piperidines and Child-Development-Disorders--Pervasive

The present study was designed as a 12-week, randomized, double-blind, placebo-controlled pilot study to evaluate the effectiveness and safety of donepezil in boys with fragile X syndrome. Twenty boys with fragile X syndrome were randomized to receive 12 weeks of treatment with either placebo or donepezil (2.5 mg daily for initial 4 weeks followed by 5 mg daily for next 8 weeks). The outcome measures included change in intelligence quotient scores on Stanford-Binet Intelligence Scale (Hindi adaptation by Kulshrestha), change in behavioral scores by Conners 3 Parent Rating Scale (Short) and Childhood Autism Rating Scale, safety, and tolerability of donepezil. The study failed to show significant difference in intelligence quotient and behavioral scales with donepezil therapy over 12 weeks. However, donepezil appeared to be safe and well tolerated.

Topics: Adolescent; Child; Child Behavior Disorders; Child Development Disorders, Pervasive; Donepezil; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fragile X Syndrome; Humans; Indans; Intelligence; Male; Nootropic Agents; Personality Assessment; Pilot Projects; Piperidines; Stanford-Binet Test; Treatment Outcome

Rapid eye movement (REM) sleep is greatest in the developing brain, is driven by acetylcholine, and may represent a protected time for neuroplasticity. Recently published data from our lab observed that children with autism spent significantly less time in this state during a single night recording than did typically developing children and those with developmental delay without autism. The objective of this study was to determine whether or not donepezil can increase the REM % in children with diagnosed autism spectrum disorder (ASD) found to have REM % values of at least two standard deviations below expected for age.. Five subjects found to have an ASD (ages 2.5-6.9 years) and demonstrated deficits in REM sleep compared with within-lab controls were enrolled in a dose finding study of donepezil. Each subject was examined by polysomnography for REM sleep augmentation after drug administration.. REM sleep as a percentage of Total Sleep Time was increased significantly and REM latency was decreased significantly after drug administration in all subjects. No other observed sleep parameter was changed significantly.. Donepezil can increase the amount of time that children with an ASD spend in the REM sleep state. A double-blind, placebo-controlled trial is needed to assess the association between REM sleep augmentation and learning, cognition, and behavior in such children.

Topics: Autistic Disorder; Child; Child Development Disorders, Pervasive; Child, Preschool; Developmental Disabilities; Donepezil; Dose-Response Relationship, Drug; Electrocardiography; Humans; Indans; Male; Nootropic Agents; Piperidines; Polysomnography; Sleep; Sleep Wake Disorders; Sleep, REM; Treatment Outcome

Recent studies reported ADHD-like symptoms and cognitive deficits in pervasive developmental disorder (PDD). Because work in dementia documents improvement in executive function deficits with the acetylcholinesterase inhibitor donepezil, the authors reason that similar benefits could be obtained in PDD.. The authors describe eight cases of PDD youth ages 10 to 17 treated with donepezil targeting ADHD-like symptoms associated with PDD.. Most participants improve ADHD-like symptomatology. In addition, improvement in communication and socialization is noted.. Donepezil may have a role in treating ADHD-like symptoms in children with PDD.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Child Development Disorders, Pervasive; Cholinesterase Inhibitors; Communication; Donepezil; Drug Administration Schedule; Female; Humans; Indans; Male; Piperidines; Social Behavior

Both neuropsychological and functional magnetic resonance imaging studies have shown deficiencies in face perception in subjects with autism spectrum disorders (ASD). The fusiform gyrus has been regarded as the key structure in face perception. The cholinergic system is known to regulate the function of the visual pathway, including the fusiform gyrus.. To determine whether central acetylcholinesterase activity, a marker for the cholinergic system, is altered in ASD and whether the alteration in acetylcholinesterase activity, if any, is correlated with their social functioning.. Using positron emission tomography and a radiotracer, N-[(11)C]methyl-4-piperidyl acetate ([(11)C]MP4A), regional cerebrocortical acetylcholinesterase activities were estimated by reference tissue-based linear least-squares analysis and expressed in terms of the rate constant k(3). Current and childhood autism symptoms in the adult subjects with ASD were assessed by the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised, respectively. Voxel-based analyses as well as region of interest-based methods were used for between-subject analysis and within-subject correlation analysis with respect to clinical variables.. Participants recruited from the community.. Twenty adult subjects with ASD (14 male and 6 female; age range, 18-33 years; mean [SD] intelligence quotient, 91.6 [4.3]) and 20 age-, sex-, and intelligence quotient-matched healthy controls.. Both voxel- and region of interest-based analyses revealed significantly lower [(11)C]MP4A k(3) values in the bilateral fusiform gyri of subjects with ASD than in those of controls (P < .05, corrected). The fusiform k(3) values in subjects with ASD were negatively correlated with their social disabilities as assessed by Autism Diagnostic Observation Schedule as well as Autism Diagnostic Interview-Revised.. The results suggest that a deficit in cholinergic innervations of the fusiform gyrus, which can be observed in adults with ASD, may be related to not only current but also childhood impairment of social functioning.

Topics: Acetates; Acetylcholinesterase; Adolescent; Adult; Brain Mapping; Carbon Radioisotopes; Child; Child Development Disorders, Pervasive; Communication; Female; Humans; Image Processing, Computer-Assisted; Male; Piperidines; Positron-Emission Tomography; Reference Values; Social Behavior; Stereotyped Behavior; Temporal Lobe; Young Adult

Elevated concentrations of blood serotonin have been documented in autistic children and mentally retarded adults. Antiserotonergic pharmacotherapy has been partially effective in treating a subgroup of children with autistic disorder. Therefore, the possibility is raised that an antiserotonergic treatment may be of value to adult psychiatric patients with a history of pervasive developmental disorder. Two such cases are described where the patients underwent psychiatric and neuropsychological examination before and after treatment with risperidone, a potent 5-HT2 antagonist with additional D2 antagonistic properties. Particular improvements were documented in both patients, despite long histories of cognitive compromise and high likelihood of damage to the central nervous system.

Topics: Adolescent; Adult; Antipsychotic Agents; Autistic Disorder; Child; Child Development Disorders, Pervasive; Follow-Up Studies; Humans; Intellectual Disability; Isoxazoles; Male; Neuropsychological Tests; Piperidines; Risperidone; Serotonin; Stereotyped Behavior