1. Derecki NC, Privman E, Kipnis J. {{Rett syndrome and other autism spectrum disorders-brain diseases of immune malfunction?}}. {Mol Psychiatry} (Feb 23)
Neuroimmunology was once referred to in terms of its pathological connotation only and was generally understood as covering the deleterious involvement of the immune system in various diseases and disorders of the central nervous system (CNS). However, our conception of the function of the immune system in the structure, function, and plasticity of the CNS has undergone a sea change after relevant discoveries over the past two decades, and continues to be challenged by more recent studies of neurodevelopment and cognition. This review summarizes the recent advances in understanding of immune-system participation in the development and functioning of the CNS under physiological conditions. Considering as an example Rett syndrome a devastating neurodevelopmental disease, we offer a hypothesis that might help to explain the part played by immune cells in its etiology, and hence suggests that the immune system might be a feasible therapeutic target for alleviation of some of the symptoms of this and other autism spectrum disorders.Molecular Psychiatry advance online publication, 23 February 2010; doi:10.1038/mp.2010.21.
2. Dichter GS, Sikich L, Mahorney S, Felder JN, Lam KS, Turner-Brown L, Bodfish J. {{fMRI tracks reductions in repetitive behaviors in autism: Two case studies}}. {Neurocase} (Feb 22):1-10.
Autism is characterized by abnormal prefrontal brain activation during cognitive control, a potential biomarker of repetitive behaviors. In this proof-of-principle study, functional magnetic resonance imaging (fMRI) was used to examine brain activity during an oddball task in two high-functioning males with autism before and after 12 weeks of treatment with citalopram, a selective serotonin reuptake inhibitor. One participant showed marked reductions in repetitive behaviors whereas the other showed mild worsening. Brain activation in relevant prefrontal regions increased in only the participant whose repetitive behavior symptoms improved. These findings suggest that fMRI may elucidate potential mechanisms of action of targeted autism interventions.
3. Matson JL, Wilkins J, Fodstad JC. {{The Validity of the Baby and Infant Screen for Children with aUtIsm Traits: Part 1 (BISCUIT: Part 1)}}. {J Autism Dev Disord} (Feb 23)
A top priority in the field of autism spectrum disorders (ASD) is the development of precise early diagnostic tools that can be completed with minimal time and training. We report on the convergent and divergent validity of the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT), specifically the BISCUIT-Part 1. Previous research with this scale has determined its reliability and sensitivity/specificity. In this study, a sample of 1,007 toddlers 17-37 months of age were assessed individually. The BISCUIT-Part 1 demonstrated good convergent validity with the Modified CHecklist for Autism in Toddlers (M-CHAT) and the Personal Social domain from the Battelle Developmental Inventory, Second Edition (BDI-2). Additionally, divergent validity was demonstrated by its small correlation with the Adaptive and Motor domains from the BDI-2.
4. Mattila ML, Hurtig T, Haapsamo H, Jussila K, Kuusikko-Gauffin S, Kielinen M, Linna SL, Ebeling H, Bloigu R, Joskitt L, Pauls DL, Moilanen I. {{Comorbid Psychiatric Disorders Associated with Asperger Syndrome/High-functioning Autism: A Community- and Clinic-based Study}}. {J Autism Dev Disord} (Feb 23)
The present study identifies the prevalence and types of comorbid psychiatric disorders associated with Asperger syndrome (AS)/high-functioning autism (HFA) in a combined community- and clinic-based sample of fifty 9- to 16-year-old subjects using the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version. The level of functioning was estimated using the Children’s Global Assessment Scale. The results support common (prevalence 74%) and often multiple comorbid psychiatric disorders in AS/HFA; behavioral disorders were shown in 44%, anxiety disorders in 42% and tic disorders in 26%. Oppositional defiant disorder, major depressive disorder and anxiety disorders as comorbid conditions indicated significantly lower levels of functioning. To target interventions, routine evaluation of psychiatric comorbidity in subjects with AS/HFA is emphasized.
5. Odent M. {{Autism and anorexia nervosa: Two facets of the same disease?}}. {Med Hypotheses} (Feb 20)
We compiled data included in the Primal Health Research Database (www.primalhealthresearch.com) to test the hypothesis that when two pathological conditions or personality traits share the same critical period for gene-environment interaction, we should expect further similarities, particularly from clinical and pathophysiological perspectives. The keywords ‘autism’ and ‘anorexia nervosa’ (but not bulimia nervosa) lead to studies suggesting that for both conditions the perinatal period is critical. We take this example to look at other possible links between these pathological entities. From a clinical perspective, several teams have independently emphasized the importance of autistic traits in anorexia nervosa. Deficits in the processing of oxytocin have been demonstrated in both cases. Autistic groups have significantly lower blood oxytocin levels than normal groups, and oxytocin levels increase with age in the normal group only. In autistic groups there is a high ratio of intermediates of oxytocin synthesis (OX-T) to the nonapeptide oxytocin (OT). On the other hand, it has been reported that the level of oxytocin in the cerebrospinal fluid of anorexic women is significantly lower than the level of oxytocin in bulimic and control subjects. Scanning data reveal similar asymmetric functions with left hemisphere preponderance in autistic spectrum disorders and anorexia. A comparative study of the mirror neurons systems is another promising avenue for research. Such an accumulation of similarities from a great diversity of perspectives suggests that anorexia nervosa might be considered a female variant of the autistic spectrum. A plausible interpretation is that prenatal exposure to male hormones might protect against the expression of this disease: girls who have a twin brother are at low risk for anorexia nervosa, compared with girls who have a twin sister, and with controls; furthermore genetic linkage analyses do not detect change on the X chromosome. From an overview of the database, the perinatal period appears to be critical for all disorders related to the capacity to love (including love of oneself), to the potential for aggression (including self-destructive behaviours), or to sociability. Is the perinatal period critical for the organisation of the oxytocin system? This is an important question at a time when we learn that the widely used synthetic oxytocin can probably diffuse across the placenta. On the other hand, where the genesis of metabolic types is concerned, it is prenatal life that appears to be critical.
6. Tan GC, Doke TF, Ashburner J, Wood NW, Frackowiak RS. {{Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2}}. {Neuroimage} (Feb 19)
Recent genetics studies have implicated a number of candidate genes in the pathogenesis of Autism Spectrum Disorder (ASD). Polymorphisms of CNTNAP2 (Contactin associated like protein -2), a member of the Neurexin family, have already been implicated as a susceptibility gene for autism by at least 3 separate studies. We investigated variation in white and grey matter morphology using structural MRI and Diffusion Tensor Imaging. We compared volumetric differences in white and grey matter and fractional anisotropy values in control subjects characterised by genotype at rs7794745, a single nucleotide polymorphism in CNTNAP2. Homozygotes for the risk allele showed significant reductions in grey and white matter volume and fractional anisotropy in the several regions that have already been implicated in ASD, including the cerebellum, fusiform gyrus, occipital and frontal cortices. Male homozygotes.for the risk alleles showed greater reductions in grey matter in the right frontal pole and in FA in the right rostral fronto-occipital fasciculus compared to their female counterparts who showed greater reductions in FA of the anterior thalamic radiation. Thus a risk allele for autism results in significant cerebral morphological variation, despite the absence of overt symptoms or behavioural abnormalities. The results are consistent with accumulating evidence of CNTNAP2’s function in neuronal development. The finding suggests the possibility that the heterogeneous manifestations of ASD can be aetiologically characterised into distinct subtypes through genetic-morphological analysis.
