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P McGuffin

Publications and source records attributed to P McGuffin.

At least 19 recordsLinked to original sources
PubMed1992

Bi-directional changes in the levels of messenger RNAs encoding gamma-aminobutyric acidA receptor alpha subunits after flurazepam treatment.

Changes in gamma-aminobutyric acidA (GABAA) receptor function have been observed following chronic benzodiazepine administration. The molecular mechanisms responsible are unknown, but one possibility is that benzodiazepines induce alterations in the expression of genes which encode subunits of the GABAA receptor complex, resulting in changes in the receptor structure and function. We have investigated this hypothesis by evaluating the effect of flurazepam 40 mg/kg i.p. on brain levels of the mRNAs which encode the alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6 subunits of the GABAA receptor complex. Rats were treated with flurazepam or vehicle for up to 32 days. No changes were found in the levels of alpha 1 and alpha 2 mRNA. A rapid decrease was found in the level of alpha 5 mRNA; alpha 3 mRNA was increased by 4 days of treatment and this was followed by an increase in alpha 6 levels. These results support the hypothesis that the alteration in GABAA receptor function after benzodiazepine administration results from changes in subunit gene expression. Furthermore, the predicted consequences of the pattern of mRNA changes we have observed suggest that altered gene expression may be important in the genesis of benzodiazepine tolerance.

Animals↗
PubMed1992

Changes in dopamine D1, D2 and D3 receptor mRNA levels in rat brain following antipsychotic treatment.

The effects of administration of antipsychotic drugs (1-32 days, twice per day) on the rat brain mRNA levels of dopamine D1, D2 and D3 receptors has been assessed by a novel procedure utilising solution hybridisation with oligonucleotides. Saline and sulpiride (10 mg/kg/injection) had no effect on D1, D2 and D3 receptor mRNA levels. Haloperidol (1.5 mg/kg/injection) elicited increases in D1, D2 and D3 receptor mRNA levels of 100%, 100% and 300% respectively, after 32 days and loxapine (2 mg/kg/injection) elicited increases of 450%, 150% and 550%, respectively. These results indicate that the up-regulation of dopamine receptors may be associated with the occurrence of tardive dyskinesia but not the clinical mode of action of antipsychotics.

Animals↗
PubMed1992

Changes in dopa decarboxylase mRNA but not tyrosine hydroxylase mRNA levels in rat brain following antipsychotic treatment.

The effects of antipsychotic administration (1-32 days, twice per day) on the levels of mRNA coding for dopa decarboxylase (DDC) and tyrosine hydroxylase (TH) in rat brain has been assessed by a procedure utilising solution hybridisation with oligonucleotides. Saline and sulpiride (20 mg/kg/day) had no apparent effect on DDC mRNA levels. Haloperidol (3 mg/kg/day) elicited increases in DDC mRNA levels of 240% after 32 days and loxapine (4 mg/kg/day) elicited increases of 180% in DDC mRNA levels. None of the drugs affected TH mRNA levels. These results indicate that DDC may be more important than TH in the long term regulation of dopamine production.

Animals↗
PubMed1992

Lack of effect of chronic antipsychotic treatment on dopamine D5 receptor mRNA level.

The effects of administration of antipsychotic drugs (haloperidol, loxapine, sulpiride; 1-32 day time course) on the rat brain mRNA levels of the dopamine D5 receptor has been assessed using solution hybridisation with oligonucleotides. In contrast with the previously reported increases of D1, D2 and D3 receptor mRNA levels in identical experiments, no changes were found in dopamine D5 receptor mRNA levels, suggesting that the mechanism of regulation of D5 receptor mRNA is different to the other cloned dopamine receptors. We also conclude that up-regulation of the D5 receptor is not likely to be involved in the mechanism of action of antipsychotic drugs.

Animals↗
PubMed1992

Pre- and perinatal factors and the risk of subsequent referral for hyperactivity.

Possible pre- and perinatal risk factors for subsequent referral for hyperactivity were assessed by comparing birth records of 129 referrals with the remaining 24,656 members of a geographically defined birth cohort. Relationships between the risk factors were accounted for using logistic regression methods. The significant factors were: social class, maternal age, antepartum haemorrhage, length of labour (second stage), 1-min Apgar and sex. Associations between referral for hyperactivity and the pregnancy, labour and birth outcome factors were not explained by the socio-demographic variables. The results suggest that such factors have a statistically significant association with referral for hyperactivity and may be of modest aetiological importance. However, the predictive power of the final set of factors remained low even on the original data set.

Apgar Score↗
PubMed1992

The genetics of personality disorder.

Most measurable aspects of normal personality appear to be at least moderately heritable, with direct evidence coming from family, twin and adoption studies and indirect support deriving from psychophysiological research and breeding experiments on animals. Interestingly, genetic studies also shed light on the environmental sources of variation in personality and suggest that shared family environment rarely, if ever, has any positive effect on similarity between relatives. Despite problems of classification, and variations in the use of terms, a survey of the literature provides reasonably consistent evidence of a genetic contribution to several categories of abnormal personality, which we here divide into three groups, antisocial, anxious/avoidant, and schizoid-schizotypal personalities. However, personality disorders are complex traits that do not show simple mendelian patterns of inheritance and so far molecular genetics has been of no help in understanding their aetiology. Fortunately, techniques are now becoming available that enable the detection and potential localisation of genes of small effect and which may help elucidate the molecular basis even of (probably) polygenic traits such as abnormal personality.

Animals↗
PubMed1992

No evidence for a pseudoautosomal locus for schizophrenia. Linkage analysis of multiply affected families.

Evidence for a pseudoautosomal locus for a schizophrenia susceptibility gene was sought by two forms of analysis of 25 multiply affected families. Firstly, in the sample as a whole there was an excess of same-sex over mixed-sex siblings compared with that expected. Secondly, linkage analysis was performed in six of the families. The genotypes were studied for DXYS14, a highly polymorphic marker in the telomeric pseudoautosomal region. No evidence for positive linkage was found with two-point analysis under eight different genetic models for the mode of transmission. A non-parametric, sibling-pair analysis also failed to detect linkage. Our findings provide no evidence for linkage within the pseudoautosomal region; same-sex concordance must arise from some other mechanism.

Blotting, Southern↗
PubMed1992

Methodological issues in using a polydiagnostic approach to define psychotic illness.

Although a polydiagnostic approach to the definition of psychotic disorder provides many advantages to the researcher, there are also disadvantages. A comparison between several different sets of operational criteria using the OPCRIT computer program on a consecutive series of 397 psychotic subjects is described. The results show that although current diagnostic procedures are generally reliable, such approaches can still only supplement skilled clinical judgement, and there remain many pitfalls for the unwary.

Humans↗
PubMed1991

DNA and classical genetic markers in schizophrenia.

Interest in genetic marker studies of schizophrenia has been considerably enhanced by the advent of recombinant DNA technology, which has dramatically increased the number of available markers. In the present paper, we review studies that have been carried out using classical markers as well as the more recent molecular studies. The problems that arise when schizophrenia is studied in this way are discussed and attempts are made to account for some of the conflicting findings in this area.

DNA↗
PubMed1991

The reliability of the SADS-LA in a family study setting.

The joint-rater and test-retest reliability study of two translated versions of the SADS-LA (Schedule for Affective Disorders and Schizophrenia--Lifetime version--modified for the study of anxiety disorders), one in French and the other in German, have been tested in family study settings, in a sample of patients and first-degree relatives. The test-retest reliability study demonstrated that identification of major affective disorders and schizophrenia was performed with sufficient reliability; however, diagnoses of subtypes of major disorders (e.g. bipolar II disorder) and identification of minor disorders was less reliable. The implications of these findings in phenotype identification during family studies in psychiatry are discussed.

Adult↗
PubMed1991

The effects of antidepressant drugs on kainate receptor mRNA levels.

We have measured the levels of kainate receptor mRNA in rat brains following the injection of antidepressant drugs over a time course up to 32 days. Over this period imipramine and fluvoxamine elicited a rise in kainate receptor mRNA levels to a maximum of three and two fold increase respectively, relative to untreated rat brain samples. Mianserin and amitriptyline did not induce significantly elevated kainate mRNA levels compared to untreated specimens, but were elevated compared to vehicle injected controls.

Animals↗