Mental illness is an ongoing problem in our world. In America alone, one in five adults experience a mental health issue. One in 25 Americans have a serious mental illness such as schizophrenia, bipolar disorder, or major depressive disorder. Even children can experience mental health problems. Several mental health disorders, including schizophrenia, show signs of development before a person turns 14, and 75% of disorders begin before age 24. That being said, less than 20% of children/adolescents with mental health problems receive treatment. Some mental health disorders are easily treatable with either therapy, medication, or both. Some of the more serious mental disorders, such as schizophrenia, are not so easily treatable. One reason why is because there has not been a ton of research regarding treatments.

What is schizophrenia?

Schizophrenia is a mental health disorder in which people interpret reality abnormally. Symptoms of schizophrenia include a range of problems in cognition, behavior, and emotion. Some symptoms include delusions, hallucinations, disorganized thinking, disorganized or abnormal motor behavior, and negative symptoms such as lack of emotion, loss of interest in everyday activities, or being socially withdrawn. Schizophrenia symptoms usually show up during adolescence. In men, it typically starts around early 20s, while in women it starts in the late 20s. People with schizophrenia require lifelong treatment. Early treatment is best but isn’t always the easiest.

Why is it so hard to treat?

Schizophrenia is a complicated illness to treat because we do not know the cause of it. Researchers have ideas that it is a combination of genetics, brain chemistry, and environmental factors, but are still unsure as to what causes the disorder to develop. Some believe neurotransmitters such as dopamine and glutamate may contribute to schizophrenia. Others believe it has to do with specific signaling pathways in the brain. These pathways include the Wnt signaling pathway, an important pathway in organism development Research has shown that problems with this pathway can lead to cognitive deficits in animal models, implying that it is involved in cognitive development. Problems in development may contribute to abnormalities resulting in mental disorders such as schizophrenia.

• https://magellanhealthinsights.com/2018/05/23/7-mental-health-myths-and-facts/#targetText=Fact%3A%20Mental%20health%20problems%20are,bipolar%20disorder%2C%20or%20major%20depression
• https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443
• https://www.psychiatrictimes.com/schizophrenia/schizophrenia-treatment-challenges
• https://moodle.cord.edu/pluginfile.php/798923/mod_resource/content/2/2013%20wnt%20GSK%20and%20schizophrenia.pdf
• Images
  • <p style=”font-size: 0.9rem;font-style: italic;”><a href=”https://www.flickr.com/photos/141608731@N06/38843081961″>”schizophrenia”</a><span>by <a href=”https://www.flickr.com/photos/141608731@N06″>johnbill552</a></span> is licensed under <a href=”https://creativecommons.org/licenses/by/2.0/?ref=ccsearch&atype=html” style=”margin-right: 5px;”>CC BY 2.0</a><a href=”https://creativecommons.org/licenses/by/2.0/?ref=ccsearch&atype=html” target=”_blank” rel=”noopener noreferrer” style=”display: inline-block;white-space: none;opacity: .7;margin-top: 2px;margin-left: 3px;height: 22px !important;”><img style=”height: inherit;margin-right: 3px;display: inline-block;” src=”https://search.creativecommons.org/static/img/cc_icon.svg” /><img style=”height: inherit;margin-right: 3px;display: inline-block;” src=”https://search.creativecommons.org/static/img/cc-by_icon.svg” /></a></p>
  • <p style=”font-size: 0.9rem;font-style: italic;”><a href=”https://www.behance.net/gallery/81938079/Schizophrenia”>”Schizophrenia”</a><span> by <span>Ahmed Emad Eldin</span></span> is licensed under <a href=”https://creativecommons.org/licenses/by-nc-nd/4.0/?ref=ccsearch&atype=html” style=”margin-right: 5px;”>CC BY-NC-ND 4.0</a><a href=”https://creativecommons.org/licenses/by-nc-nd/4.0/?ref=ccsearch&atype=html” target=”_blank” rel=”noopener noreferrer” style=”display: inline-block;white-space: none;opacity: .7;margin-top: 2px;margin-left: 3px;height: 22px !important;”><img style=”height: inherit;margin-right: 3px;display: inline-block;” src=”https://search.creativecommons.org/static/img/cc_icon.svg” /><img style=”height: inherit;margin-right: 3px;display: inline-block;” src=”https://search.creativecommons.org/static/img/cc-by_icon.svg” /><img style=”height: inherit;margin-right: 3px;display: inline-block;” src=”https://search.creativecommons.org/static/img/cc-nc_icon.svg” /><img style=”height: inherit;margin-right: 3px;display: inline-block;” src=”https://search.creativecommons.org/static/img/cc-nd_icon.svg” /></a></p>

Most people’s first thoughts are that there is no connection between Alzheimer’s disease and type II diabetes. Years ago that may have been true, but research today proves otherwise. In fact, people with type II diabetes are more likely to develop Alzheimer’s, and vice versa. More than 30 million people in the United States have diabetes – about 1 in 10 people. Between 90% and 95% of people with diabetes have type II diabetes. About 5.8 million people, of all ages, in the United States have Alzheimer’s. Roughly 1 in 10 people over the age of 65 has this disease. Alzheimer’s disease is the sixth-leading cause of death in the United States.

What is Alzheimer’s Disease?

Alzheimer’s Disease (AD) is a type of dementia that effects memory, thinking, and behavior. AD usually occurs in old age, most people being over 65, but it can occur in younger people (early-onset Alzheimer’s). It is a progressive disease where symptoms become worse over time. This disease is only diagnosable post-mortem (after death).

               What is going on in the brain?

Though it is unknown exactly how AD starts, scientists do know two major abnormal structures that play a role in the pathology of the disease. The first are the presence of beta-amyloid plaques. These plaques are build-ups of the protein fragment, beta-amyloid. The second indicator is the presence of neurofibrillary tangles. These tangles are twisted fibers of the tau protein.

What is Type II Diabetes?

Type II diabetes (T2D) occurs when cells in the body, including in the brain, do not respond normally to insulin. Insulin is a hormone secreted by the pancreas to help regulate glucose (blood sugar) levels. Cells need glucose for energy. Normally, cells willingly take up glucose with the help of insulin. In T2D, cells don’t respond to the insulin, therefore not taking up glucose. This is called insulin resistance. Since glucose doesn’t enter the cells, the pancreas secretes more and more insulin until it eventually can’t keep up. Why T2D occurs is unknown but there are some risk factors including being overweight, fat distribution, inactivity, age, etc.

How are they connected?

• https://www.alz.org/alzheimers-dementia/facts-figures#targetText=An%20estimated%205.8%20million%20Americans,who%20have%20younger%2Donset%20Alzheimer’s.
• https://www.cdc.gov/diabetes/basics/type2.html
• https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193
• https://www.alz.org/alzheimers-dementia/what-is-alzheimers

What really goes on in your brain when you experience a stressful event? And the memories that are formed, what makes them shift from a helpful reminder of a trepidatious situation to a triggering event? These are questions that neuroscientists are asking about memories formed after stressful events. While it seems obvious that stress is a part of human life and remembering past events contributes to learning and success in our futures, there are some stressful events that create memories upon whose recall manifests as anxiety or PTSD symptoms. Are these memories a coping mechanism for dealing with extreme stress and trauma, or do they exacerbate the trauma such that it adversely affects someone’s life experience long after the fact?

The molecular pathway outlined in Reul’s article involves a stress hormone stimulus that causes a protein to be modified in such a way that it allows two genes to be transcribed. These genes code for proteins that are important for the growth of neurons and memory consolidation. In a stressful situation, these genes are transcribed in higher amounts, allowing for a stressful event to be recorded and remembered in the brain. If a more anxious person experiences a stressful event, more proteins are synthesized, and the memory consolidation is stronger.

Here are three proposed molecular differences in brains that experience stressful events and develop stress-related disorders and brains that do not:

1. Epigenetics: the differing expression of genes related to external stimulation. Genetic predisposition to stress-related disorders (including PTSD and general anxiety) are implicated in studies showing that the same stressful experiences are recorded differently in the brain. While many people experience extreme stress in their lives, only between 10-20% of them develop a stress-related disorder.[1]
2. GABA: the brain’s primary inhibitory neurotransmitter. When a lot of GABA is present in the dentate gyrus, there is less of an anxious response to a stressful situation: the molecular pathway outlined above is inhibited. Congruently, increased excitability of neurons leads to higher expression of memory consolidation genes.
3. Hippocampus: the emotion processor involved with memory formation. A region of the hippocampus is important for the integration of emotional and cognitive data. When this area is functioning improperly, learning and memory are impaired. Additionally, the interplay between this region and the amygdala leads to decreased memory storage in the dentate gyrus. The lack of memory formation would directly affect the chance that someone who experiences a stressful event would remember it or develop a stress-related disorder.

It’s definitely a tricky situation with lots of interplay between genetic make-up, individual environment, and so many other factors that we as scientists do not understand and we as humans simply have to live with and help each other to live with.

[1] Reul, Johannes M.J.M. 2014. Making memories of stressful events: a journey along epigenetic, gene transcription, and signaling pathways. Frontiers in Psychiatry 5(5):1-11.

With current research enlightening a link between Type II Diabetes and the development of Alzheimer’s Disease through many mechanisms and risk factors, the role of insulin in the pathologies of both conditions is becoming a hot topic in medicine. Type II Diabetes increases the risk factor of developing dementia by two, and according to a 2004 study, the risk of developing Type II Diabetes is higher in Alzheimer’s patients.[1] Since the risk of developing either disease goes both ways, it is important to explore the big picture ways each disease advances and their overlap.

Insulin is a hormone that is synthesized in the pancreas, and has long been associated with Type II Diabetes. In a healthy system, insulin is released from the pancreas following a rise in blood sugar levels (after eating), and can bind to insulin receptors on a variety of cells throughout our bodies including fat, liver, muscles and even brain cells. The cellular pathways initiated by insulin binding to its receptors are myriad: they can have downstream effects as different as sugar storage and cell growth, among others.[2]

However, since the discovery of insulin receptors in the brain, scientists have investigated many more functions of insulin. Fascinatingly, insulin has been shown to play a role in protection of neurons, aiding with neuronal growth and survival, improving verbal memory and selective attention in healthy humans (Vieira et al., 2017). Most pertaining to Alzheimer’s is the implication of insulin in gene expression related to long term memory.

This crazy, tiny hormone does so many things for our bodies! It is chilling to think about what happens when insulin signalling goes wrong. When these signalling pathways do not get initiated the way they are supposed to (by insulin), we say that the system is exhibiting insulin resistance.

Both Alzheimer’s Disease and Type II Diabetes display insulin resistance as a primary molecular mechanism that leads to their development and worsening, but it is difficult to decide what really causes insulin resistance, and therefore what causes either disease. Many potential starting points have been proposed and are plausible: it is almost as if insulin resistance is cyclical, and we are jumping on to the mechanistic wheel in the middle of the disease propagation regardless of where we start.

After briefly examining the overlap between Type II Diabetes and Alzheimer’s, serious questions must be asked of the current health care system and its ability to provide effective and accessible healthcare to those living with Type II Diabetes and Alzheimer’s. The inventors of synthetic insulin sold their patent for only one dollar, with the intention that everyone who should need the drug would have access to it. Unfortunately, their desire to make their insulin accessible and affordable is not a reality, with the price of insulin nearly tripling within ten years (2002 to 2013). At a standard price of 480$ per vial, each of the 30 million Americans experiencing diabetes can pay thousands of dollars per year to get enough insulin to survive. If insulin mediation and other treatments for Type II Diabetes might be effective treatments for Alzheimer’s, as Vieira’s review article suggests, then the disadvantaged population has increased by almost 6 million.[3] Further, if Type II Diabetes and Alzheimer’s both play roles in the development of the other, then effective and affordable education and management options for Type II Diabetes are necessary to reduce the risk of Alzheimer’s, a brutal and debilitating disease.

[1]Vieira MNN, Lima-Filho RAS, De Felice FG. 2017. Connecting Alzheimer’s disease to diabetes: Underlying mechanisms and potential therapeutic targets. Neuropharmacology 136(2018):160-171.Neurochem Artstract 1Neurochem Artstract 1

[2] Vieira MNN, Lima-Filho RAS, De Felice FG. 2017. Connecting Alzheimer’s disease to diabetes: Underlying mechanisms and potential therapeutic targets. Neuropharmacology 136(2018):160-171.

[3] https://www.alz.org/alzheimers-dementia/facts-figures