Behavioral and neural responses to social exclusion in women: the role of facial attractiveness and friendliness.

The behavioral and neural responses to social exclusion were examined in women randomized to four conditions, varying in levels of attractiveness and friendliness. Informed by evolutionary theory, we predicted that being socially excluded by attractive unfriendly women would be more distressing than being excluded by unattractive women, irrespective of their friendliness level. Our results contradicted most of our predictions but provide important insights into women's responses to interpersonal conflict. Accounting for rejection sensitivity, P300 event-related potential amplitudes were largest when women were excluded by unattractive unfriendly women. This may be due to an expectancy violation or an annoyance with being excluded by women low on social desirability. An examination of anger rumination rates by condition suggests the latter. Only attractive women's attractiveness ratings were lowered in the unfriendly condition, indicating they were specifically punished for their exclusionary behavior. Women were more likely to select attractive women to compete against with one exception-they selected the Black attractive opponent less often than the White attractive opponent when presented as unfriendly. Finally, consistent with studies on retaliation in relation to social exclusion, women tended to rate competitors who rejected them as being more rude, more competitive, less attractive, less nice, and less happy than non-competitors. The ubiquity of social exclusion and its pointed emotional and physiological impact on women demands more research on this topic.

Stress-related cellular pathophysiology as a crosstalk risk factor for neurocognitive and psychiatric disorders.

In this narrative review, we examine biological processes linking psychological stress and cognition, with a focus on how psychological stress can activate multiple neurobiological mechanisms that drive cognitive decline and behavioral change. First, we describe the general neurobiology of the stress response to define neurocognitive stress reactivity. Second, we review aspects of epigenetic regulation, synaptic transmission, sex hormones, photoperiodic plasticity, and psychoneuroimmunological processes that can contribute to cognitive decline and neuropsychiatric conditions. Third, we explain mechanistic processes linking the stress response and neuropathology. Fourth, we discuss molecular nuances such as an interplay between kinases and proteins, as well as differential role of sex hormones, that can increase vulnerability to cognitive and emotional dysregulation following stress. Finally, we explicate several testable hypotheses for stress, neurocognitive, and neuropsychiatric research. Together, this work highlights how stress processes alter neurophysiology on multiple levels to increase individuals' risk for neurocognitive and psychiatric disorders, and points toward novel therapeutic targets for mitigating these effects. The resulting models can thus advance dementia and mental health research, and translational neuroscience, with an eye toward clinical application in cognitive and behavioral neurology, and psychiatry.

Integrative Brain Dynamics in Childhood Bullying Victimization: Cognitive and Emotional Convergence Associated With Stress Psychopathology.

Bullying victimization is a form of psychological stress that is associated with poor outcomes in the areas of mental health and learning. Although the emotional maladjustment and memory impairment following interpersonal stress are well documented, the mechanisms of complex cerebral dysfunctions have neither been outlined nor studied in depth in the context of childhood bullying victimization. As a contribution to the cross-disciplinary field of developmental psychology and neuroscience, we review the neuropathophysiology of early life stress, as well as general psychological stress to synthesize the data and clarify the versatile dynamics within neuronal networks linked to bullying victimization. The stress-induced neuropsychological cascade and associated cerebral networks with a focus on cognitive and emotional convergence are described. The main findings are that stress-evoked neuroendocrine reactivity relates to neuromodulation and limbic dysregulation that hinder emotion processing and executive functioning such as semantic cognition, cognitive flexibility, and learning. Developmental aspects and interacting neural mechanisms linked to distressed cognitive and emotional processing are pinpointed and potential theory-of-mind nuances in targets of bullying are presented. The results show that childhood stress psychopathology is associated with a complex interplay where the major role belongs to, but is not limited to, the amygdala, fusiform gyrus, insula, striatum, and prefrontal cortex. This interplay contributes to the sensitivity toward facial expressions, poor cognitive reasoning, and distress that affect behavioral modulation and emotion regulation. We integrate the data on major brain dynamics in stress neuroactivity that can be associated with childhood psychopathology to help inform future studies that are focused on the treatment and prevention of psychiatric disorders and learning problems in bullied children and adolescents.

Mental Resilience and Coping With Stress: A Comprehensive, Multi-level Model of Cognitive Processing, Decision Making, and Behavior.

Aversive events can evoke strong emotions that trigger cerebral neuroactivity to facilitate behavioral and cognitive shifts to secure physiological stability. However, upon intense and/or chronic exposure to such events, the neural coping processes can be maladaptive and disrupt mental well-being. This maladaptation denotes a pivotal point when psychological stress occurs, which can trigger subconscious, "automatic" neuroreactivity as a defence mechanism to protect the individual from potential danger including overwhelming unpleasant feelings and disturbing or threatening thoughts.The outcomes of maladaptive neural activity are cognitive dysfunctions such as altered memory, decision making, and behavior that impose a risk for mental disorders. Although the neurocognitive phenomena associated with psychological stress are well documented, the complex neural activity and pathways related to stressor detection and stress coping have not been outlined in detail. Accordingly, we define acute and chronic stress-induced pathways, phases, and stages in relation to novel/unpredicted, uncontrollable, and ambiguous stressors. We offer a comprehensive model of the stress-induced alterations associated with multifaceted pathophysiology related to cognitive appraisal and executive functioning in stress.

Autonomic Modulation of Cardiac Activity Across Levels of Sleep Depth in Individuals With Depression and Sleep Complaints.

OBJECTIVE: We assessed mean heart rate (HR) and HR variability (HRV) across wake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep, and across varying levels of NREM sleep depth in individuals with depression and sleep complaints. METHODS: Retrospective polysomnographic data were obtained for 25 individuals diagnosed as having depression (84% female; mean age = 33.8 ± 12.2 years) and 31 mentally healthy controls (58.1% female; mean age = 37.2 ± 12.4 years). All were free of psychotropic and cardiovascular medication, cardiovascular disease, and sleep-related breathing disorders. HR and time-domain HRV parameters were computed on 30-second electrocardiography segments and averaged across the night for each stage of sleep and wake. RESULTS: Compared with the control group, the depression group had higher HR across wake, REM, and all levels of NREM depth (F(1,51) = 6.3, p = .015). Significant group by sleep stage interactions were found for HRV parameters: SD of normal-to-normal intervals (SDNN; F(2.1,107.7) = 4.4, p = .014) and root mean square differences of successive R-R intervals (RMSSD; F(2.2,113.5) = 3.2, p = .041). No significant group difference was found for SDNN or RMSSD during wake (all, p ≥ .32). However, compared with the control group, the depression group had significantly lower SDNN in REM (p = .040) and all NREM stages (all p ≤ .045), and lower RMSSD during NREM 2 (p = .033) and NREM 3 (p = .034). CONCLUSIONS: This study suggests that the abnormalities in autonomic cardiac regulation associated with depression and sleep problems are more prominent during sleep, especially NREM sleep, than during wake. This may be due to abnormalities in parasympathetic modulation of cardiac activity.

Using heart rate profiles during sleep as a biomarker of depression.

BACKGROUND: Abnormalities in heart rate during sleep linked to impaired neuro-cardiac modulation may provide new information about physiological sleep signatures of depression. This study assessed the validity of an algorithm using patterns of heart rate changes during sleep to discriminate between individuals with depression and healthy controls. METHODS: A heart rate profiling algorithm was modeled using machine-learning based on 1203 polysomnograms from individuals with depression referred to a sleep clinic for the assessment of sleep abnormalities, including insomnia, excessive daytime fatigue, and sleep-related breathing disturbances (n = 664) and mentally healthy controls (n = 529). The final algorithm was tested on a distinct sample (n = 174) to categorize each individual as depressed or not depressed. The resulting categorizations were compared to medical record diagnoses. RESULTS: The algorithm had an overall classification accuracy of 79.9% [sensitivity: 82.8, 95% CI (0.73-0.89), specificity: 77.0, 95% CI (0.67-0.85)]. The algorithm remained highly sensitive across subgroups stratified by age, sex, depression severity, comorbid psychiatric illness, cardiovascular disease, and smoking status. CONCLUSIONS: Sleep-derived heart rate patterns could act as an objective biomarker of depression, at least when it co-occurs with sleep disturbances, and may serve as a complimentary objective diagnostic tool. These findings highlight the extent to which some autonomic functions are impaired in individuals with depression, which warrants further investigation about potential underlying mechanisms.

The utility of Valsalva maneuver in the diagnoses of orthostatic disorders.

The objective of this study was to assess hemodynamic responses and baroreflex sensitivity (BRS) indexes during Valsalva maneuver (VM) and head-up tilt (HUT) testing in orthostatic intolerance (OI). Patients with neurogenic orthostatic hypotension (NOH, n = 26), postural tachycardia syndrome (n = 26) and symptomatic OI (n = 14) were compared with healthy population (control, n = 107) and inappropriate sinus tachycardia (n = 7). Hemodynamic assessment included patterning and quantification with vagal and adrenergic BRS (BRSa/BRSa1). In NOH, cardiovagal systolic blood pressure (SBP) decrements in VM and HUT were correlated (r = 0.660, P < 0.001); a "V" pattern of VM indicated α-BRSa failure. Yet BRSa1 did not reveal changes vs. control (P > 0.05) or was not applicable in 60% of NOH. In symptomatic OI, compared with control, cardiovagal SBP decrements were larger (P < 0.05); higher BRSa1 contradicted higher adrenergic index (Composite Autonomic Severity Score). Overshoot in phase IV dipped below baseline or dropped ≥ 10 mmHg over 8 s in postural tachycardia syndrome ("N" pattern), but by 3 s in inappropriate sinus tachycardia ("M" pattern). Visualization of distinct VM patterns allows primary evaluation of autonomic dysfunction and differentiation of the various forms of OI. BRSa1 evaluation is compromised by pathological SBP patterns. VM patterning is a valuable nonpostural supplement to HUT capable of detecting and differentiating OI.

Non-invasive measurement of baroreflex during Valsalva maneuver: Evaluation of alpha and beta-adrenergic components.

OBJECTIVE: To evaluate alpha and beta components of adrenergic baroreflex sensitivity (BRSa) in Valsalva maneuver (VM). METHODS: BRSa was studied in 89 healthy subjects aged 30±13 [16-75] years. Subjects were divided into three groups per blood pressure (BP) patterns associated with relatively balanced or increased alpha-adrenergic modulation: (1) BAR (n=43) - Balanced Autonomic Response with a BP dip below baseline in late phase II (IIL) and recovery in phase IV; (2) SAR (n=16) - Suppressed Autonomic Response with a non-dipping BP; and (3) AAR (n=30) - Augmented Autonomic Response with a BP recovery in phase IIL. Discrete (alpha and beta) BRSa formulae were produced using alpha- or beta-adrenergic phases: α-BRSa (phase IIL) and ß-BRSa (phase IV), respectively. Discrete BRSa were studied to determine potential correlations to BRSa1 (validated BRSa evaluation) and evaluated for reliability. RESULTS: Patterns with higher α-adrenergic influence showed correlation between α-BRSa and BRSa1 (AAR: r=0.447, p<0.05; SAR: r=0.774, p<0.01). BAR showed correlation between ß-BRSa and BRSa1 (r=-0.566, p<0.01), and α- and ß-adrenergic coefficients (r=-0.381, p<0.05). Discrete BRSa were more reliable than BRSa1 (n=33; p<0.05). CONCLUSIONS: Discrete BRSa are reproducible and correlated with BRSa1. SIGNIFICANCE: If validated, discrete BRSa may differentiate physiologic variances and vague dysautonomia.

Non-invasive measurement of adrenergic baroreflex during Valsalva maneuver reveals three distinct patterns in healthy subjects.

OBJECTIVE: To investigate hemodynamic trans-phasic fluctuations in Valsalva maneuver (VM) and relate them to adrenergic baroreflex sensitivity (BRSa) indices. METHODS: In a healthy population (n=107) with a young age predominance (32 ± 15 years) systolic blood pressure (SBP) and BRSa indices in VM were studied. RESULTS: Augmented and Suppressed Autonomic Responses (AAR, 28%; SAR, 15%, respectively), in addition to Balanced Autonomic Response (BAR, 40%), were found. There was a predominance for an unbalanced SBP response (67% in AAR, 69% in SAR, vs. 53% in BAR) in subjects ages 20-29. Compared to BAR and AAR, SAR had insignificant female predominance (51% and 47% vs. 75% respectively, p>0.05). AAR had the highest alternative BRSa (BRSa1) compared to SAR and BAR (26.73 ± 17.97 mmHg/s vs. 8.64 ± 5.33 mmHg/s and 15.68 ± 10.40 mmHg/s respectively, p<0.01). CONCLUSIONS: Qualitative evaluation revealed three distinct patterns in response to VM. Late phase II was found to be a key factor in VM patterns and as such, argues to include late phase II parameters such as hemodynamic and time indices in BRSa evaluation. SIGNIFICANCE: These findings may be of use in future evaluations when identifying mild autonomic dysfunction and/or distinguishing typical and atypical SBP patterns in a healthy population.

Differences in cardiac autonomic function contributes to heart rate abnormalities in POTS and IST.

Our objective was to examine the differences in cardiac autonomic function in Postural Tachycardia Syndrome (POTS) versus inappropriate sinus tachycardia (IST). Subjects (IST, n = 8; POTS, n = 12) were studied using standard measurements of the autonomic reflex screen, baroreflex function and spectral analysis. Data was compared to age/gender-matched controls (n = 20). The components of the autonomic reflex screen did not differ between groups. The exception was the significant but expected difference in postural heart rate increment on head-up tilt in POTS (47.9 ± 13.8; n = 12) compared to IST (30.9 ± 9.7; n = 8; p = 0.008). Accordingly the Orthostatic Intolerance Scale showed significantly greater orthostatic symptoms in POTS (2.6 ± 0.5; n = 12) versus IST patients (0.4 ± 0.5; n = 8; p < 0.001). Conversely, IST patients had a significantly higher resting heart rate (96 ± 12; n = 8) when compared to POTS patients (73 ± 12; n = 12; p = 0.001). There was a significant difference in vagal baroreflex sensitivity (BRSv) in POTS (8.21 ± 2.3, n = 12) compared to IST patients (5.30 ± 2.94, n = 8, p = 0.036) during the Valsalva maneuver. Only POTS subjects showed a significant increase in sympathovagal balance (LF/HF) with tilt (FFT, 8.29 ± 6.38; AR, 7.84 ± 5.24) compared to the supine position (FFT, 2.25 ± 1.75; AR, 1.99 ± 1.38; p < 0.05) for both frequency domains. Differences in cardiac autonomic function contribute to changes in positional and non-positional heart rate in postural tachycardia syndrome versus inappropriate sinus tachycardia. These findings shed further light on the autonomic dysfunction underlying POTS and IST.

Baroreflex sensitivity: reliability of baroreflex components of the Valsalva maneuver.

The reliability of the baroreflex sensitivity measurement has not yet been established. Thus, the objective of this study was to define intra-rater reliability of baroreflex sensitivity (BRS) measurements of the Valsalva maneuver (VM) in healthy individuals. Twenty-two healthy volunteers underwent VM testing at two time points. Intra-rater reliability was determined by the intra-class correlation coefficient (ICC), standard error of measurement and minimal detectable difference. Vagal BRS showed good reliability (ICC=0.84), while alternative adrenergic BRS was moderately reproducible (ICC=0.61). Vagal and alternative adrenergic components of BRS in VM are reliable measurements.

Nocturnal deterioration after ischemic stroke and autonomic dysfunction: hypothesis and implications.

BACKGROUND: A significant number of patients admitted to hospital after acute ischemic stroke deteriorate clinically. Deterioration is generally noted within the first 48 h after stroke onset. The mechanisms leading to this deterioration are not fully understood. SUMMARY: One potential cause of this deterioration may be altered or impaired autonomic function. We expect the hemodynamic changes regulated by the autonomic nervous system that are dysregulated after stroke to be exaggerated during sleep, resulting in arrhythmia and blood pressure fluctuations in these patients. Such physiological changes could result in worsening the overall outcome of the ischemic stroke patient or in sudden death. Therefore, it is necessary to summarize yet unrelated observations and hypothesize on their individual effects and interactions as they relate to poststroke deterioration. KEY MESSAGES: If the hypothesis is correct that dysautonomia occurs to the degree that it affects clinical outcomes negatively, this would have important implications for the prevention of neurological deterioration and sudden death after ischemic stroke.