Wnt signaling pathway in schizophrenia

Schizophrenia is a fairly common psychiatric disorder. It is currently top ten disabling conditions worldwide for young adults. It is known for causing positive symptoms including hallucinations, delusions, and racing thoughts. However, it also has negative symptoms attributed such as cognitive disfunction.
Effective therapeutics for schizophrenia is difficult to come by mainly because of a lack of understanding of the disease. The most popular hypothesis is that schizophrenia is a developmental brain disorder causing a disfunction in neural connections. The exact area of the brain this is happening is a bit of a gray area, but from the symptoms it is thought to occur mainly in the pre-frontal cortex and the basal ganglia (the main dopamine output center in the brain).
Recent research has found Wnt signaling in the brain may have a significant role in schizophrenia etiology. Wnt signaling starts out by Wnt protein binding to a frizzled receptor (FZ) which causes an activation of the Disheveled (Dvl). This molecule breaks up the destruction complex which would have inhibited β-catanin, an important molecule in gene transcription. Another part of the puzzle is dopamine signaling. Schizophrenia patients have an increase in dopamine signaling which results in the inhibition of AKT enzyme which would have inhibited the destruction complex. Schizophrenics were also found to have a smaller number of AKT proteins which again, leads to an activation of the destruction complex and ultimately, a decrease in β-catanin activity resulting in a loss of gene transcription.
There are a few treatments that target certain areas of this signaling process, but many have proven ineffective such as Lithium. Lithium directly inhibits GSK3β, a key player in the destruction complex. However, for whatever reason it has shown ineffective for a majority of schizophrenic patients.
Anti-psychotics target the dopamine signaling in this process and has proven effective, however new treatments are needed for not all antipsychotics were effective in treating schizophrenia.
This research has opened a new door for schizophrenia treatments. With the discovery of the Wnt pathway’s role in schizophrenia, new drugs can be synthesized and possibly more effective treatments can be discovered.
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Image citation:
https://www.emaze.com/@ALFWTCCI/Schizophrenia