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.

Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown.

Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. CBD) and linear between-group relationships, such that placebo > CBD > controls or controls > CBD > placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses.

Placebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo.

These findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.

Equipping our medical students with as many tools as possible to cope with the challenges that they will inevitably face has never been more important than it is today.

The aim of this study was to examine the effectiveness of a reflective practice (RP) group for medical students, particularly with adaptation to COVID-19 and transition to video.

A pilot programme of RP for 3rd year medical students commencing their clinical placement was run by the Sligo Medical Academy, NUIG in Ireland between January – April 2020. This group for nine students was initially run face-to-face but pivoted to an online group in March 2020 with the COVID-19 pandemic. Data was collected through one-to-one interviews with all student participants and the facilitator (n=10). Interviews were recorded and transcribed. Data were analysed using thematic content analysis.

Our analysis identified four main discussion themes: transition to clinical environment, gender in the workplace, building professional identity and family and support systems. The students who continued the RP group over zoom during the COVID-19 pandemic particularly identified with the theme of support systems and solidarity. The smooth transition to zoom and its effectiveness in a time of social distancing were discussed. Identified challenges related primarily to timing of the RP group, particularly after a full day of placements or time differences for international students overseas.

Reflective practice programmes are not routinely offered to medical students in Ireland currently and this study gives recommendations on implementing and improving experiences of undergraduate training based on RP.

No significant relationships.

Suicide accounts for 2.2% of all years of life lost worldwide. We aimed to establish whether infectious epidemics are associated with any changes in the incidence of suicide or the period prevalence of self-harm, or thoughts of suicide or self-harm, with a secondary objective of establishing the frequency of these outcomes.

In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO and AMED were searched from inception to 9 September 2020. Studies of infectious epidemics reporting outcomes of (a) death by suicide, (b) self-harm or (c) thoughts of suicide or self-harm were identified. A random-effects model meta-analysis for the period prevalence of thoughts of suicide or self-harm was conducted.

In total, 1354 studies were screened with 57 meeting eligibility criteria, of which 7 described death by suicide, 9 by self-harm, and 45 thoughts of suicide or self-harm. The observation period ranged from 1910 to 2020 and included epidemics of Spanish Flu, severe acute respiratory syndrome, human monkeypox, Ebola virus disease and coronavirus disease 2019 (COVID-19). Regarding death by suicide, data with a clear longitudinal comparison group were available for only two epidemics: SARS in Hong Kong, finding an increase in suicides among the elderly, and COVID-19 in Japan, finding no change in suicides among children and adolescents. In terms of self-harm, five studies examined emergency department attendances in epidemic and non-epidemic periods, of which four found no difference and one showed a reduction during the epidemic. In studies of thoughts of suicide or self-harm, one large survey showed a substantial increase in period prevalence compared to non-epidemic periods, but smaller studies showed no difference. As a secondary objective, a meta-analysis of thoughts of suicide and self-harm found that the pooled prevalence was 8.0% overall (95% confidence interval (CI) 5.2–12.0%; 14 820 of 99 238 cases in 24 studies) over a time period of between seven days and six months. The quality assessment found 42 studies were of low quality, nine of moderate quality and six of high quality.

There is little robust evidence on the association of infectious epidemics with suicide, self-harm and thoughts of suicide or self-harm. There was an increase in suicides among the elderly in Hong Kong during SARS and no change in suicides among young people in Japan during COVID-19, but it is unclear how far these findings may be generalised. The development of up-to-date self-harm and suicide statistics to monitor the effect of the current pandemic is an urgent priority.

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.

Thyroid lobectomy is recommended with total laryngectomy for laryngeal cancer in the National Comprehensive Cancer Network (‘NCCN’) guidelines. However, it is associated with a 32–89 per cent risk of hypothyroidism, with or without adjuvant radiotherapy.

The study aimed to determine whether preserving the whole thyroid, compared to a single lobe, does indeed significantly lower the incidence of hypothyroidism in the setting of total laryngectomy.

A retrospective study was conducted at Groote Schuur Hospital in Cape Town, South Africa.

Eighty-four patients met the inclusion criteria. The overall incidence of hypothyroidism was 45.2 per cent. The incidence of hypothyroidism was significantly reduced in patients who underwent thyroid-sparing total laryngectomy compared to hemithyroidectomy (p = 0.037). Adjuvant radiotherapy was associated with a higher incidence of hypothyroidism (p = 0.001).

Thyroid-preserving laryngectomy should be advocated in carefully selected patients with advanced laryngeal carcinoma, as it reduces the incidence of hypothyroidism.

To estimate the prevalence of unmet needs for assistance among middle-aged and older adults with subjective cognitive decline (SCD) in the US and to evaluate whether unmet needs were associated with health-related quality of life (HRQOL).

Cross-sectional

US – 50 states, District of Columbia, and Puerto Rico

Community-dwelling adults aged 45 years and older who completed the Cognitive Decline module on the 2015-–2018 Behavioral Risk Factor Surveillance System reported experiencing SCD and always, usually, or sometimes needed assistance with day-to-day activities because of SCD (n = 6,568).

We defined SCD as confusion or memory loss that was happening more often or getting worse over the past 12 months. Respondents with SCD were considered to have an unmet need for assistance if they sometimes, rarely, or never got the help they needed with day-to-day activities. We measured three domains of HRQOL: (1) mental (frequent mental distress, ≥14 days of poor mental health in the past 30 days), (2) physical (frequent physical distress, ≥14 days of poor physical health in the past 30 days), and (3) social (SCD always, usually, or sometimes interfered with the ability to work, volunteer, or engage in social activities outside the home). We used log-binomial regression models to estimate prevalence ratios (PRs). All estimates were weighted.

In total, 40.2% of people who needed SCD-related assistance reported an unmet need. Among respondents without depression, an unmet need was associated with a higher prevalence of frequent mental distress (PR = 1.55, 95% CI: 1.12–2.13, p = 0.007). Frequent physical distress and social limitations did not differ between people with met and unmet needs.

Middle-aged and older adults with SCD-related needs for assistance frequently did not have those needs met, which could negatively impact their mental health. Interventions to identify and meet the unmet needs among people with SCD may improve HRQOL.

Basic Self disturbances (BSD), including changes of the 'pre-reflexive' sense of self and the loss first-person perspective, are characteristic of the schizophrenic spectrum disorders and highly prevalent in subjects at 'ultra high risk' for psychosis (UHR). The current literature indicates that cortical midline structures (CMS) may be implicated in the neurobiological substrates of the 'basic self' in healthy controls.

Neuroanatomical investigation of BSD in a UHR sample

To test the hypotheses :(i) UHR subjects have higher 'Examination of Anomalous Self Experience, EASE' scores as compared to controls, (ii) UHR subjects have neuroanatomical alterations as compared to controls in CMS, (iii) within UHR subjects, EASE scores are directly related to structural CMS alterations.

32 HR subjects (27 antipsychotics-naïve) and 17 healthy controls (HC) were assessed with the 57-items semi-structured EASE interview. Voxel-Based Morphometry (VBM) was conducted in the same subjects, with a-priori Region of Interests (ROIs) defined in the CMS (anterior/posterior cingulate and medial-prefrontal cortex).

Despite high variability in the HR group, the overall EASE score was higher (t-test >0.01, Cohen's d =2.91) in HR (mean=30.15, SD=16.46) as compared to HC group (mean=1.79, SD=2.83). UHR subjects had gray matter reduction in CMS as compared to HC (p>0.05 FWE-corrected). Across the whole sample, lower gray matter volume in the anterior cingulate was correlated with higher EASE scores (p>0.05).

This study provides preliminary evidence that gray matter reductions in the CMS are correlated with BSD in UHR people.

The long-term clinical validity of the At Risk Mental State (ARMS) for the prediction of non-psychotic mental disorders is unknown.

Clinical register-based cohort study including all non-psychotic individuals assessed by the Outreach And Support in South London (OASIS) service (2002–2015). The primary outcome was risk of developing any mental disorder (psychotic or non-psychotic). Analyses included Cox proportional hazard models, Kaplan–Meier survival/failure function and C statistics.

A total of 710 subjects were included. A total of 411 subjects were at risk (ARMS+) and 299 not at risk (ARMS−). Relative to ARMS−, the ARMS+ was associated with an increased risk (HR = 4.825) of developing psychotic disorders, and a reduced risk (HR = 0.545) of developing non-psychotic disorders (mainly personality disorders). At 6-year, the ARMS designation retained high sensitivity (0.873) but only modest specificity (0.456) for the prediction of psychosis onset (AUC 0.68). The brief and limited intermittent psychotic symptoms (BLIPS) subgroup had a higher risk of developing psychosis, and a lower risk of developing non-psychotic disorders as compared to the attenuated psychotic symptoms (APS) subgroup (P < 0.001).

In the long-term, the ARMS specifically predicts the onset of psychotic disorders, with modest accuracy, but not of non-psychotic disorders. Individuals meeting BLIPS criteria have distinct clinical outcomes.

In the long-term, the ARMS designation is still significantly associated with an increased risk of developing psychotic disorders but its prognostic accuracy is only modest. There is no evidence that the ARMS is associated with an increased risk of developing non-psychotic mental disorders. The BLIPS subgroup at lower risk of developing non-psychotic disorders compared to the APS subgroup.

While incident diagnoses employed in this study are high in ecological validity they have not been subjected to formal validation with research-based criteria.

Primary indicated prevention is reliant on accurate tools to predict the onset of psychosis. The gold standard assessment for detecting individuals at clinical high risk (CHR-P) for psychosis in the UK and many other countries is the Comprehensive Assessment for At Risk Mental States (CAARMS). While the prognostic accuracy of CHR-P instruments has been assessed in general, this is the first study to specifically analyse that of the CAARMS. As such, the CAARMS was used as the index test, with the reference index being psychosis onset within 2 years. Six independent studies were analysed using MIDAS (STATA 14), with a total of 1876 help-seeking subjects referred to high risk services (CHR-P+: n = 892; CHR-P–: n = 984). Area under the curve (AUC), summary receiver operating characteristic curves (SROC), quality assessment, likelihood ratios, and probability modified plots were computed, along with sensitivity analyses and meta-regressions. The current meta-analysis confirmed that the 2-year prognostic accuracy of the CAARMS is only acceptable (AUC = 0.79 95% CI: 0.75–0.83) and not outstanding as previously reported. In particular, specificity was poor. Sensitivity of the CAARMS is inferior compared to the SIPS, while specificity is comparably low. However, due to the difficulties in performing these types of studies, power in this meta-analysis was low. These results indicate that refining and improving the prognostic accuracy of the CAARMS should be the mainstream area of research for the next era. Avenues of prediction improvement are critically discussed and presented to better benefit patients and improve outcomes of first episode psychosis.

Evidence has been accumulating regarding alterations in components of the endocannabinoid system in patients with psychosis. Of all the putative risk factors associated with psychosis, being at clinical high-risk for psychosis (CHR) has the strongest association with the onset of psychosis, and exposure to childhood trauma has been linked to an increased risk of development of psychotic disorder. We aimed to investigate whether being at-risk for psychosis and exposure to childhood trauma were associated with altered endocannabinoid levels.

We compared 33 CHR participants with 58 healthy controls (HC) and collected information about previous exposure to childhood trauma as well as plasma samples to analyse endocannabinoid levels.

Individuals with both CHR and experience of childhood trauma had higher N-palmitoylethanolamine (p < 0.001) and anandamide (p < 0.001) levels in peripheral blood compared to HC and those with no childhood trauma. There was also a significant correlation between N-palmitoylethanolamine levels and symptoms as well as childhood trauma.

Our results suggest an association between CHR and/or childhood maltreatment and elevated endocannabinoid levels in peripheral blood, with a greater alteration in those with both CHR status and history of childhood maltreatment compared to those with either of those risks alone. Furthermore, endocannabinoid levels increased linearly with the number of risk factors and elevated endocannabinoid levels correlated with the severity of CHR symptoms and extent of childhood maltreatment. Further studies in larger cohorts, employing longitudinal designs are needed to confirm these findings and delineate the precise role of endocannabinoid alterations in the pathophysiology of psychosis.

Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.

We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.

16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).

PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.