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.

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.