miR143-3p–Mediated NRG-1–Dependent Mitochondrial Dysfunction Contributes to Olanzapine Resistance in Refractory Schizophrenia

Sun, Jing; Zhang, Xiaoya; Cong, Qijie; Chen, Dong; Yi, Zhenghui; Huang, Hailiang; Li, Mo; Zeng, Rongsen; Liu, Yunxi; Cong, Hui; Chen, Luan; Liu, Chuanxin; Zhang, Yan; Xu, Yong; Fan, Lingzi; Wang, Guoqiang; Song, Chuanfu; Wei, Muyun; Du, Huihui; Zhu, Jiaquan; Qin, Shengying

doi:10.1016/j.biopsych.2022.03.012

Cited by 6 publications

(5 citation statements)

References 63 publications

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“…In the past few years, a considerable amount of research has been conducted to examine the role of miRNAs in neuropsychiatric disease [147][148][149][150][151][152][153][154][155][156]. We and other investigators have examined the expression of miRNAs in human postmortem brains of depressed subjects, in the brain of animals showing depression-like behavior, and in peripheral tissues such as blood, urine, and saliva [6,96,144,150,[157][158][159][160][161][162][163][164][165][166][167].…”

Section: Studies Of Dna Methylation In Adolescents With Elsmentioning

confidence: 99%

Dissecting early life stress-induced adolescent depression through epigenomic approach

Ochi

Dwivedi

2022

Mol Psychiatry

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Early life stress (ELS), such as abuse and neglect during childhood, can lead to psychiatric disorders in later life. Previous studies have suggested that ELS can cause profound changes in gene expression through epigenetic mechanisms, which can lead to psychiatric disorders in adulthood; however, studies on epigenetic modifications associated with ELS and psychiatric disorders in adolescents are limited. Moreover, how these epigenetic modifications can lead to psychiatric disorders in adolescents is not fully understood. Commonly, DNA methylation, histone modification, and the regulation of noncoding RNAs have been attributed to the reprogramming of epigenetic profiling associated with ELS. Although only a few studies have attempted to examine epigenetic modifications in adolescents with ELS, existing evidence suggests that there are commonalities and differences in epigenetic profiling between adolescents and adults. In addition, epigenetic modifications are sex-dependent and are influenced by the type of ELS. In this review, we have critically evaluated the current evidence on epigenetic modifications in adolescents with ELS, particularly DNA methylation and the expression of microRNAs in both preclinical models and humans. We have also clarified the impact of ELS on psychiatric disorders in adolescents to predict the development of neuropsychiatric disorders and to prevent and recover these disorders through personalized medicine.

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Section: Studies Of Dna Methylation In Adolescents With Elsmentioning

confidence: 99%

Dissecting early life stress-induced adolescent depression through epigenomic approach

Ochi

Dwivedi

2022

Mol Psychiatry

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“…NRG1 regulates both excitatory and inhibitory synaptic transmission in the adult brain, and abnormal neurotransmission and/or synaptic plasticity have been reported in both glutamatergic and GABAergic pathways in the brain of schizophrenia patients (e.g., [ 74 ]). In our included studies, NRG1 rs7834206 was found to be associated with TRS [ 49 ]. AKT serine/threonine kinase 1 ( AKT1 ) acts downstream of the dopamine D2 receptor and has also been associated with schizophrenia in several studies [ 75 , 76 , 77 ].…”

Section: Resultsmentioning

confidence: 99%

Treatment-Resistant Schizophrenia, Clozapine Resistance, Genetic Associations, and Implications for Precision Psychiatry: A Scoping Review

Ying

Chew

McIntyre

et al. 2023

Genes

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Treatment-resistant schizophrenia (TRS) is often associated with severe burden of disease, poor quality of life and functional impairment. Clozapine is the gold standard for the treatment of TRS, although it is also known to cause significant side effects in some patients. In view of the burgeoning interest in the role of genetic factors in precision psychiatry, we conducted a scoping review to narratively summarize the current genetic factors associated with TRS, clozapine resistance and side effects to clozapine treatment. We searched PubMed from inception to December 2022 and included 104 relevant studies in this review. Extant evidence comprised associations between TRS and clozapine resistance with genetic factors related to mainly dopaminergic and serotoninergic neurotransmitter systems, specifically, TRS and rs4680, rs4818 within COMT, and rs1799978 within DRD2; clozapine resistance and DRD3 polymorphisms, CYP1A2 polymorphisms; weight gain with LEP and SNAP-25 genes; and agranulocytosis risk with HLA-related polymorphisms. Future studies, including replication in larger multi-site samples, are still needed to elucidate putative risk genes and the interactions between different genes and their correlations with relevant clinical factors such as psychopathology, psychosocial functioning, cognition and progressive changes with treatment over time in TRS and clozapine resistance.

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“…Fifth, by means of induced pluripotent stem cells from patients with TRS, it has been shown that mitochondrial alterations related to neuregulin-1 deficiency were significantly associated with olanzapine treatment outcomes and that miR143-3p levels correlated with the severity of olanzapine resistance [ 100 ]. Mitochondrial proteomic studies as well as investigation of specific patterns of mitochondrial functions and components, showed a unique and distinct effect for each antipsychotic [ 270 , 292 , 293 ].…”

Section: Discussionmentioning

confidence: 99%

“…A clinical trial of FEP patients naïve to antipsychotics found higher total antioxidant status (TAS) levels than healthy controls. Baseline TAS levels were a predictor of symptom reduction after monotherapy of risperidone treatment, with a significant association between increased TAS levels and cognitive factor reduction, suggesting antioxidant protection related to risperidone treatment [ 100 ]. Sex differences in response to antipsychotic treatment and antioxidant defense system (ADS) have been reported.…”

Section: Molecular Abnormalities Driven By Inflammation and Oxidative...mentioning

confidence: 99%

Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment

et al. 2023

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Schizophrenia is a worldwide mental illness characterized by alterations at dopaminergic and glutamatergic synapses resulting in global dysconnectivity within and between brain networks. Impairments in inflammatory processes, mitochondrial functions, energy expenditure, and oxidative stress have been extensively associated with schizophrenia pathophysiology. Antipsychotics, the mainstay of schizophrenia pharmacological treatment and all sharing the common feature of dopamine D2 receptor occupancy, may affect antioxidant pathways as well as mitochondrial protein levels and gene expression. Here, we systematically reviewed the available evidence on antioxidants’ mechanisms in antipsychotic action and the impact of first- and second-generation compounds on mitochondrial functions and oxidative stress. We further focused on clinical trials addressing the efficacy and tolerability of antioxidants as an augmentation strategy of antipsychotic treatment. EMBASE, Scopus, and Medline/PubMed databases were interrogated. The selection process was conducted in respect of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Several mitochondrial proteins involved in cell viability, energy metabolism, and regulation of oxidative systems were reported to be significantly modified by antipsychotic treatment with differences between first- and second-generation drugs. Finally, antioxidants may affect cognitive and psychotic symptoms in patients with schizophrenia, and although the evidence is only preliminary, the results indicate that further studies are warranted.

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miR143-3p–Mediated NRG-1–Dependent Mitochondrial Dysfunction Contributes to Olanzapine Resistance in Refractory Schizophrenia

Cited by 6 publications

References 63 publications

Dissecting early life stress-induced adolescent depression through epigenomic approach

Dissecting early life stress-induced adolescent depression through epigenomic approach

Treatment-Resistant Schizophrenia, Clozapine Resistance, Genetic Associations, and Implications for Precision Psychiatry: A Scoping Review

Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment

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