Biomedical subjects

E C Johnstone

Publications and source records attributed to E C Johnstone.

At least 37 records · Page 2Linked to original sources

PubMed2000

Edinburgh high risk study--findings after four years: demographic, attainment and psychopathological issues.

This study reports findings of the Edinburgh High Risk Study four years after it began. This study is designed to explore the pathogenesis of schizophrenia by examining a large sample of young adults aged 16-25 years who are at enhanced risk of developing schizophrenia by having two close relatives with the disorder, and comparing them with matched controls. This paper presents comparisons of the high risk subjects, well controls and subjects with first-episode schizophrenia in terms of demographic, childhood, psychopathological, educational and employment, forensic and social work variables. High risk subjects have more psychological difficulties, poorer educational and employment attainment, and more social work contact than controls. The enhanced social work involvement related to the presence of a schizophrenic parent (especially a mother) but the other difficulties could not be attributed to that situation. Neurotic, partially held psychotic and fully held psychotic symptoms all occurred in both subjects and controls, but all were significantly more common in high risk subjects. Clinical schizophrenia has so far developed in 10 high risk subjects and in no controls. Possible confounding effects of drug or alcohol misuse were considered but were found unlikely to be important.

Adolescent↗

PubMed2000

Ifosfamide metabolism and DNA damage in tumour and peripheral blood lymphocytes of breast cancer patients.

PURPOSE: This study was designed to determine individual variation in the metabolism of ifosfamide (IF) and any influence this may have on the degree of DNA damage produced in both peripheral blood lymphocytes (PBL) and in tumour tissue. METHODS: The pharmacokinetics and metabolism of IF and also of doxorubicin (DOX) were determined in patients receiving IF/DOX neoadjuvant chemotherapy for the treatment of advanced breast cancer. The DNA-damaging effects of this regimen were measured using the comet assay in PBL and in breast tumour tissue obtained by fine needle aspirate. Parallel in vitro studies were carried out in order to establish if DNA damage caused by IF metabolites or DOX was predictive of cytotoxicity in breast cancer cell lines. RESULTS: The median AUC, half-life and clearance of IF were found to be 291 microM.min, 5.2 h and 66 ml/min per m2, respectively. A high degree of interpatient variability (up to sevenfold) was observed in the metabolism of both IF and DOX and also in their metabolites. Treatment-related changes in the amount of DNA damage were observed in both PBL and tumour cells. That in PBL peaked 48 h after the end of IF infusion (median 17% damaged cells at 48 h compared to 4% damaged before treatment). DNA damage in tumour cells was not elevated above low pretreatment values (median 1.5% damaged cells) until 3 weeks after IF and DOX treatment (median 30% damaged cells), by which time damage in PBL showed almost complete resolution to basal levels. The DNA damage in PBL determined 24 h after the start of chemotherapy was found to be related to the AUC of 4-hydroxyifosfamide (4OHI; P = 0.05). The amount of damage in either tissue did not significantly correlate with clinical response or toxicity, but lower amounts of damage were observed in the tumour cells 3 weeks after treatment in those patients that subsequently relapsed, compared to those that remained disease free. DNA damage (more than 20% damaged cells) was observed after exposure to active IF metabolites at concentrations equal to or greater than the IC50 in MCF-7 and MDA-MB231 cell lines. At concentrations of 4OHI similar to those determined in vivo, an equivalent level of DNA damage was observed in PBL and in cell lines and was associated with significant growth inhibition. DNA damage induced by DOX was not predictive of cytotoxicity. CONCLUSION: Systemic DNA damage appeared to be related to levels of the active metabolite, consistent with the results of in vitro investigations of DNA damage. Further studies are warranted to substantiate this observation and to explore the relationship between metabolism, DNA damage and antitumour activity.

Adult↗

PubMed2000

Should the treatment of schizophrenia include old antipsychotic drugs?

Clozapine, although not suitable as a first-line drug, is superior to all other antipsychotics in terms of minimizing positive symptoms, reducing side effects, and treating treatment-resistant patients. There is little evidence that other newer drugs share these benefits. For certain patients it is not difficult to justify, on clinical grounds, the additional cost of prescribing clozapine. The case for prescribing one of the other newer drugs in preference to a traditional antipsychotic is often less clear-cut. Traditional antipsychotics clearly still have a role in the treatment of schizophrenia and they remain the authors' preferred choice of first-line therapy.

Antipsychotic Agents↗

PubMed2000

Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study.

BACKGROUND: Studies of groups of individuals who have a genetically high risk of developing schizophrenia, have found neuropsychological impairments that highlight likely trait markers of the schizophrenic genotype. This paper describes the change in neuropsychological function and associations with psychiatric state of high risk participants during the first two assessments of the Edinburgh High Risk Study. METHODS: Seventy-eight high risk participants and 22 normal controls, age and sex matched completed two neuropsychological assessments 18 months to 2 years apart. The areas of function assessed include intellectual function, executive function, learning and memory, and verbal ability and language. RESULTS: The high risk participants performed significantly worse on particular tests of verbal memory and executive function over the two assessments than matched controls. Those high risk participants who experienced psychotic symptoms were found to exhibit a decline in IQ and perform worse on tests of verbal memory and executive function than those without symptoms. An increase in psychotic symptoms between the two assessments in the high risk group was found to be associated with an apparent decline in IQ and memory. CONCLUSIONS: The results suggest that the development of psychotic symptoms is preceded by a decline in IQ and memory. This may reflect a general and a more specific disease process respectively.

Adolescent↗

PubMed2000

Differences between patients with schizophrenia within and without a high security psychiatric hospital.

OBJECTIVE: To report and discuss differences between schizophrenic patients in the community and those in maximum security care. METHOD: Comparison of 193 community schizophrenic patients with 169 in high security care. Data included case notes, interviews and cognitive tests. RESULTS: Compared to high security patients, community patients tended to be female and married. They had higher school achievement, higher premorbid IQ and better occupational levels, were less likely to have a family history of alcohol abuse, to have had police contact and to have attempted suicide. They had more frequent shorter psychiatric admissions and fewer current and lifetime schizophrenic symptoms. Logistic regression models discriminated the groups with considerable accuracy. CONCLUSION: Patients needing high security care may be recognizable when schizophrenia is first diagnosed. Progression to the State Hospital seems to result from schizophrenia together with other factors such as deprivation rather than from a worse schizophrenic process per se.

Adult↗

PubMed2000

Predictors of admission to a high-security hospital of people with intellectual disability with and without schizophrenia.

Admission to secure hospital facilities is a rare outcome for people with intellectual disability with or without concomitant psychosis. The present study compares people with mild intellectual disability with and without schizophrenia resident in the Scottish and Northern Irish State Hospital, Carstairs, to matched mild intellectual disability controls, also with and without schizophrenia, in the community. It is hoped that this study may identify socio-demographic, clinical or historical predictors which may lead to admission to secure hospital facilities for people with mild intellectual disability. One hundred and eight subjects were identified from two previous studies which concerned State Hospital patients and patients with intellectual disability with and without schizophrenia. Four experimental groups were derived: (1) 14 individuals with comorbid intellectual disability and schizophrenia who had been resident in the State Hospital; (2) 34 comorbid community control subjects; (3) 33 individuals with intellectual disability and no psychosis who had been resident in the State Hospital; and (4) 27 community control subjects with mild intellectual disability. The four groups were compared on a range of socio-demographic, historical and clinical variables obtained from case records and subject interviews. Relative to community controls, people with intellectual disability and no psychosis in the State Hospital are likely to be single, to have a later age of first psychiatric hospital admission, and to have a history of previous suicide attempts, alcohol abuse or drug misuse. Subjects with comorbid intellectual disability and schizophrenia in the State Hospital are more likely to be male, to have an early age of first psychiatric admission, and to have no family history of either schizophrenia or intellectual disability. Strategies aimed at addressing suicidal behaviour, alcohol and drug misuse amongst people with intellectual disability may facilitate a reduction in the number of admissions to high-security hospitals in the UK. In people with comorbid intellectual disability and schizophrenia, males with an early age of onset and no known family history are more likely to require care and treatment in a secure psychiatric setting. Such comorbid subjects may be suffering from a particular malignant form of schizophrenia, manifesting in childhood as cognitive impairment prior to the early onset of psychosis in teenage years.

Adolescent↗

PubMed1999

Neuroanatomy of comorbid schizophrenia and learning disability: a controlled study.

BACKGROUND: Reasons for the higher frequency of schizophrenia in learning-disabled populations are uncertain. We investigated the neuroanatomical basis for this phenomenon by structural magnetic resonance imaging (MRI) in patients with learning disability and schizophrenia, learning-disabled patients, and patients with schizophrenia. METHODS: Age-matched and sex-matched patients with learning disability (20 cases), schizophrenia (25), and both disorders (23) underwent MRI scans of the brain. Whole brain areas and specific regions of interest were examined. 29 normal controls were also scanned. FINDINGS: The scans of the group with both disorders were closely similar to those of the schizophrenic group, in terms of both general structures and the structure of the amygdala-hippocampus. However, the amygdala-hippocampus was significantly smaller on both sides than that of normal controls (left 4.1 vs 4.5 cm3, p=0.011; right 4.2 vs 4.99 cm3, p<0.0001). The brains of learning-disabled patients were generally smaller than those of the other three groups, but the amygdalohippocampal complexes were larger. INTERPRETATION: In terms of brain structure, patients with comorbid learning disability and schizophrenia resemble patients with schizophrenia and not those with learning disability. We suggest that the higher frequency of schizophrenia in learning-disabled patients is due to a greater tendency of schizophrenic patients to develop cognitive deficits, and that within the learning-disabled population there may be individuals whose deficits result from undiagnosed schizophrenia.

Adolescent↗

PubMed1999

Methodological issues in volumetric magnetic resonance imaging of the brain in the Edinburgh High Risk Project.

The Edinburgh High Risk Project is a longitudinal study of brain structure (and function) in subjects at high risk of developing schizophrenia in the next 5-10 years for genetic reasons. In this article we describe the methods of volumetric analysis of structural magnetic resonance images used in the study. We also consider potential sources of error in these methods: the validity of our image analysis techniques; inter- and intra-rater reliability; possible positional variation; and thresholding criteria used in separating brain from cerebro-spinal fluid (CSF). Investigation with a phantom test object (of similar imaging characteristics to the brain) provided evidence for the validity of our image acquisition and analysis techniques. Both inter- and intra-rater reliability were found to be good in whole brain measures but less so for smaller regions. There were no statistically significant differences in positioning across the three study groups (patients with schizophrenia, high risk subjects and normal volunteers). A new technique for thresholding MRI scans longitudinally is described (the 'rescale' method) and compared with our established method (thresholding by eye). Few differences between the two techniques were seen at 3- and 6-month follow-up. These findings demonstrate the validity and reliability of the structural MRI analysis techniques used in the Edinburgh High Risk Project, and highlight methodological issues of general concern in cross-sectional and longitudinal studies of brain structure in healthy control subjects and neuropsychiatric populations.

Adolescent↗

PubMed1999

Correlates of insight and insight change in schizophrenia.

Various theories have been proposed to account for poor insight in schizophrenia. This study examined the relationships between insight, mood, schizophrenic symptoms and cognitive functioning. The relationship between longitudinal changes in insight and changes in symptoms and mood was also investigated. One-hundred patients with DSM-III-R schizophrenia, recently recovered from a relapse of their illness, were rated on the Insight and Treatment Attitudes Questionnaire (ITAQ), the Positive and Negative Syndrome Scale (PANSS), the Montgomery Asberg Depression Rating Scale (MADRS), the Rivermead Behavioural Memory Test and tests of current and premorbid IQ. A random sample of 53 were then given an educational package (video and booklets) designed to improve their insight. Follow-up ratings on the ITAQ, PANSS and MADRS were subsequently obtained. At baseline, better insight was significantly correlated with lower mood and fewer positive symptoms. It was not related to cognitive functioning. Improvement in insight at follow up was related to worsening of mood, but not to change in positive symptoms. The results are consistent with the concept that poor insight, at least in part, results from the psychotic disease process itself. In addition, they suggest that poor insight may protect against depression in the early stages of recovery from schizophrenia.

Adolescent↗

PubMed1999

Magnetic resonance imaging of brain in people at high risk of developing schizophrenia.

BACKGROUND: Schizophrenia is a multifactorial disorder that is associated with disturbed cerebral development. Structural brain-imaging studies have consistently shown that the volumes of some parts of the brain, particularly the mesial temporal lobes, are smaller in patients with schizophrenia than in healthy people. Whether these abnormalities of brain structure predate the onset of symptoms is not known. METHODS: 100 people at high risk of developing schizophrenia (two or more first-degree or second-degree relatives affected), 20 patients in their first episode of schizophrenia, and 30 healthy controls underwent magnetic resonance imaging of the brain. The volumes of regions of interest were measured by standard techniques. FINDINGS: Mean whole-brain volume was 1356 cm3 (SD 178) in the first-episode group, 1347 cm3 (122) in the high-risk group, and 1334 cm3 (149) in the controls (p=0.8). The mean volume of the left amygdala-hippocampal complex (AHC) was lower in the first-episode group (4.3 cm3 [0.6]) than in the high-risk group (4.6 cm3 [0.6]), and in turn than in the controls (4.8 cm3 [0.7]); these differences were significant (p<0.05) both for absolute volumes and values adjusted for brain volume and other confounders. The right AHC showed a similar pattern (absolute volumes 4.5 cm3 [0.7], 4.8 cm3 [0.6], 4.9 cm3 [0.9], respectively). Both thalamic nuclei were significantly smaller in the high-risk group than in the control group. INTERPRETATION: People at high risk of developing schizophrenia for genetic reasons have several structural brain abnormalities that are similar to those in patients with the disorder. If at-risk individuals with particularly small AHC or thalami are most likely to develop schizophrenia, this feature might assist in early detection and treatment.

Adolescent↗

PubMed1999

Life events in suicide and undetermined death in south-east Scotland: a case-control study using the method of psychological autopsy.

BACKGROUND: Adverse life events have been associated with increased risk of suicide. Mental disorders are also major risk factors for suicide. Matching cases and controls for mental disorder is thus appropriate in studies of suicide. This procedure was used to study the degree to which excess adversity was more common in cases who committed suicide as opposed to living controls matched for mental disorder. METHODS: The study formed part of a retrospective case-control comparison of cases of suicide/undetermined death with living controls using psychological autopsy in south-east Scotland. Cases and controls were matched for age, sex and mental disorder. Informants were those closest to cases and controls. Cases and controls were assessed for life events using the Interview for Life Events. The subjects were 45 cases of suicide/undetermined death and 40 living controls. RESULTS: Cases and controls did not differ significantly in severity of mental disorder. Adverse interpersonal events within the family (P = 0.01) with an odds ratio (OR) of 9.0 (95% CI, 1.3-399) and adverse physical health-related events (OR 5.0, 95% CI 1.1-47, P = 0.04) were significantly more common in cases than controls. CONCLUSIONS: Cases had significantly more adverse life events than controls overall. The categories accounting for these differences were interpersonal family adversity and physical ill-health. There were no significant differences in either the number or severity of ongoing difficulties between cases and controls. Recent adverse life events contribute to the increased risk of suicide even when age, sex and mental disorder are controlled for. Future research should examine interactions between social support and acute and chronic adversity.

Adult↗

PubMed1999

Errorless learning and the cognitive rehabilitation of memory-impaired schizophrenic patients.

BACKGROUND: In recent years, evidence has accumulated that a significant proportion of schizophrenic patients have severe memory impairment, which cannot be attributed to the effects of medication, chronicity or institutionalization. Our group has demonstrated that memory impairment is associated with poor psychosocial outcome and treatment resistance. Work on the classical amnesic syndrome has suggested that memory training is facilitated by adopting an 'errorless learning' approach, where subjects do not experience failure during learning. This is based on the theory that the preserved implicit memory of amnesic patients results in implicitly remembered incorrect responses interfering with target items, in the absence of a functioning explicit memory system to allow differentiation. METHOD: We compared three groups of subjects, memory-impaired schizophrenic patients, memory unimpaired schizophrenic patients and healthy controls. RESULTS: An errorless learning approach conferred a significant advantage on the memory-impaired schizophrenic group, bringing their performance up to the level of both control groups. In contrast, adopting a traditional trial and error, or errorful approach resulted in markedly impaired performance in the memory-impaired schizophrenic group only. CONCLUSIONS: We conclude that errorless learning approaches may be worthy of further evaluation in the cognitive rehabilitation of memory-impaired schizophrenic patients.

Adult↗

PubMed1999

Neuropsychological assessment of young people at high genetic risk for developing schizophrenia compared with controls: preliminary findings of the Edinburgh High Risk Study (EHRS).

BACKGROUND: Finding risk indicators for schizophrenia among groups of individuals at high genetic risk for the disorder, has been the driving force of the high risk paradigm. The current study describes the preliminary results of a neuropsychological assessment battery conducted on the first 50% of subjects from the Edinburgh High Risk Study. METHODS: One hundred and four high risk subjects and 33 normal controls, age and sex matched, were given a neuropsychological assessment battery. The areas of function assessed and reported here include intellectual function, executive function, perceptual motor speed, mental control/ encoding, verbal ability and language, learning and memory measures, and handedness. RESULTS: The high risk subjects performed significantly more poorly than the control subjects in the following domains of neuropsychological function: intellectual function, executive function, mental control/encoding and learning, and memory. Controlling for IQ, high risk subjects made significantly more errors on the Hayling Sentence Completion Test (HSCT), took longer to complete section A of the HSCT, had lower scores on the delayed recall condition of the visual reproductions subtest of the Wechsler Memory Scale-Revised, and had significantly poorer Rivermead Behavioural Memory Test (RBMT) standardized scores. The presence of significant group by IQ interactions for the RBMT and time to complete section A of the HSCT suggested that differences among the groups were more marked in the lower IQ range. Performance on the HSCT was found to be related to the degree of family history of schizophrenia. CONCLUSIONS: High risk subjects performed more poorly than controls on all tests of intellectual function and on aspects of executive function and memory.

Adult↗

PubMed1999

Suicide and undetermined death in south east Scotland. A case-control study using the psychological autopsy method.

BACKGROUND: Mental disorders are major risk factors for suicide. Not all those who suffer from mental disorders kill themselves. Additional information is required to differentiate higher and lesser risk patients. METHODS: Retrospective case-control comparison was made of cases of suicide/undetermined death with living controls using psychological autopsy in South East Scotland. Cases and controls were matched for age, sex and mental disorder. Informants were those closest to cases and controls. The subjects were 45 cases of suicide/undetermined death and 40 living controls. RESULTS: Cases and controls did not differ significantly in severity of mental disorder. The main factors independently associated with undetermined death or suicide were: a history of deliberate self-harm (adjusted OR 4 1); physical ill health (adjusted OR 7.8); and engagement by mental health services (adjusted OR 0.01). Other antecedents associated with increased risk (criminal record, police involvement, financial problems and failure to vote) and those associated with decreased risk (contact with a doctor and in-patient care) did not exert effects after controlling for confounding. CONCLUSIONS: Controls were receiving more care of whatever kind. Treatment of mental disorder comorbid with physical illness and a history of deliberate self-harm may be especially important. Factors that separate those with mental disorder at high risk from those at lesser risk relate to care levels provided, which may be a function of engagement by and with health services. The role of mental health professionals is beneficial in suicide prevention. The focusing of that role towards engaging alienated or 'difficult' patients should be addressed.

Adult↗

PubMed1999

Criminality and antisocial behaviour in unselected men with sex chromosome abnormalities.

BACKGROUND: Previous studies on male patients with sex chromosome abnormalities (SCA), namely XYY and XXY, suggest that such patients commit criminal acts more frequently than expected. Most of these studies are affected by ascertainment bias. METHODS: Using a population-based sample of men with SCA, identified by screening 34380 infants at birth between 1967 and 1979, comparison between 16 XYY men, 13 XXY men and 45 controls were made in terms of frequency of antisocial personality disorder (APD) using the Schedule for Affective Disorders and Schizophrenia lifetime version. Rates of criminal convictions were examined in 17 XYY men, 17 XXY men and 60 controls. RESULTS: XYY males showed a significantly higher frequency of antisocial behaviour in adolescence and adulthood and of criminal convictions than the controls, but multiple regression analysis showed this to be mediated mainly through lowered intelligence. Property offences constituted the majority of offences in all groups. The XXY men did not show an increased rate of criminal convictions. It is possible that this apparently negative result relates to the relatively small numbers of cases and hence low power of this study. CONCLUSIONS: The findings of this study carry the advantage of not being affected by ascertainment bias and the disadvantage of having low power. It provides evidence for a slightly increased liability to antisocial behaviour in XYY men.

Adolescent↗

PubMed1999

Group psychological treatment for chest pain with normal coronary arteries.

We used a psychological treatment package (education, relaxation, breathing training, graded exposure to activity and exercise, and challenging automatic thoughts about heart disease) to treat 60 patients who had continuing chest pain despite cardiological reassurance following haemodynamically normal angiography. The treatment was delivered in six sessions over eight weeks to groups of up to six patients. The patients kept daily records of chest pain episode frequency and nitrate use. Questionnaires were used to assess anxiety, depression and disability. Exercise tolerance was tested by treadmill electrocardiography, with capnographic assessment of hyperventilation. The results were compared with waiting-list controls. Treatment significantly reduced chest pain episodes (p < 0.01) from median 6.5 to 2.5 per week. There were significant improvements in anxiety and depression scores (p < 0.05), disability rating (p < 0.0001) and exercise tolerance (p < 0.05), and these were maintained at six month follow-up. Treatment reduced the prevalence of hyperventilation from 54% to 34% (p < 0.01) but not the prevalence of ECG-positive exercise tests. Patients continuing to attribute their pain to heart disease had poorer outcomes. Group psychological treatment for non-cardiac chest pain is feasible, reduces pain, psychological morbidity and disability, and improves exercise tolerance.

Breathing Exercises↗

PubMed1999

Volumetric magnetic resonance imaging study of the brain in subjects with sex chromosome aneuploidies.

OBJECTIVES: Cognitive impairment has been reported in people with sex chromosome aneuploides (SCAs) and it has been proposed that the presence of an extra sex chromosome may have an adverse effect on neurodevelopment. This study examines the hypothesis with structural MRI of the brain. METHODS: Thirty two subjects with SCA (XXX (n=12), XYY (n=10), and XXY (n=10)) from a birth cohort study were matched groupwise for age, parental social class, and height with normal controls (13 female, 26 male). Brain MRI, measurements of IQ, and a structured psychiatric interview were performed. RESULTS: The XXX females and XXY males had significantly smaller whole brain volumes than controls of the same phenotypic sex (p=0.003 and p</=0.05 respectively). The XXY group also had bilaterally enlarged lateral ventricles (p</=0.05). No significant differences were found between the XYY group and controls. IQ scores in all SCA groups were lower than in the control groups. CONCLUSIONS: The main result of reduced brain volumes in XXX and XXY subjects, but not in XYY subjects, indicates that the presence of a supernumerary X chromosome has a demonstrable effect on brain development.

Adolescent↗

PubMed1999

Does a four-week delay in the introduction of medication alter the course of functional psychosis?

This study is an analysis of findings of a follow-up study of 105 patients with functional psychotic illness who had participated in a random and blind 4-week trial of pimozide, lithium, both and placebo. The intention was to examine the question of whether a 4-week delay in initiating antipsychotic treatment has a detrimental effect 2.5 years later. Detailed follow-up measures included need for care over the 2.5 years, treatments required, occupational decline, police contact, substance misuse, psychopathology and cognitive function. There was no evidence at all that those initially randomized to placebo had a poorer outcome in terms of any of these variables. It is concluded that a 4-week delay in initiating active treatment in patients with functional psychosis has no long-term adverse effects.

Adolescent↗