Abstract Measures of social competence are closely related to actual community functioning in patients with schizophrenia. However, the neurobiological mechanisms underlying competence in ...schizophrenia are not fully understood. We hypothesized that social deficits in schizophrenia are explained, at least in part, by abnormally lateralized patterns of brain activation in response to tasks engaging social cognition, as compared to healthy individuals. We predicted such patterns would be partly heritable, and therefore affected in patients' nonpsychotic siblings as well. We used a functional magnetic resonance image paradigm to characterize brain activation induced by theory of mind tasks, and two tests of social competence, the Test of Adaptive Behavior in Schizophrenia (TABS), and the Social Skills Performance Assessment (SSPA) in siblings discordant for schizophrenia and comparable healthy controls ( n = 14 per group). Healthy individuals showed the strongest correlation between social competence and activation of right hemisphere structures involved in social cognitive processing, whereas in patients, the correlation pattern was lateralized to left hemisphere areas. Unaffected siblings of patients exhibited a pattern intermediate between the other groups. These results support the hypothesis that schizophrenia may be characterized by an abnormal functioning of nondominant hemisphere structures involved in the processing of socially salient information.
Previous studies have observed reduced vagal modulation in patients with acute schizophrenia and their first-degree relatives, thus suggesting a genetic predisposition.
To investigate vagal ...modulation, we analyzed the coupling between heart rate and breathing as a putative measure of central autonomic function in 19 patients, 19 of their relatives and 19 matched control subjects. The interaction of heart rate and breathing was investigated in all groups applying the non-linear parameter cross-ApEn, indicating the asynchrony between both time series. In addition, measures of the time and frequency domain of heart rate variability (HRV) were obtained.
The main finding of our study is a significantly increased cross-ApEn value, indicating reduced central vagal modulation both in relatives and patients suffering from schizophrenia. Non-linear measures of HRV proved to more sensitively differentiate relatives from control subjects. Furthermore, we observed a correlation between psychopathology and breathing, indicating that positive symptoms are associated with a higher degree of regularity in the breathing pattern.
Our results suggest that autonomic dysfunction previously described for patients suffering from schizophrenia is also present in first-degree relatives. This might relate to changes of brainstem activity in patients and relatives, and a common genetic background in patients and their family members can be assumed.
Early neuropathological changes characteristic of late-onset Alzheimer's disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep-wake rhythm. ...Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 ± 0.4 vs. 8.6 ± 0.6,
= 4.97,
= 49,
< 0.01) and language (Weschler's vocabulary 51.4 ± 1.3 vs. 44.3 ± 1.5,
= 2.49,
= 49,
< 0.001) compared to CS, even though all participants had results within the clinically normal range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 ± 0.47 h vs. 3.8 ± 0.26 h,
= 2.48,
= 40,
= 0.031). Cognitive performance in O-LOAD was associated with a series of cardiac autonomic sleep-wake variables; specifically indicators of greater sympathetic activity at night were related to poorer cognition. The present results suggest sleep pattern deserves further study as a potential neurobiological signature in LOAD, even in middle-aged, at risk individuals.
Abstract Moral decision-making involves complex social cognitive processes which are known to be altered in patients with schizophrenia and first-degree relatives. Traditional philosophical views on ...human moral behavior have distinguished between utilitarian views (which emphasize outcomes) and deontological approaches (defining what is right to do according to certain norms). Since emotions have been suggested to play a determining role in moral behavior, we hypothesized patients with schizophrenia and unaffected siblings would make more utilitarian choices and show faulty activation of brain areas concerned with emotion regulation during such tasks. Unexpectedly, all participants ( n = 13 per group) made the same proportion of utilitarian and deontological decisions. Brain activation common to all groups induced by moral decisions included two circumscribed portions of right ventromedial and dorsolateral prefrontal cortex, adding to previous evidence on a right prosencephalic cognitive network involved in ethical decisions. However, brain activation induced by moral decisions was different in healthy persons, schizophrenia patients, and nonpsychotic siblings in regards to areas directly concerned with emotion processing. These results seem to underscore the role of acquired norms in moral decisions, a frequently overlooked concept in the neurobiological characterization of human ethical behavior, and add to previous evidence of abnormal social cognitive processing in schizophrenia.
Rumination is associated with greater cognitive dysfunction and treatment resistance in major depressive disorder (MDD), yet its underlying neural mechanisms are not well understood. Since rumination ...is characterized by difficulty in controlling negative thoughts, the present study investigated whether rumination is associated with aberrant cognitive control in the absence of negative emotional information.
Individuals with MDD (n=176) and healthy volunteers (n=52) completed the Stop Signal Task with varied stop signal difficulty during functional magnetic resonance imaging. In the task, a longer stop signal asynchrony made stopping difficult (Hard-stop) while a shorter stop signal asynchrony allowed more time for stopping (Easy-stop).
In MDD participants, higher rumination intensity was associated with greater neural activity in response to difficult inhibitory control in the frontoparietal regions. Greater activation for difficult inhibitory control associated with rumination was also positively related to state fear. The imaging results provide compelling evidence for the neural basis of inhibitory control difficulties in MDD individuals with high rumination.
The association between higher rumination intensity and greater neural activity in regions involved in difficult inhibitory control tasks may provide treatment targets for interventions aimed at improving inhibitory control and reducing rumination in this population.
Major depressive disorder is one of the most common psychiatric disorders, with a worldwide lifetime prevalence rate of 10%-20% in women and a slightly lower rate in men. While many patients are ...successfully treated using established therapeutic strategies, a significant percentage of patients fail to respond. This report describes the successful recovery of a previously treatment-resistant patient following right unilateral deep brain stimulation of Brodmann's area 25. Current therapeutic approaches to treatment-resistant patients are reviewed in the context of this case with an emphasis on the role of the right and left hemispheres in mediating disease pathogenesis and clinical recovery.
Abstract Heart rate variability (HRV) is a complex signal that results from the contribution of different sources of oscillation related to the autonomic nervous system activity. Although linear ...analysis of HRV has been applied to sleep studies, the nonlinear dynamics of HRV underlying frequency components during sleep is less known. We conducted a study to evaluate nonlinear HRV within independent frequency components in wake status, slow-wave sleep (SWS, stages III or IV of non-rapid eye movement sleep), and rapid-eye-movement sleep (REM). The sample included 10 healthy adults. Polysomnography was performed to detect sleep stages. HRV was studied globally during each phase and then very low frequency (VLF), low frequency (LF) and high frequency (HF) components were separated by means of the wavelet transform algorithm. HRV nonlinear dynamics was estimated with sample entropy (SampEn). A higher SampEn was found when analyzing global variability (Wake: 1.53 ± 0.28, SWS: 1.76 ± 0.32, REM: 1.45 ± 0.19, p = 0.005) and VLF variability (Wake: 0.13 ± 0.03, SWS: 0.19 ± 0.03, REM: 0.14 ± 0.03, p < 0.001) at SWS. REM was similar to wake status regarding nonlinear HRV. We propose nonlinear HRV is a useful index of the autonomic activity that characterizes the different sleep–wake cycle stages.
Abstract Background Schizophrenia patients exhibit an abnormal autonomic response to mental stress. We sought to determine the cardiac autonomic response to mental arithmetic stress in their ...unaffected first-degree relatives. Methods Heart rate variability (HRV) analysis was performed on recordings obtained before, during, and after a standard mental arithmetic task to induce mental stress. 22 unaffected first-degree relatives of patients meeting DSM-IV criteria for schizophrenia (R) and 22 healthy individuals (C) were included in this study. Results Patients' relatives (R) had a normal response to the mental arithmetic stress test, showing an increased heart rate compared with controls. They also displayed the characteristic pattern of relative contributions of HRV components that consists of increased low-frequency (LF) HRV and decreased high-frequency (HF) HRV. Recovery of the resting pattern of HRV immediately after stress termination was observed in healthy subjects (LF 62 ± 16% vs. 74 ± 10% , HF 37 ± 16% vs. 25 ± 10%, F = 9.616, p = 0.004), but not in patients' relatives (LF 60 ± 19% vs. 70 ± 13%, HF 40 ± 19% vs. 29 ± 13%, F = 8.4, p = 0.056). Conclusions First-degree relatives of schizophrenia patients exhibit an abnormal pattern of protracted response to mental arithmetic stress, though less intense than that observed in patients in a previous study. This suggests that a pattern of autonomic response to stress may therefore be familial and heritable.
To evaluate the relationship between the autonomic nervous system basal state and performance in decision-making tasks.
The link between performance in decision-making tasks and acute changes in ...autonomic parameters during their execution has been extensively investigated. However, there is lacking evidence regarding the relationship between decision making and basal autonomic state.
Resting autonomic nervous system activity in 18 healthy individuals was assessed by means of heart rate variability (HRV) analysis before conducting 3 different decision-making tasks: an ambiguous one, the Iowa Gambling Task; a test that assesses risk-taking behavior, the Game of Dice Task; and a test that assesses reversal learning behavior, the Reversal Learning Task. The tasks were administered in a random manner.
There was a direct correlation between the Iowa Gambling Task net score and the resting low frequency HRV (r = 0.73; P < 0.001), which is strongly influenced by sympathetic activity. No correlations were found between HRV and the Game of Dice Task net score or the Reversal Learning Task last error trial.
The results are compatible with the idea that a higher basal activation of autonomic nervous system is beneficial for subsequent decision-making process.
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