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Persistent, severe pain negatively impacts health and wellbeing, but half of patients do not receive adequate relief from current treatments. Understanding signals that modulate central pain processing could point to new strategies to manage severe pain. Administering Neurotensin (Nts) or Nts receptor (NtsR) agonists into the brain provides analgesia comparable to pharmacologic opioids. However, the endogenous sources of Nts that modify pain processing and might be leveraged for pain relief remained unknown. We previously characterized a large population of Nts-expressing neurons in the lateral hypothalamic area (LHA Nts neurons) that project to brain regions that participate in descending control of pain processing. We hypothesized that LHA Nts neurons are an endogenous source of Nts and activating them would alleviate pain dependent on Nts signaling via NtsRs. To test this, we injected Nts Cre mice in the LHA with AAVs to cre-dependently express either mCherry (Control) or the excitatory hM3Dq in LHA Nts neurons, permitting their stimulation after treatment with the hM3Dq ligand clozapine N-oxide (CNO). Activating LHA Nts neurons had no effect on thermal pain and mechanical responses in naïve mice. By contrast, both spared nerve injury- (SNI) and complete Freund's adjuvant (CFA)-induced mechanical hypersensitivity was completely reversed by CNO-stimulation of LHA Nts neurons. Pretreatment with the Nts receptor antagonist SR142948 reduced CNO-mediated analgesia, indicating that LHA Nts neurons alleviate chronic pain in an Nts receptor-dependent manner. Taken together these data identify LHA Nts neurons as an endogenous source of Nts that modulates central pain processing and may inform future development of Nts-based targets to treat severe pain., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: While most research has largely focused on medical risks associated with reduced health-related quality of life (HRQOL) in survivors, sociodemographic and family factors may also play a role. Thus, we longitudinally examined sociodemographic factors and family factors associated with survivor HRQOL, including adolescent's cancer-specific stress, mother's general stress, and mother-adolescent communication., Methods: Mothers (N = 80) and survivors (ages 10-23, N = 50) were assessed 5 years following initial diagnosis. Mothers completed measures regarding sociodemographic background adolescent's cancer-specific stress, mother's general stress, mother-adolescent communication, and adolescent HRQOL. Survivors also reported on their own HRQOL. Two hierarchical multiple regressions examined predictors of (a) mother's report of adolescent HRQOL, and (b) survivor's self-report of HRQOL., Results: The final model predicting mother-reported adolescent HRQOL was significant, F(5,74) = 21.18, p < .001, and explained 59% of the variance in HRQoL. Significant predictors included adolescent stress (β = -.37, p < .001), mothers' stress (β = -.42, p < .001), and communication (β = .19, p = .03). The final model predicting survivor-reported HRQOL was also significant, F(5,44) = 5.16, p < .01 and explained 24% of the variance in HRQOL. Significant predictors included adolescent stress (β = -.37, p = .01) and communication (β = -.31, p = .04). Sociodemographic factors were not a significant predictor of HRQOL in any model., Conclusion: Family stress and communication offer potential points of intervention to improve HRQOL of pediatric cancer survivors from mother and survivor perspectives. While additional research is needed, healthcare professionals should encourage stress management and strong mother-child communication to enhance survivors' long-term HRQOL. Such interventions may be complimentary to efforts targeting the known sociodemographic factors that often affect health., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Objective: Children diagnosed with cancer experience stress associated with their diagnosis and treatment and are at heightened risk for problems in social adjustment. This study investigated the association between coping with cancer-related stress and problems in social adjustment across the first year after a pediatric cancer diagnosis., Methods: Mothers of children (ages 5-17 years) with cancer (N = 312) were recruited from two children's hospitals. Mother's reported on their child's social adjustment and coping near diagnosis (T1) and 12 months (T2)., Results: Primary, secondary control, and disengagement coping were significantly associated with concurrent social adjustment at 12 months. The bivariate associations between baseline primary and secondary control coping and social problems 12 months later were no longer significant in a multivariate regression model., Conclusions: These findings inform our understanding of the association between coping with cancer-related stress and social adjustment of children diagnosed with cancer. Interventions teaching primary and secondary control coping strategies for cancer-related stressors may offer some benefit to concurrent youth social adjustment. Further research is needed on how best to support social adjustment in this population over time., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Children with sickle cell disease (SCD) are at increased risk for cognitive impairment as a result in part from biological characteristics of the disease; however, limited research has explored possible social and contextual factors associated with risk for cognitive problems. The primary aim of the present study was to examine the relation between children's cognitive functioning and responsive parenting, a potentially important contextual factor in children with SCD, accounting for family socioeconomic disadvantage, child disease severity, and caregivers' perceived stress., Methods: Forty-eight children completed standardized cognitive assessments and caregivers provided self-reports of general and disease-related stress. Parent-child dyads completed a video recorded puzzle-solving task and observed parenting was quantified using two coding systems. Bivariate Pearson correlations were used to assess preliminary hypotheses, and linear multiple regression analyses were used to assess the primary hypothesis., Results: Results suggested that increased levels of parental stress were related to fewer observations of responsive parenting and provided evidence of an association between children's cognitive function and responsive parenting. Specifically, increased disease-related parent stress and reduced parental use of expansive language were associated with significantly lower cognitive functioning in children with SCD., Conclusions: Findings suggest that social environmental factors along with disease characteristics are sources of risk for cognitive problems with children with SCD. Further, these findings highlight the need to develop targeted interventions for parents of children with SCD to decrease levels of stress and enhance parenting skills, with the aim improving cognitive functioning in youth., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Children with sickle cell anemia (SCA) have elevated cerebral blood velocity relative to healthy peers. The primary aim of this study was to evaluate the association between cerebral blood velocity, measured by transcranial Doppler (TCD) ultrasound, age, and gender with cognitive function in children with SCA in Nigeria. Eighty-three children (M age  = 9.10, SD = 1.90 years; 55% female) with SCA in Nigeria completed cognitive assessments and a TCD ultrasound. The association between TCD velocity and measures of perceptual reasoning (Raven's Progressive Matrices), working memory (WISC-IV Digit Span), and executive planning (Tower of London, TOL) were assessed. Results showed that elevated TCD velocity significantly predicted lower scores on TOL Time Violations and Total Problem-Solving Time when controlling for BMI, hemoglobin level, and parent education, suggesting that TCD velocity is related to the efficiency of executive function. Further, age was negatively related to children's performance on the Ravens Matrices and TOL Total Correct, and boys showed greater deficits on the TOL Total Correct relative to girls. Moderation analyses for gender showed that there was a conditional negative association between TCD velocity and Digit Span for boys, but not for girls. Findings suggest that children with SCA in Nigeria with elevated TCD velocity are at risk for deficits in efficiency of executive planning, and boys with elevated TCD velocity are particularly at increased risk for deficits in auditory working memory. Implications of this study are important for interventions to reduce cerebral blood velocity and the use of TCD in this population.

Research has shown that children experience increased emotional distress when engaging in emotional caretaking of a parent. The current study is the first to examine this process in families in which the source of the stress is the child's illness. Prospective associations were tested among mothers' depressive symptoms near the time of their child's cancer diagnosis, mothers' expressed distress and their child's emotional caretaking during an interaction task, and child anxious/depressed symptoms at 1 year postdiagnosis. Families ( N = 78) were recruited from two pediatric hospitals soon after their child's (Ages 5-18) new diagnosis or relapse of cancer. Mothers reported on their own depressive symptoms and their child's anxious/depressed symptoms near the time of diagnosis or recurrence (Time 1) and 1 year later (Time 3). At Time 2 (4 months after Time 1), mother-child dyads completed a video-recorded discussion of their experience with cancer that was coded for observed maternal expressed distress (anxiety, sadness) and observed child emotional caretaking. Maternal expressed distress during the interaction was significantly related to more emotional caretaking behaviors by both boys and girls. Results of a moderated mediation model showed that child emotional caretaking at Time 2 significantly mediated the relation between maternal depressive symptoms at Time 1 and child anxious/depressed symptoms at Time 3 for girls but not for boys. The findings suggest that children's emotional caretaking behaviors contribute to subsequent anxious/depressed symptoms for girls, but not for boys, with cancer. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Objective: This study aimed to characterize mothers' communication with their children in a sample of families with a new or newly relapsed pediatric cancer diagnosis, first using factor analysis and second using structural equation modeling to examine relations between self-reported maternal distress (anxiety, depression, and posttraumatic stress) and maternal communication in prospective analyses. A hierarchical model of communication was proposed, based on a theoretical framework of warmth and control., Methods: The sample included 115 children (age 5-17 years) with new or newly relapsed cancer (41% leukemia, 18% lymphoma, 6% brain tumor, and 35% other) and their mothers. Mothers reported distress (Beck Anxiety Inventory, Beck Depression Inventory-II, and Impact of Events Scale-Revised) 2 months after diagnosis (Time 1). Three months later (Time 2), mother-child dyads were video-recorded discussing cancer. Maternal communication was coded with the Iowa Family Interaction Ratings Scales., Results: Confirmatory factor analysis demonstrated poor fit. Exploratory factor analysis suggested a six-factor model (root mean square error of approximation = .04) with one factor reflecting Positive Communication, four factors reflecting Negative Communication (Hostile/Intrusive, Lecturing, Withdrawn, and Inconsistent), and one factor reflecting Expression of Negative Affect. Maternal distress symptoms at Time 1 were all significantly, negatively related to Positive Communication and differentially related to Negative Communication factors at Time 2. Maternal posttraumatic stress and depressive symptoms each predicted Expression of Negative Affect., Conclusions: Findings provide a nuanced understanding of maternal communication in pediatric cancer and identify prospective pathways of risk between maternal distress and communication that can be targeted in intervention.

Objective: The objective of this study was to investigate the association between cognitive functioning, coping, and depressive symptoms in children and adolescents with sickle cell disease (SCD)., Method: Forty-four children (M age = 9.30, SD = 3.08; 56.8% male) with SCD completed cognitive assessments measuring working memory (Wechsler Intelligence Scale for Children-Fourth Edition) and verbal comprehension (Wechsler Abbreviated Scale of Intelligence-Second Edition). Participants' primary caregivers completed questionnaires assessing their child's coping and depressive symptoms., Results: Verbal comprehension was significantly positively associated with secondary control coping (cognitive reappraisal, acceptance, distraction), and both working memory and secondary control coping were negatively associated with depressive symptoms. In partial support of the primary study hypothesis, verbal comprehension had an indirect association with depressive symptoms through secondary control coping, whereas working memory had a direct association with depressive symptoms., Conclusions: The results provide new evidence for the associations between cognitive function and coping, and the association of both of these processes with depressive symptoms in children with SCD. Findings provide potential implications for clinical practice, including interventions to improve children's cognitive functioning to attenuate depressive symptoms.

Objective: The purpose of this study was to prospectively examine adolescent and maternal posttraumatic stress symptoms (PTSS) and maternal communication from time near cancer diagnosis to 12-month follow-up to identify potential risk factors for adolescent PTSS., Methods: Forty-one adolescents with cancer (10-17 years, 54% female) and their mothers self-reported PTSS at T1 (two months after cancer diagnosis) and T3 (1-year follow-up). At T2 (3 months after T1), mother-adolescent dyads were videotaped discussing cancer, and maternal communication was coded with macro (harsh and withdrawn) and micro (solicits and validations) systems., Results: Adolescent PTSS at T1 was associated with adolescent PTSS at T3. Greater maternal PTSS at T1 predicted greater harsh maternal communication at T2. There was an indirect effect of maternal PTSS at T1 on adolescent PTSS at T3 through maternal validations at T2., Conclusions: Findings underscore the importance of maternal PTSS, maternal communication, and subsequent adolescent PTSS over the course of treatment of childhood cancer. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: This study sought to identify possible associations between maternal coping and depression and subsequent mother-child communication about cancer following the child's diagnosis. , Method: Mothers (N = 100) reported on coping and depressive symptoms shortly after the child's diagnosis (M = 1.9 months). Subsequently, we observed children (age 5-17 years; M = 10.2 years; 48% female; 81% White) and mothers discussing cancer and coded maternal communication. , Results: Higher primary and secondary control coping, and lower depressive symptoms, were generally correlated with more positive, and less harsh and withdrawn communication. In regression models, higher primary control coping (i.e., coping efforts to change the stressor or one's emotional reaction to the stressor) independently predicted less withdrawn communication, and depressive symptoms mediated relations between coping and harsh communication. , Conclusions: Maternal primary control coping and depressive symptoms predict mothers' subsequent harsh and withdrawn communication about cancer., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To examine associations between sociodemographic factors (single parenthood, family income, education level, race), stress, and psychological distress among pediatric cancer patients and their mothers., Methods: Participants completed measures assessing sociodemographic variables, depressive symptoms, posttraumatic stress symptoms, general stress, and cancer-related stress within the first year of the child's (ages 5-17 years) cancer diagnosis or relapse. Mothers (N = 318) provided self-reports and parent report of their children; children aged 10-17 years (N = 151) completed self-reports., Results: Each sociodemographic variable demonstrated unique associations with mothers' and children's stress and distress in bivariate analyses. A cumulative sociodemographic risk measure was positively correlated with all stress and distress variables. In regression analyses predicting mothers' and children's distress, independent and cumulative sociodemographic measures were no longer significant when accounting for levels of stress., Conclusions: Findings highlight the need to consider the ecological context of pediatric cancer, particularly the impact of sociodemographic disadvantage on stress and distress in this population., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To examine individual and interpersonal processes of coping and emotional distress in a sample of mothers and fathers of children with recently diagnosed cancer., Method: A sample of 317 mothers and 166 fathers of 334 children were recruited near the time of the child's cancer diagnosis or relapse (M = 1.4 months, SD = 1.2). Mothers and fathers completed standardized measures of coping and depressive symptoms., Results: Analyses of individual coping responses revealed that, for both mothers and fathers, primary control coping (e.g., problem solving, emotional modulation) and secondary control coping (e.g., acceptance, cognitive reappraisal) were associated with lower depressive symptoms. Interpersonal analyses of coping and distress indicated that mothers' and fathers' coping as well as depressive symptoms were significantly correlated. Actor-partner interdependence model analyses indicated that mothers' coping was associated with fathers' depressive symptoms. Significant interactions also suggested that mothers' secondary control coping may have a compensatory effect against fathers' use of disengagement coping, both for themselves and their husbands., Conclusion: Mothers' and fathers' adaptation to a child's cancer diagnosis and treatment are characterized by both individual and interpersonal processes, with secondary control coping playing a central role in both of these processes. Implications for interventions to enhance effective coping for parents of children with cancer are highlighted., ((c) 2015 APA, all rights reserved).)

Objective: The diagnosis and treatment of cancer present children and adolescents with significant stress. However, research on the ways that children and adolescents cope with cancer-related stress has not yielded clear findings on the efficacy of different coping strategies, and has been limited by reliance primarily on self-reports of both coping and distress. To address this gap, the current study used a control-based model of coping to examine self- and parent reports of child/adolescent coping and symptoms of anxiety and depression in a sample of children with cancer., Method: Children and adolescents (5 to 17 years old) and their parents were recruited near the time of a child's diagnosis or relapse of cancer (M = 1.30 months postdiagnosis). Child self-reports (n = 153), mother reports (n = 297), and father reports (n = 161) of children's coping and symptoms of anxiety/depression were obtained., Results: Bivariate correlations revealed significant associations for secondary control coping (efforts to adapt to source of stress; e.g., acceptance, cognitive reappraisal) and disengagement coping (e.g., avoidance, denial) with anxiety/depression within and across informants. Linear multiple regression analyses indicated that secondary control coping accounted for unique variance in symptoms of anxiety/depression both within and across informants., Conclusions: Secondary control coping appears important for children and adolescents during early phases of treatment for cancer, and it may serve as an important target for future interventions to enhance adjustment in these children.

Introduction: Patients with terminal cancer often experience marked anxiety that is associated with poor quality of life. Although cognitive-behavioral therapy (CBT) is an evidence-based treatment for anxiety disorders, the approach needs to be adapted to address realistic concerns related to having cancer, such as worries about disease progression, disability, and death. In this pilot randomized controlled trial (clinicaltrials.gov identifier NCT00706290), we examined the feasibility and potential efficacy of brief CBT to reduce anxiety in patients with terminal cancer., Methods: We adapted CBT by developing treatment modules targeting skills for relaxation, coping with cancer worries, and activity pacing. Adults with incurable malignancies and elevated anxiety based on the Hamilton Anxiety Rating Scale (HAM-A) were randomly assigned to individual CBT or a waitlist control group. Primary outcomes included the number of completed CBT visits and the change in HAM-A scores from baseline to 8-week follow-up per a treatment-blind evaluator. The feasibility criterion was 75% adherence to the intervention., Results: We randomized 40 patients with terminal cancers to CBT (n = 20) or waitlist control (n = 20) groups; 70% completed posttreatment assessments. Most patients who received CBT (80%) participated in at least five of the required six therapy sessions. Analysis of covariance models, adjusted for baseline scores, showed that those assigned to CBT had greater improvements in HAM-A scores compared to the control group, with an adjusted mean difference of -5.41 (95% confidence interval: -10.78 to -0.04) and a large effect size for the intervention (Cohen's d = 0.80)., Conclusion: Providing brief CBT tailored to the concerns of patients with terminal cancer was not only feasible but also led to significant improvements in anxiety.

Introduction: Depression appears to be associated with worse survival from cancer, but underlying mechanisms for this association are unknown. In the present study, we explored the degree to which tumor genotype may be associated with depression in patients with non-small cell lung cancer (NSCLC). We examined differences in depression severity and rates of positive screens for major depressive disorder among newly diagnosed patients with stage IV NSCLC and known epidermal growth factor receptor (EGFR) genotype., Methods: Newly diagnosed patients (n = 53) with metastatic NSCLC attending an initial thoracic oncology consultation completed self-report questionnaires regarding demographics, smoking behavior, and depression before meeting with their oncologist. Biopsy samples were subsequently genotyped, including screening for EGFR mutations. We conducted a retrospective chart review to obtain clinical data, including tumor stage, performance status, and EGFR genotype., Results: Twelve patients (22.6%) tested positive for EGFR mutation. No EGFR mutation-positive cases met the screening criteria for major depressive disorder, in comparison with 29.3% of patients with wild-type EGFR (p = .03). Mutations of EGFR were also associated with lower depression severity than with wild-type EGFR, independent of gender, performance status, and smoking history (p < .05). This finding persisted for both the cognitive-affective and somatic domains of depression symptoms., Conclusions: EGFR mutations were associated with lower depression severity and lower rates of probable major depressive disorder in patients with metastatic NSCLC, based on mood screening performed before results of genotyping were known. Findings support further work to explore the directionality of the associations and potential biological pathways to depression.