1. Joshi G, Petty C, Wozniak J, Henin A, Fried R, Galdo M, Kotarski M, Walls S, Biederman J. {{The Heavy Burden of Psychiatric Comorbidity in Youth with Autism Spectrum Disorders: A Large Comparative Study of a Psychiatrically Referred Population}}. {J Autism Dev Disord} (Mar 23)
The objective of the study was to systematically examine patterns of psychiatric comorbidity in referred youth with autism spectrum disorders (ASD) including autistic disorder and pervasive developmental disorder not otherwise specified. Consecutively referred children and adolescents to a pediatric psychopharmacology program were assessed with structured diagnostic interview and measures of psychosocial functioning. Comparisons were made between those youth satisfying diagnostic criteria for ASD and age and sex matched youth without ASD referred to the same clinical program. 9.3% (217/2323) of the referred youth (age range: 3-17 years) met DSM-III-R criteria for ASD. ASD youth suffered from significantly higher number of comorbid disorders than comparisons (6.4 +/- 2.7 vs. 5.2 +/- 2.9; p < 0.001). Ninety-five percent of the youth with ASD had three or more comorbid psychiatric disorders and 74% had five or more comorbid disorders. ASD youth were also more functionally impaired and required extra-assistance in school and therapeutic interventions at higher rates than age and sex matched non-ASD referred youth. Youth with ASD have high levels of psychiatric comorbidity and dysfunction comparable to the referred population of youth without ASD. These findings emphasize the heavy burden of psychiatric comorbidity afflicting youth with ASD and may be important targets for intervention.
2. St Clair MC, Durkin K, Conti-Ramsden G, Pickles A. {{Growth of reading skills in children with a history of specific language impairment: the role of autistic symptomatology and language-related abilities}}. {Br J Dev Psychol} (Mar);28(Pt 1):109-131.
Individuals with a history of specific language impairment (SLI) often have subsequent problems with reading skills, but there have been some discrepant findings as to the developmental time course of these skills. This study investigates the developmental trajectories of reading skills over a 9-year time-span (from 7 to 16 years of age) in a large sample of individuals with a history of SLI. Relationships among reading skills, autistic symptomatology, and language-related abilities were also investigated. The results indicate that both reading accuracy and comprehension are deficient but that the development of these skills progresses in a consistently parallel fashion to what would be expected from a normative sample of same age peers. Language-related abilities were strongly associated with reading skills. Unlike individuals with SLI only, those with SLI and additional autistic symptomatology had adequate reading accuracy but did not differ from the individuals with SLI only in reading comprehension. They exhibited a significant gap between what they could read and what they could understand when reading. These findings provide strong evidence that individuals with SLI experience continued, long-term deficits in reading skills from childhood to adolescence.
3. Vorstman JA, van Daalen E, Jalali GR, Schmidt ER, Pasterkamp RJ, de Jonge M, Hennekam EA, Janson E, Staal WG, van der Zwaag B, Burbach JP, Kahn RS, Emanuel BS, van Engeland H, Ophoff RA. {{A double hit implicates DIAPH3 as an autism risk gene}}. {Mol Psychiatry} (Mar 23)
Recent studies have shown that more than 10% of autism cases are caused by de novo structural genomic rearrangements. Given that some heritable copy number variants (CNVs) have been observed in patients as well as in healthy controls, to date little attention has been paid to the potential function of these non-de novo CNVs in causing autism. A normally intelligent patient with autism, with non-affected parents, was identified with a maternally inherited 10 Mb deletion at 13q21.2. Sequencing of the genes within the deletion identified a paternally inherited nonsynonymous amino-acid substitution at position 614 of diaphanous homolog 3 (DIAPH3) (proline to threonine; Pro614Thr). This variant, present in a highly conserved domain, was not found in 328 healthy subjects. Experiments showed a transient expression of Diaph3 in the developing murine cerebral cortex, indicating it has a function in brain development. Transfection of Pro614Thr in murine fibroblasts showed a significant reduction in the number of induced filopodia in comparison to the wild-type gene. DIAPH3 is involved in cell migration, axon guidance and neuritogenesis, and is suggested to function downstream of SHANK3. Our findings strongly suggest DIAPH3 as a novel autism susceptibility gene. Moreover, this report of a ‘double-hit’ compound heterozygote for a large, maternally inherited, genomic deletion and a paternally inherited rare missense mutation shows that not only de novo genomic variants in patients should be taken seriously in further study but that inherited CNVs may also provide valuable information.Molecular Psychiatry advance online publication, 23 March 2010; doi:10.1038/mp.2010.26.
