Altered Thalamocortical Connectivity in 6-Week-Old Infants at High Familial Risk for Autism Spectrum Disorder.

Converging evidence from neuroimaging studies has revealed altered connectivity in cortical-subcortical networks in youth and adults with autism spectrum disorder (ASD). Comparatively little is known about the development of cortical-subcortical connectivity in infancy, before the emergence of overt ASD symptomatology. Here, we examined early functional and structural connectivity of thalamocortical networks in infants at high familial risk for ASD (HR) and low-risk controls (LR). Resting-state functional connectivity and diffusion tensor imaging data were acquired in 52 6-week-old infants. Functional connectivity was examined between 6 cortical seeds-prefrontal, motor, somatosensory, temporal, parietal, and occipital regions-and bilateral thalamus. We found significant thalamic-prefrontal underconnectivity, as well as thalamic-occipital and thalamic-motor overconnectivity in HR infants, relative to LR infants. Subsequent structural connectivity analyses also revealed atypical white matter integrity in thalamic-occipital tracts in HR infants, compared with LR infants. Notably, aberrant connectivity indices at 6 weeks predicted atypical social development between 9 and 36 months of age, as assessed with eye-tracking and diagnostic measures. These findings indicate that thalamocortical connectivity is disrupted at both the functional and structural level in HR infants as early as 6 weeks of age, providing a possible early marker of risk for ASD.

Fragile x syndrome and elimination disorders in a 6-year-old girl.

A case of a 6-year-old girl with multiple elimination disorders (nocturnal enuresis, functional urinary incontinence and fecal incontinence) and a fragile X-syndrome is described. The late diagnosis of the fragile X-syndrome had implications for treatment as well as for family interaction. With the knowledge of the diagnosis the parents reacted in a more understanding manner regarding the behavioral problems of the child, whereby the elimination problems were reduced. The need for further research on elimination disorders in children with genetic disorders is discussed.

Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice.

Fragile X syndrome (FXS) is the most common single gene (FMR1) disorder affecting cognitive and behavioral function in humans. This syndrome is characterized by a cluster of abnormalities including lower IQ, attention deficits, impairments in adaptive behavior and increased incidence of autism. Here, we show that young males with FXS have profound deficits in prepulse inhibition (PPI), a basic marker of sensorimotor gating that has been extensively studied in rodents. Importantly, the magnitude of the PPI impairments in the fragile X children predicted the severity of their IQ, attention, adaptive behavior and autistic phenotypes. Additionally, these measures were highly correlated with each other, suggesting that a shared mechanism underlies this complex phenotypic cluster. Studies in Fmr1-knockout mice also revealed sensorimotor gating and learning abnormalities. However, PPI and learning were enhanced rather than reduced in the mutants. Therefore, these data show that mutations of the FMR1 gene impact equivalent processes in both humans and mice. However, since these phenotypic changes are opposite in direction, they also suggest that murine compensatory mechanisms following loss of FMR1 function differ from those in humans.

[One-sided thinking within child psychiatry. The holistic view of the child in the family is in danger to be lost]. / Ensidigt tänkande inom barnpsykiatrin. Helhetsbilden av barnet i familjen riskerar att förloras.

From the perspective of contemporary neurobiology, genetics and developmental psychology, the traditional psychiatric diagnostic system DSM-IV is out of date. It is based on a 19th century medical model of disease with an untenable dualistic view of brain, mind and body, a mechanistic concept of causality, and retification of diagnoses. This makes DSM inadequate for the clinical child psychiatrist who needs a holistic view of the child, its family and social environment.

Problem behaviors associated with 15q- Angelman syndrome.

Caregivers of persons with Angelman syndrome completed the Aberrant Behavior Checklist and Reiss Screen for Maladaptive Behavior. Seventy-three replies were received, and comparisons were made with other published data. Responses indicated that 15q- Angelman syndrome is associated with such problems as lack of speech, overactivity, restlessness, and eating and sleep problems. Episodes of inappropriate laughter were only reported for 57%, despite being considered a cardinal feature of the syndrome; eating problems (64%) and a fascination with water (68%) were reported more frequently. Overactivity was more of a problem for children; Aberrant Behavior Checklist Factor IV (Hyperactivity) was negatively correlated with age. Scores were mostly lower than for previously studied etiological groups. Therapeutic effort should be put into programs to address these problems.

Children and adolescents with neurofibromatosis 1: a behavioral phenotype.

Twenty 6- to 17-year-old children with neurofibromatosis 1. (NF1) were compared to 20 age- and sex-matched siblings on a wide range of neuropsychological and behavioral dimensions. In familial cases, diagnostic status was confirmed by gene linkage with greater than 98% accuracy. Visual examinations that included assessments of visual evoked responses (VER) were performed on subjects with NF1. Forty-two percent of NF1 subjects had abnormal VER and underwent magnetic resonance imagery or computed tomography scans of the brain. On a variety of skills, subjects with NF1 performed more poorly than unaffected siblings. Children with NF1 were found to be less competent on measures of cognitive, language, and motor development, visual-spatial judgment, visual-motor integration, and academic achievement. Learning disabilities were common in children with NF1. Parents and teachers reported that NF1 subjects had internalizing problems and difficulty interacting with peers. A behavioral phenotype for NF1 and recommendations for preventative interventions are proposed.

Familial subtypes of childhood hyperactivity.

On the basis of family history data we defined two subtypes of childhood hyperactivity: family history-positive (FH+), in which at least one biological parent of the child had a diagnosis in the antisocial spectrum; and family history-negative (FH-), in which neither parent had such a diagnosis. While children in both subgroups were equally deviant on measures of the core components of childhood hyperactivity (e.g., inattention and reactivity), the FH+ children were also deviant on dimensions of conduct disturbance and had siblings with a high prevalence of conduct disorder. FH- children showed little evidence of conduct disturbance, had more learning and academic problems, and had siblings with attentional and learning disabilities, but not conduct disorder. These findings suggest that the study of family constellations should be a fruitful method for resolving the heterogeneity of the hyperactive child syndrome.