20 results on '"Libove RA"'
Search Results
2. Characterizing Emotion Recognition and Theory of Mind Performance Profiles in Unaffected Siblings of Autistic Children.
- Author
-
Uljarević M, Bott NT, Libove RA, Phillips JM, Parker KJ, and Hardan AY
- Abstract
Emotion recognition skills and the ability to understand the mental states of others are crucial for normal social functioning. Conversely, delays and impairments in these processes can have a profound impact on capability to engage in, maintain, and effectively regulate social interactions. Therefore, this study aimed to compare the performance of 42 autistic children (Mage = 8.25 years, SD = 2.22), 45 unaffected siblings (Mage = 8.65 years, SD = 2.40), and 41 typically developing (TD) controls (Mage = 8.56 years, SD = 2.35) on the Affect Recognition (AR) and Theory of Mind (TOM) subtests of the Developmental Neuropsychological Assessment Battery. There were no significant differences between siblings and TD controls. Autistic children showed significantly poorer performance on AR when compared to TD controls and on TOM when compared to both TD controls and unaffected siblings. An additional comparison of ASD, unaffected sibling and TD control subsamples, matched on full-scale IQ, revealed no group differences for either AR or TOM. AR and TOM processes have received less research attention in siblings of autistic children and remain less well characterized. Therefore, despite limitations, findings reported here contribute to our growing understanding of AR and TOM abilities in siblings of autistic children and highlight important future research directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Uljarević, Bott, Libove, Phillips, Parker and Hardan.) more...
- Published
- 2022
- Full Text
- View/download PDF
Catalog
3. Psychiatric Characteristics Across Individuals With PTEN Mutations.
- Author
-
Steele M, Uljarević M, Rached G, Frazier TW, Phillips JM, Libove RA, Busch RM, Klaas P, Martinez-Agosto JA, Srivastava S, Eng C, Sahin M, and Hardan AY
- Abstract
Germline heterozygous PTEN mutations have been associated with high prevalence of autism spectrum disorder (ASD) and elevated rates and severity of broadly defined behavioral problems. However, limited progress has been made toward understanding whether PTEN mutation is associated with specific psychiatric co-morbidity profiles when compared to idiopathic ASD. The current study aimed to utilize a cross-measure approach to compare concurrent psychiatric characteristics across children and adolescents with PTEN mutation with ( PTEN -ASD; n = 38) and without ASD ( PTEN -No ASD; n = 23), and ASD with macrocephaly but no PTEN mutation (macro-ASD; n = 25) using the Child Behavior Checklist (CBCL) and the Aberrant Behavior Checklist (ABC). There were significant group effects for the CBCL Internalizing and Externalizing broad symptom score, the majority of specific CBCL syndrome scores, and all ABC subscale scores. Post-hoc comparisons revealed greater behavioral symptoms in the ASD groups ( PTEN -ASD and macro-ASD) compared to the PTEN -no ASD group on nearly all subtest scores examined. There were no statistically significant differences between the PTEN -ASD and macro-ASD groups; however, there was a trend for the macro-ASD group showing higher levels of aggressive behaviors. Our findings provide evidence of specific behavior profiles across PTEN -No ASD, PTEN -ASD, and macro-ASD groups and highlight the importance of early identification of behavioral vulnerabilities in individuals with PTEN mutations in order to provide access to appropriate evidence-based interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Steele, Uljarević, Rached, Frazier, Phillips, Libove, Busch, Klaas, Martinez-Agosto, Srivastava, Eng, Sahin and Hardan.) more...
- Published
- 2021
- Full Text
- View/download PDF
4. A case-control study of visual, auditory and audio-visual sensory interactions in children with autism spectrum disorder.
- Author
-
Norcia AM, Lee A, Meredith WJ, Kohler PJ, Pei F, Ghassan SA, Libove RA, Phillips JM, and Hardan AY
- Subjects
- Attention, Case-Control Studies, Child, Electroencephalography, Humans, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder
- Abstract
To assess the relative integrity of early visual and auditory processes in autism spectrum disorder (ASD), we used frequency-tagged visual and auditory stimulation and high-density electroencephalogram recordings of unimodal and dual-modality responses in a case-control design. To test for the specificity of effects on ASD, we recorded from a smaller group of children with attention-deficit hyperactivity disorder (ADHD). Horizontal 3 cycle per degree (cpd) gratings were presented at 5 Hz, and a random stream of /ba/, /da/, /ga/ syllables was presented at 6 Hz. Grating contrast response functions were measured unimodally and in the presence of a 64-dB auditory input. Auditory response functions were measured unimodally and in the presence of a 40% contrast grating. Children with ASD (n = 34) and ADHD (n = 13) showed a common lack of audio-visual interaction compared to typically developing children (n = 40) when measured at the first harmonic of the visual stimulus frequency. Both patient groups also showed depressed first harmonic responses at low contrast, but the ADHD group had consistently higher first-harmonic responses at high contrast. Children with ASD had a preferential loss of second-harmonic (transient) responses. The alteredtransient responses in ASD are likely to arise very early in the visual pathway and could thus have downstream consequences for many other visual mechanisms and processes. The alteration in audio-visual interaction could be a signature of a comorbid phenotype shared by ASD and ADHD, possibly due to alterations in attentional selection systems. more...
- Published
- 2021
- Full Text
- View/download PDF
5. Complex Interplay Between Cognitive Ability and Social Motivation in Predicting Social Skill: A Unique Role for Social Motivation in Children With Autism.
- Author
-
Itskovich E, Zyga O, Libove RA, Phillips JM, Garner JP, and Parker KJ
- Subjects
- Child, Cognition, Humans, Motivation, Social Skills, Autism Spectrum Disorder, Autistic Disorder
- Abstract
Impairment in social interaction is a core feature of autism spectrum disorder (ASD), but the factors which contribute to this social skill deficiency are poorly understood. Previous research has shown that cognitive ability can impact social skill development in ASD. Yet, children with ASD whose cognitive abilities are in the normal range nevertheless demonstrate deficits in social skill. More recently, the social motivation theory of ASD has emerged as a framework by which to understand how failure to seek social experiences may lead to social skill deficits. This study was designed to better understand the relationships between cognitive ability, social motivation, and social skill in a well-characterized cohort of children with ASD (n = 79), their unaffected siblings (n = 50), and unrelated neurotypical controls (n = 60). The following instruments were used: The Stanford-Binet intelligence quotient (IQ), the Social Responsiveness Scale's Social Motivation Subscale, and the Vineland Adaptive Behavior Scales' Socialization Standard Score. We found that lower cognitive ability contributed to diminished social skill, but did so universally in all children. In contrast, social motivation strongly predicted social skill only in children with ASD, such that those with the lowest social motivation exhibited the greatest social skill impairment. Notably, this relationship was observed across a large range of intellectual ability but was most pronounced in those with IQs ≥ 80. These findings establish a unique link between social motivation and social skill in ASD and support the hypothesis that low social motivation may impair social skill acquisition in this disorder, particularly in children without intellectual disability. LAY SUMMARY: The relationships between cognitive ability, social motivation, and social skill are poorly understood. Here we report that cognitive ability predicts social skill in all children, whereas social motivation predicts social skill only in children with autism. These results establish a unique link between social motivation and social skill in autism, and suggest that low social motivation may impair social skill acquisition in this disorder, particularly in those without intellectual disability., (© 2020 International Society for Autism Research and Wiley Periodicals LLC.) more...
- Published
- 2021
- Full Text
- View/download PDF
6. Exploring Social Subtypes in Autism Spectrum Disorder: A Preliminary Study.
- Author
-
Uljarević M, Phillips JM, Schuck RK, Schapp S, Solomon EM, Salzman E, Allerhand L, Libove RA, Frazier TW, and Hardan AY
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Male, Motivation, Autism Spectrum Disorder classification, Autism Spectrum Disorder psychology, Social Skills
- Abstract
Impairments in social functioning are considered a hallmark diagnostic feature of autism spectrum disorder (ASD). Yet, individuals diagnosed with ASD vary widely with respect to specific presentation, severity, and course across different dimensions of this complex symptom domain. The aim of this investigation was to utilize the Stanford Social Dimensions Scale (SSDS), a newly developed quantitative measure providing parental perspective on their child's social abilities, in order to explore the existence of homogeneous subgroups of ASD individuals who share unique profiles across specific dimensions of the social domain. Parents of 164 individuals with ASD (35 females, 129 males; mean
age = 7.54 years, SD = 3.85) completed the SSDS, the Social Responsiveness Scale (SRS-2) and the Child Behavior Checklist (CBCL). Data on children's verbal and nonverbal intellectual functioning (FSIQ) were also collected. The Latent Profile Analysis was used to classify participants according to the pattern of SSDS subscale scores (Social Motivation, Social Affiliation, Expressive Social Communication, Social Recognition, and Unusual Approach). Five profiles were identified. Profiles did not differ in terms of chronological age nor gender distribution but showed distinct patterns of strengths and weaknesses across different social components rather than simply reflecting a severity gradient. Profiles were further differentiated in terms of cognitive ability, as well as ASD and internalizing symptom severity. The implications of current findings and the necessary further steps toward identifying subgroups of individuals with ASD who share particular constellation of strengths and weaknesses across key social domains as a way of informing personalized interventions are discussed. Autism Res 2020. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism spectrum disorder (ASD) vary greatly in terms of their social abilities and social motivation. However, researchers lack measures that can fully assess different components of social functioning. This paper provides initial evidence for capturing subgroups of individuals with ASD with specific strengths and weakness across different aspects of social functioning. Autism Res 2020, 13: 1335-1342. © 2020 International Society for Autism Research, Wiley Periodicals, Inc., (© 2020 International Society for Autism Research, Wiley Periodicals, Inc.) more...- Published
- 2020
- Full Text
- View/download PDF
7. Development of the Stanford Social Dimensions Scale: initial validation in autism spectrum disorder and in neurotypicals.
- Author
-
Phillips JM, Uljarević M, Schuck RK, Schapp S, Solomon EM, Salzman E, Allerhand L, Libove RA, Frazier TW, and Hardan AY
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Male, Models, Statistical, Reproducibility of Results, Autism Spectrum Disorder psychology, Psychometrics, Surveys and Questionnaires
- Abstract
Background: The aim of this paper was to provide an initial validation of a newly developed parent questionnaire-the Stanford Social Dimensions Scale (SSDS), designed to capture individual differences across several key social dimensions including social motivation in children and adolescents with and without psychiatric disorders., Methods: The initial validation sample was comprised of parents of 175 individuals with autism spectrum disorder (ASD) (35 females, 140 males; M
age = 7.19 years, SDage = 3.96) and the replication sample consisted of 624 parents of children who were either typically developing or presented with a range of neurodevelopmental and neuropsychiatric disorders (302 females, 322 males; Mage = 11.49 years, SDage = 4.48). Parents from both samples completed the SSDS and the Social Responsiveness Scale (SRS-2)., Results: Exploratory Structural Equation Modeling indicated that a 5-factor model provided adequate to excellent fit to the data in the initial ASD sample (comparative fit index [CFI] = .940, Tucker-Lewis Index [TLI] = .919, root mean square error of approximation [RMSEA] = .048, standardized root mean square residual [SRMR] = .038). The identified factors were interpreted as Social Motivation, Social Affiliation, Expressive Social Communication, Social Recognition, and Unusual Approach. This factor structure was further confirmed in Sample 2 (CFI = 946, TLI = .930, RMSEA = .044, SRMR = .026). Internal consistency for all subscales was in the good to excellent range across both samples as indicated by Composite Reliability scores of ≥ .72. Convergent and divergent validity was strong as indexed by the pattern of correlations with relevant SRS-2 and Child Behavior Checklist domains and with verbal and non-verbal intellectual functioning scores in Sample 1 and with the Need to Belong Scale and Child Social Preference Scale scores in Sample 2. Across both samples, females had higher social motivation and expressive social communication scores. Discriminant validity was strong given that across all SSDS subscales, the ASD sample had significantly higher impairment than both the typically developing group and the group with other clinical conditions, which in turn, had significantly higher impairment than the typically developing group., Conclusions: Our findings provide initial validation of a new scale designed to comprehensively capture individual differences in social motivation and other key social dimensions in ASD., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.) more...- Published
- 2019
- Full Text
- View/download PDF
8. Blood oxytocin concentration positively predicts contagious yawning behavior in children with autism spectrum disorder.
- Author
-
Mariscal MG, Oztan O, Rose SM, Libove RA, Jackson LP, Sumiyoshi RD, Trujillo TH, Carson DS, Phillips JM, Garner JP, Hardan AY, and Parker KJ
- Subjects
- Child, Female, Humans, Male, Social Behavior, Autism Spectrum Disorder blood, Autism Spectrum Disorder physiopathology, Empathy physiology, Oxytocin blood, Photic Stimulation methods, Yawning physiology
- Abstract
Research suggests that children with autism spectrum disorder (ASD) may have reduced empathy, as measured by an impaired contagious yawn response, compared to typically developing (TD) children. Other research has failed to replicate this finding, instead attributing this phenomenon to group differences in attention paid to yawn stimuli. A third possibility is that only a subgroup of children with ASD exhibits the impaired contagious yawn response, and that it can be identified biologically. Here we quantified blood concentrations of the "social" neuropeptide oxytocin (OXT) and evaluated yawning behavior and attention rates during a laboratory task in children with ASD (N = 34) and TD children (N = 30) aged 6-12 years. No group difference in contagious yawning behavior was found. However, a blood OXT concentration × group (ASD vs. TD) interaction positively predicted contagious yawning behavior (F
1,50 = 7.4987; P = 0.0085). Specifically, blood OXT concentration was positively related to contagious yawning behavior in children with ASD, but not in TD children. This finding was not due to delayed perception of yawn stimuli and was observed whether attention paid to test stimuli and clinical symptom severity were included in the analysis or not. These findings suggest that only a biologically defined subset of children with ASD exhibits reduced empathy, as measured by the impaired contagious yawn response, and that prior conflicting reports of this behavioral phenomenon may be attributable, at least in part, to variable mean OXT concentrations across different ASD study cohorts. Autism Res 2019, 12: 1156-1161. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism may contagiously yawn (i.e., yawn in response to another's yawn) less often than people without autism. We find that people with autism who have lower levels of blood oxytocin (OXT), a hormone involved in social behavior and empathy, show decreased contagious yawning, but those who have higher blood OXT levels do not differ in contagious yawning from controls. This suggests that decreased contagious yawning may only occur in a biologically defined subset of people with autism., (© 2019 International Society for Autism Research, Wiley Periodicals, Inc.) more...- Published
- 2019
- Full Text
- View/download PDF
9. A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism.
- Author
-
Parker KJ, Oztan O, Libove RA, Mohsin N, Karhson DS, Sumiyoshi RD, Summers JE, Hinman KE, Motonaga KS, Phillips JM, Carson DS, Fung LK, Garner JP, and Hardan AY
- Subjects
- Administration, Intranasal, Child, Female, Humans, Male, Pilot Projects, Placebos, Treatment Outcome, Vasopressins adverse effects, Autism Spectrum Disorder drug therapy, Social Behavior, Vasopressins administration & dosage, Vasopressins therapeutic use
- Abstract
The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 International Units (IU); participants aged 9.6 to 12.9 years received the maximum daily target dose of 32 IU. Intranasal AVP treatment compared to placebo enhanced social abilities as assessed by change from baseline in this phase 2 trial's primary outcome measure, the Social Responsiveness Scale, 2nd Edition total score (SRS-2 T score; F
1,20 = 9.853; P = 0.0052; ηp 2 = 33.0%; Cohen's d = 1.40). AVP treatment also diminished anxiety symptoms and some repetitive behaviors. Most of these findings were more pronounced when we accounted for pretreatment AVP concentrations in blood. AVP was well tolerated with minimal side effects. No AVP-treated participants dropped out of the trial, and there were no differences in the rate of adverse events reported between treatment conditions. Last, no changes from baseline were observed in vital signs, electrocardiogram tracings, height and body weight, or clinical chemistry measurements after 4 weeks of AVP treatment. These preliminary findings suggest that AVP has potential for treating social impairments in children with ASD., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) more...- Published
- 2019
- Full Text
- View/download PDF
10. Effects of a parent-implemented Developmental Reciprocity Treatment Program for children with autism spectrum disorder.
- Author
-
Gengoux GW, Schapp S, Burton S, Ardel CM, Libove RA, Baldi G, Berquist KL, Phillips JM, and Hardan AY
- Subjects
- Child, Child, Preschool, Female, Humans, Male, Pilot Projects, Treatment Outcome, Autism Spectrum Disorder psychology, Autism Spectrum Disorder therapy, Interpersonal Relations, Parents psychology, Patient Education as Topic methods
- Abstract
Developmental approaches to autism treatment aim to establish strong interpersonal relationships through joint play. These approaches have emerging empirical support; however, there is a need for further research documenting the procedures and demonstrating their effectiveness. This pilot study evaluated changes in parent behavior and child autism symptoms following a 12-week Developmental Reciprocity Treatment parent-training program. A total of 22 children with autism spectrum disorder between 2 and 6 years (mean age = 44.6 months, standard deviation = 12.7) and a primary caregiver participated in 12 weekly sessions of Developmental Reciprocity Treatment parent training, covering topics including introduction to developmental approaches, supporting attention and motivation, sensory regulation and sensory-social routines, imitation/building nonverbal communication, functional language development, and turn taking. Results indicated improvement in aspects of parent empowerment and social quality of life. Improvement in core autism symptoms was observed on the Social Responsiveness Scale total score (F(1,19): 5.550, p = 0.029), MacArthur-Bates Communicative Development Inventories number of words produced out of 680 (F(1,18): 18.104, p = 0.000), and two subscales of the Repetitive Behavior Scale, Revised (compulsive, p = 0.046 and restricted, p = 0.025). No differences in sensory sensitivity were observed on the Short Sensory Profile. Findings from this pilot study indicate that Developmental Reciprocity Treatment shows promise and suggest the need for future controlled trials of this developmentally based intervention. more...
- Published
- 2019
- Full Text
- View/download PDF
11. Plasma anandamide concentrations are lower in children with autism spectrum disorder.
- Author
-
Karhson DS, Krasinska KM, Dallaire JA, Libove RA, Phillips JM, Chien AS, Garner JP, Hardan AY, and Parker KJ
- Subjects
- Biomarkers blood, Case-Control Studies, Child, Child, Preschool, Female, Humans, Male, Arachidonic Acids blood, Autistic Disorder blood, Cannabinoid Receptor Agonists blood, Endocannabinoids blood, Polyunsaturated Alkamides blood
- Abstract
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children with and without ASD ( N = 112)., Findings: Anandamide concentrations significantly differentiated ASD cases ( N = 59) from controls ( N = 53), such that children with lower anandamide concentrations were more likely to have ASD ( p = 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children ( p = 0.034)., Conclusions: These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD., Competing Interests: All research procedures were approved by the Stanford University Institutional Review Board prior to participant enrollment. Participants’ parents provided written consent prior to initiation of any experimental procedures, and written assent was obtained from participants when appropriate (e.g., children ≥ 7 years of age and deemed intellectually capable).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. more...
- Published
- 2018
- Full Text
- View/download PDF
12. Biomarker discovery for disease status and symptom severity in children with autism.
- Author
-
Oztan O, Jackson LP, Libove RA, Sumiyoshi RD, Phillips JM, Garner JP, Hardan AY, and Parker KJ
- Subjects
- Arginine Vasopressin metabolism, Autism Spectrum Disorder genetics, Autistic Disorder diagnosis, Biomarkers blood, Child, Female, Humans, Male, Neuropeptides analysis, Neuropeptides blood, Oxytocin metabolism, Receptors, Neuropeptide analysis, Receptors, Neuropeptide genetics, Receptors, Oxytocin analysis, Receptors, Oxytocin genetics, Receptors, Vasopressin analysis, Receptors, Vasopressin genetics, Social Behavior, Stereotyped Behavior, Arginine Vasopressin physiology, Autistic Disorder metabolism, Oxytocin physiology
- Abstract
Autism spectrum disorder (ASD) is characterized by social impairments and repetitive behaviors, and affects 1 in 68 US children. Despite ASD's societal impact, its disease mechanisms remain poorly understood. Recent preclinical ASD biomarker discovery research has implicated the neuropeptides oxytocin (OXT) and arginine vasopressin (AVP), and their receptors, OXTR and AVPR1A, in animal models. Efforts to translate these findings to individuals with ASD have typically involved evaluating single neuropeptide measures as biomarkers of ASD and/or behavioral functioning. Given that ASD is a heterogeneous disorder, and unidimensional ASD biomarker studies have been challenging to reproduce, here we employed a multidimensional neuropeptide biomarker analysis to more powerfully interrogate disease status and symptom severity in a well characterized child cohort comprised of ASD patients and neurotypical controls. These blood-based neuropeptide measures, considered as a whole, correctly predicted disease status for 57 out of 68 (i.e., 84%) participants. Further analysis revealed that a composite measure of OXTR and AVPR1A gene expression was the key driver of group classification, and that children with ASD had lower neuropeptide receptor mRNA levels compared to controls. Lower neuropeptide receptor mRNA levels also predicted greater symptom severity for core ASD features (i.e., social impairments and stereotyped behaviors), but were unrelated to intellectual impairment, an associated feature of ASD. Findings from this research highlight the value of assessing multiple related biological measures, and their relative contributions, in the same study, and suggest that low blood neuropeptide receptor availability may be a promising biomarker of disease presence and symptom severity in ASD., (Copyright © 2018 Elsevier Ltd. All rights reserved.) more...
- Published
- 2018
- Full Text
- View/download PDF
13. Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism.
- Author
-
Parker KJ, Oztan O, Libove RA, Sumiyoshi RD, Jackson LP, Karhson DS, Summers JE, Hinman KE, Motonaga KS, Phillips JM, Carson DS, Garner JP, and Hardan AY
- Subjects
- Administration, Inhalation, Autism Spectrum Disorder blood, Child, Female, Humans, Male, Oxytocics blood, Oxytocics pharmacology, Oxytocin blood, Oxytocin pharmacology, Autism Spectrum Disorder drug therapy, Oxytocics therapeutic use, Oxytocin therapeutic use, Social Skills
- Abstract
Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients' underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6-12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial's primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment., Competing Interests: The authors declare no conflict of interest. more...
- Published
- 2017
- Full Text
- View/download PDF
14. A Longitudinal Pilot Study of Behavioral Abnormalities in Children with Autism.
- Author
-
Libove RA, Frazier TW, O'Hara R, Phillips JM, Jo B, and Hardan AY
- Abstract
This longitudinal investigation examined the development of emotional and behavioral functioning in school-age children with autism. The Child Behavior Checklist was obtained at baseline and after an average interval of 28.5 months from 13 boys with autism and 14 age- and gender-matched controls between the ages of 7 and 12 years at baseline. Children with autism demonstrated clinically significant elevations in several domains including Social, Thought, and Attention Problems. Children with autism exhibited significant improvements over time in Total, Externalizing, Social, and Oppositional Defiant Problems and Aggressive Behavior, while there were no changes over time in the controls. These findings suggest that children with autism may demonstrate improvements over time in some clinical domains such as social and behavioral functioning., Competing Interests: 6. Conflict of Interest The authors did not report any conflict of interest. more...
- Published
- 2017
- Full Text
- View/download PDF
15. A randomized controlled trial of Pivotal Response Treatment Group for parents of children with autism.
- Author
-
Hardan AY, Gengoux GW, Berquist KL, Libove RA, Ardel CM, Phillips J, Frazier TW, and Minjarez MB
- Subjects
- Age Factors, Child, Child, Preschool, Female, Humans, Male, Treatment Outcome, Autistic Disorder complications, Behavior Therapy, Language Development Disorders complications, Language Development Disorders therapy, Parents education, Parents psychology
- Abstract
Background: With rates of autism diagnosis continuing to rise, there is an urgent need for effective and efficient service delivery models. Pivotal Response Treatment (PRT) is considered an established treatment for autism spectrum disorder (ASD); however, there have been few well-controlled studies with adequate sample size. The aim of this study was to conduct a randomized controlled trial to evaluate PRT parent training group (PRTG) for targeting language deficits in young children with ASD., Methods: Fifty-three children with autism and significant language delay between 2 and 6 years old were randomized to PRTG (N = 27) or psychoeducation group (PEG; N = 26) for 12 weeks. The PRTG taught parents behavioral techniques to facilitate language development. The PEG taught general information about ASD (clinical trial NCT01881750; http://www.clinicaltrials.gov)., Results: Analysis of child utterances during the structured laboratory observation (primary outcome) indicated that, compared with children in the PEG, children in the PRTG demonstrated greater improvement in frequency of utterances (F(2, 43) = 3.53, p = .038, d = 0.42). Results indicated that parents were able to learn PRT in a group format, as the majority of parents in the PRTG (84%) met fidelity of implementation criteria after 12 weeks. Children also demonstrated greater improvement in adaptive communication skills (Vineland-II) following PRTG and baseline Mullen visual reception scores predicted treatment response to PRTG., Conclusions: This is the first randomized controlled trial of group-delivered PRT and one of the largest experimental investigations of the PRT model to date. The findings suggest that specific instruction in PRT results in greater skill acquisition for both parents and children, especially in functional and adaptive communication skills. Further research in PRT is warranted to replicate the observed results and address other core ASD symptoms., (© 2014 Association for Child and Adolescent Mental Health.) more...
- Published
- 2015
- Full Text
- View/download PDF
16. Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism.
- Author
-
Carson DS, Garner JP, Hyde SA, Libove RA, Berquist SW, Hornbeak KB, Jackson LP, Sumiyoshi RD, Howerton CL, Hannah SL, Partap S, Phillips JM, Hardan AY, and Parker KJ
- Subjects
- Adolescent, Adult, Autism Spectrum Disorder cerebrospinal fluid, Biomarkers blood, Biomarkers cerebrospinal fluid, Brain metabolism, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Siblings psychology, Social Behavior, Young Adult, Autism Spectrum Disorder blood, Autism Spectrum Disorder psychology, Neurophysins blood, Neurophysins cerebrospinal fluid, Protein Precursors blood, Protein Precursors cerebrospinal fluid, Vasopressins blood, Vasopressins cerebrospinal fluid
- Abstract
Brain arginine vasopressin (AVP) critically regulates normative social behavior in mammals, and experimental disruption of the AVP signaling pathway produces social impairments in rodent models. We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD). Since blood measures (which are far easier to obtain than brain measures) of AVP are most meaningful if they are related to brain AVP activity, Study 1 tested the relationship between AVP concentrations in concomitantly collected blood and CSF samples from children and adults (N = 28) undergoing clinical procedures. Study 2 tested whether blood AVP concentrations: 1) differed between children with ASD (N = 57), their ASD discordant siblings (N = 47), and neurotypical controls (N = 55); and 2) predicted social functioning (using the NEPSY-II Theory of Mind and Affect Recognition tasks and the Social Responsiveness Scale) in this large, well-characterized child cohort. Blood AVP concentrations significantly and positively predicted CSF AVP concentrations (F1,26 = 7.17, r = 0.46, p = 0.0127) in Study 1. In Study 2, blood AVP concentrations did not differ between groups or by sex, but significantly and positively predicted Theory of Mind performance, specifically in children with ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017). Blood AVP concentrations can be used: 1) as a surrogate for brain AVP activity in humans; and 2) as a robust biomarker of theory of mind ability in children with ASD. These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD. more...
- Published
- 2015
- Full Text
- View/download PDF
17. Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder.
- Author
-
Fung LK, Libove RA, Phillips J, Haddad F, and Hardan AY
- Subjects
- Adolescent, Adult, Child Development Disorders, Pervasive psychology, Female, Humans, Male, Pilot Projects, Pregnenolone pharmacology, Treatment Outcome, Young Adult, Child Development Disorders, Pervasive drug therapy, Irritable Mood drug effects, Pregnenolone therapeutic use
- Abstract
The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 ± 7.4 at baseline to 11.2 ± 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD. more...
- Published
- 2014
- Full Text
- View/download PDF
18. Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder.
- Author
-
Parker KJ, Garner JP, Libove RA, Hyde SA, Hornbeak KB, Carson DS, Liao CP, Phillips JM, Hallmayer JF, and Hardan AY
- Subjects
- Case-Control Studies, Child, Child Development Disorders, Pervasive blood, Child Development Disorders, Pervasive genetics, Child, Preschool, Female, Humans, Male, Phenotype, Child Development Disorders, Pervasive psychology, Oxytocin blood, Polymorphism, Genetic, Receptors, Oxytocin genetics, Social Behavior
- Abstract
The neuropeptide oxytocin (OXT) and its receptor (OXTR) regulate social functioning in animals and humans. Initial clinical research suggests that dysregulated plasma OXT concentrations and/or OXTR SNPs may be biomarkers of social impairments in autism spectrum disorder (ASD). We do not know, however, whether OXT dysregulation is unique to ASD or whether OXT biology influences social functioning more generally, thus contributing to, but not causing, ASD phenotypes. To distinguish between these possibilities, we tested in a child ASD cohort, which included unaffected siblings and unrelated neurotypical controls (ages 3-12 y; n = 193), whether plasma OXT concentrations and OXTR SNPs (i) interact to produce ASD phenotypes, (ii) exert differential phenotypic effects in ASD vs. non-ASD children, or (iii) have similar phenotypic effects independent of disease status. In the largest cohort tested to date, we found no evidence to support the OXT deficit hypothesis of ASD. Rather, OXT concentrations strongly and positively predicted theory of mind and social communication performance in all groups. Furthermore, OXT concentrations showed significant heritability between ASD-discordant siblings (h(2) = 85.5%); a heritability estimate on par with that of height in humans. Finally, carriers of the "G" allele of rs53576 showed impaired affect recognition performance and carriers of the "A" allele of rs2254298 exhibited greater global social impairments in all groups. These findings indicate that OXT biology is not uniquely associated with ASD, but instead exerts independent, additive, and highly heritable influences on individual differences in human social functioning, including the severe social impairments which characterize ASD. more...
- Published
- 2014
- Full Text
- View/download PDF
19. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism.
- Author
-
Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, Frazier TW, and Tirouvanziam R
- Subjects
- Child, Child, Preschool, Double-Blind Method, Female, Humans, Irritable Mood drug effects, Male, Pilot Projects, Stereotyped Behavior drug effects, Treatment Outcome, Acetylcysteine therapeutic use, Autistic Disorder drug therapy, Free Radical Scavengers therapeutic use
- Abstract
Background: An imbalance in the excitatory/inhibitory systems with abnormalities in the glutamatergic pathways has been implicated in the pathophysiology of autism. Furthermore, chronic redox imbalance was also recently linked to this disorder. The goal of this pilot study was to assess the feasibility of using oral N-acetylcysteine (NAC), a glutamatergic modulator and an antioxidant, in the treatment of behavioral disturbance in children with autism., Methods: This was a 12-week, double-blind, randomized, placebo-controlled study of NAC in children with autistic disorder. Subjects randomized to NAC were initiated at 900 mg daily for 4 weeks, then 900 mg twice daily for 4 weeks and 900 mg three times daily for 4 weeks. The primary behavioral measure (Aberrant Behavior Checklist [ABC] irritability subscale) and safety measures were performed at baseline and 4, 8, and 12 weeks. Secondary measures included the ABC stereotypy subscale, Repetitive Behavior Scale-Revised, and Social Responsiveness Scale., Results: Thirty-three subjects (31 male subjects, 2 female subjects; aged 3.2-10.7 years) were randomized in the study. Follow-up data was available on 14 subjects in the NAC group and 15 in the placebo group. Oral NAC was well tolerated with limited side effects. Compared with placebo, NAC resulted in significant improvements on ABC irritability subscale (F = 6.80; p < .001; d = .96)., Conclusions: Data from this pilot investigation support the potential usefulness of NAC for treating irritability in children with autistic disorder. Large randomized controlled investigations are warranted., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2012
- Full Text
- View/download PDF
20. A preliminary longitudinal magnetic resonance imaging study of brain volume and cortical thickness in autism.
- Author
-
Hardan AY, Libove RA, Keshavan MS, Melhem NM, and Minshew NJ
- Subjects
- Affective Symptoms physiopathology, Autistic Disorder physiopathology, Brain physiopathology, Case-Control Studies, Cerebral Cortex physiopathology, Child, Humans, Intelligence Tests, Longitudinal Studies, Male, Organ Size, Severity of Illness Index, Stereotyped Behavior physiology, Autistic Disorder pathology, Brain pathology, Cerebral Cortex pathology, Magnetic Resonance Imaging
- Abstract
Background: Autism is a developmental neurobiologic disorder associated with structural and functional abnormalities in several brain regions including the cerebral cortex. This longitudinal study examined developmental changes in brain volume and cortical thickness (CT) using magnetic resonance imaging (MRI) in children with autism., Methods: MRI scans and behavioral measures were obtained at baseline and after a 30-month interval in a sample of male subjects with autism (n = 18) and healthy age-, and sex-matched control subjects (n = 16) between ages 8 and 12 years at baseline., Results: No differences in brain volumes were observed between the autism and control subjects at baseline or follow-up. However, differences in total gray matter volumes were observed over time with significantly greater decreases in the autism group compared with control subjects. Differences in CT were observed over time with greater decreases in the autism group compared with control subjects in several brain regions including the frontal lobe. When accounting for multiple comparisons, differences between the two groups became nonsignificant except for changes in occipital CT. Furthermore, associations were observed between several clinical features and changes in CT with greater thinning of the cortex being correlated with more severe symptomatology., Conclusions: Findings from this study provide preliminary evidence for age-related changes in gray matter volume and CT in children with autism that are associated with symptoms severity. Future longitudinal studies of larger sample sizes are needed to evaluate developmental changes and examine the relationships between structural abnormalities and clinical expressions of the disorder. more...
- Published
- 2009
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.