Polygenetic risk scores and phenotypic constellations of obsessive-compulsive disorder in clozapine-treated schizophrenia.

Obsessive-compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clozapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive-compulsive disorder (OCD) in this subgroup and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores (PRS) in individuals with SCZ and OCS. A multicenter cohort of 91 individuals with SCZ who were treated with CLZ was recruited and clinically and genetically assessed. Symptom severity was examined using the Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI), the Calgary Depression Scale for Schizophrenia (CDSS), Global Assessment of Functioning Scale (GAF) and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Participants were divided into subgroups based on phenotypic OCS or OCD using Y-BOCS scores. Genomic-wide data were generated, and PRS analyses were performed to evaluate the association between either phenotypic OCD or OCS severity and genotype-predicted predisposition for OCD, SCZ, cross-disorder, and CLZ/norclozapine (NorCLZ) ratio, CLZ metabolism and NorCLZ metabolism. OCS and OCD were frequent comorbidities in our sample of CLZ-treated SCZ individuals, with a prevalence of 39.6% and 27.5%, respectively. Furthermore, the Y-BOCS total score correlated positively with the duration of CLZ treatment in years (r = 0.28; p = 0.008) and the PANSS general psychopathology subscale score (r = 0.23; p = 0.028). A significant correlation was found between OCD occurrence and PRS for CLZ metabolism. We found no correlation between OCS severity and PRS for CLZ metabolism. We found no correlation for either OCD or OCS and PRS for OCD, cross-disorder, SCZ, CLZ/NorCLZ ratio or NorCLZ metabolism. Our study was able to replicate previous findings on clinical characteristics of CLZ-treated SCZ individuals. OCS is a frequent comorbidity in this cohort and is correlated with CLZ treatment duration in years and PANSS general psychopathology subscale score. We found a correlation between OCD and PRS for CLZ metabolism, which should be interpreted as incidental for now. Future research is necessary to replicate significant findings and to assess possible genetic predisposition of CLZ-treated individuals with SCZ to OCS/OCD. Limitations attributed to the small sample size or the inclusion of subjects on co-medication must be considered. If the association between OCD and PRS for CLZ metabolism can be replicated, it should be further evaluated if CYP1A2 alteration, respectively lower CLZ plasma level, is relevant for OCD development.

Police-referred psychiatric emergency presentations during the first and second wave of COVID-19 in Berlin, Germany: a retrospective chart review.

BACKGROUND: Literature on psychiatric emergency services (PES) presentations during the COVID-19 pandemic showed heterogeneous results regarding patients brought in by police (BIBP). This is the first study primarily focusing on patients BIBP in a PES during the COVID-19-period. METHODS: Case documentation records during the first and second wave of the COVID-19 pandemic in a PES in Berlin, Germany were analyzed using descriptive data analysis and binomial logistic regression analysis to detect factors that predict presentations BIBP. RESULTS: 5440 PES presentations: 20.4% BIBP during the first wave vs. 16.3% during its control period; second wave: 17.6% BIBP vs. 14.9% during its control period. In both waves, absolute increases in presentations BIBP were seen compared to control (p = .029, p = .028, respectively). COVID-19-period was a predictor for presentations BIBP during the first and the second wave. The following factors also predicted presentations BIBP: younger age, male gender, aggressive behavior, suicide attempt prior to presentation and diagnosis of psychotic or substance use disorders; depressive disorders were negatively associated. CONCLUSIONS: During the two first waves of the COVID-19 pandemic, there was an increase in presentations BIBP in a PES in Berlin. Regression analysis shows that the pandemic itself was a predictor of presentations BIBP. The underlying factors of this association need to be further elucidated in future research. Additionally, general factors predicting PES presentations BIBP are reported that replenish the present literature.

Does compulsion explain addiction?

One of the leading drug addiction theories states that habits and the underlying neural process of a ventral to dorsal striatal shift are the building blocks of compulsive drug-seeking behaviour and that compulsion is the maladaptive persistence of responding despite adverse consequences. Here we discuss that compulsive behaviour as defined primarily from the perspective of animal experimentation falls short of the clinical phenomena and their neurobiological correlates. Thus for the human condition, the concept of compulsive habbits should be critically addressed and potentially revised.

[Challenges in the treatment of opioid dependence]. / Aktuelle Herausforderungen in der Behandlung der Opioidabhängigkeit.

BACKGROUND: The number of persons using opioids has increased worldwide in the last decade, particularly the use of opioid analgesics in North America and Africa. In Germany, the prevalence of heroin addiction has remained relatively stable. METHOD: Narrative review of the literature. RESULTS: Opioid-assisted maintenance treatment (OMT) with the established substances methadone, levomethadone, slow-release morphine and buprenorphine is recommended as the first-line treatment for heroin dependence. The OMT reduces the use of heroin, mortality and individual suffering and improves the quality of life and physical health. A diamorphine and heroine-assisted treatment is an option for people who do not benefit from conventional OMT. An alternative to the use of diamorphine could be treatment with hydromorphone hydrochloride. The regulations on carrying out maintenance treatment in the Controlled Substances Prescription Act and the guidelines of the Federal Medical Association in Germany have been loosened based on the experiences of the COVID-19 pandemic, for example with respect to take-home prescriptions. There is an ongoing intensive discussion on how to deal with the decreasing number of outpatient clinics offering OMT. CONCLUSION: The first-line treatment for opioid addiction is opioid-assisted substitution treatment, including diamorphine and heroin-assisted treatment. Long-acting depot medications and implants still play a subordinate role.

Suicidality in psychiatric emergency department situations during the first and the second wave of COVID-19 pandemic.

Psychiatric patients are prone to mental health deterioration during the Covid-19 pandemic. Little is known about suicidality in psychiatric patients during the Covid-19 pandemic. This study is a retrospective chart review of psychiatric emergency department (pED) presentations with present or absent suicidality (5634 pED attendances, 4110 patients) in an academic pED in Berlin, Germany. Poisson regression analysis was performed on the effect of Covid-19 period on suicidality (suicidal ideation (SI), suicide plans (SP) or suicide attempt (SA)) during the first (3/2/2020-5/24/2020 "first-wave") and second (9/15/2020-3/1/2021 "second-wave") wave of the Covid-19 pandemic compared to the same periods one year earlier. During the first-wave the number of pED visits per person with SI, SP and SA was higher compared to one year earlier (SI RR = 1.614; p = 0.016; SP RR = 2.900; p = 0.004; SA RR = 9.862; p = 0.003). SI and SP were predicted by interaction between substance use disorder (SUD) and second-wave (SI RR = 1.305, p = 0.043; SP RR = 1.645, p = 0.018), SA was predicted by interaction between borderline personality disorder (BPD) and second-wave (RR = 7.128; p = 0.012). Suicidality increased during the first-wave of Covid-19 pandemic in our sample. In the second-wave this was found in patients with SUD and BPD. These patients may be at particular risk of suicidality during the Covid-19 pandemic.

The Prevalence of Problem Gambling and Gambling Disorder Among Homeless People: A Systematic Review And Meta-Analysis.

Gambling problems are often associated with homelessness and linked to elevated psychiatric morbidity and homelessness chronicity. We performed a systematic review and meta-analysis on prevalence rates of problem gambling (PG) and gambling disorder (GD) in homeless people. Following PRISMA guidelines, we searched databases Medline, Embase and PsycINFO from inception of databases to 4th may 2021. We included studies reporting prevalence estimates on clinical gambling problems in representative samples of homeless people based on standardized diagnostics. Risk of bias was assessed. A random effects meta-analysis was performed, and subgroup analyses based on methodological characteristics of primary studies were conducted. We identified eight studies from five countries, reporting information on 1938 participants. Prevalence rates of clinically significant PG and GD ranged from 11.3 to 31.3%. There was evidence for substantial heterogeneity with I2 = 86% (95% CI 63-97%). A subgroup of four low risk of bias studies displayed a significantly lower results ranging from 11.3 to 23.6%. Additionally, high rates of subclinical problem gambling were reported (11.6-56.4%). At least one in ten homeless persons experiences clinically significant PG or GD. Social support and health care services for the homeless should address this problem by implementing models for early detection and treatment.

Offspring's risk for suicidal behaviour in relation to parental death by suicide: systematic review and meta-analysis and a model for familial transmission of suicide.

BACKGROUND: Exposure to parental suicide has been associated with increased risk for suicide and suicide attempts, although the strength of this association is unclear as evidence remains inconsistent. AIMS: To quantify this risk using meta-analysis and identify potential effect modifiers. METHOD: A systematic search in PubMed, PsycInfo and Embase databases to 2020 netted 3614 articles. Inclusion criteria were: observation of history of parental death by suicide, comparison with non-exposed populations and definition of suicide and suicide attempt according to standardised criteria. We focused on population-based studies. The primary outcome was the pooled relative risk (RR) for incidence of suicide attempt and suicide in offspring of a parent who died by suicide compared with offspring of two living parents. Additionally, we compared the RR for attempted and completed suicide after parental suicide with the RR for attempted and completed suicide after parental death by other causes. RESULTS: Twenty studies met our inclusion criteria. Offspring exposed to parental suicide were more likely to die by suicide (RR = 2.97, 95% CI 2.50-3.53) and attempt suicide (RR = 1.76, 95% CI 1.58-1.96) than offspring of two living parents. Furthermore, their risk of dying by or attempting suicide was significantly higher compared with offspring bereaved by other causes of death. CONCLUSIONS: The experience of losing a parent to suicide is a strong and independent risk factor for suicidal behaviour in offspring. Our findings highlight the need for prevention strategies, outreach programmes and support interventions that target suicide-related outcomes in the exposed population.

Accumbens D2-MSN hyperactivity drives antipsychotic-induced behavioral supersensitivity.

Antipsychotic-induced dopamine supersensitivity, or behavioral supersensitivity, is a problematic consequence of long-term antipsychotic treatment characterized by the emergence of motor abnormalities, refractory symptoms, and rebound psychosis. The underlying mechanisms are unclear and no approaches exist to prevent or reverse these unwanted effects of antipsychotic treatment. Here we demonstrate that behavioral supersensitivity stems from long-lasting pre, post and perisynaptic plasticity, including insertion of Ca2+-permeable AMPA receptors and loss of D2 receptor-dependent inhibitory postsynaptic currents (IPSCs) in D2 receptor-expressing medium spiny neurons (D2-MSNs) in the nucleus accumbens core (NAcore). The resulting hyperexcitability, prominent in a subpopulation of D2-MSNs (21%), caused locomotor sensitization to cocaine and was associated with behavioral endophenotypes of antipsychotic treatment resistance and substance use disorder, including disrupted extinction learning and augmented cue-induced cocaine-seeking behavior. Chemogenetic restoration of IPSCs in D2-MSNs in the NAcore was sufficient to prevent antipsychotic-induced supersensitivity, pointing to an entirely novel therapeutic direction for overcoming this condition.

Multisensory Processing Can Compensate for Top-Down Attention Deficits in Schizophrenia.

Studies on schizophrenia (SCZ) and aberrant multisensory integration (MSI) show conflicting results, which are potentially confounded by attention deficits in SCZ. To test this, we examined the interplay between MSI and intersensory attention (IA) in healthy controls (HCs) (N = 27) and in SCZ (N = 27). Evoked brain potentials to unisensory-visual (V), unisensory-tactile (T), or spatiotemporally aligned bisensory VT stimuli were measured with high-density electroencephalography, while participants attended blockwise to either visual or tactile inputs. Behaviorally, IA effects in SCZ, relative to HC, were diminished for unisensory stimuli, but not for bisensory stimuli. At the neural level, we observed reduced IA effects for bisensory stimuli over mediofrontal scalp regions (230-320 ms) in SCZ. The analysis of MSI, using the additive approach, revealed multiple phases of integration over occipital and frontal scalp regions (240-364 ms), which did not differ between HC and SCZ. Furthermore, IA and MSI effects were both positively related to the behavioral performance in SCZ, indicating that IA and MSI mutually facilitate bisensory stimulus processing. Multisensory processing could facilitate stimulus processing and compensate for top-down attention deficits in SCZ. Differences in attentional demands, which may be differentially compensated by multisensory processing, could account for previous conflicting findings on MSI in SCZ.

[ICD-11: changes in the diagnostic criteria of substance dependence]. / ICD-11: Änderungen der diagnostischen Kriterien der Substanzabhängigkeit.

BACKGROUND: In ICD(International Classification of Diseases)-11 the criteria for the diagnosis of substance dependence have been revised. OBJECTIVE: Discussion of the advantages and disadvantages of the revised diagnostic criteria. MATERIAL AND METHODS: Discussion of criteria with respect to neurobiological, social and clinical research. RESULTS: In the new ICD-11, harmful drug use and substance dependence remain separate diagnostic categories. Regarding substance dependence, the former six diagnostic criteria are condensed into three pairs, two of which must be fulfilled to diagnose this disorder. Within the pairs, one affirmed symptom or aspect is sufficient for the new criterion to be fulfilled. With reference to scientific findings in the field of addiction, this appears to provide advantages as well as disadvantages. The specificity of the diagnosis of substance dependence might get worse compared to ICD-10, because only one symptom of the syndrome pairs has to be fulfilled in each newly constructed pair in order to fulfill the criterion. Therefore, the risk of false positive diagnosis of substance dependence could increase. This is a potential reason for concern because the definition of ICD-10 "persisting substance use despite clear evidence of overtly harmful consequences", is more broadly reworded in ICD-11 as "substance use often continues despite the occurrence of problems". This criterion may hence simply be fulfilled because a substance is illegal in a certain country. In the largest multinational study in 10 countries concerning concordance of diagnostic systems, alcohol dependence was diagnosed approximately 10% more often using ICD-11 compared to ICD-10. CONCLUSION: In ICD-11 the well-established distinction between substance dependence and harmful drug use is preserved. Systematic studies are required to assess whether the new diagnostic criteria are clinically helpful or increase social problems by increasing false positive diagnoses of addiction.

[Associations of mental illness and homelessness: results of a secondary data analysis at a Berlin health center for the homeless]. / Zusammenhänge zwischen psychischen Erkrankungen und Wohnungslosigkeit: Ergebnisse einer Sekundärdatenanalyse in einem Berliner Gesundheitszentrum für Obdachlose.

BACKGROUND: Homelessness is an expression and consequence of a complex problem situation that poses major challenges to the medical and social care systems in Germany. About three quarters of homeless people suffer from mental illness. The aim of this study was to investigate associations between mental illness and homelessness. MATERIAL AND METHODS: A secondary data analysis of patients' records from a Berlin health center for homeless people was conducted. Data from 112 homeless patients who received care at the center between the years 2006 and 2020 were included in the explorative study. RESULTS: Mental illness was present in 84.9% of patients before the onset of homelessness. The factors associated with an early onset of homelessness were low school education and drug abuse. A long duration of homelessness was associated with the factors alcohol abuse as well as imprisonment. Each new episode of street homelessness was associated with an average increase in the duration of homelessness by 7.9 months. DISCUSSION: Since mental illnesses are important factors influencing the development and maintenance of homelessness, preventive strategies as well as specialized services for this vulnerable group need to be increasingly created. In particular, recurring episodes of street homelessness should be prevented as far as possible. The link between imprisonment and homelessness suggests that more intensive support is needed for reintegration after release from prison.

The prevalence of mental disorders among homeless people in high-income countries: An updated systematic review and meta-regression analysis.

BACKGROUND: Homelessness continues to be a pressing public health concern in many countries, and mental disorders in homeless persons contribute to their high rates of morbidity and mortality. Many primary studies have estimated prevalence rates for mental disorders in homeless individuals. We conducted a systematic review and meta-analysis of studies on the prevalence of any mental disorder and major psychiatric diagnoses in clearly defined homeless populations in any high-income country. METHODS AND FINDINGS: We systematically searched for observational studies that estimated prevalence rates of mental disorders in samples of homeless individuals, using Medline, Embase, PsycInfo, and Google Scholar. We updated a previous systematic review and meta-analysis conducted in 2007, and searched until 1 April 2021. Studies were included if they sampled exclusively homeless persons, diagnosed mental disorders by standardized criteria using validated methods, provided point or up to 12-month prevalence rates, and were conducted in high-income countries. We identified 39 publications with a total of 8,049 participants. Study quality was assessed using the JBI critical appraisal tool for prevalence studies and a risk of bias tool. Random effects meta-analyses of prevalence rates were conducted, and heterogeneity was assessed by meta-regression analyses. The mean prevalence of any current mental disorder was estimated at 76.2% (95% CI 64.0% to 86.6%). The most common diagnostic categories were alcohol use disorders, at 36.7% (95% CI 27.7% to 46.2%), and drug use disorders, at 21.7% (95% CI 13.1% to 31.7%), followed by schizophrenia spectrum disorders (12.4% [95% CI 9.5% to 15.7%]) and major depression (12.6% [95% CI 8.0% to 18.2%]). We found substantial heterogeneity in prevalence rates between studies, which was partially explained by sampling method, study location, and the sex distribution of participants. Limitations included lack of information on certain subpopulations (e.g., women and immigrants) and unmet healthcare needs. CONCLUSIONS: Public health and policy interventions to improve the health of homeless persons should consider the pattern and extent of psychiatric morbidity. Our findings suggest that the burden of psychiatric morbidity in homeless persons is substantial, and should lead to regular reviews of how healthcare services assess, treat, and follow up homeless people. The high burden of substance use disorders and schizophrenia spectrum disorders need particular attention in service development. This systematic review and meta-analysis has been registered with PROSPERO (CRD42018085216). TRIAL REGISTRATION: PROSPERO CRD42018085216.

Drug Checking and Its Potential Impact on Substance Use.

OBJECTIVES: Drug checking as a tool for harm reduction is offered in certain cities throughout Europe, the USA, and Australia, but in general, it is internationally still scarcely available and controversially discussed. This study aimed at investigating the potential impact of a drug-checking offer on Berlin nightlife attendees' illicit drug use and at identifying the encouraging and discouraging factors for using or refraining from such an offer. METHODS: Using an online questionnaire, we conducted a cross-sectional survey in a Berlin party scene. A total of 719 people participated in the survey that took part in 2019. RESULTS: The vast majority of participants (92%) stated that they would use drug checking, if existent. If the test revealed the sample to contain a high amount of active ingredient, 91% indicated to take less of the substance than usual. Two-thirds (66%) would discharge the sample if it contained an unexpected/unwanted agent along with the intended substance. If the sample contained only unexpected/unwanted substances and not the intended substance at all, 93% stated to discharge the sample. Additional brief counseling was stated to be useful. Participants showed a comparatively high substance use. CONCLUSIONS: Drug checking as a harm reduction tool was highly accepted in the scene, and the majority of participants stated to align their consumption behavior accordingly, in a reasonable manner. A concomitant consultation would be appreciated, which may be used to direct educational information about harms and risks to users.

[Debts, loans and unpaid bills among day patients and inpatients in psychiatric care in Berlin, Germany]. / Schulden, Kredite und unbezahlte Rechnungen unter Nutzer*Innen teilstationärer und stationärer psychiatrischer Behandlung in Berlin.

BACKGROUND: Previous studies among the general population indicated an association between mental illnesses and different forms of financial difficulties, such as indebtedness. OBJECTIVE: Investigation of the financial burden and associated factors among inpatients and day clinic patients in psychiatric care. MATERIAL AND METHODS: A total of 488 patients in psychiatric care in the catchment area of the Psychiatric University Hospital Charité at St. Hedwig Hospital participated in a cross-sectional patient survey carried out with a structured interview regarding financial burden, sociodemographic and clinical variables. RESULTS: Of the participants 269 (55.1%) showed outstanding debts, loans or unpaid bills. Among the participants who were willing to give information about the amount of debts, the majority (47.0%) had debts between 1000 € and 9999 € and 36.3% between 10,000 € and 99,999 €. In the binary regression models, younger age and substance use disorders were factors significantly associated with outstanding debts. Of the participants 22.3% had outstanding debts >10,000 € and were depending on social welfare, so that indebtedness could be assumed. CONCLUSION: Financial burdens and outstanding debts among patients in psychiatric care should be inquired about and considered more intensively in practice. Suitable models of support need to be developed and evaluated.

Attitudes towards psychopharmacology and psychotherapy in psychiatric patients with and without migration background.

BACKGROUND: Sociodemographic factors, attitude towards treatment and acculturation may be important factors influencing the decision of immigrants to seek and maintain psychiatric treatment. A better understanding of these factors may significantly improve treatment adherence and outcome in these patients. Therefore, we investigated factors associated the attitude towards psychotherapy and medication in a sample of psychiatric outpatients with and without migration background. METHODS: N = 381 patients in a psychiatric outpatient unit offering specialized treatment for migrants were included in this study. Attitude towards psychotherapy was assessed using the Questionnaire on Attitudes Toward Psychotherapeutic Treatment, attitude towards medication with the Drug Attitude Inventory-10. Acculturation, symptom load and sociodemographic variables were assessed in a general questionnaire. Statistical analyses included analyses of covariance and hierarchical regression. RESULTS: Patients of Turkish and Eastern European origin reported a significantly more positive attitude towards medication than patients without migration background. When controlling for sociodemographic and clinical variables, we did not observe any significant differences in attitude towards psychotherapy. Acculturation neither influenced the attitude towards psychotherapy nor towards medication. CONCLUSION: Our study indicates that sociodemographic and clinical factors may be more relevant for patients´ attitudes towards treatment than acculturation. Considering these factors in psychiatric treatment of patients with migration background may improve treatment outcome and adherence.

Effects of Smoking Status on Remission and Metabolic and Cognitive Outcomes in Schizophrenia Patients Treated with Clozapine.

BACKGROUND: Even though clozapine is the recommended last-resort antipsychotic, many patients fail to respond and show treatment-refractory psychotic symptoms. Smoking has been suggested as a possible risk factor for poor clozapine response, hampering remission and negatively impacting somatic outcomes. METHODS: Our aim was to test whether smoking status is associated with remission rates and other symptomatic and somatic outcomes. We therefore assessed remission rates according to The Remission in Schizophrenia Working Group (RSWG) criteria, and metabolic and cognitive outcomes among patients with schizophrenia-spectrum disorders treated with clozapine for at least 6 months. For analyses, we grouped our cohort into 3 groups according to clozapine treatment duration (6 months, 2 years, 5 years). RESULTS: One hundred five patients were included in our analyses and grouped according to their clozapine treatment duration. In the 6-months analyses, patients who smoked were significantly more likely to be younger of age (p=0.002) despite on average shorter duration of clozapine treatment (p=0.041) and significantly more likely to be treated with mood-stabilizing co-medication (p=0.030) compared to nonsmokers. Remission rates (p=0.490), as well as a set of metabolic and cognitive variables did not differ between the 2 groups. A related pattern could be observed for the 2- and 5-years analyses. CONCLUSIONS: Smoking behavior among clozapine-treated schizophrenia patients might delineate a cohort with an earlier onset of the disease. Nevertheless, most findings comparing disease-specific and clinical outcomes among smokers and nonsmokers were negative. Further research is needed to identify strategies to overcome insufficient remission rates in this patient group.

Drink and Think: Impact of Alcohol on Cognitive Functions and Dementia - Evidence of Dose-Related Effects.

Regular alcohol consumption affects cognitive performance and the development of dementia. So far, findings are contradicting, which might be explained in part by dose-related effects. For this narrative review, we undertook a literature search for surveys investigating the impact of alcohol consumption on cognitive performance and the development of dementia. The majority of studies observed a U-shaped relationship between regular alcohol consumption and cognitive function: frequent heavy consumption of alcohol alters brain functions and decreases cognitive performance; regular light and moderate consumption may have protective impact. In many studies, total abstainers show an inferior cognitive performance than people with moderate or light consumption. Nevertheless, policy implications are difficult to draw for at least 2 reasons: (1) the possible risks associated with alcohol consumption and (2) the potential confounders in the group of non-consumers and heavy consumers.

To drink or not to drink: Harmful drinking is associated with hyperactivation of reward areas rather than hypoactivation of control areas in men.

BACKGROUND: The maintenance of harmful alcohol use can be considered a reiterated decision in favour of alcohol in concrete drinking occasions. These decisions are often made despite an intention to quit or reduce alcohol consumption. We tested if a hyperactive reward system and/or an impaired cognitive control system contribute to such unfavourable decision-making. METHODS: In this fMRI study, men with modest to harmful drinking behaviour, which was measured using the Alcohol Use Disorders Identification Test (AUDIT), repeatedly made decisions between alcoholic and nonalcoholic drinks. Based on prior individual ratings, decision pairs were created with an alcoholic decision option considered more desirable but less beneficial by the participant. By correlating AUDIT scores with brain activation during decision-making, we determined areas explicitly related to pro-alcohol decisions in men with greater drinking severity. RESULTS: Thirty-eight men participated in our study. Behaviourally, we found a positive correlation between AUDIT scores and the number of decisions for desired alcoholic drinks compared with beneficial nonalcoholic drinks. The fMRI results show that AUDIT scores were positively associated with activation in areas associated with reward and motivation processing (i.e., ventral striatum, amygdala, medial prefrontal cortex) during decisions favouring a desired, nonbeneficial alcoholic drink. Conversely, we did not find hypoactivation in areas associated with self-control (dorsolateral prefrontal cortex). These effects were not present when participants chose a desired, nonbenefical, nonalcoholic drink. LIMITATIONS: The men participating in our study had to be abstinent and would potentially consume an alcoholic drink at the end of the experiment. Hence, we did not define manifest alcohol dependence as an inclusion criterion and instead focused on less severely affected individuals. CONCLUSION: Our results indicate that with growing drinking severity, decisions for alcoholic drinks are associated with increasing activity in reward-associated neural systems, rather than decreasing activity in self-control-associated systems.

Opioid tolerance in methadone maintenance treatment: comparison of methadone and levomethadone in long-term treatment.

BACKGROUND: This study aimed to investigate the development of opioid tolerance in patients receiving long-term methadone maintenance treatment (MMT). METHODS: A region-wide cross-sectional study was performed focusing on dosage and duration of treatment. Differences between racemic methadone and levomethadone were examined. All 20 psychiatric hospitals and all 110 outpatient clinics in Berlin licensed to offer MMT were approached in order to reach patients under MMT fulfilling the DSM IV criteria of opiate dependence. In the study, 720 patients treated with racemic methadone or levomethadone gave information on the dosage of treatment. Out of these, 679 patients indicated the duration of MMT. RESULTS: Treatment with racemic methadone was reported for 370 patients (54.5%), with levomethadone for 309 patients (45.5%). Mean duration of MMT was 7.5 years. We found a significant correlation between dosage and duration of treatment, both in a conjoint analysis for the two substances racemic methadone and levomethadone and for each substance separately. These effects remained significant when only patients receiving MMT for 1 year or longer were considered, indicating proceeding tolerance development in long-term treatment. When correlations were compared between racemic methadone and levomethadone, no significant difference was found. CONCLUSIONS: Our data show a tolerance development under long-term treatment with both racemic methadone and levomethadone. Tolerance development did not differ significantly between the two substances.

Neural activation during processing of aversive faces predicts treatment outcome in alcoholism.

Neuropsychological studies reported decoding deficits of emotional facial expressions in alcohol-dependent patients, and imaging studies revealed reduced prefrontal and limbic activation during emotional face processing. However, it remains unclear whether this reduced neural activation is mediated by alcohol-associated volume reductions and whether it interacts with treatment outcome. We combined analyses of neural activation during an aversive face-cue-comparison task and local gray matter volumes (GM) using Biological Parametric Mapping in 33 detoxified alcohol-dependent patients and 33 matched healthy controls. Alcoholics displayed reduced activation toward aversive faces-neutral shapes in bilateral fusiform gyrus [FG; Brodmann areas (BA) 18/19], right middle frontal gyrus (BA46/47), right inferior parietal gyrus (BA7) and left cerebellum compared with controls, which were explained by GM differences (except for cerebellum). Enhanced functional activation in patients versus controls was found in left rostral anterior cingulate cortex (ACC) and medial frontal gyrus (BA10/11), even after GM reduction control. Increased ACC activation correlated significantly with less (previous) lifetime alcohol intake [Lifetime Drinking History (LDH)], longer abstinence and less subsequent binge drinking in patients. High LDH appear to impair treatment outcome via its neurotoxicity on ACC integrity. Thus, high activation of the rostral ACC elicited by affective faces appears to be a resilience factor predicting better treatment outcome. Although no group differences were found, increased FG activation correlated with patients' higher LDH. Because high LDH correlated with worse task performance for facial stimuli in patients, elevated activation in the fusiform 'face' area may reflect inefficient compensatory activation. Therapeutic interventions (e.g. emotion evaluation training) may enable patients to cope with social stress and to decrease relapses after detoxification.