Impact of motor dysfunction on neuropsychiatric symptom profile in patients with autopsy-confirmed Alzheimer's disease.

Motor dysfunction, which includes changes in gait, balance, and/or functional mobility, is a lesser-known feature of Alzheimer's Disease (AD), especially as it relates to the development of neuropsychiatric symptoms (NPS). This study (1) compared rates of NPS between autopsy-confirmed AD patients with and without early-onset motor dysfunction and (2) compared rates of non-AD dementia autopsy pathology (Lewy Body disease, Frontotemporal Lobar degeneration) between these groups. This retrospective longitudinal cohort study utilized National Alzheimer's Coordinating Center (NACC) data. Participants (N = 856) were required to have moderate-to-severe autopsy-confirmed AD, Clinical Dementia Rating-Global scores of ≤1 at their index visit, and NPS and clinician-rated motor data. Early motor dysfunction was associated with significantly higher NPI-Q total scores (T = 4.48, p < .001) and higher odds of delusions (OR [95%CI]: 1.73 [1.02-2.96]), hallucinations (2.45 [1.35-4.56]), depression (1.51 [1.11-2.06]), irritability (1.50 [1.09-2.08]), apathy (1.70 [1.24-2.36]), anxiety (1.38 [1.01-1.90]), nighttime behaviors (1.98 [1.40-2.81]), and appetite/eating problems (1.56 [1.09-2.25]). Early motor dysfunction was also associated with higher Lewy Body disease pathology (1.41 [1.03-1.93]), but not Frontotemporal Lobar degeneration (1.10 [0.71-1.69]), on autopsy. Our results suggest that motor symptoms in early AD are associated with a higher number and severity of NPS, which may be partially explained by comorbid non-AD neuropathology.

Associations of conservatism and jumping to conclusions biases with aberrant salience and default mode network.

AIM: While conservatism bias refers to the human need for more evidence for decision-making than rational thinking expects, the jumping to conclusions (JTC) bias refers to the need for less evidence among individuals with schizophrenia/delusion compared to healthy people. Although the hippocampus-midbrain-striatal aberrant salience system and the salience, default mode (DMN), and frontoparietal networks ("triple networks") are implicated in delusion/schizophrenia pathophysiology, the associations between conservatism/JTC and these systems/networks are unclear. METHODS: Thirty-seven patients with schizophrenia and 33 healthy controls performed the beads task, with large and small numbers of bead draws to decision (DTD) indicating conservatism and JTC, respectively. We performed independent component analysis (ICA) of resting functional magnetic resonance imaging (fMRI) data. For systems/networks above, we investigated interactions between diagnosis and DTD, and main effects of DTD. We similarly applied ICA to structural and diffusion MRI to explore the associations between DTD and gray/white matter. RESULTS: We identified a significant main effect of DTD with functional connectivity between the striatum and DMN, which was negatively correlated with delusion severity in patients, indicating that the greater the anti-correlation between these networks, the stronger the JTC and delusion. We further observed the main effects of DTD on a gray matter network resembling the DMN, and a white matter network connecting the functional and gray matter networks (all P < 0.05, family-wise error [FWE] correction). Function and gray/white matter showed no significant interactions. CONCLUSION: Our results support the novel association of conservatism and JTC biases with aberrant salience and default brain mode.

Neuropsychiatric Features of Fregoli Syndrome: An Individual Patient Meta-Analysis.

OBJECTIVE: Fregoli syndrome is a rare delusion characterized by the belief that familiar people are presenting themselves disguised as others to the affected person. Theories of delusional misidentification have suggested secondary ("organic") underlying mechanisms; however, the pathoetiology of Fregoli syndrome has not been systematically evaluated. The investigators aimed to compare the neuropsychiatric features of Fregoli syndrome in primary and secondary psychoses. METHODS: A systematic review and patient-level meta-analysis were conducted. Five databases were searched, ultimately yielding 83 studies that met selection criteria. Demographic characteristics, diagnosis, delusional content, neuropsychiatric features, investigations, and treatment information were extracted. Random-effects models were calculated, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: A total of 119 patients with Fregoli syndrome were identified: 62 patients (52%) with primary psychosis, 50 (42%) with secondary psychosis, and seven (6%) with an unclear etiology. Patients with secondary psychosis were less likely than patients with primary psychosis to experience persecutory features (OR=0.26, 95% CI=0.10, 0.67; p=0.0057). Moreover, patients with secondary psychosis were more likely to experience Fregoli syndrome during a first episode of psychosis (OR=11.00, 95% CI=2.45, 49.39; p=0.0017). Right-sided brain lesions were more prominent than left-sided brain lesions in the total sample (χ2=5.0, df=1, p=0.025) and in the secondary psychosis subgroup (χ2=4.26, df=1, p=0.039). CONCLUSIONS: This is the first meta-analysis to investigate Fregoli syndrome. An estimated 42% of the reported cases involved a secondary etiology. These findings provide clinicians with a better understanding of the symptomatology of Fregoli syndrome and have potential to be applied in future research and clinical practice.

A novel way to quantify schizophrenia symptoms in clinical trials.

BACKGROUND: A major problem in quantifying symptoms of schizophrenia is establishing a reliable distinction between enduring and dynamic aspects of psychopathology. This is critical for accurate diagnosis, monitoring and evaluating treatment effects in both clinical practice and trials. MATERIALS AND METHODS: We applied Generalizability Theory, a robust novel method to distinguish between dynamic and stable aspects of schizophrenia symptoms in the widely used Positive and Negative Symptom Scale (PANSS) using a longitudinal measurement design. The sample included 107 patients with chronic schizophrenia assessed using the PANSS at five time points over a 24-week period during a multi-site clinical trial of N-Acetylcysteine as an add-on to maintenance medication for the treatment of chronic schizophrenia. RESULTS: The original PANSS and its three subscales demonstrated good reliability and generalizability of scores (G = 0.77-0.93) across sample population and occasions making them suitable for assessment of psychosis risks and long-lasting change following a treatment, while subscales of the five-factor models appeared less reliable. The most enduring symptoms represented by the PANSS were poor attention, delusions, blunted affect and poor rapport. More dynamic symptoms with 40%-50% of variance explained by patient transient state including grandiosity, preoccupation, somatic concerns, guilt feeling and hallucinatory behaviour. CONCLUSIONS: Identified dynamic symptoms are more amendable to change and should be the primary target of interventions aiming at effectively treating schizophrenia. Separating out the dynamic symptoms would increase assay sensitivity in trials, reduce the signal to noise ratio and increase the potential to detect the effects of novel therapies in clinical trials.

A distinct inferential mechanism for delusions in schizophrenia.

Delusions, a core symptom of psychosis, are false beliefs that are rigidly held with strong conviction despite contradictory evidence. Alterations in inferential processes have long been proposed to underlie delusional pathology, but previous attempts to show this have failed to yield compelling evidence for a specific relationship between inferential abnormalities and delusional severity in schizophrenia. Using a novel, incentivized information-sampling task (a modified version of the beads task), alongside well-characterized decision-making tasks, we sought a mechanistic understanding of delusions in a sample of medicated and unmedicated patients with schizophrenia who exhibited a wide range of delusion severity. In this novel task, participants chose whether to draw beads from one of two hidden jars or to guess the identity of the hidden jar, in order to minimize financial loss from a monetary endowment, and concurrently reported their probability estimates for the hidden jar. We found that patients with higher delusion severity exhibited increased information seeking (i.e. increased draws-to-decision behaviour). This increase was highly specific to delusion severity as compared to the severity of other psychotic symptoms, working-memory capacity, and other clinical and socio-demographic characteristics. Delusion-related increases in information seeking were present in unmedicated patients, indicating that they were unlikely due to antipsychotic medication. In addition, after adjusting for delusion severity, patients as a whole exhibited decreased information seeking relative to healthy individuals, a decrease that correlated with lower socioeconomic status. Computational analyses of reported probability estimates further showed that more delusional patients exhibited abnormal belief updating characterized by stronger reliance on prior beliefs formed early in the inferential process, a feature that correlated with increased information seeking in patients. Other decision-making parameters that could have theoretically explained the delusion effects, such as those related to subjective valuation, were uncorrelated with both delusional severity and information seeking among the patients. In turn, we found some preliminary evidence that subjective valuation (rather than belief updating) may explain group differences in information seeking unrelated to delusions. Together, these results suggest that abnormalities in belief updating, characterized by stronger reliance on prior beliefs formed by incorporating information presented earlier in the inferential process, may be a core computational mechanism of delusional ideation in psychosis. Our results thus provide direct empirical support for an inferential mechanism that naturally captures the characteristic rigidity associated with delusional beliefs.

A case of mirror image agnosia and mirrored self-misidentification syndrome in schizophrenia without dementia or structural abnormalities.

Delusional misidentification syndrome (DMS) is an umbrella term encompassing a variety of disorders. One rare form of DMS is the delusional misidentification of one's own reflection, known as "mirrored self-misidentification syndrome". In "mirror image agnosia", the ability to identify the image of self and/or others in the mirror is lost, while the ability to identify the mirror itself is preserved. To our knowledge, mirror image agnosia has never been described in a patient with schizophrenia. Herein we present a case of a patient with schizophrenia with severe delusions of both mirrored self-misidentification and mirror image agnosia without any structural abnormalities or dementia.

Delusions and theories of belief.

Cognitive neuropsychiatry is a branch of cognitive psychology that seeks to explain neuropsychiatric symptoms in terms of disruptions or damage to normal cognitive processes. A key objective of this approach is to use insights derived from the study of pathological symptoms to inform accounts of premorbid cognitive systems. Delusions, in particular, can be considered to represent dysfunction of the cognitive processes underlying belief formation, so studying delusions may provide unique insights into nonpathological belief. While this approach has provided compelling accounts for a range of delusions in terms of putative cognitive dysfunctions, it is less clear that it has achieved progress in its reciprocal goal of informing understanding of belief more generally. In this review, we trace the origins of the cognitive neuropsychiatric approach and consider the reasons for the lack of progress. We propose a tentative framework to overcome these challenges and suggest directions for future research.

Jumping to conclusions in the less-delusion-prone? Further evidence from a more reliable beads task.

BACKGROUND: A single meta-analysis has found that healthy people with higher delusion-proneness tend to gather less information (i.e., make fewer draws to decision, or DTD) on the beads task, although the findings of contributing studies were mixed, and the pooled effect size was small. However, using a new and more reliable "distractor sequences" beads task, we recently found a positive relationship between delusion-proneness and DTD in a healthy sample. In the current study, we re-tested this relationship in a new sample, and tested the possibility that the relationship is driven by participant's ability to understand and use odds or likelihood information ("odds literacy"). METHODS: Healthy participants (N = 167) completed the distractor sequences beads task, the Peters Delusions Inventory (PDI) which measures delusion-proneness, a measure of odds literacy, and the Depression, Anxiety, and Stress scale. RESULTS: PDI and DTD were positively correlated, and comparing PDI quartiles on DTD confirmed a statistically significant trend of increasing DTD with PDI quartile. Odds literacy was positively rather than negatively associated with both DTD and PDI. Anxiety was positively correlated with PDI and DTD. CONCLUSIONS: We replicated our earlier finding that DTD and delusion-proneness were positively related in a non-clinical sample, but found that increased odds-literacy did not drive lower PDI and DTD, and hence did not explain their covariance. It is possible however that anxiety and co-occurring risk aversion drive increased delusion-proneness and information-gathering, potentially accounting for the positive relationship between PDI and DTD.

Hallucinations, somatic-functional disorders of PD-DLB as expressions of thalamic dysfunction.

Hallucinations, delusions, and functional neurological manifestations (conversion and somatic symptom disorders) of Parkinson's disease (PD) and dementia with Lewy bodies increase in frequency with disease progression, predict the onset of cognitive decline, and eventually blend with and are concealed by dementia. These symptoms share the absence of reality constraints and can be considered comparable elements of the PD-dementia with Lewy bodies psychosis. We propose that PD-dementia with Lewy bodies psychotic disorders depend on thalamic dysfunction promoting a theta burst mode and subsequent thalamocortical dysrhythmia with focal cortical coherence to theta electroencephalogram rhythms. This theta electroencephalogram activity, also called fast-theta or pre-alpha, has been shown to predict cognitive decline and fluctuations in Parkinson's disease with dementia and dementia with Lewy bodies. These electroencephalogram alterations are now considered a predictive marker for progression to dementia. The resulting thalamocortical dysrhythmia inhibits the frontal attentional network and favors the decoupling of the default mode network. As the default mode network is involved in integration of self-referential information into conscious perception, unconstrained default mode network activity, as revealed by recent imaging studies, leads to random formation of connections that link strong autobiographical correlates to trivial stimuli, thereby producing hallucinations, delusions, and functional neurological disorders. The thalamocortical dysrhythmia default mode network decoupling hypothesis provides the rationale for the design and testing of novel therapeutic pharmacological and nonpharmacological interventions in the context of PD, PD with dementia, and dementia with Lewy bodies. © 2019 International Parkinson and Movement Disorder Society.

Aberrant myelination of the cingulum and Schneiderian delusions in schizophrenia: a 7T magnetization transfer study.

BACKGROUND: The structural integrity of the anterior cingulum has been repeatedly observed to be abnormal in patients with schizophrenia. More recently, aberrant myelination of frontal fasciculi, especially, cingulum has been proposed to underlie delayed corollary discharges that can affect sense of agency and contribute to delusions of control (Schneiderian delusions). Using the magnetization transfer phenomenon at an ultra-high field 7T MRI, we investigated the putative myelin content of cingulum bundle in patients with schizophrenia. METHODS: Seventeen clinically stable patients with schizophrenia and 20 controls were recruited for this 7T MRI study. We used a region-of-interest method and extracted magnetization transfer ratio (MTR) from left and right dorsal cingulum bundles and estimated patients v. controls differences. We also related the cingulum MTR values to the severity of Schneiderian delusions. RESULTS: Patients had a significant reduction in the MTR, indicating reduced myelin content, in the cingulum bundle (right cingulum Hedges' g = 0.91; left cingulum g = 0.03). The reduced MTR of left cingulum was associated with higher severity of Schneiderian delusions (τ = -0.45, p = 0.026) but no such relationship was seen for the right cingulum MTR (τ = -0.136, p = 0.50) among patients. The association between the left cingulum MTR and Schneiderian delusions was not explained by the presence of other delusions, hallucinations, disorganization or negative symptoms. CONCLUSIONS: Dysmyelination of the cingulum bundle is seen in a subgroup of patients with schizophrenia and may be involved in the mechanism of Schneiderian delusions.

Reduced parietofrontal effective connectivity during a working-memory task in people with high delusional ideation

Background: Working-memory impairment is a core cognitive dysfunction in people with schizophrenia and people at mental high risk. Recent imaging studies on working memory have suggested that abnormalities in prefrontal activation and in connectivity between the frontal and parietal regions could be neural underpinnings of the different stages of psychosis. However, it remains to be explored whether comparable alterations are present in people with subclinical levels of psychosis, as experienced by a small proportion of the general population who neither seek help nor show constraints in daily functioning. Methods: We compared 24 people with subclinical high delusional ideation and 24 people with low delusional ideation. Both groups performed an n-back working-memory task during functional magnetic resonance imaging. We characterized frontoparietal effective connectivity using dynamic causal modelling. Results: Compared to people who had low delusional ideation, people with high delusional ideation showed a significant increase in dorsolateral prefrontal activation during the working-memory task, as well as reduced working-memory-dependent parietofrontal effective connectivity in the left hemisphere. Group differences were not evident at the behavioural level. Limitations: The current experimental design did not distinguish among the working-memory subprocesses; it remains unexplored whether differences in connectivity exist at that level. Conclusion: These findings suggest that alterations in the working-memory network are also present in a nonclinical population with psychotic experiences who do not display cognitive deficits. They also suggest that alterations in working-memory-dependent connectivity show a putative continuity along the spectrum of psychotic symptoms.

The Nose Knows or Does it? Olfactory Reference Syndrome in Patients Presenting for Assessment of Unusual Body Odor.

Olfactory reference syndrome (ORS) is a rarely diagnosed psychiatric disorder in which individuals falsely believe that they emit an offensive body odor. This retrospective cohort study characterizes the clinical and demographic features of 54 individuals who presented to a Canadian genetics clinic for query trimethylaminuria (TMAU), an inherited disorder in which a pungent fishy odor is produced. The majority (83%) were found to have a likely diagnosis of ORS and a high rate (73.3%) of concomitant psychiatric disorders; only two patients were diagnosed with TMAU. This study highlights the genetics clinic as an unexpected and major ascertainment point for ORS, and shows that ORS can be differentiated from TMAU by age of onset (~28 years), odor characterization (refuse-related), and the presence of associated comorbid psychiatric diagnoses. There is a low diagnostic rate of ORS, attesting to the need for improved education and awareness.

Explaining delusional beliefs: a hybrid model.

Introduction: In this paper we present and defend a hybrid theory of the development of delusions that incorporates the central ideas of two influential (yet sometimes bitterly opposing) theoretical approaches to delusions-the two-factor theory and the prediction error theory. Method: After introducing the central ideas of the two-factor theory and the prediction error theory, we describe the motivations for our conciliatory project, explain the theoretical details of the hybrid theory we propose, and answer potential objections to our proposal. Results: According to the hybrid theory we advance, the first factor of a delusion is physically grounded in an abnormal prediction error, and the second factor is physically grounded in the overestimation of the precision of the abnormal prediction error. Against anticipated objections, we argue that the hybrid theory is internally coherent, and that it constitutes a genuine hybrid between the two-factor theory and the prediction error theory. Conclusion: A rapprochement between the two-factor theory and the prediction error theory is both possible and desirable. In particular, our hybrid theory provides a parsimonious and unified account of delusions, whether monothematic or polythematic, across a wide variety of medical conditions.

Does Change over Time in Delusional Beliefs as Measured with PDI Predict Change over Time in Belief Flexibility Measured with MADS?

Delusional beliefs and their behavioral consequences are predominant symptoms in patients with psychosis and play an important role in the treatment. Delusional beliefs are a multidimensional concept which can be divided into three components: distress, preoccupation and conviction of delusions. These can be measured using Peters delusions inventory (PDI-21). We question, whether changes in delusional beliefs over time during treatment measured with the PDI-21 can predict changes in belief flexibility measured with the Maudsley assessment of delusions schedule (MADS). We used a group of patients from a randomized controlled trial for a cognitive intervention for psychosis or psychotic symptoms. Aside standard treatment for psychosis, half of the patients took part in a group treatment "Michael's game". Patients were assessed at baseline (T1), at 3 months (T2), and at 9 months (T3). We measured delusional beliefs using PDI-21 and belief flexibility with the MADS. One hundred seventy-two patients were included in the analysis. We measured a main effect of PDI-21scores on belief flexibility measured with MADS. PDI-21 Conviction scores predicted outcomes for all measured MADS items. Increasing PDI Distress and Preoccupation scores were predictors for being more likely to dismiss beliefs and change conviction. Time itself was a predictor for changing conviction and being able to plan a behavioral experiment. Overall the changes in PDI scores predicted outcomes for belief flexibility measured with MADS items. The PDI-21 could be a simple and effective way to measure progress in treatment on delusional beliefs.

'I am dead': Cotard syndrome and dementia.

Background: Cotard syndrome is a rare condition whose main feature is a nihilistic delusion ranging from the denial of body parts to that of the existence of one's own life or even the entire universe. Objectives: The aim of this article is to review the nosological significance of Cotard syndrome and to explore the disorder among patients with dementia. Methods: Medline and Google Scholar searches were conducted for relevant articles, chapters and books published before 2018. Search terms used included Cotard delusion, Cotard syndrome and dementia, nihilistic delusion. Publications found through this indexed search were reviewed for further relevant references. Results and conclusion: In this narrative review we emphasise the fact that cases of Cotard syndrome involving patients with dementia are reported quite infrequently. Published studies are limited to very short series or isolated cases. Clinicians are obliged to treat the disorder. They should be alert to the potential high risk inherent in this condition. Keypoints Cotard syndrome is a rare condition characterised by nihilistic delusions that may range from negation of existence of parts of the body to delusion of being dead. The prevalence and incidence of this rare syndrome are not known. Since Cotard's syndrome is conceptualised as part of an underlying disorder, several psychiatric and somatic diseases have been associated with the syndrome. The syndrome may occur in patients suffering from dementia.

Psychosis and Clinical Outcomes in Alzheimer Disease: A Longitudinal Study.

OBJECTIVE: Psychotic symptoms are a common feature in Alzheimer disease (AD), occurring in approximately 40% of patients. These symptoms are associated with worse clinical outcomes. Comparatively little research, however, has distinguished delusions and hallucinations, which may have distinct clinical, neuropathological, and genetic correlates. To address this, the current study examined the clinical outcomes associated with delusions and hallucinations in AD. DESIGN: Three-year observational study. SETTING: Nine memory clinics in Australia. PARTICIPANTS: A total of 445 patients with AD. MEASUREMENTS: Measures of neuropsychiatric symptoms, dementia severity, cognition, function, caregiver burden, and medication use were completed annually for 3 years with additional assessments at 3 months and 6 months in the first year. Mortality data were obtained from state registries approximately 5 years after the study. RESULTS: Of 445 patients, 102 (22.9%) developed only delusions, 39 (8.8%) developed only hallucinations, and 84 (18.9%) developed both symptoms. Delusions and hallucinations were both associated with greater dementia severity, poorer cognition and function, higher levels of other neuropsychiatric symptoms, and greater caregiver burden. The presence of both symptoms was associated with worse outcomes than only one of these symptoms. Delusions, both by themselves and in combination with hallucinations, predicted institutionalization. Antipsychotic medication use predicted mortality. CONCLUSIONS: Delusions and hallucinations independently and in combination are associated with poor clinical outcomes. The findings highlight the challenges managing these patients, particularly given the high levels of caregiver burden associated with psychotic symptoms and the likely mortality arising from antipsychotic medication.

Delusional disorder: The role of personality and emotions on delusional ideation.

The relationship between personality and Delusional Disorder in still debated. The present study aimed to evaluate the role of personality features and emotional dispositions on the proneness to delusional beliefs, through the lens of a dimensional approach. 91 outpatients were administered the Structured Interview for DSM-IV Personality Disorders, the Pathological Narcissism Inventory, the Positive and Negative Affect Schedule and the Peters et al. Delusions Inventory. Delusion proneness was positively related to the "Hiding the Self" domain of narcissistic vulnerability and to paranoid traits and negatively related to "Positive Affect". Paranoid traits and "Hiding the Self" significantly interacted in influencing delusion ideation. These data suggest that proneness to delusion depends, at least in part, on a complex interplay between specific emotional and paranoid dispositions within personality.

A latent class analysis of psychotic symptoms in the general population.

OBJECTIVE: Individuals with psychotic symptoms may actually correspond to various subgroups, characterized by different patterns of psychotic symptoms as well as specific sociodemographic and clinical correlates. We aimed to identify groups of individuals from the general population with specific patterns of psychotic symptoms. METHODS: In a 38,694-subject survey, a latent class analysis was performed to identify subgroups based on the distribution of seven psychotic symptoms taken from the Mini International Neuropsychiatric Interview. The different classes were subsequently compared according to sociodemographic and clinical correlates. RESULTS: The best fit was obtained with a four-class solution, including the following: (1) a class with a low prevalence of all psychotic symptoms ('LOW', 85.9%); (2) a class with a high prevalence of all psychotic symptoms ('HAL + DEL', 1.7%); and classes with a high prevalence of (3) hallucinations ('HAL', 4.5%) or (4) delusions ('DEL', 7.9%). The HAL + DEL class displayed higher rates of history of trauma, social deprivation and migrant status, while the HAL and DEL classes displayed intermediate rates between HAL + DEL and LOW. HAL + DEL displayed the highest rates of psychotic and non-psychotic disorders and the use of mental health treatment, while HAL and DEL displayed intermediate rates of these disorders between HAL + DEL and LOW. In comparison to the HAL class, psychotic and substance use disorders were more frequent in the DEL class, while anxiety and mood disorders were less frequent. CONCLUSION: These findings support the hypothesis of a continuum model relating the level of psychotic symptoms to the level of global psychopathology.

Contradiction processing in schizophrenia.

INTRODUCTION: Patients with schizophrenia present clinically with difficulties in manipulating contradictory information in the form of loose associations, surface contradictions and delusional beliefs. It is to date unclear whether patients can detect and process information that contradicts their beliefs and prior knowledge and whether this capacity is related to their symptoms and the nature of contradictory stimuli (e.g., personally significant information, emotional information). METHODS: We probed contradiction processing in patients with schizophrenia and healthy controls using sentence verification tasks that involve self-referential judgements (Experiment 1) and general knowledge (Experiment 2), while manipulating the emotional content of the stimuli. RESULTS: We found no differences between patients and controls either on reaction time (Experiment 1 & 2) or accuracy measures (Experiment 1). CONCLUSIONS: Our results show no general impairment in contradiction processing in schizophrenia. Rather, failures to detect and correct contradictions in symptoms such as formal though disorder or delusions could arise through a complex interplay between executive dysfunctions, stress and the emotional content of the information.

Shift toward prior knowledge confers a perceptual advantage in early psychosis and psychosis-prone healthy individuals.

Many neuropsychiatric illnesses are associated with psychosis, i.e., hallucinations (perceptions in the absence of causative stimuli) and delusions (irrational, often bizarre beliefs). Current models of brain function view perception as a combination of two distinct sources of information: bottom-up sensory input and top-down influences from prior knowledge. This framework may explain hallucinations and delusions. Here, we characterized the balance between visual bottom-up and top-down processing in people with early psychosis (study 1) and in psychosis-prone, healthy individuals (study 2) to elucidate the mechanisms that might contribute to the emergence of psychotic experiences. Through a specialized mental-health service, we identified unmedicated individuals who experience early psychotic symptoms but fall below the threshold for a categorical diagnosis. We observed that, in early psychosis, there was a shift in information processing favoring prior knowledge over incoming sensory evidence. In the complementary study, we capitalized on subtle variations in perception and belief in the general population that exhibit graded similarity with psychotic experiences (schizotypy). We observed that the degree of psychosis proneness in healthy individuals, and, specifically, the presence of subtle perceptual alterations, is also associated with stronger reliance on prior knowledge. Although, in the current experimental studies, this shift conferred a performance benefit, under most natural viewing situations, it may provoke anomalous perceptual experiences. Overall, we show that early psychosis and psychosis proneness both entail a basic shift in visual information processing, favoring prior knowledge over incoming sensory evidence. The studies provide complementary insights to a mechanism by which psychotic symptoms may emerge.