Insider's Guide to Depression, Part 2: What Really Causes Depression?

Have you ever wondered what actually causes depression? Why some people seem to move through heartbreak, stress, hormone changes, or loss and recover, while others find themselves sinking into a darkness they cannot simply think, pray, or “push” their way out of?

I have wondered that too.

Years ago, I started researching depression because I wanted better answers—not just for clients, but for anyone who has ever sat across from me and asked, “Why do I feel this way?” The more I read, the more I realized the answer was not simple. Depression is not caused by one thing. It is not just a chemical imbalance. It is not just negative thinking. It is not just stress. It is not just childhood pain. It is not just hormones, genetics, inflammation, loneliness, insomnia, or spiritual struggle.

Most often, depression develops when several factors come together at the same time.

Think of it less like one switch flipping and more like a system becoming overloaded. Your body, brain, relationships, history, sleep, stress response, hormones, and environment are all talking to one another. When enough pressure builds in enough places, depression can emerge.

That matters because if you believe depression has only one cause, you may look for only one solution. The current research points us toward a fuller, more compassionate picture: depression is real, it is complex, and it is treatable.

Depression Is Not “All in Your Head”

One of the most important things to understand is that depression affects the whole person. It changes mood, motivation, energy, appetite, sleep, concentration, self-worth, relationships, and the way you experience your own future. Current research describes major depressive disorder as a complex condition shaped by genetic, environmental, psychological, and biological factors rather than one single pathway (Marx et al., 2023). (PubMed)

That means your depression may have roots in your body, your nervous system, your life story, your current stress load, your relationships, your hormones, your sleep, your inflammation levels, your medications, your medical conditions, or some combination of these.

This is why two people can go through the same event and respond differently. One person may grieve deeply and slowly recover. Another may develop a depressive episode. That difference does not mean one person is stronger. It means each person arrives at the moment with a different nervous system, history, biology, support system, and capacity.

The Serotonin Story Got More Complicated

For years, many people were told depression was caused by low serotonin. That explanation was simple, memorable, and comforting in some ways. It helped people understand that depression had a biological component. It also helped reduce shame.

But the research has become more nuanced.

A major umbrella review by Moncrieff and colleagues (2023) concluded that there is not convincing evidence that depression is caused by low serotonin alone. This does not mean antidepressants never help. It means the “low serotonin causes depression” explanation is too simplistic. Other researchers have responded that serotonin may still be relevant as one piece of a much larger biological picture, especially when thinking about how medications affect mood, stress response, neuroplasticity, and emotional processing (Möller et al., 2023). (Nature)

For you, the takeaway is this: depression is not proof that your brain is defective. It is also not proof that medication is pointless. The better explanation is that depression involves many interacting systems, and medication may be one helpful tool for some people, especially when paired with therapy, sleep repair, nervous system regulation, movement, nutrition, medical care, and social support.

Stress Can Change the Brain and Body

Stress is one of the most researched contributors to depression. Acute stress can be manageable and even motivating. Chronic stress is different. When your body stays in survival mode for too long, the stress-response system can become dysregulated.

Researchers often talk about the HPA axis—the hypothalamic-pituitary-adrenal axis—which helps regulate cortisol and the body’s response to stress. In depression, this system can become overactive or poorly regulated. Over time, chronic stress may affect sleep, appetite, immune function, energy, concentration, and emotional resilience (Marx et al., 2023).

This helps explain why depression often shows up after long periods of caregiving, work pressure, financial strain, marital stress, grief, infertility, trauma recovery, or simply carrying too much for too long. Sometimes depression comes after one painful event. Other times, it comes after years of being “fine” while your body has been quietly absorbing the cost.

Loss and Life Events Still Matter

Painful life events remain one of the clearest contributors to depression. Loss, divorce, betrayal, job changes, medical diagnoses, infertility, major transitions, and ongoing relational stress can all become catalysts.

Grief and depression are not the same thing, but grief can open the door to depression. You can miss someone deeply and still be emotionally healthy. You can also experience a loss that overwhelms your coping capacity and triggers changes in sleep, appetite, motivation, guilt, hopelessness, and isolation.

This is one reason it is so important to look at what happened before the depression began. Your symptoms may be telling a story. They may be connected to something your body and mind have been trying to carry.

Sleep Is a Major Piece of the Puzzle

Sleep research has become even more important in the last several years. A 2022 systematic review and meta-analysis of longitudinal studies found that sleep disorders and circadian rhythm disruptions can predict later depression. Insomnia, hypersomnia, short sleep, long sleep, obstructive sleep apnea, restless legs syndrome, and eveningness patterns were all associated with increased risk of subsequent depression (Zhang et al., 2022). (ScienceDirect)

This matters because sleep is often treated like a side issue. It is not. Sleep is one of the primary ways your brain regulates mood, processes emotion, restores energy, manages stress hormones, and supports memory and concentration.

If you are sleeping poorly, waking in the night, staying up too late, sleeping too much, or feeling exhausted no matter how long you sleep, your mood will usually be affected. For some people, treating insomnia through evidence-based approaches like CBT-I can significantly improve depression symptoms.

Inflammation Is Getting More Attention

Another major area of research is inflammation. Scientists are continuing to study the relationship between the immune system and depression. Inflammatory cytokines, including markers such as IL-6 and TNF-α, have been associated with major depressive disorder severity in some studies (Min et al., 2023). A 2024 review described inflammation as a potentially important pathway in at least some forms of depression, while also making clear that this area is still developing (Yin et al., 2024). (Frontiers)

For everyday life, this does not mean every depressed person has an “inflammation problem.” It means the body and brain are connected. Chronic illness, autoimmune disease, poor sleep, high stress, sedentary living, gut health, nutrition, and unresolved trauma may all influence inflammatory processes.

This is one reason whole-person care matters. Depression treatment may need to include therapy and medication, but it may also need medical evaluation, nutrition support, movement, sleep repair, and stress recovery.

Hormones Can Increase Vulnerability

For women, hormone transitions deserve more attention. Depression can become more likely during reproductive and hormonal shifts, including postpartum, perimenopause, and menopause transition. A 2024 systematic review and meta-analysis found that perimenopausal women had a significantly higher risk of depressive symptoms and diagnoses compared with premenopausal women (Badawy et al., 2024). (PubMed)

This does not mean hormones are the whole cause. It means hormone changes can lower the threshold. If you are already stressed, sleep-deprived, grieving, inflamed, unsupported, or carrying a history of depression, hormone shifts may make symptoms more likely to surface.

If your depression seems connected to your cycle, pregnancy, postpartum, perimenopause, thyroid changes, or menopause, it is worth bringing that into the conversation with both your mental health provider and medical provider.

Your History Can Shape Your Stress Response

Childhood adversity, abuse, neglect, chronic criticism, emotional insecurity, and chaotic environments can increase vulnerability to depression later in life. This does not mean your past determines your future. It means early experiences can shape how your nervous system learns to respond to threat, closeness, conflict, failure, and stress.

Research continues to connect adverse childhood experiences with depression risk and severity. Early adversity may influence stress biology, attachment patterns, emotion regulation, inflammation, sleep, and the way a person interprets themselves and others.

For many people, depression is not only sadness. It is shutdown. It is the body saying, “This is too much.” Therapy can help you understand what your nervous system learned and begin building new patterns of safety, connection, and self-trust.

Loneliness and Disconnection Affect Mood

One of the more important shifts in the research is the growing recognition that depression is not only individual; it is relational. Loneliness and depression can feed one another. A 12-year population study found a bidirectional relationship between loneliness and depressive symptoms, meaning loneliness can contribute to later depressive symptoms and depressive symptoms can increase later loneliness (Luo et al., 2023). (PubMed)

This is important because depression often tells you to withdraw. It convinces you that you are a burden, that no one understands, that you should wait until you feel better before you reconnect. But isolation can deepen the depression loop.

Healing often requires safe connection: one trustworthy person, a group, a therapist, a class, a faith community, a walking partner, a support space, or a place where you do not have to perform.

So, What Causes Depression?

The most honest answer is: usually, a combination of things.

Depression may be caused or influenced by genetics, stress, sleep disruption, trauma history, inflammation, hormone shifts, grief, loneliness, medical illness, medication side effects, relationship strain, major life transitions, and the way your brain and body have adapted over time.

That complexity is not bad news. It means there are multiple places to intervene.

You can begin with therapy. You can talk with your doctor. You can check labs, medications, thyroid function, hormones, vitamin levels, and sleep disorders. You can address insomnia. You can move your body in small, realistic ways. You can reduce isolation. You can learn to regulate your nervous system. You can process grief and trauma. You can rebuild rhythms of nourishment, rest, meaning, and connection.

You do not need to know the exact cause before you ask for help. You only need to recognize that your symptoms are worth paying attention to.

Depression is treatable. And because depression is whole-person, healing often works best when we care for the whole person too: mind, body, relationships, story, and soul.

At Every Girl Living, this is why we believe in a Wellness 360 approach. You are not a diagnosis. You are a whole person with a body, a history, a nervous system, relationships, responsibilities, hopes, and a life that still matters.

If you have been feeling unlike yourself, it may be time to stop trying to figure it out alone. A 30-minute consultation can help you name what is going on, explore what kind of support fits, and begin creating your personalized Roadmap to Living Well.

Book a FREE 30 minute consultation

References

Badawy, Y., Spector, A., Li, Z., & Desai, R. (2024). The risk of depression in the menopausal stages: A systematic review and meta-analysis. Journal of Affective Disorders, 357, 126–134. https://doi.org/10.1016/j.jad.2024.04.041

Luo, M., Ding, D., Bauman, A., Negin, J., & Phongsavan, P. (2023). Social isolation, loneliness, and depressive symptoms: A twelve-year population study of temporal dynamics. The Journals of Gerontology: Series B, 78(2), 280–290. https://doi.org/10.1093/geronb/gbac174

Marx, W., Penninx, B. W. J. H., Solmi, M., Furukawa, T. A., Firth, J., Carvalho, A. F., & Berk, M. (2023). Major depressive disorder. Nature Reviews Disease Primers, 9(1), Article 44. https://doi.org/10.1038/s41572-023-00454-1

Min, X., Wang, G., Cao, L., Tang, M., Xu, W., Zhang, Y., Wang, X., & Chen, Y. (2023). Association between inflammatory cytokines and symptoms of major depressive disorder: A systematic review and meta-analysis. Frontiers in Immunology, 14, Article 1110775. https://doi.org/10.3389/fimmu.2023.1110775

Möller, H.-J., Volz, H.-P., Reimann, I. W., & Stoll, K.-D. (2023). Is the serotonin hypothesis/theory of depression still relevant? Methodological reflections motivated by a recently published umbrella review. European Archives of Psychiatry and Clinical Neuroscience, 273, 1–3. https://doi.org/10.1007/s00406-023-01575-1

Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2023). The serotonin theory of depression: A systematic umbrella review of the evidence. Molecular Psychiatry, 28, 3243–3256. https://doi.org/10.1038/s41380-022-01661-0

Yin, Y., Ju, T., Zeng, D., Duan, F., Zhu, Y., Liu, J., Li, Y., & Lu, W. (2024). “Inflamed” depression: A review of the interactions between depression and inflammation and current anti-inflammatory strategies for depression. Pharmacological Research, 207, Article 107322. https://doi.org/10.1016/j.phrs.2024.107322

Zhang, M.-M., Ma, Y., Du, L.-T., Wang, K., Li, Z., Zhu, W., Sun, Y.-H., Lu, L., Bao, Y.-P., & Li, S.-X. (2022). Sleep disorders and non-sleep circadian disorders predict depression: A systematic review and meta-analysis of longitudinal studies. Neuroscience & Biobehavioral Reviews, 134, Article 104532. https://doi.org/10.1016/j.neubiorev.2022.104532