Different learning aberrations relate to delusion-like beliefs with different contents.

The prediction error account of delusions has had success. However, its explanation of delusions with different contents has been lacking. Persecutory delusions and paranoia are the common unfounded beliefs that others have harmful intentions towards us. Other delusions include believing that one's thoughts or actions are under external control or that events in the world have specific personal meaning. We compare learning in two different cognitive tasks, probabilistic reversal learning and Kamin blocking, that have relationships to paranoid and non-paranoid delusion-like beliefs, respectively. We find that clinical high-risk status alone does not result in different behavioural results in the probabilistic reversal learning task but that an individual's level of paranoia is associated with excessive switching behaviour. During the Kamin blocking task, paranoid individuals learned inappropriately about the blocked cue. However, they also had decreased learning about the control cue, suggesting more general learning impairments. Non-paranoid delusion-like belief conviction (but not paranoia) was associated with aberrant learning about the blocked cue but intact learning about the control cue, suggesting specific impairments in learning related to cue combination. We fit task-specific computational models separately to behavioural data to explore how latent parameters vary within individuals between tasks and how they can explain symptom-specific effects. We find that paranoia is associated with low learning rates in the probabilistic reversal learning task and the blocking task. Non-paranoid delusion-like belief conviction is instead related to parameters controlling the degree and direction of similarity between cue updating during simultaneous cue presentation. These results suggest that paranoia and other delusion-like beliefs involve dissociable deficits in learning and belief updating, which, given the transdiagnostic status of paranoia, might have differential utility in predicting psychosis.

Pediatric traumatic brain injury as a risk factor for psychosis and psychotic symptoms: a systematic review and meta-analysis.

BACKGROUND: Psychosis is one of the most disabling psychiatric disorders. Pediatric traumatic brain injury (pTBI) has been cited as a developmental risk factor for psychosis, however this association has never been assessed meta-analytically. METHODS: A systematic review and meta-analysis of the association between pTBI and subsequent psychotic disorders/symptoms was performed. The study was pre-registered (CRD42022360772) adopting a random-effects model to estimate meta-analytic odds ratio (OR) and 95% confidence interval (CI) using the Paule-Mandel estimator. Subgroup (study location, study design, psychotic disorder v. subthreshold symptoms, assessment type, and adult v. adolescent onset) and meta-regression (quality of evidence) analyses were also performed. The robustness of findings was assessed through sensitivity analyses. The meta-analysis is available online as a computational notebook with an open dataset. RESULTS: We identified 10 relevant studies and eight were included in the meta-analysis. Based on a pooled sample size of 479686, the pooled OR for the association between pTBI and psychosis outcomes was 1.80 (95% CI 1.11-2.95). There were no subgroup effects and no outliers. Both psychotic disorder and subthreshold symptoms were associated with pTBI. The overall association remained robust after removal of low-quality studies, however the OR reduced to 1.43 (95% CI 1.04-1.98). A leave-one-out sensitivity analysis showed the association was robust to removal of all but one study which changed the estimate to marginally non-significant. CONCLUSIONS: We report cautious meta-analytic evidence for a positive association between pTBI and future psychosis. New evidence will be key in determining long-term reliability of this finding.

Cross-cultural validation of the revised Green et al., paranoid thoughts scale.

BACKGROUND: With efforts increasing worldwide to understand and treat paranoia, there is a pressing need for cross-culturally valid assessments of paranoid beliefs. The recently developed Revised Green et al., Paranoid Thoughts Scale (R-GPTS) constitutes an easy to administer self-report assessment of mild ideas of reference and more severe persecutory thoughts. Moreover, it comes with clinical cut-offs for increased usability in research and clinical practice. With multiple translations of the R-GPTS already available and in use, a formal test of its measurement invariance is now needed. METHODS: Using data from a multinational cross-sectional online survey in the UK, USA, Australia, Germany, and Hong Kong (N = 2510), we performed confirmatory factory analyses on the R-GPTS and tested for measurement invariance across sites. RESULTS: We found sufficient fit for the two-factor structure (ideas of reference, persecutory thoughts) of the R-GPTS across cultures. Measurement invariance was found for the persecutory thoughts subscale, indicating that it does measure the same construct across the tested samples in the same way. For ideas of reference, we found no scalar invariance, which was traced back to (mostly higher) item intercepts in the Hong Kong sample. CONCLUSION: We found sufficient invariance for the persecutory thoughts scale, which is of substantial practical importance, as it is used for the screening of clinical paranoia. A direct comparison of the ideas of reference sum-scores between cultures, however, may lead to an over-estimation of these milder forms of paranoia in some (non-western) cultures.

Network Localization of Spontaneous Confabulation.

OBJECTIVE: Spontaneous confabulation is a symptom in which false memories are conveyed by the patient as true. The purpose of the study was to identify the neuroanatomical substrate of this complex symptom and evaluate the relationship to related symptoms, such as delusions and amnesia. METHODS: Twenty-five lesion locations associated with spontaneous confabulation were identified in a systematic literature search. The network of brain regions functionally connected to each lesion location was identified with a large connectome database (N=1,000) and compared with networks derived from lesions associated with nonspecific (i.e., variable) symptoms (N=135), delusions (N=32), or amnesia (N=53). RESULTS: Lesions associated with spontaneous confabulation occurred in multiple brain locations, but they were all part of a single functionally connected brain network. Specifically, 100% of lesions were connected to the mammillary bodies (familywise error rate [FWE]-corrected p<0.05). This connectivity was specific for lesions associated with confabulation compared with lesions associated with nonspecific symptoms or delusions (FWE-corrected p<0.05). Lesions associated with confabulation were more connected to the orbitofrontal cortex than those associated with amnesia (FWE-corrected p<0.05). CONCLUSIONS: Spontaneous confabulation maps to a common functionally connected brain network that partially overlaps, but is distinct from, networks associated with delusions or amnesia. These findings lend new insight into the neuroanatomical bases of spontaneous confabulation.

Grief as a Risk Factor for Psychosis: A Systematic Review.

PURPOSE OF REVIEW: The assessment of the risk of triggering psychosis upon exposure to grief is a challenge in clinical practice. Adequate diagnosis and early prevention are essential and may be helpful in the evolution of normal grief. We aimed to identify studies exploring grief as a risk factor for developing psychosis. RECENT FINDINGS: A systematic review of 3 databases (PubMed, EMBASE, and Cochrane Library) was conducted. RESULTS: In the first approach 618 studies were identified. After the selection process, 15 studies were included in the review. The association between grief and the risk of developing psychosis occurred at younger ages (before 18 years of age) in a first-degree relative and as a consequence of suicide or accidental death. We found that risk factors such as comorbidity, mental problems, unemployment, economic difficulties, and close ties with the deceased have a negative impact on health causing greater vulnerability to psychosis with a risk of developing complicated grief, with statistically significant results regarding the associations between early parental death and the probability of developing psychosis in adulthood.

Non-Pharmacological Interventions in the Management of Dementia-Related Psychosis: A Systematic Review and Meta-Analysis.

OBJECTIVE: As populations age globally, there is an increasing prevalence of dementia, with an estimated 153 million living with dementia by 2050. Up to 70% of people with dementia experience dementia-related psychosis (D-RP). Antipsychotic medications are associated with many adverse effects in older people. This review aims to evaluate the evidence of non-pharmacological interventions in managing D-RP. METHOD: The search of Medline, EMBASE, Web of Science, CINAHL, PsycINFO, and Cochrane included randomised controlled trials that evaluated non-pharmacological interventions. Data extraction and assessment of quality were assessed independently by two researchers. Heterogenous interventions were pooled using meta-analysis. RESULTS: A total of 18 articles (n = 2040 participants) were included and categorised into: sensory-, activity-, cognitive- and multi-component-orientated. Meta-analyses showed no significant impact in reducing hallucinations or delusions but person-centred care, cognitive rehabilitation, music therapy, and robot pets showed promise in single studies. CONCLUSIONS AND IMPLICATIONS: Future interventions should be developed and evaluated with a specific focus on D-RP as this was not the aim for many of the included articles.

Everything in its right place: a case report of reduplicative paramnesia with therapeutic and theoretical considerations.

Introductions: Reduplicative paramnesia (RP) is a rare and poorly understood phenomenon in which a person believes the place they are in has been replicated and exists in two places at once. There is minimal extant theoretical work addressing possible cognitive mechanisms subtending RP.Method: We present a new case of RP and discuss the therapeutic and theoretical implications of this case for the management and understanding of this phenomenon. Using the hypothetico-deductive approach to a neuropsychological case, we examine the phenomenon in the light of one and two-factor approaches to understanding the genesis of delusions.Results: The individual discussed in this case showed some evidence of relatively efficient incorporation of new evidence (belief updating) despite concurrently maintaining a delusional belief system.Conclusion: This case raises novel challenges for the two-factor account of neurological delusions.

Impact of Delusions and Hallucinations on Clinical Insight Dimensions in Schizophrenia Spectrum Disorders.

INTRODUCTION: Insight in psychosis has been conceptualized as a continuous, dynamic, and multidimensional phenomenon. This study aims to determine the impact of delusions and hallucinations in different dimensions of clinical insight in schizophrenia spectrum disorders. METHODS: Cross-sectional multicenter study including 516 patients (336 men) diagnosed with schizophrenia spectrum disorders. Based on dichotomized scores of Positive and Negative Syndrome Scale (PANSS) items P1 (delusions) and P3 (hallucinations), patients were assigned to four groups according to current clear presence of delusions (scores 4 or above 4 in PANSS item P1) and/or hallucinations (scores 4 or above 4 in PANNS item P3). Insight was assessed using the three main dimensions of the Scale of Unawareness of Mental Disorder (SUMD). RESULTS: Around 40% of patients showed unawareness of illness; 30% unawareness of the need for treatment; and 45% unawareness of the social consequences of the disorder. Patients with current clear presence of delusions had higher overall lack of awareness, regardless of current clear presence of hallucinations. Similarly, the clear presence of delusions showed a greater predictive value on insight than the presence of hallucinations, although the implication of both in the prediction was modest. CONCLUSIONS: Our results confirm that lack of insight is highly prevalent in schizophrenia spectrum disorders, particularly when patients experience delusions. This study adds insight-related data to the growing symptom-based research, where specific types of psychotic experiences such as hallucinations and delusions could form different psychopathological patterns, linking the phenomenology of delusions to a lack of clinical insight.

Eight-month intensive meditation-based intervention improves refractory hallucinations and delusions and quality of life in male inpatients with schizophrenia: a randomized controlled trial.

AIM: This study investigated the impact of an 8-month daily-guided intensive meditation-based intervention (iMI) on persistent hallucinations/delusions and health-related quality of life (QoL) in male inpatients with schizophrenia with treatment-refractory hallucinations and delusions (TRHDs). METHODS: A randomized controlled trial assigned 64 male inpatients with schizophrenia and TRHD equally to an 8-month iMI plus general rehabilitation program (GRP) or GRP alone. Assessments were conducted at baseline and the third and eighth months using the Positive and Negative Syndrome Scale (PANSS), 36-Item Short Form-36 (SF-36), and Five Facet Mindfulness Questionnaire (FFMQ). Primary outcomes measured PANSS reduction rates for total score, positive symptoms, and hallucinations/delusions items. Secondary outcomes assessed PANSS, SF-36, and FFMQ scores for psychotic symptoms, health-related QoL, and mindfulness skills, respectively. RESULTS: In the primary outcome, iMI significantly improved the reduction rates of PANSS total score, positive symptoms, and hallucination/delusion items compared with GRP at both the third and eighth months. Treatment response rates (≥25% reduction) for these measures significantly increased in the iMI group at the eighth month. Concerning secondary outcomes, iMI significantly reduced PANSS total score and hallucination/delusion items, while increasing scores in physical activity and mindfulness skills at both the third and eighth months compared with GRP. These effects were more pronounced with an 8-month intervention compared with a 3-month intervention. CONCLUSIONS: An iMI benefits patients with TRHDs by reducing persistent hallucinations/delusions and enhancing health-related QoL. Longer iMI duration yields superior treatment outcomes.

Daydreaming and grandiose delusions: development of the Qualities of Daydreaming Scale.

BACKGROUND: Daydreaming may contribute to the maintenance of grandiose delusions. Repeated, pleasant and vivid daydreams about the content of grandiose delusions may keep the ideas in mind, elaborate the details, and increase the degree of conviction in the delusion. Pleasant daydreams more generally could contribute to elevated mood, which may influence the delusion content. AIMS: We sought to develop a brief questionnaire, suitable for research and clinical practice, to assess daydreaming and test potential associations with grandiosity. METHOD: 798 patients with psychosis (375 with grandiose delusions) and 4518 non-clinical adults (1788 with high grandiosity) were recruited. Participants completed a daydreaming item pool and measures of grandiosity, time spent thinking about the grandiose belief, and grandiose belief conviction. Factor analysis was used to derive the Qualities of Daydreaming Scale (QuOD) and associations were tested using pairwise correlations and structural equation modelling. RESULTS: The questionnaire had three factors: realism, pleasantness, and frequency of daydreams. The measure was invariant across clinical and non-clinical groups. Internal consistency was good (alpha-ordinals: realism=0.86, pleasantness=0.93, frequency=0.82) as was test-retest reliability (intra-class coefficient=0.75). Daydreaming scores were higher in patients with grandiose delusions than in patients without grandiose delusions or in the non-clinical group. Daydreaming was significantly associated with grandiosity, time spent thinking about the grandiose delusion, and grandiose delusion conviction, explaining 19.1, 7.7 and 5.2% of the variance in the clinical group data, respectively. Similar associations were found in the non-clinical group. CONCLUSIONS: The process of daydreaming may be one target in psychological interventions for grandiose delusions.

The effects of the COVID-19 pandemic on the activities of Initial-phase Intensive Support Team for Dementia in Kobe City.

BACKGROUND: This study aimed to review the activities of the Kobe City Initial-phase Intensive Support Team for Dementia pre- and during the coronavirus disease 2019 (COVID-19) pandemic, to compare the characteristics of the target population and the performance of the team's activities, and determine the impact of the pandemic on the team's project. METHODS: The summary data obtained at the time of consultation, team activities, and participants' characteristics were extracted from 662 participants who started to receive support between April 2018 and March 2022. Statistical analysis was performed by dividing the participants into the following two groups: pre- and during COVID-19 pandemic groups. RESULTS: There was no significant difference in the number of new cases or cases that led to a dementia diagnosis between the pre- and during COVID-19 pandemic groups. However, there were significant differences in the number of home visits and rate of introduction of medical care between the two groups. In our study population, the number of participants with financial management difficulties and delusions increased and the number of participants who refused visitations slightly decreased. CONCLUSION: The Kobe City Initial-phase Intensive Support Team was able to continue its activities during the pandemic partly because the team is an independent, dedicated team. During the pandemic, there was an increase in the number of participants who were isolated because they were deprived of opportunities to interact with others, and who developed delusions and other psychiatric symptoms. Despite this situation, the professional team responded quickly through individual assessment of the individual needs by continuous outreach, taking into account the infection situation, and thus this outreach team functioned well even under the COVID-19 pandemic.

A description of COVID-19 related delusional content in admissions to an acute psychiatric unit.

Background: The COVID-19 pandemic had a profound global impact, affecting individuals, including those with mental illness, through early and widespread information dissemination. Although the neurobiological basis of delusions remains unclear, external stimuli and historical events are known to influence them. The pandemic provided a unique opportunity to explore this phenomenon. Aim: To determine the prevalence of COVID-19-related delusional content, among individuals presenting for treatment of psychosis during the peak of the COVID-19 pandemic and investigate associated clinical and demographic factors. Setting: Chris Hani Baragwanath Academic Hospital in-patient psychiatry department. Methods: Data were extracted retrospectively from adult psychiatric admissions spanning April to September 2020 on patients whose presenting complaints included delusions. Demographic factors, symptoms, psychiatric, medical and substance use history, and a documented Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis by the attending psychiatrist were collected. Results: The prevalence of COVID-19-related delusional content was 25.5%. Significant demographic association was observed with education level of Grade 12 and above (p = 0.000338). The odds of a diagnosis of schizophrenia and related disorders were 2.72 times greater than mood and psychotic disorder due to another medical condition in those with COVID- 19-related delusional content (OR 2.19, 95% CI: [1.4-3.4]). Conclusion: The presence of COVID-19-related delusional content in patients admitted to hospital with psychosis provides further evidence of the role of external stimuli in the formation of delusions. Contribution: This study underscores the influence of socio-cultural factors on delusions and advocates for interventions and expanded research to address mental health outcomes.

Body image concerns in patients with persecutory delusions.

BACKGROUND: Persecutory fears build on feelings of vulnerability that arise from negative views of the self. Body image concerns have the potential to be a powerful driver of feelings of vulnerability. Body image concerns are likely raised in patients with psychosis given the frequent weight gain. We examined for the first-time body esteem - the self-evaluation of appearance - in relation to symptom and psychological correlates in patients with current persecutory delusions. METHODS: One-hundred and fifteen patients with persecutory delusions in the context of non-affective psychosis completed assessments of body image, self-esteem, body mass index (BMI), psychiatric symptoms and well-being. Body esteem was also assessed in 200 individuals from the general population. RESULTS: Levels of body esteem were much lower in patients with psychosis than non-clinical controls (d = 1.2, p < 0.001). In patients, body esteem was lower in women than men, and in the overweight or obese BMI categories than the normal weight range. Body image concerns were associated with higher levels of depression (r = -0.55, p < 0.001), negative self-beliefs (r = -0.52, p < 0.001), paranoia (r = -0.25, p = 0.006) and hallucinations (r = -0.21, p = 0.025). Body image concerns were associated with lower levels of psychological wellbeing (r = 0.41, p < 0.001), positive self-beliefs (r = 0.40, p < 0.001), quality of life (r = 0.23, p = 0.015) and overall health (r = 0.31, p = 0.001). CONCLUSIONS: Patients with current persecutory delusions have low body esteem. Body image concerns are associated with poorer physical and mental health, including more severe psychotic experiences. Improving body image for patients with psychosis is a plausible target of intervention, with the potential to result in a wide range of benefits.

Longitudinal associations between stroke and psychosis: a population-based study.

BACKGROUND: The co-occurrence of stroke and psychosis is a serious neuropsychiatric condition but little is known about the course of this comorbidity. We aimed to estimate longitudinal associations between stroke and psychosis over 10 years. METHODS: A 10-year population-based study using data from the English Longitudinal Study of Ageing. A structured health assessment recorded (i) first-occurrence stroke and (ii) psychosis, at each wave. Each were considered exposures and outcomes in separate analyses. Logistic and Cox proportional hazards regression and Kaplan-Meier methods were used. Models were adjusted for demographic and health behaviour covariates, with missing covariates imputed using random forest multiple imputation. RESULTS: Of 19 808 participants, 24 reported both stroke and psychosis (median Wave 1 age 63, 71% female, 50% lowest quintile of net financial wealth) at any point during follow-up. By 10 years, the probability of an incident first stroke in participants with psychosis was 21.4% [95% confidence interval (CI) 12.1-29.6] compared to 8.3% (95% CI 7.8-8.8) in those without psychosis (absolute difference: 13.1%; 95% CI 20.8-4.3, log rank p < 0.001; fully-adjusted hazard ratio (HR): 3.57; 95% CI 2.18-5.84). The probability of reporting incident psychosis in participants with stroke was 2.3% (95% CI 1.4-3.2) compared to 0.9% (95% CI 0.7-1.1) in those without (absolute difference: 1.4%; 95% CI 0.7-2.1, log rank p < 0.001; fully-adjusted HR: 4.98; 95% CI 2.55-9.72). CONCLUSIONS: Stroke is an independent predictor of psychosis (and vice versa), after adjustment for potential confounders.

Neural correlates of referential/persecutory delusions in schizophrenia: examination using fMRI and a virtual reality underground travel paradigm.

BACKGROUND: The brain functional correlates of delusions have been relatively little studied. However, a virtual reality paradigm simulating travel on the London Underground has been found to evoke referential ideation in both healthy subjects and patients with schizophrenia, making brain activations in response to such experiences potentially identifiable. METHOD: Ninety patients with schizophrenia/schizoaffective disorder and 28 healthy controls underwent functional magnetic resonance imaging while they viewed virtual reality versions of full and empty Barcelona Metro carriages. RESULTS: Compared to the empty condition, viewing the full carriage was associated with activations in the visual cortex, the cuneus and precuneus/posterior cingulate cortex, the inferior parietal cortex, the angular gyrus and parts of the middle and superior temporal cortex including the temporoparietal junction bilaterally. There were no significant differences in activation between groups. Nor were there activations associated with referentiality or presence of delusions generally in the patient group. However, patients with persecutory delusions showed a cluster of reduced activation compared to those without delusions in a region in the right temporal/occipital cortex. CONCLUSIONS: Performance of the metro task is associated with a widespread pattern of activations, which does not distinguish schizophrenic patients and controls, or show an association with referentiality or delusions in general. However, the finding of a cluster of reduced activation close to the right temporoparietal junction in patients with persecutory delusions specifically is of potential interest, as this region is believed to play a role in social cognition.

Aberrant adapting of beliefs under stress: a mechanism relevant to the formation of paranoia?

BACKGROUND: Difficulties in the ability to adapt beliefs in the face of new information are associated with psychosis and its central symptom - paranoia. As cognitive processes and psychotic symptoms are both known to be sensitive to stress, the present study investigated the exact associations between stress, adapting of beliefs [reversal learning (RL), bias against disconfirmatory evidence (BADE), and jumping to conclusions (JTC)] and paranoia. We hypothesized that paranoia would increase under stress and that difficulties in adapting of beliefs would mediate or moderate the link between stress and paranoia. Furthermore, we hypothesized that the investigated effects would be strongest in the group of individuals diagnosed with a psychotic disorder. METHODS: We exposed 155 participants (38 diagnosed with a psychotic disorder, 40 individuals with attenuated psychotic symptoms, 39 clinical controls diagnosed with an obsessive-compulsive disorder, and 38 healthy controls) to a control condition and a stress condition, in which we assessed their levels of paranoia and their ability to adapt beliefs. We applied multilevel models to analyze the data. RESULTS: Paranoia was higher in the stress condition than in the control condition, b = 1.142, s.e. = 0.338, t(150) = 3.381, p < 0.001. RL, BADE, and JTC did not differ between conditions and did not mediate or moderate the association between stress and paranoia (all ps > 0.05). CONCLUSIONS: The results support the assumption that stress triggers paranoia. However, the link between stress and paranoia does not seem to be affected by the ability to adapt beliefs.

Substance use and psychotic-like experiences in young people: a systematic review and meta-analysis.

This study aimed to systematically review and synthesise the available evidence on the prevalence and associations between psychotic-like experiences (PLEs) and substance use in children and adolescents aged ⩽17 years, prior to the typical age of development of prodromal symptoms of psychosis. As substance use has been associated with earlier age of psychosis onset and more severe illness, identifying risk processes in the premorbid phase of the illness may offer opportunities to prevent the development of prodromal symptoms and psychotic illness. MEDLINE, PsycINFO, and CINAHL databases were searched for chart review, case-control, cohort, twin, and cross-sectional studies. Study reporting was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist, and pooled evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Searches identified 55 studies that met inclusion criteria. Around two-in-five substance users reported PLEs [rate = 0.41, 95% confidence interval (CI) 0.32-0.51; low quality evidence], and one-in-five with PLEs reported using substances (rate = 0.19, 95% CI 0.12-0.28; moderate-to-high quality evidence). Substance users were nearly twice as likely to report PLEs than non-users [odds ratio (OR) 1.77, 95% CI 1.55-2.02; moderate quality evidence], and those with PLEs were twice as likely to use substances than those not reporting PLEs (OR 1.93, 95% CI 1.55-2.41; very low quality evidence). Younger age was associated with greater odds of PLEs in substance users compared to non-users. Young substance users may represent a subclinical at-risk group for psychosis. Developing early detection and intervention for both substance use and PLEs may reduce long-term adverse outcomes.

Clinical presentation and neural correlates of stroke-associated spatial delusions.

BACKGROUND AND PURPOSE: Incongruent beliefs about self-localization in space markedly disturb patients' behavior. Spatial delusions, or reduplicative paramnesias, are characterized by a firm conviction of place reduplication, transformation, or mislocation. Evidence suggests they are frequent after right hemisphere lesions, but comprehensive information about their clinical features is lacking. METHODS: We prospectively screened 504 acute right-hemisphere stroke patients for the presence of spatial delusions. Their behavioral and clinical features were systematically assessed. Then, we analyzed the correlation of their duration with the magnitude of structural disruption of belief-associated functional networks. Finally, we described the syndrome subtypes and evaluated whether the clinical categorization would be predicted by the structural disruption of familiarity-associated functional networks using an unsupervised k-means clustering algorithm. RESULTS: Sixty patients with spatial delusions were identified and fully characterized. Most (93%) localized the misidentified places closer to home than the hospital. The median time duration was 3 days (interquartile range = 1-7 days), and it was moderately correlated with the magnitude of structural-functional decoupling of belief-associated functional networks (r = 0.39, p = 0.02; beta coefficient regressing for lesion volume = 3.18, p = 0.04). Each clinical subtype had characteristic response patterns, which were reported, and representative examples were provided. Clustering based on structural disruption of familiarity- and unfamiliarity-associated functional networks poorly matched the clinical categorization (lesion: Rand index = 0.47; structural disconnection: Rand index = 0.51). CONCLUSIONS: The systematic characterization of the peculiar clinical features of stroke-associated spatial delusions may improve the syndrome diagnosis and clinical approaches. The novel evidence about their neural correlates fosters the clarification of the pathophysiology of delusional misidentifications.

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.

Accelerated atrophy in dopaminergic targets and medial temporo-parietal regions precedes the onset of delusions in patients with Alzheimer's disease.

People with Alzheimer's disease (AD) and delusions have worse quality of life and prognosis. However, early markers of delusions have not been identified yet. The present study investigated whether there are any detectable differences in grey matter (GM) volume and cognitive changes in the year before symptom onset between patients with AD who did and did not develop delusions. Two matched samples of AD patients, 63 who did (PT-D) and 63 who did not develop delusions (PT-ND) over 1 year, were identified from the Alzheimer's Disease Neuroimaging Initiative database. The Neuropsychiatric Inventory (NPI) was used to assess the presence of delusions. Sixty-three additional matched healthy controls (HC) were selected. Repeated-measures ANCOVA models were used to investigate group-by-time effects on the volume of selected GM regions of interest and on cognitive performance. No neurocognitive differences were observed between patient groups prior to symptom onset. Greater episodic memory decline and GM loss in bilateral caudate nuclei, medio-temporal and midline cingulo-parietal regions were found in the PT-D compared with the PT-ND group. A pattern of faster GM loss in brain areas typically affected by AD and in cortical and subcortical targets of dopaminergic pathways, paralleled by worsening of episodic memory and behavioural symptoms, may explain the emergence of delusions in patients with AD.