- Email: [email protected]
42.2 CORTISOL IN INDIVIDUALS WITH AUTISM SPECTRUM DISORDER: META-ANALYSIS AND SYSTEMATIC REVIEW
SYMPOSIA 42.1 – 42.4
42.1 TOWARD BETTER MEASUREMENT OF ANXIETY IN YOUTH WITH AUTISM SPECTRUM DISORDER Lawrence Scahill, PhD, Emory University, Marcus Autism Center, 1920 Briarcliff Road, Atlanta, GA 30329 Objectives: Intervention trials targeting anxiety in youth with ASD are hindered because of a lack of appropriate anxiety outcome measures. The objective of this study is to describe new qualitative and quantitative findings on anxiety in youth with ASD. Methods: We conducted six focus groups with 48 parents (ages 26–55 years; 85 percent female) of youth with parent-reported ASD and at least mild anxiety. The semistructured group sessions discussed the manifestations of anxiety in youth with ASD. The six sessions (mean group size ¼ 7) were recorded and transcribed verbatim. The children of participants included 32 boys and 13 girls (ages 3–17 years). Coding of focus group transcripts resulted in six broad themes and 45 subthemes. Results: Systematic coding of the transcripts followed by expert panel review generated 72 potential items for a parent-rated checklist for anxiety in youth with ASD (grade 7.1 reading level). The 72-item survey (each scored 0 to 3) was placed on a secure website and completed by 990 parents of children with a community diagnosis of ASD. Redundant and rarely endorsed items were dropped. Factor analysis resulted in a one-factor model of 41 items (mean 47.3 22.81; range 1–119). Scores of <32 and 62 marked the 25th and 75th percentiles, respectively. We are currently evaluating internal consistency, test-retest reliability, and discriminant validity of the parent rating. Conclusions: This study followed the guidance of the US Food and Drug Administration monograph in 2009 emphasizing the importance of integrating the voice of patients in measuring development. Children with ASD may be unable to provide direct input on anxiety. Thus, caregiver input is needed.
ANX ASD RI http://dx.doi.org/10.1016/j.jaac.2016.07.366
42.2 CORTISOL IN INDIVIDUALS WITH AUTISM SPECTRUM DISORDER: META-ANALYSIS AND SYSTEMATIC REVIEW Lawrence K. Fung, MD, PhD, Stanford University, 401 Quarry Rd., Stanford, CA 94301 Objectives: ASD is a neurodevelopmental disorder with multiple etiologies. Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been demonstrated in multiple studies with individuals with ASD. In particular, severity of anxiety was found to correlate with levels of cortisol in individuals with ASD. Morning cortisol levels, cortisol awakening response, cortisol daily decline, and variability of cortisol levels were studied by many investigators. However, results were not consistent because of differences in experimental design (subject characteristics, cortisol endpoints, time of collection of sample, salivary versus plasma versus urinary and so on). In this study, we performed a systematic review and meta-analysis, focusing on morning salivary cortisol in individuals with ASD. Methods: The systematic search was performed in MEDLINE/PubMed from inception to February 2016. Eligibility of studies included the following: study population of ASD, morning (before 10:00 AM) collection of salivary cortisol, inclusion of neurotypical control group, and written in English. Reviews, editorials, and commentaries were excluded. Data abstraction components included study design, sample size, population description, and cortisol levels (mean and standard deviation). Meta-analysis, including generation of Forest plots, was performed by STATA (version 14.1). Results: A search of articles using keywords “autism” and “cortisol” yielded 107 studies. Based on the selection criteria, 82 studies were eliminated. Sixteen more were not included because of irretrievable data. Eight studies representing 217 individuals with ASD and 188 neurotypical control subjects met criteria for salivary cortisol meta-analysis. Morning salivary cortisol levels in individuals with ASD (overall mean 10.3 nM) were found to be higher than
J OURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT P SYCHIATRY VOLUME 55 NUMBER 10S OCTOBER 2016
levels in neurotypical control subjects (8.7 nM) [pooled standardized mean difference ¼ 0.63 (CI 0.42, 0.84); p < 0.0001; df ¼ 8; heterogeneity c2 ¼ 51 percent; I2 ¼ 84 percent]. Conclusions: Collective evidence from the present meta-analysis supports the theory that morning salivary cortisol levels are higher in individuals with ASD than in neurotypical control subjects.
ANX ASD NEURO Supported by the Mosbacher Family Fund http://dx.doi.org/10.1016/j.jaac.2016.07.367
42.3 COGNITIVE AND BEHAVIORAL INTERVENTIONS FOR ANXIETY IN CHILDREN WITH AUTISM Denis G. Sukhodolsky, PhD, Yale School of Medicine, Child Study Center, Yale University, 230 S. Frontage Rd., New Haven, CT 06510 Objectives: Approximately 40 percent of children with ASD exhibit clinically significant anxiety. CBT can be helpful for anxiety in ASD but little is known about the neural mechanisms of this potentially effective intervention. The objective of this presentation is to discuss the principles and evidence base of CBT for anxiety in children with ASD. Methods: Subjects included three boys and two girls (mean age ¼ 12.2 1.2 years and mean IQ ¼ 109.2 14.7) who were characterized with regard to ASD diagnosis and comorbid psychopathology. Anxiety was evaluated using a Pediatric Anxiety Rating Scale (PARS). Subjects completed tasks of emotion regulation during fMRI before and after treatment. CBT consisted of 12 to 15 weekly sessions that were conducted using a structured manual that was adapted for children with ASD by increasing parent participation and allowing flexible implementation. The unique combination of anxiety and ASD symptoms of social impairment and restricted/repetitive behavior was addressed in dedicated child and parent modules. Results: There was a significant reduction in the mean PARS total score from 19.2 1.5 at baseline to 8.2 3.5 at endpoint. A whole-brain fMRI analysis revealed increased activation in the emotion regulation circuit, including ventromedial, ventrolateral, and dorsolateral prefrontal cortices after CBT. We also observed reduction of left amygdala and bilateral insula activation in the emotional reactivity contrast. The magnitude of the effects of CBT on the levels of blood oxygenation level-dependent activation were calculated as the Cohen’s d range from 0.68 to 1.23. Conclusions: CBT can engage the neural circuitry of emotion regulation in children with ASD and co-occurring anxiety. Clinical implications for adaptations of CBT to address anxiety symptoms in ASD are discussed.
ANX ASD CBT http://dx.doi.org/10.1016/j.jaac.2016.07.368
42.4 PSYCHOPHARMACOLOGICAL TREATMENT OF ANXIETY SYMPTOMS IN AUTISM SPECTRUM DISORDER Antonio Hardan, MD, Stanford University, 401 Quarry Road, Stanford, CA 94305 Objectives: Anxiety symptoms are frequently observed in individuals with ASD. Despite their high prevalence rates, a limited number of clinical trials have examined the efficacy of psychopharmacological interventions in the treatment of anxiety in children and adolescents with ASD. Available evidence suggests that investigations have consisted essentially of uncontrolled trials. The objectives of this presentation is to review the evidencebased pharmacological treatment of anxiety symptoms in ASD and to present preliminary findings from two pilot studies examining the effectiveness of two novel compounds, arginine-vasopressin (AVP) and N-acetylcysteine (NAC), in the treatment of anxiety symptoms in children with ASD. Methods: The first pilot trial consisted of a four-week double-blind, randomized, controlled trial of intranasal AVP (up to 16 IU twice daily) in the treatment of children with ASD between the ages of six and 12 years. By use
www.jaacap.org
S325
42.1 TOWARD BETTER MEASUREMENT OF ANXIETY IN YOUTH WITH AUTISM SPECTRUM DISORDER Lawrence Scahill, PhD, Emory University, Marcus Autism Center, 1920 Briarcliff Road, Atlanta, GA 30329 Objectives: Intervention trials targeting anxiety in youth with ASD are hindered because of a lack of appropriate anxiety outcome measures. The objective of this study is to describe new qualitative and quantitative findings on anxiety in youth with ASD. Methods: We conducted six focus groups with 48 parents (ages 26–55 years; 85 percent female) of youth with parent-reported ASD and at least mild anxiety. The semistructured group sessions discussed the manifestations of anxiety in youth with ASD. The six sessions (mean group size ¼ 7) were recorded and transcribed verbatim. The children of participants included 32 boys and 13 girls (ages 3–17 years). Coding of focus group transcripts resulted in six broad themes and 45 subthemes. Results: Systematic coding of the transcripts followed by expert panel review generated 72 potential items for a parent-rated checklist for anxiety in youth with ASD (grade 7.1 reading level). The 72-item survey (each scored 0 to 3) was placed on a secure website and completed by 990 parents of children with a community diagnosis of ASD. Redundant and rarely endorsed items were dropped. Factor analysis resulted in a one-factor model of 41 items (mean 47.3 22.81; range 1–119). Scores of <32 and 62 marked the 25th and 75th percentiles, respectively. We are currently evaluating internal consistency, test-retest reliability, and discriminant validity of the parent rating. Conclusions: This study followed the guidance of the US Food and Drug Administration monograph in 2009 emphasizing the importance of integrating the voice of patients in measuring development. Children with ASD may be unable to provide direct input on anxiety. Thus, caregiver input is needed.
ANX ASD RI http://dx.doi.org/10.1016/j.jaac.2016.07.366
42.2 CORTISOL IN INDIVIDUALS WITH AUTISM SPECTRUM DISORDER: META-ANALYSIS AND SYSTEMATIC REVIEW Lawrence K. Fung, MD, PhD, Stanford University, 401 Quarry Rd., Stanford, CA 94301 Objectives: ASD is a neurodevelopmental disorder with multiple etiologies. Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been demonstrated in multiple studies with individuals with ASD. In particular, severity of anxiety was found to correlate with levels of cortisol in individuals with ASD. Morning cortisol levels, cortisol awakening response, cortisol daily decline, and variability of cortisol levels were studied by many investigators. However, results were not consistent because of differences in experimental design (subject characteristics, cortisol endpoints, time of collection of sample, salivary versus plasma versus urinary and so on). In this study, we performed a systematic review and meta-analysis, focusing on morning salivary cortisol in individuals with ASD. Methods: The systematic search was performed in MEDLINE/PubMed from inception to February 2016. Eligibility of studies included the following: study population of ASD, morning (before 10:00 AM) collection of salivary cortisol, inclusion of neurotypical control group, and written in English. Reviews, editorials, and commentaries were excluded. Data abstraction components included study design, sample size, population description, and cortisol levels (mean and standard deviation). Meta-analysis, including generation of Forest plots, was performed by STATA (version 14.1). Results: A search of articles using keywords “autism” and “cortisol” yielded 107 studies. Based on the selection criteria, 82 studies were eliminated. Sixteen more were not included because of irretrievable data. Eight studies representing 217 individuals with ASD and 188 neurotypical control subjects met criteria for salivary cortisol meta-analysis. Morning salivary cortisol levels in individuals with ASD (overall mean 10.3 nM) were found to be higher than
J OURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT P SYCHIATRY VOLUME 55 NUMBER 10S OCTOBER 2016
levels in neurotypical control subjects (8.7 nM) [pooled standardized mean difference ¼ 0.63 (CI 0.42, 0.84); p < 0.0001; df ¼ 8; heterogeneity c2 ¼ 51 percent; I2 ¼ 84 percent]. Conclusions: Collective evidence from the present meta-analysis supports the theory that morning salivary cortisol levels are higher in individuals with ASD than in neurotypical control subjects.
ANX ASD NEURO Supported by the Mosbacher Family Fund http://dx.doi.org/10.1016/j.jaac.2016.07.367
42.3 COGNITIVE AND BEHAVIORAL INTERVENTIONS FOR ANXIETY IN CHILDREN WITH AUTISM Denis G. Sukhodolsky, PhD, Yale School of Medicine, Child Study Center, Yale University, 230 S. Frontage Rd., New Haven, CT 06510 Objectives: Approximately 40 percent of children with ASD exhibit clinically significant anxiety. CBT can be helpful for anxiety in ASD but little is known about the neural mechanisms of this potentially effective intervention. The objective of this presentation is to discuss the principles and evidence base of CBT for anxiety in children with ASD. Methods: Subjects included three boys and two girls (mean age ¼ 12.2 1.2 years and mean IQ ¼ 109.2 14.7) who were characterized with regard to ASD diagnosis and comorbid psychopathology. Anxiety was evaluated using a Pediatric Anxiety Rating Scale (PARS). Subjects completed tasks of emotion regulation during fMRI before and after treatment. CBT consisted of 12 to 15 weekly sessions that were conducted using a structured manual that was adapted for children with ASD by increasing parent participation and allowing flexible implementation. The unique combination of anxiety and ASD symptoms of social impairment and restricted/repetitive behavior was addressed in dedicated child and parent modules. Results: There was a significant reduction in the mean PARS total score from 19.2 1.5 at baseline to 8.2 3.5 at endpoint. A whole-brain fMRI analysis revealed increased activation in the emotion regulation circuit, including ventromedial, ventrolateral, and dorsolateral prefrontal cortices after CBT. We also observed reduction of left amygdala and bilateral insula activation in the emotional reactivity contrast. The magnitude of the effects of CBT on the levels of blood oxygenation level-dependent activation were calculated as the Cohen’s d range from 0.68 to 1.23. Conclusions: CBT can engage the neural circuitry of emotion regulation in children with ASD and co-occurring anxiety. Clinical implications for adaptations of CBT to address anxiety symptoms in ASD are discussed.
ANX ASD CBT http://dx.doi.org/10.1016/j.jaac.2016.07.368
42.4 PSYCHOPHARMACOLOGICAL TREATMENT OF ANXIETY SYMPTOMS IN AUTISM SPECTRUM DISORDER Antonio Hardan, MD, Stanford University, 401 Quarry Road, Stanford, CA 94305 Objectives: Anxiety symptoms are frequently observed in individuals with ASD. Despite their high prevalence rates, a limited number of clinical trials have examined the efficacy of psychopharmacological interventions in the treatment of anxiety in children and adolescents with ASD. Available evidence suggests that investigations have consisted essentially of uncontrolled trials. The objectives of this presentation is to review the evidencebased pharmacological treatment of anxiety symptoms in ASD and to present preliminary findings from two pilot studies examining the effectiveness of two novel compounds, arginine-vasopressin (AVP) and N-acetylcysteine (NAC), in the treatment of anxiety symptoms in children with ASD. Methods: The first pilot trial consisted of a four-week double-blind, randomized, controlled trial of intranasal AVP (up to 16 IU twice daily) in the treatment of children with ASD between the ages of six and 12 years. By use
www.jaacap.org
S325