Mutation in Shank3 Gene Can Lead to Different Psychiatric Disorders

Diagnosing and treating psychiatric disorders is a complex task, understanding the causes of these diseases is even more intricate and complex.  Neuroscientists at MIT are examining mutations on one gene, Shank3, that has been linked to autism and schizophrenia.  Shank3 encodes for a scaffold protein which organizes hundreds of other proteins found on the post-synaptic cell membrane.  Synapses are structures between neurons that help transmit electrical and chemical signals across the brain and nervous system.  Through ongoing research the scientist found that different mutations on the Shank3 gene, in mice, produce different psychiatric behaviors.  In 2011 scientists found that the absence of the Shank3 protein induced two common behaviors of autism- social avoidance and compulsive, repetitive behavior.  Years earlier, researchers at the University of Montreal found a mutation in the Shank3 gene in patients schizophrenia.

The scientists interested with the current research on Shank3 engineered mice to have the two different mutations of the Shank3 gene; one in which the protein was truncated and caused schizophrenic behavior and the other in which the absence of the Shank3 protein caused autistic behavior.  The mice also shared many common behaviors but also possessed the hallmark behaviors of their respective disorders.  By activating the mutations in different parts of the brain at different stages of development researchers were able to narrow down the brain circuits these mutations effected.  The autism mutation exerted its effects early in development, primarily in the region of the brain known as the striatum, these region is responsible for coordinating motor planning, habitual behavior and motivation.  The schizophrenia mutation exerted its effects later in development, suggesting that the truncated protein can function sufficiently early in development.  However as development continued the truncated proteins interfered with the synapses of the cortex, where executive function occur.

The brain is by far the most complex organ in our bodies, it is remarkable to think that essentially a pile of jelly is responsible for all of the thought, behavior, emotion, and movement that occurs in everyday life.  As if the brain isn't complex enough to understand, psychiatric disorders and the causes of those disorders are equally as complex.  The research being conducted by this group of scientists is aiming to understand the potential cause of these psychiatric orders and to also understand the brain circuits these defective proteins effect in order to tailor treatments for individuals affected by these disorders.