The current assessment of behaviors in the inventories to diagnose autism spectrum disorders (ASD) focus on observation and discrete categorizations. Behaviors require movements, yet measurements of physical movements are seldom included. Their inclusion however, could provide an objective characterization of behavior to help unveil interactions between the peripheral and the central nervous systems (CNSs). Such interactions are critical for the development and maintenance of spontaneous autonomy, self-regulation, and voluntary control. At present, current approaches cannot deal with the heterogeneous, dynamic and stochastic nature of development. Accordingly, they leave no avenues for real time or longitudinal assessments of change in a coping system continuously adapting and developing compensatory mechanisms. We offer a new unifying statistical framework to reveal re-afferent kinesthetic features of the individual with ASD. The new methodology is based on the non-stationary stochastic patterns of minute fluctuations (micro-movements) inherent to our natural actions. Such patterns of behavioral variability provide re-entrant sensory feedback contributing to the autonomous regulation and coordination of the motor output. From an early age, this feedback supports centrally driven volitional control and fluid, flexible transitions between intentional and spontaneous behaviors. We show that in ASD there is a disruption in the maturation of this form of proprioception. Despite this disturbance, each individual has unique adaptive compensatory capabilities that we can unveil and exploit to evoke faster and more accurate decisions. Measuring the kinesthetic re-afference in tandem with stimuli variations we can detect changes in their micro-movements indicative of a more predictive and reliable kinesthetic percept. Our methods address the heterogeneity of ASD with a personalized approach grounded in the inherent sensory-motor abilities that the individual has already developed.

Objective Many children with Pervasive Developmental Disorders (PDDs) have serious, functionally-impairing behavioral problems. We tested whether Combined Treatment (COMB) with risperidone and parent training (PT) in behavior management is superior to Medication alone (MED) in improving severe behavioral problems in children with PDDs. Method This 24-week, three-site, randomized, parallel-groups clinical trial enrolled 124 children, aged 4 through 13 years, with PDDs, accompanied by frequent tantrums, self injury, and aggression. Children were randomized 3:2 to COMB (n= 75) or MED (n= 49). Participants received risperidone monotherapy from 0.5 to 3.5 mg/day (with switch to aripiprazole if risperidone was ineffective). Parents in COMB group (N=75; 60.5%) received a mean of 10.9 PT sessions. The primary measure of compliance was the Home Situations Questionnaire (HSQ) score. Results Primary: Intent-to-treat random effects regression showed that COMB was superior to MED on HSQ (p=.006) [effect size at Week 24 (d)= 0.34]. The HSQ score declined from 4.31 (±1.67) to 1.23 (±1.36) for COMB compared with 4.16 (±1.47) to 1.68 (±1.36) for MED. Secondary: Groups did not differ on Clinical Global Impressions–Improvement scores at end-point; compared with MED, COMB showed significant reductions on Aberrant Behavior Checklist Irritability (d=0.48; p= .01), Stereotypic Behavior (d=0.23; p= .04), and Hyperactivity/Noncompliance subscales (d=0.55; p= .04). Final risperidone mean dose for MED was 2.26 mg/day (0.071 mg/kg), compared to 1.98 mg/day for COMB (0.066 mg/kg) (p=.04). Conclusion Medication plus PT resulted in greater reduction of serious maladaptive behavior than medication alone in children with PDDs, with a lower risperidone dose.

The neurobiology of autism spectrum disorders (ASDs) has become increasingly understood since the advent of magnetic resonance imaging (MRI). Initial observations of an above-average head circumference were supported by structural MRI studies that found evidence of increased total brain volume and early rapid brain overgrowth in affected individuals. Subsequent research revealed consistent abnormalities in cortical gray and white matter volume in ASDs. The structural integrity and orientation of white matter have been further elucidated via diffusion tensor imaging methods. The emergence of functional MRI techniques led to an enhanced understanding of the neural circuitry of ASDs, demonstrating areas of dysfunctional cortical activation and atypical cortical specialization. These studies have provided evidence of underconnectivity in distributed cortical networks integral to the core impairments associated with ASDs. Abnormalities in the default-mode network during the resting state have also been identified. Overall, structural and functional MRI research has generated important insights into the neurobiology of ASDs. Additional research is needed to further delineate the underlying brain basis of this constellation of disorders.

Atypical antipsychotics have become indispensable in the treatment of a variety of symptoms in autism. They are frequently used to treat irritability and associated behaviors including aggression and self injury. They may also be efficacious for hyperactivity and stereotyped behavior. This review presents the rationale for the use of this drug class in autism and reviews the most important studies published on this topic to date. Significant adverse effects, including weight gain and the possibility of tardive dyskinesia, are reviewed. Future research directions are discussed.

Interest in the gastrointestinal (GI) factors of autistic disorder (autism) has developed from descriptions of symptoms such as constipation and diarrhea in autistic children and advanced towards more detailed studies of GI histopathology and treatment modalities. This review attempts to critically and comprehensively analyze the literature as it applies to all aspects of GI factors in autism, including discussion of symptoms, pathology, nutrition, and treatment. While much literature is available on this topic, a dearth of rigorous study was found to validate GI factors specific to children with autism.

In this open-label retrospective study, memantine was effective in a number of patients with PDDs. Controlled studies are warranted to further assess the efficacy and safety of memantine in PDDs.

Placebo-controlled studies are indicated to determine atomoxetine's efficacy for ADHD symptoms in PDDs.

Parent delivered interventions based on applied behavior analysis (ABA) for children with Pervasive Developmental Disorders (PDDs) have been evaluated using primarily single-subject design methodology or small case series. While the results of these evaluations are encouraging, an important next step is to standardize the interventions to allow for replication across sites, in studies with large samples and measures of long-term, clinically meaningful outcomes such as improvements in children's functioning and their relationships with parents. Accordingly, the Research Units on Pediatric Psychopharmacology and Psychosocial Interventions (RUPP Autism Network) assembled a detailed manual for a structured behavioral parent training (PT) program, developed treatment fidelity and training procedures, and conducted a pilot, feasibility study. The PT program is part of a large scale, multisite study intended to determine the efficacy of combined pharmacological treatment and behavioral intervention to improve behavior and adaptive functioning in children with PDD. This paper discusses the rationale for this project. A companion paper provides the results of our feasibility study on the PT program.