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The bidirectional association of nonalcoholic fatty liver disease with depression, bipolar disorder, and schizophrenia

Published online by Cambridge University Press:  21 October 2022

Muhammad Youshay Jawad ,
Shakila Meshkat ,
Aniqa Tabassum ,
Andrea Mckenzie ,
Joshua D. Di Vincenzo ,
Ziji Guo ,
Nabiha Batool Musavi ,
Lee Phan ,
Felicia Ceban  and
Angela TH Kwan
...Show all authors
Muhammad Youshay Jawad
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Shakila Meshkat
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada
Aniqa Tabassum
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada
Andrea Mckenzie
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada
Joshua D. Di Vincenzo
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada
Ziji Guo
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Nabiha Batool Musavi
Affiliation:
Liaquat National Medical College, Karachi, Pakistan
Lee Phan
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada
Felicia Ceban
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Angela TH Kwan
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada Brain and Cognition Discovery Foundation, Toronto, ON, Canada Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
Ranuk Ramachandra
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Gia Han Le
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Rodrigo B. Mansur
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Joshua D. Rosenblat
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Roger Ho
Affiliation:
Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore
Taeho Greg Rhee
Affiliation:
Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA VA New England Mental Illness, Research, Education and Clinical Center (MIRECC), VA Connecticut Healthcare System, West Haven, CT, USA Department of Public Health Sciences, School of Medicine, University of Connecticut, Farmington, CT, USA
Roger S. McIntyre*
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada Brain and Cognition Discovery Foundation, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
*
*Author for correspondence: Roger S. McIntyre Email: roger.mcintyre@bcdf.org
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Abstract

Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic-inflammatory disease associated with poor outcomes and decreased quality of life. NAFLD is overrepresented in patients with psychiatric disorders like depression, bipolar disorder, and schizophrenia; however, a comprehensive review on NAFLD and psychiatric disorders remains to be delineated. This review endeavors to investigate the association of NAFLD with psychiatric disorders, including shared pathogenesis and future clinical derivatives. Extant literature suggests that patients with psychiatric disorders (in particular, mood disorders) are more susceptible to the development of NAFLD due to multiple reasons, including but not limited to hypothalamic–pituitary–adrenal axis dysregulation, metabolic syndrome, and chronic perceived stress. Moreover, the clinical manifestations of mood disorders (e.g., anhedonia, psychomotor retardation, lifestyle modification, etc.), and potentially long-term treatment with weight-gaining agents, differentially affect these patients, making them more prone to NAFLD. Considering the increased morbidity associated with both mood disorders and NAFLD, our review recommends regular screenings for NAFLD in select patients with mood disorders exhibiting signs of increased risk (i.e., obesity, metabolic syndrome, diabetes, or family history of NAFLD) for better diagnosis and holistic care of both potentially interrelated conditions.

Keywords

DepressionBipolar disorderMood DisordersSchizophreniaNAFLDNASHFatty LiverMetabolic SyndromeInflammationinsulin resistance
Type
Review
Information
CNS Spectrums , Volume 28 , Issue 5 , October 2023 , pp. 541 - 560
Copyright
© The Author(s), 2022. Published by Cambridge University Press

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References

Brunt, EM, Wong, VW-S, Nobili, V, et al. Nonalcoholic fatty liver disease. Nat Rev Dis Primers. 2015;1(1):1–22. doi:10.1038/nrdp.2015.80.CrossRefGoogle ScholarPubMed
Machado, MV, Diehl, AM. Pathogenesis of nonalcoholic steatohepatitis. Gastroenterology. 2016;150(8):1769–1777. doi:10.1053/j.gastro.2016.02.066.CrossRefGoogle ScholarPubMed
Rostama, B, Beauchemin, M, Bouchard, C, et al. Understanding mechanisms underlying non-alcoholic fatty liver disease (NAFLD) in mental illness: risperidone and olanzapine alter the hepatic proteomic signature in mice. Int J Mol Sci. 2020;21(24):9362. doi:10.3390/ijms21249362.CrossRefGoogle ScholarPubMed
Lonardo, A. Renaming NAFLD to MAFLD: could the LDE system assist in this transition? J Clin Med. 2021;10(3):492. doi:10.3390/jcm10030492.CrossRefGoogle ScholarPubMed
Younossi, ZM, Koenig, AB, Abdelatif, D, et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84. doi:10.1002/hep.28431.CrossRefGoogle ScholarPubMed
Lazarus, JV, Mark, HE, Anstee, QM, et al. Advancing the global public health agenda for NAFLD: a consensus statement. Nat Rev Gastroenterol Hepatol. 2022;19(1):60–78. doi:10.1038/s41575-021-00523-4.CrossRefGoogle ScholarPubMed
Mansur, RB, Brietzke, E, McIntyre, RS. Is there a “metabolic-mood syndrome”? A review of the relationship between obesity and mood disorders. Neurosci Biobehav Rev. 2015;52:89–104. doi:10.1016/j.neubiorev.2014.12.017.CrossRefGoogle Scholar
Mansur, RB, Lee, Y, McIntyre, RS, et al. What is bipolar disorder? A disease model of dysregulated energy expenditure. Neurosci Biobehav Rev. 2020;113:529–545. doi:10.1016/j.neubiorev.2020.04.006.CrossRefGoogle ScholarPubMed
McIntyre, RS, Berk, M, Brietzke, E, et al. Bipolar disorders. The Lancet. 2020;396(10265):1841–1856. doi:10.1016/S0140-6736(20)31544-0.CrossRefGoogle ScholarPubMed
Otte, C, Gold, SM, Penninx, BW, et al. Major depressive disorder. Nat Rev Dis Primers. 2016;2(1):1–20. doi:10.1038/nrdp.2016.65.CrossRefGoogle ScholarPubMed
Soczynska, JK, Kennedy, SH, Woldeyohannes, HO, et al. Mood disorders and obesity: understanding inflammation as a pathophysiological nexus. Neuromol Med. 2011;13(2):93–116. doi:10.1007/s12017-010-8140-8.CrossRefGoogle ScholarPubMed
World Health Organization. 2017. https://apps.who.int/iris/bitstream/handle/10665/254610/WHOMSD?sequence=1. Accessed May 17, 2022.Google Scholar
Gu, Y, Zhang, W, Hu, Y, et al. Association between nonalcoholic fatty liver disease and depression: a systematic review and meta-analysis of observational studies. J Affect Disord. 2022;301:8–13. doi:10.1016/j.jad.2021.12.128.CrossRefGoogle ScholarPubMed
Cho, IY, Chang, Y, Sung, E, et al. Depression and increased risk of non-alcoholic fatty liver disease in individuals with obesity. Epidemiol Psychiatr Sci. 2021;30:e23 doi:10.1017/S204579602000116X.CrossRefGoogle ScholarPubMed
Noon, SL, D’Annibale, DA, Schwimmer, MH, et al. Incidence of depression and anxiety in a cohort of adolescents with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2021;72(4):579–583. doi:10.1097/MPG.0000000000003024.CrossRefGoogle Scholar
Choi, JM, Chung, GE, Kang, SJ, et al. Association between anxiety and depression and nonalcoholic fatty liver disease. Front Med (Lausanne). 2020;7:585618 doi:10.3389/fmed.2020.585618.CrossRefGoogle ScholarPubMed
Elwing, JE, Lustman, PJ, Wang, HL, et al. Depression, anxiety, and nonalcoholic steatohepatitis. Psychosom Med. 2006;68(4):563–569. doi:10.1097/01.psy.0000221276.17823.df.CrossRefGoogle ScholarPubMed
Jung, JY, Park, SK, Oh, CM, et al. Non-alcoholic fatty liver disease and its association with depression in Korean general population. J Korean Med Sci. 2019;34(30):e199. doi:10.3346/jkms.2019.34.e199.CrossRefGoogle ScholarPubMed
Lee, JW, Park, SH. Association between depression and nonalcoholic fatty liver disease: contributions of insulin resistance and inflammation. J Affect Disord. 2021;278:259–263. doi:10.1016/j.jad.2020.09.073.CrossRefGoogle ScholarPubMed
Lee, K, Otgonsuren, M, Younoszai, Z, et al. Association of chronic liver disease with depression: a population-based study. Psychosomatics. 2013;54(1):52–59. doi:10.1016/j.psym.2012.09.005.CrossRefGoogle ScholarPubMed
Shaheen, AA, Kaplan, GG, Sharkey, KA, et al. Impact of major depression and antidepressant use on alcoholic and non-alcoholic fatty liver disease: a population-based study. Liver Int. 2021;41(10):2308–2317. doi:10.1111/liv.14973.CrossRefGoogle ScholarPubMed
Tomeno, W, Kawashima, K, Yoneda, M, et al. Non-alcoholic fatty liver disease comorbid with major depressive disorder: the pathological features and poor therapeutic efficacy. J Gastroenterol Hepatol. 2015;30(6):1009–1014. doi:10.1111/jgh.12897.CrossRefGoogle ScholarPubMed
Youssef, NA, Abdelmalek, MF, Binks, M, et al. Associations of depression, anxiety and antidepressants with histological severity of nonalcoholic fatty liver disease. Liver Int. 2013;33(7):1062–1070. doi:10.1111/liv.12165.CrossRefGoogle ScholarPubMed
Fuller, BE, Rodriguez, VL, Linke, A, et al. Prevalence of liver disease in veterans with bipolar disorder or schizophrenia. Gen Hosp Psychiatry. 2011;33(3):232–237. doi:10.1016/j.genhosppsych.2011.03.006.CrossRefGoogle ScholarPubMed
Godin, O, Leboyer, M, Belzeaux, R, et al. Non-alcoholic fatty liver disease in a sample of individuals with bipolar disorders: results from the FACE-BD cohort. Acta Psychiatr Scand. 2021;143(1):82–91. doi:10.1111/acps.13239.CrossRefGoogle Scholar
Nabi, O, Lacombe, K, Boursier, J, et al. Prevalence and risk factors of nonalcoholic fatty liver disease and advanced fibrosis in general population: the French nationwide NASH-CO study. Gastroenterology. 2020;159(2):791–793.e2. doi:10.1053/j.gastro.2020.04.048.CrossRefGoogle ScholarPubMed
Casey, DE, Haupt, DW, Newcomer, JW, et al. Antipsychotic-induced weight gain and metabolic abnormalities: implications for increased mortality in patients with schizophrenia. J Clin Psychiatry. 2004;65(Suppl 7):4–18. quiz 19-20.Google ScholarPubMed
Cha, DS, McIntyre, RS. Treatment-emergent adverse events associated with atypical antipsychotics. Expert Opin Pharmacother. 2012;13(11):1587–1598. doi:10.1517/14656566.2012.656590.CrossRefGoogle ScholarPubMed
Pillinger, T, McCutcheon, RA, Vano, L, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry. 2020;7(1):64–77. doi:10.1016/S2215-0366(19)30416-X.CrossRefGoogle ScholarPubMed
Bayat, M, Jalali, N, Poursadeghfard, M, et al. Metabolic syndrome and insulin resistance in sodium valproate or carbamazepine monotherapy: a case-control study. JKMU. 2021;28(6):548–558 doi:10.22062/jkmu.2021.91826.Google Scholar
Luef, GJ, Waldmann, M, Sturm, W, et al. Valproate therapy and nonalcoholic fatty liver disease. Ann Neurol. 2004;55(5):729–732. doi:10.1002/ana.20074.CrossRefGoogle ScholarPubMed
Jawad, MY, Alnefeesi, Y, Lui, LMW, et al. Olanzapine and samidorphan combination treatment: a systematic review. [published correction appears in J Affect Disord. 2022 Feb 15;:]. J Affect Disord. 2022;301:99–106. doi:10.1016/j.jad.2022.01.004.CrossRefGoogle ScholarPubMed
Hsu, J-H, Chien, I-C, Lin, C-H, et al. Increased risk of chronic liver disease in patients with schizophrenia: a population-based cohort study. Psychosomatics. 2014;55(2):163–171. doi:10.1016/j.psym.2013.06.001.CrossRefGoogle ScholarPubMed
Koreki, A, Mori, H, Nozaki, S, et al. Risk of nonalcoholic fatty liver disease in patients with schizophrenia treated with antipsychotic drugs: a cross-sectional study. J Clin Psychopharmacol. 2021;41(4):474–477. doi:10.1097/JCP.0000000000001421.CrossRefGoogle ScholarPubMed
Ma, Q, Yang, F, Ma, B, et al. Prevalence of nonalcoholic fatty liver disease in mental disorder inpatients in China: an observational study. Hepatol Int. 2021;15(1):127–136. doi:10.1007/s12072-020-10132-z.CrossRefGoogle Scholar
Yan, J, Hou, C, Liang, Y. The prevalence and risk factors of young male schizophrenics with non-alcoholic fatty liver disease. Neuropsychiatr Dis Treat. 2017;13:1493–1498. doi:10.2147/NDT.S137183.CrossRefGoogle ScholarPubMed
Yang, S, Cheng, J, Zhang, R, et al. Metabolic dysfunction-associated fatty liver disease and liver fibrosis: prevalence and associated factors in the middle-aged and older US population. Hepatol Res. 2022;52(2):176–186. doi:10.1111/hepr.13728.CrossRefGoogle ScholarPubMed
Morlán-Coarasa, MJ, Arias-Loste, MT, Ortiz-García de la Foz, V, et al. Incidence of non-alcoholic fatty liver disease and metabolic dysfunction in first episode schizophrenia and related psychotic disorders: a 3-year prospective randomized interventional study. Psychopharmacology (Berl). 2016;233(23–24):3947–3952. doi:10.1007/s00213-016-4422-7.CrossRefGoogle ScholarPubMed
Pan, Z, Park, C, Brietzke, E, et al. Cognitive impairment in major depressive disorder. CNS Spectrums. 2019;24(1):22–29. doi:10.1017/S1092852918001207.CrossRefGoogle ScholarPubMed
McIntyre, RS, Cha, DS, Soczynska, JK, et al. Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depression and Anxiety. 2013;30(6):515–527. doi:10.1002/da.22063.CrossRefGoogle ScholarPubMed
Huang, R, Fan, J-G, Shi, J-P, et al. Health-related quality of life in Chinese population with non-alcoholic fatty liver disease: a national multicenter survey. Health Qual Life Outcomes. 2021;19(1):140 doi:10.1186/s12955-021-01778-w.CrossRefGoogle ScholarPubMed
Tahmi, M, Palta, P, Luchsinger, JA. Metabolic syndrome and cognitive function. Curr Cardiol Rep. 2021;23(12):180 doi:10.1007/s11886-021-01615-y.CrossRefGoogle ScholarPubMed
Celikbilek, A, Celikbilek, M, Bozkurt, G. Cognitive assessment of patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2018;30(8):944–950. doi:10.1097/MEG.0000000000001131.CrossRefGoogle ScholarPubMed
Filipović, B, Marković, O, Đurić, V, et al. Cognitive changes and brain volume reduction in patients with nonalcoholic fatty liver disease. Can J Gastroenterol Hepatol. 2018;2018:9638797. doi:10.1155/2018/9638797.CrossRefGoogle ScholarPubMed
Balp, M-M, Krieger, N, Przybysz, R, et al. The burden of non-alcoholic steatohepatitis (NASH) among patients from Europe: a real-world patient-reported outcomes study. JHEP Rep. 2019;1(3):154–161. doi:10.1016/j.jhepr.2019.05.009.CrossRefGoogle ScholarPubMed
Arab, JP, Arrese, M, Trauner, M. Recent insights into the pathogenesis of nonalcoholic fatty liver disease. Annu Rev Pathol: Mech Dis. 2018;13(1):321–350. doi:10.1146/annurev-pathol-020117-043617.CrossRefGoogle ScholarPubMed
Papadimitriou, A, Priftis, KN. Regulation of the hypothalamic-pituitary-adrenal axis. Neuroimmunomodulation. 2009;16(5):265–271. doi:10.1159/000216184.CrossRefGoogle ScholarPubMed
Smith, SM, Vale, WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci. 2006;8(4):383–395.CrossRefGoogle ScholarPubMed
Shields, GS, Bonner, JC, Moons, WG. Does cortisol influence core executive functions? A meta-analysis of acute cortisol administration effects on working memory, inhibition, and set-shifting. Psychoneuroendocrinology. 2015;58:91–103. doi:10.1016/j.psyneuen.2015.04.017.CrossRefGoogle ScholarPubMed
Thau, L, Gandhi, J, Sharma, S. Physiology, Cortisol. StatPearls Publishing; 2021; https://www.ncbi.nlm.nih.gov/books/NBK538239/. Accessed May 30, 2022.Google Scholar
Baumeister, D, Lightman, SL, Pariante, CM. The interface of stress and the HPA axis in behavioural phenotypes of mental illness. Curr Top Behav Neurosci. 2014;18:13–24. doi:10.1007/7854_2014_304.CrossRefGoogle ScholarPubMed
Daskalakis, NP, Bagot, RC, Parker, KJ, et al. The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome. Psychoneuroendocrinology. 2013;38:1858–1873. doi:10.1016/j.psyneuen.2013.06.008.CrossRefGoogle ScholarPubMed
Heim, C, Nemeroff, CB. Neurobiology of early life stress: clinical studies. Semin Clin Neuropsychiatry. 2002;7:147–159. doi:10.1053/scnp.2002.33127.CrossRefGoogle ScholarPubMed
Lecic-Tosevski, D, Vukovic, O, Stepanovic, J. Stress and personality. Psychiatriki. 2011;22(4):290–297.Google ScholarPubMed
Dienes, KA, Hazel, NA, Hammen, CL. Cortisol secretion in depressed, and at-risk adults. Psychoneuroendocrinology. 2012;38:927–940. doi:10.1016/j.psyneuen.2012.09.019.CrossRefGoogle ScholarPubMed
Shea, S, Lionis, C, Kite, C, et al. Non-alcoholic fatty liver disease (NAFLD) and potential links to depression, anxiety, and chronic stress. Biomedicines. 2021;9(11):1697. doi:10.3390/biomedicines9111697.CrossRefGoogle ScholarPubMed
Wang, N, Chen, Y, Ning, Z, et al. Exposure to famine in early life and nonalcoholic fatty liver disease in adulthood. J Clin Endocrinol Metabo. 2016;101(5):2218–2225. doi:10.1210/jc.2016-1076.CrossRefGoogle ScholarPubMed
Kang, D, Zhao, D, Ryu, S, et al. Perceived stress and non-alcoholic fatty liver disease in apparently healthy men and women. Sci Rep. 2020;10(1):38 doi:10.1038/s41598-019-57036-z.CrossRefGoogle ScholarPubMed
Brenner, K, Liu, A, Laplante, DP, et al. Cortisol response to a psychosocial stressor in schizophrenia: blunted, delayed, or normal? Psychoneuroendocrinology. 2009;34. doi:10.1016/j.psyneuen.2009.01.002.CrossRefGoogle ScholarPubMed
Steudte, S, Kolassa, IT, Stalder, T, et al. Increased cortisol concentrations in hair of severely traumatized Ugandan individuals with PTSD. Psychoneuroendocrinology. 2011;36:1193–1200. doi:10.1016/j.psyneuen.2011.02.012.CrossRefGoogle ScholarPubMed
Steptoe, A, Kivimäki, M. Stress and cardiovascular disease. Nat Rev Cardiol. 2012;9(6):360–370. doi:10.1038/nrcardio.2012.45.CrossRefGoogle ScholarPubMed
Ahmed, A, Rabbitt, E, Brady, T, et al. A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease. PLoS One. 2012;7(2):e29531 doi:10.1371/journal.pone.0029531.CrossRefGoogle ScholarPubMed
Targher, G, Bertolini, L, Rodella, S, et al. Associations between liver histology and cortisol secretion in subjects with nonalcoholic fatty liver disease. Clin Endocrinol. 2006;64(3):337–341. doi:10.1111/j.1365-2265.2006.02466.x.CrossRefGoogle ScholarPubMed
Von-Hafe, M, Borges-Canha, M, Vale, C, et al. Nonalcoholic fatty liver disease and endocrine axes—a scoping review. Metabolites. 2022;12(4):298 doi:10.3390/metabo12040298.CrossRefGoogle ScholarPubMed
Dantzer, R, O’Connor, JC, Freund, GG, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9:46–56. doi:10.1038/nrn2297.CrossRefGoogle ScholarPubMed
Soto-Angona, Ó, Anmella, G, Valdés-Florido, MJ, et al. Non-alcoholic fatty liver disease (NAFLD) as a neglected metabolic companion of psychiatric disorders: common pathways and future approaches. BMC Med. 2020;18(1):261 doi:10.1186/s12916-020-01713-8.CrossRefGoogle ScholarPubMed
Nolan, CJ, Prentki, M. Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: time for a conceptual framework shift. Diab Vasc Dis Res. 2019;16(2):118–127. doi:10.1177/1479164119827611.CrossRefGoogle ScholarPubMed
Alberti, KGMM, Eckel, RH, Grundy, SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation. 2009;120(16):1640–1645. doi:10.1161/CIRCULATIONAHA.109.192644.CrossRefGoogle Scholar
Cetinkalp, S, Simsir, IY, Ertek, S. Insulin resistance in brain and possible therapeutic approaches. Curr Vasc Pharmacol. 2014;12(4):553–564. doi:10.2174/1570161112999140206130426.CrossRefGoogle ScholarPubMed
Watt, MJ, Miotto, PM, De Nardo, W, et al. The liver as an endocrine organ—linking NAFLD and insulin resistance. Endocr Rev. 2019;40(5):1367–1393. doi:10.1210/er.2019-00034.CrossRefGoogle ScholarPubMed
Ferrante, AW. Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J Intern Med. 2007;262(4):408–414. doi:10.1111/j.1365-2796.2007.01852.x.CrossRefGoogle ScholarPubMed
Liu, Y, Ho, RC-M, Mak, A. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord. 2012;139(3):230–239. doi:10.1016/j.jad.2011.08.003.CrossRefGoogle ScholarPubMed
Ho, CSH, Zhang, MWB, Mak, A, et al. Metabolic syndrome in psychiatry: advances in understanding and management. Adv Psychiatr Treat. 2014;20(2):101–112. doi:10.1192/apt.bp.113.011619.CrossRefGoogle Scholar
Rodríguez-Hernández, H, Simental-Mendía, LE, Rodríguez-Ramírez, G, et al. Obesity and inflammation: epidemiology, risk factors, and markers of inflammation. Int J Endocrinol. 2013;2013:e678159. doi:10.1155/2013/678159.CrossRefGoogle ScholarPubMed
Chait, A, Kim, F. Saturated fatty acids and inflammation: who pays the toll? Arterioscler Thromb Vasc Biol. 2010;30(4):692–693. doi:10.1161/ATVBAHA.110.203984.CrossRefGoogle ScholarPubMed
McIntyre, RS, Danilewitz, M, Liauw, SS, et al. Bipolar disorder and metabolic syndrome: an international perspective. J Affect Disord. 2010;126(3):366–387. doi:10.1016/j.jad.2010.04.012.CrossRefGoogle ScholarPubMed
McIntyre, RS, Rasgon, NL, Kemp, DE, et al. Metabolic syndrome and major depressive disorder: co-occurrence and pathophysiologic overlap. Curr Diab Rep. 2009;9(1):51–59. doi:10.1007/s11892-009-0010-0.CrossRefGoogle ScholarPubMed
SayuriYamagata, A, Brietzke, E, Rosenblat, JD, et al. Medical comorbidity in bipolar disorder: the link with metabolic-inflammatory systems. J Affect Disord. 2017;211:99–106. doi:10.1016/j.jad.2016.12.059.CrossRefGoogle ScholarPubMed
Rosenblat, JD, Cha, DS, Mansur, RB, et al. Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog Neuro-Psychopharmacol Biol Psychiatry. 2014;53:23–34. doi:10.1016/j.pnpbp.2014.01.013.CrossRefGoogle ScholarPubMed
Tossani, E. The concept of mental pain. PPS. 2013;82(2):67–73. doi:10.1159/000343003.Google ScholarPubMed
Hammen, C. Stress and Depression. Ann Rev Clin Psychol. 2005;1(1):293–319. doi:10.1146/annurev.clinpsy.1.102803.143938.CrossRefGoogle ScholarPubMed
Wang, W, Yang, J, Xu, J, et al. Effects of high-fat diet and chronic mild stress on depression-like behaviors and levels of inflammatory cytokines in the hippocampus and prefrontal cortex of rats. Neuroscience. 2022;480:178–193. doi:10.1016/j.neuroscience.2021.11.015.CrossRefGoogle ScholarPubMed
Lloyd, C, Smith, J, Weinger, K. Stress and diabetes: a review of the links. Diabetes Spectrum. 2005;18(2):121–127. doi:10.2337/diaspect.18.2.121.CrossRefGoogle Scholar
Targher, G, Byrne, CD, Tilg, H. NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications. Gut. 2020;69(9):1691–1705. doi:10.1136/gutjnl-2020-320622.CrossRefGoogle ScholarPubMed
Tilg, H, Moschen, AR, Roden, M. NAFLD and diabetes mellitus. Nat Rev Gastroenterol Hepatol. 2017;14(1):32–42. doi:10.1038/nrgastro.2016.147.CrossRefGoogle ScholarPubMed
McIntyre, RS, Lee, Y, Mansur, RB. Treating to target in major depressive disorder: response to remission to functional recovery. CNS Spectr. 2015;20(S1):17–31. doi:10.1017/S1092852915000826.CrossRefGoogle ScholarPubMed
Stubbs, B, Vancampfort, D, Smith, L, et al. Physical activity and mental health. Lancet Psychiatry. 2018;5(11):873 doi:10.1016/S2215-0366(18)30343-2.CrossRefGoogle ScholarPubMed
Tarantino, G, Cataldi, M, Citro, V. Could alcohol abuse and dependence on junk foods inducing obesity and/or illicit drug use represent danger to liver in young people with altered psychological/relational spheres or emotional problems? Int J Mol Sci. 2022;23(18):10406 doi:10.3390/ijms231810406.CrossRefGoogle ScholarPubMed
Rodriguez, B, Torres, DM, Harrison, SA. Physical activity: an essential component of lifestyle modification in NAFLD. Nat Rev Gastroenterol Hepatol. 2012;9(12):726–731. doi:10.1038/nrgastro.2012.200.CrossRefGoogle ScholarPubMed
Kahn, RS, Sommer, IE, Murray, RM, et al. Schizophrenia. Nat Rev Dis Primers. 2015;1(1):1–23. doi:10.1038/nrdp.2015.67.CrossRefGoogle ScholarPubMed
Buchanan, RW, Kreyenbuhl, J, Kelly, DL, et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull. 2010;36(1):71–93. doi:10.1093/schbul/sbp116.CrossRefGoogle ScholarPubMed
Roshanaei-Moghaddam, B, Katon, WJ, Russo, J. The longitudinal effects of depression on physical activity. Gen Hosp Psychiatry. 2009;31(4):306–315. doi:10.1016/j.genhosppsych.2009.04.002.CrossRefGoogle ScholarPubMed
Gafoor, R, Booth, HP, Gulliford, MC. Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study. BMJ. 2018;361:k1951. doi:10.1136/bmj.k1951.CrossRefGoogle ScholarPubMed
Lee, SH, Paz-Filho, G, Mastronardi, C, et al. Is increased antidepressant exposure a contributory factor to the obesity pandemic? Transl Psychiatry. 2016;6(3):e759. doi:10.1038/tp.2016.25.CrossRefGoogle Scholar
Luppino, FS, de Wit, LM, Bouvy, PF, et al. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010;67(3):220–229. doi:10.1001/archgenpsychiatry.2010.2.CrossRefGoogle ScholarPubMed
Manu, P, Dima, L, Shulman, M, et al. Weight gain and obesity in schizophrenia: epidemiology, pathobiology, and management. Acta Psychiatrica Scandinavica. 2015;132(2):97–108. doi:10.1111/acps.12445.CrossRefGoogle ScholarPubMed
Caussy, C. Should we screen high-risk populations for NAFLD?. Curr Hepatology Rep. 2019;18(4):433–443. doi:10.1007/s11901-019-00497-7.CrossRefGoogle Scholar
Pandyarajan, V, Gish, RG, Alkhouri, N, et al. Screening for nonalcoholic fatty liver disease in the primary care clinic. Gastroenterol Hepatol (N Y). 2019;15(7):357–365.Google ScholarPubMed
Hamer, JA, Testani, D, Mansur, RB, et al. Brain insulin resistance: a treatment target for cognitive impairment and anhedonia in depression. Exp Neurol. 2019;315:1–8. doi:10.1016/j.expneurol.2019.01.016.CrossRefGoogle ScholarPubMed
Mundi, MS, Velapati, S, Patel, J, et al. Evolution of NAFLD and Its Management. Nutr Clin Pract. 2020;35(1):72–84. doi:10.1002/ncp.10449.CrossRefGoogle ScholarPubMed
Lee, Y, Subramaniapillai, M, Brietzke, E, et al. Anti-cytokine agents for anhedonia: targeting inflammation and the immune system to treat dimensional disturbances in depression. Ther Adv Psychopharmacol. 2018;8(12):337–348. doi:10.1177/2045125318791944.CrossRefGoogle ScholarPubMed
Lu, Y, Ho, CS, Liu, X, et al. Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression. PLoS One. 2017;12(10):e0186700 doi:10.1371/journal.pone.0186700.CrossRefGoogle Scholar
Kenneson, A, Funderburk, JS. Patatin-like phospholipase domain-containing protein 3 (PNPLA3): a potential role in the association between liver disease and bipolar disorder. J Affect Disord. 2017;209:93–96. doi:10.1016/j.jad.2016.11.035.CrossRefGoogle ScholarPubMed