Cobbers on the Brain

Are you an addict? I know, the term “addiction” is quickly associated with a sour taste in our mouths, but it is quite more diverse than with substances as many may have initially imagined. How many times do you check your phone per day? Ok, too many to keep track. How about per hour? Still too many? Ok what about every 10 minutes? Do you hear little voices in your head telling you just 5 more minutes on Instagram or how you just need another new pair of shoes or how you get so antsy about not having been to the gym yet today that your throat starts to tighten, sweat runs down your forehead and your mind seems unable to concentrate on anything until you’ve finished your daily workout? Addiction comes in many forms, and so I ask the question again, are you an addict?

Behavioral Addiction

Just like in substance addiction, behavioral addiction can be summed up by having or feeling any compulsive/repetitive involvement in an act that results in a rewarding experience. Interestingly, the individual will still seek this reward even if they are aware of the consequences to follow. Some examples of behavioral addiction include gambling, shopping, exercising, and pretty much anything technology-wise. With all of the spotlight on substance addiction, just how similar are behavioral addictions?

Similarities via Symptoms

Imagine this, someone is trying a drug for the first time and it makes them feel incredible, so they continue use in order to get that same pleasant feeling, until day after day, it starts to become less enjoyable and feeling more like a chore. This is the result of a shift in a positive reinforcement to a negative reinforcement, which can also be seen with a behavioral addiction, and can be explored more here. Have you ever downloaded a new app that was at first fun to play but then over time you found yourself only logging on to collect the “daily reward”, or how beginning your journey at the gym to relieve stress turned into going due to fear of returning to what you looked like from a time before. Just like substance addiction, behavioral addicts can suffer from

• Strong sense of craving
• Loss of control over their behavior
• Tolerance build-up
• Difficulty during withdrawal period and preventative relapse

Two similar forms of treatment for both cases of addiction include psychosocial and pharmacological, although since many behavioral addictions cannot be diagnosed the same as substance addictions are (except gambling), current issues include getting people properly diagnosed and treated.

Similarities via Neurochemistry

Would you believe me if I told you that your brain can change how it is “wired”? Well, it actually can, and this is referred to as neural plasticity. Individuals who are addicted have more than likely developed changes in their neural circuits that can give rise to new meanings and reward perceptions to drugs/shopping/technology/etc. Studies have actually shown that there is an increase in the dopamine “dump off” at the nucleus accumbens (NAc), which gives a more pleasurable feeling to the individual and is heavily involved in the reward system. These changes can alter the function and shape of neurons in the brain, which currently, seems like in an irreversible way.

Are you still there? How many times have you checked your phone since reading this blog? Ok, just checking…

An interesting study was performed with rats, where there were two groups. They were all provided with drugs in a cage and had the ability to self-administer them, except one group additionally had an exercise wheel they could run around in. What researchers noticed was that the rats who had used the wheel in their cage showed increased levels of dynorphin, delta FosB, and increased levels of dopamine at the NAc– all of which are seen in addiction! These rats also did not end up self-administering drugs after their run either. Is exercising a way to help with addiction? Did the wheel act as an environmental variable instead of an exercising factor? As you can see, there are still many questions left unanswered, but maybe researchers are on to something.

A Future Full of…

With the rise of technology, what is our world going to look like in 5,10, 20 years from now? What are we going to do to prevent this? Is anything actually needed to be prevented? It only seems like a matter of time before there are ways for diagnosing not only substance addictions but behavioral addictions too. Until then, we might just have to continue on with our days, checking our phones once they “ding” with a notification, briefly pausing, thinking, “Wait, do I have an addiction?”.

Addiction is a term that almost everyone seems familiar with. People can be addicted to a variety of things, whether it be substance use like alcohol or pills, a food addiction like sugar, or a behavioral addiction like gambling. One of the most common forms of addiction seems to be alcoholism, affecting approximately 14.5 million Americans age 12 and up and over half of all Americans have family history of alcoholism. This form of addiction is incredibly prevalent in our society and doesn’t seem to be stopping anytime soon. Researchers have been looking into the action of binge drinking as it occurs within the younger generations, age 15-25, to see if it could possibly be a source of etiology for chronic alcoholism.

Chronic vs. Binging Alcoholism

Chronic alcoholism is defined as partaking in a long period of excessive alcohol intake in which a person develops a dependence for the substance, a high tolerance, and experiences severe withdrawal symptoms. In comparison, binge alcoholism is considered to be a drinking heavily in an episodic manner, but these drinkers do not have a dependence, tolerance, withdrawal, or increased preference for the substance after the drinking episodes. Binge drinking is incredibly common within high schoolers and college-aged students and is actually three to four more times common than chronic use; it also seems to add more risk to becoming a chronic user, with 15% of binge drinkers going on to become a chronic alcoholic. The biggest question is, why does binge drinking not have the same effects as chronic drinking? The answers lie within the neurochemical background of addiction.

What’s Going on in the Brain?

During addiction, the reward pathway (mesolimbic dopamine pathway) seems to be impaired, especially within the ventral tegmental area (VTA) and the nucleus accumbens (NAc). This happens due to excessive drug exposure. In chronic alcoholism, repeated drug use sensitizes the brain’s response to the drug, creating a vicious cycle of relapsing and withdrawal. When the drug is excessively being used, CREB (cAMP response element-binding protein) is released within the NAc, which promotes a rewarding behavior. The chronic drug use causes the brain’s receptors to change so they can become more tolerant to the drug and require a higher dosage for the same pleasure. The constant intake of drugs causes long-term depression of the NMDA receptors on the dendritic spines to change and increases the presence of AMPA receptors instead and creates long-term potentiation. This conformational change that takes place at the postsynaptic site adapts to the amount of drug use and allows tolerance and dependence to form. To read more about this you can read here: https://thebrain.mcgill.ca/flash/i/i_07/i_07_m/i_07_m_tra/i_07_m_tra.htmlContinue reading →

Introduction

When I think of a hereditary gene, I often think of physical appearances such as eye and hair color. If both parents of a child have brown eyes and brown hair, then there is a particularly good chance that the child will follow suit. To my surprise, this same process is shown in the psychiatric disorder, schizophrenia. Schizophrenia is a disorder that Merriam-Webster describes as, “a mental illness that is characterized by disturbances in thought (such as delusions), perception (such as hallucinations), and behavior (such as disorganized speech or catatonic behavior), by a loss of emotional responsiveness and extreme apathy, and by noticeable deterioration in the level of functioning in everyday life.” Genetics play a crucial role in the development for Schizophrenia. If an individual has a sibling or parent with the disorder, their probability of being diagnosed with the disease rise from one to ten percent. With this knowledge it is evident that there is something going on within the genetic makeup.

What Are the Contributing Genes?

Schizophrenia has been under extensive research for a long period of time. Due to the complications that are involved with this disorder, researchers have and still are having a tough time to determine the site where gene mutations are taking place. Although the disease is severely complicated, advancements in technology have allowed for bits of new information. The breach of this new information started with a study that looked at the genetic makeup of 186 Irish pedigrees. These pedigrees all had one thing in common right off the bat and that was Schizophrenia. After scans, researchers had noticed a vulnerable location in which there was activity. This activity was occurring on chromosome 6p.

The findings that the early Irish studied provided opened for a more detailed and extensive research. Scientist who were curious about this disorder were given a target to concentrate on. Studies would continue to become more and more in hopes to gain more knowledge on this complex disease. Results started to support that chromosome 6p was in fact a location with a lot of gene activity for Schizophrenia. Researchers however have not been able to target which gene or genes are accounting for this genetic vulnerability to schizophrenia.

What’s Next?

Chromosome 6p has now been a “hot-spot” for schizophrenia research. Researchers are continuing to try and pinpoint certain genes, but progress is not coming as fast as they would like. The goal would be to eventually identify these genes which would allow for future treatments and the possible deletion of the disease. Although this would be ideal, the complexity of Schizophrenia will not be allowing for that to happen anytime soon.

Conclusion

As one can tell, schizophrenia is an overly complicated disease. This complication causes many unknowns with treatments and identifications for the disease. Studies can prove that there is a hereditary gene or genes associated with the disorder but pinpointing these genes has been impossible to date. One positive note that studies did show at least gives research an area to study and that is within the 6p chromosome. Continuing with this data it is in hopes that one day we will be able to unravel this mysterious disorder.

Imagine if a skyscraper were constructed in such a way where they needed constant maintenance, and if they did not get it would be there natural state to collapse and be destroyed. It seems like a real backwards way to construct a building, or to maintain anything man-made or natural for that matter. So it is surprising to find out that a major chemical signaling pathway, the Wnt and GSK pathway, operates in manner that aligns with this metaphor. The natural state of this critical signaling pathway is that of destruction. The pathway must be activated by a Wnt ligand that triggers cellular events that stop a complex that is involved with destruction. If that seems a bit confusing, I was with you but bear with me. The pathway must be activated, to stop intracellular destruction, which maintains normal cell development.

So why does this matter?

The Wnt signaling pathway is integral in the development of the brain. For example, Schizophrenia is a well-known condition typically associated with disruption of this pathway. Schizophrenia and this pathway, in a nutshell, involves the destruction complex in the cell running wild and not being hindered by Wnt signaling as it should be. This makes sense because there are notable brain changes in schizophrenia involving the anatomy, and key developmental differences. These anatomical changes have some significant consequences for individuals afflicted with such a disease.

Symptoms of Schizophrenia

Most people are familiar with the positive symptoms common of schizophrenia. These would include hearing voices, and grand delusions of government conspiracies for example. These symptoms are only a small part of the wide varieties of symptoms schizophrenia is associated with. For example there are negative symptoms such as flat affect, and low motivation. These symptoms can also be accompanied with cognitive issues which can also have a substantial impact on quality of life.

Cognition and Schizophrenia

Along with positive and negative symptoms, there is a myriad of cognitive deficits typical of schizophrenia some of which are:

• Attention: a common cognitive deficit involved with schizophrenia involves attentional issues. While a neurotypical individual can multitask and focus on several objects, those with schizophrenia tend to hyper-focus on one object at a time.
• Working Memory: Attention and working memory work hand in hand. Working memory is your ability to take in information and briefly maintain and use it in an ongoing task. Generally working memory capacity is 3 to 4 simple items but it is considered less in schizophrenia. If you can only focus on one thing at a time you can only bring that one thing into your memory.
• Executive Functioning: Executive Functioning is a broad and complex topic, but it generally includes things such as planning and goal-oriented behavior. These are all considered impaired in schizophrenia as it is more difficult to bring in new information and adjust to changes.

Conclusion

It is a little wild to think that a simple, and strange signaling pathway going wrong can have such broad consequences for an organism. A signaling pathway gone awry and causing cell death in its resting state is responsible for positive, negative, and cognitive symptoms alike. How such a small molecule, such as the GSK kinase that is responsible for the destruction, can have such broad implication for an overall organism.

“Too much of anything is a bad thing”, right? The idea of balance is integral to our understanding of the world across different belief systems and at various levels. Yin and Yang are perhaps the most notable examples of opposite forces evening out a greater whole, but the concept guides our beliefs and actions in many ways, from how we prioritize commitments in our lives to what kinds of foods we consume. While a disrupted balance in how we live our life can certainly make us feel anxious, It turns out that internal balance plays a key role in anxiety as well, with two neurotransmitters called Glutamate and GABA keeping each other in check- or at least supposed to be. 

Glutamate and GABA – How do they Relate?

In terms of anxiety, Glutamate and GABA could be considered the ‘yin’ and ‘yang’ of the central nervous system. Both are highly important for sending messages between neurons; in fact, they are responsible for over 90% of neurotransmission in the brain! They have directly opposite effects, however, with glutamate sending excitatory signals that make neurons more likely to ‘pass on a message’ and GABA sending inhibitory signals that make this communication less likely. Physiological homeostasis of the nervous system is needed for proper functioning, and it requires regulation of opposing forces such as these. So, when there is an abundance of Glutamate and low levels of GABA, stress and anxiety responses are more likely to occur.  

In many areas of the brain, glutamate and GABA are intertwined within neural circuits and pathways, and this close interaction allows them to balance each other through tight regulation. For example, axons of a specific type of cell called granule cells synapse with interneurons that release GABA in the the dentate gyrus, an area of the brain’s hippocampus. The granule cells release glutamate when excited, but because the neurons they synapse on release inhibitory GABA, the glutamatergic neurons (neurons that release glutamate) that these neurons project to will in turn be inhibited. In short: excitation stimulates inhibition, and this leads to inhibition of excitation. Pathways like these provide a mechanism for regulation of anxiety, because higher levels of GABA will result in lower levels of glutamate as a way to create balance – in fact, anti-anxiety medications such as benzodiazepines work in a similar fashion to this, by enhancing inhibitory effects of GABA on glutamatergic neurons. 

Another area involved in balancing these two neurotransmitters is the amygdala, whose general function is processing fearful and unpleasant stimuli. Specifically, the Basolateral nucleus (BLA), Central Amygdala (CeA) and Bed Nucleus of Stria Terminalis (BNST), are all locations involved within the amygdala. Glutamatergic neurons in the BLA are regulated by GABAergic interneurons that lie within this area as well. The CeA has only GABAergic neurons and receives input from the BLA. All of these connections and communications serve to modulate balance of GABA in the amygdala, with GABAergic neurotransmission helping to inhibit the amygdala’s interaction with stress and anxiety. On the flip side, however, stress may cause interneuronal networks to reduce, which disrupts the excitatory and inhibitory balance and can therefore lead to neuropsychiatric disorders. Animal studies back this up: in one experiment, for example, subjecting rats to social isolation reduced the expression of GABAergic neurons in the BLA.

Balance on a Societal Scale  

While these physiological mechanisms certainly offer insight for how anxiety responses can be regulated or dysregulated in the brain, they do not explain the rapidly rising rates of mental illness in the U.S. On a societal level, the argument has been made that people with mental disorders such as anxiety and depression are “canaries” of our cultural coal mine. Just like canaries were said to warn miners of an incoming explosion by singing, people suffering from mental illness are early warning signs of imbalance in society. The canaries did not survive the explosions, and people with mental health problems are victims of what some might view as an impending ‘cultural collapse’. I’ve always held the view that the ultimate priority should be fixing the underlying problems, not masking the symptoms. So, if the ‘canary in a coal mine’ hypothesis is correct, what could be causing the degradation of balance and harmony in the U.S? I’ve seen fingers pointed at many different elements in society, ranging from stress to technology to consumerism. Let me know what you think could be behind the rise of anxiety and other mental disorders in the comments!