Olfactory Dysfunction Evaluation Is Not Affected by Comorbid Depression in Parkinson's Disease.

BACKGROUND: Olfactory function assessment is an important screening tool for Parkinson's disease (PD) diagnosis. It is debated whether olfaction is affected by comorbid depression. We assessed the relationship between depression and olfaction in PD and determined whether depression may limit the usefulness of olfactory testing for PD diagnosis. METHODS: Olfaction was evaluated using the Sniffin' Sticks test and the Hyposmia Rating Scale in four groups of subjects: PD patients without depression (n = 30); PD patients with major depression (PDD; n = 30); major depressive disorder (MDD) patients (n = 29); and healthy controls (HCs; n = 30). RESULTS: No differences were found between PD and PDD patients for total Sniffin' Sticks test, threshold, discrimination or identification scores, or in Hyposmia Rating Scale, although both groups differed from HCs and MDD patients (P < 0.05), which, in turn, showed similar olfactory scores. CONCLUSIONS: Lack of differences in olfactory impairment between PD and PDD suggest that depression may not contribute to olfactory dysfunction in PD.

Childhood adversity modulates structural brain changes in borderline personality but not in major depression disorder.

Adverse childhood experiences (ACEs) negatively affect the function and structure of emotion brain circuits, increasing the risk of various psychiatric disorders. It is unclear if ACEs show disorder specificity with respect to their effects on brain structure. We aimed to investigate whether the structural brain effects of ACEs differ between patients with major depression (MDD) and borderline personality disorder (BPD). These disorders share many symptoms but likely have different etiologies. To achieve our goal, we obtained structural 3T-MRI images from 20 healthy controls (HC), 19 MDD patients, and 18 BPD patients, and measured cortical thickness and subcortical gray matter volumes. We utilized the Adverse Childhood Experiences (ACE) questionnaire to quantify self-reported exposure to childhood trauma. Our findings suggest that individuals with MDD exhibit a smaller cortical thickness when compared to those with BPD. However, ACEs showed a significantly affected relationship with cortical thickness in BPD but not in MDD. ACEs were found to be associated with thinning in cortical regions involved in emotional behavior in BPD, whereas HC showed an opposite association. Our results suggest a potential mechanism of ACE effects on psychopathology involving changes in brain structure. These findings highlight the importance of early detection and intervention strategies.

Abnormal brain network community structure related to psychological stress in schizophrenia.

Recent functional imaging studies in schizophrenia consistently report a disruption of brain connectivity. However, most of these studies analyze the brain connectivity during resting state. Since psychological stress is a major factor for the emergence of psychotic symptoms, we sought to characterize the brain connectivity reconfiguration induced by stress in schizophrenia. We tested the hypothesis that an alteration of the brain's integration-segregation dynamic could be the result of patients with schizophrenia facing psychological stress. To this end, we studied the modular organization and the reconfiguration of networks induced by a stress paradigm in forty subjects (twenty patients and twenty controls), thus analyzing the dynamics of the brain in terms of integration and segregation processes by using 3T-fMRI. Patients with schizophrenia did not show statistically significant differences during the control task compared with controls, but they showed an abnormal community structure during stress condition and an under-connected reconfiguration network with a reduction of hub nodes, suggesting a deficit of integration dynamic with a greater compromise of the right hemisphere. These results provide evidence that schizophrenia has a normal response to undemanding stimuli but shows a disruption of brain functional connectivity between key regions involved in stress response, potentially leading to altered functional brain dynamics by reducing integration capacity and showing deficits recruiting right hemisphere regions. This could in turn underlie the hyper-sensitivity to stress characteristic of schizophrenia.

Autonomic nervous system activation during social cognition tasks in patients with schizophrenia and their unaffected relatives.

OBJECTIVE: The objective of the study was to determine whether patients with schizophrenia and their unaffected first-degree relatives have abnormal autonomic nervous system (ANS) responses to social cognition tasks. BACKGROUND: Social cognition impairments are significant in schizophrenia. ANS activity has been shown to be abnormal in schizophrenia patients, and some of the abnormalities seem to be shared by patients' unaffected relatives. METHOD: Heart rate variability (HRV) was measured at rest and during social cognition tasks, in patients with schizophrenia, their nonpsychotic first-degree relatives, and matched healthy controls (n=19 in each group). RESULTS: Social cognition tasks induced a shortening of the RR interval in unaffected relatives, but not in patients. Social cognition tasks generated decreases in high-frequency (indicating cardiac vagal activity) and low-frequency (reflecting predominantly sympathetic activity) HRV in patients. In relatives, the decrease occurred in the high-frequency component only. Low-frequency HRV was higher in patients during a theory of mind task than a control task. These changes were not observed in the controls. CONCLUSIONS: Social cognitive tasks induce a pattern of peripheral autonomic activity different from that seen in generic arousal responses, and this pattern is abnormal in schizophrenia patients. Autonomic abnormalities in unaffected first-degree relatives seem restricted to the parasympathetic division of the ANS.

Asymmetrical contribution of brain structures to treatment-resistant depression as illustrated by effects of right subgenual cingulum stimulation.

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.

Heart rate variability response to mental arithmetic stress is abnormal in first-degree relatives of individuals with schizophrenia.

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.

Social Cognition in a Clinical Sample of Personality Disorder Patients.

Social cognition was assessed in a clinical sample of personality disorder (PD) stable patients receiving ambulatory treatment (N = 17) and healthy matched controls (N = 17) using tests of recognition of emotions in faces and eyes, in a test of social faux pas and in theory of mind (ToM) stories. Results indicated that when compared with healthy controls, individuals with PD showed a clear tendency to obtain lower scoring in tasks assessing recognition of emotion in faces (T = -2.602, p = 0.014), eyes (T = -3.593, p = 0.001), ToM stories (T = -4.706, p = 0.000), and Faux pas (T = -2.227, p = 0.035). In the present pilot study, PD individuals with a normal cognitive efficiency showed an impaired performance at social cognition assessment including emotion recognition and ToM.

Hemispheric specialization in affective responses, cerebral dominance for language, and handedness: Lateralization of emotion, language, and dexterity.

Hemispheric specialization in affective responses has received little attention in the literature. This is a fundamental variable to understand circuit dynamics of networks subserving emotion. In this study we put to test a modified "valence" hypothesis of emotion processing, considering that sadness and happiness are processed by each hemisphere in relation to dominance for language and handedness. Mood induction and language activation during functional magnetic resonance imaging (fMRI) were used in 20 right-handed and 20 nonright-handed subjects, focusing on interconnected regions known to play critical roles in affective responses: subgenual cingulate cortex, amygdala, and anterior insular cortex. We observed a consistent relationship between lateralization of affective processing, motor dexterity, and language in individuals with clear right-handedness. Sadness induces a greater activation of right-hemisphere cortical structures in right-handed, left-dominant individuals, which is not evident in nonright-handed subjects who show no consistent hemispheric dominance for language. In anterior insula, right-handed individuals displayed reciprocal activation of either hemisphere depending upon mood valence, whereas amygdala activation was predominantly left-sided regardless of mood valence. Nonright-handed individuals exhibited less consistent brain lateralization of affective processing regardless of language and motor dexterity lateralization. In contrast with traditional views on emotion processing lateralization, hemispheric specialization in affective responses is not a unitary process but is specific to the brain structure being activated.

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.

Pattern of brain activation during social cognitive tasks is related to social competence in siblings discordant for schizophrenia.

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.

Activation of brain areas concerned with social cognition during moral decisions is abnormal in schizophrenia patients and unaffected siblings.

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.

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.

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.

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)-alpha, interferon (IFN)-gamma, 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-alpha 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.