By Dr Ananya Mandal, MD
Autism is a spectrum of disorders with no specific only cause. This is the reason why its mechanism of pathophysiology is difficult to understand.
In addition to its complexity, no two individuals with autism are the same. Autism is a lifelong neurodevelopmental disorder. There is disorder of brain development. While a genetic basis is recognised, the pathophysiology of autism is unknown.
Brain scans using FMRI have shown abnormalities in the amygdala, hippocampus, septum, mamillary bodies, and the cerebellum of the brain. This suggests that autistic symptoms may be a consequence of abnormal function in these structures.
Autistic brains are slightly larger and heavier. Just after birth, the brain of an autistic child grows faster than usual, followed by normal or relatively slower growth in childhood. The early overgrowth seems to be most prominent in areas underlying the development of higher cognitive specialization. This may lead to disturbed neuronal migration during early gestation and a imbalance between excitatory–inhibitory networks. There may be a poorly regulated synthesis of synaptic protein. Disrupted synaptic development may also contribute to epilepsy, which may explain why the two conditions are associated.
There are excessive cells in the limbic system and they are too small. The neurons themselves seem developmentally immature. The dendritic branches appear to be truncated. Purkinje cells are affected in a widespread fashion in the cerebellum. These changes in the brain anatomy may occur at some point earlier than 30 weeks gestation (before birth).
At the subcellular level research shows that there is an elevation in a major neurotransmitter, serotonin, which affects potentiation at synapses and may play a role in the development of the nervous system.
Neurocognitive theories for autism
There are 3 neurocognitive theories of autism. These include:
Problems with executive functions - this means difficulties with problem solving and forward planning in order to achieve a goal. In other words acting as one’s own executive or secretary.
Problems with central coherence – this means failure to integrate information to form meaningful whole ideas.
Problems with understanding the way others think or might react to a particular situation.
Rapid shifts in attention and modulation of sensory input have been associated with the cerebellum. The under-connectivity theory of autism hypothesizes that autism is marked by under-functioning high-level neural connections and synchronization, along with an excess of low-level processes.
Autism and the immune system
Interactions between the immune system and the nervous system begin early during the embryonic stage of life, and successful neurodevelopment depends on a balanced immune response. Disturbed immune activity during critical periods of neurodevelopment is part of the mechanism of some forms of ASD. However, as autoantibodies are found in conditions other than ASD, and are not always present in ASD, the relationship between immune disturbances and autism remains unclear.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)