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Biomedical subjects

S M Lawrie

Publications and source records attributed to S M Lawrie.

At least 19 recordsLinked to original sources
PubMed2002

Childhood behaviour, psychotic symptoms and psychosis onset in young people at high risk of schizophrenia: early findings from the edinburgh high risk study.

BACKGROUND: Several studies suggest that many patients with schizophrenia have pre-morbid neurodevelopmental abnormalities. This study examines how behavioural abnormalities are associated with mild psychotic symptoms and later schizophrenic illness. METHODS: Maternal ratings on the Child Behavior Checklist (CBCL) of the early behaviour of 155 subjects were obtained at entry to the Edinburgh study of people at high risk of schizophrenia. These maternal ratings were compared in those with and without psychotic symptoms and used to predict the later onset of psychosis. RESULTS: The CBCL syndrome scores for the children prior to age 13 did not distinguish any of the study groups at entry to the study. In the ratings made for the subjects when aged from 13 to 16, delinquent behaviour and 'other problems' were weakly associated with these symptoms. However, with the exception of somatic symptoms and thought problems, the age 13-16 scales were significant predictors of later schizophrenic illness. This was true also for some of the ratings prior to age 13. CONCLUSIONS: Various behaviours, in particular, withdrawn and delinquent-aggressive behaviour in adolescents at risk of schizophrenia may predict later onset of the illness. These behaviours, however, are far less predictive of isolated psychotic symptoms prior to psychosis onset.

Adolescent↗
PubMed2002

Sustained attention in young people at high risk for schizophrenia.

BACKGROUND: Sustained attention has been found to be impaired in individuals suffering from schizophrenia and their close relatives. This has led to the hypothesis that impaired sustained attention is an indicator of vulnerability to schizophrenia. METHODS: The Edinburgh High Risk Study used the Continuous Performance Test-Identical Pairs version (CPT-IP) to assess sustained attention in 127 high risk participants, 30 controls and 15 first-episode schizophrenic patients. A second assessment was completed by 59 high risk and 18 control participants 18 months to 2 years after the first. RESULTS: No differences in attentional capacity were found between the high risk and control groups and there was no association between genetic liability to schizophrenia and poor performance on the CPT-IP. Additionally, no association between occurrence of psychotic symptoms in the high risk group and impaired attentional capacity was found. CONCLUSIONS: The results suggest that deficits in sustained attention are not indicative of a genetic vulnerability to schizophrenia, and are not associated with the occurrence of psychotic symptoms.

Adult↗
PubMed2002

Self-rated schizotypal cognitions, psychotic symptoms and the onset of schizophrenia in young people at high risk of schizophrenia.

OBJECTIVE: To examine the associations between the Rust Inventory of Schizotypal Cognitions (RISC) and psychotic symptoms measured by the Present State Examination (PSE) and to assess the predictive validity of the RISC for later onset of schizophrenia. METHOD: A total of 154 subjects at high risk for schizophrenia but who were currently well, 35 well controls and 28 first episode schizophrenic patients were assessed on specified PSE symptoms and completed the RISC. A subsample of the high risk group was subsequently monitored for onset of schizophrenia over 39 months. RESULTS: RISC scores at entry were significantly higher in subjects with psychotic symptoms on PSE. There were indications that high scorers on the RISC were likely to develop schizophrenia. However, less than half of those falling ill exhibited high RISC scores on entry. CONCLUSION: The RISC scale is highly associated with presence of psychotic symptoms on PSE and high scorers may be at increased risk of schizophrenia onset.

Adolescent↗
PubMed2002

Structural MRI of the brain in presumed carriers of genes for schizophrenia, their affected and unaffected siblings.

BACKGROUND: Schizophrenia is a highly heritable disorder associated with structural brain abnormalities. The aim of this study was to establish if the gene(s) for schizophrenia are associated with specific abnormalities of brain structure. SUBJECTS: Six sibships from multiple affected families were recruited. Each sibship consisted of one patient with schizophrenia, one "obligate carrier" without the disorder but with an affected child, and one "non-affected non-carrier". Such sibships are very rare, but present a powerful opportunity to separate the associations of genotype and phenotype. Obligates presumably have the gene(s) but not the disorder, affected siblings have both, whereas non-affected non-carrier siblings have neither. METHOD: Brain MRI was conducted with a semiautomated region of interest analysis. The risk of false positive findings was reduced by collapsing brain regions and sides into five regions and comparing groups by repeated measures analysis of variance. RESULTS: In terms of whole brain volumes and volumes of cortical structures, obligates resembled their non-affected non-carrier siblings, both groups having significantly greater volumes than their schizophrenic siblings (p=0.01 and p=0.04). Obligates also had significantly smaller ventricles than their schizophrenic siblings (p=0.03). However, with respect to the amygdalohippocampal complex, the obligates' brains resembled those of their schizophrenic siblings, both groups showing a significant reduction in volume when compared with their non-affected non-carrier siblings (p=0.001). CONCLUSIONS: In the families studied, reductions in volumes of cortical structures and reductions in whole brain volume seem to be associated with the phenotype of schizophrenia. By contrast, reduced volume of the amygdalohippocampal complex seems to be associated with genetic risk for the disorder even in the absence of disease.

Adult↗
PubMed2001

Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) in schizophrenic subjects and normal controls.

Several proton magnetic resonance spectroscopy (1H MRS) studies in schizophrenia have found reduced N-acetyl aspartate (NAA) concentrations in pre-frontal and temporal regions of the brain. Reductions in NAA may reflect abnormalities of neuronal structure (e.g. reduced neuronal density or viability) or abnormalities of neuronal function. Diffusion tensor imaging (DTI) measures diffusion anisotropy, an indicator of the structural integrity of a neuronal tract. Both techniques were used to examine the anatomical basis of pre-frontal dysfunction in schizophrenia. Ten patients with DSM-IV schizophrenia were compared with 10 healthy controls. 1H MRS and DTI were performed on a clinical MR system and analysed with a region of interest approach. NAA concentrations and diffusion anisotropy were measured in the same pre-frontal white matter region. Diffusion anisotropy was also measured in a control region (occipital white matter). 1H MRS revealed non-significant but consistently reduced NAA concentrations (by 10-15%) in the pre-frontal white matter in schizophrenic subjects. Diffusion anisotropy measures revealed no such differences between schizophrenics and controls. It is concluded that the abnormalities of 'connectivity' reported in brain-imaging studies of schizophrenia may not be attributable to structural abnormalities of white matter and that reduced NAA in the pre-frontal white matter may reflect abnormal function of structurally intact neurons.

Adult↗
PubMed2001

Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia.

BACKGROUND: Structural magnetic resonance imaging (MRI) of the brain in patients with schizophrenia has consistently demonstrated several abnormalities. These are thought to be neurodevelopmental in origin, as they have also been described in first episode cases, although there may be a progressive component. It is not known at which point in development these abnormalities are evident, nor to what extent they are genetically or environmentally mediated. METHODS: One hundred forty-seven high-risk subjects (with at least two affected first or second degree relatives), 34 patients in their first episode, and 36 healthy control subjects received an MRI scan covering the whole brain. After inhomogeneity correction, regions of interest were traced by three group-blind raters with good inter-rater reliability. Regional brain volumes were related to measures of genetic liability to schizophrenia and to psychotic symptoms elicited at structured psychiatric interviews. RESULTS: High-risk subjects had statistically significantly reduced mean volumes of the left and right amygdalo-hippocampus and thalamus, as compared to healthy control subjects. They also had bilaterally larger amygdalo-hippocampi and bilaterally smaller lenticular nuclei than the schizophrenics. High-risk subjects with symptoms had smaller brains than those without. The volumes of the prefrontal lobes and the thalamus were the only consistent associates of genetic liability. CONCLUSIONS: Subjects at high risk of developing schizophrenia have abnormalities of brain structure similar to but not identical to those found in schizophrenia. Our results suggest that some structural abnormalities are genetic trait or vulnerability markers, others are environmentally mediated, and that the development of symptoms is associated with a third overlapping group of structural changes. Particular risk factors for schizophrenia may interact at discrete time points of neurodevelopment with different effects on specific brain regions and may represent relatively distinct disease processes.

Amygdala↗
PubMed2001

Haloperidol versus placebo for schizophrenia.

BACKGROUND: Haloperidol was developed in the late 1950s for use in the field of analgesia. Research subsequently demonstrated effects on hallucinations, delusions, aggressiveness, impulsiveness and states of excitement and led to the introduction of haloperidol as an antipsychotic. OBJECTIVES: To evaluate the clinical effects of haloperidol for the management of schizophrenia and other similar serious mental illnesses compared to placebo. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1985-1998), CINAHL (1982-1998), The Cochrane Library (1998, Issue 4), The Cochrane Schizophrenia Group's Register (December 2000), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1998), and SCISEARCH (January 1974-December 1998) were undertaken. References of all identified studies were searched for further trial citations. Authors of trials and pharmaceutical companies were contacted for further information and archive material. SELECTION CRITERIA: All relevant randomised controlled trials comparing use of haloperidol (any dose) with placebo for those with schizophrenia or other similar serious, non-affective psychotic illnesses (however diagnosed). The main outcomes of interest were death, loss to follow up, clinical and social response, relapse and severity of adverse effects. DATA COLLECTION AND ANALYSIS: Reviewers evaluated data independently and analysed on an intention-to-treat basis, assuming that people who left the study early, or were lost to follow up, had no improvement. Where possible and appropriate, dichotomous data were analysed using relative risk (RR) and their 95% confidence intervals (CI) calculated. If appropriate, the number needed to treat (NNT) or number needed to harm (NNH) was estimated. For continuous data, weighted mean differences were calculated. Continuous data were excluded if loss to follow up was greater than 50%. All data were inspected for heterogeneity. MAIN RESULTS: Seventy-four trials were identified but only 20 included. More people allocated to haloperidol improved in the first six weeks of treatment than those given placebo (three trials, n=159, RR failing to produce a marked improvement 0.44 CI 0.3 to 0.6, NNT 3 CI 2 to 5). A further eight trials (n=313) also found a difference favouring haloperidol across the 6-24 week period (RR no marked global improvement 0.68 CI 0.6 to 0.8 NNT 3 CI 2.5 to 5) but this may be an overestimate of effect as small negative studies were not identified. About half of those entering studies failed to complete the short trials, although, at 0-6 weeks, 10 studies found a difference that favoured haloperidol (n=686, RR 0.82 CI 0.7 to 0.95, NNT 8 CI 5 to 17). Limited adverse effect data do, nevertheless, support the clinical impression that haloperidol is a potent cause of movement disorders, at least in the short term. Haloperidol promotes acute dystonia (three trials, n=135, RR 4.7 CI 1.7 to 44, NNH 5 CI 3 to 9 - not assuming those who left early from placebo suffered dystonis), akathisia (three trials, n=129, RR 6.5 CI 1.5 to 28, NNH 6 CI 4 to 14) and parkinsonism (four trials, n=165, RR 8.9 CI 2.6 to 31, NNH 3 CI 2 to 5). REVIEWER'S CONCLUSIONS: Haloperidol is a potent antipsychotic drug but with a high propensity to cause adverse effects. Given no choice of drug, use of haloperidol to counter the damaging and potentially dangerous consequences of untreated schizophrenia is justified. If a choice of drug is available, however, people with schizophrenia and clinicians may wish to start another antipsychotic with less likelihood of causing parkinsonism, akathisia and acute dystonias. For countries where haloperidol is not widely used, it should not be a control drug of choice for randomised trials of new antipsychotics.

Antipsychotic Agents↗
PubMed2001

Genetic liability, illicit drug use, life stress and psychotic symptoms: preliminary findings from the Edinburgh study of people at high risk for schizophrenia.

BACKGROUND: Studies of groups at high risk of developing schizophrenia have tended to be based on subjects recruited to the study in their infancy. This paper reports on subjects at genetic high risk for schizophrenia assessed as young adults, close to the age when most onsets of schizophrenia occur. METHODS: One hundred and fifty-five young people at elevated risk for the development of schizophrenia and 36 controls not at increased risk were assessed on entry to the Edinburgh High Risk Study. The measures included current psychotic symptoms, past and present cannabis and other drug use, lifetime life events and two aspects of genetic liability to schizophrenia. RESULTS: Cannabis and other illicit drug use were significantly associated with symptoms in both groups. The same held true for the more upsetting life events experienced, but not for less upsetting ones. Within the high-risk group, there was no relationship between symptoms and a measure of genetic loading, but there was some slight evidence of a higher risk of symptoms when affected relatives were on the father's rather than the mother's side of the family. CONCLUSIONS: Cannabis use, use of other illicit substances and upsetting life events may all lead to psychotic symptoms in vulnerable young people.

Adolescent↗
PubMed2001

A factor model of the functional psychoses and the relationship of factors to clinical variables and brain morphology.

BACKGROUND: Despite more than 100 years of study, there remains no definitive diagnostic validation of the functional psychoses. Factor analysis suggests the presence of three or more psychopathological syndromes in functional psychoses as a whole. The relationship between these factors and cerebral anatomy has been investigated in schizophrenia only. This study aimed to address the relationship of symptom factors to clinically important variables and cerebral anatomy in a sample of psychotic patients with a spread of diagnoses. METHODS: In a sample of patients with functional psychoses, symptom data was obtained on four consecutive admissions using the OPCRIT symptom checklist. OPCRIT data was used to generate operational diagnoses in accordance with pre-set criteria and a principle components analysis was performed on symptom data. Factor loadings were compared between each admission to examine factor stability over time. Factor scores at first admission were also correlated with clinical variables obtained from patients' case notes. From the sample of 204 patients, 64 subjects were recruited and underwent an MRI scan of the brain. Regional anatomical volumes were compared with diagnosis and factor loadings at first admission. RESULTS: A principal components analysis gave a four-factor solution of 'manic', 'depressive', 'disorganization' and 'reality distortion' factors at each admission. Factors showed a high degree of stability over the four admissions studied. The factors were significantly associated with several clinical variables. Three of the four factors were associated with a specific pattern of cerebral anatomy. CONCLUSIONS: This study suggests that factors may correspond to relatively specific disease processes underlying functional psychotic illness. We propose that the use of symptom factors may facilitate the investigation of the underlying mechanisms of psychotic illness.

Activities of Daily Living↗
PubMed2001

Neurodevelopmental indices and the development of psychotic symptoms in subjects at high risk of schizophrenia.

BACKGROUND: Neurological 'soft signs' and minor physical anomalies (MPAs) are reported to be more frequent in patients with schizophrenia than in controls. AIMS: To determine whether these disturbances are genetically mediated, and whether they are central to the genesis of symptoms or epiphenomena. METHOD: We obtained ratings in 152 individuals who were antipsychotic drug-free and at high risk, some of whom had experienced psychotic symptoms, as well as 30 first-episode patients and 35 healthy subjects. RESULTS: MPAs and Neurological Evaluation Scale (NES) 'sensory integration abnormalities' were more frequent in high-risk subjects than in healthy controls, but there were no reliable differences between high-risk subjects with and without psychotic symptoms. MPAs were most frequent in high-risk subjects with least genetic liability and NES scores showed no genetic associations. CONCLUSIONS: The lack of associations with psychotic symptoms and genetic liability to schizophrenia suggests that soft signs and physical anomalies are nonspecific markers of developmental deviance that are not mediated by the gene(s) for schizophrenia.

Abnormalities, Multiple↗
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

Depression after stroke and lesion location: a systematic review.

BACKGROUND: There is conflicting evidence on the hypothesis that the risk of depression after stroke is influenced by the location of the brain lesion. We undertook a systematic review to examine the hypotheses that depression is more commonly associated with left-hemisphere strokes than with right-hemisphere strokes and with lesions of the left anterior brain than with other regions. METHODS: We did a computer-aided search of MEDLINE, BIDS ISI, and PsychLit databases supplemented by hand searches of key journals. We included all reports on the association of depression after stroke with the location of the brain lesion. Studies were systematically and independently examined by two investigators. Fixed-effects and random-effects meta-analyses were done. FINDINGS: 143 reports were identified by the search strategy. 48 were eligible for inclusion. Not all reports included original data. Only two reports of original data supported the hypotheses and seven clearly did not. The pooled (random-effects) relative risk of depression after a left-hemisphere stroke, compared with a right-hemisphere stroke, was 0.95 (95% CI 0.83-1.10). For depression after a left anterior lesion compared with all other brain areas the pooled (random-effects) relative risk was 1-17 (0.87-1.62). Restriction of the analyses to reports from high-quality studies or major depressive disorder did not substantially affect the findings. Nor were they affected by stratification of the time between stroke and the assessment of depression. Multiple publications from the same samples of patients were apparent. INTERPRETATION: This systematic review offered no support for the hypothesis that the risk of depression after stroke is affected by the location of the brain lesion.

Aphasia↗
PubMed2000

The difference in patterns of motor and cognitive function in chronic fatigue syndrome and severe depressive illness.

BACKGROUND: Chronic fatigue syndrome (CFS) and major depressive disorder (MDD) share many symptoms and aetiological factors but may have different neurobiological underpinnings. We wished to determine the profile of the biological variables disturbed in CFS and MDD, and identify any critical factors that differentiate the disorders. METHODS: Thirty patients with CFS, 20 with MDD and 15 healthy controls matched group-wise for age and sex were recruited. Subjects were given a detailed battery of motor and cognitive tests, including measures of psychomotor speed, memory and maximal voluntary muscle contraction in both the morning and evening that were balanced to avoid order effects. RESULTS: CFS patients generally performed worse on cognitive tests than healthy controls, but better than patients with MDD. Both patient groups had markedly impaired motor function compared with healthy controls. MDD subjects showed a significantly greater diurnal improvement in maximal voluntary contraction than healthy controls. CONCLUSIONS: Patients with CFS and MDD show similarly substantial motor impairment, but cognitive deficits are generally more marked in MDD. Diurnal changes in some functions in MDD may differentiate the disorder from CFS.

Adult↗