The prodrome of autism: early behavioral and biological signs, regression, peri‐ and post‐natal development and genetics

Abstract

Autism is one of the most heritable neurodevelopmental conditions and has an early onset, with symptoms being required to be present in the first 3 years of life in order to meet criteria for the 'core' disorder in the classification systems. As such, the focus on identifying a prodrome over the past 20 years has been on pre-clinical signs or indicators that will be present very early in life, certainly in infancy. A number of novel lines of investigation have been used to this end, including retrospective coding of home videos, prospective population screening and 'high risk' sibling studies; as well as the investigation of pre- and peri-natal, brain developmental and other biological factors. While no single prodromal sign is expected to be present in all cases, a picture is emerging of indicative prodromal signs in infancy and initial studies are being undertaken to attempt to ameliorate early presentation and even 'prevent' emergence of the full syndrome.

Social and attention factors during infancy and the later emergence of autism characteristics

“…In the hope of discovering early markers of the condition, attention has recently turned to the study of infant siblings of children with autism (Elsabbagh & Johnson, 2010;Yirmiya & Charman, 2010;Zwaigenbaum et al, 2007). Since the condition is highly heritable, later-born siblings of diagnosed children are at substantially higher risk for developing the condition than the general population (Bolton, Pickles, Murphy, & Rutter, 1998).…”

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

“…As noted by Yirmiya and Charman [104] ''the primary motivation for identifying the earliest signs of emerging ASDs is the desire to develop and test early or even 'preventative' interventions to lessen morbidity by changing the course of early emerging developmental perturbation, thus preventing 'secondary' neurodevelopmental disturbances.'' Towards evaluating the potential of CD38 as a hallmark in ASD, reduced CD38 expression needs firstly to be verified in circulating lymphocytes.…”

“…It is prognostic for HIV infected subjects [105], chronic lymphoid leukemia [106] and for diabetic patients with nephropathy [107]. Hence reduced CD38 transcription cannot be pathognomonic for ASD but nevertheless might prove of salient clinical value in a disorder diagnosed solely using behavioral assessments reliably carried out only at the age of three [104]. Moreover, CD38 expression changes throughout the lifespan [71] and age-dependent CD38 expression in circulating lymphocytes are potential confounds in its use as a diagnostic indicator in ASD.…”

Particularités cognitives dans le trouble du spectre de l'autisme : la théorie de l'esprit et les fonctions exécutives

“…Ces particularités sont présentes dans les signes précoces de l'autisme. Yirmiya et Charman [6] relèvent les indices les plus précoces de l'autisme: les enfants passent moins de temps envers les stimuli sociaux, ils répondent moins à l'appel de leur prénom, développent moins de comportements d'attention conjointe et mani festent moins d'expressions émotionnelles.…”