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Biomedical subjects

G P Reynolds

Publications and source records attributed to G P Reynolds.

At least 19 recordsLinked to original sources
PubMed1992

Clozapine has sub-micromolar affinity for 5-HT1A receptors in human brain tissue.

The affinities of a range of antipsychotic drugs at human hippocampal 5-HT1A receptors, defined by specific [3H]8-OH-DPAT binding, were determined. Clozapine demonstrated the highest affinity; all other antipsychotics studied demonstrated pK(i) values below 6.0 5-HT1A receptors are found on cortical glutamatergic neurons, a dysfunction of which may occur in schizophrenia. Binding at this site indicates a possible mechanism contributing to the unique efficacy of clozapine in the treatment of some schizophrenic patients.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Increased brain concentrations of a neurotoxin, 3-hydroxykynurenine, in Huntington's disease.

Concentrations of the neurotoxic tryptophan metabolite, 3-hydroxykynurenine, were determined in brain tissue taken post-mortem from patients with Huntington's disease and Alzheimer's disease. 3-Hydroxykynurenine was substantially and significantly increased in all three brain areas studied in Huntington's disease, but not significantly increased in the cortex in Alzheimer's disease, when compared to matched controls. These results demonstrate a possible dysfunction of tryptophan metabolism, via the kynurenine pathway, in Huntington's disease.

Aged↗
PubMed1992

Monoamine neurotransmitters and their metabolites in brain regions in Alzheimer's disease: a postmortem study.

1. Concentrations of the neurotransmitter amines noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) and the acid metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in four regions of postmortem brains of demented patients with or without Alzheimer's disease (AD). 2. NA was deficient in the temporal cortex (BA 21) of AD, but not of non-AD, patients. 3. Caudate, in particular, had an impaired dopaminergic system in AD patients, with low HVA levels. 4. In all regions investigated [amygdala, caudate, putamen, temporal cortex (BA 21)] 5-HT was significantly depleted in AD patients, and 5-HIAA was also depleted in amygdala and caudate. 5. These results indicate that neurotransmitter systems other than cholinergic systems are also widely affected in AD and suggest that these deficits may also play an important role in determining the symptomatology of AD.

Aged↗
PubMed1992

Dopamine receptor abnormalities in the striatum and pallidum in tardive dyskinesia: a post mortem study.

Dopamine D1 and D2 receptors were determined in brain tissue taken post mortem from schizophrenic patients previously known to have had tardive dyskinesia and yet who had not received neuroleptic drug treatment for over one year prior to death. In comparison with age-matched control subjects, diminished D2 receptor density was observed in striatal regions, while these receptors appeared to be increased in the pallidum, an area of the brain particularly implicated in the production of dyskinesias. D 1 receptors showed similar tendencies to lower numbers in the striatum in tardive dyskinesia.

Aged↗
PubMed1992

Developments in the drug treatment of schizophrenia.

Despite its efficacy in many cases, the drug treatment of schizophrenia remains problematic. A substantial proportion of patients do not improve, and many others suffer from unpleasant side-effects. In this review, Gavin Reynolds describes the new approaches to antipsychotic drug development that attempt to address these problems, and relates some of these approaches to growing evidence for neuronal pathology in the brain in schizophrenia.

Antipsychotic Agents↗
PubMed1992

Pre-frontal structural and functional deficits associated with individual differences in schizotypal personality.

This study tests the hypothesis that pre-frontal deficits underlie schizotypal personality in the normal population. Personality measures assessing features of DSM-IIIR schizotypal personality disorder (SPD) were related to left and right pre-frontal brain area assessed by magnetic resonance imaging (MRI), and neuropsychological measures of pre-frontal functioning (Wisconsin Card Sorting Task, WCST) in a group of non-institutionalized, unmedicated normal subjects. High schizotypal scores were significantly associated with reduced pre-frontal area and more WCST perseveration errors; conversely no relationships were observed between these pre-frontal measures and measures of psychosis-proneness unrelated to SPD traits. Pre-frontal structural findings were not found to be mediated by temporal lobe and posterior cortical structural deficits, height, weight, socio-economic status, education level and sex differences, while pre-frontal functional findings were not mediated by non-prefrontal cognitive ability. These findings of pre-frontal structural and functional deficits associated with schizotypal personality provide some initial converging support for a pre-frontal explanation of individual differences in schizotypal personality in the general population.

Adult↗
PubMed1992

An evaluation of structural and functional prefrontal deficits in schizophrenia: MRI and neuropsychological measures.

Magnetic resonance imaging was used to assess prefrontal brain structure in 17 schizophrenic, 18 psychiatric control, and 19 normal control subjects of comparable age, social background, and educational status, while three neuropsychological measures were used to assess prefrontal functioning. Schizophrenic patients had significantly smaller prefrontal areas than both psychiatric control and normal control subjects in all three planes. When posterior brain area and temporal lobe were entered into statistical analysis as covariates, they did not explain the prefrontal deficits. Schizophrenic patients made more perseveration errors on the Wisconsin Card Sorting Task and had fewer correct responses on the Spatial Delayed Response Task than normal control subjects. Schizophrenic patients performed more poorly than psychiatric control subjects on the Block Design Test. No group differences were found on three other nonfrontal tasks. These data lend some support to the role of prefrontal deficits in the development of schizophrenia.

Adult↗
PubMed1991

Determination of 3-hydroxykynurenine in human brain and plasma by high-performance liquid chromatography with electrochemical detection. Increased concentrations in hepatic encephalopathy.

A simple and specific method was developed for the determination of 3-hydroxykynurenine in brain tissue and blood plasma using high-performance liquid chromatography with electrochemical detection. This involved an extraction procedure using strong cation-exchange columns and also permitted the determination of 3-hydroxyanthranilic acid in brain tissue. The method was applied to the investigation of post mortem brain tissue from patients with hepatic encephalopathy. Cortical 3-hydroxykynurenine concentrations were substantially increased in such patients above control values, providing evidence for a dysfunction of tryptophan metabolism in this disease.

Brain↗
PubMed1991

Electrochemical detection of human brain transmitter amino acids by high-performance liquid chromatography of stable o-phthalaldehyde-sulphite derivatives.

A simple, sensitive, reliable and reproducible isocratic HPLC technique for the measurement of OPA/sulphite derivatives of human brain amino acid neurotransmitters is described. This employs a sample preparation that is also compatible with the concurrent determination of monoamines and their metabolites on a separate HPLC system. The method has been applied to the determination of GABA and glutamate in brain tissue taken post-mortem from patients with Huntington's disease and control subjects.

Amino Acids↗
PubMed1991

Neuroanatomical correlates of skin conductance orienting in normal humans: a magnetic resonance imaging study.

Although little is known about the neuroanatomical basis of skin conductance orienting in intact normal humans, the limited literature on animals and humans with neurological and clinical disorders implicate prefrontal, temporal/amygdala, and pons brain areas in mediating skin conductance orienting. This study relates area of these structures using magnetic resonance imaging techniques to skin conductance orienting responses in 17 normal humans in order to test hypotheses that larger area of these excitatory structures will be associated with more orienting responses. Left and right hand skin conductance orienting was significantly associated with left and right prefrontal area (r = .44-.60), area of the pons (r = .43-.54), and left but not right temporal/amygdala area (r = .47-.53). No relationships were observed with areas thought to be unrelated to skin conductance activity (cerebellum, nonfrontal cortical area), medial prefrontal cortex, or the third ventricle. This appears to be the first study relating brain structure to skin conductance orienting in intact normal humans. Although preliminary at the present time, these results implicate prefrontal, pons, and temporal/amygdala areas in the mediation of skin conductance orienting in normal humans.

Adult↗
PubMed1990

Dementia in Huntington's disease is associated with neurochemical deficits in the caudate nucleus, not the cerebral cortex.

Choline acetyltransferase (ChAT) and the neurotransmitter amino acids gamma-aminobutyric acid (GABA) and glutamic acid were measured in brain tissue taken post-mortem from control subjects and from patients with Huntington's disease (HD). Two subgroups of HD patients were defined with either severe dementia or no dementia. It was found that ChAT exhibited no greater decrease in cortical tissue from severely demented patients. While there were also no significant deficits associated with dementia in cortical concentrations of the amino acids, a substantial and regionally-specific decrease in both GABA and glutamate was observed in the caudate nucleus of severely demented HD patients.

Adult↗
PubMed1990

Deficit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophrenia.

There is increasing evidence of a deficit or disturbance of neurons in the brains of schizophrenic patients--evidence that particularly implicates the frontal or temporal lobes. As yet there is no direct neurochemical correlate of the transmitter systems involved, although changes in some neurotransmitters in the temporal lobe have been reported. Radiolabeled nipecotic acid, a specific inhibitor of uptake sites to gamma-aminobutyric acid (GABA), has provided a marker of GABAergic neurons. The binding of this ligand to brain tissue taken at autopsy has demonstrated a decreased density of GABA uptake sites in the hippocampus in schizophrenia. This decrease was found to correlate in the left hemisphere with increased concentration of dopamine in the amygdala, providing a link between neuropathology, evidence of laterality, and the dopamine hypothesis of the disease.

Aged↗
PubMed1990

Structural and functional characteristics of the corpus callosum in schizophrenics, psychiatric controls, and normal controls. A magnetic resonance imaging and neuropsychological evaluation.

In 1986 Nasrallah and colleagues found that increased thickness of the corpus callosum may be specific to right-handed female schizophrenics. Male and female right-handed schizophrenics were compared with normal and psychiatric controls of comparable age, sex, education, and social class on measures of callosal thickness from a midsagittal magnetic resonance imaging cut and neuropsychological tests of interhemispheric transfer. The sex difference in anterior and posterior callosal thickness in normal controls was reversed in schizophrenics, with the corpus callosum being thicker in female schizophrenics and thinner in male schizophrenics. Similar findings were also observed in the psychiatric control group. These structural differences were not paralleled by evidence of impaired interhemispheric transfer on neuropsychological tasks. These results support the finding of sex-dependent callosal abnormalities in schizophrenia but indicate that these abnormalities may not be specific to this illness.

Adult↗
PubMed1990

Pallidal GABA and chorea in Huntington's disease.

Neurochemical correlates of chorea in Huntington's disease were studied using striatal and pallidal tissue taken post mortem from patients with mild and severe chorea. While GABA was decreased in all these areas in Huntington's disease, patients with mild chorea had significantly less GABA in the medial pallidum than did those with severe chorea. There was no relationship between the degree of chorea and concentrations of dopamine or its metabolite. Thus the chorea of Huntington's disease may relate to the balance of residual GABAergic innervation between specific areas of the basal ganglia, consistent with primate models of dyskinesias.

Adult↗