Philip Cowen

Philip Cowen
University of Oxford | OX · Department of Psychiatry

About

652
Publications
66,126
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
32,566
Citations

Publications

Publications (652)
Article
Full-text available
Depression has a large burden, but the development of new drugs for its treatment has proved difficult. Progresses in neuroscience have highlighted several physiopathological pathways, notably inflammatory and metabolic ones, likely involved in the genesis of depressive symptoms. A novel strategy proposes to repurpose established medical treatments...
Article
Full-text available
Rationale Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin’s influence on mood...
Article
Background Adolescent major depressive disorder (MDD) is associated with disrupted processing of emotional stimuli and difficulties in cognitive reappraisal. Little is known however about how current pharmacotherapies act to modulate the neural mechanisms underlying these key processes. The current study therefore investigated the neural effects of...
Article
Full-text available
Background: Patients with Parkinson's disease (PD) show impaired performance in taste recognition tests, which suggests a possible dopaminergic influence on gustatory functioning. To experimentally test this hypothesis, we assessed whether pharmacological manipulation of dopaminergic signalling in healthy volunteers can affect performance in a sta...
Article
Full-text available
Introduction Statins have been proposed as a strategy for treating depression, but their benefit in the absence of concurrent antidepressant treatment is unclear. This meta-analysis investigated the antidepressant effects of statin monotherapy in the general population. Methods We conducted a literature search of randomised controlled trials using...
Article
Full-text available
Ebselen is an organoselenium compound developed as an antioxidant and subsequently shown to be a glutathione peroxidase (GPx) mimetic. Ebselen shows some efficacy in post-stroke neuroprotection and is currently in trial for the treatment and prevention of hearing loss, Meniere’s Disease and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-...
Article
Full-text available
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-HT4 receptor agonists show promise in both animal models of depression and cognitive deficit. We therefore...
Preprint
Full-text available
Background: Dopamine D2-like receptor agonists show promise as treatments for depression. They are thought to act by altering how individuals learn from rewarding experiences. However, the nature of these reward learning alterations, and the mechanisms by which they are produced is not clear. Reinforcement learning accounts describe three distinct...
Article
Full-text available
Rationale Chronic fatigue syndrome (CFS) is a common and burdensome illness with a poorly understood pathophysiology, though many of the characteristic symptoms are likely to be of brain origin. The use of high-field proton magnetic resonance spectroscopy (MRS) enables the detection of a range of brain neurochemicals relevant to aetiological proces...
Article
Full-text available
Rationale Bright light treatment (BLT) is an efficacious antidepressant intervention, but its mechanism of action is not well understood. Antidepressant drugs acutely affect how emotional information is processed, pushing the brain to prioritise positive relative to negative input. Whether BLT could have a similar effect is not known to date. Obje...
Article
Full-text available
Background Growing evidence from clinical trials and epidemiological studies suggests that statins can have clinically significant antidepressant effects, potentially related to anti-inflammatory action on several neurobiological structures. However, the underlying neuropsychological mechanisms of these effects remain unexplored. Aims In this expe...
Article
Full-text available
Helping other people can entail risks for the helper. For example, when treating infectious patients, medical volunteers risk their own health. In such situations, decisions to help should depend on the individual’s valuation of others’ well-being (social preferences) and the degree of personal risk the individual finds acceptable (risk preferences...
Article
Full-text available
Cognitive deficits commonly accompany psychiatric disorders but are often underrecognised, and difficult to treat. The 5-HT4 receptor is a promising potential treatment target for cognitive impairment because in animal studies 5-HT4 receptor agonists enhance hippocampal-dependent memory processes. To date, there has been little work translating the...
Article
The use of SSRIs for the treatment of depression and anxiety in young people is increasing. However, the effects of SSRIs in adolescence, a time when there are substantial changes in neural, cognitive, and social functioning, are not well understood. Here, we review evidence from clinical trials about the benefits and risks of SSRIs in young people...
Article
Full-text available
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...
Article
Full-text available
The increasingly compelling data supporting the involvement of immunobiological mechanisms in Major Depressive Disorder (MDD) might provide some explanation forthe variance in this heterogeneous condition. Peripheral blood measures of cytokines and chemokines constitute the bulk of evidence, with consistent meta-analytic data implicating raised pro...
Article
Full-text available
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 c...
Article
Full-text available
Anhedonia, a pronounced reduction in interest or pleasure in any of life’s daily activities, is a cardinal symptom of major depression. In this Perspective article, we synthesise the recent evidence from rodent, monkey and human neuroimaging literature to highlight how the habenula, a small evolutionarily conserved subcortical structure located in...
Article
Full-text available
Abnormalities in glutamate neurotransmission are linked to psychotic symptoms and cognitive dysfunction in schizophrenia. magnetic resonance spectroscopy (MRS) provides an acceptable means of measuring glutamate in the human brain but findings from patient studies at conventional magnetic field strength show considerable heterogeneity. Ultra-high-f...
Article
Full-text available
Background The burden of depressive disorder is large and new treatment approaches are required. Repurposing widely available drugs such as statins may be a time- and cost-effective solution. Statins have anti-inflammatory and anti-oxidant properties which have been shown to be relevant to the pathophysiology of depression. This study assesses the...
Article
Full-text available
Background Depression and overweight are each associated with abnormal immune system activation. We sought to disentangle the extent to which depressive symptoms and overweight status contributed to increased inflammation and abnormal cortisol levels. Methods Participants were recruited through the Wellcome Trust NIMA Consortium. The sample of 216...
Article
Full-text available
Rationale Lithium is an effective prophylactic and anti-manic treatment in bipolar disorder; however, its use is declining through perceived poor tolerance and toxicity. Lithium inhibits inositol monophosphatase (IMPase), a probable key therapeutic mechanism. The anti-inflammatory drug, ebselen, also inhibits IMPase and appears well-tolerated and s...
Article
Full-text available
We have corrected this Article post-publication, because Dr. Cattaneo’s affiliation details were originally incorrect (she was affiliated with three institutions but is in fact only linked to one: Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia). These changes reflect in both the PDF and HTML versions...
Article
Full-text available
Importance Maternal depression during pregnancy is associated with emotional and behavioral difficulties of offspring during childhood that can increase the risk of depression in adolescence and adulthood. Objective To investigate the association between perinatal maternal depression and an increased long-term risk of depression in their adolescen...
Article
Full-text available
Background Meta-analytic evidence showed increased levels of peripheral endocannabinoid metabolites in psychotic illness. Alterations in the endocannabinoid system are believed to compromise glutamate and dopamine transmission, which play a central role in pathophysiological models of psychosis. I will present preliminary data from an ongoing high-...
Article
Full-text available
Minocycline has shown therapeutic promise in pre-clinical animal models and early phase clinical trials for a variety of psychiatric disorders. Previous studies on minocycline have shown its ability to suppress microglia activity and reduce inflammatory cytokine levels, and its amelioration of depressive-like behaviour in animals and humans. Howeve...
Article
Background Studies suggest that d-cycloserine (DCS) may have antidepressant potential through its interaction with the glycine site of the N-methyl-D-aspartate receptor; however, clinical evidence of DCS's efficacy as a treatment for depression is limited. Other evidence suggests that DCS affects emotional learning which may also be relevant for th...
Article
Full-text available
Animal experimental studies suggest that 5-HT 4 receptor activation holds promise as a novel target for the treatment of depression and cognitive impairment. 5-HT 4 receptors are post-synaptic receptors that are located in striatal and limbic areas known to be involved in cognition and mood. Consistent with this, 5-HT 4 receptor agonists produce ra...
Article
Full-text available
Background 5-HT 4 receptor stimulation has pro-cognitive and antidepressant-like effects in animal experimental studies; however, this pharmacological approach has not yet been tested in humans. Here we used the 5-HT 4 receptor partial agonist prucalopride to assess the translatability of these effects and characterise, for the first time, the cons...
Article
We report an electrochemical sensor for the detection of lithium ions (Li⁺) in authentic human saliva at lithium manganese oxide (LiMn2O4)-modified glassy carbon electrodes (LMO-GCE) and screen-printed electrodes (LMO-SPE). The sensing strategy is based on an initial galvanostatic delithiation of LMO followed by linear stripping voltammetry (LSV) t...
Article
Full-text available
Depression in adolescence is frequently characterised by symptoms of irritability. Fluoxetine is the antidepressant with the most favourable benefit:risk ratio profile to treat adolescent depression, but the neural mechanisms underlying antidepressant drugs in the young brain are still poorly understood. Previous studies have characterised the neur...
Article
Full-text available
There has been increasing interest in the antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine. Here we assess, for the first time, whether a transdermal scopolamine patch is sufficient to induce changes in cognition that are consistent with the reported cognitive and antidepressant effects of scopolamine. A scopolam...
Article
Full-text available
Background Lamotrigine is a useful treatment in bipolar depression but requires several weeks of dose titration before its clinical effects can be assessed. Animal experimental studies suggest that lamotrigine lowers glutamate release. The aim of the current study was to assess the effect of lamotrigine on brain glutamate in depressed bipolar patie...
Article
Background:: The neurocognitive model of antidepressant treatment in depression states that antidepressants work by producing relatively immediate positive shifts in emotional processing, which translate into clinical improvement with time. St John's Wort has shown antidepressant potential in randomised controlled trials; however, its pharmacologi...
Article
Full-text available
Background: Identification of biomarkers predicting therapeutic outcome to antidepressant treatment is one of the most important tasks in current research because it may transform the lengthy process of finding the right treatment for a given individual with depression. In the current study we explored the potential of pre-treatment pregenual ante...
Article
Background: Deficits in impulse control feature in many psychiatric conditions including bipolar disorder, suicidality and addictions. Lithium lowers impulsivity in clinical populations and decreases pathological gambling in experimental medicine studies, but suffers from adverse effects, poor compliance and a low therapeutic index. Aims: Recent...
Article
Background: Glutathione (GSH) is an important cellular antioxidant and its levels are decreased in some studies of bipolar patients. Saliva provides a simple and feasible means of measuring GSH but has not yet been applied to the study of bipolar disorder. The purpose of the study was to compare salivary levels of GSH and oxidized glutathione (GSS...
Article
Background: Static and dynamic functional connectivity are being increasingly used to measure the effects of disease and a range of different interventions on brain networks. While preliminary evidence suggests that static connectivity can be modulated by chronic antidepressants administration in healthy individuals and in major depression, much l...
Article
Full-text available
Background The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in a...
Article
How do drugs for psychiatric disorders work? - C. J. Harmer, P. J. Cowen
Preprint
Full-text available
Background: C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder. Methods: We recruited 102 treatment-resistant, depressed MDD patients, 48 treatment-responsive, non-depressed MDD patients, 48 depressed but u...
Article
Full-text available
Background Treatment of medical patients with the inflammatory cytokine, interferon- α (IFN- α ), is frequently associated with the development of clinical depressive symptomatology. Several important biological correlates of the effect of IFN- α on mood have been described, but the neuropsychological changes associated with IFN- α treatment are la...
Article
Full-text available
A subset of patients started on a selective serotonin reuptake inhibitor (SSRI) initially experience increased anxiety, which can lead to early discontinuation before therapeutic effects are manifest. The neural basis of this early SSRI effect is not known. Presynaptic dorsal raphe neuron (DRN) 5-HT1A receptors are known to play a critical role in...
Article
Full-text available
The advantages of ultra-high-field (UHF≥7T) MR have been demonstrated in a variety of MR acquisition modalities. Magnetic resonance spectroscopy (MRS) can particularly benefit from substantial gains in signal-to-noise ratio (SNR) and spectral resolution at UHF, enabling the quantification of numerous metabolites including, glutamate, glutamine, glu...
Article
Full-text available
The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands...