Addiction: Is It Really A Choice?

Posted on February 26, 2023 by / 0 Comment

Artwork by Olivia Pederson

What is Addiction?

In simple terms, addiction is a loss of control of drug use. The word “drug” doesn’t mean you can only be addicted to actual drugs. There are many things people can be addicted to such as, shopping, drinking, gambling, sex, social media, sugar, and the list goes on. The hot topic along with addiction is whether it is a choice or not to become addicted to a certain something. There are many people on either side of that topic but knowing all of the science and chemistry behind it is the only way to truly argue if it is a choice or not.

People see ‘addicts’ and assume that they have no self-control, no impulse control, and are untrustworthy. When looking at the science and understand just what is happening in the brain during this vicious cycle of addiction, we can see that is goes way further than just making a choice or simply getting short-term treatment.

Statistically, over half of Americans have experienced some type of substance abuse problem within their families. This is only looking at alcohol and drug use, not taking into account the many other types of addiction families can struggle with. The statistics look a little different for recovery of addiction, but that will be talked about at the end.

What is going on in the brain?

Specifically, the most common drugs of abuse are cocaine, heroin, and methamphetamines. These drugs all act by increasing the levels of dopamine in the brain. Dopamine has more to it than just being the “happy” chemical. It is responsible for motivation and reward, which is why an increase is so addictive because it is what the drugs of abuse are providing. These drugs of abuse happen to activate our reward pathway within the brain. This pathway includes the VTA and nucleus accumbens (NAc). Once a drug is taken and the pathway is activated and dopamine is increased the feeling will be reinforced within the brain. This will lead to people wanting to use over and over again to achieve this feeling or “high”.

Addicts will choose this feeling over anything else in their life because eventually their brains don’t feel motivation or reward for any other activity other than using their drug of choice. Even with their drug of choice, they will eventually need to increase the amount they take to keep that high.

These drugs of abuse effect the brain much more than other types of natural rewards (food, social interaction). The brain is overwhelmed with the amount of dopamine that is being released because of the drugs, so it tries to adapt by reducing the amount of dopamine receptors on the neurons. This makes the brain less responsive to the drug but in turn decreases the brains natural reward system. After these changes, a person will need to take more drugs to get to the same level of high that they were at before building up their tolerance.

Part of the brain responsible for reason, judgment, learning, and memory begin to have changes as well. In some spots, the neurons are pruned back whereas in other regions there are more connections, completely changing the shape of the neuron. After all of these changes, the drug-seeking behavior becomes habit and the person becomes addicted.

These changes to the neurons don’t just “go away” after the person quits the drugs of abuse. These changes can last for months or even years! The brain will not immediately return toward normal, which is why relapse and conditioning is an important factor that can effect successful recovery.

Role of Relapse and Conditioning:

Relapse is defined as when a person returns to using drugs or alcohol after a period of sobriety. There are many factors that contribute to relapsing, which can be seen in this image. After the neurons are changed and the feeling and memories of drugs are implanted into someones brain it can be extremely hard to just give it up. The brain is still searching for this increased reward feeling and it isn’t getting it from ‘normal’ daily activities which can make turning back to drugs really tempting.

Conditioning is defined as a higher dose of drugs that can be tolerated when external stimuli is associated with prior administration of the drug is present. Basically, this means that if someone is doing drugs in the same room at the same time everyday they will eventually build up a tolerance because their brain will release the the effects of the drug before it is even taken. This leads to a tolerance, and if the drug is taken with any of the external factors changed it can lead to an overdose.

In the End:

Recovery is much more complex than it is made out to be. There are many factors that play a part in the life of an addict. It is not as simple as quitting cold turkey sometimes. There are memories and outside factors that can effect the ability to remain sober. Being educated on all the facts of addiction can help stop the stigma that it is just a simple choice. It truly goes down to the cellular and molecular level and changes are happening at those levels making it difficult to change behaviors right away. Treatment for addiction can be very expensive and difficult. A lot of people are not even getting the help that they need because they are not sure where to even begin in their recovery journey, or they might not think it will even work. Every person is so unique and it can be hard to find the right treatment and the right length of treatment to fully recover. Also, returning to a routine can be difficult when the external factors are still a part of someones life. Patience and education is key when talking to someone with an addiction or talking to someone about addiction.

References:

naatp.org/addiction-treatment-statistics

learn.genetics.utah.edu/…tion/brainchange

pubmed.ncbi.nlm.nih.gov/16251986

statista.com/…/us-families-affected-by-substance-abuse

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A New Model for Schizophrenia?

Posted on February 22, 2023 by / 0 Comment

A New Model for Schizophrenia?

What is Schizophrenia?

Schizophrenia is a mental illness that is heavily stigmatized. Once diagnosed, it has an impact on both the patients and those around them. The symptoms are so severe and complicated that they are nearly impossible to fully treat. The most commonly used treatments target the positive symptoms of schizophrenia, such as delusions and hallucinations.

How is Stress Related to Schizophrenia?

Stress is extremely harmful to all populations. The most vulnerable are children who have predisposed genes linked to schizophrenia. They will almost certainly develop schizophrenia if they have a stressful childhood. Early childhood environmental disturbances can disrupt the biological development clock and processes, and can later manifest as brain abnormalities that lead to psychosis.

The Role of Wnt Signaling

In a paper by Singh, Schizophrenia was defined as a neurodevelopmental disorder caused by a wnt pathway malfunction. The underlying pathology and biology of the disease are unclear at the molecular level. In addition to positive and negative symptoms, schizophrenia is associated with cognitive delay and early brain function deficits.

Frontiers | Wnt Signaling and Its Significance Within the Tumor Microenvironment: Novel Therapeutic Insights — Figure 1: On and Off canonical Wnt Signaling Pathways

The authors bring up a novel way to study schizophrenia and its underlying molecular pathway by linking it to the wnt pathway. Beta catenin is a key player in the wnt signaling pathway. In the absence of wnt as a ligand, a destruction complex is active. The destruction complex composed of gsk3beta, axin, apc, and ck1 alpha reduces the cytosolic concentration of beta catenin via proteasomal degradation. The destruction complex dissociates when wnt is present. The subsequent increase in beta catenin activates the nucleus’ TCF/LEF transcription factors, inducing transcription of a target gene. The figure below is a good schematic of this signaling pathway.

The mystery of schizophrenia | Mint — Figure 2: Coronal View of: Schizophrenic brain (left) and normal brain (right)

In the study, the authors point out that in schizophrenia, gsk3beta is overactive due to absence of AKT-its inhibitory regulator. This ensures continued degradation of beta catenin, thereby silencing transcription of TCF/LEF genes. This can cause cellular responses that build up to become development abnormalities in tissues and organs like the hippocampus, hypothalamus, and even the cortex. This hypothesis explains why schizophrenia tends to decrease brain volume as shown in the image here.

In addition to gsk3beta, Singh discusses 3 other pointers that link schizophrenia to wnt signaling:

– In schizophrenia patients, the expression of several Wnt-related genes was significantly reduced in the prefrontal cortex.
– Genetic variations in genes (DISC1) involved in the Wnt signaling pathway may increase the risk of developing schizophrenia.
– Antipsychotic drugs used to treat schizophrenia modulate the Wnt signaling pathway.

All things considered, the connection between schizophrenia and the Wnt signaling pathway is complicated and still not entirely understood. Evidence, however, points to the possibility that abnormalities in the Wnt signaling pathway may contribute to the pathophysiology of schizophrenia, and that focusing on this pathway could be a promising route for the creation of novel therapies.

The medical research field needs more such advances because they are critical to drug and therapy enhancement. Identifying patient populations with specific biological pathway markers could identify them as the best candidates for medications, resulting in the personal pharmacology needed to treat psychiatric disorders, making treatment more efficient and effective. This type of research could aid in explaining how and why medications work. For example, how and why some antipsychotics that target GSK3 are effective in the treatment of schizophrenia.

https://moodle.cord.edu/pluginfile.php/1239779/mod_resource/content/2/2013%20wnt%20GSK%20and%20schizophrenia.pdf

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Disease

What Wnt wrong in Schizophrenia

Posted on February 21, 2023 by / 0 Comment

What is Schizophrenia:

Schizophrenia is a chronic brain disorder that is characterized by delusions and hallucinations. Delusions are false beliefs that an individual believes to be true. Delusions can be misinterpreting someone’s actions to be something more to the person with schizophrenia. Another symptom is hallucinations, hallucinations are where the individual experiences auditory and visual stimuli of something that does not exist. A majority of hallucinations are linked to hearing voices that are not present. Currently little is known about the cause of Schizophrenia and there are not any definite treatments.

Schizophrenia causes:

Numerous studies have looked at Schizophrenia to determine what causes and no clear-cut definite result has been determined. However, it has been observed that infection in utero has been linked to disrupting fetal brain development and contribute towards the child developing schizophrenia. A marker for schizophrenia at a young age is the delay of reaching cognitive milestones. Additionally, there has been a link between brain size and those diagnosed with Schizophrenia. Those diagnosed with schizophrenia have been observed to have less gray matter due to synaptic pruning and to have a smaller hippocampus and amygdala compared to an individual without schizophrenia.

Research has also looked at the genetics of schizophrenia and found that it is heritable. However, through exome sequencing it was discovered that a chromosomal mutation was responsible for the disease. A mutation on chromosome 14q32 reduces the production of the protein Akt. An imbalance of Akt has been linked to schizophrenia due to the protein’s role in the Wnt pathway.

Wnt pathway:

The Wnt signaling pathway is responsible for neural circuitry development and synaptic plasticity. The Wnt pathway is activated by the binding of Wnt ligands to the frizzled receptor which results in the dissociation of the destruction complex and the decreased phosphorylation of β-catenin. This allows for the accumulation of β-catenin and for the translocation to the nucleus for gene transcription. However, in the absence of the Wnt ligand binding the Axin, APC, CK1α complex is destroyed. The destruction of this complex leads to the activation of GSK-3β and the proteasomal degradation of β-catenin. The consequence of this is that GSK-3β will continue to tag β-catenin for degradation not allowing it to continue to the nucleus. Without proceeding to the nucleus for gene transcription cell differentiation, proliferation, and apoptosis are not able to be carried out.

Schizophrenia treatments

Schizophrenia is characterized by a reduction in β-catenin. Due to β-catenin being produced by the Wnt pathway dysfunction of the pathway is the leading cause of Schizophrenia. Therefore, activation of the Wnt signaling pathway is hypothesized to aid in the treatment of schizophrenia. One treatment method would be to inhibit dopamine signaling on the D2 receptor. Overabundance of dopamine has been recorded as a precursor to schizophrenia and directly activates GSK-3β, in turn degrading β-catenin. Therefore, by inhibiting dopamine Wnt signaling could be stabilized. Another potential treatment is Lithium, lithium directly inhibits GSK-3β since it competes with the binding of magnesium. Lastly, treatments that target metabotropic glutamate receptors could be a potential treatment. Targeting these receptors would increase Akt activation, decrease GSK-3β activation, ultimately resulting in β-catenin accumulation.

Conclusion

Schizophrenia is a life altering disorder that leaves individuals with numerous debilitating symptoms. However, with the help of current research a link between the Wnt signaling pathway and schizophrenia has been found. With this knowledge schizophrenia may be more effectively treated since the dysfunctional pathway is known. By knowing that reduced β-catenin levels due to the dysfunction of Wnt signaling are the culprit for schizophrenia drugs that target the activation of the Wnt pathway, inhibit D2 dopamine receptors, inhibit GSK-3β, or activate Akt are potential treatments for raising β-catenin levels and ultimately treating schizophrenia.

References

Feature image: https://www.tpr.org/bioscience-medicine/2018-12-06/san-antonio-man-working-to-erase-stigma-of-schizophrenia
Pathway schematic: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-017-0471-6

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Treatment of Schizophrenia

Posted on February 21, 2023 by / 0 Comment

Treatment of Schizophrenia

Schizophrenia is a very consequential mental illness, its effects can alter how someone can think, feel, and act. Often it tends to go untreated. According to WHO only 31.3% of people with schizophrenia get treatment from specialists. You might ask yourself “if help is offered, why don’t people get the help?” Well, it isn’tthat easy.

Pathways Targeted by Anti-Psychotics.

There are four major pathways that anti-psychotics can target. The mesolimbic pathway is altered because people with schizophrenia have too much dopamine. This can cause satisfaction, emotions, and thoughts not be the same. Anti-psychotics lower dopamine transmission. The mesocortical pathway controls cognition and reward processing. The nigrostriatal pathway controls movement can cause things like tics. The tuberoinfundibular pathway gets effected by the high dopamine levels by causing too much prolactin. This causes the hysteria and hallucinations.

Most anti-psychotics target dopamine receptors in the brain. They block the receptors so that dopamine isn’t processed that cause the symptoms of schizophrenia. Which again you still might be asking yourself “why don’t they take the treatment?”

What Happens at These Receptors?

Antipsychotics cause D2 receptors to inhibit the enzyme Akt. Akt is responsible for the phosphorylation of GSK3β. Antipsychotics cause the GSK3β to be inhibited.

In medicated schizophrenia patients compared to ones not treated with an anti-psychotic, non- medicated had 5.8% more active D2 receptors.

The dopamine D2 receptor releases clozapine and quetiapine (both are commonly used to treat schizophrenia) more rapidly than it do any of the other antipsychotic drugs.

Perceived Effects of Anti-Psychotics

It inhibits dopamine transmission; it can cause people’s lives to become dull. Sadly, it seems to be a hit or miss acting. Yes, anti-psychotics can stop extreme symptoms, but it also inhibits dopamine transmission for typical everyday life. There are things in life that naturally produce dopamine you don’t even think of. Any sort of action or activity that gives you satisfaction gets dulled while on anti-psychotics. I am not sure about you, but simple things even like selfcare Sunday night to get ready for the upcoming week is something I look forward too. I get so much satisfaction from doing a facemask and crawling into a freshly washed and made bed. While on anti-psychotics, that wouldn’t be rewarding. It can cause people to be a lot less motivated.

Another factor that often gets mentioned is the stigmatism about taking “anti-psychotics.” Think of the word means, I personally think “undoing-the delusion.” As much as I don’t want to say it, but in society it is made to seem if you take anti-psychotics you are “crazy.” Which I can understand how that stigmatism happened due to some cases of symptoms. Yet, if we all had the same unbalance within ours brains we’d be “crazy” too. At the end of the day, we don’t and we can’t undo it for others that do. So truly tagging such negative ideals to something so impacting such a schizophrenia is unfair. Those that deal with it are already just trying to deal with impacts.

The Future of Treatment

As time goes on so does research, more suitable treatment plans are being investigated. A middle ground, not an all or nothing strategy is the goal. Recently an oral compound SEP-363856, has been studied as a medication for schizophrenia. A 2020 study posted to the New England Medical Journal has studied SEP-363856. It isn’t a D2 inhibitor, but an agonist at TAAR1. TAAR1 is a G-coupled protein receptor that has been shown to alter dopamine, serotonin, and glutamate activity. It is currently in phase 3 of clinical testing. Most studies were short, (around 4 months long) yet have shown positive results. The only one thing negative thing I can find so far on this drug is that it may be suitable for mild Schizophrenia cases. Another note on treatment plans I found is that majority of treatment is being done to treat Schizophrenia. There isn’t much being done or real definitive answers to help the physical brain matter of people with Schizophrenia. That not too much can be done for preventative care.

A Peak into Schizophrenia

I found this little youtube video that has a young boy with schizophrenia and his treatment team. I think it is worth the watch. You can read as much as you want to try to understand what symptoms may be like, this video helps me see what it is somewhat like going off of this real life story. It also mentions another treatment plan that is in clinical trial, this one focuses on the auditory system. Which personally blows my mind that so far it seems to be effective. It doesn’t effect dopamine pathways which cuts out the bad effects of anti-psychotics. Instead it helps with auditory hallucinations. It targets the processings within the brain.

Sources

https://www.who.int/news-room/fact-sheets/detail/schizophrenia

https://pubmed.ncbi.nlm.nih.gov/32294346/

https://psychopharmacologyinstitute.com/publication/the-four-dopamine-pathways-relevant-to-antipsychotics-pharmacology-2096

https://www.nature.com/articles/s41398-021-01331-9#:~:text=SEP%2D363856%20is%20a%20trace,for%20the%20treatment%20of%20schizophrenia

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Schizophrenia in the developing mind

Posted on February 21, 2023 by / 0 Comment

Schizophrenia is hypothesized to be a brain developmental disorder that can be diagnosed or evident in late adolescence or early adulthood. This mental illness disorder can be characterized by hallucinations, delusions, social withdrawal, and cognitive disabilities. The main concern with this disorder is that the onset can be in adolescence childhood, which is a critical period for the brain’s neural development and growth. Therefore, the main question is how do we focus more on prevention along with treatment for Schizophrenia?

In a brain with Schizophrenia it is evident that there is cortical thinning in the superior temporal gyrus and patients with Schizophrenia have a smaller hippocampus, amygdala, thalamus. Suggesting a possible correlation to Alzheimer’s disease as the hippocampus is the first portion of the brain to be affected. Therefore, with a smaller brain volume there is greater lateral and ventricle volumes and as a result greater cerebrospinal fluid. In terms of genes, the protein C4 from a C4 gene on chromosome 6 puts an individual at greater risk for Schizophrenia.

As related to the article, An emerging role for Wnt and GSK3 signaling pathways in schizophrenia, the pathway related to Schizophrenia is the Wnt signaling pathway. This pathway is based in the role it plays in the neural development to adult neural circuit function as it relates to Schizophrenia. During developmental stages patients with schizophrenia may show delays in certain milestones such as problems with neuromotor development, poor performance on cognitive tests, problems with speech, and difficulties in social adjustment. As it relates to development, studies have suggested that there is a correlation between utero and early environmental factors like infection that could play a role during pregnancy in later development of Schizophrenia. Therefore, disrupting fetal brain development from unfortunate events during pregnancy and increasing the risk of child to develop Schizophrenia.

https://doi.org/10.1111/cge.12111

As briefly discussed in small break out groups, prenatal vitamins were suggested to possibly have part to increase the likelihood of developing schizophrenia in the child later on. However, from a nutrition standpoint prenatal vitamins contain important nutrients such as folic acid or folate that help to drastically decrease the risk of the fetus having spina bifida. On the argument that prenatal vitamins could increase the risk, I question the role folate plays with schizophrenia. As a result in vitro and in vivo studies suggest that folate deficiency increases risk of Schizophrenia in the developing fetus. Considering that with folate deficiency there is also higher levels of homocysteine that can build up in the blood. Homocysteine creates greater risk for not only cardiovascular disease but also negatively impacting brain development from neuronal dysfunction in a developing fetus. Higher homocysteine levels have also been seen in patients with Alzheimer’s disease or other forms of dementia.

Along with this, a prenatal supplement in the nutrition world is understood as a supplement; a supplement should go along with proper nutrition from food otherwise the effects and benefits could be impacted. Nutrition plays a key role in fetal development early on and as a more recently discovered mental illness there is still a lot to learn about Schizophrenia. More research is needed on the topic of when Schizophrenia develops and whether or not there are ways to prevent it or better treat this disorder.

Citations:

Schizophrenia’s strongest known genetic risk deconstructed. NIH, 2016. https://www.nih.gov/news-events/news-releases/schizophrenias-strongest-known-genetic-risk-deconstructed

An emerging role for Wnt and GSK3 signaling pathways in Schizophrenia. Singh, KK. Developmental Biology: Frontiers for clinical genetics, 2013. Wiley Online Library. https://doi.org/10.1111/cge.12111

Childhood developmental abnormalities in Schizophrenia: evidence from high-risk studies. Suvisaari, J., tuulio-Henriksson, A., Lonnqvist, J. Schizophrenia Research, 2003. Science Direct. https://www.sciencedirect.com/science/article/pii/S0920996402002347?via%3Dihub#BIB12

The Origins of Schizophrenia, edited by Alan Brown, and Paul Patterson, Columbia University Press, 2011. ProQuest Ebook Central, https://ebookcentral.proquest.com/lib/cord-ebooks/detail.action?docID=909358.

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What causes Schizophrenia and how can we stop it before it becomes a problem?

Posted on February 21, 2023 by / 0 Comment

Bipolar disorder, major depression, and schizophrenia are psychiatric conditions that make daily life difficult for many in society. Whether it’s the person who suffers from the disease, their family and friends, or even their caretaker, schizophrenia can be especially difficult to handle. Characterised broadly as a condition where someone’s reality is viewed abnormally, those with schizophrenia can experience disorderly thinking that can lead all the way to having hallucinations and delusions. This can impair their daily life often leading to the need for full time care and oversight. Current schizophrenia treatments include the use of antipsychotic medications which often have multiple side effects to the patient, ultimately leading to a low patient compliance. Beyond the lack of current treatment, the factors that contribute to the diagnosis are still under scrutiny. At a basic level, schizophrenia can see its rise from interruption of proper neural development in adolescence. A review by Michaud and Pourquie dove into the molecular pathways that have shown potential contributing factors to this developmental dysfunction.

Two Important Molecules

Michaud and Pourquie devoted their attention to a molecular pathway that involves two molecules, Wnt and GSK3β. Wnt is a molecule that binds outside of the cell and is responsible for maintaining the activation of GSK3β inside of the cell. GSKβ, when it is activated by Wnt receptors, will inhibit the action of another molecule called β-Catenin. β-Catenin is responsible for the transcription of genes in the cell nucleus that are pivotal for proper neurological development. Thus, schizophrenia at its simplest form may be linked to the inhibition of β-Catenin by Wnt and GSK3β signalling.

Above is Figure 2 from the review placed next to a simplified depiction of the two factors that affect β-Catenin and subsequent development of schizophrenia.

Multiple different factors are being studied that affect Wnt-GSK3β signalling. One of the biggest molecules that contributes to this is dopamine. When there is a high amount of dopamine signalling, a cell will allow GSK3β to remain in its active state. When this occurs, β-Catenin will remain inhibited. This will lead to dysfunction of cell development.

Genetics

Genetics are also being considered as a factor that contributes to the development of schizophrenia. Research has assessed specific genes that may contribute to the disease along with specific changes to the individual “codes” that make up a DNA message; these are called single nucleotide variants. There are also copy number variants, which are composed of multiple genes. These can contribute to the development of schizophrenia by affecting the proper development of neurons whether it be through its affect to signalling mechanisms or other factors. Animal models are currently being used to assess these genetic factors but more research is needed.

Looking Into The Future

Schizophrenia can appear in adolescence and can occur from both interruptions to normal cellular signalling along with other genetic factors. Seeing that it has a strong relation to neural development, monitoring of the conditions that lead to schizophrenia development may serve valuable. Developing monitoring systems for chemical signalling like Wnt and GSKbeta may help assess abnormality in neural development before it becomes a problem. This can also apply to assessing for genetic variation in an individual through genome sequencing. These two interventions, however, both come with costs and ethical considerations. However, as we build understanding, we may soon have ways of assessing the development of schizophrenia before it becomes too late to fix it.

Jacques L. Michaud and Oliver Pourquie, “An emerging role for Wnt and GSK3 signaling pathways in schizophrenia.” Clinical Genetics 83, 511-517, (2013)

Disease

Schizophrenia: Cell Signaling to Hallucinations

Posted on February 21, 2023 by / 0 Comment

Introduction to schizophrenia

Schizophrenia is a psychiatric disorder affecting millions worldwide. Most commonly, schizophrenia is associated with positive symptoms such as hallucinations and delusions, and negative symptoms such as impaired day-to-day task functioning and decreased social interest. Although the disorder is common and easily identifiable and diagnosed, schizophrenia is not highly understood biologically, leaving effective treatments and preventative actions having yet to be discovered.

Schizophrenic patients are typically diagnosed in late teen or early adult years and symptoms can begin to arise years prior to diagnosis. But what causes or triggers the onset of this disorder in children or young adults? Studies have revealed that schizophrenia begins early in life with disrupted brain development (infection in utero, cognitive delays in early childhood, etc.). A key player in brain and cognitive development is the Wnt signaling pathway, and disruption of this signaling cascade is when schizophrenic symptoms develop.

Wnt signaling and schizophrenia

Wnt binds to frizzled receptors and recruits proteins to the membrane which causes dissociation of a beta-catenin destruction complex, and beta-catenin then transports to the nucleus for transcription. Without Wnt binding, this destruction complex containing the protein GSK3-beta, phosphorylates beta-catenin, targeting it for destruction. Beta-catenin gene transcription in the nucleus is crucial for cell proliferation, differentiation, and apoptosis (programmed cell death). Schizophrenia patients have been found to have decreased beta-catenin levels, implying Wnt signaling dysfunction in these patients.

Wnt signaling is essential for synaptic plasticity – change that occurs in response to neuronal activity at synapses that strengthen or weaken communication between neurons over time. With the dysfunction of Wnt signaling in schizophrenic patients, synaptic plasticity is decreased and with that decrease comes the loss of neuronal excitability. A doctor studying the correlation between Wnt signaling, synaptic plasticity, and schizophrenia symptoms inferred that the altered cognitive function, or the onset of negative symptoms, of those with schizophrenia begins with this loss of neuronal excitability. Then, the positive symptoms arise by the brain and body compensating for this loss of excitability – essentially, inhibiting the inhibition – which causes randomized firing that causes the hallucinations most often associated with schizophrenia.

References

Guildford, A. (2021, September 9). Schizophrenia: synaptic dysfunction plays a key role. Medical News Today. Retrieved February 19, 2023, from https://www.medicalnewstoday.com/articles/schizophrenia-synaptic-dysfunction-plays-key-role

Jia, L.; Pina-Crespo, J.; Li, Y. (2019). Restoring Wnt/B-catenin signaling is a promising therapeutic strategy for Alzheimer’s Disease. Molecular brain, 104(2019). https://doi.org/10.1186/s13041-019-0525-5

Singh, K. K. (2013). An emerging role for Wnt and GSK3 signaling pathways in Schizophrenia. Clinical Genetics, 83(6), 511–517. https://doi.org/10.1111/cge.12111

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Wnt Signaling’s Role in Schizophrenia

Posted on February 21, 2023 by / 0 Comment

What is Schizophrenia

Schizophrenia is a psychiatric disorder that is hallmarked by an individual’s abnormal interpretation of reality that interferes with their everyday lives. There are two categories of symptoms which are positive and negative symptoms. People with schizophrenia can display both types of symptoms at different times. The positive symptoms include delusions, hallucinations, disorganized thinking, and disorganized behavior. The negative symptoms include things such as lethargy, lack of emotion, and general loss of interest in social activities.

Delusions: beliefs that are false and have no foundation in reality. Like if a person believes that they are the president of the United States.

Hallucinations: having a sensory experience without the presence of any actual stimulus. Like when you think you hear your name, but no one has said anything in the last five minutes.

Disorganized thinking patterns: this is marked by impaired speech patterns. Usually, people displaying this symptom may answer questions with words that aren’t relevant to the question, or they will string a bunch of random words together to make an incoherent sentence.

Disorganized behavior: this is marked by things such as strange posture and actions that have no clear goals, such as excessive movement.

Wnt Signaling Overview

Wnt signaling is a type of cell signaling that cells use to initiate gene transcription so they can make proteins. These proteins then are used for the normal functioning of the cell. The goal of Wnt signaling is to activate a chemical called B-catenin that is used to initiate gene transcription. Wnt is a signal that binds to a certain receptor in the cell membrane (called frizzled). Once frizzled is activated it recruits this complex of proteins called the destruction complex. Normally, this destruction complex is deactivating B-catenin, but when it is called away by frizzled than B-catenin is free to enter the nucleus and do its thing.

Michaud, J. L & Pourguie, O. (2013) an emerging role for Wnt and GSK3 signaling pathways in schizophrenia. Clinical Genetics 83, 511-517. Doi: 10.1111/cge.12111.

Wnt Signaling in Schizophrenia

Schizophrenia is marked by a decrease of activity from a neurotransmitter (a chemical that neurons used to communicate with each other) called dopamine (DA). This is bad because DA indirectly helps to regulate the Wnt signaling pathway. As I mentioned before the destruction complex used to deactivate B-catenin contains a certain enzyme called GSK3B. Usually DA is able to indirectly activate this enzyme which helps keep the B-catenin levels under control. But when DA isn’t able to help out then B-catenin is overactive, and this can cause problems in the cell.

This is why many antipsychotic drugs that are used as a treatment for schizophrenia target DA levels. Specifically, they try to increase DA levels. When DA is more active it is better able to keep the GSK3B enzyme active and B-catenin inactive. This results in better control over the gene transcription in the nucleus so the cell can better control what proteins are being produced and run better.

Michaud, J. L & Pourguie, O. (2013) an emerging role for Wnt and GSK3 signaling pathways in schizophrenia. Clinical Genetics 83, 511-517. Doi: 10.1111/cge.12111.

How to Help People with Schizophrenia

Unfortunately, there is not much that the everyday person can do if they have a loved one with schizophrenia. The most important thing is to offer your love and support for them when they are struggling. Try to encourage them to seek professional help from a psychiatrist. Of course, if there is an emergency where their health and safety is at risk then 911 should be contacted.

References

Michaud, J. L & Pourguie, O. (2013) an emerging role for Wnt and GSK3 signaling pathways in schizophrenia. Clinical Genetics 83, 511-517. Doi: 10.1111/cge.12111.

https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443

Disease/Health

The Maze of the Mind: Navigating the Complexities of Schizophrenia

Posted on February 21, 2023 by / 0 Comment

Artstract by Timea Vrabcová (using DALL.E)

Schizophrenia is a complex mental disorder that is characterized by a range of symptoms including delusions, hallucinations, disordered thinking, and abnormal behaviors. It is a chronic illness that typically appears in early adulthood and can have a significant impact on individual’s perception of reality [1]. While the exact cause of schizophrenia is not fully understood, recent studies have suggested a link between schizophrenia and the Wnt signaling pathway.

Symptoms

One of the hallmark symptoms of schizophrenia is the presence of hallucinations and delusions [2].

Hallucinations = perceptual experiences that occur in the absence of external stimuli
Delusions = fixed, false beliefs that are not based on reality

These symptoms can be extremely distressing and can interfere with a person’s ability to function in daily life. The exact neural mechanisms underlying these symptoms are not yet fully understood, but it is thought that they may result from abnormalities in the brain’s sensory processing systems, as well as abnormalities in the connectivity between different brain regions.

Causes

One of the primary causes of schizophrenia is the dysfunction of dopamine signaling in the brain. This leads to an overstimulation of dopamine receptors, which causes an imbalance in the communication between the neurons.

Another significant factor in schizophrenia is the reduction in the size of certain brain structures, including the hippocampus and prefrontal cortex. The hippocampus is responsible for memory formation and retrieval, while the prefrontal cortex controls decision-making, planning, and attention.

One of the prevailing theories of schizophrenia is that it results from a combination of genetic and environmental factors. Environmental factors such as prenatal exposure to viruses, early childhood trauma, and drug use may also increase the risk of developing schizophrenia.

How is Schizophrenia Studied?

The brain abnormalities associated with schizophrenia have been extensively studied using advanced imaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET). These studies have shown that people with schizophrenia have structural and functional abnormalities in prefrontal cortex and hippocampus.

Wnt Pathway
The Wnt signaling pathway is a complex network of proteins that play a critical role in embryonic development, tissue homeostasis, and cell differentiation [3]. The pathway is activated by the binding of Wnt ligands to cell surface receptors, leading to the activation of downstream signaling pathways. Alterations in Wnt signaling may contribute to the dysfunction of neurotransmitter systems involved in schizophrenia, such as dopamine and glutamate and disrupt emotional and cognitive processing [4].
Animal Models [5]
Studies investigating the development of schizophrenia use animal models, especially mice and rats due to their complex social behavior and genetic similarity to humans [6]. Blocking the Wnt pathway during brain development led to the development of schizophrenia-like symptoms in mice. Specifically, the mice exhibited deficits in working memory, social behavior, and sensory gating, which are all symptoms commonly seen in schizophrenia. These findings provide further evidence of a link between Wnt signaling and schizophrenia.

What is the Treatment for Schizophrenia?

The most commonly used treatments are antipsychotic medications, which work by blocking dopamine receptors in the brain. While these medications can be effective in reducing the positive symptoms of schizophrenia such as hallucinations and delusions, they may not be effective for all individuals and can cause significant side effects, such as weight gain, sedation, and movement disorders. Other treatments that may be helpful for people with schizophrenia include cognitive behavioral therapy (CBT) and family therapy, which can help individuals and their families manage the condition and improve their quality of life.

Conclusion

Schizophrenia is a complex mental disorder that affects millions of people worldwide. Further research is needed to fully understand the mechanisms by which Wnt signaling contributes to schizophrenia and to develop effective treatments for this debilitating condition. By increasing awareness and understanding of schizophrenia, we can help to reduce the stigma associated with mental illness and improve outcomes for those affected by this challenging disorder.

Sources

https://www.nimh.nih.gov/health/topics/schizophrenia
https://www.verywellhealth.com/schizophrenia-sign-symptoms-5095511
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967064/#:~:text=Axin%2C%20a%20key%20component%20of,6%20and%20facilitates%20the%20recruitment ▲
doi: 10.1111/cge.12111
https://elifesciences.org/articles/54020
https://www.cyagen.com/us/en/community/technical-bulletin/mice-vs-rats.html

Disease/Health/Uncategorized

Reducing the Risk of Schizophrenia Through Prenatal Nutrition

Posted on February 21, 2023 by / 0 Comment

Schizophrenia is a mental illness characterized by negative and positive symptoms. Positive symptoms include delusions and hallucinations. Delusions are beliefs that are untrue. Hallucinations are things that people see or hear that are not really there. Negative symptoms include loss of interest in daily activities, loss of motivation, and social withdrawal. Those with Schizophrenia are usually diagnosed between the ages of 16 and 30. Unfortunately, little is understood about the causes of schizophrenia, but it is believed to emerge from a combination of genetic and environmental factors.¹

Genetic Factors

The gene primarily associated with schizophrenia is DISC1 (disrupted in schizophrenia 1 protein). DISC1 was found in a Scottish family that had cases of schizophrenia, bipolar disorder, and major depressive disorder. DISC1 plays a role in developing new neurons in the hippocampus, which is involved in memory and learning, during embryonic development and in adulthood. Abnormalities in this gene is linked to schizophrenia.²

Additionally, DISC1 also plays a role in Wnt signaling. In this figure we see that GKS3β acts on β-catenin, a protein. When Wnt is not active, GSK3β causes the phosphorylation of β-catenin which leads to degradation. If GSK3β is inhibited through Wnt binding, β-catenin is not phosphorylated and is able to enter the nucleus to stimulate TCF/LEF gene transcription.

DISC1 directly inhibits GSK3β which allows β-catenin to stimulate TCF/LEF gene transcription.³ (paper) But, if DISC1 is abnormal, TCF/LEF is not stimulated and cells in the hippocampus cannot form during development.⁴

Environmental Factors

One possible hypothesis is that schizophrenia stems from issues in brain development. Some studies show that disruptions during pregnancy can increase the risk of schizophrenia in offspring. In general, those with schizophrenia have been shown to have lower cognitive ability than the general population. Further, people with schizophrenia had experienced developmental cognitive delays in their childhood.³

One environmental factor is fetal exposure to infection. One study has shown that pregnant women that become infected with influenza during the first half of the pregnancy produced an increased risk of schizophrenia in the child. Maternal exposure to herpes simplex virus 2 and rubella also showed an increased risk of schizophrenia in the child.

But prenatal malnutrition has also shown to create a risk for schizophrenia. Specifically, a maternal lack of vitamin D and homocysteine, a micronutrient, can increase the occurrence of schizophrenia. Additionally, in times of famine, schizophrenia had increased in offspring.⁵

What Can We Do?

One option to decrease the risk for schizophrenia would be addressing environmental issues, specifically, nutrition. In a study looking at the effects of nutrition on fetal development’s association with offspring’s mental health, it was found that proper nutrition during pregnancy promoted healthy fetal development and decreased the incidence of mental illness. Supplementing vitamins A and D was found to decrease the risk for schizophrenia while the use of omega-3 fatty acid before 20 weeks gestation increased the risk for schizophrenia.⁶Although there are many environmental factors that affect fetal development, like malnutrition and exposure to infection, focusing on controlling nutrients may be a way to prevent schizophrenia.

https://www.nimh.nih.gov/health/topics/schizophrenia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722990/
Singh, K. K. (2013). An emerging role for wnt and gsk3 signaling pathways in schizophrenia. Clinical Genetics, 83(6), 511–517. https://doi.org/10.1111/cge.12111
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763761/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691516/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984656/#:~:text=Omega%2D3%2Dfatty%20acid%20supplementation,childhood%20wheezing%20and%20premature%20birth.