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Previous research showed that dysfunctions of fronto-striatal neural networks are implicated in the pathophysiology of obsessive–compulsive disorder (OCD). Accordingly, patients with OCD showed altered performances during decision-making tasks. As P300, evoked by oddball paradigms, is suggested to be related to attentional and cognitive processes and generated in the medial temporal lobe and orbitofrontal and cingulate cortices, it is of special interest in OCD research. Therefore, this study aimed to investigate P300 in OCD and its associations with brain activity during decision-making: P300, evoked by an auditory oddball paradigm, was analysed in 19 OCD patients and 19 healthy controls regarding peak latency, amplitude and source density power in parietal cortex areas by sLORETA. Afterwards, using a fMRI paradigm, Blood–oxygen-level-dependent (BOLD) contrast imaging was conducted during a delay-discounting paradigm. We hypothesised differences between groups regarding P300 characteristics and associations with frontal activity during delay-discounting. The P300 did not differ between groups, however, the P300 latency over the P4 electrode correlated negatively with the NEO-FFI score openness to experience in patients with OCD. In healthy controls, P300 source density power correlated with activity in frontal regions when processing rewards, a finding which was absent in OCD patients. To conclude, associations of P300 with frontal brain activation during delay-discounting were found, suggesting a contribution of attentional or context updating processes. Since this association was absent in patients with OCD, the findings could be interpreted as being indeed related to dysfunctions of fronto-striatal neural networks in patients with OCD.

Negative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (SIPS-N), whole-brain gyrification, or both to forecast negative symptoms of at least moderate severity in 94 CHR. We also conducted sequential risk stratification to stratify CHR into different risk groups based on the SIPS-N and gyrification model. Additionally, we assessed the models’ ability to predict functional outcomes in CHR and their transdiagnostic generalizability to predict negative symptoms in 96 patients with recent-onset psychosis (ROP) and 97 patients with recent-onset depression (ROD). Baseline SIPS-N and gyrification predicted moderate/severe negative symptoms with significant balanced accuracies of 68 and 62%, while the combined model achieved 73% accuracy. Sequential risk stratification stratified CHR into a high (83%), medium (40–64%), and low (19%) risk group regarding their risk of having moderate/severe negative symptoms at 9 months follow-up. The baseline SIPS-N model was also able to predict social (61%), but not role functioning (59%) at above-chance accuracies, whereas the gyrification model achieved significant accuracies in predicting both social (76%) and role (74%) functioning in CHR. Finally, only the baseline SIPS-N model showed transdiagnostic generalization to ROP (63%). This study delivers a multimodal prognostic model to identify those CHR with a clinically relevant negative symptom severity and functional impairments, potentially requiring further therapeutic consideration.

Background Research on patients at clinical high risk (CHR) for psychosis has so far mainly focused on those with transition to frank psychosis (CHR-T patients). However, the majority of CHR patients do not transition (CHR-NT patients) and relatively little information is available on their clinical and functional outcome. Methods We conducted a systematic review on clinical and functional long-term outcome of CHR-NT patients. Studies were included if they had an average follow-up period of at least 24 months and reported on long-term outcome of CHR-NT patients in one or more of the following domains: (non-)remission from CHR, prevalence of clinical symptoms and/or clinical diagnoses (axis I and II), and psychosocial functioning. Results Ten publications from seven different single or multicenter studies with average follow-up durations of 2–7.5 years could be included. At the last follow-up assessment 28–71% of CHR-NT patients were not remitted from their CHR and 22–82% still had at least one clinical diagnosis. Approximately half of CHR-NT patients presented with poor psychosocial outcome at 2-year and 6-year follow-up. Conclusions The results suggest that, in the long-term, the majority of CHR-NT patients are not in full clinical remission and seem to suffer from one or more clinical disorders and psychosocial impairments. Since relatively few studies could be identified, further research is required to better understand the trajectories and clinical needs of CHR-NT patients.

SUMMARYEarly detection and specialised early intervention for people at high risk for psychotic disorders have received growing attention in the past few decades, with the aim of delaying or preventing the outbreak of explicit psychotic symptoms and improving functional outcomes. This article summarises criteria for a diagnosis of high psychosis risk, the implications for such a diagnosis and recommendations for treatment.LEARNING OBJECTIVESAfter reading this article you will be able to: •recognise signs and symptoms indicating increased psychosis risk•understand uses and limitations of screening for high psychosis risk, and interpretation of results•recognise evidence-based treatment options for patients at clinical high risk for psychosis.DECLARATION OF INTERESTC.A. has received non-financial support from Sunovion and Lundbeck in the past 36 months.

Schizophrenia has a prodromal phase of several years in most patients, making it possible to identify patients at clinical high risk (CHR) for developing the disorder. So far, these individuals are identified based on clinical criteria alone, and there is no reliable biomarker for predicting the transition to psychosis. It is well-established that reductions in brain volume, especially in the hippocampus, are associated with schizophrenia. Therefore, hippocampal volume may serve as a biomarker for psychosis. Several studies have already investigated hippocampal volume in CHR groups. Based on these studies, the present meta-analysis compares the baseline left and right hippocampal volume of CHR patients who developed a psychosis with that of CHR patients without such a transition. Our results show no statistically significant effect of the hippocampal volume on the transition risk for psychosis.

Resting-state EEG microstates are brief (50–100 ms) periods, in which the spatial configuration of scalp global field power remains quasi-stable before rapidly shifting to another configuration. Changes in microstate parameters have been described in patients with psychotic disorders. These changes have also been observed in individuals with a clinical or genetic high risk, suggesting potential usefulness of EEG microstates as a biomarker for psychotic disorders. The present study aimed to investigate the potential of EEG microstates as biomarkers for psychotic disorders and future transition to psychosis in patients at ultra-high-risk (UHR). We used 19-channel clinical EEG recordings and orthogonal contrasts to compare temporal parameters of four normative microstate classes (A–D) between patients with first-episode psychosis (FEP; n = 29), UHR patients with (UHR-T; n = 20) and without (UHR-NT; n = 34) later transition to psychosis, and healthy controls (HC; n = 25). Microstate A was increased in patients (FEP & UHR-T & UHR-NT) compared to HC, suggesting an unspecific state biomarker of general psychopathology. Microstate B displayed a decrease in FEP compared to both UHR patient groups, and thus may represent a state biomarker specific to psychotic illness progression. Microstate D was significantly decreased in UHR-T compared to UHR-NT, suggesting its potential as a selective biomarker of future transition in UHR patients.

Background: Targeting the N-methyl-d-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with schizophrenia, but also in healthy controls receiving ketamine. Accordingly, it was the aim of the present study to investigate whether changes of MMN amplitudes during ketamine administration are associated with the emergence of schizophrenia-like negative symptoms in healthy volunteers. Methods: We examined the impact of ketamine during an MMN paradigm with 64-channel electroencephalography (EEG) and assessed the psychopathological status using the Positive and Negative Syndrome Scale (PANSS) in healthy male volunteers using a single-blind, randomized, placebo-controlled crossover design. Low-resolution brain electromagnetic tomography was used for source localization. Results: Twenty-four men were included in our analysis. Significant reductions of MMN amplitudes and an increase in all PANSS scores were identified under the ketamine condition. Smaller MMN amplitudes were specifically associated with more pronounced negative symptoms. Source analysis of MMN generators indicated a significantly reduced current source density (CSD) under the ketamine condition in the primary auditory cortex, the posterior cingulate and the middle frontal gyrus. Limitations: The sample included only men within a tight age range of 20–32 years. Conclusion: The MMN might represent a biomarker for negative symptoms in schizophrenia related to an insufficient NMDAR system and could be used to identify patients with schizophrenia with negative symptoms due to NMDAR dysfunction.

Study drop-out during follow-up and service disengagement frequently occur in patients at clinical high risk for psychosis (CHR-P). However, little is known about their predictors. Therefore, we aimed to analyze the rate and reasons for drop-out and service disengagement in CHR-P patients and investigate their sociodemographic and clinical predictors. Data from 200 patients of the prospective Fruherkennung von Psychosen (FePsy) study were analyzed with competing risks survival models, considering drop-out and transition to psychosis as competing events. To investigate whether symptoms changed immediately before drop-out, t tests were applied. Thirty-six percent of patients dropped out within 5 years. Almost all drop-outs also disengaged from our service. Hence, study drop-out was used as a proxy for service disengagement. Patients with more severe baseline disorganized symptoms and a late inclusion into the study were significantly more likely to disengage. Immediately before disengagement, there was significant improvement in negative symptoms only. A considerable proportion of CHR-P patients disengaged from our clinical study and service. Patients who were included during a later study period with more assessments disengaged more often, which might have been due to more frequent invitations to follow-up assessments and thereby increasing participation burden. Hence, our study provides a cautionary note on high-frequency follow-up assessments. Larger-scale studies evaluating predictors on multiple domains would help to further elucidate drop-out and disengagement.

Depressive symptoms in subjects at Clinical High Risk for Psychosis (CHR-P) or at first-episode psychosis (FEP) are often treated with antidepressants. Our cross-sectional study investigated whether brain morphology is altered by antidepressant medication. High-resolution T1-weighted structural MRI scans of 33 CHR-P and FEP subjects treated with antidepressants, 102 CHR-P and FEP individuals without antidepressant treatment and 55 controls, were automatically segmented using Freesurfer 6.0. Linear mixed-effects modelling was applied to assess the differences in subcortical volume, surface area and cortical thickness in treated, non-treated and healthy subjects, taking into account converted dosages of antidepressants. Increasing antidepressant dose was associated with larger volume of the pallidum and the putamen, and larger surface of the left inferior temporal gyrus. In a pilot subsample of separately studied subjects of known genomic risk loci, we found that in the right postcentral gyrus, the left paracentral lobule and the precentral gyrus antidepressant dose-associated surface increase depended on polygenic schizophrenia-related-risk score. As the reported regions are linked to the symptoms of psychosis, our findings reflect the possible beneficial effects of antidepressant treatment on an emerging psychosis.

Background:Few studies have followed up patients with a clinical high risk (CHR) for psychosis for more than 2–3 years. We aimed to investigate the rates and baseline predictors for remission from CHR and transition to psychosis over a follow-up period of up to 16 years. Additionally, we examined the clinical and functional long-term outcome of CHR patients who did not transition.Methods:We analyzed the long-term course of CHR patients that had been included in the longitudinal studies “Früherkennung von Psychosen” (FePsy) or “Bruderholz” (BHS). Those patients who had not transitioned to psychosis during the initial follow-up periods (2/5 years), were invited for additional follow-ups.Results:Originally, 255 CHR patients had been included. Of these, 47 had transitioned to psychosis during the initial follow-ups. Thus, 208 were contacted for the long-term follow-up, of which 72 (34.6%) participated. From the original sample of 255, 26%, 31%, 35%, and 38% were estimated to have transitioned after 3, 5, 10, and 16 years, respectively, and 51% had remitted from their high risk status at the latest follow-up. Better psychosocial functioning at baseline was associated with a higher rate of remission. Of the 72 CHR patients re-assessed at long-term follow-up, 60 had not transitioned, but only 28% of those were fully recovered clinically and functionally.Conclusions:Our study shows the need for follow-ups and clinical attention longer than the usual 2–3 years as there are several CHR patients with later transitions and only a minority of CHR those without transition fully recovers.

AIM Ultrahigh risk (UHR) criteria, consisting of brief limited intermittent psychotic symptoms (BLIPS), attenuated psychotic symptoms (APS) and genetic risk and deterioration (GRD) syndrome are the most widely used criteria for assessing the clinical high-risk state for psychosis (CHR-P). The Basel Screening Instrument for Psychosis (BSIP) includes a further risk category, the unspecific risk category (URC). However, little is known about the predictive power of this risk category compared to other risk categories. METHODS Two hundred CHR-P patients were detected as part of the Fruherkennung von Psychosen (FePsy) study using the BSIP. Transition to psychosis was assessed in regular intervals for up to 7 years. RESULTS Patients meeting only the URC criterion (n = 40) had a significantly lower risk of transition to psychosis than the UHR group (including BLIPS, APS and GRD) (HR 0.19 [0.05; 0.80] (P = 0.024). Furthermore, the URC only risk group had a lower transition risk than the APS without BLIPS group (P = 0.015) and a trendwise lower risk than the BLIPS group (P = 0.066). However, despite the lower transition risk in the URC only group, there were still two patients (5%) in this group with a later transition to psychosis. CONCLUSIONS The URC includes patients who have a lower risk of transition than those included by the UHR categories and thereby increases the sensitivity of the BSIP. This offers the possibility of a stratified intervention, with these subjects receiving low intensity follow-up and treatment.

Objectives: Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive processes. Since cognitive deficits are a core feature of psychotic disorders, the investigation of BDNF levels in psychosis and their correlation with cognition has received increased attention. However, there are no studies investigating BDNF levels in individuals with an at-risk mental state (ARMS) for psychosis. Hence, the aims of the present study were: (1) assessing peripheral BDNF levels across different (potential) stages of psychosis; (2) investigating their association with cognition. Methods: Plasma and serum BDNF levels and neuropsychological performance were assessed in 16 ARMS, six first-episode psychosis (FEP), and 11 chronic schizophrenia (CS) patients. Neuropsychological assessment covered intelligence, verbal memory, working memory, attention and executive functioning. Results: Both plasma and serum BDNF levels were highest in CS, intermediate in FEP and lowest in ARMS. Multiple regression analysis revealed a significant positive association of plasma BDNF levels with planning ability across all groups. Conclusions: The lower peripheral BDNF levels in ARMS compared to FEP and CS might point towards an important drop of this neurotrophin prior to the onset of frank psychosis. The associations of peripheral BDNF with planning-abilities match previous findings.

Association Splitting, a novel cognitive intervention, was tested in patients with alcohol dependence as an add-on intervention in an initial randomized controlled trial. Preliminary support for Association Splitting has been found in patients with obsessive-compulsive disorder, as well as in an online pilot study of patients with alcohol use disorders. The present variant sought to reduce craving by strengthening neutral associations with alcohol-related stimuli, thus, altering cognitive networks. Eighty-four inpatients with verified diagnoses of alcohol dependence, who were currently undergoing inpatient treatment, were randomly assigned to Association Splitting or Exercise Therapy. Craving was measured at baseline, 4-week follow-up, and six months later with the Obsessive-Compulsive Drinking Scale (primary outcome) and the Alcohol Craving Questionnaire. There was no advantage for Association Splitting after three treatment sessions relative to Exercise Therapy. Among Association Splitting participants, 51.9% endorsed a subjective decline in craving and 88.9% indicated that they would use Association Splitting in the future. Despite high acceptance, an additional benefit of Association Splitting beyond standard inpatient treatment was not found. Given that participants were concurrently undergoing inpatient treatment and Association Splitting has previously shown moderate effects, modification of the study design may improve the potential to detect significant effects in future trials.

Several studies using electroencephalography (EEG) demonstrate that the processing of feedback in patients suffering from borderline personality disorder (BPD) is altered in comparison to healthy controls. Differences occur in the theta (ca. 5 Hz) and high-beta frequency-ranges (ca. 20 Hz) of oscillations in response to negative and positive feedback, respectively. However, alpha (ca. 10 Hz) and low-beta (ca. 15 Hz) oscillations have also been shown to be involved in feedback processing. We hypothesized that additional alterations might occur in these frequency ranges in BPD. Eighteen patients with BPD and twenty-two healthy controls performed a gambling task while 64-channel-EEG was recorded. Induced oscillatory responses to positive (i.e. gain) and negative (i.e. loss) feedback in the alpha and low-beta frequency range were investigated. No significant differences were found in the alpha frequency range. Regarding the low-beta frequency range a significant Group (i.e. BPD vs. healthy controls) × Valence (i.e. gain vs. loss) interaction in the time frame between 600 and 700 milliseconds after feedback was found. This effect showed a significant correlation with symptom severity (assessed with the BSL-23). The results indicate that feedback processing in BPD could be more heavily altered than previously expected, with more severe symptomatology being linked to stronger alterations in oscillatory responses to feedback in the low-beta range.

Grey matter (GM) volume alterations have been repeatedly demonstrated in patients with first episode psychosis (FEP). Some of these neuroanatomical abnormalities are already evident in the at-risk mental state (ARMS) for psychosis. Not only GM alterations but also neurocognitive impairments predate the onset of frank psychosis with verbal learning and memory (VLM) being among the most impaired domains. Yet, their interconnection with alterations in GM volumes remains ambiguous. Thus, we evaluated associations of different subcortical GM volumes in the medial temporal lobe with VLM performance in antipsychotic-naive ARMS and FEP patients. Data from 59 ARMS and 31 FEP patients, collected within the prospective Fruherkennung von Psychosen study, were analysed. Structural T1-weighted images were acquired using a 3 Tesla magnetic resonance imaging scanner. VLM was assessed using the California Verbal Learning Test and its factors Attention Span, Learning Efficiency, Delayed Memory and Inaccurate Memory. FEP patients showed significantly enlarged volumes of hippocampus, pallidum, putamen and thalamus compared to ARMS patients. A significant negative association between amygdala and pallidum volume and Attention Span was found in ARMS and FEP patients combined, which however did not withstand correction for multiple testing. Although we found significant between-group differences in subcortical volumes and VLM is among the most impaired cognitive domains in emerging psychosis, we could not demonstrate an association between low performance and subcortical GM volumes alterations in antipsychotic-naive patients. Hence, deficits in this domain do not appear to stem from alterations in subcortical structures.

Auditory verbal hallucinations (AVH) are a common positive symptom of schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed N-methyl-D-aspartate receptor (NMDAR) functioning has been suggested as a possible mechanism underlying altered connectivity and AVH in schizophrenia. The current study examined the effects of ketamine, a NMDAR antagonist, on glutamate-related mechanisms underlying interhemispheric gamma-band connectivity, conscious auditory perception during dichotic listening (DL), and the emergence of auditory verbal distortions and hallucinations (AVD/AVH) in healthy volunteers. In a single-blind, pseudo-randomized, placebo-controlled crossover design, nineteen male, right-handed volunteers were measured using 64 channel electroencephalography (EEG). Psychopathology was assessed with the PANSS interview and the 5D-ASC questionnaire, including a subscale to detect auditory alterations with regard to AVD/AVH (AUA-AVD/AVH). Interhemispheric connectivity analysis was performed using eLORETA source estimation and lagged phase synchronization (LPS) in the gamma-band range (30-100 Hz). Ketamine induced positive symptoms such as hallucinations in a subgroup of healthy subjects. In addition, interhemispheric gamma-band connectivity was found to be altered under ketamine compared to placebo, and subjects with AUA-AVD/AVH under ketamine showed significantly higher interhemispheric gamma-band connectivity than subjects without AUA-AVD/AVH. These findings demonstrate a relationship between NMDAR functioning, interhemispheric connectivity in the gamma-band frequency range between bilateral auditory cortices and the emergence of AVD/AVH in healthy subjects. The result is in accordance with the interhemispheric miscommunication hypothesis of AVH and argues for a possible role of glutamate in AVH in schizophrenia.

Background Verbal learning and memory are impaired not only in patients with a first episode of psychosis (FEP) but also–to a lower extent–in those with an at-risk mental state for psychosis (ARMS). However, little is known about the specific nature of these impairments. Hence, we aimed to study learning and memory processes in ARMS and FEP patients by making use of structural equation modelling. Methods Verbal learning was assessed with the California Verbal Learning Test (CVLT) in 98 FEP patients, 126 ARMS patients and 68 healthy controls (HC) as part of the Basel early detection of psychosis (FePsy) study. The four-factorial CFA model of Donders was used to estimate test performance on latent variables of the CVLT and growth curve analysis was used to model the learning curve. The latter allows disentangling initial recall, which is strongly determined by attentional processes, from the learning rate. Results The CFA model revealed that ARMS and FEP patients were impaired in Attention Span, Learning Efficiency and Delayed Memory and that FEP patients were additionally impaired in Inaccurate Memory. Additionally, ARMS-NT, but not ARMS-T, performed significantly worse than HC on Learning Efficiency. The growth curve model indicated that FEP patients were impaired in both initial recall and learning rate and that ARMS patients were only impaired in the learning rate. Conclusions Since impairments were more pronounced in the learning rate than the initial recall, our results suggest that the lower scores in the CVLT reported in previous studies are more strongly driven by impairments in the rate of learning than by attentional processes.

The aim of the present study was to investigate the effects of comorbid obsessive-compulsive symptoms (OCS) on the perception of insincere speech (e.g., sarcasm and white lies) in patients with first-episode psychosis.Participants were 65 patients with nonaffective first-episode psychosis (FEP) and 47 healthy controls. The patient group was divided into two subgroups, those with (FEP+; n= 38) and those without OCS (FEP-; n = 27). The ability to process sarcasm and lie was assessed with the Perception of Social Inference Test (PESIT). Severity of psychotic symptoms and OCS was assessed with the Positive and Negative Syndrome Scale (PANSS) and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), respectively.Deficits in the perception of sarcasm and lie were confirmed in patients with nonaffective first-episode psychosis compared to healthy controls. In patients, comorbidity with OCS was associated with worse performance on certain aspects of insincere speech (i.e., lie) compared to FEP- patients. Y-BOCS scores correlated significantly with the perception of lying. The cognitive factor of the PANSS predicted accuracy on the perception of sincere speech, paradoxical sarcasm, and white lies, while the presence of OCS predicted accuracy on the perception of sincere speech and white lies.Our finding of impaired counterfactual information processing in patients with first-episode psychosis suggests that these deficits are already present at illness onset. Presence of OCS appears to have additional deleterious effects on the successful interpretation of intentional lying, further supporting that these patients are characterized by more extensive cognitive impairment.

Patients with delusions exhibit an increased tendency to arrive at decisions based on very limited evidence (jumping-to-conclusions; JTC), making this reasoning bias relevant for the treatment of delusions. Neurocognitive deficits contribute to JTC, but it is not known whether this has any bearing on the clinical syndrome of delusions. We addressed this question by reanalyzing data from an efficacy study of non-pharmacological interventions as adjunctive treatments in schizophrenia. We investigated the longitudinal associations of cognitive functioning, JTC and delusions in patients with psychotic disorders receiving either a metacognitive intervention addressing reasoning biases (n=59), or cognitive remediation (n=58). Both interventions improved JTC; in the cognitive remediation group, tentative evidence suggested that better neurocognitive performance contributed to this improvement. However, JTC gains were associated with delusion improvement only in the metacognitive intervention group, suggesting a content-specific mechanism of action.

Antipsychotics represent the first-choice treatment for schizophrenia. However, the cognitive and emotional pathways through which symptom reduction is achieved have remained unclear. We recently proposed that the induction of doubt is a core mechanism of action of antipsychotics. In the framework of a randomized, double-blind, placebo-controlled, crossover design, 39 nonclinical participants filled out a questionnaire tapping into cognitive and emotional changes (Effect of Antipsychotic Medication on Emotion and Cognition-revised (EAMEC-r)) each time they had received one of three substances (haloperidol, placebo, L-dopa). Participants reported more doubt under haloperidol than under L-dopa lending support to the theory that antipsychotics decrease delusional conviction via the reduction of confidence. Key points from this study are: (a) antipsychotics induce doubt, and (b) doubt may represent a core mechanism of action for the reduction of delusional ideas

Our understanding of the neural correlates of auditory-verbal-hallucinations (AVH) has substantially increased during the last few years, but is far from sufficient. One current hypothesis, the interhemispheric miscommunication theory, is based on findings from fMRI, DTI and EEG, but there is only limited evidence so far concerning underlying functional coupling mechanisms. Here we report a 64-channel EEG study using lagged phase synchronization analysis and eLORETA source estimation to examine the functional connectivity between bilateral auditory cortices in the gamma-band in 26 schizophrenia patients (13 with and 13 without AVH) and 26 matched healthy controls (HC) while performing a dichotic listening task. We found a significantly reduced right-ear-advantage (REA) in AVH but not in non-AVH patients compared to HC. The major finding was significantly stronger gamma-band connectivity between bilateral auditory cortices during conscious perception of left (versus right) ear syllables in patients with AVH compared to HC and patients without AVH. A significant positive correlation was found between this connectivity alteration and the AVH symptom score in schizophrenia patients. These findings provide further support for the interhemispheric miscommunication hypothesis of AVH pathophysiology by indicating that aberrant gamma-band coupling between auditory cortices is related to the emergence of AVH in schizophrenia.

This is the peer-reviewed but unedited manuscript version of the following article: Moritz, S., Ludtke, T., Pfuhl, G., Balzan, R. P. & Andreou, C. (2017). Liberale akzeptanz als kognitiver mechanismus bei psychose: Eine 2-stufen-theorie der pathogenese schizophrener positivsymptome. Verhaltenstherapie (Basel), 27(2), 108-118. http://doi.org/10.1159/000464256. The final, published version is available at http://www.karger.com/?doi=10.1159/000464256. Positivsymptome wie Wahn und Halluzinationen stellen definierende Symptome einer (schizophrenen) Psychose dar. In dieser Übersichtsarbeit wird ein 2-stufiges heuristisches Modell für die Entstehung und Aufrechterhaltung psychotischer Positivsymptome vorgelegt. Im Kern der Theorie steht die Hypothese, dass von Psychose betroffene Menschen eine erniedrigte Entscheidungsschwelle aufweisen, die zu einer frühzeitigen Annahme von Hypothesen führt (liberale Akzeptanz). Im Unterschied zu nichtpsychotischen Personen ist die Konfidenz in falsche Urteile bei Betroffenen, als Folge dieser liberalen Akzeptanz, erhöht. Postuliert werden 2 Stufen der Wahnentwicklung. Auf Stufe 1 (Wahnentstehung) ist die subjektive Wahrscheinlichkeit für akzeptierte Hypothesen bei Menschen mit Psychose zunächst vergleichsweise gering. Wahnhafte Ideen sind in diesem Stadium häufig nicht voll entfaltet bzw. fragil und können zwischen 2 sich gegenseitig ausschließenden Ansichten oszillieren («doppelte Buchführung»). Im Zuge der 2. Stufe (Überzeugung, Aufrechterhaltung) verfestigen sich die flüchtigen wahnhaften Ideen zu falschen Überzeugungen aufgrund eines 2-gliedrigen Konsolidierungsprozesses – indem einerseits Gegenbeweise ignoriert und andererseits Belege zugunsten der Leithypothese einen Verarbeitungsvorteil erhalten (Bestätigungstendenz). Alternative Hypothesen rü- cken in den Hintergrund. Aufrechterhaltend für eine Wahnidee sind vielfältige psychologische Faktoren und Motive, wie die Kongruenz des Wahns mit dem emotionalen Befinden, persönliche Bedeutsamkeit und die temporäre Steigerung des Selbstwertgefühls sowie das Spannen eines Erklärungsrahmens für ein breites Spektrum von Beschwerden zur Reduktion kognitiver Dissonanz. Aus unserer Sicht können viele Formen von Halluzinationen und Erstrangsymptomen (z.B. Gedankeneingebung) ebenfalls durch liberale Akzeptanz erklärt werden. Diese Symptome basieren unseres Erachtens nicht zwingend auf fehlerhaften oder abnormalen Wahrnehmungen, sondern repräsentieren eine Fehlinterpretation von (teilweise) normalen sensorischen Phänomenen, die sich von einem (normalen) «Als-ob»-Gefühl bis hin zu einer wahnhaften Überzeugung steigern. Im Einklang mit dem erläuterten Modell werden Positivsymptome durch Interventionen wie das metakognitive Training (MKT) verringert, die Betroffene dazu anhalten, mehr Informationen zu sammeln und ihre Urteilssicherheit zu reduzieren (Säen von Zweifel). Die antipsychotische Wirkung von Antipsychotika/Neuroleptika wird im Rahmen der Theorie zum Teil durch ihre Eigenschaft erklärt, Zweifel zu induzieren. Die Bedeutung der Emotionsregulation bei der Reduktion von Positivsymptomen wird ebenfalls aufgezeigt, und zukünftige Forschungsrichtungen sowie offene Fragen diskutiert. Liberal Acceptance as a Cognitive Mechanism in Psychosis: A 2-Step-Therory on the Pathogenesis of Positive Symptoms in Schizophrenia Positive symptoms, such as delusions and hallucinations, are defining features of psychosis and schizophrenia, respectively. In this review article, we present a 2-stage heuristic model for the formation and maintenance of psychotic positive symptoms. At the heart of our theory is the assumption that individuals with psychosis have a lowered decision threshold resulting in the liberal acceptance of hypotheses. In contrast to non-psychotic persons, confidence in errors is enhanced as a result of liberal acceptance. Two stages are put forward here. At stage 1 (delusion formation), the subjective probability of an accepted hypothesis is relatively low. Delusional ideas at this stage are often fragile and may oscillate between mutually exclusive views (‘double book keeping’). During the 2. stage (conviction, maintenance), flighty delusional ideas crystallize due to a 2-fold consolidation process: a) counter-evidence is ignored and b) cues in favor of the dominant hypothesis have a processing advantage (confirmation bias). Alternative hypotheses are degraded in the course of this process. A number of psychological factors and motifs act as maintenance factors, for example the congruence between the delusion and present emotional states, personal importance and the temporary elevation of self-esteem, as well as a superstructure that may explain a broad range of impairments to reduce cognitive dissonance. From our point of view, some forms of hallucinations and first-rank symptoms (e.g., thought broadcasting) can be explained by liberal acceptance as well. These symptoms are not necessarily based on erroneous or abnormal perception but on the misinterpretation of (partially) normal sensory phenomena which evolve from an ‘as if’ feeling to delusional conviction. In accordance with the model, positive symptoms are decreased by interventions such as metacognitive training (MCT) which encourage individuals with psychosis to search for more information and to reduce their level of certainty (i.e., ‘sowing the seeds of doubt’). The antipsychotic properties of antipsychotics/neuroleptics are explained by their potential to induce doubt. The role of emotion regulation for the amelioration of positive symptoms is demonstrated, and further research directions and open questions are outlined.

Background Hyperprolactinemia is a known side effect of antipsychotics. In recent reports it has also been shown in antipsychotic-naive at-risk mental state (ARMS) and first-episode psychosis (FEP) patients. Prolactin is not only involved in reproduction and lactation, but is also synthesized in response to stress. As stress is thought to play an important role in the onset and relapse of schizophrenia, the aim of this study was to further elucidate the influence of prolactin in emerging psychosis. Methods The data analysed in this study were collected within the prospective Fruherkennung von Psychosen (FePsy) study. Blood sample collection took place under standardized conditions between 8 and 10 am after an overnight fast and 30 minutes of rest. All patients were antipsychotic-naive and did not take any prolactin influencing medication. Results Our sample consisted of 116 antipsychotic-naive ARMS and 49 FEP patients. Hyperprolactinemia was shown in 32% of ARMS and 35% of FEP patients. After correction for the normal biological variation between the sexes, we still found higher average prolactin levels in female than in male patients (β = 0.42; t = 2.47; p = 0.01) but no difference in prolactin levels between ARMS and FEP patients (β = − 0.05; t = − 0.30; p = 0.76). The survival analysis revealed no significant predictive value for prolactin levels to predict transition to psychosis. Conclusion Our findings support a possible role of prolactin in emerging psychosis and it could be speculated that stress, which can induce hyperprolactinemia, has a stronger effect on women than on men in emerging psychosis.

Converging evidence suggests that frontostriatal abnormalities underlie OCD symptoms. The event-related potential P300 is generated along a widely distributed network involving several of the areas implicated in OCD. P300 abnormalities reported in patients with OCD suggest increased activity in these areas. The aim of the present study was to investigate this assumption in unmedicated patients with OCD, and to assess the effects of OCD treatment on P300 brain activity patterns. Seventy-one unmedicated patients with a DSM-IV diagnosis of OCD and 71 age- and gender-matched healthy control subjects participated in the study. The P300 was obtained through 32-channel EEG during an auditory oddball paradigm. Forty-three patients underwent a second EEG assessment after treatment with sertraline and behavioural therapy. Low-resolution electromagnetic tomography (LORETA) was used to localize the sources of brain electrical activity. Results: Increased P300-related activity was observed predominantly in the left orbitofrontal cortex, but also in left prefrontal, parietal and temporal areas, in patients compared to controls at baseline. After treatment, reduction of left middle frontal cortex hyperactivity was observed in patients. Conclusions: Findings of increased activity in frontoparietal areas in patients are consistent with several previous studies. Importantly, OCD treatment led to reduction of hyperactivity in the left middle frontal cortex, an area associated with context processing and uncertainty that might be important for the emergence of OCD symptoms. Thus, the present study is the first to show an association between P300 abnormalities and activity in brain regions postulated to be involved in the pathophysiology of OCD.

Background Symptom reduction under antipsychotic agents is incomplete for most schizophrenia patients. In order to enhance outcome, cognitive approaches are increasingly adopted as add-on interventions. The present study aimed to determine the efficacy of group Metacognitive Training (MCT), which targets cognitive biases putatively involved in the pathogenesis of delusions. Methods A two-center, randomized, assessor-blind, controlled trial between MCT group training and cognitive training was carried out (ISRCTN95205723). A total of 150 in- and outpatients with DSM diagnoses of schizophrenia spectrum disorders were enrolled. All patients were concurrently prescribed antipsychotic medication. Assessments were made at baseline, four weeks and six months later. The primary outcome was a delusion score derived from the Positive and Negative Syndrome Scale (PANSS). The Psychotic Symptom Rating Scales (PSYRATS) as well as cognitive measures served as secondary outcomes. Results Completion at follow-up was 86%. According to intention-to-treat (ITT) analyses, patients in the MCT group showed significantly greater symptom reduction on the PANSS delusion subscore (follow-up), PANSS positive score (post-treatment) and PSYRATS delusion score (post-treatment and follow-up). Improvement on the PANSS positive scale at post-treatment and follow-up was positively correlated with the number of attended MCT sessions. No changes were seen for other psychopathological syndromes. Discussion MCT, a low-intensity training aimed at enhancing patients' awareness of cognitive biases subserving paranoia, led to improvement in delusion symptoms relative to the control condition and over and above the effects of antipsychotic medication. This improvement was sustained at follow-up.

Antipsychotic medication represents the first-line treatment for schizophrenia. While it is undisputed that antipsychotics ameliorate positive symptoms, the exact cognitive and emotional pathways through which the effect is exerted has remained unclear. The present study investigated the subjective effects of antipsychotics across various domains of cognition and emotion in both patients with psychotic symptoms and patients with other psychiatric diagnoses. A total of 69 patients with a probable history of psychosis or psychotic symptoms and 26 patients with psychiatric diagnoses other than psychosis participated in a survey conducted over the Internet. Multiple control measures aimed to secure response validity. All patients were currently or had previously been treated with antipsychotic agents. A questionnaire comprising 49 items and measuring possible effects of antipsychotics on cognition and emotion was administered. For 30 out of 49 items a clear response pattern emerged, which was similar for patients with psychotic disorders and patients with other diagnoses. Factor analysis of these items revealed three main effects of antipsychotic medication related to doubt and self-doubt, cognitive and emotional numbing, and social withdrawal. Antipsychotic treatment appears to be connected to a number of negative subjective effects on cognition and emotion. Further studies are warranted to assess how these effects impact on the patients' subjective well-being and quality of life, as well as their association with antipsychotic efficacy on one hand, and adherence rates on the other. Induction of doubt and dampening of emotion may be one reason why antipsychotics work and at the same time offer an explanation why they are experienced as rather unpleasant and are eventually discontinued by many patients. (C) 2013 Elsevier Ltd. All rights reserved.

Background and objectives Semantic priming disturbances are increasingly recognized as a feature of schizophrenia, and increased priming has been suggested to constitute a “cognitive correlate” of positive formal thought disorder (FTD). The present study aimed to investigate semantic priming in patients with bipolar disorder (BD). Methods A primed lexical decision task with strongly related (STR), weakly related (WR), or unrelated (UR) prime-target pairs (SOA = 250 ms) was administered to fourteen remitted patients with BD and twelve control subjects matched on key demographic variables. FTD was measured by means of the Scale for Thought, Language and Communication (TLC). Results Control subjects showed a robust (59.6 ms) and statistically significant priming effect for STR words, while priming for UR words was non-significant. In patients there was no evidence of priming in either condition. In patients, there were no significant correlations between priming magnitude and TLC scores. However, the only patient with a positive score on the TLC disorganization factor exhibited evidence of hyperpriming. Limitations The present patient sample exhibited very low TLC scores, and no direct comparison to patients with schizophrenia was possible. Conclusions The finding of decreased priming in patients with BD raises the possibility that semantic processing abnormalities in BD are of a different nature than those encountered in schizophrenia. Due to the small size and very low TLC scores of the present patient sample, no definite conclusions can be drawn as to the relationship of formal thought disorder and semantic processing abnormalities in BD.

Background\ud \ud Depression is common in schizophrenia. Whereas the improvement of mood and self-esteem represents a subjective treatment priority for many patients, depression is rarely a primary target for clinical intervention. The present trial examined whether an online intervention for depression can ameliorate depressive symptoms in schizophrenia.\ud \ud Methods\ud \ud A total of 58 individuals with schizophrenia were invited to participate in an online survey which encompassed the Center for Epidemiologic Studies-Depression Scale (CES-D, primary outcome), the Patient-Health-Questionnaire-9 (PHQ-9) and the Paranoia Checklist. Subsequently, telephone interviews were conducted to verify diagnostic status and assess symptoms (Positive and Negative Syndrome Scale, PANSS). Participants were randomized either to the experimental condition (online depression intervention) or to a waitlist control condition. Three months after inclusion, a reassessment was carried out (self-report and telephone interview blind for group condition). The trial was registered (registration: DRKS00007888).\ud \ud Results\ud \ud Participants in the treatment group showed a significant decline of depressive symptoms at a medium-to-large effect size, as assessed with the CES-D and the PANSS depression item, in comparison to the waitlist control group (completer (CC) and intention-to-treat analyses (ITT)). For the PHQ-9 (CC and ITT) and the PANSS distress subscale (CC only) significance was bordered at a medium effect size. Completion at the post-assessment after three months was 84%.\ud \ud Discussion\ud \ud Depression in schizophrenia is both underdiagnosed and undertreated. To reduce the large treatment gap in the disorder, low threshold strategies are urgently needed. Online treatment and bibliotherapy may represent valuable tools to address patients' needs beyond the treatment of the core positive syndrome.

Prior studies have confirmed a bias against disconfirmatory evidence (BADE) in schizophrenia which has been associated with delusions. However, its role in the pathogenesis of psychosis is yet unclear. The objective was to investigate BADE for the first time in subjects with an at-risk-mental-state for psychosis (ARMS), patients with a first episode of psychosis without antipsychotic treatment (FEP) and healthy controls (HC). A standard BADE test presenting written scenarios was employed. In addition, psychometric rating scales and a neuropsychological test battery were applied. A three-staged image was revealed. FEP-patients showed a significant BADE compared to the other groups. The performance of ARMS-patients lay in between HC and FEP-patients. A trend towards significance became evident for a bias against confirmatory evidence (BACE) in FEP-patients. Results were not attributable to antipsychotic or other medication or depressive symptoms. Correlations with delusions reached medium effect sizes but failed significance after Bonferroni-corrections. These results provide evidence for aberrations in evidence integration in the pathogenesis of psychosis and contribute to our knowledge of metacognitive functioning which can be used for (meta-)cognitive intervention in psychosis. published

Antipsychotic medication represents the treatment of choice in psychosis according to clinical guidelines. Nevertheless, studies show that half to almost three-quarter of all patients discontinue medication with antipsychotics after some time, a fact which is traditionally ascribed to side-effects, mistrust against the clinician and poor illness insight. The present study investigated whether positive attitudes toward psychotic symptoms (ie, gain from illness) represent a further factor for medication noncompliance. An anonymous online survey was set up in order to prevent conservative response biases that likely emerge in a clinical setting. Following an iterative selection process, data from a total of 113 patients with a likely diagnosis of schizophrenia and a history of antipsychotic treatment were retained for the final analyses (80%). While side-effect profile and mistrust emerged as the most frequent reasons for drug discontinuation, 28% of the sample reported gain from illness (eg, missing voices, feeling of power) as a motive for noncompliance. At least every fourth patient reported the following reasons: stigma (31%), mistrust against the physician/therapist (31%), and rejection of medication in general (28%). Approximately every fifth patient had discontinued antipsychotic treatment because of forgetfulness. On average, patients provided 4 different explanations for noncompliance. Ambivalence toward symptoms and treatment should thoroughly be considered when planning treatment in psychosis. While antipsychotic medication represents the evidence-based cornerstone of the current treatment in schizophrenia, further research is needed on nonpharmacological interventions for noncompliant patients who are willing to undergo intervention but refuse pharmacotherapy.

IntroductionNegative symptoms and cognitive impairments are both present in patients with an at risk mental state (ARMS) for psychosis and negatively affect functioning and outcome. According to previous studies in patients with first-episode psychosis, negative symptoms are negatively associated with cognitive functioning while positive symptoms do not seem to be associated. Yet, little is known about the specific relationship of negative symptoms and cognitive functioning in ARMS patients.ObjectiveTo evaluate, the relationship between negative symptoms and cognitive functioning in ARMS patients.MethodsData of 154 ARMS patients were collected within the prospective Basel early detection of psychosis (FePsy) study. Negative symptoms were assessed with the SANS, positive psychotic symptoms with the BPRS, cognitive functioning with an extensive neuropsychological test battery. Multiple regressions were applied and results were controlled for age and gender.ResultsRegression analyses showed a significant, negative association between negative but not positive psychotic symptoms and cognitive functioning, showing the strongest association with verbal fluency (see Fig. 1). However, results mainly did not withstand correction for multiple testing.ConclusionsThe association found between verbal fluency and negative symptoms may be indicative of an overlap between those constructs. Finally, verbal fluency might have a strong influence on the clinical impression of negative symptoms, especially on alogia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Although cognitive deficits are recognized as a core feature in schizophrenia, their evolution over the course of the illness is still debated. Longitudinal studies of cognition in patients after a first episode of psychosis (FEP) provide extremely useful information, in that they include an adequate and realistic baseline measure of cognitive performance, while at the same time minimizing the effect of confounding variables associated with chronicity. The aim of this systematic review was to summarize findings of studies assessing the longitudinal course of neuropsychological deficits in patients with FEP for durations of at least one year. Overall, the neuropsychological deficits that are present following a first episode of psychosis appeared to remain stable over time for periods of up to ten years, the only possible exception being verbal memory deficits, where there is some evidence of further deterioration over the long term. However, further studies are needed to confirm this conclusion, especially in the (somewhat inconsistently defined) domain of executive function. Improvements in psychopathology appear to positively influence the course of cognitive deficits, although the effects of antipsychotic medication are not as clear.

Delusions are defined as fixed erroneous beliefs that are based on misinterpretation of events or perception, and cannot be corrected by argumentation to the opposite. Cognitive theories of delusions regard this symptom as resulting from specific distorted thinking styles that lead to biased integration and interpretation of perceived stimuli (i.e., reasoning biases). In previous studies, we were able to show that one of these reasoning biases, overconfidence in errors, can be modulated by drugs that act on the dopamine system, a major neurotransmitter system implicated in the pathogenesis of delusions and other psychotic symptoms. Another processing domain suggested to involve the dopamine system and to be abnormal in psychotic disorders is sensory perception. The present study aimed to investigate whether (lower-order) sensory perception and (higher-order) overconfidence in errors are similarly affected by dopaminergic modulation in healthy subjects. Thirty-four healthy individuals were assessed upon administration of L-dopa, placebo, or haloperidol within a randomized, double-blind, cross-over design. Variables of interest were hits and false alarms in an illusory perception paradigm requiring speeded detection of pictures over a noisy background, and subjective confidence ratings for correct and incorrect responses. There was a significant linear increase of false alarm rates from haloperidol to placebo to L-dopa, whereas hit rates were not affected by dopaminergic manipulation. As hypothesized, confidence in error responses was significantly higher with L-dopa compared to placebo. Moreover, confidence in erroneous responses significantly correlated with false alarm rates. These findings suggest that overconfidence in errors and aberrant sensory processing might be both interdependent and related to dopaminergic transmission abnormalities in patients with psychosis.

Objectives. Gamma-band oscillations (e.g., the early auditory evoked gamma-band response, aeGBR) have been suggested to mediate cognitive and perceptual processes by driving the synchronization of local neuronal populations. Reduced aeGBR is a consistent finding in patients with schizophrenia and high-risk subjects, and has been proposed to represent an endophenotype for the illness. However, it is still unclear whether this reduction represents a deficit in sensory or cognitive processes, or a combination of the two. The present study investigated this question by manipulating the difficulty of an auditory reaction task in patients with first-episode schizophrenia and healthy controls. Methods. A 64-channel EEG was recorded in 23 patients with first-episode schizophrenia and 22 healthy controls during two conditions of an auditory reaction task: an easy condition that merely required low-level vigilance, and a difficult condition that placed significant demands on attention and working memory. Results. In contrast to healthy controls, patients failed to increase aeGBR power and phase-locking in the difficult condition. In patients, aeGBR power and phase-locking indices were associated with working memory deficits. Conclusions. The observed results confirm the applicability of aeGBR disturbances as a stable endophenotype of schizophrenia, and suggest a cognitive, rather than sensory, deficit at their origin.

BackgroundMetamemory describes the monitoring and knowledge about one's memory capabilities. Patients with schizophrenia have been found to be less able in differentiating between correct and false answers (smaller confidence gap) when asked to provide retrospective confidence ratings in previous studies. Furthermore, higher proportions of very-high-confident but false responses have been found in this patient group (high knowledge corruption). Whether and how these biases contribute to the early pathogenesis of psychosis is yet unclear. This study thus aimed at investigating metamemory function in the early course of psychosis.MethodPatients in an at-risk mental state for psychosis (ARMS, n = 34), patients with a first episode of psychosis (FEP, n = 21) and healthy controls (HCs, n = 38) were compared on a verbal recognition task combined with retrospective confidence-level ratings.ResultsFEP patients showed the smallest confidence gap, followed by ARMS patients, followed by HCs. All groups differed significantly from each other. Regarding knowledge corruption, FEP patients differed significantly from HCs, whereas a statistical trend was revealed in comparison of ARMS and FEP groups. Correlations were revealed between metamemory, measures of positive symptoms and working memory performance.ConclusionsThese data underline the presence of a metamemory bias in ARMS patients which is even more pronounced in FEP patients. The bias might represent an early cognitive marker of the beginning psychotic state. Longitudinal studies are needed to unravel whether metacognitive deficits predict the transition to psychosis and to evaluate therapeutic interventions.

Pellagra is caused by nicotinic acid deficiency; it is rarely encountered in developed countries, and it is mainly related to poverty and malnutrition, as well as with chronic alcoholism. We report the case of an alcoholic patient who was diagnosed with pellagra and administered B-complex vitamin tablets that did not contain niacin. A few weeks later, the patient developed nervousness, irritability, insomnia and, consequently, delusional ideas and hallucinations, for which he had to be hospitalized. After his admission, the patient manifested loss of consciousness and myoclonus. All of his symptoms (cutaneous, neurological, and psychiatric) resolved fully with treatment with niacin in combination with other B-complex vitamins. All undiagnosed encephalopathies in alcoholic patients should be treated with multiple vitamin therapy, including nicotinic acid.

IntroductionIn the growing research field of early psychosis detection in patients with an at risk mental state (ARMS), most studies focus on the transition to frank psychosis. However, the majority of ARMS patients do not go on to develop frank psychosis and reported transition rates are declining. Little is known about the long-term outcome of these non-transitioned patients (ARMS-NT).ObjectivesTo investigate in preliminary analyses the long-term outcome of ARMS-NT patients with respect to persistence of ARMS signs and symptoms and the rates of late psychotic transition.MethodsThe ongoing study “FePsy-BHS-NT” follows up ARMS-NT without transition during at least the first two years for up to 15 years after their initial assessment. ARMS status is ascertained with the Basel Screening Instrument for Psychosis (BSIP). ARMS remission is defined as the absence of attenuated psychotic symptoms or brief limited intermittent psychotic symptoms for at least 12 consecutive months.ResultsIn this preliminary sample of 51 ARMS-NT, the majority of patients (70.6%) have remitted from their at risk mental state, 13.7% remain at risk and 15.7% have made a late psychotic transition during the course of long-term follow up (median = 5.75, range 4–11 years after initial assessment).ConclusionsThe considerable rates of ARMS persistence and late psychotic transition indicate that longer follow-up durations than commonly recommended should be contemplated in ARMS patients. Potential predictors of favorable long-term clinical outcome, as well as psychosocial, neurocognitive and other outcomes of ARMS-NT patients will be further evaluated in the present study.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionNon-psychotic axis I diagnoses are highly prevalent in at-risk mental state (ARMS) and first episode psychosis (FEP) patients, the most common being affective and anxiety disorders. Few studies have examined differences between ARMS and FEP patients or gender effects regarding such diagnoses.ObjectiveTo examine current and lifetime comorbidities in ARMS and FEP patients. Furthermore, to examine gender differences, and differences between patients with (ARMS-T) and without later transition to psychosis (ARMS-NT).MethodsThis study was part of the Früherkennung von Psychosen (FePsy) study. Current and lifetime axis I comorbidities were assessed using the Structured Clinical Interview for DSM-IV (SCID-I).ResultsOne hundred and thirty-two ARMS and 98 FEP patients were included. Current comorbidities were present in 53.1% of FEP and 64.4% of ARMS patients, the most common being affective, anxiety and substance use disorders. Current affective disorders were significantly more common in ARMS than FEP. Lifetime comorbidities were diagnosed in 58.2% of FEP and 69.7% of ARMS patients, with significantly more affective and anxiety disorders in ARMS than FEP. Male FEP patients had more current and lifetime substance use disorders (across all substances) compared to female FEP. No differences emerged between ARMS-T and ARMS-NT.ConclusionsAs expected ARMS patients have many comorbidities, while clearly diagnosed FEP have less comorbidities. There were few gender differences in axis I comorbidities. Moreover, no differences between ARMS-T and NT emerged, suggesting that axis I comorbidities do not improve prediction of transition. Nevertheless, the high comorbidity prevalence is relevant for global functioning and clinical treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionClinical, epidemiological and basic research studies have confirmed that estradiol can have protective effects in schizophrenic psychoses. At the same time many patients with schizophrenic psychoses – even antipsychotic naïve at-risk mental state (ARMS) patients show hyperprolactinemia and gonadal dysfunction with estrogen deficiency in women and possibly testosterone deficiency in men.AimTo investigate the relation between the stress hormone prolactin and the sex hormones estradiol in women and testosterone in men in emerging psychosis.MethodsForty-seven antipsychotic-naïve ARMS (38 men and 9 women) and 17 antipsychotic-naive first episode psychosis (FEP) (14 men and 3 women) patients were recruited via the Basel Früherkennung von Psychosen (FePsy) study. Blood was taken under standardized conditions between 8 and 10 am after an overnight fast and 30 minutes of rest. We performed a linear regression model to evaluate the association between prolactin and sex hormones including age and current antidepressant use as covariates.ResultsIn women, estradiol was negatively associated with prolactin (β = −1.28, P = 0.01) whereas in men there was a positive association of testosterone with prolactin (β = 0.52, P = 0.031).ConclusionThe often observed estrogen deficiency in women with psychosis could therefore be explained by the stress hormone prolactin suppressing the gonadal axis already in very early untreated stages of the emerging disease.In ARMS or FEP men prolactin does not seem to influence the gonadal axis in the same way as in women.Disclosure of interestThe authors have not supplied their declaration of competing interest.

While the role of synchronized oscillatory activity in the gamma-band frequency range for conscious perception is well established in the visual domain, there is limited evidence concerning neurophysiological mechanisms in conscious auditory perception. In the current study, we addressed this issue with 64-channel EEG and a dichotic listening (DL) task in twenty-five healthy participants. The typical finding of DL is a more frequent conscious perception of the speech syllable presented to the right ear (RE), which is attributed to the supremacy of the contralateral pathways running from the RE to the speech-dominant left hemisphere. In contrast, the left ear (LE) input initially accesses the right hemisphere and needs additional transfer via interhemispheric pathways before it is processed in the left hemisphere. Using lagged phase synchronization (LPS) analysis and eLORETA source estimation we examined the functional connectivity between right and left primary and secondary auditory cortices in the main frequency bands (delta, theta, alpha, beta, gamma) during RE/LE-reports. Interhemispheric LPS between right and left primary and secondary auditory cortices was specifically increased in the gamma-band range, when participants consciously perceived the syllable presented to the LE. Our results suggest that synchronous gamma oscillations are involved in interhemispheric transfer of auditory information.

Background: The processing of reward and punishment stimuli in humans appears to involve brain oscillatory activity of several frequencies, probably each with a distinct function. The exact nature of associations of these electrophysiological measures with impulsive or risk-seeking personality traits is not completely clear. Thus, the aim of the present study was to investigate event-related oscillatory activity during reward processing across a wide spectrum of frequencies, and its associations with impulsivity and sensation seeking in healthy subjects. Methods: During recording of a 32-channel EEG 22 healthy volunteers were characterized with the Barratt Impulsiveness and the Sensation Seeking Scale and performed a computerized two-choice gambling task comprising different feedback options with positive vs. negative valence (gain or loss) and high or low magnitude (5 vs. 25 points). Results: We observed greater increases of amplitudes of the feedback-related negativity and of activity in the theta, alpha and low-beta frequency range following loss feedback and, in contrast, greater increase of activity in the high-beta frequency range following gain feedback. Significant magnitude effects were observed for theta and delta oscillations, indicating greater amplitudes upon feedback concerning large stakes. The theta amplitude changes during loss were negatively correlated with motor impulsivity scores, whereas alpha and low-beta increase upon loss and high-beta increase upon gain were positively correlated with various dimensions of sensation seeking. Conclusions: The findings suggest that the processing of feedback information involves several distinct processes, which are subserved by oscillations of different frequencies and are associated with different personality traits. Einfuhrung: Die Verarbeitung von Feedback-Informationen uber Belohnung oder Bestrafung involviert im menschlichen Gehirn oszillatorische Aktivitat in mehreren Frequenzbandern, wobei wahrscheinlich jedem dieser Bander eine unterschiedliche, spezifische Funktion zukommt. Bisher ist noch nicht geklart, inwieweit diese elektrophysiologischen Befunde mit Personlichkeitsmerkmalen wie Impulsivitat oder Risikobereitschaft assoziiert sind. Das Ziel der aktuellen Untersuchung war, oszillatorische Aktivitat in einem weiten Frequenzbereich wahrend der Verarbeitung von Belohnungsprozessen bei gesunden Probanden zu detektieren und Verknupfungen zu den Personlichkeitszugen Impulsivitat und Sensationslust herzustellen. Methoden: 22 gesunde Probanden wurden anhand von Fragebogen [Barratt Impulsiveness Scale (BIS) und Sensation Seeking Scale (SSS)] charakterisiert und fuhrten wahrend einer 32-Kanal-EEG-Messung standardisiert einen computergestutzten, 2 Auswahlmoglichkeiten beinhaltenden Glucksspiel-Test durch, welcher als Feedback sowohl die Wertigkeit (Gewinn versus Verlust) als auch das Ausmas (hoch versus niedrig) des entsprechenden Ereignisses darstellte. Resultate: Wir konnten eine grossere Amplitudenzunahme der Feedback-Related-Negativity (FRN) und der Aktivitat im Theta-, Alpha- und Low-Beta-Bereich nach negativem Feedback (Verlust) finden, wohingegen sich vermehrte Aktivitat im High-Beta-Frequenzbereich folgend auf positives Feedback (Gewinn) zeigte. Signifikante Unterschiede konnten fur Theta- und Delta-Oszillationen hinsichtlich der Hohe des Gewinnspieleinsatzes dargestellt werden, wobei sich grossere Amplituden bei Feedback nach hoherem (25) Gewinnspieleinsatz zeigten. Desweiteren konnte eine negative Korrelation zwischen den Amplitudenanderungen nach negativem Feedback (Verlust) im Theta-Bereich und dem Punktewert im BIS (Impulsivitatsskala) aufgezeigt werden. Eine Erhohung im Alpha- und Low-Beta-Bereich bei negativem Feedback (Verlust) sowie eine Erhohung im High-Beta-Bereich bei positivem Feedback (Gewinn) war positiv mit unterschiedlichen Auspragungen des Personlichkeitsmerkmales Sensationlust korreliert. Folgerung: Die Resultate weisen darauf hin, dass bei der kognitiven Verarbeitung von Feedback-Informationen (positiv vs. negativ) mehrere verschiedenartige Prozesse beteiligt sind, die in unterschiedlichen Frequenzen abgebildet werden, und ein direkter Zusammenhang zu spezifischen Personlichkeitsmerkmalen besteht.

Introduction Resting-state EEG microstates are thought to reflect the momentary local states and interactions of distributed neural networks in the brain. Several changes in resting-state EEG microstates have been described in acutely ill patients with schizophrenia, but it is not known whether these represent trait or state abnormalities. The present study aimed to investigate this issue by assessing EEG microstate characteristics in high-risk individuals (HR) and clinically stable first-episode patients with schizophrenia (SZ) with low symptom levels, compared to each other and healthy controls (HC). Method Participants were 18 HR, 18 SZ, and 22 HC subjects. 64-channel resting-state EEG recordings were used for microstate analyses. Microstates were clustered into four classes (A–D) according to their topography. Temporal parameters and topographies of microstates were compared among groups. Results Microstate class A displayed higher coverage and occurrence in HR than SZ and HC, while microstate class B covered significantly more time in SZ compared to both HR and HC. Microstate class B displayed an aberrant spatial configuration in SZ, and to a lesser extent also in HR, compared to HC, with patients exhibiting significantly higher activity in the vicinity of the left posterior cingulate. Discussion Microstate abnormalities observed in HR were similar to those previously reported in acutely ill patients with schizophrenia. Moreover, there was evidence that HR and SZ might share specific disturbances in brain functional connectivity. These findings raise the possibility that certain abnormalities in resting-state EEG microstates might be associated with an increased risk for psychosis.

The aim of the present study was to investigate the effects of comorbid obsessive-compulsive symptoms on emotional perception and theory of mind (ToM) in patients with first-episode psychosis. Participants were 65 patients with non-affective first episode psychosis (FEP) and 47 healthy controls. The patient group was divided into two subgroups, those with (FEP+; n=38) and those without obsessive-compulsive symptomatology (FEP-; n=27). Emotion perception and ToM were assessed with the Perception of Social Inference Test. Severity of psychotic and obsessive-compulsive symptoms was assessed with the Positive and Negative Syndrome Scale (PANSS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), respectively. Deficits in emotion recognition and theory of mind were confirmed in patients with non-affective first-episode psychosis compared to healthy controls. In patients, comorbidity with obsessive-compulsive symptoms was associated with worse performance on certain aspects of social cognition (ToM 2nd order) compared to FEP- patients. Our findings of impaired emotion perception and ToM in patients with first-episode psychosis support the hypothesis that deficits are already present at illness onset. Presence of OCS appears to have further deleterious effects on social cognition, suggesting that these patients may belong to a schizo-obsessive subtype of schizophrenia characterized by more extensive neurobiological impairment.

Online studies are increasingly utilized in applied research. However, lack of external diagnostic verification in many of these investigations is seen as a threat to the reliability of the data. The present study examined the robustness of internet studies on psychosis against simulation. We compared the psychometric properties of the Community Assessment of Psychic Experiences scale (CAPE), a self-report instrument measuring psychotic symptoms, across three independent samples: (1) participants with a confirmed diagnosis of schizophrenia, (2) participants with self-reported schizophrenia who were recruited over the internet, and (3) clinical experts on schizophrenia as well as students who were asked to simulate a person with schizophrenia when completing the CAPE. The CAPE was complemented by a newly developed 4-item psychosis lie scale. Results demonstrate that experts asked to simulate schizophrenia symptoms could be distinguished from real patients: simulators overreported positive symptoms and showed elevated scores on the psychosis lie scale. The present study suggests that simulated answers in online studies on psychosis can be distinguished from authentic responses. Researchers conducting clinical online studies are advised to adopt a number of methodological precautions and to compare the psychometric properties of online studies to established clinical indices to assert the validity of their results.

Neuropsychological deficits and severity of initial psychopathology have been repeatedly associated with poor symptomatic outcomes in schizophrenia. The role of higher-order cognitive biases on symptomatic outcomes of the disorder has not yet been investigated. The present study aimed to assess the contribution of cognitive biases, psychopathology and neuropsychological deficits on the probability of achieving early symptomatic remission after a psychotic episode in patients with schizophrenia. Participants were 79 patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder undergoing an acute psychotic episode, and 25 healthy controls. According to psychopathology assessments, patients were split into those who had achieved remission after an average follow-up interval of 7 months, and those who had not (NR). Patients who achieved remission exhibited higher premorbid IQ and better performance on the TMT-B, as well as lower baseline positive, disorganized and distress symptoms than NR patients. TMT-B performance and positive symptoms at baseline were the best predictors of remission. Cognitive biases and negative symptoms were not associated with later remission. The findings highlight the significance of initial symptom severity for at least short-term symptomatic outcomes and, thus, the importance of adequate symptomatic treatment and prevention of psychotic outbreaks in patients.

Summary Component: role limitations-emotional, social functioning, and mental health] and the Health Status item from the EUROQoL-5D. Psychopathology was assessed with the five symptom dimensions from PANSS: positive, negative, cognitive, depression, and excitement symptoms. Results Significant intercorrelations were found among QLS subscales: IRP with IRF [r(38) = 0.65, p < 0.001], IF [r(38) = 0.85, p < 0.001], and COA [r(38) = 0.70, p

Background It is well known that semantic characteristics of words have differential effects on word recognition. Recently, attention has been drawn to the effects of the type of ambiguity, i.e. whether a word has different meanings that correspond to different entries in the dictionary and have different derivations (homonymy), or related senses that are all enlisted under the same entry in the dictionary (polysemy). The aim of this study was to investigate the effects of ambiguity type on visual single-word recognition in greek.

Materials and methods Participants were 29 (18 men) outpatients with schizophrenia (SZ), 19 (8 men) remitted patients with bipolar disorder I (BP), and 30 (15 men) healthy controls (HC); all groups were matched to each other for age, sex, and level of education. Symptom severity (positive symptoms, negative symptoms, and general psychopathology) of patients with SZ were assessed with the Greek version of the Positive and Negative Syndrome Scale (PANSS); residual affective symptoms of patients with BP were assessed with the Young Mania Rating Scale (YMRS) and the Montgomery-Asberg Depression Rating Scale (MADRS). Sustained attention was measured by means of the Penn Continuous Performance Test (PCPT).