Principal Investigator:  Thomas F. Anders, M.D.
Co-Principal Investigator:  Beth Goodlin-Jones, Ph.D.

Children with autism and other neurodevelopmental disorders are known to have significant sleep problems. However, less is known about the kind of sleep problem, the severity of the problem and the continuity of the problem over time. This study uses actigraphy and videosomnography in the child's home to study the kinds of sleep disorders with which children with autism present. Two comparison groups (typically developing children and children with developmental delay but without autism) are matched in chronological age and developmental level, and contrasted to a group of children with autism. Each group of 60 children is studied on three occasions of one week's duration over a six month period. In addition daytime measures of sleepiness and attention are obtained on each occasion. This study will attempt to define the types of sleep disorders present in these children and determine whether any of the sleep disorders are specific to diagnosis. Moreover, the study will assess whether daytime performance is impacted by night time sleep disruption.

Principal Investigator:  Blythe Corbett, Ph.D.

Converging evidence from neuropathological, neuropsychological, lesion and neuroimaging studies support an important role for the amygdala in the neuropathology of autism. A central hypothesis of this series of studies is that dysregulation of the amygdala may contribute to various impairments in autism including increased response to potentially threatening stimuli, deficits in implicit and explicit emotion perception and limited social cognition. Functional magnetic resonance imaging (fMRI) permits the in vivo study of underlying brain regions involved in the execution of a cognitive, affective, motor or perceptual task. The goal of this project is to use established fMRI probes of amygdalar function to study the processing of various social and emotional stimuli in children with autism and neurotypical children 8 to 12 years of age.

Principal Investigator:  Blythe A. Corbett, Ph.D.
Co-Principal Investigator:  Seymour Levine, Ph.D.

Autism is a severe neurodevelopmental disorder characterized by impairment in communication, social interaction, repetitive behaviors and difficulty adapting to novel experiences. The hypothalamic-pituitary-adrenocortical (HPA) system responds consistently to novel or unfamiliar situations and can serve as an important biomarker of the response to a variety of different stimuli. There is evidence  that regulation of the HPA system may be dysfunctional in children with autism. In order to provide preliminary data concerning HPA regulation and responsiveness our laboratory we compared circadian rhythms and response to a non-social, environmental stressor (mock MRI scanner) in children with and without autism. The children with autism, but not typical children, showed a more variable circadian rhythm as well as statistically significant elevations in cortisol following exposure to a novel, nonsocial stimulus.  The results suggest that children with autism process and respond idiosyncratically to novel and threatening events resulting in an exaggerated cortisol response. Currently, we are conducting a series of studies to evaluate the responsiveness and regulation of the HPA axis in children with and without autism following exposure to a variety of social and nonsocial stimuli and situations. These investigations are funded by the M.I.N.D. Institute Investigator-Initiated Award (2004) and the Department of Psychiatry Tupin Award (2005).

Principal Investigator:  Sally J. Ozonoff, Ph.D.

This study tracks the early development of younger siblings of children with autism, children with other developmental delays, and children with typical development. Through this study, we hope to learn more about the early warning signs of later developmental problems and possible genetic markers for speech and language delay. Studies have indicated a 5-10% risk of having a second child with an autism spectrum disorder, with the risk potentially rising to as high as 35% for a third child. Babies are followed for three to four years and their social, communicative, cognitive, physical, and motor development is studied using a combination of behavioral methods, eye tracking paradigms, and gene assays. Once the participants have passed through the window of risk for the development of autism, we will be able to examine which behaviors differentiate the children who are affected from those who develop typically. The goal of this investigation is to develop a set of behavioral criteria that predict which infants will be later diagnosed with autism. Early recognition and intervention are very important in order to achieve the best long-term outcomes for children with autism.

Principal Investigator:   Sally Rogers, Ph.D.

Autism affects development from quite early in life, but the symptoms that differentiate autism from other developmental disorders change over time.  We do not know the relationship between very early symptoms of autism involving problems with imitation, emotional responsivity, joint attention,  and sensory symptoms, with later, classic symptoms involving theory of mind, executive dysfunction, repetitive behaviors. Longitudinal studies of autism from toddlerhood to middle childhood are only now being carried out. This program of research involves three research projects being carried out at two sites: the M.I.N.D. Institute and the University of Colorado Health Sciences Center. One project examines preschoolers with autism and the nature of their difficulties in imitating actions on objects. A second project examines early onset patterns and the phenomenon of regression in autism using home videotapes of infnacy, current neuropsychological profiles of behavior, and biological measures of environmental exposures. These two projects involve 40 children with autism, 20 children with other delays, and 20 children with typical development. A third project examines continuities and discontinuities between autism symptoms and neuropsychological abilities at ages two, five, and eight and includes 35 children with autism, 25 with fragile X syndrome, 25 with other devleopmental delays, and 25 with typical development.  With these studies we will try to determine to what extent later symptoms and symptom severity can be predicted at the time of first diagnosis, and which early features seem most predictive of later outcomes.

Principal Investigator:   Sally Rogers, Ph.D.

Autism is a neurobiological disorder that is thought to be due to differences in brain function that occur during prenatal development. However, autism is not usually diagnosed before children are two or three years old.  While parental reports and stuides of early videos document some differences in infants who will later be diagnosed with autism, no studies have thus far been published  that involved prospective information on infants in the first six months of life who alter develop autism. The purpose of this pilot study  is to examine social and motoric behavior of neonatal siblings of children with autism and a comparison group of typically developing neonates across the first 12 months of life. This project will use several new paradigms for assessing infant siblings of children with autism, including neonatal behavioral measures and analysis of gaze patterns during ongoing social interactions at 3 and 6 months. Autism symptoms at 12 months will be assessed and relationships between early social behaviors and autism symptoms at 12 month will be examined.   Participants include 60 infant siblings of children with autism and 60 infant siblings of typically developing children.

Principal Investigator:   Marjorie Solomon, Ph.D.
Autism spectrum disorders (ASDs), including autism, high functioning autism, Asperger's disorder, and pervasive developmental disorder NOS (PDDNOS) have a prevalence of one in 150. Male predominance of these disorders is four to one, although prevalence in females may be underestimated. Studies of gender differences in ASDs have reported that girls are more severely impaired than boys on measures of social skills and executive functions, however most of these studies did not adequately control for IQ. The goal of the current study is to use behavioral measures and functional magnetic resonance imaging (fMRI) to test hypotheses about gender differences in the manifestation of social and cognitive deficits and symptoms of psychopathology in a high functioning sample of girls with ASDs.

Prinicipal Investigator:  Marjorie Solomon, Ph.D.

Cognitive control refers to the ability to flexibly allocate mental resources to guide thoughts and actions in light of internal goals. Given the behavioral inflexibility exhibited by individuals with autism spectrum disorders (ASDs), it would appear they experience cognitive control deficits. My principal research program investigates cognitive control in high functioning individuals with autism spectrum disorders, and the relationship between cognitive control and behavioral symptoms. A career development award from the National Institute of Mental Health (1 K08 MH074967-01; Mentors: Drs. Cameron Carter, Sally Ozonoff, David Amaral, and Mark Lewis) will enable me to study cognitive neuroscience methods including fMRI to better investigate the neural mechanisms underlying control deficits, including functioning of the prefrontal cortex, the anterior cingulate cortex, and the basal ganglia and their relationship to restricted and repetitive behavior symptoms and formal thought disorder.

Principal Investigator:  Marjorie Solomon, Ph.D.

Autism involves dysregulated motivation in interpersonal relationships, goal-directed behavior, and learning. Theories about social aspects of motivation impairments, including those found in joint attention and face processing, recently have been articulated, however, there has been little study of non-social forms of motivation that also can create profound problems in adaptive functioning. The behavioral intervention literature also suggests that learning is dysregulated in autism spectrum disorders (ASDs) since acquisition of new skills may require multiple discrete learning trials with very explicit reinforcement schedules. Paradoxically, while some rewards are not motivating enough, some are too attractive to children with ASDs. For example, engagement in repetitive behavior may be self-reinforcing and circumscribed interests can be so seductive that adaptive functioning is disrupted when the person with ASD becomes absorbed in them. I am the principal investigator on a grant funded by Autism Speaks to examine non-social aspects of reward processing in ASDs using behavioral and functional neuroimaging measures.