The Underlying Mechanisms of Depression

The Underlying Mechanisms of Depression

[Music] depression is one of the most common psychiatric disorders in the world the World Health Organization estimates that more than 350 million individuals of all ages have depression and approximately one-third of all people with depression fail to respond to conventional antidepressant therapies to put that into perspective that’s more people in the world with depression than the entire population of the United States that’s a lot of people when you consider that worldwide there’s as many people with depression for which conventional treatment does not work as nearly half of the adult population of the United States but what causes depression mounting evidence suggests that chronic systemic inflammation plays a major role in depression in other words the overactivity of our own immune systems inflammation is a part of a complex biological response to infection or injury that involves the activation of the immune system which produces pro-inflammatory cytokines including il-6 interferon gamma TNF alpha and other inflammatory molecules while this is a normal and healthy response an exaggerated and prolonged inflammatory response can come about as a consequence of many lifestyle factors including obesity poor nutrition and gut health sedentary lifestyle poor sleep and social stress when this occurs this excessive inflammatory response resulting in a great number of circulating inflammatory cytokines can promote a state of systemic inflammation this has been shown to have a detrimental effect on the brain as well as other tissues by now you probably see where I’m going with this maybe there’s a link between depression and systemic inflammation evidence seemed to suggest this take for example the fact that people suffering from clinical depression have higher concentrations of the inflammatory bowel markers c-reactive protein and il-6 by up to 50% in fact elevated biomarkers of inflammation such as C reactive protein have been shown to predict the risk for major depression one study showed that the risk of major depression increased by 44% for each standard deviation increase in log C reactive protein that however is an association more important is the evidence that suggests this relationship between inflammation and depression is actually causal several double-blinded placebo-controlled studies have been conducted in healthy people where they were injected with either lipopolysaccharide also known as endotoxin which is a component of bacterial cell membranes that elicits an immune response or injected with the pro-inflammatory cytokine interferon gamma or with placebo which is saline water both the endotoxin and interferon gamma but not the placebo caused people to have an increase in circulating levels of pro-inflammatory cytokines including il-6 and TNF alpha as we might have expected but very interestingly in both cases they also experienced an acute increase in depressive symptoms anxiety feelings of social disconnection and a lack of reactivity to pleasurable stimuli known as anhedonia moreover this coincided with the peak of the pro-inflammatory response but what if we decide to try to mitigate some of that inflammation those people that were injected with the pro-inflammatory cytokine but were also given the omega-3 fatty acid known as a cosas pentanoic acid or EPA that I have talked about quite a bit for a variety of reasons and also is renowned for its anti-inflammatory properties did not experience depressive symptoms it’s important to note that some studies have suggested that high EPA fish oil often in the neighborhood of around 2 grams of EPA per day may itself have an effect on depression but why and how might inflammation be affecting depressive symptoms in the first place cytokines and inflammatory molecules such as the e2 series prostaglandins cross the blood-brain barrier either by passing through leaky parts of the blood-brain barrier or by buying into transport molecules on the blood-brain barrier and hitching a ride in or through transport by way of the recently discovered lymphatic vessels in the meninges that surround the brain and spinal cord and thus directly connect the immune system to the brain once these pro inflammatory mediators are in the brain they can affect brain function by a couple of mechanisms first they are able to inhibit the release of neurotransmitters from presynaptic neurons these neurotransmitters play a fundamental role in mood anxiety and motivation and include serotonin norepinephrine and dopamine dopamine levels have been shown to decrease in the brain and a reduction in the activation of reward circuitry occurred in people that were injected with the pro-inflammatory cytokine interferon gamma but not placebo in addition to just inhibiting neurotransmitter release however in the case of serotonin the inflammatory cytokines such as TNF alpha actually increase the metabolism or reuptake of serotonin and thus decrease the amount of serotonin is actively in the synapse where it exerts all of its effects on mood and anxiety inflammatory cytokines also lower the amount of serotonin that is produced by diverting the precursor to serotonin tryptophan into a competing pathway through the activation of an enzyme called endo Lamine 2 3 dioxygen ease or I do which is responsible for converting tryptophan into kaneen instead of serotonin can urinate is a compound that can be converted into a metabolite that is actually neurotoxic and associated with depression known as Quin Olynyk acid interestingly in humans exercise has been shown to cause Kim yearning to be taken up into muscle and prevent it from becoming this toxic metabolite so there you have it while depression is a complex disorder that is affected by several factors ranging from genetics to nutrition to environmental stress an emerging research may even reveal many more factors that affect depression this mechanism by which the immune system has a direct effect on mood and behavior may serve as a rich avenue for further exploration for both prevention and treatment of depression well not necessarily precluding existing therapies in the future we may see a shift in disease management to include mitigating inflammation as a primary objective and may even go as far as to monitoring inflammatory biomarkers as a marker or measure of therapeutic success my prediction is that the ultimate cure for depression will not just be a magic pill pharmaceutical or otherwise but instead will be a multi-pronged lifestyle intervention that focuses among other things on influencing the levels of chronic inflammation this might include programs targeted at reducing things like this roll fat and making sure all the dietary and nutritional requirements are met for reducing inflammation if that means getting a whole lot healthier in the process and possibly even living longer all the better dr. Rhonda Patrick over and out today’s video was really fun experiment in format if you like the video be sure to click like tell your friends perhaps even share a link with them to sign up for my email newsletter on my website where I send out lots of articles I send out interviews announcements and also fun science and news stories and more but if you really like the video I’d like you to consider one other option I really love working on fun and creative projects like these however I’m not an animator that means in order to do things like these I have to work with others to make them happen you can learn more about supporting fun and interesting team projects like these through a monthly pay what you can pledge in other words any amount that you like by heading over to found my fitness com forward slash crowd sponsor that’s found my fitness comm /cr owd SP ons our proud sponsor you


  • FoundMyFitness says:

    I'm not an animator… but getting to work with one on this experiment was a lot of fun! With as fruitful as this project was, I'd really like to take on MORE creative projects that go beyond what my own set of talents can produce. Consider making a pay-what-you-can pledge (any amount you like) at and we'll see what other really cool things we can cook up. Thank you for your consideration!

  • Buysome Bitcoin says:

    How do you know the depression doesn't cause the inflammation?

  • Virt Real says:

    Can a 23andme test reveal certain polymorphisms who are related to depression?

  • Magnus Dahlqvist says:

    Excellent video @FoundMyFitness 👍 Have you also looked at the role of inflammation in chronic pain and the relationship between depression and pain? I found the book "Total Recovery" by Gary Kaplan giving me a good insight into the problems my wife is suffering with since 10 years. She is devastaded by some of her doctors who tell her that the pain is just "psycic" 😢

  • Brian Kaul says:

    Rhonda contributes so much to the public's understanding of nutrition I can barely stand it. What a great human being!!

  • Amy Virginia says:

    Rhonda, I love your videos. They are so well researched and fascinating. Even if I understand only half of them, I usually get the gist. Okay, now here is a question I have had for a very long time, and I have been waiting impatiently for studies to give me some information, but have heard nothing real yet. Hoping you can investigate. Here's the deal – I have a high LDL, and I lean vegan in my diet. I have lowered my LDL as a result, which is great (my HDL is high, and my other numbers are perfect). My question is this: Is the effect of coconut oil as a saturated fat the same as saturated animal fats when it comes to raising blood LDL? I hear so many people lump them together as all bad, but isn't the chemical makeup, and therefore effect on blood, going to be very different? Thanks so much – I will jump for joy if I ever see you address this topic.

  • zEvo Mb1B says:

    Super well put together! Thank you 🙂

  • Soph T says:

    rhonda patrick is smart and hot. a role model 2 people everywhere

  • F S says:

    Wow really nice job on the graphics and animation. especially considering it is a first. The designers you worked were obviously talented (designer myself). You should definitely keep trying to do these as it helps to visually absorb the content.

    Just a little confused as to offering these animated videos to paid memberships only. From a brand standpoint, adding this kind of quality could attract more viewers if it remains free which in turn could increase viewers and add YouTube revenue. Now I understand it cost money but maybe there's another way to absorb the cost? Just a thought…

  • Adam Zu says:

    I absolutely endorse this video format

  • John Smith says:

    Hello, thank you for the video. I think that too much animation is unnecesary and will take time and money, because of your topics you do not need animations most of the time. I like when we can see you in half od the screen and anymations show up only if needed.

  • Sway P says:

    Thanks for the good information. Sorry to say you have an irritating voice though.

  • Barbyl W says:

    Depression is also a learned program from childhood. Most depressed people have a depressed parent

  • Stahpitt says:

    You are freaking epic, FINALLY a source of lifestyle health that actually follows Empirical Data. You would not believe how much misinformation floats around the health food community. I'd like to add that depression can't simply be cured by diet alone, we are behaviorally driven animals and depression doesn't happen overnight. However that would be the first step in a long road of recovery through CBT. It's actually interesting how we can re-remember memories and remember them differently based on the mood state in which we last evaluated the memory.

  • Chris says:

    'Inflammation' sounds like the new scary health buzzword that is used as a catchall for the source of ailments. Like 'gluten intolerance'.

  • Daniel says:

    This format was great Rhonda! So much easier to follow along and understand.

  • Josh Kulchin says:

    Animations were fantastic! loved the format

  • Michael Proud says:

    How much EPA is too much? I am about to start supplementing with Viva Naturals Omega 3 Fish Oil to help with inflammation, but also to help with a depressive/dysthymic condition. Each dose claims to have 1,400 mg of EPA and 480 mg of DHA. Would doubling up on that to take it up to 2,800 mg of EPA and 960mg of DHA have any additional benefits on mood and overall inflammation? Or would that not be advised due to potential health risks? I think I've read in some sources that up to 3 grams/day of EPA is okay, while other sources have said to keep it under 2 grams. Any info would be much appreciated! Thank you!

  • Anibal Arauz says:

    22 prozac distributors disliked this video…

  • Rasmessi says:

    Your the shit Rhonda!!! And very hawt haha

  • Jeff Gass says:

    awesome listen: Psychedelics vs. Inflammation with Dr. Charles Nichols –

  • Lindsey Frazier says:

    i thought the animation was awesome.

  • Michael Calvano says:

    Eat a healthy dinner with your friends then go outside and play kickball till you're really tired. Smoke a j and have a good laugh then get a good nights rest. Repeat.

  • John Raisor says:

    I'd like to hear a podcast, or see a video of you, and Dr. Kelly Brogan having a conversation about the relationships between gut, physical, and mental health. Discovered both of you wonderful ladies through Joe Rogan.

  • 69birdboy says:

    Hi Dr. Do you have any views of the role of histamine in mental illness and cfs /fibro?

  • The1RobynHode says:

    nnEMFs… we are built out of DC electromagnetic energy. End of story. We need to clean up our environments. Do some Pubmed searches on magnetic fields and RF/Microwave frequencies. Far more people now with personal behaviors having 24/7 exposures, especially during sleep cycles.

  • Johannes-Sebastian Kremer says:

    Hey Hey!

    Your videos really make me think and motivate me to read more and inquire more scientifically it is so great

    Those videos increase my happiness level incredibly

    Thank you so much

    Please make more !

    They’re badass awesome!

    Love the format!

  • Logan West says:

    Dr. Rhonda Patrick can you please make a video on gut health issues. Such as leaky gut, SIBI, dysbiosis, candida, etc. A lot of people are stuffing from IBS, Chrons, etc and modern medicine hasn't really pinned down a solution so we are left to search the web. There's so much contradicting information and sales schemes that finding a solution seams almost impossible and overwhelming that it's depressing. Please make a video on what you would do to get yourself back in order. Such as which tests to get & which direction to go. I really hope you can make a video that makes all of this a little more understandable.

  • Neophyte says:

    I guess the broader lesson learned here is that there is no sharp separation between physical and mental health. One affects the other as much as the other way around.

  • Neophyte says:

    Dr Michael Greger postulated a while ago that another way to stimulate serotonin synthesis is to increase the ratio of tryptophan to other amino acids by eating kiwi's, banana's and seeds and to increase carbohydrate intake so that amino acids other than tryptophan are diverted to the muscles and away from the brain where they muscle out tryptophan at the narrow passages of the blood-brain barrier.

  • what the says:

    Do you have any knowledge or opinion of Dr Shoemaker's work on what he calls Chronic Inflammation Response Syndrome from biotoxins found in water damaged buildings?

  • Adam Jerzy Experience says:

    Thank you so much for all these informations!


    So informative!! Might I only request for a CC for this video? With my poor hearing I had to rely on auto-generated CC and some of the words weren't accurate. Thank for this content still!

  • Aimee Moore says:

    Do a video on Sv3rige's diet! He's a German YouTuber that eats nothing but raw meat and animal products (including organ meats – raw).

  • /ibestr says:

    'oh wait you got depression? let me prescribe you Zoloft' – Doc

  • Dylan Tanner says:

    Hi Dr Patrick, I love your videos and I've heard you speak on the Joe Rogan podcast and the Tim Ferriss podcast, love your work thank you!!

    I'm so intrigued by the human body and I want to learn more about nutrition without pursuing it academically, mainly for personal health.

    Do you have any suggestions on exactly where I could start learning? A source that is totally evidence based, perhaps a book that isn't boring like a text book. Do you have any suggestions?

    Thank you in advance!!

  • dontstartevil says:

    I really loved this presentation!!! 💕

  • Busk You says:

    You are an AMAZING person I am learning so much from your videos! May peace and prosperity be upon your family and may your lineage live long!

  • William Read says:

    Do a video on AMLA fruit indian gooseberry, it has the highest antioxidant of any other fruit according to Dr. Gregor

  • XO says:

    I switched from the SAD diet to paleo and my depression and anxiety are pretty much gone

  • Cassandra Etc says:

    I have autoimmune disease and chronic fatigue and Fibromyalgia. Thank you for this info, I'm trying to reduce inflammation with diet (using your smoothies) and exercise I also suffer with depression and BPD. I hope there will be more on inflammation.

  • Lucky Tiger Yoga says:

    Respect! Dr. Rhonda, You are so intelligent and also have a very approachable vibe. Really appreciate your work!

  • Shai Ella says:

    I have low homocysteine levels with two mutations for MTHFR. I have been using your videos to help me, and thank you very much! I wish you would do a video on Homocysteine levels and what to do for low vs high levels!!! Just a fan dying for help!

  • islanti says:

    Can you upload like a 5 minute video or PDF that just says exactly what food (vegetables, fruit, etc) a human should consume everyday and exactly how many supplements (omega, vitamin d, etc) a human should have per day? And maybe some brand recommendations as well?

    If you told me exactly what I should be putting in my body, then I will just eat that for the rest of my life.

    Seems like hours and hours of videos beating around the bush when it could all be summed up pretty easily. Don't get me wrong, it's super informative, but I think a lot of people just need a quick rundown/grocery list. Apologizes if you've already done this.


  • 99dynasty says:

    Great explanation! How does this “ inflammation is involved in causation of depression “ stance find mutual ground with Dr. Brant Cortright’s position regarding neurogenesis as the focal point of treatment and diagnosis. Your thoughts?

  • Sean F says:

    Great Video, cool animations, thank you !

  • kardrasa says:

    Can we get some human subtitles on this vid? T. Hanks

  • David Schneider says:

    Good information but did not like the format. Good color of lipstick.

  • Francis Tran says:

    Dr. Patrick –

  • Somethin Aint Right Here says:

    nice to see alternative theories with real evidence for depression
    talk therapy can only do so much, and if there is indeed a significant bio-chem component then we ought to focus our efforts in the right direction. thanks for sharing !

  • Laser Sharp says:

    How I kicked depression:

    1. Prioritize sleep (think quality)
    2. Exercise daily (varying types)
    3. Meditate and practice gratitude
    4. Eat variety of plants and animals
    5. Have goals and work on them
    6. Organize your possessions and obligations.
    7. Renew your zest for life regularly (music, dance, art, museums, hiking, etc.)
    8. Be social.

  • Coach Rob Bendana says:

    Dr. Rhonda Patrick; does this also apply to Bipolar Disorder? If not, why? Thank you

  • Jay Rama says:

    This was an excellent video. Very informative and easy to understand.

  • Robin Busch says:

    eating fish and taking fishoilcapsles , still depressed lel

  • M. Benstein says:

    Awesome as always

  • ChefButterz says:

    PLEASE HELP. There is so much information on diets.. However I have a specific problem.. I have hypoglycemia. With all the diet misinformation for hypoglycemia I don't know what to do… I want to eat healthy.. I have healthy smoothies often I make my own broccoli sprouts.. But if I got example eat a big meal in the morning and don't eat till afternoon… ( because I am away from home) just for a day.. My face breaks out in a rash and I become sick… It is becoming very serious as it also starts to slur my speech.. I really try to eat healthy… Sadly the information given on hypoglycemia is telling me to avoid meat? And eat more sugar than average? This seems to be counter intuitive… IDK what to do doctors are clueless on what is the right approach.

  • Not Me says:

    why you so sweaty napoleon

  • Jon Talkasquan says:

    Can I lick your booty-hole, Dr. Rhonda Patrick?

  • Wilfredo Cuevas says:

    Dr. Patrick is awesome. I love watching her videos.

  • XO says:

    Following the food guide in The Ultramind Solution completely eliminated my depression and anxiety

  • Ecphantus the Pythagorean says:

    Great video! Subscribed!

  • Anthony Gato says:

    so, if the majority of people in civilization wouldnt that mean those who are not depressed are the ones who are having an incorrect response to stimuli?

  • Automatic Monk says:

    You are amazing

  • Pete Shand says:

    This is great Rhonda!! I'm an animator, perhaps one day we can work together.

  • Jose Miguel Mandolesi says:

    I admire this woman. Keep on helping mankind!

  • Tim Burke says:

    So awesome. I'm one to recognize good info and she is providing extremely valuable information. But why is her face so oily?

  • Nick Badry says:

    Exercise helps me the most,there are times ill exercise for hours.(cardio helps the most for me)

  • The Hungry Gringo says:

    This video was awesome!

  • Ashraf Ali says:

    Hi Rhonda. For those trying to manage depression through nutrition, would you suggest just trying Fish oils capsules forthe EPA or are there other

  • American man1967 says:

    Man!!! Why O why don't they tells us this!!!!!!

  • Brady Bowers says:

    Hey Dr. Patrick! I recently listened to your podcast with Dr. Charles Raison about depression and have listened to some of your other talks on depression (what may cause it, exacerbate it, help/treat etc.) I love it and have been trying to adopt some of the beneficial habits to mitigate it, however, I mainly deal with anxiety more than depression. Do you have any talks/research that address that?

  • Rawderson Amaral says:

    Thank you
    You changed my life!

  • David R. Walsh says:

    I wonder? I am dying of cancer. Should I be depressed? I realize this is an old video but I had to comment. What do I do to help myself? I have good nutrition and exercise. I am almost 70. Great energy. I work outside. Difficult work. Still working. However, my cancer has complete metastatic travel. Not a long time to go. What to do to help me with this enormous depression?

  • Robert Huang says:

    I have been reading a bunch on depression, exercise physiology and immune function and I must say, it takes me FOREVER to come up with that kind of narrative for the information. It really makes me appreciate how much work you must put into these videos! Even after reading the papers first-hand, this video was extremely helpful for organization. Keep up the superb work! Much appreciated!

  • anthony short says:

    My god I would pash her face off. Such a sexy woman…. her brain makes me a bit randy.

  • Mike Trainor says:

    clean up on IL-6 please

  • gabriel aponte says:

    Such a helpful video

  • Bronson says:

    Fuck depression

  • John 4.5 says:

    53 depressed people watched this video

  • Tom Higgins says:

    Great JRE Podcast!
    PLEASE stop lip smacking so much though, it's insanely irritating..

  • havadatequila says:

    So we're tossing any psychological cause?

  • Bridie Rose Photography says:

    loved the animation – reminded me of the animations that the meditation app headspace uses

  • Murray Webb says:

    Doc, you are the biz! So fresh w/ your knowledge game! Appreciate you helping educate and inspire the masses!

  • Paul Harrison says:

    2:45 would this be one of the reasons why alcohol is a depressant? I sure I'm right in saying that alcohol puts endotoxins from the gut in the bloodstream.

  • Max Berson says:

    Do the inflammatory factors that you discuss in this video respond to NSAID's? In other words, can I test theory by popping a naproxen and observing my mood?

  • salmonjawn says:

    Meat and dairy cause inflammation. And this lady beats around the bush and won't admit on the Joe Rogan podcast that an all meat diet is idiotic.

  • Bitcoin 1E3g4c36XrV5jNg2nQdB3d1keWvEdZTcwc says:

    I Went Keto(few veg still but mostly meat) 3 months ago I cured my depression and was able to stop taking medication (fluoxetine) by reducing inflammation of my body and brain. Carbohydrates were the cause of my inflammation and by adopting the Ketogenic diet I was able to cure my clinical depression of 25 years.
    I also lost 30lbs, have significantly improved my sleep, reduced my anxiety, eliminated chronic fatigue, removed brain fog/memory issues, improved my eyesight, eliminated excessive sweating, eliminated restless leg syndrome, Less gas, a shoulder problem I had for 5 years has totally repaired, and I've started exercising more due to wanting too
    and not having too.

  • Zachary Zimmerman says:

    She is awesome.

  • Agatha Sanzone says:

    Thank You Very Much 4taking everything out of the dark ages:-) wish I could donate$ …. I'll pray that you can get the $'s needed

  • Name: Learning says:

    Dr. Rhonda Patrick, I greatly appreciate all your efforts. Thank you for being you!

  • Michael Ethan says:

    I still remember the time when I got myself out from depression months ago thanks to this depression treatment method “fetching kafon press” (Google it). I was jobless on crutches in a foreign country residing in a shoebox with a busted heart. But I`m a totally different individual now, happy and very contented in life..

  • Jamjam Bambam says:

    Having kids with this woman having unhealthy kids is a impossibility

  • kim says:

    Lactic Acidosis

  • AyooitsReese says:

    omg the serotonin is so cute i wish i had some :c

  • 027christy says:

    I cured my depression with a CARNIVORE DIET explain that Rhonda? stop scare mongering the diet isn't you suffering.

  • Amrita Ramesh says:

    Just as a possibly useful personal experience: if you are female and have a menstrual cycle, taking fish oil is good in the first half of your cycle, the follicular phase. For the second half, I personally found that evening primrose oil has a huge positive effect on the severity of cramping or PMS, whichfor me is straight up mini-depression, usually. Seed cycling is also something that works for me pretty well, in that it reinforces the same balance of omega 3-6-9s. The female body is different from the male body! I can't believe there isn't research about this, but in my experience taking omega 3s consistently is NOT always anti inflammatory, and is actually the opposite in my luteal phase. Being a chronic cortisol soup-brain from childhood on, I can testify to the constant inflammation, and I hope this personal experience helps someone. Handling a menstrual cycle with mental illness is a special kind of gymnastics!

  • K. L says:

    You're a Godsend. Thank you Dr. Patrick.

  • Voxterx says:

    I really wish i could meet you in person Dr you are trying hard for humanity

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