Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-22T19:39:40.689Z Has data issue: false hasContentIssue false
  • English
  • Français

Mediator effects of parameters of inflammation and neurogenesis from a N-acetyl cysteine clinical-trial for bipolar depression

Published online by Cambridge University Press:  16 July 2018

Bruna Panizzutti ,
Chiara Bortolasci ,
Kyoko Hasebe ,
Srisaiyini Kidnapillai ,
Laura Gray ,
Ken Walder ,
Michael Berk ,
Mohammadreza Mohebbi ,
Seetal Dodd  and
Clarissa Gama
...Show all authors
Bruna Panizzutti
Affiliation:
Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA) and Programa de Pós-graduação em Psiquiatria e Ciências do Comportamento, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
Chiara Bortolasci
Affiliation:
Graduation Program in Health Sciences, State University of Londrina (UEL), Londrina, Brazil Deakin University, School of Medicine, Centre for Molecular and Medical Research, Geelong, Australia
Kyoko Hasebe
Affiliation:
Deakin University, School of Medicine, Centre for Molecular and Medical Research, Geelong, Australia
Srisaiyini Kidnapillai
Affiliation:
Deakin University, School of Medicine, Centre for Molecular and Medical Research, Geelong, Australia
Laura Gray
Affiliation:
Deakin University, School of Medicine, Centre for Molecular and Medical Research, Geelong, Australia The Florey Institute of Neuroscience and Mental Health, Parkville, Australia
Ken Walder
Affiliation:
Deakin University, School of Medicine, Centre for Molecular and Medical Research, Geelong, Australia
Michael Berk
Affiliation:
Deakin University, School of Medicine, IMPACT Strategic Research Centre, Barwon Health, Geelong, Australia Department of Psychiatry, The University of Melbourne, Parkville, Australia The Florey Institute of Neuroscience and Mental Health, Parkville, Australia Orygen Centre for Youth Mental Health, University of Melbourne, Parkville, Australia
Mohammadreza Mohebbi
Affiliation:
Deakin University, Biostatistics Unit, Faculty of Health, Geelong, Australia
Seetal Dodd
Affiliation:
Deakin University, School of Medicine, IMPACT Strategic Research Centre, Barwon Health, Geelong, Australia Department of Psychiatry, The University of Melbourne, Parkville, Australia Orygen Centre for Youth Mental Health, University of Melbourne, Parkville, Australia
Clarissa Gama
Affiliation:
Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA) and Programa de Pós-graduação em Psiquiatria e Ciências do Comportamento, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
Pedro V. Magalhães
Affiliation:
Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA) and Programa de Pós-graduação em Psiquiatria e Ciências do Comportamento, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
Susan M. Cotton
Affiliation:
Orygen Centre for Youth Mental Health, University of Melbourne, Parkville, Australia The National Centre of Excellence in Youth Mental Health, Parkville, Australia
Flávio Kapczinski
Affiliation:
Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA) and Programa de Pós-graduação em Psiquiatria e Ciências do Comportamento, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
Ashley I. Bush
Affiliation:
Department of Psychiatry, The University of Melbourne, Parkville, Australia The Florey Institute of Neuroscience and Mental Health, Parkville, Australia
Gin S. Malhi
Affiliation:
Academic Department of Psychiatry, Northern Sydney Local Health District, St Leonards, NSW, Australia Sydney Medical School Northern, University of Sydney, NSW, Australia CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia
Olivia M. Dean*
Affiliation:
Deakin University, School of Medicine, IMPACT Strategic Research Centre, Barwon Health, Geelong, Australia Department of Psychiatry, The University of Melbourne, Parkville, Australia The Florey Institute of Neuroscience and Mental Health, Parkville, Australia
*
Author for correspondence: Dr. Olivia Dean, IMPACT SRC, School of Medicine, Deakin University, Kitchener House, P.O. Box 281, Geelong, VIC 3220, Australia. Tel: +61 3 4215 3300; Fax: 61 3 4215 3491; E-mail: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

This study aimed to explore effects of adjunctive treatment with N-acetyl cysteine (NAC) on markers of inflammation and neurogenesis in bipolar depression.

Methods

This is a secondary analysis of a placebo-controlled randomised trial. Serum samples were collected at baseline, week 8, and week 32 of the open-label and maintenance phases of the clinical trial to determine changes in interleukin (IL)-6, IL-8, IL-10, tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following adjunctive NAC treatment, and to explore mediation and moderator effects of the listed markers.

Results

Levels of brain-derived neurotrophic factor (BDNF), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukins (IL) -6, 8, or 10 were not significantly changed during the course of the trial or specifically in the open-label and maintenance phases. There were no mediation or moderation effects of the biological factors on the clinical parameters.

Conclusion

The results suggest that these particular biological parameters may not be directly involved in the therapeutic mechanism of action of adjunctive NAC in bipolar depression.

Keywords

biomarkersbipolar disorderclinical trialdepressionN-acetyl cysteine
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 30 , Issue 6 , December 2018 , pp. 334 - 341
Copyright
© Scandinavian College of Neuropsychopharmacology 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Vancampfort, D, Vansteelandt, K, Correll, CU, Mitchell, AJ, De Herdt, A Sienaert, P, Probst, M De Herdt, M (2013) Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. Am J Psychiatry 170, 265–274.Google Scholar
2. Alonso, J, Petukhova, M, Vilagut, G, Chatterji, S, Heeringa, S, Üstün, TB, Alhamzawi, AO, Viana, MC, Angermeyer, M, Bromet, E, Bruffaerts, R, de Girolamo, G, Florescu, S, Gureje, O, Haro, JM, Hinkov, H, Hu, CY, Karam, EG, Kovess, V, Levinson, D, Medina-Mora, ME, Nakamura, Y, Ormel, J, Vilagut, G, Posada-Villa, J, Sagar, R, Scott, KM, Tsang, A, Williams, DR Kessler, RC (2011) Days out of role due to common physical and mental conditions: results from the WHO World Mental Health surveys. Mol Psychiatry 16, 1234–1246.Google Scholar
3. Grande, I, Berk, M, Birmaher, B Vieta, E (2016) Bipolar disorder. Lancet Lond Engl 387, 1561–1572.Google Scholar
4. Rosenblat, JD, Kakar, R, Berk, M, Kessing, LV, Vinberg, M, Baune, BT, Mansur, RB, Brietzke, E, Goldstein, BI McIntyre, RS (2016) Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis. Bipolar Disord 18, 89–101.Google Scholar
5. Sigitova, E, Fišar, Z, Hroudová, J, Cikánková, T Raboch, J (2017) Biological hypotheses and biomarkers of bipolar disorder: hypotheses of bipolar disorder. Psychiatry Clin Neurosci 71, 77–103.Google Scholar
6. Magalhães, PV, Dean, OM, Bush, AI, Copolov, DL, Weisinger, D, Malhi, GS, Kohlmann, K, Jeavons, S, Schapkaitz, I, Anderson-Hunt, M Berk, M (2011) N-acetylcysteine for major depressive episodes in bipolar disorder. Rev Bras Psiquiatr Sao Paulo Braz 1999 33, 374–378.Google Scholar
7. Magalhães, PV, da, S, Dean, OM, Bush, AI, Copolov, DL, Malhi, GS, Kohlmann, K, Jeavons, S, Schapkaitz, I, Anderson-Hunt, M Berk, M (2013) A preliminary investigation on the efficacy of N-acetyl cysteine for mania or hypomania. Aust N Z J Psychiatry 47, 564–568.Google Scholar
8. Minarini, A, Ferrari, S, Galletti, M, Giambalvo, N, Perrone, D, Rioli, G Galeazzi, GM (2017) N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects. Expert Opin Drug Metab Toxicol 13, 279–292.Google Scholar
9. Berk, M, Malhi, GS, Gray, LJ Dean, OM (2013) The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci 34, 167–177.Google Scholar
10. Samuni, Y, Goldstein, S, Dean, OM Berk, M (2013) The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 1830, 4117–4129.Google Scholar
11. Dean, O, Giorlando, F Berk, M (2011) N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci JPN 36, 78–86.Google Scholar
12. Berk, M, Dean, O, Cotton, SM, Gama, CS, Kapczinski, F, Fernandes, BS, Kohlmann, K, Jeavons, S, Hewitt, K, Allwang, C, Allwang, C, Cobb, H, Bush, AI, Schapkaitz, I, Dodd, S Malhi, GS (2011) The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. J Affect Disord 135, 389–394.Google Scholar
13. Berk, M, Dean, OM, Cotton, SM, Gama, CS, Kapczinski, F, Fernandes, B, Kohlmann, K, Jeavons, S, Hewitt, K, Moss, K, Allwang, C, Schapkaitz, I, Cobb, H, Bush, AI, Dodd, S Malhi, GS (2012) Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial. BMC Med. 10, 91.Google Scholar
14. Kraemer, HC, Wilson, GT, Fairburn, CG Agras, WS (2002) Mediators and moderators of treatment effects in randomized clinical trials. Arch Gen Psychiatry 59, 877–883.Google Scholar
15. NCSS (2017) PASS 15 power analysis and sample size software. NCSS, LLC: Kaysville, Utah, USA.Google Scholar
16. Nascimento, MM, Suliman, ME, Silva, M, Chinaglia, T, Marchioro, J, Hayashi, SY, Riella, MC, Lindholm, B Anderstam, B (2010) Effect of oral N-acetylcysteine treatment on plasma inflammatory and oxidative stress markers in peritoneal dialysis patients: a placebo-controlled study. Perit Dial Int J Int Soc Perit Dial 30, 336–342.Google Scholar
17. Paintlia, MK, Paintlia, AS, Singh, AK Singh, I (2008) Attenuation of lipopolysaccharide-induced inflammatory response and phospholipids metabolism at the feto-maternal interface by N-acetyl cysteine. Pediatr Res 64, 334–339.Google Scholar
18. Paterson, RL, Galley, HF Webster, NR (2003) The effect of N-acetylcysteine on nuclear factor-kappa B activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis. Crit Care Med 31, 2574–2578.Google Scholar
19. Lasram, MM, Dhouib, IB, Annabi, A, El Fazaa, S Gharbi, N (2015) A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development. Clin Biochem 48, 1200–1208.Google Scholar
20. Rabie, MA, Mohsen, M, Ibrahim, M El-Sawy Mahmoud, R (2014) Serum level of brain derived neurotrophic factor (BDNF) among patients with bipolar disorder. J Affect Disord 162, 67–72.Google Scholar
21. Holdiness, MR (1991) Clinical pharmacokinetics of N-acetylcysteine. Clin Pharmacokinet 20, 123–134.Google Scholar
22. Dean, O, Bush, AI, Berk, M, Copolov, DL van den Buuse, M (2009) Glutathione depletion in the brain disrupts short-term spatial memory in the Y-maze in rats and mice. Behav Brain Res 198, 258–262.Google Scholar
23. Berk, M, Dean, OM, Cotton, SM, Jeavons, S, Tanious, M, Kohlmann, K, Hewitt, K, Moss, K, Allwang, C, Schapkaitz, I, Robbins, J, Cobb, H, Ng, F, Dodd, S, Bush, AI Malhi, GS (2014) The Efficacy of Adjunctive em N/em-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry 75, 628–636.Google Scholar
24. Fernandes, BS, Dean, OM, Dodd, S, Malhi, GS Berk, M (2016) N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. J Clin Psychiatry 77, 457–466.Google Scholar