Developing Better Treatments for Depression through the Molecular Level

 Everyone gets sad, you may have just gotten dumped, or just watched the beginning of UP, or you may have reached the bottom your box of ice cream and still crave more. This sadness is usually fleeting though, and doesn’t change your psychology long term. However, some people struggle with depression, a serious long term psychological illness that negatively affects a person’s mood, thoughts, feelings, or sense of self-worth. Depression is a debilitating psychological illness that affects a large portion of the United States. 

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Depression is a disorder of the brain that can be caused by a variety of factors. Some mutations in certain genes may lead to increased risk of depression. Not only that, but certain trauma, stressful situations, or loss of loved ones can lead to episodes of serious depression. Other things that change the physical composition of the brain, such as drug and alcohol abuse, other medical conditions, and imbalance of hormones can also put individuals at higher risk for depression.

People with depression generally have feelings of hopelessness, as they often feel empty and see life as pointless. Others feel inadequate and worthless, possibly due to serious trauma such as abuse that seriously messed with the psychology of their brain. Often those with depression show the inability to even get out of bed in the morning and lose interest in a lot of the things in life that once brought them great pleasure. People with depression often exhibit difficulty in sleeping and changes in appetite. 

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While depression is still prevalent among our population, what exactly causes it is still unclear. Researchers are still unsure what the molecular pathway of the illness is. To shed some light on this predicament, Dias et. al. recently published a study that examines how a protein called ᵦ-catenin affects other downstream proteins such as Dicer1 and microRNAs. ᵦ-catenin is a protein involved in a lot of the synaptic signaling of other neuropsychiatric illnesses, and is thought to have some sort of effect on depression in a certain regions of the brain. To study its effects, researchers studied groups of mice with and without ᵦ-catenin expressed and measured the amount of proteins of the downstream targets. What they found is that ᵦ-catenin activates a network that mediates behavior resilience. Behavior resilience is the ability to “bounce back” from a tragic or traumatic event and cope and recover from the effects. 

Mice with a defect had a decreased amount of downstream targeting proteins activated by ᵦ-catenin and thus had a decreased behavior resilience. Without behavior resilience, individuals can get overwhelmed by traumatic experiences and have difficulty coming back from them, if they do at all. To measure their resilience, they put mice in traumatic situations and examined how they interacted with other mice afterwards. Mice with a lack of ᵦ-catenin had adverse reactions to interacting with other mice and showed behavior or lethargy and loss of appetite and sleep.

            The researchers also had a group of mice with enhanced ᵦ-catenin, where they observed that the mice had an increased in behavioral flexibility. This allows them to overcome these traumatic experiences and interact with other mice shortly afterwards, despite receiving the same trauma as the mice with a lack of ᵦ-catenin. 

a: Indicates viral expression of β-catenin b: Compares social interaction of mice with and without transfected β-catenin c: Compared two groups in a swim test d: Compared the groups in a maze test e: Expression of downstream targets of β-catenin f/g: Showing more data comparing the groups as they socially interacting with one another http://www.nature.com/nature/journal/v516/n7529/full/nature13976.html

 

            This study has a parallel to humans, as many of ᵦ-catenin’s downstream targets, such as Dicer1 and microRNAs in the brain are present in human. MicroRNAs are small molecules that can modify RNA after transcription to regulate gene expression and ultimately change protein function. These miRNAs provide crucial roles to the regulation of neural development and plasticity. Since there is a small number of them already to regulate proper brain function, having a reduced amount of mutations in miRNA could lead to serious psychological disorders, such as depression. The researchers in this case were able to identify some of these miRNAs as a template for future studies. 

            Depression is still difficult to treat and do not always offer perfect solutions. As of now, we have a lot of common treatments such as antidepressants that work to increase certain neurotransmitters like serotonin that help brighten mood. Psychotherapy is also an option that allows an individual with depression to speak to a specialist so they can deal with everyday problems together. However, this usually isn’t sufficient for more serious forms of depression. Serious cases may have to rest to electroconvulsive therapy, which is designed to physically alter the electric waves in the brain to stimulate them. People with depression usually have areas of low activity, and this therapy helps brings those activities to a normal level. However, by better understanding this ᵦ-catenin pathway and how it affects downstream miRNA targets, perhaps researchers in the future can develop better treatments to help those battling the illness.

Sources: 

Dias C., Feng J., Sun H., Shao NY., et. al. (2014) ᵦ-catenin mediates stress resilience through Dicer1/microRNA regulation. Nature: International Weekly Journal of Science. 516: 51-55

 
Cherry, Kendra. "What Is Resilience? (And Why It Matters)." Abouthealth. N.p., n.d. Web. 24 Apr. 2015. <http://psychology.about.com/od/crisiscounseling/a/resilience.htm>. 

 

"Depression." NAMI: National Alliance on Mental Illness. National Alliance on Mental Illness, n.d. Web. 24 Apr. 2015. <https://www.nami.org/Learn-More/Mental-Health-Conditions/Depression>. 

 

"Depression." NIMH RSS. National Institute of Health, n.d. Web. 24 Apr. 2015. <http://www.nimh.nih.gov/health/topics/depression/index.shtml>.