Blunted midbrain reward activation during smoking withdrawal: a preliminary study.

Introduction: Tobacco smoking is the leading preventable cause of death, causing more than six million deaths annually worldwide, mainly due to cardiovascular disease and cancer. Many habitual smokers try to stop smoking but only about 7% are successful, despite widespread knowledge of the risks. Development of addiction to a range of substances is associated with progressive blunting of brain reward responses and sensitisation of stress responses, as described by the allostasis theory of addiction. There is pre-clinical evidence from rodents for a dramatic decrease in brain reward function during nicotine withdrawal. Methods: Here we tested the hypothesis that habitual smokers would also exhibit blunted reward function during nicotine withdrawal using a decision-making task and fMRI. Results: Our findings supported this hypothesis, with midbrain reward-related responses particularly blunted. We also tested the hypothesis that smokers with a longer duration of smoking would have more pronounced abnormalities. Contrary to expectations, we found that a shorter duration of smoking in younger smokers was associated with the most marked abnormalities, with blunted midbrain reward related activation including the dopaminergic ventral tegmental area. Discussion: Given the substantial mortality associated with smoking, and the small percent of people who manage to achieve sustained abstinence, further translational studies on nicotine addiction mechanisms are indicated.

A Pan-European Review of Good Practices in Early Intervention Safeguarding Practice with Children, Young People and Families: Evidence Gathering to Inform a Multi-disciplinary Training Programme (the ERICA Project) in Preventing Child Abuse and Neglect in Seven European Countries.

Child maltreatment has detrimental social and health effects for individuals, families and communities. The ERICA project is a pan-European training programme that equips non-specialist threshold practitioners with knowledge and skills to prevent and detect child maltreatment. This paper describes and presents the findings of a rapid review of good practice examples across seven participating countries including local services, programmes and risk assessment tools used in the detection and prevention of child maltreatment in the family. Learning was applied to the development of the generic training project. A template for mapping the good practice examples was collaboratively developed by the seven participating partner countries. A descriptive data analysis was undertaken organised by an a priori analysis framework. Examples were organised into three areas: programmes tackling child abuse and neglect, local practices in assessment and referral, risk assessment tools. Key findings were identified using a thematic approach. Seventy-two good practice examples were identified and categorised according to area, subcategory and number. A typology was developed as follows: legislative frameworks, child health promotion programmes, national guidance on child maltreatment, local practice guidance, risk assessment tools, local support services, early intervention programmes, telephone or internet-based support services, COVID-19 related good practices. Improved integration of guidance into practice and professional training in child development were highlighted as overarching needs. The impact of COVID-19 on safeguarding issues was apparent. The ERICA training programme formally responded to the learning identified in this international good practice review.

Compulsivity and impulsivity in opioid dependence.

OBJECTIVE: Chronic exposure to illicit opioid drugs can cause serious health and social problems. However, less is known about the differential effect of various opioid treatments, such as methadone and buprenorphine, on neurocognitive domains such as compulsivity and impulsivity, despite their relevance to the treatment of opioid dependence. METHODS: A total of 186 participants were recruited with a cross-sectional design: i) illicit heroin users (n = 27), ii) former heroin users stabilized on methadone MMT (n = 48), iii) a buprenorphine maintenance treatment (BMT) group (n = 18), iv) an abstinent (ABS) group with a history of opioid dependence who were previously stabilized on MMT or BMT (n = 29) and v) healthy controls (HC) (n = 64). We used the Intra-Extra Dimensional Shift (IED) and Cambridge Gambling Task (CGT) paradigms for measuring compulsivity and impulsivity constructs respectively. RESULTS: Heightened compulsivity persisted in the heroin, buprenorphine and abstinent groups. Heroin, methadone and buprenorphine groups exhibited impaired behavioral responses to feedback, consisting of increased deliberation time and poorer risk adjustment. Higher compulsivity measures were negatively associated with opioid dose which may reflect sedation effects. CONCLUSIONS: Our results suggest that compulsivity and impulsivity are core neurocognitive dimensions for opioid dependence which differ in their presentation according to the stage of treatment. Participants taking higher morphine equivalent doses performed better in compulsivity measures. These findings have implications for the treatment of opioid dependence and longitudinal studies are warranted.

Severity of negative mood and anxiety symptoms occurring during acute abstinence from tobacco: A systematic review and meta-analysis.

This review was conducted with the following goals: To quantify the severity of mood and anxiety symptoms emerging during acute abstinence from tobacco (1). To explore sex differences related to the experience of specific symptoms (2). To investigate the early time course of symptoms (3). A meta-analysis was performed from 28 studies assessing mood and anxiety symptoms during the earliest phases of tobacco abstinence (up to 24 hrs post-quit) conducted from 1999 to 2019. Results revealed a significant (p < 0.0001) increase in 'anxiety', 'anger/irritability', 'depressed mood /sadness', and composite negative affect ('NA') in the 24 hours following smoking cessation. The largest effect size was detected for 'anxiety' (0.63). A qualitative analysis was performed to investigate sex differences and the time course of the specific symptoms. Results indicated that female smokers may experience worse mood symptoms compared to male smokers and that these symptoms may emerge within 3 hrs post-quit. Smoking cessation programs should implement sex-tailored interventions in order to improve their effectiveness, while future research should focus on alternative methods of nicotine administration.

Chronic tobacco smoking and neuropsychological impairments: A systematic review and meta-analysis.

The link between neuropsychological impairments and chronic tobacco smoking is not clear and in the current literature there is a lack of robust analyses investigating this association. A systematic review of the literature was conducted in order to identify relevant longitudinal and cross-sectional studies conducted from 1946 to 2017. A meta-analysis was performed from 24 studies testing the performance of chronic tobacco smokers compared with non-smokers on neuropsychological tests related to eight different neuropsychological domains. The results revealed a cross-sectional association between neuropsychological impairments and chronic tobacco smoking in cognitive impulsivity, non-planning impulsivity, attention, intelligence, short term memory, long term memory, and cognitive flexibility, with the largest effect size being related to cognitive impulsivity (SDM = 0.881, p <0.005), and the smallest effect size being related to intelligence (SDM = 0.164, p < 0.05) according to Cohen's benchmark criteria. No association was found between chronic smoking and motor impulsivity (SDM = 0.105, p = 0.248). Future research is needed to investigate further this association by focusing on better methodologies and alternative methods for nicotine administration.

Profiles of visuospatial memory dysfunction in opioid-exposed and dependent populations.

BACKGROUND: Chronic opioid exposure is common world-wide, but behavioural performance remains under-investigated. This study aimed to investigate visuospatial memory performance in opioid-exposed and dependent clinical populations and its associations with measures of intelligence and cognitive impulsivity. METHODS: We recruited 109 participants: (i) patients with a history of opioid dependence due to chronic heroin use (n = 24), (ii) heroin users stabilised on methadone maintenance treatment (n = 29), (iii) participants with a history of chronic pain and prescribed tramadol and codeine (n = 28) and (iv) healthy controls (n = 28). The neuropsychological tasks from the Cambridge Neuropsychological Test Automated Battery included the Delayed Matching to Sample (DMS), Pattern Recognition Memory, Spatial Recognition Memory, Paired Associate Learning, Spatial Span Task, Spatial Working Memory and Cambridge Gambling Task. Pre-morbid general intelligence was assessed using the National Adult Reading Test. RESULTS: As hypothesised, this study identified the differential effects of chronic heroin and methadone exposures on neuropsychological measures of visuospatial memory (p < 0.01) that were independent of injecting behaviour and dependence status. The study also identified an improvement in DMS performance (specifically at longer delays) when the methadone group was compared with the heroin group and also when the heroin group was stabilised onto methadone. Results identified differential effects of chronic heroin and methadone exposures on various neuropsychological measures of visuospatial memory independently from addiction severity measures, such as injecting behaviour and dependence status.

Association of opioid prescribing practices with chronic pain and benzodiazepine co-prescription: a primary care data linkage study.

BACKGROUND: Opioid prescribing is increasing worldwide with associated increases in misuse and other harms. We studied variations in national opioid prescription rates, indicators of prescribing quality, co-prescribing of benzodiazepines and relationship with pain severity in Scotland. METHODS: Electronic linkages of opioid prescribing in Scotland were determined from: (i) national data from Information Services Division, NHS Scotland (2003-2012); and (ii) individual data from Generation Scotland: Scottish Family Health Study. Descriptive analyses were conducted on national data, multilevel modelling to examine factors associated with variations in prescribing rates. χ2 tests examined associations between individual pain severity and opioid prescriptions. RESULTS: The number of strong opioid prescriptions more than doubled from 474 385 in 2003 to 1 036 446 in 2012, and weak opioid prescribing increased from 3 261 547 to 4 852 583. In Scotland, 938 674 individuals were prescribed an opioid in 2012 (18% of the population). Patients in the most deprived areas were 3.5 times more likely to receive a strong opioid than patients in the least deprived. There was significant variation in prescribing rates between geographical areas, with much of this explained by deprivation. Of women aged 25-40 yr prescribed a strong opioid, 40% were also prescribed a benzodiazepine. There was significant association between pain severity and receipt of opioid prescription. Over 50% of people reporting severe pain were not prescribed an opioid analgesic. CONCLUSIONS: We found opioid prescribing in primary care to be common and increasing in Scotland, particularly for severe pain. Co-prescribing of opioids and benzodiazepines was common.

Aberrant splicing of the tumor suppressor CYLD promotes the development of chronic lymphocytic leukemia via sustained NF-κB signaling.

The pathogenesis of chronic lymphocytic leukemia (CLL) has been linked to constitutive NF-κB activation but the underlying mechanisms are poorly understood. Here we show that alternative splicing of the negative regulator of NF-κB and tumor suppressor gene CYLD regulates the pool of CD5+ B cells through sustained canonical NF-κB signaling. Reinforced canonical NF-κB activity leads to the development of B1 cell-associated tumor formation in aging mice by promoting survival and proliferation of CD5+ B cells, highly reminiscent of human B-CLL. We show that a substantial number of CLL patient samples express sCYLD, strongly implicating a role for it in human B-CLL. We propose that our new CLL-like mouse model represents an appropriate tool for studying ubiquitination-driven canonical NF-κB activation in CLL. Thus, inhibition of alternative splicing of this negative regulator is essential for preventing NF-κB-driven clonal CD5+ B-cell expansion and ultimately CLL-like disease.

Neuropsychological functioning and chronic methadone use: A systematic review and meta-analysis.

INTRODUCTION: There is a presumption that neurocognition is commonly impaired in chronic methadone exposed individuals (CM) when compared with healthy controls (HP). Additionally, it remains unclear if short term (<1year) abstinence (AP) is associated with an altered cognitive profile when compared with CM. METHOD: A random effect model approach was used on data assembled into the Comprehensive Meta-Analysis programme. Cohen's d effect sizes and a significance levels of p<0.01 were calculated for each domain. RESULTS: Data from a total cohort of 1063 CM, 412 AP and 879 HP participants, from 23 independent studies indicate global impairments in neurocognitive function in CM relative to HP participants. The smaller body of evidence comparing CM to AP participants is inconclusive. CONCLUSION: Methodological issues such as small sample sizes, heterogeneity and poor quality limited the interpretation of the results and does not address whether the observed impairments reflect co-morbid functioning, methadone-related sedation and/or other factors. Only higher quality longitudinal studies will permit confident interpretation of the results observed in this meta-analysis.

Decision support in addiction: The development of an e-health tool to assess and prevent risk of fatal overdose. The ORION Project.

BACKGROUND AND OBJECTIVE: The application of e-health technology to the field of substance use disorders is at a relatively early stage, and methodological quality is still variable. Few have explored the extent of utilization of communication technology in exploring risk perception by patients enrolled in substance abuse services. The Overdose RIsk InfOrmatioN (ORION) project is a European Commission funded programme, aimed to develop and pilot an e-health psycho-educational tool to provide information to drug using individuals about the risks of suffering a drug overdose. METHODS: In this article, we report on phase 1 (risk estimation), phase 2 (design), and phase 3 (feasibility) of the ORION project. RESULTS: The development of ORION e-health tool underlined the importance of an evidence-based intervention aimed in obtaining reliable evaluation of risk. The ORION tool supported a decision making process aimed at influencing the substance users' self-efficacy and the degree to which the substance users' understand risk factors. Therefore, its innovative power consisted in translating risks combination into a clear estimation for the user who will then appear more likely to be interested in his/her risk perception. CONCLUSION: Exploratory field testing and validation confirmed the next stage of evaluation, namely, collection of routine patient samples in study clinics. The associations between risk perception of overdose, engagement with the ORION tool and willingness to alter overdose risk factors, in a clinical setting across various EU member states will further confirm the ORION tool's generalisability and effectiveness.

Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence.

BACKGROUND: Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare. METHOD: The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50). RESULTS: Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain-thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group. CONCLUSIONS: Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.

Electronic communication based interventions for hazardous young drinkers: A systematic review.

Previous reviews have specifically looked at computer-based or Internet-based approaches. However, there has been no systematic review focused upon electronic communication based interventions for hazardous young drinkers. Out of 3298 relevant citations, 13 papers consisting of 11 studies met the inclusion criteria. Effectiveness of intervention delivery was assessed using behavioural outcomes. Eight papers delivered interventions using the Web, three implemented text messaging, one used a mobile phone app and the remaining paper used a social networking site. The ability to provide personalized electronic feedback resulted in a reduction in alcohol consumption, frequency of binge drinking, and drinking in a non-risky way. However, intervention length did not appear to have an impact on overall effectiveness. Usage of text messaging and Social Network Sites (SNS) increased accessibility and ease of engaging in an intervention that is appealing and acceptable for young adults.

Impulsivity and opioid drugs: differential effects of heroin, methadone and prescribed analgesic medication.

BACKGROUND: Previous studies have provided inconsistent evidence that chronic exposure to opioid drugs, including heroin and methadone, may be associated with impairments in executive neuropsychological functioning, specifically cognitive impulsivity. Further, it remains unclear how such impairments may relate of the nature, level and extent of opioid exposure, the presence and severity of opioid dependence, and hazardous behaviours such as injecting. METHOD: Participants with histories of illicit heroin use (n = 24), former heroin users stabilized on prescribed methadone (methadone maintenance treatment; MMT) (n = 29), licit opioid prescriptions for chronic pain without history of abuse or dependence (n = 28) and healthy controls (n = 28) were recruited and tested on a task battery that included measures of cognitive impulsivity (Cambridge Gambling Task, CGT), motor impulsivity (Affective Go/NoGo, AGN) and non-planning impulsivity (Stockings of Cambridge, SOC). RESULTS: Illicit heroin users showed increased motor impulsivity and impaired strategic planning. Additionally, they placed higher bets earlier and risked more on the CGT. Stable MMT participants deliberated longer and placed higher bets earlier on the CGT, but did not risk more. Chronic opioid exposed pain participants did not differ from healthy controls on any measures on any tasks. The identified impairments did not appear to be associated specifically with histories of intravenous drug use, nor with estimates of total opioid exposure. CONCLUSION: These data support the hypothesis that different aspects of neuropsychological measures of impulsivity appear to be associated with exposure to different opioids. This could reflect either a neurobehavioural consequence of opioid exposure, or may represent an underlying trait vulnerability to opioid dependence.

Neuropsychological consequences of chronic opioid use: a quantitative review and meta-analysis.

INTRODUCTION: It is widely assumed within the accumulated literature that neuropsychological function is commonly impaired as a consequence of chronic opioid use. METHOD: Quantitative and systematic review of the literature on the neuropsychology of chronic opioid use using the meta-analysis of observational studies in epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. RESULTS: This meta-analysis suggests that chronic opioid exposure is associated with deficits across a range of different neuropsychological domains. However, the only domains where meta-analysis suggests robust impairment were those of verbal working memory, cognitive impulsivity (risk taking) and cognitive flexibility (verbal fluency). The magnitude of effect across these cognitive domains was medium according to Cohen's benchmark criteria. DISCUSSION: This analysis highlighted methodological problems present in the literature used and the value of utilising meta-analytic techniques to help further elucidate the neuropsychological consequences of chronic opioid use from 'core' addiction phenotypes.

Comorbidity patterns in dual diagnosis across seven European sites

Background and Objectives: Psychiatric inpatients with substance use disorders are a significant public health concern due to grave consequences including increased risk of self harm, homicide as well as poor clinical outcome. The present study aims to examine and compare patterns of comorbidity (i.e. concurrent substance use disordersand severe mental illness) among psychiatric inpatients across seven European sites. Methods: 352 patients were included consecutively from psychiatric inpatients units at7 European sites and interviewed with the Mini- International Neuropsychiatric Interview and the European version of the Addiction Severity Index questionnaires. For analysis the psychiatric diagnostic groups were organized into broader categories. Results: Concurrent alcohol use disorder and mood disorder was found to be the most prevalent comorbidity pattern (30.8%) across Europe. Alcohol or drug use disorder combined with mood disorder was most prevalent among females and in the older age group where as mixed substance use and psychosis was more frequent among males and younger participants. Finally, differences in comorbidity patterns were found at different European sites. Conclusions: The prevalence of different comorbidity patterns varied across European clinical settings. Significant differences between comorbidity subgroups were found with regard to age and gender(AU)

Differences in 5-year survival after a 'homeless' or 'housed' drugs-related hospital admission: a study of 15--30-year olds in Scotland.

BACKGROUND: Young drug misusers and the homeless both have a greater risk of death than their peers. This study sought to estimate the additional impact of homelessness on the risk of death for young drugs misusers. METHODS: From all admissions to NHS hospitals in Scotland between 1986 and 2001, those that were: drug misuse related, for people born between 1970 and 1986 and aged over 15 years (n=13 303), were selected. All subsequent admissions and registrations of death were linked to this dataset. Each admission was coded as homeless if the health board of residence was coded as 'no fixed abode'. 5-year survival after an admission was modelled using (1) life table and (2) proportional hazard models and then (3) differences in causes of deaths were explored. RESULTS: Immediately after a drugs-related hospital admission there was no difference in survival between the homeless and those with a 'fixed address'. However, over a 3-year period the risk for those who were homeless was 3.5 times greater (CI 95% 1.2 to 12.8). This elevated risk seemed to be particularly focused on the second year after an admission. The causes of death were similar for the two groups. CONCLUSION: Although a homeless hospital admission is associated with a greater risk of death for young drug users, it is also a point in time when a young person is in contact with public services. An attempt to link their discharge with housing services would seem a potentially productive policy.

Recording of clinical information in a Scotland-wide drug deaths study.

The aim of this study was to analyse the nature and extent of data extracted from case files of deceased individuals in contact with services 6 months prior to drug deaths in Scotland during 2003. A cross-sectional descriptive analysis of 317 case notes of 237 individuals who had drug-related deaths was undertaken, using a data linkage process. All contacts made with services in the 6 months prior to death were identified. Information on clinical and social circumstances obtained from social care, specialist drug treatment, mental health, non-statutory services, the Scottish Prison Service and Criminal Records Office was collated. More than 70% (n = 237) were seen 6 months prior to their drug death. Sociodemographic details were reported much more frequently than medical problems, for example, ethnicity (49%), living accommodation (66%), education and income (52%) and dependent children (73%). Medical and psychiatric history was recorded in only 12%, blood-borne viral status in 17% and life events in 26%. This paucity of information was a feature of treatment plans and progress recorded. The 237 drug deaths were not a population unknown to services. Highly relevant data were missing. Improved training to promote in-depth recording and effective monitoring may result in better understanding and reduction of drug deaths.

Social exclusion in clients with comorbid mental health and substance misuse problems.

BACKGROUND: The concept of comorbid mental health problems and substance misuse has gained prominence in the last two decades, due in part to the closure of large psychiatric hospitals and to the increasing prevalence of drug use in the community. This client group has a dual requirement for both medical and social care needs and is at risk for social exclusion. METHODS: A retrospective matched case-control study to examine aspects of social exclusion between service users who have comorbid diagnoses and those with a single diagnosis. Samples were drawn from the service users of a mental health Trust in the South-East of England, from both Adult Mental Health (n = 400) and Drug and Alcohol services (n = 190). Data were collected from Care Programme Approach assessment forms and medical records. McNemar's chi(2) and odds ratios via a conditional logit regression model are used to test for differences in the social exclusion indicators. RESULTS: There were significant differences in social exclusion between the comorbid and singly diagnosed clients of the Adult Mental Health service, but differences were less pronounced between the comorbid and singly diagnosed clients of the specialist Drug and Alcohol service. CONCLUSIONS: Recent Government policy advocates treating comorbid clients within mainstream mental health services. Health care workers need to recognise the likelihood of high levels of social exclusion among clients with comorbid problems.

Defining dual diagnosis of mental illness and substance misuse: some methodological issues.

This paper discusses methodological issues arising in the initial stages of a larger epidemiological case-control study. Practitioners from both Generic Mental Health and Substance Misuse Services (n = 170) were asked to identify which of their clients, from a time-limited caseload (n = 2341), had comorbid mental health and substance misuse problems. Although practitioners were provided with a definition of 'singly diagnosed' and 'dually diagnosed', it became apparent that these definitions were applied pragmatically, depending on the nature of the client's primary problem and the agency they were presenting to. Issues raised include the time period in which a client was considered to have a concurrent mental health problem and substance misuse, how a 'mental health problem' was defined and whether a personality disorder should be categorized as a 'mental health problem'. There was also some disagreement about whether clients who were being treated primarily by Substance Misuse Services, but were also taking prescribed antidepressants, implicitly had a 'mental health problem'. We raise these methodological issues, as they have implications for determining the prevalence of 'dual diagnosis' and the subsequent provision of services.

Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers.

Groups of subjects whose primary drug of abuse was amphetamine or heroin were compared, together with age- and IQ-matched control subjects. The study consisted of a neuropsychological test battery which included both conventional tests and also computerised tests of recognition memory, spatial working memory, planning, sequence generation, visual discrimination learning, and attentional set-shifting. Many of these tests have previously been shown to be sensitive to cortical damage (including selective lesions of the temporal or frontal lobes) and to cognitive deficits in dementia, basal ganglia disease, and neuropsychiatric disorder. Qualitative differences, as well as some commonalities, were found in the profile of cognitive impairment between the two groups. The chronic amphetamine abusers were significantly impaired in performance on the extra-dimensional shift task (a core component of the Wisconsin Card Sort Test) whereas in contrast, the heroin abusers were impaired in learning the normally easier intra-dimensional shift component. Both groups were impaired in some of tests of spatial working memory. However, the amphetamine group, unlike the heroin group, were not deficient in an index of strategic performance on this test. The heroin group failed to show significant improvement between two blocks of a sequence generation task after training and additionally exhibited more perseverative behavior on this task. The two groups were profoundly, but equivalently impaired on a test of pattern recognition memory sensitive to temporal lobe dysfunction. These results indicate that chronic drug use may lead to distinct patterns of cognitive impairment that may be associated with dysfunction of different components of cortico-striatal circuitry.