Genetic Association of Olanzapine Treatment Response in Han Chinese Schizophrenia Patients

Zhou, Wei; Xu, Yong; Lv, Qing; Sheng, Yong-hui; Chen, Luan; Li, M; Shen, Lu; Cong, Hui; Yi, Zhenghui; Cui, Donghong; Qin, Shengying

doi:10.3389/fphar.2019.00177

Cited by 15 publications

(5 citation statements)

References 48 publications

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“…The same study identified novel associations of GPR12 and MAP2K3 , two genes involved in glutamatergic pathways, with response using WES techniques, although no finding was replicated by both strategies. Finally, a sequencing study of 143 genes revealed statistically significant association between polymorphisms in DRD3 (rs342026) and in a neighbouring gene ( PLK5 rs1261027) with olanzapine response, confirming the findings of candidate-gene studies [ 54 ].…”

Section: Pharmacogenomic Studiessupporting

confidence: 73%

Clinical Utility and Implementation of Pharmacogenomics for the Personalisation of Antipsychotic Treatments

Hernandez,

Cullell,

Cendros

et al. 2024

Pharmaceutics

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Decades of pharmacogenetic research have revealed genetic biomarkers of clinical response to antipsychotics. Genetic variants in antipsychotic targets, dopamine and serotonin receptors in particular, and in metabolic enzymes have been associated with the efficacy and toxicity of antipsychotic treatments. However, genetic prediction of antipsychotic response based on these biomarkers is far from accurate. Despite the clinical validity of these findings, the clinical utility remains unclear. Nevertheless, genetic information on CYP metabolic enzymes responsible for the biotransformation of most commercially available antipsychotics has proven to be effective for the personalisation of clinical dosing, resulting in a reduction of induced side effects and in an increase in efficacy. However, pharmacogenetic information is rarely used in psychiatric settings as a prescription aid. Lack of studies on cost-effectiveness, absence of clinical guidelines based on pharmacogenetic biomarkers for several commonly used antipsychotics, the cost of genetic testing and the delay in results delivery hamper the implementation of pharmacogenetic interventions in clinical settings. This narrative review will comment on the existing pharmacogenetic information, the clinical utility of pharmacogenetic findings, and their current and future implementations.

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Section: Pharmacogenomic Studiessupporting

confidence: 73%

Clinical Utility and Implementation of Pharmacogenomics for the Personalisation of Antipsychotic Treatments

Hernandez,

Cullell,

Cendros

et al. 2024

Pharmaceutics

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“…For example, by demonstrating correlations between specific markers of plasticity and individuals who respond to treatment, future clinical trials can use this information to predict whether a patient is likely to improve through changes in brain plasticity [ 87 ]. One example of a clinical biomarker currently in use is the presence of single nucleotide polymorphisms that correlate with greater efficacy of olanzapine in schizophrenia [ 88 ]. Epigenetic markers are also useful to predict drug efficacy such as the absence of methylated exon 4 of BDNF which is associated with reduced response to anti-depressants [ 89 ].…”

Section: Future Research Directions—challenges and Opportunitiesmentioning

confidence: 99%

Synaptic plasticity and mental health: methods, challenges and opportunities

Appelbaum

Shenasa

Stolz

et al. 2022

Neuropsychopharmacol.

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Activity-dependent synaptic plasticity is a ubiquitous property of the nervous system that allows neurons to communicate and change their connections as a function of past experiences. Through reweighting of synaptic strengths, the nervous system can remodel itself, giving rise to durable memories that create the biological basis for mental function. In healthy individuals, synaptic plasticity undergoes characteristic developmental and aging trajectories. Dysfunctional plasticity, in turn, underlies a wide spectrum of neuropsychiatric disorders including depression, schizophrenia, addiction, and posttraumatic stress disorder. From a mechanistic standpoint, synaptic plasticity spans the gamut of spatial and temporal scales, from microseconds to the lifespan, from microns to the entire nervous system. With the numbers and strengths of synapses changing on such wide scales, there is an important need to develop measurement techniques with complimentary sensitivities and a growing number of approaches are now being harnessed for this purpose. Through hemodynamic measures, structural and tracer imaging, and noninvasive neuromodulation, it is possible to image structural and functional changes that underlie synaptic plasticity and associated behavioral learning. Here we review the mechanisms of neural plasticity and the historical and future trends in techniques that allow imaging of synaptic changes that accompany psychiatric disorders, highlighting emerging therapeutics and the challenges and opportunities accompanying this burgeoning area of study.

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“…A strong connection has been reported between genetic polymorphisms (in the HSPG2, CNR1, DPP6 and SLC18A2 genes) and antipsychotic drugs, and even the side effects of these drugs ( 84 ). Another study identified 12 SNPs from 143 genes of 79 Han Chinese patients with SCZ via HaloPlex technology, with 2/12 SNPs determined to be significantly associated with the response to olanzapine, using the MassARRAY platform in two independent cohorts ( 85 ). Other studies confirmed that the effectiveness of antipsychotic drugs is closely associated with the variation of drug target genes in patients with TRS ( 86 – 89 ).…”

Section: Discussionmentioning

confidence: 99%

Investigating aberrantly expressed microRNAs in peripheral blood mononuclear cells from patients with treatment‑resistant schizophrenia using miRNA sequencing and integrated bioinformatics

Zhang

Long

et al. 2020

Mol Med Rep

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Treatment-resistant schizophrenia (TrS) is a common phenotype of schizophrenia that places a considerable burden on patients as well as on society. TrS is known for its tendency to relapse and uncontrollable nature, with a poor response to antipsychotics other than clozapine. Therefore, it is urgent to identify objective biological markers, so as to guide its treatment and associated clinical work. in the present study, the peripheral blood mononuclear cells (PBMcs) of patients with TrS and a healthy control group, which were gender-, age-and ethnicity-matched, were subjected to microrna (mirna/mir) sequencing to screen out the top three mirnas with the highest fold change values. These were then validated in the TrS (n=34) and healthy control (n=31) groups by reverse transcription-quantitative Pcr. For two of the top three mirnas, the Pcr results were in accordance with the sequencing result (P<0.01), while the third mirna exhibited the opposite trend (P<0.01). To elucidate the functions of these two mirnas, Homo sapiens (hsa)-mir-218-5p and hsa-mir-1262 and their regulatory network, target gene prediction was first performed using online TargetScan and diana-micro T software. Bioinformatics analysis was then performed using functional enrichment analysis to determine the Gene ontology terms in the category biological process and the Kyoto encyclopedia of Genes and Genomes pathways. it was revealed that these target genes were markedly associated with the nervous system and brain function, and it was obvious that the differentially expressed mirnas most likely participated in the pathogenesis of TrS. a receiver operating characteristic curve was generated to confirm the distinct diagnostic value of these two mirnas. it was concluded that aberrantly expressed mirnas in PMBcs may be implicated in the pathogenesis of TrS and may serve as specific peripheral blood-based biomarkers for the early diagnosis of TrS.

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Genetic Association of Olanzapine Treatment Response in Han Chinese Schizophrenia Patients

Cited by 15 publications

References 48 publications

Clinical Utility and Implementation of Pharmacogenomics for the Personalisation of Antipsychotic Treatments

Clinical Utility and Implementation of Pharmacogenomics for the Personalisation of Antipsychotic Treatments

Synaptic plasticity and mental health: methods, challenges and opportunities

Investigating aberrantly expressed microRNAs in peripheral blood mononuclear cells from patients with treatment‑resistant schizophrenia using miRNA sequencing and integrated bioinformatics

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