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Author: Philip McGuire (375)


Feb
2018

Dysfunctional reward processing is associated with a number of psychiatric disorders, such as addiction and schizophrenia. It is thought that reward is regulated mainly by dopamine transmission in the ventral striatum. Contemporary animal models suggest that striatal dopamine concentrations and associated behaviours are related to glutamatergic functioning in the ventral hippocampus.

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Jan
2018

Preclinical models propose that the onset of psychosis is associated with hippocampal hyperactivity, thought to be driven by cortical GABAergic interneuron dysfunction and disinhibition of pyramidal neurons. Recent neuroimaging studies suggest that resting hippocampal perfusion is increased in subjects at ultra-high risk (UHR) for psychosis, but how this may be related to GABA concentrations is unknown. The present study used a multimodal neuroimaging approach to address this issue in UHR subjects.

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Feb
2018

Neurocognitive models and previous neuroimaging work posit that auditory verbal hallucinations (AVH) arise due to increased activity in speech-sensitive regions of the left posterior superior temporal gyrus (STG). Here, we examined if patients with schizophrenia (SCZ) and AVH could be trained to down-regulate STG activity using real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF). We also examined the effects of rtfMRI-NF training on functional connectivity between the STG and other speech and language regions.

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Jan
2018

We report on the first open-label, parallel group randomised controlled trial of automated appointment reminders in a psychosis community service in the UK. Ninety-five patients were randomly allocated to receiving/not receiving automated messaging reminders 7 days and 1 day before appointments. All 'Attended' and 'Missed' appointment outcomes over 6 months were analysed using cluster regression analysis.

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Jan
2018

Reduction of duration of untreated psychosis (DUP) is the key strategy of early interventions for improving the outcomes of first-episode psychosis. Although several controlled interventional studies have been conducted with the aim of reducing DUP, the results are highly inconsistent and conflicting. The current study systematically searches Web of Science and Ovid for English original articles investigating interventions adopted to reduce DUP, compared to a control intervention, up to April 6, 2017.

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Feb
2018

Psychosis is a heterogeneous psychiatric condition for which a multitude of risk and protective factors have been suggested. This umbrella review aimed to classify the strength of evidence for the associations between each factor and psychotic disorders whilst controlling for several biases. The Web of Knowledge database was searched to identify systematic reviews and meta-analyses of observational studies which examined associations between socio-demographic, parental, perinatal, later factors or antecedents and psychotic disorders, and which included a comparison group of healthy controls, published from 1965 to January 31, 2017.

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Dec
2017

We recently reported that resting hippocampal, basal ganglia and midbrain perfusion is elevated in people at ultra high risk (UHR) for psychosis. The present study sought to replicate our previous finding in an independent UHR cohort, and examined the relationship between resting perfusion in these regions, psychosis and depression symptoms, and traumatic experiences in childhood. Pseudo-Continuous Arterial Spin Labelling (p-CASL) imaging was used to measure resting cerebral blood flow (rCBF) in 77 UHR for psychosis individuals and 25 healthy volunteers in a case-control design.

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Dec
2017

Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties. The authors assessed the safety and effectiveness of CBD in patients with schizophrenia.
In an exploratory double-blind parallel-group trial, patients with schizophrenia were randomized in a 1:1 ratio to receive CBD (1000 mg/day; N=43) or placebo (N=45) alongside their existing antipsychotic medication.

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Mar
2018

This meta-analysis summarizes research examining whether deficits in verbal learning are related to bilateral hippocampal volume reductions in patients with or at risk for schizophrenia and in healthy controls. 17 studies with 755 patients with schizophrenia (SCZ), 232 Genetic High Risk (GHR) subjects and 914 healthy controls (HC) were included. Pooled correlation coefficients were calculated between hemisphere (left, right or total) and type of recall (immediate or delayed) for each diagnostic group individually (SCZ, GHR and HC).

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Dec
2017

Cognitive models of psychosis propose that appraisals (ie, the interpretation and meaning attributed to experiences) are central to the transition from anomalous experiences to psychotic symptoms. In the Unusual Experiences Enquiry (UNIQUE) study, we investigated the role of appraisals by comparing individuals with persistent psychotic experiences without a need for care with patients and people without psychotic experiences.
Eligible participants were patients with diagnosed psychotic disorders (clinical group) and adults in the general population with persistent psychotic experiences (non-clinical group) and without psychotic experiences (controls).

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Nov
2017

Perinatal brain injuries, including hippocampal lesions, cause lasting changes in dopamine function in rodents, but it is not known if this occurs in humans. We compared adults who were born very preterm with perinatal brain injury to those born very preterm without perinatal brain injury, and age-matched controls born at full term using [18F]-DOPA PET and structural MRI. Dopamine synthesis capacity was reduced in the perinatal brain injury group relative to those without brain injury (Cohen's= 1.

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Nov
2017

Childhood emotional and behaviour problems are antecedents for later psychopathology. This study investigated genetic and environmental influences shaping the longitudinal association between childhood emotional and behaviour problems and specific PEs.
In a community-based twin sample, parents reported on emotional and behaviour problems when twins were ages 7 and 12 years.

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Nov
2017

Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing fearful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man.

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Dec
2017

The dopamine hypothesis suggests that dopamine abnormalities underlie psychosis, irrespective of diagnosis, implicating dopamine dysregulation in bipolar affective disorder and schizophrenia, in line with the research domain criteria approach. However, this hypothesis has not been directly examined in individuals diagnosed with bipolar disorder with psychosis.
To test whether dopamine synthesis capacity is elevated in bipolar disorder with psychosis and how this compares with schizophrenia and matched controls and to examine whether dopamine synthesis capacity is associated with psychotic symptom severity, irrespective of diagnostic class.

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Feb
2018

Whilst robust preclinical and postmortem evidence suggests that altered GABAergic function is central to the development of psychosis, little is known about whether it is altered in subjects at ultra-high risk of psychosis, or its relationship to prodromal symptoms.
Twenty-one antipsychotic naïve ultra-high risk individuals and 20 healthy volunteers underwent proton magnetic resonance imaging at 3T. Gamma-aminobutyric acid levels were obtained from the medial prefrontal cortex using MEGA-PRESS and expressed as peak-area ratios relative to the synchronously acquired creatine signal.

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Aug
2017

Self-reported psychotic experiences (PEs) are associated with psychopathology of all kinds, not just psychoses. However, systematic reviews on the relevance of this for health services are unavailable. Furthermore, whether association with service use is confounded by other psychopathology is unknown, and is relevant to prevention and treatment.

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Jan
2018

Blood-brain barrier pathology is recognised as a central factor in the development of many neurological disorders, but much less is known about the role of the blood-brain barrier in psychiatric disorders. We review post-mortem, serum-biomarker, CSF-biomarker, and neuroimaging studies that have examined blood-brain barrier structure and function in schizophrenia and related psychoses. We consider how blood-brain barrier dysfunction could relate to glutamatergic and inflammatory abnormalities, which are increasingly understood to play a part in the pathogenesis of psychosis.

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Nov
2017

Circulating autoantibodies against glutamatergic N-methyl-D-aspartate receptor (NMDAR) have been reported in a proportion of patients with psychotic disorders, raising hopes for more appropriate treatment for these antibody-positive patients. However, the prevalence of circulating autoantibodies against glutamatergic NMDAR in psychotic disorders remains controversial, with detection prevalence rates and immunoglobulin classes varying considerably between studies, perhaps because of different detection methods. Here, we compared the results of serum assays for a large cohort of patients with first-episode psychosis using classical cell-based assays in three labs and a single molecule-based imaging method.

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Jul
2017

Formal thought disorder is a cardinal feature of psychosis. However, the extent to which formal thought disorder is evident in ultra-high-risk individuals and whether it is linked to the progression to psychosis remains unclear.
Examine the severity of formal thought disorder in ultra-high-risk participants and its association with future psychosis.

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Jun
2017

Persecutory delusions are the most common type of delusions in psychosis and present in around 10-15% of the general population. Persecutory delusions are thought to be sustained by biased cognitive and emotional processes. Recent advances favour targeted interventions, focussing on specific symptoms or mechanisms.

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Mar
2018

One of the major challenges facing psychiatry is how to incorporate biological measures in the classification of mental health disorders. Many of these disorders affect brain development and its connectivity. In this study, we propose a novel method for assessing brain networks based on the combination of a graph theory measure (eigenvector centrality) and a one-class support vector machine (OC-SVM).

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May
2017

The diagnostic and prognostic significance of the DSM-5-defined Attenuated Psychosis Syndrome (DSM-5-APS) in individuals undergoing an ultra high risk (UHR) clinical assessment for suspicion of psychosis risk is unknown.
Prospective cohort study including all consecutive help-seeking individuals undergoing both a DSM-5-APS and a Comprehensive Assessment of At Risk Mental States (CAARMS 12/2006) assessment for psychosis risk at the Outreach and Support in South London (OASIS) UHR service (March 2013-April 2014). The diagnostic significance of DSM-5-APS was assessed with percent overall agreement, prevalence bias adjusted kappa, Bowker's test, Stuart-Maxwell test, residual analysis; the prognostic significance with Cox regression, Kaplan-Meier failure function, time-dependent area under the curve (AUC) and net benefits analysis.

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Dec
1969

Schizophrenia is associated with brain glutamate dysfunction, but it is currently unclear whether antipsychotic administration can reduce the extent of glutamatergic abnormality. We conducted a systematic review of proton magnetic resonance spectroscopy (H-MRS) studies examining the effects of antipsychotic treatment on brain glutamate levels in schizophrenia. The Medline database was searched to identify relevant articles published until December 2016.

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Oct
2017

There is no consensus as to whether magnetic resonance imaging (MRI) should be used as part of the initial clinical evaluation of patients with first-episode psychosis (FEP).(a) To assess the logistical feasibility of routine MRI; (b) to define the clinical significance of radiological abnormalities in patients with FEP.Radiological reports from MRI scans of two FEP samples were reviewed; one comprised 108 patients and 98 healthy controls recruited to a research study and the other comprised 241 patients scanned at initial clinical presentation plus 66 healthy controls.

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Apr
2017

Available evidence suggests that nicotine may enhance cognitive functioning. Moreover, it has been suggested that the high prevalence of smoking in people with schizophrenia is in part due to self-medication behaviour to alleviate cognitive deficits. We assessed the association between tobacco smoking and cognitive functioning in a large population of first episode psychosis (FEP) patients (n=304) and healthy controls (n=156).

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Dec
1969

Bipolar disorder (BPD) is associated with altered regional brain function during the performance of cognitive tasks. The relative contribution of genetic and environmental risk factors for BPD to these changes has not yet been quantified. We sought to address this issue in a functional neuroimaging study of people who varied in their risk for BPD.

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Oct
2017

Diffusion tensor imaging has revealed differences in all examined white matter tracts in schizophrenia, with a range of explanations for why this may be. The distribution and timing of differences may help explain their origin; however, results are usually dependent on the analytical method. We therefore sought to examine the extent of differences and their relationship with age using two different methods.

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Mar
2017

Although psychotic experiences in people without diagnosed mental health problems are associated with mental health service use, few studies have assessed this prospectively or measured service use by real-world clinical data.
To describe and investigate the association between psychotic experiences and later mental health service use, and to assess the role of symptoms of common mental health disorders in this association.
We linked a representative survey of south-east London (SELCoH-1,=1698) with health records from the local mental healthcare provider.

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May
2017

The overall effect of At Risk Mental State (ARMS) services for the detection of individuals who will develop psychosis in secondary mental health care is undetermined.
To measure the proportion of individuals with a first episode of psychosis detected by ARMS services in secondary mental health services, and to develop and externally validate a practical web-based individualized risk calculator tool for the transdiagnostic prediction of psychosis in secondary mental health care.
Clinical register-based cohort study.

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Dec
1969

The proportion of people with mental health disorders who participate in clinical research studies is much smaller than for those with physical health disorders. It is sometimes assumed that this reflects an unwillingness to volunteer for mental health research studies. We examined this issue in a large sample of patients with psychosis.

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Dec
1969

Studies of psychiatric populations have reported associations between childhood adversity and volumes of stress-related brain structures. This meta-analysis investigated these associations in non-clinical samples and therefore independent of the effects of severe mental health difficulties and their treatment.
The MEDLINE database was searched for magnetic resonance imaging studies measuring brain structure in adults with and without childhood adversity.

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Aug
2017

Can we make cannabis safer?

Lancet Psychiatry 2017 Aug 2;4(8):643-648. Epub 2017 Mar 2.
Amir Englund, Tom P Freeman, Robin M Murray, Philip McGuire
Cannabis use and related problems are on the rise globally alongside an increase in the potency of cannabis sold on both black and legal markets. Additionally, there has been a shift towards abandoning prohibition for a less punitive and more permissive legal stance on cannabis, such as decriminalisation and legalisation. It is therefore crucial that we explore new and innovative ways to reduce harm.

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Mar
2017

Reductions in whole brain and grey matter volumes are robust features of schizophrenia, yet their etiological influences are unclear.
We investigated the association between the genetic and environmental risk for schizophrenia and brain volumes. Whole brain, grey matter and white matter volumes were established from structural MRIs from twins varying in their zygosity and concordance for schizophrenia.

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Dec
1969

Several integrated models of psychosis have implicated adverse, stressful contexts and experiences, and affective and cognitive processes in the onset of psychosis. In these models, the effects of stress are posited to contribute to the development of psychotic experiences via pathways through affective disturbance, cognitive biases, and anomalous experiences. However, attempts to systematically test comprehensive models of these pathways remain sparse.

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Dec
1969

Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis.

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Dec
1969

Brief Limited Intermittent Psychotic Symptoms (BLIPS) are key inclusion criteria to define individuals at ultra high risk for psychosis (UHR). Their diagnostic and prognostic significance is unclear.
To address the baseline diagnostic relationship between BLIPS and the ICD-10 categories and examine the longitudinal prognostic impact of clinical and sociodemographic factors.

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Jun
2017

Recent studies have reported an association between psychopathology and subsequent clinical and functional outcomes in people at ultra-high risk (UHR) for psychosis. This has led to the suggestion that psychopathological information could be used to make prognostic predictions in this population. However, because the current literature is based on inferences at group level, the translational value of the findings for everyday clinical practice is unclear.

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Dec
2016

Pretest risk estimation is routinely used in clinical medicine to inform further diagnostic testing in individuals with suspected diseases. To our knowledge, the overall characteristics and specific determinants of pretest risk of psychosis onset in individuals undergoing clinical high risk (CHR) assessment are unknown.
To investigate the characteristics and determinants of pretest risk of psychosis onset in individuals undergoing CHR assessment and to develop and externally validate a pretest risk stratification model.

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Oct
2016

Increasing evidence indicates that psychosis is associated with abnormal reward processing. Imaging studies in patients with first-episode psychosis (FEP) have revealed reduced activity in diverse brain regions, including the ventral striatum, insula and anterior cingulate cortex (ACC), during reward prediction. However, whether these reductions in local brain activity are due to altered connectivity has rarely been explored.

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Dec
1969

Emotional processing dysfunction is widely reported in patients with chronic schizophrenia and first-episode psychosis (FEP), and has been linked to functional abnormalities of corticolimbic regions. However, corticolimbic dysfunction is less studied in people at ultra-high risk for psychosis (UHR), particularly during processing prosodic voices. We examined corticolimbic response during an emotion recognition task in 18 UHR participants and compared them with 18 FEP patients and 21 healthy controls (HC).

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Dec
1969

A key problem in the management of first episode psychosis is that patients are often reluctant to take antipsychotic medication, especially once their presenting symptoms have resolved. Clinicians may be tempted to trial a 'break in treatment' in such patients.
To assess the impact of interruptions in the antipsychotic treatment of first episode psychosis.

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Mar
2017

Research suggests that tobacco smokers may develop psychosis at an earlier age than non-smokers, with effects on psychotic symptoms. We aimed to test the difference in age of onset of psychosis between smokers and non-smokers.
Self-report data were collected from smokers and non-smokers in a population of first-episode psychosis patients.

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Dec
1969

Clinical outcomes in people identified as at ultra-high risk (UHR) for psychosis are remarkably heterogeneous, and are difficult to predict on the basis of the presenting clinical features. Individuals at UHR are at risk of poor functional outcome regardless of development of psychotic disorder. The aim of the present study was to assess whether there is a relationship between functional neuroimaging measures at presentation and functional outcome as measured by the GAF three years after scanning.

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Dec
1969

Grey matter (GM) abnormalities are robust features of schizophrenia and of people at ultra high-risk for psychosis. However the extent to which neuroanatomical alterations are evident in non-clinical subjects with isolated psychotic experiences is less clear.
Individuals (mean age 20 years) with (n = 123) or without (n = 125) psychotic experiences (PEs) were identified from a population-based cohort.

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Oct
2016


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