Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence

Cocaine reward and reinforcing effects are mediated mainly by dopaminergic neurotransmission. In this study, we aimed at evaluating gene expression changes induced by acute cocaine exposure on SH-SY5Y-differentiated cells, which have been widely used as a dopaminergic neuronal model. Expression changes and a concomitant increase in neuronal activity were observed after a 5 μ cocaine exposure, whereas no changes in gene expression or in neuronal activity took place at 1 μ cocaine. Changes in gene expression were identified in a total of 756 genes, mainly related to regulation of transcription and gene expression, cell cycle, adhesion and cell projection, as well as mitogen-activeated protein kinase (MAPK), CREB, neurotrophin and neuregulin signaling pathways. Some genes displaying altered expression were subsequently targeted with predicted functional single-nucleotide polymorphisms (SNPs) in a case-control association study in a sample of 806 cocaine-dependent patients and 817 controls. This study highlighted associations between cocaine dependence and five SNPs predicted to alter microRNA binding at the 3'-untranslated region of the NFAT5 gene. The association of SNP rs1437134 with cocaine dependence survived the Bonferroni correction for multiple testing. A functional effect was confirmed for this variant by a luciferase reporter assay, with lower expression observed for the rs1437134G allele, which was more pronounced in the presence of hsa-miR-509. However, brain volumes in regions of relevance to addiction, as assessed with magnetic resonance imaging, did not correlate with NFAT5 variation. These results suggest that the NFAT5 gene, which is upregulated a few hours after cocaine exposure, may be involved in the genetic predisposition to cocaine dependence

Gambling Problems among Community Cocaine Users

Cocaine use is highly prevalent and a major public health problem. While some studies have reported frequent comorbidity problems among cocaine users, few studies have included evaluation of gambling problems. This study aimed to estimate the prevalence of gambling problems and compare those who were at-risk gamblers with non-problem gamblers in terms of mental health problems, substance use problems, and some risk factors (i.e. family antecedents, erroneous perceptions and coping strategies) among individuals who smoke or inject cocaine. METHOD: A total of 424 smoked or injected cocaine users recruited through community-based programs in Montreal, Quebec completed the questionnaire, including the Canadian Pathological Gambling Index, the Composite International Diagnostic Interview (CIDI), the CAGE, and the Severity Dependence Scale (SDS). RESULTS: Of the sample, 18.4 % were considered at-risk gamblers, of whom 7.8 % had problems gambling and 10.6 % were moderate-risk gamblers. The at-risk group was more likely to have experienced a recent phobic disorder and alcohol problems than the non-problem group. A multivariate analysis showed that, compared to those who were non-problem gamblers, the at-risk ones were more likely to have lost a large sum of money when they first started gambling, believed that their luck would turn, and gambled in reaction to painful life events. These results indicate the need to include routines for screening to identify gambling problem among cocaine user

European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe. METHODS: The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated. RESULTS: Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated? CONCLUSIONS: ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group

International consensus statement for the screening, diagnosis, and treatment of adolescents with concurrent Attention-Deficit/Hyperactivity Disorder and substance use disorder

Education and Child Studie

Anxiety and Depression in Drug-Dependent Patients with Cluster C Personality Disorders

ObjectiveComorbidity between personality disorders (PD) and substance-use disorders (SUD) is one of the most common findings in the psychiatric field. The patients with Cluster C disorders present maladjustment traits often characterized by high levels of anxiety. The main aim of this study was to find evidences about higher anxiety and depression prevalence on Cluster C than others Clusters, analyzing similarities and differences within, with other Cluster A and B PD patients and patients without PD.MethodA total of 822 substance dependent patients (ages18–78; Mean = 38.35, SD = 10.14) completed the structured clinical interview for DSM-IV Axis I and Axis II disorders, Beck Depression Inventory, and State-Trait Anxiety Inventory.ResultsResults supported poly-consumption in Cluster C patients, being greater alcohol consumption as well as abuse of both stimulants and depressants. Anxiety and depression did not show just one pattern for all patients with SUD-Cluster C PD. There was a relation between anxiety and depression for all the groups except for the Dependent-PD.ConclusionInterventions should focus on aspects like depression and anxiety more than on the substance consumed

Clinical differences between cocaine-dependent patients with and without antisocial personality disorder

The aim of this study is to compare the features of two groups of cocaine dependent patients in treatment, one of them with co-morbid diagnosis of antisocial personality disorder and the other not. Cross-sectional design, with 143 cocaine-dependent patients attending a drug unit, distributed in two groups: patients with and without Antisocial Personality Disorder. As results, we found that the 15.38% of the sample were diagnosed with an Antisocial Personality Disorder. In relation to socio-demographic variables, Antisocial Personality Disorder patients have less probability of being working or studying (9.1% vs. 47.9%). After multivariate analysis it was found that significantly Antisocial Personality Disorder patients have more opiates dependence (OR: 0.219; 95% IC 0.072-0.660), sedative dependence (OR: 0.203; 95% IC 0.062-0.644) and in more cases show Borderline Personality Disorder (OR: 0.239; 95% IC 0.077-0.746). This study highlights significant differences between cocaine addicts with or without an Antisocial Personality Disorder. All these differences are good indicators of the complexity of the patients with this personality disorder. Better knowledge of their profile will help us to improve the design of specific treatment programs

Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence

Contains fulltext : 152880.pdf (publisher's version ) (Open Access)Cocaine reward and reinforcing effects are mediated mainly by dopaminergic neurotransmission. In this study, we aimed at evaluating gene expression changes induced by acute cocaine exposure on SH-SY5Y-differentiated cells, which have been widely used as a dopaminergic neuronal model. Expression changes and a concomitant increase in neuronal activity were observed after a 5 muM cocaine exposure, whereas no changes in gene expression or in neuronal activity took place at 1 muM cocaine. Changes in gene expression were identified in a total of 756 genes, mainly related to regulation of transcription and gene expression, cell cycle, adhesion and cell projection, as well as mitogen-activeated protein kinase (MAPK), CREB, neurotrophin and neuregulin signaling pathways. Some genes displaying altered expression were subsequently targeted with predicted functional single-nucleotide polymorphisms (SNPs) in a case-control association study in a sample of 806 cocaine-dependent patients and 817 controls. This study highlighted associations between cocaine dependence and five SNPs predicted to alter microRNA binding at the 3'-untranslated region of the NFAT5 gene. The association of SNP rs1437134 with cocaine dependence survived the Bonferroni correction for multiple testing. A functional effect was confirmed for this variant by a luciferase reporter assay, with lower expression observed for the rs1437134G allele, which was more pronounced in the presence of hsa-miR-509. However, brain volumes in regions of relevance to addiction, as assessed with magnetic resonance imaging, did not correlate with NFAT5 variation. These results suggest that the NFAT5 gene, which is upregulated a few hours after cocaine exposure, may be involved in the genetic predisposition to cocaine dependence