Is Depression Caused by Low Serotonin, and do anti-depressants work?

Andrew Visagie • May 16, 2023

We need to talk about how effective psychiatric medication is, especially with the ever rising cases world wide of depression and suicide.

Is Depression Caused by Low Serotonin?


Serotonin is a chemical in your brain that helps you feel happy and calm. Some medicines for depression, called antidepressants, work by making more serotonin available in your brain. But does this mean that depression is caused by low serotonin levels, or that increasing serotonin can cure it? In this article, we will look at the evidence from different kinds of research and question this idea.

The idea that depression is caused by low serotonin levels or activity in the brain is called the serotonin theory of depression. This idea came up in the 1960s and 1970s, when researchers noticed that some drugs that affect serotonin levels, such as LSD and reserpine, could make people feel depressed, while others, such as tryptophan and fenfluramine, could make people feel better. However, these observations were not consistent or conclusive, and did not prove that serotonin causes depression.


Since then, many researchers have tried to test the serotonin theory of depression using different methods and measures.

These include:

  • Measuring serotonin and its breakdown product (5-HIAA) in body fluids, such as blood, spinal fluid, and urine.
  • Measuring how much serotonin sticks to its receptors in the brain using special scans or after death.
  • Measuring how much of the protein that moves serotonin back into the nerve cells after it is released is present in the brain using special scans or after death.
  • Reducing the amount of tryptophan, the building block of serotonin, in healthy people or people with depression and seeing how they feel.
  • Looking at whether differences in the gene that makes the protein that moves serotonin back into the nerve cells are linked to depression or make people more sensitive to stress.


However, a recent review of 17 studies that covered these areas of research found little evidence to support the serotonin theory of depression1. The review found that:

  • Two studies that combined results from other studies measuring 5-HIAA found no link with depression (largest number of people = 1002)1.
  • One study that combined results from other studies measuring serotonin in blood found no link with depression, and evidence that lower serotonin levels were linked to taking antidepressants (number of people = 1869)1.
  • Two studies that combined results from other studies measuring how much serotonin sticks to its receptors in the brain found weak and inconsistent evidence of less sticking in some areas1. This could mean more serotonin is available in the brain for people with depression. However, they could not rule out the effects of taking antidepressants before.
  • Three studies that combined results from other studies measuring how much of the protein that moves serotonin back into the nerve cells is present in the brain found weak and inconsistent evidence of less protein in some areas1. This could also mean more serotonin is available in the brain for people with depression. Again, they could not rule out the effects of taking antidepressants before.
  • One study that combined results from other studies reducing tryptophan in healthy people or people with depression found no effect in most healthy people (number of people = 566), but weak evidence of an effect in those with a family history of depression (number of people = 75)1.
  • One study looking at differences in the gene that makes the protein that moves serotonin back into the nerve cells found no link with depression1.
  • One review looking at whether differences in the gene that makes the protein that moves serotonin back into the nerve cells interact with stress to cause depression found no link1.


The authors of the review concluded that there is little evidence to support the idea that depression is caused by low serotonin levels or activity1They also suggested that antidepressants may work by other ways than increasing serotonin1, such as making new brain cells grow, reducing inflammation, or making people feel better because they expect to.

 

Therefore, based on the current evidence, it seems that the idea that depression is caused by low serotonin levels or activity is not well supported by facts. This does not mean that serotonin has nothing to do with mood or depression, but rather that its role is more complicated and involves other chemicals and systems1. Depression is likely to be influenced by many things, such as your genes, your thoughts, your relationships, and your environment2 , and making it about one chemical may be simplifying a complex problem.

 

Natural treatments


Some natural substances may have some effects on serotonin levels or mood, but there is not much evidence to support their effectiveness or safety. Some of them are:

  • SAM-e. This is a compound that is naturally found in the body and helps make serotonin and other chemicals. It may have some antidepressant effects, but it may also cause side effects such as nausea, headache and anxiety3.
  • Saffron. This is a spice that may have some antidepressant effects, but it may also cause side effects such as bleeding, allergic reactions and interactions with other drugs3.
  • St. John’s Wort. This is a herb that may have some antidepressant effects, but it may also cause side effects such as photosensitivity, nausea and interactions with many drugs.
  • Lifestyle changes. Some changes in your diet, exercise, sleep and stress management may improve your mood and brain health. Some of them are:
  • Cutting sugar, processed food and artificial sweeteners. These foods may cause inflammation, blood sugar spikes and cravings that can affect your mood.
  • Increasing protein, fruits, vegetables and omega-3 fatty acids. These foods may provide nutrients, antioxidants and healthy fats that can support your brain function and mood.
  • Exercising regularly. Physical activity can release endorphins, reduce stress and improve your self-esteem and body image.
  • Getting enough sleep. Sleep can help regulate your mood, hormones and immune system.
  • Practicing relaxation techniques. Meditation, yoga, breathing exercises and other methods can help you cope with stress, anxiety and negative emotions.

 

Supplements

  • Some supplements may help regulate serotonin levels or mood, but they may also interact with other medications or cause side effects. Some of them are:
  • Tryptophan. This is an amino acid that is the building block of serotonin. It may have some antidepressant effects, but it may also cause side effects such as nausea, drowsiness and headache.
  • 5-HTP. This is a compound that is made from tryptophan and is a step closer to serotonin. It may have some antidepressant effects, but it may also cause side effects such as nausea, drowsiness and headache.
  • L-theanine. This is an amino acid that is found in green tea and may have some calming effects on the brain.


These are some of the alternatives to SSRIs for treating depression. However, before you try any of them, you should talk to your health care provider about the benefits, risks and interactions of each option. You should also not stop taking your SSRI without consulting your health care provider first, as this may cause withdrawal symptoms or worsen your depression.

 

Future research should explore other aspects of serotonin function and interaction with other chemicals and systems, as well as other possible causes and treatments for depression.


References

: Depression and serotonin: Review questions decades-old theory. (2022, July 26). Medical News Today. https://www.medicalnewstoday.com/articles/low-serotonin-might-not-cause-depression-but-why-do-ssris-still-work

: Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2022). The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular Psychiatry. https://doi.org/10.1038/s41380-022-01661-0

: Gowers, E. (1954). The Complete Plain Words. Her Majesty’s Stationery Office.

: Serotonin: The natural mood booster. (2021, July 20). Harvard Health Publishing. https://www.health.harvard.edu/mind-and-mood/serotonin-the-natural-mood-booster

: Brighten, J. (2021, May 21). How Does Serotonin Affect Depression? Dr. Jolene Brighten. https://drbrighten.com/how-does-serotonin-affect-depression/

From Healing to Happiness: A Clinical Psychologist’s Guide to Overcoming Depression and Anxiety

By Andrew Visagie 31 Aug, 2023
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By Andrew Visagie 21 Aug, 2023
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By Andrew Visagie 03 Aug, 2023
Ikigai is a Japanese concept that means “a reason for being”. It is the source of happiness and fulfillment that makes you feel alive and motivated. It is the intersection of what you love, what you are good at, what the world needs, and what you can be paid for. Finding and living your ikigai can have many benefits for your mental health and longevity. Studies have shown that people who have a strong sense of purpose and meaning in life tend to live longer, healthier, and happier lives. They also have lower levels of stress, depression, and anxiety, and higher levels of resilience, optimism, and self-esteem. But how can you find and live your ikigai? Here are 10 rules that can help you on your journey, along with the neurological and hormonal explanations of why they are important: 1. Find your ikigai The first step is to discover your ikigai, your reason for being. To do this, you can ask yourself four questions: What do you love to do? What are you good at? What does the world need from you? What can you be paid for? Try to find the common thread that connects these four aspects of your life. This is your ikigai, your passion and mission that gives you joy and satisfaction. Finding your ikigai can activate the reward system in your brain, which involves the release of neurotransmitters such as dopamine, serotonin, and endorphins. These chemicals can enhance your mood, motivation, and pleasure. 2. Pursue your ikigai with balance and harmony Once you have found your ikigai, the next step is to pursue it with passion and perseverance. However, this does not mean that you should overwork yourself or neglect other aspects of your life. You should also seek balance and harmony in your activities and relationships. Remember that ikigai is not a goal, but a process. It is not something that you achieve once and for all, but something that you constantly work on and improve. It is also something that can change over time, as you grow and evolve as a person. Pursuing your ikigai with balance and harmony can regulate the stress response in your body, which involves the secretion of hormones such as cortisol and adrenaline. These hormones can help you cope with challenges and threats, but too much of them can harm your health. 3. Cultivate a sense of gratitude and appreciation Another rule for living your ikigai is to cultivate a sense of gratitude and appreciation for your ikigai and everything else in your life. Be mindful of the present moment and enjoy the small pleasures that make you happy. Gratitude can help you appreciate what you have, rather than focusing on what you lack. It can also help you cope with challenges and difficulties, by reminding you of the positive aspects of your situation. Gratitude can also enhance your well-being, by boosting your mood, health, and relationships. Cultivating a sense of gratitude and appreciation can modulate the immune system in your body, which involves the production of cytokines and antibodies. These molecules can help you fight off infections and diseases, but too little or too much of them can cause inflammation. 4. Connect with others who share your ikigai or support your journey You are not alone in your quest for finding and living your ikigai. You can connect with others who share your ikigai or support your journey. These people can be your friends, family, colleagues, mentors, or role models. One way to find such people is to join a moai, a close-knit group of friends who provide social and emotional support. Moais are common in Okinawa, Japan, where people live longer than anywhere else in the world. Moais can help you stay motivated, inspired, accountable, and happy. Another way to find such people is to seek mentorship and guidance from those who have more experience or wisdom in your field. They can offer you valuable advice, feedback, and insights that can help you improve your skills and knowledge. Connecting with others who share your ikigai or support your journey can stimulate the social system in your brain, which involves the release of neurotransmitters such as oxytocin and vasopressin. These chemicals can enhance your trust, bonding, and empathy. 5. Keep learning and growing in your ikigai Learning and growing are essential parts of living your ikigai. You should always challenge yourself to improve your skills and knowledge, and seek feedback from others. You should also be open to new ideas and perspectives that can enrich your understanding. Learning and growing can help you stay curious, creative, and innovative in your ikigai. They can also help you adapt to changing circumstances and overcome obstacles. Learning and growing can also increase your self-confidence, self-efficacy, and self-actualization. Learning and growing in your ikigai can strengthen the cognitive system in your brain, which involves the formation of new neurons and synapses. These structures can enhance your memory, learning, and creativity. 6. Share your ikigai with the world Your ikigai is not only for yourself, but also for the world. You should use your talents and passions to contribute to the common good and make a positive difference. You should also inspire others with your work and your story. Sharing your ikigai with the world can help you create value and meaning for yourself and others. It can also help you connect with like-minded people who appreciate your work and support your vision. Sharing your ikigai with the world can also increase your sense of fulfillment, recognition, and impact. Sharing your ikigai with the world can activate the altruistic system in your brain, which involves the release of neurotransmitters such as dopamine and serotonin. These chemicals can enhance your happiness, generosity, and meaning. 7. Embrace change and uncertainty as opportunities for growth and innovation Change and uncertainty are inevitable parts of life. They can be scary or stressful, but they can also be opportunities for growth and innovation. You should embrace change and uncertainty as challenges that can help you learn and grow in your ikigai. To embrace change and uncertainty, you should adopt a growth mindset, which is the belief that you can improve your abilities and outcomes through effort and feedback. You should also adopt a positive attitude, which is the tendency to focus on the bright side of things and expect the best possible outcomes. Embracing change and uncertainty as opportunities for growth and innovation can stimulate the adaptive system in your brain, which involves the activation of neural networks that enable flexible thinking and behavior. These networks can enhance your resilience, curiosity, and innovation. 8. Respect and care for your body, mind, and spirit Your body, mind, and spirit are the foundations of your ikigai. You should respect and care for them, by eating well, exercising regularly, sleeping enough, and avoiding unhealthy habits. You should also meditate, relax, and have fun. You should seek professional help if you need it. Respecting and caring for your body, mind, and spirit can optimize the homeostatic system in your body, which involves the maintenance of a stable internal environment. This system can enhance your health, well-being, and quality of life. 9. Honor your ancestors and traditions, but also embrace diversity and modernity Your ancestors and traditions are the roots of your ikigai. They are the sources of your values, beliefs, and customs that shape your identity and worldview. You should honor them, by learning from them, following them, or preserving them. However, you should also embrace diversity and modernity, which are the branches of your ikigai. They are the sources of new experiences, ideas, and opportunities that enrich your life and broaden your horizons. You should embrace them, by exploring them, accepting them, or adapting to them. Honor your ancestors and traditions, but also embrace diversity and modernity can help you balance continuity and change in your ikigai. They can also help you respect other cultures and beliefs, but also maintain your own identity. 10. Live each day as if it were your last, but also plan for the future The final rule for living your ikigai is to live each day as if it were your last, but also plan for the future. This means that you should make the most of every moment, but also prepare for the next one. Living each day as if it were your last can help you appreciate every opportunity, experience every emotion, and express every feeling. It can also help you avoid regrets, procrastination, and complacency. Living each day as if it were your last can also increase your happiness, satisfaction, and gratitude. Planning for the future can help you set goals, make plans, and take actions that align with your ikigai. It can also help you anticipate challenges, overcome difficulties, and achieve success. Planning for the future can also increase your optimism, hopefulness, and resilience. These are the 10 rules for finding and living your ikigai. By following these rules, you can discover your reason for being that makes you feel alive and fulfilled. You can also enjoy the benefits of having a strong sense of purpose and meaning in life that can boost your mental health and longevity.
By Andrew Visagie 26 Jun, 2023
10 Stoic Principles for Depression with SHIP Therapy
By Andrew Visagie 20 Jun, 2023
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By Andrew Visagie 13 Jun, 2023
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