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Schizophrenia pharmacogenetics

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https://www.readbyqxmd.com/read/29891954/variations-in-dysbindin-1-are-associated-with-cognitive-response-to-antipsychotic-drug-treatment
#1
Diego Scheggia, Rosa Mastrogiacomo, Maddalena Mereu, Sara Sannino, Richard E Straub, Marco Armando, Francesca Managò, Simone Guadagna, Fabrizio Piras, Fengyu Zhang, Joel E Kleinman, Thomas M Hyde, Sanne S Kaalund, Maria Pontillo, Genny Orso, Carlo Caltagirone, Emiliana Borrelli, Maria A De Luca, Stefano Vicari, Daniel R Weinberger, Gianfranco Spalletta, Francesco Papaleo
Antipsychotics are the most widely used medications for the treatment of schizophrenia spectrum disorders. While such drugs generally ameliorate positive symptoms, clinical responses are highly variable in terms of negative symptoms and cognitive impairments. However, predictors of individual responses have been elusive. Here, we report a pharmacogenetic interaction related to a core cognitive dysfunction in patients with schizophrenia. We show that genetic variations reducing dysbindin-1 expression can identify individuals whose executive functions respond better to antipsychotic drugs, both in humans and in mice...
June 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29528898/new-findings-in-pharmacogenetics-of-schizophrenia
#2
Clement C Zai, Arun K Tiwari, Gwyneth C Zai, Miriam S Maes, James L Kennedy
PURPOSE OF REVIEW: This review highlights recent advances in the investigation of genetic factors for antipsychotic response and side effects. RECENT FINDINGS: Antipsychotics prescribed to treat psychotic symptoms are variable in efficacy and propensity for causing side effects. The major side effects include tardive dyskinesia, antipsychotic-induced weight gain (AIWG), and clozapine-induced agranulocytosis (CIA). Several promising associations of polymorphisms in genes including HSPG2, CNR1, and DPP6 with tardive dyskinesia have been reported...
May 2018: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/29517519/sudden-death-in-schizophrenia
#3
Kevin J Li, Aaron P Greenstein, Lynn E Delisi
PURPOSE OF REVIEW: To examine the recent literature regarding sudden death in patients with schizophrenia and synthesize salient conclusions based on this evidence. RECENT FINDINGS: Sudden cardiac death (SCD) is the largest subset of sudden unexpected death (SUD), with up to 40% of SUD from cardiovascular causes. SCD has been associated with exposure to both first and second-generation antipsychotics. Clozapine [odds ratio (OR) 3.67, 95% confidence interval (CI) 1...
May 2018: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/29503163/five-novel-loci-associated-with-antipsychotic-treatment-response-in-patients-with-schizophrenia-a-genome-wide-association-study
#4
Hao Yu, Hao Yan, Lifang Wang, Jun Li, Liwen Tan, Wei Deng, Qi Chen, Guigang Yang, Fuquan Zhang, Tianlan Lu, Jianli Yang, Keqing Li, Luxian Lv, Qingrong Tan, Hongyan Zhang, Xiao Xiao, Ming Li, Xin Ma, Fude Yang, Lingjiang Li, Chuanyue Wang, Tao Li, Dai Zhang, Weihua Yue
BACKGROUND: Antipsychotic drugs improve schizophrenia symptoms and reduce the frequency of relapse, but treatment response is highly variable. Little is known about the genetic factors associated with treatment response. We did a genome-wide association study of antipsychotic treatment response in patients with schizophrenia. METHODS: The discovery cohort comprised patients with schizophrenia from 32 psychiatric hospitals in China that are part of the Chinese Antipsychotics Pharmacogenomics Consortium...
April 2018: Lancet Psychiatry
https://www.readbyqxmd.com/read/29298994/cost-effectiveness-of-hla-dqb1-hla-b-pharmacogenetic-guided-treatment-and-blood-monitoring-in-us-patients-taking-clozapine
#5
François R Girardin, Antoine Poncet, Arnaud Perrier, Nathalie Vernaz, Mark Pletscher, Caroline F Samer, Jeffrey A Lieberman, Jean Villard
Less than 1% of adult patients with schizophrenia taking clozapine develop agranulocytosis, and most of these cases occur within the first weeks of treatment. The human leukocyte antigen (HLA) region has been associated with genetic susceptibility to clozapine-induced agranulocytosis (single amino acid changes in HLA-DQB1 (126Q) and HLA-B (158T)). The current study aimed to evaluate the cost-effectiveness, from a healthcare provider's perspective, of an HLA genotype-guided approach in patients with treatment-resistant schizophrenia who were taking clozapine and to compare the results with the current absolute neutrophil count monitoring (ANCM) schemes used in the USA...
January 3, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29017764/dna-methylation-and-antipsychotic-treatment-mechanisms-in-schizophrenia-progress-and-future-directions
#6
REVIEW
Ellen S Ovenden, Nathaniel W McGregor, Robin A Emsley, Louise Warnich
Antipsychotic response in schizophrenia is a complex, multifactorial trait influenced by pharmacogenetic factors. With genetic studies thus far providing little biological insight or clinical utility, the field of pharmacoepigenomics has emerged to tackle the so-called "missing heritability" of drug response in disease. Research on psychiatric disorders has only recently started to assess the link between epigenetic alterations and treatment outcomes. DNA methylation, the best characterised epigenetic mechanism to date, is discussed here in the context of schizophrenia and antipsychotic treatment outcomes...
October 7, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28991183/orexin-receptor-multimerization-versus-functional-interactions-neuropharmacological-implications-for-opioid-and-cannabinoid-signalling-and-pharmacogenetics
#7
Miles D Thompson, Takeshi Sakurai, Innocenzo Rainero, Mary C Maj, Jyrki P Kukkonen
Orexins/hypocretins are neuropeptides formed by proteolytic cleavage of a precursor peptide, which are produced by neurons found in the lateral hypothalamus. The G protein-coupled receptors (GPCRs) for these ligands, the OX₁ and OX₂ orexin receptors, are more widely expressed throughout the central nervous system. The orexin/hypocretin system has been implicated in many pathways, and its dysregulation is under investigation in a number of diseases. Disorders in which orexinergic mechanisms are being investigated include narcolepsy, idiopathic sleep disorders, cluster headache and migraine...
October 8, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28919802/abcb1-and-abcc1-single-nucleotide-polymorphisms-in-patients-treated-with-clozapine
#8
Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Trudi Jones, Steven C Boyages, Mark McLean
Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood-brain barrier. Genetic variations in these proteins can account for differences in treatment response. We investigated the influence of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs) on CZ serum level, clinical outcome, and changes in body mass index (BMI) in the first year of CZ treatment...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28892404/mechanisms-underlying-metabolic-disturbances-associated-with-psychosis-and-antipsychotic-drug-treatment
#9
Gavin P Reynolds, Olga O McGowan
The increase in cardiovascular disease and reduced life expectancy in schizophrenia likely relate to an increased prevalence of metabolic disturbances. Such metabolic risk factors in schizophrenia may result from both symptom-related effects and aetiological factors. However, a major contributory factor is that of treatment with antipsychotic drugs. These drugs differ in effects on body weight; the underlying mechanisms are not fully understood and may vary between drugs, but may include actions at receptors associated with the hypothalamic control of food intake...
August 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28782490/unmet-needs-in-schizophrenia
#10
Maurizio Pompili, Gloria Giordano, Mario Luciano, Dorian A Lamis, Valeria Del Vecchio, Gianluca Serafini, Gaia Sampogna, Denise Erbuto, Peter Falkai, Andrea Fiorillo
BACKGROUND: Schizophrenia is a complex psychiatric disorder that represents a challenge for all clinicians. Although treatment must address both positive and negative symptoms, several authors have reported the importance of managing unmet needs among patients with schizophrenia. Unmet needs in schizophrenia include difficulties at various clinical, psychosocial, relational, economic, and occupational levels. An important unmet need is represented by insight into the illness that is associated with treatment adherence and compliance with medical prescriptions...
2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28758583/new-trends-in-the-treatment-of-schizophrenia
#11
Herbert Y Meltzer
OBJECTIVES: This article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments. RESULTS: Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine- type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects are becoming appreciated...
2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28664816/cyp2c19-17-protects-against-metabolic-complications-of-clozapine-treatment
#12
Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Micheline Coelho, Trudi Jones, Tristan Nguyen, Steven Boyages, Mark McLean
OBJECTIVES: Clozapine (CZ) is the most effective drug for managing treatment-resistant schizophrenic disorders. Its use has been limited due to adverse effects, which include weight gain and new-onset diabetes, but the incidence of these varies between patients. METHODS: We investigated 187 Clozapine Clinic patients (of whom 137 consented for genotyping) for the presence of CYP2C19*17 and its association with CZ and norclozapine (NCZ) levels, and clinical outcomes...
October 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28653280/clozapine-as-a-model-for-antipsychotic-development
#13
REVIEW
Frederick C Nucifora, Marina Mihaljevic, Brian J Lee, Akira Sawa
Schizophrenia is a devastating illness that affects up to 1% of the population; it is characterized by a combination of positive symptoms, negative symptoms, and cognitive impairment. Currently, treatment consists of one class of medications known as antipsychotics, which include typical (first-generation) and atypical (second-generation) agents. Unfortunately, antipsychotic medications have limited efficacy, with up to a third of patients lacking a full response. Clozapine, the first atypical antipsychotic developed, is the only medication shown to be superior to all other antipsychotics...
July 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28474173/-genetics-of-bipolar-disorder
#14
REVIEW
M Budde, A J Forstner, K Adorjan, S K Schaupp, M M Nöthen, T G Schulze
Bipolar disorder (BD) has a multifactorial etiology. Its development is influenced by genetic as well as environmental factors. Large genome-wide association studies (GWAS), in which genetic risk allelic variants for the disorder could be replicated for the first time, marked the breakthrough in the identification of the responsible risk genes. In addition to these common genetic variants with moderate effects identified by GWAS, rare variants with a higher penetrance are expected to play a role in disease development...
July 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28384469/altered-cortical-ensembles-in-mouse-models-of-schizophrenia
#15
Jordan P Hamm, Darcy S Peterka, Joseph A Gogos, Rafael Yuste
In schizophrenia, brain-wide alterations have been identified at the molecular and cellular levels, yet how these phenomena affect cortical circuit activity remains unclear. We studied two mouse models of schizophrenia-relevant disease processes: chronic ketamine (KET) administration and Df(16)A+/- , modeling 22q11.2 microdeletions, a genetic variant highly penetrant for schizophrenia. Local field potential recordings in visual cortex confirmed gamma-band abnormalities similar to patient studies. Two-photon calcium imaging of local cortical populations revealed in both models a deficit in the reliability of neuronal coactivity patterns (ensembles), which was not a simple consequence of altered single-neuron activity...
April 5, 2017: Neuron
https://www.readbyqxmd.com/read/28332719/rs7968606-polymorphism-of-anks1b-is-associated-with-improvement-in-the-panss-general-score-of-schizophrenia-caused-by-amisulpride
#16
Seung-Gul Kang, Ik-Seung Chee, Kwanghun Lee, Jonghun Lee
A recent genome-wide pharmacogenomics study showed that the rs7968606 single-nucleotide polymorphism (SNP) of the ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B) gene approached the threshold of statistical significance. The aim of this study was to determine the association between the rs7968606 SNP of ANKS1B and the treatment response to amisulpride in schizophrenia patients. In total, 154 participants were enrolled from six university hospitals in Korea. All the subjects were interviewed before and after 6 weeks of amisulpride treatment with the aid of the positive and negative syndrome scale and the clinical global impression-severity scale...
March 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28277565/pharmacogenetic-analysis-of-functional-glutamate-system-gene-variants-and-clinical-response-to-clozapine
#17
Danielle L Taylor, Arun K Tiwari, Jeffrey A Lieberman, Steven G Potkin, Herbert Y Meltzer, Joanne Knight, Gary Remington, Daniel J Müller, James L Kennedy
Altered glutamate neurotransmission is implicated in the etiology of schizophrenia (SCZ) and the pharmacogenetics of response to clozapine (CLZ), which is the drug of choice for treatment-resistant SCZ. Response to antipsychotic therapy is highly variable, although twin studies suggest a genetic component. We investigated the association of 10 glutamate system gene variants with CLZ response using standard genotyping procedures. GRM2 (rs4067 and rs2518461), SLC1A2 (rs4354668, rs4534557, and rs2901534), SLC6A9 (rs12037805, rs1978195, and rs16831558), GRIA1 (rs2195450), and GAD1 (rs3749034) were typed in 163 European SCZ/schizoaffective disorder patients deemed resistant or intolerant to previous pharmacotherapy...
February 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28252572/pharmacogenetics-of-ketamine-induced-emergence-phenomena-a-pilot-study
#18
Edwin N Aroke, Sybil L Crawford, Jennifer R Dungan
BACKGROUND: Up to 55% of patients who are administered ketamine experience an emergence phenomena (EP) that closely mimics schizophrenia and increases their risk of injury; however, to date, no studies have investigated genetic association of ketamine-induced EP in healthy patients. OBJECTIVES: The aim of the study was to investigate the feasibility and sample sizes required to explore the relationship between CYP2B6*6 and GRIN2B single-nucleotide polymorphisms and ketamine-induced EP...
March 2017: Nursing Research
https://www.readbyqxmd.com/read/28159590/pharmacogenetics-of-antidepressant-response-a-polygenic-approach
#19
Judit García-González, Katherine E Tansey, Joanna Hauser, Neven Henigsberg, Wolfgang Maier, Ole Mors, Anna Placentino, Marcella Rietschel, Daniel Souery, Tina Žagar, Piotr M Czerski, Borut Jerman, Henriette N Buttenschøn, Thomas G Schulze, Astrid Zobel, Anne Farmer, Katherine J Aitchison, Ian Craig, Peter McGuffin, Michel Giupponi, Nader Perroud, Guido Bondolfi, David Evans, Michael O'Donovan, Tim J Peters, Jens R Wendland, Glyn Lewis, Shitij Kapur, Roy Perlis, Volker Arolt, Katharina Domschke, Gerome Breen, Charles Curtis, Lee Sang-Hyuk, Carol Kan, Stephen Newhouse, Hamel Patel, Bernhard T Baune, Rudolf Uher, Cathryn M Lewis, Chiara Fabbri
BACKGROUND: Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. METHODS: Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia...
April 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27606316/inflammatory-cytokines-and-antipsychotic-induced-weight-gain-review-and-clinical-implications
#20
REVIEW
Trehani M Fonseka, Daniel J Müller, Sidney H Kennedy
Antipsychotic medications (APs), particularly second-generation APs, are associated with significant weight gain in schizophrenia patients. Recent evidence suggests that the immune system may contribute to antipsychotic-induced weight gain (AIWG) via AP-mediated alterations of cytokine levels. Antipsychotics with a high propensity for weight gain, such as clozapine and olanzapine, influence the expression of immune genes, and induce changes in serum cytokine levels to ultimately down-regulate neuroinflammation...
May 2016: Molecular Neuropsychiatry
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