Biobehavioral approach to distinguishing panic symptoms from medical illness.

Panic disorder is a common psychiatric diagnosis characterized by acute, distressing somatic symptoms that mimic medically-relevant symptoms. As a result, individuals with panic disorder overutilize personal and healthcare resources in an attempt to diagnose and treat physical symptoms that are often medically benign. A biobehavioral perspective on these symptoms is needed that integrates psychological and medical knowledge to avoid costly treatments and prolonged suffering. This narrative review examines six common somatic symptoms of panic attacks (non-cardiac chest pain, palpitations, dyspnea, dizziness, abdominal distress, and paresthesia), identified in the literature as the most severe, prevalent, or critical for differential diagnosis in somatic illness, including long COVID. We review somatic illnesses that are commonly comorbid or produce panic-like symptoms, their relevant risk factors, characteristics that assist in distinguishing them from panic, and treatment approaches that are typical for these conditions. Additionally, this review discusses key factors, including cultural considerations, to assist healthcare professionals in differentiating benign from medically relevant symptoms in panic sufferers.

fMRI BOLD responses to film stimuli and their association with exhaled nitric oxide in asthma and health.

Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FENO) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen-dependent (BOLD) brain activation to negative (blood-injection-injury themes) and neutral films in 31 participants (15 with asthma). Regions-of-interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top-down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross-baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO.

End-of-Life Care, Symptom Burden, and Quality of Life in Couples Facing Stage IV Lung Cancer: The Role of Patient and Spousal Psychospirituality and Discussions Around Fear of Death and Disease Progression.

Background: As patients live longer with stage IV nonsmall cell lung cancer, correlates of end-of-life (EOL) care and experience are increasingly relevant. Methods: We, therefore, prospectively examined associations among psychospirituality (Center for Epidemiologic Studies Depression Scale, Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being), discussions around fear of death and disease progression, and hospital-based EOL care in patients and caregivers. Patients additionally reported symptom burden (MD Anderson Symptom Inventory-Lung Cancer total) and quality of life (QOL) (quality-of-life at EOL). Results: Of the baseline patients (n = 75), 32% were alive at time of the analyses (mean = 4.6 years postbaseline). Deceased patients (n = 51) were middle aged (mean = 65.3 years) and non-Hispanic White (81%). Caregiver spiritual well-being (r = 0.34, p = 0.02) and depression (r = -0.31, p = 0.03) were associated with EOL care metrics. Patients who "held back" more of their fear of death or disease progression experienced greater symptom burden (r = 0.41, p < 0.001) and poorer QOL (r = -0.44, p < 0.001). Conclusion: For couples facing prolonged metastatic disease, psychospirituality is highly relevant to EOL care with potential sequelae of withholding one's fear regarding death or disease progression.

Asthma, the central nervous system, and neurocognition: Current findings, potential mechanisms, and treatment implications.

Accumulating behavioral evidence suggests that asthma is associated with cognitive deficits. A number of studies have identified potential biological contributions to cognition in asthma; however, mechanistic pathways of central nervous system (CNS) involvement in asthma are yet to be established. We therefore conducted a literature review to identify studies examining potential CNS contributions to cognition in asthma. In this review, we discuss our general understanding of the CNS in asthma in the context of cognitive performance and outline a working model of mechanistic pathways linking the proposed neural influences of asthma pathology with cognition. To this extent, we incorporate neural, behavioral, psychological, social and environmental factors. Finally, we underscore the clinical significance of the CNS and neurocognitive sequelae in asthma, highlighting potential opportunities for routine monitoring, therapeutic intervention, and recommend key areas for future research.

Moderators of the association between stigma and psychological and cancer-related symptoms in women with non-small cell lung cancer.

OBJECTIVE: Lung cancer patients, particularly women, are vulnerable to experience disease-related stigma, which is linked to greater psychological distress and worse treatment outcomes. To inform future stigma-resilience interventions, we examined if mindfulness, self-compassion, and social support might buffer the associations between perceived lung cancer stigma and psychological and cancer-related symptoms. METHODS: In this cross-sectional study, women with recently diagnosed non-small cell lung cancer undergoing cancer treatment completed measures of Cataldo Lung Cancer Stigma Scale, depressive (Center for Epidemiologic Studies Depression Scale), stress (Impact of Events Scale) and cancer-related (MD Anderson Symptom Inventory-Lung Cancer) symptoms, mindfulness (Mindful Attention Awareness Scale), self-compassion (Self-Compassion Scale), and social support (Social Provisions Scale). RESULTS: The sample included 56 women (mean age = 65 years; 71% non-Hispanic White; 50% college educated; 74% advanced stage) who had consented to participate in an online support group study. Most (70%) had a smoking history and reported moderate levels of stigma (M = 36.28, SD = 10.51). Based on general linear modeling, mindfulness moderated the associations between stigma and depressive symptoms (F = 5.78, p = 0.02), cancer-related stress (F = 12.21, p = 0.002), and cancer-related symptom severity (F = 4.61, p = 0.04), such that, only for women scoring low in mindfulness, the associations between stigma and symptoms were significant. For those scoring high in mindfulness, the associations between stigma and symptoms were not significant supporting a buffering effect. Self-compassion and social support did not significantly moderate the stigma and symptom associations. CONCLUSIONS: Higher levels of mindfulness may protect women from psychological and cancer-related symptoms typically associated with the stigmatizing experience of a lung cancer diagnosis. Yet, longitudinal studies and randomized controlled designs are needed to identify mindfulness as a causal protective factor.

Social support, exhaled nitric oxide, and upper respiratory symptoms in health and asthma.

Accumulating research identifies a role of psychological process, particularly negative affect, in the expression of airway nitric oxide (NO), yet directional associations tend to vary across methodologies and samples. Recent findings indicate higher social support to be associated with higher airway NO; however, consequences for respiratory infection remain unexplored. NO has a key role in the first line of epithelial defense against pathogens, thus, social support could unfold airway protective effects through enhanced production of NO. We therefore examined the associations among social support, negative affect, airway NO, and cold symptoms in a sample of undergraduate students. In this cross-sectional study, 637 participants completed questionnaires of social support, negative affect, medical history, and current cold symptoms followed by measurements of fractional exhaled NO (FENO) to study airway NO during a semester period of relative low stress. Findings showed that greater social support was associated with higher FENO and fewer cold symptoms, controlling for key covariates. Further analysis suggested an additional indirect effect of social support on FENO through cold symptoms such that higher social support was related to lower cold symptoms, which were related to lower FENO. These results, coupled with longitudinal findings in the previous research, suggest that social support can affect FENO and cold symptoms through a complex pattern of direct and indirect effects. Overall, findings support the role of psychological processes - particularly social support - as relevant to FENO and cold symptoms in young adults.

Navigating financial toxicity in patients with cancer: A multidisciplinary management approach.

Approximately one-half of individuals with cancer face personal economic burdens associated with the disease and its treatment, a problem known as financial toxicity (FT). FT more frequently affects socioeconomically vulnerable individuals and leads to subsequent adverse economic and health outcomes. Whereas multilevel systemic factors at the policy, payer, and provider levels drive FT, there are also accompanying intervenable patient-level factors that exacerbate FT in the setting of clinical care delivery. The primary strategy to intervene on FT at the patient level is financial navigation. Financial navigation uses comprehensive assessment of patients' risk factors for FT, guidance toward support resources, and referrals to assist patient financial needs during cancer care. Social workers or nurse navigators most frequently lead financial navigation. Oncologists and clinical provider teams are multidisciplinary partners who can support optimal FT management in the context of their clinical roles. Oncologists and clinical provider teams can proactively assess patient concerns about the financial hardship and employment effects of disease and treatment. They can respond by streamlining clinical treatment and care delivery planning and incorporating FT concerns into comprehensive goals of care discussions and coordinated symptom and psychosocial care. By understanding how age and life stage, socioeconomic, and cultural factors modify FT trajectory, oncologists and multidisciplinary health care teams can be engaged and informative in patient-centered, tailored FT management. The case presentations in this report provide a practical context to summarize authors' recommendations for patient-level FT management, supported by a review of key supporting evidence and a discussion of challenges to mitigating FT in oncology care. CA Cancer J Clin. 2022;72:437-453.

Financial distress and its associated burden in couples coping with an advanced cancer.

PURPOSE: In efforts to understand financial distress (FD) associated with advanced cancer care from the perspective of both patients with incurable disease and their spousal caregivers, we assessed FD in both members of the couple, identified symptom and quality of life (QOL) correlates, and examined the potential role of illness communication. METHODS: Patients undergoing treatment for stage III/IV lung cancer or a grade III/IV primary brain tumor and their spousal caregivers (n = 76 dyads) completed measures of somatic and affective symptoms including FD, physical and mental QOL, and ease of engaging in illness communication. Patients and caregivers additionally rated their perception of each other's symptoms, including FD. RESULTS: FD was endorsed by both patients (any FD 62.7%; high FD 24%) and spousal caregivers (any FD 64.7%; high FD 32.3%). Self-reported FD was significantly correlated (partial r = .52, p < .001) within couples. FD was associated with greater symptoms of anxiety (r = .29, p = .01; r = .31, p = .01), depression (r = 29, p = 01; r = .39, p = .001), and poorer physical QOL(r = - .25, p = .03; r = - .25, p = .001) for patients and caregivers, respectively. For patients, FD was additionally associated with poorer mental QOL(r = - .44, p < .001). Caregivers accurately perceived patient FD, yet patients tended to underreport their caregiver's FD by almost an entire point (t = 2.8, p = .007). A 3-way interaction (FD X role X illness communication) revealed (b = .40, p = .041) that illness communication moderated the association between FD and physical QOL for spouses so that spouses who reported less ease of illness communication demonstrated a stronger association between financial distress and physical QOL (b = - 2.08, p < .001) than those reporting greater ease of engaging in illness communication (b = .49, p = .508). CONCLUSION: In the advanced cancer setting, FD is prevalent in both patients and their spousal caregivers and associated with psychological distress and poor physical QOL. Results suggest that optimal FD assessment should include patients and spouses, and spouse's ease of engaging with illness communication may be a potential target for future intervention studies.

Chronic stress experience, sleep, and physical activity: Relations with change in negative affect and acute stress response to a naturalistic stressor.

OBJECTIVES: Prior research indicates that chronic stress increases allostatic load and alters individuals' affective response to stress. Recent studies have linked health-related behaviours including poor sleep and physical inactivity with elevated negative affect responses to stress. This study extends prior work to investigate chronic stress experience, sleep, and physical activity as predictors of negative affect and acute stress experience during acute, sustained naturalistic stress. DESIGN: Students (N = 637) were assessed during an academic semester and end-of-term final exam period. METHODS: Self-report ratings of chronic stress experience, negative affect, acute stress experience, sleep, physical activity, demographics, and health were obtained. Hierarchical multiple regression analyses examined the extent to which chronic stress experience, sleep duration and sleep quality, habitual physical activity, and their interactions, predicted changes in negative affect and acute stress experience during final exams. Health-related behaviours were also examined as mediators between chronic stress experience and changes in negative affect and acute stress experience. RESULTS: Greater chronic stress experience and shorter exam period sleep duration, but not habitual sleep duration or physical activity, predicted greater increases in negative affect and acute stress experience. Poorer overall sleep quality was a significant predictor in these models and partially mediated the relation between chronic stress experience and negative affect and acute stress experience. CONCLUSIONS: Findings highlight the importance of chronic stress experience and sleep in predicting individuals' affective health during naturalistic stress. Interventions that reduce chronic stress experience and improve sleep may help individuals' buffer against impairments to affective health during these episodes.

Subcortical gray matter volumes in asthma: associations with asthma duration, control, and anxiety.

Asthma as a chronic inflammatory disease can be expected to affect central nervous system structures but little is known about subcortical structures in asthma and their potential association with illness-specific outcomes and anxiety. A total of 40 young adults (20 with asthma and 20 gender- and age-matched controls) underwent high-resolution T1-weighted MRI scan, viewed short distressing film clips, and filled in questionnaires about anxious and depressed mood, as well as asthma history, control, and catastrophizing thoughts about asthma, for those with asthma. The structural scans were processed in FSL's FIRST program to delineate subcortical structures of interest: amygdala, hippocampus, putamen, pallidum, caudate nucleus, nucleus accumbens, and thalamus. Findings showed no general reduction in subcortical gray matter volumes in asthma compared to controls. Asthma duration, asthma control, and catastrophizing of asthma and asthma attacks were negatively associated with volumes of putamen and pallidum, and to a weaker extent thalamus and amygdala, while controlling for gender, age, and corticosteroid inhaler use. In addition, stronger anxiety in response to distressing films was associated with lower volume of the pallidum, whereas general anxious and depressed mood was unrelated to subcortical structures. Thus, although there are no subcortical structural differences between young adults with asthma and healthy controls, longer asthma history, suboptimal management, and illness-related anxiety are reflected in lower gray matter volumes of subcortical structures, further emphasizing the importance of maintaining optimal asthma control.

Central nervous system signatures of affect in asthma: associations with emotion-induced bronchoconstriction, airway inflammation, and asthma control.

The effects of asthma on affect have been noted for some time, but little is known about associated brain processes. We therefore examined whether emotion-induced bronchoconstriction, airway inflammation, and asthma control are related to specific patterns of brain activity during processing negative affective stimuli. Fifteen adults with asthma viewed alternating blocks of distressing film clips (negative condition), affectively neutral film clips (neutral condition), and a crosshair image (baseline condition) while undergoing blood oxygenation level-dependent (BOLD) functional MRI (fMRI). Block-design fMRI analysis evaluated the BOLD response to "negative-baseline" and "neutral-baseline" contrasts. Airway response to these film clips was also assessed with impulse oscillometry in a separate session. Measures of airway inflammation [fractional exhaled nitric oxide (FENO)] and asthma control [Asthma Control Questionnaire (ACQ)] were additionally obtained. A whole brain voxel-based regression analysis of contrast maps was performed against respiratory resistance increase during negative and neutral films, FENO, and ACQ. Peak airway obstruction to negative affective stimulation was associated with stronger activation of the anterior and middle cingulate gyrus, including the dorsal anterior cingulate cortex (dACC). Stronger airway inflammation and lower asthma control were associated with reduced activation to negative stimuli in the superior frontal gyrus, middle cingulate gyrus, and supplementary motor area. Activation of the dACC in negative-affect-induced airway obstruction could be part of an integrated defensive response to critical environmental change. In addition, reduced frontal and limbic activation during processing of negative affect may reflect consequences of pathophysiological processes for CNS functioning. NEW & NOTEWORTHY This functional magnetic resonance imaging study shows, for the first time, that the degree of airway constriction due to negative affective stimuli in asthma is associated with stronger response to these stimuli in the dorsal anterior and middle cingulate cortex. Asthma patients with stronger airway inflammation and reduced asthma control also show reduced activation in a number of cortical and subcortical areas relevant for affective processing and breathing control.

Beetroot juice supplementation for the prevention of cold symptoms associated with stress: A proof-of-concept study.

OBJECTIVES: Psychological stress has been linked to common cold symptoms. Nitric oxide (NO) is part of the first line of epithelial defense against pathogens, and beetroot juice is a source of dietary nitrate that increases NO availability. We therefore tested whether beetroot juice protects against cold symptoms in a period of sustained acute stress. DESIGN: Seventy-six students, 16 of these with asthma, were randomly assigned to seven daily doses of beetroot juice or no supplementation control during their final exams. METHODS: Participants completed stress ratings, a cold symptom questionnaire, and exhaled NO measurements at a low-stress period and two periods during their final exams, with one questionnaire follow-up assessment seven days after finals. RESULTS: Beetroot juice was associated with reduced symptoms of cold and sickness during and following finals. Those with asthma showed the greatest benefits. Higher exhaled NO was concurrently and prospectively associated with reduced symptomatology. CONCLUSION: Beetroot juice during periods of psychological stress protects against cold symptoms. Preliminary evidence suggests particular benefits in asthma, which could translate into reduced asthma exacerbations due to respiratory infections. Clinical Trial ID: NCT03159273.

Hippocampal metabolites in asthma and their implications for cognitive function.

Emerging research indicates that individuals with asthma have an increased risk of cognitive impairment, yet the associations of asthma with neural correlates of memory remain relatively unknown. The hippocampus is the predominant neural structure involved in memory, and alterations in the hippocampal metabolic profile are observed in individuals with mild cognitive impairment. We therefore hypothesized that individuals with asthma may have altered hippocampal metabolites compared to healthy controls. Structural magnetic resonance imaging (sMRI) and proton magnetic resonance spectroscopy (1H-MRS) were used to compare hippocampal volume and metabolites of otherwise healthy adults with and without asthma (N = 40), and to study the association of these measures with cognitive function and asthma-related variables. Participants underwent 3-Tesla sMRI and 1H-MRS, with the volume of interest placed in the left hippocampus to measure levels of N-acetylaspartate (NAA), glutamate (Glu), creatine (Cr), and myo-inositol (MI), as indicators of neuronal viability, cellular activity, cellular energy reserve, as well as glial activation. Individuals with asthma had lower hippocampal NAA compared to healthy controls. For all participants, poorer cognitive function was associated with reduced NAA and Glu. For individuals with asthma, poorer cognitive function was associated with reduced disease control. Additionally, short-acting rescue bronchodilator use was associated with significantly lower NAA, and Glu, whereas inhaled corticosteroid use was related to significantly higher Cr and in tendency higher NAA and Glu. All findings controlled for left hippocampal volume, which was not different between groups. These findings highlight that asthma and/or its treatment may affect hippocampal chemistry. It is possible that the observed reductions in hippocampal metabolites in younger individuals with asthma may precede cognitive and hippocampal structural deficits observed in older individuals with asthma.

Acute ingestion of beetroot juice increases exhaled nitric oxide in healthy individuals.

BACKGROUND AND OBJECTIVE: Nitric oxide (NO) plays an important role in the airways' innate immune response, and the fraction of exhaled NO at a flow rate of 50mL per second (FENO50) has been utilized to capture NO. Deficits in NO are linked to loss of bronchoprotective effects in airway challenges and predict symptoms of respiratory infection. While beetroot juice supplements have been proposed to enhance exercise performance by increasing dietary nitrate consumption, few studies have examined the impact of beetroot juice or nitrate supplementation on airway NO in contexts beyond an exercise challenge, which we know influences FENO50. METHODS: We therefore examined the influence of a beetroot juice supplement on FENO50 in healthy males and females (n = 38) during periods of rest and in normoxic conditions. FENO50, heart rate, blood pressure, and state affect were measured at baseline, 45 minutes, and 90 minutes following ingestion of 70ml beetroot juice (6.5 mmol nitrate). Identical procedures were followed with ingestion of 70ml of water on a control day. RESULTS: After beetroot consumption, average values of the natural log of FENO50 (lnFENO50) increased by 21.3% (Cohen's d = 1.54, p < .001) 45 minutes after consumption and by 20.3% (Cohen's d = 1.45, p < .001) 90 min after consumption. On the other hand, only very small increases in FENO50 were observed after consumption of the control liquid (less than 1% increase). A small subset (n = 4) of participants completed an extended protocol lasting over 3 hours, where elevated levels of FENO50 persisted. No significant changes in cardiovascular measures were observed with this small single dose of beetroot juice. CONCLUSION: As NO serves a key role in innate immunity, future research is needed to explore the potential clinical utility of beetroot and dietary nitrate to elevate FENO50 and prevent respiratory infection.

Sensitivity of salivary hydrogen sulfide to psychological stress and its association with exhaled nitric oxide and affect.

BACKGROUND: Hydrogen sulfide (H2S) is the third gasotransmitter recently discovered after nitric oxide (NO) and carbon monoxide. Both NO and H2S are involved in multiple physiological functions. Whereas NO has been shown to vary with psychological stress, the influence of stress on H2S and the relationship between H2S and NO are unknown. We therefore examined levels of salivary H2S and NO in response to a stressful final academic exam period. METHODS: Measurements of stress, negative affect, and fraction of exhaled NO (FENO), were obtained from students (N=16) and saliva was collected at three time points: low-stress period in the semester, early exam period, and late exam period. Saliva was immediately analyzed for H2S with the fluorescent probe Sulfidefluor-4. RESULTS: H2S increased significantly during the early exam period and FENO decreased gradually towards the late exam period. H2S, FENO, negative affect, and stress ratings were positively associated with each other: as stress level and negative affect increased, values of H2S increased; in addition, as FENO levels decreased, H2S also decreased. Asthma status did not modify these associations. CONCLUSION: Sustained academic stress increases H2S and these changes are correlated with NO and the experience of stress and negative affect. These findings motivate research with larger samples to further explore the interaction and function of H2S and FENO during psychological stress.