Elvina M. Chu

Emotion processing and theory of mind in schizophrenia patients and their unaffected first-degree relatives

Previous studies have suggested that social cognition is affected in individuals with schizophrenia. The purpose of this study was to explore to what extent social cognition deficits are shared by unaffected first-degree relatives, and the nature of the relationship between performance in different paradigms of social cognition. 20 Schizophrenia patients (7 females, 31+/-10 years), 20 healthy age- and gender-matched individuals, 20 unaffected first-degree relatives of the schizophrenia patients (11 females, 50+/-20 years), and 20 healthy individuals matched for age and gender were recruited. Patients showed deficits in the detection of social Faux Pas (0.80+/-0.17 vs. controls: 0.94+/-0.09, p=0.025) and the correct identification of Theory of Mind stories (0.71+/-0.13 vs. controls: 0.82+/-0.12, p=0.038). Relatives performed poorly in the Faces Test (0.83+/-0.14 vs. controls: 0.9+/-0.08, p=0.048), the Reading the Mind in the Eyes Test (0.59+/-0.17 vs. controls: 0.71+/-0.14, p=0.046) and the detection of social Faux Pas (0.8+/-0.2 vs. controls: 0.93+/-0.09, p=0.024). Abnormalities were independent of age, years of education, and general cognitive performance in patients and their relatives. Performance in an Emotion Processing task (Faces Test) was correlated with performance in theory of mind tests in healthy individuals and relatives of patients with schizophrenia only. These results suggest that schizophrenia patients and their unaffected first-degree relatives display similar but nonidentical patterns of social cognition processing.

Changes in the Frontotemporal Cortex and Cognitive Correlates in First-Episode Psychosis

Background Loss of cortical volume in frontotemporal regions has been reported in patients with schizophrenia and their relatives. Cortical area and thickness are determined by different genetic processes, and measuring these parameters separately may clarify disturbances in corticogenesis relevant to schizophrenia. Our study also explored clinical and cognitive correlates of these parameters. Methods Thirty-seven patients with first-episode psychosis (34 schizophrenia, 3 schizoaffective disorder) and 38 healthy control subjects matched for age and sex took part in the study. Imaging was performed on an magnetic resonance imaging 1.5-T scanner. Area and thickness of the frontotemporal cortex were measured using a surface-based morphometry method (Freesurfer). All subjects underwent neuropsychologic testing that included measures of premorbid and current IQ, working and verbal memory, and executive function. Results Reductions in cortical area, more marked in the temporal cortex, were present in patients. Overall frontotemporal cortical thickness did not differ between groups, although regional thinning of the right superior temporal region was observed in patients. There was a significant association of both premorbid IQ and IQ at disease onset with area, but not thickness, of the frontotemporal cortex, and working memory span was associated with area of the frontal cortex. These associations remained significant when only patients with schizophrenia were considered. Conclusions Our results suggest an early disruption of corticogenesis in schizophrenia, although the effect of subsequent environmental factors cannot be excluded. In addition, cortical abnormalities are subject to regional variations and differ from those present in neurodegenerative diseases.

Heart rate variability response to mental arithmetic stress in patients with schizophrenia: Autonomic response to stress in schizophrenia

BACKGROUND The vulnerability-stress hypothesis is an established model of schizophrenia symptom formation. We sought to characterise the pattern of the cardiac autonomic response to mental arithmetic stress in patients with stable schizophrenia. METHODS We performed heart rate variability (HRV) analysis on recordings obtained before, during, and after a standard test of autonomic function involving mental stress in 25 patients with DSM-IV schizophrenia (S) and 25 healthy individuals (C). RESULTS Patients with schizophrenia had a normal response to the mental arithmetic stress test. Relative contributions of low-frequency (LF) HRV and high-frequency (HF) HRV influences on heart rate in patients were similar to controls both at rest (LF 64+/-19% (S) vs. 56+/-16% (C); HF 36+/-19% (S) vs. 44+/-16% (C), t=1.52, p=0.136) and during mental stress, with increased LF (S: 76+/-12%, C: 74+/-11%) and decreased HF (S: 24+/-12%, C: 26+/-11%) in the latter study condition. Whilst healthy persons recovered the resting pattern of HRV immediately after stress termination (LF 60+/-15%, HF 40+/-15%, F=18.5, p<0.001), in patients HRV remained unchanged throughout the observed recovery period, with larger LF (71+/-17%) and lower HF (29+/-17%) compared with baseline (F=7.3, p=0.013). CONCLUSIONS Patients with schizophrenia exhibit a normal response to the mental arithmetic stress test as a standard test of autonomic function but in contrast with healthy individuals, they maintain stress-related changes of cardiac autonomic function beyond stimulus cessation.

Brain pathology in first-episode psychosis: magnetization transfer imaging provides additional information to MRI measurements of volume loss.

Background Loss of brain volume in first-episode psychosis can be detected using conventional magnetic resonance imaging (MRI), but subtle changes – not leading to reduction in volume – that may contribute to clinical and cognitive abnormalities, may go undetected. Magnetization transfer imaging (MTI), a technique more sensitive to subtle neuropathological changes than conventional MRI, could yield important information on the extent and nature of structural abnormalities. Methods Forty-eight patients (33 males) from a population-based sample with first-episode psychosis (41 with schizophrenia and 7 with schizoaffective psychosis) and 47 healthy volunteers (27 males) were studied. Differences in magnetization transfer ratio (MTR) and white and grey matter volumes between groups were investigated. Results In patients, MTR was reduced in right entorhinal cortex, fusiform, dentate and superior frontal gyri and in left superior frontal and inferior/rostral cingulate gyri. Grey matter volume was reduced in right insula, frontal operculum and middle and superior temporal gyri and in left middle temporal gyrus. Grey matter volume increases were seen in patients in the superior frontal gyrus. White matter volume loss was found adjacent to grey matter loss. In patients MTR was lower in all areas of volumetric differences between groups suggesting that both changes may be related. Similar findings were observed when patients with schizoaffective psychosis were removed from the analysis. The correlations between clinical and MRI parameters did not survive correction for multiple comparisons. Conclusions MTI frontal and temporal abnormalities suggesting neuroaxonal and myelin changes were more extensive in our patients than those detected with conventional MRI. Our findings also suggest that there is regional variation in the severity of structural brain abnormalities.

Decreased activity in right-hemisphere structures involved in social cognition in siblings discordant for schizophrenia

BACKGROUND Social cognitive deficits contribute to functional disability in schizophrenia. Social cognitive tasks in healthy persons consistently evoke activation of medial prefrontal cortex, inferior frontal gyrus, temporoparietal gyrus, and posterior cingulate cortex/precuneus. We tested the hypothesis that patients with schizophrenia and their unaffected siblings share dysfunction of the same neural networks. METHODS Neural activation during emotion processing (EP), theory of mind (ToM), and control tasks was measured using functional magnetic resonance imaging (fMRI) in 14 patients with schizophrenia, 14 nonpsychotic siblings of patients with schizophrenia, and 14 matched healthy subjects. RESULTS Compared with healthy controls, patients with schizophrenia showed reduced activation of right hemisphere structures involved in EP and ToM including inferior frontal gyrus, middle frontal gyrus, and right temporoparietal junction. These deficits were shared, in part, by unaffected siblings. The latter group demonstrated deficits in bilateral precuneus activation during ToM, not present in patients. CONCLUSIONS Schizophrenia appears to be associated with a deficit in activation of right hemisphere components of a ToM network. Such deficits are shared in part by those at high genetic risk but unaffected by schizophrenia.

A window into the brain: An in vivo study of the retina in schizophrenia using optical coherence tomography

Retinal nerve fibre layer (RNFL) thickness and macular volume (MV) can be measured in vivo using optical coherence tomography (OCT) providing a “window into the brain”. RNFL and MV are promising biomarkers in neurological diseases. This study explores the potential of RNFL and MV to detect axonal abnormalities in vivo in schizophrenia and their correlations with clinical features. OCT was performed in 49 patients (38 schizophrenia, 11 schizoaffective disorder) and 40 healthy controls matched for age and gender. Group comparisons were made between whole retina and quadrant RNFL thickness and MV using multi-level analyses. In patients, associations were sought between RNFL and MV with symptom severity (positive/negative). Patients and controls had similar whole retina RNFL thickness (p = 0.86) and MV (p = 0.64), but RNFL in the right nasal quadrant of the schizoaffective group was thinner than in the schizophrenia group (p = 0.02). In patients, positive symptom severity was associated with smaller MV (right β = − 0.54, p = 0.02; left β = − 0.49, p = 0.04). Normal MV and RNFL thickness suggests unmyelinated axons in patients with schizophrenia/schizoaffective disorder remain unaffected. Longitudinal studies using higher resolution OCT will clarify whether progressive RNFL and MV changes occur and whether they can be used as state or trait markers in schizophrenia.