Pathophysiology of autism (book based) Source: Bridging from cells to Cognition in Autism Pathohysiology Biological Pathways to Defective Brain

Function and Plasticity by American Journal of Biochemistry and Biotechnology (2008 Science publication) Non modifiable factors Metabolic disorder Genetic Infection Modifiable factors Environmental factors (exposure to toxin or medications)

Serotonin deficiency Impaired methionine metabolism and hyperaccumulation of homocysteine Mitochondrial swelling

Maternal infected cells

Genetic and Molecular changes MET ( Hepatocyte growth factor receptor) Mediate reversal of the microgliosis and astrogliosis in post-ischemic repair

HGF Oxidation stress response

Inflammatory, cytokines that cross the placenta Fat cells increase interleukin 1, interleukin 6, TNFa, interferon

Cytochrome release

free radicals

Mitochondrial fragmentation/damage Poly ADP ribose Polymerase(PARP) caspase activation

ROS inhibit specific protein(S1(transcription factor)which initiates c met expressions Suppress dendrites cell function

DNA damage Signal transduction pathways

Loss of mitochondrial function

Activate both astroglia and microglia Initiate a broad spectrum proimflammatory gene response cytokines, chemokines, lipid metabolites in CSF and tissue of the brain Suppression of neural circuit function during innate immune response Developed a defense against excitotoxic cell death and other forms of permanent cells

Excess reactive O2 species and reactive Nitrogen species activation in the brain (Superoxide, nitric oxide, peroxynitrite

Impaired social communication, social interaction and behavior

Signs and symptoms: Failure to form interpersonal relationship: -unresponsiveness to people -lack of eye contact and facial responsiveness -indifference or aversion to affection and physical contact -unable to develop cooperative play and friendships

Signs and symptoms: Impairment in communication -absence of language -immature grammatical structure -incorrect use of words -echolalia -inability to use abstract terms Nonverbal expressions may be inappropriate or absent

Signs and symptoms: Bizarre responses to the environment: -resistance or extreme behavioral reactions to minor occurrences -abnormal obsessive attachment to peculiar objects; ritualistic behaviors

Signs and symptoms: -Extreme fascination for objects that move (e.i. fans, trains) -interest in music, playing with water, buttons, or parts of the body -unreasonable insistence on following routines in precise detail -marked distress over changes in trivial aspects of environment -stereotyped body movements (hand flicking or twisting, spinning, head banging, complex whole-body movement).