6 results on '"Cowen, Philip J."'
Search Results
2. The Effect of the 5-HT4 Agonist, Prucalopride, on a Functional Magnetic Resonance Imaging Faces Task in the Healthy Human Brain.
- Author
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de Cates, Angharad N., Martens, Marieke A. G., Wright, Lucy C., Gould van Praag, Cassandra D., Capitão, Liliana P., Gibson, Daisy, Cowen, Philip J., Harmer, Catherine J., and Murphy, Susannah E.
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FUNCTIONAL magnetic resonance imaging ,DEFAULT mode network - Abstract
Depression is a common and often recurrent illness with significant negative impact on a global scale. Current antidepressants are ineffective for up to one third of people with depression, many of whom experience persistent symptomatology. 5-HT
4 receptor agonists show promise in both animal models of depression and cognitive deficit. We therefore studied the effect of the 5-HT4 partial agonist prucalopride (1 mg daily for 6 days) on the neural processing of emotional faces in 43 healthy participants using a randomised placebo-controlled design. Participants receiving prucalopride were more accurate at identifying the gender of emotional faces. In whole brain analyses, prucalopride was also associated with reduced activation in a network of regions corresponding to the default mode network. However, there was no evidence that prucalopride treatment produced a positive bias in the neural processing of emotional faces. Our study provides further support for a pro-cognitive effect of 5-HT4 receptor agonism in humans. While our current behavioural and neural investigations do not suggest an antidepressant-like profile of prucalopride in humans, it will be important to study a wider dose range in future studies. [ABSTRACT FROM AUTHOR]- Published
- 2022
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- View/download PDF
3. Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies.
- Author
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De Giorgi, Riccardo, Rizzo Pesci, Nicola, Quinton, Alice, De Crescenzo, Franco, Cowen, Philip J., and Harmer, Catherine J.
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MEDICAL research ,MENTAL depression ,SLEEP interruptions ,STATINS (Cardiovascular agents) ,ANHEDONIA ,SYMPTOMS - Abstract
Background: Depression is a leading cause of disability, burdened by high levels of non-response to conventional antidepressants. Novel therapeutic strategies targeting non-monoaminergic pathways are sorely needed. The widely available and safe statins have several putative mechanisms of action, especially anti-inflammatory, which make them ideal candidates for repurposing in the treatment of depression. A large number of articles has been published on this topic. The aim of this study is to assess this literature according to evidence-based medicine principles to inform clinical practise and research. Methods: We performed a systematic review of the electronic databases MEDLINE, CENTRAL, Web of Science, CINAHL, and ClinicalTrials.gov, and an unstructured Google Scholar and manual search, until the 9th of April 2021, for all types of clinical studies assessing the effects of statins in depression. Results: Seventy-two studies were retrieved that investigated the effects of statins on the risk of developing depression or on depressive symptoms in both depressed and non-depressed populations. Fifteen studies specifically addressed the effects of statins on inflammatory-related symptoms of anhedonia, psychomotor retardation, anxiety, and sleep disturbances in depression. Most studies suggested a positive effect of statins on the occurrence and severity of depression, with fewer studies showing no effect, while a minority indicated some negative effects. Limitations: We provide a narrative report on all the included studies but did not perform any quantitative analysis, which limits the strength of our conclusions. Conclusions: Robust evidence indicates that statins are unlikely to lead to depressive symptoms in the general population. Promising data suggest a potential role for statins in the treatment of depression. Further clinical studies are needed, especially in specific subgroups of patients identified by pre-treatment assessments of inflammatory and lipid profiles. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Early increase in marker of neuronal integrity with antidepressant treatment of major depression: 1H-magnetic resonance spectroscopy of N-acetyl-aspartate.
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Taylor, Matthew J., Godlewska, Beata R., Norbury, Ray, Selvaraj, Sudhakar, Near, Jamie, and Cowen, Philip J.
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ANTIDEPRESSANTS ,MENTAL depression ,THERAPEUTICS ,ESCITALOPRAM ,NUCLEAR magnetic resonance spectroscopy ,NEUROPROTECTIVE agents ,NEUROTROPHINS ,ASPARTATES - Abstract
Increasing interest surrounds potential neuroprotective or neurotrophic actions of antidepressants. While growing evidence points to important early clinical and neuropsychological effects of antidepressants, the time-course of any effect on neuronal integrity is unclear. This study used magnetic resonance spectroscopy to assess effects of short-term treatment with escitalopram on N-acetyl-aspartate (NAA), a marker of neuronal integrity. Thirty-nine participants with major depression were randomly assigned to receive either 10 mg escitalopram or placebo daily in a double-blind, parallel group design. On the seventh day of treatment, PRESS data were obtained from a 30×30×20 mm voxel placed in medial frontal cortex. Age and gender-matched healthy controls who received no treatment were also scanned. Levels of NAA were significantly higher in patients treated with escitalopram than in either placebo-treated patients (p<0.01) or healthy controls (p<0.01). Our findings are consistent with the proposition that antidepressant treatment in depressed patients can produce early changes in neuronal integrity. [ABSTRACT FROM PUBLISHER]
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- 2012
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5. An Experimental Medicine Investigation of the Effects of Subacute Pramipexole Treatment on Emotional Information Processing in Healthy Volunteers.
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Martens, Marieke Annie Gerdine, Kaltenboeck, Alexander, Halahakoon, Don Chamith, Browning, Michael, Cowen, Philip J., and Harmer, Catherine J.
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ANTIDEPRESSANTS ,PRAMIPEXOLE ,EXPERIMENTAL medicine ,FUNCTIONAL magnetic resonance imaging ,DOPAMINE agonists ,INFORMATION processing - Abstract
Treatment with the dopamine D2/D3 receptor agonist pramipexole has demonstrated promising clinical effects in patients with depression. However, the mechanisms through which pramipexole might alleviate depressive symptoms are currently not well understood. Conventional antidepressant drugs are thought to work by biasing the processing of emotional information in favour of positive relative to negative appraisal. In this study, we used an established experimental medicine assay to explore whether pramipexole treatment might have a similar effect. Employing a double-blind, parallel-group design, 40 healthy volunteers (aged 18 to 43 years, 50% female) were randomly allocated to 12 to 15 days of treatment with either pramipexole (at a peak daily dose of 1.0 mg pramipexole salt) or placebo. After treatment was established, emotional information processing was assessed on the neural level by measuring amygdala activity in response to positive and negative facial emotional expressions, using functional magnetic resonance imaging (MRI). In addition, behavioural measures of emotional information processing were collected at baseline and on drug, using an established computerized task battery, tapping into different cognitive domains. As predicted, pramipexole-treated participants, compared to those receiving placebo, showed decreased neural activity in response to negative (fearful) vs. positive (happy) facial expressions in bilateral amygdala. Contrary to our predictions, however, pramipexole treatment had no significant antidepressant-like effect on behavioural measures of emotional processing. This study provides the first experimental evidence that subacute pramipexole treatment in healthy volunteers modifies neural responses to emotional information in a manner that resembles the effects of conventional antidepressant drugs. [ABSTRACT FROM AUTHOR]
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- 2021
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6. Fronto-limbic effective connectivity as possible predictor of antidepressant response to SSRI administration
- Author
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Benedetta Vai, Philip J. Cowen, Francesco Benedetti, Chiara Bulgarelli, Beata R. Godlewska, Catherine J. Harmer, Vai, Benedetta, Bulgarelli, Chiara, Godlewska, Beata R., Cowen, Philip J., Benedetti, Francesco, and Harmer, Catherine J.
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Male ,0302 clinical medicine ,Neural Pathways ,Image Processing, Computer-Assisted ,Limbic System ,SSRI ,Pharmacology (medical) ,Depression ,Middle Aged ,Serotonin Uptake Inhibitor ,Magnetic Resonance Imaging ,Antidepressive Agents ,Diagnostic and Statistical Manual of Mental Disorder ,Frontal Lobe ,Diagnostic and Statistical Manual of Mental Disorders ,Psychiatry and Mental health ,Treatment Outcome ,medicine.anatomical_structure ,Neurology ,Psychiatry and Mental Health ,Antidepressive Agent ,Biomarker (medicine) ,Antidepressant ,Female ,Psychology ,Selective Serotonin Reuptake Inhibitors ,psychological phenomena and processes ,Human ,medicine.drug ,Adult ,medicine.medical_specialty ,Ventrolateral prefrontal cortex ,Models, Neurological ,Citalopram ,Amygdala ,behavioral disciplines and activities ,Neural Pathway ,03 medical and health sciences ,mental disorders ,medicine ,Humans ,Escitalopram ,BOLD fMRI ,Psychiatry ,Emotional bias ,Biological Psychiatry ,Anterior cingulate cortex ,Emotion ,Pharmacology ,Depressive Disorder, Major ,Fusiform gyrus ,030227 psychiatry ,nervous system ,Dynamic causal modeling ,Neurology (clinical) ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The timely selection of the optimal treatment for depressed patients is critical to improve remission rates. The detection of pre-treatment variables able to predict differential treatment response may provide novel approaches for treatment selection. Selective serotonin reuptake inhibitors (SSRIs) modulate the fronto-limbic functional response and connectivity, an effect preceding the overt clinical antidepressant effects. Here we investigated whether the cortico-limbic connectivity associated with emotional bias measured before SSRI administration predicts the efficacy of antidepressant treatment in MDD patients. fMRI and Dynamic Causal Modeling (DCM) were combined to study if effective connectivity might differentiate healthy controls (HC) and patients affected by major depression who later responded (RMDD, n=21), or failed to respond (nRMDD, n=12), to 6 weeks of escitalopram administration. Sixteen DCMs exploring connectivity between anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), Amygdala (Amy), and fusiform gyrus (FG) were constructed. Analyses revealed that nRMDD had reduced endogenous connectivity from Amy to VLPFC and to ACC, with an increased connectivity and modulation of the ACC to Amy connectivity when processing of fearful emotional stimuli compared to HC. RMDD and HC did not significantly differ among themselves. Pre-treatment effective connectivity in fronto-limbic circuitry could be an important factor affecting antidepressant response, and highlight the mechanisms which may be involved in recovery from depression. These results suggest that fronto-limbic connectivity might provide a neural biomarker to predict the clinical outcome to SSRIs administration in major depression.
- Published
- 2016
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