Case-ControlMolecular autism2025

Molecular architecture of the altered cortical complexity in autism.

Makliya Mamat, Yiyong Chen, Wenwen Shen and 1 others

PMID 39763008

WHAT IT FOUND

Autism was associated with differences in brain-surface complexity across attention, movement and vision networks.

Genes associated with those differences involved synaptic signalling and mitochondrial function. This is a brain imaging finding, not evidence for changing therapy.

Key findings

01Significant cortical complexity differences were found between individuals with ASD and typically developing controls in several key brain networks.

02Upregulated genes associated with cortical complexity changes were enriched for synaptic transmission and mitochondrial membrane or respirasome terms.

03Downregulated genes associated with cortical complexity changes were enriched for chromatin organization and regulation of cellular response to stress.

STILL TO COME

How it was doneWhat they found

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What it does not show

The ABIDE datasets did not consistently report comorbid psychiatric, genetic or neuropsychiatric conditions. The authors state that further validation is needed. The gene-expression data came from only six postmortem adult brains, with right-hemisphere data from only two donors. Some gene categories may appear enriched because of their spatial expression pattern, so specificity is hard to characterise. The MRI data came from many sites with heterogeneous acquisition parameters, so site effects had to be harmonised.

Declared interests

The supplied metadata lists the study as supported by non-U.S. government research. The article text provided does not include a funding statement or author conflict-of-interest declaration.

The easy way to misread this

Do not read the altered cortical complexity and gene associations as a cause of autism or a target for therapy. The study compares brain images and postmortem gene-expression patterns across groups, and the gene-expression data come from only six adult donors.

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The study

Participants
1829 participants (460 individuals with ASD and 515 typically developing controls in ABIDE I; 379 individuals with ASD and 475 typically developing controls in ABIDE II)
Certainty of evidence
Low

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    Makliya Mamat, Yiyong Chen, Wenwen Shen, et al. Molecular architecture of the altered cortical complexity in autism. Molecular autism. 2025.

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