Anagnostou E.,Bloorview Research Institute |
Anagnostou E.,University of Toronto |
Hansen R.,MIND Institute |
Hansen R.,University of California at Davis
Current Opinion in Pediatrics | Year: 2011
PURPOSE OF REVIEW: Up to 35% of children and youth with autism spectrum disorder (ASD) receive at least one psychotropic medication. 50-70% of this population also receives biologically based complementary and alternative medicine (CAM). The data evaluating such practices are being reviewed. RECENT FINDINGS: There are accumulating data to suggest that atypical antipsychotics and stimulants may be useful for the treatment of irritability and hyperactivity in children and youth with ASD. The data for the use of selective serotonin reuptake inhibitors are less promising. New avenues of pharmacologic research targeting molecular targets identified by genomics, animal models and neuropathology are being evaluated. Areas of interest include glutamate/gamma-aminobutyric acid systems, neuropeptides such as oxytocin, and immune dysfunction, among others. In the case of biologically based CAM, a few compounds have been shown to be well tolerated, although efficacy is still being evaluated, such as melatonin, certain vitamins, and omega 3 fatty acids. Others have safety concerns without demonstrated efficacy, such as chelation therapies. SUMMARY: Accumulating data suggest a series of existing medications may be useful in ASD and large randomized clinical trials are necessary to evaluate safety and efficacy of both pharmaceuticals and alternative treatments. © 2011 Wolters Kluwer Health | Lippincott Williams &Wilkins.
Solomon M.,University of California at Davis |
Solomon M.,Mind Institute |
Yoon J.H.,University of California at Davis |
Ragland J.D.,University of California at Davis |
And 5 more authors.
Biological Psychiatry | Year: 2014
Background Autism spectrum disorders (ASDs) involve impairments in cognitive control. In typical development (TYP), neural systems underlying cognitive control undergo substantial maturation during adolescence. Development is delayed in adolescents with ASD. Little is known about the neural substrates of this delay. Methods We used event-related functional magnetic resonance imaging and a cognitive control task involving overcoming a prepotent response tendency to examine the development of cognitive control in young (ages 12-15; n = 13 with ASD and n = 13 with TYP) and older (ages 16-18; n = 14 with ASD and n = 14 with TYP) adolescents with whole-brain voxelwise univariate and task-related functional connectivity analyses. Results Older ASD and TYP showed reduced activation in sensory and premotor areas relative to younger ones. The older ASD group showed reduced left parietal activation relative to TYP. Functional connectivity analyses showed a significant age by group interaction with the older ASD group exhibiting increased functional connectivity strength between the ventrolateral prefrontal cortex and the anterior cingulate cortex, bilaterally. This functional connectivity strength was related to task performance in ASD, whereas that between dorsolateral prefrontal cortex and parietal cortex (Brodmann areas 9 and 40) was related to task performance in TYP. Conclusions Adolescents with ASD rely more on reactive cognitive control, involving last-minute conflict detection and control implementation by the anterior cingulate cortex and ventrolateral prefrontal cortex, versus proactive cognitive control requiring processing by dorsolateral prefrontal cortex and parietal cortex. Findings await replication in larger longitudinal studies that examine their functional consequences and amenability to intervention. © 2014 Society of Biological Psychiatry.
Solomon M.,University of California at Davis |
Solomon M.,MIND Institute |
Ragland J.D.,University of California at Davis |
Niendam T.A.,University of California at Davis |
And 6 more authors.
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2015
Objective To investigate the neural mechanisms underlying impairments in generalizing learning shown by adolescents with autism spectrum disorder (ASD). Method A total of 21 high-functioning individuals with ASD aged 12 to 18 years, and 23 gender-, IQ-, and age-matched adolescents with typical development (TYP), completed a transitive inference (TI) task implemented using rapid event-related functional magnetic resonance imaging (fMRI). Participants were trained on overlapping pairs in a stimulus hierarchy of colored ovals where A>B>C>D>E>F and then tested on generalizing this training to new stimulus pairings (AF, BD, BE) in a "Big Game." Whole-brain univariate, region of interest, and functional connectivity analyses were used. Results During training, the TYP group exhibited increased recruitment of the prefrontal cortex (PFC), whereas the group with ASD showed greater functional connectivity between the PFC and the anterior cingulate cortex (ACC). Both groups recruited the hippocampus and caudate comparably; however, functional connectivity between these regions was positively associated with TI performance for only the group with ASD. During the Big Game, the TYP group showed greater recruitment of the PFC, parietal cortex, and the ACC. Recruitment of these regions increased with age in the group with ASD. Conclusion During TI, TYP individuals recruited cognitive control-related brain regions implicated in mature problem solving/reasoning including the PFC, parietal cortex, and ACC, whereas the group with ASD showed functional connectivity of the hippocampus and the caudate that was associated with task performance. Failure to reliably engage cognitive control-related brain regions may produce less integrated flexible learning in individuals with ASD unless they are provided with task support that, in essence, provides them with cognitive control; however, this pattern may normalize with age. © 2015 American Academy of Child and Adolescent Psychiatry.
Solomon M.,MIND Institute |
Solomon M.,Imaging Research Center |
Olsen E.,Imaging Research Center |
Niendam T.,Imaging Research Center |
And 4 more authors.
Schizophrenia Research | Year: 2011
Objective: Individuals with autism and schizophrenia exhibit atypical language and social symptoms. The extent to which these symptoms are evident during development and in current functioning is unclear. Method: Three groups of patients aged 11-20 diagnosed as clinical-high-risk for psychosis (CHR; n = 15), first episode psychosis (FEP; n = 16), and autism spectrum disorders (ASD; n = 20), plus typically developing individuals (TYP; n = 20) were compared on common autism parent-report questionnaires assessing social and language development and current functioning including the Social Communication Questionnaire, the Children's Communication Checklist, and the Social Reciprocity Scale. Results: All clinical groups demonstrated atypical social and language development, with social impairment highest in ASD. Twenty percent of participants with CHR and FEP met diagnostic criteria for ASD as assessed by parent-report. ASD exhibited greater current syntactic, and pragmatic language symptoms including delayed echolalia, pedantic speech, and deficits in appreciating irony and sarcasm. All clinical groups exhibited current deficits in social functioning. CHR and FE had similar and intermediate levels of functioning relative to ASD and TYP, with CHR generally scoring closer to TYP, providing construct validity for the CHR diagnostic label. Conclusions: The results of this study suggest that ASDs, CHR, and FEP share common features of atypical neurodevelopment of language and social function. Evidence of impaired social reciprocity across both disorders and distinct language symptoms in ASDs provides important information for differential diagnosis and psychosis prevention, as well as leads for future investigations of comparative genetics and pathophysiology. © 2011 Elsevier B.V.
Lozano R.,MIND institute |
Lozano R.,University of California at Davis |
Hare E.B.,MIND institute |
Hare E.B.,University of California at Davis |
And 2 more authors.
Neuropsychiatric Disease and Treatment | Year: 2014
Fragile X syndrome (FXS) is the most common genetic cause of intellectual disability and the most common single-gene cause of autism. It is caused by mutations on the fragile X mental retardation gene (FMR1) and lack of fragile X mental retardation protein, which in turn, leads to decreased inhibition of translation of many synaptic proteins. The metabotropic glutamate receptor (mGluR) hypothesis states that the neurological defcits in individuals with FXS are due mainly to downstream consequences of overstimulation of the mGluR pathway. The main efforts have focused on mGluR5 targeted treatments; however, investigation on the gamma-aminobutyric acid (GABA) system and its potential as a targeted treatment is less emphasized. The fragile X mouse models (Fmr1-knock out) show decreased GABA subunit receptors, decreased synthesis of GABA, increased catabolism of GABA, and overall decreased GABAergic input in many regions of the brain. Consequences of the reduced GABAergic input in FXS include oversensitivity to sensory stimuli, seizures, and anxiety. Deficits in the GABA receptors in different regions of the brain are associated with behavioral and attentional processing deficits linked to anxiety and autistic behaviors. The understanding of the neurobiology of FXS has led to the development of targeted treatments for the core behavioral features of FXS, which include social deficits, inattention, and anxiety. These symptoms are also observed in individuals with autism and other neurodevelopmental disorders, therefore the targeted treatments for FXS are leading the way in the treatment of other neurodevelopmental syndromes and autism. The GABAergic system in FXS represents a target for new treatments. Herein, we discuss the animal and human trials of GABAergic treatment in FXS. Arbaclofen and ganaxolone have been used in individuals with FXS. Other potential GABAergic treatments, such as riluzole, gaboxadol, tiagabine, and vigabatrin, will be also discussed. Further studies are needed to determine the safety and efficacy of GABAergic treatments for FXS. © 2014 Lozano et al.
Tassone F.,University of California at Davis |
Tassone F.,MIND Institute |
Greco C.M.,MIND Institute |
Greco C.M.,University of California at Davis |
And 12 more authors.
Genes, Brain and Behavior | Year: 2012
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder associated with premutation alleles of the fragile X mental retardation 1 (FMR1) gene. Approximately 40% of older male premutation carriers, and a smaller proportion of females, are affected by FXTAS; due to the lower penetrance the characterization of the disorder in females is much less detailed. Core clinical features of FXTAS include intention tremor, cerebellar gait ataxia and frequently parkinsonism, autonomic dysfunction and cognitive deficits progressing to dementia in up to 50% of males. In this study, we report the clinical, molecular and neuropathological findings of eight female premutation carriers. Significantly, four of these women had dementia; of the four, three had FXTAS plus dementia. Post-mortem examination showed the presence of intranuclear inclusions in all eight cases, which included one asymptomatic premutation carrier who died from cancer. Among the four subjects with dementia, three had sufficient number of cortical amyloid plaques and neurofibrillary tangles to make Alzheimer's disease a highly likely cause of dementia and a fourth case had dementia with cortical Lewy bodies. Dementia appears to be more common than originally reported in females with FXTAS. Although further studies are required, our observation suggests that in a portion of FXTAS cases there is Alzheimer pathology and perhaps a synergistic effect on the progression of the disease may occur. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
News Article | April 22, 2016
The Simons Foundation Autism Research Initiative (SFARI) launched the Simons Foundation Powering Autism Research for Knowledge (SPARK) today, an online campaign that will lead to the largest autism study in the United States. SPARK is looking for 50,000 individuals diagnosed with autism. The online initiative will collect DNA as well as information from these individuals and their families. The good news is that you can participate! Findings from this study aim to better analyze the cause of autism as well as speed up the developments of new therapies, treatments and support systems that can help families living with the condition. To date, researchers have identified about 50 genes that are involved in autism. Scientists are also estimating that approximately 300 more genes play a role in its development. Through SPARK, experts aim to study the biological mechanisms involved in autism as well as the impacts of genetics' interaction with environmental factors. "Knowledge is power, and SPARK was created because we simply haven't learned enough about the genetics and other possible causes of autism," said Wendy Chung, SPARK's chief investigator and SFARI's clinical research director. "Together, we can 'spark' a movement in autism research." Under SPARK, there are several studies that interested parties can become involved in and this initiative will connect these participants to the researchers. SFARI partnered with 21 clinical sites affiliated by participating universities as well as various local and national autism organizations. The list of university-affiliated clinical sites includes the University of California, Davis MIND Institute, University of Minnesota and the University of North Carolina at Chapel Hill to name a few. Autism Science Foundation, Mid-Michigan Autism Association and Autism Society the Heartland are also part of the several partner organizations. These sites and groups are currently recruiting participants for this historical autism study. To join, interested parties can create an account on the SPARK website to kick off their journey. According to the U.S. Centers for Disease Control and Prevention (CDC), 1 in 68 American children have been diagnosed with autism spectrum disorder (ASD). About 1 in 42 boys are diagnosed with ASD compared to 1 in 189 among girls. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.
Brookman-Frazee L.,University of California at San Diego |
Stahmer A.,Mind Institute |
Stadnick N.,University of California at San Diego |
Chlebowski C.,University of California at San Diego |
And 2 more authors.
Administration and Policy in Mental Health and Mental Health Services Research | Year: 2016
This study characterized the use of research community partnerships (RCPs) to tailor evidence-based intervention, training, and implementation models for delivery across different childhood problems and service contexts using a survey completed by project principal investigators and community partners. To build on previous RCP research and to explicate the tacit knowledge gained through collaborative efforts, the following were examined: (1) characteristics of studies using RCP models; (2) RCP functioning, processes, and products; (3) processes of tailoring evidence-based practices for community implementation; and (4) perceptions of the benefits and challenges of collaborating with community providers and consumers. Results indicated that researchers were solely or jointly involved in the formation of almost all of the RCPs; interpersonal and operational processes were perceived as primary challenges; community partners’ roles included greater involvement in implementation and participant recruitment than more traditional research activities; and the partnership process was perceived to increase the relevance and “fit” of interventions and research. © 2015, Springer Science+Business Media New York.
Srivastava S.,Mind Institute |
Buonocore M.H.,Mind Institute |
Buonocore M.H.,Imaging Research Center |
Simon T.J.,Mind Institute
Human Brain Mapping | Year: 2012
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder associated with neurocognitive impairments. This article focuses on the cortical gyrification changes that are associated with the genetic disorder in 6-15-year-old children with 22q11.2DS, when compared with a group of age-matched typically developing (TD) children. Local gyrification index (lGI; Schaer et al. : IEEE Trans Med Imaging 27:161-170) was used to characterize the cortical gyrification at each vertex of the pial surface. Vertex-wise statistical analysis of lGI differences between the two groups revealed cortical areas of significant reduction in cortical gyrification in children with 22q11.2DS, which were mainly distributed along the medial aspect of each hemisphere. To gain further insight into the developmental trajectory of the cortical gyrification, we examined age as a factor in lGI changes over the 6-15 years of development, within and across the two groups of children. Our primary results pertaining to the developmental trajectory of cortical gyrification revealed cortical regions where the change in lGI over the 6-15 years of age was significantly modulated by diagnosis, implying an atypical development of cortical gyrification in children with 22q11.2DS, when compared with the TD children. Significantly, these cortical areas included parietal structures that are associated, in typical individuals, with visuospatial, attentional, and numerical cognition tasks in which children with 22q11.2DS show impairments. © 2011 Wiley Periodicals, Inc.
News Article | November 22, 2016
To make the donation of toys and other gifts easier for generous businesses, non-profit organizations and individuals who would like to make the season brighter for hospitalized children, UC Davis Children's Hospital is offering donors the opportunity to drive up and drop off donations for the holidays. The holiday toy drive will be held at the circular driveway of the UC Davis MIND Institute, 2825 50th St., Sacramento. The drop-off opportunity will be held from Tuesday, Dec. 20 through Friday, Dec. 23 from 9:30 a.m. to 4:30 p.m. Donors dropping off donations will be greeted in the driveway. "We really appreciate all of our donors who make the holiday season brighter with their gifts," said Diana Sundberg, manager of the UC Davis Child Life and Creative Arts Therapy Department. "The kindness of donors will make an important difference in the lives of many families who have a sick child in the hospital this time of year." The gifts will be given to hospitalized children during the holidays and throughout the year to mark the end of treatment and for completing tests and other procedures. Toys and gifts also will be used in hospital playrooms and waiting areas throughout the year. Please note: Even slightly used toys cannot be accepted because of infection-control precautions. UC Davis Children's Hospital is the Sacramento region's only nationally ranked, comprehensive hospital providing care for infants, children, adolescents and young adults with primary, subspecialty and critical care. It includes the Central Valley's only pediatric emergency department and Level I pediatric trauma center, which offers the highest level of care for its critically ill patients, as well as the West Coast's only Level I children's surgery center. The 129-bed children's hospital includes the state-of-the-art 49-bed neonatal and 24-bed pediatric intensive care and pediatric cardiac intensive care units. For more information, visit children.ucdavis.edu.