Early Pharmacological Treatment of Autism: A Rationale for Developmental Treatment

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Biological Psychiatry (Impact Factor: 10.26). 03/2007; 61(4):521-37. DOI: 10.1016/j.biopsych.2006.09.021
Source: PubMed


Autism is a dynamic neurodevelopmental syndrome in which disabilities emerge during the first three postnatal years and continue to evolve with ongoing development. We briefly review research in autism describing subtle changes in molecules important in brain development and neurotransmission, in morphology of specific neurons, brain connections, and in brain size. We then provide a general schema of how these processes may interact with particular emphasis on neurotransmission. In this context, we present a rationale for utilizing pharmacologic treatments aimed at modifying key neurodevelopmental processes in young children with autism. Early treatment with selective serotonin reuptake inhibitors (SSRIs) is presented as a model for pharmacologic interventions because there is evidence in autistic children for reduced brain serotonin synthesis during periods of peak synaptogenesis; serotonin is known to enhance synapse refinement; and exploratory studies with these agents in autistic children exist. Additional hypothetical developmental interventions and relevant published clinical data are described. Finally, we discuss the importance of exploring early pharmacologic interventions within multiple experimental settings in order to develop effective treatments as quickly as possible while minimizing risks.

13 Reads
  • Source
    • "Neurodevelopmental theories stress the importance of timing and transactions between genetic susceptibilities to ASD and environmental factors that shape neural connections through experience [2] [3] [22] [23]. These theories, along with evidence that neural shaping processes become highly prevalent at the end of the first year of life [24], lend support to the hypothesis that behavioral interventions beginning as soon as risk for ASD can be detected will be efficacious [25]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study examined the (a) feasibility of enrolling 12-month-olds at risk of ASD from a community sample into a randomized controlled trial, (b) subsequent utilization of community services, and (c) potential of a novel parent-mediated intervention to improve outcomes. The First Year Inventory was used to screen and recruit 12-month-old infants at risk of ASD to compare the effects of 6–9months ofAdapted Responsive Teaching (ART) versus referral to early intervention and monitoring (REIM). Eighteen families were followed for ∼20 months. Assessments were conducted before randomization, after treatment, and at 6-month followup. Utilization of community services was highest for the REIM group. ART significantly outperformed REIM on parent-reported and observed measures of child receptive language with good linear model fit. Multiphase growth models had better fit for more variables, showing the greatest effects in the active treatment phase, where ART outperformed REIM on parental interactive style (less directive), child sensory responsiveness (less hyporesponsive), and adaptive behavior (increased communication and socialization).This study demonstrates the promise of a parent-mediated intervention for improving developmental outcomes for infants at risk of ASD in a community sample and highlights the utility of earlier identification for access to community services earlier than standard practice.
    01/2015; Article ID 386951:1-16. DOI:10.1155/2015/386951
  • Source
    • "Serotonin is known to enhance synaptic modulation and refinement [34]. During the period of peak synaptogenesis in early brain development (the first 5 years of life), there is evidence in children with ASD that brain synthesis of serotonin is reduced [35] [36] [37]. Serotonin can upregulate neurogenesis in the animal and human hippocampus [38] [39] [40] [41]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Young children with fragile X syndrome (FXS) often experience anxiety, irritability, and hyperactivity related to sensory hyperarousal. However, there are no medication recommendations with documented efficacy for children under 5 years old of age with FXS. We examined data through a chart review for 45 children with FXS, 12-50 months old, using the Mullen Scales of Early Learning (MSEL) for baseline and longitudinal assessments. All children had clinical level of anxiety, language delays based on MSEL scores, and similar early learning composite (ELC) scores at their first visit to our clinic. Incidence of autism spectrum disorder (ASD) was similar in both groups. There were 11 children who were treated with sertraline, and these patients were retrospectively compared to 34 children who were not treated with sertraline by chart review. The baseline assessments were done at ages ranging from 18 to 44 months (mean 26.9, SD 7.99) and from 12 to 50 months (mean 29.94, SD 8.64) for treated and not treated groups, respectively. Mean rate of improvement in both expressive and receptive language development was significantly higher in the group who was treated with sertraline (P < 0.0001 and P = 0.0071, resp.). This data supports the need for a controlled trial of sertraline treatment in young children with FXS.
    05/2012; 2012:104317. DOI:10.1155/2012/104317
  • Source
    • "Reduced sociability during this sensitive period for social behavior development contributes to impaired development of social reciprocity, social cognition, and social skills [3,4,7–11]. Because sociability is so important for propelling the many aspects of social behavior development, there is a strong need for improved understanding of the biological factors that influence sociability across development [12] [13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sociability--the tendency to seek social interaction--propels the development of social cognition and social skills, but is disrupted in autism spectrum disorders (ASD). BALB/cJ and C57BL/6J inbred mouse strains are useful models of low and high levels of juvenile sociability, respectively, but the neurobiological and developmental factors that account for the strains' contrasting sociability levels are largely unknown. We hypothesized that BALB/cJ mice would show increasing sociability with age but that C57BL/6J mice would show high sociability throughout development. We also hypothesized that littermates would resemble one another in sociability more than non-littermates. Finally, we hypothesized that low sociability would be associated with low corpus callosum size and increased brain size in BALB/cJ mice. Separate cohorts of C57BL/6J and BALB/cJ mice were tested for sociability at 19-, 23-, 31-, 42-, or 70-days-of-age, and brain weights and mid-sagittal corpus callosum area were measured. BALB/cJ sociability increased with age, and a strain by age interaction in sociability between 31 and 42 days of age suggested strong effects of puberty on sociability development. Sociability scores clustered according to litter membership in both strains, and perinatal litter size and sex ratio were identified as factors that contributed to this clustering in C57BL/6J, but not BALB/cJ, litters. There was no association between corpus callosum size and sociability, but smaller brains were associated with lower sociability in BALB/cJ mice. The associations reported here will provide directions for future mechanistic studies of sociability development.
    Behavioural brain research 12/2011; 228(2):299-310. DOI:10.1016/j.bbr.2011.12.001 · 3.03 Impact Factor
Show more

Preview (2 Sources)

13 Reads
Available from