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The recent emergence of new psychoactive compounds (novel psychoactive substances (NPS)) has raised prominent challenges in the fields of drug policy, substance use research, public health and service provision. The Recreational Drugs European Network project, funded by the European Commission, was implemented to improve the information stream to young people and professionals about effects/risks of NPS by identifying online products and disseminating relevant information through technological tools.Regular multilingual qualitative assessments of websites, drugs fora and other online resources were carried out using the Google search engine in eight languages from collaborating countries. These included the following: the UK, Norway, Belgium, Germany, Hungary, Poland, Italy and Spain. Products were tested and prevention messages were developed and disseminated via technological tools such as interactive websites, SMS alert, social networking (Facebook, Twitter), Multimedia (You Tube), Smartphone applications (iPhone) and virtual learning environments (Second Life).The Recreational Drugs European Network project established itself as the first Europe-wide prevention programme designed for NPS based on the efficacy of novel information and communication technology-based forms of intervention. More than 650 NPS products and combinations were identified; relevant information was disseminated to target population and advice was given to both European Union/international agencies and national policy makers.Web-monitoring activities are essential for mapping the diffusion of NPS and the use of technological tools can be successfully incorporated in specific prevention programmes. Furthermore, the involvement of multi-disciplinary international partnerships was and continues to be fundamental for responding to such a prominent challenge.

Methods: Twenty-two patients receiving (R)-methadone maintenance treatment were switched to a double dose of (R, S)-methadone: blood samples were collected before and after the change, and the concentrations of the enantiomers were measured. In the second period, during racemic methadone treatment, important interindividual variability in the stereoselective disposition of the enantiomers of methadone was measured, with (R)/(S) ratios ranging from 0.63 to 2.40. This point should be taken into account particularly with respect to therapeutic drug monitoring of racemic methadone. Results: A significant decrease P < 0.005 in the mean serum concentration/dose ratios of the active (R)-enantiomer before and after the change was measured (mean 3.97 and 3.33). Conclusion: Although of small amplitude (16%), this decrease confirms previously described adaptive changes in methadone pharmacokinetics during racemic methadone maintenance treatment and may necessitate, in some patients, a dose adjustment.

The present study reports results of the ICD-10 research criteria trial concerning the diagnosis of affective disorders (section F3). On the basis of written case reports and videotapes a total of 451 clinicians from 34 centres in German-speaking countries prepared 2.228 diagnostic ratings on 39 different psychiatric patients. Three of the 39 cases met the diagnostic criteria for affective disorders, and 248 of the diagnostic assessments referred to these cases. The majority of clinicians rated the reliability, the ease and the suitability of the diagnostic criteria positively. The reliability of the affective disorders was extremely good, with a kappa of 0.93 in the range of 2-character diagnoses. The reliability of the 3-character categories was much smaller: Kappa values for depressive episode (F31) and recurrent depressive disorder (F33) were 0.68 and 0.54, respectively. The lowest concordance had a kappa value of 0.22 and was found in the case report of dysthymia (F34.1). Therefore a more precise definition of the diagnostic criteria for dysthymia would be desirable.

Little is known about sexual dysfunctions associated with psychiatric disorders and psychopharmacological treatment. In the present study schizophrenic patients (n = 45, mostly under neuroleptic treatment), neurotic patients (n = 50, mostly treated without medication), methadone-substituted opiate addicts (n = 37), and normal controls (n = 41) were included. They were interviewed with the aid of a sex-differentiated semistructured questionnaire on sexual function. All the methadone-substituted opiate addicts and nearly all the schizophrenic patients suffered from dysfunctions in at least one criterion. The three clinical groups differed significantly from the controls in sexual interest, emotional arousal, physiological arousal (erectile function/vaginal lubrication), performance (ejaculatory function/vaginism, dyspareunia), and orgasm satisfaction. Characteristic patterns of dysfunction were found in the male patients. The schizophrenic patients had significantly more dysfunctions of interest, physiological arousal, performance, and orgasm than the controls. Emotional arousal, erectile and ejaculatory functions, and orgasm satisfaction were impaired more frequently in the male schizophrenics than in the neurotic patients. Reduced sexual interest, emotional arousal, and orgasm satisfaction were reported more frequently by the methadone-substituted opiate addicts than by the neurotic men. Emotional arousal was even more frequently reduced than in the schizophrenic men. There was no correlation between sexual dysfunction and particular neuroleptics or neuroleptic or methadone dosage. The results are compared with the literature and suggestions made for further investigations.

IntroductionOnly few international studies have focused on mental diseases among the hearing-impaired population. However, Fellinger et al. (2012) underline the high discrepancy between the current and future demand of mental treatment and the simultaneous impeded access to health care.AimsThe aim of this multicenter project is to conduct the first analysis of mental diseases among the hearing-impaired population in Germany in order to quantify and qualify the specific demands of treatment.ObjectivesIn order to achieve this aim, we compiled an extensive questionnaire battery.MethodsThis questionnaire battery measured sociodemographic data, non-verbal intelligence, quality of life, perception and suffering from stress, psychosomatic symptoms as well as personality traits.ResultsOur three samples consisted of 21 hearing-impaired patients with a history of mental diseases (EG-HI), 21 hearing-impaired subjects without mental diseases (CG-HI) and 21 hearing participants without any psychological disease (CG-H). Compared to the two control groups, the EG-HI shows significantly higher rates in different fields, i.e. participants perceive a lower quality of life, suffer from more psychosomatic symptoms and show more pronounced personality traits. The two control groups did not differ significantly from each other.ConclusionsCertain psychological characteristics among hearing-impaired patients can be detected which need to be accounted for in treatment. Furthermore, a hearing impairment is not inevitably linked to a reduced quality of life or even mental disorders. Therefore, future research should focus on risk factors and protective factors which could prevent mental diseases among the hearing-impaired population.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Poster-Abstract

In most cases, restless legs syndrome (RLS) is an idiopathic disorder affecting patients of middle and older age. Usually, the intensity of symptoms is constant or progressive. Here, we describe two opiate addicts developing RLS during opiate withdrawal. Their RLS disappeared along with the remission of withdrawal symptoms. Both cases responded well to a treatment with Madopar® (L-dopa plus benserazid). This observation encouraged us to perform a retrospective analysis of all cases of opiate addicts detoxified in our unit during a 5-month period. This analysis revealed 15 out of 120 patients who had described the symptoms of transient RLS emerging during opiate detoxification treatment. Transient RLS during opiate detoxification merits further interst in order to improve the treatment of sleep disturbances during detoxification and as a model of interaction of the dopaminergic and endorphine system in motor activity.

Background: Though an important percentage of patients with chronic hepatitis C virus (HCV) undergoing interferon (IFN) therapy develop depressive symptoms, the role of the IFN system in the pathogenesis of depressive disorders is not well understood. Methods: 50 patients with HCV infection were treated with standard combination therapy (pegylated IFN-α2a/ribavirin). IFN-induced gene expression was analyzed to identify genes which are differentially regulated in patients with or without IFN-induced depression. For validation, PBMC from 22 psychiatric patients with a severe depressive episode (SDE) and 11 controls were cultivated in vitro with pegylated IFN-α2a and gene expression was analyzed. Results: IFN-induced depression in HCV patients was associated with selective upregulation of 15 genes, including 6 genes that were previously described to be relevant for major depressive disorders or neuronal development. In addition, increased endogenous IFN-production and selective hyper-responsiveness of these genes to IFN stimulation were observed in SDE patients. Conclusions: Our data suggest that selective hyper-responsiveness to exogenous (IFN therapy) or endogenous (depressive disorders) type I IFNs may lead to the development of depressive symptoms. These data could lead to the discovery of novel therapeutic approaches to treat IFN-induced and major depressive disorders.

We set out to examine the impact of treatment for heroin dependence on drug use, injecting behavior, health problems, criminality, and physical and mental health over 18 months among heroin-dependent Londoners. A total of 100 heroin users were recruited for this longitudinal prospective cohort study with repeated measures (T0 as baseline, T1 after 9 months, and T2 after 18 months). The psychiatric evaluation and assessment of drug abuse levels were determined by the CIDI and the EuropASI. Additional evaluations included the WHO-DAS II for disability assessment and the UCLA-SSI for social support. The number of days of heroin use in the 30 days previous to each single assessment significantly reduced over time (p.001). Similar reduction levels were observed for cocaine (p.05), benzodiazepines (p.001), and polydrug abuse (p.001), but not for cannabis and alcohol. The number of injecting occasions reduced in parallel, with increase in days in work and reduction of money spent for drug acquisition activities and money obtained from criminal/illegal activities. The number of subjects experiencing suicidal ideation reduced over time (p.05). In line with previous suggestions, significant reductions in drug use, criminality, psychopathology, and injecting behavior following treatment exposure for heroin dependence were observed. It is, however, of concern that alcohol and cannabis misuse levels remained unchanged.

Objectives Unprotected sexual intercourse between men who have sex with men (MSM) is the most common route of HIV infection in Germany. Approximately 70% of newly infected people are MSM. Substance use is a determinant of sexual risk behaviour in the general population, but also in the MSM subpopulation. There are only a few studies, from the USA, on the correlation between substance use and sexual risk behaviour in HIV-infected MSM in specialized care. Methods In a German sample of 445 HIV-infected MSM treated in specialized out-patient clinics, the influence of substance use on sexual risk behaviour was investigated. Information was obtained from subjects using self-report questionnaires and a structured interview. Results Recreational drug use was common. The prevalences of cannabis addiction (4.5%), harmful use of cannabis (4.3%) and harmful use of dissociative anaesthetics (0.4%) were higher than in the general German male population. A substantial proportion of patients reported unprotected insertive (32.9%) and receptive (34.6%) anal intercourse during the last 12 months. Use of cannabis, amyl nitrite, dissociative anaesthetics, cocaine, amphetamines and erectile dysfunction medication was significantly correlated with unprotected sexual contacts. Substance use in the context of sexual activity significantly increased sexual risk behaviour. Conclusions Substance use, especially in the context of sexual activity, should be taken into account when developing new prevention and intervention programmes aimed at reducing sexual risk behaviour in HIV-infected MSM currently in specialized care.

The impact of alcoholism (ALC) or alcohol dependence on the neural mechanisms underlying cognitive and affective empathy (i.e. the different routes to understanding other people's minds) in schizophrenic patients and non-schizophrenic subjects is still poorly understood. We therefore aimed at determining the extent to which the ability to infer other people's mental states and underlying neural mechanisms were affected by ALC. We examined 48 men, who suffered either from ALC, schizophrenia, both disorders or none of these disorders, using functional magnetic resonance imaging while performing on a mind reading task that involves both cognitive and affective aspects of empathy. Using voxel-based morphometry, we additionally examined whether between-group differences in functional activity were associated with deficits in brain structural integrity. During mental state attribution, all clinical groups as compared with healthy controls exhibited poor performance as well as reduced right-hemispheric insular function with the highest error rate and insular dysfunction seen in the schizophrenic patients without ALC. Accordingly, both behavioral performance and insular functioning revealed schizophrenia × ALC interaction effects. In addition, schizophrenic patients relative to non-schizophrenic subjects (regardless of ALC) exhibited deficits in structural integrity and task-related recruitment of the left ventrolateral prefrontal cortex (vlPFC). Our data suggest that ALC-related impairment in the ability to infer other people's mental states is limited to insular dysfunction and thus deficits in affective empathy. By contrast, mentalizing in schizophrenia (regardless of ALC) may be associated with insular dysfunction as well as a combination of structural and functional deficits in the left vlPFC.

In der Psychiatrie hat die Begutachtungskunde eine wesentlich grosere Bedeutung als in den anderen medizinischen Fachgebieten. Neben den von allen Arzten zu beantwortenden sozialrechtlichen Fragestellungen hat der Psychiater zu einem viel weiteren Bereich rechtlicher Probleme Stellung zu nehmen.

Hintergrund: Der Anteil von Männern, die Sex mit Männern haben (MSM) ist unter HIV-Neuinfizierten in vielen westlichen Industriestaaten konstant auf hohem Niveau. Die Einnahme von Suchtmitteln ist mit vermehrtem Risikoverhalten für sexuell übertragbare Krankheiten assoziiert. Der Suchtmittelkonsum von MSM und seine Assoziation mit sexuellem Risikoverhalten sind von Bedeutung für die HIV-Verbreitung. Methodik: Literaturübersicht ab 1999 publizierter Studien zur Prävalenz von Suchtmittelkonsum bei MSM. Ergebnisse: Die meisten Untersuchungen zum Thema wurden in den USA durchgeführt. Das Ausmaß von Alkoholkonsum und alkoholbezogenen Störungen bei MSM war generell vergleichbar mit der Allgemeinbevölkerung. Erhöhte Prävalenzraten unter MSM wurden für den Konsum illegaler Substanzen gefunden. Besonders für Cannabis, Amylnitrit, Halluzinogenen, Stimulantien und Kokain. Es gibt zudem Subgruppen von MSM, die im Kontext gesellschaftlicher Aktivitäten intensiv sog. Club Drugs konsumieren. Dieser Konsum ist mit sexuellem Risikoverhalten assoziiert. Schlussfolgerungen: Bei der Entwicklung zielgruppenspezifischer Interventionen zur Prävention sexuell übertragbarer Krankheiten in der Gruppe der MSM sollte der Suchtmittelkonsum als wichtiger Einflussfaktor verstärkt berücksichtigt werden.

Hintergrund: In monozentrischen Untersuchungen ist der Erfolg einer Entzugsbehandlung Drogenabhangiger sehr unterschiedlich. In dieser multizentrischen Untersuchung (Benchmarking-Projekt des Fachverbandes qualifizierte Akutbehandlung Drogenabhangiger NRW) wird gepruft, welchen Einfluss Patientencharakteristika sowie die durchfuhrende Klinik auf den Erfolg einer qualifizierten Entzugsbehandlung Drogenabhangiger haben. Methodik: Behandlungsepisoden von 1017 opiatabhangigen Patienten in 12 Entzugsstationen in Nordrhein-Westfalen wurden untersucht. Die Stationen waren hinsichtlich Therapieprogramm und grundsatzlicher Personalausstattung vergleichbar. Patientencharakteristika und Behandlungsergebnis wurden von den Behandlern auf einem standardisierten Bogen dokumentiert. Ergebnisse: Das Erreichen eines regularen Behandlungsendes variierte stark zwischen den Behandlungszentren (14%–49%). Ein regulares Behandlungsende war assoziiert mit vorbestehenden Planen fur die Nachbehandlung, vorhergehenden erfolgreichen Entzugs- und Entwohnungsbehandlungen, weniger vorhergehenden erfolglosen Entzugsbehandlungen, hoherem Alter, spaterem Beginn des Opiatkonsums sowie langerer Dauer des Opiatkonsums. Die erhebliche Spannbreite der Ergebnisse zwischen den Zentren blieb auch bei statistischer Kontrolle der Patientencharakteristika weitgehend bestehen. Patientencharakteristika erklarten 9,1% der Ergebnisvarianz, der Zentrums-Faktor erklarte 5,6%. Schlussfolgerung: In Hinblick auf die Patientencharakteristika, die mit einem Erfolg einer Entzugsbehandlung assoziiert sind, wurden in dieser in Deutschland durchgefuhrten Untersuchung Vorbefunde bestatigt. Von Bedeutung ist der Nachweis eines Zentrumseffektes. Dies lasst vermuten, dass trotz grundsatzlicher Ahnlichkeit zwischen den teilnehmenden Stationen in den Behandlungsprozessen Unterschiede bestehen, die fur den Erfolg der Behandlung relevant sind. Hierzu ist weitere Forschung notwendig. Literatur: Backmund M, Meyer K, Eichenlaub D, Schuetz CG: Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients. Drug Alcohol Depend 2001;64:173-180 Erbas B, Jaedike JP, Tretter F: Strukturdaten von 2387 Drogenpatienten in stationarer Entzugsbehandlung in Bayern. Sucht 2003;49:188-196 Haettenschwiler J, Rueesch P, Hell D: Effectiveness of Inpatient Drug Detoxification, Links between Process and Outcome Variables. Eur Addict Res 2000;6:123-131 Kuhlmann T, Hasse HE, Sawalies D: Die qualifizierte stationare Akutbehandlung Drogenabhangiger in NRW. Psychiatr Prax 1994;21:13-18 Mattick RP, Hall W: Are Detoxification programs effective? Lancet 1996;347:97-100 McCusker J, Bigelow C, Luippold R, Zorn M, Lewis BF: Outcomes of a 21-day drug detoxification program, retention, transfer to further treatment, and HIV risk reduction. Am J Drug Alcohol Abuse 1995:21:1-16 Smyth BP, Barry J, Lane A, Cotter M, O’Neill M, Quinn C, Keenan E: In-patient treatment of opiate dependence, medium-term follow-up outcomes. Br J Psychiatry 2005;187:360-365

The definitive version can be found at: http://onlinelibrary.wiley.com/ Copyright John Wiley & Sons [Full text of this article is not available in the UHRA]

Cross-sectional studies show that considerable proportions of opiate dependents in methadone maintenance treatment (MMT) consume benzodiazepines (BZD). The longitudinal patterns of BZD use over time were described here.After admission to MMT, patients from two outpatient MMT clinics (n = 345) were observed for up to 2 years whilst in treatment. The use of BZD, cannabis, opiates and cocaine was assessed by urine sampling carried out twice a month.For the whole sample, the mean BZD-positive urine specimen rate was 0.36 during the first 3 months. Rates slightly decreased during the first year and remained stable afterwards (last observation carried forward). For study completers (n = 152), the rate decreased over time, from 0.31 (first 3-month period) to 0.19 (last period; p0.001). According to a longitudinal cluster analysis, 26% of all patients showed a pattern of constantly high BZD-positivity rates, mostly in combination with other substances. Inpatient detoxifications from BZD (carried out in 18% of cases) did not have a sustained effect on levels of BZD use.BZD consumption in MMT is often part of a polydrug consumption pattern and is associated with poorer treatment retention. It is necessary to further investigate the reasons for BZD use in MMT patients and to develop effective interventions to reduce levels of BZD consumption.

1 „ReDNet‟ and „Psychonaut Web Mapping‟ Projects; University of Hertfordshire School of Pharmacy, Hatfield, UK 2 Psychiatry and Clinical Psychology Department, Umberto I, “La Sapienza” University of Rome Medical School, Rome, Italy; Viale Regina Elena 244, 00161, Rome,Italy; doffizi.stefano@gmail.com; michele.piccione@uniroma1.it 3 Psychonaut Web Mapping Project; National Addiction Centre, Institute of Psychiatry, King's College London, London, UK; 4 Windsor Walk; SE5 AF; paolo.deluca@kcl.ac.uk; zoe.davey@kcl.ac.uk 4 Psychonaut Web Mapping Project; Servizio Salute Regione Marche, Ancona, Italy; Assessorato Salute Regione Marche. Address. Via Gentile da Fabriano 3. Ancona 60100; lucia.difuria@regione.marche.it; stefy.pagani@gmail.com 5 Psychonaut Web Mapping Project; IAPS-IMIM-Hospital del Mar-UAB, Barcelona, Spain; Passeig Maritim 25-29. Barcelona 08003; MTorrens@imim.es; Mfarre@imim.es 6 Psychonaut Web Mapping Project; Bergen Clinics Foundation, Centre of Competence, Bergen, Norway; Vestre Torggate 11 5015 Bergen; arvid.skutle@bergenclinics.no; liv.holmefjord.flesland@bergenclinics.no 7 Psychonaut Web Mapping Project; A-Clinic Foundation, Department of Communications, Helsinki, Finland; Paasivuorenkatu 2A; 00530; Helsinki; teuvo.peltoniemi@a-klinikka.fi; aino.majava@a-klinikka.fi; miia.mannonen@a-klinikka.fi 8 Psychonaut Web Mapping Project; Addiction Research Group at the Department of Psychiatry and Psychotherapy, LVR-Hospital Essen, Hospital of the University Duisburg-Essen, Germany; Virchowstrase 174. D-45122 Essen; norbert.scherbaum@uni-due.de; holger.siemann@lvr.de 9 Psychonaut Web Mapping Project; De Sleutel Technische Bedrijfseen heid Provincialaat der Broeders van Liefde, Merelbeke, Jozef Guislainstraat 43 a; B-9000; Gent Belgium; peer.van.der.kreeft@fracarita.org

CONTEXT: Studies aimed at identifying structural brain alterations associated with persistent violent behavior or psychopathy have not adequately accounted for a lifetime history of substance misuse. Thus, alterations in gray matter (GM) volume that have been reported to be correlates of violent behavior and/or psychopathy may instead be related to lifelong substance use disorders (SUDs). OBJECTIVE: To identify alterations in GM volume associated with violent behavior and those associated with lifelong SUDs. DESIGN: Cross-sectional study. SETTING: Participants were recruited from penitentiaries, forensic hospitals, psychiatric outpatient services, and communities in Germany. Structural magnetic resonance imaging was performed at a university hospital. PARTICIPANTS: Four groups of men were compared: 12 men with SUDs who exhibited violent behavior (hereafter referred to as violent offenders), 12 violent offenders without SUDs, 13 men with SUDs who did not exhibit violent behavior (hereafter referred to as nonoffenders), and 14 nonoffenders without SUDs. MAIN OUTCOME MEASURES: Voxel-based morphometry was used to analyze high-resolution magnetic resonance imaging scans. Assessments of mental disorders, psychopathy (using the Psychopathy Checklist-Screening Version), aggressive behavior, and impulsivity were conducted by trained clinicians. RESULTS: Compared with nonoffenders, violent offenders presented with a larger GM volume in the amygdala bilaterally, the left nucleus accumbens, and the right caudate head and with less GM volume in the left insula. Men with SUDs exhibited a smaller GM volume in the orbitofrontal cortex, ventromedial prefrontal cortex, and premotor cortex than did men without SUDs. Regression analyses indicated that the alterations in GM volume that distinguished the violent offenders from nonoffenders were associated with psychopathy scores and scores for lifelong aggressive behavior. The GM volumes of the orbitofrontal cortex and prefrontal cortex that distinguished the men with SUDs from the men without SUDs were correlated with scores for response inhibition. CONCLUSIONS: These findings suggest that a greater GM volume in the mesolimbic reward system may be associated with violent behavior and that reduced GM volumes in the prefrontal cortex, orbitofrontal cortex, and premotor area characterize men with SUDs. Language: en

The majority of opiate-dependent patients in substitution treatment show additional substance-related disorders. Concomitant use of heroin, alcohol, benzodiazepines or cocaine compromises treatment success. Concomitant drug use may be treated by using contingency management (CM) which is based on learning theory. In CM, abstinence from drugs, as verified by drug screenings, is reinforced directly and contingently. Reinforcers used in CM studies with substituted patients were, amongst others, vouchers and take-home privileges. Studies in the USA show a medium average effect of CM on drug consumption rates and abstinence. The effects decrease markedly after the end of the intervention. We discuss whether CM is applicable within the German substitution treatment system and how it can be combined with other interventions such as selective detoxification treatments or cognitive-behavioural programmes.

Aims: To compare two inpatient symptom-triggered pharmacological treatments of acute alcohol withdrawal (AWS) (clomethiazole vs. clonazepam). Methods: Prospective observational comparison within a quality improvement project. Because of a need for extra precautions against complications such as seizures and severe respiratory complaints, patients with a history of withdrawal seizures or complications with clomethiazole in their history were automatically assigned to the clonazepam group. The remaining patients were alternately assigned either to the clonazepam group ( n = 38 altogether) or the clomethiazole group ( n = 36). Rescue medication could consist of adding either extra clonazepam or clomethiazole. Effectiveness was measured by Clinical Global Impression Scale, Revised Clinical Institute Withdrawal Assessment for Alcohol Scale, Mainz Alcohol Withdrawal Scale, Essen Self-Assessment-Alcohol Withdrawal and attrition rate. Safety and tolerability was estimated from adverse clinical events. Secondary outcome values were heart rate, blood and pulse pressure. Results: There were no significant differences between the treatments with respect to primary and secondary effectiveness measures, safety or tolerability or duration of medication treatment. Both reduced the severity of initial withdrawal symptoms below 20% up to the ending of withdrawal medications. No withdrawal seizure or delirium occurred. Conclusion: Both score-driven treatments were equally effective, safe and well tolerated in this setting. This is the first study demonstrating the utility of clonazepam in the treatment of AWS syndrome.

Given the contradictory results reported in the literature on the relationship between neuroticism and blood pressure, it was decided to reexamine this topic. This was done with a large sample very homogeneous for age, sex, food intake and life style and basically unselected in terms of medical history. In the frame of a blood donation program blood pressure was measured in 810 conscripts. In addition, subjects completed either form A or form B of the Eysenck Personality Inventory (EPI). Data from a total of 624 subjects were suitable for evaluation. No significant correlations were obtained between systolic or diastolic blood pressure and scores of neuroticism or extraversion (r = -0.10 to 0.06) nor did groups with different blood pressure values differ substantially in terms of these variables. This supports work showing that there is no essential connection between blood pressure and emotional lability as measured by the EPI.

Background & Aims Hepatitis C virus (HCV) acquires mutations that allow it to escape the CD8 + T-cell response, although the extent to which this process contributes to viral evolution at the population level is not clear. We studied viral adaptation using data from a large outbreak of HCV genotype 1b infection that occurred among women immunized with contaminated immunoglobulin from 1977 to 1978. Methods The HCV nonstructural protein coding regions NS3−NS5B were sequenced from 78 patients, and mutations were mapped according to their location inside or outside previously described CD8 + T-cell epitopes. A statistical approach was developed to identify sites/regions under reproducible selection pressure associated with HLA class I. Results The frequency of nonsynonymous mutations was significantly higher inside previously described CD8 + T-cell epitopes than outside—particularly in NS3/4A and NS5B. We identified new regions that are under selection pressure, indicating that not all CD8 + T-cell epitopes have been identified; 6 new epitopes that interact with CD8 + T cells were identified and confirmed in vitro. In some CD8 + T-cell epitopes mutations were reproducibly identified in patients that shared the relevant HLA allele, indicating immune pressure at the population level. There was statistical support for selection of mutations in 18 individual epitopes. Interestingly, 14 of these were restricted by HLA-B allele. Conclusions HLA class I−associated selection pressure on the nonstructural proteins and here predominantly on NS3/4A and NS5B promotes evolution of HCV. HLA-B alleles have a dominant effect in this selection process. Adaptation of HCV to the CD8 + T-cell response at the population level creates challenges for vaccine design.

Drug dependence of anaesthetists occurs more often than in other physicians, especially the noxious usage of common substances in anaesthesiology and pain management like opioids and anaesthetics. Opioids are the most frequent abusively taken medication followed by benzodiazepines, illegal drugs, Propofol and Ketamine. Determining for the behavioral pattern is the easy access to the drugs. Especially as some of the addictive-drugs (e. g. Propofol, Ketamine) are not underlying any release-control. Recent German surveys confirm the American figures. For the development of drug dependence many factors like biographic, social and genetic aspects as well as the substances and their potential itself are significant. Furthermore, the presence of many stimuli encourages the relapse-risk for addicted people despite earlier abstinence. At least 16% of all cases and 37% of the Propofol-addiction cases proceed deadly. American studies with structured therapy-, rehabilitation- and follow-up surveillance-programs show a positive prognosis for anaesthetists. In Germany it requires rethinking and the establishment of comparable therapy-offers and facilities.

Background To assess comorbid DSM-IV-TR Axis I disorders in adolescent inpatients referred for treatment of substance use disorders. Methods 151 patients (mean age 16.95 years, SD = 1.76; range 13 - 22) were consecutively assessed with the Composite International Diagnostic Interview (CIDI) and standardized clinical questionnaires to assess mental disorders, symptom distress, psychosocial variables and detailed aspects of drug use. A consecutively referred subgroup of these 151 patients consisting of 65 underage patients (mean age 16.12, SD = 1.10; range 13 - 17) was additionally assessed with the modules for attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) using The Schedule for Affective Disorders and Schizophrenia for school-aged children (K-SADS-PL). Results 128 (84.8%) of the 151 patients were dependent on at least one substance, the remaining patients fulfilled diagnostic criteria for abuse only. 40.5% of the participants fulfilled criteria for at least one comorbid present Axis I disorder other than substance use disorders (67.7% in the subgroup additionally interviewed with the K-SADS-PL). High prevalences of present mood disorder (19.2%), somatoform disorders (9.3%), and anxiety disorders (22.5%) were found. The 37 female participants showed a significantly higher risk for lifetime comorbid disorders; the gender difference was significantly pronounced for anxiety and somatoform disorders. Data from the underage subgroup revealed a high prevalence for present CD (41.5%). 33% of the 106 patients (total group) who were within the mandatory school age had not attended school for at least a two-month period prior to admission. In addition, 51.4% had been temporarily expelled from school at least once. Conclusions The present data validates previous findings of high psychiatric comorbidity in adolescent patients with substance use disorders. The high rates of school refusal and conduct disorder indicate the severity of psychosocial impairment.

Background: Monocentric studies of inpatient opiate detoxification treatment show considerable variability regarding treatment success rates. This multicentric study investigates whether patient characteristics explain the different rates of regular discharge between treatment units. Methods: 1,017 opiate-dependent patients from 12 detoxification units with similar treatment programs, funding, staffing and equipment were analyzed. Patient data and outcomes were documented by treatment staff using a standard form. Results: Controlling for center, regular discharge (range: 14–49% between centers) was significantly associated with pre-existing plans for follow-up treatment, previous completed long-term residential and detoxification treatments, fewer unsuccessful detoxification treatments, higher age, later onset of opiate use, and longer duration of use. Controlling for patient characteristics, the center variable was significantly associated with outcome in a multiple logistic regression analysis. Conclusions: Regular discharge could best be predicted by patients’ plans for follow-up treatment and previous treatment outcomes. Although treatment units had equivalent resources and regulations, and although patient effects were statistically controlled for, there were still considerable center effects. Setting factors as well as actual drop-out processes should be investigated more closely in the future.

Unhindered sexuality plays an important role in the quality of life and this also holds true for patients with psychiatric illnesses. Knowledge concerning the complex neuronal and endocrine control mechanisms of sexual function reveals areas of possible dysfunction caused by the interactions between the control system, psychiatric drugs and addictive psychoactive substances. The differentiation of the cause of the dysfunction between being caused by the underlying illness and caused by other factors is difficult in practice. Both classical tri-cyclic antidepressants and selective serotonin uptake inhibitors can frequently cause adverse effects in multiple dimensions of sexual function. This same is true for neuroleptics, whereby the differentiation between symptoms of schizophrenia and side-effects from the medication can make an evaluation difficult. The medication-based strategy used to treat opiate dependency by administration of methadone causes sexual dysfunction in many cases. The consideration of medication-induced sexual dysfunction has a great importance with regard to compliance. Possible solutions can be modification of the medication regime, additional medication, e.g. partial antagonists and PD5 inhibitors, as well as dysfunction-specific psychotherapy and psychoeducation.

The aim of this study was to detect electrocardiographic abnormalities during recovery from ultra-short opiate detoxification, using a retrospective study design conducted at a university hospital. Twenty-two consecutive patients (mean±SD, age 30.0±6.3 years) receiving daily oral methadone underwent ultrashort opiate detoxification under general anaesthesia. In the post-anaesthetic stages they received oral clonidine and naltrexone, and in some cases trimipramine was dispensed. Heart rate, rate-corrected QT interval (msec) and repolarization abnormalities of 12-lead electrocardiographic recordings before and after detoxification were examined. The serum electrolyte concentrations (mmol/l) including Na⁺, K⁺ and Ca2⁺ were assessed. Eighty-one ECGs were evaluated in total. Compared to the initial values, heart rate was significantly lowered in the first two tracings after detoxification (median values 60.0/min. vs. 52,5/min; p=0.0006). The lowest heart rate measured after detoxification was 44/min. The cQT interval was significantly lengthened (median value 420 msec vs. 453 msec after detoxification). In 16 tracings (20%) taken from 10 patients (45%) cQT rose above 460 msec and in two tracings (2%) it topped 500 msec. Modest hypokalaemia (2.9-3.5 mmol/l) was linked to cQT prolongation (460 msec) in 10 ECG tracings. Spearman's correlation coefficient indicated that prolonged cQT intervals correlated with decreased potassium values. Twelve tracings (15%) taken from 10 patients (45%) after detoxification showed T-wave inversion and in two cases sinus rhythm was turned into a rhythm arising from the atrioventricular node. Serum potassium was significantly lowered (median values 4.3 v.s 3.8 mmol/l, p=0.0001). The Ca2⁺ concentration fell significantly (2.4 vs. 2.2 mmol/l, p=0.0001) but not below the normal range. It was concluded that ultra-short opiate detoxification carries the risk of QT prolongation and bradycardia. These side effects are reversible and can be explained by hypokalaemia and clonidine medication, the effects of which might reinforce each other. To avoid arrhythmic complications, ECG tracings should be carried out regularly during recovery, i.e. at least daily, for a span of 3 days after discharge from the intensive care unit.

Background Methadone is administered as a chiral mixture of (R,S)- methadone. The opioid effect is mainly mediated by (R) -methadone, whereas (S) -methadone blocks the human ether-a-go-go–related gene (hERG) voltage-gated potassium channel more potently, which can cause drug-induced long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias. Methods To investigate whether substitution of (R,S) -methadone by (R) -methadone could reduce the corrected QT (QTc) interval, (R,S) -methadone was replaced by (R) -methadone (half-dose) in 39 opioid-dependent patients receiving maintenance treatment for 14 days. (R) -methadone was then replaced by the initial dose of (R,S) -methadone for 14 days (n = 29). Trough (R) -methadone and (S) -methadone plasma levels and electrocardiogram measurements were taken. Results The Fridericia-corrected QT (QTcF) interval decreased when (R,S) -methadone was replaced by a half-dose of (R) -methadone; the median (interquartile range [IQR]) values were 423 (398-440) milliseconds (ms) and 412 (395-431) ms ( P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of −3.9 ms (95% confidence interval [CI], −7.7 to −0.2) per week ( P = .04). The QTcF value increased when (R) -methadone was replaced by the initial dose of (R,S) -methadone for 14 days; median (IQR) values were 424 (398-436) ms and 424 (412-443) ms ( P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3-8.1) per week ( P = .006). Conclusions Substitution of (R,S) -methadone by (R)- methadone reduces the QTc interval value. A safer cardiac profile of (R) -methadone is in agreement with previous in vitro and pharmacogenetic studies. If the present results are confirmed by larger studies, (R)- methadone should be prescribed instead of (R,S) -methadone to reduce the risk of cardiac toxic effects and sudden death.

Despite a high prevalence of schizophrenia patients with comorbid substance abuse, little is known about possible impacts on the brain. Hence, our goal was to determine whether addicted and non-addicted schizophrenic patients suffer from different brain deficits. We were especially interested to determine if grey matter volumes were affected by impulsivity. We hypothesized that (comorbid) substance abuse would be associated with enhanced impulsivity and that this enhanced impulsivity would be related to grey matter volume deficits in prefrontal areas. We employed a voxel-based morphometry approach as well as neuropsychological assessment of executive functions and trait impulsivity in 51 participants (age range 23-55). The schizophrenia group comprised 24 patients (12 patients with paranoid schizophrenia and 12 with additional comorbid substance use disorders). The comparison group comprised 27 non-schizophrenic individuals, matched by age and education (14 healthy individuals and 13 patients with substance use disorders). Total grey matter volume deficits were found in all patient groups as compared with healthy controls but were largest (~8%) in both addicted groups. While grey matter volume losses in lateral orbitofrontal and temporal regions were affected by schizophrenia, volume decreases of the medial orbitofrontal, anterior cingulate and frontopolar cortex were associated with addiction. Compared with non-addicted schizophrenics, comorbid patients showed significant volume decreases in anterior cingulate, frontopolar and superior parietal regions. Additionally, they showed an increased non-planning impulsivity that was negatively related to grey matter volumes in the same regions, except for parietal ones. The present study indicates severe grey matter volume and functional executive deficits in schizophrenia, which were only partially exacerbated by comorbid addiction. However, the relationship between non-planning impulsivity and anterior cingulate and frontopolar grey matter volumes points to a specific structure-function relationship that seems to be impaired in schizophrenia-addiction comorbidity.

Aims: Anticonvulsants are increasingly being advocated for the treatment of acute alcohol withdrawal syndrome (AWS) to avoid the addictive properties of established medications. Because earlier works showed that moderate gabapentin doses were too low to clearly ameliorate severe AWS, we tested a higher gabapentin entry dose. Methods: Inpatients ( n = 37) with severe alcohol withdrawal symptoms (Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-AR) score ≥15 points) were given gabapentin 800 mg, and if their symptom score reduced within 2 h, they were termed ‘early responders’ and were then treated for 2 days with 600 mg gabapentin q.i.d. (i.e. a total of 3200 mg in the first 24 h) before beginning a taper. Results: Twenty-seven (73%) were early responders (baseline CIWA-AR improved from 17.3 ± 2.6 to 8.0 ± 3.6 points). In the remaining 10 patients, baseline CIWA-AR deteriorated within 2 h (from 20.1 ± 4.6 to 21.5 ± 4.65 points). These patients were switched to clomethiazole ( n = 4) or clonazepam ( n = 6), which is the usual treatment. Three of the ‘early responders’ worsened in the next 36 h and were then reclassified and treated as ‘non-responders’. Among them, two developed an epileptic seizure. Conclusion: Oral 800 mg gabapentin (loaded up to 3200 mg in the first 24 h) is helpful only in reducing less severe and less complicated acute AWS.

BackgroundImmigration is a factor with effects on the course of substance abuse and treatment response, however there is little consistent data regarding outcome of inpatient opiate detoxification treatment in immigrants as compared to native patients.MethodsPatient history and the success of current detoxification treatment were systematically documented in a multicenter study in Germany which included 10 psychiatric hospitals with specialized detoxification wards.ResultsOut of 893 patients, 240 (27%) had a migration history. We further analyzed the three main groups (German, n = 653; Turkish, n = 58; Russian origin, n = 103). There were significant differences between groups regarding sociodemographic data, drug history, treatment experience and success of current treatment. However, considering the younger age of patients with Russian origin, analysis of younger patients (< 31 years) detected only minor group differences. In multiple logistic regressions age and center showed statistically significant associations with all outcome variables (early dropout, achievement of drug-free urine screen, regular completion of detoxification treatment, and referral to further treatment), while (Russian) origin was associated only with premature termination of treatment.ConclusionYoung men were the main problem group regardless of origin. Significant center effects raise doubts regarding results from monocenter research.

We present the course of a mania most likely induced by cannabis in a young cannabis-dependent patient, but apart from this, healthy male adult. Mania developed in parallel to increasing cannabis inhalation and remitted quickly and completely within one week of abstinence without any antimanic medication in a protective inpatient setting. Simultaneously, the THC-COOH level decreased in serum and urine.

We aimed at investigating whether attendance of a drug consumption facility (DCF) was associated with both a reduction of drug-associated at-risk behavior and referral to the health care treatment system.A sample of 129 consecutive clients out of those 256 who self-referred to the DCF during the 13-month observation period (i.e., from November 2002 to December 2003) was interviewed both at baseline and at 1-, 2-, 3-, and 6-month follow-ups. Subjects were repeatedly assessed using a structured approach based on both the European Addiction Severity Index (EuropASI) and the Deutsche Gesellschaft fuer Suchtforschung und Therapie (DG-Sucht).Typical DCF clients were males, in their early 30s, single, with no vocational training, and with a long history of injectable opiate addiction in the context of polydrug misuse. A recent discharge from prison was recorded in 37% of cases. Median length of DCF attendance was of 5 weeks; 22% of clients attended for less than 1 week. Although with respect to the period previous to recruitment at-risk behavior rates remained unchanged, by the 3-month follow-up 13 (10%) clients out of those 129 who had initially enrolled had taken advantage of the DCF counseling opportunities. Some 37% of clients were referred on to start a methadone treatment following their DCF experience.DCF attendance was not associated with reduction in at-risk behavior over time, but a need was here identified for additional intervention to be available in the DCF to address clients' psychosocial issues. Limitations of the present study include both issues related to the representativeness of the sample of clients here recruited and the lack of a control/comparison group.

According to the so-called telescoping effect, there is a gender-specific course of alcohol dependence with women starting alcohol use later than men and having a faster development of harmful consequences. There are inconsistent data regarding a telescoping effect in opiate dependence. In each of six European centres, 100 opiate addicts were investigated by a structured interview (mainly the EuropASI and CIDI) at admission to various kinds of treatment (TREAT project). In a secondary analysis of the TREAT data, women and men were compared regarding age at onset of heroin use and the current severity of addiction. In addition, a comparison of female (n = 140) and male (n = 140) addicts matched for age and study centre were carried out. Eventually, multiple logistic and linear regressions were done with the interaction term of gender and time of regular consumption as predictor for the severity of dependence, besides, other sociodemographic variables. There was no difference between genders regarding the age at onset of regular heroin consumption. Up to 4 years of regular consumption, there are gender-specific differences in the course of opiate dependence, e.g. a faster progression of legal problems in men and social problems in women. There were no differences in the severity of dependence other than more economic problems for women. A telescoping effect could only partially be observed in this large sample of opiate addicts. A gender-specific course was limited to the first years of consumption, and included domains with a faster progression for men. It has to be assumed that opiate dependence is a rapidly developing disorder with early chronification. Afterwards, only individual courses with influences of the national treatment system were observed.

Unlike many psychiatrists around 1900, Eugen Bleuler had a friendly, even partly affirmative attitude towards psychoanalysis. In his famous book "Dementia Praecox or Group of Schizophrenias" (1911) he emphasized the influence of psychoanalysis on his theory about schizophrenia. In this article we describe Bleuler's fundamental thoughts on psychology and psychotherapy in order to look for a special disposition to accept psychoanalysis. Psychoanalysis seemed to him to be one of the most promising attempts to develop a systematic psychotherapy founded on a scientific psychology. In particular, Freud's hypothesis about the wish-fulfilling character of dreams influenced Bleuler's understanding of delusion and other symptoms of schizophrenia.

The intracellular pH (pHi) of neurones is tightly regulated by, for example, membrane-bound acid-exchangers and loaders. Nevertheless, excessive bioelectric activity lowers steady-state pHi. In turn, even a moderate acidification can inhibit neuronal activity, a process believed to be part of a negative feedback loop controlling neuronal excitation. As moclobemide, an antidepressant, and also some antiepileptic drugs can reduce neuronal pHi in hippocampus slices in vitro, we screened a panel of currently used neuropsychopharmaca for comparable effects.BCECF-AM loaded hippocampal slices were superfused with 16 different neuroleptics, antidepressants and antiepileptics under bicarbonate-buffered conditions. Changes in steady-state pHi of CA3 neurones were measured fluorometrically.The antipsychotics haloperidol, clozapine, ziprasidone, and the antidepressants amitriptyline, doxepin, trimipramine, citalopram, mirtazapine, as well as the anticonvulsive drug tiagabine reversibly reduced the steady-state pHi by up to 0.35 pH-units in concentrations of 5-50 microM. In contrast, venlafaxine, the anticonvulsants carbamazepine, clonazepam, gabapentin, lamotrigine, zonisamide, and the mood stabilizer lithium had no effect on neuronal pHi.These data substantiate the view that clinically relevant concentrations of neuroleptics and antidepressants can mediate changes in neuronal pHi, which may contribute to their pharmacological mode of action. Effects on pHi should be taken into account when therapeutic or even harmful effects of these drugs are evaluated.