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E C Johnstone

Publications and source records attributed to E C Johnstone.

At least 19 recordsLinked to original sources
PubMed2007

Association of the mu-opioid receptor gene with smoking cessation.

We investigated the association of the OPRM1 genotype with long-term smoking cessation and change in body mass index (BMI) following a smoking cessation attempt among smokers who attempted to quit using the nicotine replacement therapy (NRT) patch or placebo in a randomized controlled trial, and were followed-up over an 8-year period following their initial cessation attempt. We also investigated possible sex differences in these relationships, given evidence for sex differences in smoking cessation and central opioid mechanisms, as well as some evidence for sex differences in response to NRT. Our results indicate that OPRM1 genotype may moderate the effect of transdermal nicotine patch compared to placebo during active treatment, with a benefit of active NRT treatment evident in the OPRM1 AA genotype group only and those carrying one or more copies of the G allele demonstrating no benefit of active NRT versus placebo patch. Our results also indicate a sex difference in change in BMI at 8-year follow-up following a smoking cessation attempt, with ex-smokers demonstrating an increase in BMI, and this increase being greater in female subjects than in male subjects. We did not observe any association of OPRM1 genotype with change in BMI, although there was a trend for genotype to influence the observed sex difference in change in BMI over time. Future studies should attempt to replicate these findings, and investigate the relationship between both short- and long-term weight gain and smoking cessation and investigate possible mechanisms that may underlie these processes. Future studies should also investigate the role of OPRM1 genotype and smoking cessation on other appetitive and reward behaviours such as alcohol consumption.

Administration, Cutaneous↗
PubMed2005

Association between the DRD2 gene Taq1A (C32806T) polymorphism and alcohol consumption in social drinkers.

An association between the DRD2 Taq1A (C32806T) polymorphism and social alcohol consumption in the opposite direction to that reported for alcoholism has recently been reported in a male Finnish sample. We attempted to replicate these findings in two independent samples, and extend on previous work by including female participants. The DRD2 A1 allele was significantly associated with reduced alcohol consumption in sample one (P=0.004) and sample two (P=0.015). In sample two there was a significant genotype x sex interaction (P=0.016), with the association of the A1 allele and reduced alcohol consumption significant in men only. This interaction was marginally significant (P=0.042) in a meta-analysis of combined data from both samples, and the main effect of genotype highly significant (P<0.001). Age at time of data collection and cigarette consumption were entered as covariates in all analyses. These results replicate recent previous findings and suggest a possibility that this association may exist in men only, or be stronger in men.

Adult↗
PubMed2004

fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia.

Schizophrenia is a highly heritable disorder that typically develops in early adult life. Structural imaging studies have indicated that patients with the illness, and to some extent their unaffected relatives, have subtle deficits in several brain regions, including prefrontal and temporal lobes. It is, however, not known how this inherited vulnerability leads to psychosis. This study used a covert verbal initiation fMRI task previously shown to elicit frontal and temporal activity (the Hayling sentence completion task) to examine this issue. A large (n = 69) number of young participants at high risk of developing schizophrenia for genetic reasons took part, together with a matched group of healthy controls (n = 21). At the time of investigation, none had any psychotic disorder, but on detailed interview some of the high-risk participants (n = 27) reported isolated psychotic symptoms. The study aimed to determine: (i) whether there were activation differences that occurred in all subjects with a genetic risk of schizophrenia (i.e. 'trait' effects); and (ii) whether there were activation differences that only occurred in those at high risk who had isolated psychotic symptoms ('state' effects). No activation differences were found in regions commonly reported to be abnormal in the established illness, namely the dorsolateral prefrontal cortex or in the temporal lobes, but group differences of apparent genetic cause were evident in medial prefrontal, thalamic and cerebellar regions. In addition, differences in activation in those with symptoms were found in the intraparietal sulcus. No significant differences in performance were found between the groups, and all subjects were antipsychotic naïve. These findings therefore suggest that vulnerability to schizophrenia may be inherited as a disruption in a fronto-thalamic-cerebellar network, and the earliest changes specific to the psychotic state may be related to hyperactivation in the parietal lobe.

Adult↗
PubMed2003

Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study.

BACKGROUND: There is growing evidence that schizophrenia is a disorder of cortical connectivity. Specifically, frontotemporal and frontoparietal connections are thought to be functionally impaired. Diffusion tensor magnetic resonance imaging (DT-MRI) is a technique that has the potential to demonstrate structural disconnectivity in schizophrenia. AIMS: To investigate the structural integrity of frontotemporal and frontoparietal white matter tracts in schizophrenia. METHOD: Thirty patients with DSM-IV schizophrenia and thirty matched control subjects underwent DT-MRI and structural MRI. Fractional anisotropy - an index of the integrity of white matter tracts - was determined in the uncinate fasciculus, the anterior cingulum and the arcuate fasciculus and analysed using voxel-based morphometry. RESULTS: There was reduced fractional anisotropy in the left uncinate fasciculus and left arcuate fasciculus in patients with schizophrenia compared with controls. CONCLUSIONS: The findings of reduced white matter tract integrity in the left uncinate fasciculus and left arcuate fasciculus suggest that there is frontotemporal and frontoparietal structural disconnectivity in schizophrenia.

Anisotropy↗
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↗
PubMed2002

Maternal recall bias, obstetric history and schizophrenia.

BACKGROUND: This study sought to clarify the role of obstetric complications (OCs) and maternal recall bias for patients with first episodes of schizophrenia and those at increased risk of the disorder. METHOD: Subjects at high risk of schizophrenia were compared with people with first-episode schizophrenia and with healthy volunteers. Consenting mothers of subjects were interviewed using a standardised questionnaire for the recall of OCs, and OCs were also measured from records collected at the time of pregnancy and delivery. RESULTS: High-risk subjects and first-episode patients had higher rates of OCs recalled by their mother than controls, but hospital records showed no differences in OCs between groups. The number of OCs recalled by mothers of the high-risk group was not related to whether the mother had schizophrenia or not, but was related to the maternally rated abnormal childhood behaviour as measured by the Child Behaviour Checklist. CONCLUSIONS: These results suggest that studies that rely on maternal recall alone are susceptible to bias. The excess of OCs recalled by the mother could be related to abnormal behaviour in their child rather than maternal illness, family history or psychotic symptoms.

Adolescent↗
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

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

Diagnostic stability in subjects with multiple admissions for psychotic illness.

BACKGROUND: Although studies investigating changes in diagnosis between psychotic episodes have differed in design, some consistent findings have emerged. This study seeks to clarify and extend these findings by describing and comparing clinical and operationally defined diagnostic stability in a group of subjects with multiple episodes of functional psychotic illness. METHODS: The OPCRIT programme was applied to case notes of 204 subjects with multiple admissions for psychotic illness. Clinical and operationally defined diagnoses were compared and the spread and stability of diagnoses determined. RESULTS: An increase in the frequency of diagnosis of schizophrenia from initial to subsequent episodes was demonstrated. High levels of stability were found for schizophrenia (58 to 98%), moderate levels for affective disorders (24 to 83%), low levels for other non-organic psychotic conditions (27 to 54%) and atypical psychosis (27 to 53%), and very low levels for schizoaffective disorder (5 to 39%) and other conditions (0 to 4%). CONCLUSIONS: The stability levels for schizophrenia and affective disorders are adequate, but the low levels for a range of other psychotic conditions raise questions regarding their predictive validity.

Adult↗
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

A randomized, controlled trial of a brief interventional package for schizophrenic out-patients.

OBJECTIVE: To evaluate the impact on outcome of a simple educational intervention in schizophrenic patients at risk of relapse. METHOD: At discharge, 114 schizophrenic patients with at least one previous episode were assigned randomly to a simple educational intervention which had no resource implications, or standard care. RESULTS: The intervention failed to improve outcome. While insight and treatment attitudes improved, suicidal ideation increased. Systematic management of treatment-emergent adverse effects offered no benefits, although incapacitation from extrapyramidal side-effects at discharge predicted relapse. CONCLUSION: There are limits to which psychoeducational interventions can be simplified without loss of effectiveness in terms of relapse prevention in schizophrenia. Enhanced insight may be associated with increased suicidal ideation.

Adolescent↗
PubMed2001

Correlations between clinical and historical variables, and cerebral structural variables in people with mild intellectual disability and schizophrenia.

The increased prevalence of schizophrenia in the population with mildly intellectual disability (ID) remains unexplained. The present study explores several possibilities by examining historical/clinical findings in relation to structural neuroimaging findings in three groups: (1) comorbid mild ID and schizophrenia; (2) schizophrenia alone; and (3) mild ID alone. Information about clinical and historical variables was obtained from 101 subjects (39 with comorbidity, 34 with schizophrenia and 28 with mild ID), out of whom 68 (23, 25 and 20, respectively) had had a cerebral magnetic resonance imaging (MRI) scan. Although a number of significant correlations exist between clinical variables and structural MRI abnormalities in all three groups, no clearly predictive inter- or between-group differences emerged. More striking was the finding that showed small amygdalo-hippocampal size to be associated with a history of central nervous system injury, especially meningitis. These findings provide support for the view that cognitive impairment and comorbid psychosis can result from a common cause, such as meningitis or obstetric complications, possibly interacting with other factors, such as family history.

Adolescent↗
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↗