Herpes simplex virus: a role in the aetiology of Alzheimer's disease?
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Alzheimer Disease↗
Biomedical subjects
T J Crow
Publications and source records attributed to T J Crow.
The Northwick Park Study of first episodes of schizophrenia. I. Presentation of the illness and problems relating to admission.
Patients referred over 28 months from nine medical centres for a trial of prophylactic neuroleptic medication following first episodes of schizophrenic illness (462) were assessed with the Present State Examination, WHO scales for disability, past history, and sociodemographic factors, and a rating of disturbed behaviour; 253 fulfilled the study criteria; of the 209 who did not, 54 did not meet the diagnostic criteria, 65 had a history of a previous episode, and in 15 the psychotic illness was found to have an organic basis. The interval between onset of illness and admission varied widely, but was often more than one year and associated with severe behavioural disturbance and family difficulty e.g. in arranging appropriate care. Current arrangements for initiating management of first schizophrenic illnesses are frequently unsatisfactory.
Adolescent↗
A randomised controlled trial of prophylactic neuroleptic treatment.
Out of 253 patients fulfilling criteria for a first episode of schizophrenic illness, 120 entered a randomised placebo-controlled trial of maintenance neuroleptic medication on discharge; they were followed to relapse or loss to follow-up, for two years or to the end of the study. Of those on active medication, 46% relapsed, as did 62% of those on placebo; the most important determinant of relapse was duration of illness prior to starting neuroleptic medication. This finding might be because extended duration of symptoms before admission is more likely to be present in illnesses which in any case will have poor prognosis, or because susceptibility to relapse is reduced by early institution of treatment. The study provides no data on which a decision between these alternative explanations can be based.
Adolescent↗
Short-term outcome in trial entrants and trial eligible patients.
Of 253 patients from nine medical centres identified with first episodes of schizophrenic illness, 17 did not achieve discharge during the period of trial recruitment. 120 entered a randomised controlled trial of neuroleptic medication and were followed-up, as were 116 who were eligible for the trial but did not enter it. Overall, 60% of the sample had relapsed within two years of discharge; age, sex, ethnic origin, duration of admission, social withdrawal before admission, and type of onset of illness were not significantly related to relapse. Relapse rates were lower on active trial or standard medication than placebo, but however assessed, outcome at this early stage was poor for many patients.
Adolescent↗
Expressed emotion and relapse.
The relatives of 82 patients in a study of first episodes of schizophrenia were interviewed within six weeks of the index admission; 77 patients were subsequently discharged, and were followed to relapse or readmission. Analysis of relapse-free survival time was used to examine whether the components of 'expressed emotion' predicted relapse or response to neuroleptic medication: 'critical comments' by relatives was the only component present often enough to be used and was inversely related to 'social contact'. When preadmission duration of illness, and neuroleptic medication following discharge (identified previously as significant predictors of outcome) were taken into account, neither 'critical comments' nor 'social contact' were related to outcome nor to response to medication. The constellation of factors suggested as pathogenic was present only in a minority of cases: many patients lived alone and of those that were with families, most were not in high face-to-face contact with other members. The failure of the components of 'expressed emotion' to predict outcome or response to neuroleptic medication suggests that at best, such factors are weak predictors of liability to relapse. Their influence is unlikely to be comparable in magnitude to that of neuroleptic medication.
Adolescent↗
Hypothyroidism as a correlate of lateral ventricular enlargement in manic-depressive and neurotic illness.
Lateral ventricular size, as assessed by computed tomography, was not significantly greater in manic-depressive cases than in neurotic patients, but 19% of manic-depressive cases had ventricular brain ratios (VBR) more than two standard deviations above the neurotic mean. Few correlates of VBR were found in the features of the illness and the treatment given, apart from the fact that in the outpatient sample, there was a significant association between increased VBR and hypothyroidism. Hypothyroidism was relatively common in this sample, but was treated and not associated with cognitive impairment. There was no relationship between lithium administration and VBR.
Aged↗
The continuum of psychosis and its implication for the structure of the gene.
Three observations challenge Kraepelin's binary view of the functional psychoses: a bimodal distribution of the clinical features of manic-depressive illness and schizophrenia has not been demonstrated; affective illness appears to predispose to schizophrenia in later generations; and 'schizoaffective' illnesses cannot be separated in family studies from either of the prototypical psychoses. The alternative concept is that psychosis is a continuum extending from unipolar, through bipolar affective illness and schizoaffective psychosis, to typical schizophrenia, with increasing degrees of defect. According to this concept the genes predisposing to psychosis have a degree of stability that ensures that the form of the psychosis tends to remain the same within families, but there is also the possibility of change, implying that the genetic mechanisms themselves are variable. It is proposed that quantal changes in the 'virogene' are due to replications within the genome (e.g. the generation of tandem repeats of the element or a component of it); that such replications occur at a critical stage (e.g. gametogenesis, fertilisation, very early embryogenesis) in the course of reproduction; and that the 'season of birth effect' reflects the operation of the mechanism responsible for these replications.
Adult↗
The two-syndrome concept and neuroendocrinology of schizophrenia.
Schizophrenia sometimes remits and sometimes responds to neuroleptic drugs but is a disease that also has a poor long-term outcome, sometimes including behavioral deterioration and intellectual decline. It is proposed that there are two components to pathology: a neurochemical component, perhaps associated with a change in D-2 DA receptors, which is potentially reversible and neuroleptic-responsive and a structural and probably irreversible component, which includes changes in structures bordering the temporal horn of the lateral ventricle and perhaps elsewhere in the brain.
Antipsychotic Agents↗
Is schizophrenia a viral or immunologic disorder?
The literature that schizophrenia may be a viral or immunologic disorder is reviewed. Although these hypotheses were formulated more than half a century ago, researchers have failed to establish clear evidence for their support. Nevertheless, epidemiologic issues addressed in this article provide impetus for further pursuit of research in this area.
Animals↗
Expressed emotion and relapse in schizophrenia.
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Emotions↗
Experimental transmission of an autosomal dominant spongiform encephalopathy: does the infectious agent originate in the human genome?
Marmosets inoculated intracerebrally with brain tissue from a woman with Gerstmann-Straussler syndrome (an autosomal dominant dementia associated with spongiform change and amyloid deposition) developed an encephalopathy indistinguishable from that seen in marmosets inoculated with brain tissue from a typical case of Creutzfeldt-Jakob disease. As in Huntington's disease, in the pedigree of the patient with Gerstmann-Straussler syndrome women who subsequently developed the illness had increased fecundity. The pathogen in human transmissible dementia may arise from a sequence (which itself sometimes confers a selective advantage) located within the human genome.
Aged↗
Dissociation of neuropeptide Y and somatostatin in Parkinson's disease.
The concentration of neuropeptide Y has been determined in the cortex and hippocampus of subjects with Parkinson's disease and compared to changes of activity of dopamine beta-hydroxylase and concentration of somatostatin. Despite a marked reduction in the concentration of somatostatin in the severely demented subject, in both cortex and hippocampus, no significant change in concentration of NPY was found in either region. This finding therefore suggests that the majority of NPY within the cortex is independent of somatostatin. This study provides some further evidence of neurochemical similarities between the dementia of Parkinson's disease and Alzheimer's disease.
Brain Chemistry↗
Reduced high affinity cholecystokinin binding in hippocampus and frontal cortex of schizophrenic patients.
Cholecystokinin (CCK) binding sites were assessed in post-mortem brain membrane preparations from controls and schizophrenic patients. 125I-BH CCK33 specific binding was reduced by 40% (p less than 0.02) in the hippocampus and by 20% (p less than 0.01) in the frontal cortex of schizophrenic patients compared with controls. There were no differences in 125I-BH CCK33 binding between the two groups in the amygdala, temporal cortex or caudate nucleus.
Adult↗
Chemical and structural changes in the brain in patients with movement disorder.
Neurochemical indices of dopaminergic function were assessed in basal ganglia of post-mortem brains of control subjects and schizophrenic patients who had been rated in life for the presence of movement disorder and neuroleptic intake. In schizophrenics who had been treated chronically with doses of neuroleptics, concentrations of dopamine D2 receptors were significantly increased above controls, whereas dopamine D1 receptors and dopamine metabolism were unchanged. Increased D2 receptors were also observed in basal ganglia of drug-free patients. Concentrations of dopamine D1 and D2 receptors in schizophrenics with movement disorder. Moreover, no relationship was found between dopamine receptor levels and the severity of movement disorder. Concentrations of the dopamine metabolite homovanillic acid were increased in the putamen and nucleus accumbens in a small number of patients with movement disorder compared with controls or patients without movement disorder. No changes were observed in markers of cholinergic and GABA-containing neurones. The present findings are not consistent with a "dopamine receptor hypersensitivity" concept of movement disorder in schizophrenia.
3,4-Dihydroxyphenylacetic Acid↗
MHPG excretion in endogenous depression: relationship to clinical state and the effects of ECT.
In a group of 70 patients with endogenous depression entering a controlled trial of real versus sham ECT, urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was significantly reduced by comparison with previously studied groups of control subjects, of acute and chronic schizophrenic patients and of anxious patients. However, urinary MHPG was unrelated to severity of depression, or to the presence of delusions, retardation or agitation. MHPG excretion did not predict clinical outcome, or the response to ECT. Urinary MHPG content at trial entry was unrelated to past tricyclic antidepressant or benzodiazepine medication, although an influence of the latter on the findings cannot be excluded, since all patients received benzodiazepine (nitrazepam) night sedation during the trial. During the 4-week trial MHPG excretion remained low and did not increase in relation to change in clinical state, although there was a small but significant increase in patients who received real ECT. The findings confirm that urinary MHPG excretion is reduced in depression, but establish that such reductions are not state dependent. Since the increase in MHPG excretion with ECT is not related to changes in clinical state, the former presumably does not reflect the mechanism of action of ECT.
Adult↗
Selective impairment of paired associate learning after administration of a centrally-acting adrenergic agonist (clonidine).
Eight normal volunteers had IV infusions of 200 micrograms clonidine (a centrally-acting adrenergic agonist which reduces noradrenaline release), and saline in a "double-blind" cross-over design. Clonidine reduced subjective estimates of arousal but did not affect performance on the Digit Symbol Substitution Test. Clonidine impaired paired-associate learning, but it did not affect performance on a number of measures of short and long term memory. The findings suggest either 1) that there is a specific (adrenergic) mechanism involved in the acquisition of novel associations, but not in other types of learning, or 2) that paired associate learning is more vulnerable than other learning tasks to disruption of adrenergic transmission.
Adrenergic Fibers↗
Cytopathogenic cerebrospinal fluid from neurological and psychiatric patients.
Cerebrospinal fluids (CSFs) were examined for the presence of a cytopathogenic component by an in vitro assay. No abnormal proteins were detected in CSF which produced cytopathic effects. The cytopathic effect was associated with high-molecular-weight material which was resistant to enzyme treatment. The effect persisted after extensive ultraviolet irradiation. The presence of the cytopathic effect was associated with increased CSF enolase levels.
Cells, Cultured↗