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1.
Psychiatr Danub ; 31(2): 162-171, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31291220

RESUMO

In this project, we recruited a sample of 150 patients with first episode of psychosis with schizophrenia features (FEP) and 100 healthy controls. We assessed the differences between these two groups, as well as the changes between the acute phase of illness and subsequent remission among patients over 18-month longitudinal follow-up. The assessments were divided into four work packages (WP): WP1- psychopathological status, neurocognitive functioning and emotional recognition; WP2- stress response measured by saliva cortisol during a stress paradigm; cerebral blood perfusion in the resting state (with single photon emission computed tomography (SPECT) and during activation paradigm (with Transcranial Ultrasonography Doppler (TCD); WP3-post mortem analysis in histologically prepared human cortical tissue of post mortem samples of subjects with schizophrenia in the region that synaptic alteration was suggested by WP1 and WP2; WP4- pharmacogenetic analysis (single gene polymorphisms and genome wide association study (GWAS). We expect that the analysis of these data will identify a set of markers that differentiate healthy controls from patients with FEP, and serve as an additional diagnostic tool in the first episode of psychosis, and prediction tool which can be then used to help tailoring individualized treatment options. In this paper, we describe the project protocol including aims and methods and provide a brief description of planned post mortem studies and pharmacogenetic analysis.


Assuntos
Biomarcadores/análise , Transtornos Psicóticos/genética , Feminino , Seguimentos , Estudo de Associação Genômica Ampla , Humanos , Hidrocortisona/análise , Masculino , Farmacogenética , Estudos Prospectivos , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Saliva/química , Esquizofrenia/complicações
2.
Tijdschr Psychiatr ; 61(6): 421-425, 2019.
Artigo em Holandês | MEDLINE | ID: mdl-31243752

RESUMO

Genetic factors play an important role in the development of psychotic disorders. With increasing evidence, several rare copy number variants (cnvs) have been identified as risk factors. We describe a patient who had two psychotic episodes during his adolescence. In this patient, a 16p11.2 duplication was detected. This duplication is a recurrent cnv associated with various somatic and psychiatric phenotypes including psychosis and schizophrenia. The potential clinical relevance of this finding is discussed.


Assuntos
Transtornos Psicóticos/genética , Adolescente , Cromossomos Humanos Par 16 , Variações do Número de Cópias de DNA , Predisposição Genética para Doença , Humanos , Masculino , Fenótipo , Transtornos Psicóticos/diagnóstico , Adulto Jovem
4.
Nat Genet ; 51(5): 793-803, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31043756

RESUMO

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.


Assuntos
Transtorno Bipolar/genética , Loci Gênicos , Transtorno Bipolar/classificação , Estudos de Casos e Controles , Transtorno Depressivo Maior/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/genética , Esquizofrenia/genética , Biologia de Sistemas
5.
Gene ; 704: 68-73, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30986448

RESUMO

AIM: The purpose of the present study is to evaluate and understand the association of global and MTHFR gene specific methylation in preeclampsia and recurrent miscarriages in light of MTHFR C677T polymorphism. METHODS: The subjects comprised of recurrent miscarriage cases, their gestation matched controls, preeclampsia cases and matched controls. A set of women at full term were also recruited. Fasting blood sample (~5 ml) was drawn from all the participants followed by DNA extraction, global DNA methylation and MTHFR gene specific methylation. MTHFR C677T polymorphism was analysed by PCR followed by RFLP. RESULTS HIGHER: Global DNA methylation at maternal front (p = 0.04) and hypomethylation of MTHFR gene at fetal front (p = 0.001) might be a characteristic of preeclampsia. Recurrent miscarriage cases were having significantly (p = 0.002) hyper MTHFR gene specific methylation as compared to controls. Women carrying CT genotype were found to be having significantly (p = 0.001) higher global DNA methylation in PE cases and MTHFR gene specific methylation (p = 0.005) in RM cases. Intergenerational analysis revealed similar patterns of global DNA methylation and MTHFR gene specific methylation among both PE and RM cases at maternal and fetal fronts. CONCLUSION: The study highlights the importance of global DNA methylation in Preeclampsia and MTHFR gene specific methylation in recurrent miscarriages. MTHFR C677T gene polymorphism in association with global and gene specific methylation seem to play a pivotal role in PE and RM respectively.


Assuntos
Aborto Habitual/genética , Metilação de DNA , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pré-Eclâmpsia/genética , Adulto , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Homocistinúria/complicações , Homocistinúria/genética , Humanos , Índia , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Espasticidade Muscular/complicações , Espasticidade Muscular/genética , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/diagnóstico , Gravidez , Segundo Trimestre da Gravidez/genética , Terceiro Trimestre da Gravidez/genética , Transtornos Psicóticos/complicações , Transtornos Psicóticos/genética
6.
Psychiatry Res ; 274: 391-394, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30901624

RESUMO

We investigated the role of DGCR2, a corticogenesis-related gene, on schizophrenia (SZ) and its subphenotypes, including brain morphology. A total of 221 SZ patients, 263 controls and 70 antipsychotic-naïve first episode of psychosis (FEP) were genotyped for 17 DGCR2 polymorphisms. While no association between DGCR2 polymorphisms and SZ was found, the missense variant rs2072123 was associated to left rostral anterior cingulate thickness, showing that DGCR2 seems not to be associated directly with the SZ but might be influencing the brain morphology. We also showed a DGCR2 downregulation in SZ patients when compared to controls and FEP.


Assuntos
Giro do Cíngulo/patologia , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Esquizofrenia/genética , Esquizofrenia/patologia , Adulto , Feminino , Genótipo , Humanos , Masculino , Mutação de Sentido Incorreto , Transtornos Psicóticos/genética , Transtornos Psicóticos/patologia
7.
Transl Psychiatry ; 9(1): 60, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718465

RESUMO

We searched for genetic causes of major psychiatric disorders (bipolar disorder, schizoaffective disorder, and schizophrenia) in a large, densely affected pedigree from Northern Sweden that originated with three pairs of founders born around 1650. We applied a systematic genomic approach to the pedigree via karyotyping (N = 9), genome-wide SNP arrays (N = 418), whole-exome sequencing (N = 26), and whole-genome sequencing (N = 10). Comprehensive analysis did not identify plausible variants of strong effect. Rather, pedigree cases had significantly higher genetic risk scores compared to pedigree and community controls.


Assuntos
Transtorno Bipolar/genética , Genômica/métodos , Transtornos Psicóticos/genética , Esquizofrenia/genética , Adulto , Idoso , Transtorno Bipolar/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Cariotipagem/métodos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Linhagem , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/epidemiologia , Esquizofrenia/epidemiologia , Suécia/epidemiologia , Sequenciamento Completo do Exoma/métodos , Sequenciamento Completo do Genoma/métodos
8.
Nervenarzt ; 90(2): 114-120, 2019 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-30659310

RESUMO

The handling of predictive genetic tests especially in the field of mental diseases requires a sensitive approach. In particular internet-based direct-to-consumer offers cannot provide an appropriate interpretation of the onset probabilistic data. Instead, a doctor-patient relationship should cater for clarity through hermeneutic and non-technicistic assistance with respect to the necessity of a test as well as with a view to the interpretation of the test results.


Assuntos
Relações Médico-Paciente , Transtornos Psicóticos , Aconselhamento Genético , Testes Genéticos/ética , Humanos , Internet , Relações Médico-Paciente/ética , Transtornos Psicóticos/genética
9.
Artigo em Inglês | MEDLINE | ID: mdl-30118824

RESUMO

The ZNF804A gene and cannabis use are risk factors for psychosis and both have also been associated with schizotypal traits. This study aimed to investigate: i) the association of lifetime cannabis use (and its dose effect) with schizotypal personality traits, and ii) whether the genetic variability at ZNF804A gene modulates that association. Our sample consisted of 385 Spanish non-clinical subjects (43.1% males, mean age = 21.11(2.19)). Schizotypy was evaluated using the three factors of the Schizotypal Personality Questionnaire-Brief (SPQ-B): Cognitive-Perceptual (SPQ-CP), Interpersonal (SPQ-I) and Disorganized (SPQ-D). Subjects were classified according to their frequency of cannabis consumption, and dichotomized as users or non-users. The effects of a genetic variant of ZNF804A (rs1344706) and cannabis use, as well as their interaction, on each of the three SPQ-B factors were assessed using linear models and permutation tests. Sex, SCL anxiety scores and use of other drugs were included as covariates. Our analysis showed a significant relationship between ZNF804A and SPQ-I: AA genotype was associated with higher scores (ß = 0.885 pFDR = .018). An interaction between the AA genotype and lifetime cannabis use was found in SPQ-CP (ß = 1.297 pFDR = 0.018). This interaction showed a dose-effect pattern among AA subjects: schizotypy scores increased with increasing frequency of cannabis use (sporadic users: ß = 0.746 pFDR = 0.208; monthly users: ß = 1.688 pFDR = 0.091; intense users: ß = 1.623 pFDR = 0.038). These results add evidence on that the ZNF804A gene is associated with schizotypy and suggest that the interaction between cannabis use and ZNF804A genotype could modulate psychosis proneness.


Assuntos
Fatores de Transcrição Kruppel-Like/genética , Uso da Maconha/genética , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/genética , Transtorno da Personalidade Esquizotípica/epidemiologia , Transtorno da Personalidade Esquizotípica/genética , Cannabis , Feminino , Interação Gene-Ambiente , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/complicações , Transtornos Psicóticos/psicologia , Transtorno da Personalidade Esquizotípica/complicações , Transtorno da Personalidade Esquizotípica/psicologia , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-30149093

RESUMO

BACKGROUND: Approximately 5% of patients with schizophrenia commit suicide, and 20% to 40% of them have at least one suicide attempt during their lifetime. Previous research has identified childhood trauma as a potential risk factor for suicide attempt in schizophrenia. The Psychiatric Genetics Consortium found 108 common genetic risk loci associated with schizophrenia. Moreover, familial, adoption, and twin studies suggested that suicidal behaviour is under genetic influence. OBJECTIVE: Our objective was to determine the effect of childhood trauma and schizophrenia polygenic risk in leading to suicide attempt, as well as to determine any interaction effect between the polygenic scores with childhood trauma. METHODS: The study design was cross-sectional and retrospective considering lifetime suicide attempt as the main dependent variable. Childhood trauma was assessed using the Childhood Trauma Questionnaire. Polygenic Risk Score calculation was done using the genome-analysis toolkit, PLINK. The suicide attempts were recorded using the Columbia Suicide Severity Rating Scale. RESULTS: We included 224 subjects in our sample and 93 attempted suicide at least once in their lifetime. When comparing the weighted scores in attempters and non-attempters, we found no association (p > .05). CONCLUSION: Although our results do not support our hypothesis, the interaction analysis of genetic risk for schizophrenia in combination with the history of childhood trauma requires larger samples with high-quality suicide risk assessment.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância , Predisposição Genética para Doença , Herança Multifatorial , Transtornos Psicóticos/genética , Esquizofrenia/genética , Tentativa de Suicídio , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Estudos Transversais , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico , Transtornos Psicóticos/psicologia , Estudos Retrospectivos , Psicologia do Esquizofrênico , Tentativa de Suicídio/psicologia
11.
Cell Physiol Biochem ; 48(3): 1201-1214, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30045020

RESUMO

BACKGROUND: Reductions in the volume of brain white matter are a common feature in schizophrenia and bipolar disorder while the association between white matter and polygenic schizophrenia-related risk is unclear. To look at the intermediate state between health and the full-blown disorder, we investigated this aspect in groups of patients before and after the onset of psychosis. METHODS: On a 3 Tesla scanner, total and regional white matter volumes were investigated by structural magnetic resonance imaging (MRI) in the following groups: 37 at-risk mental state patients (ARMS), including 30 with no transition to psychosis (ARMS-NT) and 7 with a transition to psychosis (ARMS-T) pooled with 25 first episode psychosis (FEP) patients. These T1-weighted images were automatically processed with the FreeSurfer software and compared with an odds-ratio-weighted polygenic schizophrenia-related risk score (PSRS) based on the publicly available top white matter single-nucleotide polymorphisms. RESULTS: We found no association, only a trend, between PSRS and white matter volume over all groups (ß = 0.24, p = 0.07, 95% confidence interval = [-0.02 - 0.49]). However, a higher PSRS was significantly associated with a higher probability of being assigned to the ARMS-T + FEP group rather than to the ARMS-NT group (ß = 0.70, p = 0.02, 95% confidence interval = [0.14 - 1.33]); there was no such association with white matter volume. Additionally, a positive association was found between PSRS and the Brief Psychiatric Rating Scale (BPRS) total score for the pooled ARMS-NT/ARMS-T+FEP sample and for the ARMS-T + FEP group also, but none for the ARMS-NT group only. CONCLUSION: These findings suggest that at-risk mental state patients with a transition and first-episode psychosis patients have a higher genetic risk for schizophrenia than at-risk mental state patients with no transition to psychosis; this risk was associated with psychopathological symptoms. Further analyses may allow polygenic schizophrenia-related risk scores to be used as biomarkers to predict psychosis.


Assuntos
Encéfalo/patologia , Transtornos Psicóticos/patologia , Esquizofrenia/patologia , Substância Branca/patologia , Adulto , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/genética , Fatores de Risco , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Esquizofrenia/genética , Adulto Jovem
13.
Mol Biol Rep ; 45(4): 621-624, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29855758

RESUMO

Deep vein thrombosis (DVT) is a common disease, especially among elderly patients, which is associated with high costs of treatment and high rates of recurrence. The risk factors for venous thrombosis are primarily related to hypercoagulability, which can be genetic or acquired, or because of immobilization and venous stasis. Among relevant genetic markers are a number of common polymorphisms and mutations in the genes coding for Factor V leiden and methylenetetrahydrofolate reductase. Differential associations of these polymorphisms have been reported in different populations with DVT due to ethnic variations. However, no study has been reported with respect to these polymorphisms in DVT in Iran. Thus, the aim of the present study is to determine the prevalence of FVL, MTHFR C677T and MTHFR A1298C gene polymorphisms in patients with DVT in central Iran. In the present cross-sectional study, a total of 100 patients with first and recurrent episodes of DVT and age less than 70 years were recruited during 2016-2017. Blood sample was collected from the recruited patients and FVL mutation was screened using ARMS-PCR method, MTHFR C677T and MTHFR A1298C mutations were screened using PCR-RFLP method. The results revealed that MTHFR A1298C gene polymorphism in both homozygote and heterozygote form was found to be most frequent i.e. 77% among cases, followed by MTHFR C677T (67%) and FVL (17%). The study highlights the importance of screening of these genetic markers among patients with DVT in this region.


Assuntos
Fator V/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Trombose Venosa/genética , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Fator V/metabolismo , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Homocistinúria/genética , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Espasticidade Muscular/genética , Mutação , Polimorfismo de Nucleotídeo Único/genética , Prevalência , Transtornos Psicóticos/genética , Fatores de Risco , Trombose Venosa/etiologia
14.
Tijdschr Psychiatr ; 60(3): 161-165, 2018.
Artigo em Holandês | MEDLINE | ID: mdl-29521403

RESUMO

BACKGROUND: Personalised medicine (pm) means treatment that specifically targets the needs of individual patients on the basis of genetic, biomarker, phenotypic or psychosocial characteristics.
AIM: To update our knowledge about the current use of pm in the treatment of psychotic disorders.
METHOD: Review of the literature on pm for psychoses.
RESULTS: At the moment, genetic and other biological characteristics cannot be used for the diagnosis and treatment of psychotic disorders because they are not sensitive enough and their specificity is too low. We investigated immunulogical, oxidative, metabolic, hormonal and dopaminergic aspects that could lead to the use of pm. pm is already being used on the basis of phenotypical, cognitive and psychosocial characteristics; those characteristics include substance abuse, cognitive dysfunction, ethnicity and childhood trauma.
CONCLUSION: In the next years there may be more opportunities for using for pm in psychosis. The increase may results from large genetic network studies and treatment studies involving stratification based on hypothetical specific mechanisms instead of on the categorical diagnosis of illnesses such as schizophrenia.


Assuntos
Medicina de Precisão , Transtornos Psicóticos/diagnóstico , Redes Reguladoras de Genes , Humanos , Classificação Internacional de Doenças , Transtornos Psicóticos/genética
16.
PLoS One ; 13(2): e0192658, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29444152

RESUMO

BACKGROUND: Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. OBJECTIVE: A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). DATA SOURCES: PubMed, Embase, PsychInfo. STUDY ELIGIBILITY CRITERIA: All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. STUDY APPRAISAL AND SYNTHESIS METHODS: A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions". RESULTS: For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05-2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16-0.08). LIMITATION: A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects. CONCLUSION: The interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing.


Assuntos
Cannabis , Catecol O-Metiltransferase/genética , Metionina/genética , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/genética , Humanos , Transtornos Psicóticos/diagnóstico , Valina/genética
17.
Psychiatry Res ; 261: 148-153, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29306175

RESUMO

Several studies have indicated infectious and immune-related abnormalities in schizophrenia (Scz), including elevated serum C-reactive protein (CRP) - a well-known proxy for infections/immune abnormalities. A portion of the genetic risk for Scz can be estimated using the polygenic risk score (PGRS). It is not known whether there is an interaction in the risks traceable to CRP and PGRS. Patients with Scz and individuals without psychosis were evaluated systematically using DSM IV criteria (N=794, N=446, respectively). To estimate risk for Scz attributable to CRP and PGRS, serum from these participants was assayed for CRP levels using enzyme linked immunosorbent assays. PGRS was estimated from common DNA polymorphisms associated with Scz from genome wide association studies. CRP level and PGRS were not significantly correlated. Using a generalized linear logistic model, case/control status was evaluated in relation to the following predictors: CRP, PGRS, and demographic variables. CRP and PGRS were individually associated with case status; CRP: odds ratio (OR) 1.27, 95% confidence intervals (95% CI) 1.12, 1.43; p = 0.0001; PGRS: OR 1.66, 95% CI 1.47, 1.89; p = 1.28 ×10-15. There were no significant interactions between PGRS and CRP for predicting Scz versus control status.


Assuntos
Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Predisposição Genética para Doença/genética , Herança Multifatorial/genética , Esquizofrenia/sangue , Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/sangue , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/genética , Fatores de Risco , Esquizofrenia/diagnóstico
18.
Eur J Med Genet ; 61(5): 280-283, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29307791

RESUMO

22q11.2 microduplication (22q11.2DupS) is associated with a broad spectrum of phenotypes, including normality. Psychiatric disorders are described in 13% of these patients, including Attention Deficit and Hyperactivity Disorder (ADHD), Intellectual Deficiency (ID), and Autism Spectrum Disorder (ASD), but not schizophrenia. We report changes in the psychiatric symptom profile in the course of development of a young boy with a 22q11.2DupS syndrome, from early childhood to adolescence. The boy's psychiatric presentation was characterized by features of Pervasive Developmental Disorder (PDD), with ADHD in early childhood, a single psychotic episode in mid-infancy, and executive impairment in adolescence. We discuss the importance of an in-depth assessment of cognitive functions in children with22q11.2DupS throughout their development.


Assuntos
Anormalidades Múltiplas/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Síndrome de DiGeorge/diagnóstico , Transtornos Psicóticos/diagnóstico , Anormalidades Múltiplas/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Transtornos Globais do Desenvolvimento Infantil/genética , Duplicação Cromossômica/genética , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/genética , Função Executiva , Humanos , Masculino , Linhagem , Transtornos Psicóticos/genética
19.
Eur J Med Genet ; 61(4): 230-234, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29225144

RESUMO

The genetic association between autism spectrum disorder (ASD) and psychotic disorders such as schizophrenia is complicated and mirrors the clinical overlap between these conditions to some degree. However, no studies to date have examined the genetics of individuals dually diagnosed with both ASD and psychosis. In this study, we present findings of copy number variants (CNVs) from a study of 116 well-characterised individuals with this dual diagnosis. DNA was extracted and arrayed using the Affymetrix CytoScan HD 2.8M array or the Affymetrix Cytogenetics arrays and compared with existing samples from the Database of Genomic Variants and the Simons Simplex Collection of CNVs from individuals with ASD and their families. Twenty-seven novel CNVs ≥20k base pairs were identified in the sample, most occurring in only a single individual, although two were found in two female participants. Forty-nine rare CNVs (<1.5% rate in general population) were also found at significantly higher frequencies than expected. The findings may provide evidence for areas of further study in the understanding of the development of both ASD and psychosis due to the number of affected genetic regions that have not previously been linked to these conditions.


Assuntos
Transtorno do Espectro Autista/genética , Variações do Número de Cópias de DNA , Transtornos Psicóticos/genética , Transtorno do Espectro Autista/complicações , Humanos , Transtornos Psicóticos/complicações
20.
Schizophr Res ; 195: 190-196, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28958479

RESUMO

The rs1625579 variant near the microRNA-137 (MIR137) gene is one of the best-supported schizophrenia variants in genome-wide association studies (GWAS), and microRNA-137 functionally regulates other GWAS identified schizophrenia risk variants. Schizophrenia patients with the MIR137 rs1625579 risk genotype (homozygous for the schizophrenia risk variant) also have aberrant brain structure. It is unclear if the effect of MIR137 among schizophrenia patients is due to potential epistasis with genetic risk for schizophrenia or other factors of the disorder. Here, we investigated the effect of MIR137 genotype on white matter fractional anisotropy (FA), cortical thickness (CT), and surface area (SA) in a sample comprising healthy control subjects, and individuals with familial risk for psychosis (first-degree relatives of patients with schizophrenia or bipolar disorder; N=426). In voxel-wise analyses of FA, we observed a significant genotype-by-group interaction (PFWE<0.05). The familial risk group with risk genotype had lower FA (PFWE<0.05), but there was no genetic association in controls. In vertex-wise analyses of SA, we also observed a significant genotype-by-group interaction (PFWE<0.05). Relatives with MIR137 risk genotype had lower SA, however the risk genotype was associated with higher SA in the controls (all PFWE<0.05). These results show that MIR137 risk genotype is associated with lower FA in psychosis relatives that is similar to previous imaging-genetics findings in patients with schizophrenia. Furthermore, MIR137 genotype may also be a risk factor in a subclinical population with wide reductions in white matter FA and cortical SA.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único/genética , Transtornos Psicóticos/genética , Substância Branca/diagnóstico por imagem , Adulto , Anisotropia , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/diagnóstico por imagem
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