Schizophrenia in a genomic era: a review from the pathogenesis, genetic and environmental etiology to diagnosis and treatment insights

Zamanpoor, Mansour

doi:10.1097/ypg.0000000000000245

Cited by 60 publications

(45 citation statements)

References 114 publications

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“…Schizophrenia is a disorder with an unclear, most likely multifactorial etiology and results from a complex interplay between both genetic and environmental factors [ 16 ]. The molecular mechanisms of schizophrenia are not yet elucidated, although it is thought that there is a general hyperexcitation of the central nervous system, mediated by dysregulation in neurotransmitters dopamine and glutamate.…”

Section: Introductionmentioning

confidence: 99%

Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells

Rački

Marcelić

Štimac

et al. 2021

IJMS

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Microglial cells are resident macrophages in the brain that have been implicated in the pathophysiology of schizophrenia. There is a lack of studies covering the effects of antipsychotics on microglial cells. The current literature points to a possible anti-inflammatory action without clear mechanisms of action. The aim of this study is to characterize the effects of haloperidol, risperidone and aripiprazole on BV-2 microglial cells in in vitro conditions. We have used immunofluorescence and flow cytometry to analyze the classical pro and anti-inflammatory markers, while a real-time metabolic assay (Seahorse) was used to assess metabolic function. We analyzed the expression of p70S6K to evaluate the mTOR pathway activity with Western blot. In this study, we demonstrate the varying effects of haloperidol, risperidone and aripiprazole administration in BV-2 microglial cells. All three tested antipsychotics were successful in reducing the pro-inflammatory action of microglial cells, although only aripiprazole increased the expression of anti-inflammatory markers. Most significant differences in the possible mechanisms of action were seen in the real-time metabolic assays and in the mTORC1 signaling pathway activity, with aripiprazole being the only antipsychotic to reduce the mTORC1 activity. Our results shed some new light on the effects of haloperidol, risperidone and aripiprazole action in microglial cells, and reveal a novel possible mechanism of action for aripiprazole.

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Section: Introductionmentioning

confidence: 99%

Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells

Rački

Marcelić

Štimac

et al. 2021

IJMS

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“…Genetic factors play important roles in SCZ pathogenesis as indicated by epidemiological data (1). The genetic basis for SCZ may not be related to a single genetic variant but may be influenced by multiple genes acting synergistically with environmental factors to increase the likelihood of the disease developing.…”

Section: Discussionmentioning

confidence: 99%

“…Both environmental and genetic factors play an important role in schizophrenia (SCZ), which is a multifactorial common psychiatric disorder (1)(2)(3). Given the lack of diagnostic neuropathology and defined biological markers for SCZ, it is hard to monitor the disease progression and treatment response.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the Human Aquaporin 4 Gene Are Associated With Schizophrenia in the Southern Chinese Han Population: A Case–Control Study

Sytwu

Lung

2020

Front. Psychiatry

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Background: In psychiatric illness, pathogenic role of neuroinflammation has been supported by multiple lines of evidence. Astrocytes contribute to the blood-brain barrier (BBB) with formation of the "glymphatic" drainage system of the central nervous system (CNS) through perivascular processes. Found primarily at the end-feet of astrocytes, the aquaporin 4 (AQP4) gene has been suspected to play putative roles in the development of psychiatric disorders as well as the clearance of the glymphatic system. However, there remain many uncertainties because of the limited research on AQP4. The present study is focused on the association between AQP4 gene polymorphisms and schizophrenia (SCZ) in the Southern Chinese Han population. Methods: Two hundred ninety-two patients and 100 healthy controls were enrolled in this study. To study the relationship of AQP4 gene polymorphisms and SCZ, genetic information was drawn from a cohort of 100 healthy controls and 100 matched patients with SCZ of Southern Han Chinese descent. Comparisons of the allele and genotype distributions between control and case groups were made using the c2 test. Two-group comparisons were made to assess the linkage equilibrium and haplotype. Results: Three SNPs were found. In comparison to healthy controls, patients had higher T-allele frequencies at rs1058424 and G-allele frequencies at rs3763043 (p = 0.043 and p = 0.045, respectively). Furthermore, there is an association between the decreased risk of SCZ and the AA genotype at both rs1058424 (p = 0.021, OR = 2.04) and rs3763043 (p = 0.018, OR = 2.25) The TCG haplotype (p = 0.036) was associated with a potential risk of SCZ, while the ACA haplotype (p = 0.0007) was associated with a decreased risk of SCZ and retained statistical significance after Bonferroni correction (p = 0.006). Conclusions: An etiological reference for SCZ is provided by the association between AQP4 gene polymorphisms and SCZ in Southern Han Chinese population.

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“…The occurrence of schizophrenia as a multifactorial disease is related to genetics, environment, and pathophysiological factors, it shows a combination of behavioral and mental problems ultimately. 18 Schizophrenia is a testament to the intense interaction between genetics 19 and the environment. 18 The neurochemical hypothesis, 18 genetic susceptibility, 20 immunological alteration, 21 and environmental factors such as multiple infections are the primary etiological response of schizophrenia.…”

Section: Schizophrenia Etiologymentioning

confidence: 99%

Schizophrenia; Recent Cognitive and Treatment Approaches Using Induced Pluripotent Stem Cells

Rastgar

2020

Int Clin Neurosci J

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One of the most severe mental disorder which leads to a disturbance in the percipience of reality is named schizophrenia. Schizophrenia is a combination of hallucinations, delusions, and mental disorders that the severity of them impairs healthy thinking and behavior, and in general, the inability to perform daily activities. Behavioral, intellectual, and emotional disorders indicate the widespread impact of schizophrenia on various aspects of mental health. Schizophrenia's signs and symptoms of schizophrenia are varied, although delusions, hallucinations, or disorganized speech included in common symptoms. Dopamine has been the main subject of much research on schizophrenia for decades. Molecular neuroimaging studies to explore the dopamine system (DA system) in vivo have revealed that Schizophrenia is first associated with a defect in the striatum and then with a defect in extrastriatal regions with centralizing on cortex and midbrain. Also, the gamma-aminobutyric acid (GABA) mRNA dysregulation and neuroinflammatory mechanisms can be useful in schizophrenia. Various medications such as antipsychotic drugs used to the aim of treating this disease, but they can just decline or improve the positive symptoms. Modeling neurodevelopment and synaptic connection defects by induced human pluripotent stem cells have made appropriate circumstances to eliminate schizophrenia treatment barriers. With the development of cell therapies and induced pluripotent stem cells (iPSCs), there is a hope that the negative symptoms can be improved.

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Schizophrenia in a genomic era: a review from the pathogenesis, genetic and environmental etiology to diagnosis and treatment insights

Cited by 60 publications

References 114 publications

Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells

Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells

Polymorphisms in the Human Aquaporin 4 Gene Are Associated With Schizophrenia in the Southern Chinese Han Population: A Case–Control Study

Schizophrenia; Recent Cognitive and Treatment Approaches Using Induced Pluripotent Stem Cells

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