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Author: Philip K McGuire (147)


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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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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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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Jul
2016

Alterations in glutamatergic neurotransmission may be fundamental to the pathophysiology of schizophrenia, and the glutamatergic system is a target for novel therapeutic interventions in the disorder.
To investigate the nature of brain glutamate alterations in schizophrenia by conducting a meta-analysis of glutamate proton magnetic resonance (MRS) spectroscopy studies.
The MEDLINE database was searched for studies published from January 1, 1980, to April 1, 2015.

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Dec
1969

Using diffusion tensor imaging, we conducted an exploratory investigation of the relationship between white matter tract microstructure and age in 200 healthy adult subjects using tract-based spatial statistics (TBSS). Though most tracts showed the slight decline in microstructural organization with age widely noted, in both superior cerebellar peduncles (SCP) it correlated positively with age, a result not previously reported. We confirmed this by using an alternative method, and by repeating our TBSS analysis in an additional sample of 133 healthy adults.

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Mar
2016

The prognostic significance of competing constructs and operationalizations for brief psychotic episodes (acute and transient psychotic disorder [ATPD], brief psychotic disorder [BPD], brief intermittent psychotic symptoms [BIPS], and brief limited intermittent psychotic symptoms [BLIPS]) is unknown.
To provide a meta-analytical prognosis of the risk of psychotic recurrence in patients with remitted first-episode ATPD, BPD, BIPS, and BLIPS and in a benchmark group of patients with remitted first-episode schizophrenia (FES). We hypothesized a differential risk: FES > ATPD > BPD > BIPS > BLIPS.

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Feb
2016

Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown.
To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-).

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Aug
2015

It is unknown whether prodromal services improve outcomes in those who go on to develop psychosis, and whether these patients are demographically different from the overall first-episode population.
To compare sociodemographic features, duration of untreated psychosis, hospital admission and frequency of compulsory treatment in the first year after the onset of psychosis in patients who present to prodromal services with patients who did not present to services until the first episode of psychosis.
We compared two groups of patients with first-episode psychosis: one who made transition after presenting in the prodromal phase and the other who had presented with a first episode.

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Aug
2015

Deficits in motivational salience processing have been related to psychotic symptoms and disturbances in dopaminergic neurotransmission. We aimed at exploring changes in salience processing and brain activity during different stages of psychosis and antipsychotic medication effect.
We used fMRI during the Salience Attribution Task to investigate hemodynamic differences between 19 healthy controls (HCs), 34 at-risk mental state (ARMS) individuals and 29 individuals with first-episode psychosis (FEP), including a subgroup of 17 FEP without antipsychotic medication (FEP-UM) and 12 FEP with antipsychotic medication (FEP-M).

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Dec
1969

Individuals who were born very preterm (VPT; <33 gestational weeks) are at risk of experiencing deficits in tasks involving executive function in childhood and beyond. In addition, the type and severity of neonatal brain injury associated with very preterm birth may exert differential effects on executive functioning by altering its neuroanatomical substrates. Here we addressed this question by investigating with functional magnetic resonance imaging (fMRI) the haemodynamic response during executive-type processing using a phonological verbal fluency and a working memory task in VPT-born young adults who had experienced differing degrees of neonatal brain injury.

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Nov
2014

Alterations in brain glutamate levels may be associated with psychosis risk, but the relationship to clinical outcome in at-risk individuals is unknown. Glutamate concentration was measured in the left thalamus and anterior cingulate cortex (ACC) using 3-Tesla proton magnetic resonance spectroscopy in 75 participants at ultra high risk (UHR) of psychosis and 56 healthy controls. The severity of attenuated positive symptoms and overall functioning were assessed.

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Dec
1969

Sexual dimorphism in human brain structure is well recognised, but less is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore gender differences in fractional anisotropy (FA), an index of microstructural integrity. We previously found increased FA in the corpus callosum in women, and increased FA in the cerebellum and left superior longitudinal fasciculus (SLF) in men, using a whole-brain voxel-based analysis.

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Jul
2014

Recent evidence has revealed abnormal functional connectivity between the frontal and parietal brain regions during working memory processing in patients with schizophrenia and first-episode psychosis. However, it still remains unclear whether abnormal frontoparietal connectivity during working memory processing is already evident in the psychosis high-risk state and whether the connection strengths are related to psychopathological outcomes.
Healthy controls and antipsychotic-naive individuals with an at-risk mental state (ARMS) performed an n-back working memory task while undergoing functional magnetic resonance imaging.

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Nov
2014

Very preterm (VPT) birth is considered a risk factor not only for neurological impairment, but also for reduced function in several cognitive domains in childhood and later in life. Individuals who were born VPT are more likely to demonstrate learning and memory difficulties compared to term-born controls. These problems contribute to more VPT-born children repeating grades and underachieving in school.

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Dec
2013

Although translational medicine has become a priority for medical science, advances in neuroscience have failed to be translated for the benefit of patients. In populations at high risk of psychosis, neuroimaging could stratify those mostly likely to develop psychosis. This is an example of potentially translatable psychiatry.

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Dec
1969

Pauses during speech may reflect the planning and monitoring of discourse, two processes putatively impaired in patients with schizophrenia, particularly those with formal thought disorder (FTD). We used functional MRI to examine the neural correlates of between-clause and of filled pauses, which are respectively associated with speech planning and speech monitoring.
BOLD contrast was measured while six schizophrenia patients with FTD and six healthy subjects spoke about Rorshach inkblots.

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Nov
2013

Elevated in vivo markers of presynaptic striatal dopamine activity have been a consistent finding in schizophrenia, and include a large effect size elevation in dopamine synthesis capacity. However, it is not known if the dopaminergic dysfunction is limited to the striatal terminals of dopamine neurons, or is also evident in the dopamine neuron cell bodies, which mostly originate in the substantia nigra. The aim of our studies was therefore to determine whether dopamine synthesis capacity is altered in the substantia nigra of people with schizophrenia, and how this relates to symptoms.

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Sep
2013

Brain imaging studies have identified robust changes in brain structure and function during the development of psychosis, but the contribution of abnormal brain connectivity to the onset of psychosis is unclear. Furthermore, antipsychotic treatment can modulate brain activity and functional connectivity during cognitive tasks.
To investigate whether dysfunctional brain connectivity during working memory (WM) predates the onset of psychosis and whether connectivity parameters are related to antipsychotic treatment.

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Jul
2013

Using positron emission tomography (PET), we previously observed increases in 3,4-dihydroxy-6-[(18)F]fluoro-L-phenylalanine ((18)F-DOPA) uptake in the striatum of subjects at ultra-high risk (UHR) for psychosis, indicating elevated presynaptic dopamine synthesis capacity. The purpose of this study was to test if this finding would be replicated in a second UHR cohort.
(18)F-DOPA PET was used to estimate dopamine synthesis capacity in the striatum of an entirely new cohort of 26 individuals at UHR for psychosis (14 males, mean±SD age = 22.

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Jan
2014

The current diagnostic system for subjects at enhanced clinical risk of psychosis allows concurrent comorbid diagnoses of anxiety and depressive disorders. Their impact on the presenting high-risk psychopathology, functioning, and transition outcomes has not been widely researched.
In a large sample of subjects with an At-Risk Mental State (ARMS, n = 509), we estimated the prevalence of DSM/SCID anxiety or depressive disorders and their impact on psychopathology, functioning, and psychosis transition.

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Nov
2012

Elevated presynaptic striatal dopaminergic function is a robust feature of schizophrenia. However, the relationship between this dopamine abnormality and the response to dopamine-blocking antipsychotic treatments is unclear. The authors tested the hypothesis that in patients with schizophrenia the response to antipsychotic treatment would be related to the severity of presynaptic dopamine dysfunction, as indexed using [(18)F]-DOPA uptake positron emission tomography (PET).

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Oct
2012

Many patients with schizophrenia show a limited symptomatic response to treatment with dopaminergic antipsychotics. This may reflect the additional involvement of non-dopaminergic neurochemical dysfunction in the pathophysiology of the disorder. We tested the hypothesis that brain glutamate levels would differ between patients with first-episode psychosis who were symptomatic compared with those with minimal symptoms following antipsychotic treatment.

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Dec
1969

Δ(9)-tetrahydrocannabinol (Δ(9)-THC) is the main compound of the Cannabis Sativa responsible for most of the effects of the plant. Another major constituent is cannabidiol (CBD), formerly regarded to be devoid of pharmacological activity. However, laboratory rodents and human studies have shown that this cannabinoid is able to prevent psychotic-like symptoms induced by high doses of Δ(9)- THC.

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Dec
1969

Pharmacological challenge in conjunction with neuroimaging techniques has been employed for over two decades now to understand the neural basis of the cognitive, emotional and symptomatic effects of the main ingredients of cannabis, the most widely used illicit drug in the world. This selective critical review focuses on the human neuroimaging studies investigating the effects of delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD), the two main cannabinoids of interest present in the extract of the cannabis plant. These studies suggest that consistent with the polymorphic and heterogeneous nature of the effects of cannabis, THC and CBD have distinct and often opposing effects on widely distributed neural networks that include medial temporal and prefrontal cortex and striatum, brain regions that are rich in cannabinoid receptors and implicated in the pathophysiology of psychosis.

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Dec
1969

Sexual dimorphism in human brain structure is well recognised, but little is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore differences in fractional anisotropy (FA), an index of microstructural integrity.
A whole brain analysis of 135 matched subjects (90 men and 45 women) using a 1.

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Aug
2012

Sexual dysfunction is common in psychotic disorder but it is not clear whether it is intrinsic to the development of the illness or secondary to other factors.
To compare sexual function in people at ultra-high risk (UHR) of a psychotic disorder, patients with first-episode psychosis predominantly taking antipsychotic drugs and healthy volunteers.
Sexual function was assessed in a UHR group (n = 31), a group with first-episode psychosis (n = 37) and a matched control group of healthy volunteers (n = 56) using the Sexual Function Questionnaire.

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Nov
2012

Psychotic disorders are associated with widespread reductions in white matter (WM) integrity. However, the stage at which these abnormalities first appear and whether they are correlates of psychotic illness, as opposed to an increased vulnerability to psychosis, is unclear. We addressed these issues by using diffusion tensor imaging (DTI) to study subjects at ultra high risk (UHR) of psychosis before and after the onset of illness.

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Apr
2013

Voxel-based morphometry (VBM) studies demonstrate grey matter volume (GMV) deficits in schizophrenia. This method is also applied for detecting associations between specific psychotic symptoms and brain structure, such as auditory verbal hallucinations (AVHs). However, due to differing methodological approaches, the available findings are inconsistent and difficult to integrate.

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Dec
1969

Whilst there is a growing body of evidence relating to the effectiveness of early detection and early intervention services there have been relatively few studies which have provided information on whether they are cost-effective.
The aim of this paper is to review the cost-effectiveness evidence for early detection and early intervention in psychosis.
Full economic evaluations, cost studies, and studies which do not report costs but do provide important resource use information were included in the review.

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Jan
2012

The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing.

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Feb
2012

Among the general population, individuals with subthreshold psychotic-like experiences, or psychosis proneness (PP), can be psychometrically identified and are thought to have a 10-fold increased risk of psychosis. They also show impairments in measures of emotional functioning parallel to schizophrenia. Whilst previous studies have revealed altered brain activation in patients with schizophrenia during emotional processing, it is unclear whether these alterations are also expressed in individuals with high PP.

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Sep
2011

In this study, the first to explore the cortical correlates of signed language (SL) processing under point-light display conditions, the observer identified either a signer or a lexical sign from a display in which different signers were seen producing a number of different individual signs. Many of the regions activated by point-light under these conditions replicated those previously reported for full-image displays, including regions within the inferior temporal cortex that are specialised for face and body-part identification, although such body parts were invisible in the display. Right frontal regions were also recruited - a pattern not usually seen in full-image SL processing.

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Feb
2012

Individuals with an at risk mental state (ARMS) are at greatly increased risk of developing a psychotic illness. Risk of transition to psychosis is associated with regionally reduced cortical gray matter volume. There has been considerable interest in the interaction between psychosis risk and substance use.

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Sep
2012

Neuroimaging studies in humans have implicated both dysfunction of the medial temporal lobe (MTL) and the dopamine system in psychosis, but the relationship between them is unclear. We addressed this issue by measuring MTL activation and striatal dopaminergic function in individuals with an At Risk Mental State (ARMS) for psychosis, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), respectively.
Thirty-four subjects (20 ARMS and 14 Controls), matched for age, gender, digit span performance, and premorbid IQ, were scanned using fMRI, while performing a verbal encoding and recognition task, and using 18F-DOPA PET.

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Sep
2012

It remains unclear whether brain structural abnormalities observed before the onset of psychosis are specific to schizophrenia or are common to all psychotic disorders. This study aimed to measure regional gray matter volume prior to the onset of schizophreniform and of affective psychoses. We investigated 102 subjects at ultrahigh risk (UHR) of developing psychosis recruited from the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia.

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Jun
2011

Although the effects of cannabis on perception are well documented, little is known about their neural basis or how these may contribute to the formation of psychotic symptoms. We used functional magnetic resonance imaging (fMRI) to assess the effects of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) during visual and auditory processing in healthy volunteers. In total, 14 healthy volunteers were scanned on three occasions.

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Jan
2012

The D-Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis. It is thought to regulate D-amino acid oxidase (DAO), which metabolizes D-serine, a co-agonist of NMDA-type glutamate receptors and to be involved in dendritic arborization. Linkage, genetic association and expression studies have implicated the G72 gene in both schizophrenia and bipolar disorder.

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Jan
2011

Impairments in executive function and language processing are characteristic of both schizophrenia and bipolar disorder. Their functional neuroanatomy demonstrate features that are shared as well as specific to each disorder. Determining the distinct pattern of neural responses in schizophrenia and bipolar disorder may provide biomarkers for their diagnoses.

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Jan
2011

Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging.

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Oct
2010

The present study aimed to investigate the presence of corpus callosum (CC) volume deficits in a population-based recent-onset psychosis (ROP) sample, and whether CC volume relates to interhemispheric communication deficits. For this purpose, we used voxel-based morphometry comparisons of magnetic resonance imaging data between ROP (n =122) and healthy control (n = 94) subjects. Subgroups (38 ROP and 39 controls) were investigated for correlations between CC volumes and performance on the Crossed Finger Localization Test (CFLT).

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Aug
2010

Thalamic neurochemical abnormalities may underlie psychotic symptoms and auditory event-related potential (ERP) abnormalities in schizophrenia. We investigated this hypothesis in subjects at risk of psychosis using magnetic resonance spectroscopy and electroencephalography (EEG). Reduced thalamic glutamate plus glutamine and N-acetyl aspartate levels were associated with abnormal frontal ERPs, supporting a thalamic basis for filtering impairments.

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Jul
2010

Alterations in dopaminergic neurotransmission and function of the prefrontal cortex are thought to be central to the pathophysiology of schizophrenia, but the relationship between these factors in the development of psychosis is unclear.
To investigate the relationship between striatal dopamine activity and prefrontal function in people at ultra high risk of psychosis.
Subjects were studied using functional magnetic resonance imaging while performing a working memory (N-back) task.

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Oct
2010

The extent to which psychotic disorders fall into distinct diagnostic categories or can be regarded as lying on a single continuum is controversial. We compared lateral ventricle volumes between a large sample of patients with first-episode schizophrenia or bipolar disorder and a healthy control group from the same neighbourhood.
Population-based MRI study with 88 first-episode psychosis (FEP) patients, grouped into those with schizophrenia/schizophreniform disorder (N=62), bipolar disorder (N=26) and 94 controls.

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Jan
2012

Frontostriatal networks mediating important cognitive and motor functions have been shown to be abnormal structurally and functionally in schizophrenia. However, the influence of genetic risk for schizophrenia on structural abnormalities in these areas is not well established. This study therefore aimed to investigate prefrontal and striatal volume alterations in schizophrenia and to define the extent to which they are dependent on genetic vulnerability for the condition.

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Sep
2010

Cognitive deficits are a key feature of recent-onset psychosis, but there is no consensus on whether such deficits are generalized or confined to specific domains. Besides, it is unclear whether cognitive deficits: a) are found in psychotic patients in samples from outside high-income countries; and b) whether they progress uniformly over time in schizophrenia and affective psychoses. We applied 12 tests organized into eight cognitive domains, comparing psychosis patients (n = 56, time from initial contact = 677.

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Jun
2010

To determine whether preterm birth influences functional neuronal development in adulthood.
We evaluated adults born very preterm (VPT; < 33 weeks of gestation) using a verbal paired-associate learning task within a functional magnetic resonance imaging paradigm. Hippocampi and parahippocampal gyri gray matter volumes were also quantified.

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Apr
2010

Impaired cognitive function has been identified as a core feature of schizophrenia. However, a significant proportion of patients do not show any cognitive deficits. The aim of this study was to assess if there were differences in white matter integrity between patients with and without cognitive impairment.

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