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Biomedical subjects

J F Deakin

Publications and source records attributed to J F Deakin.

At least 19 recordsLinked to original sources
PubMed1992

Regionally selective deficits in uptake sites for glutamate and gamma-aminobutyric acid in the basal ganglia in schizophrenia.

In a post-mortem study of schizophrenic and control subjects, the sodium-dependent binding of D-[3H]aspartate and [3H]nipecotic acid were used to investigate uptake sites of glutamate and gamma-aminobutyric acid (GABA), respectively, in subcortical brain regions. Binding to the glutamate uptake site was substantially reduced in both the putamen and lateral pallidum of the schizophrenic subjects. Binding to the GABA uptake site was substantially reduced in the putamen; smaller reductions were apparent in the caudate nucleus and lateral pallidum. The results suggest that glutamatergic and GABAergic mechanisms in the basal ganglia are abnormal in schizophrenia. These abnormalities could be relevant to the development of psychosis but could also relate to the spectrum of mild motor disturbances often described in the disease.

Aspartic Acid↗
PubMed1991

Evaluation of a psychophysiological model of classical fear conditioning in anxious patients.

Skin conductance variables have been compared in 30 anxious patients and 30 controls to investigate the extent to which anxiety is associated with increased autonomic arousal, reduced habituation or enhanced aversive conditioning. Skin conductance level, variability (spontaneous fluctuations) and response amplitudes to tones were significantly greater in patients than controls. Habituation of skin conductance responses to a series of ten innocuous tones (80 dB, 1 s) did not differ between the groups. Aversively conditioned skin conductance responses were measured to a further series of ten tones after a conditioning trial in which a loud white noise (100 dB) followed tone 11. All subjects showed enhanced (conditioned) responses to the tones after the conditioning trial, but patients did not show greater conditioning than controls. The results indicate that anxious neurotic out-patients have greater sweat gland activity and reactivity than controls but fail to demonstrate differences in central mechanisms of habituation or conditioning.

Acoustic Stimulation↗
PubMed1991

Effects of ritanserin on aversive classical conditioning in humans.

According to one formulation of the behavioural functions of 5HT, aversive conditioned stimuli mediate their behavioural and emotional effects through activation of 5HT projections from dorsal raphe nucleus to receptors of the 5HT2 family in amygdala and elsewhere. To test this theory in humans, groups of ten normal volunteers received placebo, the 5HT2 lc antagonist ritanserin (10 mg PO) and no pill. Ritanserin had no effect on skin conductance level, variability (spontaneous fluctuations) or habituation to a sequence of ten neutral tones. After a conditioning trial in which tone 11 was followed by an aversive white noise, skin conductance responses to a further ten tones were enhanced. This effect was abolished by ritanserin. The results indicate a selective involvement of 5HT2/lc receptors in modulating aversively conditioned skin conductance responses.

Adult↗
PubMed1991

Characterization of a psychophysiological model of classical fear conditioning in healthy volunteers: influence of gender, instruction, personality and placebo.

Two experiments are described which evaluate the role of associative mechanisms and placebo effects on aversively conditioned skin conductance responses in groups of healthy volunteers. In both experiments, skin conductance level (SCL), variability (spontaneous fluctuations, SF) and amplitude (SCR) were recorded during a sequence of tone stimuli (80 dB, 1 s, 360 Hz). All the variables habituated during the first ten presentations of the tones. Tone 11 was immediately followed by a loud (100 dB) aversive brief (1 s) white noise UCS. The conditioning trial significantly enhanced SCRs to a further ten presentations of the tones and increased SCL and variability (SF). No enhancement of SCRs occurred when tone 11 was omitted and the UCS occurred in temporal isolation (experiment 1). Thus enhanced SCRs to tones following paired tone-noise presentation involves an associative mechanism. Increased "spontaneous" variability was shown to involve both conditioning and sensitization following the UCS. In both experiments females showed greater conditioned SCRs than males. In experiment 2 no effect of "anxiolytic" placebo could be discerned and there were no general relationships between questionnaires scores of extraversion or neuroticism with skin conductance measures in a group of 40 volunteers. The results question the role of conditionability and autonomic lability as major determinants of extraversion and neuroticism. These studies validate the use of the psychophysiological model of aversive conditioning in pharmacological studies of the mechanisms of habituation, conditioning and sensitization.

Adult↗
PubMed1991

Analysis of laminar distribution of kappa opiate receptor in human cortex: comparison between schizophrenia and normal.

Quantitative receptor autoradiography using the ligand [3H]U 69593 and tritium sensitive film was used to visualize the kappa subtype of opiate receptor in sections from 4 normal human postmortem brains. Data obtained from cortical scans, which measured receptor densities across the left and right parahippocampal gyri, were subject to Fourier analysis. This revealed that the kappa receptor distribution was described by a curve having significant first and second component harmonics. This analysis method can be used to describe a binding pattern mathematically, thus enabling a comparison to be made between normal and diseased brains. The same analysis was applied to [3H]U 69593 autoradiograms prepared from sections of 4 schizophrenic postmortem brains. The kappa receptor distribution in the schizophrenic group not only failed to produce the same pattern as the controls, but also showed no consistent pattern within the group. The method described can be used to investigate alterations in receptor distribution which occur in neuropsychiatric diseases involving neuronal dysplasia or atrophy.

Adult↗
PubMed1991

Blunted growth hormone and prolactin responses to L-tryptophan in depression; a state-dependent abnormality.

We have investigated whether attenuated growth hormone (GH) and prolactin (PRL) responses to L-tryptophan in depression return to normal with clinical recovery. Ten patients who had received intravenous infusions of L-tryptophan (100 mg/kg) when depressed were retested at least 3 months after full recovery and cessation of treatment. In recovered depressives growth hormone responses showed considerable recovery, in all but three cases to within a few units of their healthy age- and sex-matched controls. Prolactin responses increased with clinical recovery in all six male subjects. Results in females were inconclusive because of the effect of weight loss on prolactin responses. The results suggest that GH and PRL responses to tryptophan are state-dependent abnormalities rather than indicators of predisposition to depression. This allows the possibility that impaired functioning in systems with a 5HT1A or 5HT1D receptor link may be part of the causal chain in depression.

Adult↗
PubMed1991

Alterations in phencyclidine and sigma binding sites in schizophrenic brains. Effects of disease process and neuroleptic medication.

The specific binding of [3H]TCP and [3H](+)3-PPP, radioligands which respectively label PCP-NMDA and sigma binding sites was measured in tissue homogenates prepared from dissected areas of control and schizophrenic postmortem brains. [3H]TCP binding was bilaterally increased in orbital frontal cortex (Brodmann area 11) of schizophrenic brains. This finding may be due to an increased glutamatergic innervation of orbital frontal cortex since it parallels our findings of increased [3H]kainate and [3H]D-aspartate binding in this area. In contrast, [3H](+)3-PPP binding was reduced in each of the four brain regions examined. The reductions were greatest in brains from the schizophrenic subjects receiving neuroleptics at the time of death. Neuroleptics remaining in the brains of these subjects may compete in vitro with [3H](+)3-PPP for binding to the sigma site.

Antipsychotic Agents↗
PubMed1991

Depression and 5HT.

5HT has been implicated in mechanisms of anxiety and depression for many years but the evidence is contradictory. Perhaps one error has been to think of 5HT as a unitary system when in reality it is highly differentiated. There has been an explosive increase in knowledge about different 5HT receptor subtypes and it has long been known that there are different anatomical subsystems. Evidence will be summarised that the different systems subserve different psychological functions and that dysfunction in the different systems results in depression, anxiety, panic and OCD in an understandable way. Much evidence is compatible with the idea that 5HT systems reduce the impact of impending or actual aversive events. Anticipation of an aversive event is associated with anxiety and this motivates avoidance behaviour--a normal adaptive response. There is evidence that this is mediated by projections of the dorsal raphe nucleus and associated 5HT2 and 5HT3 receptors. Projections of the median raphe nucleus and associated 5HT1A receptors appear to mediate resilience to aversive events once they have occurred or if they persist. When this system breaks down depression results. It will be argued that all effective antidepressants act on 5HT1A, natural mechanisms of resilience.

Anxiety Disorders↗
PubMed1990

Identification and distribution of 5-HT3 recognition sites within the human brainstem.

The present studies demonstrate the presence of specific [3H]GR65630 binding sites within the human brainstem using the techniques of in vitro receptor autoradiography and ligand binding to homogenates. Autoradiography revealed the greatest accumulation of specific binding in the area postrema and subpostrema (AP/ASP). A lower level of specific binding was identified in the nucleus tractus solitarius (excluding area subpostrema). No specific binding was evident in the remainder of the hindbrain at this level. Discrete dissection followed by ligand binding to homogenates revealed that the specific binding of [3H]GR65630 (defined by the presence of 30 microM metoclopramide) was differentially distributed with highest levels in the AP/ASP (112.1 fmol/mg protein) and lower levels in the dorsal vagal complex (nucleus tractus solitarius--excluding the area subpostrema--dorsal motor nucleus of the vagus and hypoglossal nucleus) (DVC) and olivary nucleus (ON) (22.9 and 3.9 fmol/mg, respectively). No specific binding was detectable in the reticular formation (RF) located ventral to the dorsal vagal complex. The specific [3H]GR65630 binding site was pharmacologically similar to the 5-HT3 receptor since the potent and selective 5-HT3 receptor antagonists ICS 205-930 and zacopride (100 nM) and the agonist 5-HT (10 microM) inhibited binding to the same extent as metoclopramide in each of the individual areas (90, 60 and 20% in the AP/ASP, DVC and ON, respectively). The 5-HT1-like and 5-HT2 receptor antagonist methysergide (10 microM) failed to compete for the binding site. 5-HT3 receptor recognition sites within the AP/ASP and the DVC may be functionally involved in the ability of 5-HT3 receptor antagonists to control emesis.

Adult↗
PubMed1990

A neuroendocrine study of 5HT function in depression: evidence for biological mechanisms of endogenous and psychosocial causation.

To investigate whether depression is a consequence of disturbed function in 5HT systems, neuroendocrine responses to infusions of the 5HT precursor L-tryptophan (LTP) were studied in patients and controls. After an overnight fast and 60 min bed rest, a solution of LTP (10 g/l) was infused intravenously to a dose of 100 mg/kg over 30 min. Circulating growth hormone (GH), prolactin (PRL), cortisol and tryptophan concentrations were followed from 60 min pre-infusion to 60 min post-infusion. GH responses were attenuated in 23 major depressives (DSM-III) compared with 22 controls and were almost absent in endogenous depressives (New-castle criteria). PRL responses were normal in depressives who had lost more than 3 kg body weight but attenuated in those who had not. GH and PRL responses did not correlate with each other. Reduced basal tryptophan concentrations and more rapid tryptophan clearance were observed in the depressives, but there were no correlations with GH or PRL responses. However, basal cortisol concentrations, which were raised in depressives with chronic psychosocial difficulties, were strongly and inversely predictive of PRL responses in depressives and controls. Blunted GH and PRL responses to LTP appear to be distinct abnormalities in depression which may relate to two processes; (1), an endogenous mechanism indicated by reduced GH responses, and (2), an impairment in 5HT systems, indicated by blunted PRL responses and perhaps caused by raised circulating cortisol or reduced tryptophan concentrations.

Adolescent↗
PubMed1990

Hormonal response to L-tryptophan infusion: effect of propranolol.

There is circumstantial evidence that increases in prolactin secretion evoked by L-tryptophan infusion involve 5-HT1 receptors, whereas growth hormone responses do not. Propranolol is a beta-adrenoceptor antagonist that also possesses antagonist properties at 5-HT1 receptors. Propranolol (80 mg, PO) failed to attenuate the prolactin response to L-tryptophan infusion (100 mg/kg, IV) in seven volunteers; the role of 5-HT1 receptors in this response remains uncertain. The growth hormone response to tryptophan was enhanced by propranolol, consistent with previous reports of an inhibitory beta-adrenoceptor influence on GH secretion. Excessive beta-adrenoceptor function might explain the blunted growth hormone response to tryptophan in depression.

Adult↗
PubMed1979

Ascending 5-HT pathways and behavioural habituation.

Microinjections of 5,7 -dihydroxytryptamine into both the dorsal and median raphe nuclei resulted in 70-85% depletions in striatal and hippocampal 5-HT concentrations but did not affect habituation of orienting in the lick-distraction test, habituation of activity in an open-field or habituation of exploration in the holeboard test. Lesioned animals were hypoactive in the latter two tests and defaecated more than control rats in the open-field suggesting an increase in emotionality or fear. Rats with selective 5,7 -dihydroxtryptamine lesions of either the dorsal or the median raphe nucleus also showed no impairment of habituation of orienting or exploration. However, median raphe lesioned animals were hyperactive at some stages of the holeboard test. In contrast to previous studies, the results suggest intact ascending 5-HT pathways are not necessary for behavioural habituation of orienting, activity or exploration. Rather, 5-HT neurones may be involved in modulation of activity or responsiveness to aversive environments.

Acoustic Stimulation↗
PubMed1979

Personality and male-female influences on the EEG alpha rhythm.

The amplitude and frequency of the alpha rhythm was measured in electroencephalic recordings from 45 male and 46 female university students. The mean alpha frequency of the female group was significantly greater than the male group. There was no significant difference in alpha frequency between females in the first half of the menstrual cycle and those in the second half. The relationship between questionnaire measures of psychoticism, extraversion and neuroticism, and the alpha rhythm was investigated using analysis of variance, correlation analysis and factor analysis. Alpha amplitude was significantly greater in extraverted subjects, alpha amplitude and extraversion scores were significantly correlated and both had high loadings on a single factor. No relationship between psychoticism or neuroticism and alpha frequency or amplitude was observed.

Adult↗