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.

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    • "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]. "
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    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.
    Full-text · Article · Jan 2015
    • "Typical brain development during the first year of life is characterized by rapid proliferation of neurons and neural connections, with a relative lack of efficiency in functioning (Webb, Monk, & Nelson, 2001). Neural connections are shaped by experience, some strengthened and elaborated and others weakened or eliminated, depending on differential stimulation (Bethea & Sikich, 2007). Some have proposed that ASD reflects a disruption in the shaping of neural connectivity (Courchesne & Pierce, 2005). "

    No preview · Article · Feb 2013 · Perspectives on Language Learning and Education
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    • "(E.S. Brodkin). understanding of the biological factors that influence sociability across development [12] [13]. Mouse models are indispensable for studies of the fundamental neurobiology of sociability because of the experimental control and genetics resources that they afford [14]. "
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    ABSTRACT: BALB/cJ and C57BL/6J inbred mouse strains have been proposed as useful models of low and high levels of sociability (tendency to seek social interaction), respectively, based primarily on behaviors of ∼30-day-old mice in the Social Approach Test (SAT). In the SAT, approach and sniffing behaviors of a test mouse toward an unfamiliar stimulus mouse are measured in a novel environment. However, it is unclear whether such results generalize to a familiar environment with a familiar social partner, such as with a littermate in a home cage environment. We hypothesized that C57BL/6J mice would show higher levels of social behaviors than BALB/cJ mice in the home cage environment, particularly at 30 days-of-age. We measured active and passive social behaviors in home cages by pairs of BALB/cJ or C57BL/6J littermates at ages 30, 41, and 69 days. The strains did not differ robustly in their active social behaviors. C57BL/6J mice were more passively social than BALB/cJ mice at 30 days, and C57BL/6J levels of passive social behaviors declined to BALB/cJ levels by 69 days. The differences in passive social behaviors at 30 days-of-age were primarily attributable to differences in huddling. These results indicate that different test conditions (SAT conditions vs. home cage conditions) elicit strain differences in distinct types of behaviors (approach/sniffing vs. huddling behaviors, respectively). Assessment of the more naturalistic social interactions in the familiar home cage environment with a familiar littermate will provide a useful component of a comprehensive assessment of social behaviors in mouse models relevant to autism.
    Full-text · Article · Sep 2012 · Behavioural brain research
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