Neuroanatomic Alterations and Social and Communication Deficits in Monozygotic Twins Discordant for Autism Disorder

Mitchell, Staci; Reiss, Allan L.; Tatusko, B.S. Danielle H.; Ikuta, Ichiro; Kazmerski, B.S. Dana B.; Botti, B.A. Jo-Anna C.; Burnette, Courtney P.; Kates, Wendy R.

doi:10.1176/appi.ajp.2009.08101538

Cited by 64 publications

(64 citation statements)

References 68 publications

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“…The solid line represents normal average. Each number represents a separate study: 1, Hashimoto et al, 1995; 2, Courchesne et al, 2001; 3, Akshoomoff et al, 2004; 4, Webb et al, 2009; 5, Carper et al, 2000; 6, Kleiman et al, 1992; 7, Kaufmann et al, 2003; 8, Kates et al, 2004; 9, Mitchell et. al., 2009; 10, Herbert et al, 2003; 11, Elia et al, 2000; 12, Cleavinger et.…”

Section: Figurementioning

confidence: 99%

Brain growth across the life span in autism: Age-specific changes in anatomical pathology

Courchesne¹,

Campbell²,

Solso³

2011

Brain Research

586

451

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Autism is marked by overgrowth of the brain at the earliest ages but not at older ages when decreases in structural volumes and neuron numbers are observed instead. This has lead to the theory of age-specific anatomic abnormalities in autism. Here we report age-related changes in brain size in autistic and typical subjects from 12 months to 50 years of age based on analyses of 586 longitudinal and cross-sectional MRI scans. This dataset is several times larger than the largest autism study to date. Results demonstrate early brain overgrowth during infancy and the toddler years in autistic boys and girls, followed by an accelerated rate of decline in size and perhaps degeneration from adolescence to late middle age in this disorder. We theorize that underlying these age-specific changes in anatomic abnormalities in autism there may also be age-specific changes in gene expression, molecular, synaptic, cellular and circuit abnormalities. A peak age for detecting and studying the earliest fundamental biological underpinnings of autism is prenatal life and the first three postnatal years. Studies of the older autistic brain may not address original causes but are essential to discovering how best to help the older aging autistic person. Lastly, the theory of age-specific anatomic abnormalities in autism has broad implications for a wide range of work on the disorder including the design, validation and interpretation of animal model, lymphocyte gene expression, brain gene expression, and genotype/CNV-anatomic phenotype studies.

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Section: Figurementioning

confidence: 99%

Brain growth across the life span in autism: Age-specific changes in anatomical pathology

Courchesne¹,

Campbell²,

Solso³

2011

Brain Research

586

451

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“…Although the significance of these expression patterns remains to be determined they are consistent with distinct and non-overlapping roles for the two eNHE isoforms. The robust expression levels of eNHE in areas potentially associated with ASD (Santangelo and Tsatsanis, 2005; Mitchell et al, 2009) may reflect the importance of ion and pH homeostasis on the normal functions of the cells in these regions of the brain.…”

Section: Distribution Of Enhe In the Brainmentioning

confidence: 99%

An inside job: how endosomal Na+/H+ exchangers link to autism and neurological disease

Kondapalli¹,

Prasad²,

Rao³

2014

Front. Cell. Neurosci.

109

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Autism imposes a major impediment to childhood development and a huge emotional and financial burden on society. In recent years, there has been rapidly accumulating genetic evidence that links the eNHE, a subset of Na+/H+ exchangers that localize to intracellular vesicles, to a variety of neurological conditions including autism, attention deficit hyperactivity disorder (ADHD), intellectual disability, and epilepsy. By providing a leak pathway for protons pumped by the V-ATPase, eNHE determine luminal pH and regulate cation (Na+, K+) content in early and recycling endosomal compartments. Loss-of-function mutations in eNHE cause hyperacidification of endosomal lumen, as a result of imbalance in pump and leak pathways. Two isoforms, NHE6 and NHE9 are highly expressed in brain, including hippocampus and cortex. Here, we summarize evidence for the importance of luminal cation content and pH on processing, delivery and fate of cargo. Drawing upon insights from model organisms and mammalian cells we show how eNHE affect surface expression and function of membrane receptors and neurotransmitter transporters. These studies lead to cellular models of eNHE activity in pre- and post-synaptic neurons and astrocytes, where they could impact synapse development and plasticity. The study of eNHE has provided new insight on the mechanism of autism and other debilitating neurological disorders and opened up new possibilities for therapeutic intervention.

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“…The study found no neurovolumetric or area differences between the twin pairs; however, most brain structure volume measures of the lessaffected co-twins tended to be midrange between twins with autism and typically developing comparison subjects. 87 Finally, a functional MRI study of unaffected siblings of individuals with autism showed that unaffected siblings had significantly reduced gaze fixation and right fusiform activation in response to images of human faces when compared with controls. 35 In the same study, amygdala volume in the sibling group was found to be similar to the autism group and was significantly reduced compared with the control group.…”

Section: Commentmentioning

confidence: 99%

Similar White Matter Aberrations in Children With Autism and Their Unaffected Siblings

Barnea-Goraly¹,

Lotspeich²,

Reiss³

2010

Arch Gen Psychiatry

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153

127

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Neuroanatomic Alterations and Social and Communication Deficits in Monozygotic Twins Discordant for Autism Disorder

Cited by 64 publications

References 68 publications

Brain growth across the life span in autism: Age-specific changes in anatomical pathology

Brain growth across the life span in autism: Age-specific changes in anatomical pathology

An inside job: how endosomal Na+/H+ exchangers link to autism and neurological disease

Similar White Matter Aberrations in Children With Autism and Their Unaffected Siblings

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