Schizophrenia: The Nature, The Nurture, The Ghosts
Ghosts
While sitting on a bench at the park enjoying the lovely weather, you notice a stranger sitting a couple of benches down from yours. They appear to be conversing with someone, but this person is out of your line of sight. After a couple more minutes of peaceful rest, you stand up to continue on with your day and to tend to the other responsibilities and events you have planned. You look over once more at the stranger who still appears to be in a conversation, but this time with a clear view you notice there doesn’t seem to be anyone near this individual besides yourself. You think back to an article you recently read describing the condition of schizophrenia.
Schizophrenia is a relatively common neurological disorder affecting an individual’s psyche. An exact cause for this condition remains elusive, but it is believed that there are strong genetic components and or altered brain chemistry or structures along with environmental factors in a percentage ratio of roughly 70:30 respectively contributing to the development of this disorder. The condition of schizophrenia is characterized by disconnected thoughts or experiences with reality. The most recognized and well-known symptoms fall under the category of positive symptoms (hallucinations, delusions, scrabbled thoughts, disorganized speech, movement irregularities) which are falsely believed to have a more debilitating effect on schizophrenics when in reality it’s the negative symptoms (lack of motivation, pleasure, emotion, inattention to cognitive input) that have a greater crippling effect.
Nature
One mechanism by which schizophrenia may occur is through malfunctions within the Wnt and GSK3 signaling pathways within the brain. The Wnt pathway functions to regulate the activity of an important molecule called Beta-catenin. In short, when the Wnt pathway is active within the brain, Beta-catenin is being produced which causes the cell to create proteins that are important for cellular functions. When the Wnt signaling pathway is off, the Beta-catenin is actively destroyed through the signaling of GSK3 which is another molecule within the Wnt signaling pathway. Schizophrenia occurs when there is insufficient Beta-catenin transcription. So, in simple terms:
- active Wnt = Beta-catenin = no schizophrenia
- high Beta-catenin = transcription of proteins = no schizophrenia
- low Beta-catenin = schizophrenia
- active GSK3 = destroyed Beta-catenin = schizophrenia
There are a number of factors that interplay with the Wnt signaling pathway making the study of schizophrenia and its cause complex. Drugs such as lithium show effects of increasing Wnt signaling pathway activation and inhibiting GSK3 which prevents GSK3 from destroying the needed Beta-catenin. Antipsychotic medications also regulate the production of Beta-catenin by interacting with the Dopamine pathway and Dopamine receptors which interlink with molecules within the Wnt pathway such as GSK3. Typically, Dopamine pathways activate GSK3, but antipsychotic medications block the dopamine pathways preventing the activation of GSK3 which also leads to an increase in Beta-catenin. Because of the significant factors of GSK3 and Wnt in the development of schizophrenia, it’s thought that inactivity of the Wnt pathway or overstimulation of GSK3 can lead to the development of schizophrenia.
Nurture
There are numerous details and complexities within cellular signaling which we could further explore, but it’s also important to consider the contributions of environmental factors as well. Proper prenatal care can significantly decrease the risk of developing schizophrenia. Factors such as illness, infection, and drug use while pregnant can put the child at risk of development. While pregnant, diabetes can increase the risk of a child’s development of the condition by 800% and a vitamin D deficiency can increase the risk by 4-fold. Proper management of diabetes, immunization of women prior to pregnancy, and other similar precautions can decrease the risk of development by 30%. Outside of prenatal care, complications in labor, urbanicity such as living in regions with populations of a million or more, increase risk by 500% and sexual abuse between the ages of 5 and 6 drastically increase the risk of development. The contributions from both the complex signaling pathways and the environmental factors make schizophrenia a challenging condition to study and even more so to fully understand. Further research is needed to illuminate the mysteries of this condition.
Sources
https://onlinelibrary.wiley.com/doi/full/10.1111/cge.12111
https://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml
https://www.mdedge.com/psychiatry/article/66140/schizophrenia-other-psychotic-disorders/negative-symptoms-schizophrenia-how#:~:text=Negative%20symptoms%20include%20blunting%20of,to%20social%20or%20cognitive%20input.