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Biomedical subjects

Hugh M Jones

Publications and source records attributed to Hugh M Jones.

11 recordsLinked to original sources
PubMed2006

Temporal context discrimination in patients with schizophrenia: associations with auditory hallucinations and negative symptoms.

BACKGROUND: A deficit in remembering the temporal context of events (a type of source memory) has been observed in schizophrenia, and suggested to be associated with positive symptoms. METHODS: In order to investigate memory for temporal context, we administered a list discrimination task to a sample of schizophrenia patients and a sample of healthy controls. Participants were required to learn two lists of mixed high- and low-frequency words separated by 10 min, then to remember whether each word had been presented in the first or in the second list. RESULTS: The number of misattributions to the wrong list was significantly higher in patients than in healthy controls. However, the group difference was eliminated when recall efficiency was covaried. The number of list misattributions was higher in patients with auditory hallucinations than in the other patients, independently of verbal recall efficiency. By contrast, affective flattening and anhedonia were associated with fewer list misattributions of the high-frequency words. CONCLUSIONS: It is suggested that auditory hallucinations are associated with deficit in processing or remembering the temporal context. Conversely, certain negative symptoms are associated with reduced temporal context errors. The possible neural mechanisms involved in temporal context deficit as well as in these specific clinical symptoms are discussed.

Adult↗
PubMed2004

Cortical effects of quetiapine in first-episode schizophrenia: a preliminary functional magnetic resonance imaging study.

BACKGROUND: Quetiapine improves both psychotic symptoms and cognitive function in schizophrenia. The neural basis of these actions is poorly understood. METHODS: Three subject groups underwent a single functional magnetic resonance imaging (fMRI) session: drug-naive (n = 7) and quetiapine-treated samples of patients with schizophrenia (n = 8) and a healthy control group (n = 8). The fMRI session included an overt verbal fluency task and a passive auditory stimulation task. RESULTS: In the verbal fluency task, there was significantly increased activation in the left inferior frontal cortex in the quetiapine-treated patients and the healthy control sample compared with the drug-naive sample. During auditory stimulation, the healthy control group and stably treated group produced significantly greater activation in the superior temporal gyrus than the drug-naive sample. CONCLUSIONS: Quetiapine treatment is associated with altered blood oxygen level-dependent responses in both the prefrontal and temporal cortex that cannot be accounted for by improved task performance subsequent to drug treatment.

Acoustic Stimulation↗
PubMed2004

Clinical effectiveness in first-episode patients.

Managing patients with first-episode schizophrenia is a challenging task for psychiatrists. Early diagnosis and effective intervention are vital to achieving long-term positive clinical outcomes among first-episode patients. Although these patients are the most responsive to treatment, they are also more susceptible to adverse events. The efficacy and improved tolerability associated with the newer atypical antipsychotics means that these drugs can be used successfully in the treatment and long-term management of schizophrenia from the onset of illness. However, as well as managing the symptoms of the disease, pharmacological treatments need to meet the broader requirements of clinical effectiveness that encompass all of the outcome domains associated with schizophrenia. This article will discuss available data on atypical antipsychotics in first-episode patients and present the primary results from the F1RST (Southwark first-onset psychosis) study, which examined the use of quetiapine for the first-line management of schizophrenia as part of a specialist episode psychosis service.

Antipsychotic Agents↗
PubMed2004

Atypical antipsychotic drugs and tardive dyskinesia: relevance of D2 receptor affinity.

Evidence suggests atypical antipsychotic treatment is associated with a lower incidence of tardive dyskinesia (TD) than typical antipsychotic drugs, and is a potential antidyskinetic treatment. We present the case of a middle-aged woman never previously exposed to antipsychotic treatment who developed TD after 6 months of olanzapine monotherapy. Substitution of quetiapine for olanzapine alleviated her TD symptoms. The case demonstrates that atypical antipsychotic drugs have different effects in relation to TD. Potential psychopharmacological mechanisms explaining these differences are discussed, highlighting the importance of D2 receptor occupancy by atypical antipsychotic drugs for TD.

Adult↗
PubMed2003

Optimizing limbic selective D2/D3 receptor occupancy by risperidone: a [123I]-epidepride SPET study.

Selective action at limbic cortical dopamine D2-like receptors is a putative mechanism of atypical antipsychotic efficacy with few extrapyramidal side effects. Although risperidone is an atypical antipsychotic with high affinity for D2 receptors, low-dose risperidone treatment is effective without inducing extrapyramidal symptoms. The objective was to test the hypothesis that treatment with low-dose risperidone results in 'limbic selective' D2/D3 receptor blockade in vivo. Dynamic single photon emission tomography (SPET) sequences were obtained over 5 hours after injection of [123I]-epidepride (approximately 150 MBq), using a high-resolution triple-headed brain scanner (Marconi Prism 3000XP). Kinetic modelling was performed using the simplified reference region model to obtain binding potential values. Estimates of receptor occupancy were made relative to a normal volunteer control group (n = 5). Six patients treated with low-dose risperidone (mean = 2.6 mg) showed moderate levels of D2/D3 occupancy in striatum (49.9%), but higher levels of D2/D3 occupancy in thalamus (70.8%) and temporal cortex (75.2%). Occupancy values in striatum were significantly different from thalamus (F (1,4) = 26.3, p < 0.01) and from temporal cortex (F (1,4) = 53.4, p < 0.01). This is the first study to evaluate striatal and extrastriatal occupancy of risperidone. Low dose treatment with risperidone achieves a similar selectivity of limbic cortical over striatal D2/D3 receptor blockade to that of atypical antipsychotics with lower D2/D3 affinity such as clozapine, olanzapine and quetiapine. This finding is consistent with the relevance of 'limbic selective' D2/D3 receptor occupancy to the therapeutic efficacy of atypical antipsychotic drugs.

Adult↗
PubMed2003

Is regionally selective D2/D3 dopamine occupancy sufficient for atypical antipsychotic effect? an in vivo quantitative [123I]epidepride SPET study of amisulpride-treated patients.

OBJECTIVE: Atypical antipsychotic drug treatment is clinically effective with a low risk of extrapyramidal symptoms. Explanations for the mechanism underlying this beneficial therapeutic profile of atypical over typical antipsychotic agents include 1) simultaneous antagonism of dopamine D(2) and serotonin 5-HT(2A) receptors or 2) selective action at limbic cortical dopamine D(2)-like receptors with modest striatal D(2) receptor occupancy. Amisulpride is an atypical antipsychotic drug with selective affinity for D(2)/D(3) dopamine receptors and provides a useful pharmacological model for examining these hypotheses. The authors' goal was to evaluate whether treatment with amisulpride results in "limbic selective" D(2)/D(3) receptor blockade in vivo. METHOD: Five hours of dynamic single photon emission tomography data were acquired after injection of [(123)I]epidepride (approximately 150 MBq). Kinetic modeling was performed by using the simplified reference region model to obtain binding potential values. Estimates of receptor occupancy were made relative to a healthy volunteer comparison group (N=6). RESULTS: Eight amisulpride-treated patients (mean dose=406 mg/day) showed moderate levels of D(2)/D(3) receptor occupancy in the striatum (56%), and significantly higher levels were seen in the thalamus (78%) and temporal cortex (82%). CONCLUSIONS: Treatment with amisulpride results in a similar pattern of limbic cortical over striatal D(2)/D(3) receptor blockade to that of other atypical antipsychotic drugs. This finding suggests that modest striatal D(2) receptor occupancy and preferential occupancy of limbic cortical dopamine D(2)/D(3) receptors may be sufficient to explain the therapeutic efficacy and low extrapyramidal symptom profile of atypical antipsychotic drugs, without the need for 5-HT(2A) receptor antagonism.

Adult↗
PubMed2002

Typical antipsychotic drugs -- D(2) receptor occupancy and depressive symptoms in schizophrenia.

We tested the hypothesis that the degree of striatal dopamine D(2) receptor blockade induced by typical antipsychotic treatment directly correlates with the presence and severity of depressive symptoms in schizophrenia. Clinical and [(123)I]-IBZM single-photon emission tomography (SPET) scan data obtained from 18 typical antipsychotic treated schizophrenic patients was analysed to evaluate the relationship between striatal D(2) receptor occupancy and the depressive subscale of the Brief Psychiatric Rating Scale (BPRS-D). Striatal D(2) receptor occupancy by typical antipsychotic drugs was significantly positively correlated with BPRS-D scores (r=0.52, p=0.025). This study suggests that high striatal dopamine D(2) blockade by typical antipsychotic drugs may contribute to the emergence of depressive symptoms in typical antipsychotic treated schizophrenic patients.

Adult↗