Mechanism of autism

The mechanisms of autism are the molecular and cellular processes believed to cause or contribute to the symptoms of autism. Multiple processes are hypothesized to explain different autistic features. These hypotheses include defects in synapse structure and function, reduced synaptic plasticity, disrupted neural circuit function, gut–brain axis dyshomeostasis, neuroinflammation, and altered brain structure or connectivity. Autism symptoms stem from maturation-related changes in brain systems. The mechanisms of autism are divided into two main areas: pathophysiology of brain structures and processes, and neuropsychological linkages between brain structures and behaviors, with multiple pathophysiologies linked to various autism behaviors.

Evidence suggests gut–brain axis abnormalities may contribute to autism. Studies propose that immune, gastrointestinal inflammation, autonomic nervous system dysfunction, gut microbiota alterations, and dietary metabolites may contribute to brain neuroinflammation and dysfunction. Additionally, enteric nervous system abnormalities could play a role in neurological disorders by allowing disease pathways from the gut to impact the brain.

Synaptic dysfunction also appears to be implicated in autism, with some mutations disrupting synaptic pathways involving cell adhesion. Evidence points to teratogens affecting the early developmental stages, suggesting autism arises very early, possibly within the first eight weeks after conception.

Neuroanatomical studies support that autism may involve abnormal neuronal growth and pruning, leading to brain enlargement in some areas and reduction in others. Functional neuroimaging studies show reduced activation in somatosensory cortices during theory of mind tasks in autistic individuals and highlight potential imbalances in neurotransmitters like glutamate and Γ-aminobutyric acid that may underlie autism's behavioral manifestations.

Unlike some brain disorders which have clear molecular hallmarks that can be observed in every affected individual, such as Alzheimer's disease or Parkinson's disease, autism does not have a unifying mechanism at the molecular, cellular, or systems level. The autism spectrum may comprise a small set of disorders that converge on a few common molecular pathways, or it may be a large set of disorders with diverse mechanisms. Autism appears to result from developmental factors that affect many or all functional brain systems. Some factors may disturb the timing of brain development rather than the final product.

Listed below are some characteristic findings in ASD brains on molecular and cellular levels regardless of the specific genetic variation or mutation contributing to autism in a particular individual:

Neuroanatomical studies and the association between autism and teratogens strongly suggest that autism affects brain development soon after conception. This anomaly appears to start a cascade of pathological events in the brain that are significantly influenced by environmental factors. Just after birth, the brains of children with autism tend to grow faster than usual, followed by normal or relatively slower growth in childhood. It is unknown whether early brain overgrowth occurs in all children with autism. It appears to be most prominent in the frontal and temporal lobes, which are associated with higher cognitive specializations such as social cognition, and language development. Hypotheses for the cellular and molecular bases of pathological early overgrowth include an excess of neurons that causes local overconnectivity in key brain regions, and disturbed neuronal migration during early gestation.

Synapse and dendritic spine growth may be disrupted in autism due to impaired neurexin–neuroligin cell-adhesion signaling or dysregulated synthesis of synaptic proteins. Disrupted synaptic development may also contribute to epilepsy, which may explain why the two conditions are associated.Studies have suggested that excitatory–inhibitory networks may be imbalanced in autism.