Full-field electroretinogram in autism spectrum disorder
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To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes.
Light-adapted (LA) and dark-adapted (DA) ERGs were produced by a range of flash strengths that included and extended the ISCEV standard from two subject groups: a high-functioning ASD group N = 11 and a Control group N = 15 for DA and N = 14 for LA ERGs who were matched for mean age and range. Flash strengths ranged from DA −4.0 to 2.3 log phot cd s m−2 and LA −0.5 to 1.0 log phot cd s m−2, and Naka-Rushton curves were fitted to DA b-wave amplitude over the first growth limb (−4.0 to −1.0 log phot cd s m−2). The derived parameters (V max, K m and n) were compared between groups. Scotopic 15-Hz flicker ERGs (14.93 Hz) were recorded to 10 flash strengths presented in ascending order from −3.0 to 0.5 log Td s to assess the slow and fast rod pathways, respectively. LA 30-Hz flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120-ms ON–OFF stimuli were also recorded.
The ISCEV LA b-wave amplitude produced by 0.5 log phot cd s m−2 was lower in the ASD group (p < 0.001). Repeated measures ANOVA for the LA b-wave amplitude series forming the photopic hill was significantly (p = 0.01) different between groups. No group differences were observed for the distributions of the time to peaks of LA a-wave, b-wave or the photopic negative responses (phNR) (p > 0.08) to the single flash stimuli, but there was a significant difference in the distribution for the LA b-wave amplitudes (corrected p = 0.006). The prolonged 120-ms ON responses were smaller in the ASD group (corrected p = 0.003), but the OFF response amplitude (p > 0.6) and ON and OFF times to peaks (p > 0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants; however, no other differences were apparent in the OPs or 30-Hz flicker waveforms. DA b-wave amplitudes fell below the control 5th centile of the controls for some individuals including four ASD participants (36 %) at the 1.5 log phot cd s m−2 flash strength and two (18 %) ASD participants at the lower −2 log phot cd s m−2 flash strength. However, across the 13 flash strengths, there were no significant group differences for b-wave amplitude’s growth (repeated measures ANOVA p = 0.83). Nor were there any significant differences between the groups for the Naka-Rushton parameters (p > 0.09). No group differences were observed in the 15-Hz scotopic flicker phase or amplitude (p > 0.1), DA ERG a-wave amplitude or time to peak (p > 26). The DA b-wave time to peak at 0.5 log phot cd s m−2 was longer in the ASD group (p = 0.04).
Under LA conditions, the b-wave is reduced across the ASD group, along with the ON response of the prolonged flash ERG. Some ASD individuals also show subnormal DA ERG b-wave amplitudes. These exploratory findings suggest there is altered cone-ON bipolar signalling in ASD.
KeywordsAutism spectrum disorder Electroretinogram Naka-Rushton ON pathway 15-Hz scotopic flicker
This study was funded by the College of Optometrists, and parts of this work were presented at the 52nd ISCEV conference in Boston. The study was nominated for the Marmor prize for clinical innovation in electrophysiology at the meeting. The authors thank the anonymous reviewers for their helpful comments on this paper.
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Conflict of interest
All authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
- 1.Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D et al (2006) Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet 368(9531):210–215. doi: 10.1016/s0140-6736(06)69041-7 CrossRefPubMedGoogle Scholar
- 3.Rattazzi A (2014) The importance of early detection and early intervention for children with autism spectrum conditions. Vertex (Buenos Aires, Argentina) 25(116):290–294Google Scholar
- 6.Ecker C, Marquand A, Mourao-Miranda J, Johnston P, Daly EM, Brammer MJ et al (2010) Describing the brain in autism in five dimensions—magnetic resonance imaging-assisted diagnosis of autism spectrum disorder using a multiparameter classification approach. J Neurosci 30(32):10612–10623. doi: 10.1523/jneurosci.5413-09.2010 CrossRefPubMedGoogle Scholar
- 9.St. Pourcain B, Wang K, Glessner JT, Golding J, Steer C, Ring SM et al (2010) Association between a high-risk autism locus on 5p14 and social communication spectrum phenotypes in the general population. Am J Psychiatry 167(11):1364–1372. doi: 10.1176/appi.ajp.2010.09121789 CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Pathania M, Davenport EC, Muir J, Sheehan DF, Lopez-Domenech G, Kittler JT (2014) The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines. Transl Psychiatry 4:e423. doi: 10.1038/tp.2014.36 CrossRefPubMedCentralGoogle Scholar
- 42.Daluwatte C, Miles JH, Sun J, Yao G (2014) Association between pupillary light reflex and sensory behaviors in children with autism spectrum disorders. Res Dev Disabil 37C:209–215Google Scholar
- 49.American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders (DSM-IV-TR). American Psychiatric Association, WashingtonGoogle Scholar
- 50.The Psychological Corporation (2000) Wechsler Adult Intelligence Scale. The Psychological Corporation, LondonGoogle Scholar
- 62.Enoch MA, Rosser AA, Zhou Z, Mash DC, Yuan Q, Goldman D (2014) Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine. Genes Brain Behav 13(8):758–768. doi: 10.1111/gbb.12179 CrossRefPubMedPubMedCentralGoogle Scholar