Ghrelin receptor deletion reduces binge‐like alcohol drinking in rats

Ghrelin is a gastric hormone that has been implicated in the neurobiology of alcohol drinking. We have recently developed a ghrelin receptor (growth hormone secretagogue receptor; GHSR) knockout (KO) rat model, which exhibits reduced food consumption and body weight. In addition, recent preliminary work suggests that the gut‐microbiome, which appears to interact with the ghrelin system, may modulate alcohol drinking. In the present study, we investigated the effects of GHSR deletion on alcohol consumption utilising GHSR KO and wild‐type (WT) rats in three separate alcohol consumption paradigms: (i) operant self‐administration (30‐minute sessions); (ii) drinking in the dark (DID) (4‐hour sessions); and (iii) intermittent access (24‐hour sessions). These paradigms model varying degrees of alcohol consumption. Furthermore, we aimed to investigate the gut‐microbiome composition of GHSR KO and WT rats before and after alcohol exposure. We found that the GHSR KO rats self‐administered significantly less alcohol compared to WT rats in the operant paradigm, and consumed less alcohol than WT in the initial stages of the DID paradigm. No genotype differences were found in the intermittent access test. In addition, we found a significant decrease in gut‐microbial diversity after alcohol exposure in both genotypes. Thus, the present results indicate that the ghrelin system may be involved in drinking patterns that result in presumably increased alcohol exposure levels. Furthermore, GHSR may constitute a potential pharmacological target for the reduction of binge‐alcohol consumption. The potential functional role of the gut‐microbiome in alcohol drinking, as well as interaction with the ghrelin system, is an interesting topic for further investigation.     

Long‐Term Outcomes of Continuous Intrathecal Baclofen Infusion for Treatment of Spasticity: A Prospective Multicenter Follow‐Up Study

Long‐term outcomes of 115 patients treated with continuous intrathecal baclofen infusion are reported. A prospective follow‐up study was conducted in eight centers. Patients were followed up over a 12‐month period. The follow‐up scores on the three spasticity scales (Ashworth, spasm, and clonus scales) were significantly lower at every follow‐up visit in comparison to the intake score, except for the clonus scale scores at 12 months. Improvements in health‐related quality of life (EQ‐5D) and functionality (SIP‐68, functional independence measure) were small and nonsignificant. A significant reduction in severity of self‐reported personal problems rating scale was observed. Sixty‐six patients had no adverse events. Types of adverse events reported were wound complications (22%), catheter problems (36%), cerebrospinal fluid leakage (25%), and other complications (17%). Intrathecal baclofen reduces spasticity and severity of patient‐reported problems but its effect on quality of life and functionality is less apparent. Improvements are desired in selection criteria, design of spinal catheters, and outcome scales.     

Tobacco and alcohol‐related interventions for people with mild/moderate intellectual disabilities: a systematic review of the literature

Background The behavioural determinants of health among people with mild/moderate intellectual disabilities (ID) are of increasing concern. With the closure of long‐stay institutions, more people with ID are living in the community. As they lead more ordinary and less restricted lives, people with ID may be exposed to social and environmental pressures that encourage them to adopt behaviours that impact negatively on their health. Levels of smoking and alcohol consumption in this client group are of particular concern. Methods We undertook a mixed method review of the literature, aiming to assess the Feasibility, Appropriateness, Meaningfulness and Effectiveness (FAME) of interventions designed to address the use of tobacco and/or alcohol in people with mild/moderate ID. Key electronic databases were searched (e.g. Medline, Cochrane Register of Controlled Trials, PsycINFO) from 1996 to 2011. The search was developed using appropriate subject headings and key words (e.g. intellectual disability, tobacco use, alcohol drinking, health promotion). On completion of the database searches, inclusion/exclusion criteria, based on an adaptation of the PICO framework (Population, Intervention, Comparison, Outcomes), were applied. Methodological quality was assessed using a seven‐point rating scale. Results Database searches identified 501 unique records, of which nine satisfied the inclusion criteria. Four focused on tobacco, three on alcohol and two on both tobacco and alcohol. Located in the UK, the USA and Australia, the studies aimed to increase knowledge levels and/or change behaviour (e.g. to encourage smoking cessation). One was a randomised controlled trial, one a quasi‐experiment and the others were before and after studies and/or case studies. Methodological quality was poor or moderate. The combined studies had a sample size of 341, with ages ranging from 14 to 54 years. The interventions were delivered by professionals (e.g. in health, social care, education) during sessions that spanned a period of three weeks to one academic year. The studies highlighted a number of important issues linked to the appropriateness of interventions for this client group (e.g. use of pictures, quizzes, role play, incentives); however, in the majority of cases the interventions appeared to lack a theoretical framework (e.g. behaviour change theory). The appropriateness of the outcome measures for use with this client group was not tested. One study discussed feasibility (teachers delivering lessons on alcohol and tobacco) and only one was informative in terms of effectiveness i.e. increasing knowledge of the health and social dangers of smoking and excessive alcohol consumption. Conclusions This review is the first to systematically collate evidence on tobacco and alcohol‐related interventions for people with ID. While there is currently little evidence to guide practice, the review delivers clear insights for the development of interventions and presents a strong case for more robust research methods. In particular there is a need to test the effectiveness of interventions in large‐scale, well‐designed trials and to ensure that outcome measures are developed/tailored appropriately for this client group.     

THE MORE IT IS NEEDED,THE LESS IT IS WANTED: ATTITUDES TOWARD FACE‐TO‐FACE INTERVENTION AMONG DEPRESSED PATIENTS UNDERGOING ONLINE TREATMENT

Many individuals suffering from depression do not actively seek treatment. Self‐help strategies represent low‐threshold treatment options that are particularly relevant for milder cases. The present study addressed two important issues: (1) we examined depressed individuals’ motives and attitudes that may represent barriers to face‐to‐face treatment; (2) we examined if the participation in an online treatment program facilitates or compromises their willingness to undergo face‐to‐face treatment. We recruited 210 participants with depression for a trial on the efficacy of an online treatment program for depression. Participants were randomly allocated either to a self‐help treatment (Deprexis) or to a wait‐list control group. All participants filled out a newly developed 42‐item questionnaire called Psychotherapy Expectations, Concerns, and Hopes Inventory (PECHI). The scale measures attitudes toward face‐to‐face treatment and was administered at baseline and 8 weeks later. Principal component analysis of the PECHI revealed five dimensions: hope for symptomatic improvement, fear of poor alliance with the therapist, skill acquisition, skepticism and resentment of psychotherapy, and self‐stigma. Attitudes toward treatment were stable over time and neither modulated by group status nor by self‐reported or objective symptom decline. Correlation analyses revealed that current levels of depression and well‐being were potent predictors of attitudes toward treatment, suggesting that when the patient feels more depressed, doubts about the effectiveness of therapy emerge more strongly. To conclude, results suggest that Deprexis neither promotes nor reduces negative attitudes toward psychotherapy, nor does it increase barriers to enter face‐to‐face treatments. An alarming paradox emerged: when a depressed person is in greatest need of help, motivation to seek face‐to‐face treatment is lowest. Depression and Anxiety 00:1‐11, 2012. © 2012 Wiley Periodicals, Inc.     

Striatal modulation of BDNF expression using microRNA124a‐expressing lentiviral vectors impairs ethanol‐induced conditioned‐place preference and voluntary alcohol consumption

Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non‐coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol‐induced conditioned‐place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso‐lateral striatum (DLS) following alcohol drinking. Then, we identified brain‐derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol‐induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV‐miR124a in the DLS enhances ethanol‐induced CPP as well as voluntary alcohol consumption in a two‐bottle choice drinking paradigm. Moreover, miR124a‐silencer (LV‐siR124a) as well as LV‐BDNF infusion in the DLS attenuates ethanol‐induced CPP as well as voluntary alcohol consumption. Importantly, LV‐miR124a, LV‐siR124a and LV‐BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward.     

Development of 2‐hour suicide intervention program among medical residents: First pilot trial

Aim: Suicide is associated not only with primary psychiatric disorders but also with physical disorders. Physicians' education on suicide prevention contributes to reducing suicide. Therefore, medical residents, who contact patients daily and who eventually become primary physicians in each specialty, might be the most appropriate candidates for intervention. In this article, we introduce our newly developed suicide intervention program among medical residents. Methods: We developed a 2‐hour suicide intervention program among medical residents, based on the Mental Health First Aid (MHFA), which had originally been developed for the public. The program contains a 1‐hour lecture and a 1‐hour role‐play session. As the first pilot trial, we conducted the program among 44 first‐year medical residents at a university hospital and evaluated its effectiveness. Changes in confidence, attitudes and behavior toward suicidal people were evaluated using self‐reported questionnaires before, immediately after, and 6 months after the program. Results: Participants' confidence and attitudes significantly improved after the program. The total mean score (standard deviation) of the Suicide Intervention Response Inventory improved from 18.4 (2.0) before the intervention to 19.4 (2.0) immediately after the intervention. However, the effectiveness was limited after 6 months. In the course of 6 months, the participants learned to apply the MHFA principles in their daily clinical practice. Conclusion: Our newly developed brief suicide intervention program demonstrating its effectiveness among medical residents should be modified in order to be more effective in the long term. The next trial with a control group ought to be conducted to evaluate our developed program.     

Outcome of mentalization‐based and supportive psychotherapy in patients with borderline personality disorder: a randomized trial

Objective: This study presents data from a randomized outcome study comparing mentalization‐based and supportive psychotherapy for patients with borderline personality disorder (BPD). Method: Eighty‐five SCID‐II diagnosed borderline patients were randomized to either i) 2 years of intensive (twice weekly) combined (individual and group), mentalization‐based psychotherapy (MBT) or ii) 2 years of less‐intensive (biweekly) supportive group therapy. Treatment outcome was assessed using a battery of self‐report questionnaires, SCID‐II interviews and therapist‐rated global assessment of functioning (GAF). Results: Fifty‐eight patients completed 2 years of treatment. Significant changes in both treatment groups were identified for several outcome measures, including self‐reported measures of general functioning, depression, social functioning and number of diagnostic criteria met for BPD, as outlined by the SCID‐II interview. General linear modelling was used to compare treatment outcome in the two groups. Only GAF showed a significantly higher outcome in the MBT group. A trend was found for a higher rate of recovery from BPD in the MBT group. Pre‐post effect sizes were high (0.5–2.1) and for the most part highly significant in both groups. Conclusion: The study indicates that both MBT and supportive treatment are highly effective in treating BPD when conducted by a well‐trained and experienced psychodynamic staff in a well‐organized clinic.     

International Guillain‐Barré Syndrome Outcome Study: protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain‐Barré syndrome

Guillain‐Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow‐up of 1–3 years. Data are collected via a web‐based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long‐term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS.     

Efficacy of interpersonal therapy‐group format adapted to post‐traumatic stress disorder: an open‐label add‐on trial

Background: Post‐traumatic stress disorder (PTSD) is a highly prevalent condition, yet available treatments demonstrate only modest efficacy. Exposure therapies, considered by many to be the “gold‐standard” therapy for PTSD, are poorly tolerated by many patients and show high attrition. We evaluated interpersonal therapy, in a group format, adapted to PTSD (IPT‐G PTSD), as an adjunctive treatment for patients who failed to respond to conventional psychopharmacological treatment. Methods: Research participants included 40 patients who sought treatment through a program on violence in the department of psychiatry of Federal University of São Paulo (UNIFESP). They had received conventional psychopharmacological treatment for at least 12 weeks and failed to have an adequate clinical response. After signing an informed consent, approved earlier by the UNIFESP Ethics Review Board, they received a semi‐structured diagnostic interview (SCID‐I), administered by a trained mental health worker, to confirm the presence of a PTSD diagnosis according to DSM‐IV criteria. Other instruments were administered, and patients completed out self‐report instruments at baseline, and endpoint to evaluate clinical outcomes. Results: Thirty‐three patients completed the trial, but all had at least one second outcome evaluation. There were significant improvements on all measures, with large effect sizes. Conclusions: IPT‐G PTSD was effective not only in decreasing symptoms of PTSD, but also in decreasing symptoms of anxiety and depression. It led to significant improvements in social adjustment and quality of life. It was well tolerated and there were few dropouts. Our results are very preliminary; they need further confirmation through randomized controlled clinical trials. Depression and Anxiety, 2010. © 2009 Wiley‐Liss, Inc.     

Achieving symptomatic remission in out‐patients with schizophrenia – a naturalistic study with quetiapine

Objective: Symptomatic remission was defined as a score of mild or less on each of eight key schizophrenia symptoms on the Positive and Negative Syndrome Scale (PANSS‐8). To evaluate the symptomatic remission criterion in clinical practice and to determine predictors for achieving symptomatic remission, a 12‐week non‐interventional study (NIS) with quetiapine was conducted in Germany. Method: For the comparison of patients with and without symptomatic remission, sociodemographic and clinical variables of 693 patients were analyzed by logistic regression for their predictive value to achieve remission. Results: Four hundred and four patients (58.3%) achieved symptomatic remission after 12 weeks’ treatment with quetiapine. Remission was significantly predicted by a low degree of PANSS‐8 total score, PANSS single items blunted affect (N1), social withdrawal (N4), lack of spontaneity (N6), mannerism and posturing (G5), and low disease severity (CGI‐S) at baseline. Predictors of non‐remission were older age, diagnosis of schizophrenic residuum, multiple previous episodes, longer duration of current episode, presence of concomitant diseases, and alcohol abuse. Conclusion: This study demonstrated that the majority of schizophrenia out‐patients achieved symptomatic remission after 12 weeks treatment and confirms the importance of managing negative symptoms in order to achieve disease remission.     

Cocaine self‐administration is increased after frontal traumatic brain injury and associated with neuroinflammation

Traumatic brain injury (TBI) has been linked to the development of numerous psychiatric diseases, including substance use disorder. However, it can be difficult to ascertain from clinical data whether the TBI is cause or consequence of increased addiction vulnerability. Surprisingly few studies have taken advantage of animal models to investigate the causal nature of this relationship. In terms of a plausible neurobiological mechanism through which TBI could magnify the risk of substance dependence, numerous studies indicate that TBI can cause widespread disruption to monoaminergic signaling in striatal regions, and also increases neuroinflammation. In the current study, male Long‐Evans rats received either a mild or severe TBI centered over the frontal cortex via controlled cortical impact, and were subsequently trained to self‐administer cocaine over 10 6‐hour sessions. At the end of the study, markers of striatal dopaminergic function, and levels of inflammatory cytokine levels in the frontal lobes, were assessed via western blot and multiplex ELISA, respectively. There was significantly higher cocaine intake in a subset of animals with either mild or severe TBI. However, many animals within both TBI groups failed to acquire self‐administration. Principal components analysis suggested that both dopaminergic and neuroinflammatory proteins were associated with overall cocaine intake, yet only an inflammatory component was associated with acquisition of self‐administration, suggesting neuroinflammation may make a more substantial contribution to the likelihood of drug‐taking. Should neuroinflammation play a causal role in mediating TBI‐induced addiction risk, anti‐inflammatory therapy may reduce the likelihood of substance abuse in TBI populations.     

Potential use of Internet‐based screening for anxiety disorders: a pilot study

Background: The Internet is a widely used resource for obtaining health information. Internet users are able to obtain anonymous information on diagnoses and treatment, seek confirmatory information, and are able to self‐diagnose. We posted a self‐report diagnostic screening questionnaire for DSM‐IV anxiety and mood disorders (MACSCREEN) on our clinic website. Method: Three hundred and two individuals completed the MACSREEN. For those who qualified for a DSM‐IV disorder, self‐report symptom severity measures were completed for the specified disorder: Quick Inventory of Depressive Symptomatology, self‐report, Social Phobia Inventory, GAD‐7, Davidson Trauma Scale, Panic and Agoraphobia Scale, and Yale/Brown Obsessive Compulsive Scale, self‐report. Cutoff scores for each self‐report measure were used to evaluate clinically significant symptom severity. Respondents were also asked to complete a series of questions regarding their use of the Internet for health information. Results: The mean age of the MACSCREEN sample was 35.2 years (±13.9), where the majority (67.2%) were female. The most frequently diagnosed conditions were social phobia (51.0%), major depressive disorder (32.4%), and generalized anxiety disorder (25.5%). Sixty‐five percent of the sample met criteria for at least one disorder. Most respondents reported completing the MACSCREEN, as they were concerned they had an anxiety problem (62.3%). The majority of respondents reported seeking health information concerning specific symptoms they were experiencing (54.6%) and were planning to use the information to seek further assessment (60.3%). Conclusion: Individuals with clinically significant disorder appear to be using the Internet to self‐diagnose and seek additional information. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

A randomized, double-blind, placebo-controlled clinical trial of acamprosate in alcohol-dependent individuals with bipolar disorder: a preliminary report

Tolliver BK, DeSantis SM, Brown DG, Prisciandaro JJ, Brady KT. A randomized, double‐blind, placebo‐controlled clinical trial of acamprosate in alcohol‐dependent individuals with bipolar disorder: a preliminary report. Bipolar Disord 2012: 14: 54–63. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Background: Alcohol use disorders commonly co‐occur with bipolar disorder and are associated with a more severe course of bipolar illness, yet treatment research in this important clinical population is scarce. The current study assessed the effects of acamprosate on alcohol use and mood symptoms in subjects with co‐occurring bipolar disorder and active alcohol dependence. Methods: Thirty‐three adults meeting criteria for bipolar I or bipolar II disorder and current alcohol dependence were randomized to receive add‐on acamprosate (1998 mg/day) or placebo while concurrently maintained on mood stabilizing medications. Participants were assessed weekly for frequency and quantity of alcohol consumption and general clinical severity for eight weeks. Depressive symptoms, manic symptoms, and alcohol craving were assessed biweekly. Biomarkers of alcohol use were assessed at study baseline and endpoint. Results: Of the 33 subjects randomized, 23 (69.7%) completed all active phase visits. Over the trial as a whole, no statistically significant treatment differences were detected in drinking outcomes. Post‐hoc analysis revealed lower Clinical Global Impression scores of substance use severity in acamprosate‐treated participants in weeks 7–8 of the trial. No significant differences in depressive symptoms, manic symptoms, or adverse events were observed between groups. Conclusions: Acamprosate was well‐tolerated, with no worsening of depressive or manic symptoms, and appeared to confer some clinical benefit in study completers in the last two weeks of the trial. Larger studies of longer duration are required to fully explore the utility of acamprosate in this population.     

Response to nicotine dependence treatment in smokers with current and past alcohol problems

Smoking prevalence among alcoholics is high, and evidence indicates that smokers with a history of alcohol abuse may have more difficulty quitting cigarette smoking. This study is a post hoc analysis comparing the smoking cessation rates of smokers with active or past alcohol problems to the rates in smokers with no history of alcohol problems who were participants in a randomized, controlled trial of smoking cessation therapy. Subjects received either 44 mg/24 hour or 22 mg/24 hour nicotine patch for 4 or 6 weeks, respectively, followed by a tapering schedule to complete 8 weeks of therapy and a randomly assigned behavioral intervention (minimal, brief individual counseling, group therapy). The Self-Administered Alcoholism Screening Test (SAAST) score was used to determine alcohol group assignment (no alcohol problems <7; active alcohol problems ≥7 and still drinking; past alcohol problems if not drinking due to a past history of alcohol problems). Among 382 subjects (171 men and 211 women), 281 had no alcohol problems (74%), 53 had past alcohol problems (14%), and 48 had active alcohol problems (13%). Smoking cessation rates assessed at both weeks 4 and 8 were significantly different across groups (p=0.026 and 0.002 at weeks 4 and 8, respectively) with lower rates in the groups with past and active alcohol problems when compared to the “no problem” group. At week 26, subjects with past alcohol problems were less likely to be abstinent from smoking than no problem group subjects, but this was not statistically significant (odds ratio =0.49, 95% confidence interval 0.22→1.08). In the short term, smokers with past or active alcohol problems are less likely to quit smoking compared to those with no alcohol problems when treated with nicotine patch therapy for smoking cessation.     

Aripiprazole for the treatment of pediatric bipolar I disorder: a 30‐week,randomized, placebo‐controlled study

Objective: To evaluate the long‐term efficacy, safety, and tolerability of aripiprazole in pediatric subjects with bipolar I disorder. Methods: A randomized, double‐blind, 30‐week, placebo‐controlled study of aripiprazole (10 or 30 mg/day) in youths (10–17 years) with bipolar I disorder (manic or mixed) ± psychotic features (n = 296) was performed. After four weeks, acute treatment completers continued receiving ≤26 weeks of double‐blind treatment (n = 210). The primary outcome was Young Mania Rating Scale (YMRS) total score change. Results: Of the 210 subjects who entered the 26‐week extension phase, 32.4% completed the study (45.3% for aripiprazole 10 mg/day, 31.0% for aripiprazole 30 mg/day, and 18.8% for placebo). Both aripiprazole doses demonstrated significantly (p < 0.001) greater improvements in YMRS total score at endpoint compared with placebo in protocol‐specified last observation carried forward analyses, but not in observed case or mixed‐model repeated measures at week 30. Overall time to all‐cause discontinuation was longer for aripiprazole 10 mg/day (15.6 weeks) and aripiprazole 30 mg/day (9.5 weeks) compared with placebo (5.3 weeks; both p < 0.05 versus placebo). Both aripiprazole doses were significantly superior to placebo regarding response rates, Children’s Global Assessment of Functioning and Clinical Global Impressions‐Bipolar severity of overall and mania scores at endpoint in all analyses. Commonly reported adverse events included headache, somnolence, and extrapyramidal disorder. Conclusions: Aripiprazole 10 mg/day and 30 mg/day were superior to placebo and generally well tolerated in pediatric subjects with bipolar I disorder up to 30 weeks. Despite the benefits of treatment, completion rates were low in all treatment arms.     

Abnormal fronto‐striatal activation as a marker of threshold and subthreshold Bulimia Nervosa

This study aimed to determine whether functional disturbances in fronto‐striatal control circuits characterize adolescents with Bulimia Nervosa (BN) spectrum eating disorders regardless of clinical severity. FMRI was used to assess conflict‐related brain activations during performance of a Simon task in two samples of adolescents with BN symptoms compared with healthy adolescents. The BN samples differed in the severity of their clinical presentation, illness duration and age. Multi‐voxel pattern analyses (MVPAs) based on machine learning were used to determine whether patterns of fronto‐striatal activation characterized adolescents with BN spectrum disorders regardless of clinical severity, and whether accurate classification of less symptomatic adolescents (subthreshold BN; SBN) could be achieved based on patterns of activation in adolescents who met DSM5 criteria for BN. MVPA classification analyses revealed that both BN and SBN adolescents could be accurately discriminated from healthy adolescents based on fronto‐striatal activation. Notably, the patterns detected in more severely ill BN compared with healthy adolescents accurately discriminated less symptomatic SBN from healthy adolescents. Deficient activation of fronto‐striatal circuits can characterize BN early in its course, when clinical presentations are less severe, perhaps pointing to circuit‐based disturbances as useful biomarker or risk factor for the disorder, and a tool for understanding its developmental trajectory, as well as the development of early interventions.     

Long‐term follow‐up of impulse control disorders in Parkinson's disease

Recent studies have linked dopamine agonist (DA) usage with the development of impulse control disorders (ICDs) in Parkinson's disease (PD). Little is known about optimal management strategies or the long‐term outcomes of affected patients. To report on the clinical interventions and long‐term outcomes of PD patients who developed an ICD after DA initiation. Subjects contacted by telephone for a follow‐up interview after a mean time period of 29.2 months. They were administered a modified Minnesota Impulse Disorder Interview for compulsive buying, gambling, and sexuality, and also self‐rated changes in their ICD symptomatology. Baseline and follow‐up dopamine replacement therapy use was recorded and verified by chart review. Of 18 subjects, 15 (83.3%) participated in the follow‐up interview. At follow‐up, patients were receiving a significantly lower DA levodopa equivalent daily dosage (LEDD) (Z = ?3.1, P = 0.002) and a higher daily levodopa dosage (Z = ?1.9, P = 0.05), but a similar total LEDD dosage (Z = ?0.47, P = 0.64) with no changes in Unified Parkinson's Disease Rating Scale motor score (Z = ?1.3, P = 0.19). As part of ICD management, 12 (80.0%) patients discontinued or significantly decreased DA treatment, all of whom experienced full or partial remission of ICD symptoms by self‐report, and 10 (83.3%) of whom no longer met diagnostic criteria for an ICD. For PD patients who develop an ICD in the context of DA treatment, discontinuing or significantly decreasing DA exposure, even when offset by an increase in levodopa treatment, is associated with remission of or significant reduction in ICD behaviors without worsening in motor symptoms. © 2007 Movement Disorder Society     

Pre‐stroke use of beta‐blockers does not affect ischaemic stroke severity and outcome

Background and purpose: It is unclear whether pre‐stroke beta‐blockers use may influence stroke outcome. This study evaluates the independent effect of pre‐stroke use of beta‐blockers on ischaemic stroke severity and 3 months functional outcome. Methods: Pre‐stroke use of beta‐blockers was investigated in 1375 ischaemic stroke patients who had been included in two placebo‐controlled trials with lubeluzole. Stroke severity was assessed by either the National Institute of Health Stroke Scale (NIHSS) or the European Stroke Scale (ESS). A modified Rankin scale (mRS) score of >3 at 3 months was used as measure for the poor functional outcome. Results: Two hundred and sixty four patients were on beta‐blockers prior to stroke onset, and 105 patients continued treatment after their stroke. Pretreatment with beta‐blockers did not influence baseline stroke severity. There was no difference in stroke severity between nonusers and those on either a selective beta₁‐blocker or a non‐selective beta‐blocker. The likelihood of a poor outcome at 3 months was not influenced by pre‐stroke beta‐blocker use or beta‐blocker use before and continued after stroke onset. Conclusions: Pre‐stroke use of beta‐blockers does not appear to influence stroke severity and functional outcome at 3 months.     

Striatal alcohol cue‐reactivity is stronger in male than female problem drinkers

Despite apparent sex differences in the development and treatment of alcohol use disorder, relatively little is known about the underlying neural mechanisms. In this study, we therefore investigated neural cue‐reactivity in a sample of male (n = 28) and female (n = 27) problem drinkers (matched on age and alcohol use severity) with an average alcohol use disorder identification test score of 12 which is indicative of a likely alcohol use disorder. Neural cue‐reactivity data were extracted from four regions of interest: the ventral and dorsal striatum and the ventral and dorsal anterior cingulate cortex, with a significance level set at p < 0.05. While the cue‐reactivity paradigm induced similar levels of self‐reported craving in men and women, visual alcohol cues induced significantly stronger striatal activation in men compared to drinkers. While sex differences in ventral striatal cue‐reactivity were partly explained by sex differences in alcohol intake, cannabis use, negative affect and anxiety, this was not the case for sex differences in dorsal striatal cue‐reactivity. These results suggest that alcohol cues are differentially processed by men and women and that the neurobiological mechanisms behind cue‐reactivity differ between the sexes. Consequently, paradigms using alcohol‐related pictures may not be optimal to induce cue‐reactivity in female drinkers and may not be optimal to measure neurobiological markers of alcohol use severity and relapse. Future alcohol cue‐reactivity studies should, in addition to including both men and women, include different types of cues (e.g., stressors and imagery in addition to pictures) to assess sex differences in alcohol cue‐reactivity.