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Review
. 2007 Feb 15;61(4):521-37.
doi: 10.1016/j.biopsych.2006.09.021.

Early pharmacological treatment of autism: a rationale for developmental treatment

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Review

Early pharmacological treatment of autism: a rationale for developmental treatment

Terrence C Bethea et al. Biol Psychiatry. .

Erratum in

  • Biol Psychiatry. 2007 Mar 15;61(6):826

Abstract

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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Figures

Figure 1
Figure 1. Neurotransmitters and neuromodulators associated with autism
During prenatal and early infant development, neurotransmitters may have trophic, morphogenic, and synaptic signaling roles. ‘Maturity’ pathways represent the primary communications between neurons capable of appropriate receptor-mediated synaptic neurotransmission. Accordingly, aspects of both pathways may overlap temporally and spatially during both in utero and childhood development. The complexity and reciprocal connections of the pathways is notable.
Figure 2
Figure 2. Developmental Similarities in Serotonin Synthesis and Synapse Number
These two schematics depict the capacity of the brain for serotonin synthesis and the number of synapses in frontal cortex. They are based on our interpretation of results from other researchers who examined a limited number of individuals. The serotonin synthesis schematic (A) is based on PET scans of 30 children with autism and 24 controls (8 siblings and 24 children with epilepsy) (Chugani et al 1999). The synapse schematic (B) is based on 12 postmortem specimens (Huttenlocher 1079.) Thus, the exact shapes of the curves is not known.

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