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Biomedical subjects

Stephen M Lawrie

Publications and source records attributed to Stephen M Lawrie.

At least 37 records · Page 2Linked to original sources
PubMed2005

Functional disconnectivity in subjects at high genetic risk of schizophrenia.

Schizophrenia is a highly heritable psychotic disorder. It has been suggested that deficits of the established state arise from abnormal interactions between brain regions. We sought to examine whether such connectivity abnormalities would be present in subjects at high genetic risk for the disorder. Functional connectivity analysis was carried out on functional MRI images from 21 controls and 69 high risk subjects performing the Hayling sentence completion task; 27 high risk subjects reported isolated psychotic symptoms, the remaining high risk subjects and controls did not. There were no significant differences in task performance between the groups. Based on previous findings we hypothesized: (i) state-related differences in connectivity between dorsolateral prefrontal cortex and lateral temporal lobe; (ii) genetically mediated reductions in a medial prefrontal-thalamic-cerebellar network; and (iii) increased prefrontal-parietal connectivity in high risk subjects (to a greater extent in those with isolated psychotic symptoms). Connectivity analysis was performed in two ways: with and without variance associated with task effects modelled and removed from the data. We did not find evidence to support our first hypothesis with either analysis method. However, consistent with hypothesis (ii), decreased connectivity between right medial prefrontal regions and contralateral cerebellum was found. This was only statistically significant in the analysis with task effects modelled and removed from the data. Finally, consistent with hypothesis (iii), increased connectivity between the left parietal and left prefrontal regions in high risk subjects was found in both analyses. These results, all in a situation uncontaminated by the effects of anti-psychotic medication, performance differences and prolonged illness, suggest there are abnormalities in functional connectivity over and above those attributable to task effects in high risk subjects. These connectivity abnormalities may underlie the diverse deficits seen in the established condition and the more subtle deficits seen in close relatives of those with the disorder.

Adolescent↗
PubMed2005

Grey matter changes over time in high risk subjects developing schizophrenia.

Schizophrenia affects approximately 1% of the population and is associated with reductions in brain volume, but when these are first evident is unknown. Magnetic resonance imaging (MRI) has demonstrated abnormalities of brain structure, particularly of the temporal lobes, in schizophrenia. A study of brain structure in individuals destined to develop schizophrenia, before they do so, is crucial to understanding the illness. We used Voxel Based Morphometry (VBM) to map changes in Grey Matter Density (GMD) in 65 young adults at high risk of schizophrenia, for familial reasons, and 19 healthy young adults, over a period of approximately 2 years. All subjects were anti-psychotic naive at both scans. No increases in GMD were found in any of the groups. Within the high-risk group significant declines in GMD were found in the temporal lobes, the right frontal lobe and right parietal lobe. In the control group a decline was found in the right gyrus rectus. No significant differences over time were found between any of the groups. Those individuals at high risk who had transient or isolated psychotic symptoms showed a different spatial pattern of reductions in GMD than those who did not in within group comparisons. In addition, those individuals at high risk who later developed schizophrenia also showed a different spatial pattern of reductions in GMD in the left temporal lobe and right cerebellum, from 2 to 3 years before they were diagnosed. These particular reductions may therefore be able to predict the later onset of schizophrenia.

Adult↗
PubMed2005

Symptomatology and social inference: a theory of mind study of schizophrenia and psychotic affective disorder.

INTRODUCTION: There is evidence that certain patients with schizophrenia have deficits in theory of mind (ToM) capabilities. It is, however, unclear whether these are symptom or diagnosis-specific. METHODS: A ToM hinting task was given to 15 patients with a DSM-IV diagnosis of schizophrenia, 15 patients with affective disorder and 15 healthy controls. Severity of the current psychopathology was measured using the Krawiecka standardised scale of psychotic symptoms (Krawiecka, Goldberg, & Vaughan, 1977); IQ was estimated via the Ammons and Ammons Quick Test (Ammons & Ammons, 1962). RESULTS: The group with schizophrenia performed significantly worse than the affective and control groups. Poor performance on the hinting task was found to be significantly related to the presence of positive symptoms (instead of negative ones) and specifically related to delusions and hallucinations. These findings remained when covariance for potentially confounding variables was applied. CONCLUSIONS: Individuals with high levels of delusions and hallucinations performed significantly worse on this ToM task, regardless of diagnosis, implying ToM impairment is not exclusive to schizophrenia but is evident in other forms of psychosis. Between-group analyses showed the schizophrenia group had a significantly poorer performance on this task than the others.

Journal Article↗
PubMed2005

Cannabis as a risk factor for psychosis: systematic review.

Various lines of evidence suggest an association between cannabis and psychosis. Five years ago, the only significant case-control study addressing this question was the Swedish Conscript Cohort. Within the last few years, other studies have emerged, allowing the evidence for cannabis as a risk factor to be more systematically reviewed and assessed. Using specific search criteria on Embase, PsychINFO and Medline, all studies examining cannabis as an independent risk factor for schizophrenia, psychosis or psychotic symptoms, published between January 1966 and January 2004, were examined. Additional studies were also reviewed from references found in retrieved articles, reviews, and a cited reference search (ISI-Web of Science). Studies selected for meta-analysis included: (i) case-control studies where exposure to cannabis preceded the onset of schizophrenia or schizophrenia-like psychosis and (ii) cohort studies of healthy individuals recruited before the median age of illness onset, with cannabis exposure determined prospectively and blind to eventual diagnosis. Studies of psychotic symptoms were also tabulated for further discussion. Eleven studies were identified examining the relationship between cannabis use and psychosis. Seven were included in the meta-analysis, with a derived odds ratio (fixed effects) of 2-9 (95 % confidence interval = 2.4-3.6). No evidence of publication bias or heterogeneity was found. Early use of cannabis did appear to increase the risk of psychosis. For psychotic symptoms, a dose-related effect of cannabis use was seen, with vulnerable groups including individuals who used cannabis during adolescence, those who had previously experienced psychotic symptoms, and those at high genetic risk of developing schizophrenia. In conclusion, the available evidence supports the hypothesis that cannabis is an independent risk factor, both for psychosis and the development of psychotic symptoms. Addressing cannabis use, particularly in vulnerable populations, is likely to have beneficial effects on psychiatric morbidity.

Adolescent↗
PubMed2005

Neural correlates of enhanced genetic risk for schizophrenia.

Schizophrenia is a disabling psychotic disorder characterized by hallucinations, delusions, and impaired functioning in many aspects of everyday life. The established condition generally becomes manifest in early adulthood, and evidence suggests that one of the most important risk factors for developing the disorder is inherited vulnerability. The established illness has been shown to be associated with deficits in many domains of cognitive function, along with structural and functional brain abnormalities, most notably in pre-frontal and temporal lobes. However, such studies have not been able to determine the extent to which such deficits relate to the presence of a schizophrenic predisposition, the presence of symptoms, and/or medication effects. A number of research groups have therefore turned to the study of relatives of affected individuals with the aim of determining if similar cognitive deficits and brain abnormalities are also found in those with increased genetic vulnerability to the disorder. In this article, studies on such individuals are discussed. It is concluded that deficits are apparent in relatives that are similar to but less marked than those seen in patients with schizophrenia.

Animals↗
PubMed2005

Predicting schizophrenia: findings from the Edinburgh High-Risk Study.

BACKGROUND: The hypothesis that schizophrenia is neurodevelopmental was investigated in a prospective study of young people with a postulated 10-15% risk for the development of schizophrenia. AIMS: To determine premorbid variables distinguishing high-risk people who will go on to develop schizophrenia from those who will not. METHOD: A high-risk sample of 163 young adults with two relatives with schizophrenia was recruited. They and 36 controls were serially examined. Baseline measures were compared between those who did develop schizophrenia, a well control group, a well high-risk group and high-risk participants with partial or isolated psychotic symptoms. RESULTS: Of those at high risk, 20 developed schizophrenia within 2(1/2) years. More experienced isolated or partial psychotic symptoms. Those who developed schizophrenia differed from those who did not on social anxiety, withdrawal and other schizotypal features. The whole high-risk sample differed from the control group on developmental and neuropsychological variables. CONCLUSIONS: The genetic component of schizophrenia affects many more individuals than will develop the illness, and partial impairment can be found in them. Highly significant predictors of the development of schizophrenia are detectable years before onset.

Adolescent↗
PubMed2005

Neuropsychological impairments in people with schizophrenia or bipolar disorder and their unaffected relatives.

BACKGROUND: Neuropsychological abnormalities in schizophrenia are well replicated and are present in unaffected relatives. Cognitive findings in bipolar disorder are less clearly established. AIMS: To examine the possibility that these abnormalities may provide a means by which the disorders might be separated and to clarify the associations of phenotypic expression and genetic liability. METHOD: A neuropsychological test battery was administered to 50 control participants, 74 patients and 76 unaffected relatives recruited for the study. Patients included those with schizophrenia from families affected by schizophrenia alone, those with bipolar disorder from families affected by bipolar disorder alone and those with bipolar disorder from families affected by both disorders. Unaffected relatives were also recruited. RESULTS: Current, verbal and premorbid IQ were impaired in people with schizophrenia and in their close relatives. Memory was impaired in all patient and relative groups. Psychomotor performance and performance IQ were impaired in patients, regardless of diagnosis. CONCLUSIONS: This study finds evidence that intellectual abnormalities are related to a genetic liability to schizophrenia. Abnormalities of memory appear to be related to an increased liability to psychosis in general. No impairment was specific to bipolar disorder.

Analysis of Variance↗
PubMed2005

Pathogenesis of schizophrenia: a psychopathological perspective.

BACKGROUND: Despite interest in early treatment of schizophrenia, premorbid and prodromal symptomatology remain poorly delineated. AIMS: To compare pre-illness symptomatology in patients at high risk of schizophrenia who progress to illness with that of high-risk subjects who remain well and with normal controls. METHOD: Using Present State Examination (PSE) data, symptomatic scales were devised from participants of the Northwick Park Study of first-episode schizophrenia and scores were compared on the first and last PSEs of participants of the Edinburgh High Risk Study. RESULTS: At entry, when still well, high-risk individuals who subsequently became ill (mean time to diagnosis 929 days; s.e.=138 days) scored significantly higher on'situational anxiety', 'nervous tension', 'depression', 'changed perception'and 'hallucinations'than those remaining well and normal controls, who did not differ. With illness onset, affective symptomatology remained high but essentially stable. CONCLUSIONS: In genetically predisposed individuals, affective and perceptual disorders are prominent before any behavioural or subjective change that usually characterises the shift to schizophrenic prodrome or active illness.

Adolescent↗
PubMed2004

Voxel-based morphometry of patients with schizophrenia or bipolar disorder and their unaffected relatives.

BACKGROUND: Structural brain abnormalities in schizophrenia are well replicated; many emerge before the onset of illness and are present in relatives who remain well. Structural changes in bipolar disorder are less clearly established. The possibility that structural abnormalities might provide a means by which the disorders might be separated is one that has attracted limited research effort. This study sought to examine these issues and clarify the associations of phenotypic expression and genetic liability. METHODS: Forty-nine control subjects, 71 patients, and 72 unaffected relatives were recruited for the study. Patients included those with schizophrenia from families affected by schizophrenia alone, those with bipolar disorder from families affected by bipolar disorder alone, and those with bipolar disorder from families affected by both bipolar disorder and schizophrenia. Unaffected relatives were recruited from the families of the three patient groups. Subjects underwent a magnetic resonance imaging scan of the brain, which was analyzed with a grey-matter-optimized, voxel-based morphometry technique. RESULTS: Compared with control subjects, all patient and relative groups showed evidence of reduced anterior thalamic gray matter. Reductions in middle prefrontal gyrus and dorsomedial thalamus were specific to participants with schizophrenia. CONCLUSIONS: Whereas prefrontal and dorsomedial thalamic gray matter reductions seem to be specific to schizophrenia, anterior thalamic reductions seem to be a marker of liability to psychosis in general. These results are discussed in the context of their functional role and in terms of their connections with other cortical and subcortical structures.

Adult↗
PubMed2004

Abnormal cortical folding in high-risk individuals: a predictor of the development of schizophrenia?

BACKGROUND: A number of studies have found localized differences in the appearance and extent of cortical folding between the brains of schizophrenic patients and healthy control subjects. This study aimed to determine whether, within individuals at genetic high risk for schizophrenia, there are pre-existing differences in gyral folding between those who subsequently develop the disease and those who remain unaffected. METHODS: Assessment was conducted on baseline magnetic resonance imaging scans of 30 young adults grouped into 14 who remained unaffected and 16 who subsequently developed schizophrenia. The gyrification index (GI), the ratio of the inner and outer cortical surface contours, was measured bilaterally on every second 1.88-mm image slice in four specifically defined lobar regions. Independent t tests and volume and genetic liability correlations were conducted for each region, followed by a post hoc examination. RESULTS: Right prefrontal lobe GI values were significantly increased in individuals who subsequently developed schizophrenia. Post hoc examination suggested that the areas of greatest increase lay anteriorly and laterally in Brodmann areas 9 and 10. Correlations with volume and analysis of covariance suggested some overlap between GI and volume measures. CONCLUSIONS: Differences in frontal lobe GI might reflect disturbed or abnormal connectivity predictive of subsequent schizophrenia.

Adolescent↗
PubMed2004

Measurement of lateral preferences and schizophrenia: results of the Edinburgh High-Risk Study and methodological issues.

The assessment and measurement of handedness has varied across studies, limiting the comparability of results. Data from the Edinburgh High Risk for Schizophrenia Study were analyzed to investigate the effect of different methods of assessment and scoring of hand preferences on the prevalence of handedness type and on between-group differences in handedness. Handedness was measured using both the Edinburgh Handedness Inventory and the Annett Handedness Scale in 143 subjects at high risk for schizophrenia, 31 control subjects, and 27 patients with a first episode of schizophrenia. Hand preferences were identified through demonstration of items and by verbal report. No group differences were found, although the prevalence of hand preferences changed substantially depending on the definition used. Significant correlations with socio-demographic factors were found in some instances, but these correlations depended on the definition of handedness. No sex differences were identified. The magnitude of group differences remained similar, although the prevalence of handedness types varied greatly with changes in definition of handedness. Care should be taken in correlation studies to avoid spurious relationships between handedness and other factors. To allow for comparability of results across studies, researchers should adopt a standard definition of handedness.

Adolescent↗
PubMed2004

Gyrification in first-episode schizophrenia: a morphometric study.

BACKGROUND: A number of studies have found localized differences in the appearance and extent of cortical folding between the brains of schizophrenic patients and healthy control subjects. This study aimed to determine whether there are differences in gyral folding in schizophrenia by conducting a detailed analysis of magnetic resonance images. METHODS: Thirty-four young adults in their first episode of schizophrenia and 36 age-matched, healthy control subjects were studied. The gyrification index (GI), the ratio of the inner and outer cortical surface contours, was measured bilaterally on every second 1.88-mm image slice in four specifically defined lobar regions. Independent t tests were conducted for each region, followed by post hoc analysis of variance testing for the effects of laterality. RESULTS: Gyrification index values between groups corresponded closely in the occipital and parietal regions but were significantly increased in the right temporal lobe of the schizophrenic patients. Calculating the GI by two different methods (used in previous studies) notably affected results. Gyrification index values were significantly lateralized in the frontal and temporal regions, with no group x side interactions. CONCLUSIONS: Differences in the temporal lobe GI of first-episode schizophrenic patients might reflect disturbed or abnormal connectivity. Further examination of specific sources of sulco-gyral difference in schizophrenia is required to clarify this.

Adolescent↗
PubMed2004

Voxel-based morphometry of comorbid schizophrenia and learning disability: analyses in normalized and native spaces using parametric and nonparametric statistical methods.

We employed voxel-based morphometry (VBM) to compare the distributions of grey matter found in structural magnetic resonance imaging (MRI) brain scans of patients with comorbid learning disability with schizophrenia, schizophrenia alone, learning disability alone, and normal controls. Our primary aim was to replicate a previous region of interest (ROI) finding that comorbids and schizophrenics belong to the same population. Nonparametric analysis in normalized space showed no significant differences in grey matter distribution between the comorbid and schizophrenia groups. Furthermore, this analysis showed significant grey matter reductions in the comorbid and schizophrenia groups when compared to the learning-disabled or the normal controls. Parametric analysis localized the significant grey matter reductions between the normal controls and the comorbid and schizophrenia groups to the prefrontal and temporal lobes. It also identified an area of increased grey matter, on the inferior aspect of the postcentral gyrus, in the learning-disabled alone compared to the other groups. Native space parametric and nonparametric analyses, based on modulation of the normalized scans, confirmed the similarity in grey matter distribution of the comorbid and schizophrenia groups. Results confirm the ROI finding that in native space the learning-disabled group possesses the least and normal controls the most grey matter for the cohort. An increase in the basal ganglia of patients with schizophrenia vs. the learning-disabled, probably attributable to antipsychotic medication, was identified in the native space analysis. The native space results did not however register statistically significant temporal lobe reductions found under normalized analysis between schizophrenics and normal controls. This may be attributable to minor physical anomalies (MPA) in the schizophrenic cranium. Overall, these VBM results replicate previous ROI findings and are compatible with the view that comorbid learning disability with schizophrenia is a severe form of schizophrenia, rather than a consequence of learning disability. VBM has the facility to compare grey matter distributions in this structurally diverse cohort.

Adult↗
PubMed2004

Social cognition and face processing in schizophrenia.

Summary Studies of face processing have begun to elucidate the brain regions involved in social cognition, which include frontal and temporal regions known to be reduced in volume in schizophrenia. In this case-control study participants with schizophrenia (n=20) showed marked deficits in their ability to interpret social cues from faces, and those experiencing positive symptoms were impaired in recognising even basic facial emotions.

Adult↗
PubMed2003

Voxel-based morphometry of grey matter densities in subjects at high risk of schizophrenia.

The grey matter (GM) segments from T1 structural magnetic resonance (MR) images of the brain in subjects at high risk of schizophrenia (n=146) were compared with normal control subjects (n=36) and first episode schizophrenic subjects (n=34) using automated voxel-based morphometry (VBM). The subjects were recruited for the Edinburgh High Risk Study (EHRS) and regional brain volumes had previously been measured using a semi-automated volumetric region of interest (ROI) method of analysis. For the current report, the images were processed using a study specific template and statistically analysed using the SPM99 program. The small volume correction tool in SPM was also used to restrict the analyses to specific voxels. Reductions in the probability of grey matter (GM) density were seen bilaterally in the anterior cingulate, and as a trend in the left parahippocampal gyrus for the high-risk vs. control subjects. In contrast, first episode schizophrenia subjects had less GM than high-risk subjects in several frontal and temporal regions. These results are compatible with the findings of our previous volumetric ROI analysis.

Acute Disease↗
PubMed2003

Abnormal cerebral asymmetry and schizophrenia in a subject with Klinefelter's syndrome (XXY).

BACKGROUND: A high incidence of schizophrenia has been reported in individuals with sex chromosome aneuploides (SCAs), and extra-X aneuploidy appears to adversely affect neurodevelopment. We previously examined neurodevelopment in SCA subjects with structural magnetic resonance imaging (MRI) of the brain. We present an XXY subject who subsequently developed schizophrenia. Further examination of the MRI data was undertaken. METHODS: Graphs of MRI-determined regional brain to whole brain volume proportions and cerebral asymmetry indexes were generated for Klinefelter (n = 10) and male control subjects (n = 25) to allow inter-individual comparisons. RESULTS: The index case had reversed prefrontal and temporal lobe asymmetries, and these findings were more marked than in any other subject. CONCLUSIONS: It has been suggested that a genetic locus for schizophrenia may be found on the X chromosome and that the gene(s) concerned are implicated in the development of normal cerebral asymmetries. This case supports these arguments.

Adolescent↗
PubMed2003

Structural and functional abnormalities of the amygdala in schizophrenia.

Schizophrenia is characterized by delusions and hallucinations, which tend to respond to treatment with dopamine receptor blockers, and a loss of motivation and affect, which do not. Structural magnetic resonance imaging (sMRI) has convincingly demonstrated reduced volumes of the amygdala-hippocampal complex (AHC) and other limbic and paralimbic structures, on both manual tracing and automated analyses. The Edinburgh High-Risk Study (EHRS) of initially healthy adolescents with at least two affected relatives has found that AHC volumes are reduced pre-morbidly but not to schizophrenic levels, suggesting that further volume reductions may be associated with the onset of schizophrenia. AHC volumes appear to be genetically mediated in families with a dominant pattern of transmission, whereas prefrontal lobe and basal ganglia volumes are related to genetic liability to schizophrenia in the generality of high-risk subjects. Temporal lobe volumes may fall as psychotic symptoms develop, in the context of drug abuse and stress. Neuropsychological testing has also demonstrated pre-morbid impairments and symptom-related deterioration. More detailed analyses of the temporal lobe changes on sMRI and fronto-temporal dysconnectivity on fMRI are in progress. These findings are discussed with reference to other indications of pre-morbid developmental disturbance in our high-risk subjects, animal models of schizophrenia, and reliable findings from neuropathological, neuropsychological, and functional imaging studies of patients with schizophrenia.

Amygdala↗