Role of proline residues in the expression and function of the human noradrenaline transporter

The aim was to investigate the roles of proline residues in extracellular loop 2 (P172, P183, P188 and P209) and transmembrane domains 2, 5, 11 and 12 (P108, P270, P526, P551, P552 and P570) in determining noradrenaline transporter (NET) expression and function. Mutants of human NET with these residues mutated to alanine were pharmacologically characterized. Mutation of P108, P270 and P526 disrupted cell surface expression, from [H-3]nisoxetine binding and confocal microscopy data. Mutations of P526, P551 and P570 reduced transporter turnover (V-max of [H-3]noradrenaline uptake/B-max of [H-3]nisoxetine binding) by 1.5-1.7-fold compared with wild-type NET, so these residues might be involved in conformational changes associated with substrate translocation. Conversely, mutations of P172, P183, P188 and P209 increased V-max/B-max by 2-3-fold compared with wild-type, indicating that the presence of these proline residues limits turnover of the NET. The mutations had few effects on apparent affinities of substrates or affinities of inhibitors, except decreases in inhibitor affinities after mutations of the P270 and P570 residues, and increases after mutation of the P526 residue. Hence, proline residues in extracellular loop 2 and in transmembrane domains have a range of roles in determining expression and function of the NET.

Alcohol dependence: the impact of cognitive behaviour therapy with or without naltrexone on subjective health status

Objectives: To examine the health-related quality of life of alcohol-dependent patients across a 12-week cognitive behaviour treatment (CBT) program and identify whether the patient selection of the anticraving medication naltrexone further enhanced these outcomes. Method: One hundred and thirty-six consecutive alcohol-dependent subjects voluntarily participated and were offered naltrexone, of which 73 (54%) participants declined medication. A matched design was used. Of the 136 subjects, 86 (43 naltrexone and CBT; 43 CBT only) could be individually matched (blind to outcome measures) for gender, age, prior alcohol detoxification and dependence severity. Measures of health status and mental health wellbeing included the Rand Corporation Medical Outcomes Short Form 36 Health Survey (SF-36) and the General Health Questionnaire (GHQ-28). Results: Pre-treatment, all had SF-36 and GHQ-28 scores markedly below national norms. Post-treatment, significant improvement in seven of the eight SF-36 subscales and all of the GHQ-28 subscales occurred, approximating national normative levels. Patients in the CBT + naltrexone group were significantly more likely to have increased days abstinent (p = 0.002) and to complete the program abstinent (p = 0.051). The adjunctive use of naltrexone did not provide additional benefit as reflected in SF-36 and GHQ-28 scores, beyond CBT alone. Conclusions: Patients who completed the CBT-based treatment program reported significant improvements in self-reported health status (SF-36) and wellbeing (GHQ-28). The adjunctive use of naltrexone demonstrated no additional improvement in these measures.

The role of drinking restraint in alcohol dependence: validation of the temptation and restraint inventory in an alcohol dependent sample

Objective: The Temptation and Restraint Inventory (TRI) is commonly used to measure drinking restraint in relation to problem drinking behavior. However, as yet the TRI has not been validated in a clinical group with alcohol dependence. Method: Male (n = 111) and female (n = 57) inpatients with DSM-IV diagnosed alcohol dependence completed the TRI and measures of problem drinking severity, including the Alcohol Dependence Scale and the quantity, frequency and week total of alcohol consumed. Results: The factor structure of the TRI was replicated in the alcohol dependent sample. Cognitive Emotional Preoccupation (CEP), one of the two higher order factors of the TRI, demonstrated sound predictive power toward all dependence severity indices. The other higher order factor, Cognitive Behavioral Control (CBC), was related to frequency of drinking. There was limited support for the CEP/CBC interactional model of drinking restraint. Conclusions: Although the construct validity of the TRI was sound, the measure appears more useful in understanding the development, maintenance and severity of alcohol-related problems in nondependent drinkers. The TRI may show promise in detecting either continuous drinking or heavy episodic type dependent drinkers.

Do nations' mental health policies, programs and legislation influence their suicide rates? An ecological study of 100 countries

Objective: To test the hypothesis that the presence of national mental health policies, programs and legislation would be associated with lower national suicide rates. Method: Suicide rates from 100 countries were regressed on mental health policy, program and legislation indicators. Results: Contrary to the hypothesized relationship, the study found that after introducing mental health initiatives (with the exception of substance abuse policies), countries' suicide rates rose. Conclusion: It is of concern that most mental health initiatives are associated with an increase in suicide rates. However, there may be acceptable reasons for the observed findings, for example initiatives may have been introduced in areas of increasing need, or a case-finding effect may be operating. Data limitations must also be considered.

Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD)

Aims The study estimated serious adverse event (SAE) rates among entrants to pharmacotherapies for opioid dependence, during treatment and after leaving treatment. Design A longitudinal study based on data from 12 trials included in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Participants and settings A total of 1.244 heroin users and methadone patients treated in hospital, community and GP settings. Intervention Six trials included detoxification; all included treatment with methadone, buprenorphine, levo-alpha-acetyl-methadol (LAAM) or naltrexone. Findings During 394 person-years of observation, 79 SAEs of 28 types were recorded. Naltrexone participants experienced 39 overdoses per 100 person-years after leaving treatment (44% occurred within 2 weeks after stopping naltrexone). This was eight times the rate recorded among participants who left agonist treatment. Rates of all other SAEs were similar during treatment versus out of treatment, for both naltrexone-treated and agonist-treated participants. Five deaths occurred, all among participants who had left treatment, at a rate of six per 100 person-years. Total SAE rates during naltrexone and agonist treatments were similar (20, 14 per 100 person-years, respectively). Total SAE and death rates observed among participants who had left treatment were three and 19 times the corresponding rates during treatment. Conclusions Individuals who leave pharmacotherapies for opioid dependence experience higher overdose and death rates compared with those in treatment. This may be due partly to a participant self-selection effect rather than entirely to pharmacotherapy being protective. Clinicians should alert naltrexone treatment patients in particular about heroin overdose risks. Duty of care may extend beyond cessation of dosing.

A cost-effectiveness analysis of buprenorphine-assisted heroin withdrawal

The purpose of this study was to conduct a cost - effectiveness analysis of detoxification from heroin using buprenorphine in a specialist clinic versus a shared care setting. A randomized controlled trial was conducted with a total of 115 heroin-dependent patients receiving a 5-day treatment regime of buprenorphine. The specialist clinic was a community-based treatment agency in inner-city Sydney. Shared care involved treatment by a general practitioner supplemented by weekend dispensing and some concurrent counselling at the specialist clinic. Quanti. cation of resource use was limited to inputs for treatment provision. The primary outcome measure used in the economic analysis was the proportion of each group that completed detoxification and achieved an initial 7-day period of abstinence. Buprenorphine detoxification in the shared care setting was estimated to be $24 more expensive per patient than treatment at the clinic, which had an average treatment cost of $332 per patient. Twenty-three per cent of the shared care patients and 22% of the clinic patients reported no opiate use during the withdrawal period. These results suggest that the provision of buprenorphine treatment for heroin dependence in shared care and clinic appear to be equally cost - effective.

Encouraging practitioners to use resources: evaluation of the national implementation of a resource to improve the clinical management of alcohol-related problems in Indigenous primary care settings

This paper reports on the evaluation of the implementation of the National Recommendations for the Clinical Management of Alcohol-Related Problems in Indigenous Primary Care Settings undertaken in 2001 through 74 standardized workshops, which sought to determine: ( 1) whether this approach to implementation influenced the likelihood that the National Recommendations would be used; ( 2) whether it influenced participants' willingness to engage with Indigenous patients regarding alcohol-related issues; and ( 3) whether the implementation as a whole influenced both practice and clinicians' willingness to engage. Evaluation included pre-/post-workshop and follow-up questionnaires and a focus group. The findings presented indicate that distribution of clinical resources alone is not sufficient to ensure use and that, particularly for medical practitioners, appropriate introduction not only increases use but also positively influences willingness to engage with alcohol-related problems as part of primary clinical care. Further, the enthusiasm for guideline production should be tempered by the need to develop effective implementation strategies.

Correlates of victimisation amongst people with psychosis

Background While much attention has been given to the prediction of violent offending behaviour amongst people with psychotic disorders, less attention has been given to the fact that these same individuals are often the victims of violence. In this paper, we examine victimisation amongst participants in a prevalence study of psychosis, and describe demographic and clinical correlates of victimisation. Method The study was based on the Australian National Survey of Mental Health and Wellbeing - Low Prevalence (Psychotic) Disorders. The participants were asked if they had been a victim of violence in the previous year. The association between selected demographic and clinical variables and being a victim of violence was examined using logistic regression. Results Of the 962 individuals with psychosis, 172 reported being a victim of violence in the past 12 months (17.9 %). The odds of being a victim were increased in those who: (a) were female, (b) were homeless, (c) had a lifetime history of substance abuse, (d) had been arrested in the previous 12 months, (e) had poorer social and occupational function, and (f) had higher scores on the disorganisation summary score. Conclusions Clinicians should remain mindful that one out of every six individuals with a psychotic disorder reports being a victim of violence in the previous year. Models of care that address issues related to symptom relief, accommodation, and exposure to high-crime areas may reduce the rates of victimisation amongst those with psychotic disorders.

The gambling related cognitions scale (GRCS): development, confirmatory factor validation and psychometric properties

Aims The aims of this study are to develop and validate a measure to screen for a range of gambling-related cognitions (GRC) in gamblers. Design and participants A total of 968 volunteers were recruited from a community-based population. They were divided randomly into two groups. Principal axis factoring with varimax rotation was performed on group one and confirmatory factor analysis (CFA) was used on group two to confirm the best-fitted solution. Measurements The Gambling Related Cognition Scale (GRCS) was developed for this study and the South Oaks Gambling Screen (SOGS), the Motivation Towards Gambling Scale (MTGS) and the Depression Anxiety Stress Scale (DASS-2 1) were used for validation. Findings Exploratory factor analysis performed using half the sample indicated five factors, which included interpretative control/bias (GRCS-IB), illusion of control (GRCS-IC), predictive control (GRCS-PC), gambling-related expectancies (GRCS-GE) and a perceived inability to stop gambling (GRCS-IS). These accounted for 70% of the total variance. Using the other half of the sample, CFA confirmed that the five-factor solution fitted the data most effectively. Cronbach's alpha coefficients for the factors ranged from 0.77 to 0.91, and 0.93 for the overall scale. Conclusions This paper demonstrated that the 23-item GRCS has good psychometric properties and thus is a useful instrument for identifying GRC among non-clinical gamblers. It provides the first step towards devising/adapting similar tools for problem gamblers as well as developing more specialized instruments to assess particular domains of GRC.

Desire to drink in low- and high-risk social drinkers: An experimental analogue of impaired control

This study used a novel cue exposure paradigm to investigate the differences between high- and low-risk drinkers in their desire to drink during a drinking session. Fifty-three self-selected participants were assigned to high- or low-risk drinking groups based on their self-reported consumption of alcohol, then compared on their desire to drink over a 90 min paced drinking session. High-risk drinkers showed increasing desire over the session, while low-risk drinkers' desire began to decrease after only a short drinking period. The perceived and actual effects of the alcohol did not appear to be able to account for the difference. Results are discussed with reference to issues of impaired control. Suggestions for future research directions are also offered.

The gambling urge scale: Development, confirmatory factor validation, and psychometric properties

The urge to gamble is a physiological, psychological, or emotional motivational state, often associated with continued gambling. The authors developed and validated the 6-item Gambling Urge Questionnaire (GUS), which was based on the 8-item Alcohol Urge Questionnaire (M. J. Bohn, D. D. Krahn, & B. A. Staehler, 1995), using 968 community-based participants. Exploratory factor analysis using half of the sample indicated a 1-factor solution that accounted for 55.18% of the total variance. This was confirmed using confirmatory factor analysis with the other half of the sample. The GUS had a Cronbach's alpha coefficient of .81. Concurrent, predictive, and criterion-related validity of the GUS were good, suggesting that the GUS is a valid and reliable instrument for assessing gambling urges among nonclinical gamblers.

A cognitive model of binge drinking: The influence of alcohol expectancies and drinking refusal self-efficacy

While binge drinking-episodic or irregular consumption of excessive amounts of alcohol-is recognised as a serious problem affecting our youth, to date there has been a lack of psychological theory and thus theoretically driven research into this problem. The current paper develops a cognitive model using the key constructs of alcohol expectancies (AEs) and drinking refusal self-efficacy (DRSE) to explain the acquisition and maintenance of binge drinking. It is suggested that the four combinations of the AE and DRSE can explain the four drinking styles. These are normal/social drinkers, binge drinkers, regular heavy drinkers, and problem drinkers or alcoholics. Since AE and DRSE are cognitive constructs and therefore modifiable, the cognitive model can thus facilitate the design of intervention and-prevention strategies for binge drinking. (C) 2003 Elsevier Ltd. All rights reserved.

The relationship between personality and drinking restraint in an alcohol dependent sample

Consistent relationships have been demonstrated between problem drinking and certain personality characteristics. A contemporary cognitive model of alcohol misuse, drinking restraint, has recently shown promise in furthering our understanding of problematic drinking. This study examined the potential association between drinking restraint and personality characteristics in 168 alcohol dependent inpatients. Subjects completed the short-scale Revised Eysenck Personality Scales (EPS-R; Eysenck, Eysenck, & Barrett, 1985), Temptation and Restraint Inventory (TRI; Collins & Lapp, 1992), Alcohol Dependence Scale (ADS; Skinner & Allen, 1982) and drinking measures including quantity, frequency and weekly drinking total. Results indicated that although there was some conceptual overlap between drinking restraint and personality factors, the TRI had a unique relationship with indices of problem drinking once personality factors were taken into account. This indicates that restrained drinking and personality, although related, are discrete constructs. While restrained drinking may aid in the understanding of current drinking behavior, personality characteristics appear to contribute to the etiology and maintenance of drinking problems. (c) 2005 Elsevier Ltd. All rights reserved.