Future Treatment of Depression

The treatment of depression has been shown historically to be extremely difficult.  Patients suffering from major depressive disorder may seek treatment in the form of therapy, prescription medications, or a combination of both. Often times, prescribed medications do not help to relieve the oppressive symptoms of depression, or they may cease to work over time. Many patients find themselves in an endless cycle of trying different medications or combinations of medications, none of which aiding to alleviate their depression. Research continues to be conducted to further our understanding of the pathology of depression and related disorders.

Rebecca Silton and colleagues recently conducted a study regarding positive affect and its association to prefrontal cortical activity in those with remitted depression. They used electroencephalography to study the brain activity of individuals with remitted depression. Their study found that low positive affect was associated with decreased frontal brain activity. This was consistent with other research that suggested that low positive affect was correlated with high levels of prefrontal alpha, or decreased frontal brain activity. High levels of prefrontal alpha may indicate the increased potential for a future depressive episode. Further research like this will continue to aid in our understanding of mood disorders, and therefore the development of better treatments for depression.

New Jersey psychiatrist Steven Levine first prescribed ketamine as a treatment for depression in 2011 to a patient whose severe depression could not be treated with any commercially available antidepressant. Levine was the first psychiatrist in the United States to offer ketamine in a clinical setting. Since then, Levine has given ketamine to over 600 patients to treat their depression, with a success rate close 85 percent, far above the 45 percent success rate for traditional antidepressants, and there have now been hundreds of research studies done on the treatment of depression with ketamine. Though traditionally used as an anesthetic, to help treat depression ketamine is given intravenously in a series of small doses over the course of a few weeks followed by maintenance doses. The drug can help lift depression in as little as a few hours after the first administration. Traditional depression medications, like selective serotonin reuptake inhibitors (SSRIs), may take two weeks or more to begin functioning. The American Psychological Association is currently making guidelines for the administration of ketamine, and the hope is that coverage from insurance companies will soon follow after the guidelines are created.

The work of Rebecca Silton and Steven Levine emphasizes the importance of continued research on the etiology of depression from a variety of perspectives. A greater understanding of the causes of depression will allow for the development of better treatments for patients in the future.

Olksman, Olga. “Depressed? Your Doctor Might Soon Prescribe Ketamine.” The Guardian. 3  
         Mar. 2016.  Web. 4 May  2016. 

http://www.theguardian.com/lifeandstyle/2016/mar/03/depression-medication-fda-psychadelics-ketamine-psilocybin-johnson-and-johnson-mdma

 Silton, Rebecca et al. “Low Positive Affect is Associated with Reduced Prefrontal Cortical
          Activity in Remitted Depression.” Psychophysiology. Article under review. Web. 4 May
          2016.

Your Heart says Treat Depression

           Depression has become an increasing concern in society. It is often said that my generation, millennials as we are called, are even more susceptible to depression. While I have had my low points, the TED talk introduced to me in class by Dr. Silton, Depression, the Secret We Share presented by Andrew Solomon was really insightful concerning the effect depression had on him. It really made the concept of anhedonia and the issue of decreased vitality more salient for me. The talk by Dr. Rebecca Silton really hit me as I have loved ones who have suffered from depression and it seems to be something that is commonly underrated. I know I did not understand it when I used to think depression was just sadness that a person could get over when I was young and ignorant. Sometimes psychological disorders with vague diagnostic criteria and little mechanistic understanding are given less emphasis than physiological diseases, such as heart disease. If it’s something psychological, it’s easy for others to say, “Just get over it.” However, an article in the Scientific American, Treating Depression Early May Protect the Heart, points out that “heart disease and depression often go hand in hand” and this probably begins at an early age. The news article mentions a study that used questionnaires to measure mental health and depression symptoms while also measuring the diameter of retinal blood vessels, which could indicate early cardiovascular disease. They came across a correlation and found that “participates with more symptoms of depression and anxiety had wider retinal arterioles than others, which could reflect the quality of blood vessels in their heart and brain” (Rodriguez). In the article, one of the researchers from Arizona State University does admit that they are unsure if this relationship is causal but that the symptoms of the psychological disorders could indicate who is at risk for cardiovascular disease.

            So, I think this news article emphasizes the importance of identifying those at risk for depression and treating their depressive symptoms earlier, it can possibly prevent heart disease in some people. The study "Low positive affect and reduced PFC activity" done by Dr. Silton, explains the association between low positive affect and depression. Low positive affect, which is also associated with anhedonia (the inability to feel pleasure), correlated with increased alpha waves in the left prefrontal cortex. Alpha Waves (8-13 Hz) in the prefrontal cortex might correlate with the attentional network whose decreased efficiency may play a role in depression. While the mechanism is still not completely clear, the study does offer more insight. Dr. Silton’s findings may be helpful for identifying those at risk for depression so that the negative symptoms do not keep escalating. Her study looked at individuals with remitted depression, so they were not currently in a major depressive episode. Yet, the increase in alpha waves within the prefrontal cortex remained, indicating that positive affect and negative affect could be “trait-like” and, therefore, provide significant clues for early identification. This seems to suggest thinking about depression as a chronic disease rather than something that is there and then suddenly gone. Something I found interesting between the two articles was that Dr. Silton’s study distinguishes the characteristics of anxiety and depression, with low positive affect being distinct to depression while high negative affect was associated with anxiety, but the studies mentioned in the articles seemed to clump the symptoms of anxiety and depression. I think this goes to show that more research and understanding of brain mechanics for each condition is needed.  

            The article from the Scientific American does also cite another study from Psychosomatic Medicine that states treating the symptoms of the psychological disorders early may help prevent heart disease. In my opinion, I believe depression is a very real issue but our understanding of its neurological mechanism and cause is limited and hazy. I think studies like this one performed by Dr. Silton and the article in the Scientific American really demonstrate the importance and urgency of discovering more and treating the debilitating disorder of depression that affects so many people. While I think improving the overall quality of life for the people suffering from depression through early action and detection is enough in itself, adding on the possible prevention of heart disease by treating depressive symptoms is an added incentive to learn more about depression, its workings and its effects and how to better treat it. These correlations exemplify the significance of depression and the importance of treatment.

References:

Ted Talk by Andrew Solomon

https://www.ted.com/talks/andrew_solomon_depression_the_secret_we_share?language=en

Rodriguez, Tori. “Treating Depression Early May Protect the Heart.” Scientific American. 1 May 2015. Web. http://www.scientificamerican.com/article/treating-depression-early-may-protect-the-heart/

Rebecca Silton et al. “Low positive affect and reduced PFC activity”

https://luc.app.box.com/v/neuroscienceseminar/1/5783525629/62930100982/1

E-Cigarettes The Way To Go or No?

    

            Dr. Daniel McGehee a professor at the University of Chicago came to Loyola University Chicago to speak at a neuroscience seminar on February 23rd about research regarding Nicotine intake, and its effect on neurological activity influencing addiction. Dr.McGehee’s presentation included research that his laboratory is conducting regarding the intake of nicotine. The substance nicotine was introduced into brain slices from mice and was further studied on how it activates nicotinic receptors (nAChRs) in the brain and increases the excitability of dopamine (DA) neurons in the ventral tegmental area (VTA). According to other studies there have been results where scientists have seen this before specifically with drugs. With the excitation of DA neurons in the VTA, this directly facilitated the long-term potentiation in VTA dopamine neurons that increased glutamate release by naChRs. This illustrates the strength of nicotine and its ability to alter synaptic strength of the dopaminergic neurons to long term rather than short term. The significance of this alteration to the neuron activity in the brain is that it is happening in the VTA where many studies have shown to be the local source of addiction. Current research is ongoing on how to better understand nicotine, its effects on neurological activity when it is present in the VTA. Discoveries presented from Dr. McGehee’s presentation will allow further investigation on the long-term synaptic strength issues and smoking addiction. 

 

              Through a more societal perspective, there has been an uprising in the new e-cigarettes or aka -vape pens. An article from the New York Times but Sabrina Tavernise talks about how E-Cigarette Use by U.S. teenagers is increasing, “About 5 percent of middle- school students reported using e-cigarettes in 2015, up from about 4 percent in 2014, according to data from the Centers for Disease Control and Prevention.” Also the popularity of electronic cigarettes have soared since their introduction in the mid-200s, “ Bonnie Herzog, an analyst with Wells Fargo, estimates the total vapor market, including e- cigarettes and other related products, such as liquids and personal vaporizers, totaled about $3.3 billion in the United States 2015.”  It is clear that e-cigarettes are starting to become popular and appeal to the youth. With the discoveries made by Dr. McGehee it should be concerning that the rise of electronic cigarettes is replacing the everyday tobacco cigarrete , even though this alternative is claimed to be “healthier”. The fact is that there is still tobacco in the product, and Dr.Thomas R. Frieden, the director of the C.D.C. states, “No form of youth tobacco is safe. Nicotine is an addictive drug and use during adolescence may cause lasting harm to brain development.” This is an interesting statement made given the results of Dr.McGehee’s experiments in changing DA levels in the VTA and its correlation to longer lasting DA that affects the VTA- a source commonly known for addiction. And so all this is something to think about when you or someone you know picks up an electronic cigarette risking the chances of leading to addiction.

Mao,D., Gallagher, K., McGehee, D. “Nicotine Potentiation of Excitatory Inputs to Ventral Tegmental Area Dopamine Neurons.” The Journal of Neuroscience 31. 18 (2011): 6710-6720. Print.

 Tavernise, Sabrina. "E-Cigarette Use by U.S. Teenagers Rose Last Year, Report Says." New York Times. New York Times, 14 Apr. 2016. Web.

Where Do Forgotten Memories Go?

Our memory is an important process that is used daily throughout our whole life. We can use it to store information such as the knowledge learned in school or even a person's name and appearance. Memory also allows us to recollect information and past experiences that can be useful for many things in our daily lives. Our memory is very significant in our life it is basically the entirety of what we remember and it gives us the ability to adapt from former experiences and allows us the capability to learn. Even though our memory is a remarkable part of our life, it is not always perfect. Many flaws can accompany our memory and these problems can have a great influence on our life.

Absent-mindedness is one of the biggest flaws in our memory and these lapses in attention happens to all of us. It is an irritating feeling since it stops us from recalling bits of information and can lead us to be disorganized and frustrated. Every person has felt being forgetful, whether it be forgetting a key fact for a history test or even trying to figure out a person's name. This leads us to a key question, what happens to these forgotten memories?

There are two main theories that scientists have held for a long time. One theory predicts that memory does not decay but simply becomes overshadowed by new memories. The seconds theory predicts that older memories start to become weaker and new information degrades old recollections in order to not interfere. There is significant difference between these two theories because if the first theory is correct there is a possibility for recovery, but if the second theory is correct it can allow for a strategy of lessening traumatic memories. Both of these theories have positive benefits for our memory, but which one is correct?

In the article “Memories Weaken without Reinforcement, Study Finds” by Pam Belluck, it states that scientists in Birmingham and Cambridge, England, have conducted a study and were able to claim and provide evidence of memory’s weakening. The experiment “involved several stages with 24 participants first trained to associate words to two unrelated black and white pictures from lists of famous people, ordinary objects or scenes” (Belluck). They were then shown a cue word and asked to recall the image they had been trained to link the word to in order to cause that image to become the dominant memory. To test this they first had the word sand associated with Marylyn Monroe and then hat. The scientists then told the participants to press a button if they were recalling Monroe. This allowed them to see that when participants would choose the word Monroe when looking at the word sand instead of choosing the competing memory of the hat. From the brain scans they were able to find unique patterns of brain activity, also known as a neural fingerprint. They received these neural fingerprints by recording brain activity in the prefrontal cortex of the participants when they were viewing each picture of Monroe and the hat.

Scientists then wanted to see what happened to the memory of the hat, and to test this they showed the participants two different pictures of Monroe and two different pictures of the hat. They then asked which version they had been trained to recognize. The scientists reasoned that if the had memory had not degraded the participants would pick the right hat more often as they would with the right Monroe.

They they then obtained and identified a neural fingerprint like the cue word test. The results showed that when the word sand was first shown, the participants brain activity showed both Monroe and hat patterns, but with consecutive showing of the sand cues their brains showed fewer hat traces. According to Dr. Wimber, this meant that “we watched the memories being suppressed, actively degraded...it’s not just that the target memories get stronger; the other memories get weaker”(Belluck). From this, they were able to conclude that the results don't support the first theory of forgotten memories in which they get overshadowed.

In relation to this study, Dr. Anthony Ryals came to Loyola University Chicago to discuss his research on implicit memory the the limits. In his talk he introduces to us that memory has two different ways of remembering information and they are implicit and explicit memories. Implicit memory, also known as non-declarative memory, is the main topic of his research and this memory type is where information is remembered unconsciously and is unintentional. Information that you are trying to intentionally remember is stored in your explicit memory, also known as declarative memory. With this explains how it is possible for memory processes to occur without conscious awareness. He also states that a key fact in his research is that implicit unconscious processing may be involved and influence performance in explicit memory tasks and cognitive functioning. With evidence from brain studies that show some regions like the MTL cortex are active under certain circumstances in both implicit and explicit tasks. His study shows us that more information and research is needed to identify association and disassociation in memory and to expand our understandings of the implicit and explicit phenomena.

Both of these studies shows the many processes that our memory contains and goes through. They provide us with possible explanations with things like forgetfulness and also show us how we recall our information. These studies can benefit each other by providing information on brain activity and what regions of the brain are active. They can also be useful to help improve techniques in memory and possibly in future treatments of diseases like Alzheimer's. The research done in both studies provide an enormous amount of knowledge that can lead to more information about the brain and its ability in memory. These studies are important and allow us to take home information that is useful for us since memory is a huge part of our daily lives.

References

Belluck, Pam. "Memories Weaken Without Reinforcement, Study Finds." The New York Times. The New York Times, 2015. Web. 05 May 2016.

Ryals, Anthony J. "The Outer Limits of Implicit Memory." The Wiley Handbook on the Cognitive Neuroscience of Memory,. Ed. Joel L. Voss. Print.

To keep, or not to keep ‒ that is the question.

(Cohen 2016)

Memory is very a interesting yet highly complex process and therefore mostly still a mystery. However, much work is currently being done to help us understand the mechanism by which we encode, store and retrieve memories.

The article titled “Memory replay prioritizes high-reward memories,” recently published by ScienceDaily, discusses a study that looked at how high-rewards can affect our memory. Professor Charan Ranganath, a neuroscientist at UC Davis, and his postdoctoral fellow, Matthias Gruber conducted the study using fMRI scanning to view brain activity during reward-motivated learning as well as at rest both before and after learning. During the test, participants were asked questions like, “Do these objects weigh more than a basketball?” and were told that they would receive either a large or small monetary reward for providing a correct answer. The objects on a background image for context were presented and at the end of a series, the participants were told how much money they had accumulated. After a resting period, they were given a surprise memory test for objects that were shown. Data collected showed that for objects that had been associated with a high value reward, participants were able to remember both the objects and their backgrounds. Researchers also found that the pattern of activity that had been observed while participants performed the task was also seen during the period of rest that followed it. They concluded that during this period they were strengthening connections and fixing memories in place by replaying the rewarding memories. In essence, the study shows that our brain prioritizes memories that are deemed to be more valuable by replaying them while we are at rest.

A very similar study performed by Michael Cohen, a postdoctoral researcher at Northwestern University looked the neural mechanisms by which the brain does the prioritizing observed in the previous study. In his paper, titled,  Effects of aging on value-directed modulation of semantic network activity during verbal learning, Dr. Cohen discusses a study done in which he looked at whether the temporal and spatial patterns of brain activation differed in older adults when compared to younger adults during encoding of high and low value words. In the study, participants were given a cue indicating how many points they would receive if they remembered the word they were about to see in a future memory recall test. Using fMRI scanning, researchers analyzed the brain activity that occurred and found that individuals regulated activity depending on whether the word had a high value or a low one across the left-lateralized brain regions that are involved in semantic processing. In particular, young adults showed increased activity in those areas when the word was associated with a high value while older adults refrained from using those areas when words associated with low values were presented.

By using a similar reward-based paradigm, both studies offer interesting insights into the process by which the brain decides to keep what it does. In Dr. Cohen’s study we see that both younger and older adults use left lateralized brain regions to encode information they deem valuable although through different mechanisms. Dr. Gruber’s study explains what happens after we have decided that information should be kept. His study suggests we replay memories that are rewarding in order to fix them in place. Therefore the answer to question, to keep or not to keep, depends on whether the information is of high value.

References

• Cohen, M. S., Rissman, J., Suthana, N. A., Castel, A. D., & Knowlton, B. J. (2016). Effects of aging on value-directed modulation of semantic network activity during verbal learning. NeuroImage, 125, 1046-1062.

• University of California - Davis. (2016, February 12). Memory replay prioritizes high-reward memories. ScienceDaily. www.sciencedaily.com/releases/2016/02/160212130132.htm

Will You be a SuperAger with Me?

Will You be a SuperAger with Me?

To be young and free. To be vibrant and lively. To feel fully, and age gracefully.  These are some of our deepest desires as we look ahead. Our youth represents some of our best moments and most of us hopelessly wish we could freeze ourselves in this young, vibrant, full life we live now. Unfortunately, staying young forever is not possible. In our society, old age is associated with dependency, illness, and a slew of doctors’ visits. Lately, researchers have been studying SuperAgers. This group of men and women “age successfully”. Old age is associated with dementia and Alzheimer’s but this group of people seem to miraculously miss those illnesses. To combat this question, scientists study post-mortem brains as well as healthy seniors and compare their results to younger adults.

In class, we had the opportunity to listen to Dr. Tamar Gefen give a talk about the research she and her team conducted. Dr. Tamar and her fellow researchers studied a group of “SuperAgers”. This cohort of men and women are aged 80 and older “with episodic memory function at a level equal to, or better than, individuals 20-30 years younger” (Gefen et al.). In their study, Gefen and her team tested the memories of their subjects and saw that these participants performed at the same level as the cohort between the ages of 50 and 65. To take this a step farther, the scientists used MRI scans on both of the groups to find any differences in the brain matter. To their surprise, they found that the SuperAgers’ brains matched the thickness of the younger group. They also found that SuperAgers’ anterior cingulate was thicker than the younger participants. According to Dr. Gefen et al., this suggests that SuperAgers seem to have a better attention to detail which can be an explanation of why their memory is so successful.

The secret behind their good health? Well, an article by Kerry Sheridan, titled ‘Super-agers’ study may reveal secrets to staying young suggests that these men and women’s good mental health is an attribute to a number of factors such as good genes, environment, and socioeconomic status.

            In her article Sheridan talks about David Lowenstein, a neuropsychologist from the University of Miami. Loweonsein states that although studying Alzheimer’s disease is important and there needs to be more scientific discovery for that disease, “to unlock the mysteries of the brain, we also have to know why some people age successfully,” (Sheridan). Lowenstein believes that spending the time to research success stories on memory will help us better understand the human mind.  Science is at a loss for an explanation why one third of the autopsies on people 85 years old and over have signs of dementia yet show no symptoms when they were alive. This is rather puzzling considering the fact that these people biologically possessed symptoms of memory failure yet they experienced absolutely no side effects. Loewenstein and his team hope to find the answer to this question and more. 

            Loewenstein’s study includes 100 participants and of those 100 people, 40% live in a suburban retirement facility. Many of these seniors are highly active and hold jobs within their community. In the article we learn about Gwen North, an 85-year-old who runs the local thrift shop, working six days a week. Gwen and her husband are SuperAgers and together they are quite happy and upbeat in their neighborhood. In the article, it states that on top of having good genes, maintaining a healthy lifestyle attributes to a healthier mind, “work…may improve cognitive functioning” (Sheridan). Sheridan shows that because these seniors live in this community, they are able to lead healthy lives.

            On top of maintaining their healthy lifestyles, another significant factor to consider is that fact that many of these SuperAgers in Lowenstein’s study are “educated and white” (Sheridan). Because, they grew up in a privileged environment, they were able to save their earnings which helped them build a comfortable life in their old age. On the other hand, according to the article, it states that the African-American and Hispanic senior population faced “disproportionately higher rates of dementia than the country’s whites” (Sheridan). This statistic does not come as a shock. Unfortunately, people of color tend to fall low on the socioeconomic ladder. This means that minority groups face more problems regarding money, resources, and livelihood. This shows that mental health can be greatly affected by stressors induced early on in life such as financial burdens, job instability, and poor access to healthcare.

Building social connections, maintaining an active lifestyle, volunteering and working all help facilitate a healthy, functioning mind. Through Dr. Tamar Gefen’s talk and Kerry Sheridan’s article it is clear to see that there is a slew of factors that go into living a healthy life. With the continuation of studies from people like Dr. Tamar Gefen and David Loewenstein’s, maybe one day we will crack the code on aging with grace. Until then, our best bet to a healthy mind is making sure we lead stress-free, active lives.

**Works Cited**

Gefen, T., Peterson, M., Papastefan, S. T., Martersteck, A., Whitney, K., Rademaker, A., . . . Geula, C. (2015). Morphometric and Histologic Substrates of Cingulate Integrity in Elders with Exceptional Memory Capacity. Journal of Neuroscience, 35(4), 1781-1791. doi:10.1523/jneurosci.2998-14.2015

Sheridan, K. (2015). 'Super-agers' study may reveal secrets to staying young. Retrieved May 04, 2016, from http://www.businessinsider.com/afp-super-agers-study-may-reveal-secrets-to-staying-young-2015-11