A randomized, placebo-controlled trial of N-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers.

Objective: Pathological gambling is associated with elevated proportions of nicotine dependence, and tobacco smoking in pathological gamblers has been associated with increased problem-gambling severity. This study examined the addition of N-acetylcysteine to imaginal desensitization in adults with co-occurring nicotine dependence and pathological gambling.

Method: Twenty-eight individuals with co-occurring DSM-IV nicotine dependence and pathological gambling who were receiving behavioral therapy were recruited from December 2009 to February 2012 and randomized to augmentation with N-acetylcysteine or placebo in an 12-week, double-blind trial.

Pharmacotherapy for trichotillomania.

Background: Trichotillomania (TTM) (hair-pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair-pulling. The effect of medication on trichotillomania has not been systematically evaluated.

Objectives: To assess the effects of medication for trichotillomania in adults compared with placebo or other active agents.

Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides.

We herein report the application of the phosphorodiamidate phosphate prodrug approach to a series of thirteen nucleoside analogs with antiviral or anticancer activity. Twenty-five symmetrical phosphorodiamidates were synthesized, bearing esterified l-Alanine (and in one case d-Alanine) in the prodrug moiety, each as single stereoisomer. The presence of an achiral phosphorus represents a potential advantage over the phosphoramidate ProTide approach, where diastereoisomeric mixtures are routinely obtained, and different biological profiles may be expected from the diastereoisomers.

A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment.

Through the combined use of (18)F-fallypride positron emission tomography and magnetic resonance imaging this study examined the neural mechanisms underlying the attentional deficits associated with attention deficit/hyperactivity disorder and their potential reversal with a single therapeutic dose of methylphenidate. Sixteen adult patients with attention deficit/hyperactivity disorder and 16 matched healthy control subjects were positron emission tomography and magnetic resonance imaging scanned and tested on a computerized sustained attention task after oral methylphenidate (0.5 mg/kg) and placebo administration in a within-subject, double-blind, cross-over design.

Animal models of obsessive-compulsive spectrum disorders.

Obsessive-compulsive disorder (OCD) and related conditions (trichotillomania, pathological skin-picking, pathological nail-biting) are common and disabling. Current treatment approaches fail to help a significant proportion of patients. Multiple tiers of evidence link these conditions with underlying dysregulation of particular cortico-subcortical circuitry and monoamine systems, which represent targets for treatment.

Topoisomerases facilitate transcription of long genes linked to autism.

Topoisomerases are expressed throughout the developing and adult brain and are mutated in some individuals with autism spectrum disorder (ASD). However, how topoisomerases are mechanistically connected to ASD is unknown. Here we find that topotecan, a topoisomerase 1 (TOP1) inhibitor, dose-dependently reduces the expression of extremely long genes in mouse and human neurons, including nearly all genes that are longer than 200 kilobases.

A proof of concept study of tolcapone for pathological gambling: relationships with COMT genotype and brain activation.

Pathological gambling (PG) is a disabling disorder experienced by 1-3% of adults, and empirically validated treatments are lacking. Perturbations of prefrontal-dependent cognitive functions are implicated in the pathophysiology of PG. The enzyme catechol-O-methyl-transferase (COMT) is responsible for degradation of dopamine in the cortices and thereby is known to regulate such cognitive functions and their neural substrates.

Efficacy of clonidine versus phenobarbital in reducing neonatal morphine sulfate therapy days for neonatal abstinence syndrome. A prospective randomized clinical trial.

Objective: To compare the efficacy of clonidine versus phenobarbital in reducing morphine sulfate treatment days for neonatal abstinence syndrome (NAS).

Study Design: Prospective, non-blinded, block randomized trial at a single level III NICU (Neonatal Intensive Care Unit). Eligible infants were treated with a combination of medications as per protocol.

Where on the obsessive impulsive-compulsive spectrum does hair-pulling disorder belong?

Objective: Hair-pulling disorder (HPD) is a putative obsessive-compulsive spectrum disorder, but proper categorization is challenging. Distinct subgroups of HPD may exist, depending on the primary motivation in the act of pulling. Two notable proposed subgroups are "relief pullers" (pulling primarily to reduce anxiety- a "compulsive" subgroup) and "pleasure/gratification pullers" (pulling primarily for reward- an "impulsive" subgroup) which we sought to examine in order to contribute to conversations on the categorization of HPD.

Association between tobacco smoking and cognitive functioning in young adults.

Background: Tobacco smoking represents a considerable public health burden globally. Smoking in older adults is associated with cognitive impairment and more rapid age-associated cognitive decline, but there is a paucity of studies in younger people.

Method: Adults aged 18-29 years were recruited from a longitudinal study investigating impulsivity in young people.

Sexual and relationship satisfaction and vestibular pain sensitivity among women with provoked vestibulodynia.

Introduction: Provoked vestibulodynia (PVD) is a common cause of painful intercourse. Despite the fact that PVD is associated with high levels of pain and negative impact on women's sexuality, research has not examined associations between affected women's pain sensitivity and their sexual and relationship satisfaction.

Aims: This study aimed to examine sexual and relationship functioning/satisfaction and vestibular pain sensitivity among PVD-affected women, and potential associations between these variables.

Long-term depression of synaptic kainate receptors reduces excitability by relieving inhibition of the slow afterhyperpolarization.

Kainate receptors (KARs) are ionotropic glutamate receptors that also activate noncanonical G-protein-coupled signaling pathways to depress the slow afterhyperpolarization (sAHP). Here we show that long-term depression of KAR-mediated synaptic transmission (KAR LTD) at rat hippocampal mossy fiber synapses relieves inhibition of the sAHP by synaptic transmission. KAR LTD is induced by high-frequency mossy fiber stimulation and natural spike patterns and requires activation of adenosine A2A receptors.

Noradrenergic modulation of cognition: therapeutic implications.

The noradrenaline (norepinephrine) system exerts profound influences on cognition via ascending projections to the forebrain, mostly originating from the locus coeruleus. This paper provides an overview of available infrahuman and healthy human studies, exploring the effects of specific noradrenergic manipulations on dissociable cognitive functions, including attention, working memory, cognitive flexibility, response inhibition and emotional memory. Remarkable parallels across species have been reported which may account for the mechanisms by which noradrenergic medications exert their beneficial effects in disorders such as depression and attention-deficit hyperactivity disorder (ADHD).

Synthesis and evaluation against hepatitis C virus of 7-deaza analogues of 2'-C-methyl-6-O-methyl guanosine nucleoside and L-Alanine ester phosphoramidates.

7-Deazapurines are known to possess broad antiviral activity, however the 2'-C-methylguanosine analogue displays poor cell permeation and limited phosphorylation, thus is not an efficient inhibitor of hepatitis C virus (HCV) replication. We previously reported the 6-O-methyl entity as a prodrug moiety to increase liphophilicity of guanine nucleosides and the ProTide approach applied to 2'-C-methyl-6-O-methylguanosine has lead to potent HCV inhibitors now in clinical trials. In this Letter, we report the synthesis and biological evaluation of 2'-C-methyl-6-O-methyl-7-deaza guanosine and ProTide derivatives.

White matter abnormalities in skin picking disorder: a diffusion tensor imaging study.

Skin picking disorder (SPD) is characterized by the repetitive and compulsive picking of skin, resulting in tissue damage. Neurocognitive findings in SPD implicate difficulty with response inhibition (suppression of pre-potent motor responses). This function is dependent on the integrity of the right frontal gyrus and the anterior cingulate cortices, and white-matter tracts connecting such neural nodes.

What things make people with a learning disability happy and satisfied with their lives: an inclusive research project.

Background: We looked at the research that other people have done about what makes people with a learning disability happy and satisfied with their lives. Researchers call being happy and satisfied with your life 'subjective well-being'. They found out that having things like money and good health does not always mean people are happy.

Age at onset in trichotillomania:clinical variables and neurocognitive performance.

Objective: Trichotillomania (TTM), or compulsive hair pulling, is a common psychiatric disorder characterized by psychosocial impairment and reduced quality of life. The aim of this retrospective study was to characterize the impact of age at TTM onset on clinical variables and neuropsychological function using a variety of clinical and neurocognitive measures.

Method: The study sample included 98 adult treatment-seeking individuals with a DSM-IV diagnosis of TTM.

Neural and behavioral effects of a novel mu opioid receptor antagonist in binge-eating obese people.

Background: Binge eating is associated with obesity and has been conceptualized as "food addiction." However, this view has received only inconsistent support in humans, and limited evidence relates key neurocircuitry to the disorder. Moreover, relatively few studies have used pharmacologic functional magnetic resonance imaging to probe the underlying basis of altered eating behaviors.

RNAs of the human chromosome 15q11-q13 imprinted region.

The human chromosome 15q11-q13 region hosts a wide variety of coding and noncoding RNAs, and is also the site of nearly every imaginable type of RNA processing. To deepen the intrigue, the transcripts in the human chromosome 15q11-q13 region are subject to regulation by genomic imprinting, and some of these transcripts are imprinted in a tissue-specific manner. As the region is critically important for three human neurogenetic disorders, Angelman syndrome, Prader-Willi syndrome, and 15q duplication syndrome, there is intense interest in understanding the types of RNA and RNA processing that occurs among the imprinted genes.