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Antipsychotics impair regulation of glucose metabolism by central glucose

Molecular Psychiatry volume 27, pages 4741–4753 (2022)Cite this article

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Abstract

Hypothalamic detection of elevated circulating glucose triggers suppression of endogenous glucose production (EGP) to maintain glucose homeostasis. Antipsychotics alleviate symptoms associated with schizophrenia but also increase the risk for impaired glucose metabolism. In the current study, we examined whether two acutely administered antipsychotics from different drug classes, haloperidol (first generation antipsychotic) and olanzapine (second generation antipsychotic), affect the ability of intracerebroventricular (ICV) glucose infusion approximating postprandial levels to suppress EGP. The experimental protocol consisted of a pancreatic euglycemic clamp, followed by kinomic and RNA-seq analyses of hypothalamic samples to determine changes in serine/threonine kinase activity and gene expression, respectively. Both antipsychotics inhibited ICV glucose-mediated increases in glucose infusion rate during the clamp, a measure of whole-body glucose metabolism. Similarly, olanzapine and haloperidol blocked central glucose-induced suppression of EGP. ICV glucose stimulated the vascular endothelial growth factor (VEGF) pathway, phosphatidylinositol 3-kinase (PI3K) pathway, and kinases capable of activating KATP channels in the hypothalamus. These effects were inhibited by both antipsychotics. In conclusion, olanzapine and haloperidol impair central glucose sensing. Although results of hypothalamic analyses in our study do not prove causality, they are novel and provide the basis for a multitude of future studies.

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Fig. 1: Current hypothalamic glucose sensing pathway, pancreatic euglycemic clamp protocol, and glucose kinetics results.
Fig. 2: Kinome array results.
Fig. 3: Pathway analyses based on kinome array results.
Fig. 4: Leading edge gene analyses.
Fig. 5: Cross-pod common pathway analyses.
Fig. 6: Perturbagens from mechanism of action (MoA) analyses and proposed hypothalamic glucose sensing mechanisms altered by antipsychotics.

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References

  1. Rajkumar AP, Horsdal HT, Wimberley T, Cohen D, Mors O, Borglum AD, et al. Endogenous and antipsychotic-related risks for diabetes mellitus in young people with schizophrenia: a Danish population-based cohort study. Am J Psychiatry. 2017;174:686–94.

    PubMed  Google Scholar 

  2. Boyda HN, Tse L, Procyshyn RM, Wong D, Wu TK, Pang CC, et al. A parametric study of the acute effects of antipsychotic drugs on glucose sensitivity in an animal model. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:945–54.

    CAS  PubMed  Google Scholar 

  3. Hahn MK, Wolever TM, Arenovich T, Teo C, Giacca A, Powell V, et al. Acute effects of single-dose olanzapine on metabolic, endocrine, and inflammatory markers in healthy controls. J Clin Psychopharmacol. 2013;33:740–6.

    CAS  PubMed  Google Scholar 

  4. Teff KL, Rickels MR, Grudziak J, Fuller C, Nguyen HL, Rickels K. Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease. Diabetes. 2013;62:3232–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Kowalchuk C, Castellani LN, Chintoh A, Remington G, Giacca A, Hahn MK. Antipsychotics and glucose metabolism: how brain and body collide. Am J Physiol Endocrinol Metab. 2019;316:E1–5.

    CAS  PubMed  Google Scholar 

  6. López-Gambero AJ, Martínez F, Salazar K, Cifuentes M, Nualart F. Brain glucose-sensing mechanism and energy homeostasis. Mol Neurobiol. 2019;56:769–96.

    PubMed  Google Scholar 

  7. Donovan CM, Watts AG. Peripheral and central glucose sensing in hypoglycemic detection. Physiology. 2014;29:314–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Lam TK, Gutierrez-Juarez R, Pocai A, Rossetti L. Regulation of blood glucose by hypothalamic pyruvate metabolism. Science. 2005;309:943–7.

    CAS  PubMed  Google Scholar 

  9. Osundiji MA, Lam DD, Shaw J, Yueh CY, Markkula SP, Hurst P, et al. Brain glucose sensors play a significant role in the regulation of pancreatic glucose-stimulated insulin secretion. Diabetes. 2012;61:321–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Carey M, Lontchi-Yimagou E, Mitchell W, Reda S, Zhang K, Kehlenbrink S, et al. Central K(ATP) channels modulate glucose effectiveness in humans and rodents. Diabetes. 2020;69:1140–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Abraham MA, Rasti M, Bauer PV, Lam TKT. Leptin enhances hypothalamic lactate dehydrogenase A (LDHA)-dependent glucose sensing to lower glucose production in high-fat-fed rats. J Biol Chem. 2018;293:4159–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Li RJW, Zhang SY, Lam TKT. Interaction of glucose sensing and leptin action in the brain. Mol Metab. 2020;39:101011.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Guay C, Madiraju SR, Aumais A, Joly E, Prentki M. A role for ATP-citrate lyase, malic enzyme, and pyruvate/citrate cycling in glucose-induced insulin secretion. J Biol Chem. 2007;282:35657–65.

    CAS  PubMed  Google Scholar 

  14. Wang Y, Yu W, Li S, Guo D, He J, Wang Y. Acetyl-CoA carboxylases and diseases. Front Oncol. 2022;12:836058.

    PubMed  PubMed Central  Google Scholar 

  15. Larsson O, Deeney JT, Bränström R, Berggren PO, Corkey BE. Activation of the ATP-sensitive K+ channel by long chain acyl-CoA. A role in modulation of pancreatic beta-cell glucose sensitivity. J Biol Chem. 1996;271:10623–6.

    CAS  PubMed  Google Scholar 

  16. Gribble FM, Proks P, Corkey BE, Ashcroft FM. Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA. J Biol Chem. 1998;273:26383–7.

    CAS  PubMed  Google Scholar 

  17. Yang HQ, Martinez-Ortiz W, Hwang J, Fan X, Cardozo TJ, Coetzee WA. Palmitoylation of the K(ATP) channel Kir6.2 subunit promotes channel opening by regulating PIP(2) sensitivity. Proc Natl Acad Sci USA. 2020;117:10593–602.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Chai Y, Lin YF. Stimulation of neuronal KATP channels by cGMP-dependent protein kinase: involvement of ROS and 5-hydroxydecanoate-sensitive factors in signal transduction. Am J Physiol Cell Physiol. 2010;298:C875–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Lin YF, Chai Y. Functional modulation of the ATP-sensitive potassium channel by extracellular signal-regulated kinase-mediated phosphorylation. Neuroscience. 2008;152:371–80.

    CAS  PubMed  Google Scholar 

  20. Lin YF, Jan YN, Jan LY. Regulation of ATP-sensitive potassium channel function by protein kinase A-mediated phosphorylation in transfected HEK293 cells. Embo J. 2000;19:942–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Light PE, Bladen C, Winkfein RJ, Walsh MP, French RJ. Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium channels. Proc Natl Acad Sci USA. 2000;97:9058–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Ross R, Wang PY, Chari M, Lam CK, Caspi L, Ono H, et al. Hypothalamic protein kinase C regulates glucose production. Diabetes. 2008;57:2061–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Obici S, Zhang BB, Karkanias G, Rossetti L. Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med. 2002;8:1376–82.

    CAS  PubMed  Google Scholar 

  24. Kowalchuk C, Teo C, Wilson V, Chintoh A, Lam L, Agarwal SM, et al. In male rats, the ability of central insulin to suppress glucose production is impaired by olanzapine, whereas glucose uptake is left intact. J Psychiatry Neurosci. 2017;42:424–31.

    PubMed  PubMed Central  Google Scholar 

  25. Kowalchuk C, Castellani L, Kanagsundaram P, McIntyre WB, Asgariroozbehani R, Giacca A, et al. Olanzapine-induced insulin resistance may occur via attenuation of central K(ATP) channel-activation. Schizophr Res. 2021;228:112–7.

    CAS  PubMed  Google Scholar 

  26. Routh VH, Hao L, Santiago AM, Sheng Z, Zhou C. Hypothalamic glucose sensing: making ends meet. Front Syst Neurosci. 2014;8:236.

    PubMed  PubMed Central  Google Scholar 

  27. Kapur S, Wadenberg ML, Remington G. Are animal studies of antipsychotics appropriately dosed? Lessons from the bedside to the bench. Can J Psychiatry. 2000;45:241–6.

    CAS  PubMed  Google Scholar 

  28. Kapur S, VanderSpek SC, Brownlee BA, Nobrega JN. Antipsychotic dosing in preclinical models is often unrepresentative of the clinical condition: a suggested solution based on in vivo occupancy. J Pharm Exp Ther. 2003;305:625–31.

    CAS  Google Scholar 

  29. Chintoh AF, Mann SW, Lam L, Giacca A, Fletcher P, Nobrega J, et al. Insulin resistance and secretion in vivo: effects of different antipsychotics in an animal model. Schizophr Res. 2009;108:127–33.

    PubMed  Google Scholar 

  30. Ziotopoulou M, Mantzoros CS, Hileman SM, Flier JS. Differential expression of hypothalamic neuropeptides in the early phase of diet-induced obesity in mice. Am J Physiol Endocrinol Metab. 2000;279:E838–45.

    CAS  PubMed  Google Scholar 

  31. Bentea E, Depasquale EAK, O’Donovan SM, Sullivan CR, Simmons M, Meador-Woodruff JH, et al. Kinase network dysregulation in a human induced pluripotent stem cell model of DISC1 schizophrenia. Mol Omics. 2019;15:173–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Armitage P, Berry G, Matthews JNS. Statistical methods in medical research. 4th ed. Malden, Massachusetts, USA: Blackwell Science; 2002.

  33. Shukla R, Newton DF, Sumitomo A, Zare H, McCullumsmith R, Lewis DA, et al. Molecular characterization of depression trait and state. Mol Psychiatry. 2022;27:1083–94.

    CAS  PubMed  Google Scholar 

  34. Albaugh VL, Judson JG, She P, Lang CH, Maresca KP, Joyal JL, et al. Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis. Mol Psychiatry. 2011;16:569–81.

    CAS  PubMed  Google Scholar 

  35. Girault EM, Alkemade A, Foppen E, Ackermans MT, Fliers E, Kalsbeek A. Acute peripheral but not central administration of olanzapine induces hyperglycemia associated with hepatic and extra-hepatic insulin resistance. PLOS ONE. 2012;7:e43244.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Faes S, Dormond O. PI3K and AKT: unfaithful partners in cancer. Int J Mol Sci. 2015;16:21138–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Natarajan R, Bai W, Lanting L, Gonzales N, Nadler J. Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells. Am J Physiol. 1997;273:H2224–31.

    CAS  PubMed  Google Scholar 

  38. Zhao T, Zhu Y, Morinibu A, Kobayashi M, Shinomiya K, Itasaka S, et al. HIF-1-mediated metabolic reprogramming reduces ROS levels and facilitates the metastatic colonization of cancers in lungs. Sci Rep. 2014;4:3793.

    PubMed  PubMed Central  Google Scholar 

  39. Harms KM, Li L, Cunningham LA. Murine neural stem/progenitor cells protect neurons against ischemia by HIF-1alpha-regulated VEGF signaling. PLoS ONE. 2010;5:e9767.

    PubMed  PubMed Central  Google Scholar 

  40. Yu T, Robotham JL, Yoon Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci USA. 2006;103:2653–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Wang X, Bove AM, Simone G, Ma B. Molecular bases of VEGFR-2-mediated physiological function and pathological role. Front Cell Dev Biol. 2020;8:599281.

    PubMed  PubMed Central  Google Scholar 

  42. Simons M, Gordon E, Claesson-Welsh L. Mechanisms and regulation of endothelial VEGF receptor signalling. Nat Rev Mol Cell Biol. 2016;17:611–25.

    CAS  PubMed  Google Scholar 

  43. Gerber AN, Newton R, Sasse SK. Repression of transcription by the glucocorticoid receptor: a parsimonious model for the genomics era. J Biol Chem. 2021;296:100687.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Wang JC, Gray NE, Kuo T, Harris CA. Regulation of triglyceride metabolism by glucocorticoid receptor. Cell Biosci. 2012;2:19.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Wakamori M, Kaneda M, Oyama Y, Akaike N. Effects of chlordiazepoxide, chlorpromazine, diazepam, diphenylhydantoin, flunitrazepam and haloperidol on the voltage-dependent sodium current of isolated mammalian brain neurons. Brain Res. 1989;494:374–8.

    CAS  PubMed  Google Scholar 

  46. Lenkey N, Karoly R, Lukacs P, Vizi ES, Sunesen M, Fodor L, et al. Classification of drugs based on properties of sodium channel inhibition: a comparative automated patch-clamp study. PLoS ONE. 2010;5:e15568.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Davis JD, Wirtshafter D, Asin KE, Brief D. Sustained intracerebroventricular infusion of brain fuels reduces body weight and food intake in rats. Science. 1981;212:81–3.

    CAS  PubMed  Google Scholar 

  48. Miselis RR, Epstein AN. Feeding induced by intracerebroventricular 2-deoxy-D-glucose in the rat. Am J Physiol. 1975;229:1438–47.

    CAS  PubMed  Google Scholar 

  49. Lam TK, Gutierrez-Juarez R, Pocai A, Bhanot S, Tso P, Schwartz GJ, et al. Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins. Nat Med. 2007;13:171–80.

    CAS  PubMed  Google Scholar 

  50. Borg WP, Sherwin RS, During MJ, Borg MA, Shulman GI. Local ventromedial hypothalamus glucopenia triggers counterregulatory hormone release. Diabetes. 1995;44:180–4.

    CAS  PubMed  Google Scholar 

  51. Castellani LN, Wilkin J, Abela AR, Benarroch L, Ahasan Z, Teo C, et al. Effects of acute olanzapine exposure on central insulin-mediated regulation of whole body fuel selection and feeding. Psychoneuroendocrinology. 2018;98:127–30.

    CAS  PubMed  Google Scholar 

  52. Mevorach M, Giacca A, Aharon Y, Hawkins M, Shamoon H, Rossetti L. Regulation of endogenous glucose production by glucose per se is impaired in type 2 diabetes mellitus. J Clin Investig. 1998;102:744–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Morland C, Andersson KA, Haugen ØP, Hadzic A, Kleppa L, Gille A, et al. Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1. Nat Commun. 2017;8:15557.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Gaspar JM, Mendes NF, Corrêa-da-Silva F, Lima-Junior JC, Gaspar RC, Ropelle ER, et al. Downregulation of HIF complex in the hypothalamus exacerbates diet-induced obesity. Brain Behav Immun. 2018;73:550–61.

    CAS  PubMed  Google Scholar 

  55. Freitas-Andrade M, Carmeliet P, Stanimirovic DB, Moreno M. VEGFR-2-mediated increased proliferation and survival in response to oxygen and glucose deprivation in PlGF knockout astrocytes. J Neurochem. 2008;107:756–67.

    CAS  PubMed  Google Scholar 

  56. Luck R, Urban S, Karakatsani A, Harde E, Sambandan S, Nicholson L, et al. VEGF/VEGFR2 signaling regulates hippocampal axon branching during development. Elife. 2019;8:e49818.

    PubMed  PubMed Central  Google Scholar 

  57. Stapel B, Kotsiari A, Scherr M, Hilfiker-Kleiner D, Bleich S, Frieling H, et al. Olanzapine and aripiprazole differentially affect glucose uptake and energy metabolism in human mononuclear blood cells. J Psychiatr Res. 2017;88:18–27.

    PubMed  Google Scholar 

  58. Sacks W, Esser AH, Sacks S. Inhibition of pyruvate dehydrogenase complex (PDHC) by antipsychotic drugs. Biol Psychiatry. 1991;29:176–82.

    CAS  PubMed  Google Scholar 

  59. Vestri HS, Maianu L, Moellering DR, Garvey WT. Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. Neuropsychopharmacology. 2007;32:765–72.

    CAS  PubMed  Google Scholar 

  60. Dwyer DS, Pinkofsky HB, Liu Y, Bradley RJ. Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells. Prog Neuropsychopharmacol Biol Psychiatry. 1999;23:69–80.

    CAS  PubMed  Google Scholar 

  61. Chari M, Yang CS, Lam CK, Lee K, Mighiu P, Kokorovic A, et al. Glucose transporter-1 in the hypothalamic glial cells mediates glucose sensing to regulate glucose production in vivo. Diabetes. 2011;60:1901–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Jais A, Solas M, Backes H, Chaurasia B, Kleinridders A, Theurich S, et al. Myeloid-cell-derived VEGF maintains brain glucose uptake and limits cognitive impairment in obesity. Cell. 2016;165:882–95.

    CAS  PubMed  Google Scholar 

  63. Li G, Wang HQ, Wang LH, Chen RP, Liu JP. Distinct pathways of ERK1/2 activation by hydroxy-carboxylic acid receptor-1. PLoS ONE. 2014;9:e93041.

    PubMed  PubMed Central  Google Scholar 

  64. Lu Y, Xiong Y, Huo Y, Han J, Yang X, Zhang R, et al. Grb-2-associated binder 1 (Gab1) regulates postnatal ischemic and VEGF-induced angiogenesis through the protein kinase A-endothelial NOS pathway. Proc Natl Acad Sci USA. 2011;108:2957–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Yang SB, Proks P, Ashcroft FM, Rupnik M. Inhibition of ATP-sensitive potassium channels by haloperidol. Br J Pharm. 2004;143:960–7.

    CAS  Google Scholar 

  66. Chen PC, Kryukova YN, Shyng SL. Leptin regulates KATP channel trafficking in pancreatic β-cells by a signaling mechanism involving AMP-activated protein kinase (AMPK) and cAMP-dependent protein kinase (PKA). J Biol Chem. 2013;288:34098–109.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Koppel J, Jimenez H, Adrien L, Greenwald BS, Marambaud P, Cinamon E, et al. Haloperidol inactivates AMPK and reduces tau phosphorylation in a tau mouse model of Alzheimer’s disease. Alzheimers Dement. 2016;2:121–30.

    Google Scholar 

  68. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev. 2010;90:291–366.

    CAS  PubMed  Google Scholar 

  69. Szeto V, Chen NH, Sun HS, Feng ZP. The role of K(ATP) channels in cerebral ischemic stroke and diabetes. Acta Pharm Sin. 2018;39:683–94.

    CAS  Google Scholar 

  70. Gribble FM, Tucker SJ, Ashcroft FM. The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide. Embo J. 1997;16:1145–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Yang CS, Lam CK, Chari M, Cheung GW, Kokorovic A, Gao S, et al. Hypothalamic AMP-activated protein kinase regulates glucose production. Diabetes. 2010;59:2435–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Claret M, Smith MA, Batterham RL, Selman C, Choudhury AI, Fryer LG, et al. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J Clin Investig. 2007;117:2325–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Münzberg H, et al. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. J Clin Investig. 2006;116:1886–901.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Albaugh VL, Vary TC, Ilkayeva O, Wenner BR, Maresca KP, Joyal JL, et al. Atypical antipsychotics rapidly and inappropriately switch peripheral fuel utilization to lipids, impairing metabolic flexibility in rodents. Schizophr Bull. 2012;38:153–66.

    PubMed  Google Scholar 

  75. Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, et al. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell. 2011;144:810–23.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

MKH is supported in part by an Academic Scholars Award from the Department of Psychiatry, University of Toronto, and has grant support from the Banting and Best Diabetes Centre (BBDC), the Canadian Institutes of Health Research (CIHR), PSI Foundation, Ontario, holds the Kelly and Michael Meighen Chair in Psychosis Prevention, and the Cardy Schizophrenia Research Chair. She is also supported by the Danish Diabetes Academy, and a Steno Diabetes Centre Fellowship Award. This work was also supported by The National Institute of Mental Health [grant numbers MH107487, MH121102] and National Institute of Health [grant number AG057598], both awarded to REM. SMA is supported in part by an Academic Scholars Award from the Department of Psychiatry, University of Toronto, and has grant support from CIHR, PSI Foundation, Ontario, and the CAMH Discovery Fund. SP was supported by a Discovery Fund Postdoctoral Fellowship from CAMH. RS is supported by Bebensee Schizophrenia Research Fellowship, by the Ian Douglas Bebensee Foundation, Toronto, Canada. SW was supported by the Ontario Graduate Scholarship and the Banting & Best Diabetes Centre—Novo Nordisk Studentship from the University of Toronto.

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Author notes

  1. These authors contributed equally: Laura N. Castellani, Sandra Pereira, Chantel Kowalchuk.

  2. These authors jointly supervised this work: Adria Giacca, Robert E. Mccullumsmith, Margaret K. Hahn.

Authors and Affiliations

  1. Centre for Addiction and Mental Health, Toronto, ON, Canada

    Laura N. Castellani, Sandra Pereira, Chantel Kowalchuk, Roshanak Asgariroozbehani, Raghunath Singh, Sally Wu, Laurie Hamel, Emily Au, Araba Chintoh, Gary Remington, Sri Mahavir Agarwal & Margaret K. Hahn

  2. Department of Physiology, University of Toronto, Toronto, ON, Canada

    Sandra Pereira & Adria Giacca

  3. Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada

    Roshanak Asgariroozbehani, Sally Wu, Adria Giacca & Margaret K. Hahn

  4. Department of Neurosciences, University of Toledo, Toledo, OH, USA

    Khaled Alganem, William G. Ryan, Xiaolu Zhang & Robert E. Mccullumsmith

  5. Department of Pharmacology, University of Toronto, Toronto, ON, Canada

    Emily Au & Margaret K. Hahn

  6. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Araba Chintoh, Gary Remington, Sri Mahavir Agarwal & Margaret K. Hahn

  7. Department of Psychological Clinical Science, University of Toronto Scarborough, Toronto, ON, Canada

    Gary Remington

  8. Banting & Best Diabetes Centre, Toronto, ON, Canada

    Sri Mahavir Agarwal, Adria Giacca & Margaret K. Hahn

  9. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Adria Giacca

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  1. Laura N. Castellani
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Contributions

LNC, CK, and MKH conceived the study. LNC, SP, CK, LH, KA, WGR, XZ, AC, GR, SMA, AG, REM, MKH designed experiments. LNC, SP, CK, RA, RS, SW, KA, WGR, XZ, and EA performed experiments. LNC, SP, KA, WGR, and XZ analyzed the data. SP wrote the paper and KA, WGR, XZ, AG, REM, and MKH assisted with interpretation of the data. The paper was reviewed and approved by all authors.

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Correspondence to Margaret K. Hahn.

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MKH received consultant fees from Alkermes.

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Castellani, L.N., Pereira, S., Kowalchuk, C. et al. Antipsychotics impair regulation of glucose metabolism by central glucose. Mol Psychiatry 27, 4741–4753 (2022). https://doi.org/10.1038/s41380-022-01798-y

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