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.

Is intuition allied with jumping to conclusions in decision-making? An intensive longitudinal study in patients with delusions and in non-clinical individuals.

Research suggests that a jumping-to-conclusions (JTC) bias, excessive intuition, and reduced analysis in information processing may favor suboptimal decision-making, both in non-clinical and mentally disordered individuals. The temporal relationship between processing modes and JTC bias, however, remains unexplored. Therefore, using an experience sampling methodology (ESM) approach, this study examines the temporal associations between intuitive/analytical information processing, JTC bias, and delusions in non-clinical individuals and patients with schizophrenia. Specifically, we examine whether a high use of intuitive and/or a low use of analytical processing predicts subsequent JTC bias and paranoid conviction. In a smartphone-based ESM study, participants will be prompted four times per day over three consecutive days to answer questionnaires designed to measure JTC bias, paranoid conviction, and preceding everyday-life intuition/analysis. Our hierarchical data will be analyzed using multilevel modelling for hypothesis testing. Results will further elucidate the role of aberrant human reasoning, particularly intuition, in (non-)clinical delusions and delusion-like experiences, and also inform general information processing models.

Delusional thinking and action binding in healthy individuals.

Action binding is the effect that the perceived time of an action is shifted towards the action related feedback. A much larger action binding effect in schizophrenia compared to normal controls has been shown, which might be due to positive symptoms like delusions. Here we investigated the relationship between delusional thinking and action binding in healthy individuals, predicting a positive correlation between them. The action binding effect was evaluated by comparing the perceived time of a keypress between an operant (keypress triggering a sound) and a baseline condition (keypress alone), with a novel testing method that massively improved the precision of the subjective timing measurement. A positive correlation was found between the tendency of delusional thinking (measured by the 21-item Peters et al. delusions inventory) and action binding across participants after controlling for the effect of testing order between operant and baseline conditions. The results indicate that delusional thinking in particular influences action time perception and support the notion of a continuous distribution of schizotypal traits with normal controls at one end and clinical patients at the other end.

Clinical Phenotypes of Behavioral Variant Frontotemporal Dementia by Age at Onset.

BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is generally considered a young-onset dementia, although age at onset is highly variable. While several studies indicate clinical differences regarding age at onset, no biomarker validated cohort studies with updated clinical criteria have been performed. OBJECTIVE: We aimed to examine behavior, cognition, and mortality over the full age spectrum in a cohort of bvFTD patients with neuroimaging, genetic, or histopathological confirmation and exclusion of positive Alzheimer's disease biomarkers or severe cerebrovascular damage. METHODS: In total, 315 patients with a clinical diagnosis of probable or definite bvFTD were included from the Amsterdam Dementia Cohort and grouped into quartiles by age-at-diagnosis. Neuropsychiatric symptoms and cognitive functioning were assessed with the neuropsychiatric inventory, the geriatric depression scale and a neuropsychological test battery. Data on mortality was obtained from the Dutch municipal register. Associations between age-at-diagnosis and clinical features and mortality risk were examined. RESULTS: Age-at-diagnosis ranged from 26 to 85 years and established quartiles with mean ages of 52±6, 61±2, 66±2, and 74±3 years. In the total sample, 44.4%exceeded an age of 65 years at time of diagnosis. Earlier age-at-diagnosis was associated with more severe behavioral symptoms, while later age-at-diagnosis was associated with more severe memory impairment. Unexpectedly, mortality risk was not associated with age-at-diagnosis. CONCLUSION: In bvFTD, symptom profile is associated with age-at-diagnosis. This should be taken into account with regard to diagnostics, patient management, and trial design. Additionally, based on our sample, the prevalence of late-onset bvFTD is higher than generally thought.

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.

Looking into a Deluded Brain through a Neuroimaging Lens.

Delusions are irrational, tenacious, and incorrigible false beliefs that are the most common symptom of a range of brain disorders including schizophrenia, Alzheimer's, and Parkinson's disease. In the case of schizophrenia and other primary delusional disorders, their appearance is often how the disorder is first detected and can be sufficient for diagnosis. At this time, not much is known about the brain dysfunctions leading to delusions, and hindering our understanding is that the complexity of the nature of delusions, and their very unique relevance to the human experience has hampered elucidation of their underlying neurobiology using either patients or animal models. Advances in neuroimaging along with improved psychiatric and cognitive modeling offers us a new opportunity to look with more investigative power into the deluded brain. In this article, based on data obtained from neuroimaging studies, we have attempted to draw a picture of the neural networks involved when delusion is present and evaluate whether different manifestations of delusions engage different regions of the brain.

Managing the Burden of Dementia Related Delusions and Hallucinations.

Identify the burden experienced by patients with dementia-related delusions and hallucinations. Assess patients with dementia for the presence of delusions and hallucinations. Individualize treatment in patients with dementia-related delusions and hallucinations. Align treatment of patients with Parkinson's psychosis with current recommendations.

Factor Structure of Cotard's Syndrome: Systematic Review of Case Reports. / Estructura factorial del Síndrome de Cotard: revisión sistemática de reportes de caso.

INTRODUCTION: Cotard's syndrome is a rare psychiatric condition. As a result, current information is mainly based on reports and case series. OBJECTIVE: To analyse the psychopathological characteristics and the grouping of the symptoms of the Cotard's syndrome cases reported in the medical literature. METHODS: A systematic review of the literature of all reported cases of Cotard's syndrome from 2005 to January 2018 was performed in the MEDLINE/PubMed database. Demographic variables and clinical characteristics of each case were collected. An exploratory factor analysis of the symptoms was performed. RESULTS: The search identified 86 articles, of which 69 were potentially relevant. After reviewing the full texts, 55 articles were selected for the systematic review, in which we found 69 cases. We found that the diagnosis of major depression (P<0.001) and organic mental disorder (P=0.004) were more frequent in the older group with Cotard's syndrome. An exploratory factor analysis extracted 3 factors: psychotic depression, in which it includes patients with delusions of guilt (0.721), suicidal ideas (0.685), delusions of damnation (0.662), nihilistic delusions of the body (0.642), depression (0.522), and hypochondriacal delusions (0.535); delusive-hallucinatory, with patients who presented delusions of immortality (0.566), visual hallucinations (0.545) and nihilistic delusions of existence (0.451), and mixed, with patients who presented nihilistic delusions of concepts (0.702), anxiety (0.573), and auditory hallucinations (0.560). CONCLUSIONS: The psychopathology of Cotard's syndrome is more complex than the simple association with the delusion of being dead, since it encompasses a factorial structure organised into 3 factors.

The impact of theory of mind and neurocognition on delusionality in anorexia nervosa.

The current study aimed to examine the impact of theory of mind (ToM) deficits on body image delusionality in anorexia nervosa (AN) while accounting for the effect of other cognitive functions. ToM and other cognitive functions were assessed in 46 patients with AN and 42 healthy controls. We used the Brown Assessment of Beliefs Scale to assess the degree of delusionality of body image beliefs in AN patients. Delusional body image beliefs were identified in 26.1% and overvalued ideas in 30.4% of the AN patients. Moderate but significant associations were found between impairments in ToM-overall capacity, cognitive and affective components-and body image delusionality. The effect of overall ToM performance on delusionality remained significant after controlling for other cognitive factors. General intelligence was also significantly associated with delusionality. Our findings support the notion that difficulties in taking the perspective of others contribute to insight impairment in AN. Further investigation is required to examine the effect of failures in social cognition and metacognition on insight in AN.

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.

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.

Coronovirus infection as a novel delusional topic.

Delusional topics tend to rapidly incorporate popular hot topical issues. Thus, the current coronavirus COVID-19 pandemic has rapidly reached delusional themes in patients with psychiatric disorders. Here we present the clinical case of a Spanish woman with bipolar disorder that included coronavirus infection in her delusional themes even faster than the real infection reached mainland Spain.

Parietal-Prefrontal Feedforward Connectivity in Association With Schizophrenia Genetic Risk and Delusions.

OBJECTIVE: Conceptualizations of delusion formation implicate deficits in feedforward information updating across the posterior to prefrontal cortices, resulting in dysfunctional integration of new information about contexts in working memory and, ultimately, failure to update overfamiliar prior beliefs. The authors used functional MRI and machine learning models to address individual variability in feedforward parietal-prefrontal information updating in patients with schizophrenia. They examined relationships between feedforward connectivity, and delusional thinking and polygenic risk for schizophrenia. METHODS: The authors studied 66 schizophrenia patients and 143 healthy control subjects during performance of context updating in working memory. Dynamic causal models of effective connectivity were focused on regions of the prefrontal and parietal cortex potentially implicated in delusion processes. The effect of polygenic risk for schizophrenia on connectivity was examined in healthy individuals. The authors then leveraged support vector regression models to define optimal normalized target connectivity tailored for each patient and tested the extent to which deviation from this target could predict individual variation in severity of delusions. RESULTS: In schizophrenia patients, updating and manipulating context information was disproportionately less accurate than was working memory maintenance, with an interaction of task accuracy by diagnosis. Patients with delusions also tended to have relatively reduced parietal-prefrontal feedforward effective connectivity during context updating in working memory manipulation. The same connectivity was adversely influenced by polygenic risk for schizophrenia in healthy subjects. Individual patients' deviation from predicted "normal" feedforward connectivity based on the support vector regression models correlated with severity of delusions. CONCLUSIONS: These computationally derived observations support a role for feedforward parietal-prefrontal information processing deficits in delusional psychopathology and in genetic risk for schizophrenia.

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.

Main Symptomatic Treatment Targets in Suspected and Early Psychosis: New Insights From Network Analysis.

The early detection and intervention in psychoses prior to their first episode are presently based on the symptomatic ultra-high-risk and the basic symptom criteria. Current models of symptom development assume that basic symptoms develop first, followed by attenuated and, finally, frank psychotic symptoms, though interrelations of these symptoms are yet unknown. Therefore, we studied for the first time their interrelations using a network approach in 460 patients of an early detection service (mean age = 26.3 y, SD = 6.4; 65% male; n = 203 clinical high-risk [CHR], n = 153 first-episode psychosis, and n = 104 depression). Basic, attenuated, and frank psychotic symptoms were assessed using the Schizophrenia Proneness Instrument, Adult version (SPI-A), the Structured Interview for Psychosis-Risk Syndromes (SIPS), and the Positive And Negative Syndrome Scale (PANSS). Using the R package qgraph, network analysis of the altogether 86 symptoms revealed a single dense network of highly interrelated symptoms with 5 discernible symptom subgroups. Disorganized communication was the most central symptom, followed by delusions and hallucinations. In line with current models of symptom development, the network was distinguished by symptom severity running from SPI-A via SIPS to PANSS assessments. This suggests that positive symptoms developed from cognitive and perceptual disturbances included basic symptom criteria. Possibly conveying important insight for clinical practice, central symptoms, and symptoms "bridging" the association between symptom subgroups may be regarded as the main treatment targets, in order to prevent symptomatology from spreading or increasing across the whole network.