Pathophysiology Autism

autism affects amygdala, cerebellum, , many other parts of brain.

unlike many other brain disorders, such parkinson s, autism not have clear unifying mechanism @ either molecular, cellular, or systems level; not known whether autism few disorders caused mutations converging on few common molecular pathways, or (like intellectual disability) large set of disorders diverse mechanisms. autism appears result developmental factors affect many or functional brain systems, , disturb timing of brain development more final product. neuroanatomical studies , associations teratogens suggest autism s mechanism includes alteration of brain development after conception. anomaly appears start cascade of pathological events in brain influenced environmental factors. after birth, brains of children autism tend grow faster usual, followed normal or relatively slower growth in childhood. not known whether overgrowth occurs in children autism. seems prominent in brain areas underlying development of higher cognitive specialization. hypotheses cellular , molecular bases of pathological overgrowth include following:

an excess of neurons causes local overconnectivity in key brain regions.
disturbed neuronal migration during gestation.
unbalanced excitatory–inhibitory networks.
abnormal formation of synapses , dendritic spines, example, modulation of neurexin–neuroligin cell-adhesion system, or poorly regulated synthesis of synaptic proteins. disrupted synaptic development may contribute epilepsy, may explain why 2 conditions associated.

the immune system thought play important role in autism. children autism have been found researchers have inflammation of both peripheral , central immune systems indicated increased levels of pro-inflammatory cytokines , significant activation of microglia. biomarkers of abnormal immune function have been associated increased impairments in behaviors characteristic of core features of autism such deficits in social interactions , communication. interactions between immune system , nervous system begin during embryonic stage of life, , successful neurodevelopment depends on balanced immune response. thought activation of pregnant mother s immune system such environmental toxicants or infection can contribute causing autism through causing disruption of brain development. supported recent studies have found infection during pregnancy associated increased risk of autism.

the relationship of neurochemicals autism not understood; several have been investigated, evidence role of serotonin , of genetic differences in transport. role of group metabotropic glutamate receptors (mglur) in pathogenesis of fragile x syndrome, common identified genetic cause of autism, has led interest in possible implications future autism research pathway. data suggests neuronal overgrowth potentially related increase in several growth hormones or impaired regulation of growth factor receptors. also, inborn errors of metabolism associated autism, account less 5% of cases.

the mirror neuron system (mns) theory of autism hypothesizes distortion in development of mns interferes imitation , leads autism s core features of social impairment , communication difficulties. mns operates when animal performs action or observes animal perform same action. mns may contribute individual s understanding of other people enabling modeling of behavior via embodied simulation of actions, intentions, , emotions. several studies have tested hypothesis demonstrating structural abnormalities in mns regions of individuals asd, delay in activation in core circuit imitation in individuals asperger syndrome, , correlation between reduced mns activity , severity of syndrome in children asd. however, individuals autism have abnormal brain activation in many circuits outside mns , mns theory not explain normal performance of children autism on imitation tasks involve goal or object.

autistic individuals tend use different areas of brain (yellow) movement task compared control group (blue).

asd-related patterns of low function , aberrant activation in brain differ depending on whether brain doing social or nonsocial tasks. in autism there evidence reduced functional connectivity of default network, large-scale brain network involved in social , emotional processing, intact connectivity of task-positive network, used in sustained attention , goal-directed thinking. in people autism 2 networks not negatively correlated in time, suggesting imbalance in toggling between 2 networks, possibly reflecting disturbance of self-referential thought.

the underconnectivity theory of autism hypothesizes autism marked underfunctioning high-level neural connections , synchronization, along excess of low-level processes. evidence theory has been found in functional neuroimaging studies on autistic individuals , brainwave study suggested adults asd have local overconnectivity in cortex , weak functional connections between frontal lobe , rest of cortex. other evidence suggests underconnectivity within each hemisphere of cortex , autism disorder of association cortex.

from studies based on event-related potentials, transient changes brain s electrical activity in response stimuli, there considerable evidence differences in autistic individuals respect attention, orientation auditory , visual stimuli, novelty detection, language , face processing, , information storage; several studies have found preference nonsocial stimuli. example, magnetoencephalography studies have found evidence in children autism of delayed responses in brain s processing of auditory signals.

in genetic area, relations have been found between autism , schizophrenia based on duplications , deletions of chromosomes; research showed schizophrenia , autism more common in combination 1q21.1 deletion syndrome. research on autism/schizophrenia relations chromosome 15 (15q13.3), chromosome 16 (16p13.1) , chromosome 17 (17p12) inconclusive.

functional connectivity studies have found both hypo- , hyper-connectivity in brains of people autism. hypo-connectivity seems dominate, interhemispheric , cortico-cortical functional connectivity.