Using Transdermal Alcohol Monitoring to Detect Low-Level Drinking.

Background: Several studies demonstrate the utility of Alcohol Monitoring Systems' (AMS) transdermal alcohol concentration (TAC) monitor to objectively quantify drinking. AMS standard criteria (i.e.

The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors.

Chronic pain is a highly prevalent and poorly managed human health problem. We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia, a prominent symptom of chronic pain. We identified expression levels of Chrna6, which encodes the α6 subunit of the nicotinic acetylcholine receptor (nAChR), as highly associated with allodynia.

DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS.

Obsessive-compulsive disorder (OCD) is a chronic, severe mental illness with up to 2-3% prevalence worldwide. In fact, OCD has been classified as one of the world's 10 leading causes of illness-related disability according to the World Health Organization, largely because of the chronic nature of disabling symptoms.([1]) Despite the severity and high prevalence of this chronic and disabling disorder, there is still relatively limited understanding of its pathophysiology.

Heterologous expression and nonsense suppression provide insights into agonist behavior at α6β2 nicotinic acetylcholine receptors.

The α6-containing subtypes of the nicotinic acetylcholine receptor (nAChR) are localized to presynaptic terminals of the dopaminergic pathways of the central nervous system. Selective ligands for these nAChRs are potentially useful in both Parkinson's disease and addiction. For these and other goals, it is important to distinguish the binding behavior of agonists at the α6-β2 binding site versus other subtypes.

Using contingency management procedures to reduce at-risk drinking in heavy drinkers.

Background: Treatments for alcohol use disorders typically have been abstinence based, but harm reduction approaches that encourage drinkers to alter their drinking behavior to reduce the probability of alcohol-related consequences, have gained in popularity. This study used a contingency management procedure to determine its effectiveness in reducing alcohol consumption among heavy drinkers.

Methods: Eighty-two nontreatment-seeking heavy drinkers (ages 21 to 54, M = 30.

Health care utilization behavior of veterans who deployed to Afghanistan and Iraq.

Background: Previous assessments of Afghanistan/Iraq Veterans have lacked a systematic overview of all injury and illness experiences captured by the Veterans Health Administration (VHA) health care services. In this initial study, we quantify the health care utilization behavior of eligible Veterans and describe the level and type of usage among them.

Methods: A roster of service members who have served in Afghanistan/Iraq and became eligible for VHA care between 2002 and 2010 and their corresponding administrative VA medical encounter data were abstracted from the VHA Office of Public Health Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Health Surveillance System.

Neuromodulation of conditioned placebo/nocebo in heat pain: anodal vs cathodal transcranial direct current stimulation to the right dorsolateral prefrontal cortex.

Placebo and nocebo play an important role in clinical practice and medical research. Modulating placebo/nocebo responses using noninvasive brain stimulation methods, such as transcranial direct current stimulation (tDCS), has the potential to harness these effects to therapeutic benefit in a clinical setting. In this study, we assessed the effect of anodal and cathodal tDCS over the right dorsolateral prefrontal cortex (rDLPFC) on conditioned placebo/nocebo cue response to heat pain.

Increased Pre- and Early-Adolescent Stress in Youth with a Family History of Substance Use Disorder and Early Substance Use Initiation.

Individuals with a family history of substance use disorders (Family History Positive) are more likely to have early-onset substance use (i.e., prior to age 15), which may contribute to their higher rates of substance use disorders.

Assessing the Validity of Participant-Derived Compared to Staff-Derived Values to Compute a Binge Score.

Aims: This study examined the validity of two methods of classifying binge drinkers.

Methods: Adult drinkers (n = 166) completed the Alcohol Use Questionnaire (AUQ) and a Timeline Followback (TLFB) interview to characterize drinking during the past 28 days. Using Townshend and Duka's (2005) recommendations, answers on three AUQ items (average drinks per hour, number of times drunk within the prior 6 months and percentage of times drunk when drinking) were used to derive a binge score that was then used to classify drinkers as Binge, Non-Binge and Unclassifiable.

Effects of tryptophan depletion and a simulated alcohol binge on impulsivity.

Researchers have suggested binge drinkers experience disproportionate increases in impulsivity during the initial period of drinking, leading to a loss of control over further drinking, and that serotonergic mechanisms may underlie such effects. We examined the effects of a simulated alcohol binge and tryptophan depletion on 3 types of impulsivity-response initiation (immediate memory task [IMT]), response inhibition (GoStop task), and delay discounting (single key impulsivity paradigm [SKIP])-and tested whether observed effects were related to real-world binging. Adults (N = 179) with diverse drinking histories completed a within-subject crossover design over 4 experimental days.

A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression.

Background: Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published.

Methods: Thirty patients with TRD participated in a sham-controlled trial of DBS at the ventral capsule/ventral striatum target for TRD.

Functional activation and effective connectivity differences in adolescent marijuana users performing a simulated gambling task.

Background. Adolescent marijuana use is associated with structural and functional differences in forebrain regions while performing memory and attention tasks. In the present study, we investigated neural processing in adolescent marijuana users experiencing rewards and losses.

Treatment Needs of Driving While Intoxicated Offenders: The Need for a Multimodal Approach to Treatment.

Objective: This study aimed to characterize and compare the treatment needs of adults with driving while intoxicated (DWI) offenders recruited from a correctional residential treatment facility and the community to provide recommendations for treatment development.

Method: A total of 119 adults (59 residential, 60 community) with at least one DWI offense were administered clinical diagnostic interviews to assess substance use disorders and completed a battery of questionnaires assessing demographic characteristics, legal history, psychiatric diagnoses, medical diagnoses, and health care utilization.

Results: Almost all (96.

Open-label study of duloxetine for the treatment of obsessive-compulsive disorder.

Background: This study sought to investigate the efficacy of duloxetine for the treatment of obsessive-compulsive disorder (DSM-IV).

Methods: Twenty individuals were enrolled in a 17-week, open-label trial of duloxetine at Massachusetts General Hospital. Data were collected between March 2007 and September 2012.

Standardization of formulations for the acute amino acid depletion and loading tests.

The acute tryptophan depletion and loading and the acute tyrosine plus phenylalanine depletion tests are powerful tools for studying the roles of cerebral monoamines in behaviour and symptoms related to various disorders. The tests use either amino acid mixtures or proteins. Current amino acid mixtures lack specificity in humans, but not in rodents, because of the faster disposal of branched-chain amino acids (BCAAs) by the latter.

Transdermal alcohol concentration data collected during a contingency management program to reduce at-risk drinking.

Background: Recently, we demonstrated that transdermal alcohol monitors could be used in a contingency management procedure to reduce problematic drinking; the frequency of self-reported heavy/moderate drinking days decreased and days of no to low drinking increased. These effects persisted for three months after intervention. In the current report, we used the transdermal alcohol concentration (TAC) data collected prior to and during the contingency management procedure to provide a detailed characterization of objectively measured alcohol use.

Affective Brain-Computer Interfaces As Enabling Technology for Responsive Psychiatric Stimulation.

There is a pressing clinical need for responsive neurostimulators, which sense a patient's brain activity and deliver targeted electrical stimulation to suppress unwanted symptoms. This is particularly true in psychiatric illness, where symptoms can fluctuate throughout the day. Affective BCIs, which decode emotional experience from neural activity, are a candidate control signal for responsive stimulators targeting the limbic circuit.

Features: Health Care Use Among Iraq and Afghanistan Veterans With Infectious Diseases.

Qualified veterans were no more likely to take advantage of health care services after the VA presumptive infectious disease determination streamlined the qualification process.

Allosteric activation of the 5-HT3AB receptor by mCPBG.

The 5-HT3AB receptor contains three A and two B subunits in an A-A-B-A-B order. However, serotonin function at the 5-HT3AB receptor has been shown to depend solely on the A-A interface present in the homomeric receptor. Using mutations at sites on both the primary (E122) and complementary (Y146) faces of the B subunit, we demonstrate that meta-chlorophenyl biguanide (mCPBG), a 5-HT3 selective agonist, is capable of binding to and activating the 5-HT3AB receptor at all five subunit interfaces of the heteromer.

Neuroanatomical characteristics associated with response to dorsal anterior cingulotomy for obsessive-compulsive disorder.

Importance: Approximately 10% of patients with obsessive-compulsive disorder (OCD) have symptoms that are refractory to pharmacologic and cognitive-behavioral therapies. Neurosurgical interventions can be effective therapeutic options in these patients, but not all individuals respond. The mechanisms underlying this response variability are poorly understood.

Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline.

The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

Structural requirements in the transmembrane domain of GLIC revealed by incorporation of noncanonical histidine analogs.

The cyanobacterial pentameric ligand-gated ion channel GLIC, a homolog of the Cys-loop receptor superfamily, has provided useful structural and functional information about its eukaryotic counterparts. X-ray diffraction data and site-directed mutagenesis have previously implicated a transmembrane histidine residue (His234) as essential for channel function. Here, we investigated the role of His234 via synthesis and incorporation of histidine analogs and α-hydroxy acids using in vivo nonsense suppression.

Mechanisms of the pellagragenic effect of leucine: stimulation of hepatic tryptophan oxidation by administration of branched-chain amino acids to healthy human volunteers and the role of plasma free tryptophan and total kynurenines.

The pellagragenic effect of leucine (Leu) has been proposed to involve modulation of L-tryptophan (Trp) metabolism along the hepatic kynurenine pathway. Here, we discuss some of the mechanisms suggested and report the effects in healthy volunteers of single doses of Leu (4.05-6.