizophrenia. Diabet Med 24:481–445PubMedCrossRefGoogle Scholar
  15. 15.
    Steiner J, Walter M, Guest P, Myint AM, Schiltz K, Panteli B et al (2010) Elevated S100B levels in schizophrenia are associated with insulin resistance. Mol Psychiatry 15(1):3–4PubMedCrossRefGoogle Scholar
  16. 16.
    Guest PC, Wang L, Harris LW, Burling K, Levin Y, Ernst A et al (2010) Increased levels of circulating insulin-related peptides in first-onset, antipsychotic naive schizophrenia patients. Mol Psychiatry 15:118–119PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Guest PC, Schwarz E, Krishnamurthy D, Harris LW, Leweke FM, Rothermundt M et al (2011) Altered levels of circulating insulin and other neuroendocrine hormones associated with the onset of schizophrenia. Psychoneuroendocrinology 36:1092–1096PubMedCrossRefGoogle Scholar
  18. 18.
    Serretti A, De Ronchi D, Lorenzi C, Berardi D (2004) New antipsychotics and schizophrenia: a review on efficacy and side effects. Curr Med Chem 11(3):343–358PubMedCrossRefGoogle Scholar
  19. 19.
    Haupt DW, Newcomer JW (2001) Hyperglycemia and antipsychotic medications. J Clin Psychiatry 62(Suppl 27):15–26PubMedGoogle Scholar
  20. 20.
    Mitchell AJ, Vancampfort D, Sweers K, van Winkel R, Yu W, De Hert M (2013) Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders--a systematic review and meta-analysis. Schizophr Bull 39(2):306–318PubMedCrossRefGoogle Scholar
  21. 21.
    American Psychiatric Association (1997) American Psychiatric Association practice guideline for the treatment of patients with schizophrenia (American Psychiatric Association practice guidelines). American Psychiatric Press Inc, Washington, DC. ISBN-10: 0890423091Google Scholar
  22. 22.
    Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO et al (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353:1209–1223PubMedCrossRefGoogle Scholar
  23. 23.
    McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA et al (2006) Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 163:600–610PubMedCrossRefGoogle Scholar
  24. 24.
    Leucht S, Komossa K, Rummel-Kluge C, Corves C, Hunger H, Schmid F et al (2009) A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry 166(2):152–163PubMedCrossRefGoogle Scholar
  25. 25.
    Siskind DJ, Leung J, Russell AW, Wysoczanski D, Kisely S (2016) Metformin for clozapine associated obesity: a systematic review and Meta-analysis. PLoS One 11(6):e0156208. Scholar
  26. 26.
    Henderson DC, Nguyen DD, Copeland PM, Hayden DL, Borba CP et al (2005) Clozapine, diabetes mellitus, hyperlipidemia, and cardiovascular risks and mortality: results of a 10-year naturalistic study. J Clin Psychiatry 66:1116–1121PubMedCrossRefGoogle Scholar
  27. 27.
    Aringhieri S, Carli M, Kolachalam S, Verdesca V, Cini E, Rossi M et al (2018) Molecular targets of atypical antipsychotics: from mechanism of action to clinical differences. Pharmacol Ther. pii: S0163-7258(18)30114-1. [Epub ahead of print]
  28. 28.
    Deng C, Weston-Green K, Huang XF (2010) The role of histaminergic H1 and H3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain? Prog Neuro-Psychopharmacol Biol Psychiatry 34(1):1–4CrossRefGoogle Scholar
  29. 29.
    Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P et al (2003) H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 28:519–526PubMedCrossRefGoogle Scholar
  30. 30.
    Matsui-Sakata A, Ohtani H, Sawada Y (2005) Receptor occupancy-based analysis of the contributions of various receptors to antipsychotics-induced weight gain and diabetes mellitus. Drug Metab Pharmacokinet 20:368–378PubMedCrossRefGoogle Scholar
  31. 31.
    Chen J, Huang XF, Shao R, Chen C, Deng C (2017) Molecular mechanisms of antipsychotic drug-induced diabetes. Front Neurosci 11:643. Scholar
  32. 32.
    Burghardt KJ, Seyoum B, Mallisho A, Burghardt PR, Kowluru RA, Yi Z (2018) Atypical antipsychotics, insulin resistance and weight; a meta-analysis of healthy volunteer studies. Prog Neuro-Psychopharmacol Biol Psychiatry 83:55–63CrossRefGoogle Scholar
  33. 33.
    Arranz B, Rosel P, Ramirez N, Duenas R, Fernandez P, Sanchez JM et al (2004) Insulin resistance and increased leptin concentrations in noncompliant schizophrenia patients but not in antipsychotic-naive first-episode schizophrenia patients. J Clin Psychiatry 65(10):1335–1342PubMedCrossRefGoogle Scholar
  34. 34.
    Correll CU, Lencz T, Malhotra AK (2011) Antipsychotic drugs and obesity. Trends Mol Med 17(2):97–107PubMedCrossRefGoogle Scholar
  35. 35.
    Saddichha S, Ameen S, Akhtar S (2008) Predictors of antipsychotic-induced weight gain in first-episode psychosis: conclusions from a randomized, double-blind, controlled prospective study of olanzapine, risperidone, and haloperidol. J Clin Psychopharmacol 28(1):27–31PubMedCrossRefGoogle Scholar
  36. 36.
    Taylor JH, Jakubovski E, Gabriel D, Bloch MH (2018) Predictors and moderators of antipsychotic-related weight gain in the treatment of early-onset schizophrenia spectrum disorders study. J Child Adolesc Psychopharmacol 28(7):474–484PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Musil R, Obermeier M, Russ P, Hamerle M (2015) Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf 14(1):73–96PubMedCrossRefGoogle Scholar
  38. 38.
    Wirshing DA, Wirshing WC, Kysar L, Berisford MA, Goldstein D, Pashdag J et al (1999) Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychiatry 60(6):358–363PubMedCrossRefGoogle Scholar
  39. 39.
    Schwarz E, Steiner J, Guest PC, Bogerts B, Bahn S (2015) Investigation of molecular serum profiles associated with predisposition to antipsychotic-induced weight gain. World J Biol Psychiatry 16(1):22–30PubMedCrossRefGoogle Scholar
  40. 40.
    Meyer JM (2010) Antipsychotics and metabolics in the post-CATIE era. Curr Top Behav Neurosci 4:23–42PubMedCrossRefGoogle Scholar
  41. 41.
    Guina J, Gupta A, Langleben DD, Elman I (2016) Clinical correlates of oral glucose tolerance test performance in olanzapine-treated patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry 77(12):e1650–e1651PubMedCrossRefGoogle Scholar
  42. 42.
    Tsuneyama N, Suzuki Y, Sawamura K, Sugai T, Fukui N, Watanabe J et al (2016) Effect of serum leptin on weight gain induced by olanzapine in female patients with schizophrenia. PLoS One 11(3):e0149518. Scholar
  43. 43.
    Cohn TA, Remington G, Zipursky RB, Azad A, Connolly P, Wolever TM (2006) Insulin resistance and adiponectin levels in drug-free patients with schizophrenia: a preliminary report. Can J Psychiatr 51:382–386CrossRefGoogle Scholar
  44. 44.
    Timonen MJ, Saari KM, Jokelainen JJ, Meyer-Rochow VB, Räsänen PK, Koponen HJ (2009) Insulin resistance and schizophrenia: results from the Northern Finland 1966 Birth Cohort. Schizophr Res 113(1):107–108PubMedCrossRefGoogle Scholar
  45. 45.
    van Nimwegen LJ, Storosum JG, Blumer RM, Allick G, Venema HW, de Haan L et al (2008) Hepatic insulin resistance in antipsychotic naive schizophrenic patients: stable isotope studies of glucose metabolism. J Clin Endocrinol Metab 93:572–577PubMedCrossRefGoogle Scholar
  46. 46.
    Uher R (2014) Gene-environment interactions in severe mental illness. Front Psych 5:48. Scholar
  47. 47.
    Davis J, Eyre H, Jacka FN, Dodd S, Dean O, McEwen S et al (2016) A review of vulnerability and risks for schizophrenia: beyond the two hit hypothesis. Neurosci Biobehav Rev 65:185–194PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    van de Leemput J, Hess JL, Glatt SJ, Tsuang MT (2016) Genetics of schizophrenia: historical insights and prevailing evidence. Adv Genet 96:99–141PubMedCrossRefGoogle Scholar
  49. 49.
    Misiak B, Stramecki F, Gawęda Ł, Prochwicz K, Sąsiadek MM, Moustafa AA et al (2018) Interactions between variation in candidate genes and environmental factors in the etiology of schizophrenia and bipolar disorder: a systematic review. Mol Neurobiol 55(6):5075–5100PubMedCrossRefGoogle Scholar
  50. 50.
    Sengupta S, Parrilla-Escobar MA, Klink R, Fathalli F, Ng YK, Stip E et al (2008) Are metabolic indices different between drug-naïve first-episode psychosis patients and healthy controls? Schizophr Res 102(1–3):329–336PubMedCrossRefGoogle Scholar
  51. 51.
    Verma SK, Subramaniam M, Liew A, Poon LY (2009) Metabolic risk factors in drug-naive patients with first-episode psychosis. J Clin Psychiatry 70(7):997–1000PubMedCrossRefGoogle Scholar
  52. 52.
    Zhai D, Lang Y, Feng Y, Liu Y, Dong G, Wang X et al (2017) Early onset of cardiometabolic risk factor profiles in drug naïve adolescents and young adults with first-episode schizophrenia. Schizophr Res 190:60–62PubMedCrossRefGoogle Scholar
  53. 53.
    Hutton JC (1994) Insulin secretory granule biogenesis and the proinsulin-processing endopeptidases. Diabetologia 37(Suppl 2):S48–S56PubMedCrossRefGoogle Scholar
  54. 54.
    Steiner J, Berger M, Guest PC, Dobrowolny H, Westphal S, Schiltz K et al (2017) Assessment of insulin resistance among drug-naive patients with first-episode schizophrenia in the context of hormonal stress axis activation. JAMA Psychiat 74(9):968–970CrossRefGoogle Scholar
  55. 55.
    Petruzzelli MG, Margari M, Peschechera A, de Giambattista C, De Giacomo A, Matera E et al (2018) Hyperprolactinemia and insulin resistance in drug naive patients with early onset first episode psychosis. BMC Psychiatry 18(1):246. Scholar
  56. 56.
    Walker E (2002) Risk factors, and the neurodevelopmental course of schizophrenia. Eur Psychiatry 17(Suppl 4):363s–369sPubMedCrossRefGoogle Scholar
  57. 57.
    Trotman HD, Holtzman CW, Ryan AT, Shapiro DI, MacDonald AN, Goulding SM et al (2013) The development of psychotic disorders in adolescence: a potential role for hormones. Horm Behav 64(2):411–419PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Soria V, González-Rodríguez A, Huerta-Ramos E, Usall J, Cobo J, Bioque M et al (2018) Targeting hypothalamic-pituitary-adrenal axis hormones and sex steroids for improving cognition in major mood disorders and schizophrenia: a systematic review and narrative synthesis. Psychoneuroendocrinology 93:8–19PubMedCrossRefGoogle Scholar
  59. 59.
    Qiu H, Yang JK, Chen C (2017) Influence of insulin on growth hormone secretion, level and growth hormone signalling. Sheng Li Xue Bao 69(5):541–556PubMedGoogle Scholar
  60. 60.
    Melmed S (1984) Insulin suppresses growth hormone secretion by rat pituitary cells. J Clin Invest 73(5):1425–1433PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Krishnamurthy D, Harris LW, Levin Y, Koutroukides TA, Rahmoune H, Pietsch S et al (2013) Metabolic, hormonal and stress-related molecular changes in post-mortem pituitary glands from schizophrenia subjects. World J Biol Psychiatry 14(7):478–489PubMedCrossRefGoogle Scholar
  62. 62.
    Iglesias P, Bernal C, Díez JJ (2014) Curious cases: acromegaly and schizophrenia: an incidental association? Schizophr Bull 40(4):740–743PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Hofmann G (1953) Demonstration of a case of schizophrenia in acromegaly. Wien Z Nervenheilkd Grenzgeb 7:244–251PubMedGoogle Scholar
  64. 64.
    Schiffter R (1971) Problems of schizophrenic-like psychoses in pituitary disorders. Psychiatr Clin (Basel) 4:82–99Google Scholar
  65. 65.
    Schulte DB (1976) Paranoid-hallucinatory psychoses in acromegaly. Schweiz Arch Neurol Neurochir Psychiatr 118:357–377PubMedGoogle Scholar
  66. 66.
    Pinto D, Safeekh AT, Trivedi M (2005) Psychotic symptoms in acromegaly. Indian J Psychiatry 47:58–59PubMedCentralCrossRefPubMedGoogle Scholar
  67. 67.
    Kannabiran M, Singh V, Grewal S (2006) Acromegaly presenting as psychotic disorder in a patient with familial autosomal dominant polycystic kidney disease. Ger J Psychiatry 9:136–138Google Scholar
  68. 68.
    Koroglu A, Hocaoglu C (2012) Risperidone-induced acromegaly: a case report. Ther Adv Psychopharmacol 2:85–89PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Künzel H, Held K, Schmidt D, Ziegenbein M, Murck H, Steiger A (2018) Sleep-endocrine effects of growth hormone-releasing hormone (GHRH) in patients with schizophrenia. J Psychiatr Res 101:1–4PubMedCrossRefGoogle Scholar
  70. 70.
    Joseph JJ, Golden SH (2017) Cortisol dysregulation: the bidirectional link between stress, depression, and type 2 diabetes mellitus. Ann N Y Acad Sci 1391(1):20–34PubMedCrossRefGoogle Scholar
  71. 71.
    Nordholm D, Rostrup E, Mondelli V, Randers L, Nielsen MØ, Wulff S et al (2018) Multiple measures of HPA axis function in ultra high risk and first-episode schizophrenia patients. Psychoneuroendocrinology 92:72–80PubMedCrossRefGoogle Scholar
  72. 72.
    Azcoitia I, Doncarlos LL, Garcia-Segura LM (2002) Estrogen and brain vulnerability. Neurotox Res 4(3):235–245PubMedCrossRefGoogle Scholar
  73. 73.
    Seeman MV, Lang M (1990) The role of estrogens in schizophrenia gender differences. Schizophr Bull 16(2):185–194PubMedCrossRefGoogle Scholar
  74. 74.
    Lindamer LA, Lohr JB, Harris MJ, Jeste DV (1997) Gender, estrogen, and schizophrenia. Psychopharmacol Bull 33(2):221–228PubMedGoogle Scholar
  75. 75.
    Kulkarni J (2005) Oestrogen--a new treatment approach for schizophrenia? Med J Aust 190(4 Suppl):S37–S38Google Scholar
  76. 76.
    Huber TJ, Tettenborn C, Leifke E, Emrich HM (2005) Sex hormones in psychotic men. Psychoneuroendocrinology 30(1):111–114PubMedCrossRefGoogle Scholar
  77. 77.
    Ramsey JM, Schwarz E, Guest PC, van Beveren NJ, Leweke FM, Rothermundt M et al (2013) Distinct molecular phenotypes in male and female schizophrenia patients. PLoS One 8(11):e78729. Scholar
  78. 78.
    Walker JJ, Terry JR, Lightman SL (2010) Origin of ultradian pulsatility in the hypothalamic-pituitary-adrenal axis. Proc Biol Sci 277(1688):1627–1633PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Daimon M, Kamba A, Murakami H, Mizushiri S, Osonoi S, Yamaichi M et al (2017) Association between serum prolactin levels and insulin resistance in non-diabetic men. PLoS One 12(4):e0175204. Scholar
  80. 80.
    Tannenbaum GS, Martin JB, Colle E (1976) Ultradian growth hormone rhythm in the rat: effects of feeding, hyperglycemia, and insulin-induced hypoglycemia. Endocrinology 99:720–727PubMedCrossRefGoogle Scholar
  81. 81.
    Akamine EH, Marçal AC, Camporez JP, Hoshida MS, Caperuto LC, Bevilacqua E et al (2010) Obesity induced by high-fat diet promotes insulin resistance in the ovary. J Endocrinol 206(1):65–74PubMedCrossRefGoogle Scholar
  82. 82.
    Helle KB, Corti A, Metz-Boutigue MH, Tota B (2007) The endocrine role for chromogranin A: a prohormone for peptides with regulatory properties. Cell Mol Life Sci 64:2863–2886PubMedCrossRefGoogle Scholar
  83. 83.
    Garcia GE, Gabbai FB, O’Connor DT, Dinh TQ, Kennedy B, Ziegler MG et al (1994) Does chromostatin influence catecholamine release or blood pressure in vivo? Peptides 15:195–197PubMedCrossRefGoogle Scholar
  84. 84.
    Tatemoto K, Efendić S, Mutt V, Makk G, Feistner GJ, Barchas JD (1986) Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 324(6096):476–478PubMedCrossRefGoogle Scholar
  85. 85.
    Efendić S, Tatemoto K, Mutt V, Quan C, Chang D, Ostenson CG (1987) Pancreastatin and islet hormone release. Proc Natl Acad Sci U S A 84(20):7257–7260PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Asakawa A, Inui A, Yuzuriha H, Ueno N, Katsuura G, Fujimiya M et al (2003) Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 124:1325–1336PubMedCrossRefGoogle Scholar
  87. 87.
    Kurzthaler I, Fleischhacker WW (2001) The clinical implications of weight gain in schizophrenia. J Clin Psychiatry 62(Suppl 7):32–37PubMedGoogle Scholar
  88. 88.
    Warren KR, Ball MP, Feldman S, Liu F, McMahon RP, Kelly DL (2011) Exercise program adherence using a 5-kilometer (5K) event as an achievable goal in people with schizophrenia. Biol Res Nurs 13(4):383–390PubMedCrossRefGoogle Scholar
  89. 89.
    Kimhy D, Khan S, Ayanrouh L, Chang RW, Hansen MC, Lister A et al (2016) Use of active-play video games to enhance aerobic fitness in schizophrenia: feasibility, safety, and adherence. Psychiatr Serv 67(2):240–243PubMedCrossRefGoogle Scholar
  90. 90.
    Yoon S, Ryu JK, Kim CH, Chang JG, Lee HB, Kim DH et al (2016) Preliminary effectiveness and sustainability of group aerobic exercise program in patients with schizophrenia. J Nerv Ment Dis 204(9):644–650PubMedCrossRefGoogle Scholar
  91. 91.
    Zheng W, Li X-B, Tang Y-L, Xiang Y-Q, Wang C-Y, de Leon J (2015) Metformin for weight gain and metabolic abnormalities associated with antipsychotic treatment: meta-analysis of randomized placebo-controlled trials. J Clin Psychopharmacol 35:499–509PubMedCrossRefGoogle Scholar
  92. 92.
    Stroup TS, Gray N (2018) Management of common adverse effects of antipsychotic medications. World Psychiatry 17(3):341–356PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Hendrick V, Dasher R, Gitlin M, Parsi M (2017) Minimizing weight gain for patients taking antipsychotic medications: The potential role for early use of metformin. Ann Clin Psychiatry 29(2):120–124PubMedGoogle Scholar
  94. 94.
    Kirpichnikov D, McFarlane SI, Sowers JR (2002) Metformin: an update. Ann Intern Med 137:25–33PubMedCrossRefGoogle Scholar
  95. 95.
    Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM et al (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403PubMedCrossRefGoogle Scholar
  96. 96.
    Salpeter SR, Buckley NS, Kahn JA, Salpeter EE (2008) Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am J Med 121:149–157PubMedCrossRefGoogle Scholar
  97. 97.
    Siskind D, Friend N, Russell A, McGrath JJ, Lim C, Patterson S et al (2018) CoMET: a protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine. BMJ Open 8(3):e021000. Scholar
  98. 98.
    Labrie F, Luu-The V, Bélanger A, Lin SX, Simard J, Pelletier G et al (2005) Is dehydroepiandrosterone a hormone? J Endocrinol 187(2):169–196PubMedCrossRefGoogle Scholar
  99. 99.
    Mo Q, Lu SF, Simon NG (2006) Dehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activity. J Steroid Biochem Mol Biol 99(1):50–58PubMedCrossRefGoogle Scholar
  100. 100.
    Seeman E (2001) Raloxifene. J Bone Miner Metab 19(2):65–75PubMedCrossRefGoogle Scholar
  101. 101.
    Henderson E, Weinberg M, Wright WA (1950) Pregnenolone. J Clin Endocrinol Metab 10(4):455–474PubMedCrossRefGoogle Scholar
  102. 102.
    Guest PC, Chan MK, Gottschalk MG, Bahn S (2014) The use of proteomic biomarkers for improved diagnosis and stratification of schizophrenia patients. Biomark Med 8(1):15–27PubMedCrossRefGoogle Scholar
  103. 103.
    Joyce DW, Kehagia AA, Tracy DK, Proctor J, Shergill SS (2017) Realising stratified psychiatry using multidimensional signatures and trajectories. J Transl Med 15(1):15. Scholar
  104. 104.
    Guest FL, Guest PC (2018) Point-of-care testing and personalized medicine for metabolic disorders. Methods Mol Biol 1735:105–114PubMedCrossRefGoogle Scholar
  105. 105.
    Pratt J, Hall J (2018) Biomarkers in neuropsychiatry: a Prospect for the twenty-first century? Curr Top Behav Neurosci. [Epub ahead of print]

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Paul C. Guest
    • 1
  1. 1.Department of Biochemistry and Tissue Biology, Institute of BiologyUniversity of Campinas (UNICAMP)CampinasBrazil

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