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Clinical profile in schizophrenia spectrum : relation with unconjugated bilirubin (UCB) and other psychophysiological features - a longitudinal exploratory study
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Objectivo: O nosso objectivo consistiu em avaliar a bilirrubina não conjugada (UCB) como candidato a biomarcador no espectro e na gravidade da esquizofrenia e perturbação esquizoafectiva. Para esse fim preparámos dois estudos: um estudo transversal restrospetivo de cinco anos, e um estudo longitudinal prospectivo com um ano de duração.
Métodos: No nosso estudo transversal retrospetivo de 5 anos procurámos correlação entre os níveis médios de UCB, duração média de internamento e o diagnóstico em 255 indivíduos, incluindo 56 controlos saudáveis e 199 doentes (nomeadamente 44 com esquizofrenia, 99 com perturbação esquizoafectiva e 56 com perturbação bipolar). No nosso estudo longitudinal prospetivo 88 doentes psicóticos completaram a primeira avaliação durante internamento psiquiátrico em contexto de episódio psicótico agudo, metade com esquizofrenia, metade com perturbação esquizoafectiva. Nesta fase 44 doentes com perturbação bipolar, foram usados como controlos. Aos doze meses de seguimento completámos o protocolo longitudinal (dados laboratoriais, psicopatológicos e psicossociais) de 60 doentes, metade com esquizofrenia, metade com perturbação esquizoafectiva.
Resultados: No nosso estudo transversal retrospetivo de 5 anos encontrámos diferença estatisticamente significativa, após teste de multicomparações de Bonferroni, entre os níveis médios de UCB dos doentes com esquizofrenia (0.41 mg/dL) e os doentes com perturbação esquizoafectiva (0.34 mg/dL) (p<0.03), os doentes com perturbação bipolar (0.28mg/dL) (p<0.001) e também os controlos saudáveis (0.28) (p<0.001). Encontrámos ainda diferença estatisticamente significativa entre os níveis médios de UCB de doentes com perturbação esquizoafectiva (0.34 mg/dL) e perturbação bipolar (0.28 mg/dL) (p<0.04). Relativamente à duração média de internamentos durante o período dos 5 anos, ao diagnóstico e ao nível de UCB, quando aplicámos um modelo de regressão linear ANOVA, com a duração média dos internamentos como variável dependente, encontrámos uma diferença estatisticamente significativa (p<0.001) entre os doentes com esquizofrenia (29 dias) e os doentes com perturbação bipolar (16 dias) mas não com os doentes com perturbação esquizoafectiva. No nosso estudo longitudinal prospetivo de 1 ano, encontrámos, aquando da primeira avaliação durante o episódio psicótico agudo (N=88): uma diferença estatisticamente significativa (ANOVA; p=0.002), confirmada após teste de multicomparações de Bonferroni, entre doentes com esquizofrenia (N=44), quer com os doentes com perturbação esquizoafectiva (N=44) (p=0.05), quer com os controlos com perturbação bipolar (N=44) (p=0.05). Encontrámos também uma correlação positiva (Pearson’s r=0.314) entre os valores médios de UCB e o item d) “disturbing and aggressive behavior” da escala de Personal and Social Performance; e ainda uma correlação positiva (R2=0.223), com significância estatística (p=0.008), entre os níveis médios de UCB e a duração média de internamento psiquiátrico dos doentes com perturbação esquizoafectiva que completaram o protocolo (N=30). Durante a remissão parcial, aquando da segunda avaliação (N=60), encontrámos: uma diferença estatisticamente significativa (ANOVA; p=0.006), confirmada após teste de multicomparações de Bonferroni (p=0.05) entre os doentes com esquizofrenia (N=30) e perturbação esquizoafectiva (N=30); bem como uma correlação negativa (Pearson’s r=−0.399) entre os níveis médios de UCB e o item G7 “psychomotor retardation” da Positive And Negative Syndrome Scale. Ao compararmos a primeira com a segunda avaliação (teste T Student para amostras emparelhadas) encontrámos uma diferença estatisticamente significativa (p=0.034) nos valores médios apenas entre doentes com perturbação esquizoafectiva (N=30).
Conclusão: existe um interessante potencial na investigação da UCB como biomarcador das psicoses e respectiva gravidade, quer no espectro da esquizofrenia, quer no da perturbação esquizoafectiva, seja na recaída ou na remissão
Objective: Our objective was to assess unconjugated bilirubin (UCB) as a biomarker candidate for schizophrenia and schizoaffective spectrums disorder and its clinical severity. For that purpose we prepared two different studies: a five year transversal restrospective study, and a one year longitudinal prospective study. Methods: For our five years transversal restrospetive study we searched for an eventual correlation between UCB mean levels, duration of psychiatric admission, and diagnosis in 255 individuals, including 56 healthy controls and 199 acute patients (namely 44 with schizophrenia, 99 with schizoaffective disorder and 56 with bipolar disorder). For our one year longitudinal prospective study 88 psychotic patients completed a first assessment during relapse at ward admission, half with schizophrenia half with schizoaffective disorder. Forty−four acute bipolar patients were used as controls. In a twelve−month follow−up we collected longitudinal protocol (laboratory, psychopathological and psychosocial data) from 60 of those patients, half with schizophrenia half with schizoaffective disorder. Results: In our five year transversal retrospective study we found a statistically significant difference between UCB mean levels of patients with schizophrenia (0.41 mg/dL) versus patients with schizoaffective (0.34 mg/dL) (p<0.03), bipolar disorders (0.28mg/dL) (p<0.001) and healthy controls (0.28)(p<0.001) using Bonferroni multiple comparison test. We also found a statistically significant difference (p<0.04) between UCB mean levels of patients with schizoaffective disorder (0.34 mg/dL) and bipolar disorder (0.28 mg/dL). Regarding average admissions duration for the five−year period, diagnosis and UCB level, when applying a linear regression ANOVA model, with average admissions duration as a dependent variable we found statistically significant difference between schizophrenia (29 days) versus bipolar (16 days) (p<0.001) but not with patients with schizoaffective disorder. In our one year longitudinal prospective study during acute psychotic episode (N=88) we found: a statistically significant difference (ANOVA; p=0.002), confirmed after post−hoc Bonferroni multiple comparisons between between UCB mean levels of schizophrenia (N=44) and both schizoaffective (N=44) (p=0.05) and bipolar controls (N=44) (p=0.05); a positive Pearson’s correlation (r=0.314) between UCB mean levels and Personal and Social Performance item d) “disturbing and aggressive behavior”; and a positive correlation (R2=0.223), with statistically significance (p=0.008), between UCB mean levels and mean length of stay at the psychiatric ward in schizoaffective patients who completed full protocol (N=30). During partial remission (N=60) we found: a statistically ANOVA significant difference (p=0.006), confirmed after post−hoc Bonferroni multiple comparisons between between UCB mean levels of schizophrenia (N=30) and schizoaffective (N=30) (p=0.05); plus a negative Pearson’s correlation (r=−0.399) between UCB mean levels and Positive And Negative Syndrome Scale item G7 “psychomotor retardation”. Comparing first and second assessments, with paired samples T−test, we found a statistically significant difference (p=0.034) in UCB mean levels only among patients with schizoaffective disorder (N=30). Conclusion: there is an interesting potential in the research of UCB as a biological marker for schizophrenia and schizoaffective spectrums disorders, for both relapse and remission episodes of these syndromes.
Objective: Our objective was to assess unconjugated bilirubin (UCB) as a biomarker candidate for schizophrenia and schizoaffective spectrums disorder and its clinical severity. For that purpose we prepared two different studies: a five year transversal restrospective study, and a one year longitudinal prospective study. Methods: For our five years transversal restrospetive study we searched for an eventual correlation between UCB mean levels, duration of psychiatric admission, and diagnosis in 255 individuals, including 56 healthy controls and 199 acute patients (namely 44 with schizophrenia, 99 with schizoaffective disorder and 56 with bipolar disorder). For our one year longitudinal prospective study 88 psychotic patients completed a first assessment during relapse at ward admission, half with schizophrenia half with schizoaffective disorder. Forty−four acute bipolar patients were used as controls. In a twelve−month follow−up we collected longitudinal protocol (laboratory, psychopathological and psychosocial data) from 60 of those patients, half with schizophrenia half with schizoaffective disorder. Results: In our five year transversal retrospective study we found a statistically significant difference between UCB mean levels of patients with schizophrenia (0.41 mg/dL) versus patients with schizoaffective (0.34 mg/dL) (p<0.03), bipolar disorders (0.28mg/dL) (p<0.001) and healthy controls (0.28)(p<0.001) using Bonferroni multiple comparison test. We also found a statistically significant difference (p<0.04) between UCB mean levels of patients with schizoaffective disorder (0.34 mg/dL) and bipolar disorder (0.28 mg/dL). Regarding average admissions duration for the five−year period, diagnosis and UCB level, when applying a linear regression ANOVA model, with average admissions duration as a dependent variable we found statistically significant difference between schizophrenia (29 days) versus bipolar (16 days) (p<0.001) but not with patients with schizoaffective disorder. In our one year longitudinal prospective study during acute psychotic episode (N=88) we found: a statistically significant difference (ANOVA; p=0.002), confirmed after post−hoc Bonferroni multiple comparisons between between UCB mean levels of schizophrenia (N=44) and both schizoaffective (N=44) (p=0.05) and bipolar controls (N=44) (p=0.05); a positive Pearson’s correlation (r=0.314) between UCB mean levels and Personal and Social Performance item d) “disturbing and aggressive behavior”; and a positive correlation (R2=0.223), with statistically significance (p=0.008), between UCB mean levels and mean length of stay at the psychiatric ward in schizoaffective patients who completed full protocol (N=30). During partial remission (N=60) we found: a statistically ANOVA significant difference (p=0.006), confirmed after post−hoc Bonferroni multiple comparisons between between UCB mean levels of schizophrenia (N=30) and schizoaffective (N=30) (p=0.05); plus a negative Pearson’s correlation (r=−0.399) between UCB mean levels and Positive And Negative Syndrome Scale item G7 “psychomotor retardation”. Comparing first and second assessments, with paired samples T−test, we found a statistically significant difference (p=0.034) in UCB mean levels only among patients with schizoaffective disorder (N=30). Conclusion: there is an interesting potential in the research of UCB as a biological marker for schizophrenia and schizoaffective spectrums disorders, for both relapse and remission episodes of these syndromes.
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Unconjugated bilirubin Schizophrenia Schizoaffective Psychosis Teses de doutoramento – 2020