Dysregulation of amino acids and lipids metabolism in schizophrenia with violence

Chen, Xiacan; Xu, Jiajun; Tang, Jing; Dai, Xinhua; Huang, Haolan; Cao, Ruochen; Hu, Junmei

doi:10.1186/s12888-020-02499-y

Cited by 26 publications

(27 citation statements)

References 73 publications

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“…Enrichment of arginine, proline metabolism pathway in our analysis is in agreement with the findings of the recent metabolomics study which reported changes in amino acid signatures in SCZ affected individuals (He et al, 2012 ; Parksepp et al, 2020 ). In addition to this a study by Chen et al reported arginine and proline metabolism as one of the differential metabolic pathways in violent schizophrenia affected participants (Chen et al, 2020 ). Interestingly, 4-hydroxyproline was identified as one of the potential metabolic markers by this study (Chen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 94%

“…In addition to this a study by Chen et al reported arginine and proline metabolism as one of the differential metabolic pathways in violent schizophrenia affected participants (Chen et al, 2020 ). Interestingly, 4-hydroxyproline was identified as one of the potential metabolic markers by this study (Chen et al, 2020 ). These findings are in accordance to our observations where 4-hydroxyproline was one of the enriched metabolic processes in the gene enrichment analysis ( Table 3 ).…”

Section: Discussionmentioning

confidence: 94%

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Peripheral Blood-Based Gene Expression Studies in Schizophrenia: A Systematic Review

Wagh

Vyas

Agrawal³

et al. 2021

Front. Genet.

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Schizophrenia is a disorder that is characterized by delusions, hallucinations, disorganized speech or behavior, and socio-occupational impairment. The duration of observation and variability in symptoms can make the accurate diagnosis difficult. Identification of biomarkers for schizophrenia (SCZ) can help in early diagnosis, ascertaining the diagnosis, and development of effective treatment strategies. Here we review peripheral blood-based gene expression studies for identification of gene expression biomarkers for SCZ. A literature search was carried out in PubMed and Web of Science databases for blood-based gene expression studies in SCZ. A list of differentially expressed genes (DEGs) was compiled and analyzed for overlap with genetic markers, differences based on drug status of the participants, functional enrichment, and for effect of antipsychotics. This literature survey identified 61 gene expression studies. Seventeen out of these studies were based on expression microarrays. A comparative analysis of the DEGs (n = 227) from microarray studies revealed differences between drug-naive and drug-treated SCZ participants. We found that of the 227 DEGs, 11 genes (ACOT7, AGO2, DISC1, LDB1, RUNX3, SIGIRR, SLC18A1, NRG1, CHRNB2, PRKAB2, and ZNF74) also showed genetic and epigenetic changes associated with SCZ. Functional enrichment analysis of the DEGs revealed dysregulation of proline and 4-hydroxyproline metabolism. Also, arginine and proline metabolism was the most functionally enriched pathway for SCZ in our analysis. Follow-up studies identified effect of antipsychotic treatment on peripheral blood gene expression. Of the 27 genes compiled from the follow-up studies AKT1, DISC1, HP, and EIF2D had no effect on their expression status as a result of antipsychotic treatment. Despite the differences in the nature of the study, ethnicity of the population, and the gene expression analysis method used, we identified several coherent observations. An overlap, though limited, of genetic, epigenetic and gene expression changes supports interplay of genetic and environmental factors in SCZ. The studies validate the use of blood as a surrogate tissue for biomarker analysis. We conclude that well-designed cohort studies across diverse populations, use of high-throughput sequencing technology, and use of artificial intelligence (AI) based computational analysis will significantly improve our understanding and diagnostic capabilities for this complex disorder.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 94%

Peripheral Blood-Based Gene Expression Studies in Schizophrenia: A Systematic Review

Wagh

Vyas

Agrawal³

et al. 2021

Front. Genet.

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“…The NMR methodology is generally able to produce information on the levels of lipids, amino acids, organic acids, and other small organic molecules. Associations between lipid concentrations and aggression have previously been noted 6 , 12 – 15 , while other low-molecular-weight molecules might hold more promise for novel findings. Amino acids and ketone bodies (low-molecular-weight molecules categorized in NMR) have been associated with emotional and behavioural problems other than aggression 16 – 20 , and some studies have shown amino acids and similar molecules associated with anger and psychopathy 21 , schizophrenia-related violence 15 , and childhood aggression 22 .…”

Section: Introductionmentioning

confidence: 87%

Ketone body 3-hydroxybutyrate as a biomarker of aggression

Whipp

Vuoksimaa

Korhonen

et al. 2021

Sci Rep

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Human aggression is a complex behaviour, the biological underpinnings of which remain poorly known. To gain insights into aggression biology, we studied relationships with aggression of 11 low-molecular-weight metabolites (amino acids, ketone bodies), processed using 1H nuclear magnetic resonance spectroscopy. We used a discovery sample of young adults and an independent adult replication sample. We studied 725 young adults from a population-based Finnish twin cohort born 1983–1987, with aggression levels rated in adolescence (ages 12, 14, 17) by multiple raters and blood plasma samples at age 22. Linear regression models specified metabolites as the response variable and aggression ratings as predictor variables, and included several potential confounders. All metabolites showed low correlations with aggression, with only one—3-hydroxybutyrate, a ketone body produced during fasting—showing significant (negative) associations with aggression. Effect sizes for different raters were generally similar in magnitude, while teacher-rated (age 12) and self-rated (age 14) aggression were both significant predictors of 3-hydroxybutyrate in multi-rater models. In an independent replication sample of 960 adults from the Netherlands Twin Register, higher aggression (self-rated) was also related to lower levels of 3-hydroxybutyrate. These exploratory epidemiologic results warrant further studies on the role of ketone metabolism in aggression.

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“…Glutaric acid has also been identified as a biomarker for violent presentations in SSD (Chen et al, 2020). Although, to date, no direct associations between OCD and GCDH/GA1 have been established, it is of interest to note that late-onset GA1 can present with brain neoplasms and GA1 patients of any age may present with chronic kidney disease (CKD) (Afsoun Seddighi et al, 2015;Larson et al, 2019).…”

Section: Prevalence Of Treatable Genetic Disorder Variants Within the Study Cohortmentioning

confidence: 99%

When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population

Sriretnakumar

Harripaul

Kennedy

et al. 2021

Preprint

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Mental illnesses are one of the biggest contributors to the global disease burden. Despite the increased recognition, diagnosis and ongoing research of mental health disorders, the etiology and underlying molecular mechanisms of these disorders are yet to be fully elucidated. Moreover, despite many treatment options available, a large subset of the psychiatric patient population is non-responsive to standard medications and therapies. There has not been a comprehensive study to date examining the burden and impact of treatable genetic disorders (TGDs) that can present with neuropsychiatric features in psychiatric patient populations. In this study, we test the hypothesis that TGDs that present with psychiatric symptoms are more prevalent within psychiatric patient populations compared to the general population by performing targeted next-generation sequencing (NGS) of 129 genes associated with 108 TGDs in a cohort of 2301 psychiatric patients. In total, 72 putative affected and 293 putative carriers for TGDs were identified, with known or likely pathogenic variants in 78 genes. Despite screening for only 108 genetic disorders, this study showed an approximately four-fold (4.13%) enrichment for genetic disorders within the psychiatric population relative to the estimated 1% cumulative prevalence of all single gene disorders globally. This strongly suggests that the prevalence of these, and most likely all, genetic diseases are greatly underestimated in psychiatric populations. Increasing awareness and ensuring accurate diagnosis of TGDs will open new avenues to targeted treatment for a subset of psychiatric patients.

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Dysregulation of amino acids and lipids metabolism in schizophrenia with violence

Cited by 26 publications

References 73 publications

Peripheral Blood-Based Gene Expression Studies in Schizophrenia: A Systematic Review

Peripheral Blood-Based Gene Expression Studies in Schizophrenia: A Systematic Review

Ketone body 3-hydroxybutyrate as a biomarker of aggression

When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population

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