Effect of antipsychotic drugs on gene expression in the prefrontal cortex and nucleus accumbens in the spontaneously hypertensive rat (SHR)

Santoro, Marcos; Ota, Vanessa Kiyomi; Stilhano, Roberta Sessa; Silva, Patrícia Natália; Santos, Camila M.; Diana, M.; Gadelha, Ary; Bressan, Rodrigo A.; Melaragno, Maria Isabel; Han, Sang Won; Abı́lio, Vanessa C.; Belangero, Síntia Iole

doi:10.1016/j.schres.2014.05.015

Cited by 22 publications

(11 citation statements)

References 56 publications

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“…To ensure higher quality, we required the study to be published after 2005. In total, we curated 11 gene signatures from 7 rodent studies comparing antipsychotic-treated animals to vehicle-treated controls 79–85 . Nine of the 11 gene signatures were represented by orthologs that were expressed in our study.…”

Section: Methodsmentioning

confidence: 99%

Gene expression elucidates functional impact of polygenic risk for schizophrenia

et al. 2016

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Over 100 genetic loci harbor schizophrenia associated variants, yet how these variants confer liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of schizophrenia cases (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, ~20% of schizophrenia loci have variants that could contribute to altered gene expression and liability. In five loci, only a single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3, or SNAP91. Altering expression of FURIN, TSNARE1, or CNTN4 changes neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yields abnormal migration. Of 693 genes showing significant case/control differential expression, their fold changes are ≤ 1.33, and an independent cohort yields similar results. Gene co-expression implicates a network relevant for schizophrenia. Our findings show schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases.

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Section: Methodsmentioning

confidence: 99%

Gene expression elucidates functional impact of polygenic risk for schizophrenia

et al. 2016

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“…In addition to lacking data about the function of quetiapine on epigenetic parameters, the scientific literature also lacks data involving the profile of quetiapine and other atypical antipsychotics on DNA methylation mechanisms in the PFC. One study showed that clozapine and risperidone increased methylation of some genes, while in other genes, it appears to show reduced methylation in the PFC, possibly as a positive antipsychotic effect on behaviors related to schizophrenia, or other psychiatric disorders [52]. Therefore, further studies are needed in order to uncover a possible protective or harmful role of quetiapine and other atypical antipsychotics in epigenetic parameters in the PFC.…”

Section: Effect Of MD and Treatment With Quetiapine On The Enzymatic mentioning

confidence: 99%

Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation

Ignácio

Réus

Abelaira

et al. 2017

Behavioural Brain Research

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Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus. Maternally deprived rats had a depressive-like behavior in the forced swimming test and an increase in the HDAC and DNMT activities in the hippocampus and NAc. Treatment with quetiapine reversed depressive-like behavior and reduced the DNMT activity in the hippocampus. This is the first study to show the antidepressant-like effect of quetiapine in animals subjected to MD and a protective effect by quetiapine in reducing epigenetic changes induced by stress in early life. These results reinforce an important role of quetiapine as therapy for MDD.

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“…Moreover, previous studies revealed an effect of antipsychotics on gene expression. 11 , 12 , 13 Therefore, assessing gene expression in early stages, such as FEP, is crucial, particularly before the administration of antipsychotics, but this is only feasible in peripheral tissues.…”

Section: Introductionmentioning

confidence: 99%

Gene expression alterations related to mania and psychosis in peripheral blood of patients with a first episode of psychosis

et al. 2016

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Psychotic disorders affect ~3% of the general population and are among the most severe forms of mental diseases. In early stages of psychosis, clinical aspects may be difficult to distinguish from one another. Undifferentiated psychopathology at the first-episode of psychosis (FEP) highlights the need for biomarkers that can improve and refine differential diagnosis. We investigated gene expression differences between patients with FEP–schizophrenia spectrum (SCZ; N=53) or FEP–Mania (BD; N=16) and healthy controls (N=73). We also verified whether gene expression was correlated to severity of psychotic, manic, depressive symptoms and/or functional impairment. All participants were antipsychotic-naive. After the psychiatric interview, blood samples were collected and the expression of 12 psychotic-disorder-related genes was evaluated by quantitative PCR. AKT1 and DICER1 expression levels were higher in BD patients compared with that in SCZ patients and healthy controls, suggesting that expression of these genes is associated more specifically to manic features. Furthermore, MBP and NDEL1 expression levels were higher in SCZ and BD patients than in healthy controls, indicating that these genes are psychosis related (independent of diagnosis). No correlation was found between gene expression and severity of symptoms or functional impairment. Our findings suggest that genes related to neurodevelopment are altered in psychotic disorders, and some might support the differential diagnosis between schizophrenia and bipolar disorder, with a potential impact on the treatment of these disorders.

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Effect of antipsychotic drugs on gene expression in the prefrontal cortex and nucleus accumbens in the spontaneously hypertensive rat (SHR)

Cited by 22 publications

References 56 publications

Gene expression elucidates functional impact of polygenic risk for schizophrenia

Gene expression elucidates functional impact of polygenic risk for schizophrenia

Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation

Gene expression alterations related to mania and psychosis in peripheral blood of patients with a first episode of psychosis

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