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Clinical profile in schizophrenia and schizoaffective spectrum: relation with unconjugated bilirubin in a prospective and controlled study with psychopathological and psychosocial variables

Published online by Cambridge University Press:  19 December 2019

João Gama Marques*
Affiliation:
Consulta de Esquizofrenia Resistente, Hospital Júlio de Matos, Centro Hospitalar Psiquiátrico de Lisboa, Lisbon, Portugal Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
Sílvia Ouakinin
Affiliation:
Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
*
*João Gama Marques, Email: joaogamamarques@gmail.com

Abstract

Objective

Our objective was to assess unconjugated bilirubin (UCB) as biomarker for schizophrenia (SCZ) and schizoaffective (SAF) spectrums disorder (relapse vs. partial remission).

Methods

Eighty-eight psychotic patients completed first assessment during relapse at ward admission, half with SCZ and half with SAF disorder. Forty-four acute bipolar patients were used as controls. After 12-month follow-up, we collected longitudinal protocol (laboratory, psychopathological, and psychosocial data) from 60 patients, half with SCZ and half with SAF disorder.

Results

During psychotic relapse (N = 88), we found a statistically significant difference (analysis of variance [ANOVA]; p = .002), confirmed after post hoc multiple comparisons (Bonferroni) between SCZ (N = 44) and both SAF (N = 44; p = .05) and bipolar controls (N = 44; p = .05); a positive correlation (Pearson’s r = .314) between UCB mean levels and Personal and Social Performance item (d) “disturbing and aggressive behaviors”; and a positive correlation (R2 = .223), with statistically significance (p = .008), between UCB mean levels and mean length of stay at the psychiatric ward in SAF patients who completed full protocol (N = 30). During partial remission (N = 60) we found: a statistically significant difference (ANOVA; p = .006), confirmed after post hoc multiple comparisons (Bonferroni) between SCZ (N = 30) and SAF (N = 30; p = .05); plus a negative correlation (Pearson’s r = −.399) between UCB mean levels and Positive and Negative Syndrome Scale item G7 “psychomotor retardation.” Comparing first and second assessments (paired samples t test) we found a statistically significant difference in UCB mean levels among SAF patients (p = .034).

Conclusions

There is potential in the research of UCB as a biological marker for SCZ and SAF spectrums disorders during relapse and partial remission of both syndromes.

Type
Original Research
Copyright
© Cambridge University Press 2019

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References

Hayashida, M, Miyaoka, T, Tsuchie, K, et al. Hyperbilirubinemia-related behavioral and neuropathological changes in rats: a possible schizophrenia animal model. Prog Neuro-Psychopharmacol Biol Psychiatry. 2009;33(4):581588. doi:10.1016/j.pnpbp.2009.02.013.CrossRefGoogle ScholarPubMed
Liaury, K, Miyaoka, T, Tsumori, T, et al. Morphological features of microglial cells in the hippocampal dentate gyrus of Gunn rat: a possible schizophrenia animal model. J Neuroinflamm. 2012;9:56. doi:10.1186/1742-2094-9-56.CrossRefGoogle ScholarPubMed
Tsuchie, K, Miyaoka, T, Furuya, M, et al. The effects of antipsychotics on behavioral abnormalities of the Gunn rat (unconjugated hyperbilirubinemia rat), a rat model of schizophrenia. Asian J Psychiatr. 2013;6(2):119123. doi:10.1016/j.ajp.2012.09.007.CrossRefGoogle Scholar
Bosma, PJ, Chowdhury, JR, Bakker, C, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med. 1995;333(18):11711175. doi:10.1056/NEJM199511023331802.CrossRefGoogle ScholarPubMed
Soorani-Lunsing, I, Woltil, HA, Hadders-Algra, M. Are moderate degrees of hyperbilirubinemia in healthy term neonates really safe for the brain? Pediatr Res. 2001;50(6):701705. doi:10.1203/00006450.CrossRefGoogle ScholarPubMed
Shapiro, SM, Popelka, GR. Auditory impairment in infants at risk for bilirubin-induced neurologic dysfunction. Semin Perinatol. 2011;35(3):162170. doi:10.1053/j.semperi.2011.02.011.CrossRefGoogle ScholarPubMed
Bhutani, VK, Wong, R. Bilirubin-induced neurologic dysfunction (BIND). Semin Fetal Neonatal Med. 2015;20(1):1. doi:10.1016/j.siny.2014.12.010.CrossRefGoogle Scholar
Dalman, C, Cullberg, J. Neonatal hyperbilirubinaemia—a vulnerability factor for mental disorder? Acta Psychiatr Scand. 1999;100(6):469471. doi:http://dx.doi.org/10.1111/j.1600-0447.1999.tb10899.x.CrossRefGoogle Scholar
Jones, P, Rodgers, B, Murray, R, et al. Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet. 1994;344(8934):13981402. doi:10.1016/S0140-6736(94)90569-X.CrossRefGoogle ScholarPubMed
David, A, Malmberg, A, Lewis, G, et al. Are there neurological and sensory risk factors for schizophrenia? Schizophr Res. 1995;14(3):247251. doi:10.1016/0920-9964(94)00068-J.CrossRefGoogle Scholar
Miyaoka, T, Yasukawa, R, Mizuno, S, et al. Clinical features of schizophrenia associated with idiopathic unconjugated hyperbilirubinemia (Gilbert’s syndrome). Int J Psychiatry Clin Pract. 2003;61(11):868871. doi:10.1080/13651500310001455.Google Scholar
Powell, AJ, Hansen, LK. Gilbert’s syndrome in a patient with predominantly negative symptoms of schizophrenia. Int J Psychiatry Clin Pract. 2007;11(3):239241. doi:10.1080/13651500600811735.CrossRefGoogle Scholar
Miyaoka, T, Seno, H, Itoga, M, et al. Schizophrenia-associated idiopathic unconjugated hyperbilirubinemia (Gilbert’s syndrome). J Clin Psychiatry. 2000;61(11):868871. doi:10.4088/JCP.v61n1110.Google Scholar
Bach, DR, Kindler, J, Strik, WK. Elevated bilirubin in acute and transient psychotic disorder. Pharmacopsychiatry. 2010;43(1):1216. doi:10.1055/s-0029-1237376.CrossRefGoogle ScholarPubMed
Falcão, A, Silva, R, Pancadas, S, et al. Apoptosis and impairment of neurite network by short exposure of immature rat cortical neurons to unconjugated bilirubin increase with cell differentiation and are additionally enhanced by an inflammatory stimulus. J Neurosci Res. 2007;85:12291239. doi:10.1002/jnr.21227.CrossRefGoogle ScholarPubMed
Fernandes, A, Falcão, AS, Abranches, E, et al. Bilirubin as a determinant for altered neurogenesis, neuritogenesis, and synaptogenesis. Dev Neurobiol. 2009;69(9):568582. doi:10.1002/dneu.20727.CrossRefGoogle ScholarPubMed
Yasukawa, R, Miyaoka, T, Mizuno, S, et al. Proton magnetic resonance spectroscopy of the anterior cingulate gyrus, insular cortex and thalamus in schizophrenia associated with idiopathic unconjugated hyperbilirubinemia (Gilbert’s syndrome). J Psychiatry Neurosci. 2005;30(6):416422.Google Scholar
Radhakrishnan, R, Kanigere, M, Menon, J, et al. Association between unconjugated bilirubin and schizophrenia. Psychiatry Res. 2011;189(3):480482. doi:10.1016/j.psychres.2011.03.003.CrossRefGoogle Scholar
Semnani, Y, Nazemi, F, Azariyam, A, et al. Alteration of serum bilirubin level in schizophrenia. Int J Psychiatry Clin Pract. 2010;14(4):262267. doi:10.3109/13651501.2010.506007.CrossRefGoogle Scholar
Pradeep, JR, Acharya, MS, Radhakrishnan, R, Srinivasan, K. Elevated unconjugated bilirubin in schizophrenia compared to bipolar affective disorder. Prim Care Companion CNS Disord. 2019;21(4):19m02448. doi:10.4088/PCC.19m02448.CrossRefGoogle ScholarPubMed
Gama Marques, J, Tinoco, I, Pedro, I, et al. Unconjugated bilirubin and acute schizophrenia: a probable correlation? Actas Esp Psiquiatr. 2017;45(2):7988.Google ScholarPubMed
Gama Marques, J, Pedro, I, Ouakinin, S. Unconjugated bilirubin and acute psychosis: a five years retrospective observational and controlled study in patients with schizophrenia, schizoaffective and bipolar disorders. Int J Psychiatry Clin Pract. 2019;45:15. doi:10.1080/13651501.2019.1638940.Google Scholar
Pommerening Dornelles, E, Gama Marques, J, Ouakinin, S. Unconjugated bilirubin and schizophrenia: a systematic review. CNS Spectrums. 2019;27:112. doi:10.1017/S109285291800161X.Google Scholar
Guy, W. Clinical Global Impressions (CGI) Scale. Washington, DC: American Psychiatry Association; 2000.Google Scholar
Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261276.CrossRefGoogle Scholar
Endicott, J, Spitzer, RL, Fleiss, JL, Cohen, J. The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry. 1976;33:766771.CrossRefGoogle ScholarPubMed
Morosini, PL, Magliano, L, Brambilla, L, Ugolini, S, Pioli, R. Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta Psychiatr Scand. 2000;101(4):323329.CrossRefGoogle ScholarPubMed
Lima, MS, Soares, BG, Paoliello, G, et al. The Portuguese version of the Clinical Global Impression-Schizophrenia Scale: validation study. Braz J Psychiatry. 2007;29(3):246249.CrossRefGoogle ScholarPubMed
Higuchi, CH, Ortiz, B, Berberian, AA, et al. Factor structure of the Positive and Negative Syndrome Scale (PANSS) in Brazil: convergent validation of the Brazilian version. Braz J Psychiatry. 2014;36(4):336339. doi:10.1590/1516-4446-2013-1330.CrossRefGoogle ScholarPubMed
American Psychiatric Association. DSM-IV-TR: Manual de Diagnóstico e Estatística das Perturbações Mentais. 4ª Ed. Revista. Lisboa, Portugual: Climepsi Editores; 2002.Google Scholar
Brissos, S, Palhavã, F, Marques, JG, et al. The Portuguese version of the Personal and Social Performance Scale (PSP): reliability, validity, and relationship with cognitive measures in hospitalized and community schizophrenia patients. Soc Psychiatry Psychiatr Epidemiol. 2012;47:10771086. doi:10.1007/s00127-011-0412-6.CrossRefGoogle ScholarPubMed
Gama Marques, J, Arantes-Gonçalves, F. A perspective on a possible relation between the psychopathology of the schizophrenia/schizoaffective spectrum and Unconjugated Bilirubin: a longitudinal protocol study. Front Psychiatry. 2018;9:146. doi:10.3389/fpsyt.2018.00146.CrossRefGoogle ScholarPubMed
Gama Marques, J, Ouakinin, S. Schizophrenia-schizoaffective-bipolar spectra: an epistemological perspective. CNS Spectrums. 2019:15. doi: 10.1017/S1092852919001408.Google Scholar