D-Cycloserine and Social Skills Training in Autism Spectrum Disorders

This study will evaluate the efficacy of D-Cycloserine given 30 minutes prior to each of 10
weekly Social Skills Training Sessions for the treatment of social impairment in children
(ages 5-11 years) with PDD during a randomized placebo-controlled trial. This will examine
our central hypothesis that D-cycloserine will enhance learning of social skills in children
with PDD's.

Inclusion Criteria:

- DSM-IV-TR diagnosis of autism, Asperger's disorder, or PDD not otherwise specified
(NOS) base on a semi-structured review of DSM-IV-R criteria and mental status
examination as wll as a complete parental history obtained from the Autism Diagnostic
Interview-Revised (ADI-R) and a complete systematic patient interview utilizing the
Autism Diagnostic Observation Schedule (ADOS).

- Males and females ages 5-11 years.

- Significant social impairment as evidenced by a parent-rated Social Responsiveness
Scale (SRS) T-score of 60 or greater.

- TSSA score of 70% or less on both parent questionnaire and child assessment. Children
not showing significant impairment in the four specific social skill areas
(greetings/goodbyes, conversations, game play, and understanding emotions) targeted
by the SST are less likely to benefit from treatment.

- Communication Standard Score of 70 or greater on the Vineland-II.

- Full Scale IQ greater than 70.

- Subjects must not be taking any psychotropic drugs affecting glutamate
neurotransmission (riluzole, memantine, acamprosate, topiramate, amantadine, among
others). Subjects may not be taking more than two psychotropic drugs. Dosing of all
concomitant psychotropic drugs targeting core social and/or communication impairment
must be stable for eight weeks prior to randomization. Dosing of all concomitant
psychotropic drugs treating other features associated with pervasive developmental
disorders (insomnia, inattention, hyperactivity, anxiety, irritability among others0
must be stable for two weeks (with the exception of four weeks for fluoxetine) prior
to randomization.

- Able to participate in group SST based on semi-structured parent and child interview.

- Legal guardian has provided written informed consent and the subject has provided
written informed assent. Expectation that a majority of subjects will be able to
assent but the potential for the younger children and/or those that are cognitively
impaired will not be able to assent.

Exclusion Criteria:

- Subjects with diagnoses of Rett's disorder or childhood integrative disorder will not
be enrolled since these disorders have a different etiology, course, and treatment
response. Furthermore, children with these disorders may not function at a high
enough level in terms of cognition or language in order to benefit from the SST.

- Initiation of a new psychosocial intervention within 90 days prior to randomization.
Participants who have recently had a significant change in their psychosocial
interventions will not be eligible until this intervention has been stable for 90
days in order to avoid confounding results of the study. Stable interventions (e.g.,
speech and occupational therapy), with the exception of concurrent social skills
training, will be allowed to continue during the course of the study. Minor changes
in ongoing treatment (e.g., missed therapy sessions due to holiday/vacation; planned
break in therapy due to school holidays) are not considered significant.

- Subjects exhibiting significant disruptive, aggressive, self-injurious, or sexually
inappropriate behavior will not be eligible for enrollment.

- Presence of current DSM-IV-TR psychiatric disorders that require alternative
pharmacotherapy or different treatment including psychotic disorders, or major
affective disorders, obsessive-compulsive disorder, panic disorder, or substance
related disorders.

- Presence of any medical condition that would make treatment with DCS less safe.
Subjects with significant cardiac, hepatic, or renal disease will be excluded due to
concerns about pharmacokinetic alterations or adverse effects. Subjects with a
history of a seizure disorder are permitted if the subject has been seizure free for
6 months and is currently treated with an anticonvulsant that has been stable for 4
weeks. D-Cycloserine is an U.S. FDA Pregnancy Category C drug. Because of the unknown
effects of DCS on the developing human fetus, females of childbearing potential will
be given a urine pregnancy test and required to use a suitable form of birth control
during the study. A positive pregnancy test result excludes the subject.

- Presence of any other condition that would make the participants unable to comply
with the requirements of the study for any reason.