Increases in stress and adverse childhood experiences are associated with the co-occurrence of anxiety and depression in oncology patients.

PURPOSE: Identify subgroups of patients with distinct joint anxiety AND depression profiles and evaluate for differences in demographic and clinical characteristics, as well as stress, resilience, and coping. DESIGN: Longitudinal study. PARTICIPANTS: Patients (n = 1328) receiving chemotherapy. METHODS: Measures of state anxiety and depression were done six times over two cycles of chemotherapy. All of the other measures were completed prior to second or third cycle of chemotherapy. Latent profile analysis was used to identify the distinct joint anxiety and depression profiles. FINDINGS: Three classes were identified (i.e. Low Anxiety and Low Depression (57.5%); Moderate Anxiety and Moderate Depression (33.7%), High Anxiety and High Depression (8.8%)). For all of the stress measures, a dose response effect was seen among the profiles. Two worst profiles reported higher occurrence rates for a number of adverse childhood experiences. IMPLICATIONS FOR PROVIDERS: Patients need referrals for stress reduction techniques and mental health and social services.

Is it worth it? Greater risk aversion with lower life satisfaction among depressed individuals.

Decisions of individuals with depression are often risk-averse. Risk-aversion may also extend to decisions regarding treatment, which may cause individuals to forgo or delay treatment. It is also well established that depression is associated with lower satisfaction with life. However, whether life satisfaction is associated with risk aversion for individuals with depression is not yet known. Three groups of participants (Depressed: n = 61; Chronic pain: n = 61; Comorbid depression and pain: n = 58) completed a clinical interview and several self-report questionnaires, including the Satisfaction with Life Scale (SWLS). Participants also completed two utility elicitation tasks: time trade-off (TTO), which measures utilities of health states without implied risks, and standard gamble (SG), which measures utilities of health states in the presence of risk (presented in this study as a hypothetical clinical trial described as having both potential harms and benefits). Risk aversion is defined as the difference in the utility ratings generated via SG and via TTO. For both TTO and SG, individuals evaluated their own depression or pain. When perfect health was used as a hypothetical benefit in TTO and SG tasks, satisfaction with life was not associated with risk preferences, for either depressed participants or participants with chronic pain (all ps ns). However, for participants with depression, when the hypothetical benefit was a more ecologically valid 'mild' depression in TTO and SG tasks, lower satisfaction with life was associated with greater risk aversion (p < .005; p < .03). For depressed individuals, therefore, lower satisfaction with life may be associated with risk aversion regarding treatments when benefits are seen as minor, which may result in treatment avoidance and, consequently, further worsening of both symptoms and life satisfaction.

Epigenetic Regulation of Inflammatory Mechanisms and a Psychological Symptom Cluster in Patients Receiving Chemotherapy.

BACKGROUND: A psychological symptom cluster is the most common cluster identified in oncology patients. Although inflammatory mechanisms are hypothesized to underlie this cluster, epigenetic contributions are unknown. OBJECTIVES: This study's purpose was to evaluate associations between the occurrence of a psychological symptom cluster and levels of DNA methylation for inflammatory genes in a heterogeneous sample of patients with cancer receiving chemotherapy. METHODS: Prior to their second or third cycle of chemotherapy, 1,071 patients reported the occurrence of 38 symptoms using the Memorial Symptom Assessment Scale. A psychological cluster was identified using exploratory factor analysis. Differential methylation analyses were performed in two independent samples using Illumina Infinium 450K and EPIC microarrays. Expression-associated CpG (eCpG) loci in the promoter region of 114 inflammatory genes on the 450K and 112 genes on the EPIC microarray were evaluated for associations with the psychological cluster. Robust rank aggregation was used to identify differentially methylated genes across both samples. Significance was assessed using a false discovery rate of 0.05 under the Benjamini-Hochberg procedure. RESULTS: Cluster of differentiation 40 ( CD40 ) was differentially methylated across both samples. All six promoter eCpGs for CD40 that were identified across both samples were hypomethylated in the psychological cluster group. CONCLUSIONS: This study is the first to suggest associations between a psychological symptom cluster and differential DNA methylation of a gene involved in tissue inflammation and cell-mediated immunity. Our findings suggest that increased CD40 expression through hypomethylation of promoter eCpG loci is involved in the occurrence of a psychological symptom cluster in patients receiving chemotherapy. These findings suggest a direction for mechanistic studies.

Risk factors for worse anxiety trajectories among patients undergoing cancer chemotherapy.

PURPOSE: Patients undergoing chemotherapy for cancer often experience heightened anxiety. While receipt of chemotherapy occurs over multiple cycles, limited research has examined anxiety longitudinally. The purposes of this study, in a large sample of patients with breast, gynecological, gastrointestinal, or lung cancer, were to evaluate, over the course of two cycles of chemotherapy, for inter-individual differences in the trajectories of anxiety and identify associations between demographic, clinical, symptom, and psychological adjustment characteristics and initial levels and trajectories of anxiety. METHODS: Patients with breast, gynecologic, lung, or gastrointestinal cancer (n = 1323) were assessed with the Spielberger State Anxiety Inventory (STAI-S) six times over two cycles of chemotherapy. At enrollment, patients completed self-report instruments assessing demographic, symptom, stress, and coping characteristics. We used hierarchical linear modeling to identify risk factors associated with initial levels and trajectories of state anxiety. RESULTS: Inter-individual differences in initial levels of anxiety were associated with functional status, sleep disturbance, morning fatigue, cognitive function, global and cancer-specific stress, resilience, and several coping characteristics (i.e., sense of coherence, acceptance, using emotional support, self-distraction, denial, venting, and self-blame). Demographic and clinical characteristics associated with interindividual differences in anxiety trajectories were age, employment status, and MAX-2 score. CONCLUSION: This study provides novel data on the course and predictors of anxiety during two cycles of chemotherapy among a large sample of patients with varied cancer types. Further research focused on risk factors for heightened levels of anxiety during chemotherapy may help point toward more effective interventions for this commonly experienced symptom.

Anxiety trajectories: An observational study of women undergoing chemotherapy for breast or gynecological cancer.

BACKGROUND: While anxiety is prevalent among women who undergo chemotherapy for breast or gynecologic cancer, research on its predictors has focused primarily on cross-sectional evaluations or on assessments of anxiety prior to and after receipt of chemotherapy. Few studies have evaluated for predictors of inter-individual variability in levels of anxiety during chemotherapy. This study evaluated for inter-individual differences in anxiety across two cycles of chemotherapy and identified demographic, clinical, symptom, and psychological adjustment (e.g., stress, coping) characteristics associated with initial levels and trajectories of anxiety. METHODS: Patients with breast (n = 530) or gynecologic (n = 233) cancer completed the Spielberger State Anxiety Inventory six times over two cycles of chemotherapy. At enrollment, self-report measures were used to assess demographic, symptom, stress, and coping characteristics. Hierarchical linear modeling was used to evaluate for risk factors associated with initial levels and trajectories of state anxiety. RESULTS: At enrollment, demographic, clinical, symptom, and psychological adjustment characteristics associated with inter-individual differences of anxiety were: marital status, functional status, sleep disturbance, cognitive function, global stress, cancer-specific stress, resilience, sense of coherence, and the coping strategies of venting and self-blame. Employment status and morning fatigue were the only characteristics associated with inter-individual differences in the trajectories of anxiety. Denial was the only characteristic associated with both initial levels and the trajectories of anxiety. CONCLUSIONS: A variety of patient characteristics predicted initial levels of anxiety. Fewer characteristics predicted trajectories of anxiety. Identification of specific risk factors, such as avoidant coping, suggests the need for targeted interventions among higher-risk patients.

Influence of Dispositional Optimism on Ethically Salient Research Perspectives: A Pilot Study.

Research participants should be drawn as fairly as possible from the potential volunteer population. Underlying personality traits are underexplored as factors influencing research decision-making. Dispositional optimism, known to affect coping, physical health, and psychological well-being, has been minimally studied with respect to research-related attitudes. We conducted an exploratory, online survey with 151 individuals (with self-reported mental illness [n = 50], physical illness [n = 51], or neither [n = 50]) recruited via MTurk. We evaluated associations between dispositional optimism (assessed with the Life Orientation Test-Revised) and general research attitudes, perceived protectiveness of five research safeguards, and willingness to participate in research using safeguards. Strongly optimistic respondents expressed more positive research attitudes and perceived four safeguards as more positively influencing willingness to participate. Optimism was positively associated with expressed willingness to participate in clinical research. Our findings add to a limited literature on the influence of individual traits on ethically salient research perspectives.

Oncology outpatients with worse depression and sleep disturbance profiles are at increased risk for a higher symptom burden and poorer quality of life outcomes.

OBJECTIVE: /Background - Depression and sleep disturbance are significant problems during chemotherapy. Study purposes were to identify subgroups of patients with distinct joint depression AND sleep disturbance profiles and evaluate for differences in demographic and clinical characteristics, severity of symptoms, and quality of life (QOL) outcomes among these subgroups. PATIENTS/METHODS: Oncology outpatients (n = 1331) completed measures of depression and sleep disturbance six times over two chemotherapy cycles. Latent profile analysis, that modeled the two symptoms together, was done to identify the distinct joint depression and sleep disturbance profiles. RESULTS: Five distinct profiles were identified (i.e., no depression or sleep disturbance (None, 21.4%); no depression and moderate sleep disturbance (32.3%); subsyndromal depression and very high sleep disturbance (20.4%); moderate depression and moderate sleep disturbance (17.7%); and high depression and very high sleep disturbance (8.2%)). Compared to the None class, the other four classes were more likely to be female; less likely to be employed; had a higher comorbidity burden; and had a lower functional status. Patients in the two very high sleep disturbance classes had problems with both sleep initiation and maintenance. These patients reported higher levels of depressive symptoms, trait and state anxiety, and fatigue as well as lower levels of energy, cognitive function, and poorer QOL. CONCLUSIONS: Over 45% of the patients had subsyndromal to high levels of depression AND moderate or very high levels of sleep disturbance. Characteristics associated with the higher risk profiles can be used to screen patients at increased risk for both symptoms.

A high stress profile is associated with severe pain in oncology patients receiving chemotherapy.

PURPOSE: Oncology patients receiving chemotherapy can experience both cancer and non-cancer pain. In addition, oncology patients face numerous stressors and their responses are highly variable. Stress and pain are intricately linked. The purpose of this study was to evaluate for differences in pain characteristics and mood disturbance among oncology patients with distinct stress profiles. METHODS: From a sample of 957 patients with and without pain, latent profile analysis identified three groups of patients with distinct stress profiles (i.e., Stressed, Normative, Resilient). In the subset of 671 patients with pain, receiving chemotherapy for breast, lung, gastrointestinal, or gynecologic cancer, we evaluated for differences among the stress profiles in terms of pain characteristics (e.g., intensity, qualities, interference) and mood disturbance (anxiety, depressive symptoms). RESULTS: Compared to Normative patients (n = 333; 49.6%), Stressed patients (n = 305; 45.5%) reported higher levels of pain intensity, pain interference, anxiety, and depressive symptoms and more commonly described pain as throbbing, shooting, burning, exhausting, tiring, penetrating, nagging, miserable, and unbearable. Compared to Resilient patients (n = 33; 4.9%), Stressed patients reported significantly higher mood-related pain interference scores and more severe anxiety and depressive symptoms. CONCLUSIONS: A high stress profile is common (45.5%) and is associated with more severe pain and associated symptoms. Efforts to identify and target this group for interventions may improve patient outcomes.

Characteristics associated with inter-individual variability in financial distress in patients with breast cancer prior to and for 12 months following surgery.

PURPOSE: To evaluate for inter-individual differences in financial distress and identify demographic, clinical, and symptom characteristics associated with higher levels of financial distress. METHODS: Patients (n = 387) were enrolled prior to breast cancer surgery and followed for 12 months. Financial distress was measured using a 0 (no problem) to 10 (severe problem) numeric rating scale. Hierarchical linear modeling was used to evaluate for inter-individual differences in trajectories of financial distress and characteristics associated with financial distress at enrollment and over 12 months. RESULTS: Patients' mean age was 55.0 (± 11.7) years and the majority underwent breast conservation surgery (80.6%). Mean financial distress score prior to surgery was 3.3 (± 3.4; range 0 to 10). Unconditional model for financial distress demonstrated no significant changes over time (-0.006/month). Younger age, lower income, receipt of an axillary lymph node dissection and adjuvant chemotherapy, and lower attentional function were associated with higher preoperative levels of financial distress. CONCLUSION: Risk factors identified in this study can be used to inform clinicians regarding the need to initiate financial discussions and social work referrals for some patients. Additional clinical or system level interventions should be considered for vulnerable groups with these risk factors.

Stakeholders' Perspectives regarding Participation in Neuromodulation-Based Dementia Intervention Research.

This study evaluated stakeholders' perspectives regarding participation in two hypothetical neuromodulation trials focused on individuals with Alzheimer's disease and related disorders (ADRDs). Stakeholders (i.e., individuals at risk for ADRDs [n = 56], individuals with experience as a caregiver for someone with a cognitive disorder [n = 60], and comparison respondents [n = 124]) were recruited via MTurk. Primary outcomes were willingness to enroll (or enroll one's loved one), feeling lucky to have the opportunity to enroll, and feeling obligated to enroll in two protocols (transcranial magnetic stimulation, TMS; deep brain stimulation, DBS). Relative to the Comparison group, the At Risk group endorsed higher levels of "feeling lucky" regarding both research protocols, and higher willingness to participate in the TMS protocol. These findings provide tentative reassurance regarding the nature of decision making regarding neurotechnology-based research on ADRDs. Further work is needed to evaluate the full range of potential influences on research participation.

Multimedia Psychotherapy: brief report of a pilot study.

INTRODUCTION: Multimedia Psychotherapy is a new form of brief psychotherapy based on narrative medicine and ethnopsychoanalytic theories, developed to help patients affected by prolonged grief disorder (ICD-11). It consists of eight sessions, during which an 'audio-video memory object' is produced by using pictures, video clips, and music chosen by the bereaved patient. The audio-video montage is focused on remembering the deceased relative and help the patient to move on. Considering initial positive results, we ran a first controlled pilot study comparing experimental and control group. METHODS: We enrolled a sample of bereaved patients who were referred for prolonged grief disorder (ICD-11) by their general practitioners or psychiatrists. Patients were randomly assigned to the experimental group (n=18) or to the control group (n=18). Patients in the experimental group received psycho-pharmacological therapy and multimedia psychotherapy, while patients in the control group received psycho-pharmacological therapy and psycho-oncological support. All patients were assessed with Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Prolonged Grief-13 (PG-13) prior to beginning treatment (pre-treatment), and with PG-13 after six months from the end of the treatment (post-treatment). RESULTS: Patients in the experimental group (i.e., Multimedia Psychotherapy treatment) after six months performed better than patients in the control group in Criteria B, D, and E of PG-13 (i.e.: Separation Distress, Cognitive, Emotional, and Behavioral Symptoms, Functional Impairment). DISCUSSION: We will discuss our results, issues related to the screening of patients (due to possible contraindications of Multimedia Psychotherapy), and methodological limitations. Finally, we will discuss new future applications in other clinical situations. CONCLUSIONS: These findings suggest that multimedia psychotherapy may hold promise for the treatment of prolonged grief disorder (ICD-11).

Perceived protectiveness of research safeguards and influences on willingness to participate in research: A novel MTurk pilot study.

Little is known about how individuals with mood disorders view the protectiveness of research safeguards, and whether their views affect their willingness to participate in psychiatric research. We conducted an online survey with 80 individuals (self-reported mood disorder [n = 25], self-reported good health [n = 55]) recruited via MTurk. We assessed respondents' perceptions of the protectiveness of five common research safeguards, as well as their willingness to participate in research that incorporates each safeguard. Perceived protectiveness was strongly related to willingness to participate in research for four of the safeguards. Our findings add to a limited literature on the motivations and perspectives of key stakeholders in psychiatric research.

Who comes to a self-help depression prevention website? Characteristics of Spanish- and English-speaking visitors.

OBJECTIVE: To describe demographic and clinical characteristics of Spanish- and English-speaking visitors to a "Healthy Mood" website. METHODS: An online study intended to prevent depression by teaching users mood management skills recruited participants globally using primarily Google Ads. Those who consented responded to the Patient Health Questionnaire (PHQ-9) and the MDE Screener (Muñoz, 1998) upon entry into the study. RESULTS: 1423 participants consented, 437 English speakers and 986 Spanish speakers. Of the 1271 participants with sufficient depression symptom data, 65% screened positive for a current major depressive episode, 30% were at high risk for onset of a major depressive episode, and 5% were in the low-risk category. CONCLUSION: Websites intended to be preventive appear to attract primarily individuals who are currently experiencing enough symptoms to screen positive for a major depressive episode. Only 30% of participants were appropriate for a depression prevention intervention. Therefore, such sites must be ready to encourage those with current depression to obtain professional help as well as ensure that the online self-help interventions are appropriate for participants who could benefit from both preventive and treatment interventions.

Distinct profiles of multiple co-occurring symptoms in patients with gastrointestinal cancers receiving chemotherapy.

PURPOSE: Identify subgroups of gastrointestinal (GI) cancer patients with distinct multiple co-occurring symptom profiles and evaluate for differences among these subgroups in demographic and clinical characteristics and quality of life (QOL) outcomes. METHODS: Patients with GI cancers (n = 399) completed the Memorial Symptom Assessment Scale (MSAS) that was used to assess for multiple co-occurring symptoms. Latent class analysis (LCA) was used to identify subgroups of patients with distinct symptom profiles using symptom occurrence ratings. Differences in demographic and clinical characteristics and QOL outcomes among the subgroups were evaluated using parametric and nonparametric tests. RESULTS: All Low (36.6%), Moderate (49.4%), and All High (14.0%) classes were identified. Compared to the All Low class, patients in the other two classes were significantly younger and were more likely to report depression and back pain. Compared to the other two classes, patients in the All High class had fewer years of education and a higher number of comorbidities. Significant differences were found among the three classes for comorbidity burden and total number of MSAS symptoms (i.e., All Low < Moderate < All High), as well as for performance status (i.e., All Low > Moderate > All High). A higher symptom burden was associated with poorer QOL outcomes. CONCLUSIONS: The first study to identify subgroups of patients with GI cancers based on distinct symptom profiles. LCA allowed for the identification of risk factors associated with a higher symptom burden. Clinicians can use this information to identify high-risk patients and develop personalized symptom management interventions.

Higher Levels of Stress Are Associated With a Significant Symptom Burden in Oncology Outpatients Receiving Chemotherapy.

CONTEXT: A cancer diagnosis and associated treatments, as well as the uncertainty of the disease course, are stressful experiences for most patients. However, little information is available on the relationship between stress and symptom burden. OBJECTIVES: The study purpose was to evaluate for differences in the severity of fatigue, lack of energy, sleep disturbance, and cognitive function, among three groups of patients with distinct stress profiles. METHODS: Patients receiving chemotherapy (n = 957) completed measures of general, cancer-specific, and cumulative life stress and symptom inventories. Latent profile analysis was used to identify subgroups of patients with distinct stress profiles. RESULTS: Three distinct subgroups of patients were identified (i.e., stressed [39.3%], normative [54.3%], resilient [5.7%]). For cognitive function, significant differences were found among the latent classes (stressed < normative < resilient). For both sleep disturbance and morning and evening fatigue, compared to the normative and resilient classes, the stressed class reported higher severity scores. Compared to the normative and resilient classes, the stressed class reported low levels of morning energy. Compared to the normative class, the stressed class reported lower levels of evening energy. CONCLUSIONS: Consistent with our a priori hypothesis, patients in the stressed class had the highest symptom severity scores for all four symptoms and all these scores were above the clinically meaningful cutoffs for the various instruments.

Co-occurrence of decrements in physical and cognitive function is common in older oncology patients receiving chemotherapy.

PURPOSE: Older adults receiving cancer chemotherapy are at increased risk for decrements in physical (PF) and cognitive (CF) function. OBJECTIVES: Study identified subgroups of patients with distinct PF and CF profiles; risk factors associated with subgroup membership; and impact of subgroup membership on quality of life (QOL). METHODS: In 366 older oncology patients, PF and CF were assessed using the Physical Component Summary (PCS) of the SF-12 and Attentional Function Index, respectively. Latent profile analysis was used to identify subgroups of older patients with distinct PF/CF profiles. RESULTS: Three distinct PF/CF profiles were identified (i.e., Very Low PF + Moderate CF (15.6%); Low PF + Low CF (39.3%), Normal PF + Normal CF (45.1%)). Compared to the both Normal class, patients in the other two classes had a lower functional status, a worse comorbidity profile, and were less likely to exercise on a regular basis. Compared to the Both Normal class, patients in the Both Low class were less likely to be married/partnered, more likely to live alone, less likely to be employed, and more likely to report depression and back pain. Compared to the other two classes, patients in the Both Low class had a lower annual household income and were receiving chemotherapy with a worse toxicity profile. CONCLUSION: First study to use a person-centered analytic approach to identify subgroups of older adults with distinct PF/CF profiles. Fifty-five percent of the older adults had statistically significant and clinically meaningful decrements in both PF AND CF that had negative effects on all aspects of QOL.

Gender Differences in the Use of Engagement and Disengagement Coping Strategies in Patients With Cancer Receiving Chemotherapy.

OBJECTIVES: To evaluate the relationship between gender and coping strategies in patients with cancer undergoing chemotherapy in outpatient settings. SAMPLE & SETTING: Women (N = 277) and men (N = 293) were recruited from two comprehensive cancer centers, one Veterans Affairs hospital, and four community-based oncology programs. METHODS & VARIABLES: Coping data were obtained from patients with gastrointestinal (n = 412) or lung (n = 158) cancer through the Brief COPE scale. RESULTS: In terms of engagement coping strategies, women reported higher scores for positive reframing, religion, and using instrumental support. Men reported higher scores for humor. In terms of disengagement coping strategies, women reported higher scores for denial, venting, and self-distraction. Men reported higher scores for substance use. IMPLICATIONS FOR NURSING: Gender-based stereotypes of emotional expectations may affect how patients express themselves and the ways in which support is offered. Clinicians should be aware of their own preconceived notions about sex and gender and reflect on how these may influence the psychosocial care they provide.

Brain-Responsive Neurostimulation for Loss of Control Eating: Early Feasibility Study.

BACKGROUND: Loss of control (LOC) is a pervasive feature of binge eating, which contributes significantly to the growing epidemic of obesity; approximately 80 million US adults are obese. Brain-responsive neurostimulation guided by the delta band was previously found to block binge-eating behavior in mice. Following novel preclinical work and a human case study demonstrating an association between the delta band and reward anticipation, the US Food and Drug Administration approved an Investigational Device Exemption for a first-in-human study. OBJECTIVE: To assess feasibility, safety, and nonfutility of brain-responsive neurostimulation for LOC eating in treatment-refractory obesity. METHODS: This is a single-site, early feasibility study with a randomized, single-blinded, staggered-onset design. Six subjects will undergo bilateral brain-responsive neurostimulation of the nucleus accumbens for LOC eating using the RNS® System (NeuroPace Inc). Eligible participants must have treatment-refractory obesity with body mass index ≥ 45 kg/m2. Electrophysiological signals of LOC will be characterized using real-time recording capabilities coupled with synchronized video monitoring. Effects on other eating disorder pathology, mood, neuropsychological profile, metabolic syndrome, and nutrition will also be assessed. EXPECTED OUTCOMES: Safety/feasibility of brain-responsive neurostimulation of the nucleus accumbens will be examined. The primary success criterion is a decrease of ≥1 LOC eating episode/week based on a 28-d average in ≥50% of subjects after 6 mo of responsive neurostimulation. DISCUSSION: This study is the first to use brain-responsive neurostimulation for obesity; this approach represents a paradigm shift for intractable mental health disorders.