Exercise for Depression and Anxiety: How Movement Can Change Brain Chemistry
Exercise makes you happy? That is too simple. Movement can trigger growth factors in the brain, dampen inflammation and influence tryptophan metabolism. A look at the biology, honestly framed as a building block alongside therapy.
“Why don't you go for a jog? You'll feel better.” Many people with depression hear this line. It is well meant, and yet it often feels like a reproach. Exercise is not a test of character. It is biology, and you can work with biology in small steps.
Depression and anxiety disorders are serious illnesses. They belong in the care of a physician or psychotherapist. Exercise can be a complementary building block. It replaces neither therapy nor medication. Never stop prescribed medication on your own.
If you are thinking about suicide right now or are in an acute crisis, please get help immediately. In an emergency, you can reach the emergency services in Germany at 112. The German crisis line TelefonSeelsorge is available day and night, free of charge and anonymously: 0800 111 0 111, 0800 111 0 222 or 116 123.
Exercise can moderately ease depressive symptoms and anxiety symptoms. Biologically, this might work through several pathways. These include more of the growth factor BDNF, an interplay with serotonin, anti-inflammatory signals from muscle and a shift in kynurenine metabolism. Some of these pathways are documented in humans, others so far mainly in animal models. Exercise is a complementary building block, not a substitute for medical or psychotherapeutic treatment.
Why “exercise makes you happy” falls short
Your running shoes have been standing in the hallway for weeks. You see them every morning. And every morning, the way to the door feels like a marathon.
Maybe you also know the other side. You pulled yourself together and went for a walk. For an hour, the fog lifted a little. The next day it was back.
Both are human. And both show something important: exercise is not a switch. It is more like a signal that your body can adapt to over weeks.
What does the research show? The largest analysis so far dates from 2024.
Walking, yoga and strength training showed the clearest effects
Noetel and colleagues from the University of Queensland pooled 218 randomized trials with 14,170 people with depression.
Compared with active control conditions, walking or jogging, yoga and strength training showed moderate effects on symptoms. The more intensely the training was prescribed, the larger the effect. However, only a single study had a low risk of bias. The certainty of the evidence is therefore rated low to very low.
For you, this means: exercise is an option worth taking seriously. The authors see it alongside psychotherapy and antidepressants, not in their place.
Noetel M et al. Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2024;384:e075847. DOI: 10.1136/bmj-2023-075847A second large overview confirms this picture, this time for anxiety as well. Singh and colleagues from Adelaide brought together 97 systematic reviews covering 1,039 studies.
There, higher intensity was associated with greater improvements. However, many of the included reviews were of critically low methodological quality. That, too, is part of an honest assessment.
Psychotherapy and, where needed, medication are the main pillars of treatment. What an integrative view can add is a look at the body, the immune system and lifestyle. You can find the bigger picture in the article Treating depression holistically.
These numbers answer the question of whether exercise can change something. They do not answer why. That is exactly what this article is about. When you understand what is happening in your body, a well-meant piece of advice becomes your own decision.
Exercise is not a substitute for therapy. Nor is it proof that you “just need to try harder.” Imagine it more like physical therapy for your nervous system: a stimulus that your brain, immune system and metabolism can adapt to over weeks.
And now you know why it is worth looking behind the phrase “exercise makes you happy.”
BDNF: fertilizer for a brain that feels stuck
Depression often feels stuck. Your thoughts keep running the same laps. New perspectives just don't seem to take root.
This image is surprisingly close to the biology. Your brain is not a computer with finished wiring. It is more like a garden in which connections constantly grow, strengthen or recede. Experts call this neuroplasticity.
One of the most important fertilizers in this garden is called BDNF, short for brain-derived neurotrophic factor. This growth factor supports the survival of nerve cells and the formation of new connections. A lack of BDNF has been linked to depression for years.
Even a single training session can raise BDNF
Szuhany, Bugatti and Otto from Boston University pooled 29 studies on exercise and BDNF in humans.
A single session raised BDNF levels in the blood with a moderate effect size. After a regular training program, this increase per session was even more pronounced. Resting levels rose only slightly with regular training. In studies with more women, the change was smaller.
For you, this means: the effect seems to be triggered anew with each session, and training can amplify it. However, it was measured in the blood, not directly in the brain.
Szuhany KL, Bugatti M, Otto MW. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J Psychiatr Res. 2015;60:56-64. DOI: 10.1016/j.jpsychires.2014.10.003A similar pattern appears in people with depression. A meta-analysis by da Cunha and colleagues included twelve studies with 757 adults with major depression. Training increased circulating BDNF and reduced depressive symptoms. In the meta-regression, a rise in BDNF went hand in hand with a decline in symptoms.
The hippocampus remains malleable even in older age
Erickson and colleagues from the University of Pittsburgh randomly assigned 120 older adults to aerobic training or a control group.
In the training group, the anterior hippocampus grew by 2 percent. This corresponded roughly to reversing one to two years of age-related loss. A larger volume was associated with higher BDNF levels in the blood. In the control group, the volume decreased.
For you, this means: the hippocampus is important for memory and involved in stress regulation. The study examined memory in older adults, not depression. But it shows that exercise can measurably change brain structure.
Erickson KI et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011;108(7):3017-3022. DOI: 10.1073/pnas.1015950108If you feel stuck, that is not a sign of weakness. It can be a hint that your brain is currently lacking growth signals. Exercise is one way to help trigger such signals yourself.
And now you know why exercise may have more to do with brain growth than with calories.
Serotonin: more than a happiness hormone
Maybe you have heard that depression is simply a serotonin deficiency. The image is catchy. It turns a complex illness into something like an empty fuel gauge.
Research today paints a more layered picture. Serotonin is not a happiness switch. It is a messenger that, among other things, helps regulate how adaptable your brain remains. Things get exciting where serotonin and exercise meet.
Without serotonin, running no longer boosts new nerve cells
A team led by Klempin at the Max Delbrück Center in Berlin studied mice whose brains cannot produce serotonin.
The baseline formation of new nerve cells in the hippocampus was normal in these animals. But the additional boost from running on a wheel did not occur. This boost required the release of serotonin in the brain.
For you, this means: serotonin and exercise seem to work together. This is an animal study. In humans, this mechanism has not yet been directly demonstrated.
Klempin F et al. Serotonin is required for exercise-induced adult hippocampal neurogenesis. J Neurosci. 2013;33(19):8270-8275. DOI: 10.1523/JNEUROSCI.5855-12.2013Serotonin is made from the amino acid tryptophan, which you take in with protein-rich food. And this is where the tracks split. Because most of the tryptophan never becomes serotonin at all. It is broken down via another route, the kynurenine pathway.
Tryptophan
An amino acid from food. It is the shared starting material of both pathways.
Path A: serotonin
A smaller share becomes serotonin. This messenger is involved in mood, sleep and gut motility and is the precursor of melatonin.
Path B: kynurenine
The main breakdown route. Inflammatory signals and your nutrient status can influence how heavily it is used.
Kynurenine in the brain
Kynurenine can enter the brain. An accumulation there is linked to depression.
Kynurenic acid from muscle
Trained muscle can convert kynurenine into kynurenic acid. This does not cross the blood-brain barrier.
Serotonin is not a tank you simply top up. It is part of a metabolic network in which nutrition, inflammation and exercise all have a say. That makes things more complex. But it also opens up more levers you can work with yourself.
And now you know why one and the same amino acid stands at a junction that can help shape your mood.
Your muscle as a purification plant: the kynurenine pathway
Imagine your body has a drainage system for stress. Under constant strain, something backs up. And of all things, your leg muscles might be among the purification plants.
Kynurenine is a normal intermediate product. Its breakdown products can influence, among other things, the excitability of nerve cells and immune responses. In a review in Science, Cervenka, Agudelo and Ruas describe how inflammation in the body can contribute to the accumulation of kynurenine in the brain. It is precisely this accumulation that is linked to depression.
Trained muscles can take kynurenine out of circulation
In 2014, Agudelo and colleagues from the Karolinska Institutet in Stockholm described a mechanism in the journal Cell that links muscle and mind.
Training activates the gene switch PGC-1α1 in muscle. There, it increases enzymes that convert kynurenine into kynurenic acid. Kynurenic acid cannot cross the blood-brain barrier. Mice with this activated muscle program were more resilient to depression-like changes caused by chronic stress.
For you, this means: your muscle could be an organ of your mind. This is well shown in the animal model. In humans, it is still being researched.
Agudelo LZ et al. Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell. 2014;159(1):33-45. DOI: 10.1016/j.cell.2014.07.051Traces of this mechanism are found in humans too
A team led by Schlittler from Stockholm and Kaunas tested whether the finding from the mouse model also holds in humans.
Endurance-trained people had more of these converting enzymes in their muscles than untrained people. After an endurance session, kynurenic acid in the blood rose within the first hour. A high-intensity eccentric load did not show this increase.
For you, this means: not every kind of exertion seems to be the same. So far, the evidence for this pathway points more toward regular endurance stimuli.
Schlittler M et al. Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans. Am J Physiol Cell Physiol. 2016;310(10):C836-C840. DOI: 10.1152/ajpcell.00053.2016In depression, the picture is not yet clear
Millischer and colleagues measured kynurenine levels in 117 people with mild to moderate depression before and after twelve weeks of training.
The levels of kynurenine and kynurenic acid in the blood did not change lastingly, regardless of training intensity. The researchers found no link with improvements in fitness or mood.
For you, this means: measurements were taken within a week after training ended, so acute effects were not captured. The kynurenine pathway is a promising building block, but not yet a proven main mechanism.
Millischer V et al. Twelve-week physical exercise does not have a long-lasting effect on kynurenines in plasma of depressed patients. Neuropsychiatr Dis Treat. 2017;13:967-972. DOI: 10.2147/NDT.S131746The meta-analysis by da Cunha does not quite fit the simple picture either. There, circulating kynurenine rose slightly with training instead of falling. How that fits with the animal data is an open question. This is where the reliable study evidence ends.
I don't use this knowledge to prescribe a training program to people. I use it to reduce shame. Many people with depression consider their lack of drive a personal failure.
This is a clinical observation, not a study finding.
Maybe until now you have seen exercise as something you do for your body. From the perspective of this research, you are also doing it for your mind. Your muscle is not an opponent of your psyche. It could be its ally.
And now you know why a trained muscle may also be a protective factor for your mood.
Inflammation: when the immune system helps steer your mood
Think back to your last flu. You didn't want to see anyone. Everything felt heavy, nothing brought joy, and you withdrew.
This feeling has a name: sickness behavior. In a widely cited review, Dantzer and colleagues describe how messengers of the immune system act on the brain. In the short term, this is considered useful, because the body conserves its energy for defense. But if immune activation persists, depressive symptoms can develop in susceptible people.
Certain inflammatory messengers are elevated in depression
Dowlati and colleagues from Toronto analyzed 24 studies that measured inflammatory messengers in people with major depression and in healthy individuals.
Concentrations of TNF-alpha and interleukin-6 were significantly higher in depressed people. No differences were found for the other messengers studied.
For you, this means: depression can also have a physical, inflammatory side. This probably does not apply equally to everyone. You can read more about this in the article Depression and inflammation.
Dowlati Y et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67(5):446-457. DOI: 10.1016/j.biopsych.2009.09.033And this is where muscle comes into play. Imagine interleukin-6 from working muscle as a fire crew that brings its own extinguishers.
Muscle interleukin-6 can trigger an anti-inflammatory environment
Steensberg and colleagues from the Copenhagen Muscle Research Centre infused interleukin-6 into healthy young volunteers. The amount matched the levels seen during strenuous exercise.
In response, the anti-inflammatory messengers IL-1 receptor antagonist and IL-10 rose, as did cortisol. The pro-inflammatory messenger TNF-alpha did not rise.
For you, this means: the same molecule that can be elevated in chronic inflammation can send a short-term extinguishing signal from working muscle. It depends on the context.
Steensberg A et al. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab. 2003;285(2):E433-E437. DOI: 10.1152/ajpendo.00074.2003High inflammatory levels at baseline, stronger decline in symptoms
Rethorst and colleagues from Dallas studied people with depression who had only partially responded to an SSRI antidepressant. For twelve weeks, they additionally received exercise at one of two doses.
The higher the TNF-alpha level at baseline, the more the depressive symptoms declined. Changes in interleukin-1-beta were related to changes in symptoms. Overall, however, the mean inflammatory levels did not change significantly.
For you, this means: people with an inflammatory component might respond particularly well to exercise. This is a hint, not yet a rule.
Rethorst CD et al. Pro-inflammatory cytokines as predictors of antidepressant effects of exercise in major depressive disorder. Mol Psychiatry. 2013;18(10):1119-1124. DOI: 10.1038/mp.2012.125The dose matters, too. Paolucci and colleagues from McMaster University divided 61 students into three groups for six weeks during the semester. Without training, depressive symptoms increased over the course of the semester. Moderate continuous training lowered depressive symptoms and TNF-alpha.
High-intensity interval training also improved symptoms. Compared with moderate training, however, it increased perceived stress, TNF-alpha and interleukin-6. You can read how HIIT and endurance training can affect your nervous system in the article HIIT or endurance.
A 2026 meta-analysis from Chongqing screened 21 randomized trials with 1,572 participants. Six of them could be analyzed together. It found no established effect of training on long-term changes in IL-1-beta, IL-6 and TNF-alpha in depression. The certainty of the evidence was very low. The inflammatory pathway is therefore plausible, but not yet cleanly demonstrated in people with depression.
If you feel like you have the flu without being sick, you are not imagining it. It can be a signal from your immune system. And this system can be engaged through exercise, most likely through moderate, regular stimuli rather than going full throttle.
And now you know why moderate exercise can sometimes do more for your mood than an exhausting workout.
The KPNI bridge: muscle, immune system and brain in conversation
Does this sound like a lot of separate puzzles? BDNF here, serotonin there, inflammation and kynurenine next to them. From the perspective of Clinical Psychoneuroimmunology, KPNI for short, it is one single conversation.
KPNI looks at how the nervous system, immune system, metabolism and hormonal system communicate with one another. Exercise is a particularly good example of this. Because a single walk can engage all four levels at the same time.
Nervous system
Exercise can raise BDNF and, in animal models, promote the formation of new nerve cells in a serotonin-dependent way. In mice, the anxiety relief after running also depends on receptors of the body's own endocannabinoid system.
Immune system
Working muscle releases interleukin-6, which can trigger anti-inflammatory counterparts such as IL-10. This could be particularly relevant in people with elevated TNF-alpha.
Metabolism
Via PGC-1α1, trained muscle can convert kynurenine into kynurenic acid. In this way, metabolism in your legs may help decide what reaches the brain.
Hormonal system
Exercise is a dosed stress stimulus. Interleukin-6 from muscle can briefly raise cortisol. Repeated regularly, this could make the stress axis more flexible. This is plausible, but not conclusively demonstrated in humans.
In their review, Kandola and colleagues from University College London add the psychological side. Exercise can also strengthen self-esteem, social support and self-efficacy. Biology and experience interlock here. You can find out how myokines and mitochondria work in general in the article Exercise as medicine.
Your muscle, your immune system and your brain are having a conversation. Exercise is one way to have your say in that conversation.
What is established and what is still open
Supported by meta-analyses
Exercise can moderately ease depressive symptoms and anxiety symptoms. However, the methodological quality of many studies is limited.
Shown in humans, significance open
BDNF can rise with training. Interleukin-6 from muscle can trigger anti-inflammatory messengers. Whether this directly explains the effect on mood is still open.
Mainly in animal models
Kynurenine clearance in muscle, serotonin-dependent formation of new nerve cells and the role of endocannabinoids in the runner's high.
What I observe clinically
People who understand the biology often start with less shame and more patience. That is experience, not a study.
You don't need to know which mechanism is most prominent in your case. Exercise is not a drug with a single target. It is a stimulus that can engage many systems at once. That is exactly what makes it such an interesting building block.
And now you know why KPNI sees exercise not as a leisure topic, but as a bridge between body and mind.
Anxiety: how your body can reinterpret a pounding heart
Your heart races. Your breathing becomes shallow. Your hands get clammy. For many people with anxiety, these exact signals mark the beginning of a panic attack.
And exercise produces exactly these signals too. That is why many people with anxiety avoid any exertion. That is understandable, because their body has learned to read a pounding heart as danger.
Experts call this anxiety sensitivity, meaning the fear of the bodily sensations of anxiety. Exercise can act like gentle training here. You experience a pounding heart in a safe setting and learn: it passes.
Two weeks of exercise reduced the fear of fear
Smits and colleagues from Dallas randomly assigned 60 people with elevated anxiety sensitivity to a two-week exercise program, exercise with additional cognitive training, or a waiting list.
Both exercise groups showed clinically meaningful improvements compared with the waiting list, with a large effect size. The cognitive add-on brought no further benefit. The decline in anxiety sensitivity helped explain the improvement in anxious and low mood.
For you, this means: exercise can be a kind of habituation to your own body signals. In panic disorder, it belongs within an overall therapeutic plan.
Smits JA et al. Reducing anxiety sensitivity with exercise. Depress Anxiety. 2008;25(8):689-699. DOI: 10.1002/da.20411Group training for people with anxiety disorders
Henriksson and colleagues from Gothenburg randomly assigned 286 primary care patients with anxiety disorders to two twelve-week group programs or a control group. The training covered endurance and strength.
Both training groups improved anxiety and depressive symptoms more than the control group. The odds of a marked improvement in anxiety were about 3.6 times as high after light training and about 4.9 times as high after moderate to vigorous training. For anxiety, there was a trend in favor of higher intensity.
For you, this means: even a light program can make a difference. If you feel up to more, you may gain an additional benefit for anxiety.
Henriksson M et al. Effects of exercise on symptoms of anxiety in primary care patients: a randomized controlled trial. J Affect Disord. 2022;297:26-34. DOI: 10.1016/j.jad.2021.10.006And what about the famous runner's high? For a long time, endorphins were considered the explanation. Fuss and colleagues from Mannheim investigated this in mice in 2015. The anxiety-relieving effect after running depended on cannabinoid receptors, that is, on the body's own endocannabinoid system. The euphoric feeling itself, however, cannot be studied in mice.
One honest point belongs here. In the large Norwegian HUNT cohort, regular exercise was associated with fewer later cases of depression, but not with fewer later anxiety symptoms. At least in this cohort, there was no preventive association for anxiety. Studies on the treatment of anxiety, by contrast, point to a benefit.
People with panic attacks often tell me that they avoid stairs or stop exercising as soon as their heart beats faster. That is an understandable protective response. In those cases, I don't recommend jumping in at the deep end, but taking careful steps, ideally coordinated with psychotherapy.
This observation does not replace a study. But it fits with what research describes about anxiety sensitivity.
If your breathing becomes shallow when you are anxious, breathing exercises can be a useful addition. You can find more on this in the article Breathing techniques for the nervous system.
Your heartbeat when climbing stairs is not an alarm. It is information. With every movement, your nervous system can learn to read a pounding heart again as what it usually is: a body at work.
And now you know why exercise can be more than a distraction when it comes to anxiety.
How much exercise does your brain need?
Maybe you're thinking right now: that's all well and good, but I can't manage five training sessions a week. Good news: that is not what it is about at first.
The biggest differences are at the beginning
Pearce and colleagues from Cambridge analyzed 15 large cohort studies with more than 191,000 adults.
People who reached half the recommended amount of physical activity had an 18 percent lower risk of depression than people with no activity. At the full recommendation, it was 25 percent. Beyond that, the additional benefit became smaller and less certain.
For you, this means: every step away from the couch counts, and the first ones count the most. These are observational data, so they show associations, not proof of cause and effect.
Pearce M et al. Association between physical activity and risk of depression: a systematic review and meta-analysis. JAMA Psychiatry. 2022;79(6):550-559. DOI: 10.1001/jamapsychiatry.2022.0609Is this just a coincidence, because depressed people move less? To answer this, Choi and colleagues from Boston used genetic data from more than 600,000 people. With this method, called Mendelian randomization, they found evidence of a protective role for objectively measured physical activity. For self-reported activity, this association did not appear.
And intensity? In Noetel's network meta-analysis, the effect was larger the more intensely the training was prescribed. Paolucci, on the other hand, showed that very intense training can also increase perceived stress and inflammatory markers in stressed people. Both fit together if you see intensity as a goal, not as a starting point.
Running group and antidepressant compared
Verhoeven and colleagues from Amsterdam followed 141 people with depression or an anxiety disorder for 16 weeks. They received either an antidepressant from the SSRI class or ran in a group at least twice a week.
Remission rates were almost identical, at 44.8 percent with the antidepressant and 43.3 percent in the running group. The running group did better on weight, waist circumference, blood pressure, heart rate and heart rate variability. Only a minority agreed to random assignment, while most chose their treatment themselves.
For you, this means: exercise can be a building block in its own right, with additional physical benefits. That is not a reason to stop medication on your own. This decision always belongs in a conversation with your doctor.
Verhoeven JE et al. Antidepressants or running therapy: comparing effects on mental and physical health in patients with depression and anxiety disorders. J Affect Disord. 2023;329:19-29. DOI: 10.1016/j.jad.2023.02.064You don't have to stick to an exercise program in order to start. The data speak more for getting started than for peak performance. A walk that happens today is worth more than a training plan that never begins.
And now you know why regularity comes first and intensity only later.
Three levers you can start with today
If you are going through a difficult phase right now, even this section can feel like too much. Then read only the first lever. That is enough for today.
Small and regular
A short walk outside your front door counts. Plan it like an appointment, not like a performance. Studies show the biggest differences at the low end of the activity scale.
Together instead of alone
Many study programs took place in groups. Social support and the experience of self-efficacy are considered psychological mechanisms of action. A plan made with someone else can carry you even on days without drive.
Start moderately, involve your therapy
Increase the intensity only once exercise feels safe. Talk to your doctor or therapist about how exercise fits into your treatment. If you have a heart condition, a medical check beforehand is part of it.
This is not about fitness. It is about the feeling of being able to make a difference again. When you experience your own body responding, you regain a piece of freedom.
Rudolf Steiner distinguished between thinking, feeling and willing. This image stays with me when it comes to depression. Often, thinking goes in circles, feeling is muted, and willing seems paralyzed. Exercise starts with willing, not with thinking. You act before you feel like it. This is a perspective from anthroposophic medicine, not a study finding.
One important exception: if you truly crash for days after exertion, a different condition may be behind it, such as ME/CFS or post-COVID. Then different rules apply to exercise. You can find more on this in the article Exercise with chronic fatigue.
The first step doesn't have to be big. It just has to be yours. And if it doesn't work out today, tomorrow is a new day with a new opportunity, entirely free of guilt.
And now you know why exercise for depression and anxiety is not advice handed down from above, but an invitation to your own biology.
Frequently asked questions about exercise for depression and anxiety
Can exercise really make a difference for depression?
Yes, exercise can measurably reduce depressive symptoms, but it is not a substitute for treatment. The largest network meta-analysis to date, by Noetel and colleagues in the BMJ, included 218 randomized trials with 14,170 participants. Walking or jogging, yoga and strength training showed moderate effects compared with active control conditions, and more intensely prescribed training was associated with larger effects.
However, the certainty of the evidence was rated low to very low, because only one study had a low risk of bias. The authors therefore see exercise as an option alongside psychotherapy and antidepressants.
What happens in the brain during exercise?
Exercise can engage several biological systems at once. A meta-analysis of 29 studies with 1,111 participants found a moderate increase in blood levels of the growth factor BDNF after a single training session. BDNF supports nerve cells and their connections. In animal studies, the formation of new nerve cells through running required serotonin, and the anxiety relief after running depended on cannabinoid receptors.
On top of this come anti-inflammatory signals from muscle and influences on kynurenine metabolism. Not all of this has yet been directly demonstrated in people with depression.
What is the kynurenine pathway and what does it have to do with depression?
The kynurenine pathway is the main breakdown route of the amino acid tryptophan, from which serotonin is also made. Inflammation can contribute to kynurenine accumulating in the brain, and this accumulation is linked to depression. In mice, trained muscle was able to convert kynurenine into kynurenic acid, which does not cross the blood-brain barrier, and the animals were more resilient to stress-induced depression-like changes.
In humans, kynurenic acid in the blood rose after an endurance session. In 117 people with depression, however, twelve weeks of training did not lastingly change the blood levels, so the mechanism has not yet been conclusively clarified.
Can exercise lower inflammation in depression?
Possibly, but the evidence is mixed. A meta-analysis of 24 studies found elevated levels of TNF-alpha and interleukin-6 in people with major depression. Working muscle releases interleukin-6, which raised anti-inflammatory messengers such as IL-10 and IL-1ra in a human infusion study. In the TREAD study, high baseline TNF-alpha levels went hand in hand with a stronger decline in symptoms with exercise.
However, a 2026 meta-analysis found no established effect on long-term changes in IL-1-beta, IL-6 and TNF-alpha in depression, with very low certainty of evidence.
Can exercise also help with anxiety disorders?
The evidence suggests that exercise can ease anxiety symptoms. In a Swedish randomized trial with 286 primary care patients with anxiety disorders, twelve weeks of group training improved anxiety and depressive symptoms more than the control condition. The odds of a marked improvement in anxiety were about 3.6 times as high after light training and about 4.9 times as high after moderate to vigorous training.
One possible mechanism is a declining fear of bodily sensations such as a pounding heart. In anxiety disorders, exercise belongs within an overall therapeutic plan.
How much exercise does it take to lower the risk of depression?
Even less than the official recommendations is associated with a lower risk. In a meta-analysis of 15 cohort studies with 191,130 adults, people who reached half the recommended amount of physical activity had an 18 percent lower risk of depression than inactive people. At the full recommendation it was 25 percent, and beyond that the additional benefit became smaller.
In the Norwegian HUNT cohort, 12 percent of new cases of depression could statistically have been prevented if everyone had been active for at least one hour per week. These are observational data that show associations, not proof of cause and effect.
Is intense training better than moderate training?
That depends on your starting point. In Noetel's network meta-analysis, the effects on depression were larger the more intensely the training was prescribed, and the Swedish anxiety study showed a trend in favor of higher intensity. In a study with 61 students, however, moderate continuous training lowered depression and TNF-alpha, while high-intensity interval training increased perceived stress and inflammatory markers by comparison.
It therefore makes sense to start moderately and to increase intensity only once exercise feels safe. If you are exhausted or have pre-existing conditions, the right dose belongs in a conversation with your doctor.
Can exercise replace antidepressants?
There is no blanket answer to this, and you should never make this decision alone. In a Dutch study with 141 people with depression or an anxiety disorder, remission rates after 16 weeks were almost identical, at 44.8 percent with an antidepressant and 43.3 percent in the running group. The running group did better on physical measures such as blood pressure and weight.
However, most participants chose their treatment themselves, and only a minority were randomly assigned. Stopping antidepressants on your own can carry risks and always belongs under medical supervision.
What is the runner's high, and does it come from endorphins?
The runner's high describes a feeling of euphoria with less anxiety and pain after a longer run. For a long time, endorphins were considered the cause. However, a study by Fuss and colleagues in mice showed that the anxiety relief and pain relief after running depended on cannabinoid receptors, that is, on the body's own endocannabinoid system.
For the anxiety relief, CB1 receptors on certain nerve cells in the forebrain were necessary. The euphoric feeling itself cannot be studied in mice, so in humans the question has not been conclusively answered.
What can I do if depression leaves me unable to get going at all?
Lack of drive is a symptom of depression and not a personal failure. A first step is to get support from a doctor or psychotherapist, because treatment can make your drive more accessible again. Exercise can then start very small, for example with a few minutes outside your front door, ideally together with someone who accompanies you.
Studies show the biggest differences at the low end of the activity scale. If you are thinking about suicide, immediately call the emergency number 112 in Germany or the TelefonSeelsorge crisis line at 0800 111 0 111, 0800 111 0 222 or 116 123.
Is lack of exercise a cause or a consequence of depression?
The direction has not been fully clarified, but genetic data point to a protective role for exercise. Choi and colleagues used genetic data from a total of 611,583 adults for a Mendelian randomization analysis. More objectively measured activity was associated with a lower risk of major depression, with an odds ratio of 0.74 per standard deviation.
No significant association was found for self-reported activity or for the reverse direction. Even with this method, it cannot be ruled out entirely that other factors play a role.
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Sources
All studies were checked via PubMed for title, authors, year, journal and DOI, and key DOIs were additionally verified via Crossref. Figures are taken from the respective abstracts. Several mechanisms in this article, including kynurenine clearance in muscle, the serotonin-dependent formation of new nerve cells and the role of endocannabinoids, come from animal studies and have not yet been conclusively demonstrated in humans. The perspectives from clinical practice are clinical observations, not study results. This article does not replace a medical or psychotherapeutic examination and treatment.
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