We have obtained previous evidence of limbic dysfunction in middle-aged, asymptomatic offspring of late-onset Alzheimer's 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.
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.
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.
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.
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.
•Patients with major depression or borderline personality disorder display similar peripheral autonomic stress response.•Central processing abnormalities are different in major depression and ...borderline personality disorders.•The present findings might help discern diverse pathophysiological mechanisms in two syndromes with a significant clinical overlap.
Major depressive disorder (MDD) and borderline personality disorder (BPD) are highly prevalent and often comorbid psychiatric conditions, with abnormal processing of negative affect resulting from psychological stress. Characteristics of central processing of autonomic response to stress in each disorder are not clearly settled.
We obtained whole brain 3T fMRI with concurrent skin conductance, respiration rate, and heart rate variability measures in a cohort of MDD (N=19), BPD (N=19) patients, and healthy (N=20) individuals. Experiments were conducted in resting conditions, during a control mental arithmetic task, during highly stressful mental arithmetic, and in the period immediately following psychological stress.
Widespread activation of central autonomic network (CAN) structures was observed during stress compared to a control task in the group of healthy participants, whereas CAN activation during stress was less intense in both BPD and MDD. Both patient groups displayed increased sympathetic and decreased parasympathetic activation compared to healthy subjects, as previously reported. The relationship between peripheral sympathetic or parasympathetic activity and simultaneous regional brain BOLD activity was similar in BPD patients and healthy subjects, and markedly different from that seen in MDD patients.
The sample size, the fact it belonged to a single study site, and low grade affective symptomatology in both patient groups limit the generalizability of the present findings.
The diverging neurobiological signature in the homeostatic response to stress in MDD and BPD possibly represents a heuristically valuable candidate biomarker to help discern MDD and BPD patients.
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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.
To determine whether depression is associated with cardiac autonomic alterations in elderly patients with recent acute coronary syndromes (ACSs).
Cross-sectional study on the association between a ...major depressive episode or isolated depressive symptoms (21-item Hamilton depression score) and heart rate variability abnormalities in 56 adults (31 women, 55%) 60 years of age and older with a recent (24–72 h) myocardial infarction (MI) or unstable angina (UA).
Spectral and nonspectral parameters of respiratory sinus arrhythmia, indicative of parasympathetic activity on the heart, were decreased in patients with depression (high-frequency heart rate variability log ms
2 2.12±0.4 vs. 2.52±0.5,
P=.024; pNN50 % 1±2 vs. 9±15,
P=.006; and rMSNN ms 16±6 vs. 28±22,
P=.009). Also, high-frequency heart rate variability decreased with increasing depressive symptom severity.
In a sample of older adults suffering from ACSs, depression was associated with impaired parasympathetic control of the heart.
Depression is common among older patients and it has been related to a worsened coronary prognosis. The basis for this association is controversial. The aim of this study was to ascertain whether ...patients with a recent acute coronary event show depression-related changes of heart rate variability (HRV) nonlinear dynamics. Alterations of the HRV have been recently shown to predict mortality in patients recovering from an acute myocardial infarction. In 52 patients ≥60 years (52% women) with recent (within 24 to 72 hours) unstable angina pectoris or myocardial infarction, we obtained conventional time- and frequency-domain HRV measurements, along with nonlinear HRV measurements, including SD of the instantaneous beat-to-beat variability (SD1), scaling exponent α1 (α1), and approximate entropy (ApEn) from 10-minute RR-interval recordings. We also evaluated the presence of clinical depression and measured its severity by means of a 21-item Hamilton Depression Scale. On admission to the coronary care unit, 19 patients (37%) were depressed; α1 was higher (1.23 ± 0.21 vs 1.03 ± 0.30, p <0.05), whereas SD1 (10.4 ± 3.7 vs 14.4 ± 7.3, p <0.05) and ApEn (0.98 ± 0.22 vs 1.16 ± 0.15, p <0.001) were lower in depressed patients. Also, α1 increased (r = 0.31, p <0.05) and both SD1 (r = −0.46, p <0.01) and ApEn (r = −0.28, p <0.05) decreased with worsening depressive symptoms. In our sample, depression was associated with increased correlation and decreased complexity of the interbeat interval time series in older adults who had recently developed an acute coronary syndrome.
•Childhood adversity affects engagement of central autonomic components during effortful emotion regulation in patients with MDD.•Central-peripheral autonomic integration during cognitive reappraisal ...is abnormal in individuals with BPD.•Disruption of the central control of the autonomic response may underlie childhood-adversity related emotion dysregulation in MDD.
Adverse childhood experiences (ACEs) have lifelong effects on emotional behavior and are frequent in Borderline Personality Disorder (BPD) and Major Depressive Disorder (MDD). The Central Autonomic Network (CAN), which modulates heart rate variability (HRV), comprises brain regions that mediate emotion regulation processes. However, it remains unclear the effect of ACEs on CAN dynamics and its relationship with HRV in these disorders. We studied the effects of ACEs on the brain and HRV simultaneously, during regulation of psychological stress in 19 BPD, 20 MDD and 20 healthy controls (HC). Participants underwent a cognitive reappraisal task during fMRI with simultaneous ECG acquisition. ACEs exposure was associated with increased activity of CAN and salience network components in patients with MDD compared to BPD during cognitive reappraisal. A brain-autonomic coupling was found in BPD relative to HC during emotion regulation, whereby greater activity of left anterior cingulate and medial superior frontal gyrus areas was coupled with increased HRV. Results suggest that ACEs exposure is associated with a distinct activation of the CAN and salience network regions governing responses to psychological stress in MDD compared to BPD. These alterations may constitute a distinctive neurobiological mechanism for abnormal emotion processing and regulation related to ACEs in MDD.
Background: Depression increases mortality of coronary patients, and autonomic dysfunction has been proposed as an explanation for this association.
Methods: In a sample of 38 adults ≥ 60 years with ...myocardial infarction or unstable angina, we studied depression (presence of a major depressive episode and 21-item Hamilton depression score) and heart rate variability (HRV) of 550 normal beats shortly after admission to the coronary care unit (CCU). Thirty patients were alive at 6 months and were studied at that time as well. Spectral HRV measurements included power in the high-frequency range (HF, 0.15—0.55 Hz, a measure of parasympathetic activity) and low-frequency range (LF, 0.03—0.15 Hz). Nonspectral HRV measurements included standard deviation of normal beats (SDNN) and two measures of vagal activity: percentage of adjacent cycles differing by >50 ms (pNN50) and the root-mean-square of differences in successive beats (rMSNN).
Results: Patients who died within 6 months (
n=8) had a higher Hamilton-D score than survivors (13.9±6.5 vs. 18.4±5.6,
P=0.039) and were more likely to have an episode of major depression upon admission to the CCU (71 vs. 27%,
P=0.027). An increase in Hamilton-D score at 6 months correlated with a decrease in total (
r=–0.48,
P=0.014), high-frequency (
r=–0.49,
P=0.007), and low-frequency HRV (
r=–0.46,
P=0.014).
Limitations: Patients belonged to a single institution and there was a small proportion of men.
Conclusions: Progression of mood symptoms 6 months after an acute coronary event is associated with an impairment of autonomic control of the heart in elderly individuals.
Clinical depression (MDD) has been associated with poor prognosis in patients with coronary heart disease (CHD). Possible pathophysiologic pathways linking depression and CHD that have received ...attention recently include immune-inflammatory abnormalities, lifestyle attitudes, and autonomic nervous system dysfunction. MDD is characterized by circadian abnormalities and CHD onset displays a diurnal rhythm, but to our knowledge the influence of depression on the circadian rhythm of cardiac autonomic activity has not been studied among acute CHD patients in a prospective manner.
Depression is common among older patients and it has been related to a worsened coronary prognosis. The basis for this association is controversial. The aim of this study was to ascertain whether ...patients with a recent acute coronary event show depression-related changes of heart rate variability (HRV) nonlinear dynamics. Alterations of the HRV have been recently shown to predict mortality in patients recovering from an acute myocardial infarction. In 52 patients =60 years (52% women) with recent (within 24 to 72 hours) unstable angina pectoris or myocardial infarction, we obtained conventional time- and frequency-domain HRV measurements, along with nonlinear HRV measurements, including SD of the instantaneous beat-to-beat variability (SD1), scaling exponent 1 (1), and approximate entropy (ApEn) from 10-minute RR-interval recordings. We also evaluated the presence of clinical depression and measured its severity by means of a 21-item Hamilton Depression Scale. On admission to the coronary care unit, 19 patients (37%) were depressed; 1 was higher (1.23 +/- 0.21 vs 1.03 +/- 0.30, p <0.05), whereas SD1 (10.4 +/- 3.7 vs 14.4 +/- 7.3, p <0.05) and ApEn (0.98 ± 0.22 vs 1.16 +/- 0.15, p <0.001) were lower in depressed patients. Also, 1 increased (r = 0.31, p <0.05) and both SD1 (r = -0.46, p <0.01) and ApEn (r = -0.28, p <0.05) decreased with worsening depressive symptoms. In our sample, depression was associated with increased correlation and decreased complexity of the interbeat interval time series in older adults who had recently developed an acute coronary syndrome. PUBLICATION ABSTRACT
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