M. Elsabbagh, G. Divan, Y. J. Koh, Y. S. Kim, S. Kauchali et al., Global prevalence of autism and other pervasive developmental disorders, Autism Res, vol.5, pp.160-79, 2012.

T. Bourgeron, From the genetic architecture to synaptic plasticity in autism spectrum disorder, Nat Rev Neurosci, vol.16, pp.551-63, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01576592

C. Pagan, R. Delorme, J. Callebert, H. Goubran-botros, F. Amsellem et al., The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders, Transl Psychiatry, vol.4, p.479, 2014.

X. Ming, M. Brimacombe, J. H. Malek, J. N. Wagner, and G. C. , Autism spectrum disorders and identified toxic land fills: co-occurrence across States, Environ Health Insights, vol.2, pp.55-64, 2008.

M. C. Souders, T. B. Mason, O. Valladares, M. Bucan, S. E. Levy et al., Sleep behaviors and sleep quality in children with autism spectrum disorders, Sleep, vol.32, pp.1566-78, 2009.

J. A. Hollway, M. G. Aman, and E. Butter, Correlates and risk markers for sleep disturbance in participants of the Autism Treatment Network, J Autism Dev Disord, vol.43, pp.2830-2873, 2013.

P. Chaste, N. Clement, O. Mercati, J. L. Guillaume, R. Delorme et al., Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population, PLoS ONE, vol.5, 2010.

D. A. Rossignol and R. E. Frye, Melatonin in autism spectrum disorders: a systematic review and meta-analysis, Dev Med Child Neurol, vol.53, pp.783-92, 2011.

A. Masters, S. R. Pandi-perumal, A. Seixas, J. L. Girardin, and S. I. Mcfarlane, Melatonin, the hormone of darkness: from sleep promotion to ebola treatment, Brain Disord Ther, vol.4, p.1000151, 2014.

C. Liu, D. R. Weaver, J. X. Shearman, L. P. Pieschl, R. L. Gribkoff et al., Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock, Neuron, vol.19, pp.91-102, 1997.

X. Jin, C. Gall, R. L. Pieschl, V. K. Gribkoff, J. H. Stehle et al., Targeted disruption of the mouse Mel(1b) melatonin receptor, Mol Cell Biol, vol.23, pp.1054-60, 2003.

Z. M. Weil, A. K. Hotchkiss, M. L. Gatien, S. Pieke-dahl, and R. J. Nelson, Melatonin receptor (MT1) knockout mice display depression-like behaviors and deficits in sensorimotor gating, Brain Res Bull, vol.68, pp.425-434, 2006.

T. Bourgeron, The possible interplay of synaptic and clock genes in autism spectrum disorders, Cold Spring Harb Symp Quant Biol, vol.72, pp.645-54, 2007.

K. M. Evely, R. L. Hudson, M. L. Dubocovich, and S. Haj-dahmane, Melatonin receptor activation increases glutamatergic synaptic transmission in the rat medial lateral habenula, Synapse, vol.70, pp.181-187, 2016.

M. Jasinska and E. Pyza, Circadian plasticity of mammalian inhibitory interneurons, Neural Plast, p.6373412, 2017.

S. Tordjman, I. Najjar, E. Bellissant, G. M. Anderson, M. Barburoth et al., Advances in the research of melatonin in autism spectrum disorders: literature review and new perspectives, Int J Mol Sci, vol.14, pp.20508-20550, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00933211

M. C. Lopez-wagner, C. D. Hoffman, D. P. Sweeney, D. Hodge, and J. E. Gilliam, Sleep problems of parents of typically developing children and parents of children with autism, J Genet Psychol, vol.169, pp.245-59, 2008.

A. J. Schwichtenberg, G. S. Young, T. Hutman, A. M. Iosif, M. Sigman et al., Behavior and sleep problems in children with a family history of autism, Autism Res, vol.6, pp.169-76, 2013.

B. Malow, K. W. Adkins, S. G. Mcgrew, L. Wang, S. E. Goldman et al., Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes, J Autism Dev Disord, vol.42, p.1738, 2012.

B. M. Cuomo, S. Vaz, E. Lee, C. Thompson, J. M. Rogerson et al., Effectiveness of sleep-based interventions for children with autism spectrum disorder: a meta-synthesis, Pharmacotherapy, vol.37, pp.555-78, 2017.

P. Gringras, Sleep disorders in cerebral palsy, Dev Med Child Neurol, vol.59, pp.349-50, 2017.

J. Melke, G. Botros, H. Chaste, P. Betancur, C. Nygren et al., Abnormal melatonin synthesis in autism spectrum disorders, Mol Psychiatry, vol.13, pp.90-98, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00166901

P. Chaste, N. Clement, H. G. Botros, J. L. Guillaume, M. Konyukh et al., Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders, J Pineal Res, vol.51, pp.394-403, 2011.

C. Pagan, H. Goubran-botros, R. Delorme, M. Benabou, N. Lemiere et al., Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders, vol.7, p.2096, 2017.
URL : https://hal.archives-ouvertes.fr/pasteur-01577974

B. Sun, D. Wang, Y. Tang, L. Fan, X. Lin et al., The pineal volume: a threedimensional volumetric study in healthy young adults using 3.0 T MR data

, Int J Dev Neurosci, vol.27, pp.655-60, 2009.

I. Nolte, A. T. Lutkhoff, B. A. Stuck, B. Lemmer, M. Schredl et al., Pineal volume and circadian melatonin profile in healthy volunteers: an interdisciplinary approach, J Magn Reson Imaging, vol.30, pp.499-505, 2009.

J. M. Bumb, C. Schilling, F. Enning, L. Haddad, F. Paul et al., Pineal gland volume in primary insomnia and healthy controls: a magnetic resonance imaging study, J Sleep Res, vol.23, pp.274-80, 2014.
DOI : 10.1111/jsr.12125

URL : https://onlinelibrary.wiley.com/doi/pdf/10.1111/jsr.12125

A. E. Hanish, J. A. Butman, F. Thomas, J. Yao, and J. C. Han, Pineal hypoplasia, reduced melatonin and sleep disturbance in patients with PAX6 haploinsufficiency, J Sleep Res, vol.25, pp.16-22, 2016.
DOI : 10.1111/jsr.12345

URL : https://onlinelibrary.wiley.com/doi/pdf/10.1111/jsr.12345

D. Li, H. O. Karnath, and X. Xu, Candidate biomarkers in children with autism spectrum disorder: a review of MRI studies, vol.33, pp.219-256, 2017.

R. L. Horner and J. H. Peever, Brain circuitry controlling sleep and wakefulness, Continuum, vol.23, pp.955-72, 2017.
DOI : 10.1212/con.0000000000000495

L. S. Liebrich, M. Schredl, P. Findeisen, C. Groden, J. M. Bumb et al., Morphology and function: MR pineal volume and melatonin level in human saliva are correlated, J Magn Reson Imaging, vol.40, pp.966-71, 2014.
DOI : 10.1002/jmri.24449

R. Toro, J. B. Poline, G. Huguet, E. Loth, V. Frouin et al., Genomic architecture of human neuroanatomical diversity, Mol Psychiatry, vol.20, pp.1011-1017, 2015.
DOI : 10.1101/001198

URL : https://hal.archives-ouvertes.fr/pasteur-01967180

M. Benabou, T. Rolland, C. S. Leblond, G. A. Millot, G. Huguet et al., Heritability of the melatonin synthesis variability in autism spectrum disorders. Sci Rep, vol.7, p.17746, 2017.

C. Lord, M. Rutter, L. Couteur, and A. , Autism diagnostic interview-revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders, J Autism Dev Disord, vol.24, pp.659-85, 1994.

C. Lord, S. Risi, L. Lambrecht, E. H. Cook, B. L. Leventhal et al., The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism, J Autism Dev Disord, vol.30, pp.205-228, 2000.

A. Maruani, G. Huguet, A. Beggiato, M. Elmaleh, R. Toro et al., 2-25 micro-rearrangements in autism spectrum disorders: relation to brain structures, Am J Med Genet A, vol.167, pp.3019-3049, 2015.
DOI : 10.1002/ajmg.a.37345

URL : https://hal.archives-ouvertes.fr/pasteur-01579742

A. Bischoff-grethe, I. B. Ozyurt, E. Busa, B. T. Quinn, C. Fennema-notestine et al., A technique for the deidentification of structural brain MR images, Hum Brain Mapp, vol.28, pp.892-903, 2007.

Y. Zhang, M. Brady, and S. Smith, Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm, IEEE Trans Med Imaging, vol.20, pp.45-57, 2001.

S. M. Smith, M. Jenkinson, M. W. Woolrich, C. F. Beckmann, T. E. Behrens et al., Advances in functional and structural MR image analysis and implementation as FSL, Neuroimage, pp.208-227, 2004.
DOI : 10.1016/j.neuroimage.2004.07.051

URL : http://www.fmrib.ox.ac.uk/analysis/techrep/tr04ss2/tr04ss2.pdf

R. Toro, M. Chupin, L. Garnero, G. Leonard, M. Perron et al., Brain volumes and Val66Met polymorphism of the BDNF gene: local or global effects?, Brain Struct Funct, vol.213, pp.501-510, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00805413

S. Sarrazin, B. Etain, F. E. Vederine, M. A. Albis, N. Hamdani et al., MRI exploration of pineal volume in bipolar disorder, J Affect Disord, vol.135, pp.377-386, 2011.

Y. Pu, S. Mahankali, J. Hou, J. Li, J. L. Lancaster et al., High prevalence of pineal cysts in healthy adults demonstrated by high-resolution, noncontrast brain MR imaging, AJNR Am J Neuroradiol, vol.28, pp.1706-1715, 2007.

A. F. Marquand, I. Rezek, J. Buitelaar, and C. F. Beckmann, Understanding heterogeneity in clinical cohorts using normative models: beyond case-control studies, Biol Psychiatry, vol.80, pp.552-61, 2016.
DOI : 10.1016/j.biopsych.2015.12.023

URL : https://doi.org/10.1016/j.biopsych.2015.12.023

W. S. Cleveland, Robust locally weighted regression and smoothing scatterplots, J Am Statis Assoc, vol.74, pp.829-865, 1979.
DOI : 10.1080/01621459.1979.10481038

S. Tordjman, G. M. Anderson, N. Pichard, H. Charbuy, and Y. Touitou, Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder, Biol Psychiatry, vol.57, pp.134-142, 2005.

S. Gabriele, R. Sacco, and A. M. Persico, Blood serotonin levels in autism spectrum disorder: a systematic review and meta-analysis, Eur Neuropsychopharmacol, vol.24, pp.919-948, 2014.
DOI : 10.1016/j.euroneuro.2014.02.004

W. Braam, F. Ehrhart, A. Maas, M. G. Smits, and L. Curfs, Low maternal melatonin level increases autism spectrum disorder risk in children, Res Dev Disabil, vol.82, pp.79-89, 2018.
DOI : 10.1016/j.ridd.2018.02.017

S. Y. Shin, E. B. Fauman, A. K. Petersen, J. Krumsiek, R. Santos et al., An atlas of genetic influences on human blood metabolites, Nat Genet, vol.46, pp.543-50, 2014.

G. Bersani, A. Garavini, A. Iannitelli, A. Quartini, M. Nordio et al., Reduced pineal volume in male patients with schizophrenia: no relationship to clinical features of the illness, Neurosci Lett, vol.329, pp.246-254, 2002.

E. Findikli, M. F. Inci, M. Gokce, H. A. Findikli, H. Altun et al., Pineal gland volume in schizophrenia and mood disorders, Psychiatr Danub, vol.27, pp.153-161, 2015.

L. Billeci, S. Calderoni, E. Conti, C. Gesi, C. Carmassi et al., The broad autism (endo)phenotype: neurostructural and neurofunctional correlates in parents of individuals with autism spectrum disorders, Front Neurosci, vol.10, p.346, 2016.

M. M. Pruitt, M. Rhoden, and N. V. Ekas, Relationship between the broad autism phenotype, social relationships and mental health for mothers of children with autism spectrum disorder, Autism, vol.22, pp.171-80, 2018.

M. J. Gandal, J. R. Haney, N. N. Parikshak, V. Leppa, G. Ramaswami et al., Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap, Science, vol.359, pp.693-700, 2018.
DOI : 10.1126/science.aad6469

URL : http://science.sciencemag.org/content/sci/359/6376/693.full.pdf

V. Warrier, R. Toro, B. Chakrabarti, A. D. Borglum, and J. Grove, Genome-wide analyses of self-reported empathy: correlations with autism, schizophrenia, and anorexia nervosa, Transl Psychiatry, vol.8, p.35, 2018.
DOI : 10.1101/050682

URL : https://hal.archives-ouvertes.fr/pasteur-01967229

A. Levin and A. Scher, Sleep problems in young children with autism spectrum disorders: a study of parenting stress, mothers' sleep-related cognitions, and bedtime behaviors, CNS Neurosci Ther, vol.22, pp.921-928, 2016.

C. R. Johnson, T. Smith, A. Demand, L. Lecavalier, V. Evans et al., Exploring sleep quality of young children with autism spectrum disorder and disruptive behaviors, Sleep Med, vol.44, pp.61-67, 2018.

X. Liu, J. A. Hubbard, R. A. Fabes, and J. B. Adam, Sleep disturbances and correlates of children with autism spectrum disorders, Child Psychiatry Hum Dev, vol.37, pp.179-91, 2006.
DOI : 10.1007/s10578-006-0028-3

T. Matsuoka, A. Imai, H. Fujimoto, Y. Kato, K. Shibata et al., Reduced pineal volume in alzheimer disease: a retrospective cross-sectional MR imaging study, Radiology, vol.286, pp.239-287, 2018.
DOI : 10.1148/radiol.2017170188

V. Simonneaux and C. Ribelayga, Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters, Pharmacol Rev, vol.55, pp.325-95, 2003.

C. Graham, M. R. Cook, R. Kavet, A. Sastre, D. Smith et al., Individual variations in serum melatonin levels through time: implications for epidemiologic studies, J Pineal Res, vol.24, pp.230-238, 1998.

I. Nolte, M. A. Brockmann, L. Gerigk, C. Groden, and J. Scharf, TrueFISP imaging of the pineal gland: more cysts and more abnormalities, Clin Neurol Neurosurg, vol.112, pp.204-212, 2010.
DOI : 10.1016/j.clineuro.2009.11.010

L. G. Sigurdardottir, S. C. Markt, S. Sigurdsson, T. Aspelund, K. Fall et al., Pineal gland volume assessed by MRI and its correlation with 6-sulfatoxymelatonin levels among older men, J Biol Rhythms, vol.31, pp.461-470, 2016.
DOI : 10.1177/0748730416656948

URL : http://europepmc.org/articles/pmc5393913?pdf=render

, Conflict of Interest Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest

©. Copyright, . Maruani, . Dumas, . Beggiato, . Traut et al., This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, 2019.