In ESCAPE-TRD esketamine nasal spray (ESK-NS) significantly increased the probability of achieving remission at Week (Wk) 8 and being relapse‑free through Wk32 after remission at Wk8 versus (vs) quetiapine extended release (Q-XR) in patients (pts) with treatment resistant depression (TRD) (Reif et al. DGPPN 2022; P-01-04). We report ESK-NS vs Q-XR effects on pt-reported health-related quality of life (HRQoL) over 32 wks.

Evaluate pt-reported HRQoL using the generic 36-item Short-Form Health Survey version 2 (SF-36v2, 4-wk recall, 2009 US population norms) in ESCAPE-TRD.

ESCAPE‑TRD (NCT04338321) was a randomised phase IIIb trial comparing the efficacy of ESK-NS vs Q-XR, both alongside an ongoing selective serotonin/serotonin-norepinephrine reuptake inhibitor, in pts with TRD. SF-36v2 was assessed every 4 wks (on-treatment and retrieved dropout visits). Domain scores and change from baseline (CfB) were analysed using a mixed model for repeated measures (MMRM; observed cases) adjusted for age, prior treatment failures, baseline score. Higher scores indicate better HRQoL. P values were not adjusted for multiple testing.

336 and 340 pts were randomised to ESK-NS and Q-XR. Baseline domain scores were below general population norms and lowest in Role Emotional, Mental Health and Social Functioning (Figure 1A). All scores improved to Wk32 in both arms (Figure 1B). At Wk4, CfB was significantly higher (better HRQoL) with ESK-NS vs Q-XR across domains (all p<0.01). At Wk8, CfB was significantly higher with ESK-NS vs Q-XR across all domains (p<0.05) except Bodily Pain and Role Physical. At Wk32, CfB was significantly higher with ESK-NS vs Q-XR for Mental Health (p=0.014), Role Emotional (p=0.001), Role Physical (p=0.046) and Social Functioning (p=0.006); a trend of numerical advantage was seen for all other domains (Figure 2).

Image:

Image 2:

In addition to the superior clinical benefits provided by ESK-NS vs Q-XR in ESCAPE-TRD, pts receiving ESK-NS experienced significantly greater improvements in HRQoL vs Q-XR over 32 wks.

We thank the patients who participated. Study funding: Janssen, medical writing: Costello Medical, UK.

A. Young Grant / Research support from: Received grants from Janssen; independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London; the views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health, Consultant of: Received consulting fees from Allegan, AstraZeneca, Bionomics, Eli Lilly, Janssen, Johnson & Johnson, LivaNova, Lundbeck, Servier, and Sumitomo Dainippon Pharma and Sunovion, Speakers bureau of: Received speaker’s honoraria from Allegan, AstraZeneca, Bionomics, Eli Lilly, Janssen, Johnson & Johnson, LivaNova, Lundbeck, Servier, and Sumitomo Dainippon Pharma and Sunovion, B. Baune Grant / Research support from: Received research grants from private industries or non-profit funds from AstraZeneca, Lundbeck, and Sanofi-Synthélabo; received research grants from the BMBF and BMG Germany, the DFG, Germany, the National Health and Medical Research Council, Australia, and Horizon Europe 2021; received research grants from the Fay Fuller Foundation, and James & Diana Ramsay Foundation, Adelaide, Consultant of: Received consulting fees for roles with the National Health and Medical Research Council, Australia; received honoraria from Angelini, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Johnson & Johnson, LivaNova, Lundbeck, Otsuka, Pfizer, Roche, Servier, Sumitomo Dainippon Pharma and Sunovion, and Wyeth; served on advisory boards for Biogen, Boehringer-Ingelheim, Janssen-Cilag, LivaNova, Lundbeck, Novartis, and Otsuka, N. Cardoner Grant / Research support from: Received research grants from the Ministry of Health, Ministry of Science and Innovation (CIBERSAM), and the Strategic Plan for Research and Innovation in Health (PERIS) for the period 2016–2020, as well as from Marato TV3 and Recercaixa, Consultant of: Served on advisory boards for Angelini, Esteve, Janssen, Lundbeck, Novartis, Pfizer and Viatris, Speakers bureau of: Received speaker’s honoraria from Angelini, Esteve, Janssen, Lundbeck, Novartis, Pfizer and Viatris, R. Frey Grant / Research support from: Received travel fees from Janssen and LivaNova; received grants or contracts from Alkermes (Principal Investigator), Janssen (Principal Investigator), LivaNova (Principal Investigator) and Medizinisch‑Wissenschaftlicher Fonds des Bürgermeisters von Wien (academic study), Consultant of: Received consulting fees from Boehringer Ingelheim and Janssen, Speakers bureau of: Received speaker’s honoraria from Janssen and Lundbeck, T. Ito Shareolder of: Johnson & Johnson, Employee of: Janssen, Y. Kambarov Employee of: Janssen, A. Lacerda Grant / Research support from: Received grants from Azidus, Biophytis, Boehringer-Ingelheim, Cellavita, Celltrion, CNPq, Eli Lilly, EOM, FAPESP, Genova, IQVIA, Janssen, Nordisk, Novartis, Novo, Parexel and PPD, Consultant of: Received consulting fees from Aché, Apsen, Biogen, Boehringer-Ingelheim, Cristalia, Daiichi, Eurofarma, Sankyo, EMS, Janssen, Libbs, LivaNova, Lundbeck, Sanofi and Torrent, Speakers bureau of: Received speaker’s honoraria from Aché, Apsen, Biogen, Boehringer-Ingelheim, Cristalia, Daiichi, Eurofarma, Sankyo, EMS, Janssen, Libbs, LivaNova, Lundbeck, Sanofi and Torrent, B. Rive Employee of: Janssen, C. von Holt Shareolder of: Johnson & Johnson, Employee of: Janssen, A. Oliveira-Maia Grant / Research support from: Received grants from Compass Pathways, Ltd., Janssen, and Schuhfried GmBH; investigator‑driven research funded by Fundação para Ciência e Tecnologia (PTDC/SAU-NUT/3507/2021; PTDC/MED-NEU/1552/2021; PTDC/MED‑NEU/31331/2017), Fundação para Ciência e Tecnologia and FEDER (PTDC/MED-NEU/30845/2017_LISBOA-01-0145-FEDER-030845; PTDC/MEC-PSQ/30302/2017_LISBOA-01-0145-FEDER-30302), the European Research Council (ERC-2020-STG-Grant 950357), the European Commission Horizon 2020 Research and Innovation program (H2020‑SC1‑2017‑CNECT‑2‑777167‑ΒΟUNCE; H2020‑SC1‑DTH‑2019‑875358‑FAITH), and the European Joint Programme in Rare Diseases (Joint Translational Call 2019) through Fundação para Ciência e Tecnologia (EJPRD/0001/2020), Consultant of: Received payment or honoraria from MSD (Portugal), Neurolite AG, and the European Monitoring Centre for Drugs and Drug Addiction; received support for attending meetings from Janssen (Portugal); participated in advisory boards for Angelini (Portugal) and Janssen (Portugal), Employee of: Vice-President of the Portuguese Society for Psychiatry and Mental Health; Head of the Psychiatry Working Group for the National Board of Medical Examination (GPNA) at the Portuguese Medical Association and Portuguese Ministry of Health

Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.

Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.

Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).

Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.

Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions.

Data came from n = 999 patients ages 18–75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models.

Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31–1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65–2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43–2.87) and bullying (RR = 1.44; 95% CI = 0.99–2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE.

Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.

Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.

Prospective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.

We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.

Psychiatry in the UK has longstanding recruitment problems (1). Evidence suggests the positive effects of clinical attachments on attitudes towards psychiatry are often transient (2). We therefore created the Psychiatry Early Experience Programme (PEEP) where year 1 medical students are paired with psychiatry trainees and shadow them at work. Students will ideally remain in PEEP throughout medical school, providing consistent exposure to psychiatry and a broad experience of its subspecialties.

1. 1. To present PEEP

2. 2. To assess:

   1. a. Students’ baseline attitudes to psychiatry

   2. b. PEEPs’ impact on students’ attitudes to psychiatry

Design

A prospective survey based cohort study of King’s College London medical students.

PEEP started in 2013. In this cohort all students that signed up were accepted.

Students’ attitudes towards psychiatry were assessed on recruitment using the ATP-30 questionnaire (3), and will be re-assessed annually.

127 students were recruited. Attitudes were positive overall. 73% listed psychiatry in their top three specialities. 95.3% agreed or strongly agreed that ‘psychiatric illness deserves at least as much attention as physical illness.’ 84.3% disagreed or strongly disagreed that ‘at times it is hard to think of psychiatrists as equal to other doctors.’

Baseline attitudes to psychiatry were positive. By March 2015 we aim to collect and analyse data on students’ attitudes after one year in PEEP. Through on-ongoing analysis of this and future cohorts, we aim to assess the impact of PEEP on improving attitudes to psychiatry and whether this will ultimately improve recruitment.

The authors have not supplied their declaration of competing interest.

Nosocomial outbreaks due to multidrug-resistant microorganisms in rehabilitation centers have rarely been reported. We report an outbreak of extended-spectrum beta-lactamase (ESBL)–producing Klebsiella pneumoniae (ESBL-K. pneumoniae) on a single ward in a rehabilitation center in Rotterdam, The Netherlands.

Outbreak description.

A 40-bed ward of a rehabilitation center in the Netherlands.

In October 2016, 2 patients were found to be colonized by genetically indistinguishable ESBL-K. pneumoniae isolates. Therefore, an outbreak management team was installed, by whom a contact tracing plan was made. In addition to general outbreak measures, specific measures were formulated to allow continuation of the rehabilitation process. Also, environmental cultures were taken. Multiple-locus variable-number tandem-repeat analysis and amplification fragment-length polymorphism were used to determine strain relatedness. Selected isolates were subjected to whole-genome multilocus sequence typing.

The outbreak lasted 8 weeks. In total, 14 patients were colonized with an ESBL-K. pneumoniae, of whom 11 patients had an isolate belonging to sequence type 307. Overall, 163 environmental cultures were taken. Several sites of a household washing machine were repeatedly found to be contaminated with the outbreak strain. This machine was used to wash lifting slings and patient clothing contaminated with feces. The outbreak was contained after taking the machine temporarily out of service and implementing a reinforced and adapted protocol on the use of this machine.

We conclude that in this outbreak, the route of transmission of the outbreak strain via the household washing machine played a major role.

Subclinical delusional ideas, including persecutory beliefs, in otherwise healthy individuals are heritable symptoms associated with increased risk for psychotic illness, possibly representing an expression of one end of a continuum of psychosis severity. The identification of variation in brain function associated with these symptoms may provide insights about the neurobiology of delusions in clinical psychosis.

A resting-state functional magnetic resonance imaging scan was collected from 131 young adults with a wide range of severity of subclinical delusional beliefs, including persecutory ideas. Because of evidence for a key role of the amygdala in fear and paranoia, resting-state functional connectivity of the amygdala was measured.

Connectivity between the amygdala and early visual cortical areas, including striate cortex (V1), was found to be significantly greater in participants with high (n = 43) v. low (n = 44) numbers of delusional beliefs, particularly in those who showed persistence of those beliefs. Similarly, across the full sample, the number of and distress associated with delusional beliefs were positively correlated with the strength of amygdala-visual cortex connectivity. Moreover, further analyses revealed that these effects were driven by those who endorsed persecutory beliefs.

These findings are consistent with the hypothesis that aberrant assignments of threat to sensory stimuli may lead to the downstream development of delusional ideas. Taken together with prior findings of disrupted sensory-limbic coupling in psychosis, these results suggest that altered amygdala-visual cortex connectivity could represent a marker of psychosis-related pathophysiology across a continuum of symptom severity.