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Biomedical subjects

J E Christie

Publications and source records attributed to J E Christie.

At least 19 recordsLinked to original sources

Diurnal variation of plasma corticosterone in depression.

Hypersecretion of cortisol is associated with depression. Because corticosterone may show greater responsiveness than cortisol to exogenous ACTH in depression and it has behavioural effects in rodents, we determined whether depression is also associated with hypersecretion of corticosterone. Both cortisol and corticosterone were significantly elevated in depression, with greatest differences from control subjects during the afternoon and evening. The ratio of corticosterone/cortisol was constant and similar throughout the day in both depressed patients and controls. We conclude that there is no disproportionate endogenous hypersecretion of corticosterone in depression.

Adolescent

Cholinergic enzymes in the spinal cord in Alzheimer-type dementia.

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were measured in anterior and posterior grey matter of the lumbar spinal cord and in temporal and frontal cortex from six cases of Alzheimer-type dementia (ATD), one case of Down's syndrome, three cases of schizophrenia (SZ) and six controls. Compared with control and SZ values, ChAT and AChE were reduced in ATD cerebral cortex. ChAT was reduced, and AChE unaltered, in ATD spinal cord. Decreased cord ChAT may be related to electrophysiological abnormalities which have been reported in motor nerves of patients with Alzheimer's disease.

Acetylcholinesterase

The pattern of function-related regional cerebral blood flow investigated by single photon emission tomography with 99mTc-HMPAO in patients with presenile Alzheimer's disease and Korsakoff's psychosis.

Single photon emission tomography (SPET) with the lipophilic blood flow marker 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO) has been used to determine regional uptake of radiolabel into brain regions of patients with presenile Alzheimer's disease and Korsakoff's psychosis, and age-matched controls. Using occipital cortical uptake as reference area, the pattern of relative regional cerebral blood flow (rCBF) was determined in other cortical areas and basal ganglia. In Alzheimer's disease, reduction in rCBF occurred most strikingly in posterior temporal and parietal areas. By contrast, in Korsakoff's psychosis, posterior temporal rCBF was maintained, although there was a trend to reduced tracer uptake in other cortical areas. These impairments of flow were correlated with impairments of neuropsychological function. In Alzheimer's disease, left posterior temporal and left parietal regions in particular showed rCBF to be strongly correlated with most aspects of cognitive function. In Korsakoff's psychosis, however, impaired flow in frontal regions was correlated with impaired performance on tests of memory and orientation. The findings in Alzheimer's disease show quantitative parallels with those from studies using Positron Emission Tomography (PET), and extend our understanding of the relationship between cognition and regional brain function in dementia. The findings in Korsakoff's psychosis offer the first direct evidence linking frontal lobe dysfunction with the cognitive impairment seen in the disorder.

Adult

Luteinizing hormone responses to luteinizing hormone releasing hormone (LHRH) in acute mania and the effects of lithium on LHRH and thyrotrophin releasing hormone tests in volunteers.

The endocrine responses to Luteinizing Hormone Releasing Hormone (LHRH) of eight drug-free males with mania were determined. Basal levels of Luteinizing Hormone (LH) and the plasma levels following injection of LHRH were elevated in patients compared with controls; Follicle Stimulating Hormone (FSH) and testosterone were not different. Elevated levels of LH have been described previously in recovered manic patients and have been suggested to be state-independent features of mania. In order to clarify the status of this finding, the effects of lithium administration upon hormone responses to LHRH in six male volunteers were also investigated, together with the effects upon Thyrotrophin Releasing Hormone (TRH) stimulation of Thyroid Stimulating Hormone (TSH) and prolactin release. Lithium increased the basal levels of LH and levels after injection of LHRH without effect upon FSH and testosterone. Lithium also increased basal and TRH stimulated release of TSH and basal prolactin levels. Lithium was without effect upon prolactin responses to TRH. The results are discussed in relation to current information on the mechanism of lithium's action. The implications for neuroendocrine work on recovered patients taking lithium are also explored.

Adult

Cerebral vascular transit time in Alzheimer's disease and Korsakoff's psychosis and its relation to cognitive function.

The cerebral vascular transit time of 17 patients with pre-senile dementia of the Alzheimer type (ATD), nine abstinent patients with alcoholic Korsakoff's psychosis (KOR), and ten age-matched controls was determined by the bolus intravenous injection of pertechnetate. A gamma camera was used to estimate the median transit time (MTT) of the radioactive bolus in a planar (non-tomographic) projection normal to the vertex. The spread of the bolus arriving at the aortic arch was measured independently by a single external detector over the chest, and correction made for the transit time of this input function in calculating the net MTT for the head. Both ATD and KOR groups showed lengthened net MTTs, compatible with reduced cerebral blood flow, and which were correlated with reduced cognitive function. It is concluded that the method employed gives a simple, inexpensive estimate of function-related blood flow to the brain in pre-senile dementia.

Aged

Disturbed endocrine function in the psychoses. I: Disordered homeostasis or disease process?

Plasma concentrations of prolactin, growth hormone, cortisol, TSH, and the neurophysins were measured over 17 hours in 98 newly admitted psychiatric patients and 35 control subjects. Seventy patients had been free of psychotropic medication for three months. Patients with schizoaffective mania (SAM) differed significantly from control subjects by increased plasma cortisol concentrations and decreased night-time TSH concentrations. The latter were also significantly lower than in both schizophrenic and manic disorder patients. Plasma cortisol was increased to a lesser extent in other psychotic subgroups, and increases in prolactin were most marked in the affective psychoses. There was little diagnostic specificity for psychoses other than SAM. Higher cortisol and prolactin levels may be due to the stimulatory effect of serotonergic pathways, but the neural mechanisms underlying lower night-time TSH levels in SAM are not known. The findings are not consistent with the view (a) that the hormonal changes of the psychoses simply reflect a non-specific response to stress, or (b) that the biological abnormalities of the psychoses can be accounted for by a single continuum of disturbance.

Adult

Disturbed endocrine function in the psychoses. II: Discriminant function analysis of multihormone data.

Discriminant function analyses were performed on plasma concentrations of prolactin, growth hormone, cortisol, TSH, and the neurophysins measured over 17 hours in 70 newly admitted drug-free psychiatric patients and 35 control subjects. The hormone data distinguished between patients with different classes of drug-free psychosis (26 schizophrenic, 12 with manic disorder, 10 with major depressive disorder, psychotic subtype, 9 with schizoaffective mania (SAM]. Higher plasma cortisol and lower TSH concentrations separated eight of nine SAM patients from all others.

Bipolar Disorder

Solubility of neurofibrillary tangles and ultrastructure of paired helical filaments in sodium dodecylsulphate.

Temporal cortex from 14 cases of Alzheimer-type dementia and 6 cases of Down's syndrome, all selected for severe Alzheimer pathology, was homogenised in distilled water, NaOH, or sodium dodecylsulphate (SDS) containing 0.1% beta-mercaptoethanol. The homogenates were stained with Congo red, and the neurofibrillary tangles and plaque cores were counted under crossed-polarisation microscopy. The number of tangles and plaque cores in the water-treated extracts was not related to age, sex, post-mortem interval or duration of dementia. The number of tangles after extraction in SDS or NaOH, as a percentage of tangles in water-treated extracts, was 57 +/- 25 (mean +/- SD) for 1% SDS, 43 +/- 17 for 5% SDS and 37 +/- 22 for 0.2 M NaOH. Plaque cores were essentially insoluble in all three agents. The percentage of tangles insoluble in 1% SDS did not correlate with age or post-mortem interval but decreased with increasing duration of dementia. Enhanced tangle solubility with increasing duration of dementia suggests that the nature of tangles changes with time; one possibility is that this reflects transformation of intracellular to extracellular tangles. Paired helical filament (PHF) length and the number of repeats per PHF were measured in electron micrographs of PHF prepared with and without treatment by 1% SDS. There was no significant multimodality of PHF length to suggest that PHF broke at regular intervals. The mean repeat length (PHF length/number of repeats) was greater for PHF isolated in the presence of 1% SDS than in its absence, showing that SDS affects ultrastructure by untwisting PHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Magnetic resonance imaging in pre-senile dementia of the Alzheimer-type, multi-infarct dementia and Korsakoff's syndrome.

Magnetic resonance imaging T1 values in Alzheimer's disease (ATD) were similar to age-matched controls although frontal T1 values tended to increase intraindividually with progression of the dementia. T1 values were raised, in both cortical grey and white matter, in Korsakoff's syndrome and multi-infarct dementia. T1 values appear of little value in studying the neuropathological changes in ATD in relationship to the neuropsychological deficits, but can assist in the differential diagnosis of pre-senile dementia.

Aged

Elevated plasma luteinizing hormone concentrations, cryptorchidism and mania.

A young man with acute mania and unilateral cryptorchidism had plasma luteinizing hormone (LH) concentrations that were much higher than the maximum LH concentrations we have found in normal subjects and patients with schizophrenia. Plasma concentrations of testosterone and sex hormone binding globulin were not abnormal, showing that the elevated plasma LH concentrations were probably due to increased secretion of LH-releasing hormone (LHRH). This case supports our previous results which suggest that an abnormally high secretion of LHRH, due presumably to an abnormality in central neurotransmission, may be a feature of acute mania in young men.

Acute Disease

Changes in auditory P3 event-related potential in schizophrenia and depression.

Event-related potentials during a two-tone discrimination task were recorded in 24 schizophrenic patients, 16 depressed patients and 59 control subjects. Recordings were made when patients were medication-free. Fourteen schizophrenic and 13 depressed patients were retested at 1 and 4 weeks after the start of treatment, and 13 schizophrenic patients were also tested between 6 and 24 months after the initial recordings. In the schizophrenic group, the P3 latency was significantly prolonged compared with that in the control and the depressed groups, and remained unchanged both after 4 weeks treatment with therapeutic doses of neuroleptic drugs and at long-term follow-up. In the depressed group, the P3 latency did not differ from that of controls. P3 amplitude by contrast was reduced in both the acutely depressed and schizophrenic groups and following treatment became normal in the depressed group but remained reduced in the schizophrenic group. It is suggested that a prolonged P3 latency and reduced P3 amplitude indicate an impairment of auditory information processing in some patients with schizophrenia which is independent of the presence of acute psychotic symptoms and is not influenced by neuroleptic medication.

Adult

Characteristic plasma hormone changes in Alzheimer's disease.

A systematic endocrine investigation in dementia, depression and control subjects showed that plasma growth hormone (GH) was higher in the morning and plasma TSH concentrations were higher throughout the day in Alzheimer-type dementia (ATD) than in age-matched depressed patients (MDD), and plasma TSH concentrations were also higher throughout the day in female ATD compared with age-matched female control subjects. The increased plasma TSH concentrations could not be due to reduced negative feedback because plasma T3, T4 and rT3 were in the normal range. Plasma concentrations of oestrogen-stimulated neurophysin (ESN) were lower throughout the day in ATD compared with MDD and controls and lower in the morning compared with other dementias. The high plasma GH and TSH concentrations in ATD may reflect the reduced hypothalamic content of somatostatin in ATD, and the reduced concentrations of ESN may reflect reduced cholinergic activity in ATD brain. These selective hormonal changes provide a useful diagnostic test for Alzheimer's disease.

Adult

Glucocorticoid receptors and depression.

The number of glucocorticoid receptor sites in lymphocytes was estimated and plasma cortisol concentrations measured in 17 depressed patients, 12 patients with chronic schizophrenia, and 31 healthy control subjects. The number of receptor sites was significantly lower in the depressed patients than in either the controls or the patients with chronic schizophrenia, but there were no differences between the groups in the dissociation constants of the glucocorticoid receptors or the plasma cortisol concentrations. When two control subjects were studied intensively over 28 hours a slight diurnal variation in the number of glucocorticoid receptors was detected. The lower numbers of glucocorticoid receptors in the lymphocytes of depressed patients may explain why such patients, who often have hypercortisolaemia, do not show the clinical features of excess production of cortisol.

Adult

Autoantibodies to Alzheimer and normal brain structures from virus-transformed lymphocytes.

B-Lymphocytes from two patients with Alzheimer's disease and one healthy subject were transformed into lymphoblastoid cells by exposure to Epstein-Barr virus. In culture, more than 50% of these cells secreted sufficient IgM or IgG antibody (mainly IgM) to allow immunohistochemical screening against cryostat sections of normal and Alzheimer temporal cortex. More than 30% of the IgM antibodies from each subject recognised brain components, namely: neurons, astrocytes, nuclei, nucleoli, and Alzheimer plaques and neurofibrillary tangles. This methodology represents a major addition to the procedures currently available for the generation of antibodies towards normal and pathological structures in human brain.

Alzheimer Disease