Five novel loci associated with antipsychotic treatment response in patients with schizophrenia: a genome-wide association study

Yu, Hao; Yan, Hao; Wang, Lifang; Li, Jun; Tan, Liwen; Deng, Wei; Chen, Qi; Yang, Guigang; Zhang, Fuquan; Lu, Tianlan; Yang, Jianli; Li, Keqing; Lv, Luxian; Tan, Qingrong; Zhang, Hongyan; Xiao, Xiao; Li, Ming; Ma, Xin; Yang, Fude; Li, Lingjiang; Wang, Chuanyue; Li, Tao; Zhang, Dai; Yue, Weihua

doi:10.1016/s2215-0366(18)30049-x

Cited by 115 publications

(83 citation statements)

References 41 publications

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“…Positive And Negative Syndrome Scale (PANSS) and Hamilton Depression Rating Scale (HAMD)/Hamilton Anxiety Rating Scale (HAMA) (needed by partial patients) that evaluated symptoms of patients at the time of MRI scans and before discharging were used for the following analysis. Percentage change on PANSS score was used to assess treatment responses: PANSS percentage change = (PANSS endpoint score — PANSS baseline score) × 100 ÷ (PANSS baseline score — 30) (Obermeier et al, ; Yu et al, ). A responder was defined if there was >30% reduction in PANSS total scores (Beitinger, Lin, Kissling, & Leucht, ; Leucht, Arbter, Engel, Kissling, & Davis, ).…”

Section: Methodsmentioning

confidence: 99%

Prediction of early response to overall treatment for schizophrenia: A functional magnetic resonance imaging study

et al. 2019

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Introduction Treatment response at an early stage of schizophrenia is of considerable value with regard to future management of the disorder; however, there are currently no biomarkers that can inform physicians about the likelihood of response. Objects We aim to develop and validate regional brain activity derived from functional magnetic resonance imaging (fMRI) as a potential signature to predict early treatment response in schizophrenia. Methods Amplitude of low‐frequency fluctuation (ALFF) was measured at the start of the first/single episode resulting in hospitalization. Inpatients were included in a principal dataset ( n = 79) and a replication dataset ( n = 44). Two groups of healthy controls ( n = 87; n = 106) were also recruited for each dataset. The clinical response was assessed at discharge from the hospital. The predictive capacity of normalized ALFF in patients by healthy controls, ALFF ratio , was evaluated based on diagnostic tests and clinical correlates. Results In the principal dataset, responders exhibited increased baseline ALFF in the left postcentral gyrus/inferior parietal lobule relative to non‐responders. ALFF ratio of responders before treatment was significantly higher than that of non‐responders ( p < 0.001). The area under the receiver operating characteristic curve was 0.746 for baseline ALFF ratio to distinguish responders from non‐responders, and the sensitivity, specificity, and accuracy were 72.7%, 68.6%, and 70.9%, respectively. Similar results were found in the independent replication dataset. Conclusions Baseline regional activity of the brain seems to be predictive of early response to treatment for schizophrenia. This study shows that psycho‐neuroimaging holds promise for influencing the clinical treatment and management of schizophrenia.

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Section: Methodsmentioning

confidence: 99%

Prediction of early response to overall treatment for schizophrenia: A functional magnetic resonance imaging study

et al. 2019

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“…To examine the associations between GRM7 variations and treatment response in patients with SCZ, we performed a pharmacogenetics study using our previous data 22 . Briefly, all subjects were of Chinese Han ethnicity, and were born and residing in China.…”

Section: Pharmacogenetics Study Of Grm7 Gene Participantsmentioning

confidence: 99%

“…For each patient, the PANSS reduction rate was defined as 100× (PANSS score at endpoint-PANSS score at baseline)/ (PANSS score at baseline -30). Different from our previous study 22 , the antipsychotic response was classed into two groups, clinical good responders were defined as patients with 50% or even higher reduction in PANSS scores; poor responders were defined as patients with lower reduction than 50% in PANSS scores. A detailed description of the participants can be found in our previous study 22 .…”

Section: Pharmacogenetics Study Of Grm7 Gene Participantsmentioning

confidence: 99%

Variants of GRM7 as risk factor and response to antipsychotic therapy in schizophrenia

Liang

et al. 2020

Transl Psychiatry

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Genome-wide association study (GWAS) has determined the metabotropic glutamate receptor 7 (GRM7) gene as potential locus for schizophrenia risk variants; However, the relationship between the GRM7 variants and the risk of schizophrenia is still uncertain, and there are significant individual variations in response to the antipsychotic drugs. In order to identify susceptible gene and drug-response-related markers, 2413 subjects in our research were chosen for determining drug-response-related markers in schizophrenia. The rs1516569 variant (OR = 0.95, P < 3.47 × 10 −4 ) was a significant risk factor, and a single-nucleotide polymorphism of GRM7 gene-rs9883258 (OR = 0.84, P = 2.18 × 10 −3 ) has been determined as potential biomarkers for therapeutic responses of seven commonly used antipsychotic drugs (aripiprazole, haloperidol, olanzapine, perphenazine, quetiapine, risperidone and ziprasidone) in Chinese Han population; Significant associations with treatment response for several single-nucleotide polymorphisms in every antipsychotic drugs, such as rs779746 (OR = 1.39, P = 0.03), rs480409 (OR = 0.73, P = 0.04), rs78137319 (OR = 3.09, P = 0.04), rs1154370 (OR = 1.51, P = 0.006) have been identified in our study. Hence our research elucidates that GRM7 variants play the critical role of predicting the risk of schizophrenia and antipsychotic effect of seven common drugs.

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“…The open-targets-platform (https://www.targetvalidation.org/) database shows that 47 human diseases are associated with the FAM19A5 gene including Alzheimer's 11,12 , schizophrenia 13,14 , bipolar disorder 15 , pancreatic carcinoma 16 , and endometrial neoplasm 17 , among others 18 . Interestingly, the mosaic monosomy of chromosome 22, which includes disruption of the FAM19A5 gene, leads to skeletal abnormalities, low body weight, and neuropsychiatric conditions, including attention deficit hyperactivity disorder, aggression, and autistic symptoms 19 .…”

Section: Introductionmentioning

confidence: 99%

Is FAM19A5 an adipokine? Peripheral FAM19A5 in wild-type, FAM19A5 knockout, and LacZ knockin mice

Kwak¹,

Cho²,

Cho³

et al. 2020

Preprint

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FAM19A5 (also called TAFA5) is a novel secretory protein that is primarily expressed in the brain. However, a recent study reported that FAM19A5 is an adipocyte-derived adipokine that regulates vascular smooth muscle function. Furthermore, genome-wide association study (GWAS) and RNA-seq analyses revealed that the FAM19A5 was associated with a variety of diseases and tumorigenesis in peripheral tissues. We investigated FAM19A5 transcript and protein levels in the FAM19A5 peripheral expression 2 peripheral tissues, including adipose tissues from wild-type, FAM19A5 knock-out, and LacZ knock-in mice. In general, total FAM19A5 transcript levels in the central and peripheral nervous systems were higher than levels in any of the peripheral tissues including adipose tissues. Brain tissues expressed similar levels of the FAM19A5 transcript isoforms 1 and 2, whereas expression in the peripheral tissues predominantly expressed isoform 2. In the peripheral tissues, but not the brain, FAM19A5 protein levels in adipose and reproductive tissues were below detectable limits for analysis by Western blot. Additionally, we found that FAM19A5 protein did not interact with the S1PR2 receptor for G-protein-mediated signal transduction, β-arrestin recruitment, and ligandmediated internalization. Instead, FAM19A5 was internalized into HEK293 cells in an extracellular matrix protein-dependent manner. Taken together, the present study determined basal levels of FAM19A5 transcripts and proteins in peripheral tissues, which provides compelling evidence to further investigate the function of FAM19A5 in peripheral tissues under pathological conditions, including metabolic diseases and/or tumorigenesis.

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Five novel loci associated with antipsychotic treatment response in patients with schizophrenia: a genome-wide association study

Cited by 115 publications

References 41 publications

Prediction of early response to overall treatment for schizophrenia: A functional magnetic resonance imaging study

Prediction of early response to overall treatment for schizophrenia: A functional magnetic resonance imaging study

Variants of GRM7 as risk factor and response to antipsychotic therapy in schizophrenia

Is FAM19A5 an adipokine? Peripheral FAM19A5 in wild-type, FAM19A5 knockout, and LacZ knockin mice

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