Autism spectrum disorder · Lobeworks/17

Autism spectrum disorder is a neurodevelopmental condition defined by lasting differences in social communication and interaction together with restricted, repetitive behaviours or interests, present from early development and ranging so widely in degree and in its companions (language, intellectual ability, epilepsy,

Autism spectrum disorder. Autism spectrum disorder is a neurodevelopmental condition defined by lasting differences in social communication and interaction together with restricted, repetitive behaviours or interests, present from early development and ranging so widely in degree and in its companions (language, intellectual ability, epilepsy, anxiety) that it is described as a spectrum.

It is among the most heritable conditions studied: in a cohort of more than two million people across five countries, the median estimate was about 80 %, with almost nothing left to the environment families share (heritability is a share of variation in a population, never a share of one person's autism). The genetics is spread over hundreds of genes, many of them coding for synaptic proteins, plus rare mutations of large effect. Prevalence has climbed in surveillance from 1 in 150 in 2000 to about 1 in 31 eight-year-olds in 2022 in the US monitoring sites, a rise that tracks broader criteria and better identification and that varies several-fold between sites.

Pruning is one research line, not the explanation. Post-mortem temporal cortex from autistic children and adolescents had more dendritic spines than expected, with signs that developmental synaptic pruning had fallen short, tied in mice to an overactive mTOR pathway and blocked autophagy; whether this holds across the spectrum is open.

The immune line comes from epidemiology and mice: maternal infection during pregnancy raises the risk, and a maternal immune challenge in mice yields offspring with altered social behaviour (see neuroinflammation).

From hypothesis to treatment the gap is wide. No medicine treats the core features; the two approved in the United States (risperidone and aripiprazole) address irritability, and support is mostly educational and behavioural.

Bleuler coined autism in 1911 for a withdrawal he saw in schizophrenia; Kanner (1943) and Asperger (1944) used it for the childhood condition, and DSM-5 (2013) joined the subtypes into one spectrum.

Autism is a spectrum with many causes, not one mechanism.

Heritability is high, the genes are many, and every brain finding so far describes a subgroup better than the whole.

Questions: What is the maternal immune activation line of autism research? It starts from registries showing that infection during pregnancy is linked to a higher risk of autism and schizophrenia in the child. In mice, giving the pregnant mother a viral mimic (poly I:C) around mid-gestation produces offspring with altered social behaviour and brain development, an effect carried largely by maternal cytokines such as IL-6. The models vary with strain, sex and gut flora, and in people the added risk is small; it is one environmental line beside a condition that is mostly heritable. What does synaptic pruning have to do with autism research? One research line proposes that too little pruning leaves some autistic brains with too many synapses. Post-mortem temporal cortex from autistic people showed more dendritic spines on layer V pyramidal cells than controls, with less of the decline seen across development, and the excess went with an overactive mTOR pathway and impaired autophagy, the cell's recycling of its own parts (Tang et al., 2014). In mice with the same overactive mTOR, the pruning defect and the social differences were reversed by the drug rapamycin. It is one line among several, built on small post-mortem samples and mouse models, and autism is too varied for one mechanism to explain it.