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Biomedical subjects

T J Crow

Publications and source records attributed to T J Crow.

At least 289 records · Page 16Linked to original sources

Reduced cholecystokinin-like and somatostatin-like immunoreactivity in limbic lobe is associated with negative symptoms in schizophrenia.

Cholecystokinin-like immunoreactivity (CCK) and somatostatin-like immunoreactivity (SRIF) were determined in fourteen brains from patients dying with a diagnosis of schizophrenia and in twelve brains from control cases. The schizophrenics had been rated during life and were divided into two groups on the basis of the presence or absence of negative symptoms (affective flattening and poverty of speech). CCK was reduced in temporal cortex of the schizophrenics and in hippocampus and amygdala of those patients with negative symptoms. SRIF was reduced in the hippocampus in samples from the latter group. The selectivity of these changes to limbic lobe may reflect the presence of a degenerative process in that area. The association of changes in hippocampus and amygdala with negative symptoms of schizophrenia suggests a separate mechanism underlying these symptoms.

Aged↗

Immunocytochemical localization on neuropeptides in the fornix of rat, monkey and man.

Using specific antisera and immunocytochemical methods VIP, CCK, substance P, methionine-enkephalin, neurotensin and somatostatin-like immunoreactive fibers were found within the fornix and fimbria in 3 species (rat, monkey and human). Neither methionine-enkephalin- nor substance P-containing cell bodies were located within the hippocampus and so fibers containing these peptides are presumably hippocampal afferents, probably arising in the septum or caudal hypothalamus. VIP, CCK, neurotensin and somatostatin fibers may be hippocampal efferents arising from cell bodies within the subiculum.

Animals↗

Is schizophrenia an infectious disease?

The role of genetic predisposition in schizophrenia is undoubted but some of the data on family concordance cannot be explained on the basis of genes alone: for instance, the concordance rate is higher in same-sex than in different-sex dizygotic-twin and sibling pairs and in same-sex dizygotic twins than in same-sex sibling pairs. The findings can be understood if disease expression is also a function of physical proximity to an affected individual, as is suggested by the fact that the anomalous findings occur within primary but not secondary family relationships. There is some familial and epidemiological evidence to support the hypothesis of transmission from affected to nonaffected individuals. Schizophrenia could be due to a virus which is transmitted predominantly from schizophrenic patients to genetically-predisposed individuals, perhaps in some cases with a latency of approximately six months.

Diseases in Twins↗

Anterior pituitary hormone secretion in chronic schizophrenics.

Venous samples were obtained serially from 18 chronic schizophrenics and nine controls before and after the intravenous administration of protirelin and gonadorelin (gonadotropin releasing hormone [GnRH] ) and by venipuncture from 38 controls. Significant reductions in basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were found in the schizophrenic group associated with a reduction in the fluctuation of LH in serial samples. The FSH and prolactin responses to the administration of protirelin and gonadorelin were reduced in the schizophrenic group and abnormal increments of growth hormone secretion were noted in a number of patients, particularly those with reduced basal and stimulated hormone secretion. This pattern of hypothalamic-pituitary dysfunction, which is distinct from that seen in other psychiatric and endocrinological conditions, suggests a reduction in spontaneous GnRH release from the hypothalamus in schizophrenia and may be of potential pathophysiological significance.

Adult↗

Neuropeptides in Alzheimer type dementia.

Five neuropeptides (cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), somatostatin (SRIF), neurotensin (NT) and substance P (SP)) were measured in 14 brain areas (4 cortical areas, hippocampus, amygdala, 3 striatal areas, 2 thalamic areas and 3 subcortical areas-- septum, substantia innominata and hypothalamus) in 12 brains with neuropathologically confirmed Alzheimer type change and in 13 control brains. Choline acetyltransferase (CAT) activity was assessed in 6 of these areas. Levels of SRIF, but not those of the other peptides, were reduced in several cortical areas in Alzheimer-type dementia (ATD). The distribution and magnitude of the reduction in SRIF were less than that of CAT activity and the temporal cortex was the only region in which there was a significant relationship between CAT and SRIF deficits. Peptide levels were unchanged in hippocampus, amygdala, thalamus, hypothalamus and striatum (except for an increase in SP in the putamen). SRIF levels were increased in substantia innominata in ATD. NT and SRIF were significantly, and VIP and SP non-significantly, reduced in the septum in ATD. Thus, apart from these alterations in the septum, SRIF was the only neuropeptide for which major changes were identified and these did not follow either the pattern of neuropathological change (e.g. in amygdala and hippocampus) or of CAT deficits (e.g. in substantia innominata).

Aged↗

Further consideration of the learning impairment after aceperone in the marmoset: effects of the drug on shape and colour discrimination and on an alternation task.

Ten marmosets (Callithrix jacchus) learned to discriminate between pairs of small grey objects differing only in shape or small plain plaques differing only in colour, in a Wisconsin General Test Apparatus. Each day, each animal was presented with three consecutive visual discrimination problems in the order shape-colour-shape or colour-shape-colour. After aceperone, an alpha-noradrenergic antagonist, animals were impaired at learning the first but not the subsequent tasks of each trio. These results suggest that the previously observed impairment [10] on the first of a pair of object discrimination tasks after aceperone is a consequence of disruption of a mechanism common to both shape and colour discrimination learning. The fact that there is no impairment on task 2 in a dimension differing from task 1 suggests that the deficit is not one of attending to, or switching attention to, the appropriate visual dimension. Three further marmosets were trained to perform an alternation task and tested under aceperone. No impairment in performance was seen, suggesting that a variety of cognitive skills other than stimulus-reward association were intact. We conclude that the impairment following aceperone is a dysfunction of processes involved in association formation, but that it is one which is manifest only when the animal is faced with a type of task which has not recently been performed and that it can be overcome with persistence even the animal encounters novel stimuli.

Animals↗

Distribution of neuropeptides in the limbic system of the rat: the bed nucleus of the stria terminalis, septum and preoptic area.

The distribution of the neuropeptides vasoactive intestinal polypeptide, cholecystokinin octapeptide, substance P, neurotensin, methionine-enkephalin and somatostatin has been mapped immunocytochemically in the bed nucleus of the stria terminalis, one of the major sites of termination for efferent projections from the amygdala. Immunoreactive fibres and terminals were distributed more or less topographically and largely in accordance with the previously described localization of peptide-containing cell bodies in the amygdala and the amygdaloid projection fields in the bed nucleus as described by neuroanatomical techniques. Thus, vasoactive intestinal polypeptide, which was found in some of the lateral amygdaloid nuclei, had a substantial projection to the lateral bed nucleus. The lateral bed nucleus also contained cholecystokinin-octapeptide, substance P, neurotensin and methionine-enkephalin immunoreactivity which probably derived from the central amygdaloid nucleus, whilst cholecystokinin-octapeptide, and especially substance P-containing fibres, were found in the medial bed nucleus and probably arise from cells in the medial amygdala. Reciprocal amygdalopetal projections were suggested by the presence of substance P- and somatostatin-containing cell bodies in the mediodorsal bed nucleus and vasoactive intestinal polypeptide cells in the lateral bed nucleus, but somatostatin otherwise had a widespread distribution. Numerous local peptidergic connections were also noted both within the bed nucleus and between it and adjacent structures, especially the preoptic area, hypothalamus and the basal ganglia. These data provide further evidence that neuropeptides play a major role in the connectivity of the limbic system and show that the bed nucleus of the stria terminalis is an important relay station, particularly between amygdaloid efferents and other forebrain areas.

Animals↗

An investigation of the effects of intracerebral injection in the marmoset of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease.

In experiments designed to investigate transmission, cerebrospinal fluid (CSF) from patients with schizophrenia and neurological disease (huntington's chorea and multiple sclerosis) which had been found to induce cytopathic effects in human embryonic fibroblast cell culture was injected intracerebrally into mice, hamsters and marmosets (small New World primates). No evidence was obtained of transmission to mice or hamsters. A total of 15 marmosets (Callithrix jacchus) was injected intracerebrally with CSF [8 with samples from 4 patients with schizophrenia. 3 with samples from patients with neurological disease (2 with Huntington's chorea and 1 with multiple sclerosis) and 4 with samples from 3 patients without neurological or psychiatric disease] and was observed over a period of 2 1/2 years. Analysis of variance on data obtained from behavioral observations averaged over 6-month periods revealed that animals injected with CSF from patients with schizophrenia and neurological disease became progressively more inactive when compared with animals injected with CSF from control patients. The change detected by behavioural observation was confirmed as a difference 2 and 2 1/2 years after injection by automated activity monitoring. There was an incidence of reproductive anomalies (including two occipital encephalocoeles) in the females in the experimental group, but the numbers are too small to draw firm conclusions from this observation. Many reported differences in biological samples from schizophrenic patients and normal controls have subsequently been found to be due to factors unrelated to the disease state. This may prove to be the case with the changes observed in this experiment. Nevertheless, the fact that marmosets injected with CSF from patients suffering from neuropsychiatric disease, including schizophrenia, subsequently differed in their behaviour from those injected with control CSF warrants further investigation.

Animals↗

Adverse effects of anticholinergic medication on positive schizophrenic symptoms.

In a series of 36 patients with acute schizophrenia flupenthixol dosage was blindly adjusted to give a fixed level of sedation. Patients were than randomly allocated to procyclidine or placebo. The patients receiving procyclidine experienced more positive schizophrenic symptoms and less severe extrapyramidal features by comparison with placebo patients. Blood levels of prolactin and flupenthixol estimated by radioimmunoassay were not significantly changed by the addition of procyclidine. Flupenthixol dosage and levels and prolactin levels were significantly related. There was no significant association between clinical and laboratory measures, with the exception that a curvilinear (inverted U) relationship was demonstrated between flupenthixol levels and antipsychotic and extrapyramidal effects. This relationship may be due to the fact that, in a study of this design, patients resistant to the effects of neuroleptic medication are likely to be given the highest doses. The findings support earlier claims that anticholinergic medication has adverse effects on schizophrenic symptoms.

Adult↗

Integration of schematic faces and other complex objects in schizophrenia.

Twenty-one acute schizophrenic patients and 26 neurotic patients sorted each of six sets of 15 objects into three groups. A set consisted either of schematic faces, nonsense objects, or histoforms, each composed of five independently varying features. For the faces and nonsense objects these features could be integrated into a whole, whereas for the histoforms they could not. The distribution of four of the features was such that a set could be divided into three groups. The fifth feature either remained constant and had no effect on sorting performance or it varied randomly and acted as a distractor. Performance was assessed from the variance in common between the grouping actually present in a set and the grouping produced by the subject. For the control patients faces were sorted much better than histoforms if no distractor was present. However, performance with faces was massively impaired by a distractor while performance with histoforms was not. For the schizophrenic patients faces were not sorted better than histoforms and the effect of distraction was similar for every type of material. The performance of the controls suggest that the gestalt quality of the faces dominated over their constituent details. This enabled more features to be handled at once, thus achieving better sorting with faces than histoforms. However, it also made it more difficult for subjects to ignore a distracting component in the faces. The performance of the schizophrenics suggests that for them the integrated gestalt of the face was not dominant over its components.

Attention↗

Hydroxy-indole-o-methyltransferase activity in human pineals: a comparison of controls and schizophrenics.

The activity of hydroxy-indole-o-methyltransferase (HIOMT) has been assayed in pineal glands from fifteen controls and twenty-three schizophrenics. There was no significant difference between the two groups in HIOMT activity and no significant effect of age, sex or neuroleptic treatment on the activity of the enzyme. A diurnal rhythm was not discernible in HIOMT activity and it is suggested that this may be the result of terminal illness. It is concluded that HIOMT activity in pineals of schizophrenics is unlikely to differ from controls.

Acetylserotonin O-Methyltransferase↗

Effects of ECT and depression on various aspects of memory.

Seventy severely depressed patients randomly assigned to receive 8 real or sham ECT were further subdivided on the basis of degree of recovery from depression afterwards. In comparison to a non-depressed control group the depressed patients were impaired on a wide range of tests of memory and concentration prior to treatment, but afterwards performance on most of the tests had improved. Real ECT induced impairments of concentration, short-term memory and learning, but significantly facilitated access to remote memories. At 6 months follow-up all differences between real and sham ECT groups had disappeared. On the majority of tests the previously depressed patients now performed at the same level as the control group. There was some evidence that a subgroup of treatment-resistant patients (poor outcome after real ECT) were significantly more likely to complain of memory problems 6 months later.

Adult↗

Effects of ECT on pituitary hormone release: relationship to seizure, clinical variables and outcome.

Prolactin, cortisol, growth hormone and TSH serum levels (before and 15 minutes after treatment) were measured in 62 patients with endogenous depression randomly allocated to real or pseudo-ECT. Prolactin increased significantly more in those receiving real ECT than in those receiving pseudo-ECT, but the size of this effect had diminished by the time of the last (8th) treatment in the trial. Cortisol secretion was also significantly increased following the first treatment by real ECT, but this increase was of significantly smaller size in patients with delusions. Tolerance to the effects of ECT on cortisol secretion was not observed. No effects of ECT on growth hormone or TSH secretion were detected, and no clear evidence was obtained that endocrine responses can be used as a predictor of response to ECT.

Depressive Disorder↗