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Background: Patients with schizophrenia display metacognitive impairments, such as hasty decision-making during probabilistic reasoning --the 'jumping to conclusion' bias (JTC). Our recent fMRI study revealed reduced activations in the right ventral striatum (VS) and the ventral tegmental area (VTA) to be associated with decision-making in patients with schizophrenia. It is unclear whether these functional alterations occur in the at-risk mental state (ARMS). Methods: We administered the classical beads task and fMRI among ARMS patients and healthy controls matched for age, sex, education and premorbid verbal intelligence. None of the ARMS patients was treated with antipsychotics. Both tasks request probabilistic decisions after a variable amount of stimuli. We evaluated activation during decision-making under certainty versus uncertainty and the process of final decision-making. Results: We included 24 AMRS patients and 24 controls in our study. Compared with controls, ARMS patients tended to draw fewer beads and showed significantly more JTC bias in the classical beads task, mirroring findings in patients with schizophrenia. During fMRI, ARMS patients did not demonstrate JTC bias on the behavioural level, but showed a significant hypoactivation in the right VS during the decision stage. Limitations: Owing to the cross-sectional design of the study, results are constrained to a better insight into the neurobiology of risk constellations, but not prepsychotic stages. Nine of the ARMS patients were treated with antidepressants and/or lorazepam. Conclusion: As in patients with schizophrenia, a striatal hypoactivation was found in ARMS patients. Confounding effects of antipsychotic medication can be excluded. Our findings indicate that error prediction signalling and reward anticipation may be linked to striatal dysfunction during prodromal stages and should be examined for their utility in predicting transition risk., Introduction Patients with schizophrenia have metacognitive deficits--reduced competence to control their cognition ('thinking about one's thinking'). They have impaired ability to appraise and weigh information effectively; to select appropriate responses, [...]

Background: Patients with schizophrenia have an approximately 10-fold higher risk for obsessive-compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms. Methods: To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory. Results: We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level. Limitations: The main limitation of this study is its cross-sectional design. Conclusion: To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations., Introduction Patients with schizophrenia have a lifetime risk of about 25% for comorbid obsessive-compulsive symptoms (OCS), and recent meta-analyses estimated that 12% fulfil the criteria for obsessive-compulsive disorder (OCD). (1,2) [...]

Abstract: Aim: Functional disability and social consequences frequently occur at the prodromal stage of schizophrenia. Efforts to recognize an increasing risk of psychosis onset have thus become a topical issue worldwide. This is to introduce the English version of the ERIraos early‐recognition inventory. Methods: The ERIraos, developed in a systematic, empirical approach from the Instrument for the Retrospective Assessment of the Onset of Schizophrenia, incorporates basic symptoms from the Cologne Early Recognition Study. The research version also includes as further predictive items so‐called brief limited intermittent psychotic symptoms and attenuated psychotic symptoms from the Comprehensive Assessment of At‐Risk Mental States instrument. Results: The ERIraos with its 15‐item screening Checklist and 50‐item Symptom List permits early recognition of psychosis risk in three steps of decreasing sensitivity and increasing specificity. Step 1 relies on patients’ self‐perception of symptoms, which prompt them to contact a primary health service. There, in Step 2, at‐risk individuals are identified using the Checklist, characterized by a low‐risk threshold, and referred to further examination using the Symptom List (Step 3). Information on symptom accumulation and increasing symptom severity enhances the instrument's predictive power. In a validation test, psychotic transitions increased linearly up to 50% over 2 years. Compared with other instruments and on the prodromal stage of depressive disorder, the ERIraos has shown good predictive capacity. Conclusions: The ERIraos has been successfully employed as a two‐step tool for the early recognition of psychosis risk in several German studies and translated into several foreign languages. [ABSTRACT FROM AUTHOR]

Schizophrenia is associated with significant impairments in social cognition. These impairments have been shown to go along with altered activation of the posterior superior temporal sulcus (pSTS). However, studies that investigate connectivity of pSTS during social cognition in schizophrenia are sparse. Twenty-two patients with schizophrenia and 22 matched healthy controls completed a social-cognitive task for functional magnetic resonance imaging that allows the investigation of affective Theory of Mind (ToM), emotion recognition and the processing of neutral facial expressions. Moreover, a resting-state measurement was taken. Patients with schizophrenia performed worse in the social-cognitive task (main effect of group). In addition, a group by social-cognitive processing interaction was revealed for activity, as well as for connectivity during the social-cognitive task, i.e., patients with schizophrenia showed hyperactivity of right pSTS during neutral face processing, but hypoactivity during emotion recognition and affective ToM. In addition, hypoconnectivity between right and left pSTS was revealed for affective ToM, but not for neutral face processing or emotion recognition. No group differences in connectivity from right to left pSTS occurred during resting state. This pattern of aberrant activity and connectivity of the right pSTS during social cognition might form the basis of false-positive perceptions of emotions and intentions and could contribute to the emergence and sustainment of delusions. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Patients with an increased risk for psychosis (‘at‐risk mental state’ (ARMS)) present various neurocognitive deficits. Not least because of differences in identifying the ARMS, results of previous studies are inconsistent. In most studies ARMS‐patients are classified by the experience of attenuated psychotic symptoms (APS) and/or brief limited intermittent psychotic symptoms (BLIPS). Few studies additionally assessed cognitive basic symptoms (BS). A comprehensive assessment in the very early stage of the ARMS is missing. Methods: In the present study we characterized ARMS‐patients for cognitive BS (ARMS‐BS), APS and BLIPS (ARMS‐A/B) according to the Early Recognition Inventory based on IRAOS (ERIraos). Furthermore, we assessed neurocognitive deficits using the MATRICS consensus cognitive battery for schizophrenia with a primary hypothesis regarding working memory performance. Groups of 38 ARMS‐patients and 38 healthy controls were matched for age, gender, education and premorbid verbal intelligence. Results: Between‐group comparisons revealed significant poorer working memory performance in addition to lower verbal learning and problem solving, slower processing speed and lower global neurocognitive functioning in ARMS‐patients as compared to controls. ARMS‐BS did not differ from ARMS‐A/B. Conclusions: These results underscore the presence of cognitive limitations in patients only presenting with cognitive BS. Knowledge of these early cognitive deviations supports the inclusion of early ARMS‐stages into a comprehensive concept of the psychosis risk state. Therapeutic interventions already applied at this stage might prevent deterioration of constraints. Longitudinal and interventional studies investigating the interaction of cognitive BS and neurocognitive as well as metacognitive deficits are warranted. [ABSTRACT FROM AUTHOR]

We examine whether calcineurin or protein phosphatase 2B (PP2B) regulates the basolateral inwardly rectifying potassium channel Kir4.1/Kir5.1 in the distal convoluted tubule (DCT). Application of tacrolimus (FK506) or cyclosporine A (CsA) increased whole-cell Kir4.1/Kir5.1-mediated K+ currents and hyperpolarized the DCT membrane. Moreover, FK506-induced stimulation of Kir4.1/Kir5.1 was absent in kidney tubule-specific 12 kDa FK506-binding protein-knockout mice (Ks-FKBP-12-KO). In contrast, CsA stimulated Kir4.1/Kir5.1 of the DCT in Ks-FKBP-12-KO mice, suggesting that FK506-induced stimulation of Kir4.1/Kir5.1 was due to inhibiting PP2B. Single-channel patch-clamp experiments demonstrated that FK506 or CsA stimulated the basolateral Kir4.1/Kir5.1 activity of the DCT, defined by NPo (a product of channel number and open probability). However, this effect was absent in the DCT treated with Src family protein tyrosine kinase (SFK) inhibitor or hydroxyl peroxide. Fluorescence imaging demonstrated that CsA treatment increased membrane staining intensity of Kir4.1 in the DCT of Kcnj10fl/fl mice. Moreover, CsA treatment had no obvious effect on phosphorylated NaCl cotransporter (pNCC) expression in Ks-Kir4.1-KO mice. Immunoblotting showed acute FK506 treatment increased pNCC expression in Kcnj10fl/fl mice, but this effect was attenuated in Ks-Kir4.1-KO mice. In vivo measurement of thiazide-induced renal Na+ excretion demonstrated that FK506 enhanced thiazide-induced natriuresis. This effect was absent in Ks-FKBP-12-KO mice and blunted in Ks-Kir4.1-KO mice. We conclude that inhibition of PP2B stimulates Kir4.1/Kir5.1 of the DCT and NCC and that PP2B inhibition-induced stimulation of NCC is partially achieved by stimulation of the basolateral Kir4.1/Kir5.1.

Background: The objective of this study is to test the conflicting theories concerning the association of negative self and other schemata and paranoid ideation., Methods: A risk-based approach, including risk stratification, is used to gain insight into the association of the negative self and other schemata that may be shared by individuals or differentiate between individuals at clinical high risk (CHR) for a first-episode psychosis and those with full-blown psychosis. The dataset includes a sample of individuals at CHR (n = 137) and a sample of individuals with persisting positive symptoms (PPS, n = 211). The CHR sample was subdivided according to a prognostic index yielding 4 CHR sub-classes with increasing risk for transition to psychosis., Results: Negative beliefs about the self were associated with paranoid ideation in CHR and a lower risk state. In the highest risk state and full-blown psychosis, there is an association with negative beliefs about others., Conclusion: These findings are in line with theories suggesting a switch from a predominantly activated negative self-schema to a malevolent others-schema in association with paranoid ideation along the risk-continuum. However, due to methodological limitations these results should be replicated by future studies., (© 2017 John Wiley & Sons Australia, Ltd.)