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Methamphetamine-Induced Cognitive Deficits and Psychiatric Symptoms Are Associated with Serum Markers of Liver Damage

  • Tingting Zhao
  • Changping Zhai
  • Hongmei Song
  • Yanhai Wu
  • Chuanhui Ge
  • Yonglin Zhang
  • Hongxia Xu
  • Zhengsuo Chi
  • Hui Chu
  • Wei Shi
  • Xiaodong Cheng
  • Xin Li
  • Mengdi Ma
  • Mengyuan Xu
  • Jiaqi Hu
  • Ya Xie
  • Yanan Lin
  • Hongxu Chen
  • Yiting Li
  • Dongliang JiaoEmail author
Original Article

Abstract

Cognitive deficits and psychiatric disorders have been regarded as the most common clinical symptoms of methamphetamine (MA) users. Accumulating evidence has shown that liver disease may be involved in cognitive deficits and psychiatric disorders. This study examines whether cognitive deficits and psychiatric symptoms are associated with serum levels of liver biomarkers in MA users. Cognition was assessed by the Repeatable Battery for the Assessment of neuropsychological Status (RBANS). Psychiatric symptoms were assessed by the Symptom Checklist-90 (SCL-90). Liver function was assessed by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, Apolipoprotein B (ApoB), triglyceride, total cholesterol, and glucose concentrations in 106 MA addicts and 76 controls. Compared to control subjects, MA users had greater severity of psychotic symptoms on the dimension of somatization, depression, anxiety, psychoticism, addiction, and global severity index in SCL-90, and lower scores of cognition, including the total RBANS score and all five subscales. The globulin levels were increased, while the albumin, albumin/globulin, and ApoB levels were decreased. ApoB levels were positively correlated with immediate memory, attention, and total RBANS score. Furthermore, stepwise multivariate regression analysis indicated that ApoB levels were associated with immediate memory, attention, and total RBANS score. The findings of this study suggest that MA addicts might experience cognitive deficits, psychiatric disorders, and liver damage. Serum ApoB levels may be involved in cognitive deficits; thus, improving liver function may help to treat cognitive deficits and psychiatric disorders in MA addicts.

Keywords

Methamphetamine Liver disease Cognitive deficit Psychiatric disorder Apolipoprotein B 

Notes

Author Contributions

T.Z., C.Z., and D.J. conceived and designed the experiments. C.G., Y.Z., H.X., Z.C., H.C., W.S., H.C., and Y.L. carried out experiments. X.C., X.L., M.M., M.X. analyzed experimental data. J.H., Y.X., and Y.L. contributed reagents, materials, and analysis tools. H.S. and Y.W. wrote the first draft of the manuscript. D.J. provided critical revision of the manuscript for important intellectual content.

Funding

Project supported by the provincial Natural Science Foundation of Anhui (1908085MH278), Program of Bengbu Medical College Science and Technology Development (BYKF17113), Program of Bengbu Medical College Science and Technology (BYKY17186), Compulsory Isolated Drug Rehabilitation Center–funded projects, and Innovative Training Program for Chinese College Students (201810367006).

Compliance with Ethical Standards

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Akindipe T, Wilson D, Stein DJ (2014) Psychiatric disorders in individuals with methamphetamine dependence: prevalence and risk factors. Metab Brain Dis 29:351–357CrossRefPubMedPubMedCentralGoogle Scholar
  2. Artigas A, Wernerman J, Arroyo V, Vincent JL, Levy M (2016) Role of albumin in diseases associated with severe systemic inflammation: pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis. J Crit Care 33:62–70CrossRefPubMedPubMedCentralGoogle Scholar
  3. Cadet JL, Brannock C, Jayanthi S, Krasnova IN (2015) Transcriptional and epigenetic substrates of methamphetamine addiction and withdrawal: evidence from a long-access self-administration model in the rat. Mol Neurobiol 51:696–717CrossRefPubMedPubMedCentralGoogle Scholar
  4. Chojkier M (2005) Inhibition of albumin synthesis in chronic diseases: molecular mechanisms. J Clin Gastroenterol 39:S143–S146CrossRefPubMedPubMedCentralGoogle Scholar
  5. Das HK, Leff T, Breslow JL (1988) Cell type-specific expression of the human apoB gene is controlled by two cis-acting regulatory regions. J Biol Chem 263:11452–11458PubMedPubMedCentralGoogle Scholar
  6. Eskandari MR, Rahmati M, Khajeamiri AR, Kobarfard F, Noubarani M, Heidari H (2014) A new approach on methamphetamine-induced hepatotoxicity: involvement of mitochondrial dysfunction. Xenobiotica 44:70–76CrossRefPubMedPubMedCentralGoogle Scholar
  7. Farrell M, Marsden J, Ali R, Ling W (2002) Methamphetamine: drug use and psychoses becomes a major public health issue in the Asia Pacific region. Addiction 97:771–772CrossRefPubMedPubMedCentralGoogle Scholar
  8. Filipovic B, Markovic O, Duric V, Filipovic B (2018) Cognitive changes and brain volume reduction in patients with nonalcoholic fatty liver disease. Can J Gastroenterol Hepatol 2018:9638797PubMedPubMedCentralGoogle Scholar
  9. Fredrikson GN, Lindholm MW, Ljungcrantz I, Soderberg I, Shah PK, Nilsson J (2007) Autoimmune responses against the apo B-100 LDL receptor-binding site protect against arterial accumulation of lipids in LDL receptor deficient mice. Autoimmunity 40:122–130CrossRefPubMedPubMedCentralGoogle Scholar
  10. Guevara M, Baccaro ME, Gomez-Anson B, Frisoni G, Testa C, Torre A, Molinuevo JL, Rami L, Pereira G, Sotil EU, Cordoba J, Arroyo V, Gines P (2011) Cerebral magnetic resonance imaging reveals marked abnormalities of brain tissue density in patients with cirrhosis without overt hepatic encephalopathy. J Hepatol 55:564–573CrossRefPubMedPubMedCentralGoogle Scholar
  11. Halpin LE, Gunning WT, Yamamoto BK (2013) Methamphetamine causes acute hyperthermia-dependent liver damage. Pharmacol Res Perspect 1:e00008CrossRefPubMedPubMedCentralGoogle Scholar
  12. Hui L, Han M, Du XD, Zhang BH, He SC, Shao TN, Yin GZ (2017) Serum ApoB levels in depressive patients: associated with cognitive deficits. Sci Rep 7:39992CrossRefPubMedPubMedCentralGoogle Scholar
  13. Jacobs E, Fujii D, Schiffman J, Bello I (2008) An exploratory analysis of neurocognition in methamphetamine-induced psychotic disorder and paranoid schizophrenia. Cogn Behav Neurol 21:98–103CrossRefPubMedPubMedCentralGoogle Scholar
  14. Jiao D, Liu Y, Li X, Liu J, Zhao M (2015) The role of the GABA system in amphetamine-type stimulant use disorders. Front Cell Neurosci 9:162CrossRefPubMedPubMedCentralGoogle Scholar
  15. Jiao DL, Liu Y, Long JD, Du J, Ju YY, Zan GY, Liu JG, Zhao M (2016) Involvement of dorsal striatal alpha1-containing GABAA receptors in methamphetamine-associated rewarding memories. Neuroscience 320:230–238CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kamijo Y, Soma K, Nishida M, Namera A, Ohwada T (2002) Acute liver failure following intravenous methamphetamine. Vet Hum Toxicol 44:216–217PubMedPubMedCentralGoogle Scholar
  17. Kim TS, Pae CU, Yoon SJ, Jang WY, Lee NJ, Kim JJ, Lee SJ, Lee C, Paik IH, Lee CU (2006) Decreased plasma antioxidants in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 21:344–348CrossRefPubMedPubMedCentralGoogle Scholar
  18. King G, Alicata D, Cloak C, Chang L (2010) Psychiatric symptoms and HPA axis function in adolescent methamphetamine users. J NeuroImmune Pharmacol 5:582–591CrossRefPubMedPubMedCentralGoogle Scholar
  19. Kobayashi R, Tohda C (2017) Extracellular cytosolic aspartate aminotransferase promotes axonal growth and object recognition memory. Neurochem Res 42:3465–3473CrossRefPubMedPubMedCentralGoogle Scholar
  20. Koyama T, Kuriyama N, Ozaki E, Matsui D, Watanabe I, Miyatani F, Kondo M, Tamura A, Kasai T, Ohshima Y, Yoshida T, Tokuda T, Mizuta I, Mizuno S, Yamada K, Takeda K, Matsumoto S, Nakagawa M, Mizuno T, Watanabe Y (2016) Serum albumin to globulin ratio is related to cognitive decline via reflection of homeostasis: a nested case–control study. BMC Neurol 16:253CrossRefPubMedPubMedCentralGoogle Scholar
  21. Kuo CJ, Tsai SY, Liao YT, Conwell Y, Lee WC, Huang MC, Lin SK, Chen CC, Chen WJ (2012) Elevated aspartate and alanine aminotransferase levels and natural death among patients with methamphetamine dependence. PLoS One 7:e29325CrossRefPubMedPubMedCentralGoogle Scholar
  22. Li H, Yao MJ, Zhao WM, Guan J, Cai LL, Cui L (2008) A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment. Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine 6:25–31CrossRefPubMedPubMedCentralGoogle Scholar
  23. Liu Y, Shen WW, Huang YY, Zhang JB, Zhou WH (2016) Relapse motivation analysis for methamphetamine addicts. Chinese Journal of Clinical PharmacologyGoogle Scholar
  24. Llewellyn DJ, Langa KM, Friedland RP, Lang IA (2010) Serum albumin concentration and cognitive impairment. Curr Alzheimer Res 7:91–96CrossRefPubMedPubMedCentralGoogle Scholar
  25. Long JD, Liu Y, Jiao DL, Wang YJ, Zan GY, Ju YY, Zhao M, Liu JG (2017) The neuroprotective effect of memantine on methamphetamine-induced cognitive deficits. Behav Brain Res 323:133–140CrossRefPubMedPubMedCentralGoogle Scholar
  26. Luan X, Ren W, Zhao K, Su H, Shen H, Chen H, Qiu H, He J (2017) High prevalence of depressive symptoms and impulsivity as well as their relationship during subacute methamphetamine withdrawal in chronic abusers. J Clin Neurosci 39:1–3CrossRefPubMedPubMedCentralGoogle Scholar
  27. Macavei B, Baban A, Dumitrascu DL (2016) Psychological factors associated with NAFLD/NASH: a systematic review. Eur Rev Med Pharmacol Sci 20:5081–5097PubMedPubMedCentralGoogle Scholar
  28. Mahoney JJ 3rd, Kalechstein AD, De La Garza R 2nd, Newton TF (2008) Presence and persistence of psychotic symptoms in cocaine- versus methamphetamine-dependent participants. Am J Addict 17:83–98CrossRefPubMedPubMedCentralGoogle Scholar
  29. McKetin R, McLaren J, Lubman DI, Hides L (2006) The prevalence of psychotic symptoms among methamphetamine users. Addiction 101:1473–1478CrossRefPubMedPubMedCentralGoogle Scholar
  30. McKetin R, Baker AL, Dawe S, Voce A, Lubman DI (2017) Differences in the symptom profile of methamphetamine-related psychosis and primary psychotic disorders. Psychiatry Res 251:349–354CrossRefPubMedPubMedCentralGoogle Scholar
  31. Northrop NA, Yamamoto BK (2015) Methamphetamine effects on blood–brain barrier structure and function. Front Neurosci 9:69CrossRefPubMedPubMedCentralGoogle Scholar
  32. Petta S, Tuttolomondo A, Gagliardo C, Zafonte R, Brancatelli G, Cabibi D, Camma C, Di Marco V, Galvano L, La Tona G, Licata A, Magliozzo F, Maida C, Marchesini G, Merlino G, Midiri M, Parrinello G, Torres D, Pinto A, Craxi A (2016) The presence of white matter lesions is associated with the fibrosis severity of nonalcoholic fatty liver disease. Medicine 95:e3446CrossRefPubMedPubMedCentralGoogle Scholar
  33. Polcin DL, Witbrodt J, Korcha R, Gupta S, Mericle AA (2016) Course of psychiatric symptoms and abstinence among methamphetamine-dependent persons in sober living recovery homes. J Psychoactive Drugs 48:173–180CrossRefPubMedPubMedCentralGoogle Scholar
  34. Potvin S, Pelletier J, Grot S, Hebert C, Barr AM, Lecomte T (2018) Cognitive deficits in individuals with methamphetamine use disorder: a meta-analysis. Addict Behav 80:154–160CrossRefGoogle Scholar
  35. Randolph C, Tierney MC, Mohr E, Chase TN (1998) The repeatable battery for the assessment of neuropsychological status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol 20:310–319CrossRefGoogle Scholar
  36. Roche M, Rondeau P, Singh NR, Tarnus E, Bourdon E (2008) The antioxidant properties of serum albumin. FEBS Lett 582:1783–1787CrossRefGoogle Scholar
  37. Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ (2002) Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia aging study. Ann Neurol 52:168–174CrossRefGoogle Scholar
  38. Scott JC, Woods SP, Matt GE, Meyer RA, Heaton RK, Atkinson JH, Grant I (2007) Neurocognitive effects of methamphetamine: a critical review and meta-analysis. Neuropsychol Rev 17:275–297CrossRefPubMedPubMedCentralGoogle Scholar
  39. Seo SW, Gottesman RF, Clark JM, Hernaez R, Chang Y, Kim C, Ha KH, Guallar E, Lazo M (2016) Nonalcoholic fatty liver disease is associated with cognitive function in adults. Neurology 86:1136–1142CrossRefPubMedPubMedCentralGoogle Scholar
  40. Shah SS, Desai HG (2001a) Apolipoprotein deficiency and chronic liver disease. J Assoc Physicians India 49:274–278PubMedPubMedCentralGoogle Scholar
  41. Shah SS, Desai HG (2001b) Fatty liver and elevated transaminases with heterozygous apolipoprotein B deficiency. J Assoc Physicians India 49:284–285PubMedPubMedCentralGoogle Scholar
  42. Solhi H, Malekirad A, Kazemifar AM, Sharifi F (2014) Oxidative stress and lipid peroxidation in prolonged users of methamphetamine. Drug metabolism letters 7:-Google Scholar
  43. Su H, Zhang J, Ren W, Xie Y, Tao J, Zhang X, He J (2017) Anxiety level and correlates in methamphetamine-dependent patients during acute withdrawal. Medicine 96:e6434CrossRefPubMedPubMedCentralGoogle Scholar
  44. Volicer L, Crino PB (1990) Involvement of free radicals in dementia of the Alzheimer type: a hypothesis. Neurobiol Aging 11:567–571CrossRefPubMedPubMedCentralGoogle Scholar
  45. Wang Y, Liu L, Zhang H, Fan J, Zhang F, Yu M, Shi L, Yang L, Lam SM, Wang H, Chen X, Wang Y, Gao F, Shui G, Xu Z (2016) Mea6 controls VLDL transport through the coordinated regulation of COPII assembly. Cell Res 26:787–804CrossRefPubMedPubMedCentralGoogle Scholar
  46. Wang Q, Wei LW, Xiao HQ, Xue Y, Du SH, Liu YG, Xie XL (2017) Methamphetamine induces hepatotoxicity via inhibiting cell division, arresting cell cycle and activating apoptosis: in vivo and in vitro studies. Food Chem Toxicol 105:61–72CrossRefPubMedPubMedCentralGoogle Scholar
  47. Youssef NA, Abdelmalek MF, Binks M, Guy CD, Omenetti A, Smith AD, Diehl AM, Suzuki A (2013) Associations of depression, anxiety and antidepressants with histological severity of nonalcoholic fatty liver disease. Liver Int 33:1062–1070CrossRefPubMedPubMedCentralGoogle Scholar
  48. Yu S, Zhu L, Shen Q, Bai X, Di X (2015) Recent advances in methamphetamine neurotoxicity mechanisms and its molecular pathophysiology. Behav Neurol 2015:103969PubMedPubMedCentralGoogle Scholar
  49. Zhai C, Cui M, Cheng X, Ao X, Zhao T, Wu W, Shao Q, Ge D, Song H, Qi F, Ling Q, Ma M, Xu M, Jiao D (2018) Vitamin B12 levels in methamphetamine addicts. Front Behav Neurosci 12:320CrossRefPubMedPubMedCentralGoogle Scholar
  50. Zhang J, Zhang X (2013) Chinese college students’ SCL-90 scores and their relations to the college performance. Asian J Psychiatr 6:134–140CrossRefPubMedPubMedCentralGoogle Scholar
  51. Zhang BH, Tan YL, Zhang WF, Wang ZR, Yang GG, Shi C, Zhang XY, University P, Beijing (2008) Repeatable battery for the assessment of neuropsychological status as a screening test in Chinese: reliability and validity. Chin Ment Health J 22(12):865–869Google Scholar
  52. Zhang J, Liu X, Yang Z, Chen Y, Luo R (2016) The pretreatment albumin to globulin ratio, a validated biomarker, predicts prognosis in hepatocellular carcinoma. J BUON 21:925–934PubMedPubMedCentralGoogle Scholar
  53. Zhang F, Wang Y, Wang T, Yao L, Lam SM, Huang X, Fan J, Wang Q, Liu L, Jiang Y, Zhang H, Shi L, Yu M, Shui G, Wang Y, Gao F, Zhang X, Xu Z (2018a) cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development. 115:E9449-e9458Google Scholar
  54. Zhang K, Zhang Q, Jiang H, Du J, Zhou C, Yu S, Hashimoto K, Zhao M (2018b) Impact of aerobic exercise on cognitive impairment and oxidative stress markers in methamphetamine-dependent patients. Psychiatry ResGoogle Scholar
  55. Zhong N, Jiang H, Du J, Zhao Y, Sun H, Xu D, Li C, Zhuang W, Li X, Hashimoto K, Zhao M (2016) The cognitive impairments and psychological wellbeing of methamphetamine dependent patients compared with health controls. Prog Neuro-Psychopharmacol Biol Psychiatry 69:31–37CrossRefGoogle Scholar
  56. Zhuang SM, Chen F (2016) Chinese adolescents and youth with methamphetamine dependence: prevalence and concurrent psychological problems. Nurs Res 65:117–124CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Tingting Zhao
    • 1
  • Changping Zhai
    • 1
  • Hongmei Song
    • 1
  • Yanhai Wu
    • 1
  • Chuanhui Ge
    • 1
  • Yonglin Zhang
    • 1
  • Hongxia Xu
    • 1
  • Zhengsuo Chi
    • 1
  • Hui Chu
    • 1
  • Wei Shi
    • 2
  • Xiaodong Cheng
    • 2
  • Xin Li
    • 3
  • Mengdi Ma
    • 3
  • Mengyuan Xu
    • 3
  • Jiaqi Hu
    • 3
  • Ya Xie
    • 3
  • Yanan Lin
    • 3
  • Hongxu Chen
    • 3
  • Yiting Li
    • 3
  • Dongliang Jiao
    • 3
    Email author
  1. 1.Anhui Province Veterans HospitalBengbuChina
  2. 2.Compulsory Isolated Drug Rehabilitation CenterBengbuChina
  3. 3.School of Mental HealthBengbu Medical CollegeBengbuChina

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