Aberrant activity and connectivity of the posterior superior temporal sulcus during social cognition in schizophrenia

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.publishe

Early cognitive basic symptoms are accompanied by neurocognitive impairment in patients with an 'at-risk mental state' for psychosis

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.publishe

Bias against disconfirmatory evidence in the 'at-risk mental state' and during psychosis

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

Reduced activity and connectivity of left amygdala in patients with schizophrenia treated with clozapine or olanzapine

Obsessive-compulsive symptoms (OCS) in patients with schizophrenia are a common co-occurring condition, often associated with additional impairments. A subgroup of these patients develops OCS during treatment with second-generation antipsychotics (SGAs), most importantly clozapine and olanzapine. So far, little is known about possible neural mechanism of these SGAs, which seem to aggravate or induce OCS. To investigate the role of SGA treatment on neural activation and connectivity during emotional processing, patients were stratified according to their monotherapy into two groups (group I: clozapine or olanzapine, n = 20; group II: amisulpride or aripiprazole, n = 20). We used an fMRI approach, applying an implicit emotion recognition task. Group comparisons showed significantly higher frequency and severity of comorbid OCS in group I than group II. Task specific activation was attenuated in group I in the left amygdala. Furthermore, functional connectivity from left amygdala to right ventral striatum was reduced in group I. Reduced amygdala activation was associated with OCS severity. Recent literature suggests an involvement of an amygdala-cortico-striatal network in the pathogenesis of obsessive-compulsive disorder. The observed differential activation and connectivity pattern of the amygdala might thus indicate a neural mechanism for the development of SGA-associated OCS in patients with schizophrenia. Further neurobiological research and interventional studies are needed for causal inferences.publishe

Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk

Between-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature

Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder

Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients

Publisher Correction: Common brain disorders are associated with heritable patterns of apparent aging of the brain:Common brain disorders are associated with heritable patterns of apparent aging of the brain

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