Strategies to develop putative biomarkers to characterize the female phenotype with autism spectrum disorders

Abstract

Torres EB, Isenhower RW, Yanovich P, Rehrig G, Stigler K, Nurnberger J, José JV. Strategies to develop putative biomarkers to characterize the female phenotype with autism spectrum disorders. J Neurophysiol 110: 1646 -1662, 2013. First published July 17, 2013 doi:10.1152/jn.00059.2013.-Current observational inventories used to diagnose autism spectrum disorders (ASD) apply similar criteria to females and males alike, despite developmental differences between the sexes. Recent work investigating the chronology of diagnosis in ASD has raised the concern that females run the risk of receiving a delayed diagnosis, potentially missing a window of opportunity for early intervention. Here, we retake this issue in the context of the objective measurements of natural behaviors that involve decisionmaking processes. Within this context, we quantified movement variability in typically developing (TD) individuals and those diagnosed with ASD across different ages. We extracted the latencies of the decision movements and velocity-dependent parameters as the hand movements unfolded for two movement segments within the reach: movements intended toward the target and withdrawing movements that spontaneously, without instruction, occurred incidentally. The stochastic signatures of the movement decision latencies and the percent of time to maximum speed differed between males and females with ASD. This feature was also observed in the empirically estimated probability distributions of the maximum speed values, independent of limb size. Females with ASD showed different dispersion than males with ASD. The distinctions found for females with ASD were better appreciated compared with those of TD females. In light of these results, behavioral assessment of autistic traits in females should be performed relative to TD females to increase the chance of detection.

Stochastic Signatures of Involuntary Head Micro-movements Can Be Used to Classify Females of ABIDE into Different Subtypes of Neurodevelopmental Disorders

“…In this sense, physical parameters providing objective assessments of somatic-motor measures and other related physiological signatures may boost the early detection rate and help distinguish sub-types of females in the spectrum relative to neuro-typical controls. Building on prior work quantifying differences in patterns of voluntary control that differentiate between males and females with ASD (Torres et al, 2013b) during a decision-making task, the present results demonstrate the ability to detect sex differences by analyzing involuntary head motion extracted from resting state activity during fMRI experiments. Perhaps combining these levels of enquiry we can further refine our understanding between different female subgroups.…”

“…Inset highlights the non-Gaussian nature of the variability of this parameter of physical growth and the inflecion point attained earlier (at 224 days) in females than males (at 252 days). Later on in life such sex differences are less obvious (Torres et al, 2013b), but using the fluctuations in motion parameters (e.g., those changing in cross-sectional data spanning 3–77 years of age) can be informative of subtle differences in speed micro-movements denoting different degrees of skewness and dispersion along with different age-dependent rates of change in this stochastic signatures (data extracted from controls (CT) in 176 participants reported in Torres et al, 2016a) Yellow and black PDFs are from a deafferented participant for reference of a system without (or very poor) kinesthetic reafference manifested in the typically aging elderly.…”

“…Given the pervasive noisy and random somatic motor micro-movements signal in ASD across sex and ages (Torres et al, 2013b), severity (Torres and Denisova, 2016) and levels of motor control (voluntary, Torres et al, 2013a; automatic, Torres et al, 2016c), autonomic (Torres and Lande, 2015; Kalampratsidou and Torres, 2016; Torres et al, 2016b), the present work aimed to investigate if involuntary micro-movements of head motion recorded within the scanner had a statistically different rate of noise accumulation in ASD females in relation to TD control females. Further, this was examined in light of male-specific ASD-TD differential patterns to consider the impact of gender.…”

Uncovering the Social Deficits in the Autistic Brain. A Source-Based Morphometric Study

“…Action processing impairments and repetitive movements are commonly observed among subjects affected by autism. Even though motor impairments are not considered one of the main symptoms of ASD, recently increasing attention has been directed to motor aspects aiming to improve a diagnostic process (Torres et al, 2013). …”

Hidden Aspects of the Research-ADOS are Bound to Affect Autism Science

“…are routinely studied in the neuromotor control developmental literature using objective means that characterizes several types of motions (e.g. [6; 9; 10; 26; 27; 28; 29]), but that literature has not crossed paths with the ADOS.…”