Longitudinal changes in hippocampal volume in the Edinburgh High Risk Study of Schizophrenia.

Schizophrenia is associated with structural brain abnormalities that are likely to be present before disease onset. It remains unclear to what extent these represent general vulnerability indicators or are associated with the developing clinical state itself. It also remains unclear whether such state or trait alterations may be evident at any given time-point, or whether they progress over time. To investigate this, structural brain scans were acquired at two time-points (mean scan-interval 1.87years) in a cohort of young unaffected individuals at high familial risk of schizophrenia (baseline, n=142; follow-up, n=64) and healthy controls (baseline, n=36; follow-up, n=18). Sub-cortical reconstructions of the hippocampus and amygdala were generated using the longitudinal pipeline available with Freesurfer. The high risk cohort was subdivided into individuals that remained well during the study (HR[well], baseline, n=68; follow-up, n=30), transient and/or partial symptoms that were insufficient to support a formal diagnosis (HR[symp], baseline, n=57; follow-up, n=26) and individuals that subsequently developed schizophrenia according to ICD-10 criteria (HR[ill], baseline, n=17; follow-up, n=8). Longitudinal change in the hippocampus and amygdala was compared, focusing first on overall differences between high-risk individuals and controls and then on sub-group differences within the high-risk cohort. We found a significantly altered developmental trajectory for all high risk individuals compared to controls, with controls showing a significant increase in hippocampal volume over time compared to those at high risk. We did not find evidence of altered longitudinal trajectories based on clinical outcome within the high risk cohort. These results suggest that an altered developmental trajectory of hippocampal volume is associated with a general familial predisposition to develop schizophrenia, as this alteration was not related to subsequent clinical outcome.

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.

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.

Expressed emotion and relapse.

The relatives of 82 patients in a study of first episodes of schizophrenia were interviewed within six weeks of the index admission; 77 patients were subsequently discharged, and were followed to relapse or readmission. Analysis of relapse-free survival time was used to examine whether the components of 'expressed emotion' predicted relapse or response to neuroleptic medication: 'critical comments' by relatives was the only component present often enough to be used and was inversely related to 'social contact'. When preadmission duration of illness, and neuroleptic medication following discharge (identified previously as significant predictors of outcome) were taken into account, neither 'critical comments' nor 'social contact' were related to outcome nor to response to medication. The constellation of factors suggested as pathogenic was present only in a minority of cases: many patients lived alone and of those that were with families, most were not in high face-to-face contact with other members. The failure of the components of 'expressed emotion' to predict outcome or response to neuroleptic medication suggests that at best, such factors are weak predictors of liability to relapse. Their influence is unlikely to be comparable in magnitude to that of neuroleptic medication.