Demystifying The Depression Gene
Having a genetic variant can make it more likelybut not definitivethat you will develop a condition associated with that variant.
If a gene associated with a specific condition is altered, it may be more likely to contribute to the development of that condition. A benign genetic variant is less likely to influence the condition than a pathogenic variant.
In some cases, researchers identify a genetic variant but dont know what effect it has. These variants are referred to as having “unknown significance.”
Several large genome-wide studies have proposed potential genetic connections to major depressive disorder. In 2017, researchers identified two new genetic variants associated with depression.
A 2018 study published in the journal Nature Genetics identified several genetic variants that appeared to be associated with symptoms of depression and, in some cases, physical differences in the brain.
While the research has provided valuable insight into the potential heritability of mental illness, no studies have definitively identified a single gene as the cause of depression.
Scientists believe it’s more likely that all the different genes and genetic variants each make a small contribution to a person’s overall risk. Research has indicated that genes may be passed down in different ways , which is another factor that could affect someone’s genetic predisposition to depression.
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Objective
To use a large, well-phenotyped single study of MDD to investigate how different definitions of depression used in genetic studies are associated with estimation of MDD and phenotypes of MDD, using polygenic risk scores .
Design, Setting, and Participants
In this case-control polygenic risk score analysis, patients meeting diagnostic criteria for a diagnosis of MDD were drawn from the Australian Genetics of Depression Study, a cross-sectional, population-based study of depression, and controls and patients with self-reported depression were drawn from QSkin, a population-based cohort study. Data analyzed herein were collected before September 2018, and data analysis was conducted from September 10, 2020, to January 27, 2021.
Main Outcome and Measures
Polygenic risk scores generated from genome-wide association studies using different definitions of depression were evaluated for estimation of MDD in and within individuals with MDD for an association with age at onset, adverse childhood experiences, comorbid psychiatric and somatic disorders, and current physical and mental health.
Results
Transcranial Direct Current Stimulation
Transcranial direct current stimulation is another noninvasive method used to stimulate small regions of the brain with the help of a weak electric current. Increasing evidence has been gathered for its efficiency as a depression treatment. A meta-analysis was published in 2020 summarising results across nine studies concluded that active tDCS was significantly superior to sham for response , remission and depression improvement. According to a 2016 meta analysis, 34% of people treated with tDCS showed at least 50% symptom reduction compared to 19% sham-treated across 6 randomised controlled trials.
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Descriptives And Phenotypic Correlations
Means, standard deviations, and thresholds of males and females in all age-groups are provided in Table 1. The means of both maternal and self-reported ratings of depressive symptoms were significantly higher in females , with largest effect size observed at age 16 . Sex differences in well-being scores were observed and strongest in adolescence at age 14. At this age, females reported lower levels of well-being , but the effect was smaller compared to sex differences in depressive symptoms scores. In general, depressive symptoms scores tended to increase with age, whereas well-being scores were more stable, but it shows a decrease from adolescence onwards in both sexes .
Table 1. Mean and standard deviation for the raw data for all age groups, as well as the thresholds for the liability distribution and the percentages of twins in the three groups.
Well-being and depressive symptoms are significantly correlated and the correlation increases with age, ranging from 0.34 during childhood to 0.49 in adulthood .
Table 2. Phenotypic correlations, twin correlations and cross-twin cross-trait correlations for well-being and depressive symptoms.
Can Depression Be Prevented
You can help prevent depression by getting enough sleep, eating a healthy diet and practicing regular self-care activities such as exercise, meditation and yoga.
If youve had depression before, you may be more likely to experience it again. If you have depression symptoms, get help. Care can help you feel better sooner.
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Depression And The Environment
All this to say that even people who come from families with a history of depression are not guaranteed to experience depressive episodes in their life.
Family history does not necessarily dictate that someone will develop major depression, although they are at increased risk, says Sumner. Or as Dr. Robert Klitzman, a professor of clinical psychiatry and director of the masters program in bioethics at Columbia University, tells The New York Times. Doctors see much more like predicting the weather.
To predict depression, despite a strong genetic correlation, theres still that 60 percent risk that is directly related to ones environment.
Genetic risk is only a part of the equation, says Sumner. Psychosocial stress and ones interaction with their environment are important.
Adverse experiences can be a major component of depression. Relationships or employment, for example, can reveal how individuals are negatively connected to sometimes toxic and impactful situations that can be a driving force for stress and depressed mood.
Stress As A Cause Of Depressive Disorders
Chronic stress and stressful life events early in life are strong proximal predictors of the onset of depression. Although the response to stress implies stability or maintenance of homeostasis, long-time activation of the stress system can cause harmful or even fatal consequences by elevating the risk of obesity, heart diseases, depression, and other disorders . The Hypothalamicpituitaryadrenal axis and its three main componentshypothalamic neurosecretory cells, pituitary gland, and adrenal cortexare responsible for adaptation to changed environmental conditions and for mobilization of the organism’s reserves during exposure to stress of different etiologies. The HPA system operates in the following way .1). In response to a stressor, neurons in the hypothalamic paraventricular nuclei secrete corticotropin-releasing hormone , which exerts its action on the hypophysis to initiate the release into the blood circulation of adrenocorticotropic hormone , which stimulates the release of corticosteroids, particularly cortisol, from the adrenal cortex. The final hormonal product of the HPA axis, cortisol, binds to mineralocorticoid receptors and glucocorticoid receptors to form hormonereceptor complexes, which are then transported into the cell nucleus where they interact with specific DNA regions, the glucocorticoid-response elements, to activate the expression of hormone-dependent genes .
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Depression Has An Inherited Component But Genetics Is Only One Part Of The Cause We Discuss The Intermix Of Genetic And Environmental Factors That Cause Depression
Is depression genetic? The short answer is yes. However, its not quite so simple as yes or no. As with just about anything that involves the complex human body, there are many factors that affect the genetics of depression.
For one, there is no single depression gene. As of 2019, more than 80 genes that are related to depression have been identified as a result of intense research into this area, and there are probably many more yet to be uncovered.
All genes are contained in DNA. These genes decide many of an individuals physical characteristics and even personality traits. However, people are shaped biologically by two factors: nature and nurture. Nature is the genetics and nurture is the combination of environmental influences that shape people how they are brought up, their education, nutrition, life experiences and so on.
Some things are only determined by nature such as eye color while some things are determined only by nurture such as which high school a person goes to. Most characteristics result from a combination of the two, such as whether or not an individual will develop depression at some point in their lifetime.
People often have multiple copies of the same gene. The complex mix of how many depression-related genes an individual has, how many bad copies of these genes are present and how many good copies the individual possesses, all combine to form a genetic risk for depression.
The Circadian Rhythm Theory
Circadian rhythms oscillate with ~24-h periodicity and are responsible for regulating a wide variety of physiological and behavioral processes. Endogenous cyclic oscillations are regulated in humans and other mammals by the circadian pacemakerthe suprachiasmatic nucleus neurons of the anterior hypothalamus . The circadian pacemaker can change its pattern so that the circadian rhythm may be advanced, delayed, or remain constant in various pathological states or when affected by different pharmacological preparations and hormones for instance, melatonin regulates the function of the biological clock through melatoninergic receptors residing in the hypothalamic SCN . At the cellular level, the molecular clock refers to a network of clock genes, which are transcriptional regulators organized in a feedback-sustained transcriptiontranslation network. This mechanism helps maintain the rhythmic expression of target genes during a 24-h cycle . The basis of the molecular clock is the negative feedback loop, in which the expression of PER and CRY proteins is inhibited by their interactions with the transcriptional factors CLOCK and BMAL1 and by blocking their binding to E-box regulatory elements in the promoters of the genes for PER and CRY protein family members. Posttranslational modifications of the molecular clock system components by signal molecules such as casein kinase / and glycogen synthase kinase 3-beta play important roles in the maintenance of circadian rhythms .
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Also Known As Major Depressive Disorder
Steven Gans, MD, is board-certified in psychiatry and is an active supervisor, teacher, and mentor at Massachusetts General Hospital.
Clinical depression, also called major depression or major depressive disorder , is often confused with having a sad or low mood. Although feeling sad is one symptom of clinical depression, there must be several other signs and symptomsin addition to sadnessfor someone to be formally diagnosed with clinical depression.
Clinical depression is considered a potentially chronic and severe disorder with medical comorbidities and high mortality. Understanding the signs and symptoms of clinical depression are important to ensure someone can receive an accurate diagnosis and treatment.
How Can I Help A Loved One Who Is Depressed
Its important to remember that a person with depression cannot simply snap out of it. It is also important to know that he may not recognize his symptoms and may not want to get professional treatment.
If you think someone has depression, you can support him by helping him find a doctor or mental health professional and then helping him make an appointment. Even men who have trouble recognizing that they are depressed may agree to seek help for physical symptoms, such as feeling tired or run down. They may be willing to talk with their regular health professional about a new difficulty they are having at work or losing interest in doing things they usually enjoy. Talking with a primary care provider may be a good first step toward learning about and treating possible depression.
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Genome Studies On Family History Of Depression
Recent advancements in science and technology have allowed researchers to conduct large-scale genome studies to explore how our genes are related to depression.
A genome-wide association study is a type of study that involves scanning complete sets of DNA, or genomes, of large numbers of people in order to detect any genetic patterns linked to a particular disease.
Once these genetic links are found, scientists use the data to develop better ways to detect, prevent, and treat disease.
Until recently, gene studies on depression have focused primarily on candidate genes, or genes believed to be involved in the development of depression.
Some of the most commonly studied candidate genes have included those regulating serotonin or dopamine, since these neurotransmitters are believed to play a role in depression and are the targets of antidepressant drugs.
However, its been hard to repeat these findings. The newer GWAS takes a completely different approach. Rather than looking at specific candidate genes, the GWAS method allows researchers to analyze a million or more variants across the entire genome.
In a major GWAS of 1.2 million people from four separate data banks, researchers identified 178 gene variants linked to major depression. The researchers think they may just be scratching the surface, as there may be hundreds or even thousands of these gene variants to discover.
Life Expectancy And The Risk Of Suicide
Depressed individuals have a shorter life expectancy than those without depression, in part because people who are depressed are at risk of dying of suicide. Up to 60% of people who die of suicide have a mood disorder such as major depression, and the risk is especially high if a person has a marked sense of hopelessness or has both depression and borderline personality disorder. About 2â8% of adults with major depression die by suicide, and about 50% of people who die by suicide had depression or another mood disorder. The lifetime risk of suicide associated with a diagnosis of major depression in the US is estimated at 3.4%, which averages two highly disparate figures of almost 7% for men and 1% for women . The estimate is substantially lower than a previously accepted figure of 15%, which had been derived from older studies of people who were hospitalized.
Depressed people have a higher rate of dying from other causes. There is a 1.5- to 2-fold increased risk of cardiovascular disease, independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating and preventing cardiovascular disorders, further increasing their risk of medical complications.Cardiologists may not recognize underlying depression that complicates a cardiovascular problem under their care.
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Roots Of Major Depression Revealed In All Their Genetic Complexity
A massive genome-wide association study of genetic and health records of 1.2 million people from four separate data banks has identified 178 gene variants linked to major depression, a disorder that will affect as many as one in every five people during their lifetimes.
The results of the study, led by the U.S. Department of Veterans Affairs researchers at Yale University School of Medicine and University of California-San Diego , may one day help identify people most at risk of depression and related psychiatric disorders and help doctors prescribe drugs best suited to treat the disorder.
The study was published May 27 in the journal Nature Neuroscience.
For the study, the research team analyzed medical records and genomes collected from more than 300,000 participants in the V.A.s Million Veteran Program , one of the largest and most diverse databanks of genetic and medical information in the world.
These new data were combined in a meta-analysis with genetic and health records from the UK Biobank, FinnGen , and results from the consumer genetics company 23andMe. This part of the study included 1.2 million participants. The researchers crosschecked their findings from that analysis with an entirely separate sample of 1.3 million volunteers from 23andMe customers.
When the two sets of data from the different sources were compared, genetic variants linked to depression replicated with statistical significance for most of the markers tested.
Daniel Levey
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“The next major explosion is going to be when genetics and computers come together. I’m talking about an organic computer about biological substances that can function like a semiconductor.” Alvin Toffler
Progress in genetic approaches is transforming many areas of medicine, including psychiatry. While the genetics of schizophrenia have been most actively studied, major depressive disorder is a debilitating condition that affects millions of people worldwide, causing a massive toll of human suffering and economic loss, according to the World Health Organization. As with psychiatric conditions in general, the biology of MDD is worked out to a limited extent only, though that is changing. Adding the deep layer of genetic analysis to understanding the causes of MDD, identifying which genes are affected and what they actually do, will advance the prevention, diagnosis, and treatment of MDD, while also generally expanding our grasp of how the brain works to give rise to our everyday experiences in wellness and infirmity.
Where are the depression genes?
The functions of genes
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Tips To Avoid Depression And Anxiety
If youâre at risk for depression or anxiety, youâll want to do everything you can to prevent them, just as you would with any other serious medical condition:
Consider starting counseling proactively. Finding a therapist before thereâs a problem can help you learn skills to manage situations that could trigger anxiety or depression. Tell them about your familyâs history of these or other conditions. If you want a referral, ask your doctor.
Brush up on key nutrients. A healthy diet can help support your body and brain. Make sure youâre getting enough of these nutrients:
- Omega-3 fatty acids. Theyâre in some fish , flaxseed, and pumpkin seeds. These fats are needed for brain health.
- B vitamins. People with low B vitamin levels are more likely to develop depression. Foods that contain B vitamins include green vegetables, beans, lentils, whole grains, seeds, nuts, fruits, meat, eggs, and other animal products.
- Vitamin D. Low levels of vitamin D are linked to depression, but itâs not clear if they actually cause it. Your body makes vitamin D if you get some time in the sun, or you can get it from fortified foods or supplements.
Limit added sugars. Foods that naturally have sugar in them, like fruit, will keep your bodyâs energy at a more constant level.
Make exercise a habit. Research shows it can help with mild to moderate depression. And itâs a great way to release stress, boost your mood and energy level, and take care of your physical health.
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