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Autism Spectrum Disorder (ASD) is a highly heterogeneous neuropsychiatric disorder with a strong genetic component. The genetic architecture is complex, consisting of a combination of common low-risk and more penetrant rare variants. Voltage-gated calcium channels (VGCCs or Ca

We examined the potential benefits of neuroimaging measurements across the first 5 years of life in detecting early comorbid or etiological signs of autism spectrum disorder (ASD). In particular, we analyzed the prevalence of neuroradiologic findings in routine magnetic resonance imaging (MRI) scans of a group of 117 ASD children younger than 5 years old. These data were compared to those reported in typically developing (TD) children. MRI findings in children with ASD were analyzed in relation to their cognitive level, severity of autistic symptoms, and the presence of electroencephalogram (EEG) abnormalities. The MRI was rated abnormal in 55% of children with ASD with a significant prevalence in the high-functioning subgroup compared to TD children. We report significant incidental findings of mega cisterna magna, ventricular anomalies and abnormal white matter signal intensity in ASD without significant associations between these MRI findings and EEG features. Based on these results we discuss the role that brain MRI may play in the diagnostic procedure of ASD.

Autism spectrum disorder (ASD) is characterized by a complex polygenic background, but with the unique feature of a subset of cases (~15%‐30%) presenting a rare large‐effect variant. However, clinical interpretation in these cases is often complicated by incomplete penetrance, variable expressivity and different neurodevelopmental trajectories. NRXN1 intragenic deletions represent the prototype of such ASD‐associated susceptibility variants. From chromosomal microarrays analysis of 104 ASD individuals, we identified an inherited NRXN1 deletion in a trio family. We carried out whole‐exome sequencing and deep sequencing of mitochondrial DNA (mtDNA) in this family, to evaluate the burden of rare variants which may contribute to the phenotypic outcome in NRXN1 deletion carriers. We identified an increased burden of exonic rare variants in the ASD child compared to the unaffected NRXN1 deletion‐transmitting mother, which remains significant if we restrict the analysis to potentially deleterious rare variants only (P = 6.07 × 10−5). We also detected significant interaction enrichment among genes with damaging variants in the proband, suggesting that additional rare variants in interacting genes collectively contribute to cross the liability threshold for ASD. Finally, the proband's mtDNA presented five low‐level heteroplasmic mtDNA variants that were absent in the mother, and two maternally inherited variants with increased heteroplasmic load. This study underlines the importance of a comprehensive assessment of the genomic background in carriers of large‐effect variants, as penetrance modulation by additional interacting rare variants to might represent a widespread mechanism in neurodevelopmental disorders.

Pseudohypoparathyroidism (PHP) is a rare heterogeneous genetic disease characterized by end-organ resistance to parathyroid hormone. In adulthood, heterogeneous neurological and psychiatric disorders have been reported which are associated with hypoparathyroidism in general and with PHP in particular, while for childhood, data are scanty. We report a case of a boy with PHP type 1b, in whom neurological signs at the onset prevailed, characterized by tic-like dyskinesias associated with a series of heterogeneous not well-defined neurological and behavioral features, describing the diagnostic work-up performed and the follow-up. We suggest that the diagnostic hypothesis of PHP might be considered when dealing with a child with tic-like dyskinesias, especially if associated with a series of heterogeneous not well-defined neurological and behavioral features. In these cases, treatment with calcitriol and calcium has to be started as soon as possible to achieve a prompt and persistent clinical improvement.

Calati R, Pedrini L, Alighieri S, Alvarez MI, Desideri L, Durante D, Favero F, Iero L, Magnani G, Pericoli V, Polmonari A, Raggini R, Raimondi E, Riboni V, Scaduto MC, Serretti A, De Girolamo G. Is cognitive behavioural therapy an effective complement to antidepressants in adolescents? A meta-analysis.Objective: Evidence on effectiveness of combined treatments versus antidepressants alone in adolescents consists on a few studies in both major depressive and anxiety disorders. A meta-analysis of randomised 12-week follow-up studies in which antidepressant treatment was compared to combined treatment consisting of the same antidepressant with cognitive behavioural therapy has been performed.Methods: Data were entered into the Cochrane Collaboration Review Manager software and were analysed within a random effect framework. A quality assessment has been performed through Jadad Scale.Results: Higher global functioning at the Children's Global Assessment Scale was found in the combined treatment group (p < 0.0001) as well as higher improvement at the Clinical Global Impressions Improvement Scale (p = 0.04). No benefit of combined treatment was found on depressive symptomatology at the Children's Depression Rating Scale – Revised.Conclusion: Combined treatment seems to be more effective than antidepressant alone on global functioning and general improvement in adolescents with major depressive and anxiety disorders.

Introduction: Levetiracetam (LEV) is an effective antiepileptic drug also used in childhood and adolescence. Literature data regarding the long-term effects of LEV in childhood epilepsy and based on extensive neuropsychological evaluations using standardized tools are still scanty. Our study aimed to address this topic. Materials and Methods: We studied 10 patients with epilepsy characterized by focal or generalized seizures (4 boys, 6 girls; mean age: 10 years 8 months; range: 6 years 2 months - 16 years 2 months), treated with adjunctive LEV during a follow-up of 12 months. In 6 patients electroencephalogram (EEG) showed continuous spike and waves during sleep. Using standardized tools, we performed seriated assessments of cognitive and behavioral functioning in relation to seizure and EEG outcome. Results: Six patients completed the trial after 12 months of treatment; 1 patient dropped out of the study after 9 months, 3 patients after 6 months. Adjunctive LEV was effective on seizures in 3/10 patients and on EEG in 2/10 patients, and was well tolerated in all examined cases. Overall, no worsening of cognitive or behavioral functions has been detected during the period of the study; even at 6 and 12 months from baseline, an improvement in patients’ abstract reasoning has been found, that was not related to seizure or EEG outcome. Conclusions: In our population of children and adolescents, LEV had no adverse cognitive or behavioral effects, short- or long-term. We found an improvement of abstract reasoning, regardless of seizure and EEG outcome.