Meta-AnalysisMolecular autism2024

Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort.

Ting Mei, Alberto Llera, Natalie J Forde and 4 others

PMID 38229192

WHAT IT FOUND

Two brain structure patterns earlier linked to autism did not replicate in a larger independent group of 770 autistic and 924 non-autistic people.

Differences between the groups varied so much from one scanning site to another that no single average pattern held.

Key findings

01The two brain-wide gray matter patterns found in the earlier LEAP study reappeared in the new ENIGMA sample, one centred on the insula, frontal areas and caudate, the other on the amygdala, hippocampus and parahippocampal gyrus.

02The autistic and non-autistic groups differed significantly on both patterns at first (p = 0.013 and p = 0.024), but once the analysis allowed the group difference to vary from site to site, the difference between groups was no longer statistically significant.

03Among the 486 autistic participants who had symptom scores, neither brain pattern was linked to the total autism symptom score.

STILL TO COME

How it was doneWhat they found

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What it does not show

Only people who already had an IQ score were included, which the authors say likely skews the sample. IQ and sex were not matched between the autistic and non-autistic groups, or between the two datasets, even though the analysis adjusted for both. The 34 sites used different scanners, field strengths and scan settings, and collected their samples differently. This is the authors' own leading explanation for why the result did not replicate. Little clinical information was available in the ENIGMA dataset: co-occurring conditions such as ADHD and anxiety and medication use were largely unknown, and there was too little continuous behavioural data to relate brain patterns to behaviour. The study measures brain structure only. It reports no function, symptoms or treatment response, so it cannot say anything about what helps autistic people.

Declared interests

The work was funded by public and charitable sources: the China Scholarship Council, the European Union's Horizon 2020 and Seventh Framework programmes, the Netherlands Organization for Scientific Research (a VICI grant), and the Wellcome Trust. No commercial sponsor or treatment manufacturer is named.

The easy way to misread this

Do not read this as proof that autistic people have no brain differences. The study failed to reproduce two specific patterns, and the group difference disappeared once variation between scanning sites was taken into account, so the non-replication says as much about pooling sites as about autism itself.

Summarised by AI from the full paper, without a clinician reviewing it. Check it against the source before it changes what you do. Read it on PubMed →


The study

Participants
770 autistic and 924 non-autistic individuals aged 6-30 years, from 34 sites (final analysed sample)
Certainty of evidence
Moderate

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    Cite

    Ting Mei, Alberto Llera, Natalie J Forde, et al. Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort. Molecular autism. 2024.

    Read the original — we summarise, we never replace the paper.