Cobbers on the Brain – Page 5 – Student Commentary on the Neurological Sciences

A Look into Metabotropic Glutamate Receptors and Sugar vs. Drug Addiction

Posted on March 30, 2025 by rlannin1 / 0 Comment

In the article “A Review on the Role of Metabotropic Glutamate Receptors in Neuroplasticity Following Psychostimulant Use Disorder” by Roghayeh Mozafari et al., the authors look at the neurobiological mechanisms behind addiction. They specifically focus on metabotropic glutamate receptors (mGluRs) and their role in neuroplasticity. The review talks about the changes in brain structure and function in response to psychostimulant use. This suggests that mGluRs (which regulate synaptic plasticity) could be a target for treating addiction. The research mentions that drug use can affect the brain’s ability to adapt and heal, which brings forth the need for new approaches to treating addiction. These new ideas would need to be based on the neural pathways that are altered by repeated drug use [1]. In this blog post, we will look at the similarities and differences of addiction to both legal substances (sugar) and illicit (hard drugs).

Addiction Beyond Hard Drugs

Addiction is an increasingly common issue, but not all addictions are created equal. Most people think of addiction in the context of hard drugs (like cocaine, heroin, and methamphetamine), but there’s another type of addiction that is often under the radar: sugar addiction. The question is- is just as dangerous or damaging as addiction to harder substances? How do these addictions compare on a biological level? What do the latest findings in addiction research say about the brain’s response to substances, both legal and illicit?

Why Are These Addictions So Hard to Break?

Addiction to both sugar and psychostimulants alters the brain’s reward system, which causes changes in behavior and cognition. Research has shown that chronic use of both sugar and hard drugs can result in similar neuroplastic changes [2]. These are alterations in the brain’s neural pathways that make it harder for the individual to resist the substance. This neuroplasticity is regulated by metabotropic glutamate receptors (mGluRs), which are involved in both learning and memory [1]. The review by Mozafari et al. shows how these receptors could play a large role in addiction and neuroplasticity by mediating the long-term changes in brain function following repeated psychostimulant use.

Sugar – These are a few of my favorite things… — This schematic shows the effect of sugar vs. cocaine on a rat study done.

Sugar and Hard Drugs

What Mozafari and colleagues’ findings about addiction in a general sense show is the similarity between sugar addiction and addiction to psychostimulants on a neurological level. Both types of addiction appear to use the same brain systems, while both have neuroplastic changes leading to the development of compulsive behaviors [1]. This suggests that our understanding of addiction should not be limited to illegal drugs but must also include substances like sugar that can trigger similar neural pathways and behavioral outcomes.

What does this mean for future research? Firstly, it opens up new opportunities for studying addiction in a broader context. If sugar addiction involves the same receptors and pathways as hard drugs, then treatments designed for one may be applicable to the other. This could lead to newer therapies for individuals struggling with sugar addiction, such as patients with obesity or type 2 diabetes.

What Does This Mean for You?

The implications of these findings are far-reaching. Beyond the lab and clinic, this research challenges how we think about addiction and its treatment in everyday-life. If addiction to sugar works similarly to hard drugs in terms of its impact on the brain, then it’s very important to reconsider how we approach nutrition and public health. This could spark conversations about food regulations and marketing practices, especially when it comes to dangerously sugary foods and beverages that are normalized in our culture.

It’s beyond time to think about addiction recovery in a more holistic way. Perhaps we need to expand our focus beyond just illicit substances and start viewing sugar as a more widespread and dangerous addiction- one that has long-term impacts for health and society.

Sugar is bad for you: Arash Bereliani, MD, FACC: Cardiologist — This schematic shows the hidden amounts of sugar in foods you many normally eat without question.

Rethinking Our Approach to Addiction

The main takeaway is clear: addiction is not confined to illegal drugs alone. Substances like sugar can hijack the brain in similar ways. This leads to lasting changes in behavior and cognition similarly to hard drugs. The research into metabotropic glutamate receptors offers a new way to view addiction, which suggests new possibilities for treatments.

So, what’s next? It’s important to think critically about our habits, diet, and the systems that support addictive behaviors. The challenge is real, but so is the opportunity to understand and fight addiction in new ways. Stay curious and keep pushing the boundaries of what we know to help create healthier, more informed lives.

[1] Mozafari, R., Karimi-Haghighi, S., Fattahi, M., Kalivas, P., & Haghparast, A. (2023). A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder. Progress in Neuropsychopharmacology & Biological Psychiatry, 124. https://doi.org/10.1016/j.pnpbp.2023.110735

[2] Avena NM, Rada P, Hoebel BG. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 2008;32(1):20-39. doi: 10.1016/j.neubiorev.2007.04.019. Epub 2007 May 18. PMID: 17617461; PMCID: PMC2235907.

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It’s Purposely Hard to Stop Taking Drugs: How Drugs Alter the Brain

Posted on March 30, 2025 by klind2 / 0 Comment

Artstract created by Ren Lind

Society has stigmatized drug addiction, often blaming the person for going back to drugs. However, drugs alter the brain, so it’s harder to say no. Understanding the science behind addiction can help give a new understanding and greater empathy for those who are addicted to substances. Understanding the science may also help deter you from “just trying it once.” This article will specifically focus on psychostimulants: nicotine, methamphetamine, amphetamine, cocaine, NMDA, dextroamphetamine, and methylphenidate. We will also dive into some common treatment options for addiction.

Glutamate

Before we get into the science of how drug’s change the brain, let’s look at glutamate and its receptors at baseline, along with how drugs change their activity. Glutamate is one of the most influential neurotransmitters for drug addiction. Glutamate is the main excitatory neurotransmitter in the brain, in other words, it will elicit signals passing through neurons. It’s important for cognitive activities. [1]

Glutamate has 2 main groups of receptors that we’ll focus on for this article: Group 1 and Group 2.

Group 1 receptors will be on the postsynaptic neuron, and they are important for synaptic plasticity, or in other words, creating greater connections between neurons that will lead to stronger memory formation. When taking a drug, Group 1 glutamate receptors will activate drug-seeking behaviors, and an increased amount of glutamate will be released. [3] This will cause feelings associated with reward.

Group 2 glutamate receptors regulate glutamate release by decreasing the amount of glutamate released, so the feeling of reward is controlled. Group 2 can also decrease motivation for substance use. However, drugs decrease the activity of Group 2 receptors, so there is less regulation on glutamate, and therefore more feelings of reward and less motivation to stop drug use. [4] Drugs tamper the ability to stop using drug use.

A person addicted to drugs does not have a typical functioning brain, the drugs have removed protective measures in their brain that would help them stop drug use. This is why intervention and support are crucial for people addicted to substances.

Overview of Common Treatments

If someone you know, or you yourself, are struggling with drug addiction, there are resources for support. The most common form of treatment is various forms of therapy. [5] Initial medical detox is an important first step, and hospitalization or treatment facilities can help manage withdrawal symptoms and create a safe environment.

After detox, therapy is recommended for dealing with cravings, drug behaviors, life changes, and preventing relapse. Cognitive Behavioral Therapy (CBT) is a standard practice for Substance Use Disorder (SUD). [7] This therapy method helps the client understand their drug behaviors and how it’s impacting their life. The client will work on different behaviors and changing their way of thinking.

Another common practice is Contingency Management. This practice is not a therapy option, but it is often used alongside other treatment options. The client will receive rewards, such as gift cards or vouchers, for attending treatment sessions and negative urine tests. This practice has been found to be effective at helping encourage drug abstinence. [8] It uses the reward circuit commonly associated with drug behaviors to reward non-drug behaviors.

Lastly, community reinforcement encourages the client to create new social networks, find different recreational activities, and create a meaningful life outside of drugs. These therapies are some of the most common, but there is many other forms of treatment that can help someone with addictions.

As we’ve established, drugs make it much harder to stop drug use once it’s began. It’s not entirely the person’s fault that their brain has made stopping harder, but it’s never impossible to stop addiction.

Resources

[1-4] Mozafari, R., Karimi-Haghighi, S., Fattahi, M., Kalivas, P., Haghparast, A. (2022). A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder. Progress in Neuropsychopharmacology & Biological Psychiatry, 124. https://doi.org/10.1016/j.pnpbp.2023.110735

[5] Volkow, N. D., & Blanco, C. (2023). Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention. World psychiatry : official journal of the World Psychiatric Association (WPA), 22(2), 203–229. https://doi.org/10.1002/wps.21073

[6] https://carolinacenterforrecovery.com/wp-content/uploads/2020/05/different-kinds-of-treatments-for-substance-use-disorder-infographic.png

[7, 8] Volkow, N. D., & Blanco, C. (2023). Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention. World psychiatry : official journal of the World Psychiatric Association (WPA), 22(2), 203–229. https://doi.org/10.1002/wps.21073

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The Brain Mess That is Drug Addiction

Posted on March 29, 2025 by cgeraci / 0 Comment

Have you ever wondered what happens to the brain of someone who is addicted to drugs, or why they feel pain when going through withdrawal? When it comes to psychostimulants such a cocaine and amphetamine, research has shown that it involves changes in how your neurons are connected, with an amino acid called glutamate (Glu) mediating most of the synaptic transmission between these neurons.¹

Figure 1. This displays a glutamatergic synapse, with groups II and III mGluRs located on pre-synaptic neurons and mGluRIs located on post-synaptic neurons.¹

Glutamatergic Receptors

There are eight subtypes of metabotropic Glu receptors (mGluRs), and these are grouped into three groups. As seen in Figure 1, group I mGluRs (mGluRIs) are located on post-synaptic neurons and during addiction, are overactive and cause drug-related behaviors by activating phospholipase C. Groups II and III mGluRs are presynaptic autoreceptors that when active, decrease synaptic Glu levels by inhibiting cAMP levels. This then decreases Glu binding to post-synaptic receptors, decreasing the excitatory signals being sent from post-synaptic neurons.¹

Cocaine/Psychostimulants Impact on Glutamatergic Signaling

In general, psychostimulants impact the glutamatergic signaling system by increasing the amount glutamate in synapses of the of brain areas involved in learning and memory, which then excites these areas, specifically the ventral tegmental area (see Figure 1), to release dopamine (DA) (for more information on the reward circuit anatomy, click here. DA then causes the perception of pleasure, so when psychostimulants cause DA increase, neurons modify how their connections to other neurons and number of glutamatergic receptors so that more glutamate is present in synapses, reinforcing the use of psychostimulants because we perceive more reward after each dose. Looking specifically at cocaine, it works to increase mGluRIs to increase Glu and DA levels while also decreasing mGluRII levels, which both combined, significantly increases Glu levels and rewires neuronal structure to reinforce cocaine use.¹

To learn how other psychostimulants, such as nicotine and amphetamines, impact mGluRs, click here.

Drug Withdrawal & Pain Perception

So that explains why drugs are addictive, but why is trying to get off drugs so painful? Drug withdrawal often involves headaches, vomiting, diarrhea, and/or weakness², but how stimulation of the pain pathway related to the reward pathway that is so clearly impacted by drug addiction?

To research this, one study investigated the effects of chronic morphine use on cAMP-mediated synaptic actions and pain behaviors, focusing on neurons in the nucleus raphe magnus (NRM) (which is an area of the brainstem involved in opioid modulation of spinal cord pain transmission). Results showed that chronic morphine use increased cAMP levels by activating the enzyme that initiates its formation, causing increased Glu transmission, and that this was accompanied by fewer groups II and III mGluRs. Then, it was found that NRM cells increased the amount of excitatory post-synaptic currents (EPSCs) sent up to the brain to relay pain signals, but only if they contained m-receptors. Notably, cocaine has the exact same impact on the number of groups II and III mGluRs.³

Figure 2. This illustrates one pain perception pathway occurring during drug withdrawal.

Therefore, I have applied the impact of morphine on pain perception during withdrawal to be like that of cocaine. This pathway is seen in Figure 2, but to outline it in words:

Opioids (morphine) and psychostimulants (cocaine) increase Glu levels and decrease group II mGluRs.
Increased Glutamate transmission to the NRM
m-receptor-containing NRM cells relay pain signals to the cortex3

To further solidify m-receptor-containing NRM cells’ role in pain perception, it was shown that patients going through opioid withdrawal experience a more positive hyperpolarization-activated, cyclic nucleotide-gated (HCN) current (I_h). For more information on what this is, click here, but in essence, this caused increased depolarization of m-receptor-containing NRM neurons, thus increasing pain perception during drug withdrawal.³The firing of these neurons is illustrated in Figure 3.

Figure 3. This displays how inhibition of Ih with ZD7288, an Ih blocker, reduced depolarization of m-receptor-containing NRM cells down to a level similar to control rats, whereas withdrawn rats with ZD7288 administration experienced a higher frequency of action potentials.³

Conclusion

In summary, chronic drug use alters neuronal connections to make it so you perceive maximal amounts of reward when taking said drug, but the increased amounts of glutamate in your synapses also activates receptors involved in pain pathways, leading to the physical pain sensitization characteristic to drug withdrawal. Therefore, further research should be done to see if drugs that decrease excitation of pain pathways can help patients trying to recover from drug addiction but suffering through severe drug withdrawal pain.

Footnotes:

¹Mozafari, R., et. al. “A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder.” Progress in Neuropsychopharmacology & Biological Psychiatry, vol. 124, 2022, pp 1-12. doi.org/10.1016/j.pnpbp.2023.110735

²“Signs, Symptoms, & Causes of Drug Abuse & Withdrawal.” Millcreek Behavioral Health. 2025. https://www.millcreekbehavioralhealth.com/mental-health/addiction/withdrawal-side-effects/

³Bie, B., et. al. “cAMP-Mediated Mechanisms for Pain Sensitization during Opioid Withdrawal.” The Journal of Neurosci, vol. 25, no. 15, 2005, pp. 3824-3832. doi: 10.1523/JNEUROSCI.5010-04.2005

Community/Disease/Health

Addiction Rewires the Brain

Posted on March 28, 2025 by hdahlsei / 0 Comment

Artstract created by Hadlie Dahlseid.

Drug use leads to increased dopamine and glutamate, which causes alterations in the reward circuit of the brain, increasing synaptic plasticity, and reinforcing that drug use[1]. Addiction literally rewires the brain. Now it kind of makes sense why every adult is so scared of kids using drugs in high school and college. But at the same time, if we know addiction impacts our brain, it doesn’t make sense why society shames addiction as a personality fault and a choice, instead of a brain health disorder. Let’s look more into the neuroscience of how exactly drug use and addiction impacts the brain to see if it’s really as scary as everyone says, and if it really is a choice.

Neurotransmitters

Glutmate’s impact on the brain’s reward circiut[1].

Many drugs, such as psychostimulants, increase the neurotransmitter glutamate, specifically by working with mGluRs. For example, amphetamine use increases the expression of group I mGluRs in the striatum, increases mGluR1 distribution at extrasynaptic sites, and upregulates mGluR5 in the medial prefrontal cortex, leading to long-lasting plasticity[1].

Psychostimulents also increase the neurotransmitter dopamine. This happens when the drug binds DA receptors, increases the release of dopaminergic neurons, reduces reuptake, or decreases the enzyme that degrades dopamine[1].

Reward Circuit

Dopamine plays a crucial role in the reward pathways of the brain, especially in relation to drug use. It causes drugs to be rewarding. The brain gets more and more addicted to dopamine, craving more and more of the drug[1].

When drug use increases dopamine in the brain, the reward circuit causes the brain to build up a tolerance to the drug. This is dangerous with addiction, especially when the tolerance is environment specific. Specific environments can be associated with anticipation of drug use, increasing tolerance. But when using drugs not in that environment, tolerance is not as high, and overdose can occur[2].

Tolerance can also be dangerous in relation to glutamate’s role in the brain’s learning and memory processes.

Neuroplasticity

Glutamate is related to long-term potentiation, the strengthening of synapses in the brain. This means that with drug use, the brain’s extra dopamine makes drugs extra rewarding. But the extra glutamate changes the brain’s natural firing pattern, making the brain expect drugs. It makes drug use and the effects of drugs the norm for the brain. The glutamate helps the brain learn and remember how much it likes the drugs. This increase in long-term potentiation that happens with drug use is accompanied by a decrease in long-term depression[3].

Long-term depression, a decrease in synaptic strength, in the prefrontal cortex is decreased in addiction, which reduces the inhibition and control over drug use[3].

It is interesting to note, that one of the ways neuroplasticity works in the brain is glutamate synapses onto dopaminergic neurons in the ventral tegmental area[1]. This makes sense then, why a drug impacting dopamine, also impacts glutamate, and vice versa.

Repeat

This is why addiction has such a high risk of relapse. The brain is rewired to learn and remember that drugs are rewarding. And the brain has less control over it with time[3].

Brain Health

So drug use and potential addiction is scary. It rewires how the brain is rewarded, how the brain learns and remembers, and how much impulse control the brain has.

But addiction is also less of a choice than society makes it seem. One could argue that after the first time an addict uses substances, they are no longer choosing, and have become a victim of their brain. There is also the argument that the first choice to use drugs is also not a choice, but a culmination of genetic and environmental factors [4]. Regardless of how much of drug use is a choice, addiction is not. The science says that addiction causes the brain to be rewired, and usual choice making processes are impacted. Addiction is a matter of brain health, just like any other physical disorder.

References

[1] Mozafari, R., Karimi-Haghighi, S., Fattahi, M., Kalivas, P., & Haghparast, A. (2023). A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 124. https://doi.org/10.1016/j.pnpbp.2023.110735

[2] Sinha, R. (2008). Chronic stress, drug use, and vulnerability to addiction. In Annals of the New York Academy of Sciences (Vol. 1141, pp. 105–130). Blackwell Publishing Inc. https://doi.org/10.1196/annals.1441.030

[3] Robinson, T. E., & Kolb, B. (2004). Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology, 47, 33–46. https://doi.org/10.1016/j.neuropharm.2004.06.025

[4] Gerring, Z.F., Thorp, J.G., Treur, J.L. et al. The genetic landscape of substance use disorders. Mol Psychiatry 29, 3694–3705 (2024). https://doi.org/10.1038/s41380-024-02547-z

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Unlocking Schizophrenia: The Hidden Role of Non-Canonical Wnt Pathways

Posted on March 28, 2025 by smtesa / 0 Comment

Schizophrenia affects about 1% of the global population,[1] and is a chronic psychiatric disorder that significantly contributes to disability worldwide. It is usually diagnosed in late adolescence and continues into adulthood. Current treatments focus on symptoms like hallucinations but don’t address the neurodevelopmental causes. And it’s increasingly recognized as a disorder of brain development, with early factors like maternal infections during pregnancy disrupting brain development and raising the risk of schizophrenia [2].

But despite this, the molecular mechanisms linking genetic and environmental factors are still unclear. While the canonical Wnt/β-catenin pathway has been a major focus, its role remains complex. Therefore, Recent evidence points to the role of Wnt signaling [3] and glycogen synthase kinase 3 (GSK3) pathways in schizophrenia, with non-canonical Wnt pathways like PCP and Wnt/calcium now playing key roles in shaping brain circuits and synaptic function in schizophrenia.

Cracking the Code of Brain Development: Meet the Non-Canonical Wnt Pathways ✨

Our brains are like a busy traffic system, where cars (cells) need to move to the right places and follow the correct paths to keep everything running smoothly. The non-canonical Wnt pathways, Wnt/PCP (Planar Cell Polarity) and Wnt/Ca²⁺ (Calcium) act like traffic signals, guiding the cells to their proper destinations and making sure they send the right signals. When these signals get messed up, like traffic lights malfunctioning, things can go wrong, leading to problems with brain development and function, as seen in schizophrenia.

But when these pathways get messed up, especially in conditions like schizophrenia, the dance falls apart. Neurons end up in the wrong places, signals get mixed up, and inflammation increases, which leads to problems in brain development and thinking.

Therefore, understanding these pathways better could help us figure out how schizophrenia develops and maybe even lead to better treatments.

Animal Models and Wnt Signaling in Schizophrenia

To understand how these pathways are involved in schizophrenia, animal models, particularly mice, are used in research. Mice do not have the exact same symptoms as humans, but they help researchers understand how brain pathways can go wrong in schizophrenia.

According to the paper “An emerging role for Wnt and GSK3 signaling pathways in schizophrenia,” a study with Dvl1 knockout (KO) mice (mice missing a key protein) showed issues with social behavior and prepulse inhibition (PPI) [4], which are similar to symptoms seen in schizophrenia patients. Since Dvl1 works in both canonical and non-canonical Wnt pathways, scientists believe that both pathways might contribute to the disorder. These findings highlight the involvement of both pathways in shaping behavior and brain function.[1]

What Are the Non-Canonical Wnt Pathways? (No β-Catenin Here!)

So, now that we’ve seen how these pathways influence schizophrenia, let’s take a deeper dive into what the non-canonical Wnt pathways actually are, and why they’re so important for brain health.
When most people think of Wnt pathways, they imagine the one that uses β-catenin. But the non-canonical pathways take a different route skipping β-catenin entirely. Instead, they focus on regulating cell movement, shape, and signaling key factors in ensuring that the brain develops correctly and functions smoothly. These pathways are like the hidden helpers of brain development, making sure everything stays in its right place.

1. Wnt/PCP (Planar Cell Polarity) Pathway

The Wnt/PCP pathway is like a GPS for cells. It tells them where to go and how to line up properly as the brain develops.

Key Players:

Wnt Ligand: The signal that starts the process.
Frizzled (FZD) Receptor: The docking station where Wnt binds.
Coreceptors (ROR/RYK): Help guide the signal.
Disheveled (DVL): A protein that wakes up and tells the cell to move.
RhoA & Rac1: Proteins that change the cell’s shape and help it move.

How It Works:

Wnt binds to Frizzled and ROR/RYK.
Disheveled gets activated and turns on RhoA and Rac1.
- RhoA: Controls how rigid the cell is.
- Rac1: Helps the cell stretch and move.

❓ What Happens When It’s Disrupted in Schizophrenia?

When the Wnt/PCP pathway goes off track, it messes up the system that guides neurons to the right places in the brain. Here’s what happens when things go wrong:

Defective Neuronal Migration: The PCP pathway helps neurons find their spot in the brain. If disrupted, neurons can end up in the wrong places, leading to faulty brain circuits and impaired information processing.
Loss of Synaptic Organization: The pathway also helps cells line up properly. If it’s off, synapses get misaligned, making it harder for neurons to connect, affecting the brain’s ability to adapt and refine connections.
Cytoskeleton Dysfunction: RhoA and Rac1 control the cell’s shape and movement. Disrupting the PCP pathway messes with these proteins, causing irregular cell shapes and making brain development even messier.[5]

These errors in cell migration, synapse alignment, and cytoskeleton organization could be the root cause of the structural abnormalities and cognitive deficits seen in schizophrenia

2. Wnt/Ca²⁺ (Calcium) Pathway ⚡

This pathway controls calcium signals inside the cell, which are super important for learning, memory, and controlling inflammation.

Key Players:

Wnt Ligand: The signal that kicks things off.
Frizzled (FZD) Receptor: The receptor that catches the Wnt signal.
Phospholipase C (PLC): Splits a molecule called PIP2 to release calcium.
Calcium (Ca²⁺): Sends signals inside the cell.
CaMKII & PKC: Proteins that control synapses and inflammation.

How It Works:

Wnt binds to Frizzled, activating PLC.
PLC splits PIP2, which releases calcium inside the cell.
The calcium sudden increase activates proteins that control synaptic strength and inflammation.

Figure 1: Shows a comparison between the canonical and non-canonical Wnt signaling pathways. (A) The canonical β-catenin-dependent pathway stabilizes β-catenin, allowing it to enter the nucleus and activate target genes. (B) The non-canonical pathways include the JNK/PCP pathway, which controls cytoskeletal organization, and the Ca²⁺ pathway, which regulates gene expression through calcium-dependent signaling. [6]

❓ What Happens When It’s Disrupted in Schizophrenia?

When this pathway is disrupted, calcium signaling becomes unregulated, leading to a buildup of intracellular calcium (Ca²⁺). This overload can trigger:

Excessive activation of CaMKII and PKC: These proteins are important for how synapses strengthen and adapt, but too much activity can cause synaptic dysfunction, making it harder for neurons to communicate properly. [7]
Increased neuroinflammation: Uncontrolled calcium can activate inflammatory responses, which release cytokines and other inflammatory molecules. Over time, this chronic inflammation can damage neurons and disrupt normal brain function.
Oxidative stress and mitochondrial dysfunction: High levels of calcium can stress mitochondria, leading to oxidative damage, which further disrupts neuronal health.

This imbalance in calcium signaling could be one of the major reason for the synaptic dysfunction, cognitive decline, and increased inflammation often seen in schizophrenia.

Figure 2: Shows brain scans comparing inflammation in healthy individuals, high-risk individuals, and those with schizophrenia. The colored images indicate inflammation levels, with warmer colors (orange/yellow) showing higher inflammation. Inflammation increases from healthy to high-risk and is highest in individuals with schizophrenia. [8]

Conclusion: A Bright Future for Schizophrenia Treatment

Understanding how the brain develops and how disruptions in pathways like the non-canonical Wnt pathways contribute to schizophrenia is a big step forward.

The key takeaway? More research is needed! The better we understand these pathways, the more likely we are to develop treatments that focus on the cause of schizophrenia, not just its symptoms. With more knowledge, we can make real changes in the lives of those affected.

The brain is an amazing system, and with the right science, we can help restore balance, giving people with schizophrenia a brighter, healthier future. Stay hopeful science is making great progress!

Footnotes

[1] Velligan, D. I., & Rao, S. (2023). The Epidemiology and Global Burden of Schizophrenia. The Journal of Clinical Psychiatry, 84(1). https://doi.org/10.4088/jcp.ms21078com5

[2] 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

[3] Komiya, Y., & Habas, R. (2008). Wnt signal transduction pathways. Organogenesis, 4(2), 68–75. https://doi.org/10.4161/org.4.2.5851

[4] Takahashi, H., Hashimoto, R., Iwase, M., Ishii, R., Kamio, Y., & Takeda, M. (2011). Prepulse inhibition of startle response: recent advances in human studies of psychiatric disease. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 9(3), 102–110. https://doi.org/10.9758/cpn.2011.9.3.102

[5] Mulherkar, S., Uddin, M. D., Couvillon, A. D., Sillitoe, R. V., & Tolias, K. F. (2014). The small GTPases RhoA and Rac1 regulate cerebellar development by controlling cell morphogenesis, migration and foliation. Developmental biology, 394(1), 39–53. https://doi.org/10.1016/j.ydbio.2014.08.004

[6] Fortress, A. M., & Frick, K. M. (2015). Hippocampal Wnt Signaling. The Neuroscientist, 22(3), 278–294. https://doi.org/10.1177/1073858415574728

[7] Lisman, J., Yasuda, R., & Raghavachari, S. (2012). Mechanisms of CaMKII action in long-term potentiation. Nature reviews. Neuroscience, 13(3), 169–182. https://doi.org/10.1038/nrn3192

[8] FeaturedPsychology·October 16, & 2015. (2015, October 16). Inflammation in the Brain Linked to Schizophrenia Risk. Neuroscience News. https://neurosciencenews.com/neuroinflammation-schizophrenia-risk-2905/

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Understanding Schizophrenia: A Complex Interplay of Genetics, Wnt Signaling, and Treatment

Posted on March 26, 2025 by jdeitz1 / 0 Comment

Schizophrenia is a puzzle—a complex and often misunderstood disorder that disrupts lives in profound ways. For decades, scientists have worked to piece together its causes, searching for answers in genetics, brain development, and molecular pathways like Wnt signaling. While progress has been made, effective treatment remains a challenge, leaving researchers to dig deeper into the intricate ways Wnt signaling influences schizophrenia. [1] Could understanding this pathway provide new hope for treatment?

Artstract created by J. Deitz

The Role of Wnt Signaling in the Brain

Imagine the brain as a carefully choreographed symphony, with different pathways ensuring that each instrument plays in harmony. Wnt signaling is one such conductor, orchestrating key aspects of neurodevelopment. It guides the formation of the brain’s anterior-posterior axis, shapes early patterning events like the midbrain and spinal cord development, and maintains neural stem cell populations. Without it, the music falters—cells exit the cycle too soon, leading to stunted neuron development and widespread disruption. [2]

In schizophrenia, disruptions in Wnt signaling have been linked to abnormalities in brain structure and function. The delicate balance of neural communication is thrown off, affecting cognition, perception, and behavior. If Wnt signaling is so vital, could restoring its function alleviate some of the symptoms of schizophrenia? Scientists are eager to find out.

Genetic Factors and Their Influence on Schizophrenia

Genetics tell another part of the story. Certain genes have been identified as potential risk factors, each playing a different role in brain development and function. DISC1, for example, is a key player in neurodevelopment and Wnt signaling, while Akt influences cell survival and neural connectivity. Variants in genes like LRP1, DAB2IP, and PIK3CB have also been linked to schizophrenia, particularly in families with a history of the disorder. [1]

The timing of brain development appears to be just as important as genetic predisposition. Childhood-onset schizophrenia (COS) presents a more severe and genetically influenced form of the disorder, suggesting that early developmental windows may shape symptom severity. Understanding the genetic blueprint of schizophrenia not only helps in predicting the disorder but could also be the key to more targeted treatments. [3]

Wnt Signaling and Schizophrenia Treatment

If Wnt signaling plays a role in schizophrenia, then targeting this pathway could offer new therapeutic possibilities. Some existing treatments already hint at this connection. Antipsychotic drugs primarily target dopamine pathways, but some also interact with Wnt signaling, particularly through D2 receptors. Lithium, a well-known mood stabilizer, is believed to enhance Wnt signaling, offering potential benefits for schizophrenia patients. [1]

Despite these promising connections, treatment responses vary widely. What works for one patient may not work for another, highlighting the urgent need for personalized medicine. By understanding the molecular profiles of individuals with schizophrenia, scientists hope to tailor treatments more effectively, ensuring that each person receives the care best suited to their needs.

Animal Models and Future Research

Studying schizophrenia in humans is complex, so researchers often turn to animal models for clues. While no animal model can fully replicate schizophrenia, certain behaviors and brain changes linked to Wnt signaling provide valuable insights. However, these models have limitations, and findings must be interpreted with caution. Moving forward, refining these models to better mimic human schizophrenia could be a game-changer in research and drug development. [1]

Conclusion

Schizophrenia is not just one disorder—it is a spectrum of experiences shaped by genetics, brain chemistry, and environmental factors. The Wnt signaling pathway, once thought to be a niche area of study, has emerged as a major player in understanding schizophrenia’s complexities. While current treatments mainly focus on dopamine regulation, a deeper understanding of Wnt signaling could open new doors to personalized therapies and better patient outcomes. The puzzle is far from complete, but with continued research, the pieces are slowly coming together.

To read more about schizophrenia and its link to Wnt signaling, click here.

[1] Singh, “An emerging role for Wnt and GSK3 signaling pathways in schizophrenia,” Clinical Genetics, vol. 83, no. 6, pp. 511–517, Jun. 2013, doi: 10.1111/cge.12111.

[2] Noelanders and K. Vleminckx, “How Wnt Signaling Builds the Brain: Bridging Development and Disease,” Neuroscientist, vol. 23, no. 3, pp. 314–329, Jun. 2017, doi: 10.1177/1073858416667270.

[3] Gogtay, N. S. Vyas, R. Testa, S. J. Wood, and C. Pantelis, “Age of Onset of Schizophrenia: Perspectives From Structural Neuroimaging Studies,” Schizophrenia Bulletin, vol. 37, no. 3, pp. 504–513, May 2011, doi: 10.1093/schbul/sbr030.

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Types Of Antipsychotic Medications

Posted on March 26, 2025 by tchilala / 0 Comment

Why Should the Public Care About Antipsychotic Medications?

Antipsychotic medications are a crucial part of psychiatric treatment, helping millions of people manage severe mental health conditions such as schizophrenia and bipolar disorder. Understanding how these drugs work and their impact on brain chemistry is essential for reducing stigma, improving treatment outcomes, and fostering scientific advancements in mental health care. With emerging research linking antipsychotic drugs to complex biochemical pathways like Wnt and GSK3 signaling, the public must stay informed about potential breakthroughs that could lead to more effective and targeted therapies.

Summary of the Science: Wnt and GSK3 Signaling in Schizophrenia

Schizophrenia is a chronic psychiatric disorder that affects brain development and neural connectivity. Despite available treatments, the precise biological mechanisms underlying schizophrenia remain unclear. The article An Emerging Role for Wnt and GSK3 Signaling Pathways in Schizophrenia explores the role of these signaling pathways in the disorder.[1]

Wnt signaling is a crucial pathway in brain development and function. It regulates neural circuit formation, synaptic plasticity, and overall brain health. The research highlights how disruptions in Wnt and glycogen synthase kinase 3 (GSK3) signaling contribute to schizophrenia pathophysiology.

Current antipsychotic drugs, including clozapine and haloperidol, interact with these pathways, affecting dopamine signaling and modulating GSK3 activity. Notably, lithium, a common mood stabilizer, directly inhibits GSK3, potentially stabilizing Wnt signaling and improving psychiatric symptoms.

Fig. 1. Wnt signaling pathways. There are three main Wnt signaling pathways: (a) canonical Wnt signaling, (b) Wnt-calcium signaling and (c) non-canonical Wnt/planar cell polarity signaling.

Fig. 2. Psychiatric disease pathways impinge upon glycogen synthase kinase 3 signaling networks. Diagram illustrating how human genetic findings, pharmacological drug treatments directly or indirectly influence canonical and non-canonical Wnt signaling pathways.

Bridging Antipsychotics and Advanced Research

One of the most compelling aspects of this research is the intersection between dopamine and Wnt signaling. Dopamine dysregulation has long been associated with schizophrenia, and emerging findings suggest that Wnt-related mechanisms may further modulate these effects. Studies indicate that D2 dopamine receptor antagonists, a class of antipsychotics, inhibit GSK3, thereby stabilizing β-catenin, a key component in Wnt signaling (Figure 2). This interaction offers a deeper understanding of how psychiatric medications function beyond dopamine receptor blockade.[3]

Medication	Usage	Benefits	Side Effects

Haloperidol (Haldol)

Used to treat schizophrenia, acute psychosis, and severe agitation. Also used for Tourette syndrome and nausea in some cases.

– Rapid control of acute psychotic symptoms.
– Effective in managing severe agitation and hallucinations.
– Available in oral, injectable, and long-acting forms.

– Extrapyramidal symptoms (EPS) such as dystonia, akathisia, and parkinsonism.
– Tardive dyskinesia with long-term use.
– Increased risk of neuroleptic malignant syndrome (NMS).
– Sedation and low blood pressure.

Clozapine

Used for treatment-resistant schizophrenia and to reduce suicidal behavior in schizophrenia and schizoaffective disorder.

– Effective for treatment-resistant cases where other antipsychotics fail.
– Lower risk of extrapyramidal side effects compared to typical antipsychotics.
– Reduces suicidal tendencies in schizophrenia patients.

– Risk of agranulocytosis (severe drop in white blood cells requiring regular monitoring).
– Weight gain and metabolic issues (diabetes, increased cholesterol).
– Sedation and excessive drooling.
– Risk of seizures at higher doses.

Figure 3: A phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses . It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in intellectual disability and the chorea of huntington’s disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. (From AMA Drug Evaluations Annual, 1994, p279)

Figure 4: A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.

Genetic Insights and Future Directions

Recent genetic studies have identified several schizophrenia risk genes involved in Wnt signaling. For example, DISC1, a gene linked to brain development, directly interacts with Wnt signaling proteins, influencing neuronal function.[4] Additionally, AKT1, another schizophrenia risk gene, modulates GSK3 activity, further tying together genetic predisposition and molecular pathways in the disorder.[5]

Understanding these connections could pave the way for new treatment options that go beyond traditional dopamine-targeting antipsychotics. Novel drugs designed to fine-tune Wnt signaling could offer more precise and effective treatments with fewer side effects.[6]

Why This Matters

The public should be aware of these developments because they impact how we approach mental health treatment. By staying informed, we can support scientific research, advocate for improved therapies, and reduce the stigma surrounding psychiatric disorders. Additionally, recognizing that mental illnesses have a biological basis reinforces the importance of medical treatment and continued innovation in drug development.

As research into Wnt and GSK3 signaling progresses, we may witness the advent of next-generation antipsychotics that are more effective, personalized, and capable of addressing the underlying causes of psychiatric disorders rather than just their symptoms. This is an exciting time in neuroscience, and the more we understand, the better we can support those affected by schizophrenia and related conditions.

References:

Singh KK. “An emerging role for Wnt and GSK3 signaling pathways in schizophrenia.” Clinical Genetics, 2013. DOI: 10.1111/cge.12111
Clevers H, Nusse R. “Wnt/β-catenin signaling and disease.” Cell, 2012. DOI: 10.1016/j.cell.2012.05.012
Beaulieu JM, Gainetdinov RR, Caron MG. “Akt/GSK3 signaling in the action of psychotropic drugs.” Annual Review of Pharmacology and Toxicology, 2009. DOI: 10.1146/annurev.pharmtox.011009.081849
Mao Y, Ge X, Frank CL et al. “Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3β/β-catenin signaling.” Cell, 2009. DOI: 10.1016/j.cell.2009.03.033
Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. “Convergent evidence for impaired AKT1-GSK3β signaling in schizophrenia.” Nature Genetics, 2004. DOI: 10.1038/ng1296
Ripke S, Sanders AR, Kendler KS et al. “Genome-wide association study identifies five new schizophrenia loci.” Nature Genetics, 2011. DOI: 10.1038/ng.940

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Unlocking Schizophrenia’s Mysteries: The Role of Wit and GSK3 Signaling Pathways

Posted on March 26, 2025 by ealslebe / 0 Comment

Schizophrenia is a complex, debilitating psychiatric disorder that affects millions worldwide. It manifests through hallucinations, delusions, cognitive impairments, and social withdrawal, significantly diminishing quality of life. Despite extensive research, the biological roots of schizophrenia remain elusive, limiting treatment options to managing symptoms rather than addressing underlying causes. Recent advances, however, highlights the importance of Wnt signaling and Glycogen Synthase Kinase 3 (GSK3) pathways, providing new insights that could revolutionize our understanding of schizophrenia and open doors for novel treatments. [1]

Why Should You Care About Wnt and GSK3?

Schizophrenia’s global burden is immense, ranking among the top causes of disability. Treatments currently available – primarily antipsychotics – focus on alleviating positive symptoms like hallucinations but fail to tackle cognitive deficits and the disease’s biological roots. Exploring Wnt and GSK3 pathways not only deepens our understanding of schizophrenia but may also pave the way for targeted therapies that improve long-term outcomes. [1]

Beyond schizophrenia, these signaling pathways are implicated in other conditions like bipolar disorder, autism, and neurodegenerative diseases. Advances in this research may have far-reaching implications for mental health and brain development disorders as a whole. [1]

What’s the Wnt/GSK3 Pathway, and How Does it Connect to Schizophrenia?

Think of Wnt as the brain’s construction supervisor. It helps build the brain during development and keeps neurons communicating properly throughout life. When Wet signaling works, it keeps things in balance by regulating a protein called β-catenin, which helps turn on genes critical for healthy brain function. [1]

Here’s where GSK3 comes in. When Wnt is off, GSK3 tags β-catenin for destruction. But when Wnt is on, it blocks GSK3, saving β-catenin and allowing important genes to do their job (see figure 1).

Figure 1: Wnt signaling pathways—showing how GSK3 controls β-catenin levels [2]

In people with schizophrenia, scientists suspect that Wnt signaling is disrupted. That disruption might affect how the brain develops and connects, contributing to symptoms like memory issues and impaired thinking. [1]

Medications Already Target Wnt and GSK3 – Without Us Realizing It

Here’s the kicker: many common psychiatric drugs may already work by influencing this pathway – we just didn’t know it until recently.

For Example (refer to figure 2):

Antipsychotics like clozapine and haloperidol not only block dopamine (the usual target) but also alter GSK3 activity, changing β-catenin levels. [3]
Lithium, a go-to treatment for bipolar disorder, directly inhibits GSK3 and boosts Wnt signaling, which might explain its mood-stabilizing effects. [1]
Newer drugs targeting glutamate receptors (mGlu3/3) also seem to activate Wnt pathways, offering fresh hope for better treatments. [4]

Figure 2: How antipsychotics, lithium, and glutamate drugs influence Wnt/GSK3 pathways [5]

The Genetic Connection: Are Some People Born with Wnt Pathway Risks?

Recent genetic studies show that some schizophrenia risk genes directly affect Wnt signaling:

DISC1 was first discovered in a Scottish family with a history of schizophrenia. DISC1 interacts with GSK3, regulating β-catenin and impacting brain development.
AKT1, another gene involved in blocking GSK3, is often found at low levels in schizophrenia patients. [6]
Researchers have also found mutations and copy number variations (CNVs) in Wnt-related genes like BCL9, which can alter brain size and connectivity.

This genetic evidence strengthens the case that Wnt signaling isn’t just involved – but may be central to how schizophrenia develops. [1]

Animal Studies Back it Up

Mice engineered to have defects in Wnt signaling – like knocking out the Dvl1 gene – show schizophrenia-like behaviors, such as social withdrawal and memory problems. Other mouse models confirm that too much or too little GSK3 activity can trigger hyperactivity, cognitive issues, and mood swings – mirroring what we see inhuman patients. [7]

Where Do We Go From Here?

Research into Wnt and GSK3 is giving scientists a whole new roadmap to understanding schizophrenia. Instead of just treating the symptoms, future therapies might target these pathways to protect the brain, improve cognition, and possibly even prevent the illness from progressing.

And because Wnt and GSK3 are involved in so many brain functions, this research could also unlock treatments for conditions like autism, bipolar disorder, and dementia. The more we understand these pathways, the closer we get to helping those living with these conditions.

References

[1] Singh, 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

[2] McCubrey, J. A., Steelman, L. S., Bertrand, F. E., Davis, N. M., Abrams, S. L., Montalto, G., D’Assoro, A. B., Libra, M., Nicoletti, F., Maestro, R., Basecke, J., Cocco, L., Cervello, M., & Martelli, A. M. (2013, June 19). Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: Opportunities for Therapeutic Intervention. Nature News. https://www.nature.com/articles/leu2013184

[3] Freyberg, Z., Ferrando, S. J., & Javitch, J. A. (2010). Roles of the AKT/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action. American Journal of Psychiatry, 167(4), 388–396. https://doi.org/10.1176/appi.ajp.2009.08121873

[4] Dogra, S., Stansley, B. J., Xiang, Z., Qian, W., Gogliotti, R. G., Nicoletti, F., Lindsley, C. W., Niswender, C. M., Joffe, M. E., & Conn, P. J. (2021). Activating mglu3 metabotropic glutamate receptors rescues schizophrenia-like cognitive deficits through metaplastic adaptations within the Hippocampus. Biological Psychiatry, 90(6), 385–398. https://doi.org/10.1016/j.biopsych.2021.02.970

[5] Vallée, A., Vallée, J.-N., & Lecarpentier, Y. (2021, April 26). Lithium and atypical antipsychotics: The possible Wnt/? pathway target in glaucoma. MDPI. https://www.mdpi.com/2227-9059/9/5/473

[6] Thiselton, D. L., Maher, B. S., Webb, B. T., Bigdeli, T. B., O’Neill, F. A., Walsh, D., Kendler, K. S., & Riley, B. P. (2009). Association analysis of the pip4k2a gene on chromosome 10p12 and schizophrenia in the Irish study of high density schizophrenia families (ISHDSF) and the Irish case–Control Study of schizophrenia (ICCSS). American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 153B(1), 323–331. https://doi.org/10.1002/ajmg.b.30982

[7] Powell, C. M., & Miyakawa, T. (2006). Schizophrenia-relevant behavioral testing in rodent models: A uniquely human disorder? Biological Psychiatry, 59(12), 1198–1207. https://doi.org/10.1016/j.biopsych.2006.05.008

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Wnt and GSK3 Signaling: The Overlooked Keys to Schizophrenia?

Posted on March 26, 2025 by adebleye / 0 Comment

Schizophrenia has long been one of psychiatry’s most puzzling disorders. We’ve treated its symptoms for decades with antipsychotics that blunt hallucinations but fail to address the root cause. But what if the real story begins not with neurotransmitters, but with developmental pathways that shape the brain itself? Emerging research suggests that two cellular signaling systems—Wnt and GSK3—might hold critical answers.

Schizophrenia as a Neurodevelopmental Disorder

The old view of schizophrenia as simply a “chemical imbalance” is giving way to a more nuanced understanding: this may fundamentally be a disorder of brain development. Epidemiological studies show that prenatal infections, birth complications, and early cognitive delays all increase schizophrenia risk. Brain imaging reveals subtle structural differences in neural connectivity. Together, this paints a picture of a brain wired differently from the start.

This shift in perspective matters because it changes where we look for solutions. If schizophrenia stems from developmental miscues, then the pathways guiding brain construction—like Wnt signaling—become prime suspects.

Wnt Signaling: The Brain’s Blueprint

The Wnt pathway is a cornerstone of embryonic development, governing everything from stem cell proliferation to synapse formation. It operates through three main branches:

The Canonical (β-Catenin) Pathway – Regulates gene expression critical for neuronal survival and growth.
Planar Cell Polarity (PCP) Pathway – Directs the migration and positioning of neurons.
Wnt/Calcium Pathway – Fine-tunes synaptic communication.

When Wnt signaling falters, the brain’s architecture can veer off course. And intriguingly, several schizophrenia-linked genes, like DISC1 and Akt1, intersect directly with this pathway.

GSK3: The Lithium Connection

Glycogen synthase kinase 3 (GSK3) acts as a key regulator of Wnt signaling by controlling the stability of β-catenin. Normally, GSK3 keeps β-catenin in check, ensuring cells don’t overgrow. But when GSK3 is overactive, it can disrupt neural development and function.

Here’s where things get fascinating: lithium, one of psychiatry’s oldest drugs, works by inhibiting GSK3. This not only stabilizes mood in bipolar disorder but also suggests that GSK3 dysregulation might play a role in schizophrenia. Some antipsychotics, like haloperidol, appear to indirectly modulate this same pathway, hinting that their therapeutic effects might partly stem from Wnt/GSK3 interactions.

Genetic Clues Pointing to Wnt and GSK3

Several schizophrenia risk genes converge on these pathways:

DISC1 – Mutations in this gene disrupt GSK3 regulation, leading to abnormal Wnt signaling. Remarkably, lithium’s effects mimic what happens when DISC1 functions properly.
Akt1 – Reduced Akt1 activity, common in schizophrenia patients, fails to rein in GSK3, leaving β-catenin unstable.
BCL9 – Found within a schizophrenia-linked chromosomal deletion, this gene helps β-catenin regulate brain size. Errors here could alter early brain development.

Animal Models Reinforce the Link

Mouse studies further support this connection. Animals with disruptions in Wnt-related genes (like Dvl1 knockouts) exhibit behaviors resembling schizophrenia, including social deficits and sensory processing abnormalities. Conversely, boosting β-catenin produces effects similar to lithium treatment—calmer, more resilient behavior. These findings suggest that tweaking Wnt/GSK3 signaling could one day yield more precise treatments.

Why This Matters for the Future

Better Treatments – Current antipsychotics are crude tools, often causing debilitating side effects. Targeting Wnt/GSK3 could lead to therapies that correct underlying developmental errors rather than just masking symptoms.
Early Intervention – If we can identify at-risk individuals through genetic or biomarker screening, we might intervene before psychosis ever emerges.
Broader Implications – Since Wnt and GSK3 are also implicated in autism, bipolar disorder, and Alzheimer’s, understanding their role in schizophrenia could shed light on multiple conditions.

The Road Ahead

The next steps are clear but challenging:

Develop safer, more specific GSK3 inhibitors to replace lithium’s blunt approach.
Use stem cell models to study how Wnt signaling goes awry in schizophrenia patients.
Explore whether early-life interventions—perhaps even prenatal treatments—could prevent the disorder altogether.

Final Thoughts

Schizophrenia has resisted simple explanations for too long. But by shifting focus to the pathways that build the brain—Wnt and GSK3—we might finally be closing in on its origins. This isn’t just about biochemistry; it’s about how the brain assembles itself, and how slight missteps in that process can have lifelong consequences.

For anyone affected by schizophrenia, or anyone who cares about mental health research, this is a story worth following. Because if we’re right about Wnt and GSK3, we’re not just treating a disorder—we’re rewriting how we understand it.

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Wnt and GSK3 Signaling: The Overlooked Keys to Schizophrenia?

Posted on March 26, 2025 by adebleye / 0 Comment