Cry, Baby, Cry: Expression of Distress As a Biomarker and Modulator in Autism Spectrum Disorder

Abstract Background: Early diagnosis of autism spectrum disorder is critical, because early intensive treatment greatly improves its prognosis. Methods: We review studies that examined vocalizations of infants with autism spectrum disorder and mouse models of autism spectrum disorder as a potential means to identify autism spectrum disorder before the symptomatic elements of autism spectrum disorder emerge. We further discuss clinical implications and future research priorities in the field. Results: Atypical early vocal calls (i.e., cry) may represent an early biomarker for autism spectrum disorder (or at least for a subgroup of children with autism spectrum disorder), and thus can assist with early detection. Moreover, cry is likely more than an early biomarker of autism spectrum disorder; it is also an early causative factor in the development of the disorder. Specifically, atypical crying, as recently suggested, might induce a “self-generated environmental factor” that in turn, influences the prognosis of the disorder. Because atypical crying in autism spectrum disorder is difficult to understand, it may have a negative impact on the quality of care by the caregiver (see graphical abstract). Conclusions: Evidence supports the hypothesis that atypical vocalization is an early, functionally integral component of autism spectrum disorder.

[1]  Gianluca Esposito,et al.  Comparative Analysis of Crying in Children with Autism, Developmental Delays, and Typical Development , 2009 .

[2]  A. Rozga,et al.  A prospective study of the emergence of early behavioral signs of autism. , 2010, Journal of the American Academy of Child and Adolescent Psychiatry.

[3]  T. Kikusui,et al.  Maternal approaches to pup ultrasonic vocalizations produced by a nanocrystalline silicon thermo-acoustic emitter , 2007, Brain Research.

[4]  Anne-Marie Le Sourd,et al.  Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2 , 2012, Nature.

[5]  M. Wöhr,et al.  Effect of altricial pup ultrasonic vocalization on maternal behavior , 2010 .

[6]  P. Venuti,et al.  Understanding early communication signals in autism: a study of the perception of infants' cry. , 2010, Journal of intellectual disability research : JIDR.

[7]  Jennifer C. Sarrett,et al.  Commentary: Attention to Eyes Is Present but in Decline in 2–6-Month-Old Infants Later Diagnosed with Autism , 2015, Front. Public Health.

[8]  Nurcan Bektaş Türkmen,et al.  PT644. The Possible Action Mechanisms of Central Analgesic Effect of Protocatechuic Acid , 2016, International Journal of Neuropsychopharmacology.

[9]  Y. Jan,et al.  Altered ultrasonic vocalizations in a tuberous sclerosis mouse model of autism , 2010, Proceedings of the National Academy of Sciences.

[10]  Mark H. Johnson,et al.  Autism and the Social Brain: The First-Year Puzzle , 2016, Biological Psychiatry.

[11]  Kenny Q. Ye,et al.  Structure and function of neonatal social communication in a genetic mouse model of autism , 2015, Molecular Psychiatry.

[12]  R. Landa,et al.  Head lag in infants at risk for autism: a preliminary study. , 2012, The American journal of occupational therapy : official publication of the American Occupational Therapy Association.

[13]  M. Bornstein,et al.  Categorizing the cries of infants with ASD versus typically developing infants: A study of adult accuracy and reaction time. , 2016, Research in autism spectrum disorders.

[14]  M. Owen,et al.  Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: Implications for 22q11 deletion syndrome , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[15]  K. Nakayama,et al.  TBX1 Mutation Identified by Exome Sequencing in a Japanese Family with 22q11.2 Deletion Syndrome-Like Craniofacial Features and Hypocalcemia , 2014, PloS one.

[16]  Maria Luisa Scattoni,et al.  Ultrasonic vocalizations: A tool for behavioural phenotyping of mouse models of neurodevelopmental disorders , 2009, Neuroscience & Biobehavioral Reviews.

[17]  D. Amaral,et al.  Neuroanatomy of autism , 2008, Trends in Neurosciences.

[18]  Gianluca Esposito,et al.  Developmental changes in the fundamental frequency (f0) of infants’ cries: a study of children with Autism Spectrum Disorder , 2010 .

[19]  T. Kikusui,et al.  A Self-Generated Environmental Factor as a Potential Contributor to Atypical Early Social Communication in Autism , 2017, Neuropsychopharmacology.

[20]  Tony Charman,et al.  Parent-mediated intervention versus no intervention for infants at high risk of autism: a parallel, single-blind, randomised trial , 2015, The lancet. Psychiatry.

[21]  S. Rogers,et al.  Intervening in infancy: implications for autism spectrum disorders. , 2010, Journal of child psychology and psychiatry, and allied disciplines.

[22]  Aaron M. Johnson,et al.  Characterization of ultrasonic vocalizations of Fragile X mice , 2016, Behavioural Brain Research.

[23]  S. Rogers,et al.  Autism Treatment in the First Year of Life: A Pilot Study of Infant Start, a Parent-Implemented Intervention for Symptomatic Infants , 2014, Journal of Autism and Developmental Disorders.

[24]  D K Oller,et al.  Vocal Atypicalities of Preverbal Autistic Children , 2000, Journal of autism and developmental disorders.

[25]  Warren Jones,et al.  Mechanisms of Diminished Attention to Eyes in Autism. , 2017, The American journal of psychiatry.

[26]  A. Estes,et al.  Early Identification of Autism Spectrum Disorder: Recommendations for Practice and Research , 2015, Pediatrics.

[27]  Gianluca Esposito,et al.  How is crying perceived in children with Autistic Spectrum Disorder , 2008 .

[28]  K. Blomgren,et al.  Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species , 2013, Progress in Neurobiology.

[29]  Gianluca Esposito,et al.  Analysis of unsupported gait in toddlers with autism , 2011, Brain and Development.

[30]  M. Scattoni,et al.  Characterization of Neonatal Vocal and Motor Repertoire of Reelin Mutant Mice , 2013, PloS one.

[31]  R Bakeman,et al.  Kung infancy: the social context of object exploration. , 1990, Child development.

[32]  Gianluca Esposito,et al.  An exploration of symmetry in early autism spectrum disorders: Analysis of lying , 2009, Brain and Development.

[33]  G. Ehret,et al.  Low-frequency sound communication by mouse pups (Mus musculus): wriggling calls release maternal behaviour , 1986, Animal Behaviour.

[34]  R. Kucherlapati,et al.  Tbx1: identification of a 22q11.2 gene as a risk factor for autism spectrum disorder in a mouse model. , 2011, Human molecular genetics.

[35]  C. Lord,et al.  Parent-Implemented Social Intervention for Toddlers With Autism: An RCT , 2014, Pediatrics.

[36]  C. McDougle,et al.  Communication Deficits and the Motor System: Exploring Patterns of Associations in Autism Spectrum Disorder (ASD) , 2016, Journal of Autism and Developmental Disorders.

[37]  S. White,et al.  Mice with Dab1 or Vldlr insufficiency exhibit abnormal neonatal vocalization patterns , 2016, Scientific Reports.

[38]  G. Arbanas Diagnostic and Statistical Manual of Mental Disorders (DSM-5) , 2015 .

[39]  M. Bornstein,et al.  Differential brain responses to cries of infants with autistic disorder and typical development: an fMRI study. , 2012, Research in developmental disabilities.

[40]  T. Charman,et al.  Temperament in the First 2 Years of Life in Infants at High-Risk for Autism Spectrum Disorders , 2012, Journal of Autism and Developmental Disorders.

[41]  L. Kanner Autistic disturbances of affective contact. , 1968, Acta paedopsychiatrica.

[42]  A. Moles,et al.  Pups Call, Mothers Rush: Does Maternal Responsiveness Affect the Amount of Ultrasonic Vocalizations in Mouse Pups? , 2006 .

[43]  D. Zeifman Predicting adult responses to infant distress: Adult characteristics associated with perceptions, emotional reactions, and timing of intervention , 2003 .

[44]  M. Scattoni Modeling social communication deficits in mouse models of autism , 2012 .

[45]  Gianluca Esposito,et al.  Judgment of infant cry: The roles of acoustic characteristics and sociodemographic characteristics. , 2015, The Japanese psychological research.

[46]  W. Schleidt,et al.  Ultraschall-Laute bei jungen Mäusen , 2004, Naturwissenschaften.

[47]  J. Foster,et al.  Temporal and spectral differences in the ultrasonic vocalizations of fragile X knock out mice during postnatal development , 2014, Behavioural Brain Research.

[48]  Charles A Nelson,et al.  A developmental neuroscience approach to the search for biomarkers in autism spectrum disorder. , 2016, Current opinion in neurology.

[49]  G. Gustafson,et al.  On the importance of fundamental frequency and other acoustic features in cry perception and infant development. , 1989, Child development.

[50]  Gianluca Esposito,et al.  Componential deconstruction of infant distress vocalizations via tree-based models: a study of cry in autism spectrum disorder and typical development. , 2013, Research in developmental disabilities.

[51]  Daniel H. Geschwind,et al.  VoICE: A semi-automated pipeline for standardizing vocal analysis across models , 2015, Scientific Reports.

[52]  Wim E Crusio,et al.  Knockout mice: simple solutions to the problems of genetic background and flanking genes , 2002, Trends in Neurosciences.

[53]  S. Jeste,et al.  The emergence of autism spectrum disorder: insights gained from studies of brain and behaviour in high-risk infants , 2017, Current opinion in psychiatry.

[54]  B. O'neill,et al.  Folic Acid Deficiency in Lactobacillus Casei , 1970 .

[55]  Erich Seifritz,et al.  Differential sex-independent amygdala response to infant crying and laughing in parents versus nonparents , 2003, Biological Psychiatry.

[56]  N. Hiroi,et al.  Genetic Mechanisms Emerging from Mouse Models of CNV-Associated Neuropsychiatric Disorders , 2016 .

[57]  P. Teitelbaum,et al.  Movement analysis in infancy may be useful for early diagnosis of autism. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[58]  N. Hiroi,et al.  Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders , 2013, Molecular Psychiatry.

[59]  Takefumi Kikusui,et al.  Pup odor and ultrasonic vocalizations synergistically stimulate maternal attention in mice. , 2013, Behavioral neuroscience.

[60]  Tony Charman,et al.  Motor development in children at risk of autism: A follow-up study of infant siblings , 2014, Autism : the international journal of research and practice.

[61]  Scott P. Johnson,et al.  The broader autism phenotype in infancy: when does it emerge? , 2014, Journal of the American Academy of Child and Adolescent Psychiatry.

[62]  P Venuti,et al.  ASSESSMENT OF DISTRESS IN YOUNG CHILDREN: A COMPARISON OF AUTISTIC DISORDER, DEVELOPMENTAL DELAY, AND TYPICAL DEVELOPMENT. , 2011, Research in autism spectrum disorders.

[63]  E. Zackai,et al.  Mutation analysis of TBX1 in non-deleted patients with features of DGS/VCFS or isolated cardiovascular defects , 2001, Journal of medical genetics.

[64]  Jacqueline N. Crawley,et al.  Unusual Repertoire of Vocalizations in the BTBR T+tf/J Mouse Model of Autism , 2008, PloS one.

[65]  Daniel S. Messinger,et al.  Brief Report: Atypical Expression of Distress During the Separation Phase of the Strange Situation Procedure in Infant Siblings at High Risk for ASD , 2014, Journal of autism and developmental disorders.

[66]  M. Bornstein,et al.  Three physiological responses in fathers and non-fathers' to vocalizations of typically developing infants and infants with Autism Spectrum Disorder. , 2015, Research in developmental disabilities.

[67]  B. Lester,et al.  Atypical Cry Acoustics in 6‐Month‐Old Infants at Risk for Autism Spectrum Disorder , 2012, Autism research : official journal of the International Society for Autism Research.

[68]  Elodie Ey,et al.  The Autism ProSAP1/Shank2 mouse model displays quantitative and structural abnormalities in ultrasonic vocalisations , 2013, Behavioural Brain Research.

[69]  R. Dolmetsch,et al.  16p11.2 Deletion Syndrome Mice Display Sensory and Ultrasonic Vocalization Deficits During Social Interactions , 2015, Autism research : official journal of the International Society for Autism Research.