1. Constantino JN. {{How continua converge in nature: cognition, social competence, and autistic syndromes}}. {J Am Acad Child Adolesc Psychiatry}. 2009 Feb;48(2):97-8.
2. Frazier TW, Youngstrom EA, Sinclair L, Kubu CS, Law P, Rezai A, Constantino JN, Eng C. {{Autism Spectrum Disorders as a Qualitatively Distinct Category From Typical Behavior in a Large, Clinically Ascertained Sample}}. {Assessment}. 2009 Dec 29.
The present study evaluated the hypothesis that autism spectrum disorders (ASDs) are best represented as a discrete category distinct from typical behavior within autism-affected families. The latent structure, categorical versus dimensional, of ASDs informs future diagnostic revisions, clinical assessment, and the design of future research. Data were obtained from Interactive Autism Network, a registry that preferentially recruits families with at least one ASD-affected child. Caregivers reported autism symptoms for affected and unaffected children using the Social Responsiveness Scale and Social Communication Questionnaire. Taxometric and latent variable models examined whether dimensional or categorical models best fit the data. Taxometric and latent variable model comparisons consistently indicated two-group mixtures for all indicator sets, even in participants designated as unaffected by caregivers. The identified category was associated with external indicators of disability, supporting its validity. Results indicated that ASD is best characterized as a category, distinct from typical behavior within ASD-affected families.
3. Smith RG, Kember RL, Mill J, Fernandes C, Schalkwyk LC, Buxbaum JD, Reichenberg A. {{Advancing paternal age is associated with deficits in social and exploratory behaviors in the offspring: a mouse model}}. {PLoS One}. 2009;4(12):e8456.
BACKGROUND: Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism, schizophrenia and early-onset bipolar disorder. In order to establish causality, this study used an animal model to investigate the effects of advanced paternal age on behavioural deficits in the offspring. METHODS: C57BL/6J offspring (n = 12 per group) were bred from fathers of two different ages, 2 months (young) and 10 months (old), and mothers aged 2 months (n = 6 breeding pairs per group). Social and exploratory behaviors were examined in the offspring. PRINCIPAL FINDINGS: The offspring of older fathers were found to engage in significantly less social (p = 0.02) and exploratory (p = 0.02) behaviors than the offspring of younger fathers. There were no significant differences in measures of motor activity. CONCLUSIONS: Given the well-controlled nature of this study, this provides the strongest evidence for deleterious effects of advancing paternal age on social and exploratory behavior. De-novo chromosomal changes and/or inherited epigenetic changes are the most plausible explanatory factors.
4. Verhoeven WM, Csepan R, Marcelis CL, Lefeber DJ, Egger JI, Tuinier S. {{Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia}}. {Acta Psychiatr Scand}. 2009 Dec 23.
Verhoeven WMA, Csepan R, Marcelis CLM, Lefeber DJ, Egger JIM, Tuinier S. Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia. Objective: Sanfilippo B is a rare autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by a deficiency of N-acetyl-alpha-D-glucosaminidase (NAGLU). Method: A mild mentally retarded elderly female patient is described with a slowly progressive dementia who had given birth to a daughter who developed normally. Results: Metabolic screening revealed an enhanced concentration of heparan sulfate in urine. Enzymatic assay demonstrated deficiency of N-acetyl-alpha-D-glucosaminidase. Mutations in the NAGLU gene were found. One mentally retarded and hospitalized elder brother was also found to have MPS IIIB, whereas a second brother, who had died earlier, is suspected to have had the same metabolic disorder. Prior to the development of dementia, both the patient and her brother showed autistic like features, signs of ideomotor apraxia and weakness in verbal comprehension. Conclusion: Screening for metabolic disorders, in particular MPSes, should always be considered in patients with a history of mental deficit and dementia or progressive functional decline.
5. Voituron N, Zanella S, Menuet C, Lajard AM, Dutschmann M, Hilaire G. {{Early abnormalities of post-sigh breathing in a mouse model of Rett Syndrome}}. {Respir Physiol Neurobiol}. 2009 Dec 26.
Rett syndrome is a neurodevelopmental disease accompanied by complex, disabling symptoms, including breathing symptoms. Because Rett syndrome is caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2), Mecp2-deficient mice have been generated as experimental model. Males of Mecp2-deficient mice (Mecp2(-/y)) breathe normally at birth but show abnormal respiratory responses to hypoxia and hypercapnia from postnatal day 25 (P25). After P30, Mecp2(-/y) mice develop breathing symptoms reminiscent of Rett syndrome, aggravating until premature death at around P60. Using plethysmography, we analyzed the sighs and the post-sigh breathing pattern of unrestrained wild type male mice (WT) and Mecp2(-/y) mice from P15 to P60. Sighs are spontaneous large inspirations known to prevent lung atelectasis and to improve alveolar oxygenation. However, Mecp2(-/y) mice show early abnormalities of post-sigh breathing, with long-lasting post-sigh apnoeas, reduced tidal volume when eupnoea resumes and lack of post-sigh bradypnoea which develop from P15, aggravate with age and possibly contribute to breathing symptoms to come.
