Plasma bilirubin levels are reduced in first-episode psychosis patients and associates to working memory and duration of untreated psychosis

Becklén, Meneca; Orhan, Funda; Piehl, Fredrik; Červenka, Simon; Sellgren, Carl M.; Flyckt, Lena; Erhardt, Sophie; Fatouros‐Bergman, Helena

doi:10.1038/s41598-021-87096-z

Cited by 13 publications

(11 citation statements)

References 60 publications

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“…In this study, it was related to SCZ, ASD, and ADHD. As for TBIL, in addition to its antioxidant properties, it has a toxic effect on the brain, and evidence supports that it was related to cognition; the abnormal level of TBIL was also found in psychiatric disorders [ 46 , 47 , 48 ]. The result showed that MDD and ADHD were associated with decreased TBIL.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Psychiatric Disorders: Evidence from the Bidirectional Mendelian Randomization Study

Zhang

et al. 2022

Antioxidants

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Observational studies have shown that oxidative stress is highly related to psychiatric disorders, while its cause–effect remains unclear. To this end, a Mendelian randomization study was performed to investigate the causal relationship between oxidative stress and psychiatric disorders. On the one hand, all causal effects of oxidative stress injury biomarkers (OSIB) on psychiatric disorders were not significant (p > 0.0006), while the findings suggested that part of OSIB was nominally associated with the risk of psychiatric disorders (causal OR of uric acid (UA), 0.999 for bipolar disorder (BD), and 1.002 for attention-deficit/hyperactivity disorder (ADHD); OR of catalase was 0.903 for anorexia nervosa (AN); OR of albumin was 1.162 for autism; p < 0.05). On the other hand, major depressive disorder (MDD) was significantly associated with decreased bilirubin (p = 2.67 × 10−4); ADHD was significantly associated with decreased ascorbate (p = 4.37 × 10−5). Furthermore, there were also some suggestively causal effects of psychiatric disorders on OSIB (BD on decreased UA and increased retinol; MDD on increased UA and decreased ascorbate; schizophrenia on decreased UA, increased retinol and albumin; ADHD on increased UA, and decreased catalase, albumin, and bilirubin; AN on decreased UA). This work presented evidence of potential causal relationships between oxidative stress and psychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Psychiatric Disorders: Evidence from the Bidirectional Mendelian Randomization Study

Zhang

et al. 2022

Antioxidants

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“…Previous studies have established associations of serum biomarkers related to inflammatory ( 50 – 52 ), oxidative stress ( 53 ), immune ( 54 ), neuroendocrine ( 55 ), and metabolic systems ( 56 ) with the DUP. To our knowledge, the current study is the first to report that a CSF biomarker related to brain bioenergetics is correlated with the DUP.…”

Section: Discussionmentioning

confidence: 99%

Psychosocial stress moderates the relationship between cerebrospinal fluid lactate dehydrogenase and the duration of untreated psychosis in first-episode psychosis

Giné-Servén,

Boix-Quintana,

Daví-Loscos

et al. 2024

Front. Psychiatry

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IntroductionPrevious research has shown that lower lactate dehydrogenase (LDH) concentrations in cerebrospinal fluid (CSF) are associated with longer prodromal symptoms in first-episode psychosis (FEP). We aimed to study whether there is a relationship between the duration of untreated psychosis (DUP) and LDH and other CSF biomarkers in FEP and whether stressful life events moderate this association.MethodsNinety-five inpatients with FEP and with less than 6 weeks of antipsychotic treatment were included in the study. All participants were informed about the nature of the study, which was approved by the local ethics committee, and signed an informed consent form. A lumbar puncture was performed at index admission (baseline) to measure CSF parameters (glucose, total protein, LDH). The DUP was assessed with the Quick Psychosis Onset and Prodromal Symptoms Inventory (Q-POPSI). Stressful life events (SLEs) in the previous 6 months were assessed with the List of Threatening Experiences. We dichotomized the SLE variable into having experienced at least one SLE or no experience of SLEs. Statistical analyses were performed with SPSS v. 25.0. Total protein and LDH concentrations were natural log transformed (ln) to reduce skewness. Multiple linear regression analyses were conducted to explore the association between the DUP and CSF parameters (considered the dependent variable). Age, sex, DUP and SLEs were considered independent variables. We tested the DUP by SLE interaction. Significant interactions were included in the final model. The threshold for significance was set at p<0.05.ResultsFifty-four FEP patients (56.8%) reported an SLE in the previous 6 months. There were no significant differences in the DUP between patients with or without SLEs. There were no significant differences in CSF biomarkers between the SLE groups. In the multiple linear regression analyses, we found a significant DUP by SLE interaction effect on CSF LDH concentrations (standardized beta= -0.320, t= -2.084, p= 0.040). In patients with SLEs, a shorter DUP was associated with higher CSF LDH concentrations and vice versa. No significant associations were found between the DUP or SLEs and other CSF biomarkers (glucose, total proteins).ConclusionsOur study suggests that psychosocial stress moderates the relationship between the onset of psychosis and CSF biomarkers related to bioenergetic systems.

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“…Moreover, bilirubin acts as a potent endogenous antioxidant in plasma, capable of combating oxidative stress, which is implicated in the pathophysiology of SCZ. Studies have indicated that SCZ patients often exhibit reduced levels of bilirubin [ 21 , 22 ]. Correspondingly, this study observed bilirubin irregularities in patients with SCZ from both the Miao and Han Chinese populations, with a general trend of reduction when compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

A preliminary metabolomics study of the database for biological samples of schizophrenia among Chinese ethnic minorities

Ye,

Chen,

Wang

et al. 2024

BMC Psychiatry

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Background Schizophrenia (SCZ) is a profound mental disorder with a multifactorial etiology, including genetics, environmental factors, and demographic influences such as ethnicity and geography. Among these, the studies of SCZ also shows racial and regional differences. Methods We first established a database of biological samples for SCZ in China’s ethnic minorities, followed by a serum metabolomic analysis of SCZ patients from various ethnic groups within the same region using the LC-HRMS platform. Results Analysis identified 47 metabolites associated with SCZ, with 46 showing significant differences between Miao and Han SCZ patients. These metabolites, primarily fatty acids, amino acids, benzene, and derivatives, are involved in fatty acid metabolism pathways. Notably, L-Carnitine, L-Cystine, Aspartylphenylalanine, and Methionine sulfoxide demonstrated greater diagnostic efficacy in Miao SCZ patients compared to Han SCZ patients. Conclusion Preliminary findings suggest that there are differences in metabolic levels among SCZ patients of different ethnicities in the same region, offering insights for developing objective diagnostic or therapeutic monitoring strategies that incorporate ethnic considerations of SCZ.

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Plasma bilirubin levels are reduced in first-episode psychosis patients and associates to working memory and duration of untreated psychosis

Cited by 13 publications

References 60 publications

Oxidative Stress and Psychiatric Disorders: Evidence from the Bidirectional Mendelian Randomization Study

Oxidative Stress and Psychiatric Disorders: Evidence from the Bidirectional Mendelian Randomization Study

Psychosocial stress moderates the relationship between cerebrospinal fluid lactate dehydrogenase and the duration of untreated psychosis in first-episode psychosis

A preliminary metabolomics study of the database for biological samples of schizophrenia among Chinese ethnic minorities

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