Born Schizophrenic
Picture yourself at 6 1/2 years old, no responsibilities or cares in the world. Now, imagine for a moment that you spend almost every single day within the depths of your home, you get easily upset to the point of no self-control multiple times per day, and you see and hear things that are not physically present but will not leave you alone. Can you fathom living this life forever?
Meet Briana, a 6 1/2 year old dark-haired beauty who spends her days actively fighting schizophrenia. Briana often struggles through hallucinations and psychosis episodes throughout each day, some of which lead to violent actions, instead of enjoying beach days or playing dress up with her sister like I was doing at 6 1/2 years old.
How is Briana’s brain different from those without schizophrenia?
The key factor behind schizophrenic symptoms is the abnormal communication between the frontal and parietal lobes of the brain, which is due to neuronal disconnectivity between the two brain regions that likely occurs during development. Can you think back to a time when you have had to complete a group project with people who did not carry their own weight? Was it frustrating completing that group project without effectively communicating with other group members? Yeah, it is like that, except in the brain.
Cops and robbers in the brain
This neuronal disconnectivity occurs due to a disruption in what is referred to as the Wnt and GSK3 signaling pathway. Let us consider Wnt similar to a cop, B-catenin a town citizen, and the destruction complex a “robber.” GSK3 is a kinase molecule that is part of the destruction complex, or a part of the “robber.” Wnt, as a cop, likes to check up on the citizens of his town and when present, he stabilizes the safety of his citizens by “ridding” of the robbers. This allows the town citizens to carry on with their duties of helping their children develop.
When Wnt is present in the brain, it binds to a “Frizzled” receptor, which then causes the dissociation of a destruction complex that normally “robs” a molecule, B-catenin, of its normal function. The inhibition of the destruction complex allows B-catenin levels to rise and B-catenin then diffuses into the nucleus of the cell where it increases gene transcription of proteins that are vital in neural development.
Kidnapping neural development
In the schizophrenic brain, there is a dramatic increase in dopamine levels within the brain. This is a problem because dopamine will bind to its receptors, and when it binds specifically to its D2 receptors, the D2 receptors directly bind and inhibit the workings of B-catenin, and thus a lack of protein production for neural development results.
The D2 receptor is similar to a kidnapper, in that it kidnaps B-catenin and keeps it from working. The activated D2 receptors also lead to the inhibition of another molecule, Akt. Akt normally functions as the helpful citizen, aiding citizens in need by keeping the bad guys at bay. However, when Akt is not able to keep the bad guys at bay, this leads to a functional destruction complex, or more specifically an increase in GSK3 activity, a large part of the destruction complex. This results in a lack of stabilized, functional B-catenin, and thus a decrease in protein production for neural development.
Forever Schizophrenic?
Currently, antipsychotic medications are prescribed to those suffering with schizophrenia in order to reduce both the positive and negative symptoms of schizophrenia, but these drugs fail to cure the disease itself. Antipsychotic drugs reduce symptoms of schizophrenia by acting as antagonists to the D2 receptors in the brain, similar to directly blockading the D2 receptors and ceasing their effects in the brain. The use of antipsychotic drugs is questionable when we consider all of their potential side effects, including tardive dyskinesia, acute dystonias, weight gain, nausea, drowsiness, restlessness, muscle spasms, among many others.
Is there hope in creating a drug or therapy that could potentially “fix” the neural disconnectivity in the schizophrenic brain? Will schizophrenics forever have to choose between suffering the symptoms of schizophrenia or the side effects of antipsychotics? If you are born schizophrenic, will you always live as a schizophrenic? Only time and research will tell.
For more information on the neuroscience behind schizophrenia and the Wnt/GSK3 Signaling Pathway, please visit:
https://www.ncbi.nlm.nih.gov/pubmed/23379509
Featured Image from:
https://i1.wp.com/cobbersonthebrain.areavoices.com/files/2017/10/wntfig1.jpg?ssl=1
