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What causes depression? Is it genetic?

Depression and Genetics

Depression is a multifactorial disease, meaning that there are many things that contribute to the condition. For a long time, scientists have suspected a genetic element to depression, but finding those links has proven difficult. Last month, however, researchers published a paper in the journal Nature Genetics detailing 44 genetic risk factors for depression, at least 30 of which have never before been identified. (R)

Let’s dig into those genetic variants and how they might influence efforts to prevent and treat depression in the future.

New research linking genes and depression

The study in question was a meta-analysis carried out by a global consortium of over 200 scientists. Together, these researchers looked at the DNA of more than 135,000 people with depression, along with almost 350,000 people in good health. They identified 44 gene variants that appear to contribute to an increased risk of depression. Prior to this study, only around a dozen such genetic variants had been linked to the risk of depression.

The following are SNPs associated with depression:

  • rs159963
  • rs1432639
  • rs12129573
  • rs2389016
  • rs4261101
  • rs9427672
  • rs11682175
  • rs1226412
  • chr3_44287760_I
  • rs7430565
  • rs34215985
  • chr5_87992715_I
  • chr5_103942055_D
  • rs116755193
  • rs11135349
  • rs4869056
  • rs115507122
  • rs9402472
  • rs10950398
  • rs12666117
  • rs1354115
  • rs10959913
  • rs7856424
  • rs7029033
  • rs61867293
  • rs1806153
  • rs4074723
  • rs4143229
  • rs12552
  • rs4904738
  • rs915057
  • chr14_75356855_I
  • rs10149470
  • rs8025231
  • rs8063603
  • rs7198928
  • rs7200826
  • rs11643192
  • rs17727765
  • rs62099069
  • rs11663393
  • rs1833288
  • rs12958048
  • rs5758265

The genes linked to depression are also associated in many cases with other psychiatric conditions, such as schizophrenia and bipolar disorder. What’s more, some of the genes are linked to health issues that often accompany and perhaps contribute to or result from depression, such as obesity and insomnia.

A note on the difficulty of treating depression

Depression is notoriously hard to treat and in many cases is the result of socioeconomic factors, trauma, relationship dynamics, family history, physical illness, and biochemistry. The importance of this latest study lies, at least in part, in its potential to provide an explanation as to why around 50% of people with depression do not respond to standard treatments.

Understanding the genetic underpinnings of depression could help us to understand why people respond differently to common drugs used to treat depression, such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). Indeed, many of the genetic variants uncovered in this study are associated with the mechanisms by which current antidepressant medications work. For instance, some of the gene variants affect neurotransmitters such as dopamine (DRD2), the excitatory neurotransmitter glutamate (GRIK5 and GRM5), and adrenaline.

Several of the genes have no apparent link to neurotransmitters, however, which may help explain why current treatments for depression are ineffective for so many people. Now that researchers have another 30 or so genetic avenues to explore, this could lead to the development of unique drugs tailored to a patient’s specific genome.

Depression and genetics

Some of the genes associated with depression in this study are related to neuron development and brain inflammation (LRFN5), while others are involved in weight and body size (OLFM4 and NEGR1). Genes that regulate the immune system were also identified as playing a role in the risk of depression.

The functional genes identified in this study are known to affect the prefrontal and anterior cingulate cortex. These areas of the brain are involved in executive function and help us to regulate emotion and make decisions. Our old favorite, DNA methylation, also gets a look in here, with several of the genes affecting this vital process needed for regulating gene expression.

BDNF and depression

Earlier research revealed that individuals suffering from major depression tend to have a smaller hippocampus (the brain area associated with memory and mood) (R) and lower levels of brain-derived neurotrophic factor (BDNF) (R), with autopsies of people who committed suicide and sufferers of depression revealing lower than normal levels of BDNF in the brain itself. (R) (R) (R) Since BDNF’s importance in cognitive and emotional functioning was uncovered back in the late 1970s, most antidepressant drugs have been deemed viable only if they manage to normalize BDNF levels.

SSRIs, for example, are known to activate BDNF-mediated signaling, and can reverse stress-related loss of neurons in the brain. (R) Other research has found that exposure to methylmercury can lead to decreased expression of BDNF and symptoms of depression; this effect can be reversed by fluoxetine (an SSRI) which appears to act through altered methylation and acetylation of the H3K27 gene. (R) This may offer one genetic target for future therapies for depression, depending on a person’s genome.

It’s also worth noting that depression and stress can both induce epigenetic changes affecting the BDNF gene and, as a result, alter the structure and functional capacity of the hippocampus. Interventions that aim to combat these negative epigenetic changes may help avoid behavioral consequences of depression and stress and help a person to recover more quickly.

What’s next for genetics and depression?

Although it would have been nice to hit on a single genetic variant that dramatically raises the risk of depression, the researchers found that each genetic mutation contributes in a much smaller way to a person’s risk. This means that while many of us likely carry one or more of the genetic variants found in this study, these variations do not create the same risk for depression. Instead, the likelihood of depression occurring depends largely on our phenotype, informed by environmental, lifestyle, and dietary factors.

The good news, then, is that by having identified genetic risk factors for depression, we can begin to develop specific nutrigenomic strategies to decrease or increase the expression of genes, depending on their apparent role in the condition. This may help make us more resilient, even when encountering life experiences that may otherwise conspire with our genes to trigger depressive symptoms.

Supplements that help with depression

In the not-so-distant future, treatment and prevention of depression may begin by assessing a person’s genome and looking at lifestyle, dietary, and environmental influences on phenotype. Physicians could then recommend tailored interventions that target abnormal protein synthesis, inflammation, immune dysfunction, poor synaptic signaling, and underdevelopment of neurons.

Natural products such as curcumin have, for instance, demonstrated an ability to alter the expression of specific genes tied to cognitive function and mood, and have shown benefit in treating symptoms of depression. (R) (R) And, the omega-3 fatty acids docosahexanoic acid (DHA) and eicosapentanoic acid (EPA) have been shown to help lessen inflammation in brain tissue and encourage the proper development of the brain, with some studies finding benefits for symptoms of depression. (R)

You may have heard that 5-HTP is a good supplement for depression, but we disagree. For more, see John’s post on natural ways to boost serotonin.

Key takeaways

Nutrigenomics may prove especially helpful for modifying abnormal inflammatory pathways, immune activity, cell signaling, and neuronal development and proliferation in individuals with genetic variants affecting these processes in such a way as to raise their risk of depression. How that looks in practice remains to be seen, but there is certainly already evidence that what we eat can affect our mood, and that our overall dietary pattern and activity levels is closely tied to our risk of depression.

As always, it’s important that anyone experiencing symptoms of depression seek appropriate medical advice and treatment. While natural interventions can be helpful, they are not a substitute for proper medical care and should be used under the guidance of a qualified health professional.

Some of the scientists who carried out the recent study are developing an online tool that will allow volunteers with depression to contribute to further genetic studies. Anyone interested in being notified about the tool’s launch can send an email to Dr. Gerome Breen of King’s College London at [email protected]

Leigh Matthews, BA Hons, H.Dip. NT

Leigh Matthews, BA Hons, H.Dip. NT, is a health and wellness writer for Gene Food specializing in plant-based nutrition. Read her full bio here.

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  1. Rebecca Danis says:

    SSRI’s are mentioned as helping, but what is not noted is that SSRI’s block dopamine receptors. So they treat anxiety, but not depression, since with depression you need more dopamine and you can’t get it if you are taking SSRIs.
    In addition both magnesium and the b complex vitamins are needed to synthesize dopamine (brain hormone of motivation and joy), and serotonin and GABA (Gamma Amino Butyric Acid) (brain hormones/ neurotransmitters of calmness and contentedness)
    If you are deficient in magnesium and B complex vitamins, your body will not be able to properly synthesize dopamine, serotonin and GABA etc.
    SSRIs and all other meds tend to deplete the body of magnesium and B complex vitamins since these nutrients are needed in the liver to break down any meds taken.
    In fact SSRI’s deplete magnesium and B complex vitamins so much, in addition to blocking all dopamine receptors (and dopamine is needed to run the lymphatic system) that when people start taking SSRIs, they either immediately get swollen up or just start gaining weight on the same amount of calories that they’ve always been eating since these SSRIs impede the action of the lymphatic system to such a great extent.
    Woo hoo! you’re “happy” but now you’re also fat and can’t get an erection (dopamine is also needed to get an erection) or now you can’t have an orgasm (both dopamine and serotonin are needed in having an orgasm and the meds make for more serotonin in the synapse of the brain, but less serotonin elsewhere.

    At any rate, the best thing to do is to first start daily supplementation with magnesium citrate or magnesium malate or magnesium chloride in order to raise the ability of the body to make the needed neurotransmitters because SSRIs do not increase your ability to make dopamine and serotonin, they only prevent the serotonin from being dissolved in the synapse, but if you can’t make serotonin or dopamine well in the first place because you are genetically deficient in magnesium and B complex vitamins (as occurs with CBS and SUOX and MTHFR mutations) then the SSRIs will not work and will cause more problems than they solve. (aka weight gain, erection and orgasm problems, parkisonian tremors and general metabolism problems)

    So before starting any of them, it is always best to start with the cornerstone of all nutrient consumption, which is magnesium supplementation, because if you do not have magnesium, you cannot very well absorb any other nutrients, especially the B complex vitamins. And without magnesium and the B complex vitamins, no neurotransmitters can be produced at all, so this is the bottom line root cause of all mental health issues.

    It is silly to take pills that force your body to not dissolve neurotransmitters or force your body to make more, when you do not have the base materials to produce the neurotransmitters in the first place.

    Its like trying to force someone to build you a brick house, but they do not have any bricks. It ain’t gonna happen. And until the person gets their bricks, it will never happen. And this is why these psych meds are often ineffective. You cannot increase your brain levels of certain brain hormones even if you take a pill to stimulate that to happen if you do not have these brain hormones on board to begin with/ are not able to synthesize these brain hormones to begin with.

    And magnesium is the top thing needed to make all brain hormones.

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