Seizures in Sotos syndrome: Phenotyping in 49 patients.

We aimed to describe the phenotypic spectrum of seizures in Sotos syndrome, a genetic condition involving overgrowth, macrocephaly, dysmorphic features, and learning disability, in which 60%-90% have NSD1 pathogenic variants. Patients were recruited from clinics and referral from support groups. Those with seizures and a clinical diagnosis of Sotos syndrome were included. Phenotyping data were collected via structured clinical interview and chart review. Forty-nine patients were included. Twenty had NSD1 testing results available; of these, 15 (75%) had NSD1 pathogenic variants. Seizure onset age ranged from 3 months to 12 years. Staring spells (absence or focal impaired awareness seizure) were the most frequently reported semiology (33/49; 67%), followed by febrile seizures (25/49; 51%) and afebrile bilateral tonic-clonic seizures (25/49; 51%). Most patients (33/49; 67%) had multiple seizure types. The majority (33/49; 67%) had seizures controlled on a single antiseizure medication or no medication. Nine (18%) had drug-resistant epilepsy. Epilepsy syndromes included febrile seizures plus, Lennox-Gastaut syndrome, childhood absence epilepsy, and generalized tonic-clonic seizures alone. The seizure phenotype in Sotos syndrome most commonly involves staring spells, afebrile tonic-clonic seizures or febrile convulsions; however, other seizure types may occur. Seizures are typically well-controlled with medication, but drug-resistant epilepsy occurs in a minority.

Oxytocin-mediated social enrichment promotes longer telomeres and novelty seeking.

The quality of social relationships is a powerful determinant of lifetime health. Here, we explored the impact of social experiences on circulating oxytocin (OT) concentration, telomere length (TL), and novelty-seeking behaviour in male and female rats. Prolonged social housing raised circulating OT levels in both sexes while elongating TL only in females. Novelty-seeking behaviour in females was more responsive to social housing and increased OT levels than males. The OT antagonist (OT ANT) L-366,509 blocked the benefits of social housing in all conditions along with female-specific TL erosion and novelty-seeking deficit. Thus, females seem more susceptible than males to genetic and behavioural changes when the secretion of endogenous OT in response to social life is interrupted. Social enrichment may, therefore, provide a therapeutic avenue to promote stress resiliency and chances of healthy aging across generations.

Non-diagnostic symptoms in a mouse model of autism in relation to neuroanatomy: the BTBR strain reinvestigated.

Several mouse models of autism spectrum disorder (ASD), including the BTBR T + tf/J (BTBR) inbred strain, display a diverse array of behavioral deficits with particular face validity. Here we propose that phenotyping these preclinical models of ASD should avoid excessive reliance on appearance validity of the behavioral observations. BTBR mice were examined in three non-diagnostic symptoms modalities, beside an anatomical investigation for construct validity. The BTBR strain displayed poor sensorimotor integration as reflected by shorter stride length and greater latency on the balance beam task (BBT) when compared with C57BL/6 (B6) controls. Also, locomotor indices in the open-field task (OFT) revealed that BTBR mice traveled longer distances with a remarkably faster exploration than the B6 group in favor of hyperactivity and impulsiveness. Furthermore, analysis of spatial performance including search strategies in the Morris water task (MWT) indicated spatial impairment in the BTBR strain due to failure to employ spatial strategies during navigation. Quantitative cytoarchitectonics and volumetric examinations also indicated abnormal cortical and subcortical morphology in the BTBR mice. The results are discussed in relation to the neuroanatomical correlates of motor and cognitive impairments in the BTBR strain. We conclude that non-diagnostic autistic-like symptoms in the BTBR mouse strain can be impacted by autism risk factors in a similar way than the traditional diagnostic signs.

Intergenerational Sex-Specific Transmission of Maternal Social Experience.

The social environment is a major determinant of individual stress response and lifetime health. The present study shows that (1) social enrichment has a significant impact on neuroplasticity and behaviour particularly in females; and (2) social enrichment in females can be transmitted to their unexposed female descendants. Two generations (F0 and F1) of male and female rats raised in standard and social housing conditions were examined for neurohormonal and molecular alterations along with changes in four behavioural modalities. In addition to higher cortical neuronal density and cortical thickness, social experience in mothers reduced hypothalamic-pituitary-adrenal (HPA) axis activity in F0 rats and their F1 non-social housing offspring. Only F0 social mothers and their F1 non-social daughters displayed improved novelty-seeking exploratory behaviour and reduced anxiety-related behaviour whereas their motor and cognitive performance remained unchanged. Also, cortical and mRNA measurements in the F1 generation were affected by social experience intergenerationally via the female lineage (mother-to-daughter). These findings indicate that social experience promotes cortical neuroplasticity, neurohormonal and behavioural outcomes, and these changes can be transmitted to the F1 non-social offspring in a sexually dimorphic manner. Thus, a socially stimulating environment may form new biobehavioural phenotypes not only in exposed individuals, but also in their intergenerationally programmed descendants.