168 results on '"Maria Arranz"'
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2. Characteristics of prolonged noninvasive ventilation in emergency departments and impact upon effectiveness. Analysis of the VNICat registry
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O. García-Trallero, M. Sancho-Ramoneda, Maria Arranz, Javier Jacob, J.R. Cousiño-Chao, Antonio German, J. Farré-Cerdà, Àngels Lopez, M.C. Navarro-Sáez, X. López-Altimiras, José Zorrilla, and F. López i Vengut
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medicine.medical_specialty ,Noninvasive Ventilation ,business.industry ,General Medicine ,Cohort Studies ,Emergency medicine ,medicine ,Humans ,Prolonged ventilation ,Noninvasive ventilation ,Observational study ,Prospective Studies ,Registries ,Emergency Service, Hospital ,Respiratory Insufficiency ,business ,Cohort study - Abstract
To analyze the characteristics and variables associated with prolonged noninvasive ventilation performed completely in Emergency Departments (NIV-ED) and its influence upon effectiveness.A prospective, multicenter, observational multipurpose cohort study was carried out.VNICat Registry.Patients in which NIV-ED was performed in 11 Catalan hospitals in the months of February or March 2015.No.The study variable was NIV-ED, which as a function of time was defined as prolonged or not prolonged. The efficacy variable was the success of the technique in terms of patient improvement.A total of 125 patients were included, with a median NIV-ED duration of 12hours, which was the cut-off point for the comparator groups. In 60 cases (48%) NIV-ED was not prolonged (12hours), while in 65 cases (52%) ventilation was prolonged (≥12hours). Non-prolonged NIV-ED was associated to the indication of acute heart failure and prolonged ventilation to the presence of diabetes. There were no differences between non-prolonged and prolonged NIV-ED in terms of efficacy, and the success rate in terms of improvement was 68.3% and 76.9%, respectively, with an adjusted odds ratio of 1.49 (95%CI 0.61-3.60).Prolonged NIV-ED is a frequent situation, but few variables associated to it have been studied. The presence of prolonged ventilation did not influence the success rate of NIV.
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- 2021
3. Características de la ventilación no invasiva prolongada en los servicios de urgencias hospitalarios y su impacto en la eficacia. Análisis del registro VNICat
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Maria Arranz, José Zorrilla, X. López-Altimiras, O. García-Trallero, Javier Jacob, J. Farré-Cerdà, F. López i Vengut, Àngels Lopez, M.C. Navarro-Sáez, M. Sancho-Ramoneda, J.R. Cousiño-Chao, and Antonio German
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03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,business.industry ,Medicine ,030208 emergency & critical care medicine ,Critical Care and Intensive Care Medicine ,business ,Humanities - Abstract
Resumen Objetivo Analizar las caracteristicas y variables asociadas con la ventilacion no invasiva realizada completamente en los servicios de urgencias hospitalarios (VNI-SUH) de manera prolongada y su influencia en la eficacia de la tecnica. Diseno Estudio multicentrico observacional prospectivo de cohorte multiproposito. Ambito Registro VNICat. Participantes Pacientes en los que se realiza VNI-SUH en 11 hospitales catalanes en los meses de febrero o marzo de 2015. Intervencion Ninguna. Variables La variable de estudio fue la VNI-SUH, que en funcion del tiempo se definio como prolongada o no prolongada. La variable de eficacia fue el exito de la tecnica por mejoria. Resultados Se incluyeron 125 pacientes con una mediana de tiempo de VNI-SUH de 12 h, que fue el punto de corte para los 2 grupos comparados. En 60 (48%) la VNI-SUH fue no prolongada ( Conclusiones La VNI-SUH prolongada es una situacion frecuente, pero las variables estudiadas que se asocian a ella son escasas. Su presencia no influyo en el exito de la VNI.
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- 2021
4. Emergency Department capacity to initiate thromboprophylaxis in patients with atrial fibrillation and thrombotic risk after discharge: URGFAICS cohort analysis
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Alvaro Zarauza, Javier Jacob, Julia Santos, Irene Cabello, Anna Esquerrà, Maria Arranz, Oriol Yuguero, Anna Moreno, Paloma Frances, Josep-Maria Mòdol, and Jorge-Alexis Guzman
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medicine.medical_specialty ,Population ,Risk Assessment ,Risk Factors ,Atrial Fibrillation ,Internal Medicine ,Humans ,Medicine ,Sinus rhythm ,Prospective Studies ,Thromboprophylaxis ,education ,Stroke ,education.field_of_study ,business.industry ,Anticoagulants ,Thrombosis ,Atrial fibrillation ,Venous Thromboembolism ,Emergency department ,Odds ratio ,medicine.disease ,Patient Discharge ,Confidence interval ,Emergency medicine ,Emergency Medicine ,Emergency Service, Hospital ,business ,Cohort study - Abstract
Atrial fibrillation (AF) is the most prevalent heart rhythm disorder in the general population. Stroke prevention is one of the leading management objectives in the treatment of AF patients. The variables associated with the non-initiation of thromboprophylaxis in patients with thrombotic risk consulting for an episode of AF in Emergency Departments (ED) were investigated. This was a multipurpose, analytical, non-interventionist, multicenter Spanish study with a prospective 30-day follow-up. All patients >= 18 years of age consulting to the ED for the casual finding of AF in an electrocardiogram (ECG) performed 12 h prior to the consultation or with symptoms related to AF were enrolled from September 1, 2016 to February 28, 2017. Patients not previously received thromboprophylaxis were selected. Multivariate analysis was performed to calculate the odds ratio (OR) and the 95% confidence interval (CI). A total of 634 patients, not received thromboprophylaxis and at high thrombotic risk, were included. Of these, 251 (39.6%) did not receive thromboprophylaxis at ED discharge. In the multivariate analysis, non-initiation of anticoagulation at discharge from the ED was mostly related to cognitive impairment (OR 3.95; (95% CI 2.02-7.72), cancer history (OR 2.12; (95%CI 1.18-3.81), AF duration < 48 h (OR 2.49; (95% CI 1.48-4.21) and patients with re-establishment of sinus rhythm (OR 3.65; (95% CI 1.47-9.06). Reinforcement of the use of CHA(2)DS(2)-VASC as a stroke risk scale and empowerment of ED physicians is a must to improve this gap in care.
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- 2021
5. COMT gene polymorphism and corpus callosum morphometry in preterm born adults.
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Anirban Dutt, Madiha Shaikh, Taposhri Ganguly, Chiara Nosarti, Muriel Walshe, Maria Arranz, Larry Rifkin, Colm McDonald, Christopher A. Chaddock, Philip K. McGuire, Robin M. Murray, Elvira Bramon, and Matthew P. G. Allin
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- 2011
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6. Characteristics and Prognosis of Patients Who Receive Noninvasive Ventilation and Present Limitation of Life Support Treatment: The LLST-NIVCat Multicenter Cohort Study
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Olivia García-Trallero, Javier Jacob, Francesc López i Vengut, Mariona Sancho-Ramoneda, Àngels Lopez, Jose Ramon Cousiño-Chao, Ma Carmen Navarro-Sáez, Maria Arranz, José Zorrilla, Jaume Farré-Cerdà, Xavier López-Altimiras, and Antonio German
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medicine.medical_specialty ,Exacerbation ,Cohort Studies ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Aged ,COPD ,Noninvasive Ventilation ,business.industry ,Hazard ratio ,030208 emergency & critical care medicine ,Odds ratio ,Emergency department ,Prognosis ,medicine.disease ,Confidence interval ,Spain ,Cohort ,Emergency Medicine ,Respiratory Insufficiency ,business ,Cohort study - Abstract
Background Patients who receive noninvasive ventilation (NIV) in the emergency department (ED) sometimes have a limitation of life support treatment (LLST). The characteristics and prognosis in these patients may be worse, however, few studies have been carried out in this respect. Objective Analyze the differences between patients receiving NIV in the ED with LLST (NIV-LLST) or without LLST (NIV-noLLST) and their impact on in-hospital mortality, as well as investigate in-hospital mortality in the NIV-LLST group. Method We performed a secondary analysis of data from the NIVCat registry. This was a prospective, multicenter, analytical cohort study with consecutive inclusion of patients receiving NIV from February to March 2015 in 11 hospital EDs in Spain. Data on the baseline characteristics, the acute episode, and final patient destination were collected. The dependent variable was all-cause in-hospital mortality. Results We analyzed 152 cases receiving NIV, 66 (43.4%) of whom had NIV-LLTS. Age ≥ 75 years was associated with NIV-LLST. In-hospital mortality was higher in the NIV-LLST group, with an adjusted hazard ratio of 2.50 (95% confidence interval [CI] 1.03–6.06). Patients with NIV-LLST presenting an exacerbation of chronic obstructive pulmonary disease (COPD) presented the lowest mortality, with an odds ratio of 0.27 (95% confidence interval 0.08–0.93), compared with the remaining patients. Conclusion In our cohort of patients receiving NIV in the ED, the presence of LLST is frequent and is associated with high hospital mortality. The NIV-LLST patients with a COPD exacerbation have a better prognosis than NIV-LLST patients with other diseases.
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- 2020
7. Association study of polymorphisms within inflammatory genes and methylation status in treatment response in major depression
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Metodi Draganov, Javier de Diego-Adeliño, Míriam Jubero, Juliana Salazar, Maria J. Portella, Maria Arranz, Cristina Gallego-Fabrega, and Mar Carceller-Sindreu
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Interleukin-1beta ,Single-nucleotide polymorphism ,Treatment response ,Methylation status ,Logistic regression ,Methylation ,Polymorphism, Single Nucleotide ,Biomarkers, Pharmacological ,03 medical and health sciences ,0302 clinical medicine ,Inflammatory genes ,Internal medicine ,medicine ,Major depression ,Humans ,Allele ,Depressive Disorder, Major ,business.industry ,Haplotype ,Middle Aged ,medicine.disease ,Receptors, Interleukin-6 ,Antidepressive Agents ,Pharmacogenomic Testing ,030227 psychiatry ,Psychiatry and Mental health ,Treatment Outcome ,CpG site ,Major depressive disorder ,Female ,business ,030217 neurology & neurosurgery ,Pharmacogenetics - Abstract
Background:Although pharmacogenetics for major depressive disorder (MDD) is gaining momentum, the role of genetics in differences in response to antidepressant treatment is controversial, as they depend on multifactorial and polygenic phenotypes. Previous studies focused on the genes of the serotonergic system, leaving apart other pathological factors such as the inflammatory pathway. The main objective of the study was to assess whether treatment response might be associated with specific inflammation-related genetic variants or their methylation status.Methods:41 SNPs in 8 inflammatory genes: interleukin (IL) 1-β, IL2, IL6, IL6R, IL10, IL18, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were genotyped in 153 patients with MDD, who were evaluated with the Mausdley Staging Method to determine treatment response profiles. Pyrosequencing reactions and methylation quantification were performed in a PyroMark Q24 in 5 selected CpG islands of IL1- β, IL6 and IL6R. Linear and logistic regression analyses were conducted, including age and gender as covariates using PLINK 1.07.Results:Allelic distribution of IL1- β rs1143643 was significantly associated with MSM scores (FDR corrected p = 0.04). Allelic distribution of IL6R rs57569414 showed a trend towards significance with MSM scores (p = 0.002; FDR corrected p = 0.07). Haplotype analyses showed associations between allelic combinations of IL1-β and IL10 with treatment response (FDR corrected p < 0.01). Methylation percentage of treatment responders was only higher in an IL6R CpG island (p < 0.05).Conclusions:These exploratory findings suggest that IL1-β and, marginally, IL6R polymorphisms may affect treatment response in major depression. If confirmed, these results may account for the heterogeneous phenotypes of major depression that underlie differences in treatment response.
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- 2019
8. Clinical impact and cost-effectiveness of hepatitis C testing in an emergency department in Barcelona, Spain
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Jordi Llaneras, Ana Barreira, Ariadna Rando-Segura, Raquel Domínguez-Hernández, Francisco Rodríguez-Frías, Magda Campins, Miguel Ángel Casado, Mar Riveiro Barciela, Maria Arranz, Rafael Esteban, and Maria Buti
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Hepatology - Published
- 2022
9. A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex
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Jakob Grove, Eric Courchesne, Caitlin E. Carey, Adam X. Maihofer, Maria Arranz, Danny Antaki, Caroline M. Nievergelt, Jonathan Sebat, Elise B. Robinson, A. Hervas, M. Klein, Oanh Hong, A. Muotria, J. Guevara, Karen Pierce, C. Corsello, Lilia M. Iakoucheva, and Joseph G. Gleeson
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Correlation ,Genetics ,Genetic etiology ,Autism spectrum disorder ,mental disorders ,medicine ,Autism ,Polygenic risk score ,Biology ,Genetic risk ,medicine.disease ,Phenotype ,De novo mutations - Abstract
The genetic etiology of autism spectrum disorder (ASD) is multifactorial with contributions from rare variants, polygenic risk, and sex. How combinations of factors determine risk for ASD is unclear. In 11,313 ASD families (N = 37,375 subjects), we investigated the effects rare and polygenic risk individually and in combination. We show that genetic liability for ASD differs by sex, with females having a greater polygenic load, and males having a lower liability threshold as evident by a negative correlation of rare and polygenic risk. Multiple genetic factors were associated with differing sets of behavioral traits with effects that differed by sex. Furthermore, the correlation of parental age with genetic risk for ASD was attributable tode novomutations and sex-biased effects of inherited risk in parents. Our results demonstrate that a phenotypic spectrum of ASD is attributable to the relative loadings and gene-by-sex effects of rare and common variation.
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- 2021
10. El delantal y la maza : Feminismos desde la cocina
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María Arranz and María Arranz
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El delantal y la maza: dos utensilios que forman parte del paisaje doméstico. También dos caras de ese lugar lleno de contradicciones para las mujeres como es la cocina. Por un lado, ha sido un espacio de sometimiento lleno de ideales opresivos de los que escapar; por otro, un territorio para el encuentro, para la creatividad y la resistencia. En este ensayo, la periodista María Arranz indaga en el complejo vínculo que ha existido y sigue existiendo entre la teoría feminista y la cocina, porque «si las mujeres nos hemos pasado tanto tiempo metidas en una, buena parte de nuestra historia está ahí, así que vale la pena asomarnos a ella a través de las distintas perspectivas que nos brinda el feminismo». Una mirada retrospectiva, pero aún vigente, sobre la relación entre cocina, género y raza, y su reflejo en algunas de las manifestaciones artísticas firmadas por mujeres que ofrecieron nuevas formas de entender lo cotidiano en la segunda mitad del siglo XX.
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- 2024
11. A genome-wide methylation study reveals X chromosome and childhood trauma methylation alterations associated with borderline personality disorder
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Cristina Gallego-Fabrega, Juan C. Pascual, Ana Martín-Blanco, Joaquim Soler, Daniel Vega, Juliana Salazar, Elisabet Domínguez-Clavé, Laia Briones-Buixassa, Maria Arranz, and Matilde Elices
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Male ,Oncology ,medicine.medical_specialty ,X Chromosome ,Article ,Epigenesis, Genetic ,lcsh:RC321-571 ,Cellular and Molecular Neuroscience ,Borderline Personality Disorder ,Internal medicine ,mental disorders ,medicine ,Humans ,Clinical genetics ,Epigenetics ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Borderline personality disorder ,Biological Psychiatry ,X chromosome ,biology ,business.industry ,Methylation ,Epigenome ,DNA Methylation ,medicine.disease ,DNA-Binding Proteins ,Psychiatry and Mental health ,CpG site ,DNA methylation ,biology.protein ,TAP2 ,CpG Islands ,Female ,Psychiatric disorders ,business - Abstract
Borderline personality disorder (BPD) is a severe and highly prevalent psychiatric disorder, more common in females than in males and with notable differences in presentation between genders. Recent studies have shown that epigenetic modifications such as DNA methylation may modulate gene × environment interactions and impact on neurodevelopment. We conducted an epigenome wide study (Illumina Infinium HumanMethylation450k beadchip) in a group of BPD patients with (N = 49) and without (N = 47) childhood traumas and in a control group (N = 44). Results were confirmed in a replication cohort (N = 293 BPD patients and N = 114 controls) using EpiTYPER assays. Differentially methylated CpG sites were observed in several genes and intragenic regions in the X chromosome (PQBP1, ZNF41, RPL10, cg07810091 and cg24395855) and in chromosome 6 (TAP2). BPD patients showed significantly lower methylation levels in these CpG sites than healthy controls. These differences seemed to be increased by the existence of childhood trauma. Comparisons between BPD patients with childhood trauma and patients and controls without revealed significant differences in four genes (POU5F1, GGT6, TNFRSF13C and FAM113B), none of them in the X chromosome. Gene set enrichment analyses revealed that epigenetic alterations were more frequently found in genes controlling oestrogen regulation, neurogenesis and cell differentiation. These results suggest that epigenetic alterations in the X chromosome and oestrogen-regulation genes may contribute to the development of BPD and explain the differences in presentation between genders. Furthermore, childhood trauma events may modulate the magnitude of the epigenetic alterations contributing to BPD.
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- 2021
12. Pharmacogenetics of antipsychotics: Clinical utility and implementation
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Marta Hernandez, Maria Arranz, and Juliana Salazar
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0303 health sciences ,Candidate gene ,CYP2D6 ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,CYP2C19 ,Bioinformatics ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Pharmacogenetics ,Pharmacogenomics ,Medicine ,Humans ,Medical prescription ,Precision Medicine ,business ,Antipsychotic ,030217 neurology & neurosurgery ,030304 developmental biology ,Genetic testing ,Antipsychotic Agents - Abstract
Decades of research have produced extensive evidence of the contribution of genetic factors to the efficacy and toxicity of antipsychotics. Numerous genetic variants in genes controlling drug availability or involved in antipsychotic processes have been linked to treatment variability. The complex mechanism of action and multitarget profile of most antipsychotic drugs hinder the identification of pharmacogenetic markers of clinical value. Nevertheless, the validity of associations between variants in CYP1A2, CYP2D6, CYP2C19, ABCB1, DRD2, DRD3, HTR2A, HTR2C, BDNF, COMT, MC4R genes and antipsychotic response has been confirmed in independent candidate gene studies. Genome wide pharmacogenomic studies have proven the role of the glutamatergic pathway in mediating antipsychotic activity and have reported novel associations with antipsychotic response. However, only a limited number of the findings, mainly functional variants of CYP metabolic enzymes, have been shown to be of clinical utility and translated into useful pharmacogenetic markers. Based on the currently available information, actionable pharmacogenetics should be reduced to antipsychotics' dose adjustment according to the genetically predicted metabolic status (CYPs' profile) of the patient. Growing evidence suggests that such interventions will reduce antipsychotics' side-effects and increase treatment safety. Despite this evidence, the use of pharmacogenetics in psychiatric wards is minimal. Hopefully, further evidence on the clinical and economic benefits, the development of clinical protocols based on pharmacogenetic information, and improved and cheaper genetic testing will increase the implementation of pharmacogenetic guided prescription in clinical settings.
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- 2020
13. Autism risk in offspring can be assessed through quantification of male sperm mosaicism
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Javiera Uribe Fenner, Andrea B. Moffitt, William M. Brandler, Kiely N. James, Danny Antaki, Melissa Gymrek, Sara A. Wirth, An Nguyen, Jing Gu, Camila Araújo Bernardino Garcia, Renee D. George, Renatta Knox, Xiaoxu Yang, Martin W. Breuss, Joseph G. Gleeson, Jennifer McEvoy-Venneri, Orrin Devinsky, Zihua Wang, Evan Sticca, Amaia Hervás, Madhusudan Gujral, Jonathan Sebat, Maria Cárcel Pérez, Martha Cristina Cancino Botello, Maria Arranz, Damir Musaev, Morgan L. Kleiber, Oanh Hong, Ileena Mitra, and Laurel L. Ball
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0301 basic medicine ,Male ,Offspring ,Genetic counseling ,Intellectual and Developmental Disabilities (IDD) ,Autism ,Immunology ,Germline mosaicism ,Biology ,Polymorphism, Single Nucleotide ,Medical and Health Sciences ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Polymorphism (computer science) ,Recurrence ,Risk Factors ,medicine ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Autistic Disorder ,Polymorphism ,Aetiology ,Genetic testing ,Pediatric ,medicine.diagnostic_test ,Mosaicism ,Contraception/Reproduction ,Human Genome ,Chromosome ,General Medicine ,DNA ,Single Nucleotide ,medicine.disease ,Serious Mental Illness ,Sperm ,Spermatozoa ,Pedigree ,Brain Disorders ,030104 developmental biology ,Mental Health ,030220 oncology & carcinogenesis ,Mutation ,Female - Abstract
De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessing parental gonadal mosaicism has not been considered. We measured sperm mosaicism using deep-whole-genome sequencing, for variants both present in an offspring and evident only in father's sperm, and identified single-nucleotide, structural and short tandem-repeat variants. We found that mosaicism quantification can stratify autism spectrum disorders recurrence risk due to de novo mutations into a vast majority with near 0% recurrence and a small fraction with a substantially higher and quantifiable risk, and we identify novel mosaic variants at risk for transmission to a future offspring. This suggests, therefore, that genetic counseling would benefit from the addition of sperm mosaicism assessment.
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- 2020
14. Polymorphisms in the IL1-b gene are associated with increased Glu and Glx levels in treatment-resistant depression
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Maria J. Portella, Yolanda Vives-Gilabert, Dolors Puigdemont, Aina Àvila-Parcet, Míriam Jubero, Javier de Diego-Adeliño, Metodi Draganov, and Maria Arranz
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medicine.medical_specialty ,Polymorphism, Genetic ,Depression ,Interleukin 1 family ,business.industry ,Glutamine ,Interleukin-1beta ,Neuroscience (miscellaneous) ,Glutamate receptor ,Glutamic Acid ,medicine.disease ,Psychiatry and Mental health ,Endocrinology ,Inflammatory genes ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Treatment-resistant depression ,Glutamate ,business ,Gene ,Spectroscopy - Published
- 2021
15. 48. A PHENOTYPIC SPECTRUM OF AUTISM IS ATTRIBUTABLE TO THE COMBINED EFFECTS OF RARE VARIANTS, POLYGENIC RISK AND SEX
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J. Guevara, Joseph G. Gleeson, Caroline M. Nievergelt, Karen Pierce, A. Hervas, Caitlin E. Carey, Oanh Hong, Eric Courchesne, Jane I. Grove, Danny Antaki, Maria Arranz, Marieke Klein, Elise B. Robinson, Jonathan Sebat, Lilia M. Iakoucheva, C. Corsello, Adam X. Maihofer, and Alysson R. Muotri
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Pharmacology ,Genetics ,Psychiatry and Mental health ,Neurology ,medicine ,Autism ,Pharmacology (medical) ,Polygenic risk score ,Neurology (clinical) ,Biology ,medicine.disease ,Phenotype ,Biological Psychiatry - Published
- 2021
16. General Characteristics and Activity of Emergency Department Short-Stay Units in Spanish Hospitals
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Ferran Llopis, Mikel Martínez-Ortiz, José Carlos Núñez, Antonio Porras, Mª Aurora Rua, Alfonso Martín, Antoni Juan, Antonio Ferreira, Ana Álvarez, Amadeo Almela, Luis Lapuerta, C. Ferre, Pere Serra, Juan Anduiza, José A. llull, Javier González-Spinola San Gil, Victor L. Perez, Pere Llorens, Federico Guerrero, Josep Maria Guardiola, Pedro M. Valentín, Ricardo Juárez, Maria Arranz, Carmen Navarro, Francesc Sanpedro, Emilia Barrot Cortés, Gonzalo Sempere, Manuel Daza, Carlos A. Castro, Marta Guzmán, and Francisco Javier Martín-Sánchez
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Adult ,Male ,medicine.medical_specialty ,Exacerbation ,03 medical and health sciences ,Patient Admission ,0302 clinical medicine ,Surveys and Questionnaires ,medicine ,Humans ,030212 general & internal medicine ,Management practices ,Aged ,Aged, 80 and over ,Respiratory tract infections ,business.industry ,030208 emergency & critical care medicine ,Emergency department ,Overcrowding ,Length of Stay ,Middle Aged ,Readmission rate ,medicine.disease ,Hospitals ,Cross-Sectional Studies ,Crowding ,Short stay ,Spain ,Emergency medicine ,Emergency Medicine ,Female ,Christian ministry ,Medical emergency ,Emergency Service, Hospital ,business - Abstract
Background Emergency Department (ED) overcrowding mainly due to the lack of access to inpatient beds negatively affects safety and quality of care. Implementation of ED short-stay units (EDSSUs) may help to mitigate this situation. Objectives To describe the general characteristics and evaluate the activity of EDSSUs in Spanish hospitals. Methods This is a cross-sectional study. A questionnaire was sent to coordinators responsible for the EDSSUs identified among Spanish hospitals appearing on the Ministry of Health Web page. Data regarding structure, caseloads, and clinical management practices were collected. Results Among the 591 hospitals surveyed, 35 EDSSUs (5.9%) were identified and 23 participated in the study. Admissions to EDSSUs over different periods in 2011 were assessed: 12-month activity in 17 EDSSUs and between 5 and 10.5 months in six EDSSUs. A total of 25,568 patients with a mean age of 67.2 ± 9.8 years were admitted, representing between 6% and 16.3% of hospital admissions from the ED. The most frequent diagnoses were acute heart failure, chronic obstructive pulmonary disease exacerbation, and urinary and respiratory tract infections. The average length of stay (LOS) was 2.6 ± 1.1 days (range 1.2–5.3), in-hospital mortality 0.59% (range 0–2.68), and the 30-day readmission rate after discharge was 6.7% (range 0–14.6). Conclusions To date, only a few Spanish hospitals have implemented EDSSUs. Prevalent infections and exacerbation of chronic conditions are the most frequent causes for admission. Considering LOS, 30-day readmission rate and mortality, EDSSUs appear to be safe and effective and might be considered a tool to alleviate ED overcrowding.
- Published
- 2017
17. A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments
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Rosa Catalán, Laura Ibanez, Jorge A. Cervilla, Rafael Penadés, Juliana Salazar, Maria Arranz, Mercè Brunet, Blanca Gutiérrez, Bárbara Arias, A. González-Rodríguez, and Josefina Perez-Blanco
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Male ,0301 basic medicine ,medicine.medical_treatment ,Psychological intervention ,0302 clinical medicine ,Outcome Assessment, Health Care ,Antipsychotic drugs ,Precision Medicine ,Clozapine ,Schizophrenia, Paranoid ,Middle Aged ,Psychiatry and Mental health ,Safety profile ,Cytochrome P-450 CYP2D6 ,Mental illness ,Teràpia genètica ,Female ,Antipsychotic Agents ,medicine.drug ,Adult ,CYP2D6 ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,CYP2C19 ,Article ,lcsh:RC321-571 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Gene therapy ,Cytochrome P-450 CYP1A2 ,Internal medicine ,Intervention (counseling) ,medicine ,Humans ,Clinical genetics ,Antipsychotic ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Biological Psychiatry ,Polymorphism, Genetic ,business.industry ,Personalized medicine ,Cytochrome P-450 CYP2C19 ,030104 developmental biology ,Psychotic Disorders ,Pharmacogenetics ,Schizophrenia ,Antipsicòtics ,Malalties mentals ,business ,030217 neurology & neurosurgery - Abstract
Antipsychotic drugs fail to achieve adequate response in 30–50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG−, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG−), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG− patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG− clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes., This research was funded by grants from the Institute Carlos III (FIS PI11/02006; FIS PI16/01029). A.G.-R. was partially funded by a private grant from the Jové family. Genotyping was partially conducted by the CEGEN-PRB2-ISCIII node, which is supported by grant PT13/001, ISCIIISGEFI/ FEDER.
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- 2019
18. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
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Laura M. Thornton, Paul Lichtenstein, Verneri Anttila, Diego Albani, Josep Antoni Ramos-Quiroga, Roger A.H. Adan, Monika Schlögelhofer, Stephen Sanders, Enrique Castelao, Klaus Berger, Nina Dalkner, Urs Heilbronner, Engilbert Sigurdsson, Pablo Mir, Fuquan Zhang, James T.R. Walters, Patrick F. Sullivan, Fragiskos Gonidakis, F. Kyle Satterstrom, Sara Marsal, Per Hoffmann, Amy Perry, Valentina Ciullo, Beate Herpertz-Dahlmann, Catharina Lavebratt, Kieran C. Murphy, Tammy Hedderly, Hyun Ju Hong, Evald Saemundsen, Sascha B. Fischer, Hailiang Huang, Andrew D. Grotzinger, Nienke Vulink, Murray B. Stein, Mark A. Frye, Laura J. Scott, David Curtis, Todd Lencz, Janiece E. DeSocio, Richard A. Belliveau, Eduard Vieta, Andrea Dietrich, Wade H. Berrettini, Kenneth S. Kendler, Marquis P. Vawter, Paul S. Nestadt, Michael E. Talkowski, Manuel Mattheisen, Ingrid Agartz, Elisa Docampo, Bernhard T. Baune, Stefan Ehrlich, Jolanta Lissowska, Felecia Cerrato, Terje Nærland, Robin M. Murray, Jennifer Reichert, Annette M. Hartmann, Hannelore Ehrenreich, Howard J. Edenberg, Katherine A. Halmi, Qingqin S. Li, Peristera Paschou, Marie Bækvad-Hansen, Esther Walton, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Frank Bellivier, Jungeun Song, D. Blake Woodside, Young Shin Kim, Jochen Seitz, Jacques Pantel, Palmiero Monteleone, Erika L. Nurmi, Rodney J. Scott, Kang Sim, Ekaterina A. Khramtsova, Udo Dannlowski, Rolf Adolfsson, Danielle Posthuma, Melissa J. Green, Laura Ibanez-Gomez, Jakob Grove, Elvira Bramon, Gregory L. Hanna, Cynthia M. Bulik, Yiran Guo, Stephan Ripke, Mary M. Robertson, Harald N. Aschauer, Adebayo Anjorin, Joanna Martin, Bertram Müller-Myhsok, Deborah Kaminská, Jose Guzman-Parra, Benedetta Nacmias, Erik G. Jönsson, Jonathan R. I. Coleman, Douglas F. Levinson, Hamdi Mbarek, Gun Peggy Knudsen, Karin Egberts, Mette Nyegaard, Patrik K. E. Magnusson, Mark Adams, Douglas Blackwood, Elisabeth B. Binder, Marcus Ising, Anna R. Docherty, Jim van Os, Nese Direk, Lina Martinsson, Maria Arranz, Christel M. Middeldorp, Stefan Kloiber, Sintia Iole Belangero, Eske M. Derks, Ingrid Melle, Erlend Bøen, Jan Haavik, Federica Piras, Unna N. Danner, Anil K. Malhotra, Gerome Breen, Stephen V. Faraone, Amanda B Zheutlin, Timothy Poterba, Stephan Ruhrmann, Inge Joa, Ulrik Fredrik Malt, Sarah E. Bergen, Federica Tozzi, Lauren A. Weiss, Hana Papezova, Dominic Holland, Elliot S. Gershon, Jaakko Kaprio, Merete Nordentoft, Scott D. Gordon, Christopher Pittenger, Keun-Ah Cheon, Jennifer Jordan, Philip Gorwood, Myrna M. Weissman, Preben Bo Mortensen, Melissa A. Munn-Chernoff, Isobel Heyman, Eun-Young Shin, Christie L. Burton, Katherine Gordon-Smith, Sietske G. Helder, Peter Nagy, Till F. M. Andlauer, Yunpeng Wang, Young Key Kim, Kate Langley, Søren Dalsgaard, Richard Delorme, Torbjørn Elvsåshagen, Bennett L. Leventhal, Giovanni Gambaro, Christos Androutsos, Jennifer Tübing, Marion Roberts, Annelie Nordin Adolfsson, Hakon Hakonarson, Dorothy E. Grice, Vaughan J. Carr, Konstantinos Tziouvas, Stephanie Zerwas, Cathy L. Barr, Michael Conlon O'Donovan, Per Qvist, Beate St Pourcain, Samuel Kuperman, Leila Karhunen, Jack Samuels, Markus M. Nöthen, Martien J H Kas, Alfonso Tortorella, Mikael Landén, Jennifer Crosbie, Marco A. Grados, Joanna M. Biernacka, Paul D. Arnold, Irene A. Malaty, Jurjen J. Luykx, Nicholas Bass, Naomi R. Wray, Catharina A. Hartman, Christina M. Hultman, Michael S. Okun, Brandon Wormley, Michael Bauer, Daniel J. Smith, Ian Jones, Kathryn Roeder, Brien P. Riley, Caroline M. Nievergelt, Katrin Gade, Sarah Kittel-Schneider, Roy H. Perlis, James R. Mitchell, Ziarih Hawi, James Lee, Liz Forty, William E. Bunney, Thomas Damm Als, Catherine Schaefer, Digby Quested, Matteo Cassina, Anna C. Koller, Patrick Turley, Agnes A. Steixner, Anu Raevuori, Assen Jablensky, Peter Holmans, Dong-Ho Song, S. Evelyn Stewart, Jan K. Buitelaar, Fernando S. Goes, Alexander Münchau, Ayman H. Fanous, Nicolas Ramoz, James B. Potash, Monica Gratacos Mayora, Tobias Banaschewski, Céline S. Reinbold, Renata Rizzo, Arianna Di Florio, Lenka Foretova, Gianfranco Spalletta, Aarno Palotie, Eleftheria Zeggini, Lawrence W. Brown, Julie K. O'Toole, Lynn E. DeLisi, Ulrich Schall, Mary Roberson, Barbara J. Coffey, Bryan J. Mowry, Murray J. Cairns, Dan J. Stein, Glyn Lewis, Marta Ribasés, C. Robert Cloninger, Bettina Konte, John B. Vincent, Duncan S. Palmer, Radhika Kandaswamy, Christine Ladd-Acosta, Lars Alfredsson, Frank Visscher, Ulrike Schmidt, Aiden Corvin, Susan L. Santangelo, Brenda W.J.H. Penninx, David J. Porteous, Tetsuya Ando, Arne E. Vaaler, Bru Cormand, Laura Carlberg, Claire Churchhouse, Manfred Stuhrmann, Niamh Mullins, Christine Søholm Hansen, Cathy L. Budman, Hartmut Imgart, Dan E. Arking, James J. McGough, Michael Gill, Christel Depienne, Roland Burghardt, Antonio Julià, Anders M. Dale, Sven Sandin, Katharina Domschke, Maria Grigoroiu-Serbanescu, Susana Jiménez-Murcia, Marianne Giørtz Pedersen, Zsanett Tarnok, Gisli Baldursson, Michele T. Pato, David M. Hougaard, Thorgeir E. Thorgeirsson, Katharina Bey, Kerstin J. Plessen, Margaret A. Richter, Ole A. Andreassen, Claudine Laurent-Levinson, Leonid Padyukov, Jacques Mallet, Daniela Degortes, John R. Kelsoe, Robert D. Levitan, Andreas Reif, Chaim Huyser, Derek W. Morris, Sina Wanderer, William Byerley, Edna Grünblatt, E.J.C. de Geus, Hyejung Won, Josephine Elia, Rudolf Uher, Jay A. Tischfield, Andreas Karwautz, Gustavo Turecki, Pieter J. Hoekstra, Dorret I. Boomsma, Jacob Rosenthal, Daniele Cusi, Michael C. Neale, Sara Mostafavi, Gwyneth Zai, F. Anthony O'Neill, Gary Donohoe, Karola Rehnström, Harry Brandt, Helena Gaspar, Francis J. McMahon, H-Erich Wichmann, Andrew W. Bergen, Giovanni Coppola, Lea K. Davis, Lenka Slachtova, Olav B. Smeland, Erin C. Dunn, Nicholas G. Martin, Allan L. Naarden, Jo Knight, Cristina Sánchez-Mora, Masashi Ikeda, Lorraine Southam, Sandro Sorbi, Barbara Franke, Martin Schalling, Russell Schachar, Yen-Chen Anne Feng, Kirsten R. Müller-Vahl, André Scherag, Zhaozhong Zhu, Eric A. Storch, Páll Magnússon, David Cohen, Olafur O Gudmundsson, Harvey S. Singer, Brian Kelly, Jonas Bybjerg-Grauholm, Blanca Garcia-Delgar, Thomas Hansen, Carmel M. Loughland, Christine Lochner, Stacy Steinberg, Martin Woods, Jorge A. Quiroz, Raquel Rabionet, Alden Y. Huang, Janice M. Fullerton, María Soler Artigas, Hans J. Grabe, Philip Asherson, Margit Burmeister, Alicia R. Martin, Martin A. Kennedy, Janet Treasure, Anders D. Børglum, Eva C. Schulte, Andreas Hartmann, Frans Henskens, Youl-Ri Kim, Jens Treutlein, Joanna Hauser, Manfred M. Fichter, Damiaan Denys, Ann E. Pulver, Kelly L. Klump, Paul Sandor, Michael Wagner, Philippe Courtet, Sandra Van der Auwera, Susanne Lucae, Eystein Stordal, Michel G. Nivard, Maurizio Clementi, Astrid Morer, Philip B. Mitchell, Huda Akil, Edwin H. Cook, Jennifer L. Moran, Donald W. Black, Jeremiah M. Scharf, Jana Strohmaier, Colm McDonald, Meg M.-J. Wang, Richard M. Myers, Stephanie Godard, Pablo V. Gejman, Athanasios Maras, Marcella Rietschel, Nancy G. Buccola, Konstantinos Hatzikotoulas, Dalila Pinto, Jouke-Jan Hottenga, Kari Stefansson, James S. Sutcliffe, Andres Metspalu, Amaia Hervás, Joel Gelernter, Wolfgang Herzog, Paula Rovira, Gunnar Morken, Tara Murphy, Mark Weiser, Vincent Millischer, Frank Dudbridge, Dan Rujescu, Vladimir Bencko, Valdo Ricca, Kimberly Chambert, Guy A. Rouleau, James J. Crowley, Thomas G. Schulze, Toni-Kim Clarke, Triinu Peters, Gudrun Wagner, Daniel A. Geller, Henry R. Kranzler, G. Bragi Walters, Vera Golimbet, Clement C. Zai, Nigel Williams, Andreas Birgegård, Joseph D. Buxbaum, Elliot M. Tucker-Drob, Jerome C. Foo, Tracey L. Petryshen, Daniel P. Howrigan, Hunna J. Watson, Franziska Degenhardt, Peter R. Schofield, Jesper Buchhave Poulsen, Stefan Herms, Johannes Hebebrand, Mario Maj, George Kirov, Fabrizio Piras, Sara McDevitt, James T. McCracken, Carol A. Mathews, Michael John Owen, Peter Falkai, Donald L. Gilbert, Enda M. Byrne, Fernando Fernández-Aranda, Csaba Barta, Stéphane Jamain, Jubao Duan, Dongmei Yu, Danielle C. Cath, Ole Mors, Sigrun Hope, Laramie E. Duncan, Alan R. Sanders, Sang-Yun Oh, Carsten Bøcker Pedersen, Henning Tiemeier, Roseann E. Peterson, Raymond K. Walters, Margarita C T Slof-Op 't Landt, Madeline Alexander, Stephanie Le Hellard, Ina Giegling, Annemarie A. van Elburg, Steven P. Hamilton, Vesna Boraska Perica, Thomas V. Fernandez, Danielle M. Dick, Francesco Bettella, Roel A. Ophoff, Grant W. Montgomery, Gerald Nestadt, Nakao Iwata, Jessica H. Baker, Walter H. Kaye, Jeremy M. Silverman, Mark J. Daly, Robert A. King, Sarah E. Medland, Anastasios Konstantinidis, Robert D. Oades, Samuel H. Zinner, Steven Crawford, Daniel H. Geschwind, Patrick W. L. Leung, Martin Alda, Marie Navratilova, Pak C. Sham, Paul A. Tooney, Tian Ge, Veit Roessner, Martin Preisig, Thomas Werge, Eli A. Stahl, David A. Collier, Stephanie H. Witt, Dermot Walsh, Miquel Casas, Anna Keski-Rahkonen, Jane H. Christensen, Silvia De Rubeis, Giorgio Pistis, Sven Cichon, Bruno Etain, Dominique Campion, O. Joseph Bienvenu, Christian Dina, Manolis Kogevinas, Thomas Espeseth, Benjamin M. Neale, Ditte Demontis, Klaus-Peter Lesch, Marina Mitjans, Tiffany A. Greenwood, Marcos Madruga-Garrido, Sibylle G. Schwab, Oedegaard Ketil Joachim, Hreinn Stefansson, Sara A. Paciga, Monica Forzan, Dieter B. Wildenauer, Lena Backlund, A. Jeremy Willsey, Carlos N. Pato, Nicholas John Craddock, Inge A. Meijer, Sandra K. Loo, Filip Rybakowski, Tracey D. Wade, Scott J. Crow, Bernard Lerer, Valsamma Eapen, Esben Agerbo, Andrew M. McIntosh, Luis Augusto Rohde, Susan L. McElroy, Stephan Zipfel, Peter P. Zandi, Cathryn M. Lewis, Lars Klareskog, Martin Begemann, Phil Lee, Richard Anney, Mark A. Bellgrove, Lisa Jones, Andreas J. Forstner, Agnieszka Słopień, Hilary Coon, Dong Li, Alessandro Serretti, Carsten Horn, Christos Pantelis, Ryan L. Collins, David M. Howard, Lucía Colodro-Conde, Pippa A. Thomson, Martin Hautzinger, Alysa E. Doyle, Julie Hagstrøm, Oliver S. P. Davis, Karen S. Mitchell, Jordan W. Smoller, Michael Strober, John I. Nurnberger, Andrea G. Ludolph, Monika Budde, Anna Maaser, Lambertus Klei, Aribert Rothenberger, Yulia Worbe, Fabian Streit, James L. Kennedy, Barbara E. Stranger, Ashley Dumont, Jianxin Shi, Dale R. Nyholt, Craig Johnson, Jonna Kuntsi, Yun-Joo Koh, Loes M. Olde Loohuis, Robert B. Freedman, Anke Hinney, Susanne Walitza, Enrico Domenici, Margarita Rivera, Sodahm Kook, Erica Greenberg, Tetyana Zayats, Josef Frank, Gary A. Heiman, Andrew McQuillin, Abraham Reichenberg, Piotr M. Czerski, Humberto Nicolini, Lee P.H., Anttila V., Won H., Feng Y.-C.A., Rosenthal J., Zhu Z., Tucker-Drob E.M., Nivard M.G., Grotzinger A.D., Posthuma D., Wang M.M.-J., Yu D., Stahl E.A., Walters R.K., Anney R.J.L., Duncan L.E., Ge T., Adolfsson R., Banaschewski T., Belangero S., Cook E.H., Coppola G., Derks E.M., Hoekstra P.J., Kaprio J., Keski-Rahkonen A., Kirov G., Kranzler H.R., Luykx J.J., Rohde L.A., Zai C.C., Agerbo E., Arranz M.J., Asherson P., Baekvad-Hansen M., Baldursson G., Bellgrove M., Belliveau R.A., Buitelaar J., Burton C.L., Bybjerg-Grauholm J., Casas M., Cerrato F., Chambert K., Churchhouse C., Cormand B., Crosbie J., Dalsgaard S., Demontis D., Doyle A.E., Dumont A., Elia J., Grove J., Gudmundsson O.O., Haavik J., Hakonarson H., Hansen C.S., Hartman C.A., Hawi Z., Hervas A., Hougaard D.M., Howrigan D.P., Huang H., Kuntsi J., Langley K., Lesch K.-P., Leung P.W.L., Loo S.K., Martin J., Martin A.R., McGough J.J., Medland S.E., Moran J.L., Mors O., Mortensen P.B., Oades R.D., Palmer D.S., Pedersen C.B., Pedersen M.G., Peters T., Poterba T., Poulsen J.B., Ramos-Quiroga J.A., Reif A., Ribases M., Rothenberger A., Rovira P., Sanchez-Mora C., Satterstrom F.K., Schachar R., Artigas M.S., Steinberg S., Stefansson H., Turley P., Walters G.B., Werge T., Zayats T., Arking D.E., Bettella F., Buxbaum J.D., Christensen J.H., Collins R.L., Coon H., De Rubeis S., Delorme R., Grice D.E., Hansen T.F., Holmans P.A., Hope S., Hultman C.M., Klei L., Ladd-Acosta C., Magnusson P., Naerland T., Nyegaard M., Pinto D., Qvist P., Rehnstrom K., Reichenberg A., Reichert J., Roeder K., Rouleau G.A., Saemundsen E., Sanders S.J., Sandin S., St Pourcain B., Stefansson K., Sutcliffe J.S., Talkowski M.E., Weiss L.A., Willsey A.J., Agartz I., Akil H., Albani D., Alda M., Als T.D., Anjorin A., Backlund L., Bass N., Bauer M., Baune B.T., Bellivier F., Bergen S.E., Berrettini W.H., Biernacka J.M., Blackwood D.H.R., Boen E., Budde M., Bunney W., Burmeister M., Byerley W., Byrne E.M., Cichon S., Clarke T.-K., Coleman J.R.I., Craddock N., Curtis D., Czerski P.M., Dale A.M., Dalkner N., Dannlowski U., Degenhardt F., Di Florio A., Elvsashagen T., Etain B., Fischer S.B., Forstner A.J., Forty L., Frank J., Frye M., Fullerton J.M., Gade K., Gaspar H.A., Gershon E.S., Gill M., Goes F.S., Gordon S.D., Gordon-Smith K., Green M.J., Greenwood T.A., Grigoroiu-Serbanescu M., Guzman-Parra J., Hauser J., Hautzinger M., Heilbronner U., Herms S., Hoffmann P., Holland D., Jamain S., Jones I., Jones L.A., Kandaswamy R., Kelsoe J.R., Kennedy J.L., Joachim O.K., Kittel-Schneider S., Kogevinas M., Koller A.C., Lavebratt C., Lewis C.M., Li Q.S., Lissowska J., Loohuis L.M.O., Lucae S., Maaser A., Malt U.F., Martin N.G., Martinsson L., McElroy S.L., McMahon F.J., McQuillin A., Melle I., Metspalu A., Millischer V., Mitchell P.B., Montgomery G.W., Morken G., Morris D.W., Muller-Myhsok B., Mullins N., Myers R.M., Nievergelt C.M., Nordentoft M., Adolfsson A.N., Nothen M.M., Ophoff R.A., Owen M.J., Paciga S.A., Pato C.N., Pato M.T., Perlis R.H., Perry A., Potash J.B., Reinbold C.S., Rietschel M., Rivera M., Roberson M., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Serretti A., Sigurdsson E., Smeland O.B., Stordal E., Streit F., Strohmaier J., Thorgeirsson T.E., Treutlein J., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Wang Y., Witt S.H., Zandi P., Adan R.A.H., Alfredsson L., Ando T., Aschauer H., Baker J.H., Bencko V., Bergen A.W., Birgegard A., Perica V.B., Brandt H., Burghardt R., Carlberg L., Cassina M., Clementi M., Courtet P., Crawford S., Crow S., Crowley J.J., Danner U.N., Davis O.S.P., Degortes D., DeSocio J.E., Dick D.M., Dina C., Docampo E., Egberts K., Ehrlich S., Espeseth T., Fernandez-Aranda F., Fichter M.M., Foretova L., Forzan M., Gambaro G., Giegling I., Gonidakis F., Gorwood P., Mayora M.G., Guo Y., Halmi K.A., Hatzikotoulas K., Hebebrand J., Helder S.G., Herpertz-Dahlmann B., Herzog W., Hinney A., Imgart H., Jimenez-Murcia S., Johnson C., Jordan J., Julia A., Kaminska D., Karhunen L., Karwautz A., Kas M.J.H., Kaye W.H., Kennedy M.A., Kim Y.-R., Klareskog L., Klump K.L., Knudsen G.P.S., Landen M., Le Hellard S., Levitan R.D., Li D., Lichtenstein P., Maj M., Marsal S., McDevitt S., Mitchell J., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., O'Toole J.K., Padyukov L., Pantel J., Papezova H., Rabionet R., Raevuori A., Ramoz N., Reichborn-Kjennerud T., Ricca V., Roberts M., Rujescu D., Rybakowski F., Scherag A., Schmidt U., Seitz J., Slachtova L., Slof-Op't Landt M.C.T., Slopien A., Sorbi S., Southam L., Strober M., Tortorella A., Tozzi F., Treasure J., Tziouvas K., van Elburg A.A., Wade T.D., Wagner G., Walton E., Watson H.J., Wichmann H.-E., Woodside D.B., Zeggini E., Zerwas S., Zipfel S., Adams M.J., Andlauer T.F.M., Berger K., Binder E.B., Boomsma D.I., Castelao E., Colodro-Conde L., Direk N., Docherty A.R., Domenici E., Domschke K., Dunn E.C., Foo J.C., de. Geus E.J.C., Grabe H.J., Hamilton S.P., Horn C., Hottenga J.-J., Howard D., Ising M., Kloiber S., Levinson D.F., Lewis G., Magnusson P.K.E., Mbarek H., Middeldorp C.M., Mostafavi S., Nyholt D.R., Penninx B.W., Peterson R.E., Pistis G., Porteous D.J., Preisig M., Quiroz J.A., Schaefer C., Schulte E.C., Shi J., Smith D.J., Thomson P.A., Tiemeier H., Uher R., van der Auwera S., Weissman M.M., Alexander M., Begemann M., Bramon E., Buccola N.G., Cairns M.J., Campion D., Carr V.J., Cloninger C.R., Cohen D., Collier D.A., Corvin A., DeLisi L.E., Donohoe G., Dudbridge F., Duan J., Freedman R., Gejman P.V., Golimbet V., Godard S., Ehrenreich H., Hartmann A.M., Henskens F.A., Ikeda M., Iwata N., Jablensky A.V., Joa I., Jonsson E.G., Kelly B.J., Knight J., Konte B., Laurent-Levinson C., Lee J., Lencz T., Lerer B., Loughland C.M., Malhotra A.K., Mallet J., McDonald C., Mitjans M., Mowry B.J., Murphy K.C., Murray R.M., O'Neill F.A., Oh S.-Y., Palotie A., Pantelis C., Pulver A.E., Petryshen T.L., Quested D.J., Riley B., Sanders A.R., Schall U., Schwab S.G., Scott R.J., Sham P.C., Silverman J.M., Sim K., Steixner A.A., Tooney P.A., van Os J., Vawter M.P., Walsh D., Weiser M., Wildenauer D.B., Williams N.M., Wormley B.K., Zhang F., Androutsos C., Arnold P.D., Barr C.L., Barta C., Bey K., Bienvenu O.J., Black D.W., Brown L.W., Budman C., Cath D., Cheon K.-A., Ciullo V., Coffey B.J., Cusi D., Davis L.K., Denys D., Depienne C., Dietrich A., Eapen V., Falkai P., Fernandez T.V., Garcia-Delgar B., Geller D.A., Gilbert D.L., Grados M.A., Greenberg E., Grunblatt E., Hagstrom J., Hanna G.L., Hartmann A., Hedderly T., Heiman G.A., Heyman I., Hong H.J., Huang A., Huyser C., Ibanez-Gomez L., Khramtsova E.A., Kim Y.K., Kim Y.-S., King R.A., Koh Y.-J., Konstantinidis A., Kook S., Kuperman S., Leventhal B.L., Lochner C., Ludolph A.G., Madruga-Garrido M., Malaty I., Maras A., McCracken J.T., Meijer I.A., Mir P., Morer A., Muller-Vahl K.R., Munchau A., Murphy T.L., Naarden A., Nagy P., Nestadt G., Nestadt P.S., Nicolini H., Nurmi E.L., Okun M.S., Paschou P., Piras F., Pittenger C., Plessen K.J., Richter M.A., Rizzo R., Robertson M., Roessner V., Ruhrmann S., Samuels J.F., Sandor P., Schlogelhofer M., Shin E.-Y., Singer H., Song D.-H., Song J., Spalletta G., Stein D.J., Stewart S.E., Storch E.A., Stranger B., Stuhrmann M., Tarnok Z., Tischfield J.A., Tubing J., Visscher F., Vulink N., Wagner M., Walitza S., Wanderer S., Woods M., Worbe Y., Zai G., Zinner S.H., Sullivan P.F., Franke B., Daly M.J., Bulik C.M., McIntosh A.M., O'Donovan M.C., Zheutlin A., Andreassen O.A., Borglum A.D., Breen G., Edenberg H.J., Fanous A.H., Faraone S.V., Gelernter J., Mathews C.A., Mattheisen M., Mitchell K.S., Neale M.C., Nurnberger J.I., Ripke S., Santangelo S.L., Scharf J.M., Stein M.B., Thornton L.M., Walters J.T.R., Wray N.R., Geschwind D.H., Neale B.M., Kendler K.S., Smoller J.W., Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Epidemiology and Data Science, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, APH - Digital Health, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Kas lab, Adult Psychiatry, Child Psychiatry, ANS - Complex Trait Genetics, Aarno Palotie / Principal Investigator, Jaakko Kaprio / Principal Investigator, Centre of Excellence in Complex Disease Genetics, Genetic Epidemiology, Department of Public Health, University Management, Anna Keski-Rahkonen / Principal Investigator, Department of Medical and Clinical Genetics, Clinicum, HUS Psychiatry, Institute for Molecular Medicine Finland, Research Programs Unit, Genomics of Neurological and Neuropsychiatric Disorders, Biological Psychology, Complex Trait Genetics, APH - Methodology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Lee, P. H., Anttila, V., Won, H., Feng, Y. -C. A., Rosenthal, J., Zhu, Z., Tucker-Drob, E. M., Nivard, M. G., Grotzinger, A. D., Posthuma, D., Wang, M. M. -J., Yu, D., Stahl, E. A., Walters, R. K., Anney, R. J. L., Duncan, L. E., Ge, T., Adolfsson, R., Banaschewski, T., Belangero, S., Cook, E. H., Coppola, G., Derks, E. M., Hoekstra, P. J., Kaprio, J., Keski-Rahkonen, A., Kirov, G., Kranzler, H. R., Luykx, J. J., Rohde, L. A., Zai, C. C., Agerbo, E., Arranz, M. J., Asherson, P., Baekvad-Hansen, M., Baldursson, G., Bellgrove, M., Belliveau, R. A., Buitelaar, J., Burton, C. L., Bybjerg-Grauholm, J., Casas, M., Cerrato, F., Chambert, K., Churchhouse, C., Cormand, B., Crosbie, J., Dalsgaard, S., Demontis, D., Doyle, A. E., Dumont, A., Elia, J., Grove, J., Gudmundsson, O. O., Haavik, J., Hakonarson, H., Hansen, C. S., Hartman, C. A., Hawi, Z., Hervas, A., Hougaard, D. M., Howrigan, D. P., Huang, H., Kuntsi, J., Langley, K., Lesch, K. -P., Leung, P. W. L., Loo, S. K., Martin, J., Martin, A. R., Mcgough, J. J., Medland, S. E., Moran, J. L., Mors, O., Mortensen, P. B., Oades, R. D., Palmer, D. S., Pedersen, C. B., Pedersen, M. G., Peters, T., Poterba, T., Poulsen, J. B., Ramos-Quiroga, J. A., Reif, A., Ribases, M., Rothenberger, A., Rovira, P., Sanchez-Mora, C., Satterstrom, F. K., Schachar, R., Artigas, M. S., Steinberg, S., Stefansson, H., Turley, P., Walters, G. B., Werge, T., Zayats, T., Arking, D. E., Bettella, F., Buxbaum, J. D., Christensen, J. H., Collins, R. L., Coon, H., De Rubeis, S., Delorme, R., Grice, D. E., Hansen, T. F., Holmans, P. A., Hope, S., Hultman, C. M., Klei, L., Ladd-Acosta, C., Magnusson, P., Naerland, T., Nyegaard, M., Pinto, D., Qvist, P., Rehnstrom, K., Reichenberg, A., Reichert, J., Roeder, K., Rouleau, G. A., Saemundsen, E., Sanders, S. J., Sandin, S., St Pourcain, B., Stefansson, K., Sutcliffe, J. S., Talkowski, M. E., Weiss, L. A., Willsey, A. J., Agartz, I., Akil, H., Albani, D., Alda, M., Als, T. D., Anjorin, A., Backlund, L., Bass, N., Bauer, M., Baune, B. T., Bellivier, F., Bergen, S. E., Berrettini, W. H., Biernacka, J. M., Blackwood, D. H. R., Boen, E., Budde, M., Bunney, W., Burmeister, M., Byerley, W., Byrne, E. M., Cichon, S., Clarke, T. -K., Coleman, J. R. I., Craddock, N., Curtis, D., Czerski, P. M., Dale, A. M., Dalkner, N., Dannlowski, U., Degenhardt, F., Di Florio, A., Elvsashagen, T., Etain, B., Fischer, S. B., Forstner, A. J., Forty, L., Frank, J., Frye, M., Fullerton, J. M., Gade, K., Gaspar, H. A., Gershon, E. S., Gill, M., Goes, F. S., Gordon, S. D., Gordon-Smith, K., Green, M. J., Greenwood, T. A., Grigoroiu-Serbanescu, M., Guzman-Parra, J., Hauser, J., Hautzinger, M., Heilbronner, U., Herms, S., Hoffmann, P., Holland, D., Jamain, S., Jones, I., Jones, L. A., Kandaswamy, R., Kelsoe, J. R., Kennedy, J. L., Joachim, O. K., Kittel-Schneider, S., Kogevinas, M., Koller, A. C., Lavebratt, C., Lewis, C. M., Li, Q. S., Lissowska, J., Loohuis, L. M. O., Lucae, S., Maaser, A., Malt, U. F., Martin, N. G., Martinsson, L., Mcelroy, S. L., Mcmahon, F. J., Mcquillin, A., Melle, I., Metspalu, A., Millischer, V., Mitchell, P. B., Montgomery, G. W., Morken, G., Morris, D. W., Muller-Myhsok, B., Mullins, N., Myers, R. M., Nievergelt, C. M., Nordentoft, M., Adolfsson, A. N., Nothen, M. M., Ophoff, R. A., Owen, M. J., Paciga, S. A., Pato, C. N., Pato, M. T., Perlis, R. H., Perry, A., Potash, J. B., Reinbold, C. S., Rietschel, M., Rivera, M., Roberson, M., Schalling, M., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Sigurdsson, E., Smeland, O. B., Stordal, E., Streit, F., Strohmaier, J., Thorgeirsson, T. E., Treutlein, J., Turecki, G., Vaaler, A. E., Vieta, E., Vincent, J. B., Wang, Y., Witt, S. H., Zandi, P., Adan, R. A. H., Alfredsson, L., Ando, T., Aschauer, H., Baker, J. H., Bencko, V., Bergen, A. W., Birgegard, A., Perica, V. B., Brandt, H., Burghardt, R., Carlberg, L., Cassina, M., Clementi, M., Courtet, P., Crawford, S., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., Degortes, D., Desocio, J. E., Dick, D. M., Dina, C., Docampo, E., Egberts, K., Ehrlich, S., Espeseth, T., Fernandez-Aranda, F., Fichter, M. M., Foretova, L., Forzan, M., Gambaro, G., Giegling, I., Gonidakis, F., Gorwood, P., Mayora, M. G., Guo, Y., Halmi, K. A., Hatzikotoulas, K., Hebebrand, J., Helder, S. G., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Imgart, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Julia, A., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kaye, W. H., Kennedy, M. A., Kim, Y. -R., Klareskog, L., Klump, K. L., Knudsen, G. P. S., Landen, M., Le Hellard, S., Levitan, R. D., Li, D., Lichtenstein, P., Maj, M., Marsal, S., Mcdevitt, S., Mitchell, J., Monteleone, P., Monteleone, A. M., Munn-Chernoff, M. A., Nacmias, B., Navratilova, M., O'Toole, J. K., Padyukov, L., Pantel, J., Papezova, H., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Roberts, M., Rujescu, D., Rybakowski, F., Scherag, A., Schmidt, U., Seitz, J., Slachtova, L., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Southam, L., Strober, M., Tortorella, A., Tozzi, F., Treasure, J., Tziouvas, K., van Elburg, A. A., Wade, T. D., Wagner, G., Walton, E., Watson, H. J., Wichmann, H. -E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Adams, M. J., Andlauer, T. F. M., Berger, K., Binder, E. B., Boomsma, D. I., Castelao, E., Colodro-Conde, L., Direk, N., Docherty, A. R., Domenici, E., Domschke, K., Dunn, E. C., Foo, J. C., D, e. Geus E. J. C., Grabe, H. J., Hamilton, S. P., Horn, C., Hottenga, J. -J., Howard, D., Ising, M., Kloiber, S., Levinson, D. F., Lewis, G., Magnusson, P. K. E., Mbarek, H., Middeldorp, C. M., Mostafavi, S., Nyholt, D. R., Penninx, B. W., Peterson, R. E., Pistis, G., Porteous, D. J., Preisig, M., Quiroz, J. A., Schaefer, C., Schulte, E. C., Shi, J., Smith, D. J., Thomson, P. A., Tiemeier, H., Uher, R., van der Auwera, S., Weissman, M. M., Alexander, M., Begemann, M., Bramon, E., Buccola, N. G., Cairns, M. J., Campion, D., Carr, V. J., Cloninger, C. R., Cohen, D., Collier, D. A., Corvin, A., Delisi, L. E., Donohoe, G., Dudbridge, F., Duan, J., Freedman, R., Gejman, P. V., Golimbet, V., Godard, S., Ehrenreich, H., Hartmann, A. M., Henskens, F. A., Ikeda, M., Iwata, N., Jablensky, A. V., Joa, I., Jonsson, E. G., Kelly, B. J., Knight, J., Konte, B., Laurent-Levinson, C., Lee, J., Lencz, T., Lerer, B., Loughland, C. M., Malhotra, A. K., Mallet, J., Mcdonald, C., Mitjans, M., Mowry, B. J., Murphy, K. C., Murray, R. M., O'Neill, F. A., Oh, S. -Y., Palotie, A., Pantelis, C., Pulver, A. E., Petryshen, T. L., Quested, D. J., Riley, B., Sanders, A. R., Schall, U., Schwab, S. G., Scott, R. J., Sham, P. C., Silverman, J. M., Sim, K., Steixner, A. A., Tooney, P. A., van Os, J., Vawter, M. P., Walsh, D., Weiser, M., Wildenauer, D. B., Williams, N. M., Wormley, B. K., Zhang, F., Androutsos, C., Arnold, P. D., Barr, C. L., Barta, C., Bey, K., Bienvenu, O. J., Black, D. W., Brown, L. W., Budman, C., Cath, D., Cheon, K. -A., Ciullo, V., Coffey, B. J., Cusi, D., Davis, L. K., Denys, D., Depienne, C., Dietrich, A., Eapen, V., Falkai, P., Fernandez, T. V., Garcia-Delgar, B., Geller, D. A., Gilbert, D. L., Grados, M. A., Greenberg, E., Grunblatt, E., Hagstrom, J., Hanna, G. L., Hartmann, A., Hedderly, T., Heiman, G. A., Heyman, I., Hong, H. J., Huang, A., Huyser, C., Ibanez-Gomez, L., Khramtsova, E. A., Kim, Y. K., Kim, Y. -S., King, R. A., Koh, Y. -J., Konstantinidis, A., Kook, S., Kuperman, S., Leventhal, B. L., Lochner, C., Ludolph, A. G., Madruga-Garrido, M., Malaty, I., Maras, A., Mccracken, J. T., Meijer, I. A., Mir, P., Morer, A., Muller-Vahl, K. R., Munchau, A., Murphy, T. L., Naarden, A., Nagy, P., Nestadt, G., Nestadt, P. S., Nicolini, H., Nurmi, E. L., Okun, M. S., Paschou, P., Piras, F., Pittenger, C., Plessen, K. J., Richter, M. A., Rizzo, R., Robertson, M., Roessner, V., Ruhrmann, S., Samuels, J. F., Sandor, P., Schlogelhofer, M., Shin, E. -Y., Singer, H., Song, D. -H., Song, J., Spalletta, G., Stein, D. J., Stewart, S. E., Storch, E. A., Stranger, B., Stuhrmann, M., Tarnok, Z., Tischfield, J. A., Tubing, J., Visscher, F., Vulink, N., Wagner, M., Walitza, S., Wanderer, S., Woods, M., Worbe, Y., Zai, G., Zinner, S. H., Sullivan, P. F., Franke, B., Daly, M. J., Bulik, C. M., Mcintosh, A. M., O'Donovan, M. C., Zheutlin, A., Andreassen, O. A., Borglum, A. D., Breen, G., Edenberg, H. J., Fanous, A. H., Faraone, S. V., Gelernter, J., Mathews, C. A., Mattheisen, M., Mitchell, K. S., Neale, M. C., Nurnberger, J. I., Ripke, S., Santangelo, S. L., Scharf, J. M., Stein, M. B., Thornton, L. M., Walters, J. T. R., Wray, N. R., Geschwind, D. H., Neale, B. M., Kendler, K. S., and Smoller, J. W.
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Netherlands Twin Register (NTR) ,cross-disorder genetics ,Medizin ,Genome-wide association study ,Tourette syndrome ,functional genomics ,gene expression ,genetic architecture ,genetic correlation ,GWAS ,neurodevelopment ,pleiotropy ,psychiatric disorders ,Psychiatric genetics ,0302 clinical medicine ,Pleiotropy ,functional genomic ,WIDE ASSOCIATION ,cross-disorder genetic ,0303 health sciences ,Mental Disorders ,Genetic Pleiotropy ,HUMAN BRAIN ,INSIGHTS ,Autism spectrum disorder ,Schizophrenia ,DISEASES ,GENETIC CORRELATIONS ,medicine.medical_specialty ,Neurogenesis ,Quantitative Trait Loci ,BF ,Biology ,GENOTYPE IMPUTATION ,Psychiatric geneticscross-disorder geneticspsychiatric disorderspleiotropyneurodevelopmentGWASgenetic correlationgene expressiongenetic architecturefunctional genomics ,Article ,General Biochemistry, Genetics and Molecular Biology ,psychiatric disorder ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,medicine ,Humans ,Genetic Predisposition to Disease ,Bipolar disorder ,TRANSCRIPTOME ,Psychiatry ,030304 developmental biology ,Gwas ,Psychiatric Genetics ,Cross-disorder Genetics ,Functional Genomics ,Gene Expression ,Genetic Architecture ,Genetic Correlation ,Neurodevelopment ,Psychiatric Disorders ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,IDENTIFICATION ,MUTATIONS ,medicine.disease ,Genetic architecture ,DEMETHYLASE ,RC0321 ,1182 Biochemistry, cell and molecular biology ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
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- 2019
19. Quebrantamientos de medidas privativas de libertad en jóvenes infractores y factores de riesgo diferenciales
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María Arranz, Lorena Maneiro, Olalla Cutrín, and Xosé Antón Gómez-Fraguela
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Social pathology. Social and public welfare. Criminology ,HV1-9960 ,Social Sciences - Abstract
El quebrantamiento de medida en jóvenes que cumplen medidas judiciales privativas de libertad tiene graves consecuencias, tanto para los individuos como para la sociedad. Por ello, resulta necesario determinar los factores que contribuyen a la explicación de estas conductas. El objetivo de este estudio es evaluar las diferencias en una serie de factores de riesgo en función de la presencia y el tipo de quebrantamiento. La muestra estuvo compuesta por 177 jóvenes entre 16 y 22 años que cumplen alguna medida judicial privativa de libertad. La información fue obtenida a partir del Inventario de Gestión e Intervención con Jóvenes (IGI-J). Los resultados del estudio no evidenciaron diferencias en función del género. Sin embargo, algunas diferencias emergieron entre grupos analizados. Específicamente, el grupo de solo no retorno obtuvo puntuaciones significativamente más elevadas en factores de personalidad y actitudes. Estos resultados reflejan la necesidad de desarrollar herramientas de valoración del riesgo que tengan en cuenta este tipo específico de conductas.
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- 2023
- Full Text
- View/download PDF
20. SU96PHARMACOGENETICS MAY IMPROVE THE SAFETY PROFILE OF ANTIPSYCHOTIC TREATMENTS
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Jorge Cervilla Ballesteros, Maria Arranz, Bárbara Arias, Rafael Penadés, Blanca Gutiérrez, Rosa Catalan Campos, Mercè Brunet, Ibañez Laura, Juliana Salazar, Josefina Perez-Blanco, and A. González-Rodríguez
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Pharmacology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Psychiatry and Mental health ,Safety profile ,Neurology ,medicine ,Pharmacology (medical) ,Neurology (clinical) ,Intensive care medicine ,Antipsychotic ,business ,Biological Psychiatry - Published
- 2019
21. An exploratory association study of the influence of noradrenergic genes and childhood trauma in Borderline Personality Disorder
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Mónica Prat, Natalia Calvo, Marc Ferrer, Cristina Sánchez-Mora, Daniel Vega, Iris Garcia-Martínez, Marta Ribasés, Juan C. Pascual, Ana Martín-Blanco, Maria Arranz, Juliana Salazar, Joaquim Soler, Matilde Elices, Joana Bauzà, and Cristina Carmona
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Adult ,Male ,medicine.medical_specialty ,Dopamine beta-Hydroxylase ,Noradrenergic system ,Catechol O-Methyltransferase ,behavioral disciplines and activities ,Childhood trauma ,symbols.namesake ,Borderline Personality Disorder ,mental disorders ,medicine ,Humans ,Child Abuse ,Child ,Promoter Regions, Genetic ,Psychiatry ,Association (psychology) ,Gene ,Borderline personality disorder ,Genetic Association Studies ,Biological Psychiatry ,Retrospective Studies ,Norepinephrine Plasma Membrane Transport Proteins ,Polymorphism, Genetic ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Bonferroni correction ,symbols ,Female ,Psychology ,Clinical psychology - Abstract
This study investigated the possible association of 40 polymorphisms within 4 noradrenergic genes with BPD risk and the modulating effect of childhood trauma on these associations in 481 BPD subjects and 442 controls. COMT rs5993882, DBH rs77905 and SLC6A2 rs1814270 showed associations with BPD, which were modulated by childhood trauma. However, none of these findings survived Bonferroni correction. Further investigation is needed to clarify the involvement of these genes in BPD pathogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2015
22. PERTUSSIS IN THE 21ST CENTURY. EPIDEMIOLOGY AND RISK FACTORS ASSOCIATED WITH WORSE OUTCOME
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Maria Arranz Boned
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- 2017
23. Satisfaction With Methadone and Opioid Receptor Genes Polymorphisms in Treatment-Refractory Heroin-Dependent Patients
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Saul Alcaraz, Francesc Calafell, Núria Siñol, José Pérez de los Cobos, Francesca Batlle, Santiago Duran-Sindreu, Joan Trujols, Maria Arranz, and Juliana Salazar
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Adult ,Male ,Narcotics ,medicine.drug_class ,Pharmacology ,Polymorphism, Single Nucleotide ,Heroin ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Opioid receptor ,Opiate Substitution Treatment ,Medicine ,Humans ,Pharmacology (medical) ,Gene ,business.industry ,Treatment refractory ,Heroin Dependence ,Middle Aged ,030227 psychiatry ,Psychiatry and Mental health ,Patient Satisfaction ,Receptors, Opioid ,Female ,business ,030217 neurology & neurosurgery ,Methadone ,medicine.drug - Published
- 2017
24. SPARC gene variants predict clinical outcome in locally advanced and metastatic pancreatic cancer patients
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Maria Arranz, Maria Tobeña, David Páez, Agustí Barnadas, Josefina Mora, Cristina Arqueros, Ivana Sullivan, Marta Martín-Richard, J Salazar, Montserrat Baiget, and Ana Sebio
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Haploview ,Single-nucleotide polymorphism ,Biology ,Nab-paclitaxel ,Adenocarcinoma ,Bioinformatics ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Pancreatic cancer ,Internal medicine ,medicine ,Humans ,Computer Simulation ,Osteonectin ,Aged ,Univariate analysis ,Hematology ,Haplotype ,SPARC ,General Medicine ,Biomarker ,medicine.disease ,Prognosis ,Survival Analysis ,Minor allele frequency ,Pancreatic Neoplasms ,030104 developmental biology ,Treatment Outcome ,Haplotypes ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Biomarker (medicine) ,Female ,Polymorphisms ,Carcinoma, Pancreatic Ductal - Abstract
Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein of the extracellular matrix whose expression can be altered in malignant pancreatic cells and in the adjacent stromal fibroblasts. We evaluated the possible role of SPARC gene variants as prognostic markers for locally advanced and metastatic pancreatic cancer. We analyzed eight tagging single-nucleotide polymorphisms (TagSNPs) in the SPARC gene in 74 patients with pancreatic ductal adenocarcinoma treated with chemotherapy alone or combined with radiotherapy. TagSNPs were chosen using the HapMap genome browser and Haploview software 4.2 based on two predefined criteria: (1) coefficient cutoff of 0.80 and (2) minor allele frequency (MAF) >= 0.10. Univariate analyses revealed significant associations between four SNPs (rs17718347, rs2347128, rs3210714, and rs967527) and PFS. The rs3210714 genetic variant was also associated with OS. In the multivariate analyses, rs17718347 (HR 0.4; 95% CI 0.2-0.8; p = 0.013) and rs2347128 (HR 0.5; 95% CI 0.3-0.9; p = 0.049) remained statistically associated with PFS. In addition, patients harboring the T-A-G haplotype (rs17718347, rs1978707, rs2347128) had a better PFS (p = 0.002). Our findings suggest that SPARC polymorphisms may be useful in predicting outcome in patients with locally advanced and metastatic pancreatic cancer.
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- 2017
25. Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder
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Marta Ribasés, Cristina Sánchez-Mora, Joaquim Soler, Víctor Pérez, Albert Feliu-Soler, Juan C. Pascual, Maria Arranz, Daniel Vega, Ana Martín-Blanco, Marc Ferrer, Juliana Salazar, and Óscar Andión
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Adult ,Male ,Child abuse ,Oncology ,medicine.medical_specialty ,Severity of Illness Index ,Methylation ,Childhood trauma ,Young Adult ,Receptors, Glucocorticoid ,Borderline Personality Disorder ,Glucocorticoid receptor gene ,Internal medicine ,Severity of illness ,Genetics ,medicine ,Humans ,Child Abuse ,Epigenetics ,Young adult ,Child ,Promoter Regions, Genetic ,Borderline personality disorder ,Biological Psychiatry ,DNA Methylation ,medicine.disease ,Hospitalization ,Borderline personality disorder, Childhood trauma, Epigenetics, Genetics, Glucocorticoid receptor gene, Methylation ,Psychiatry and Mental health ,Physical abuse ,DNA methylation ,Female ,Gene-Environment Interaction ,Psychology ,Self-Injurious Behavior ,Clinical psychology - Abstract
The hypothalamus-pituitary-adrenal axis (HPA) is essential in the regulation of stress responses. Increased methylation of the promoter region of the glucocorticoid receptor gene (NR3C1) has been described both in subjects with history of childhood trauma and in patients with Borderline Personality Disorder (BPD). However, no data on the possible association between a higher methylation of this gene and clinical severity is available. The aim of this study was to evaluate the association between NR3C1 methylation status, the history of childhood trauma, and current clinical severity in subjects with BPD. A sample of 281 subjects with BPD (diagnosed by SCID-II and DIB-R semi-structured diagnostic interviews) was recruited. Clinical variables included previous hospitalizations, self-injurious behavior, and self-reported history of childhood trauma. DNA was extracted from peripheral blood. The results indicated a significant positive correlation between NR3C1 methylation status and childhood maltreatment (specifically physical abuse). In addition, a positive correlation between methylation status and clinical severity (DIB-R total score and hospitalizations) was observed. These findings suggest that NR3C1 methylation in subjects with BPD may be associated not only with childhood trauma but also with clinical severity, adding new evidence to the involvement of gene-environment interactions in this disorder. (C) 2014 Elsevier Ltd. All rights reserved.
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- 2014
26. Association study of polymorphisms within inflammatory genes and treatment resistant depression
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Metodi Draganov, J. de Diego-Adeliño, Maria Arranz, Maria J. Portella, Míriam Jubero, Dolors Puigdemont, and Elvira Alvarez
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Pharmacology ,Psychiatry and Mental health ,Neurology ,business.industry ,Immunology ,Medicine ,Pharmacology (medical) ,Neurology (clinical) ,business ,medicine.disease ,Treatment-resistant depression ,Biological Psychiatry ,Inflammatory genes - Published
- 2019
27. SA23STUDY OF GENETIC INFLUENCE ON TREATMENT RESPONSE IN AUTISM
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Isabel Rueda, Javiera Uribe, Martha Cancino, Aitana Bigorra, Maria Arranz, Laura Ibanez, Guijarro Silvina, Marta Carulla, Amanda Cercós, Amaia Hervás, Marta Salgado, and Sergi Bodas
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Pharmacology ,Psychiatry and Mental health ,Treatment response ,Neurology ,medicine ,Autism ,Pharmacology (medical) ,Neurology (clinical) ,medicine.disease ,Psychology ,Biological Psychiatry ,Clinical psychology - Published
- 2019
28. Pharmacogenetic Applications and Pharmacogenomic Approaches in Schizophrenia
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J. Perez, A. Hervas, Maria Arranz, Blanca Gutiérrez, and V. Perez
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Drug ,business.industry ,medicine.medical_treatment ,media_common.quotation_subject ,Coding (therapy) ,General Medicine ,Pharmacology ,medicine.disease ,Bioinformatics ,Treatment efficacy ,Schizophrenia ,Pharmacogenomics ,medicine ,Antipsychotic ,Prospective cohort study ,business ,Pharmacogenetics ,media_common - Abstract
Several genetic factors have been identified that, in combination with clinical and environmental factors, contribute to the variability in response to treatment with antipsychotic drugs. Functional polymorphisms in genes coding for cytochrome-P450 (CYP) enzymes, responsible for the metabolism of over 85 % of drugs, have been associated with the development of drug-induced side-effects, and functional polymorphisms in dopamine and serotonin genes may be associated with adverse reactions and treatment efficacy. Recent estimations have suggested that selecting the drug and clinical dose according to the patient’s genetic profile may result in a significant improvement of treatment efficacy (10–15 %) and safety (15–20 %). This information has prompted the development of commercial kits to facilitate the clinical application of pharmacogenetic information. However, prospective studies confirming the clinical and economical benefits of these tests are required before their widespread implementation in clinical practice.
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- 2013
29. Farmacogenética de las reacciones adversas a los antipsicóticos en pacientes con esquizofrenia
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Maria Arranz, Josefina Perez Blanco, Adriana Farré, Victor L. Perez, and Rosa Catalán
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Industrial and Manufacturing Engineering - Abstract
Resumen Esta revision se centra en los conocimientos actuales en el campo de la farmacogenetica que tienen relacion con las reacciones adversas a los antipsicoticos en pacientes con esquizofrenia. En el momento actual hay numerosas investigaciones que han intentado determinar variantes geneticas que permitan predecir el riesgo individual de padecer efectos secundarios al tratamiento con antipsicoticos. Multiples estudios determinan que polimorfismos de las enzimas del citocromo P450 y de los receptores dopaminergicos pueden estar relacionados con un mayor riesgo de trastornos del movimiento inducidos por antipsicoticos. Por otro lado, tanto el sistema serotoninergico como la leptina se han relacionado con el control del apetito, y variantes del receptor 5-HT2C y del gen de la leptina pueden estar asociadas al aumento de peso en el contexto del tratamiento con estos farmacos. Estudios centrados en el riesgo de agranulocitosis con clozapina han concluido que variantes del sistema mayor de histocompatibilidad pueden ser responsables de un incremento del riesgo de aparicion de esta reaccion adversa.
- Published
- 2012
30. Dopaminergic Genes Influence Early Response to Atypical Antipsychotics in Patients With First Presentation of Psychosis
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Maria Arranz, Diana Prata, Victoria Kay, Rafael Gafoor, Philip McGuire, and Janet Munro
- Subjects
Psychiatric Status Rating Scales ,Psychosis ,Receptors, Dopamine D2 ,business.industry ,media_common.quotation_subject ,Receptors, Dopamine D4 ,Dopaminergic ,Catechol O-Methyltransferase ,medicine.disease ,Bioinformatics ,Polymorphism, Single Nucleotide ,Cohort Studies ,Psychiatry and Mental health ,Presentation ,Text mining ,Psychotic Disorders ,Early Medical Intervention ,medicine ,Humans ,Pharmacology (medical) ,In patient ,business ,Gene ,Antipsychotic Agents ,media_common - Published
- 2012
31. Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients
- Author
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Juliana Salazar, Patricia Moya, Cesar Diaz-Torne, Elisabeth del Río, Hèctor Corominas, Jordi Casademont, Montserrat Baiget, and Maria Arranz
- Subjects
musculoskeletal diseases ,Oncology ,rheumatoid arthritis ,Adult ,Male ,medicine.medical_specialty ,ATP Binding Cassette Transporter, Subfamily B ,Single-nucleotide polymorphism ,Pharmacology ,RFC1 ,FPGS ,030226 pharmacology & pharmacy ,Polymorphism, Single Nucleotide ,Pharmacogenomic Variants ,methotrexate ,Arthritis, Rheumatoid ,03 medical and health sciences ,Reduced Folate Carrier Protein ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,Genetics ,medicine ,Humans ,GGH ,Peptide Synthases ,pharmacogenetics ,030203 arthritis & rheumatology ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,ABCB1 ,Middle Aged ,medicine.disease ,SLC19A1/RFC1 ,Methotrexate ,Rheumatoid arthritis ,Toxicity ,Molecular Medicine ,Female ,business ,Pharmacogenetics ,Glucosidases ,medicine.drug - Abstract
Background: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. Aim: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX. Patients & methods: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. Results: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). Conclusion: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.
- Published
- 2015
32. 6.58 Genetic Influence on IQ and Intellectual Disability in Autism Spectrum Disorder Patients
- Author
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Maria Arranz, Aitana Bigorra, Enric Duran, Ayhesa Ruiz, Amaia Hervas Zuniga, Marta Salgado, Anna Gonzalez, Silvina Guijarro Domingo, and Isabel Rueda
- Subjects
Psychiatry and Mental health ,Autism spectrum disorder ,Intellectual disability ,Developmental and Educational Psychology ,medicine ,Autism ,medicine.disease ,Psychology ,Clinical psychology - Published
- 2017
33. Pharmacogenetics of Response to Antipsychotics in Patients with Schizophrenia
- Author
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Margarita Rivera, Maria Arranz, and Janet Munro
- Subjects
Leptin ,Olanzapine ,Candidate gene ,Pharmacology ,Weight Gain ,Bioinformatics ,Dopamine receptor D3 ,Medicine ,Pharmacology (medical) ,Precision Medicine ,Clozapine ,Polymorphism, Genetic ,Risperidone ,business.industry ,medicine.disease ,Psychiatry and Mental health ,Treatment Outcome ,Pharmacogenetics ,Schizophrenia ,Pharmacogenomics ,Neurology (clinical) ,business ,Antipsychotic Agents ,medicine.drug - Abstract
This review presents the findings of pharmacogenetic studies exploring the influence of gene variants on antipsychotic treatment response, in terms of both symptom improvement and adverse effects, in patients with schizophrenia. Despite numerous studies in the field, replicating findings across different cohorts that include subjects of different ethnic groups has been challenging. It is clear that non-genetic factors have an important contribution to antipsychotic treatment response. Differing clinical, demographic and environmental characteristics of the cohorts studied have added substantial complexity to the interpretation of the positive and negative findings of many studies. Pharmacogenomic genome-wide investigations are beginning to yield interesting data although they have failed to replicate the most robust findings of candidate gene studies, and are limited by the sample size, especially given the need for studying homogeneous cohorts. Most of the studies conducted on cohorts treated with single anti-psychotics have investigated clozapine, olanzapine or risperidone response. These studies have provided some of the most replicated associations with treatment efficacy. Serotonergic system gene variants are significantly associated with the efficacy of clozapine and risperidone, but may have less influence on the efficacy of olanzapine. Dopamine D3 receptor polymorphisms have been more strongly associated with the efficacy of clozapine and olanzapine, and D2 genetic variants with the efficacy of risperidone. Serotonin influences the control of feeding behaviour and has been hypothesized to have a role in the development of antipsychotic-induced weight gain. Numerous studies have linked the serotonin receptor 2C (5-HT2C) −759-C/T polymorphism with weight gain. The leptin gene variant, −2548-G/A, has also been associated with weight gain in several studies. Pharmacogenetic studies support the role of cytochrome P450 enzymes and dopamine receptor variants in the development of antipsychotic-induced movement disorders, with a contribution of serotonergic receptors and other gene variants implicated in the mechanism of action of antipsychotics. Clozapine-induced agranulocytosis has been associated with polymorphisms in the major histocompatibility complex gene (HLA).
- Published
- 2011
34. Association between neonatal temperament,SLC6A4,DRD4and a functional polymorphism located inTFAP2B
- Author
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Ursula M. D'Souza, María Dolores Moltó, M. Jover, Brenda P. Williams, S. E. Henry, Julio Sanjuán, Jose Luis Ivorra, and Maria Arranz
- Subjects
Male ,Genotype ,media_common.quotation_subject ,Minisatellite Repeats ,Biology ,Behavioral Neuroscience ,Exon ,Genetics ,Humans ,Allele ,Temperament ,Indel ,Gene ,Alleles ,Genetic Association Studies ,media_common ,Serotonin Plasma Membrane Transport Proteins ,Polymorphism, Genetic ,Receptors, Dopamine D4 ,Infant, Newborn ,Intron ,Variable number tandem repeat ,Real-time polymerase chain reaction ,Transcription Factor AP-2 ,Neurology ,Infant Behavior ,Female - Abstract
Genetic studies on human personality have provided little satisfactory results to date mainly because of the complexity of this trait. Neonatal temperament using observational measures is an alternative phenotype to approach genetics to human behavior. An association study was conducted on 117 Caucasian newborns. Their temperament was evaluated using the Neonatal Behavior Assessment Scale 48 h after birth. Thirteen polymorphisms in the SLC6A4, DRD4 and TFAP2B genes were genotyped. Linear regression was performed to analyze data, and Bonferroni correction was applied. To check the functional effect of the TFAP2B Indel Intron 2 polymorphism, reporter gene luciferase assays using a mouse cortical neural progenitor cell line and quantitative polymerase chain reaction (qPCR) studies in human post-mortem brain samples were performed. A significant association was found between 5-HTTLPR, 5-HTTLPR + rs25531 and TFAP2B Indel Intron 2 with Range of State cluster as well as an interaction between rs25531 and TFAP2B Indel Intron 2 with Range of State. DRD4 variable number tandem repeat exon 3 was associated with orientation. A 30% increase in the luciferase levels of the TFAP2B 5-repeat alleles compared with the 6-repeat alleles (P-value = 0.03) was found using the pGL3 promoter vector. The qPCR experiments showed the same trend as the in vitro studies, although no significant results were obtained. This study supports a role of the SLC6A4, DRD4 and TFAP2B genes in the temperament, including a gene-gene interaction between SLC6A4 and TFAP2B. It also provides evidence about an effect of the TFAP2B polymorphism in TFAP2B gene transcription.
- Published
- 2011
35. Toward understanding genetic risk for differential antipsychotic response in individuals with schizophrenia
- Author
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Maria Arranz and J Munro
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,MEDLINE ,Bioinformatics ,Risk Factors ,Animals ,Humans ,Medicine ,Pharmacology (medical) ,Dosing ,General Pharmacology, Toxicology and Pharmaceutics ,Psychiatry ,Antipsychotic ,Genetic association ,Polymorphism, Genetic ,business.industry ,General Medicine ,medicine.disease ,Treatment Outcome ,Tolerability ,Pharmacogenetics ,Schizophrenia ,Pharmacogenomics ,Comprehension ,business ,Antipsychotic Agents - Abstract
Antipsychotic treatment response is highly heterogeneous and unpredictable in terms of both efficacy and side effects. A combination of factors influences treatment outcome, including clinical, demographic, environmental and genetic factors. No comprehensive studies have quantified the relative contributions of these factors to date. Two decades of pharmacogenetic and pharmacogenomic studies have attempted to identify key gene variants associated with antipsychotic response, with a dual goal of better understanding the mechanisms underlying drug response and guiding prescribing decisions in clinical care. Pharmacogenetic studies have succeeded in identifying several genes that are associated with antipsychotic treatment efficacy or side effects. However, the strength of these associations is modest and they are of limited clinical value. Genome-wide association studies, moving beyond hypothesis-based discovery, have greater potential to identify novel gene associations, although only a few genome-wide association studies have been conducted and they have not revealed clearly significant findings. The first pharmacogenetic tests to guide the selection or dosing of antipsychotic drugs are now commercially available. Their uptake has been limited by the modest level of prediction they offer, compounded by the lack of data supporting their clinical or economic benefits. Advances in genomic analysis techniques, the better characterization of larger subject cohorts and an improved understanding of the role of environmental factors and gene-environment interactions are renewing hope that future research will identify genetic variants with stronger associations with treatment outcome. Tests incorporating such genetic data, with environmental and clinical variables, may offer the potential to personalize medicine and significantly improve the efficacy and tolerability of antipsychotic treatment.
- Published
- 2011
36. COMT gene polymorphism and corpus callosum morphometry in preterm born adults
- Author
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Matthew Allin, Robin M. Murray, Anirban Dutt, Elvira Bramon, Maria Arranz, Philip McGuire, Muriel Walshe, Madiha Shaikh, Colm McDonald, Chiara Nosarti, Christopher A. Chaddock, Taposhri Ganguly, and Larry Rifkin
- Subjects
Male ,medicine.medical_specialty ,Multivariate analysis ,Adolescent ,Genotype ,Cognitive Neuroscience ,Catechol O-Methyltransferase ,Corpus callosum ,Polymorphism, Single Nucleotide ,Corpus Callosum ,White matter ,Young Adult ,Neuroimaging ,Internal medicine ,mental disorders ,Humans ,Medicine ,Polymorphism, Genetic ,Catechol-O-methyl transferase ,business.industry ,Patient Selection ,Homozygote ,Infant, Newborn ,DNA ,Low birth weight ,Endocrinology ,medicine.anatomical_structure ,Amino Acid Substitution ,nervous system ,Neurology ,Gestation ,Female ,medicine.symptom ,business ,Infant, Premature - Abstract
Introduction Preterm birth is associated with a range of neurodevelopmental deficits, including corpus callosum (CC) abnormalities, which persist into late adolescence and early adulthood. A common single-nucleotide polymorphism in the catechol-o-methyl transferase (COMT) gene (Val158Met) is associated with cognition and brain structure and may play a role in neurodevelopment. It is not known whether this polymorphism is associated with CC morphometry in individuals born preterm. Methods Structural MRI scans were acquired in 33 adults born very preterm (before 33 weeks' gestation) and 29 healthy controls. DNA was collected and COMT Val158Met polymorphism status determined using standard available assays. The mid-sagittal area of four antero-posterior subdivisions of the CC was measured. The effect of COMT Val158Met polymorphism on cross-sectional CC areas was studied using multivariate analysis and generalised linear models, adjusted for the effects of the clinical sample group (preterm vs. control), age and sex. Results The COMT Val/Val homozygous genotype was observed to be significantly associated with reduced size of the total corpus callosum, and this relationship was present for the anterior, midposterior and posterior quarters of the CC. Conclusions The COMT Val158Met polymorphism possibly influences the morphometry of the corpus callosum associated with very preterm births. Further studies with larger sample sizes are warranted to conclusively establish the effects of individual genotypes of the COMT gene on corpus callosum in preterm born adults.
- Published
- 2011
37. Effect of FTO, SH2B1, LEP, and LEPR Polymorphisms on Weight Gain Associated With Antipsychotic Treatment
- Author
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Maria Arranz, Rocío Pérez-Iglesias, Benedicto Crespo-Facorro, Ana Berja, José A. Amado, Obdulia Martínez García, Ignacio Mata, José Luis Vázquez-Barquero, and María Teresa García-Unzueta
- Subjects
Adult ,Leptin ,Male ,medicine.medical_specialty ,Genotype ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Single-nucleotide polymorphism ,Weight Gain ,Polymorphism, Single Nucleotide ,Young Adult ,SH2B1 ,Internal medicine ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,Pharmacology (medical) ,Longitudinal Studies ,Prospective Studies ,Allele frequency ,Adaptor Proteins, Signal Transducing ,Leptin receptor ,business.industry ,Proteins ,medicine.disease ,Obesity ,Psychiatry and Mental health ,Endocrinology ,Psychotic Disorders ,Schizophrenia ,Receptors, Leptin ,Female ,Aripiprazole ,medicine.symptom ,business ,Weight gain ,Antipsychotic Agents ,Follow-Up Studies ,medicine.drug - Abstract
Weight gain is one of the major adverse effects of antipsychotics. Although mechanisms remain unclear, genetic susceptibility has become increasingly attractive as a potential mechanism that could explain a significant part of interindividual variability. Most investigations have explored genes related with the mechanism of action of antipsychotic drugs. An alternative approach to investigate the role that genetic factors play in weight gain secondary to antipsychotic treatment is to study those genetic variants that have been found associated with obesity. The aim of this study was to determine whether the fat mass and obesity-associated gene (FTO) rs9939609 variant, the single nucleotide polymorphism that has shown the strongest association with common obesity in different populations, influences weight gain during the first year of antipsychotic treatment. We investigated also the genetic variants in other 3 strong candidates genes involved in the leptin-signaling pathway including leptin, leptin receptor, and Src homology 2. We carried out a prospective study on 239 patients with first-episode psychosis. Two hundred five patients completed the follow-up at 1 year (85.8%). Before antipsychotic treatment, the homozygous subjects for the risk allele A of the FTO rs9939609 variant had a higher body mass index at baseline (24.2 ± 3.8 kg/m2) than the AT/TT group (22.82 ± 3.3 kg/m2; F = 5.744; P = 0.018). After 1 year, the magnitude of weight increase was similar in the 3 genotypes defined by the rs9939609 variant. These results suggest that the pharmacological intervention accompanied by changes in energy intake and expenditure could suppress the genetic susceptibility conferred by the FTO genotype. None of the other single nucleotide polymorphisms evaluated were associated with weight gain during the first 12 months of antipsychotic therapy.
- Published
- 2010
38. Serotonin transporter polymorphisms and early response to antipsychotic treatment in first episode of psychosis
- Author
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Ignacio Mata, Maria Arranz, José María Pelayo-Terán, Rocío Pérez-Iglesias, Laura Medina-González, Eugenio Carrasco-Marín, Benedicto Crespo-Facorro, Javier Vázquez-Bourgon, and José Luis Vázquez-Barquero
- Subjects
Adult ,Male ,Olanzapine ,Oncology ,Psychosis ,medicine.medical_specialty ,Adolescent ,Genotype ,medicine.medical_treatment ,Young Adult ,Internal medicine ,Brief Psychiatric Rating Scale ,medicine ,Humans ,Longitudinal Studies ,Promoter Regions, Genetic ,Antipsychotic ,Psychiatry ,Scale for the Assessment of Negative Symptoms ,Biological Psychiatry ,Serotonin Plasma Membrane Transport Proteins ,First episode ,Chi-Square Distribution ,Polymorphism, Genetic ,Risperidone ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Schizophrenia ,Female ,Psychology ,Antipsychotic Agents ,medicine.drug - Abstract
article i nfo There is substantial evidence suggesting that individual variability in antipsychotic treatment response could be genetically determined. Variations in several serotonin transporter (5-HTT) gene polymorphisms have been associated with antipsychotic response among chronic patients with schizophrenia, although their implication in early response among first-episode patients remains unclear. Two polymorphisms in the 5- HTTgene (a 44 bp insertion/deletion in the promoter region and the functional polymorphism rs25531) were genotyped in a sample of 147 drug-naive patients experiencing a first episode of a non-affective psychosis. Early (6 weeks) response to antipsychotic treatment with haloperidol, olanzapine or risperidone was assessed with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. No clear association was found between the rs25531 variant and treatment response. However, significant associations were observed between 5-HTT-LPR variants and early negative symptom response among first-episode patients with psychosis. Our results suggest a minor contribution to antipsychotic drug response of genetic alterations in the 5-HTT gene.
- Published
- 2010
39. Do COMT, BDNF and NRG1 polymorphisms influence P50 sensory gating in psychosis?
- Author
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Timothea Toulopoulou, Maria Arranz, Ian Williams, Katja Schulze, Robin M. Murray, Marco Picchioni, David A. Collier, Elvira Bramon, John Powell, Miguel Constante, Mei-Hua Hall, Madiha Shaikh, Muriel Walshe, Fruhling Rijsdijk, and Anirban Dutt
- Subjects
Adult ,Male ,Psychosis ,Endophenotypes ,Neuregulin-1 ,Catechol O-Methyltransferase ,Neurotrophic factors ,medicine ,Humans ,Neuregulin 1 ,Applied Psychology ,Aged ,Family Health ,Brain-derived neurotrophic factor ,Polymorphism, Genetic ,Catechol-O-methyl transferase ,Sensory gating ,biology ,Brain-Derived Neurotrophic Factor ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Logistic Models ,medicine.anatomical_structure ,Psychotic Disorders ,Schizophrenia ,Endophenotype ,Evoked Potentials, Auditory ,Linear Models ,biology.protein ,Female ,Psychology ,Neuroscience - Abstract
BackgroundAuditory P50 sensory gating deficits correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The well-supported role of catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF) and neuregulin 1 (NRG1) genes in neurodevelopment and cognition make a strong theoretical case for their influence on the P50 endophenotype.MethodThe possible role of NRG1, COMT Val158Met and BDNF Val66Met gene polymorphisms on the P50 endophenotype was examined in a large sample consisting of psychotic patients, their unaffected relatives and unrelated healthy controls using linear regression analyses.ResultsAlthough P50 deficits were present in patients and their unaffected relatives, there was no evidence for an association between NRG1, COMT Val158Met or BDNF Val66Met genotypes and the P50 endophenotype.ConclusionsThe evidence from our large study suggests that any such association between P50 indices and NRG1, COMT Val158Met or BDNF Val66Met genotypes, if present, must be very subtle.
- Published
- 2010
40. Acetyl-coenzyme A carboxylase α gene variations may be associated with the direct effects of some antipsychotics on triglyceride levels
- Author
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Maria Arranz, Jose de Leon, Francisco J. Diaz, Gualberto Ruaño, Andreas Windemuth, and Alexander Meary
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Hypercholesterolemia ,Atypical antipsychotic ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Article ,Internal medicine ,Hyperlipidemia ,medicine ,Humans ,Neuropeptide Y ,Antipsychotic ,Triglycerides ,Biological Psychiatry ,ACACB ,ACACA ,business.industry ,Hypertriglyceridemia ,Acetyl-CoA carboxylase ,nutritional and metabolic diseases ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Cholesterol ,Cross-Sectional Studies ,Logistic Models ,Endocrinology ,Psychotic Disorders ,Pharmacogenetics ,Female ,business ,Acetyl-CoA Carboxylase ,Antipsychotic Agents - Abstract
Acetyl-coenzyme A carboxylase alpha (ACACA) single-nucleotide polymorphism (SNP) (rs2229416) was significantly associated with hypertriglyceridemia, during exploration of antipsychotic direct effects on lipids. Neuropeptide Y (NPY) gene (rs1468271) and ACACB gene (rs2241220) SNPs were significantly associated with severe hypercholesterolemia. In the same sample (173 patients on olanzapine, quetiapine, chlorpromazine or mirtazapine [increasing the risk of hyperlipidemia] and 184 controls taking other antipsychotics), three (rs1266175, rs12453407 and rs9906543) of eight additional ACACA SNPs were significantly associated with hypertriglyceridemia in those taking drugs of interest, but not in controls. Five other ACACA SNPs, three additional NPY SNPs, and seven additional ACACB SNPs were not significant.
- Published
- 2009
41. Pharmacogenetic Testing in Psychiatry: A Review of Features and Clinical Realities
- Author
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Jose de Leon, Gualberto Ruaño, and Maria Arranz
- Subjects
Psychiatry ,AmpliChip CYP450 Test ,medicine.medical_specialty ,Genotype ,business.industry ,Mental Disorders ,Biochemistry (medical) ,Clinical Biochemistry ,MEDLINE ,First generation ,Test (assessment) ,Clinical Practice ,Cytochrome P-450 Enzyme System ,Pharmacogenetics ,medicine ,Humans ,Mutation detection ,Genetic Testing ,business - Abstract
This article focuses on the first generation of pharmacogenetic tests that are potentially useful in psychiatry. All pharmacogenetic tests currently on the market, or soon to be marketed in psychiatry, for which some information has been published in peer-reviewed journal articles (or abstracts), were selected. Five pharmacogenetic tests are reviewed in detail: the Roche AmpliChip CYP450 Test, the Luminex Tag-It Mutation Detection Kit, the LGC clozapine response test, the PGxPredict: Clozapine test, and the Genomas PhyzioType system. After reviewing these tests, three practical aspects of implementing pharmacogenetic testing in psychiatric clinical practice are briefly reviewed: (1) the evaluation of these tests in clinical practice, (2) cost-effectiveness, and (3) regulatory oversight. Finally, the future of these and other pharmacogenetic tests in psychiatry is discussed.
- Published
- 2008
42. Catechol‐O‐methyltransferaseVal158Metpolymorphism and clinical characteristics in first episode non‐affective psychosis
- Author
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Rocío Pérez-Iglesias, José María Pelayo-Terán, Benedicto Crespo-Facorro, Maria Arranz, Eugenio Carrasco-Marín, Francisco Leyva-Cobián, Ignacio Mata, and José Luis Vázquez-Barquero
- Subjects
Adult ,Affective Disorders, Psychotic ,Male ,Oncology ,Psychosis ,medicine.medical_specialty ,Adolescent ,Genotype ,Catechol O-Methyltransferase ,behavioral disciplines and activities ,Cellular and Molecular Neuroscience ,Methionine ,Internal medicine ,mental disorders ,medicine ,Humans ,Genetic Predisposition to Disease ,Age of Onset ,Allele ,Genetics (clinical) ,First episode ,Polymorphism, Genetic ,Catechol-O-methyl transferase ,business.industry ,Valine ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Amino Acid Substitution ,Psychotic Disorders ,dup ,Schizophrenia ,Etiology ,Female ,Age of onset ,business - Abstract
Catechol-O-methyltransferase (COMT) Val158Met polymorphism has been identified as a potential etiologic factor in schizophrenia. It has been proposed that this polymorphism could be associated with specific clinical markers. The aim of the study was to evaluate the influence of COMT Val158Met polymorphism genotype in the phenotypic expression of first episode psychosis at onset. Age of onset, DUP, SANS, and SAPS (positive, disorganized, and negative dimensions) were studied in 169 Caucasian drug-naïve patients with a first-episode of non-affective psychosis. The COMT Val158Met polymorphism was typed using PCR amplification of the relevant region followed by digestion with NlaIII and electrophoresis. A multivariate ANCOVA was performed with COMT and gender as independent variables. Patients with Val/Val genotype had significantly higher levels of SANS negative dimension scores (F: 3.539; P = 0.031) and had a younger age of onset (F: 4.649; P = 0.011) than Met carriers. Our findings suggest that the Val allele is associated with onset phenotypic features related to a poor prognosis of the illness. These data would indicate that COMT genotype may have a role in the etiological model for schizophrenia and other psychotic disorders.
- Published
- 2008
43. Exploring genetic variations that may be associated with the direct effects of some antipsychotics on lipid levels
- Author
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Juan Carlos Correa, Maria Arranz, Gualberto Ruaño, Jose de Leon, Francisco J. Diaz, and Andreas Windemuth
- Subjects
Adult ,Male ,Olanzapine ,Dibenzothiazepines ,medicine.medical_specialty ,Genotype ,Chlorpromazine ,medicine.drug_class ,Hypercholesterolemia ,Atypical antipsychotic ,Hyperlipidemias ,Single-nucleotide polymorphism ,Bioinformatics ,Polymorphism, Single Nucleotide ,Benzodiazepines ,Quetiapine Fumarate ,Gene Frequency ,Internal medicine ,Hyperlipidemia ,medicine ,Humans ,SNP ,Biological Psychiatry ,Oligonucleotide Array Sequence Analysis ,Randomized Controlled Trials as Topic ,Hypertriglyceridemia ,business.industry ,Dopamine antagonist ,Genetic Variation ,medicine.disease ,Lipids ,Psychiatry and Mental health ,Cross-Sectional Studies ,Endocrinology ,Psychotic Disorders ,Pharmacogenetics ,Quetiapine ,Female ,business ,Antipsychotic Agents ,medicine.drug - Abstract
The goal of this study was to select some genes that may serve as good candidates for future studies of the direct effects (not explained by obesity) of some antipsychotics on hyperlipidemia. A search for single-nucleotide polymorphisms (SNPs) that may be associated with these direct effects was conducted. From a published cross-sectional sample, 357 patients on antipsychotics were genotyped using a DNA microarray with 384 SNPs. A total of 165 patients were taking olanzapine, quetiapine or chlorpromazine which may directly cause hypertriglyceridemia or hypercholesterolemia. Another 192 patients taking other antipsychotics were controls. A two-stage statistical analysis that included loglinear and logistic models was developed to select SNPs blindly. In a third stage, physiological knowledge was used to select promising SNPs. Known physiological mechanisms were supported for 3 associations found in patients taking olanzapine, quetiapine or chlorpromazine [acetyl-coenzyme A carboxylase α SNP (rs4072032) in the hypertriglyceridemia model, and for the neuropeptide Y (rs1468271) and ACCβ, (rs2241220) in the hypercholesterolemia model]. These genes may be promising candidates for studies of the direct effects of some antipsychotics on hyperlipidemia.
- Published
- 2008
44. Choline acetyltransferase variants and their influence in schizophrenia and olanzapine response
- Author
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D Mancama, Ignacio Mata, Robert Kerwin, and Maria Arranz
- Subjects
Olanzapine ,Psychosis ,medicine.medical_specialty ,Genotype ,medicine.drug_class ,Atypical antipsychotic ,Polymorphism, Single Nucleotide ,Choline O-Acetyltransferase ,Benzodiazepines ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Gene Frequency ,Internal medicine ,Humans ,Medicine ,Choline ,Genetic Predisposition to Disease ,Effects of sleep deprivation on cognitive performance ,Genetics (clinical) ,business.industry ,Dopamine antagonist ,Genetic Variation ,medicine.disease ,Choline acetyltransferase ,Psychiatry and Mental health ,Endocrinology ,chemistry ,Schizophrenia ,business ,Antipsychotic Agents ,medicine.drug - Abstract
Choline acetyltransferase (ChAt) is extensively distributed throughout the CNS where, by catalyzing acetylcholine synthesis, it participates in modulating wide-ranging cholinergic-dependent functions including cognitive performance, sleep, arousal, movement, and visual information processing. Recently, compelling evidence has mounted implicating ChAt in schizophrenia. In particular, studies have identified significant reductions in ChAt activity in the nucleus accumbens and pontine tegmentum of such patients, which furthermore correlate significantly with measures of cognitive performance in the disorder. Similarly, elevated levels of choline, the acetylcholine precursor, have been identified among patients, implicating altered ChAt activity in these individuals. We sought to investigate the potential contribution of three ChAt gene polymorphisms in schizophrenia, and uncovered evidence for significant association between one of these, rs1880676G/A, and disease susceptibility among Basque individuals (genotypewise χ2 = 20.7, P = 0.00003; allelewise χ2 = 10.1, P = 0.002). A similar trend for association with susceptibility was observed for a second SNP, rs3810950G/A, (genotypwise χ2 = 6.4, P = 0.05; allelewise χ2 = 3.75, P = 0.05). Evidence was also uncovered for a potential influence of these polymorphisms on olanzapine treatment outcome among Spanish patients (F-statistic = 5.02, P = 0.03; F-statistic = 6.53, P = 0.02 respectively), and on improvements in positive symptoms in the case of rs3810950 (F-statistic = 5.3, P = 0.03) and general psychopathology in the case of rs1880676 and rs3810950 (F-statistic = 5.24, P = 0.03; F-statistic = 5.31, P = 0.03 respectively) during therapy. While more comprehensive studies are warranted to determine the precise contribution of ChAt mediated mechanisms in schizophrenia, our findings tentatively implicate a genetic influence of ChAt in the disorder's susceptibility and treatment. © 2007 Wiley-Liss, Inc.
- Published
- 2007
45. Hypothalamic-pituitary-adrenal system, neurotrophic factors and clozapine response: association with FKBP5 and NTRK2 genes
- Author
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Mireia Vázquez, Alexandre Pons, Rosa Catalán, Marina Mitjans, Janet Munro, A. González-Rodríguez, Guillem Massana, Bárbara Arias, Maria Arranz, and Rafael Penadés
- Subjects
medicine.medical_specialty ,Genotype ,medicine.drug_class ,Atypical antipsychotic ,Pituitary-Adrenal System ,Tropomyosin receptor kinase B ,Polymorphism, Single Nucleotide ,Tacrolimus Binding Proteins ,Glucocorticoid receptor ,Neurotrophic factors ,Internal medicine ,Genetics ,medicine ,Humans ,Receptor, trkB ,Genetic Predisposition to Disease ,General Pharmacology, Toxicology and Pharmaceutics ,Molecular Biology ,Clozapine ,Genetics (clinical) ,Alleles ,Genetic Association Studies ,Membrane Glycoproteins ,business.industry ,Haplotype ,Protein-Tyrosine Kinases ,medicine.disease ,Endocrinology ,Haplotypes ,Schizophrenia ,Molecular Medicine ,FKBP5 ,business ,medicine.drug ,Antipsychotic Agents - Abstract
Clozapine is an atypical antipsychotic drug known as being more effective compared with traditional antipsychotics for patients with poor response or resistance to treatment. It has been demonstrated that clozapine modulates hypothalamic-pituitary-adrenal activity and affects central brain-derived neurotrophic factor levels, which could explain part of its therapeutic efficacy. In this study, we investigated the role of genes related to the hypothalamic-pituitary-adrenal axis (FKBP5 and NR3C1) and neurotrophic factors (BDNF and NTRK2) in clinical response to clozapine in 591 schizophrenia patients. We found significant allelic and genotype associations between FKBP5-rs1360780, NTRK2-rs1778929 and NTRK2-rs10465180 polymorphisms and clozapine response. The haplotypes composed of rs1360780-rs3777747-rs17542466-rs2766533 (FKBP5) and rs1619120-rs1778929-rs10465180 (NTRK2) were also nominally significant. Our results suggest that genetic variability in FKBP5 and NTRK2 genes may partially explain clinical response to clozapine. Further studies are needed to clarify the involvement of these genes in clinical response to atypical antipsychotics.
- Published
- 2015
46. The role of hypothalamus-pituitary-adrenal genes and childhood trauma in borderline personality disorder
- Author
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Mónica Prat, Matilde Elices, Ana Martín-Blanco, Maria Arranz, Natalia Calvo, Cristina Carmona, Víctor Pérez, Juan C. Pascual, Iris Garcia-Martínez, Joaquim Soler, Daniel Vega, Cristina Sánchez-Mora, Marc Ferrer, Joana Bauzà, and Juliana Salazar
- Subjects
Adult ,Male ,medicine.medical_specialty ,Hypothalamo-Hypophyseal System ,Genotype ,Pituitary-Adrenal System ,behavioral disciplines and activities ,Receptors, Corticotropin-Releasing Hormone ,Pathogenesis ,Tacrolimus Binding Proteins ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Gene Frequency ,Borderline Personality Disorder ,mental disorders ,Monoaminergic ,medicine ,Humans ,Pharmacology (medical) ,Child Abuse ,Allele ,Psychiatry ,Child ,Borderline personality disorder ,Biological Psychiatry ,Genetic Association Studies ,Psychiatric Status Rating Scales ,Haplotype ,General Medicine ,medicine.disease ,030227 psychiatry ,Psychiatry and Mental health ,Physical abuse ,Hypothalamus ,Case-Control Studies ,Female ,FKBP5 ,Psychology ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus-pituitary-adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case-control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder.
- Published
- 2015
47. Expression of the α1A-adrenergic receptor in schizophrenia
- Author
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Maria Arranz, D Mancama, Dan A. Clark, and Robert Kerwin
- Subjects
Male ,medicine.medical_specialty ,Psychosis ,Adrenergic receptor ,Gene Expression ,Adrenergic ,Biology ,Transcription (biology) ,Receptors, Adrenergic, alpha-1 ,Internal medicine ,Genotype ,Gene expression ,medicine ,Humans ,RNA, Messenger ,Receptor ,Aged ,Aged, 80 and over ,Messenger RNA ,Polymorphism, Genetic ,Reverse Transcriptase Polymerase Chain Reaction ,General Neuroscience ,Middle Aged ,medicine.disease ,Endocrinology ,Schizophrenia ,Female - Abstract
The alpha1-adrenergic receptors may contribute to cognitive functions relevant to schizophrenia. Following the discovery of an association between polymorphisms in the regulatory region of the alpha1A-adrenergic receptor and schizophrenia we investigated the expression of mRNA for this receptor between schizophrenics (n=19) and controls (n=19) using a TaqMan approach in post-mortem brains. No differences were found suggesting that mRNA levels are not altered in schizophrenia. Genotypic data for the subjects found that possession of the previously associated genotypes did not convey a difference in mRNA expression suggesting that these polymorphisms do not affect the level of transcription.
- Published
- 2006
48. Polymorphisms in the Promoter Region of the Alpha1A-Adrenoceptor Gene Are Associated with Schizophrenia/Schizoaffective Disorder in a Spanish Isolate Population
- Author
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Dan A. Clark, Ignacio Mata, Robert Kerwin, F Perez-Nievas, Maria Arranz, and J.M. López-Ilundain
- Subjects
Male ,Genotype ,Receptor expression ,DNA Mutational Analysis ,Population ,Single-nucleotide polymorphism ,Gene Frequency ,Receptors, Adrenergic, alpha-1 ,Confidence Intervals ,Odds Ratio ,Humans ,Genetic Predisposition to Disease ,Allele ,Promoter Regions, Genetic ,education ,Allele frequency ,Biological Psychiatry ,Genetic association ,Genetics ,education.field_of_study ,Polymorphism, Genetic ,Haplotype ,Psychotic Disorders ,Spain ,Schizophrenia ,Female ,Psychology - Abstract
Background Animal models have implicated the α 1 -adrenergic subtypes in cognitive functions relevant to schizophrenia, but no consensus exists with regard to the status of noradrenergic receptor populations in psychiatric patients. We focused on one α 1 -adrenergic subtype, the α 1A -adrenergic receptor, and proposed that genetic variants within the regulatory region of this gene (ADRA1A) alter the expression of this receptor, influencing susceptibility toward schizophrenia. Methods This study examined this proposal by testing the hypothesis that single nucleotide polymorphisms (SNPs) in the promoter region of the α 1A -adrenergic gene were associated with schizophrenia by performing case–control association analysis on SNPs found in a 5′ upstream region, which included the putative promoter region and 5′ untranslated region. Our sample consisted of 103 schizophrenia and 14 schizoaffective disorder patients and 176 control subjects. All recruits were from a Spanish population isolate of Basque origin that is characterized by low heterogeneity, which was selected with the intent that it might facilitate the identification of disease-related polymorphisms. Results A total of eight SNPs (−9625 G/A, −7255 A/G, −6274 C/T, −4884 A/G, −4155 C/G, −2760 A/C, −1873 G/A, and −563 C/T) were confirmed at a rare allele frequency of >5%. Association with schizophrenia and schizoaffective disorder was found for the −563 C/T SNP ( p = .0005 for allele and p = .007 for genotype, Bonferroni corrected) and −9625 G/A SNP ( p = .02 for allele and p = .03 for genotype, Bonferroni corrected). Significant differences in the 54 haplotypes formed by these eight SNPs were also found between patients and control subjects ( p = .008, Bonferroni corrected). Conclusions Because of the strength of these results and the location of these SNPs in the regulatory region of this gene, functional studies investigating the possible influence of these SNPs on receptor expression levels in schizophrenia are warranted.
- Published
- 2005
49. Impact of nicotine consumption on antipsychotic response based on genetic variants of cytochrome P450 2D6 and multi-drug resistance 1 C3435T in schizophrenia
- Author
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M. Bernardo, Maria Arranz, Rafael Penadés, Blanca Gutiérrez, A. González-Rodríguez, F. Pérez-Blanco, and R. Catalán
- Subjects
Pharmacology ,Consumption (economics) ,CYP2D6 ,business.industry ,medicine.medical_treatment ,Genetic variants ,Drug resistance ,medicine.disease ,Nicotine ,Psychiatry and Mental health ,Neurology ,Schizophrenia ,medicine ,Pharmacology (medical) ,Neurology (clinical) ,business ,Antipsychotic ,Biological Psychiatry ,medicine.drug - Published
- 2016
50. Serotonergic polymorphisms and psychotic disorders in populations from North Spain
- Author
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Ana Patiño, Felipe Ortuño, Maria Arranz, David M. Clark, M Beperet, T Lai, Robert Kerwin, Ignacio Mata, L Sierrasesumaga, Lee Richards, Pak C. Sham, and F Perez-Nievas
- Subjects
Genetics ,Psychosis ,education.field_of_study ,Population ,Biology ,medicine.disease ,Serotonergic ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Schizophrenia ,Polymorphism (computer science) ,medicine ,biology.protein ,Serotonin ,education ,Gene ,Genetics (clinical) ,Serotonin transporter - Abstract
There is strong biological evidence relating alterations in the serotonergic system with mental disorders. These alterations may be originated at the DNA level by sequence mutations that alter the functioning of serotonin receptors and transporter. To test this hypothesis we investigated three genetic variants of the 5-HT2A receptor (−1438G/A, 102T/C and His452Tyr) and two variants of the serotonin transporter (a VNTR in the second intron and a 44 bp insertion/delition in the promoter region of the gene) in a clinical sample recruited in a human isolate and in surrounding areas in Northern Spain (N = 257) and in ethnically matched controls (N = 334). No clear association was found between 5-HT2A variants and psychosis. However, marginal associations were observed between the 5-HTT LPR and VNTR variants and psychosis (P ≤ 0.05) indicating a minor contribution to psychosis of genetic alterations in this gene. © 2003 Wiley-Liss, Inc.
- Published
- 2003
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