Mariana N. Castro

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.

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.

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.

Depressive symptoms are related to decreased low-frequency heart rate variability in older adults with decompensated heart failure.

Background/Aims: Depression has been associated with increased mortality among individuals with heart failure, but the mechanism for this association is unsettled. Depression is often found to result in autonomic dysfunction which, if present in heart failure, might help explain worsened outcomes. Methods: This study was a cross-sectional evaluation of the relationship between depressive symptoms and cardiac autonomic function, as assessed by short-term heart rate variability (HRV) analysis in aged patients with acute/decompensated heart failure of coronary origin (CHF). A 21-item Hamilton Depression score and measures of short-term HRV were obtained in 31 inpatients ≧65 years of age, 24–72 h after admission to the coronary care unit with a diagnosis of CHF. Results: Clinical depression was present in 22.6% of participants. In the sample as a whole, increasing depressive symptoms were associated with decreased low-frequency HRV. Conclusion: These results may be important in light of recent indications that decreased low-frequency HRV is a predictor of mortality in patients with heart failure.

Nonlinear analysis of heart rate variability in patients with eating disorders

Patients with anorexia nervosa or bulimia nervosa often have signs of autonomic dysfunction potentially deleterious to the heart. The aim of this study was to ascertain the nonlinear properties of heart rate variability in patients with eating disorders. A group of 33 women with eating disorders (14 anorexia, 19 bulimia) and 19 healthy controls were included in the study. Conventional time- and frequency-domain heart rate variability measurements, along with nonlinear heart rate variability measurements including the short-term fractal scaling exponent α and approximate entropy (ApEn) were calculated. Anorexia nervosa patients exhibited decreased values of α, while bulimia nervosa patients had decreased values of ApEn. Low-frequency heart rate variability was decreased in patients with anorexia. In conclusion, these results are compatible with the view that a more severe alteration of cardiac autonomic function is present in anorexia than in bulimia.

Brain activation induced by psychological stress in patients with schizophrenia

Environmental influences are critical for the expression of genes putatively related to the behavioral and cognitive phenotypes of schizophrenia. Among such factors, psychosocial stress has been proposed to play a major role in the expression of symptoms. However, it is unsettled how stress interacts with pathophysiological pathways to produce the disease. We studied 21 patients with schizophrenia and 21 healthy controls aged 18 to 50years with 3T-fMRI, in which a period of 6min of resting state acquisition was followed by a block design, with three blocks of 1-min control-task, 1-min stress-task and 1-min rest after-task. Self-report of stress and PANSS were measured. Limbic structures were activated in schizophrenia patients by simple tasks and remained active during, and shortly after stress. In controls, stress-related brain activation was more time-focused, and restricted to the stressful task itself. Negative symptom severity was inversely related to activation of anterior cingulum and orbitofrontal cortex. Results might represent the neurobiological aspect of hyper-reactivity to normal stressful situations previously described in schizophrenia, thus providing evidence on the involvement of limbic areas in the response to stress in schizophrenia. Patients present a pattern of persistent limbic activation probably contributing to hypervigilance and subsequent psychotic thought distortions.

Mood, Th-1/Th-2 cytokine profile, and autonomic activity in older adults with acute/decompensated heart failure: preliminary observations.

In order to assess the relationships among mood, peripheral autonomic output and circulating immunoinflammatory mediators in older individuals with decompensated heart failure (CHF), 20 consecutive patients (78±7 years, 35% women) admitted to the coronary care unit with a clinical diagnosis of acute/decompensated CHF of coronary origin were examined. Mood was evaluated by the 21-item Hamilton Depression Scale (HAM-D). Four patients met the criteria for major depression. Heart rate variability (HRV) analysis and the levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-6 and IL-10 were measured within 24–72 h of admission. A significant positive relationship between score in HAM-D and serum IL-6 levels was detected with a similar trend as far as IL-2 levels. Circulating IL-2 levels were strongly associated with the HRV L/H quotient, an index of increased sympathetic and/or decreased parasympathetic thoracic activity. A negative correlation between vagal activity (as assessed by HRV) and IL-4 occurred. Neither TNF-α nor IL-10 were detectable in this group of elderly patients. The results add to the concept that mood and autonomic unbalance are associated with increased systemic inflammation in old patients with decompensated CHF, a potential mechanism for mood-related worsened prognosis of heart failure at an advanced age.

Cluster B personality symptoms in persons at genetic risk for schizophrenia are associated with social competence and activation of the right temporo-parietal junction during emotion processing

Personality disorders are common in nonpsychotic siblings of patients with schizophrenia, and some personality traits in this group may be associated with an increased risk for full-blown psychosis. We sought to establish if faulty right-hemisphere activation induced by social cognitive tasks, as previously described in patients with schizophrenia, is associated with specific personality symptoms in their unaffected siblings. We observed that cluster B personality symptoms in this group were inversely related to activation in the right temporo parietal junction (rTPJ, a structure critical in social cognitive processing) in response to a basic emotion processing task and also to social competence, whereas in contrast to our initial hypothesis, cluster A traits were not associated with right hemisphere activation during emotion processing or with social competence. These findings suggest the existence of clinical traits in at-risk individuals which share a common neurobiological substrate with schizophrenia, in regards to social performance.

Failure to Recover from Proactive Semantic Interference and Abnormal Limbic Connectivity in Asymptomatic, Middle-Aged Offspring of Patients with Late-Onset Alzheimer’s Disease

BACKGROUND We have obtained previous evidence of limbic dysfunction in middle-aged, asymptomatic offspring of late-onset Alzheimers disease (LOAD) patients, and failure to recover from proactive semantic interference has been shown to be a sensitive cognitive test in other groups at risk for LOAD. OBJECTIVE To assess the effects of specific proactive semantic interference deficits as they relate to functional magnetic resonance imaging (fMRI) neocortical and limbic functional connectivity in middle aged offspring of individuals with LOAD (O-LOAD) and age-equivalent controls. METHODS We examined 21 O-LOAD and 20 controls without family history of neurodegenerative disorders (CS) on traditional measures of cognitive functioning and the LASSI-L, a novel semantic interference test uniquely sensitive to the failure to recover from proactive interference (frPSI). Cognitive tests then were correlated to fMRI connectivity of seeds located in entorhinal cortex and anterodorsal thalamic nuclei among O-LOAD and CS participants. RESULTS Relative to CS, O-LOAD participants evidenced lower connectivity between entorhinal cortex and orbitofrontal, anterior cingulate, and anterior temporal cortex. In the offspring of LOAD patients, LASSI-L measures of frPSI were inversely associated with connectivity between anterodorsal thalamus and contralateral posterior cingulate. Intrusions on the task related to frPSI were inversely correlated with a widespread connectivity network involving hippocampal, insular, posterior cingulate, and dorsolateral prefrontal cortices, along with precunei and anterior thalamus in this group. Different patterns of connectivity associated with frPSI were observed among controls. CONCLUSION The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations.

Cortical thickness, brain metabolic activity, and in vivo amyloid deposition in asymptomatic, middle-aged offspring of patients with late-onset Alzheimer's disease

The natural history of preclinical late-onset Alzheimers disease (LOAD) remains obscure and has received less attention than that of early-onset AD (EOAD), in spite of accounting for more than 99% of cases of AD. With the purpose of detecting early structural and functional traits associated with the disorder, we sought to characterize cortical thickness and subcortical grey matter volume, cerebral metabolism, and amyloid deposition in persons at risk for LOAD in comparison with a similar group without family history of AD. We obtained 3T T1 images for gray matter volume, FDG-PET to evaluate regional cerebral metabolism, and PET-PiB to detect fibrillar amyloid deposition in 30 middle-aged, asymptomatic, cognitively normal individuals with one parent diagnosed with LOAD (O-LOAD), and 25 comparable controls (CS) without family history of neurodegenerative disorders (CS). We observed isocortical thinning in AD-relevant areas including posterior cingulate, precuneus, and areas of the prefrontal and temporoparietal cortex in O-LOAD. Unexpectedly, this group displayed increased cerebral metabolism, in some cases overlapping with the areas of cortical thinning, and no differences in bilateral hippocampal volume and hippocampal metabolism. Given the importance of age in this sample of individuals potentially developing early AD-related changes, we controlled results for age and observed that most differences in cortical thickness and metabolism became nonsignificant; however, greater deposition of β-amyloid was observed in the right hemisphere including temporoparietal cortex, postcentral gyrus, fusiform inferior and middle temporal and lingual gyri. If replicated, the present observations of morphological, metabolic, and amyloid changes in cognitively normal persons with family history of LOAD may bear important implications for the definition of very early phenotypes of this disorder.