Evaluation of depressive and anxiety symptoms in childhood-onset systemic lupus erythematosus: Frequency, course, and associated risk factors.

BACKGROUND: Depressive and anxiety symptoms are common in childhood-onset systemic lupus erythematosus (cSLE), yet their etiology and course remain unclear. We investigated the frequency of depressive and anxiety symptoms longitudinally in youth with cSLE, and associated socio-demographic and disease factors. METHODS: Participants 8-18 years with cSLE completed baseline measures [demographic questionnaire, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Screen for Childhood Anxiety Related Disorders (SCARED), and psychiatric interview] and follow-up measures (CES-DC and SCARED) > 6 months later. Prevalence of clinically significant depressive (score >15 on CES-DC) or anxiety symptoms (score ≥25 on SCARED) was calculated at baseline and follow-up. Baseline psychiatric interview diagnoses were tabulated. Relationships between socio-demographics (neighborhood-level material deprivation, ethnic concentration, adverse childhood event history, psychiatric condition in a first-degree relative), disease-related factors (disease duration, major organ disease, disease activity, glucocorticoid use, comorbid medical condition) and baseline depressive and anxiety scores, were examined in linear regression models. Factors with univariate associations with p < 0.2 were included in multivariable adjusted models. RESULTS: At baseline, of 51 participants with a mean disease duration of 4.3 years (SD 2.7), 35% (n = 18) and 35% (n = 18) had clinically significant depressive and anxiety symptoms, respectively. Anxiety disorder was diagnosed by psychiatric interview in 14% (n = 7), depressive disorders in 6% (n = 3), and post-traumatic stress disorder in 4% (n = 2). Adverse childhood events and first-degree relative with psychiatric condition were present in 40% (n = 20) and 37% (n = 18), respectively. In multivariable regression analysis, baseline depressive symptoms were positively correlated with neighbourhood-level material deprivation (ß = 4.2, 95% CI [1.0, 7.3], p = 0.01) and psychiatric condition in a first-degree relative (ß = 7.3, 95% CI [2.2, 12.4], p = 0.006). No associations were found between baseline anxiety scores and patient factors. At a median follow-up of 13.5 months (IQR 10.5, 18) for CES-DC (n = 34) and SCARED (n = 44), depressive and anxiety symptoms were persistent (18%, n = 6; 16%, n = 7), and newly present (24%, n = 8; 16% n = 7) at follow-up. CONCLUSION: In this sample, depressive and anxiety symptoms were prevalent and persistent. Depressive symptoms correlated with neighborhood-level material deprivation, and family psychiatric history. These findings support routine psychosocial assessment in cSLE, and provision of appropriate resources.

A multi-site pilot randomized clinical trial of the Treatment and Education Approach for Childhood-onset Lupus (TEACH) program: study design and COVID-19 adaptations.

BACKGROUND: Childhood-onset Systemic Lupus Erythematosus (cSLE) is an autoimmune disease associated with fatigue, mood symptoms, and pain. Fortunately, these symptoms are potentially modifiable with psychological intervention such as cognitive-behavioral therapy (CBT). The Treatment and Education Approach for Childhood-onset Lupus (TEACH) program is a CBT intervention developed to target these symptoms for adolescents and young adults with cSLE. This pilot randomized controlled trial (RCT) aims to determine the feasibility and effect of TEACH for youth with cSLE. Adjustments to the study protocol following the COVID-19 pandemic are also described. METHODS: This two-arm multisite RCT will explore the feasibility (primary outcome) and effect (secondary outcome) of a remotely delivered TEACH protocol. Participants will be randomized to a six-week remotely delivered TEACH program plus medical treatment as usual (TAU) or TAU alone. We will include patients ages 12-22 years presenting to rheumatology clinics from six sites. Validated measures of fatigue, depressive symptoms, and pain will be obtained at baseline and approximately eight and 20 weeks later. Protocol adjustments were also made due to the COVID-19 pandemic, in collaboration with the investigative team, which included patients and caregivers. CONCLUSIONS: Findings from this multi-site RCT aim to document the feasibility of TEACH and provide an estimate of effect of a remotely delivered TEACH protocol on fatigue, depression, and pain symptoms in youth with cSLE as compared to standard medical treatment alone. This findings may positively impact clinical care for patients with cSLE. CLINICAL TRIALS: gov registration: NCT04335643.

An ecological approach to understanding and addressing health inequities of systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is a complex chronic autoimmune disease disproportionally afflicting women and, in particular, American Indian/Alaska Native, Black, and Hispanic women. These groups of women have significantly worse SLE-related health outcomes which are partially attributable to their exposure to marginalizing and interconnecting social issues like racism, sexism, economic inequality, and more. Although these groups of women have higher rates of SLE and though it is well known that they are at risk of exposure to marginalizing social phenomena, relatively little SLE literature explicitly links and addresses the relationship between marginalizing social issues and poor SLE-health outcomes among these women. Therefore, we developed a community-engaged partnership with two childhood-SLE diagnosed women of color to identify their perspectives on which systemic issues impacted on their SLE health-related outcomes. Afterward, we used Cochrane guidelines to conduct a rapid review associated with these identified issues and original SLE research. Then, we adapted an ecological model to illustrate the connection between systems issues and SLE health outcomes. Finally, we provided recommendations for ways to research and clinically mitigate SLE health inequities.

Mental Health in Pediatric Rheumatology: An Opportunity to Improve Outcomes.

Mental health problems are more common in children with pediatric rheumatologic diseases (PRDs) than healthy peers. Mental health problems affect disease-related outcomes and health-related quality of life (HRQOL), so addressing these problems can improve clinical and psychosocial outcomes. Mental health screening tools are available, and there are resources available to aid in integrating mental health care into the clinical setting. By implementing these tools, mental health problems can be recognized and addressed.

Evaluation of self-report screening measures in the detection of depressive and anxiety disorders among children and adolescents with systemic lupus erythematosus.

BACKGROUND: There are no validated screening measures for depressive or anxiety disorders in childhood Systemic Lupus Erythematosus (cSLE). We investigated cross-sectionally (1) the prevalence of depressive and anxiety disorder in cSLE. (2) the validity of the Centre for Epidemiologic Studies Depression Scale for Children (CES-DC) and the Screen for Childhood Anxiety and Related Disorders (SCARED) measures in identifyingthese disorders. METHODS: Participants 8-18 years with cSLE/incipient cSLE completed CES-DC, SCARED, and Quality OfMy Life (QOML) measures. Parents completed the SCARED-Parent measure. Diagnosis was by gold-standard psychiatric interview and determined prevalence of psychiatric disorder. Receiver Operating Characteristics Area under the Curve (ROCAUC) evaluated screening measure diagnostic performance. RESULTS: Ofseventy-two parent-child dyads, 56 interviews were completed. Mean screen scores were: CES-DC = 15 (range 1-49, SD 12), SCARED-C = 22 (range 2-61, SD 14), SCARED-P = 13 (range 0-36, SD 8). Depressive disorder screen positivity (CES-DC ≥ 15) was 35% (vs. prevalence 5%). Anxiety disorder screen positivity (SCARED ≥ 25) was 39% (vs. prevalence 16%). CES-DC ROCAUC = 0.98 and SCARED-C ROCAUC = 0.7 (cut-points 38 and 32 respectively). CONCLUSIONS: Diagnostic thresholds for depressive and anxiety disorderscreening measures are high for both CES-DC and SCARED-C in cSLE. Brief focused interview should follow to determine whether psychiatric evaluation is warranted.

Engaging patients and parents to improve mental health intervention for youth with rheumatological disease.

BACKGROUND: Mental health disorders are common in youth with rheumatological disease yet optimal intervention strategies are understudied in this population. We examined patient and parent perspectives on mental health intervention for youth with rheumatological disease. METHODS: We conducted a mixed methods cross-sectional study, via anonymous online survey, developed by researchers together with patient/parent partners, to quantitatively and qualitatively examine youth experiences with mental health services and resources in North America. Patients ages 14-24 years with juvenile idiopathic arthritis, juvenile dermatomyositis, or systemic lupus erythematous, and parents of patients ages 8-24 with these diseases were eligible (not required to participate in pairs). Participants self-reported mental health problems (categorized into clinician-diagnosed disorders vs self-diagnosed symptoms) and treatments (e.g. therapy, medications) received for the youth. Multivariate linear regression models compared patient and parent mean Likert ratings for level of: i) comfort with mental health providers, and ii) barriers to seeking mental health services, adjusting for potential confounders (patient age, gender, disease duration, and patient/parent visual analog score for disease-related health). Participants indicated usefulness of mental health resources; text responses describing these experiences were analyzed by qualitative description. RESULTS: Participants included 123 patients and 324 parents. Patients reported clinician-diagnosed anxiety (39%) and depression (35%); another 27 and 18% endorsed self-diagnosed symptoms of these disorders, respectively. 80% of patients with clinician-diagnosed disorders reported receiving treatment, while 11% of those with self-diagnosed symptoms reported any treatment. Patients were less comfortable than parents with all mental health providers. The top two barriers to treatment for patients and parents were concerns about mental health providers not understanding the rheumatological disease, and inadequate insurance coverage. Over 60% had used patient mental health resources, and over 60% of these participants found them to be helpful, although text responses identified a desire for resources tailored to patients with rheumatological disease. CONCLUSION: Self-reported mental health problems are prevalent for youth in this sample with rheumatological disease, and obstacles to mental health treatment include disease-related and logistic factors. Strategies are needed to improve acceptance and accessibility of mental health intervention, including routine mental health screening and availability of disease-specific mental health resources.

Towards a biopsychosocial understanding of neurodevelopmental outcomes in children with hypoxic-ischemic encephalopathy: A mixed-methods study.

OBJECTIVE: Children with hypoxic-ischemic encephalopathy (HIE) are at high risk of neurodevelopmental delay despite the widespread adoption of therapeutic hypothermia. Thus, consideration of both biological and psychosocial factors is warranted to better predict outcomes. We examined the associations between various child neurodevelopmental outcomes and potentially influential factors such as brain imaging, parent mental health, previous intervention, and social risk. Qualitative themes in the parent experience were also identified from free-text questionnaire responses. Methods: Parents of 54 children with HIE (ages 6 months-6.5 years) completed questionnaires capturing sociodemographic factors, qualitative perceptions of clinical outcome, parent mental health, and ratings of child adaptive and psychosocial functioning. Neurodevelopmental assessment scores at 18 and 36 months were extracted retrospectively from the medical chart for a subset of children. Results: Linear regression analyses showed significant associations between poorer parent mental health and child psychosocial and language outcomes. In multivariable analyses, social risk served as a significant predictor of 18 and 36 month cognitive and language functioning. Qualitative analyses of parents' written reflections revealed themes of hopefulness and ongoing concern. Conclusion: In children with HIE, social context and parent mental health are strong contributing factors in the pathway of neurodevelopmental outcomes.

Neurocognitive Functioning in Early School-age Children With Intestinal Failure.

OBJECTIVES: Little is known about school-age functioning in children with intestinal failure (IF). This study examines neurocognitive outcomes of children with IF at ages 4 to 8 years treated at a single centre, along with relevant medical and demographic variables. METHODS: Between 2012 and 2016, neurocognitive assessments were administered to 28 children receiving treatment in our IF rehabilitation program, and included measures of intelligence, academics, learning/memory, language, visual-motor integration, and fine-motor dexterity. DSM-IV/V criteria were used to diagnose Learning Disability, Intellectual Disability, and/or Attention Deficit/Hyperactivity Disorder. RESULTS: Intellectual functioning ranged from extremely low to superior (Full Scale IQ range 53-123, mean = 89). Forty-six percentage received a cognitive/learning DSM diagnosis. Total number of first-year septic episodes correlated with poorer outcomes on the most cognitive measures. Adjusting for gestational age (61% were born <37 weeks), number of first-year septic episodes negatively predicted working memory, visual-motor integration, and visual memory scores. Additional factors correlating with poorer outcomes on ≥2 cognitive measures included length of first-year admissions, necrotizing enterocolitis diagnosis, and first-year sustained conjugated hyperbilirubinemia. Having ≥2 first-year septic episodes increased the likelihood of poorer outcome. Having a sibling was a significant positive predictor of working memory, processing speed, reading, and verbal learning skills. CONCLUSIONS: Our data provides preliminary evidence that children with IF are at risk of neurocognitive problems at early school age. Managing septic events during the first year is one strategy that may help reduce long-term neurocognitive risks in this population.

Verbal associative memory outcomes in pediatric surgical temporal lobe epilepsy: Exploring the impact of mesial structures.

OBJECTIVE: We examined verbal associative memory outcomes in children with left- or right-sided temporal lobe epilepsy (TLE) who received combined lateral and mesial resections versus lateral resections sparing mesial structures. We hypothesized that children who underwent left-sided resections including mesial structures would show the greatest verbal associative memory declines following surgery. METHOD: We retrospectively analyzed neuropsychology assessment results from a sample of 65 children with TLE who completed pre- and postoperative evaluation at the Hospital for Sick Children in Toronto, Canada. We examined verbal associative memory score changes between groups by laterality (left versus right) and resection type (lateral only versus lateral and mesial resection). We also explored potential associations between certain epilepsy-related characteristics and verbal associative memory changes. RESULTS: Postoperative decline was found in children with left-sided resections, but not those with right-sided resections. In children who received left-sided resections, there was some suggestion of verbal associative memory decline in those who had both lateral and mesial tissues excised, but not in those with lateral resections only. Notably, there was also a language dominance (typical versus atypical) by resection type interaction. Specifically, for the typical language group, children with left lateral plus mesial resections (but not mesial sparing resections) showed postoperative verbal associative memory declines, whereas the opposite was true for the atypical language group. SIGNIFICANCE: These data contribute to our growing understanding of verbal memory outcomes following TLE in childhood, with consideration of the extent of resection to mesial structures. Our findings also highlight the importance of language laterality when interpreting neuropsychological assessment findings and making predictions regarding risk of functional loss following surgery.

Longitudinal Academic Outcomes of Children with Secondary Attention Deficit/Hyperactivity Disorder following Pediatric Stroke.

The current longitudinal study examined academic outcomes of children diagnosed with secondary attention deficit-hyperactivity disorder (S-ADHD) following stroke in comparison to children with stroke-only and children with developmental ADHD (D-ADHD), and explored potential predictors of progress in these groups. We followed 55 children (n = 17 S-ADHD, n = 18 stroke-only, and n = 20 D-ADHD) over approximately four years. Children with S-ADHD and D-ADHD were more likely to have a comorbid learning disability, but children with S-ADHD were more likely to have declines in their reading scores over time. No individual or neurological factors accounted for declines. Math scores were equally likely to decline across all youth.

Re-examining the crowding hypothesis in pediatric epilepsy.

OBJECTIVE: In adults with left-sided epilepsy, reorganized language may "crowd out" right-hemisphere visual-spatial skills, with relative sparing of language (i.e., the crowding hypothesis). However, this effect has not consistently been demonstrated in pediatric epilepsy studies. The objective of this study was to investigate the crowding hypothesis using a heterogeneous sample of children with intractable epilepsy and typical (left) language dominance or atypical (right or bilateral) language dominance. We examined the relative contributions of seizure onset (before or after age 5), handedness (right versus left), seizure localization (temporal versus extratemporal), as well as language dominance on verbal versus visual cognitive skills. METHOD: We retrospectively analyzed neuropsychology assessment results from a sample of 91 children who completed presurgical evaluation at the Hospital for Sick Children in Toronto, Canada (34 with typical language, 57 with atypical language, mean age = 12 years). We considered a selection of verbal skills (naming, vocabulary knowledge, verbal abstract reasoning) and visual skills (visual-motor integration, block construction, visual abstract reasoning). RESULTS: Consistent with several previous adult studies supporting the crowding hypothesis, univariate analyses showed that the typical and atypical language groups were comparable on the measures of vocabulary knowledge and abstract verbal reasoning whereas the atypical language group produced lower scores across visual measures. Multivariate analyses (taking into account language dominance and associated factors) showed that language dominance was the strongest predictor of performance on two of three visual measures whereas language dominance was not a significant predictor of performance on most verbal measures. Unexpectedly, both sets of analyses indicated that the atypical language group had poorer naming abilities than the typical language group. SIGNIFICANCE: Our data provide some evidence of right-hemisphere functional crowding effects in a heterogeneous sample of children with intractable left-sided epilepsy. Specifically, those with atypical versus typical language dominance showed poorer visual-motor integration and visual-motor problem-solving skills, with comparable scores on certain verbal measures. It is critical that potential crowding effects be considered when interpreting the neuropsychological profiles of children being evaluated for epilepsy surgery.

Academic Outcomes in Individuals With Childhood-Onset Epilepsy: Mediating Effects of Working Memory.

OBJECTIVES: Academic difficulties are common in children with epilepsy, although little is known about the effect of various seizure-related and cognitive variables. Given that persistent seizures may negatively impact academics, and that working memory is predictive of academic abilities, we examined the effects of recent seizures and working memory on word reading, spelling, and arithmetic in pediatric epilepsy. We hypothesized that persistent seizures would be associated with lower working memory ability, which would in turn result in poorer academic performance. METHODS: Our sample consisted of 91 children with epilepsy being treated at the Hospital for Sick Children in Toronto, Canada, who underwent neuropsychological testing between 2002 and 2009 to help determine surgical candidacy. Four to 11 years later, follow-up testing was conducted on both surgical (n=61) and non-surgical (n=30) patients. Seizure status was defined by the presence or absence of seizures within the preceding 12 months. RESULTS: 5000 bias-corrected bootstrap resamples with replacement were used to calculate the 95% confidence intervals (CIs) for the indirect effect of seizure status on academics through working memory, controlling for baseline academic functioning. Persistent seizures were associated with reduced working memory, which was in turn associated with lower reading (B=-4.64, 95% CI [-10.21, -1.30]), spelling (B=-7.09, 95% CI [-13.97, -2.56], and arithmetic scores (B=-8.04, 95% CI [-13.66, -3.58] at follow-up. CONCLUSIONS: For children with intractable epilepsy, working memory deficits present a significant barrier to the development of academic skills. Working memory interventions may be a helpful adjunct to academic remediation in this population to facilitate academic progress. (JINS, 2017, 23, 594-604).

Semantic Neighborhood Effects for Abstract versus Concrete Words.

Studies show that semantic effects may be task-specific, and thus, that semantic representations are flexible and dynamic. Such findings are critical to the development of a comprehensive theory of semantic processing in visual word recognition, which should arguably account for how semantic effects may vary by task. It has been suggested that semantic effects are more directly examined using tasks that explicitly require meaning processing relative to those for which meaning processing is not necessary (e.g., lexical decision task). The purpose of the present study was to chart the processing of concrete versus abstract words in the context of a global co-occurrence variable, semantic neighborhood density (SND), by comparing word recognition response times (RTs) across four tasks varying in explicit semantic demands: standard lexical decision task (with non-pronounceable non-words), go/no-go lexical decision task (with pronounceable non-words), progressive demasking task, and sentence relatedness task. The same experimental stimulus set was used across experiments and consisted of 44 concrete and 44 abstract words, with half of these being low SND, and half being high SND. In this way, concreteness and SND were manipulated in a factorial design using a number of visual word recognition tasks. A consistent RT pattern emerged across tasks, in which SND effects were found for abstract (but not necessarily concrete) words. Ultimately, these findings highlight the importance of studying interactive effects in word recognition, and suggest that linguistic associative information is particularly important for abstract words.