Preclinical evidence suggests that diazepam enhances hippocampal γ-aminobutyric acid (GABA) signalling and normalises a psychosis-relevant cortico-limbic-striatal circuit. Hippocampal network dysconnectivity, particularly from the CA1 subfield, is evident in people at clinical high-risk for psychosis (CHR-P), representing a potential treatment target. This study aimed to forward-translate this preclinical evidence.

In this randomised, double-blind, placebo-controlled study, 18 CHR-P individuals underwent resting-state functional magnetic resonance imaging twice, once following a 5 mg dose of diazepam and once following a placebo. They were compared to 20 healthy controls (HC) who did not receive diazepam/placebo. Functional connectivity (FC) between the hippocampal CA1 subfield and the nucleus accumbens (NAc), amygdala, and ventromedial prefrontal cortex (vmPFC) was calculated. Mixed-effects models investigated the effect of group (CHR-P placebo/diazepam vs. HC) and condition (CHR-P diazepam vs. placebo) on CA1-to-region FC.

In the placebo condition, CHR-P individuals showed significantly lower CA1-vmPFC (Z = 3.17, PFWE = 0.002) and CA1-NAc (Z = 2.94, PFWE = 0.005) FC compared to HC. In the diazepam condition, CA1-vmPFC FC was significantly increased (Z = 4.13, PFWE = 0.008) compared to placebo in CHR-P individuals, and both CA1-vmPFC and CA1-NAc FC were normalised to HC levels. In contrast, compared to HC, CA1-amygdala FC was significantly lower contralaterally and higher ipsilaterally in CHR-P individuals in both the placebo and diazepam conditions (lower: placebo Z = 3.46, PFWE = 0.002, diazepam Z = 3.33, PFWE = 0.003; higher: placebo Z = 4.48, PFWE < 0.001, diazepam Z = 4.22, PFWE < 0.001).

This study demonstrates that diazepam can partially restore hippocampal CA1 dysconnectivity in CHR-P individuals, suggesting that modulation of GABAergic function might be useful in the treatment of this clinical group.

The macro-social and environmental conditions in which people live, such as the level of a country’s development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults.

We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country’s level of development and inequality.

Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain.

Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants’ brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.

Pre-diagnostic stages of psychotic illnesses, including ‘clinical high risk’ (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis.

Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population.

Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa.

In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population.

Mental health difficulties are often exacerbated during the perinatal period. Policy and guidelines are increasingly being used to enhance the quality of healthcare. We conducted a literature review of published research relating to pregnancy and breastfeeding in mental health policy.

Relevant terms were searched in Medline, CINAHL, APA PsycINFO and EMBASE for articles published in English from 1970 until 2020. Only papers that referenced policy, guidance, legislation or standards were included. While a systematic approach was used, the nature of the results necessitated a narrative review.

Initially, 262 papers were identified, 44 met the inclusion criteria. Reproductive health is given sparse consideration in research relating to mental health policy. Despite this, some key areas emerged. These included: the need for proactive preconception psychoeducation, proactive screening of mothers of infants and young children for perinatal mental health issues, enhanced prescribing practice for women of child-bearing age, enhanced monitoring during pregnancy, development of safe modification of coercive practices should they need to be employed in emergency circumstances and targeted measures to reduce substance misuse. Themes that arose relating to breastfeeding and bonding are also described.

Female reproductive health is often ignored in research relating to mental health policy, guidelines and standards. These tools need to be harnessed to promote good healthcare. Reproductive health should be included in the care plan of all mental health patients. These topics need to be integrated into existing relevant policies and not isolated to a separate policy.

After officer-involved shootings (OIS), rapid delivery of emergency medical care is critical but may be delayed due to scene safety concerns. The purpose of this study was to describe medical care rendered by law enforcement officers (LEOs) after lethal force incidents.

Retrospective analysis of open-source video footage of OIS occurring from February 15, 2013 through December 31, 2020. Frequency and nature of care provided, time until LEO and Emergency Medical Services (EMS) care, and mortality outcomes were evaluated. The study was deemed exempt by the Mayo Clinic Institutional Review Board.

Three hundred forty-two (342) videos were included in the final analysis; LEOs rendered care in 172 (50.3%) incidents. Average elapsed time from time-of-injury (TOI) to LEO-provided care was 155.8 (SD = 198.8) seconds. Hemorrhage control was the most common intervention performed. An average of 214.2 seconds elapsed between LEO care and EMS arrival. No mortality difference was identified between LEO versus EMS care (P = .1631). Subjects with truncal wounds were more likely to die than those with extremity wounds (P < .00001).

It was found that LEOs rendered medical care in one-half of all OIS incidents, initiating care on average 3.5 minutes prior to EMS arrival. Although no significant mortality difference was noted for LEO versus EMS care, this finding must be interpreted cautiously, as specific interventions, such as extremity hemorrhage control, may have impacted select patients. Future studies are needed to determine optimal LEO care for these patients.

Cognitive Bias Modification for paranoia (CBM-pa) is a novel, theory-driven psychological intervention targeting the biased interpretation of emotional ambiguity associated with paranoia. Study objectives were (i) test the intervention's feasibility, (ii) provide effect size estimates, (iii) assess dose–response and (iv) select primary outcomes for future trials.

In a double-blind randomised controlled trial, sixty-three outpatients with clinically significant paranoia were randomised to either CBM-pa or an active control (text reading) between April 2016 and September 2017. Patients received one 40 min session per week for 6 weeks. Assessments were given at baseline, after each interim session, post-treatment, and at 1- and 3-months post-treatment.

A total of 122 patients were screened and 63 were randomised. The recruitment rate was 51.2%, with few dropouts (four out of 63) and follow-up rates were 90.5% (1-month) and 93.7% (3-months). Each session took 30–40 min to complete. There was no statistical evidence of harmful effects of the intervention. Preliminary data were consistent with efficacy of CBM-pa over text-reading control: patients randomised to the intervention, compared to control patients, reported reduced interpretation bias (d = −0.48 to −0.76), improved symptoms of paranoia (d = −0.19 to −0.38), and lower depressed and anxious mood (d = −0.03 to −0.29). The intervention effect was evident after the third session.

CBM-pa is feasible for patients with paranoia. A fully powered randomised control trial is warranted.

To define the frequency and characteristics of acute neurologic complications in children hospitalised with infective endocarditis and to identify risk factors for neurologic complications.

Retrospective cohort study of children aged 0–18 years hospitalised at a tertiary children’s hospital from 1 January, 2008 to 31 December, 2017 with infective endocarditis.

Sixty-eight children met Duke criteria for infective endocarditis (43 definite and 25 possible). Twenty-three (34%) had identified neurologic complications, including intracranial haemorrhage (25%, 17/68) and ischaemic stroke (25%, 17/68). Neurologic symptoms began a median of 4.5 days after infective endocarditis symptom onset (interquartile range 1, 25 days), though five children were asymptomatic and diagnosed on screening neuroimaging only. Overall, only 56% (38/68) underwent neuroimaging during acute hospitalisation, so additional asymptomatic neurologic complications may have been missed. Children with identified neurologic complications compared to those without were older (48 versus 22% ≥ 13 years old, p = 0.031), more often had definite rather than possible infective endocarditis (96 versus 47%, p < 0.001), mobile vegetations >10mm (30 versus 11%, p = 0.048), and vegetations with the potential for systemic embolisation (65 versus 29%, p = 0.004). Six children died (9%), all of whom had neurologic complications.

Neurologic complications of infective endocarditis were common (34%) and associated with mortality. The true frequency of neurologic complications was likely higher because asymptomatic cases may have been missed without screening neuroimaging. Moving forward, we advocate that all children with infective endocarditis have neurologic consultation, examination, and screening neuroimaging. Additional prospective studies are needed to determine whether early identification of neurologic abnormalities may direct management and ultimately reduce neurologic morbidity and overall mortality.

Childhood trauma is associated with an elevated risk for psychosis, but the psychological mechanisms involved remain largely unclear. This study aimed to investigate emotional and psychotic stress reactivity in daily life as a putative mechanism linking childhood trauma and clinical outcomes in individuals at ultra-high-risk (UHR) for psychosis.

Experience sampling methodology was used to measure momentary stress, affect and psychotic experiences in the daily life of N = 79 UHR individuals in the EU-GEI High Risk Study. The Childhood Trauma Questionnaire was used to assess self-reported childhood trauma. Clinical outcomes were assessed at baseline, 1- and 2-year follow-up.

The association of stress with positive (β = −0.14, p = 0.010) and negative affect (β = 0.11, p = 0.020) was modified by transition status such that stress reactivity was greater in individuals who transitioned to psychosis. Moreover, the association of stress with negative affect (β = 0.06, p = 0.019) and psychotic experiences (β = 0.05, p = 0.037) was greater in individuals exposed to high v. low levels of childhood trauma. We also found evidence that decreased positive affect in response to stress was associated with reduced functioning at 1-year follow-up (B = 6.29, p = 0.034). In addition, there was evidence that the association of childhood trauma with poor functional outcomes was mediated by stress reactivity (e.g. indirect effect: B = −2.13, p = 0.026), but no evidence that stress reactivity mediated the association between childhood trauma and transition (e.g. indirect effect: B = 0.14, p = 0.506).

Emotional and psychotic stress reactivity may be potential mechanisms linking childhood trauma with clinical outcomes in UHR individuals.

The purpose of this study was to examine whether self-efficacy predicted pediatric concussion symptom severity and explore whether affective mood states (e.g., depression) influenced this relationship.

Children (8–17 years) who were diagnosed with a concussion within 30 days of injury participated in the study (n = 105). Following a clinical assessment, participants and caregivers completed questionnaires that assessed overall concussion symptom severity and current depression symptoms. Participants also completed ratings capturing self-efficacy for managing concussion recovery.

Linear regression models revealed that greater levels of self-efficacy predicted lower parent- (R2 = 0.10, p = .001) and youth-rated (R2 = 0.23, p < .001) concussion symptom severity. Interestingly, depression symptoms moderated the relationship between self-efficacy and concussion symptom severity.

Findings provide initial support for a relationship between self-efficacy and concussion outcomes and highlight the influence of depressive symptoms. Interventions that optimize youth’s self-efficacy have the potential to increase treatment adherence, reduce concussion symptom severity, and improve recovery prognosis.

Assessment of risks of illnesses has been an important part of medicine for decades. We now have hundreds of ‘risk calculators’ for illnesses, including brain disorders, and these calculators are continually improving as more diverse measures are collected on larger samples.

We first replicated an existing psychosis risk calculator and then used our own sample to develop a similar calculator for use in recruiting ‘psychosis risk’ enriched community samples. We assessed 632 participants age 8–21 (52% female; 48% Black) from a community sample with longitudinal data on neurocognitive, clinical, medical, and environmental variables. We used this information to predict psychosis spectrum (PS) status in the future. We selected variables based on lasso, random forest, and statistical inference relief; and predicted future PS using ridge regression, random forest, and support vector machines.

Cross-validated prediction diagnostics were obtained by building and testing models in randomly selected sub-samples of the data, resulting in a distribution of the diagnostics; we report the mean. The strongest predictors of later PS status were the Children's Global Assessment Scale; delusions of predicting the future or having one's thoughts/actions controlled; and the percent married in one's neighborhood. Random forest followed by ridge regression was most accurate, with a cross-validated area under the curve (AUC) of 0.67. Adjustment of the model including only six variables reached an AUC of 0.70.

Results support the potential application of risk calculators for screening and identification of at-risk community youth in prospective investigations of developmental trajectories of the PS.

Women of childbearing age often experience mental health problems, receive psychotropic medication and are admitted to mental health units. Approximately 40% of pregnancies are unplanned and many women experience perinatal mental health problems. It is therefore vital that consideration is given to reproductive health in mental health policy. We aimed to evaluate the consideration of pregnancy and breastfeeding in the policies of an inpatient mental health service.

The policies of a regional inpatient psychiatric unit were independently reviewed by two researchers. Policies that had implications for pregnancy and breastfeeding for patients were identified. Whether or not these policies considered pregnancy and breastfeeding and the detail of this consideration was evaluated.

One hundred and thirteen policies were evaluated. Forty had implications for pregnancy but only 10 of these mentioned pregnancy and only 3 in detail. Only 3 of the 28 policies that had relevance to breastfeeding mothers mentioned it and none discussed it in detail. Key areas of omission included prescribing, seclusion and restraint and cultural and religious considerations.

Pregnancy and breastfeeding were almost entirely absent in the ward policies of our inpatient unit. Their consideration in the acute setting is vital. An individual or group of individuals should be responsible for ensuring that reproductive health is considered in all policies as well as in a larger specific policy suitable for referencing. The rights of the reproductive woman should be comprehensively considered in inpatient mental health care policy.

Our objectives were to explore attitudes regarding food retail policy and government regulation among managers of small food stores and examine whether manager views changed due to the 2014 Minneapolis Staple Foods Ordinance, a city policy requiring retailers to stock specific healthy products.

Manager interviewer-administered surveys were used to assess views on food retail policy four times from 2014 to 2017. We examined baseline views across manager and store and neighbourhood characteristics using cross-sectional regression analyses and examined changes over time using mixed regression models. In 2017, open-ended survey questions asked about manager insights on the Minneapolis Staple Foods Ordinance.

Minneapolis, MN, where the ordinance was enacted, and St. Paul, MN, a control community, USA.

Managers from 147 small food retail stores.

At baseline, 48 % of managers were likely to support a policy requiring stores to stock healthy foods/beverages, 67·5 % of managers were likely to support voluntary programmes to help retailers stock healthy foods and 23·7 % agreed government regulation of business is good/necessary. There was a significant increase in overall support for food retail policies and voluntary programmes from 2014 to 2017 (P < 0·01); however, neither increase differed by city, suggesting no differential impact from the ordinance. Minneapolis store managers reported some challenges with ordinance compliance and offered suggestions for how local government could provide support.

Findings suggest that managers of small food retail stores are becoming increasingly amenable to healthy food policies; yet, challenges need to be addressed to ensure healthy food is available to all customers.

It remains poorly understood how negative symptoms are experienced in the daily lives of individuals in the early stages of psychosis. We aimed to investigate whether altered affective experience, anhedonia, social anhedonia, and asociality were more pronounced in individuals with an at-risk mental state for psychosis (ARMS) and individuals with first-episode psychosis (FEP) than in controls.

We used the experience sampling methodology (ESM) to assess negative symptoms, as they occurred in the daily life of 51 individuals with FEP and 46 ARMS, compared with 53 controls.

Multilevel linear regression analyses showed no overall evidence for a blunting of affective experience. There was some evidence for anhedonia in FEP but not in ARMS, as shown by a smaller increase of positive affect (BΔat−risk v. FEP = 0.08, p = 0.006) as the pleasantness of activities increased. Against our expectations, no evidence was found for greater social anhedonia in any group. FEP were more often alone (57%) than ARMS (38%) and controls (35%) but appraisals of the social situation did not point to asociality.

Overall, altered affective experience, anhedonia, social anhedonia and asociality seem to play less of a role in the daily life of individuals in the early stages of psychosis than previously assumed. With the experience of affect and pleasure in daily life being largely intact, changing social situations and appraisals thereof should be further investigated to prevent development or deterioration of negative symptoms.

Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.

A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.

Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.

In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.