Duration of untreated psychosis and social function: 1-year follow-up study of first-episode schizophrenia.

BACKGROUND: In first-episode schizophrenia, longer duration of untreated psychosis (DUP) predicts poorer outcomes. AIMS: To address whether the relationship between DUP and outcome is a direct causal one or the result of association between symptoms and/or cognitive functioning and social functioning at the same time point. METHOD: Symptoms, social function and cognitive function were assessed in 98 patients with first-episode schizphrenia at presentation and 1 year later. RESULTS: There was no significant clinical difference between participants with short and long DUP at presentation. Linear regression analyses revealed that longer DUP significantly predicted more severe positive and negative symptoms and poorer social function at 1 year, independent of scores at presentation. Path analyses revealed independent direct relationships between DUP and social function, core negative symptoms and positive symptoms. There was no significant association between DUP and cognition. CONCLUSIONS: Longer DUP predicts poor social function independently of symptoms. The findings underline the importance of taking account of the phenomenological overlap between measures of negative symptoms and social function when investigating the effects of DUP

Visual exploration in Parkinson's disease and Parkinson's disease dementia

Parkinson's disease, typically thought of as a movement disorder, is increasingly recognized as causing cognitive impairment and dementia. Eye movement abnormalities are also described, including impairment of rapid eye movements (saccades) and the fixations interspersed between them. Such movements are under the influence of cortical and subcortical networks commonly targeted by the neurodegeneration seen in Parkinson's disease and, as such, may provide a marker for cognitive decline. This study examined the error rates and visual exploration strategies of subjects with Parkinson's disease, with and without cognitive impairment, whilst performing a battery of visuo-cognitive tasks. Error rates were significantly higher in those Parkinson's disease groups with either mild cognitive impairment (P = 0.001) or dementia (P < 0.001), than in cognitively normal subjects with Parkinson's disease. When compared with cognitively normal subjects with Parkinson's disease, exploration strategy, as measured by a number of eye tracking variables, was least efficient in the dementia group but was also affected in those subjects with Parkinson's disease with mild cognitive impairment. When compared with control subjects and cognitively normal subjects with Parkinson's disease, saccade amplitudes were significantly reduced in the groups with mild cognitive impairment or dementia. Fixation duration was longer in all Parkinson's disease groups compared with healthy control subjects but was longest for cognitively impaired Parkinson's disease groups. The strongest predictor of average fixation duration was disease severity. Analysing only data from the most complex task, with the highest error rates, both cognitive impairment and disease severity contributed to a predictive model for fixation duration [F(2,76) = 12.52, P ≤ 0.001], but medication dose did not (r = 0.18, n = 78, P = 0.098, not significant). This study highlights the potential use of exploration strategy measures as a marker of cognitive decline in Parkinson's disease and reveals the efficiency by which fixations and saccades are deployed in the build-up to a cognitive response, rather than merely focusing on the outcome itself. The prolongation of fixation duration, present to a small but significant degree even in cognitively normal subjects with Parkinson's disease, suggests a disease-specific impact on the networks directing visual exploration, although the study also highlights the multi-factorial nature of changes in exploration and the significant impact of cognitive decline on efficiency of visual searc

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Contingency knowledge is necessary for learned motivated behaviour in humans: relevance for addictive behaviour

Aims: Many forms of human conditioned behaviour depend upon explicit knowledge of the predictive contingency between stimuli, responses and the reinforcer. However, it remains uncertain whether the conditioning of three key behaviours in drug addiction-selective attention, instrumental drug-seeking behaviour and emotional state-are dependent upon contingency knowledge. To test this possibility, we employed an avoidance procedure to generate rapidly these three forms of conditioned behaviour without incurring the methodological problems of drug conditioning. Design: In two experiments, participants (16 students) were trained on a schedule in which one stimulus (S +) predicted the occurrence of a startling noise, which could be cancelled by performing an instrumental avoidance response. Measurements : The allocation of attention to the S + and the rate and probability of the avoidance response in the presence of S + were measured. Following training, participants were tested for their knowledge of the stimulus-noise contingencies arranged in the study and rated the emotional qualities of the stimuli. Findings: Both experiments showed that S + gained control of selective attention, instrumental avoidance behaviour and subjective anxiety, but only in participants who reported explicit knowledge of the Pavlovian contingency between the S + and the startling noise. Conclusions: The implication of the present findings is that the control of selective attention, instrumental drug-seeking behaviour and emotional state by drug-paired stimuli is mediated by cognitive knowledge of the predictive contingency between the stimulus and the drug

Sex differences in scanning faces: does attention to the eyes explain female superiority in facial expression recognition?

Previous meta-analyses support a female advantage in decoding non-verbal emotion (Hall, 1978, 1984), yet the mechanisms underlying this advantage are not understood. The present study examined whether the female advantage is related to greater female attention to the eyes. Eyetracking techniques were used to measure attention to the eyes in 19 males and 20 females during a facial expression recognition task. Women were faster and more accurate in their expression recognition compared with men, and women looked more at the eyes than men. Positive relationships were observed between dwell time and number of fixations to the eyes and both accuracy of facial expression recognition and speed of facial expression recognition. These results support the hypothesis that the female advantage in facial expression recognition is related to greater female attention to the eyes

Relationship between insight, cognitive function, social function and symptomatology in schizophrenia: the West London first episode study

OBJECTIVE: To examine the nature and clinical correlates of insight in first-episode schizophrenia, and how these differ from findings in established schizophrenia. METHOD: Insight (and insight dimensions), clinical symptoms, neurocognitive function and social function were assessed in 94 patients with first-episode schizophrenia or schizophreniform disorder according to DSM-IV criteria. RESULTS: Greater global insight was associated with more severe depression. Poor overall insight was associated significantly with more severe negative and disorganisation symptoms as well as poor working memory, and at a trend level with lower current IQ. Patients with poor insight perceived themselves to have a better level of independent performance at daily living activities. CONCLUSION: In first-episode psychosis, the clinical correlates of poor insight are similar to those reported for established schizophrenia. Those patients with greater insight may be at risk of depression. The complex relationships between insight, positive and negative symptoms, neurocognitive dysfunction and social function may reflect the multidimensional nature of insight

Hypnotic suggestibility, cognitive inhibition, and dissociation

We examined two potential correlates of hypnotic suggestibility: dissociation and cognitive inhibition. Dissociation is the foundation of two of the major theories of hypnosis and other theories commonly postulate that hypnotic responding is a result of attentional abilities (including inhibition). Participants were administered the Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C. Under the guise of an unrelated study, 180 of these participants also completed: a version of the Dissociative Experiences Scale that is normally distributed in non-clinical populations; a latent inhibition task, a spatial negative priming task, and a memory task designed to measure negative priming. The data ruled out even moderate correlations between hypnotic suggestibility and all the measures of dissociation and cognitive inhibition overall, though they also indicated gender differences. The results are a challenge for existing theories of hypnosis. (C) 2009 Elsevier Inc. All rights reserved

Visual exploration in Parkinson's disease and Parkinson's disease dementia

Parkinson's disease, typically thought of as a movement disorder, is increasingly recognized as causing cognitive impairment and dementia. Eye movement abnormalities are also described, including impairment of rapid eye movements (saccades) and the fixations interspersed between them. Such movements are under the influence of cortical and subcortical networks commonly targeted by the neurodegeneration seen in Parkinson's disease and, as such, may provide a marker for cognitive decline. This study examined the error rates and visual exploration strategies of subjects with Parkinson's disease, with and without cognitive impairment, whilst performing a battery of visuo-cognitive tasks. Error rates were significantly higher in those Parkinson's disease groups with either mild cognitive impairment (P = 0.001) or dementia (P < 0.001), than in cognitively normal subjects with Parkinson's disease. When compared with cognitively normal subjects with Parkinson's disease, exploration strategy, as measured by a number of eye tracking variables, was least efficient in the dementia group but was also affected in those subjects with Parkinson's disease with mild cognitive impairment. When compared with control subjects and cognitively normal subjects with Parkinson's disease, saccade amplitudes were significantly reduced in the groups with mild cognitive impairment or dementia. Fixation duration was longer in all Parkinson's disease groups compared with healthy control subjects but was longest for cognitively impaired Parkinson's disease groups. The strongest predictor of average fixation duration was disease severity. Analysing only data from the most complex task, with the highest error rates, both cognitive impairment and disease severity contributed to a predictive model for fixation duration [F(2,76) = 12.52, P ≤ 0.001], but medication dose did not (r = 0.18, n = 78, P = 0.098, not significant). This study highlights the potential use of exploration strategy measures as a marker of cognitive decline in Parkinson's disease and reveals the efficiency by which fixations and saccades are deployed in the build-up to a cognitive response, rather than merely focusing on the outcome itself. The prolongation of fixation duration, present to a small but significant degree even in cognitively normal subjects with Parkinson's disease, suggests a disease-specific impact on the networks directing visual exploration, although the study also highlights the multi-factorial nature of changes in exploration and the significant impact of cognitive decline on efficiency of visual search

Contingency knowledge is necessary for learned motivated behaviour in humans: relevance for addictive behaviour

Aims: Many forms of human conditioned behaviour depend upon explicit knowledge of the predictive contingency between stimuli, responses and the reinforcer. However, it remains uncertain whether the conditioning of three key behaviours in drug addiction-selective attention, instrumental drug-seeking behaviour and emotional state-are dependent upon contingency knowledge. To test this possibility, we employed an avoidance procedure to generate rapidly these three forms of conditioned behaviour without incurring the methodological problems of drug conditioning. Design: In two experiments, participants (16 students) were trained on a schedule in which one stimulus (S +) predicted the occurrence of a startling noise, which could be cancelled by performing an instrumental avoidance response. Measurements : The allocation of attention to the S + and the rate and probability of the avoidance response in the presence of S + were measured. Following training, participants were tested for their knowledge of the stimulus-noise contingencies arranged in the study and rated the emotional qualities of the stimuli. Findings: Both experiments showed that S + gained control of selective attention, instrumental avoidance behaviour and subjective anxiety, but only in participants who reported explicit knowledge of the Pavlovian contingency between the S + and the startling noise. Conclusions: The implication of the present findings is that the control of selective attention, instrumental drug-seeking behaviour and emotional state by drug-paired stimuli is mediated by cognitive knowledge of the predictive contingency between the stimulus and the drug