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Background and Objectives: Individualized Metacognitive Training (MCT+) is a manualized intervention designed to improve delusional severity by reducing delusion-associated cognitive biases such as jumping-to-conclusions. Increased interest in personalized medicine stipulates the identification of patients who are more likely to benefit from specialized interventions. The present study aimed to explore baseline moderators of MCT+ efficacy on delusions and overall positive symptoms in psychosis., Methods: We analyzed data from a randomized rater-blind controlled trial, in which 92 patients with psychotic disorders and current or past delusions were randomly assigned to either MCT+ or CogPack®, a cognitive remediation software. Baseline moderator variables consisted of jumping-to-conclusions, cognitive insight, quality of life, self-esteem, selective attention, and patients' attitudes towards their symptoms. Linear mixed-effects models were applied to investigate specific moderators of MCT+ efficacy., Results: In MCT+ relative to CogPack, presence of a jumping-to-conclusions bias, a lowered decision threshold, and low self-esteem were associated with larger improvements in delusional severity and/or overall positive symptoms over time. Subjective reasoning style and insight, as well as subjective attitudes towards psychosis, did not moderate the treatment efficacy of MCT+ relative to CogPack., Limitations: Participation of both treatment groups in group MCT as a part of standard care, possibly leading to additional effects on delusional severity., Conclusions: Patients with low self-esteem and those who are prone to jumping-to-conclusions seem to particularly benefit from MCT+. Our results can help inform clinical practice as they provide specific criteria for selecting patients for whom MCT+ is most appropriate., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest in relation to the subject of this study., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: 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., Methods: Data from 200 patients of the prospective Früherkennung 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., Results: 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., Conclusion: 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.

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., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

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-naïve ARMS and FEP patients. Data from 59 ARMS and 31 FEP patients, collected within the prospective Früherkennung 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-naïve patients. Hence, deficits in this domain do not appear to stem from alterations in subcortical structures., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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 Früherkennung 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., (© 2018 John Wiley & Sons Australia, Ltd.)

In the past few decades, sex differences have been identified in a number of clinical, cognitive and functional outcomes in patients with schizophrenia spectrum disorders. However, to date, sex differences in higher-order cognitive biases have not been systematically studied. The present study aimed to examine sex differences in jumping-to-conclusions and evidence integration impairment based on data collected in two previous studies in patients with schizophrenia spectrum disorders and healthy controls. For this purpose, data from n = 58 patients and n = 60 healthy controls on the Fish Task (as a measure of jumping to conclusions) and bias against disconfirmatory evidence (BADE; as a measure of evidence integration) task were analyzed. Results indicated a lack of sex differences in jumping-to-conclusions and evidence integration impairment both in patients with schizophrenia spectrum disorders and healthy controls. Although the present study was adequately powered to detect sex differences of a low medium effect size, larger studies are warranted to exclude differences of a smaller magnitude between men and women regarding delusion-associated cognitive biases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Negative symptoms and neurocognitive performance have been reported to be negatively associated in patients with emerging psychosis. However, most previous studies focused on patients with frank psychosis and did not differentiate between subdomains of negative symptoms. Hence, we aimed to elucidate the specific relationship between negative symptoms and cognitive functioning in patients at clinical high risk (CHR) for psychosis. Data from 154 CHR patients collected within the prospective Früherkennung von Psychosen (FePsy) study were analyzed. Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and cognitive functioning with an extensive neuropsychological test battery. Regression analyses revealed significant negative associations between negative symptoms and cognitive functioning, particularly in the domains of nonverbal intelligence and verbal fluency. When analyzing each negative symptom domain separately, alogia and asociality/anhedonia were significantly negatively associated with nonverbal intelligence and alogia additionally with verbal fluency. Overall, our results in CHR patients are similar to those reported in patients with frank psychosis. The strong negative association between verbal fluency and negative symptoms may be indicative of an overlap between these constructs. Verbal fluency might have a strong influence on the clinical impression of negative symptoms (particularly alogia) and vice versa., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Patients with an at-risk mental state (ARMS) for psychosis and patients with attention-deficit/hyperactivity disorder (ADHD) have many overlapping signs and symptoms and hence can be difficult to differentiate clinically. The aim of this study was to investigate whether the differential diagnosis between ARMS and adult ADHD could be improved by neuropsychological testing., Methods: 168 ARMS patients, 123 adult ADHD patients and 109 healthy controls (HC) were recruited via specialized clinics of the University of Basel Psychiatric Hospital. Sustained attention and impulsivity were tested with the Continuous Performance Test, verbal learning and memory with the California Verbal Learning Test, and problem solving abilities with the Tower of Hanoi Task. Group differences in neuropsychological performance were analyzed using generalized linear models. Furthermore, to investigate whether adult ADHD and ARMS can be correctly classified based on the pattern of cognitive deficits, machine learning (i.e. random forests) was applied., Results: Compared to HC, both patient groups showed deficits in attention and impulsivity and verbal learning and memory. However, in adult ADHD patients the deficits were comparatively larger. Accordingly, a machine learning model predicted group membership based on the individual neurocognitive performance profile with good accuracy (AUC = 0.82)., Conclusions: Our results are in line with current meta-analyses reporting that impairments in the domains of attention and verbal learning are of medium effect size in adult ADHD and of small effect size in ARMS patients and suggest that measures of these domains can be exploited to improve the differential diagnosis between adult ADHD and ARMS patients., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Hyperprolactinemia is a known side effect of antipsychotics. In recent reports it has also been shown in antipsychotic-naïve 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 Früherkennung von Psychosen (FePsy) study. Blood sample collection took place under standardized conditions between 8 and 10am after an overnight fast and 30minutes of rest. All patients were antipsychotic-naïve and did not take any prolactin influencing medication., Results: Our sample consisted of 116 antipsychotic-naïve 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., (Copyright © 2017. Published by Elsevier B.V.)