Marina Gandione

Urinary p-cresol is elevated in small children with severe autism spectrum disorder

Several studies have described in autistic patients an overgrowth of unusual gut bacterial strains, able to push the fermentation of tyrosine up to the formation of p-cresol. We compared levels of urinary p-cresol, measured by high-performance liquid chromatography–ultraviolet, in 59 matched case-control pairs. Urinary p-cresol was significantly elevated in autistic children smaller than 8 years of age (p < 0.01), typically females (p < 0.05), and more severely affected regardless of sex (p < 0.05). Urinary cotinine measurements excluded smoking-related hydrocarbon contaminations as contributors to these differences. Hence, elevated urinary p-cresol may serve as a biomarker of autism liability in small children, especially females and more severely affected males.

Clinical, Psychological, and Personality Correlates of Asceticism in Anorexia Nervosa: From Saint Anorexia to Pathologic Perfectionism

This study investigated the personality and clinical correlates of asceticism in 154 anorectic patients. Multiple linear regression models showed that asceticism was related to angry temperament, high control over anger, perfectionism, maturity fears, and number of vomiting episodes per week. These results suggest that the self-discipline and hypercontrol of anorectic patients are related to a temperament prone to angry feelings in subjects with a fear of becoming adult and with a trait of pathologic perfectionism.

Clinical, Psychological and Personality Features Related to Age of Onset of Anorexia Nervosa

Background: To investigate the relationship between age of onset and clinical and personality features of patients with anorexia nervosa (AN). Sampling andMethod: We assessed 250 outpatients with AN with the Temperament and Character Inventory, the Eating Disorder Inventory 2, the Beck Depression Inventory and the Body Shape Questionnaire. The patients were subdivided into 3 groups: early (n = 73), intermediate (n = 96) and late onset (n = 81), based on age of onset of symptoms. Results: The early-onset group shows higher body dissatisfaction, maturity fear, impulsivity and asceticism than the other 2 groups. This group shows a greater character fragility, as described in particular by a lower self-directedness, than the other 2 groups. Conclusions: Even several years after the onset of the disorder, early-onset subjects affected by AN seem characterized by a more disturbed personality, with a higher body dissatisfaction than late-onset subjects affected by AN and a pursuit of thinness based on an ascetic drive.

Large cryptic genomic rearrangements with apparently normal karyotypes detected by array-CGH

BackgroundConventional karyotyping (550 bands resolution) is able to identify chromosomal aberrations >5-10 Mb, which represent a known cause of intellectual disability/developmental delay (ID/DD) and/or multiple congenital anomalies (MCA). Array-Comparative Genomic Hybridization (array-CGH) has increased the diagnostic yield of 15-20%.ResultsIn a cohort of 700 ID/DD cases with or without MCA, including 15 prenatal diagnoses, we identified a subgroup of seven patients with a normal karyotype and a large complex rearrangement detected by array-CGH (at least 6, and up to 18 Mb). FISH analysis could be performed on six cases and showed that rearrangements were translocation derivatives, indistinguishable from a normal karyotype as they involved a similar band pattern and size. Five were inherited from a parent with a balanced translocation, whereas two were apparently de novo. Genes spanning the rearrangements could be associated with some phenotypic features in three cases (case 3: DOCK8; case 4: GATA3, AKR1C4; case 6: AS/PWS deletion, CHRNA7), and in two, likely disease genes were present (case 5: NR2F2, TP63, IGF1R; case 7: CDON). Three of our cases were prenatal diagnoses with an apparently normal karyotype.ConclusionsLarge complex rearrangements of up to 18 Mb, involving chromosomal regions with similar size and band appearance may be overlooked by conventional karyotyping. Array-CGH allows a precise chromosomal diagnosis and recurrence risk definition, further confirming this analysis as a first tier approach to clarify molecular bases of ID/DD and/or MCA. In prenatal tests, array-CGH is confirmed as an important tool to avoid false negative results due to karyotype intrinsic limit of detection.

Parental Attitudes, Attachment Styles, Social Networks, and Psychological Processes in Autism Spectrum Disorders: A Cross-Cultural Perspective

ABSTRACT In this study the authors used a cross-cultural approach to examine parental attitudes, attachment styles, social networks, and some of the psychological processes involved in Autism Spectrum Disorders (ASD). Fifty-two children (aged 4–11 years) took part in the study: 30 Italians (15 with ASD and 15 controls) and 22 Cubans (11 with ASD and 11 controls). Findings indicated significant differences between the two cultural groups in terms of the structure of the childrens social network and parental attitudes toward their children. However, the mother–child attachment relationship and cognitive and emotional functioning of the study participants were independent of culture.

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

Array‐comparative genomic hybridization (array‐CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID).

A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity

Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array‐CGH analysis, we identified a novel familial 3q29 deletion (1.36 Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3‐year‐old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity.

Anticonvulsants for Psychiatric Disorders in Children and Adolescents: A Systematic Review of Their Efficacy

Aim: Anticonvulsant medications are frequently used in clinical practice to treat psychiatric disorders in children and adolescents, but the evidence for their efficacy is uncertain. We conducted a systematic review of published randomized controlled trials (RCT) that assessed the psychiatric benefit of anticonvulsants in patients under 18 years of age. Method: The Medline, Scopus, Web of Science, and ClinicalTrials.gov databases were systematically searched for peer-reviewed primary publications of RCTs with a minimum of 10 patients per treatment arm through December 2017. Results: Out of 355 identified non-duplicative publications, 24 met the inclusion criteria. Most RCTs were to treat bipolar disorder (n = 12) or manage recurrent aggression (n = 9). Few (n = 3) had both a multisite design and adequate statistical power. Valproate was the most frequently studied anticonvulsant (n = 15). Out of three placebo-controlled RCTs of valproate in bipolar disorder, none showed efficacy. In four RCTs, valproate was inferior to the antipsychotic risperidone. In several small, single-site RCTs, valproate and sulthiame were better than placebo for the management of recurrent aggression. Conclusions: Currently available RCTs do not support the efficacy of anticonvulsants as mood stabilizers in children. There is some preliminary evidence from small RCTs of the efficacy of some anticonvulsants in the control of aggression and behavioral dyscontrol in conduct disorder, autism, and intellectual disability.