Search

Ventricular enlargement is common in established schizophrenia; however, data from ultra high-risk for psychosis and first-episode psychosis studies are inconclusive. This study aims to investigate ventricular volumes at different stages of psychosis.Ventricular volumes were measured using a semi-automated and highly reliable method, for 89 established schizophrenia, 162 first-episode psychosis, 135 ultra high-risk for psychosis and 87 healthy controls using 1.5T magnetic resonance images. Clinical outcome diagnoses for ultra high-risk for psychosis were evaluated at long-term follow-up (mean: 7.5 years).Compared to controls, we identified significant ventricular enlargement of 36.2% in established schizophrenia ( p 0.001). Ventricular enlargement was not significant in first-episode psychosis (6%) or ultra high-risk for psychosis (-3%). Examination across stages of schizophrenia-spectrum diagnoses subgroups revealed a significant linear trend ( p = 0.006; established schizophrenia = 36.2%, first-episode psychosis schizophrenia = 18.5%, first-episode psychosis schizophreniform = -4.2% and ultra high-risk for psychosis-schizophrenia converters = -18.5%).Ventricular enlargement is apparent in patients with established schizophrenia but is not a feature at the earliest stages of illness (ultra high-risk for psychosis and first-episode psychosis). Further research is needed to fully characterize the nature and timing of ventricular volume changes early in the course of illness and how these changes impact outcomes.

Background: Lithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation.Method: Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation.Results: In a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05).Conclusion: This is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression.

Background: There is only limited agreement with respect to location, directionality and functional implications of brain structural alterations observed in patients with schizophrenia. Additionally, their link to occurrence of psychotic symptoms remains unclear. A viable way of addressing these questions is to examine populations in an at-risk mental state (ARMS) before the transition to psychosis. Methods: We tested for structural brain alterations in individuals in an ARMS compared with healthy controls and patients with first-episode psychosis (FEP) using voxel-based morphometry and measures of cortical thickness. Furthermore, we evaluated if these alterations were modified by age and whether they were linked to the observed clinical symptoms. Results: Our sample included 59 individuals with ARMS, 26 healthy controls and 59 patients with FEP. We found increased grey matter volume and cortical thickness in individuals with ARMS and a similar pattern of structural alterations in patients with FEP. We further found stronger age-related reductions in grey matter volume and cortical thickness in both patients with FEP and individuals with ARMS, linking these alterations to observed clinical symptoms. Limitations: The ARMS group comprised subgroups with heterogeneous levels of psychosis risk and medication status. Furthermore, the cross-sectional nature of our study and the reduced number of older patients limit conclusions with respect to observed interactions with age. Conclusion: Our findings on consistent structural alterations in individuals with ARMS and patients with FEP and their link to clinical symptoms have major implications for understanding their time of occurrence and relevance to psychotic symptoms. Interactions with age found for these alterations may explain the heterogeneity of findings reported in the literature.

Magnetic resonance imaging-based markers of schizophrenia have been repeatedly shown to separate patients from healthy controls at the single-subject level, but it remains unclear whether these markers reliably distinguish schizophrenia from mood disorders across the life span and generalize to new patients as well as to early stages of these illnesses. The current study used structural MRI-based multivariate pattern classification to (i) identify and cross-validate a differential diagnostic signature separating patients with first-episode and recurrent stages of schizophrenia (n = 158) from patients with major depression (n = 104); and (ii) quantify the impact of major clinical variables, including disease stage, age of disease onset and accelerated brain ageing on the signature's classification performance. This diagnostic magnetic resonance imaging signature was then evaluated in an independent patient cohort from two different centres to test its generalizability to individuals with bipolar disorder (n = 35), first-episode psychosis (n = 23) and clinically defined at-risk mental states for psychosis (n = 89). Neuroanatomical diagnosis was correct in 80% and 72% of patients with major depression and schizophrenia, respectively, and involved a pattern of prefronto-temporo-limbic volume reductions and premotor, somatosensory and subcortical increments in schizophrenia versus major depression. Diagnostic performance was not influenced by the presence of depressive symptoms in schizophrenia or psychotic symptoms in major depression, but earlier disease onset and accelerated brain ageing promoted misclassification in major depression due to an increased neuroanatomical schizophrenia likeness of these patients. Furthermore, disease stage significantly moderated neuroanatomical diagnosis as recurrently-ill patients had higher misclassification rates (major depression: 23%; schizophrenia: 29%) than first-episode patients (major depression: 15%; schizophrenia: 12%). Finally, the trained biomarker assigned 74% of the bipolar patients to the major depression group, while 83% of the first-episode psychosis patients and 77% and 61% of the individuals with an ultra-high risk and low-risk state, respectively, were labelled with schizophrenia. Our findings suggest that neuroanatomical information may provide generalizable diagnostic tools distinguishing schizophrenia from mood disorders early in the course of psychosis. Disease course-related variables such as age of disease onset and disease stage as well alterations of structural brain maturation may strongly impact on the neuroanatomical separability of major depression and schizophrenia.

IntroductionPituitary enlargement has been reported in individuals with schizophrenic psychosis or an at-risk mental state for psychosis (ARMS). In a previous study, our group could show pituitary volume increase in first episode and ARMS patients with later transition to psychosis (ARMS-T). However, there are no longitudinal studies on this issue so far. We therefore examined longitudinally whether transition to psychosis would be accompanied by a further increase of pituitary volume in antipsychotic-naïve ARMS patients.MethodsMagnetic resonance imaging (MRI) data were acquired from 23 antipsychotic-naïve individuals with an ARMS. Ten subjects developed psychosis (ARMS-T) and 13 did not (ARMS-NT). ARMS-T were re-scanned after the onset of psychosis, and ARMS-NT were re-scanned at the end of the study period.ResultsThere was no significant difference of the pituitary volume between ARMS-T and ARMS-NT in our sample, and there were no significant pituitary volume changes over time.DiscussionLongitudinally, we could not detect any further volumetric changes in the pituitary volume with transition to psychosis.ConclusionsThis, together with the result of our previous study, could indicate that the perceived level of stress in ARMS patients is constantly high from very early onward.

As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shapes. We use standard vertex-wise and global shape features computed homologously across 19 cohorts and over 7500 human-rated subjects, training kernelized Support Vector Machine and Gradient Boosted Decision Trees classifiers to detect meshes of failing quality. Our models generalize across datasets and diseases, reducing human workload by 30-70%, or equivalently hundreds of human rater hours for datasets of comparable size, with recall rates approaching inter-rater reliability.

Forming the foundations of large-scale knowledge bases, probabilistic databases have been widely studied in the literature. In particular, probabilistic query evaluation has been investigated intensively as a central inference mechanism. However, despite its power, query evaluation alone cannot extract all the relevant information encompassed in large-scale knowledge bases. To exploit this potential, we study two inference tasks; namely finding the most probable database and the most probable hypothesis for a given query. As natural counterparts of most probable explanations (MPE) and maximum a posteriori hypotheses (MAP) in probabilistic graphical models, they can be used in a variety of applications that involve prediction or diagnosis tasks. We investigate these problems relative to a variety of query languages, ranging from conjunctive queries to ontology-mediated queries, and provide a detailed complexity analysis.

Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD). Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13), a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive–compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment of MDD from the US Food and Drug Administration, representing one of the most promising alternative antidepressants under current investigation.

To compare the ward atmosphere, safety, therapeutic hold, and patients' coherence on recently opened (1 year), opened (4 years) and open ( 20 years) psychiatric wards in a longitudinal naturalistic study design. The question was if a patient shift from formerly locked to open wards might deteriorate the ward atmosphere on the open and opened wards.Ward atmosphere on two recently opened (n = 2), opened (n = 2) and open (n = 2) wards was examined using the Essen Climate Evaluation Schema (EssenCES) in a follow-up study after 4 years. Structural as well as clinical data were extracted.Global ward atmosphere, safety, and patients' coherence on the recently opened wards was significantly increased; on always opened wards and long-term opened wards it remained unchanged. Coercive measures and discharges against medical advice decreased during the open door process.Opening locked psychiatric wards can help to establish a positive therapeutic atmosphere without changing the therapeutic climate on the other already open wards. A better ward atmosphere might be connected with a better therapeutic quality.ZIEL DER STUDIE: war es, die Veränderung des Stationsklimas während eines Türöffnungsprozesses zu untersuchen.Die Essen Climate Evaluation Schema (EssenCES) wurde auf neu geöffneten (n = 2, 1 Jahr), geöffneten (n = 2, 4 Jahre) und langjährig offenen (n = 2, 20 Jahre) Stationen untersucht.Die Stationsatmosphäre auf den neu geöffneten Stationen verbesserte sich signifikant. Zwangsmaßnahmen und Entlassungen gegen ärztlichen Rat wurden reduziert.Die Öffnung von Akutstationen kann zu einem günstigeren Stationsklima führen.

Perceptions of dangerousness are an influential component of mental health stigma and can be driven by the display of psychiatric symptoms and the use of psychiatric service institutions. Yet, no previous study compared symptoms and service use associated perceptions of dangerousness. Therefore, we conducted a representative survey (N = 2,207) in the canton of Basel-Stadt, Switzerland. Participants were asked to answer the perceived dangerousness scale with respect to a vignette that either depicted psychiatric symptoms of a fictitious character or a psychiatric service institution the fictitious character had been admitted to. Between the vignettes, type of symptoms, type of psychiatric service, dangerousness, and gender were systematically varied. Perceived dangerousness was significantly lower as related to psychiatric service use than related to psychiatric symptoms. Overall, symptoms of alcohol dependency, behavior endangering others, and male gender of the fictitious character tend to increase perceived dangerousness. Furthermore, being hospitalized in a psychiatric unit at a general hospital or the rater being familiar with psychiatric services tends to decrease perceived dangerousness. Effective anti-stigma initiatives should integrate education about dangerousness as well as methods to increase familiarity with psychiatry. Additionally, an integration of modern psychiatry in somato-medical care institutions might decrease stigmatization.

In contrast to the idea that hippocampal and amygdala volume loss occur in late phases of neurodegeneration, recent contributions point to the relevance of preexisting structural deficits that are associated with aging and are independent of amyloid deposition in preclinical Alzheimer disease cases. The present work explores GM hippocampal and amygdala volumes in elderly controls displaying the first signs of cognitive decline. 455 subjects (263 females), including 374 controls (228 females) and 81 middle cognitive impairment subjects (35 females), underwent two neuropsychological evaluations (baseline and 18 months follow-up) and a MRI-T1 examination (only baseline). Clinical assessment included Mini-Mental State Examination (MMSE), Clinical Dementia Rating scale, Hospitalized Anxiety and Depression scale, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery and RI-48 Cued Recall Test (RI-48) for episodic memory. Based on their cognitive performance, we defined the controls as stable controls (sCON) and deteriorating controls (dCONs). Analyses included volumetric assessment, shape analyses and linear regressions between GM volume loss and differences in clinical scores between baseline and follow-up. Significant GM volume decrease in hippocampus bilaterally and right amygdala was found in dCON compared to sCON (p < 0.05). Lower right amygdala volumes were measured in mild cognitive impairment (MCI) compared to sCON (p < 0.05). Shape analyses revealed that atrophy was more pronounced at the superior-posterior lateral side of the hippocampus and amygdala. Significant correlations were found between GM volume of left hippocampus and the delta of MMSE and RI-48 scores in dCON and MCI groups separately. Decreased hippocampal and right amygdala volumes precede the first signs of cognitive decline in healthy elderly controls at the pre-MCI state. Left hippocampus volume may also predict short-term changes of overall cognition in these vulnerable cases.

Early intervention strategies in psychosis would significantly benefit from the identification of reliable prognostic biomarkers. Pattern classification methods have shown the feasibility of an early diagnosis of psychosis onset both in clinical and familial high-risk populations. Here we were interested in replicating our previous classification findings using an independent cohort at clinical high risk for psychosis, drawn from the prospective FePsy (Fruherkennung von Psychosen) study. The same neuroanatomical-based pattern classification pipeline, consisting of a linear Support Vector Machine (SVM) and a Recursive Feature Selection (RFE) achieved 74% accuracy in predicting later onset of psychosis. The discriminative neuroanatomical pattern underlying this finding consisted of many brain areas across all four lobes and the cerebellum. These results provide proof-of-concept that the early diagnosis of psychosis is feasible using neuroanatomical-based pattern recognition.

The brain-gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have facilitated its investigation. We systematically looked into functional and neurochemical brain imaging studies investigating how key molecules such as ghrelin, glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), cholecystokinin (CCK), leptin, glucose and insulin influence the function of brain regions regulating appetite and satiety. Of the 349 studies published before July 2016 identified in the database search, 40 were included (27 on healthy and 13 on obese subjects). Our systematic review suggests that the plasma level of ghrelin, the gut hormone promoting appetite, is positively correlated with activation in the pre-frontal cortex (PFC), amygdala and insula and negatively correlated with activation in subcortical areas such as the hypothalamus. In contrast, the plasma levels of glucose, insulin, leptin, PYY, GLP-1 affect the same brain regions conversely. Our study integrates previous investigations of the gut-brain matrix during food-intake and homeostatic regulation and may be of use for future meta-analyses of brain-gut interactions.

Objective It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system. Method 100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects. Results LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects. Conclusion Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT2A-receptor in altered states of consciousness.

In contrast to qualitative linear temporal logics, which can be used to state that some property will eventually be satisfied, metric temporal logics allow to formulate constraints on how long it may take until the property is satisfied. While most of the work on combining Description Logics (DLs) with temporal logics has concentrated on qualitative temporal logics, there has recently been a growing interest in extending this work to the quantitative case. In this paper, we complement existing results on the combination of DLs with metric temporal logics over the natural numbers by introducing interval-rigid names. This allows to state that elements in the extension of certain names stay in this extension for at least some specified amount of time.

Fuzzy Description Logics have been proposed as formalisms for representing and reasoning about imprecise knowledge by introducing intermediate truth degrees. Unfortunately, it has been shown that reasoning in these logics easily becomes undecidable, when infinitely many truth degrees are considered and conjunction is not idempotent. In this paper, we take those results to the extreme, and show that subsumption in fuzzy EL under Lukasiewicz semantics is undecidable. This provides the first instance of a Horn-style logic with polynomial-time reasoning whose fuzzy extension becomes undecidable.

The time period during which patients manifest psychotic or unspecific symptoms prior to treatment (duration of untreated psychosis, DUP, and the duration of untreated illness, DUI) has been found to be moderately associated with poor clinical and social outcome. Equivocal evidence exists of an association between DUP/DUI and structural brain abnormalities, such as reduced hippocampus volume (HV), pituitary volume (PV) and grey matter volume (GMV). Thus, the goal of the present work was to examine if DUP and DUI are associated with abnormalities in HV, PV and GMV. Using a region of interest (ROI) based approach, we present data of 39 patients from the Basel FePsy (Früherkennung von Psychosen, early detection of psychosis) study for which information about DUP, DUI and HV, PV and GMV data could be obtained. Twenty-three of them were first episode psychosis (FEP) and 16 at-risk mental state (ARMS) patients who later made the transition to frank psychosis. In unadjusted analyses, we found a significant positive correlation between DUP and PV in FEP patients. However, when adjusted for covariates, we found no significant correlation between DUP or DUI and HV, PV or GMV anymore. There only was a trend for decreasing GMV with increasing DUI in FEP. Our results do not comprehensively support the hypothesis of a "toxic" effect of the pathogenic mechanism underlying untreated psychosis on brain structure. If there is any effect, it might rather occur very early in the disease process, during which patients experience only unspecific symptoms.

Lysergic acid diethylamide (LSD) induces profound changes in various mental domains, including perception, self-awareness and emotions. We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of LSD on the neural substrate of emotional processing in humans. Using a double-blind, randomised, cross-over study design, placebo or 100 μg LSD were orally administered to 20 healthy subjects before the fMRI scan, taking into account the subjective and pharmacological peak effects of LSD. The plasma levels of LSD were determined immediately before and after the scan. The study (including the a priori-defined study end point) was registered at ClinicalTrials.gov before study start (NCT02308969). The administration of LSD reduced reactivity of the left amygdala and the right medial prefrontal cortex relative to placebo during the presentation of fearful faces (PP

Mathematical Fuzzy Logics [51, 60] have a long tradition with roots going back to the many-valued logics of Łukasiewicz, Godel, and Kleene [57, 68, 73] and the Fuzzy Set Theory of Zadeh [111]. Their purpose is to model vagueness or imprecision in the real world, by introducing new degrees of truth as additional shades of gray between the Boolean true and false. For example, one can express the distinction between a person x having a high fever or a low fever as the degree of truth of the logical statement \(\mathsf {Fever} (x)\). One of the central properties of fuzzy logics is truth functionality—the truth degree of a complex logical formula is uniquely determined by the truth degrees of its subformulas. This is a fundamental difference to other quantitative logics like probabilistic or possibilistic logics [56, 83].

In contrast to qualitative linear temporal logics, which can be used to state that some property will eventually be satisfied, metric temporal logics allow to formulate constraints on how long it may take until the property is satisfied. While most of the work on combining Description Logics (DLs) with temporal logics has concentrated on qualitative temporal logics, there has recently been a growing interest in extending this work to the quantitative case. In this paper, we complement existing results on the combination of DLs with metric temporal logics over the natural numbers by introducing interval-rigid names. This allows to state that elements in the extension of certain names stay in this extension for at least some specified amount of time.

We investigate ontology-based query answering (OBQA) in a setting where both the ontology and the query can refer to concrete values such as numbers and strings. In contrast to previous work on this topic, the built-in predicates used to compare values are not restricted to being unary. We introduce restrictions on these predicates and on the ontology language that allow us to reduce OBQA to query answering in databases using the so-called combined rewriting approach. Though at first sight our restrictions are different from the ones used in previous work, we show that our results strictly subsume some of the existing first-order rewritability results for unary predicates. This is an extended version of a paper published in the proceedings of IJCAI 2017.

Transition to psychosis in at-risk individuals has markedly declined in recent years. So far it has never been discussed in detail that with the growing awareness and increasing availability of early psychosis services, a much broader diagnostic spectrum is now being seen in these services. Subsequently, subjects present with symptoms that meet psychosis risk on a purely psychometric basis but may be the phenotypical expression of another underlying mental disorder. Here we critically review four groups of symptoms and clinical features that are frequently reported by individuals with suspected psychosis risk states, yet share strong commonalities with other mental disorders and conditions: isolated hallucinations; unusual bodily perceptions, hypochondriatic fears and cenesthetic psychotic symptoms; depersonalization; obsessive–compulsive, overvalued and delusional ideas. Of the 616 individuals so far assessed in the Bruderholz Early Psychosis Outpatient Service for Adolescents and Young Adults, 218 (30.5%) met ultra-high risk (UHR) criteria, 188 (86.2%) of whom suffered from one of the four above-mentioned symptom groups. The appraisal of the diagnostic spectra and their overlapping symptoms constitute a tremendous challenge in the clinical assessment of each referred individual. The final conclusion of a clinical assessment should not end with the mere assignment – or non-assignment – to a presumed psychosis risk group, but needs to take into account the ‘Gestalt’ of these particular symptoms and clinical features and thus be based on many more facets than solely a psychometric or nosological approach. Such an approach may break down the heterogeneous psychosis risk group and enable appropriate treatment regimes.

The combination of Fuzzy Logics and Description Logics (DLs) has been investigated for at least two decades because such fuzzy DLs can be used to formalize imprecise concepts. In particular, tableau algorithms for crisp Description Logics have been extended to reason also with their fuzzy counterparts. It has turned out, however, that in the presence of general concept inclusion axioms (GCIs) this extension is less straightforward than thought. In fact, a number of tableau algorithms claimed to deal correctly with fuzzy DLs with GCIs have recently been shown to be incorrect. In this paper, we concentrate on fuzzy \(\mathcal {A}\mathcal {L}\mathcal {C}\), the fuzzy extension of the well-known DL \(\mathcal {A}\mathcal {L}\mathcal {C}\). We present a terminating, sound, and complete tableau algorithm for fuzzy \(\mathcal {A}\mathcal {L}\mathcal {C}\) with arbitrary continuous t-norms. Unfortunately, in the presence of GCIs, this algorithm does not yield a decision procedure for consistency of fuzzy \(\mathcal {A}\mathcal {L}\mathcal {C}\) ontologies since it uses as a sub-procedure a solvability test for a finitely represented, but possibly infinite, system of inequations over the real interval [0,1], which are built using the t-norm. In general, it is not clear whether this solvability problem is decidable for such infinite systems of inequations. This may depend on the specific t-norm used. In fact, we also show in this paper that consistency of fuzzy \(\mathcal {A}\mathcal {L}\mathcal {C}\) ontologies with GCIs is undecidable for the product t-norm. This implies, of course, that for the infinite systems of inequations produced by the tableau algorithm for fuzzy \(\mathcal {A}\mathcal {L}\mathcal {C}\) with product t-norm, solvability is in general undecidable. We also give a brief overview of recently obtained (un)decidability results for fuzzy \(\mathcal {A}\mathcal {L}\mathcal {C}\) w.r.t. other t-norms.

Purpose Change of treatment policy from closed to open ward settings has been shown to reduce coercive measures. The aim of the current study was to examine the effects of the change from closed to open wards on the frequency of seclusion and forced medication in a hospital-wide setting. Subjects and methods 2-year, longitudinal observational study with 2838 inpatient cases. Results On a hospital-wide level, the percentage of patients with at least one seclusion was decreased significantly ( χ 2 ( 1) = 5.8; p = .016), while there was no significant change in forced medication ( χ 2 (1) = .08; p = .775). The frequency of seclusions and forced medication decreased significantly on newly opened wards, and there were no significant changes regarding seclusion on permanently closed or open wards, while the number of forced medications increased significantly on closed wards. The decrease in seclusions on newly opened wards remained statistically significant after controlling for diagnoses and severity of illness. Discussion Our results indicate that a reduction of overall seclusion can be successfully attained, and that, in particular, the frequency of seclusion and forced medication on newly opened wards was decreased significantly. These changes were not accompanied by a significant increase in seclusion on other wards. Conclusion Open ward treatment was successfully implemented and was associated with a significant decrease of coercive measures in our study. It might therefore provide a good care model, strengthening the patient's right to autonomy and leading to a reduction of coercive measures.

Background: Recent evidence has revealed abnormal functional connectivity between the frontal and parietal brain regions during working memory processing in patients with schizophrenia and first-episode psychosis. However, it still remains unclear whether abnor mal frontoparietal connectivity during working memory processing is already evident in the psychosis high-risk state and whether the connection strengths are related to psychopathological outcomes. Methods: Healthy controls and antipsychotic-naive individuals with an at-risk mental state (ARMS) performed an n-back working memory task while undergoing functional magnetic resonance imaging. Effect ive connectivity between frontal and parietal brain regions during working memory processing were characterized using dynamic causal modelling. Results: Our study included 19 controls and 27 individuals with an ARMS. In individuals with an ARMS, we found significantly lower task performances and reduced activity in the right superior parietal lobule and middle frontal gyrus than in controls. Furthermore, the working memory‐induced modulation of the connectivity from the right middle frontal gyrus to the right superior parietal lobule was significantly reduced in individuals with an ARMS, while the extent of this connectivity was negatively related to the Brief Psychiatric Rating Scale total score. Limitations: The modest sample size precludes a meaningful subgroup analysis for participants with a later transition to psychosis. Conclusion: This study demonstrates that abnormal frontoparietal connectivity during working memory process ing is already evident in individuals with an ARMS and is related to psychiatric symptoms. Thus, our results provide further insight into the pathophysiological mechanisms of the psychosis high-risk state by linking functional brain imaging, computational modelling and psychopathology.

To date, the MRI-based individualized prediction of psychosis has only been demonstrated in single-site studies. It remains unclear if MRI biomarkers generalize across different centers and MR scanners and represent accurate surrogates of the risk for developing this devastating illness. Therefore, we assessed whether a MRI-based prediction system identified patients with a later disease transition among 73 clinically defined high-risk persons recruited at two different early recognition centers. Prognostic performance was measured using cross-validation, independent test validation, and Kaplan-Meier survival analysis. Transition outcomes were correctly predicted in 80% of test cases (sensitivity: 76%, specificity: 85%, positive likelihood ratio: 5.1). Thus, given a 54-month transition risk of 45% across both centers, MRI-based predictors provided a 36%-increase of prognostic certainty. After stratifying individuals into low-, intermediate-, and high-risk groups using the predictor’s decision score, the high- vs low-risk groups had median psychosis-free survival times of 5 vs 51 months and transition rates of 88% vs 8%. The predictor’s decision function involved gray matter volume alterations in prefrontal, perisylvian, and subcortical structures. Our results support the existence of a cross-center neuroanatomical signature of emerging psychosis enabling individualized risk staging across different high-risk populations. Supplementary results revealed that (1) potentially confounding between-site differences were effectively mitigated using statistical correction methods, and (2) the detection of the prodromal signature considerably depended on the available sample sizes. These observations pave the way for future multicenter studies, which may ultimately facilitate the neurobiological refinement of risk criteria and personalized preventive therapies based on individualized risk profiling tools.

The compulsion to seek and use heroin is frequently driven by stress and craving during drug-cue exposure. Although previous neuroimaging studies have indicated that craving is mediated by increased prefrontal cortex activity, it remains unknown how heroin administration modulates the prefrontal cortex response. This study examines the acute effects of heroin on brain function in heroin-maintained patients. Using a crossover, double-blind, placebo-controlled design, 27 heroin-maintained patients performed functional magnetic resonance imaging 20 minutes after the administration of heroin or placebo (saline) while drug-related and neutral stimuli were presented. Images were processed and analysed with statistical parametric mapping. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Region of interest analyses showed a drug-related cue-associated blood-oxygen-level-dependent activation in the orbitofrontal cortex (OFC) in heroin-dependent patients during both treatment conditions (heroin and placebo). This activation of the OFC was significantly higher after heroin than after placebo administration. These findings may indicate the importance of OFC activity for impulse control and decision-making after regular heroin administration and may emphasize the benefit of the heroin-assisted treatment in heroin dependence.

We conducted a systematic review to assess the evidence for specific effects of cannabis on impulsivity, disinhibition and motor control. The review had a specific focus on neuroimaging findings associated with acute and chronic use of the drug and covers literature published up until May 2012. Seventeen studies were identified, of which 13 met the inclusion criteria; three studies investigated acute effects of cannabis (1 fMRI, 2 PET), while six studies investigated non-acute functional effects (4 fMRI, 2 PET), and four studies investigated structural alterations. Functional imaging studies of impulsivity studies suggest that prefrontal blood flow is lower in chronic cannabis users than in controls. Studies of acute administration of THC or marijuana report increased brain metabolism in several brain regions during impulsivity tasks. Structural imaging studies of cannabis users found differences in reduced prefrontal volumes and white matter integrity that might mediate the abnormal impulsivity and mood observed in marijuana users. To address the question whether impulsivity as a trait precedes cannabis consumption or whether cannabis aggravates impulsivity and discontinuation of usage more longitudinal study designs are warranted.

Rationale: It has been proposed that green tea extract may have a beneficial impact on cognitive functioning, suggesting promising clinical implications. However, the neural mechanisms underlying this putative cognitive enhancing effect of green tea extract still remain unknown. Objectives: This study investigates whether the intake of green tea extract modulates effective brain connectivity during working memory processing and whether connectivity parameters are related to task performance. Material and methods: Using a double-blind, counterbalanced, within-subject design, 12 healthy volunteers received a milk whey-based soft drink containing 27.5g of green tea extract or a milk whey-based soft drink without green tea as control substance while undergoing functional magnetic resonance imaging. Working memory effect on effective connectivity between frontal and parietal brain regions was evaluated using dynamic causal modeling. Results: Green tea extract increased the working memory induced modulation of connectivity from the right superior parietal lobule to the middle frontal gyrus. Notably, the magnitude of green tea induced increase in parieto-frontal connectivity positively correlated with improvement in task performance. Conclusions: Our findings provide first evidence for the putative beneficial effect of green tea on cognitive functioning, in particular, on working memory processing at the neural system level by suggesting changes in short-term plasticity of parieto-frontal brain connections. Modeling effective connectivity among frontal and parietal brain regions during working memory processing might help to assess the efficacy of green tea for the treatment of cognitive impairments in psychiatric disorders such as dementia.

Probabilistic databases (PDBs) are usually incomplete, e.g., containing only the facts that have been extracted from the Web with high confidence. However, missing facts are often treated as being false, which leads to unintuitive results when querying PDBs. Recently, open-world probabilistic databases (OpenPDBs) were proposed to address this issue by allowing probabilities of unknown facts to take any value from a fixed probability interval. In this paper, we extend OpenPDBs by Datalog+/- ontologies, under which both upper and lower probabilities of queries become even more informative, enabling us to distinguish queries that were indistinguishable before. We show that the dichotomy between P and PP in (Open)PDBs can be lifted to the case of first-order rewritable positive programs (without negative constraints); and that the problem can become NP^PP-complete, once negative constraints are allowed. We also propose an approximating semantics that circumvents the increase in complexity caused by negative constraints.

Background There is urgent need to improve the limited prognostic accuracy of psychopathology-based classifications to predict the onset of psychosis in clinical high-risk (CHR) subjects for psychosis. However, as yet no reliable biological marker has been established to differentiate CHR subjects who will develop psychosis from those who will not. This study investigated abnormalities in graph-based gyrification connectome in CHR subjects and patients with first-episode psychosis (FEP) and tested the accuracy of this systems-based approach to predict the transition to psychosis among CHR individuals. Methods 44 healthy controls (HC), 63 at-risk mental state (ARMS) subjects without later transition to psychosis (ARMS-NT), 16 ARMS subjects with later transition (ARMS-T), and 38 antipsychotic-free patients with FEP were recruited from the specialized clinic for the early detection of psychosis at the Department of Psychiatry, University of Basel, Basel, Switzerland. Gyrification-based structural covariance networks (connectomes) were constructed to quantify global integration, segregation and small-worldness. Extremely randomized trees with repeated, nested cross-validation was performed to differentiate ARMS-T from ARMS-NT individuals. Permutation testing was used to assess the significance of classification performance measures. Results Small-worldness is reduced in both ARMS-T and FEP patients, secondary to reduced integration and increased segregation in both groups. In addition, we also found that transitivity (segregation) was significantly higher in ARMS-T and FEP groups compared to both ARMS-NT and healthy controls. Using the connectome properties as features, we obtained a high classification accuracy of 90% (balanced accuracy: 81%, positive predictive value: 85%, negative predictive value: 92%.) All performance measures were highly significant as indicated by permutation tests (all p < 0.01). Discussion Our findings suggest that there is poor integration in the coordinated development of cortical folding in patients who develop psychosis. This study further indicates that gyrification-based connectomes might be a promising means to generate systems-based measures from anatomical data that improves individual prediction of psychosis transition in CHR subjects.

Background Present pharmacological treatment approaches in schizophrenia rest on “neuroleptic” drugs, all of which act as antagonists at dopamine D2/D3 receptors but additionally display major variability in their binding capacity to neurotransmitter receptors (Van Os & Kapur 2009). At present, the choice of any particular drug does not rest on any principled criteria: Once individual treatment has been started, therapeutic efficacy is monitored clinically, and a switch to a different drug is initiated when clear improvements remain absent after a few weeks. It is presently not possible to predict in advance which patients will respond well to a particular drug and who will experience little or no benefit (Case et al. 2011; Kapur et al. 2012). For instance, clozapine and olanzapine are often prescribed after other antipsychotics have shown to be ineffective in patients with schizophrenia or related disorders due to their pronounced side-effects. Both drugs, clozapine and olanzapine, share certain pharmacodynamic properties with comparatively low affinity towards dopamine D2-receptors, but very high affinity towards muscarinic receptors – a unique constellation that distinguishes them from other common antipsychotics. Importantly, previous studies have shown that a subgroup of schizophrenia patients might particularly benefit from these properties (Raedler et al. 2003, Scarr et al. 2009). Here, we present an ongoing observational study (COMPASS) which builds on these observations and addresses the question whether functional readouts of dopaminergic and muscarinic systems in individual patients could enable personalised treatment predictions. Guided by the dysconnection hypothesis of schizophrenia (Stephan et al., 2009), which postulates aberrant interactions between NMDA receptors and neuromodulators like dopamine/acetylcholine, the COMPASS study adopts a neuromodeling approach. The focus is on EEG/fMRI paradigms and computational models with empirically demonstrated sensitivity for altered function of NMDA, dopamine and muscarinic receptors, respectively. Methods To detect even small effect sizes, the study aims to recruit N=120 patients with schizophrenia who begin treatment with, switch to, or augment medication with olanzapine or clozapine. If possible, a replication sample (an additional N=120) will be recruited, too. Patients will be examined +/- 96h relative to treatment onset. Data acquisition encompasses the following measurements: Clinical interview, EEG (working memory, reward learning under volatility, auditory MMN under volatility, “resting”-state), MRI (optional; fMRI during auditory MMN under volatility, “resting”-state, and structural imaging), blood samples (genetic and biochemical analyses). After 2 and 8 weeks a clinical follow-up is conducted. Results The study is ongoing. Discussion The EEG/fMRI data will be analysed by computational models that infer functional states of glutamatergic, dopaminergic, and cholinergic systems (for review, Stephan et al. 2015). Model parameter estimates will serve as features in machine learning analyses of treatment prediction (Brodersen et al. 2014). If successful, this proof-of-concept study will lead to clinically useful tests for predicting the efficacy of clozapine/olanzapine prior to or during very early treatment. This could have a significant impact on clinical management as it would enable predicting, at an early stage, the therapeutic benefit for individual patients. Our neuromodeling approach to individual predictions may thus provide a principled basis for treatment decisions, help spare side-effects and enable informed switches in treatment strategy.

Background Psychotic disorders are associated with serious deterioration in functioning even before the first psychotic episode. Also on clinical high risk (CHR) states of developing a first psychotic episode, several studies reported a decreased global functioning. In a considerable proportion of CHR individuals, functional deterioration remains even after (transient) remission of symptomatic risk indicators. Furthermore, deficits in functioning cause immense costs for the health care system and are often more debilitating for individuals than other symptoms. However in the past, CHR research has mostly focused on clinical outcomes like transition and therefore, functioning in CHR patients is under-investigated. The current study aims at predicting functioning at a single subject level applying multi pattern recognition to clinical data for the first time. Methods PRONIA (‘Personalized Prognostic Tools for Early Psychosis Management’) is a prospective collaboration project funded by the European Union under the 7th Framework Programme (grant agreement n° 602152). Considering a broad set of variables (sMRI, rsMRI, DTI, psychopathological, life event related and sociobiographic data, neurocognition, genomics and other blood derived parameters) as well as advanced statistical methods, PRONIA aims at developing an innovative multivariate prognostic tool enabling an individualized prediction of illness trajectories and outcome. Seven university centers in five European countries and in Australia (Munich, Basel, Birmingham, Cologne, Melbourne, Milan/Udine, Turku) participate in the evaluation of three clinical groups (subjects clinically at high risk of developing a psychosis [CHR], patients with a recent onset psychosis [ROP] and patients with a recent onset depression [ROD]) as well as healthy controls. In the current study, we analysed data of 114 CHR patients. Functioning was measured by the ‘Global Functioning: Social and Role’ Scales (GF S/R). Features were derived from the large pool of clinical data that were assessed in PRONIA including questionnaires measuring CHR criteria as well as psychopathology, family history of psychotic disorders or treatment and various self-rating scales. Feature Elimination method of a strict Wrapper was used to identify most predictive variables from the multitude of clinical data included into the analysis. Results Balanced Accuracy of predicting social functioning in CHR patients was acceptable (pooled cross-validation: BAC = 74.3%, Sens = 72.8%, Spec = 60.3%; leave-site-out cross-validation: BAC = 69.9%, Sens = 84.3%, Spec = 55.6%). In contrast, applying the strict wrapper model revealed worse prediction performance for role functioning. Which might indicate that predicting level of role functioning requires more information than social functioning. As expected, prior functioning levels were identified as main predictive factor but also distinct protective and risk factors were selected into the prediction models. Discussion Identifying single predictive variables is in purpose of a much more efficient prognostic process. Moreover, understanding the mechanisms underlying functional decline and its illness related pattern might enable an improved definition of targets for intervention. Future research should aim at further maximisation of prediction accuracy and cross-centre generalisation capacity. In addition, other functioning outcomes as well as clinical outcomes need to be focused on.

Background Neuro-cognitive deficits are a core feature of psychosis. In the clinical high risk stages of psychosis, neuro-cognitive deficits qualitatively affect the same functions while being quantitatively less marked compared to those in full-blown disorder. Therefore, cognitive impairments are considered to be an important intermediate phenotype for transition to psychosis. Partially overlapping deficits were also reported in depressive disorders, so it is important to identify deficits specifically associated to psychotic symptoms from those common to other conditions. We aimed to identify and differentiate cognitive deficits specifically associated to [i] psychopathology in general (i.e., presence of clinical diagnosis); [ii] psychotic symptoms; [iii] sub- and threshold levels of psychotic symptoms. Methods We compared four groups of participants within the project Personalised Prognostic Tools for Early Psychosis Management (PRONIA; www.pronia.eu). The PRONIA Cognitive Battery (PCB) includes 10 tests selected as reliable measures of neuropsychological difficulties in patients at high-risk of psychosis. The scores were obtained from the PRONIA Discovery Sample, which included 707 participants: 278 healthy controls (HC); 138 recent-onset depression (ROD); 139 clinical high-risk (CHR); 152 recent-onset psychosis (ROP), tested in seven sites across Europe. At first the norms were calculated correcting the HC’s raw scores by sex, age, cognitive level, education, and mother language (English, Finnish, German, Italian, or other). Then, univariate analyses of variance with a priori contrasts were used for directly comparing [i] HC vs ROD/CHR/ROP; [ii] ROD vs CHR/ROP; [iii] CHR vs ROP. Results The difference in cognitive performance between the clinical groups (ROD, CHR, ROP) as compared to the HC [i], was shown in measures of: speed of execution (ωP2 range 0.016–0.123; all p≤0.035); sustained attention (ωP2: 0.024–0.080; p≤0.022); verbal fluency (ωP2: 0.020–0.031; p≤0.002); emotion recognition (ωP2=0.026; p=0.001); visuo-spatial (ωP2: 0.018–0.049; p≤0.006) and verbal (ωP2: 0.038–0.075; p

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Structural brain abnormalities are central to schizophrenia (SZ), but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness. Therefore, we investigated whether patients with SZ (N = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N = 57), and individuals in at-risk mental states for psychosis (ARMS; N = 89) deviated from the trajectory of normal brain maturation. This deviation was measured as difference between chronological and the neuroanatomical age (brain age gap estimation [BrainAGE]). Neuroanatomical age was determined by a machine learning system trained to individually estimate age from the structural magnetic resonance imagings of 800 healthy controls. Group-level analyses showed that BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and the ARMS (+1.7) groups. Earlier disease onset in MD and BPD groups correlated with more pronounced BrainAGE, reaching effect sizes of the SZ group. Second, BrainAGE increased across at-risk, recent onset, and recurrent states of SZ. Finally, BrainAGE predicted both patient status as well as negative and disorganized symptoms. These findings suggest that an individually quantifiable "accelerated aging" effect may particularly impact on the neuroanatomical signature of SZ but may extend also to other mental disorders.

Objectives To evaluate whether biases may influence the findings of whole-brain structural imaging literature. Methods Forty-seven whole-brain voxel-based meta-analyses including voxel-based morphometry (VBM) studies in neuropsychiatric conditions were included, for a total of 324 individual VBM studies. The total sample size, the overall number of foci, and different moderators were extracted both at the level of the individual studies and at the level of the meta-analyses. Results Sample size ranged from 12 to 545 (median n = 47) per VBM study. The median number of reported foci per study was six. VBM studies with larger sample sizes reported only slightly more abnormalities than smaller studies (2% increase in the number of foci per 10-patients increase in sample size). A similar pattern was seen in several analyses according to different moderator variables with some possible modulating evidence for the statistical threshold employed, publication year and number of coauthors. Whole-brain meta-analyses (median sample size n = 534) found fewer foci (median = 3) than single studies and overall they showed no significant increase in the number of foci with increasing sample size. Meta-analyses with ≥10 VBM studies reported a median of three foci and showed a significant increase with increasing sample size, while there was no relationship between sample size and number of foci (median = 5) in meta-analyses with

Aims: Despite growing research in the field of cannabis imaging, mostly in those with a psychotic illness, the possible neurotoxic effects of smoked cannabis on the healthy brain have yet to be fully understood. There appears to be a need to evaluate the existing imaging data on the neuroanatomical effects of cannabis use on non-psychotic populations. Methods: We conducted a meta-analytical review to estimate the putative neurotoxic effect of cannabis in non-psychotic subjects who were using or not using cannabis. We specifically tested the hypothesis that cannabis use can alter grey and white matter in nonpsychotic subjects. Results: Our systematic literature search uncovered 14 studies meeting the inclusion criteria for the metaanalysis. The overall database comprised 362 users and 365 non-users. At the level of the individual studies there is limited and contrasting evidence supporting a cannabis-related alteration on the white and grey matter structures of non-psychotic cannabis users. However, our meta-analysis showed a consistent smaller hippocampus in users as compared to nonusers. Heterogeneity across study designs, image acquisition, small sample sizes and limited availability of regions of interest to be included in the meta-analysis may undermine the core findings of this study. Conclusions: Our results suggest that in the healthy brain, chronic and long-term cannabis exposure may exert significant effects in brain areas enriched with cannabinoid receptors, such as the hippocampus, which could be related to a neurotoxic action.

Context Antipsychotic treatment is the first-line treatment option for schizophrenia. Individual studies suggested they can significantly affect brain structure and account for progressive brain changes observed during the illness. Objectives To quantitatively examine the effect of antipsychotics as compared to illness related factors on progressive brain changes in schizophrenia. Data sources Electronic databases were searched until April 2012. All magnetic resonance imaging studies reporting progressive brain changes in schizophrenia subjects and antipsychotic exposure were retrieved. Study selection 30 longitudinal MRI studies with antipsychotic administration in schizophrenia patients met the inclusion criteria. Data extraction Brain volumes before and after antipsychotic exposure, duration of illness, severity of psychotic symptoms as well as demographic, clinical, and methodological variables were extracted from each publication, or obtained directly from its authors. Data synthesis The overall sample was of 1046 schizophrenia patients and 780 controls for a median duration of follow-up of 72.4 weeks. At baseline, patients showed significant whole brain volume reductions and enlarged lateral ventricle (LV) volumes compared to controls. No baseline volumetric abnormalities were detected in the gray matter volumes (GMV), white matter volumes, cerebrospinal fluid and caudate nucleus. Longitudinally, there were progressive GMV decreases and LV enlargements in patients but not in controls. The GMV decreases were inversely correlated with cumulative exposure to antipsychotic treatments, while no effects were observed for duration of illness or illness severity. Conclusions Schizophrenia is characterized by progressive gray matter volume decreases and lateral ventricular volume increases. Some of these neuroanatomical alterations may be associated with antipsychotic treatment.

Hintergrund: In der vorliegenden Arbeit wird der Zusammenhang zwischen der Posttraumatischen Belastungsstörung (PTBS) nach einem einmalig vorgekommenen Trauma und dem Heroinkonsum, der Schwere der Abhängigkeit und der Schwere der psychischen Gesamtsymptomatik sowie geschlechtsspezifische Unterschiede untersucht. Methode: Bei 48 opiatabhängigen methadonsubstituierten Patienten mit einem traumatischen Ereignis in der Anamnese, welches einmalig erlebt wurde, haben wir anhand mehrerer Interviews das Vorliegen einer PTBS, sowie den Heroingebrauch, die Schwere der Abhängigkeit (Addiction Severity Index; ASI) und die Schwere der psychischen Gesamtsymptomatik (Symptom Checkliste; SCL-90-R) untersucht. Ergebnisse: Insgesamt zeigten 18 Patienten (37 %) eine PTBS (8 Frauen, 10 Männer). Der Heroingebrauch der letzten 6 Monate lag bei der Gruppe mit PTBS signifikant niedriger. Die Schwere der Abhängigkeit war bei der Gruppe mit PTBS signifikant grösser. Bezogen auf die Gesamtgruppe (mit und ohne PTBS) lag die Schwere der Abhängigkeit (ASI) bei den Frauen höher als bei den Männern, insbesondere bezüglich der Bereiche «familiär/sozial» und «Drogen». Bei der Gruppe mit PTBS zeigte sich eine signifikant schwerere Beeinträchtigung durch die Abhängigkeit bezüglich des Bereichs «Arbeit/Unterhalt». Die Schwere der psychischen Gesamtsymptomatik zeigte keinen signifikanten Unterschied zwischen dem Vorliegen oder Fehlen einer PTBS. Diskussion: Die erhobenen Befunde entsprechen dem aktuellen Stand der Forschung über PTBS mit Substanzabhängigkeit. Es konnte zusätzlich gezeigt werden, dass der Heroingebrauch bei der Gruppe mit PTBS nach einmalig aufgetretenem Trauma signifikant niedriger war als der bei der Gruppe ohne PTBS. Es macht deutlich, dass die Rolle der Opioide im Zusammenhang mit den klassischen Symptomen der PTBS komplex ist und weiterer Untersuchungen bedarf.

Hintergrund: In Basel haben wir verschiedene Studien zur Verbesserung der Methodik zur Fruherkennung von Psychosen (FePsy) durchgefuhrt. Methodik: Vom 01.03.2000 bis 29.02.2004 wurden 234 Individuen mithilfe des Basler Screening Instruments fur Psychosen (BSIP) gescreent. Bei 10 6 Patienten konnte ein Risikostatus fur Psychosen diagnostiziert werden, 53 davon konnten bis zu 7 Jahre (Mittel 5. 4 Jahre) nachuntersucht werden. Die weiteren Untersuchungen erfolgten u.a. mit einem spezifisch entwickelten Anamnese - Instrument, verschiedenen Skalen zur Psychopathologie, Untersuchungen der Neuropsychologie u n d Feinmotorik , klinische m und quantitative m EEG, MRI des Gehirns, Labor. Ergebnisse: Allein auf der Basis des BSIP konnte eine relativ zuverlassige Vorher sage getroffen werden: 21 (39.6 % ) der als „ Risikopatienten “Identifizierten entwickelten innerhalb der Beobachtungszeit tatsachlich eine Psychose. Post hoc konnte durch spezifischere Gewichtung der Psychopathologie und Einbezug neuropsychologischer Untersuchungen die Vorhersagegenauigkeit auf 81 % gesteigert werden. Die anderen oben genannten Verfahren konnen offensichtlich zur weiteren Verbesserung der Pradiktion beitragen. Schlussfolgerungen: Die Risikoabklarung fur Psychose sollte stufenweise und unter Einbezug verschiedener Untersuchungsebenen erfolgen. Background: We have conducted various studies in Basel with the aim of improving the methods for the early detection of psychosis (Fruherkennung von Psychosen, FePsy).Methods: From 1.3.2000 to 29.2.2004 234 individuals were screened using the Basel Screening Instrument for Psychosis (BSIP). 106 patients were identified as at risk for psychosis; out of these 53 remained in follow-up for up to 7 years (mean 5.4 years). The assessments were done with a specifically developed instrument for history taking, various scales for the psychopathology, assessments of neuropsychology and fine motor functioning, clinical and quantitative EEG, MRI of the brain, laboratory etc.Results: Based on the BSIP alone, a relatively reliable prediction was possible: 21 (39.6 %) of the individuals identified as at risk developed psychosis within the follow-up time. Post-hoc prediction could be improved to 81 % by weighting psychopathology and including neuropsychology. Including the other domains obviously allows further improvements of prediction.Conclusions: The risk for psychosis should be assessed in a stepwise procedure. In a first step, a clinically oriented screening should be conducted. If an at-risk status is found, further assessments in various domains should be done in a specialised centre.

Department of Psychology, University of Basel, Basel, SwitzerlandBackground: Euphoria has been described in heroin‐dependentindividuals after heroin administration. However, affective distur-bances and disorders are common in heroin dependence. The presentstudy examined the acute effects of heroin on emotions in heroin‐dependent patients.Methods: This randomized controlled crossover trial included 28heroin‐dependent patients (67.9% male, n ¼ 19) in stable heroin‐assisted treatment and 20 healthy controls. The patients wereadministered heroin or saline (placebo), the controls were adminis-tered saline. Data measuring mood, affects and heroin craving (BDI,AMRS, STAI, STAXI, and HCQ) were assessed before and60 minutes after substance injection.Results: Before substance injection, heroin‐dependent patientsshowed significantly higher levels of anxiety and depression thanhealthycontrols(p < .0001).Heroinadministration—butnotplaceboadministration—was associated with a significant decrease in allnegative emotions, including craving, and a significant increase inemotional well‐being (p < .0001), irrespective of perceived intoxi-cation and sedation. After the experiment, the patients did not differfromhealthycontrolsintheiremotions,oncetheyhadreceivedheroin.Conclusions: Heroin dampens craving, negative emotions, andincreases positive emotions. These findings indicate that heroinregulates emotions and underscore the clinical benefit of opioidsubstitution treatment for heroin‐dependent patients. (Am J Addict2013;XX:1–7)

Introduction: Pre-psychotic and early psychotic characteristics are investigated in the high-risk (HR) populations for psychosis. There are two different approaches based either on hereditary factors (genetic high risk, G-HR) or on the clinically manifested symptoms (clinical high risk, C-HR). Common features are an increased risk for development of psychosis and similar cognitive as well as structural and functional brain abnormalities. Methods: We reviewed the existing literature on longitudinal structural, and on functional imaging studies, which included G-HR and/or C-HR individuals for psychosis, healthy controls (HC) and/or first episode of psychosis (FEP) or schizophrenia patients (SCZ). Results: With respect to structural brain abnormalities, vulnerability to psychosis was associated with deficits in frontal, temporal, and cingulate regions in HR, with additional insular and caudate deficits in C-HR population. Furthermore, C-HR had progressive prefrontal deficits related to the transition to psychosis. With respect to functional brain abnormalities, vulnerability to psychosis was associated with prefrontal, cingulate and middle temporal abnormalities in HR, with additional parietal, superior temporal, and insular abnormalities in C-HR population. Transition-to-psychosis related differences emphasized prefrontal, hippocampal and striatal components, more often detectable in C-HR population. Multimodal studies directly associated psychotic symptoms displayed in altered prefrontal and hippocampal activations with striatal dopamine and thalamic glutamate functions. Conclusion: There is an evidence for similar structural and functional brain abnormalities within the whole HR population, with more pronounced deficits in the C-HR population. The most consistent evidence for abnormality in the prefrontal cortex reported in structural, functional and multimodal studies of HR population may underlie the complexity of higher cognitive functions that are impaired during HR mental state for psychosis.

The hippocampal formation has been studied extensively in schizophrenic psychoses and alterations in hippocampal anatomy have been consistently reported. Chronic schizophrenia seems to be associated with bilateral hippocampal volume (HV) reduction, while in patients with an at-risk mental state (ARMS) there are contradictory results. This is the first region of interest (ROI) based follow-up MRI study of hippocampal volume comparing ARMS individuals with and without transition to psychosis. The aim was to investigate the timing of HV changes in ARMS in the early phase of psychosis. METHODS: Magnetic resonance imaging data from 18 antipsychotic-naive individuals with an ARMS were collected within the FePsy-clinic for early detection of psychoses. During follow-up 8 subjects transitioned to psychosis (ARMS-T) and 10 did not (ARMS-NT). Subjects were re-scanned after the onset of psychosis or at the end of the follow-up if they did not develop psychosis. RESULTS: Across both groups there was a significant decrease in HV over time (p