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

Not Much Helicity is Needed to Drive Large Scale Dynamos

Understanding the in situ amplification of large scale magnetic fields in turbulent astrophysical rotators has been a core subject of dynamo theory. When turbulent velocities are helical, large scale dynamos that substantially amplify fields on scales that exceed the turbulent forcing scale arise, but the minimum sufficient fractional kinetic helicity f_h,C has not been previously well quantified. Using direct numerical simulations for a simple helical dynamo, we show that f_h,C decreases as the ratio of forcing to large scale wave numbers k_F/k_min increases. From the condition that a large scale helical dynamo must overcome the backreaction from any non-helical field on the large scales, we develop a theory that can explain the simulations. For k_F/k_min>8 we find f_h,C< 3%, implying that very small helicity fractions strongly influence magnetic spectra for even moderate scale separation.Comment: 5 pages, 4 figure

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

Downward continued multichannel seismic refraction analysis of Atlantis Massif oceanic core complex, 30°N, Mid-Atlantic Ridge

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 13 (2012): Q0AG07, doi:10.1029/2012GC004059.Detailed seismic refraction results show striking lateral and vertical variability of velocity structure within the Atlantis Massif oceanic core complex (OCC), contrasting notably with its conjugate ridge flank. Multichannel seismic (MCS) data are downward continued using the Synthetic On Bottom Experiment (SOBE) method, providing unprecedented detail in tomographic models of the P-wave velocity structure to subseafloor depths of up to 1.5 km. Velocities can vary up to 3 km/s over several hundred meters and unusually high velocities (~5 km/s) are found immediately beneath the seafloor in key regions. Correlation with in situ and dredged rock samples, video and records from submersible dives, and a 1.415 km drill core, allow us to infer dominant lithologies. A high velocity body(ies) found to shoal near to the seafloor in multiple locations is interpreted as gabbro and is displaced along isochrons within the OCC, indicating a propagating magmatic source as the origin for this pluton(s). The western two-thirds of the Southern Ridge is capped in serpentinite that may extend nearly to the base of our ray coverage. The distribution of inferred serpentinite indicates that the gabbroic pluton(s) was emplaced into a dominantly peridotitic host rock. Presumably the mantle host rock was later altered via seawater penetration along the detachment zone, which controlled development of the OCC. The asymmetric distribution of seismic velocities and morphology of Atlantis Massif are consistent with a detachment fault with a component of dip to the southeast. The lowest velocities observed atop the eastern Central Dome and conjugate crust are most likely volcanics. Here, an updated model of the magmatic and extensional faulting processes at Atlantis Massif is deduced from the seismic results, contributing more generally to understanding the processes controlling the formation of heterogeneous lithosphere at slow-rate spreading centers.NSF support was provided via grant OCE-0927442.2012-11-1

Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes.

The most virulent form of malaria is caused by waves of replication of blood stages of the protozoan pathogen Plasmodium falciparum. The parasite divides within an intraerythrocytic parasitophorous vacuole until rupture of the vacuole and host-cell membranes releases merozoites that invade fresh erythrocytes to repeat the cycle. Despite the importance of merozoite egress for disease progression, none of the molecular factors involved are known. We report that, just prior to egress, an essential serine protease called PfSUB1 is discharged from previously unrecognized parasite organelles (termed exonemes) into the parasitophorous vacuole space. There, PfSUB1 mediates the proteolytic maturation of at least two essential members of another enzyme family called SERA. Pharmacological blockade of PfSUB1 inhibits egress and ablates the invasive capacity of released merozoites. Our findings reveal the presence in the malarial parasitophorous vacuole of a regulated, PfSUB1-mediated proteolytic processing event required for release of viable parasites from the host erythrocyte

Early neutrophil trajectory following clozapine may predict clozapine response - Results from an observational study using electronic health records

Background: Clozapine has unique effectiveness in treatment-resistant schizophrenia and is known to cause immunological side-effects. A transient spike in neutrophils commonly occurs in the first weeks of clozapine therapy. There is contradictory evidence in the literature as to whether neutrophil changes with clozapine are linked to treatment response. Aims: The current study aims to further examine the neutrophil changes in response to clozapine and explore any association between neutrophil trajectory and treatment response. Methods: A retrospective cohort study of patients undergoing their first treatment with clozapine and continuing for at least 2 years identified 425 patients (69% male/31% female). Neutrophil counts at baseline, 3 weeks and 1 month were obtained predominantly by linkage with data from the clozapine monitoring service. Clinical Global Impression- Severity (CGI-S) was rated from case notes at the time of clozapine initiation and at 2 years. Latent class growth analysis (LCGA) was performed to define distinct trajectories of neutrophil changes during the first month of treatment. Logistic regression was then conducted to investigate for association between the trajectory of neutrophil count changes in month 1 and clinical response at 2 years as well as between baseline neutrophil count and response. Results: Of the original cohort, 397 (93%) patients had useable neutrophil data during the first 6 weeks of clozapine treatment. LCGA revealed significant differences in neutrophil trajectories with a three-class model being the most parsimonious. The classes had similar trajectory profiles but differed primarily on overall neutrophil count: with low, high-normal and high neutrophil classes, comprising 52%, 40% and 8% of the sample respectively. Membership of the high-normal group was associated with significantly increased odds of a positive response to clozapine, as compared to the low neutrophil group [Odds ratio (OR) = 2.10, p-value = 0.002; 95% confidence interval (95% CI) = 1.31–3.36]. Baseline neutrophil count was a predictor of response to clozapine at 2 years, with counts of ≥5 × 109/l significantly associated with positive response (OR = 1.60, p-value = 0.03; 95% CI = 1.03–2.49). Conclusions: Our data are consistent with the hypothesis that patients with low-level inflammation, reflected in a high-normal neutrophil count, are more likely to respond to clozapine, raising the possibility that clozapine exerts its superior efficacy via immune mechanisms.</p

Prevalence of Neuroradiological Abnormalities in First-Episode Psychosis: A Systematic Review and Meta-analysis

IMPORTANCE: Individuals presenting with first-episode psychosis (FEP) may have a secondary ("organic") etiology to their symptoms that can be identified using neuroimaging. Because failure to detect such cases at an early stage can have serious clinical consequences, it has been suggested that brain magnetic resonance imaging (MRI) should be mandatory for all patients presenting with FEP. However, this remains a controversial issue, partly because the prevalence of clinically relevant MRI abnormalities in this group is unclear. OBJECTIVE: To derive a meta-analytic estimate of the prevalence of clinically relevant neuroradiological abnormalities in FEP. DATA SOURCES: Electronic databases Ovid, MEDLINE, PubMed, Embase, PsychINFO, and Global Health were searched up to July 2021. References and citations of included articles and review articles were also searched. STUDY SELECTION: Magnetic resonance imaging studies of patients with FEP were included if they reported the frequency of intracranial radiological abnormalities. DATA EXTRACTION AND SYNTHESIS: Independent extraction was undertaken by 3 researchers and a random-effects meta-analysis of pooled proportions was calculated. Moderators were tested using subgroup and meta-regression analyses. Heterogeneity was evaluated using the I2 index. The robustness of results was evaluated using sensitivity analyses. Publication bias was assessed using funnel plots and Egger tests. MAIN OUTCOMES AND MEASURES: Proportion of patients with a clinically relevant radiological abnormality (defined as a change in clinical management or diagnosis); number of patients needed to scan to detect 1 such abnormality (number needed to assess [NNA]). RESULTS: Twelve independent studies (13 samples) comprising 1613 patients with FEP were included. Of these patients, 26.4% (95% CI, 16.3%-37.9%; NNA of 4) had an intracranial radiological abnormality, and 5.9% (95% CI, 3.2%-9.0%) had a clinically relevant abnormality, yielding an NNA of 18. There were high degrees of heterogeneity among the studies for these outcomes, 95% to 73%, respectively. The most common type of clinically relevant finding was white matter abnormalities, with a prevalence of 0.9% (95% CI, 0%-2.8%), followed by cysts, with a prevalence of 0.5% (95% CI, 0%-1.4%). CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found that 5.9% of patients presenting with a first episode of psychosis had a clinically relevant finding on MRI. Because the consequences of not detecting these abnormalities can be serious, these findings support the use of MRI as part of the initial clinical assessment of all patients with FEP

Molecular Identification of a Malaria Merozoite Surface Sheddase

Proteolytic shedding of surface proteins during invasion by apicomplexan parasites is a widespread phenomenon, thought to represent a mechanism by which the parasites disengage adhesin-receptor complexes in order to gain entry into their host cell. Erythrocyte invasion by merozoites of the malaria parasite Plasmodium falciparum requires the shedding of ectodomain components of two essential surface proteins, called MSP1 and AMA1. Both are released by the same merozoite surface “sheddase,” but the molecular identity and mode of action of this protease is unknown. Here we identify it as PfSUB2, an integral membrane subtilisin-like protease (subtilase). We show that PfSUB2 is stored in apical secretory organelles called micronemes. Upon merozoite release it is secreted onto the parasite surface and translocates to its posterior pole in an actin-dependent manner, a trafficking pattern predicted of the sheddase. Subtilase propeptides are usually selective inhibitors of their cognate protease, and the PfSUB2 propeptide is no exception; we show that recombinant PfSUB2 propeptide binds specifically to mature parasite-derived PfSUB2 and is a potent, selective inhibitor of MSP1 and AMA1 shedding, directly establishing PfSUB2 as the sheddase. PfSUB2 is a new potential target for drugs designed to prevent erythrocyte invasion by the malaria parasite