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Schizophrenia pharmacogenetics

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https://www.readbyqxmd.com/read/29017764/dna-methylation-and-antipsychotic-treatment-mechanisms-in-schizophrenia-progress-and-future-directions
#1
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
#2
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
#3
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
#4
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
#5
Maurizio Pompili, Gloria Giordano, Mario Luciano, Dorian A. Lamis, Valeria Del Vecchio, Gianluca Serafini, Gaia Sampogna, Denise Erbuto, Peter Falkai, Andrea Fiorillo
The objectives of 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 is becoming appreciated...
August 3, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28758583/new-trends-in-the-treatment-of-schizophrenia
#6
Herbert Y Meltzer
The objectives of 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 is becoming appreciated...
July 28, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28664816/cyp2c19-17-protects-against-metabolic-complications-of-clozapine-treatment
#7
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...
July 18, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28653280/clozapine-as-a-model-for-antipsychotic-development
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/27546373/pharmacogenetic-study-of-the-effects-of-raloxifene-on-negative-symptoms-of-postmenopausal-women-with-schizophrenia-a-double-blind-randomized-placebo-controlled-trial
#16
Javier Labad, Lourdes Martorell, Elena Huerta-Ramos, Jesús Cobo, Elisabet Vilella, Elena Rubio-Abadal, Gemma Garcia-Pares, Marta Creus, Cristian Núñez, Laura Ortega, Eva Miquel, Judith Usall
Several double-blind clinical trials have reported improvement in positive, negative and cognitive symptoms of schizophrenia with raloxifene, a selective receptor estrogen modulator. However, there are some inconsistencies in replicating findings between studies of different countries. The failure to replicate these findings may result from genetic factors that could explain some of the variability in the treatment response. However, pharmacogenetic studies exploring this topic in women with schizophrenia are lacking...
October 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27469238/pharmacogenetics-of-tardive-dyskinesia-an-updated-review-of-the-literature
#17
REVIEW
Rachel K Lanning, Clement C Zai, Daniel J Müller
Tardive dyskinesia (TD) is a serious and potentially irreversible side effect of long-term exposure to antipsychotic medication characterized by involuntary trunk, limb and orofacial muscle movements. Various mechanisms have been proposed for the etiopathophysiology of antipsychotic-induced TD in schizophrenia patients with genetic factors playing a prominent role. Earlier association studies have focused on polymorphisms in CYP2D6, dopamine-, serotonin-, GABA- and glutamate genes. This review highlights recent advances in the genetic investigation of TD...
August 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27414739/-759c-t-polymorphism-of-the-htr2c-gene-is-associated-with-second-generation-antipsychotic-induced-weight-gain-in-female-patients-with-schizophrenia
#18
Federico Manuel Daray, Demián Rodante, Laura G Carosella, María Elena Silva, Melina Martínez, María V Fernández Busch, Diego F Faccone, Rodolfo P Rothlin, Paulo C Maffía
Introduction: The HTR2C gene is an important candidate in pharmacogenetic studies of antipsychotic-induced weight gain (AIWG). However, inconsistent results have been obtained. The present study investigated the association between -759C>T, functional polymorphism of the HTR2C receptor, and AIWG. Methods: A prospective cohort of 48 female inpatients with schizophrenia and related illness treated according to normal clinical practice with second generation antipsychotics (SGAs) risperidone, clozapine, quetiapine, and olanzapine were evaluated...
January 2017: Pharmacopsychiatry
https://www.readbyqxmd.com/read/27396334/somatostatin-interneurons-control-a-key-component-of-mismatch-negativity-in-mouse-visual-cortex
#19
Jordan P Hamm, Rafael Yuste
Patients with schizophrenia have deficient sensory processing, undermining how they perceive and relate to a changing environment. This impairment can be captured by the reduced mismatch negativity (MMN) index, an electroencephalographic biomarker of psychosis. The biological factors contributing to MMN are unclear, though mouse research, in which genetic and optical methods could be applied, has given some insight. Using fast two-photon calcium imaging and multielectrode recordings in awake mice, we find that visual cortical circuits display adapted (decreased) responses to repeated stimuli and amplified responses to a deviant stimulus, the key component of human MMN...
July 19, 2016: Cell Reports
https://www.readbyqxmd.com/read/27333159/variants-in-the-drd2-locus-and-antipsychotic-related-prolactin-levels-a-meta-analysis
#20
Itaru Miura, Jian-Ping Zhang, Katsuhiko Hagi, Todd Lencz, John M Kane, Hirooki Yabe, Anil K Malhotra, Christoph U Correll
BACKGROUND: Although dopamine D2 receptor antagonists lead to dose-dependent prolactin (PRL) elevations proportionate to their D2 affinity, considerable inter-individual differences exist. We conducted a meta-analytic review of associations between genetic variations in the dopamine D2 receptor gene (DRD2) and PRL levels in antipsychotic-treated subjects. METHODS: Systematic literature search (5/8/2015) was performed to find published studies of pharmacogenetic associations between two DRD2 variants, Taq1A (rs1800497) and -141C Ins/Del (rs1799732), and PRL levels during antipsychotic treatment (excluding aripiprazole)...
October 2016: Psychoneuroendocrinology
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