Connecting Genes to Brain in the Autism Spectrum Disorders

Abrahams, Brett S.; Geschwind, Daniel H.

doi:10.1001/archneurol.2010.47

Cited by 174 publications

(118 citation statements)

References 48 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…The decrease in amygdala activity when starting gaze at the mouth further underlines amygdalar dysfunction within social saliency detection and orientation. ASD is, however, of multifactorial nature with interacting risk factors (e.g., genetic variants, epigenetic and environmental factors) producing the autistic phenotype and symptom heterogeneity (Abrahams and Geschwind, 2010;Scherer and Dawson, 2011). Variance within the autistic sample is thus very likely leading to pronounced avoidance of eye contact more than reduced orientation in some individuals or vice versa.…”

Section: Discussionmentioning

confidence: 99%

The Role of the Amygdala in Atypical Gaze on Emotional Faces in Autism Spectrum Disorders

Kliemann¹,

Dziobek²,

Hatri³

et al. 2012

Journal of Neuroscience

154

View full text Add to dashboard Cite

Reduced focus toward the eyes is a characteristic of atypical gaze on emotional faces in autism spectrum disorders (ASD). Along with the atypical gaze, aberrant amygdala activity during face processing compared with neurotypically developed (NT) participants has been repeatedly reported in ASD. It remains unclear whether the previously reported dysfunctional amygdalar response patterns in ASD support an active avoidance of direct eye contact or rather a lack of social attention. Using a recently introduced emotion classification task, we investigated eye movements and changes in blood oxygen level-dependent (BOLD) signal in the amygdala with a 3T MRI scanner in 16 autistic and 17 control adult human participants. By modulating the initial fixation position on faces, we investigated changes triggered by the eyes compared with the mouth. Between-group interaction effects revealed different patterns of gaze and amygdalar BOLD changes in ASD and NT: Individuals with ASD gazed more often away from than toward the eyes, compared with the NT group, which showed the reversed tendency. An interaction contrast of group and initial fixation position further yielded a significant cluster of amygdala activity. Extracted parameter estimates showed greater response to eyes fixation in ASD, whereas the NT group showed an increase for mouth fixation.The differing patterns of amygdala activity in combination with differing patterns of gaze behavior between groups triggered by direct eye contact and mouth fixation, suggest a dysfunctional profile of the amygdala in ASD involving an interplay of both eye-avoidance processing and reduced orientation.

show abstract

Section: Discussionmentioning

confidence: 99%

The Role of the Amygdala in Atypical Gaze on Emotional Faces in Autism Spectrum Disorders

Kliemann¹,

Dziobek²,

Hatri³

et al. 2012

Journal of Neuroscience

154

View full text Add to dashboard Cite

show abstract

“…Hippocampus is also one of the regions that has been implicated in autism. Recent data suggest that autism may be caused by multiple genetic risk factors that interrupt the development and function of brain circuits important for social cognition and language (Abrahams and Geschwind, 2010). Diverse anatomical and cellular abnormalities have been reported in brains from idiopathic ASD individuals.…”

Section: Discussionmentioning

confidence: 99%

PtenDeletion in Adult Hippocampal Neural Stem/Progenitor Cells Causes Cellular Abnormalities and Alters Neurogenesis

et al. 2012

View full text Add to dashboard Cite

Adult neurogenesis persists throughout life in restricted brain regions in mammals and is affected by various physiological and pathological conditions. The tumor suppressor gene Pten is involved in adult neurogenesis and is mutated in a subset of autism patients with macrocephaly; however, the link between the role of PTEN in adult neurogenesis and the etiology of autism has not been studied before. Moreover, the role of hippocampus, one of the brain regions where adult neurogenesis occurs, in development of autism is not clear. Here, we show that ablating Pten in adult neural stem cells in the subgranular zone of hippocampal dentate gyrus results in higher proliferation rate and accelerated differentiation of the stem/progenitor cells, leading to depletion of the neural stem cell pool and increased differentiation toward the astrocytic lineage at later stages. Pten-deleted stem/progenitor cells develop into hypertrophied neurons with abnormal polarity. Additionally, Pten mutant mice have macrocephaly and exhibit impairment in social interactions and seizure activity. Our data reveal a novel function for PTEN in adult hippocampal neurogenesis and indicate a role in the pathogenesis of abnormal social behaviors.

show abstract

“…Like schizophrenia, the autism spectrum has a complex genetic basis [280,281] and one might expect developmental disturbances similar to those that accompany schizophrenia. To the best of our knowledge, there have been no complete analyses of fluctuating asymmetry in autistic children, but pattern discordance is present in individuals having mild autism and average IQ [86].…”

Section: Psychologymentioning

confidence: 99%

Fluctuating Asymmetry of Human Populations: A Review

Graham

Özener

2016

Symmetry

View full text Add to dashboard Cite

Fluctuating asymmetry, the random deviation from perfect symmetry, is a widely used population-level index of developmental instability, developmental noise, and robustness. It reflects a population's state of adaptation and genomic coadaptation. Here, we review the literature on fluctuating asymmetry of human populations. The most widely used bilateral traits include skeletal, dental, and facial dimensions; dermatoglyphic patterns and ridge counts; and facial shape. Each trait has its advantages and disadvantages, but results are most robust when multiple traits are combined into a composite index of fluctuating asymmetry (CFA). Both environmental (diet, climate, toxins) and genetic (aneuploidy, heterozygosity, inbreeding) stressors have been linked to population-level variation in fluctuating asymmetry. In general, these stressors increase average fluctuating asymmetry. Nevertheless, there have been many conflicting results, in part because (1) fluctuating asymmetry is a weak signal in a sea of noise; and (2) studies of human fluctuating asymmetry have not always followed best practices. The most serious concerns are insensitive asymmetry indices (correlation coefficient and coefficient of indetermination), inappropriate size scaling, unrecognized mixture distributions, inappropriate corrections for directional asymmetry, failure to use composite indices, and inattention to measurement error. Consequently, it is often difficult (or impossible) to compare results across traits, and across studies.

show abstract

Connecting Genes to Brain in the Autism Spectrum Disorders

Cited by 174 publications

References 48 publications

The Role of the Amygdala in Atypical Gaze on Emotional Faces in Autism Spectrum Disorders

The Role of the Amygdala in Atypical Gaze on Emotional Faces in Autism Spectrum Disorders

PtenDeletion in Adult Hippocampal Neural Stem/Progenitor Cells Causes Cellular Abnormalities and Alters Neurogenesis

Fluctuating Asymmetry of Human Populations: A Review

Contact Info

Product

Resources

About