Cobbers on the Brain

A Developmental Issue?

While majority of Schizophrenia causation is a mystery to current scientists, the most prominent theory is one of brain development. People with schizophrenia have statistically shown delays in cognitive milestones, have smaller brain size, and are below the general population in cognitive ability. In addition, the majority of schizophrenia’s environmental factors interfere with proper brain development. These can include prenatal infection, prenatal famine, pre-eclampsia, infant infection, low birth weight, and even maternal depression.

Fig 1.  A chart displaying numerous types of environmental factors listed for schizophrenia

Biological Support:

With a new emphasis on brain development, scientists found a strong correlation between decreased Wnt pathway activity and schizophrenia. When active, the Wnt pathway increases cellular levels of a molecule called beta-catenin which activates genes critical for development. When the pathway is inactive, the body naturally creates a destruction complex that breaks down beta-catenin, reducing its concentration, and preventing developmental genes from being expressed. In conclusion, it is important for this pathway to be active during critical developmental periods.

Fig 2. The left column shows the accumulation of beta-catenin when the Wnt pathway is active and the left column depicts the breakdown of beta-catenin when the pathway is inactive.

So What Went Wrong?

There is a molecule in everybody’s brain called Akt that aids in disassembling the natural destruction complex. This means that high levels of Akt increase levels of beta-catenin and result in increased expression of developmental genes. However, postpartum schizophrenic patients were found to have significantly lower levels of Akt in their brains. People with schizophrenia, therefore, have decreased Wnt pathway activity resulting in developmental problems. Most antipsychotics prescribed to schizophrenic patients target the Wnt pathway to alleviate symptoms. They usually increase the activity of Wnt signaling by increasing Akt activity, decreasing inhibitors of Akt, or directly inhibiting the destruction complex formation. While these drugs do a phenomenal job of treating the symptoms they still do not cure or reverse the permanent damage done to their brain.

Problems of Developmental Diseases:

The hard part about developmental disorders, like schizophrenia, is that majority of the damage is completed early in life. The devastation on the brain is then usually cemented after the individual reaches adulthood and brain development has ceased. This means that even if we did know how to treat schizophrenia, the treatment would have to be done early in a patient’s life to catch the developmental periods. This would have to lead to an intensive pre-natal screening and tests made specifically for diagnosing schizophrenia. Unfortunately, these options would probably be incredibly expensive which would prevent them from reaching their true at-risk population.

Another problem is that schizophrenia is usually not diagnosed until the late teens to early twenties making it impossible to catch the disease early. Many of schizophrenia’s positive symptoms, including delusions and hallucinations, can be attributed to normal childhood behavior like imaginary friends and make-believe games. Then in the teenage years, most parents and doctors correlate symptoms to hormone imbalances and puberty. There is also a lot of maturing and development that occurs during this time so many doctors don’t want to diagnose a patient prematurely.

Together these current problems make it hard to intervein early for schizophrenic patients. Future research should focus on finding early warning signs for the disease and its progression throughout early childhood and into adolescence. Majority of our research is only on adults since they are the only ones diagnosed, but much more could be learned from researching younger patients. Additionally, more extensive research must be found about the specific genes affected by decreased Akt activity.

Source: https://www.apa.org/helpcenter/recognizing-schizophrenia.aspx

Recently in popular culture is has become a movement of acceptance and understanding when thinking about mental health. More often than not this just ends up including the more well know deviations from the norm and other disorders are left forgotten. One of the most misunderstood disorders is schizophrenia. Whether it be word of mouth, culturally, socially, or taught to us through the media there is a large misconception about what schizophrenia really is.

Dissociative Identity Disorder vs Schizophrenia

It is important to start here because this is the idea that many people have in their head when they think of schizophrenia. This tends to be one of the most common misconceptions, instead regarding schizophrenia as someone having multiple personalities. Multiple personalities, called Dissociative Identity Disorder (DID), is coupled in with three other types but of dissociative disorders but DID is characterized through the thought that one individual has multiple personalities. This stands in contrast to schizophrenia which often is disorganized speech, delusions, and hallucinations. An individual may also exhibit lesser known symptoms including abnormal behavior, unclear and confused thinking, and lack of motivation. Schizophrenia may also be presented with other mental illnesses as well, often observed in individuals with depression, anxiety, OCD, or substance abuse disorders. At its core, schizophrenia is a very different disorder from DID and it is critical to work toward understanding of both.

 

 

 

 

 

 

 

 

 

 

 

Figure 1: Here is a small table that briefly goes into more detail about the differences between DID and schizophrenia Source:http://www.differencebetween.net/science/health/difference-between-dissociative-identity-disorder-did-and-schizophrenia/

Hearing Voices

Although schizophrenia is often diagnosed through observing symptoms of delusions and hallucinations these behaviors are not exhibited 24/7. Along with the thought that schizophrenia is multiple personalities, many people also think that those with this disorder constantly hear other voices. Some people with schizophrenia do experience episodes that may include voices but about one fourths of individuals do not experience voices (auditory hallucinations). The diagnostic criteria of schizophrenia state that the patient must have at least one of the symptoms stated above, hallucinations and delusions, or disorganized speech for a period of one month.

Figure 2: An artist’s illustration of what it is like living with her bipolar disorder. Although a difference disorder than schizophrenia, the overlying message is the same: sometimes there are voices but this is not something that is experienced by everybody.

Artist: Stumbling Mind — Katie

Source: https://stumblingmind.com/2017/02/06/doubting-myself-hearing-voices/

Other behaviors that are common with schizophrenia are diminished emotional responses, depersonalization, disturbed sleep pattern, and inappropriate responses. It is the case with some individuals that they may experience voices and hallucinations frequently but that may not be the same from case to case. Because of this lack of knowledge about schizophrenia and how it affects the people who have been diagnosed it causes a general sense of fear from the public, which tends to be exacerbated by media portrayal. This misunderstanding of the disorder is also linked to the thought that those who have schizophrenia tend to be dangerous.  

People with Schizophrenia are Dangerous

Something that appears to be ingrained in human nature is to be afraid of things that we do not know. It is why people are afraid of the ocean and some fear the infinite depth of space. This is not only seen in phenomenons of nature but also throughout society. We do not understand those who are different from us in great degrees and so often the way that we view those types of people is tainted. As mentioned above, this includes the way that media shows us what is different influences our thoughts. It is far too common in movies and television shows that individuals who are behind the crime are affected by disorders such as schizophrenia. This adds to the stereotype that people with schizophrenia are violent and dangerous, which is not the case. Although schizophrenia may be unpredictable in actions most of the individuals who are affected live normal lives do not engage in violent activity. Even those who are receiving treatment for the disorder, according to one study, are no more dangerous than those who are not. It is essential to remember that the way that schizophrenia impacts someone is a spectrum and does not ring true for the next person.

Figure 3: This is a compiled image of Patrick Bateman (played by Christian Bale) in the film American Psycho. Although Bateman’s mental health is not addressed, some speculate that he suffered from undiagnosed schizophrenia and adds to the stigma of those with schizophrenia being dangerous.

Source: https://www.chess.com/clubs/forum/view/playing-chess-benefit-schizophrenia-patients

It’s an Uncommon Disorder Caused by Bad Parenting

1 out every 100 people develop schizophrenia in the general population. There is a role of genetics as well in the disorder, the risk increasing to in regards to family members. Many people think that schizophrenia is uncommon, mostly because only the very sparse extreme cases are reported on and told to the public, but it is much more common than you may think. Although symptoms don’t begin to persist and become diagnosable until early to late twenties there is another myth that coupled with genetic factors, schizophrenia is due to bad parenting. This idea was proposed by a group of researchers in the 1950s with most of the blame falling on the mother. The claim today holds no ground but like what was observed with the falsifying of vaccine records, the public tends to hold on to things even though they might not be correct. High stress situations that take place at home may make the symptoms of schizophrenia but are not the cause of the disorder.

Figure 4: The myth that bad parenting causes mental illnesses such as schizophrenia has been discredited although some still refer to it.

Source: https://wundersameslernen.de/wieviel-ungehorsam-darf-s-denn-sein/

There are many rumors that cause the idea of what schizophrenia to be distorted but it is important to know the reality of the disorder. Understanding this group of our population allows for more education about the topic and ultimately to acceptance.

 

Figure 5: A quote from someone who lives with schizophrenia. It is his, and my, aim to inform everybody about schizophrenia to end the stigma attached.

Source: https://www.rtor.org/2016/08/23/quotes-on-schizophrenia/

 

Sources:  

http://www.schizophrenia.ca/docs/Myths%20Half-truths%20and%20Common%20Misconceptions%20about%20Schizophrenia%20and%20Severe%20and%20Persistent%20Mental%20Illness%20(SPMI).pdf

 

https://www.webmd.com/schizophrenia/guide/schizophrenia-myths-and-facts#1

 

https://mentalillnesspolicy.org/medical/schizophrenia.html

 

https://www.verywellmind.com/dissociative-disorder-vs-schizophrenia-4160180

https://www.psycom.net/schizophrenia-dsm-5-definition/

What is Schizophrenia:

Schizophrenia is a long-term mental disorder where an individual has an inability to interpret reality. This is often characterized by hallucinations, delusions, extremely disorganized thinking and behavior that impairs daily functioning. Schizophrenia affects different individuals differently as the severity can range from mild to more extreme in some cases.

Toxic Media:

The media is dangerous in that it portrays only the extreme cases of any disease, Schizophrenia in this case, and often inaccurately. This creates false stereotypes and unnecessary fears surrounding this disease. Not all schizophrenics are violent, in fact only a very small portion of the population are. People with schizophrenia are normal people who just struggle with a disease just like anyone else. We as a society need to learn to better understand this disease and its implication so that we can better help those around us who struggle with this disease.

What is happening in the Brain:

The problem occurring in the brain of individual who suffers from schizophrenia is the disruption of what we call the dopamine pathway, a pathway that has a large impact on proper brain functioning. In this pathway where is a molecule called glycogen synthase kinase 3 (GSK3) which has been found to be highly overactive in individuals who suffer from schizophrenia. When dopamine binds to a D2 receptor, it activates Akt which then phosphorylates GSK3 rendering it inactive. However, this and many other checks and balances, are disrupted causing GSK3 to avoid its inhibition and thus disrupt the transcription of certain, necessary genes crucial to proper development due to it being vastly overactive in the brain.

Treatment:

Due to the complexity of the pathway, treating this disease has been difficult for scientists to figure out. Just like many mental diseases, finding a cure is difficult. Most treatments today strive to only alleviate the symptoms as we work to better understand what exactly is happening in the brain. These medications work to inhibit GSK3 and make it less active. Lithium is the most common as it directly inhibits GSK3, but hopefully more advanced treatment will continue to surface as we work to understand better how to help these individuals.

What can you do?

Making a difference in the lives of individuals who suffer from schizophrenia can seem impossible as we aren’t all scientist who study pathways on a molecular level. However, there is something very important that we can all do to make a difference. This involves getting educated, educating those around, and treating those will schizophrenia as normal people as they are. It should be our goal to erase the stereotypes and fears surrounding schizophrenia that the media and lack of education has created. We can all make a difference in this way and you should strive to do just that.

 

The Story of Schizophrenia

With symptoms ranging from quietness to experiencing hallucinations or delusions, schizophrenia is a mental health illness that is difficult to diagnose and difficult to biologically analyze. Generally, the symptoms of schizophrenia are manifested in individuals who are in their late teens to early twenties, but brain development before being born can cause varying susceptibility to the disorder.

It is thought that certain messenger chemicals in the brain (neurotransmitters) causing an imbalance of communication between neurons play a large role in the development of schizophrenia. The image below represents the hypothesized neurotransmitters/pathways responsible for the three classes of symptoms seen in schizophrenia: positive, negative, and cognitive.

Certain drug treatments target or act with these neurotransmitters to alleviate symptoms of the disorder. One example of this is a drug that blocks the receptor that dopamine (a neurotransmitter) would normally bind to. How would this help alleviate symptoms? After dopamine is bound to it’s receptor, Wnt, a signaling pathway in the brain can’t function properly. The final affect of this inhibited signaling is gene expression that is improperly regulated.

Artstract: The story of Wnt. This image depicts the Wnt signaling pathway including two scenarios, one with Wnt ligand binding and one without binding. Wnt binding is implicated in regulated gene transcription through TCF/LEF mediated transcription.

This is not a specific picture of schizophrenia, but does help to explain the large variety of symptoms and irregularities seen in the brains of individuals diagnosed with the disorder.

The unfortunate truth for schizophrenia is that there is still a long way to go before the full mechanism of the disorder is understood. For now, there is no real way to “cure” schizophrenia, and treatment options focus on alleviating the symptoms of faulty brain wiring, and hopefully leading to a more manageable and independent life. In future research, exploring treatment options including the Wnt signaling molecules as target cells could provide some relief from the wide range of symptoms. Overall, more understanding of specific mechanisms detailing the schizophrenia story is needed to truly unpack how the disorder is manifested and experienced.

References/Further research

• https://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml
• https://www.placesforpeople.org/hear-our-voices/
• http://www.mentalhealthamerica.net/conditions/schizophrenia
• https://youtu.be/6Qpl-3eR6eE
• https://www.placesforpeople.org/hear-our-voices/

WARNING: If you or your family have a history of mental illnesses or vertigo, we strongly advise that you DO NOT participate in this simulation as it could potentially trigger those illnesses to begin.

Image References

• https://progress.im/en/content/dopamine-synthesis-common-factor-genetic-and-environmental-risks-schizophrenia
• https://www.inspiremalibu.com/blog/drug-addiction/schizophrenia-and-the-risks-of-substance-abuse/
• https://www.mdpi.com/1422-0067/18/8/1689/htm

 

 

 

 

 

 

Schizophrenia is a severely debilitating disease for one’s psyche. Unfortunately, the only thing we have to separate reality from nightmares for individuals with this disease is constant use of mind-numbing anti psychotics.

 

What is the disease?

Schizophrenia is a psychiatric disease that results in severe impairments in daily life. Some common positive symptoms of schizophrenia are delusions, hallucinations, and disorganized thinking. This means that the person has a difficult time producing a normal perception of the world. Many see or hear things that are not there and have abnormal beliefs or paranoia. Some common negative symptoms of schizophrenia are lack of hygiene, reduced eye contact, and lack of emotion. The combination of all of these symptoms make it very difficult to live a normal life and people with schizophrenia are often medicated all of their life to improve these symptoms.

 

Looking beyond the symptoms

Recent research on the neural cause of schizophrenia has uncovered some clues as to why this disease occurs. The Wnt pathway in neurochemistry is a sequence of cellular events often used to facilitate the development of the central nervous system. It controls the amount of β-catenin in the cytosol of neurons which is a useful molecule for the transcription of developmental genes. It is believed that this Wnt pathway is abnormal in schizophrenia patients causing abnormalities in brain development. Neurons end up connecting incorrectly in the pre-frontal cortex and result in many of the common schizophrenic symptoms.

 

How should this disease be addressed in the future?

Reducing the severity of schizophrenic symptoms is all we have at this point in the treatment of schizophrenia. Anti psychotics are used to essentially “numb” the person from their positive symptoms to better help them to connect to reality. However, these drugs to not treat the disease at its source. The abnormal brain connections seen in schizophrenia still exist while anti psychotics are being used leaving the person still susceptible to emotional and social impairments. Although the use of anti psychotics is helpful for some symptoms, it is in no way a cure.

In the future, it may be beneficial to look deeper into the underlying causes of this disease. Recent research has uncovered many things that we did not know about schizophrenia but has created just as many new questions. What genes are involved? How is development changed from abnormal Wnt signaling? What specific brain regions are impacted? All of these questions need to be answered more entirely to begin developing a cure for this disease. Rewiring an adult brain is a tall order and perhaps we will never get to the point of curing this disease but will find effective ways at preventing it. Targeting the Wnt pathway specifically may bring new light in the treatment of schizophrenia. Perhaps at an early age everyone would get a checkup on their risk of getting the disease based on gene expression tests. We would then know if Wnt would need to be inhibited or activated to prevent abnormal development.

It has become very apparent that the neural mechanism of schizophrenia is unimaginably complex. No one in the world can tell you exactly what is going on in the brains of schizophrenic patients but one thing is certain; further research is necessary to effectively treat and prevent this disease. Treatments we have today do help but have limits. People on anti psychotics essentially have their personalities taken away from while being numbed with schizophrenic drugs. Sure their positive symptoms improve but they are stripped of who they are as a person. It is important for us to understand how treatments of complex diseases like schizophrenia have consequences that we do not always think about.