Association of Functional DBH Genetic Variants With Alcohol Dependence Risk and Related Depression and Suicide Attempt Phenotypes: Results From a Large Multicenter Association Study.

Association of functional DBH genetic variants with alcohol dependence risk and related depression and suicide attempt phenotypes: Results from a large multicenter association study.

Drug Alcohol Depend. 2013 Jul 30;
Preuss UW, Wurst FM, Ridinger M, Rujescu D, Fehr C, Koller G, Bondy B, Wodarz N, Soyka M, Zill P

Dopamine-beta-hydroxylase (DBH) metabolizes the conversion of dopamine to noradrenaline. DBH, located on chromosome 9q34.2 has variants with potential functional consequences which may be related to alterations of neurotransmitter function and several psychiatric phenotypes, including alcohol dependence (AD), depression (MD) and suicidal behavior (SA). The aim of this association study in a large multicenter sample of alcohol-dependent individuals and controls is to investigate the role of DBH SNPs and haplotypes in AD risk and associated phenotypes (AD with MD or SA).1606 inpatient subjects with DSM-IV AD from four addiction treatment centers and 1866 control subjects were included. Characteristics of AD, MD and SA were obtained using standardized structured interviews. After subjects were genotyped for 4 DBH polymorphisms, single SNP case-control and haplotype analyses were conducted.rs1611115 (near 5′) C-allele and related haplotypes were significantly associated with alcohol dependence in females. This association with female alcohol dependence also accounts for the significant relationship between this variant and comorbid conditions and traits.This study presents evidence for a potentially functional DBH variant influencing the risk for alcohol dependence while other comorbid conditions are not independently influenced by this SNP. However, the study also supports the possible role of the dopamine system in the etiology of female alcohol dependence. HubMed – addiction

Extending Therapeutic Use of Psychostimulants: Focus On Serotonin -1A Receptor.

Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jul 29;
Haleem DJ

Despite a number of medicinally important pharmacological effects, the therapeutic use of psychostimulants is limited because of abuse potential and psychosis following long term use. Development of pharmacological agents for improving and extending therapeutic use of psychostimulants in narcolepsy, attention deficit hyperactivity disorder, Parkinson’s disease, obesity and as cognitive enhancer is an important research imperative. In this regard, one potential target system is the 5-hydroxytryptamine (5-HT; serotonin) neurotransmitter system. The focus of the present article is to evaluate a potential role of 5-HT-1A receptor in the alleviation of abuse potential and psychosis-induced by prescription psychostimulants amphetamines and apomorphine.Synaptic contacts between dopamine systems and 5-HT-1A receptors are traced. Studies on serotonin-1A influences on the modulation of dopamine neurotransmission and psychostimulant-induced behavioral sensitization are accumulated.Inhibition of amphetamine and apomorphine-induced behavioral sensitization by co administration of 5-HT-1A agonists cannot be explained in terms of direct activation of 5-HT-1A receptors, because activation of pre as well as postsynaptic 5-HT-1A receptors tend to increase dopamine neurotransmission.Long term use of amphetamine and apomorphine produces adaptive changes in 5-HT-1A receptor mediated functions, which are prevented by the co-use of 5-HT-1A agonists. In view of extending medicinal use of psychostimulants, it is important to evaluate the effects of co-use of 5-HT-1A agonists on potential therapeutic profile of amphetamine and apomorphine in preclinical research. It is also important to evaluate the functional significance of 5-HT-1A receptors on psychostimulant-induced behaviors in other addiction models such as drug self-administration and reinstatement of drug seeking behavior. HubMed – addiction

Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food.

Vaccine. 2013 Jul 29;
Rüedi-Bettschen D, Wood SL, Gunnell MG, West MC, Pidaparthi RR, Carroll FI, Blough BE, Owens SM

(+)-Methamphetamine (METH) addiction is a chronic disease that interferes with fundamental brain-mediated behaviors and biological functions like eating. These studies present preclinical efficacy and safety profiles for a METH conjugate vaccine (ICKLH-SMO9) designed to treat METH abuse. ICKLH-SMO9 efficacy and safety were assessed over a 16-week period by monitoring general health and stability of responding in a food maintained behavioral paradigm. Male Sprague-Dawley rats were trained to lever press for food reinforcers until stable behavior was established. Rats (n=9/group) were then immunized with 100?g of a control antigenic carrier protein (ICKLH-Cys) or ICKLH-SMO9 in Alhydrogel® adjuvant, with booster immunizations at 4, 8 and 12weeks. Health, immunization site and behavior were assessed daily. No adverse effects were found. During weeks 14-16, when antibody titers and METH affinity (Kd=13.9±1.7nM) were maximal, all rats received progressively higher METH doses (0.3-3.0mg/kg) every 3-4days, followed by behavioral testing. Even though the lower METH doses from 0.3 to 1.0mg/kg produced no impairment in food maintained behavior, 3.0-mg/kg in control rats showed significantly (p<0.05) reduced response rates and number of reinforcers earned, as well as reduced food intake. In sharp contrast, the ICKLH-SMO9 group showed no changes in food maintained behavior at any METH dose, even though METH serum concentrations showed profound increases due to anti-METH antibody binding. These findings suggest the ICKLH-SMO9 vaccine is effective and safe at reducing adverse METH-induced effects, even at high METH doses. HubMed – addiction

Treatment adherence towards prescribed medications in bipolar-II acute depressed patients: Relationship with cyclothymic temperament and “therapeutic sensation seeking” in response towards subjective intolerance to pain.

J Affect Disord. 2013 Jul 29;
Fornaro M, De Berardis D, Iasevoli F, Pistorio ML, D’Angelo E, Mungo S, Martino M, Ventriglio A, Cattaneo CI, Favaretto E, Del Debbio A, Romano A, Ciampa G, Elassy M, Perugi G, De Pasquale C

Treatment adherence (TA) is crucial during almost any phase of bipolar disorder (BD), including type-II (BD-II) acute depression. While a number of issues have been traditionally accounted on the matter, additional factors should be likewise involved, including affective temperaments and some clinically suggestive psychopathological traits whose systematic assessment represents the aim of this study.Two hundred and twenty BD-II acute depressed outpatients were consecutively evaluated using the Structured Clinical Interviews for Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition Axis-I and II Disorders, Hamilton scales for Depression and Anxiety, Temperament Evaluation of the Memphis Pisa Paris San Diego-Auto-questionnaire-110-item, Visual Analogue Scale (VAS), Zuckerman’s Sensation-Seeking Scale-Form-V (SSS-V), Barratt’s Impulsivity Scale-11-item, State-Trait Anxiety Inventory modules, Severity module of the Clinical Global Impression Scale for BD, Morisky 8-Item Medication Adherence Scale (MMAS-8) and the Clinician Rating Scale (CRS). Patients were divided into non-adherent vs. treatment-adherent cases depending on MMAS-8+CRS scores.In the TA(-) group, higher VAS and cyclothymic temperament scores were highly correlated (r=.699; p?.001). Those latter scores, along with SSS-V scores and the occurrence of lifetime addiction to painkiller and/or homeopathic medications available over the counter defined a “therapeutic sensation seeking” pattern allowing to correctly classify as much as 93.9% [Exp(B)=3.490; p?.001] of TA(-) cases (49/220).Lack of objective TA measures and systematic pharmacological record; recall bias on some diagnoses; and relatively small sample size.Stating the burden of TA in BD, additional studies on this regard are aimed, ideally contributing to enhance the management of BD itself. HubMed – addiction

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