Evaluation of Point-of-Care Ultrasound Training for Family Physicians Using Teleultrasound.

BACKGROUND AND OBJECTIVES: The goal of this study was to assess family physicians' change in knowledge and ability to perform abdominal aorta ultrasound after implementation of a novel teleultrasound curriculum. METHODS: This was a prospective, observational study conducted at a single academic institution. Family physicians completed a preassessment, test, and objective structured clinical evaluation (OSCE). Physicians then individually completed a standard curriculum consisting of online content and an hour-long, hands-on training session on abdominal aorta ultrasound using teleultrasound technology. Physicians then performed a minimum of 10 independent examinations over a period of 8 weeks. After physicians completed the training curriculum and 10 independent scans, we administered a postassessment, test, and OSCE. We analyzed differences between pre- and postcurriculum responses using Fisher exact and Wilcoxon signed rank tests. RESULTS: Thirteen family physicians completed the curriculum. Comparing pre- to postcurriculum responses, we found significant reductions in barriers to using aorta POCUS and improved confidence in using, obtaining, and interpreting aorta POCUS (P<0.01). Knowledge improved from a median score of 70% to 90% (P<0.01), and OSCE scores improved from a median of 80% to 100% (P=0.012). Overall, 211 aorta ultrasound examinations were independently acquired with a median image quality of 4 (scale 1 to 4). CONCLUSIONS: After an 8-week teleultrasound curriculum, family physicians with minimal experience with POCUS showed improved knowledge and psychomotor skill in abdominal aorta POCUS.

Priming effects of a slot machine game and amphetamine on probabilistic risk-taking in people with gambling disorder and healthy controls.

INTRODUCTION: The Game of Dice Task (GDT) captures probabilistic risk-taking, which is an important feature of addictions and integral to gambling disorder (GD). No research appears to have assessed effects of gambling-specific priming manipulations or the pharmacological basis of such effects on the GDT. AIMS: To investigate effects of slot machine gambling (Slots) and d-amphetamine (AMPH; 20 mg) on risk-taking in people with GD and healthy controls (HCs) (n = 30/group). The role of dopamine (DA) was assessed by pre-treating participants with the D2 receptor (D2R)-preferring antagonist, haloperidol (HAL; 3-mg) or mixed D1R-D2R antagonist, fluphenazine (FLU; 3-mg). HYPOTHESES: Slots and AMPH will each increase risk-taking based on fewer (less probable) possible outcomes selected (POS) and poorer net monetary outcomes (NMO; gains minus losses) on the GDT, with stronger effects in Group GD. If DA mediates these effects, outcomes will vary with pre-treatment. METHOD: Participants attended a pre-experimental baseline session and 4 test sessions. Antagonist Group (HAL, FLU) was manipulated between-participants. Pre-treatment (antagonist, placebo) was manipulated within-participants and counterbalanced over sessions for Slots and AMPH test phases. Moderator/mediator effects of trait and neuropsychological factors and GD severity (South Oaks Gambling Screen; SOGS) were explored via covariance. RESULTS: AMPH led to an escalation in risky POS over trial blocks in both groups, regardless of pre-treatment. Cognitive inflexibility (high perseveration-proneness) moderated this effect in Group HC. In Group GD, SOGS selectively predicted riskier POS on AMPH sessions. Group GD achieved poorer NMO vs. Group HC on the pre-experimental baseline and Placebo-Slots sessions. Group HC selectively displayed poorer NMO on the Antagonist-Slots session. CONCLUSIONS: The GDT can detect behavioral and pharmacological priming effects. Cognitive inflexibility and symptom severity moderate AMPH-induced risk-taking in HC and GD participants, respectively. Sensitization-related "wanting" of risk may contribute to the latter effect in people with GD.

Gamification of POCUS: Are Students Learning?

INTRODUCTION: While gamification of point-of-care ultrasound (POCUS) is well received by learners, little is known about the knowledge gained from material taught during these events. We set out to determine whether a POCUS gamification event improved knowledge of interpretation and clinical integration of POCUS. METHODS: This was a prospective observational study of fourth-year medical students who participated in a 2.5-hour POCUS gamification event consisting of eight objective-oriented stations. Each station had one to three learning objectives associated with the content taught. Students completed a pre-assessment; they then participated in the gamification event in groups of three to five per station and subsequently completed a post-assessment. Differences between pre- and post-session responses were matched and analyzed using Wilcoxon signed-rank test and Fisher's exact test. RESULTS: We analyzed data from 265 students with matched pre- and post-event responses; 217 (82%) students reported no to little prior POCUS experience. Most students were going into internal medicine (16%) and pediatrics (11%). Knowledge assessment scores significantly improved from pre- to post-workshop, 68% vs 78% (P=0.04). Self-reported comfort with image acquisition, interpretation, and clinical integration all significantly improved from pre- to post-gamification event (P<0.001). CONCLUSION: In this study we found that gamification of POCUS, with clear learning objectives, led to improved student knowledge of POCUS interpretation, clinical integration, and self-reported comfort with POCUS.

Impulsivity moderates the effects of dopamine D2 and mixed D1-D2 antagonists in individuals with gambling disorder.

BACKGROUND: The functional role of dopamine D1 and D2 receptors in gambling disorder (GD) remains unclear. AIMS: This study aimed to investigate the role of D1 activation and the moderating effects of impulsivity, a trait linked with weaker D2-mediated inhibition of dopamine release, in GD subjects. METHODS: Thirty (nine female) non-comorbid GD subjects with low (LI), moderate (MI), or high impulsivity (HI) received the preferential D2 antagonist haloperidol (HAL; 3 mg) or the mixed D1-D2 antagonist fluphenazine (FLU; 3 mg), on separate sessions before a 15-minute slot machine game or amphetamine (AMPH; 20 mg), in a placebo-controlled, double-blind, counterbalanced design. RESULTS: On their own, HAL and FLU led to linear increases and decreases, respectively, in desire to gamble across increasing levels of impulsivity. The slot machine and AMPH each evoked an inverted-U pattern of desire to gamble across increasing impulsivity. HAL reversed this effect of the game, whereas FLU did not alter post-game desire. HAL and FLU decreased and increased psychostimulant-like effects of the game, respectively, in LI and MI subjects, but consistently reduced these effects in HI subjects. HAL also altered the salience of negative affective words on a reading task, such that greater salience of negative words coincided with lower post-game desire to gamble. CONCLUSIONS: D1 receptors appear to gauge the incentive value of gambling in GD subjects. D1 activation has negative reinforcing effects in HI gamblers and positive reinforcing effects in LI gamblers. Medications that activate D1 could curtail chasing in HI gamblers. D1 blockade could benefit HI gamblers whose main concern is craving.

The role of outcome expectancy in therapeutic change across psychotherapy versus pharmacotherapy for depression.

BACKGROUND: Patient outcome expectancy - the belief that treatment will lead to an improvement in symptoms - is linked to favourable therapeutic outcomes in major depressive disorder (MDD). The present study extends this literature by investigating the temporal dynamics of expectancy, and by exploring whether expectancy during treatment is linked to differential outcomes across treatment modalities, for both optimistic versus pessimistic expectancy. METHODS: A total of 104 patients with MDD were randomized to receive either cognitive behavioral therapy (CBT) or pharmacotherapy for 16 weeks. Outcome expectancy was measured throughout treatment using the Depression Change Expectancy Scale (DCES). Depression severity was measured using both the Hamilton Depression Rating Scale and Beck Depression Inventory-II. RESULTS: Latent growth curve models supported improvement in expectancy across both treatments. Cross-lagged panel models revealed that both higher optimistic and lower pessimistic expectancy at mid-treatment predicted greater treatment response in pharmacotherapy. For CBT, the associative patterns between expectancy and depression differed as a function of expectancy type; higher optimistic expectancy at pre-treatment and lower pessimistic expectancy at mid-treatment predicted greater treatment response. LIMITATIONS: The sample size limited statistical power and the complexity of models that could be explored. CONCLUSIONS: Results suggest that outcome expectancy improved during treatment for depression. Whether outcome expectancy represents a specific mechanism for the reduction of depression warrants further investigation.

Internet-Based Interventions for Problem Gambling: Scoping Review.

BACKGROUND: This study seeks to give an overview of academic research on internet-based interventions that are used to address problem gambling. The rate of treatment seeking has been demonstrated to be low across several research environments. This is in part because of the systemic barriers that treatment seekers face to accessing traditional face-to-face treatment. Making treatment resources for problem gambling available through the internet is one way to reduce the impact of those systemic barriers. The use of internet-based resources to address problem gambling has been growing, and a field of research evaluating it has developed as well. However, little has been done to summarize this collection of research. OBJECTIVE: This study aimed to provide a scoping review of the use of internet-based interventions for problem gambling treatment and prevention to provide an understanding of the current state of the field. METHODS: A scoping review was performed for 6 peer-reviewed research databases (Web of Science, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Social Science Abstracts, and Scopus) and 3 gray literature databases (MedEdPortal, Proquest: Dissertations, and OpenGrey). Article inclusion criteria were as follows: published over the 10-year period of 2007 to 2017, including an intervention for problem gambling, and involving the use of internet to deliver that intervention. RESULTS: A total of 27 articles were found that met the review criteria. Studies were found from several different areas, with particularly strong representation for Australia, New Zealand, and Scandinavia. Cognitive behavioral therapy was the most common form of internet-based intervention. Internet-based interventions were generally shown to be effective in reducing problem gambling scores and gambling behaviors. A wide range of interventions that made use of internet resources included text-based interactions with counselors and peers, automated personalized and normative feedback on gambling behaviors, and interactive cognitive behavioral therapies. A lack of diversity in samples, little comparison with face-to-face interventions, and issues of changes in the treatment dynamic are identified as areas that require further investigation. CONCLUSIONS: Internet-based interventions are a promising direction for treatment and prevention of problem gambling, particularly in reducing barriers to accessing professional help. The state of the current literature is sparse, and more research is needed for directly comparing internet-based interventions and their traditional counterparts.

Cognitive change in cognitive-behavioural therapy v. pharmacotherapy for adult depression: a longitudinal mediation analysis.

BACKGROUND: Although cognitive-behavioural therapy (CBT) is a well-established treatment for adult depression, its efficacy and efficiency may be enhanced by better understanding its mechanism(s) of action. According to the theoretical model of CBT, symptom improvement occurs via reductions in maladaptive cognition. However, previous research has not established clear evidence for this cognitive mediation model. METHODS: The present study investigated the cognitive mediation model of CBT in the context of a randomized controlled trial of CBT v. antidepressant medication (ADM) for adult depression. Participants with major depressive disorder were randomized to receive 16 weeks of CBT (n = 54) or ADM (n = 50). Depression symptoms and three candidate cognitive mediators (dysfunctional attitudes, cognitive distortions and negative automatic thoughts) were assessed at week 0 (pre-treatment), week 4, week 8 and week 16 (post-treatment). Longitudinal associations between cognition and depression symptoms, and mediation of treatment outcome, were evaluated in structural equation models. RESULTS: Both CBT and ADM produced significant reductions in maladaptive cognition and depression symptoms. Cognitive content and depression symptoms were moderately correlated within measurement waves, but cross-lagged associations between the variables and indirect (i.e. mediated) treatment effects were non-significant. CONCLUSIONS: The results provide support for concurrent relationships between cognitive and symptom change, but not the longitudinal relationships hypothesized by the cognitive mediation model. Results may be indicative of an incongruence between the timing of measurement and the dynamics of cognitive and symptom change.

Fluorescence detected linear dichroism spectroscopy: A selective and sensitive probe for fluorophores in flow-oriented systems.

Fluorescence detection typically enhances sensitivity and selectivity for fluorescent analytes. The potential for combining fluorescence detection with flow orientation of the sample in the normal configuration of linear dichroism experiments is explored in this work by measuring the fluorescence emitted from flow-orientated DNA-bound ligands and M13 bacteriophage. Data for ethidium bromide, Hoechst 33258, and 4,6-diamidino-2-phenyindole are presented. The theoretical basis of the technique is also presented for instruments running in both the fixed direct-current mode, which is the normal operation mode of circular dichroism spectropolarimeters, and also in fixed high-tension voltage mode. The role of the stray light reaching the detector that results in a spectral shape in fixed direct current mode that resembles the shape of a linear dichroism spectrum, rather than the expected reduced linear dichroism, is also explored.

Parallel role for the dopamine D1 receptor in gambling and amphetamine reinforcement in healthy volunteers.

This study investigated the role of dopamine, and specifically the D1 receptor (D1R), in the reinforcing effects of a slot-machine game in healthy volunteers ( n=30). To compare gambling and drug effects, subjects received the prototypic psychostimulant drug d-amphetamine (AMPH; 20 mg) in a multi-session, placebo-controlled design. To isolate D1R, half the subjects were pretreated with the preferential D2 receptor antagonist haloperidol (HAL; 3 mg), and the other half with the mixed D1-D2 antagonist fluphenazine (FLU; 3 mg) before the game (Phase I) and AMPH (Phase II). HAL decreased and FLU increased the post-game desire to gamble and post-AMPH desire to take AMPH again, as well as amphetamine scale ratings on the Addiction Research Center Inventory after gambling and AMPH. The effects of the antagonists on desire to gamble and to take AMPH again were significantly intercorrelated. HAL increased and FLU decreased the salience of negative affective words on a rapid reading task after both reinforcers. HAL also decreased the salience of gambling words after AMPH. Both reinforcers increased diastolic blood pressure equally under antagonists and placebo. Results indicate that D1R plays a parallel role in the psychostimulant-like, incentive-motivational, and salience-enhancing effects of gambling and AMPH. Moderate D1R activation appears to optimize these effects in healthy subjects.

Strong interactions between learned helplessness and risky decision-making in a rat gambling model.

Risky decision-making is characteristic of depression and of addictive disorders, including pathological gambling. However it is not clear whether a propensity to risky choices predisposes to depressive symptoms or whether the converse is the case. Here we tested the hypothesis that rats showing risky decision-making in a rat gambling task (rGT) would be more prone to depressive-like behaviour in the learned helplessness (LH) model. Results showed that baseline rGT choice behaviour did not predict escape deficits in the LH protocol. In contrast, exposure to the LH protocol resulted in a significant increase in risky rGT choices on retest. Unexpectedly, control rats subjected only to escapable stress in the LH protocol showed a subsequent decrease in riskier rGT choices. Further analyses indicated that the LH protocol affected primarily rats with high baseline levels of risky choices and that among these it had opposite effects in rats exposed to LH-inducing stress compared to rats exposed only to the escape trials. Together these findings suggest that while baseline risky decision making may not predict LH behaviour it interacts strongly with LH conditions in modulating subsequent decision-making behaviour. The suggested possibility that stress controllability may be a key factor should be further investigated.

Childhood Abuse History in Depression Predicts Better Response to Antidepressants with Higher Serotonin Transporter Affinity: A Pilot Investigation.

OBJECTIVES: Childhood abuse is a powerful prognostic indicator in adults with major depressive disorder (MDD) and is associated with numerous biological risk factors for depression. The purpose of this investigation was to explore if antidepressant medication affinity for the serotonin transporter moderates the association between childhood abuse and treatment response. METHODS: Our sample included 52 outpatients with MDD who had received up to 26 weeks of pharmacotherapy, stratifying antidepressant medications with a high versus a low affinity for the serotonin transporter. Patients completed the Hamilton Rating Scale for Depression, Beck Depression Inventory II, Home Environment Questionnaire, and Ontario Health Supplement: Child Abuse and Trauma Scale to assess depression and childhood abuse. RESULTS: Medication class moderated the link between 3 indices of childhood abuse and treatment response such that higher levels of childhood abuse were associated with higher levels of depression severity after treatment only in those patients receiving antidepressant medications with a weak affinity for the serotonin transporter. CONCLUSIONS: This pilot study suggested that prolonged exposure to stress during childhood may result in biological vulnerabilities for depression, which may in turn be differentially targeted by pharmacological agents which target serotonin to a greater or lesser degree.

Differential cardiovascular and hypothalamic pituitary response to amphetamine in male pathological gamblers versus healthy controls.

Cardiovascular and hypothalamic pituitary axis (HPA) disturbances have been observed in individuals who are pathological gamblers (PGs). These may partly derive from chronic exposure to gambling. Response to amphetamine (AMPH) may reveal such disturbances while controlling for differential conditioned responses to gambling in PGs vs healthy controls (HCs). This study assessed heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) and plasma cortisol following oral AMPH (0.4 mg/kg) in male PGs (n=12) and HCs (n=11) who underwent a positron emission tomography (PET) scan. The Stop Signal Task enabled assessment of the link between physiological and behavioral dysregulation. Trait moderating effects were explored. The responses of PGs to AMPH differed from those of HCs on every index. PGs displayed persistent elevation in DBP and concomitant reduction in HR (i.e. baroreflex) compared to HCs beyond 90 min post-dose. PGs displayed deficits in cortisol compared to HCs that were partially reversed by AMPH. Impairment on the Stop Signal Task correlated positively with HR in controls, but negatively with HR in PGs, suggesting that strong initial and compensatory cardiac responses to a stimulant may each predict disinhibition. Extraversion predicted greater disinhibition in PGs. Noradrenergic disturbances may contribute to sensitized responses to stimulant challenge and disinhibition in PGs.

Direct detection and measurement of wall shear stress using a filamentous bio-nanoparticle.

The wall shear stress (WSS) that a moving fluid exerts on a surface affects many processes including those relating to vascular function. WSS plays an important role in normal physiology (e.g. angiogenesis) and affects the microvasculature's primary function of molecular transport. Points of fluctuating WSS show abnormalities in a number of diseases; however, there is no established technique for measuring WSS directly in physiological systems. All current methods rely on estimates obtained from measured velocity gradients in bulk flow data. In this work, we report a nanosensor that can directly measure WSS in microfluidic chambers with sub-micron spatial resolution by using a specific type of virus, the bacteriophage M13, which has been fluorescently labeled and anchored to a surface. It is demonstrated that the nanosensor can be calibrated and adapted for biological tissue, revealing WSS in micro-domains of cells that cannot be calculated accurately from bulk flow measurements. This method lends itself to a platform applicable to many applications in biology and microfluidics.

Deep brain stimulation of the subthalamic nucleus increases premature responding in a rat gambling task.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option for the motor symptoms of Parkinson's disease (PD). However, several recent studies have found an association between STN-DBS and increased impulsivity. Currently, it is not clear whether the observed increase in impulsivity results from STN-DBS per se, or whether it involves an interaction with the underlying PD neuropathology and/or intake of dopaminergic drugs. We investigated the effects of STN-DBS on performance of intact rats on two tasks measuring impulsive responding: a novel rat gambling task (rGT) and a differential reinforcement of low rate responding (DRL20s) schedule. Following initial behavioural training, animals received electrode implantation into the STN (n=24) or sham surgery (n=24), and were re-tested on their assigned behavioural task, with or without STN-DBS. Bilateral STN-DBS administered for two hours immediately prior to testing, had no effects on rGT choice behaviour or on DRL response inhibition (p>0.05). However, STN-DBS significantly increased premature responding in the rGT task (p=0.0004), an effect that took several sessions to develop and persisted in subsequent trials when no stimulation was given. Consistent with the notion of distinct facets of impulsivity with unique neurochemical underpinnings, we observed differential effects of STN-DBS in the two tasks employed. These results suggest that STN-DBS in the absence of parkinsonism may not lead to a general loss of inhibitory control, but may instead affect impulsivity under specific conditions.

Family-based association analysis of serotonin genes in pathological gambling disorder: evidence of vulnerability risk in the 5HT-2A receptor gene.

Pathological gambling (PG) has become a growing public health problem in many countries around the world. PG is an impulse control disorder and its behavior and psychopathology present similarities with substance abuse disorders. Evidence from twin studies supports a significant genetic predisposition to PG, but the precise genetic loci still remain unclear. The present study investigates the allele and genotype distribution of polymorphisms of the serotonin transporter, serotonin receptor 1B and 2A genes in 140 sib-pairs discordant for the diagnosis of PG. A significant association of the C/C genotype of the serotonin receptor 2A T102C (rs 6313) polymorphism and the PG phenotype was observed [OR = 1.7 (1.1-3.4)]. This preliminary result is consistent with the hypothesis that the serotonin system is associated with addiction behavior and similar results have been reported for nicotine and alcohol dependence.

The D2/3 dopamine receptor in pathological gambling: a positron emission tomography study with [11C]-(+)-propyl-hexahydro-naphtho-oxazin and [11C]raclopride.

AIMS: Pathological gambling (PG) shares diagnostic features with substance use disorder (SUD), but the neurochemical mechanisms underlying PG are poorly understood. Because dopamine (DA), a neurotransmitter implicated in reward and reinforcement, is probably involved, we used positron emission tomography (PET) to test whether PG is associated with abnormalities in D2 and D3 receptor levels, as observed in SUD. DESIGN: Case-control study comparing PG to healthy control (HC) subjects. SETTING: Academic research imaging centre. PARTICIPANTS: Thirteen non-treatment-seeking males meeting DSM-IV criteria for PG, and 12 matched HC (11 of whom completed PET). MEASUREMENTS: Two PET scans (one with the D3 receptor preferring agonist [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) and the other with [11C]raclopride) to assess D(2/3) DA receptor availability, and behavioural measures (self-report questionnaires and slot-machine game) to assess subjective effects and relationships to PET measures. FINDINGS: Binding of both radiotracers did not differ between groups in striatum or substantia nigra (SN) (all P > 0.1). Across PG, [11C]-(+)-PHNO binding in SN, where the signal is attributable primarily to D3 receptors, correlated with gambling severity (r = 0.57, P = 0.04) and impulsiveness (r = 0.65, P = 0.03). In HC, [11C]raclopride binding in dorsal striatum correlated inversely with subjective effects of gambling (r = -0.70, P = 0.03) and impulsiveness (r = -0.70, P = 0.03). CONCLUSIONS: Unlike with substance use disorder, there appear to be no marked differences in D2 /D3 levels between healthy subjects and pathological gamblers, suggesting that low receptor availability may not be a necessary feature of addiction. However, relationships between [11C]-(+)-PHNO binding and gambling severity/impulsiveness suggests involvement of the D3 receptor in impulsive/compulsive behaviours.

The role of ANKK1 and TTC12 genes on drinking behaviour in tobacco dependent subjects.

OBJECTIVES: Alcohol use disorders (AUD) act as a risk factor for smoking relapse, and tobacco dependent (TD) subjects with comorbid AUD experience more withdrawal symptoms compared to TD subjects without AUD or other psychiatric comorbidities. Our aim was to investigate whether drinking behaviour in the past 12 months and smoking relapse due to alcohol use in TD subjects was associated with polymorphisms flanking the TTC12/ANKK1/DRD2 region since associations have been found between these genes and AUD and TD as separate disorders. METHODS: 380 TD subjects were assessed for alcohol use and relapse to smoking. Subjects were genotyped for polymorphisms located in the TTC12/ANKK1/DRD2 region. RESULTS: Associations were found between ANKK1 haplotype rs4938015C_rs11604671A and age of onset of daily smoking, as well as with hazardous drinking. No genetic association was found with smoking relapse due to alcohol consumption. CONCLUSIONS: Our findings suggest that TD subjects who present earlier age at onset and carry this haplotype may have a higher risk for developing an alcohol use disorder.

Association of functional variants in the dopamine D2-like receptors with risk for gambling behaviour in healthy Caucasian subjects.

Pathological gambling (PG) is an impulse control disorder with suggestive genetic vulnerability component. We evaluated the association of genetic variants in the dopaminergic receptor genes (DRD1-3s) with risk for gambling in healthy subjects using the Canadian Problem Gambling Index (CPGI). Healthy Caucasian subjects who had gambled at least once in their lifetime (n=242) were included in the analysis. Gender was not associated with the CPGI, while younger age was associated with higher CPGI scores. We have found that none of the single polymorphisms investigated on DRD1 and DRD3 were associated with CPGI scores in healthy subjects. However, we observed trends for association on the TaqIA/rs1800497 polymorphism (P=0.10) and the haplotype flanking DRD2 (G/C/A rs11604671/rs4938015/rs2303380; P=0.06). Both trends were associated with lower CPGI score. Our results provide further evidence for the role of dopamine D2-like receptor in addiction susceptibility.

Cocaine and amphetamine regulated transcript (CART) gene in the comorbidity of schizophrenia with alcohol use disorders and nicotine dependence.

Studies have shown a genetic susceptibility to develop schizophrenia, alcohol use disorders and nicotine dependence. Brain areas related to reward and reinforcement show high expression of the cocaine and amphetamine regulated transcript (CART). Nicotine and alcohol are also able to modulate CART expression in the hypothalamic areas. In this study, we evaluated whether CART variants would influence the predisposition of schizophrenia subjects to alcohol use disorders and nicotine dependence. Clinical and genetic data were obtained from 190 unrelated Caucasian schizophrenia subjects collected at the Centre for Addiction and Mental Health. We found no association of CART variants with alcohol use disorders or nicotine dependence. We found a trend for allelic association of rs11575893 with the heaviness of smoking behaviour (p=0.057). Our results indicate that genetic variants in the CART gene may not play a major role in the vulnerability of schizophrenia subjects to concurrent alcohol use disorders and nicotine dependence. Additional association studies in independent samples can evaluate whether CART gene is playing a role in the schizophrenia comorbidity with alcohol use disorders and nicotine dependence.

Genetic aspects of pathological gambling: a complex disorder with shared genetic vulnerabilities.

AIMS: To summarize and discuss findings from genetic studies conducted on pathological gambling (PG). METHODS: Searches were conducted on PubMed and PsychInfo databases using the keywords: 'gambling and genes', 'gambling and family' and 'gambling and genetics', yielding 18 original research articles investigating the genetics of PG. RESULTS: Twin studies using the Vietnam Era Twin Registry have found that: (i) the heritability of PG is estimated to be 50-60%; (ii) PG and subclinical PG are a continuum of the same disorder; (iii) PG shares genetic vulnerability factors with antisocial behaviours, alcohol dependence and major depressive disorder; (iv) genetic factors underlie the association between exposure to traumatic life-events and PG. Molecular genetic investigations on PG are at an early stage and published studies have reported associations with genes involved in the brain's reward and impulse control systems. CONCLUSIONS: Despite the paucity of studies in this area, published studies have provided considerable evidence of the influence of genetic factors on PG and its complex interaction with other psychiatric disorders and environmental factors. The next step would be to investigate the association and interaction of these variables in larger molecular genetic studies with subphenotypes that underlie PG. Results from family and genetic investigations corroborate further the importance of understanding the biological underpinnings of PG in the development of more specific treatment and prevention strategies.