early diagnosis


In the last 15-20 years the incidence of autism spectrum disorders (ASD) has increased significantly. The Center for Disease Control and Prevention of the United States of America has found 1 in 88 newborns, defining one of the highest rates of all neurodevelopmental disorders. The high heterogeneity of the presentation of DSA during the first 24 months of life makes the current methods of clinical evaluation unspecific and not very sensitive. Currently the diagnosis of ASD is made ​​between the fifth and the ninth year of the life of the person affected, delaying the implementation of interventions, and loses the ability to act on those stages of development and maturation in which the nervous system is more willing to adaptations. The identification of biological markers or other specific neuro-psycho-physiological indicators might support an early diagnosis and facilitate the timely implementation of therapies. Dr. Anderson and his colleagues of the Neurocognitive Development of Autism Research Laboratory at the University of Kansas studied for years the frequent dysfunctions of the autonomic nervous system (ANS) in the ASD and in particular the changes in the pupillary light reflex (PR) as a possible early marker of ASD. The PR is already observable before the 24th month and is statistically more consistent with other indicators of the activity of the ANS, such as heart rate variability and skin conductance. Furthermore, it is independent of cognitive activity of the subject. The PR is modulated by a balance between excitatory and inhibitory activity of the sympathetic and parasympathetic systems, is governed mainly by noradrenergic pathways, involving the hypothalamus and its connections with the pituitary gland and the adrenal gland. Anderson and co-workers have investigated the changes in the PR in relation to an already well-known indicator of noradrenergic activity neuroautonomic: salivary alpha-amylase (AAs), an enzyme used in the digestion of starch and secreted under control of the sympathetic and parasympathetic systems.The studies were conducted on children with ASD who had typical developing (TD), and an age range between 20 and 79 months. The RP and the concentrations of AAs seem to represent biological markers to be used in the near future for the early diagnosis of ASD. It could also provide important information on the status of specific neuropathological patients and promote the prescription of customized drug therapies.


- Corbett, B. A., Mendoza, S., Wegelin, J. A., Carmean, V., & Levine, S. (2008). Variable cortisol circadian rhythms in children with autism and anticipatory stress. Journal of Psychiatry & Neuroscience, 33(3), 227–234.
- Dawson, G. (2010). Recent advances in research on early detection, causes, biology, and treatment of autism spectrum disorders. Current Opinion in Neurology, 23(2), 95–96.
- Fan, X., Miles, J. H., Takahashi, N., & Yao, G. (2009). Abnormal transient pupillary light reflex in individuals with autism spectrum disorders. Journal of Autism and Developmental Disorders, 39, 1499–1508.
- Granger, D. A., Kivlighan, K. T., El-Sheikh, M., Gordis, E. B., & Stroud, L. R. (2007). Salivary a-amylase in biobehavioral research: Recent developments and applications. Annals of the New York Academy of Sciences, 1098, 122–144.
- Granholm, E., Asarnow, R. F., Sarkin, A. J., & Dykes, K. L. (1996). Pupillary responses index cognitive resource limitations. Psychophysiology, 33, 457–461.
- Hertz-Picciotto, I., & Delwiche, L. (2009). The rise in autism and the role of age at diagnosis. Epidemiology, 20(1), 84–90.
- Israngkun, P. P., Newman, H. A. I., & Patel, S. T. (1986). Potential biochemical markers for infantile autism. Neurochemical Pathology, 5, 51–70.
- Martineau, J., Hernandez, N., Hiebel, L., Roche, L., Metzger, A., & Bonnet-Brilhault, F. (2011). Can pupil size and pupil responses during visual scanning contribute to the diagnosis of autism spectrum disorder in children? Journal of Psychiatric Research, 45(8), 1077–1082.
- Nater, U. M., La Marca, R., Florin, L., Moses, A., Langhans, W., Koller, M. M., & Ehlert, U. (2006a). Stress-induced changes in human salivary alpha-amylase activity-assocations with adrenergic activity. Psychoneuroendocrinology, 31, 49–58.
- Nater, U. M., La Marca, R., Florin, L., Moses, A., Langhans, W., Koller, M. M., & Ehlert, U. (2006b). Stress-induced changes in human salivary alpha-amylase activity - Associations with adrenergic activity. Psychoneuroendocrinology, 31(1), 49–58.
- Nater, U. M., & Rohleder, N. (2009). Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: Current state of research. Psychoneuroendocrinology, 34(4), 486–496.
- Nater, U. M., Rohleder, N., Schlotz, W., Ehlert, U., & Kirschbaum, C. (2007). Determinants of the diurnal course of salivary alpha-amylase. Psychoneuroendocrinology, 32(4), 392–401.
- Pierce, K., Glatt, S. J., Liptak, G. S., & McIntyre, L. L. (2009). The power and promise of identifying autism early: Insights from the search for clinical and biological markers. Annals of Clinical Psychiatry: Official Journal of the American Academy of Clinical Psychiatrists, 21(3), 132–147.
- Rohleder, N., Nater, U. M., Wolf, J. M., Ehlert, U., & Kirshbaum, C. (2004). Psychosocial stress-induced activation of salivary alpha-amylase. Annals of the New York Academy of Sciences, 1032, 258–263.
- Steinhauer, S. R., Siegle, G. J., Condray, R., & Pless, M. (2004). Sympathetic and parasympathetic innervation of pupillary dilation during sustained processing. International Journal of Psychophysiology, 52, 77–86.
- Yirmiya, N., & Charman, T. (2010). The prodrome of autism: Early behavioral and biological signs, regression, peri- and post-natal development and genetics. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 51(4), 432–458.
- Zwaigenbaum, L. (2010). Advances in the early detection of autism. Current Opinion in Neurology, 23(2), 97–102.

Marco O. Bertelli, Giuliano Monteleone, Annamaria Bianco