Sains Malaysiana 48(5)(2019): 1083–1095

http://dx.doi.org/10.17576/jsm-2019-4805-17

 

Oxidative Status in Bipolar Disorder (BD) and Its Correlation with Age, Gender and Body Mass Index (BMI)

(Status Oksidatif dalam Gangguan Bikutub dan Kaitannya dengan Umur, Jantina dan Indeks Jisim Tubuh)

 

JACLYN TAN AI CHIN, GEETHA GUNASEKARAN, MOHD HANAFI AHMAD DAMANHURI, CHAN LAI FONG, LOO JIANN LIN & GOON JO AAN*

 

Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

 

Diserahkan: 23 Ogos 2017/Diterima: 25 September 2018

 

ABSTRACT

Bipolar disorder (BD) is a chronic psychiatric illness which molecular foundations have yet to be elucidated. Oxidative stress appears to be a promising field of study to understand the formation of this disease in molecular level. The objective was to investigate the oxidative status of BD and its association with age, gender and body mass index (BMI). A cross-sectional study was conducted in a tertiary university hospital in Cheras, Malaysia on 55 patients with BD diagnosed using Mini Neuropsychiatric Interview (MINI). Peripheral markers of oxidative stress which include superoxide dismutase (SOD), glutathione peroxidise (GPx), catalase (CAT), malondialdehyde (MDA) and DNA damage were examined in subjects with BD (n=55) and compared to healthy controls (n=28). BD patients had significantly higher concentrations of MDA compared to healthy controls (p<0.001). Concentration of MDA was significantly higher in BD patients aged 40 and above compared to those aged 39 years and below (p<0.05). The concentration of MDA did not show significant difference between male and female BD patients, likewise between patients with BMI below and above 25. The percentage of normal DNA in healthy controls was significantly higher than that of BD patients (p<0.001), while percentage of mildly and severely damaged DNA in BD patients was significantly higher than that of healthy controls (mildly damaged: p<0.001; severely damaged: p<0.001). The severity of DNA damage in the BD patients was similar when compared between age, gender and BMI. SOD activity of BD patients was found to be comparable to that of healthy subjects as well as when compared between gender and age, but was significantly lower in subjects with BMI above 25 (p<0.05). CAT activity was significantly higher in BD patients compared to controls (p<0.001), while no significant difference was found when compared between gender, age and BMI. GPx activity did not show significant difference when compared between BD and healthy controls, gender, age and BMI. Multiple linear regression analysis showed that the percentage of normal DNA increases with age in BD patients (p<0.001), while the percentage of damaged DNA decreases with age (mildly damaged: p<0.002; severely damaged: p<0.001). Percentage of normal and damaged DNA are not significantly correlated with BMI, while all antioxidative enzymes (SOD, GPx, CAT) and MDA concentration did not show significant correlation with age and BMI. In conclusion, age and BMI are associated with the oxidative status of BD patients regardless of gender.

 

Keywords: Bipolar disorder; catalase; glutathione peroxidase; malondialdehyde; superoxide dismutase

 

ABSTRAK

Gangguan bikutub (BD) ialah sejenis penyakit psikiatrik kronik kerana asas kejadian molekulnya masih belum ditentukan. Tekanan oksidatif adalah bidang yang berpotensi dikaji dalam memahami kejadian penyakit ini pada peringkat molekul. Objektif kajian adalah untuk menentukan status oksidatif pada pesakit BD dan kaitannya dengan umur, jantina dan indeks jisim tubuh (BMI). Satu kajian keratan rentas telah dijalankan di sebuah hospital universiti pengajian tinggi di Cheras, Malaysia ke atas 55 pesakit BD yang didiagnos menggunakan Mini Neuropsychiatric Interview (MINI). Aktiviti enzim superoksida dismutase (SOD), glutation peroksida (GPx), katalase (CAT), kepekatan malondialdehid (MDA) dan kerosakan DNA dibandingkan antara subjek dengan BD (n=55) dan kawalan sihat (n=28). Pesakit BD mempunyai kepekatan MDA yang lebih tinggi secara signifikan berbanding kepada kawalan sihat (p<0.001). Kepekatan MDA adalah lebih tinggi bagi pesakit BD berumur 40 ke atas berbanding kepada yang berumur 39 dan ke bawah (p<0.05). Kepekatan MDA tidak menunjukan perbezaan yang signifikan apabila dibandingkan antara jantina, sama juga antara pesakit dengan BMI kurang atau lebih daripada 25. Peratus DNA normal pada kawalan sihat adalah lebih tinggi secara signifikan berbanding kepada pesakit BD (p<0.001), manakala peratus DNA rosak ringan dan rosak teruk pada pesakit BD adalah lebih tinggi secara signifikan berbanding kepada kawalan sihat (rosakan DNA ringan: p<0.001; kerosakan DNA teruk: p<0.001). Tahap kerosakan DNA dalam pesakit BD adalah lebih kurang sama apabila dibandingkan antara umur, jantina dan BMI. Aktiviti SOD pesakit BD adalah lebih kurang sama dengan subjek sihat dan apabila dibandingkan antara jantina dan umur, tetapi adalah lebih rendah secara signifikan pada subjek dengan BMI lebih daripada 25 (p<0.05). Aktiviti CAT adalah lebih tinggi secara signifikan dalam pesakit BD berbanding kumpulan kawalan (p<0.001), manakala tiada perbezaan signifikan antara jantina, umur dan BMI. Aktiviti GPx tidak menunjukkan perbezaan signifikan apabila dibandingkan antara pesakit BD dan subjek sihat, jantina, umur dan BMI. Analisis regresi linear berganda menunjukkan peratus DNA normal meningkat dengan umur (p<0.001), manakala peratus DNA rosak menurun dengan umur (kerosakan DNA ringan: p<0.002; kerosakan DNA teruk: p<0.001). Peratus DNA normal dan rosak tidak menunjukkan korelasi signifikan dengan BMI, manakala semua enzim oksidatif (SOD, GPx, CAT) dan kepekatan MDA tidak menunjukkan korelasi signifikan dengan umur dan BMI. Secara kesimpulannya, umur dan BMI adalah berkaitan dengan status oksidatif pesakit BD tanpa mengira jantina.  

 

Kata kunci: Gangguan bikutub; glutation peroksidase; katalase; malondialdehid; superoksida dismutase

RUJUKAN

Aebi, H. 1984. Catalase in vitro. Methods in Enzymology 105: 121-126.

Andreazza, A.C., Gildengers, A., Rajji, T.K., Zuzarte, P.M.L., Mulsant, B.H. & Young, L.T. 2015. Oxidative stress in older patients with bipolar disorder. The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry 23(3): 314-319.

Andreazza, A.C., Kauer-Sant’anna, M., Frey, B.N., Bond, D.J., Kapczinski, F., Young, L.T. & Yatham, L.N. 2008. Oxidative stress markers in bipolar disorder: A meta-analysis. Journal of Affective Disorders 111(2): 135-144.

Andreazza, A.C., Frey, B.N., Erdtmann, B., Salvador, M., Rombaldi, F., Santin, A., Goncalves, C.A. & Kapczinski, F. 2007. DNA damage in bipolar disorder. Psychiatry Research 153(1): 27-32.

Banerjee, U., Dasgupta, A., Rout, J.K. & Singh, O.P. 2012. Effects of lithium therapy on Na+-K+-atpase activity and lipid peroxidation in bipolar disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 37(1): 56-61.

Benedetti, A., Fagiolini, A., Casamassima, F., Mian, M.S., Adamovit, A., Musetti, L., Lattanzi, L. & Cassano, G.B. 2007. Gender differences in bipolar disorder type 1: A 48- week prospective follow-up of 72 patients treated in an italian tertiary care center. The Journal of Nervous and Mental Disease 195(1): 93-96.

Bengesser, S.A., Lackner, N., Birner, A., Fellendorf, F.T., Platzer, M., Mitteregger, A., Unterweger, R., Reininghaus, B., Mangge, H., Wallner-Liebmann, S.J., Zelzer, S., Fuchs, D., Mcintyre, R.S., Kapfhammer, H.P. & Reininghaus, E.Z. 2015. Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder: Gender and obesity effects. Journal of Affective Disorders 172: 367-374.

Berk, M., Copolov, D.L., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., Anderson-Hunt, M. & Bush, A.I. 2008. N-acetylcysteine for depressive symptoms in bipolar disorder: A double-blind randomized placebo-controlled trial. Biological Psychiatry 64(6): 468-475.

Berk, M., Kapczinski, F., Andreazza, A., Dean, O., Giorlando, F., Maes, M., Yücel, M., Gama, C., Dodd, S. & Dean, B. 2011. Pathways underlying neuroprogression in bipolar disorder: Focus on inflammation, oxidative stress and neurotrophic factors. Neuroscience & Biobehavioral Reviews 35(3): 804-817.

Beyer, W.F. & Fridovich, I. 1987. Assaying for superoxide dismutase activity: Some large consequences of minor changes in conditions. Analytical Biochemistry 161(2): 559-566.

Brown, N.C., Andreazza, A.C. & Young, L.T. 2014. An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Research 218(1): 61-68.

Chin, S.F., Ibahim, J., Makpol, S., Abdul Hamid, N.A., Abdul Latiff, A., Zakaria, Z., Mazlan, M., Mohd Yusof, Y.A., Abdul Karim, A. & Wan Ngah, W.Z. 2011. Tocotrienol rich fraction supplementation improved lipid profile and oxidative status in healthy older adults: A randomized controlled study. Nutrition & Metabolism 8: 42.

Chin, S.F., Hamid, N.A., Latiff, A.A., Zakaria, Z., Mazlan, M., Mohd Yusof, Y.A., Abdul Karim, A., Ibahim, J., Hamid, Z. & Wan Ngah, W.Z. 2008. Reduction of DNA damage in older healthy adults by Tri E Tocotrienol supplementation. Nutrition 24(1): 1-10.

Choy, K.H., Dean, O., Berk, M., Bush, A.I. & van den Buuse, M. 2010. Effects of N-acety-lcysteine treatment on glutathione depletion and a short-term spatial memory defcit in 2-cyclohexene-1-one-treated rats. European Journal of Pharmacology 649(1-3): 224-228.

De Sousa, R.T., Zarate, C.A., Zanetti, M.V., Costa, A.C., Talib, L.L., Gattaz, W.F. & Machado-Vieira, R. 2014. Oxidative stress in early stage bipolar disorder and the association with response to lithium. Journal of Psychiatric Research 50: 36-41.

Dean, O., Bush, A.I., Berk, M., Copolov, D.L. & van den Buuse, M. 2009. Glutathione depletion in the brain disrupts short-term spatial memory in the Y-maze in rats and mice. Behavioural Brain Research 198(1): 258-262.

Demirbag, R., Yilmaz, R. & Kocyigit, A. 2005. Relationship between DNA damage, total antioxidant capacity and coronary artery disease. Mutatation Research 570(2): 197- 203.

Diflorio, A. & Jones, I. 2010. Is sex important? Gender differences in bipolar disorder. International Review of Psychiatry 22(5): 437-452.

Dröge, W. 2002. Free radicals in the physiological control of cell function. Physiological Reviews 82: 47-95.

Elhaik, E. & Zandi, P. 2015. Dysregulation of the Nf-Kb pathway as a potential inducer of bipolar disorder. Journal of Psychiatric Research 70: 18-27.

Fernandes, B.S., Gama, C.S., Maria Ceresér, K., Yatham, L.N., Fries, G.R., Colpo, G., De Lucena, D., Kunz, M., Gomes, F.A. & Kapczinski, F. 2011. Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: A systematic review and meta-regression analysis. Journal of Psychiatric Research 45(8): 995-1004.

Frey, B.N., Andreazza, A.C., Houenou, J., Jamain, S., Goldstein, B.I., Frye, M.A., Leboyer, M., Berk, M., Malhi, G.S. & Lopez-Jaramillo, C. 2013. Biomarkers in bipolar disorder: A positional paper from the international society for bipolar disorders biomarkers task force. Australian and New Zealand Journal of Psychiatry 47(4): 321-332.

Frey, B.N., Andreazza, A.C., Kunz, M., Gomes, F.A., Quevedo, J., Salvador, M., Gonçalves, C.A. & Kapczinski, F. 2007. Increased oxidative stress and DNA damage in bipolar disorder: A twin-case report. Progress in Neuro- Psychopharmacology & Biological Psychiatry 31(1): 283- 285.

Gao, D., Wei, C., Chen, L., Huang, J., Yang, S. & Diehl, A.M. 2004. Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease. American Journal of Physiology Gastrointestinal & Liver Physiology 287(5): G1070-G1077.

Gil, P., Fariñas, F., Casado, A. & López-Fernández, E. 2002. Malondialdehyde: A possible marker of ageing. Gerontology 48(4): 209-214.

Góth, L. & Nagy, T. 2013. Inherited catalase deficiency: Is it benign or a factor in various age related disorders? Mutation Research 753(2): 147-154.

Grande, I., Magalhaes, P.V., Kunz, M., Vieta, E. & Kapczinski, F. 2012. Mediators of allostasis and systemic toxicity in bipolar disorder. Physiology & Behaviour 106(1): 46-50.

Haouala, A.B., Amamou, B., Allègue, M., Zaafrane, F. & Gaha, F. 2016. Age at onset of bipolar disorders: Clinical implication and prognosis of early and late onset. European Neuropsychopharmacology 26: S429.

Ighodaro, O.M. & Akinloye, O.A. 2017. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine 54(4): 287-293.

Kapczinski, F., Dal-Pizzol, F., Teixeira, A.L., Magalhaes, P.V., Kauer-Sant’anna, M., Klamt, F., Moreira, J.C., De Bittencourt Pasquali, M.A., Fries, G.R., Quevedo, J., Gama, C.S. & Post, R. 2011. Peripheral biomarkers and illness activity in bipolar disorder. Journal of Psychiatric Research 45(2): 156-161.

Kawa, I., Carter, J.D., Joyce, P.R., Doughty, C.J., Frampton, C.M., Elisabeth Wells, J., Walsh, A.E. & Olds, R.J. 2005. Gender differences in bipolar disorder: Age of onset, course, comorbidity, and symptom presentation. Bipolar Disorders 7(2): 119-125.

Kessing, L.V. 2004. Gender differences in the phenomenology of bipolar disorder. Bipolar Disorders 6(5): 421-425.

Kessler, R.C., Mcgonagle, K.A., Swartz, M., Blazer, D.G. & Nelson, C.B. 1993. Sex and depression in the national comorbidity survey I: Lifetime prevalence, chronicity and recurrence. Journal of Affective Disorders 29(2-3): 85-96.

Kim, G.H., Kim, J.E., Rhie, S.J. & Yoon, S. 2015. The role of oxidative stress in neurodegenerative diseases. Experimental Neurobiology 24(4): 325-340.

Kraepelin, E. 1921. Manic depressive insanity and paranoia. The Journal of Nervous & Mental Disease 53(4): 350.

Kuloglu, M., Ustundag, B., Atmaca, M., Canatan, H., Tezcan, A.E. & Cinkilinc, N. 2002. Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. Cell Biochemistry & Function 20(2): 171-175.

Kunz, M., Gama, C.S., Andreazza, A.C., Salvador, M., Ceresér, K.M., Gomes, F.A., Belmonte-De-Abreu, P.S., Berk, M. & Kapczinski, F. 2008. Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 32(7): 1677-1681.

Kupfer, D.J. 2005. The increasing medical burden in bipolar disorder. JAMA 293(20): 2528-2530.

Laursen, T.M. 2011. Life expectancy among persons with schizophrenia or bipolar affective disorder. Schizophrenia Research 131(1-3): 101-104.

Lewis, P., Stefanovic, N., Pete, J., Calkin, A.C., Giunti, S., Thallas-Bonke, V., Jandeleit-Dahm, K.A., Allen, T.J., Kola, I., Cooper, M.E. & de Haan, J.B. 2007. Lack of the antioxidant enzyme glutathione peroxidase-1 accelerates atherosclerosis in diabetic apolipoprotein E-Deficient mice. Circulation 115: 2178-2187.

Lopresti, A.L. & Drummond, P.D. 2013. Obesity and psychiatric disorders: Commonalities in dysregulated biological pathways and their implications for treatment. Progress in Neuro-Psychopharmacology & Biological Psychiatry 45: 92-99.

Magalhaes, P.V., Jansen, K., Pinheiro, R.T., Colpo, G.D., Da Motta, L.L., Klamt, F., Da Silva, R.A. & Kapczinski, F. 2012. Peripheral oxidative damage in early-stage mood disorders: A nested population-based case-control study. International Journal of Neuropsychopharmacology 15(8): 1043-1050.

Mahadik, S.P., Evans, D. & Lal, H. 2001. Oxidative stress and role of antioxidant and Ω-3 essential fatty acid supplementation in schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 25(3): 463-493.

Malaysian Psychiatric Association, M.P.A. 2007. Malaysian Consensus Statement for the Treatment of Bipolar Disorder.

Malorni, W., Campesi, I., Straface, E., Vella, S. & Franconi, F. 2007. Redox features of the cell: A gender perspective. Antioxidants & Redox Signaling 9(11): 1779-1802.

Mcglashan, T.H. 1988. Adolescent versus adult onset of mania. American Journal of Psychiatry 145(2): 221-223.

Merikangas, K.R., Jin, R., He, J.P., Kessler, R.C., Lee, S., Sampson, N.A., Viana, M.C., Andrade, L.H., Hu, C., Karam, E.G., Ladea, M., Medina-Mora, M.E., Ono, Y., Posada-Villa, J., Sagar, R., Wells, J.E. & Zarkov, Z. 2011. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Archives of General Psychiatry 68(3): 241-251.

Merikangas, K.R., Akiskal, H.S., Angst, J., Greenberg, P.E., Hirschfeld, R.M., Petukhova, M. & Kessler, R.C. 2007. Lifetime and 12-month prevalence of bipolar spectrum disorder in the national comorbidity survey replication. Archives of General Psychiatry 64(5): 543-552.

Miquel, L., Roncero, C., Lopez-Ortiz, C. & Casas, M. 2011. Epidemiological and diagnostic axis i gender differences in dual diagnosis patients. Adicciones 23(2): 165-172.

Nivoli, A.M.A., Pacchiarotti, I., Rosa, A.R., Popovic, D., Murru, A., Valenti, M., Bonnin, C.M., Grande, I., Sanchez-Moreno, J., Vieta, E. & Colom, F. 2011. Gender differences in a cohort study of 604 bipolar patients: The role of predominant polarity. Journal of Affective Disorders 133(3): 443-449.

O’brien, S.M., Scully, P., Scott, L.V. & Dinan, T.G. 2006. Cytokine profiles in bipolar affective disorder: Focus on acutely ill patients. Journal of Affective Disorders 90(2): 263-267.

Olusi, S. 2002. Obesity is an independent risk factor for plasma lipid peroxidation and depletion of erythrocyte cytoprotectic enzymes in humans. International Journal of Obesity 26(9): 1159-1164.

Ozata, M., Mergen, M., Oktenli, C., Aydin, A., Sanisoglu, S.Y., Bolu, E., Yilmaz, M.I., Sayal, A., Isimer, A. & Ozdemir, I.C. 2002. Increased oxidative stress and hypozincemia in male obesity. Clinical Biochemistry 35(8): 627-631.

Ozcan, M.E., Gulec, M., Ozerol, E., Polat, R. & Akyol, O. 2004. Antioxidant enzyme activities and oxidative stress in affective disorders. International Clinical Psychopharmacology 19(2): 89-95.

Paglia, D.E. & Valentine, W.N. 1967. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Journal of Laboratory & Clinical Medicine 70(1): 158-169.

Pilz, J., Meineke, I. & Gleiter, C. 2000. Measurement of free and bound malondialdehyde in plasma by high-performance liquid chromatography as the 2,4-dinitrophenylhydrazine derivative. Journal of Chromatography B: Biomedical Sciences & Applications 742(2): 315-325.

Ranjekar, P.K., Hinge, A., Hegde, M.V., Ghate, M., Kale, A., Sitasawad, S., Wagh, U.V., Debsikdar, V.B. & Mahadik, S.P. 2003. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Research 121(2): 109-122.

Ringen, P., Lagerberg, T., Birkenaes, A., Engn, J., Faerden, A., Jonsdottir, H., Nesvåg, R., Friis, S., Opjordsmoen, S. & Larsen, F. 2008. Differences in prevalence and patterns of substance use in schizophrenia and bipolar disorder. Psychological Medicine 38(09): 1241-1249.

Rosa, A.R., Singh, N., Whitaker, E., de Brito, M., Lewis, A.M., Vieta, E., Churchill, G.C., Geddes, J.R. & Goodwin, G.M. 2014. Altered plasma glutathione levels in bipolar disorder indicates higher oxidative stress; A possible risk factor for illness onset despite normal brain-derived neurotrophic factor (BDNF) levels. Psychological Medicine 4(11): 2409-2418.

Roshanaei-Moghaddam, B. & Katon, W. 2009. Premature mortality from general medical illnesses among persons with bipolar disorder: A review. Psychiatric Services 60(2): 147-156.

Saetre, P., Vares, M., Werge, T., Andreassen, O.A., Arinami, T., Ishiguro, H., Nanko, S., Tan, E.C., Han, D.H. & Roffman, J.L. 2011. Methylenetetrahydrofolate reductase (Mthfr) C677t and A1298c polymorphisms and age of onset in schizophrenia: A combined analysis of independent samples. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156(2): 215-224.

Sarangarajan, R., Meera, S., Rukkumani, R., Sankar, P. & Anuradha, G. 2017. Antioxidants: Friend or foe? Asian Pacific Journal of Tropical Medicine 10(12): 1111-1116.

Savas, H.A., Gergerlioglu, H.S., Armutcu, F., Herken, H., Yilmaz, H.R., Kocoglu, E., Selek, S., Tutkun, H., Zoroglu, S.S. & Akyol, O. 2006. Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar patients: Impact of past episodes. The World Journal of Biological Psychiatry 7(1): 51-55.

Selek, S., Savas, H.A., Gergerlioglu, H.S., Bulbul, F., Uz, E. & Yumru, M. 2008. The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode. Journal of Affective Disorders 107(1-3): 89-94.

Singh, N., Stephens, R. & Schneider, E. 1994. Modifications of alkaline microgel electrophoresis for sensitive detection of DNA damage. International Journal of Radiation Biology 66(1): 23-28.

Swartz, H.A. & Fagiolini, A. 2012. Cardiovascular disease and bipolar disorder: Risk and clinical implications. Journal of Clinical Psychiatry 73(12): 1563-1565.

Uher, R. 2014. Gene-environment interactions in severe mental illness. Frontiers in Psychiatry 5: 48.

Van Vliet, I.M. & De Beurs, E. 2007. The MINI-international neuropsychiatric interview. A brief structured diagnostic psychiatric interview for DSM-IV en ICD-10 psychiatric disorders. Tijdschrift voor Psychiatrie 49(6): 393-397.

Versace, A., Andreazza, A.C., Young, L., Fournier, J.C., Almeida, J.R., Stiffler, R.S., Lockovich, J.C., Aslam, H.A., Pollock, M.H. & Park, H. 2014. Elevated serum measures of lipid peroxidation and abnormal prefrontal white matter in euthymic bipolar adults: Toward peripheral biomarkers of bipolar disorder. Molecular Psychiatry 19(2): 200-208.

Wiener, C., Rassier, G.T., Kaster, M.P., Jansen, K., Pinheiro, R.T., Klamt, F., Magalhães, P.V., Kapczinski, F., Ghisleni, G. & Da Silva, R.A. 2014. Gender-based differences in oxidative stress parameters do not underlie the differences in mood disorders susceptibility between sexes. European Psychiatry 29(1): 58-63.

 

*Pengarang untuk surat-menyurat; email: joaan@ukm.edu.my