To investigate the occurrence of traumatic stress symptoms (TSS) among healthcare workers active during the COVID-19 pandemic and to obtain insight as to which pandemic-related stressful experiences are associated with onset and persistence of traumatic stress.

This is a multicenter prospective cohort study. Spanish healthcare workers (N = 4,809) participated at an initial assessment (i.e., just after the first wave of the Spain COVID-19 pandemic) and at a 4-month follow-up assessment using web-based surveys. Logistic regression investigated associations of 19 pandemic-related stressful experiences across four domains (infection-related, work-related, health-related and financial) with TSS prevalence, incidence and persistence, including simulations of population attributable risk proportions (PARP).

Thirty-day TSS prevalence at T1 was 22.1%. Four-month incidence and persistence were 11.6% and 54.2%, respectively. Auxiliary nurses had highest rates of TSS prevalence (35.1%) and incidence (16.1%). All 19 pandemic-related stressful experiences under study were associated with TSS prevalence or incidence, especially experiences from the domains of health-related (PARP range 88.4–95.6%) and work-related stressful experiences (PARP range 76.8–86.5%). Nine stressful experiences were also associated with TSS persistence, of which having patient(s) in care who died from COVID-19 had the strongest association. This association remained significant after adjusting for co-occurring depression and anxiety.

TSSs among Spanish healthcare workers active during the COVID-19 pandemic are common and associated with various pandemic-related stressful experiences. Future research should investigate if these stressful experiences represent truly traumatic experiences and carry risk for the development of post-traumatic stress disorder.

The role of interpersonal relationship functioning in trauma recovery is well-established. However, much of this research has been done with cross-sectional samples, often years after trauma exposure, using self-report methodology only, and is focused on intimate relationship adjustment.

The current study investigated the longitudinal associations between interpersonal (intimate and non-intimate) relationship functioning and clinician- and self-reported posttraumatic stress disorder (PTSD) symptoms in 151 recently (within the past 6 months) traumatized individuals. Participants were assessed at four time points over 1 year.

Approximately 53% of the sample was diagnosed with PTSD at initial assessment, with declining rates of diagnostic status over time to 16%. Latent difference score (LDS) modeling revealed nonlinear declines in both clinician-assessed and self-reported PTSD symptom severity, with faster declines in earlier periods. Likewise, LDS models revealed nonlinear declines in negative (conflict) aspects of interpersonal relationship functioning, but linear declines in positive (support, depth) aspects. The relationship between PTSD and relationship functioning differed for clinician- and self-reported PTSD. Bivariate LDS modeling revealed significant cross-lagged effects from relationship conflict to clinician-assessed PTSD, and significant cross-lagged effects from self-reported PTSD to relationship conflict over time.

These results highlight that the variability in prior results may be related to the method of assessing PTSD symptomatology and different relational constructs. Implications for theory and early intervention are discussed.

There is international variability in whether neurological determination of death (NDD) is conceptually defined based on permanent loss of brainstem function or “whole brain death.” Canadian guidelines are not definitive. Patients with infratentorial stroke may meet clinical criteria for NDD despite persistent cerebral blood flow (CBF) and relative absence of supratentorial injury.

We performed a multicenter cohort study involving patients that died from ischemic or hemorrhagic stroke in Alberta intensive care units from 2013 to 2019, focusing on those with infratentorial involvement. Medical records were reviewed to determine the incidence and proportion of patients that met clinical criteria for NDD; whether ancillary testing was performed; and if so, whether this demonstrated the absence of CBF.

There were 95 (27%) deaths from infratentorial and 263 (73%) from supratentorial stroke. Sixteen patients (17%) with infratentorial stroke had neurological examination consistent with NDD (0.55 cases per million per year). Among patients that underwent confirmatory evaluation for NDD with an apnea test, ancillary test (radionuclide scan), or both, ancillary testing was more common with infratentorial compared with supratentorial stroke (10/12 (85%) vs. 25/47 (53%), p = 0.04). Persistent CBF was detected in 6/10 (60%) patients with infratentorial compared with 0/25 with supratentorial stroke (p = 0.0001).

Infratentorial stroke leading to clinical criteria for NDD occurs with an annual incidence of about 0.55 per million. There is variability in clinicians’ use of ancillary testing. Persistent CBF was detected in more than half of patients that underwent radionuclide scans. Canadian consensus is needed to guide clinical practice.

A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.

This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.

ES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.

Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.

Most patients with World Federation of Neurological Surgeons (WFNS) grade 5 subarachnoid hemorrhage (SAH) have poor outcomes. Accurate assessment of prognosis is important for treatment decisions and conversations with families regarding goals of care. Unjustified pessimism may lead to “self-fulfilling prophecy,” where withdrawal of life-sustaining measures (WLSM) is invariably followed by death.

We performed a cohort study involving consecutive patients with WFNS grade 5 SAH to identify variables with >= 90% and >= 95% positive predictive value (PPV) for poor outcome (1-year modified Rankin Score >= 4), as well as findings predictive of WLSM.

Of 140 patients, 38 (27%) had favorable outcomes. Predictors with >= 95% PPV for poor outcome included unconfounded 72-hour Glasgow Coma Scale motor score <= 4, absence of >= 1 pupillary light reflex (PLR) at 24 hours, and intraventricular hemorrhage (IVH) score of >= 20 (volume >= 54.6 ml). Intracerebral hemorrhage (ICH) volume >= 53 ml had PPV of 92%. Variables associated with WLSM decisions included a poor motor score (p < 0.0001) and radiographic evidence of infarction (p = 0.02).

We identified several early predictors with high PPV for poor outcome. Of these, lack of improvement in motor score during the initial 72 hours had the greatest potential for confounding from “self-fulfilling prophecy.” Absence of PLR at 24 hours, IVH score >= 20, and ICH volume >= 53 ml predicted poor outcome without a statistically significant effect on WLSM decisions. More research is needed to validate prognostic variables in grade 5 SAH, especially among patients who do not undergo WLSM.

There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.

We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.

The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).

The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.

Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.

JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.

These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.

Although the terminology of Asperger’s Syndrome has been subsumed within high functioning autism in the last edition of the DSM, the absence of a clear consensus concerning the relevance of the distinction between HFA and AS persists among researchers and clinicians. Besides, the frequent convergence of clinical signs between AS and intellectual high potential encourages to investigate the existence of parallels and their nature. The current situation contributes to maintain confusion at the diagnostically level and by extension to hamper the care system.

Explore and better define three atypical neurocognitive profiles: HFA, AS and intellectual high potential, in order to refine the criteria for a more accurate identification.

Data will be collected from 5 groups of children: 'typical HFA”, 'typical AS”, 'typical gifted children”, 'atypical” (ambiguous diagnosis) and control. These groups will be compared to each other at multiple level: cognition, language, social cognition, psychomotor assessment. Evaluations will be completed by questionnaires and by a clinical interview process (anamnestic data).

'Typical” gifted children, even when they exhibit social issues, don’t have constitutional deficit in the area of social cognition and perform normally or above average in such tasks. Children with heterogeneous psychometric profiles show neuropsychological and/or psychopathological disorders. AS group performs better in language dimension and verbal comprehension (vocabulary, verbal abstraction) than HFA group. In addition, AS children might present motor coordination difficulties and undetermined lateralization more frequently than HFA children.

Despite these differences, these children exhibit atypical developmental trajectories characterized by heterochrony.

Evidence suggests a relationship between exposure to trauma and higher levels of symptoms and poorer functional outcomes in early psychotic patients (EPP). However, the impact of the age at the time of exposure to trauma in this association is as yet unknown.

To examine the potential differential impact of trauma, according to age at the time of exposure, on the level of functioning and on the psychopathological profile of EPP followed-up prospectively.

Two hundred and fifty-five EPP aged 18–35 were followed-up prospectively over 36 months. Patients who had faced at least one experience of abuse or neglect were classified according to age at the time of first exposure (early-trauma: before age 12; late-trauma: between age 12 and 16), and then compared with unexposed patients (non-trauma). The level of symptoms was assessed using the Positive and Negative Syndrome Scale. The Young Mania Rating Scale, and the Montgomery-Asberg Depression Rating Scale. The level of functioning was assessed with the global assessment of functioning.

Comparisons over the 3 years of treatment with non-trauma patients revealed that:

– early-trauma patients showed consistently higher levels of positive (P = 0.006) depressive (P = 0.001), manic (P = 0.006) and negative (P = 0.029) symptoms and showed poorer functional level (P = 0.025);

– late-trauma patients only showed more negative symptoms (P = 0.029) as compared to non-trauma patients.

The age at the time of exposure to trauma has a modulating effect on its impact on symptoms and functional outcome in EPP and it should be systematically examined in clinical and experimental settings.

The authors have not supplied their declaration of competing interest.

An overlap between autism spectrum disorder (ASD), in particular Asperger Syndrome (AS), and high intellectual potential (HIP–Total IQ > 2 SD) is often discussed.

Explore differences between homogeneous and heterogeneous Wisc-profiles among HIP children, and between HIP and ASD children, on cognitive and clinical assessments.

Forty-nine participants (mean age 11.2 years) were divided in 4 groups: High Functioning Autism (HFA), AS, Homogenous HIP and Heterogeneous HIP. Data of WISC-IV and questionnaires – Autism Quotient (AQ), Empathy Quotient (EQ), Systemizing Quotient (SQ), Children's Communication Checklist (CCC) – were compared.

On the WISC-IV, the Z scores curves follow similar trajectories but highlight quantitative differences between AS and heterogeneous HIP: verbal comprehension is the highest index (+1,6 SD in AS; +3,1 SD in heterogeneous HIP) followed by perceptual reasoning, working memory, and processing speed indexes (–1,2 SD in AS; +0,5 SD in heterogeneous HIP), respectively. The questionnaires show that scores of Homogenous HIP children are all in the average. Heterogeneous HIP children score 2,1 SD above average on the AQ (+1,6 SD on “Social Skills” and +1,3 SD on “Local Detail” subscales), whereas ASD children score 4 SD above average on the AQ. In addition, heterogeneous HIP children show pragmatic difficulties (–2,4 SD on the CCC, with a peak on “Area of Interest” subscale), also present in ASD children (–4 SD).

AS and heterogeneous HIP children show similar cognitive profiles on the WISC-IV. Furthermore, heterogeneous HIP children exhibit high scores on the AQ and have pragmatic difficulties.

The authors have not supplied their declaration of competing interest.

The mechanism linking childhood trauma (CT) to the functional deficits observed in early psychosis (EP) patients is as yet unknown.

To examine the potential mediating effect of depressive symptoms in this well-established association.

Two hundred nine EP subjects aged 18-35 were assessed for functioning and psychopathology after 2, 6, 12, 18, 24, 30, and 36 months of treatment. Patients were classified into early-trauma if they had faced at least one experience of abuse (physical, sexual, or emotional) or neglect (physical or emotional) before age 12, and late-trauma if the exposure had occurred between ages 12 and 16. Psychopathology was assessed with the Positive and Negative Syndrome Scale and the Montgomery-Asberg Depression Rating Scale. Functioning was measured with the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS). Mediation analyses were performed in order to study whether the relationship between CT and functioning was mediated by depressive symptoms.

When compared with nonexposed patients, early but not late trauma patients showed lower levels of GAF and SOFAS scores over all the time points, excepting after the first assessment. After 30 and 36 months, the effect of early trauma on functioning was completely mediated by depressive symptoms. No mediating effect of positive or negative symptoms was highlighted at those time points.

Mild depressive symptoms mediated the impact of early trauma on long-term functional outcome. Intensifying pharmacologic and/or psychotherapeutic treatment, focused on the depressive dimension, may help traumatized EP patients to improve their functioning.

The authors have not supplied their declaration of competing interest.

It has been shown that patients with schizophrenia are super-sensitive towards dopamine-releasing agents such as amphetamine. Here, we studied the effects of amphetamine sensitization on amphetamine-induced dopamine release in healthy subjects.

To measure d-amphetamine-induced dopamine release as measured with the D2,3 agonist radioligand [11C]-(+)-PHNO-PET via change in non-displacable binding potential (BPND) and behavioral measures of d-amphetamine effects with drug effects questionnaire (DEQ) and subjective states questionnaire (SSQ).

To study d-amphetamine-induced sensitization in healthy subjects on a behavioral and neurochemical level with [11C]-(+)-PHNO-PET in order to gain more knowledge on sensitization-induced changes in the dopaminergic system.

Twelve stimulant-naïve healthy male subjects underwent three 90-min [11C]-(+)-PHNO-PET-scans and four oral administrations of d-amphetamine. After a naïve baseline scan, subjects underwent a PET scan with previous ingestion of 0.4 mg/kg bodyweight of d-amphetamine 90–120 minutes before scanning. Subsequently, subjects were sensitized to d-amphetamine with the same dose on two separate days. Thereafter, they underwent another PET scan with previous d-amphetamine ingestion. DEQ and SSQ were administered before, 60 min, 90–120 min, and 210 min after amphetamine ingestion.

We found significant sensitization effects on a behavioral level and on a neurochemical level after four administrations of amphetamine. Items of the SSQ, which showed significant sensitization effects were “outgoing”, “energetic”, “lively”, “alert” and “focused”.

We were able to induce significant behavioral and neurochemical sensitization in healthy humans, which were measured with [11C]-(+)-PHNO-PET for the first time. This sensitization model will be useful for studying the neurobiology of schizophrenia.

The authors have not supplied their declaration of competing interest.

First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.

We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.

In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.

The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.