This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is Major Depression?
Major depression is a severe form of depression also known as major depressive disorder or clinical depression. It consists of a variety of symptoms, but most prominently, it is characterized by having at least either a depressed mood or a loss of interest and pleasure in daily activities for at least a period of two weeks [1]. In some cases, it might impair the ability of individuals to conduct daily life activities. It is also the most commonly diagnosed form of depression, with 6.7% of adults above the age of 18 years old in the United States having at least one major depressive episode in 2016. It also more common in females than in males, with a prevalence of 8.5% in females compared to 4.8% in males [2].
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Symptoms
According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) published by the American Psychiatric Association, the possible symptoms of major depressive disorder are:
i. Depressed mood or feelings of sadness/hopelessness/emptiness.
ii. Loss of interest and pleasure in daily activities
iii. Significant weight loss or gain
iv. Changes in appetite nearly everyday
v. Inability to sleep or excessive sleepiness almost daily
vi. Psychomotor agitation or retardation
vii. Fatigue
viii. Difficulty focusing or indecisiveness
ix. Feelings of worthlessness or extreme guilt
x. Recurrent suicidal thoughts
A minimum of five or more of these symptoms (including i and ii) for a period of at least 2 weeks is required for a diagnosis. It is important to note that grief or responses to significant losses is different from MD. These events induce suffering but typically does not induce a major depressive episode. The main emotions of grief is emptiness and loss while in MD, it is often the feelings of the inability to foresee happiness. There is more of a preoccupation of thoughts and memories of the deceased in grief whereas in MD, there are more self-critical and pessimistic thoughts [1].
According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) published by the American Psychiatric Association, the possible symptoms of major depressive disorder are:
i. Depressed mood or feelings of sadness/hopelessness/emptiness.
ii. Loss of interest and pleasure in daily activities
iii. Significant weight loss or gain
iv. Changes in appetite nearly everyday
v. Inability to sleep or excessive sleepiness almost daily
vi. Psychomotor agitation or retardation
vii. Fatigue
viii. Difficulty focusing or indecisiveness
ix. Feelings of worthlessness or extreme guilt
x. Recurrent suicidal thoughts
A minimum of five or more of these symptoms (including i and ii) for a period of at least 2 weeks is required for a diagnosis. It is important to note that grief or responses to significant losses is different from MD. These events induce suffering but typically does not induce a major depressive episode. The main emotions of grief is emptiness and loss while in MD, it is often the feelings of the inability to foresee happiness. There is more of a preoccupation of thoughts and memories of the deceased in grief whereas in MD, there are more self-critical and pessimistic thoughts [1].
The Biology of Depression
Factors that may cause depression include neurotic temperament, stressful life events and adverse childhood experiences, which eventually interact with our genetic makeup to increase a person’s risk of developing MD. Genes encode for proteins in our bodies, including those that are involved in the functioning of our brain and nervous system. For example, genes control the way the neurons in our brain function and metabolize neurotransmitters, affecting the way we respond to stress [3]. Hence, people with more vulnerable genetic makeup are more predisposed to developing MD. First-degree family members of individuals with major depressive disorder have a two to fourfold higher risk of developing MD than the general population [1]. Moreover, monozygotic twin studies have shown that the heritability of MD is 37% [4]. Nevertheless, depression is a polygenic disease, meaning that it is a result of the combined effect of many gene variants, making understanding its heritability more difficult [5]. One of the genes that have recently been associated with major depression is Myocyte Enhancer Factor 2C (MEF2C). [6] |
What is MEF2C?
MEF2C is a gene that codes for a member of the MADS box transcription enhancer factor 2 (MEF2) family of proteins, which is responsible for muscle formation. The encoded protein, MEF2 polypeptide C, has both trans-activating and DNA binding activities and is often important for normal neuronal development and synaptic transmission. It is also essential for learning and memory based in the hippocampus and genetic variants have been associated with mental retardation and schizophrenia [5, 7]. |
In depression, genome wide association studies (GWAS) have shown that single nucleotide polymorphisms (SNPs) in the MEF2C locus is associated with self-report of depression in individuals of European descent [6] and in Australian cohorts [8]. Hence, the MEF2C locus is associated with the risk of depression although the molecular pathway and mechanism of action of MEF2C in relation to depression has yet to be determined. Nevertheless, the associations of MEF2C with disorders of the nervous system shows promising possibilities linking this gene to depression.
References:
[1] Diagnostic and Statistical Manual of Mental Disorders: https://dsm.psychiatryonline.org/doi/full/10.1176/appi.books.9780890425596.dsm04
[2] National Institutes of Mental Health: https://www.nimh.nih.gov/health/statistics/major-depression.shtml
[3] Aan het Rot, M., Mathew, S. J., & Charney, D. S. (2009). Neurobiological mechanisms in major depressive disorder. CMAJ : Canadian Medical Association Journal, 180(3), 305–313. http://doi.org/10.1503/cmaj.080697
[4] Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. 2000;157(10):1552–62.
[5] Mullins, N., & Lewis, C. M. (2017). Genetics of depression: progress at last. Current psychiatry reports, 19(8), 43.
[6] Hyde, C. L., Nagle, M. W., Tian, C., Chen, X., Paciga, S. A., Wendland, J. R., ... & Winslow, A. R. (2016). Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature genetics, 48(9), 1031.
[7] Genetics Home Reference: https://ghr.nlm.nih.gov/gene/MEF2C#
[8] Corfield, E. C., Yang, Y., Martin, N. G., & Nyholt, D. R. (2017). A continuum of genetic liability for minor and major depression. Translational psychiatry, 7(5), e1131.
Images:
Header: www.healthyplace.com/blogs/wp-content/uploads/2018/01/guilt-and-shame.jpg
Biology of Depression: www.pdhealth.mil/clinical-conditions/depression
Fig.1: https://www.nimh.nih.gov/health/statistics/major-depression.shtml
Fig.2: https://ghr.nlm.nih.gov/gene/MEF2C#location
[1] Diagnostic and Statistical Manual of Mental Disorders: https://dsm.psychiatryonline.org/doi/full/10.1176/appi.books.9780890425596.dsm04
[2] National Institutes of Mental Health: https://www.nimh.nih.gov/health/statistics/major-depression.shtml
[3] Aan het Rot, M., Mathew, S. J., & Charney, D. S. (2009). Neurobiological mechanisms in major depressive disorder. CMAJ : Canadian Medical Association Journal, 180(3), 305–313. http://doi.org/10.1503/cmaj.080697
[4] Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. 2000;157(10):1552–62.
[5] Mullins, N., & Lewis, C. M. (2017). Genetics of depression: progress at last. Current psychiatry reports, 19(8), 43.
[6] Hyde, C. L., Nagle, M. W., Tian, C., Chen, X., Paciga, S. A., Wendland, J. R., ... & Winslow, A. R. (2016). Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature genetics, 48(9), 1031.
[7] Genetics Home Reference: https://ghr.nlm.nih.gov/gene/MEF2C#
[8] Corfield, E. C., Yang, Y., Martin, N. G., & Nyholt, D. R. (2017). A continuum of genetic liability for minor and major depression. Translational psychiatry, 7(5), e1131.
Images:
Header: www.healthyplace.com/blogs/wp-content/uploads/2018/01/guilt-and-shame.jpg
Biology of Depression: www.pdhealth.mil/clinical-conditions/depression
Fig.1: https://www.nimh.nih.gov/health/statistics/major-depression.shtml
Fig.2: https://ghr.nlm.nih.gov/gene/MEF2C#location
This website is under construction by Jer Weann Ang for Genetics 564, a UW-Madison undergraduate class.
Contact: [email protected]
Last updated: 05.10.2018
Contact: [email protected]
Last updated: 05.10.2018