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Of the few studies that have directly investigated the neuroanatomical correlates of delusions in patients with recent-onset schizophrenia, a number have paradoxically reported a positive correlation between delusion severity and regional grey matter volume. In order to explore this relationship, 31 patients with first-episode schizophrenia (FES) underwent a clinical interview and a T1-weighted structural MRI scan. Patients' scores on the Delusions subscale of the Positive and Negative Syndrome Scale were correlated with the volume of every voxel in their grey matter images in SPM99. Patients' delusion scores were found to correlate with the volume of a cluster of voxels located in the dorso-medial frontal cortex, centred on the medial frontal gyrus. Post-hoc analysis revealed that this 'region-of-correlation' was volumetrically reduced in the FES patients relative to a group of 21 matched healthy controls. The results of this study support the hypothesis that while a certain level of structural brain atrophy is necessary for delusion formation in patients with FES, excessive structural atrophy may in fact preclude the formation of highly systematized delusions.

Alzheimer's disease (AD) is associated with widespread brain atrophy including structures subserving memory. We applied an improved structural detection methodology to examine the less well known progression of atrophy in early-stage AD. We sought to i) longitudinally study volumetric differences in patients with early-stage AD and healthy volunteers; and ii) test the hypothesis that hippocampal volumes would be correlated with clinically relevant cognitive function. Seven patients and eleven healthy subjects underwent two structural MRI scans and neuropsychological assessments. Scans were normalised to a study-specific template and 'morphologically opened' to reduce tissue misclassification. Using brain-parcellation, patient atrophy was localised to left fusiform and parahippocampal gyri, whilst left hippocampal volumes were correlated with a cognitive performance measure. A whole-brain search methodology, showed that patients had reduced volumes including fronto-temporal regions bilaterally, in hippocampi and amygdalae and right cerebellum. Whole-brain correlational analyses revealed that cognitive performance was correlated with volumes of both hippocampi, superior temporal gyri and left insula. Neither group exhibited significant longitudinal volumetric changes. Utilising a novel methodology, we have shown that in early-stage AD, clinically relevant cognitive deficits are correlated with regionally specific grey-matter volumes, which are detectable at an early stage of the illness.

Previous functional neuroimaging studies of posttraumatic stress disorder (PTSD) have mainly focused on symptom-provocation paradigms in combat-related PTSD. We sought to elucidate the effect of non-combat-related PTSD on the physiology of social cognition. Thirteen patients with PTSD underwent functional magnetic resonance imaging (fMRI) while they engaged in tasks that (i) involve speculation on another's intention, (ii) invoke empathy and (iii) involve making judgments of the forgivability of others' actions; each versus ‘baseline’ social reasoning judgments. A post-therapy fMRI scan followed a course of modified cognitive behavioural therapy. Post-therapy, we found increased activation in brain regions predicted on the basis of foregoing work in healthy subjects. These included significant left middle temporal gyrus activation in post-therapy response to empathy judgments and posterior cingulate gyrus activation in post-therapy response to forgivability judgments. The specific regions of the human brain activated by empathy and forgivability judgments changed with symptom resolution in PTSD. Time and therapy are likely contributory factors that lead to a degree of ‘normalisation’ of the neural response to these social cognition tasks.

Several studies have investigated grey matter reductions in first episode schizophrenia (FES), but few have examined the relationship between grey matter reduction and clinical profile. A group of 31 patients with strictly defined FES and 30 healthy controls underwent T1-weighted magnetic resonance imaging (MRI) scan. Voxel-based morphometry in SPM99 was used to identify four distinct regions of grey matter reduction in the FES subjects. The regions of interest (ROIs) were in the left ventral prefrontal cortex (ROI 1), left parietal and temporal cortices (ROI 2), right cerebellum (ROI 3), and right frontal and parietal cortices (ROI 4). These regions of reduction were transformed into binary masks, which were convolved with patients' pre-processed grey matter images. Patients' grey matter volumes in these regions were correlated with their composite scores on the following three symptom dimensions: Psychomotor Poverty, Disorganization and Reality Distortion. The volumes of ROIs 1, 2 and 4 were found to be significantly correlated with the Reality Distortion syndrome score. Our findings indicate that distinct, widespread grey matter reductions are present very early in the course of schizophrenia. The results also suggest a possible structural underpinning for the abnormal brain activity typically associated with symptoms of Reality Distortion.