Mechanism underlying a brief cognitive behavioral treatment for head and neck cancer survivors with body image distress.

PURPOSE: Body image distress (BID) among head and neck cancer (HNC) survivors is a debilitating toxicity associated with depression, anxiety, stigma, and poor quality of life. BRIGHT (Building a Renewed ImaGe after Head & neck cancer Treatment) is a brief cognitive behavioral therapy (CBT) that reduces BID for these patients. This study examines the mechanism underlying BRIGHT. METHODS: In this randomized clinical trial, HNC survivors with clinically significant BID were randomized to receive five weekly psychologist-led video tele-CBT sessions (BRIGHT) or dose-and delivery matched survivorship education (attention control [AC]). Body image coping strategies, the hypothesized mediators, were assessed using the Body Image Coping Skills Inventory (BICSI). HNC-related BID was measured with the Inventory to Measure and Assess imaGe disturbancE-Head and Neck (IMAGE-HN). Causal mediation analyses were used to estimate the mediated effects of changes in BICSI scores on changes in IMAGE-HN scores. RESULTS: Among 44 HNC survivors with BID allocated to BRIGHT (n = 20) or AC (n = 24), mediation analyses showed that BRIGHT decreased avoidant body image coping (mean change in BICSI-Avoidance scale score) from baseline to 1-month post-intervention relative to AC (p = 0.039). Decreases in BICSI-Avoidance scores from baseline to 1-month resulted in decreases in IMAGE-HN scores from baseline to 3 months (p = 0.009). The effect of BRIGHT on IMAGE-HN scores at 3 months was partially mediated by a decrease in BICSI-Avoidance scores (p = 0.039). CONCLUSIONS: This randomized trial provides preliminary evidence that BRIGHT reduces BID among HNC survivors by decreasing avoidant body image coping. Further research is necessary to confirm these results and enhance the development of interventions targeting relevant pathways to reduce BID among HNC survivors. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03831100 .

Mechanism Underlying a Brief Cognitive Behavioral Treatment for Head and Neck Cancer Survivors with Body Image Distress.

Purpose: Body image distress (BID) among head and neck cancer (HNC) survivors is a debilitating toxicity associated with depression, anxiety, stigma, and poor quality of life. BRIGHT (Building a Renewed ImaGe after Head & neck cancer Treatment) is a brief cognitive behavioral therapy (CBT) that reduces BID for these patients. This study examines the mechanism underlying BRIGHT. Methods: In this randomized clinical trial, HNC survivors with clinically significant BID were randomized to receive 5 weekly psychologist-led video tele-CBT sessions (BRIGHT) or dose-and delivery matched survivorship education (attention control [AC]). Body image coping strategies, the hypothesized mediators, were assessed using the Body Image Coping Skills Inventory (BICSI). HNC-related BID was measured with the IMAGE-HN. Causal mediation analyses were used to estimate the mediated effects of changes in BICSI scores on changes in IMAGE-HN scores. Results: Among 44 HNC survivors with BID, mediation analyses showed that BRIGHT decreased avoidant body image coping (mean change in BICSI-Avoidance scale score) from baseline to 1-month post-intervention relative to AC (p = 0.039). Decreases in BICSI-Avoidance scores from baseline to 1-month decreased IMAGE-HN scores from baseline to 3-months (p = 0.009). The effect of BRIGHT on IMAGE-HN scores at 3-months was partially mediated by a decrease in BICSI-Avoidance scores (p = 0.039). Conclusions: This randomized trial provides preliminary evidence that BRIGHT reduces BID among HNC survivors by decreasing avoidant body image coping. Further research is necessary to confirm these results and enhance the development of interventions targeting relevant pathways to reduce BID among HNC survivors. Trial Registration: This trial was registered on ClinicalTrials.gov identifier NCT03831100 on February 5, 2019.

Efficacy of a Brief Cognitive Behavioral Therapy for Head and Neck Cancer Survivors with Body Image Distress: Secondary Outcomes from the BRIGHT Pilot Randomized Clinical Trial.

Purpose: Body image distress (BID) among head and neck cancer (HNC) survivors leads to depression, social isolation, stigma, and poor quality of life. BRIGHT ( B uilding a R enewed I ma G e after H ead & neck cancer T reatment) is a brief, tailored cognitive behavioral therapy (CBT) that reduces HNC-related BID. This trial examines the effect of BRIGHT on psychosocial outcomes among HNC survivors with BID. Methods: In this pilot randomized trial, HNC survivors with clinically significant BID were randomized to 5 weekly psychologist-led tele-CBT sessions (BRIGHT) or dose-and delivery matched survivorship education (attention control [AC]). Secondary psychosocial outcomes were assessed using validated patient-reported outcomes at baseline and 1- and 3-months post-intervention. Results: Among 44 HNC survivors with BID, BRIGHT resulted in a greater reduction in depression relative to AC (mean model-based 1-month difference in Δ PROMIS SF v1.0-Depression 8a score, -3.4; 90% CI, -6.4 to -0.4; 3-month difference, -4.3; 90% CI, -7.8 to -0.8). BRIGHT also decreased shame and stigma relative to AC (mean model-based 3-month difference in Δ Shame and Stigma Scale score, -9.7; 90% CI, -15.2 to -4.2) and social isolation (mean model-based 3-month difference in Δ PROMIS SF v2.0 Social Isolation 8a score, -2.9; 90% CI, -5.8 to -0.1). Conclusions: In this planned secondary analysis of a pilot RCT, BRIGHT improved a broad array of psychosocial outcomes among HNC survivors with BID. Implications for Cancer Survivors: These promising preliminary data suggest the need for a large efficacy trial evaluating the effect of BRIGHT on psychosocial outcomes among HNC survivors with BID. Trial Registration: ClinicalTrials.gov identifier: NCT03831100.

Intranasal insulin helps overcome brain insulin deficiency and improves survival and post-stroke cognitive impairment in male mice.

Obesity increases the risk for stroke and is associated with worse post-stroke outcomes; however, the mechanisms are poorly understood. Diet-induced obesity leads to insulin resistance and subsequently, brain insulin deficiency. The purpose of this study was to investigate the potential impact of brain insulin deficiency on post-stroke outcomes. To accomplish this, brain insulin levels were assessed in male C57BL/6J (B6) mice placed on either a standard diet or 54% kcal high-fat diet, a known model of insulin resistance. Mice were subjected to either a sham surgery (control) or 30-min middle cerebral artery occlusion to induce an ischemic stroke and administered either intranasal saline (0.9%) or intranasal insulin (1.75 U) twice daily for 5 days beginning on day 1 post-stroke. High-fat diet-induced brain insulin deficiency was associated with increased mortality, neurological and cognitive deficits. On the other hand, increasing brain insulin levels via intranasal insulin improved survival, neurological and cognitive function in high-fat diet mice. Our data suggests that brain insulin deficiency correlates with worse post-stroke outcomes in a diet-induced mouse model of insulin resistance and increasing brain insulin levels may be a therapeutic target to improve stroke recovery.

Efficacy of a brief cognitive behavioral therapy for head and neck cancer survivors with body image distress: secondary outcomes from the BRIGHT pilot randomized clinical trial.

PURPOSE: Body image distress (BID) among head and neck cancer (HNC) survivors leads to depression, social isolation, stigma, and poor quality of life. BRIGHT (Building a Renewed ImaGe after Head and neck cancer Treatment) is a brief, tailored cognitive behavioral therapy (CBT) that reduces HNC-related BID. This trial examines the effect of BRIGHT on psychosocial outcomes among HNC survivors with BID. METHODS: In this pilot randomized trial, HNC survivors with clinically significant BID were randomized to 5 weekly psychologist-led tele-CBT sessions (BRIGHT) or dose and delivery-matched survivorship education (attention control [AC]). Secondary psychosocial outcomes were assessed using validated patient-reported outcomes at baseline and 1 and 3-month post-intervention. RESULTS: Among 44 HNC survivors with BID, BRIGHT resulted in a greater reduction in depression relative to AC (mean model-based 1-month difference in Δ PROMIS SF v1.0-Depression 8a score, -3.4; 90% CI, -6.4 to -0.4; 3-month difference, -4.3; 90% CI, -7.8 to -0.8). BRIGHT also decreased shame and stigma relative to AC (mean model-based 3-month difference in Δ Shame and Stigma Scale score, -9.7; 90% CI, -15.2 to -4.2) and social isolation (mean model-based 3-month difference in Δ PROMIS SF v2.0 Social Isolation 8a score, -2.9; 90% CI, -5.8 to -0.1). CONCLUSIONS: In this planned secondary analysis of a pilot RCT, BRIGHT improved a broad array of psychosocial outcomes among HNC survivors with BID. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03831100 . IMPLICATIONS FOR CANCER SURVIVORS: These promising preliminary data suggest the need for a large efficacy trial evaluating the effect of BRIGHT on psychosocial outcomes among HNC survivors with BID.

Hyperinsulinemia alters insulin receptor presentation and internalization in brain microvascular endothelial cells.

Insulin receptors are internalized by endothelial cells to facilitate their physiological processes; however, the impact of hyperinsulinemia in brain endothelial cells is not known. Thus, the aim of this study was to elucidate the impact hyperinsulinemia plays on insulin receptor internalization through changes in phosphorylation, as well as the potential impact of protein tyrosine phosphatase 1B (PTP1B). Hippocampal microvessels were isolated from high-fat diet fed mice and assessed for insulin signaling activation, a process known to be involved with receptor internalization. Surface insulin receptors in brain microvascular endothelial cells were labelled to assess the role hyperinsulinemia plays on receptor internalization in response to stimulation, with and without the PTP1B antagonist, Claramine. Our results indicated that insulin receptor levels increased in tandem with decreased receptor signaling in the high-fat diet mouse microvessels. Insulin receptors of cells subjected to hyperinsulinemic treatment demonstrate splice variation towards decreased IR-A mRNA expression and demonstrate a higher membrane-localized proportion. This corresponded with decreased autophosphorylation at sites critical for receptor internalization and signaling. Claramine restored signaling and receptor internalization in cells treated with hyperinsulinemia. In conclusion, hyperinsulinemia impacts brain microvascular endothelial cell insulin receptor signaling and internalization, likely via alternative splicing and increased negative feedback from PTP1B.