Compulsive-like rigidity may be associated with hyposerotonergia and increased kynurenine (KYN) pathway activity. Conversion of tryptophan (TRP) to kynurenine (KYN), which may contribute to hyposerotonergia, is bolstered by inflammation, and could be related to altered gut microbiota composition. Here, we studied these mechanisms in a naturalistic animal model of compulsive-like behavioural rigidity, i.e., large nest building (LNB) in deer mice (Peromyscus sp.).

Twenty-four (24) normal nest building (NNB)- and 24 LNB mice (both sexes) were chronically administered either escitalopram (a selective serotonin reuptake inhibitor; 50 mg/kg/day) or a control solution, with nesting behaviour analysed before and after intervention. After endpoint euthanising, frontal cortices and striata were analysed for TRP and its metabolites, plasma for microbiota derived lipopolysaccharide (LPS) and its binding protein (LBP), and stool samples for microbial DNA.

LNB, but not NNB, decreased after escitalopram exposure. At baseline, LNB associated with reduced frontal cortical TRP concentrations and hyposerotonergia that was unrelated to altered KYN pathway activity. In LNB mice, escitalopram significantly increased frontal-cortical and striatal TRP without altering serotonin concentrations. Treated LNB, compared to untreated LNB- and treated NNB mice, had significantly reduced plasma LPS as well as a microbiome showing a decreased inferred potential to synthesise short-chain fatty acids and degrade TRP.

These findings support the role of altered serotonergic mechanisms, inflammatory processes, and gut microbiome involvement in compulsive-like behavioural rigidity. Our results also highlight the importance of gut-brain crosstalk mechanisms at the level of TRP metabolism in the spontaneous development of such behaviour.

Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.

PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.

Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.

PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.

Migration is an established risk factor for developing a psychotic disorder in countries with a long history of migration. Less is known for countries with only a recent history of migration. This study aimed to determine the risk for developing a psychotic disorder in migrants to the Republic of Ireland.

We included all presentations of first-episode psychosis over 8.5 years to the DETECT Early Intervention for psychosis service in the Republic of Ireland (573 individuals aged 18–65, of whom 22% were first-generation migrants). Psychotic disorder diagnosis relied on SCID. The at-risk population was calculated using census data, and negative binomial regression was used to estimate incidence rate ratios.

The annual crude incidence rate for a first-episode psychotic disorder in the total cohort was 25.62 per 100000 population at risk. Migrants from Africa had a nearly twofold increased risk for developing a psychotic disorder compared to those born in the Republic of Ireland (IRR = 1.83, 95% CI 1.11–3.02, p = 0.02). In contrast, migrants from certain Asian countries had a reduced risk, specifically those from China, India, Philippines, Pakistan, Malaysia, Bangladesh and Hong Kong (aIRR = 0.36, 95% CI 0.16–0.81, p = 0.01).

Further research into the reasons for this inflated risk in specific migrant groups could produce insights into the aetiology of psychotic disorders. This information should also be used, alongside other data on environmental risk factors that can be determined from census data, to predict the incidence of psychotic disorders and thereby resource services appropriately.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.

The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.

MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.

Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.

MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.

Structural models of psychopathology consistently identify internalizing (INT) and externalizing (EXT) specific factors as well as a superordinate factor that captures their shared variance, the p factor. Questions remain, however, about the meaning of these data-driven dimensions and the interpretability and distinguishability of the larger nomological networks in which they are embedded.

The sample consisted of 10 645 youth aged 9–10 years participating in the multisite Adolescent Brain and Cognitive Development (ABCD) Study. p, INT, and EXT were modeled using the parent-rated Child Behavior Checklist (CBCL). Patterns of associations were examined with variables drawn from diverse domains including demographics, psychopathology, temperament, family history of substance use and psychopathology, school and family environment, and cognitive ability, using instruments based on youth-, parent-, and teacher-report, and behavioral task performance.

p exhibited a broad pattern of statistically significant associations with risk variables across all domains assessed, including temperament, neurocognition, and social adversity. The specific factors exhibited more domain-specific patterns of associations, with INT exhibiting greater fear/distress and EXT exhibiting greater impulsivity.

In this largest study of hierarchical models of psychopathology to date, we found that p, INT, and EXT exhibit well-differentiated nomological networks that are interpretable in terms of neurocognition, impulsivity, fear/distress, and social adversity. These networks were, in contrast, obscured when relying on the a priori Internalizing and Externalizing dimensions of the CBCL scales. Our findings add to the evidence for the validity of p, INT, and EXT as theoretically and empirically meaningful broad psychopathology liabilities.

Early intervention in psychosis is a complex intervention, usually delivered in a specialist stand-alone setting, which aims to improve outcomes for people with psychosis. Previous studies have been criticised because the control used did not accurately reflect actual practice.

To evaluate the cost-effectiveness of early intervention by estimating the incremental net benefit (INB) of an early-intervention programme, delivered in a real-world setting. INB measures the difference in monetary terms between alternative interventions.

Two contemporaneous incidence-based cohorts presenting with first-episode psychosis, aged 18–65 years, were compared. Costs and outcomes were measured over 1 year. The main outcome was avoidance of a relapse that required admission to hospital or home-based treatment.

From the health sector perspective, the probability that early intervention was cost-effective was 0.77. The INB was €2465 per person (95% CI − €4418 to €9347) when society placed a value of €6000, the cost of an in-patient relapse, on preventing a relapse requiring admission or home care. Following adjustment, the probability that early intervention was cost-effective was 1, and the INB to the health sector was €3105 per person (95% CI −€8453 to €14 663). From a societal perspective, the adjusted probability that early intervention was cost-effective was 1, and the INB was €19 928 per person (95% CI − €2075 to €41 931).

Early intervention has a modest INB from the health sector perspective and a large INB from the societal perspective. The perspective chosen is critical when presenting results of an economic evaluation of a complex intervention.