To determine whether high plasma cortisol concentrations are a distinctive feature of depression or whether plasma cortisol is also elevated in other forms of psychosis, cortisol concentrations were ...measured in 59 patients with acute functional psychoses, six non-psychotic depressed patients and 37 control subjects, all free of antidepressant and neuroleptic drugs for at least three months. Patients with schizo-affective disorder, manic type, had the highest concentrations throughout the day and those with major depressive disorder, psychotic sub-type had higher concentrations than controls in the afternoon and evening. Manic and schizophrenic patients had cortisol concentrations above controls in the afternoon only. Elevated concentrations were not related to the presence of depressed mood or to duration of stay in hospital, and a return to normal occurred irrespective of the type of treatment used. Thus raised plasma cortisol concentrations are a feature of psychotic illness, but in drug-free patients are not specific for severe depression.
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.
Forty-nine clones derived by microdissection of a schizophrenia-associated t(1;11)(q42.1;q14.3) breakpoint region have been assigned by somatic cell hybrid mapping to seven discrete intervals on the ...long arm of human chromosome 11. Eleven of the clones were shown to map to a small region immediately distal to the translocation breakpoint on 11q.A 3-Mb contiguous clone map of this region was established by isolation of corresponding YAC recombinants. The contig was oriented and shown to traverse the translocation breakpoint by FISH and microsatellite marker analysis. This contig will facilitate the isolation of candidate sequences whose expression may be affected by the translocation.
A genome-wide search for linkage of microsatellite markers to chromosomal loci containing genes responsible for the major psychoses is a laborious task which can be carried out with greater speed and ...economy by introducing automation to several steps in the procedure. We describe the use of the Automated Linkage Preprocessor (ALP) program for the computer analysis of the waveform generated by fluorescein-labelled markers after electrophoretic separation. (To obtain a copy send a request to A.F. Brown at the below MRC address or use Anonymous FTP to ftp.hgu.mrc.ac.uk. Software is in directory pub/ALP). The program runs on a PC in the Microsoft Windows environment, and is used in conjunction with an automated laser fluorescence (ALF) sequencer (Pharmacia) and its Fragment Manager software to detect and size the PCR products, filter out peaks of fluorescence due to nonallele fragments, and generate genotypes in a format suitable for direct input to standard linkage analysis programs. The method should offer the advantages of speed, accuracy, and reduced cost. Its use in linkage studies in a large family with manic-depressive illness is discussed.
P3 abnormality in fragile X syndrome St Clair, D M; Blackwood, D H; Oliver, C J ...
Biological psychiatry (1969),
03/1987, Letnik:
22, Številka:
3
Journal Article
Recenzirano
P300 (P3) and other long latency auditory event-related potentials (ERPs) were recorded in 33 adults with fragile X syndrome. All patients had an abnormal P3. It was longer in latency and smaller in ...amplitude than in controls. In several cases, it was split into two separate components, and in others, was generated in response to expected as well as unexpected events. Abnormal P3 was not related to age, percentage cell fragility, or intellectual ability, but complete splitting was associated with the presence of physical dysmorphisms. Our results are interpreted as showing that in fragile X syndrome there is dysgenesis of the hippocampus and related brain structures.
Traditional models of the genetic transmission of human diseases have often assumed that the phenotype is a simple dichotomous trait, which is unrealistic for many psychiatric conditions, and may ...result in loss of valuable information. We describe a new model for complex phenotypes, implemented in the program COMDS, which subclassifies normal and affected individuals into polychotomies correlated with the underlying genetic liability to the disorder. The model is applied to 18 Scottish pedigrees ascertained for schizophrenia, in which auditory P300 latency had been measured as a possible correlate of the genetic predisposition to schizophrenia. The results suggest that there may be a major locus for schizophrenia, but that there are also other familial determinants, possibly a second modifier locus. In addition, the results indicate that auditory P300 latency may be a useful measure of the genetic predisposition to schizophrenia among asymptomatic relatives, although the relationship between P300 latency and the degree of genetic predisposition in clinical cases was not significant, presumably because other factors are operating on P300 latency. Because of the possible selection biases in this sample, there is a need to replicate these findings in systematically ascertained pedigrees.
Linkage of bipolar disease to several markers mapping to chromosome 4p has been reported in an extended family multiply affected with bipolar affective disorder and no linkage was found at other ...locations with 106 microsatellite markers, of which 58 were dinucleotide and 48 tetranucleotide repeats Blackwood et al. (1996), Nature Genetics, 12, 427-430. Collecting these data provided the opportunity to assess the usefulness and accuracy of the automated linkage preprocessor (ALP) programme in a linkage study and to make a detailed comparison of di- and tetranucleotides with this semi-automated system. Genotypes were acquired using the automated linkage preprocessor (ALP) without any manual intervention at any stage of the procedure and results of analyses of these data were compared with results based on genotypes checked by visual inspection of the data. The ALP program was found to be timesaving and reliable and yielded similar results to non-automated reading using both di- and tetranucleotide repeat microsatellite markers. Tetranucleotides had fewer errors due to multiple genotypes and a lower incidence of stutter peaks making them more informative than dinucleotides in this linkage study.
A randomised, controlled, double-blind clinical trial designed to determine the effectiveness of phenytoin in preventing epilepsy in patients who had suffered a serious head injury is reported. One ...hundred and sixty-four patients were randomly assigned to treatment with phenytoin or placebo capsules for one year. Patients who had a fit within one week of injury were excluded. Drug levels were monitored throughout with appropriate dosage adjustment; however only 48% of the phenytoin group had plasma levels greater than 40 mumol/l. There were seven deaths during the study. Only 11 patients (six in the phenytoin group and five in the placebo group) developed post-traumatic epilepsy within one year; a further four patients developed seizures between 1 and 2 years after injury. This low incidence of post-traumatic epilepsy (7% (SE 2%) at one year and 10 (SE 2%) at two years) means that future clinical trials of prophylaxis will have to be much larger (at least six fold).
The frequency and extent of pairing failure around human translocations are unknown. We have examined the pattern of recombination around the breakpoints of a balanced autosomal translocation t(1;11) ...(q43;q21) associated with major mental illness. DNA was available from 17 carriers and 10 non-translocation carriers with meioses involving four generations. The derivative 1 and 11 chromosomes were also isolated in somatic cell hybrids and used to confirm phase. We have genotyped pedigree members using 20 polymorphic markers within 10 cM on either side of both chromosome 1 and 11 breakpoints. We find no significant reduction of recombination in the vicinity of either breakpoint. However we estimate that there are insufficient meioses even in this large family to make a meaningful interpretation and suggest that sperm typing alone can answer these interesting questions.
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