Gabriele Tripi

Metabolomics Study of Urine in Autism Spectrum Disorders Using a Multiplatform Analytical Methodology

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with no clinical biomarker. The aims of this study were to characterize a metabolic signature of ASD and to evaluate multiplatform analytical methodologies in order to develop predictive tools for diagnosis and disease follow-up. Urine samples were analyzed using (1)H and (1)H-(13)C NMR-based approaches and LC-HRMS-based approaches (ESI+ and ESI- on HILIC and C18 chromatography columns). Data tables obtained from the six analytical modalities on a training set of 46 urine samples (22 autistic children and 24 controls) were processed by multivariate analysis (orthogonal partial least-squares discriminant analysis, OPLS-DA). The predictions from each of these OPLS-DA models were then evaluated using a prediction set of 16 samples (8 autistic children and 8 controls) and receiver operating characteristic curves. Thereafter, a data fusion block-scaling OPLS-DA model was generated from the 6 best models obtained for each modality. This fused OPLS-DA model showed an enhanced performance (R(2)Y(cum) = 0.88, Q(2)(cum) = 0.75) compared to each analytical modality model, as well as a better predictive capacity (AUC = 0.91, p-value = 0.006). Metabolites that are most significantly different between autistic and control children (p < 0.05) are indoxyl sulfate, N-α-acetyl-l-arginine, methyl guanidine, and phenylacetylglutamine. This multimodality approach has the potential to contribute to find robust biomarkers and characterize a metabolic phenotype of the ASD population.

Urinary p-cresol is elevated in young French children with autism spectrum disorder: a replication study

Abstract The aromatic compound p-cresol (4-methylphenol) has been found elevated in the urines of Italian autistic children up to 8 years of age. The present study aims at replicating these initial findings in an ethnically distinct sample and at extending them by measuring also the three components of urinary p-cresol, namely p-cresylsulfate, p-cresylglucuronate and free p-cresol. Total urinary p-cresol, p-cresylsulfate and p-cresylglucuronate were significantly elevated in 33 French autism spectrum disorder (ASD) cases compared with 33 sex- and age-matched controls (p < 0.05). This increase was limited to ASD children aged ≤8 years (p < 0.01), and not older (p = 0.17). Urinary levels of p-cresol and p-cresylsulfate were associated with stereotypic, compulsive/repetitive behaviors (p < 0.05), although not with overall autism severity. These results confirm the elevation of urinary p-cresol in a sizable set of small autistic children and spur interest into biomarker roles for p-cresol and p-cresylsulfate in autism.

AUtonomic Regulation In Autism Spectrum Disorders

LUCIA PARISI1, MARGHERITA SALERNO2, AGATA MALTESE1, GABRIELE TRIPI3,4, PALMIRA ROMANO5, ANNABELLA DI FOLCO1, TERESA DI FILIPPO1, MICHELE ROCCELLA1 1Department of Psychological, Pedagogical and Educational Sciences, University of Palermo, Italy 2Sciences for Mother and Child Health Promotion, University of Palermo, Italy 3Department PROSAMI, University of Palermo, Italy 4Childhood Psychiatric Service for Neurodevelopmental Disorders, CH Chinon, France 5Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health and Physical and Preventive Medicine; Università degli Studi della Campania-Luigi Vanvitelli, Italy

Sleep habits in children affected by autism spectrum disorders: A preliminary case-control study

FRANCESCO PRECENZANO*1, MARIA RUBERTO*2, LUCIA PARISI3, MARGHERITA SALERNO4, AGATA MALTESE3, DOMENICO VERDE1, GABRIELE TRIPI5,6, PALMIRA ROMANO1, ANNABELLA DI FOLCO3, TERESA DI FILIPPO3, GIOVANNI MESSINA7, MICHELE ROCCELLA3 1Clinic of Child and Adolescent Neuropsychiatry; Headache Center for children and adolescents, Department of Mental Health and Physical and Preventive Medicine, Second University of Naples, Italy 2Department of Medical-Surgical and Dental Specialties, Second University of Naples, Italy 3Department of Psychological, Pedagogical and Educational Sciences, University of Palermo, Italy 4Sciences for Mother and Child Health Promotion, University of Palermo, Italy 5Department PROSAMI, University of Palermo, Italy6Childhood Psychiatric Service for Neurodevelopmental Disorders, CH Chinon, France7Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy

West syndrome followed by juvenile myoclonic epilepsy: a coincidental occurrence?

BackgroundWest syndrome is an age-dependent epilepsy with onset peak in the first year of life whose aetiology may be symptomatic or cryptogenic. Long-term cognitive and neurological prognosis is usually poor and seizure outcome is also variable. Over the past two decades a few patients with favourable cognitive outcome and with total recovery from seizures were identified among the cryptogenic group suggesting an idiopathic aetiology. Recent research has described two children with idiopathic WS who later developed a childhood absence epilepsy.Case presentationWe reviewed the medical records of patients with West syndrome admitted to the our Child Neuropsychiatry Unit in the last 15 years in order to know the clinical evolution of infantile spasms.We report a child with West syndrome with onset at 8 months of age followed by some clusters of bilateral, arrhythmic myoclonic jerks of the upper limbs, mainly on awakening, synchronous with the generalized discharges of 4 Hz spike-wave occurring at 12 years of age and by co-occurrence of a later generalized tonic-clonic seizure at 14 years and four months, both sensitive to Levetiracetam suggesting a juvenile myoclonic epilepsy.ConclusionsThis unusual evolution, never previously reported, suggests that both electroclinical features mentioned above may share some pathophysiological processes genetically determined which produce a susceptibility to seizure and emphasizes that the transition between different age-related epileptic phenotypes may involve also the West syndrome.

Orexin system: Network multi-tasking

RAFFAELE SPERANDEO1,§, MAURO N. MALDONATO2,§, ANTONIETTA MESSINA2,9, PASQUALE COZZOLINO3, MARCELLINO MONDA2, FRANCESCO CERRONI4, PALMIRA ROMANO4, MARGHERITA SALERNO6, AGATA MALTESE6, MICHELE ROCCELLA6, LUCIA PARISI6, GABRIELE TRIPI7, FIORENZO MOSCATELLI8, FRANCESCO SESSA8, MONICA SALERNO8, GIUSEPPE CIBELLI8, GIOVANNI MESSINA8, VINCENZO MONDA9, SERGIO CHIEFFI9, INES VILLANO9, EMANUELE MONDA9, MARIA RUBERTO10, GABRIELLA MARSALA11, ROSA MAROTTA R5, ANNA VALENZANO8* 1Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetic and Sport Medicine, Università degli Studi della Campania, Naples, Italy 2Department of Human science, Università della Basilicata, Italy 3SiPGI Postgraduate School of Integrated Gestalt Psychotherapy, D.M. 12.10.2007 Naples, Italy 4Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Italy 5Department of Health Sciences, University “Magna Graecia”, Catanzaro, Italy 6Child Neuropsychiatry, Department of Psychology and Pedagogical Sciences, University of Palermo, Palermo, Italy 7Child Neuropsychiatry, Department of Psychology and Pedagogical Sciences, University of Palermo, Palermo, Italy 8Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy 9Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy 10Centro CRD, Santa Maria del Pozzo, Somma Vesuviana, Naples 11Struttura Complessa di Farmacia, Azienda Ospedaliero-Universitaria, Foggia, Italy

Paternal shift-working and sleep disorders in children affected by primary nocturnal enuresis

LUCIA PARISI1, MARGHERITA SALERNO2, AGATA MALTESE1, GABRIELE TRIPI3,4, PALMIRA ROMANO5, ANNABELLA DI FOLCO1, TERESA DI FILIPPO1, MICHELE ROCCELLA1 1Department of Psychological, Pedagogical and Educational Sciences, University of Palermo, Italy 2Sciences for Mother and Child Health Promotion, University of Palermo, Italy 3Department PROSAMI, University of Palermo, Italy 4Childhood Psychiatric Service for Neurodevelopmental Disorders, CH Chinon, France 5Clinic of Child and Adolescent Neuropsychiatry; Department of Mental Health and Physical and Preventive Medicine, Università degli Studi della Campania-Luigi Vanvitelli, Italy

EMotional Intelligence And Obstructive Sleep Apnea Syndrome In Children: Preliminary Case-Control Study

LUCIA PARISI1, MARGHERITA SALERNO2, AGATA MALTESE1, GABRIELE TRIPI3,4, PALMIRA ROMANO5, ANNABELLA DI FOLCO1, TERESA DI FILIPPO1, GIOVANNI MESSINA6, MICHELE ROCCELLA1 1Department of Psychological, Pedagogical and Educational Sciences, University of Palermo, Italy 2Sciences for Mother and Child Health Promotion, University of Palermo, Italy 3Department PROSAMI, University of Palermo, Italy 4Childhood Psychiatric Service for Neurodevelopmental Disorders, CH Chinon, France 5Clinic of Child and Adolescent Neuropsychiatry; Department of Mental Health and Physical and Preventive Medicine, Università degli Studi della Campania-Luigi Vanvitelli, Italy 6Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy

Minor Neurological Dysfunctions (MNDs) in Autistic Children without Intellectual Disability

Background: Children with autism spectrum disorder (ASD) require neurological evaluation to detect sensory-motor impairment. This will improve understanding of brain function in children with ASD, in terms of minor neurological dysfunctions (MNDs). Methods: We compared 32 ASD children without intellectual disability (IQ ≥ 70) with 32 healthy controls. A standardized and age-specific neurological examination according to Touwen was used to detect the presence of MNDs. Particular attention was paid to severity and type of MNDs. Results: Children with ASD had significantly higher rates of MNDs compared to controls (96.9% versus 15.6%): 81.3% had simple MNDs (p < 0.0001) and 15.6% had complex MNDs (p = 0.053). The prevalence of MNDs in the ASD group was significantly higher (p < 0.0001) than controls. With respect to specific types of MNDs, children with ASD showed a wide range of fine manipulative disability, sensory deficits and choreiform dyskinesia. We also found an excess of associated movements and anomalies in coordination and balance. Conclusions: Results replicate previous findings which found delays in sensory-motor behavior in ASD pointing towards a role for prenatal, natal and neonatal risk factors in the neurodevelopmental theory of autism.

Sympathetic, metabolic adaptations, and oxidative stress in autism spectrum disorders: How far from physiology?

Autism spectrum disorders (ASD) is a complex and multifaceted neurobehavioral syndrome with no specific cause still identified, despite the worldwide increasing (prevalence for 1,000 children from 6.7 to 14.6, between 2000 and 2012). Many biological and instrumental markers have been suggested as potential predictive factors for the precocious diagnosis during infancy and/or pediatric age. Many studies reported structural and functional abnormalities in the autonomic system in subjects with ASD. Sleep problems in ASD are a prominent feature, having an impact on the social interaction of the patient. Considering the role of orexins (A and B) in wake-sleep circadian rhythm, we could speculate that ASD subjects may present a dysregulation in orexinergic neurotransmission. Conversely, oxidative stress is implicated in the pathophysiology of many neurological disorders. Nonetheless, little is known about the linkage between oxidative stress and the occurrence or the progress of autism and autonomic functioning; some markers, such as heart rate (HR), heart rate variability (HRV), body temperature, and galvanic skin response (GSR), may be altered in the patient with this so complex disorder. In the present paper, we analyzed an autism case report, focusing on the rule of the sympathetic activity with the aim to suggest that it may be considered an important tool in ASD evaluation. The results of this case confirm our hypothesis even if further studies needed.