Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain.

Perivascular macrophages (pvMs) are associated with cerebral vasculature and mediate brain drainage and immune regulation. Here, using reporter mouse models, whole brain and section immunofluorescence, flow cytometry, and single cell RNA sequencing, besides the Lyve1+F4/80+CD206+CX3CR1+ pvMs, we identify a CX3CR1- pvM population that shares phagocytic functions and location. Furthermore, the brain parenchyma vasculature mostly hosts Lyve1+MHCII- pvMs with low to intermediate CD45 expression. Using the double Cx3cr1GFP x Cx3cr1-Cre;RosatdT reporter mice for finer mapping of the lineages, we establish that CD45lowCX3CR1- pvMs are derived from CX3CR1+ precursors and require PU.1 during their ontogeny. In parallel, results from the Cxcr4-CreErt2;Rosa26tdT lineage tracing model support a bone marrow-independent replenishment of all Lyve1+ pvMs in the adult mouse brain. Lastly, flow cytometry and 3D immunofluorescence analysis uncover increased percentage of pvMs following photothrombotic induced stroke. Our results thus show that the parenchymal pvM population is more heterogenous than previously described, and includes a CD45low and CX3CR1- pvM population.

Assessment of automated craving across substances and across cultures: stability-analysis of the Craving Automated Scale (CAS).

BACKGROUND: The transition from hedonic to compulsive use in Substance Use Disorders (SUD) is a critical point in SUD progression and hence relevant for assessment and treatment. To measure the habitual patterns of substance consumption, the Craving Automated Scales (CAS) for alcohol (CAS-A), substances (CAS-S) and cigarette smoking (CAS-CS) were developed and introduced to different countries. In this study, we aimed to investigate the structural stability of CAS across substances and cultures. METHODS: This study analyzed the CAS-scores of a sample of 370 participants in Germany, China and the UK, including 262 opioid-users, 65 smokers and 43 alcohol-users. We performed stability analyses to check the stability (i. e. factorial invariance) of factor solutions. Based on confirmed stability of the general factor (gfactor) solution and the calculations rule obtained in the previous validation of CAS-alcohol (CAS-A), the factor structures of CAS-A, CAS-S and CAS-CS were compared. RESULTS: The gfactor solutions based on calculations rule shows good stability, with the mean stability coefficients of 0.990 and 0.977 for CAS-S and CAS-CS respectively. The gfactor patterns were similar for CAS-A, CAS-S and CAS-CS, as well as across samples (Germany, China and the UK), with most factor-loadings larger than 0.7. Based on these findings, CAS-S and CAS-CS were also associated with established clinical measures of SUD. CONCLUSIONS: Our findings suggest the two-gfactor solution based on a proposed calculation rule has a high stability across substances and cultures. This could be in line with common neurobiological mechanisms underlying habitual substance use. Moreover, comparing CAS with established clinical tools suggests that CAS might assess the automated behavior in substance consumption in a more sophisticated way.

• The two-gfactor solution of the Craving Automated Scale has a good stability.• The Craving Automated Scale can be used across substances.• The Craving Automated Scale is associated with established SUD measures.

Ion thrusters for electric propulsion: Scientific issues developing a niche technology into a game changer.

The transition from old space to new space along with increasing commercialization has a major impact on space flight, in general, and on electric propulsion (EP) by ion thrusters, in particular. Ion thrusters are nowadays used as primary propulsion systems in space. This article describes how these changes related to new space affect various aspects that are important for the development of EP systems. Starting with a historical overview of the development of space flight and of the technology of EP systems, a number of important missions with EP and the underlying technologies are presented. The focus of our discussion is the technology of the radio frequency ion thruster as a prominent member of the gridded ion engine family. Based on this discussion, we give an overview of important research topics such as the search for alternative propellants, the development of reliable neutralizer concepts based on novel insert materials, as well as promising neutralizer-free propulsion concepts. In addition, aspects of thruster modeling and requirements for test facilities are discussed. Furthermore, we address aspects of space electronics with regard to the development of highly efficient electronic components as well as aspects of electromagnetic compatibility and radiation hardness. This article concludes with a presentation of the interaction of EP systems with the spacecraft.

Interaction between behavioral inhibition and neural alcohol cue-reactivity in ADHD and alcohol use disorder.

RATIONALE: Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity. OBJECTIVES: In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task. METHODS: Out of 69 adult study participants, we included n = 49 in our final analyses: Individuals had a diagnosis of either AUD (n = 13), ADHD (n = 14) or both (n = 5), or were healthy controls (HC; n = 17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. RESULTS: The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. CONCLUSIONS: Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

Orbitofrontal structural markers of negative affect in alcohol dependence and their associations with heavy relapse-risk at 6 months post-treatment.

BACKGROUND: Alcohol relapse is often occurring to regulate negative affect during withdrawal. On the neurobiological level, alcoholism is associated with gray matter (GM) abnormalities in regions that regulate emotional experience such as the orbitofrontal cortex (OFC). However, no study to our knowledge has investigated the neurobiological unpinning of affect in alcoholism at early withdrawal and the associations of OFC volume with long-term relapse risk. METHODS: One hundred and eighty-two participants were included, 95 recently detoxified alcohol dependent patients (ADP) and 87 healthy controls (HC). We measured affective states using the positive and negative affect schedule (PANAS). We collected T1-weighted brain structural images and performed Voxel-based morphometry (VBM). RESULTS: Findings revealed GM volume decrease in alcoholics in the prefrontal cortex (including medial OFC), anterior cingulate gyrus, and insula. GM volume in the medial OFC was positively associated with NA in the ADP group. Cox regression analysis predicted that risk to heavy relapse at 6 months increases with decreased GM volume in the medial OFC. CONCLUSIONS: Negative affect during alcohol withdrawal was positively associated with OFC volume. What is more, increased GM volume in the OFC also moderated risk to heavy relapse at 6 months. Reduced GM in the OFC poses as risk to recovery from alcohol dependence and provides valuable insights into transient negative affect states during withdrawal that can trigger relapse. Implications exist for therapeutic interventions signifying the OFC as a neurobiological marker to relapse and could explain the inability of ADP to regulate internal negative affective states.

Comorbidity, family history and personality traits in pathological gamblers compared with healthy controls.

BACKGROUND: While DSM-5 classified pathological gambling as an addictive disorder, there is debate as to whether ICD-11 should follow suit. The debate hinges on scientific evidence such as neurobiological findings, family history of psychiatric disorders, psychiatric comorbidity, and personality variables. METHODS: In the "Baden-Württemberg Study of Pathological Gambling", we compared a group of 515 male pathological gamblers receiving treatment with 269 matched healthy controls. We studied differences in sociodemographic characteristics, gambling-related variables, psychiatric comorbidity (lifetime), family history of psychiatric conditions, as well as personality traits such as impulsivity (Barratt Impulsiveness Scale), sensation seeking (Zuckerman's Sensation Seeking Scale) and the NEO-FFI big five. Personality traits were validated in an age- and ethnicity-matched subsample of "pure" gamblers without any psychiatric comorbidity (including nicotine dependence). Data were analyzed using two-sample t-tests, Chi2 analyses, Fisher's exact test and Pearson correlation analysis, as appropriate. Bonferroni correction was applied to correct for multiple comparisons. RESULTS: Only 1% of the gamblers had been diagnosed with an impulse control disorder other than gambling (ICD-10). Notably, 88% of the gamblers in our sample had a comorbid diagnosis of substance dependence. The highest axis I comorbidity rate was for nicotine dependence (80%), followed by alcohol dependence (28%). Early age of first gambling experience was correlated with gambling severity. Compared to first-degree relatives of controls, first-degree relatives of pathological gamblers were more likely to suffer from alcohol dependence (27.0% vs. 7.4%), pathological gambling (8.3% vs. 0.7%) and suicide attempts (2.7% vs. 0.4%). Significant group differences were observed for the NEO-FFI factors neuroticism, agreeableness and conscientiousness. Gamblers were also more impulsive than controls, but did not differ from controls in terms of sensation seeking. CONCLUSIONS: Our findings support classifying pathological gambling as a behavioural addiction in the ICD-11. This decision will have a significant impact on the approaches available for prevention (e.g. age limits) and treatment.

Functional neuroimaging effects of recently discovered genetic risk loci for schizophrenia and polygenic risk profile in five RDoC subdomains.

Recently, 125 loci with genome-wide support for association with schizophrenia were identified. We investigated the impact of these variants and their accumulated genetic risk on brain activation in five neurocognitive domains of the Research Domain Criteria (working memory, reward processing, episodic memory, social cognition and emotion processing). In 578 healthy subjects we tested for association (i) of a polygenic risk profile score (RPS) including all single-nucleotide polymorphisms (SNPs) reaching genome-wide significance in the recent genome-wide association studies (GWAS) meta-analysis and (ii) of all independent genome-wide significant loci separately that showed sufficient distribution of all allelic groups in our sample (105 SNPs). The RPS was nominally associated with perigenual anterior cingulate and posterior cingulate/precuneus activation during episodic memory (PFWE(ROI)=0.047) and social cognition (PFWE(ROI)=0.025), respectively. Single SNP analyses revealed that rs9607782, located near EP300, was significantly associated with amygdala recruitment during emotion processing (PFWE(ROI)=1.63 × 10-4, surpassing Bonferroni correction for the number of SNPs). Importantly, this association was replicable in an independent sample (N=150; PFWE(ROI)<0.025). Other SNP effects previously associated with imaging phenotypes were nominally significant, but did not withstand correction for the number of SNPs tested. To assess whether there was true signal within our data, we repeated single SNP analyses with 105 randomly chosen non-schizophrenia-associated variants, observing fewer significant results and lower association probabilities. Applying stringent methodological procedures, we found preliminary evidence for the notion that genetic risk for schizophrenia conferred by rs9607782 may be mediated by amygdala function. We critically evaluate the potential caveats of the methodological approaches employed and offer suggestions for future studies.

[On the legalization debate of non-medical cannabis consumption : Position paper of the German Association for Psychiatry, Psychotherapy and Psychosomatics]. / Zur Legalisierungsdebatte des nichtmedizinischen Cannabiskonsums : DGPPN-Positionspapier.

Calls are increasing for the legalization of cannabis. Some legal experts, various politicians, political parties and associations are demanding a change in drug policy. The legalization debate is lively and receiving wide coverage in the media. The German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) comments on the most important questions from a medical scientific perspective: can cannabis consumption trigger mental illnesses, what consequences would legalization have for the healthcare system and where is more research needed?

Genome-wide association study of pathological gambling.

BACKGROUND: Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence. METHODS: Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence. RESULTS: No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value=6.63×10(-3)); 5'-adenosine monophosphate-activated protein kinase signalling (P-value=9.57×10(-3)); and apoptosis (P-value=1.75×10(-2)) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status. CONCLUSIONS: The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies.

Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample.

Variation in genes coding for nicotinic acetylcholine receptor (nAChR) subunits affect cognitive processes and may contribute to the genetic architecture of neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in the CHRNA4 gene that codes for the alpha4 subunit of alpha4/beta2-containing receptors have previously been implicated in aspects of (mostly visual) attention and smoking-related behavioral measures. Here we investigated the effects of six synonymous but functional CHRNA4 exon 5 SNPs on the N100 event-related potential (ERP), an electrophysiological endophenotype elicited by a standard auditory oddball. A total of N = 1,705 subjects randomly selected from the general population were studied with electroencephalography (EEG) as part of the German Multicenter Study on nicotine addiction. Two of the six variants, rs1044396 and neighboring rs1044397, were significantly associated with N100 amplitude. This effect was pronounced in females where we also observed an effect on reaction time. Sequencing of the complete exon 5 region in the population sample excluded the existence of additional/functional variants that may be responsible for the observed effects. This is the first large-scale population-based study investigation the effects of CHRNA4 SNPs on brain activity measures related to stimulus processing and attention. Our results provide further evidence that common synonymous CHRNA4 exon 5 SNPs affect cognitive processes and suggest that they also play a role in the auditory system. As N100 amplitude reduction is considered a schizophrenia-related endophenotype the SNPs studied here may also be associated with schizophrenia outcome measures.

[Normative definition of staff requirement for a guideline-adherent inpatient qualified detoxification treatment in alcohol dependence]. / Personalbedarfsermittlung für eine leitliniengerechte stationäre Qualifizierte Entzugsbehandlung bei Alkoholabhängigkeit.

The central element of the "qualified withdrawal treatment" of alcohol dependence is - in addition to physical withdrawal treatment - psychotherapy. The treatment of the underlying addictive disorder that is displayed by intoxication, harmful behaviour and withdrawal symptoms is only possible with a combination of somatic and psychotherapeutic treatment elements. The successfully established multimodal therapy of the "qualified alcohol withdrawal treatment", postulated in the current S3-Treatment Guidelines, requires a multi-disciplinary treatment team with psychotherapeutic competence. The aim of the present work is to calculate the normative staff requirement of a guideline-based 21-day qualified withdrawal treatment and to compare the result with the staffing regulations of the German Institute for Hospital Reimbursement. The present data support the hypothesis that even in the case of a hundred per cent implementation of these data, adequate therapy of alcohol-related disorders, according to the guidelines, is not feasible. This has to be considered when further developing the finance compensation system based on the described superseded elements of the German Institute for Hospital Reimbursement.

Strong association of serum- and glucocorticoid-regulated kinase 1 with peripheral and adipose tissue inflammation in obesity.

OBJECTIVE: The serum- and glucocorticoid-regulated kinase 1 (SGK1) is an early transcriptional target of glucocorticoids and is activated via insulin. Here we investigate the regulation of SGK1 expression in human obesity, diet-induced murine obesity and human monocytic cell line THP-1 monocytes. SUBJECTS AND METHODS: SGK1 expression was studied in subcutaneous and omental adipose tissue (AT) of 20 morbidly obese and 20 age- and gender-matched non-obese controls in murine diet-induced obesity and the THP-1 cell line. The regulation of SGK1 by inflammatory signals was tested in THP-1 cells. RESULTS: Murine diet-induced obesity is associated with a significant upregulation of Sgk1 in gonadal AT. Sgk1 expression is highest in the macrophage-rich stromal vascular fraction and lower in adipocytes. In humans, AT SGK1 is predominantly expressed in CD14(+) macrophages and significantly upregulated in omental and subcutaneous AT of obese subjects. SGK1 mRNA expression in both omental and subcutaneous AT correlates with body mass index, circulating leptin and C-reactive protein, and the local expression of inflammatory markers including monocyte chemotactic protein-1 and macrophage inflammatory protein-1α. The expression of SGK1 in THP-1 cells is upregulated by inflammatory signals, such as lipopolysaccharide and tumour necrosis factor-α, as well as during the induction of monocyte-to-macrophage maturation. CONCLUSIONS: Our data present the first link between SGK1 and obesity-associated inflammation. SGK1 expression is stimulated in response to inflammatory signals and increased in AT macrophages. The characterisation of SGK1 functions in obesity and immunity may help identify potential therapeutic targets in the treatment of obesity.

A comparison of region-of-interest measures for extracting whole brain data using survival analysis in alcoholism as an example.

BACKGROUND: Aggregation of functional magnetic resonance imaging (fMRI) data in regions-of-interest (ROIs) is required for complex statistical analyses not implemented in standard fMRI software. Different data-aggregation measures assess various aspects of neural activation, including spatial extent and intensity. NEW METHOD: In this study, conducted within the framework of the PREDICT study, we compared different aggregation measures for voxel-wise fMRI activations to be used as prognostic factors for relapse in 49 abstinent alcohol-dependent individuals in an outpatient setting using a cue-reactivity task. We compared the importance of the data-aggregation measures as prognostic factors for treatment outcomes by calculating the proportion of explained variation. RESULTS AND COMPARISON WITH EXISTING METHOD(S): Relapse risk was associated with cue-induced brain activation during abstinence in the ventral striatum (VS) and in the orbitofrontal cortex (OFC). While various ROI measures proved appropriate for using fMRI cue-reactivity to predict relapse, on the descriptive level the most "important" prognostic factor was a measure defined as the sum of t-values exceeding an individually defined threshold. Data collected in the VS was superior to that from other regions. CONCLUSIONS: In conclusion, it seems that fMRI cue-reactivity, especially in the VS, can be used as prognostic factor for relapse in abstinent alcohol-dependent patients. Our findings suggest that data-aggregation measures that take both spatial extent and intensity of cue-induced brain activation into account make better biomarkers for predicting relapse than measures that consider an activation's spatial extent or intensity alone.

[Improvement of management of hypertension by implementation of alcohol screening and subsequent interventions in primary practice]. / Verbessertes Hypertonie-Management durch Alkohol-Screening und Folgeinterventionen in der Hausarztpraxis.

Hypertension and alcohol use are both part of the five most important risk factors for burden of disease in Western Europe, mainly because of their impact on non-communicable diseases (NCD). Both risk factors are prevalent with high overlap among patients in primary care. Implementation of a screening for alcohol among patients of hypertension in primary care followed by brief intervention for problem alcohol use or formal treatment for people with alcohol dependence could constitute an important step to reach the goals of the Global WHO Action Plan for Prevention and Control of NCD. In addition, such an intervention could improve the management of hypertension. In a working group of experts from clinical practice and research the rationale and potential barriers for this intervention were discussed and steps for implementation in primary care were developed.

Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate.

Acamprosate supports abstinence in some alcohol-dependent subjects, yet predictors of response are unknown. To identify response biomarkers, we investigated associations of abstinence length with polymorphisms in candidate genes in glycine and glutamate neurotransmission pathways and genes previously implicated in acamprosate response. Association analyses were conducted in the discovery sample of 225 alcohol-dependent subjects treated with acamprosate for 3 months in community-based treatment programs in the United States. Data from 110 alcohol-dependent males treated with acamprosate in the study PREDICT were used for replication of the top association findings. Statistical models were adjusted for relevant covariates, including recruitment site and baseline clinical variables associated with response. In the discovery sample, shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between the last drink and initiation of acamprosate treatment. After adjustment for covariates, length of abstinence was associated with the GRIN2B rs2058878 (P=4.6 × 10(-5)). In the replication sample, shorter abstinence was associated with increased craving, increased depressive mood score and higher alcohol consumption. Association of abstinence length with GRIN2B rs2058878 was marginally significant (P=0.0675); as in the discovery sample, the minor A allele was associated with longer abstinence. Furthermore, rs2300272, which is in strong linkage disequilibrium with rs2058878, was also associated with abstinence length (P=0.049). This is the first report of a replicated association of genetic markers with the length of abstinence in acamprosate-treated alcoholics. Investigation of the underlying mechanisms of this association and its usefulness for individualized treatment selection should follow.

Two families of exocomets in the ß Pictoris system.

The young planetary system surrounding the star ß Pictoris harbours active minor bodies. These asteroids and comets produce a large amount of dust and gas through collisions and evaporation, as happened early in the history of our Solar System. Spectroscopic observations of ß Pictoris reveal a high rate of transits of small evaporating bodies, that is, exocomets. Here we report an analysis of more than 1,000 archival spectra gathered between 2003 and 2011, which provides a sample of about 6,000 variable absorption signatures arising from exocomets transiting the disk of the parent star. Statistical analysis of the observed properties of these exocomets allows us to identify two populations with different physical properties. One family consists of exocomets producing shallow absorption lines, which can be attributed to old exhausted (that is, strongly depleted in volatiles) comets trapped in a mean motion resonance with a massive planet. Another family consists of exocomets producing deep absorption lines, which may be related to the recent fragmentation of one or a few parent bodies. Our results show that the evaporating bodies observed for decades in the ß Pictoris system are analogous to the comets in our own Solar System.

Genetic risk prediction and neurobiological understanding of alcoholism.

We have used a translational Convergent Functional Genomics (CFG) approach to discover genes involved in alcoholism, by gene-level integration of genome-wide association study (GWAS) data from a German alcohol dependence cohort with other genetic and gene expression data, from human and animal model studies, similar to our previous work in bipolar disorder and schizophrenia. A panel of all the nominally significant P-value SNPs in the top candidate genes discovered by CFG  (n=135 genes, 713 SNPs) was used to generate a genetic  risk prediction score (GRPS), which showed a trend towards significance (P=0.053) in separating  alcohol dependent individuals from controls in an independent German test cohort. We then validated and prioritized our top findings from this discovery work, and subsequently tested them in three independent cohorts, from two continents. A panel of all the nominally significant P-value single-nucleotide length polymorphisms (SNPs) in the top candidate genes discovered by CFG (n=135 genes, 713 SNPs) were used to generate a Genetic Risk Prediction Score (GRPS), which showed a trend towards significance (P=0.053) in separating alcohol-dependent individuals from controls in an independent German test cohort. In order to validate and prioritize the key genes that drive behavior without some of the pleiotropic environmental confounds present in humans, we used a stress-reactive animal model of alcoholism developed by our group, the D-box binding protein (DBP) knockout mouse, consistent with the surfeit of stress theory of addiction proposed by Koob and colleagues. A much smaller panel (n=11 genes, 66 SNPs) of the top CFG-discovered genes for alcoholism, cross-validated and prioritized by this stress-reactive animal model showed better predictive ability in the independent German test cohort (P=0.041). The top CFG scoring gene for alcoholism from the initial discovery step, synuclein alpha (SNCA) remained the top gene after the stress-reactive animal model cross-validation. We also tested this small panel of genes in two other independent test cohorts from the United States, one with alcohol dependence (P=0.00012) and one with alcohol abuse (a less severe form of alcoholism; P=0.0094). SNCA by itself was able to separate alcoholics from controls in the alcohol-dependent cohort (P=0.000013) and the alcohol abuse cohort (P=0.023). So did eight other genes from the panel of 11 genes taken individually, albeit to a lesser extent and/or less broadly across cohorts. SNCA, GRM3 and MBP survived strict Bonferroni correction for multiple comparisons. Taken together, these results suggest that our stress-reactive DBP animal model helped to validate and prioritize from the CFG-discovered genes some of the key behaviorally relevant genes for alcoholism. These genes fall into a series of biological pathways involved in signal transduction, transmission of nerve impulse (including myelination) and cocaine addiction. Overall, our work provides leads towards a better understanding of illness, diagnostics and therapeutics, including treatment with omega-3 fatty acids. We also examined the overlap between the top candidate genes for alcoholism from this work and the top candidate genes for bipolar disorder, schizophrenia, anxiety from previous CFG analyses conducted by us, as well as cross-tested genetic risk predictions. This revealed the significant genetic overlap with other major psychiatric disorder domains, providing a basis for comorbidity and dual diagnosis, and placing alcohol use in the broader context of modulating the mental landscape.

Intraperitoneal atrial natriuretic peptide attenuates anxiety-related behaviour during alcohol withdrawal in mice.

Converging evidence from both preclinical and clinical studies suggests atrial natriuretic peptide (ANP) as a potential target for treatment of alcohol withdrawal and dependence. Since ANP tightly interacts with hypothalamic-pituitary-adrenocortical (HPA) axis activity, especially the modulation of stress-related anxiety during alcohol withdrawal might mediate these effects. We have now evaluated the anxiolytic activity of intraperitoneal ANP application during alcohol withdrawal in alcohol-habituated mice (C57/Bl6J). Anxiety related behaviour was attenuated during ethanol withdrawal following application of ANP (60 µg/kg) vs. saline. Our results support that anxiolytic effects of ANP mediate ANP-related gene effects with clinical data on withdrawal symptomatology.

[Neurobiology of behavioral addictions]. / Neurobiologische Grundlagen der Verhaltenssüchte.

Reward learning represents a crucial mechanism in the acquisition and maintenance of addictive behavior. The underlying neurobiological foundations and associated neurobiological pathways are identified in this review and similarities between substance abuse and behavioral addictions will be discussed. In the second section current neuroimaging findings on neurobiological mechanisms of pathological gambling and computer and internet addiction are discussed. The main focuses are on changes in neurocognitive processes, such as cue reactivity, reward and punishment processing and behavioral control.