Abstract
Although autism has historically been conceptualized as a condition that emerges in early childhood many autistic people are diagnosed later in life. It is unknown whether earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Using longitudinal data from four independent birth cohorts, we demonstrate that two different socioemotional and behavioural trajectories are associated with age at diagnosis. In independent cohorts of autistic individuals, common genetic variants account for approximately 11% of the variance in age at autism diagnosis, similar to the contribution of individual sociodemographic and clinical factors, which typically explain less than 15% of this variance. We further demonstrate that the polygenic architecture of autism can be broken down into two modestly genetically correlated (rg = 0.38, s.e. = 0.07) autism polygenic factors. One of these factors is associated with earlier autism diagnosis and lower social and communication abilities in early childhood, but is only moderately genetically correlated with attention deficit–hyperactivity disorder (ADHD) and mental-health conditions. Conversely, the second factor is associated with later autism diagnosis and increased socioemotional and behavioural difficulties in adolescence, and has moderate to high positive genetic correlations with ADHD and mental-health conditions. These findings indicate that earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Our findings have important implications for how we conceptualize autism and provide a model to explain some of the diversity found in autism.
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Autism diagnosed in early childhood differs genetically and developmentally from autism identified later in an individual’s development, challenging the notion that it is a single, uniform disorder, new research suggests.
Investigators found that children diagnosed early in childhood are more likely to exhibit social and behavioral challenges during infancy and early childhood, whereas those identified later have higher rates of conditions such as attention-deficit/hyperactivity disorder (ADHD) and depression. The two subtypes also exhibit distinct genetic profiles.
“We found that, on average, individuals diagnosed with autism earlier and later in life follow different developmental pathways, and surprisingly have different underlying genetic profiles,” study investigator Xinhe Zhang, PhD student, Department of Psychiatry, University of Cambridge, UK, said in a news release.
“Understanding how the features of autism emerge not just in early childhood but later in childhood and adolescence could help us recognize, diagnose, and support autistic people of all ages,” added senior author Varun Warrier, PhD, also with Cambridge University Department of Psychiatry.
The study was published online on October 1 in Nature.
No Single Known Cause
Autism is a complex neurodevelopmental condition with no single known cause. Although it has traditionally been recognized as emerging in early childhood, many individuals are diagnosed later in life. Whether autism identified in early vs later stages of life follows different developmental trajectories or exhibits distinct genetic profiles remains unclear.
To explore how autism diagnosed early in life may differ from cases identified later in life, the investigators analyzed longitudinal data from four birth cohorts, each including 89-188 autistic individuals, alongside genetic data from over 45,000 individuals across multiple international cohorts.
They found that those diagnosed with the disorder before age 7 had significantly higher rates of global developmental delay and intellectual disability, with pronounced deficits in motor and language milestones.
In contrast, individuals diagnosed later in childhood or beyond often showed typical early development but developed more subtle cognitive and behavioral difficulties over time. They were also more likely to have comorbidities, including ADHD and depression.
The genetic analyses revealed that the early-diagnosed group was enriched for rare, deleterious variants in constrained genes, while the later-diagnosed group had elevated polygenic risk scores for educational attainment and other complex traits.
The researchers have not yet identified the specific genetic variants that are associated with each of these profiles.
Notably, the researchers observed that the average genetic profile of later-diagnosed autism more closely resembled those of ADHD, depression, and posttraumatic stress disorder (PTSD) than that of autism diagnosed in early childhood.
“An important next step will be to understand the complex interaction between genetics and social factors that lead to poorer mental health outcomes among later-diagnosed autistic individuals,” Warrier said.
The researchers cautioned against overgeneralizing the study’s findings, emphasizing that age at diagnosis is shaped by social, cultural, and healthcare factors as well as biology. They noted that some children diagnosed later may have exhibited early signs that went unrecognized.
Distinct Types
In an accompanying Nature News & Views article, Elliot Tucker-Drob, PhD, professor, Department of Psychology, University of Texas at Austin, said this study provides evidence that the “developmental timing of autism diagnosis is not simply an artefact of the challenges of identifying milder cases at early ages, but rather a primary feature that distinguishes distinct forms of autism.”
“The developmental timing of first diagnosis is just one possible axis along which autism subtypes can be differentiated, and it is possible — if not probable — that other mechanistically separable subtypes of autism exist that have yet to be identified,” Tucker-Drob said.
In a statement from the UK nonprofit Science Media Centre, experts weighed in on the findings.
Uta Frith, PhD, emeritus professor of cognitive development, University College London, said the findings make her “hopeful that even more subgroups will come to light, and each will find an appropriate diagnostic label.”
“It is time to realize that ‘autism’ has become a ragbag of different conditions. If there is talk about an ‘autism epidemic,’ a ‘cause of autism,’ or a ‘treatment for autism,’ the immediate question must be, which kind of autism?” said Frith.
Michael Absoud, PhD, with King’s College London, said this study “confirms that not only is autism highly heritable and a spectrum of conditions, but the age at diagnosis of autism is also heritable.”
Absoud also noted that the behavioral profiles were derived from the Strengths and Difficulties Questionnaire (SDQ), “a general behavioral screening tool that does not capture detailed autistic and mental health traits and relies on caregiver reports rather than clinical assessments which limits the precision of the developmental trajectories described.
“Research in more diverse populations is needed to replicate the findings, with more detailed quality of life, everyday functioning, and direct assessment measures,” Absoud concluded.
This study was supported by the Wellcome Trust, the UKRI, Horizon Europe, and the Simons Foundation Autism Research Initiative. Zhang, Warrier, Tucker-Drob, Frith, and Absoud had no relevant disclosures.
Megan Brooks
https://www.medscape.com/viewarticle/autism-not-one-disorder-new-data-show-2025a1000qmm
https://www.medscape.com/viewarticle/autism-not-one-disorder-new-data-show-2025a1000qmm
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