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Identify Your Root Cause(s) of Depression

When it comes to depression, there’s no one-size-fits-all answer. It’s not always easy to pinpoint the root cause of your depression, as different genetic factors, life events, and environmental factors can all play a role. My goal here is to simplify your task of sorting through genetic data to target the right cause(s) of depression for you.

Depression: 9 genetic pathways to check

Genetics may be able to help you narrow down what is likely causing or adding to your depression on a physiological level.

Genomics is a good starting point!

  • the place to start researching, learning about solutions
  • a targeted way to make diet or supplement changes
  • a starting point for talking with your doctor

That is an exciting concept! But I do want to point out a couple of caveats here:

  1. It’s important to keep in mind that your genetic data only shows part of your genome (23andMe, AncestryDNA).
  2. Genetics is only part of the picture. Your genes interact with your lifestyle, diet, abuse, chronic disease, etc —  all coming together to change your neurotransmitters.

Caveats aside: USE what you can learn from your genetic data.

Disclaimer: This information is truly for educational purposes. Please, talk with your doctor or psychiatrist for medical advice.

Can depression be genetic?

Genetics plays a role in depression for everyone, but there are multiple pathways that can cause the physiological changes that cause someone to feel depressed.

I’ve gone in-depth on all of theses genetic causes in separate articles (links below). In this overview article, you’ll be able to hone in on which of these root causes to target.

What do I mean by root causes?

Recent research shows that for people with long-term psychiatric illnesses, such as major depressive disorder, bipolar disorder, or schizophrenia, there are structural changes that take place in the brain.[ref]

As you can see, genetics points to a number of root causes of depression. Some of these overlap and interact, so there isn’t necessarily a single genetic cause.

Here’s one way to look at the interconnected root causes of depression:

Flow diagram of multiple causes of depression linked to genetics


Pinpointing depression’s root cause:

If you have several variants highlighted in the articles below, this could indicate a physiological link to depression for you.

Most people will have one or two variants in the topics below. Some are really common variants. So what you are looking for is a bunch of variants, all pointing to the same cause.

Example case study:

If your Inflammation and Depression results show multiple risk alleles highlighted:

Steps to take:

  • Read through the article on inflammation and depression.
  • Look for sources of chronic inflammation such as eating junk food or exposure to toxicants and clean that up.
  • Read through the Lifehacks section for suggestions on how to decrease inflammation specific to your genetic variants.
  • Before implementing any supplement options, be sure to check with your doctor or pharmacist, if you are on any medications.

Depression Genotype Report: 9 Causes

Members: Log in to see your data below.
Not a member? Join here. Membership lets you see your data right in each article and also gives you access to the members-only information in the Lifehacks sections.


Click the article link for further information, including the background science as well as research-backed solutions that match the genetic variants.

Inflammation and Depression:

When inflammation is chronically high, it can cause changes in neurotransmitters and in behavior. Think about how an animal acts when sick — it instinctively retreats from others, sleeps more, and seems sad. This is a hardwired mechanism when inflammatory cytokines are high.

Targeting inflammation may be a way to reduce depression and anxiety symptoms, for some people.

Remember – if you see a lot of highlights here, read through the full inflammation and depression article.

Depression, genetics, and mitochondrial function

Your mitochondria create most of the ATP that your cells use for energy. Without enough energy in your brain, depression symptoms can occur.

For some people with major depressive disorder, mitochondrial dysfunction in the brain is a physiological cause.

There’s a lot more to this topic than can be explained in two sentences, so if you see a lot of risk alleles highlighted below, jump over and read the full article.

Depression, Genetics, and Circadian Rhythm

For some, circadian disruption can be at the heart of depression or mood disorders.

BDNF, Serotonin, and Mood Disorders

Genetic variants in the BDNF and serotonin receptor genes combine to increase the risk of depression and anxiety. Learn more about BDNF and how these variants interact — and check your genetic data to see how this applies to you.

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
BDNF rs6265 T Decreased BDNF levels
HTR1A rs6295 G Increased risk of depression with BDNF variant

Seasonal Depression

Seasonal Affective Disorder (SAD) is characterized by recurrent depression with a change in the season, usually in fall/winter for most. Scientists think this is possibly due to an aberrant response to light – either not enough brightness to the sunlight or not enough hours of light. Your genes play a significant role in this responsiveness to light.

Serotonin Genes

Serotonin is a neurotransmitter that is important in depression, sleep, and many other aspects of health. Learn how your genetic variants in the serotonin receptor genes impact their function.

MTHFR & Depression

The MTHFR gene codes for a key enzyme in the folate cycle.

Tryptophan – Conversion to Serotonin vs. Kynurenine

Tryptophan is an amino acid that the body uses to make serotonin and melatonin. Genetic variants can impact the amount of tryptophan that is used for serotonin. It can influence mood, sleep, neurotransmitters, and immune response.

Cortisol and HPA Axis Dysfunction

Cortisol is a hormone produced by the adrenal glands in times of stress, and it also plays many roles in your normal bodily functions. It is a multi-purpose hormone that needs to be in the right amount (not too high, not too low) and at the right time. Your genes play a big role in how likely you are to have problems with cortisol.

Bringing it all together:

To recap:

  • Depression can have physiological causes along with triggering life events.
  • Targeting the root physiological cause may help.
  • If you are under the care of a physician, talk with your doctor/psychiatrist, especially before adding supplements in with medications.

Flow diagram of multiple causes of depression linked to genetics

A holistic view of depression treatment can include

  • therapy (if needed)
  • medications (if needed)
  • diet
  • lifestyle
  • supplements (if needed)

Instead of just taking a stab in the dark, use your genetic data to formulate a plan. If you’re like me, writing down the plan can help. Here’s a printable form for keeping track of supplements.

Kind in mind that this process can take time, and you might find the need to switch up your strategy and plan. Resolving health questions can take a while, so be patient in finding what works best for you.

If you are in the US and find yourself or a loved one struggling with depression, you can call the national treatment referral service hotline (confidential): 1-800-662-HELP (4357) or visit the website.


Related Articles and Genes:

MTHFR and Migraines
The MTHFR C677T variant increases the risk of migraines. Learn how to check your genetic data and how to mitigate the risk.

PMS, Genetics, and Solutions
A lot of women know the moodiness and brain fog that comes with premenstrual syndrome (PMS). Studies estimate that PMS is up to 95% heritable – which means that it has a huge genetic component. Learn about the genes and find out which solutions may actually work for you. (Member’s article)

Serotonin Genes
Serotonin is a neurotransmitter that is important in depression, sleep, and many other aspects of health. Learn how your genetic variants in the serotonin receptor genes impact their function.

Histamine Intolerance
High histamine levels can cause a variety of symptoms including migraines, hives, sinus drainage, and stomach problems.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.