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  • Tianeptine in an experimental medicine model of antidepressant action.

    3 November 2018

    Changes in emotional processing have been shown following acute administration of a range of monoaminergic antidepressants, and may represent an important common neuropsychological mechanism underpinning their therapeutic effects. Tianeptine is an agent that challenges the traditional monoaminergic hypothesis of antidepressant action, though its exact mode of action remains controversial. Healthy volunteers were randomised to receive a single dose of tianeptine (12.5 mg) or placebo, and subsequently completed a battery of tasks measuring emotional processing, including facial expression recognition, emotional memory and attentional vigilance, as well as working and verbal memory. Tianeptine-treated subjects were less accurate at identifying facial expressions, though this was not valence specific. The tianeptine group also showed reduced positive affective memory and reduced attentional vigilance to positive stimuli. There were no effects on emotional categorization or non-emotional cognition. The negative biases in aspects of emotional processing observed following acute tianeptine administration are at variance with the positive biases generally seen after acute administration of conventional antidepressant drugs, despite tianeptine's putative antidepressant efficacy. This is an intriguing finding in the context of the lack of consensus regarding tianeptine's mechanism of action; however, it may be consistent with the reported ability of acute tianeptine to increase the re-uptake of serotonin.

  • Recombinant human erythropoietin for treating treatment-resistant depression: a double-blind, randomized, placebo-controlled phase 2 trial.

    3 November 2018

    Pharmacological treatments for depression have insufficient efficacy in 30-40% of patients and fail to reverse cognitive deficits. Erythropoietin (EPO) has neurotrophic actions and aids neurocognitive function. The aim of this exploratory study was to determine whether recombinant human EPO improves mood and memory in treatment-resistant depression. Forty treatment-resistant depressed unipolar patients with Hamilton Depression Rating Scale-17 (HDRS-17) score ≥ 17 were randomized to eight weekly EPO (Eprex; 40,000 IU) or saline infusions in a double-blind, placebo-controlled, parallel-group design. Patients were assessed at baseline and at weeks 5, 9, and 14. Primary outcome was reduction in HDRS-17 score. Global assessment of function (GAF) was reported in addition. Secondary outcome was remission rate, and tertiary outcomes were changes in Rey Auditory Verbal Learning Test (RAVLT), Beck Depression Inventory-21 (BDI-21), and World Health Organization Quality of life-BREF (WHOQOL-BREF). Exploratory outcomes were depression and cognition composite scores. HDRS-17, GAF, and remission rates showed no effects of EPO over saline at week 9 (P-value ≥ 0.09). However, EPO improved BDI (P=0.02) and WHOQOL-BREF (P=0.01), and this was maintained at follow-up week 14 (P-values ≤ 0.04). EPO enhanced verbal recall (P=0.02) and recognition (P=0.03), which was sustained at follow-up (P-values ≤ 0.04). Exploratory analysis in patients fulfilling depression severity criteria at trial start revealed ameliorated HDRS-17 in EPO (N=14) vs saline groups (N=17), which was sustained at week 14 (P-values ≤ 0.05). Exploratory analysis in the complete cohort showed that EPO reduced depression composite at weeks 9 and 14 (P-values=0.02). The findings of this exploratory study highlight EPO as an interesting compound for treatment-resistant depression, which deserves further investigation.

  • Satiation attenuates BOLD activity in brain regions involved in reward and increases activity in dorsolateral prefrontal cortex: an fMRI study in healthy volunteers.

    3 November 2018

    BACKGROUND: Neural responses to rewarding food cues are significantly different in the fed vs. fasted (>8 h food-deprived) state. However, the effect of eating to satiety after a shorter (more natural) intermeal interval on neural responses to both rewarding and aversive cues has not been examined. OBJECTIVE: With the use of a novel functional magnetic resonance imaging (fMRI) task, we investigated the effect of satiation on neural responses to both rewarding and aversive food tastes and pictures. DESIGN: Sixteen healthy participants (8 men, 8 women) were scanned on 2 separate test days, before and after eating a meal to satiation or after not eating for 4 h (satiated vs. premeal). fMRI blood oxygen level-dependent (BOLD) signals to the sight and/or taste of the stimuli were recorded. RESULTS: A whole-brain cluster-corrected analysis (P < 0.05) showed that satiation attenuated the BOLD response to both stimulus types in the ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex, nucleus accumbens, hypothalamus, and insula but increased BOLD activity in the dorsolateral prefrontal cortex (dlPFC; local maxima corrected to P ≤ 0.001). A psychophysiological interaction analysis showed that the vmPFC was more highly connected to the dlPFC when individuals were exposed to food stimuli when satiated than when not satiated. CONCLUSIONS: These results suggest that natural satiation attenuates activity in reward-related brain regions and increases activity in the dlPFC, which may reflect a "top down" cognitive influence on satiation. This trial was registered at clinicaltrials.gov as NCT02298049.

  • Meta-analysis of emotion recognition deficits in major depressive disorder.

    3 November 2018

    BACKGROUND: Many studies have explored associations between depression and facial emotion recognition (ER). However, these studies have used various paradigms and multiple stimulus sets, rendering comparisons difficult. Few studies have attempted to determine the magnitude of any effect and whether studies are properly powered to detect it. We conducted a meta-analysis to synthesize the findings across studies on ER in depressed individuals compared to controls. METHOD: Studies of ER that included depressed and control samples and published before June 2013 were identified in PubMed and Web of Science. Studies using schematic faces, neuroimaging studies and drug treatment studies were excluded. RESULTS: Meta-analysis of k = 22 independent samples indicated impaired recognition of emotion [k = 22, g = -0.16, 95% confidence interval (CI) -0.25 to -0.07, p < 0.001]. Critically, this was observed for anger, disgust, fear, happiness and surprise (k's = 7-22, g's = -0.42 to -0.17, p's < 0.08), but not sadness (k = 21, g = -0.09, 95% CI -0.23 to +0.06, p = 0.23). Study-level characteristics did not appear to be associated with the observed effect. Power analysis indicated that a sample of approximately 615 cases and 615 controls would be required to detect this association with 80% power at an alpha level of 0.05. CONCLUSIONS: These findings suggest that the ER impairment reported in the depression literature exists across all basic emotions except sadness. The effect size, however, is small, and previous studies have been underpowered.

  • Cognitive vulnerability and implicit emotional processing: imbalance in frontolimbic brain areas?

    3 November 2018

    It has been proposed that the neural basis for cognitive vulnerability to depression involves an imbalance in frontolimbic activity during the processing of cues with a negative affective value. Although the question is central to cognitive theory, whether this association is amplified by diagnosis of an affective disorder or recent life stress has not been investigated. A composite cognitive vulnerability score based on questionnaire assessment was used to predict neural responses to negative emotional stimuli in N = 112 participants. Potential moderating effects of psychiatric diagnosis and negative life events were examined. Main and interaction effects were tested against a threshold of p < .05, family-wise error (FWE) corrected at the cluster level, and the results were small-volume corrected in regions of interest. Cognitive vulnerability predicted higher activation of superior parietal areas (p(FWE) < .01) for negative than for positive faces. The association was significantly stronger in healthy participants. For negative versus control stimuli, cognitive vulnerability predicted higher ventrolateral prefrontal and subgenual anterior cingulate activation (p(FWE) < .05) to equal extents in both groups. We found no evidence for an association with amygdala activation. Life events did not moderate the findings. We concluded that cognitive vulnerability was associated with higher activation of frontoparietal areas during an implicit emotional task. These higher levels of activation may potentially reflect increased effort being required to ignore irrelevant negative emotional information in vulnerable populations.

  • Increasing pharmacological knowledge about human neurological and psychiatric disorders through functional neuroimaging and its application in drug discovery.

    3 November 2018

    Functional imaging methods such as fMRI have been widely used to gain greater understanding of brain circuitry abnormalities in CNS disorders and their underlying neurochemical basis. Findings suggest that: (1) drugs with known clinical efficacy have consistent effects on disease relevant brain circuitry, (2) brain activation changes at baseline or early drug effects on brain activity can predict long-term efficacy; and (3) fMRI together with pharmacological challenges could serve as experimental models of disease phenotypes and be used for screening novel drugs. Together, these observations suggest that drug related modulation of disease relevant brain circuitry may serve as a promising biomarker/method for use in drug discovery to demonstrate target engagement, differential efficacy, dose-response relationships, and prediction of clinically relevant changes.

  • Test-retest reliability and task order effects of emotional cognitive tests in healthy subjects.

    3 November 2018

    Little is known of the retest reliability of emotional cognitive tasks or the impact of using different tasks employing similar emotional stimuli within a battery. We investigated this in healthy subjects. We found improved overall performance in an emotional attentional blink task (EABT) with repeat testing at one hour and one week compared to baseline, but the impact of an emotional stimulus on performance was unchanged. Similarly, performance on a facial expression recognition task (FERT) was better one week after a baseline test, though the relative effect of specific emotions was unaltered. There was no effect of repeat testing on an emotional word categorising, recall and recognition task. We found no difference in performance in the FERT and EABT irrespective of task order. We concluded that it is possible to use emotional cognitive tasks in longitudinal studies and combine tasks using emotional facial stimuli in a single battery.

  • John Radcliffe Hospital’s Psychological Medicine Team awarded gold in the Trust's 'Team of the Year' category

    10 December 2014

    Trust lead for psychological medicine Michael Sharpe, who nominated the team, said it deserved recognition after transforming the care of patients over the past year.

  • Dementias Platform UK launches unparalleled resource for research

    20 October 2015

    The Data Portal is a secure research environment, using the latest privacy preserving methods to provide researchers with high quality information and tools to facilitate collaborative research.

  • Seena Fazel comments on German Wings crash

    30 March 2015

    "It's not so much a mental illness problem – it's young men who feel socially excluded, angry and disaffected," he said, although he noted that he couldn't say whether this was true in the case of the Germanwings co-pilot.

  • Mindfulness meditation adapted for South Asian city life

    10 June 2013

    Professor Mark Williams, director of the Oxford Mindfulness Centre at Oxford University, is among the growing number of academics and scientists who have dedicated their careers to unlocking the potential of mindfulness meditation, a Western, non-sectarian form of meditation based on Buddhist practices.

  • BMA Margaret Temple Award 2013 for Dr Anthony James and colleagues

    21 May 2013

    Research to look at olfactory stem cells and induced pluripotential stem cells from skin fibroblasts of patients with adolescent-onset schizophrenia and matched healthy controls

  • Our necessary shadow - the nature and meaning of psychiatry

    21 May 2013

    Psychiatry has been under attack throughout its history, and the last generation, despite the enormous improvement in the effectiveness and safety of its treatments, has been no different. This book sets out to describe psychiatry, warts and all, for the general public so that they can make up their own minds when they read the various critiques that crowd our bookshops and newspapers.

  • Profile: Seena Fazel

    7 October 2015

    Professor of Forensic Psychiatry at the University of Oxford is in the spotlight for October’s 'The Lancet Psychiatry'

  • Waking up to the link between a faulty body clock and mental illness

    23 July 2013

    Professor Russell Foster, professor of circadian neuroscience at the University of Oxford, writes about our biological clocks and possible links to mental illness that are emerging: ‘Our lives are ruled by time and we use time to tell us what to do. But the digital alarm clock that wakes us in the morning and the wrist-watch that tells us we are late for a meeting are not the clocks I mean. Our biology dances to a profoundly more ancient beat that probably started to tick early in the evolution of all life.’ (The Guardian, 22/07/2013)

  • The other side of the magic mushroom debate

    18 May 2016

    Professor Phil Cowen, from the University of Oxford Department of Psychiatry, writes a response to the claims that magic mushrooms could offer a magic bullet for treatment-resistant depression.