Biomedical subjects

Eve C Johnstone

Publications and source records attributed to Eve C Johnstone.

9 recordsLinked to original sources

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↗

PubMed2003

Neuropsychology, genetic liability, and psychotic symptoms in those at high risk of schizophrenia.

Neuropsychological assessments were compared among individuals at enhanced genetic risk of schizophrenia (n = 157) and controls (n = 34). The relationship between cognitive impairments and the presence of psychotic symptoms and measures of genetic risk was explored in the high-risk subjects. Neuropsychological differences were identified in many areas of function and were not accounted for by the presence of psychotic symptoms. Genetic liability was not associated with neuropsychological performance or with psychotic symptoms, but exploratory analysis showed some tests were associated with both liability measures. These results suggest that what is inherited is not the disorder itself but a state of vulnerability manifested by neuropsychological impairment, occurring in many more individuals than are predicted to develop the disorder.

Adolescent↗

PubMed2002

What does the Edinburgh high-risk study tell us about schizophrenia?

The Edinburgh High Risk Study concerns 162 young people aged 16 to 25 at ascertainment who have at least two close relatives with schizophrenia. They are compared with two control groups (1) of age-matched well subjects and (2) of age-matched subjects with first schizophrenic episodes. The interim results show that schizophrenia has developed in 10 high-risk subjects and no controls and that all categories of psychopathology are more marked in the high-risk subjects. Psychopathology shows no relationships with measures of genetic liability. Neuropsychological measures are most impaired in the individuals with first-episode schizophrenia, with high-risk subjects performing better and well controls better still. The greater the genetic liability of the high-risk subjects, the poorer the neuropsychological performance. Neuropsychological impairments occurred in more high-risk subjects than are expected to develop schizophrenia. Structural brain scans show significant differences between those with first-episode schizophrenia, high-risk subjects, and well controls. Brain structure is related to genetic liability in that high-risk subjects with higher genetic liability have smaller right and left prefrontal lobes and smaller right and left thalami. In those high-risk subjects with two scans, there was a significantly greater reduction in temporal lobe size in those with psychotic symptoms than in those without. It is suggested that in high-risk subjects, the change from vulnerability to psychosis may be preceded by reduction in size and deteriorating function of the temporal lobe.

Adolescent↗

PubMed2002

Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations.

BACKGROUND: We used functional magnetic resonance imaging (fMRI) to investigate the frontotemporal disconnection hypothesis of schizophrenia. METHODS: Eight DSM-IV schizophrenia patients and 10 control subjects were studied with fMRI while they thought of the missing last word in 128 visually presented sentences. The fMRI data were analyzed comparing the effect of sentence completion (vs. rest) using a random effects analysis. RESULTS: There were no significant group differences in regional brain responses. Correlation coefficients between left temporal cortex (x = -54, y = -42, z = 3) and left dorsolateral prefrontal cortex (x = -39, y = 12, z = 24) were significantly lower in the schizophrenic group and were negatively correlated with the severity of auditory hallucinations. CONCLUSIONS: Previous demonstrations of hypofrontality in schizophrenia may reflect particular task requirements. Frontotemporal functional connectivity is reduced in schizophrenia and may be associated with auditory hallucinations.

Adult↗

PubMed2002

Temporal lobe volume changes in people at high risk of schizophrenia with psychotic symptoms.

BACKGROUND: Magnetic resonance imaging (MRI) has demonstrated abnormalities of brain structure, particularly of the temporal lobes, in schizophrenia. These are thought to be neurodevelopmental in origin, but when they become evident is unknown. AIMS: To determine if temporal lobe volumes reduce during the development of symptoms of schizophrenia in initially well people at high risk of this disorder. METHOD: A group of 66 people who had at least two first- or second-degree relatives with schizophrenia and a control group of 20 healthy people had a structural MRI scan of the whole brain which was repeated after approximately 2 years. Regions of interest, specifically the amygdala-hippocampus complex and the temporal lobes, were traced semi-automatically by three masked raters with good inter-and intrarater reliability. RESULTS: Regional brain volume changes over 2 years did not differ between high-risk and healthy participants. Within the high-risk group, the 19 people with psychotic symptoms (12 at first assessment) had a mean reduction of 2163 mm(3) in the right temporal lobe compared with 97 mm(3) in the 47 without symptoms (P=0.02). CONCLUSIONS: Our findings suggest that people at high risk of schizophrenia with psychotic symptoms show reductions in temporal lobe volumes.

Adult↗

PubMed2002

Schizotypal components in people at high risk of developing schizophrenia: early findings from the Edinburgh High-Risk Study.

BACKGROUND: The study of high-risk groups and the development of schizophrenia. AIMS: To investigate further schizotypy, measured by the Structured Interview for Schizotypy (SIS), and to examine relationships between schizotypal components, psychotic symptoms on the Present State Examination (PSE) and subsequent schizophrenia. METHOD: The SIS and PSE were administered on entry. Schizophrenia onsets were recorded during follow-up. RESULTS: The SIS yielded four principal components labelled social withdrawal, psychotic symptoms, socio-emotional dysfunction and odd behaviour. On entry, these differentiated between controls, subjects at risk for schizophrenia with and without symptoms and patients with schizophrenia. Seven of 78 subjects at risk developed schizophrenia within 39 months. This was best predicted by combining the four SIS components. CONCLUSIONS: Schizotypy is heterogeneous and may become psychosis, particularly if several of its components are present. As psychosis develops, odd behaviour gives way to psychotic symptoms and social function deteriorates.

Adolescent↗

PubMed2002

Distinguishing characteristics of subjects with good and poor early outcome in the Edinburgh High-Risk Study.

BACKGROUND: 'High-risk' studies of schizophrenia have the potential to clarify the pathogenesis of schizophrenia. Here, results of extreme outcome groups in the Edinburgh High-Risk Study are presented. AIMS: To compare groups of good and poor outcome from the Edinburgh High-Risk Study and clarify the nature of the change from the state of vulnerability to that of developing psychosis. METHOD: The recruitment procedure is described. Good and poor outcome are defined. These groups are compared in terms of genetic liability and of baseline and change in neuropsychology and neuroanatomy. RESULTS: Demographic characteristics and genetic liability do not differ between the groups. The good outcome group perform better at baseline in some neuropsychological tests, but there is little neuroanatomical difference. The poor outcome group show consistently impaired memory function and a tendency to reduction in temporal lobe size. CONCLUSIONS: In genetically predisposed subjects, the change from vulnerability to developing psychosis may be marked by a reduced size and impaired function of the temporal lobe.

Adolescent↗

PubMed2002

Structural gray matter differences between first-episode schizophrenics and normal controls using voxel-based morphometry.

The aim of this study was to compare the gray matter segments from T1 structural MR images of the brain in first-episode schizophrenic subjects (n = 34) and normal control subjects (n = 36) using automated voxel-based morphometry (VBM). This study is novel in that few studies have examined subjects in their first episode of schizophrenia. The subjects were recruited for the Edinburgh High Risk project and regional brain volumes were previously measured using a semi-automated volumetric region of interest (ROI) method of analysis. The primary interest was to compare the results from the compatible parts of the ROI study and the primary VBM approach. Our secondary interest was to compare the results of a study-specific template that was constructed from the control group to those using the generic T1 template (152 Montreal Neurological Institute brains) supplied with SPM99 (statistical parametric mapping). The images were processed and statistically analyzed using the SPM99 program. VBM analysis identified significant decreases in gray matter in the schizophrenics relative to the normal control group at the corrected voxel level (P < 0.05) in the right anterior cingulate, right medial frontal lobe, left middle temporal gyrus, left postcentral gyrus, and the left limbic lobe. There were no increases in gray matter in the schizophrenics relative to the control group. The construction of a customized template appeared to improve the detection of structural abnormalities. The analyses were subsequently restricted to voxels within the amygdala-hippocampal complex using the SPM small-volume correction. This identified gray matter decreases in the schizophrenics, at the corrected voxel level (P < 0.05), in the left and right uncus and parahippocampal gyri and the right amygdala. These results are compatible with and extend the relevant findings of the previous volumetric ROI analysis, when allowing for the differences between the methods and interpretation of their results.

Adult↗