Stress in Huntington's Disease: Characteristics and Correlates in Patients and At-Risk Individuals.

Background: Huntington's disease (HD) is a neurodegenerative disease that presents families with significant numbers of stressful events. However, relatively little empirical research has characterized the stressors encountered by members of HD-affected families and their correlations with psychological symptoms. Objective: This study examined frequencies of specific stressors in HD patients and at-risk individuals and the correlates of these stressors with demographics, disease characteristics, and symptoms of depression and anxiety. Methods: HD patients (n = 57) and at-risk individuals (n = 81) completed the Responses to Stress Questionnaire -Huntington's Disease Version to assess HD-related stressors. Participants completed measures of depression and anxiety symptoms. Patient health records were accessed to obtain information related to disease characteristics. Results: Patients endorsed a mean number of 5.05 stressors (SD = 2.74) out of the 10-item list. Demographics were not related to total stressors, but disease characteristics were significantly related to specific stressors. At-risk individuals endorsed a mean number of 3.20 stressors (SD = 2.65) out of the 11-item list. Age and sex were significantly related to specific stressors. Total number of stressors was significantly related to depression (ß=0.67, p <  0.001) and anxiety symptoms (ß=0.58, p <  0.001) in patients and at-risk individuals (ß=0.35, p = 0.003 and ß=0.32, p = 0.006, respectively). Conclusions: hese findings emphasize the significant burden of stress experienced by HD patients and at-risk individuals. We highlight a need for more specific stress-based measures and psychosocial support interventions for HD-affected families.

Intrapersonal and Interpersonal Disengagement Coping: Associations with Emotions of Youth At-Risk for Huntington's Disease.

BACKGROUND: Families in which a parent has Huntington's disease (HD) are faced with significant stressors that can contribute to difficulties in communicating together about illness-related concerns. Family members who use more disengagement coping strategies, including denial and avoidance, to deal with illness-related stressors may have the greatest challenges to effective communication. OBJECTIVE: The current study examined the associations of intrapersonal and interpersonal disengagement coping responses with observed and reported emotions of adolescents and young adults (AYA) at genetic risk for HD. METHODS: Families included 42 AYA (n = 26 females) ages 10 to 34 (M = 19 years, 11 months; SD = 7 years, 6 months) and their parent with HD (n = 22 females, M age = 46 years, 10 months; SD = 9 years, 2 months). Dyads participated in observations of communication and completed questionnaires about disengagement coping and internalizing symptoms. RESULTS: Disengagement coping of AYA was unrelated to their observed and reported emotional difficulties (intrapersonal coping). However, there was evidence for the importance of interpersonal disengagement coping, as AYA's negative affect was observed and reported to be highest when both AYA and their parents reported using high levels of avoidance, denial, and wishful thinking to cope with HD-related stress. CONCLUSION: The findings underscore the importance of a family-oriented approach to coping and communication in families affected by HD.

Impairments to executive function in emerging adults with Huntington disease.

BACKGROUND AND OBJECTIVES: The clinical diagnosis of Huntington disease (HD) is typically made once motor symptoms and chorea are evident. Recent reports highlight the onset of cognitive and psychiatric symptoms before motor manifestations. These findings support further investigations of cognitive function across the lifespan of HD sufferers. METHODS: To assess cognitive symptoms in the developing brain, we administered assessments from the National Institutes of Health Toolbox Cognitive Battery, an age-appropriate cognitive assessment with population norms, to a cohort of children, adolescents and young adults with (gene-expanded; GE) and without (gene-not-expanded; GNE) the trinucleotide cytosine, adenine, guanine (CAG) expansion in the Huntingtin gene. These five assessments that focus on executive function are well validated and form a composite score, with population norms. We modelled these scores across age, and CAP score to estimate the slope of progression, comparing these results to motor symptoms. RESULTS: We find significant deficits in the composite measure of executive function in GE compared with GNE participants. GE participant performance on working memory was significantly lower compared with GNE participants. Modelling these results over age suggests that these deficits occur as early as 18 years of age, long before motor manifestations of HD. CONCLUSIONS: This work provides strong evidence that impairments in executive function occur as early as the second decade of life, well before anticipated motor onset. Future investigations should delineate whether these impairments in executive function are due to abnormalities in neurodevelopment or early sequelae of a neurodegenerative process.

COVID-19 stressors and symptoms of anxiety and depression in a community sample of children and adolescents.

BACKGROUND: The COVID-19 public health crisis has created abrupt and unparalleled disruptions to the daily lives of children and adolescents across the world, placing them at significant risk for developing symptoms of anxiety and depression. METHOD: The current study used two data collection periods to determine which types of COVID-19-related stressors were associated with the greatest risk of anxiety and depression symptoms in a community sample of children and adolescents in the United States (U.S.) from May-August 2020 (T1) to February-April 2021 (T2). Seventy-nine youth (ages 10-17; M = 13.41, SD = 2.10; 54.4% female) completed a battery of online standardized questionnaires about COVID-19 stress and psychiatric symptoms at T1 and 56 of these also participated at T2. RESULTS: The majority of children and adolescents reported experiencing the COVID-19-related stressors in multiple domains including daily routines, interpersonal relationships, education, finances, and health. A substantial proportion of the sample reported clinical levels of depression and anxiety symptoms at both T1 and T2. Multiple linear regression analyses revealed that, controlling for T1 anxiety and depression symptoms, T2 interpersonal stressors were significantly associated with elevated depression and anxiety scores at T2. CONCLUSIONS: The findings highlight the salience of social connection for children and adolescents, and may also underscore the risk associated with lockdown restrictions, social distancing, and school closures during the pandemic.

Inhibitory control, working memory and coping with stress: Associations with symptoms of anxiety and depression in adults with Huntington's disease.

OBJECTIVE: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by neuropsychiatric symptoms (e.g., anxiety and depression), where individuals suffer high levels of stress from the social, physical, and cognitive burden of the disease. The present study examined two factors associated with increased risk for symptoms of anxiety and depression: executive function skills (inhibitory control/attention and working memory) and skills to cope with stress. METHOD: Adults with HD completed the NIH Toolbox measures of inhibitory control/attention and working memory, as well as self-report measures of coping with HD-related stress and symptoms of anxiety and depression. Path analyses were used to test direct and indirect associations among the subtypes of executive functioning, coping, and symptoms. RESULTS: No significant associations were found in the full sample (n = 47), due to a significant portion of the sample with very low executive function abilities. Additional analyses were conducted on a subset of the sample (participants in the top three quartiles on both measures of executive functioning, n = 32). Significant indirect associations emerged among inhibitory control/attention skills, secondary control coping (e.g., acceptance and reappraisal), and symptoms of anxiety and depression in the subsample. Higher inhibitory control/attention skills were associated with greater use of secondary control coping, and greater use of these coping skills was related to lower symptoms of anxiety and depression. No direct or indirect associations were found among working memory skills, coping, and symptoms of anxiety and depression. CONCLUSIONS: Implications for interventions to enhance executive function and coping skills in adults with HD are highlighted. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Adverse childhood experiences, parenting, and socioeconomic status: Associations with internalizing and externalizing symptoms in adolescence.

BACKGROUND: Adverse childhood experiences (ACEs), low socioeconomic status (SES), and harsh parenting practices each represent well-established risk factors for mental health problems. However, research supporting these links has often focused on only one of these predictors and psychopathology, and interactions among these variables in association with symptoms are not well understood. OBJECTIVE: The current study utilized a cross-sectional, multi-informant, and multi-method design to investigate the associations of ACEs, SES, parenting, and concurrent internalizing and externalizing problems in adolescents. PARTICIPANTS AND SETTING: Data are from a volunteer sample of 97 adolescents and their caregivers recruited from 2018 to 2021 in a southern U.S. metropolitan area to sample a range of exposure to ACEs. METHODS: Multiple linear regression models were used to assess associations among adolescents' ACEs exposure, SES, observed parenting practices, and symptoms of internalizing and externalizing psychopathology. RESULTS: Lower SES was associated with higher levels of internalizing and externalizing symptoms, while higher ACEs exposure and observed parenting were related to externalizing but not internalizing symptoms. Associations of adolescents' exposure to physical abuse and perceived financial insecurity with externalizing symptoms were moderated by warm and supportive parenting behaviors. Conversely, harsh parenting was linked to increased levels of externalizing symptoms, particularly in the context of low income. CONCLUSIONS: Findings suggest that the presence of multiple risk factors may incur greater vulnerability to externalizing problems, while warm and supportive parenting practices may provide a buffer against externalizing problems for adolescents exposed to physical abuse. Links between ACEs, SES, parenting, and youth adjustment should continue to be explored, highlighting parenting as a potentially important and malleable intervention target.

Preliminary Study of Coping, Perceived Control, and Depressive Symptoms in Youth with Sickle Cell Anemia.

OBJECTIVE: The primary objective of this study was to test perceived controllability of stressors as a moderator of the association between coping and depressive symptoms in children and adolescents with sickle cell anemia (SCA). METHOD: Twenty-eight children and adolescents (Mage = 11.71, SD = 4.31; 60.7% female) with SCA were enrolled. Caregivers provided reports of child and adolescent coping using the Response to Stress Questionnaire (RSQ), perceived control of stressors using the RSQ, and depressive symptoms using the Child Behavior Checklist. Children and adolescents also completed Wechsler assessments of working memory and verbal comprehension. RESULTS: Secondary control coping (i.e., cognitive reappraisal, positive thinking, acceptance, and distraction) was a significant predictor of depressive symptoms such that greater use of secondary control coping was related to fewer reported depressive symptoms when accounting for perceived control of stress and neurocognitive variables. Furthermore, perceived control of peer-related stress was a significant moderator of the association between secondary control coping and depressive symptoms such that there was a significant negative association of secondary control coping with depressive symptoms only for low perceived control. CONCLUSION: Secondary control coping may be particularly helpful for reducing depressive symptoms when adolescents' peer-related stressors are perceived as uncontrollable. Interventions to reduce internalizing problems in this population should consider teaching children and adolescents secondary control coping skills in addition to skills in identifying uncontrollable sources of stress.

Neurobiological and Psychosocial Correlates of Communication Between Huntington's Disease Patients and Their Offspring.

OBJECTIVE: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that presents significant challenges to family communication. The investigators examined observations of communication between parents with HD and their offspring talking about the challenges of HD and explored potential correlates of their communication. METHODS: The sample included parents with HD and their adolescent and young-adult offspring (N=64). Parent communication and chorea were independently coded from video recordings. Parents and offspring completed working memory assessments and self-reports of neuropsychiatric symptoms, stress, and coping. RESULTS: Evidence was found for the association of observed parent-offspring communication with disease markers, psychosocial characteristics, and neurocognitive function. For parents, disease markers and working memory were correlates of communication, whereas offspring's psychiatric symptoms, stress, and coping were associated with their communication. CONCLUSIONS: These findings have potential implications for clinical interventions to enhance communication and quality of life for HD families.

Cerebral Hemodynamics and Executive Function in Sickle Cell Anemia.

BACKGROUND AND PURPOSE: Individuals with sickle cell anemia experience cognitive deficits, even in the absence of cerebral infarcts or strokes. This study tested the hypothesis that elevated cerebral blood flow and oxygen extraction fraction are associated with lower executive function in individuals with sickle cell anemia. METHODS: Three-Tesla brain magnetic resonance imaging was performed, including anatomic, gray matter cerebral blood flow, and global oxygen extraction fraction imaging. Executive function was measured using the working memory index from an age-appropriate Wechsler battery and tasks from the National Institutes of Health Toolbox Cognition Battery. Bivariate and multivariate models were examined (significance: P<0.05). RESULTS: Fifty-four participants (age range=6-31 years) with sickle cell anemia were enrolled. Hematocrit was positively related to fluid cognition, cerebral blood flow was inversely related to working memory and inhibitory control, and oxygen extraction fraction was inversely related to processing speed. Associations remained significant in multivariate analyses controlling for age, income, and infarcts. CONCLUSIONS: Elevated cerebral blood flow and oxygen extraction fraction, markers of hemodynamic impairment, are associated with deficits in executive function in individuals with sickle cell anemia.

Healthcare Delivery and Huntington's Disease During the Time of COVID-19.

BACKGROUND: Safer-at-home orders during the COVID-19 pandemic altered the structure of clinical care for Huntington's disease (HD) patients. This shift provided an opportunity to identify limitations in the current healthcare infrastructure and how these may impact the health and well-being of persons with HD. OBJECTIVE: The study objectives were to assess the feasibility of remote healthcare delivery in HD patients, to identify socioeconomic factors which may explain differences in feasibility and to evaluate the impact of safer-at-home orders on HD patient stress levels. METHODS: This observational study of a clinical HD population during the 'safer-at-home' orders asked patients or caregivers about their current access to healthcare resources and patient stress levels. A chart review allowed for an assessment of socioeconomic status and characterization of HD severity. RESULTS: Two-hundred and twelve HD patients were contacted with 156 completing the survey. During safer-at-home orders, the majority of HD patients were able to obtain medications and see a physician; however, 25% of patients would not commit to regular telehealth visits, and less than 50% utilized an online healthcare platform. We found that 37% of participants were divorced/single, 39% had less than a high school diploma, and nearly 20% were uninsured or on low-income health insurance. Patient stress levels correlated with disease burden. CONCLUSION: A significant portion of HD participants were not willing to participate in telehealth services. Potential explanations for these limitations may include socioeconomic barriers and caregiving structure. These observations illustrate areas for clinical care improvement to address healthcare disparities in the HD community.

Risk-Taking Behaviors in Huntington's Disease.

BACKGROUND: Risky behaviors are common in Huntington's disease (HD) and can lead to significant adverse consequences. However, the prevalence and scope of these symptoms have not been studied systematically, and no empirically validated measures are available to screen for them. OBJECTIVE: To test a novel screening tool designed to assess risk-taking behaviors in HD. METHODS: We administered the Risk Behavior Questionnaire (RBQ-HD) to HD patients and caregivers at Vanderbilt University Medical Center between 2018-2019. Patients completed the questionnaire based on self-report; caregivers provided collateral reports. Clinical and demographic information were obtained from the electronic medical record. RESULTS: 60 patients and 60 caregivers completed the RBQ-HD. 80% of patients (n = 48) and 91.7% of caregivers (n = 60) reported at least one risky behavior. Adverse social behaviors, impulsive/compulsive behaviors, and reckless driving were the most common behavioral domains reported. Male patients were more likely to report risky behaviors than females (92.3% vs. 70.6%, p = 0.04). The number of risky behaviors reported by patients and caregivers was negatively correlated with patient age (r = -0.32, p = 0.01; r = -0.47, p = 0.0001, respectively). Patient and caregiver reports were highly correlated in matched pairs (n = 30; r = 0.63, p = 0.0002). CONCLUSION: These findings emphasize that risky behaviors are highly prevalent in HD and can be effectively identified through the use of a novel screening measure. We hypothesize that early pathological involvement of frontostriatal and mesolimbic networks may be important factors in the development of these behaviors.

Investigating the interplay of working memory, affective symptoms, and coping with stress in offspring of parents with Huntington's disease.

OBJECTIVE: The offspring of parents with Huntington's disease (HD) are faced with substantial levels of chronic uncontrollable and unpredictable stress. These stressors may place them at heightened risk of psychological distress and negative effects on executive functioning. This study investigated working memory, secondary control coping strategies (e.g., cognitive reappraisal, acceptance, distraction), and symptoms of anxiety/depression in offspring at risk for HD. METHOD: Adolescent (ages 10-19) and young adult (ages 20-29) offspring (n = 33; mean [M] age = 19.12 years, standard deviation [SD] = 6.01 years; 61% female) of parents with HD were recruited in a Huntington Disease Society of America Level 1 Center of Excellence. Participants completed self-report measures of coping and neuropsychiatric symptoms (i.e., anxiety, depression) and a standardized working memory assessment. Pearson correlations and path analyses were used to test associations. RESULTS: Participant scores on the working memory assessment were significantly lower compared with normative data, and scores on a mixed anxiety/depression scale revealed a significant elevation compared with normative data. Working memory, secondary control coping, and symptoms of anxiety/depression were significantly correlated. Analyses of the full model revealed that the total indirect effect of working memory on anxiety/depression through secondary control coping was significant (ß = -0.20). CONCLUSION: Secondary control coping skills are an important factor in understanding the relationship between working memory and symptoms of anxiety/depression in the offspring of parents with HD. Future longitudinal research is needed to establish the direction of these associations. Working memory and coping skills represent potential targets for intervention to reduce the risk of anxiety/depression in this population. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Correlates of Cognitive Function in Sickle Cell Disease: A Meta-Analysis.

OBJECTIVE: To provide a comprehensive quantitative review of biological, environmental, and behavioral correlates across domains of cognitive function in sickle cell disease (SCD). METHODS: Forty-seven studies were identified in PubMed, MedLine, and PsycINFO involving 2573 participants with SCD. RESULTS: Meta-analytic findings across all identified samples indicate that hemoglobin and hematocrit were positively correlated with Full Scale IQ [FSIQ; r = .15, 95% confidence interval (CI) = .10 to .21], language and verbal reasoning (r = .18, 95% CI = .11 to .24), and executive function (r = .10, 95% CI = .01 to .19) with small effects and significant heterogeneity. Transcranial Doppler velocity was negatively associated with visual spatial and perceptual reasoning (r = -.18, 95% CI = -.31 to -.05). Socioeconomic status was positively associated with FSIQ (r = .23, 95% CI = .17 to .28), language and verbal reasoning (r = .28, 95% CI = .09 to .45), visual spatial and perceptual reasoning (r = .26, 95% CI = .09 to .41), and executive function (r = .18, 95% CI = .07 to .28) with small to medium effects. Finally, total behavioral problems were negatively associated with FSIQ (r = -.12, 95% CI = -.21 to -.02) such that participants with lower FSIQ exhibited greater behavioral and emotional problems. CONCLUSIONS: Findings provide evidence for biological, environmental, and psychosocial corelates across multiple domains of cognitive function in SCD. More research on more specific cognitive domains and psychosocial correlates is needed in addition to assessments of interactional models among risk factors.