Background The coronavirus disease 2019 (COVID-19) pandemic has had a significant psychological impact on healthcare workers (HCWs). Aims There is an urgent need to understand the risk and protective factors associated with poor mental well-being of UK HCWs working during the COVID-19 pandemic. Method Shortly after the April 2020 UK COVID-19 peak 2773 HCWs completed a survey containing measures of anxiety, depression, post-traumatic stress disorder and stress, as well as questions around potential predictors such as roles, COVID-19 risk perception and workplace-related factors. Respondents were classified as high or low symptomatic on each scale and logistic regression revealed factors associated with severe psychiatric symptoms. Change in well-being from pre- to during COVID-19 was also quantified. Results Nearlya third of HCWs reported moderate to severe levels of anxiety and depression, and the number reporting very high symptoms was more than quadruple that pre-COVID-19. Several controllable factors were associated with the most severe level of psychiatric symptoms: insufficient personal protective equipment availability, workplace preparation, training and communication, and higher workload. Being female, ‘front line’, previous psychiatric diagnoses, traumatic events, and being an allied HCW or manager were also significantly associated with severe psychiatric symptoms. Sharing stress, resilience and ethical support for treatment decisions were significantly associated with low psychiatric symptoms. Front-line workers showed greater worsening of mental health compared with non-front-line HCWs. Conclusions Poor mental well-being was prevalent during the COVID-19 response, however, controllable factors associated with severe psychiatric symptoms are available to be targeted to reduce the detrimental impact of COVID-19 and other pandemics on HCW mental health.
Rationale Schizophrenia is associated with impairments in cognitive functioning yet there are no approved drugs to treat these deficits. Objectives Based on animal models, we investigated the potential for roflumilast, a selective inhibitor of phosphodiesterase type 4 (PDE4), to improve cognition, which may act by increasing intracellular cyclic adenosine monophosphate in brain regions underlying cognitive deficits in schizophrenia. Methods This study consisted of a randomised, double-blind, placebo-controlled, crossover design involving 15 schizophrenia patients. In 3 treatment periods, patients were given 8 days of placebo or one of the two doses of roflumilast (100 and 250 μg daily) with 14 days of washout between treatments. The primary endpoints were dorsolateral prefrontal cortex (DLPFC) activation during a visuospatial working memory task measured with fMRI on dosing day 8 and verbal memory and working memory performance change from baseline to day 8. Least square mean change scores were calculated for behavioural outcomes; fMRI data were analysed in SPM12 with bilateral DLPFC as regions of interest. Results Verbal memory was significantly improved under 250 μg roflumilast (effect size (ES) = 0.77) compared to placebo. fMRI analyses revealed that increasing dose of roflumilast was associated with reduction of bilateral DLPFC activation during working memory compared to placebo, although this was not statistically significant (ES = 0.31 for the higher dose). Working memory was not improved (ES = 0.03). Conclusions Results support the mechanistic validation of potential novel strategies for improving cognitive dysfunction in schizophrenia and suggest that PDE4 inhibition may be beneficial for cognitive dysfunction in schizophrenia. Trial registration NCT02079844.
Individuals with schizophrenia typically suffer a range of cognitive deficits, including prominent deficits in working memory and executive function. These difficulties are strongly predictive of functional outcomes, but there is a paucity of effective therapeutic interventions targeting these deficits. Transcranial direct current stimulation is a novel neuromodulatory technique with emerging evidence of potential pro-cognitive effects; however, there is limited understanding of its mechanism. This was a double-blind randomized sham controlled pilot study of transcranial direct current stimulation on a working memory (n-back) and executive function (Stroop) task in 28 individuals with schizophrenia using functional magnetic resonance imaging. Study participants received 30 min of real or sham transcranial direct current stimulation applied to the left frontal cortex. The 'real' and 'sham' groups did not differ in online working memory task performance, but the transcranial direct current stimulation group demonstrated significant improvement in performance at 24 h post-transcranial direct current stimulation. Transcranial direct current stimulation was associated with increased activation in the medial frontal cortex beneath the anode; showing a positive correlation with consolidated working memory performance 24 h post-stimulation. There was reduced activation in the left cerebellum in the transcranial direct current stimulation group, with no change in the middle frontal gyrus or parietal cortices. Improved performance on the executive function task was associated with reduced activity in the anterior cingulate cortex. Transcranial direct current stimulation modulated functional activation in local task-related regions, and in more distal nodes in the network. Transcranial direct current stimulation offers a potential novel approach to altering frontal cortical activity and exerting pro-cognitive effects in schizophrenia.
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