Autism: Many Genes, Common Pathways?

Neurogenetics Program, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Cell (Impact Factor: 32.24). 11/2008; 135(3):391-5. DOI: 10.1016/j.cell.2008.10.016
Source: PubMed


Autism is a heterogeneous neurodevelopmental syndrome with a complex genetic etiology. It is still not clear whether autism comprises a vast collection of different disorders akin to intellectual disability or a few disorders sharing common aberrant pathways. Unifying principles among cases of autism are likely to be at the level of brain circuitry in addition to molecular pathways.

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    • "Autism is now called ' ' spectrum disorder ' ' because of the recognition that its manifestation and severity displays great heterogeneity depending on intellectual ability , associated symptoms , possible etiology and developmental level ( American Psychiatric Association , 2013 ) . Although there is clearly a genetic basis to ASD , the majority of cases have unknown causes ( Abrahams and Geschwind , 2008 ; Geschwind , 2008 ) . It is , moreover , now widely accepted that ASD is a neurobiological disorder , but specific biological markers are yet to be established ( McPheeters et al . "
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    ABSTRACT: Magnetic resonance spectroscopy (MRS) from voxels placed in the left anterior cingulate cortex (ACC) was measured from 14 boys with Autism Spectrum Disorder (ASD) and 24 gender and age-matched typically developing (TD) control group. Our main aims were to compare the concentration of γ-aminobutyric acid (GABA) between the two groups, and to investigate the relationship between brain metabolites and autism symptom severity in the ASD group. We did find a significant negative correlation in the ASD group between Autism Spectrum Screening Questionnaire (ASSQ) and GABA+/Cr, which may imply that severity of symptoms in ASD is associated with differences in the level of GABA in the brain, supporting the excitatory/inhibitory (E/I) imbalance theory. However we did not find a significant difference between the two groups in GABA levels.
    Frontiers in Human Neuroscience 06/2015; 9:365. DOI:10.3389/fnhum.2015.00365 · 3.63 Impact Factor
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    • "etiology (Chapters 2.1–2.4). Currently, there are several dozen genes and loci known to contribute to ASD and accounting for at most 30% of ASD cases, with more loci being discovered (Abrahams and Geschwind, 2008; Sakai et al., 2011; see also Chapters 2.1–2.4). p0025 How can a multitude of genetic variants cause the disease specificity of ASD? Emerging views of the field indicate that: 1. Functions of the susceptible genes must converge onto a few common molecular pathways that subserve the observed ASD phenotypes; 2. The core features of ASD are the most difficult tasks that involve association of multiple areas, and therefore any mild global impairment has the greatest impact on these tasks while sparing the simpler ones; and/or 3. The expression patterns of the affected genes collectively affect specific brain regions that give rise to the normal functions which are disrupted in ASD. "

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    • "This implies that ASD is heterogenetic, with the located genes reflecting various mechanisms (Geschwind 2011; Happe et al. 2006). The variation of cellular mechanisms of possible ASD-linked genes reflects the multiple pathways affected and diverse traits in autism (Geschwind 2008; Losh et al. 2009). If the multiple pathways converged in certain brain regions, this may implicate that ASD is an integrative disorder. "
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    ABSTRACT: Autism is a neurodevelopmental disorder that has been associated with atypical brain functioning. Functional connectivity MRI (fcMRI) studies examining neural networks in autism have seen an exponential rise over the last decade. Such investigations have led to the characterization of autism as a distributed neural systems disorder. Studies have found widespread cortical underconnectivity, local overconnectivity, and mixed results suggesting disrupted brain connectivity as a potential neural signature of autism. In this review, we summarize the findings of previous fcMRI studies in autism with a detailed examination of their methodology, in order to better understand its potential and to delineate the pitfalls. We also address how a multimodal neuroimaging approach (incorporating different measures of brain connectivity) may help characterize the complex neurobiology of autism at a global level. Finally, we also address the potential of neuroimaging-based markers in assisting neuropsychological assessment of autism. The quest for a neural marker for autism is still ongoing, yet new findings suggest that aberrant brain connectivity may be a promising candidate.
    Neuropsychology Review 02/2014; 24(1). DOI:10.1007/s11065-014-9250-0 · 4.59 Impact Factor
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