chemical imbalance is only a part of Depression: What Research Is Revealing About Why Depression Happens

By: Melissa Chana, MA, LPCC

Depression is not a character flaw.
It’s not laziness.
It’s not a lack of motivation or gratitude.
And it is not something you can fix by “just thinking positive” or “trying harder.”

Millions of people living with depression already know this.
You don’t choose hopelessness.
You don’t choose emotional exhaustion.
You don’t choose the fog, the heaviness, or the feeling that your system is shutting down.

What’s changing now finally is that the science is catching up to this lived reality.

The most current research shows that depression is not a simple chemical imbalance or a mindset issue. It’s a whole-body, whole-brain condition involving inflammation, trauma, metabolic shifts, gut-brain signaling, mitochondrial energy, and disrupted brain circuits.

We still don’t have all the answers.
But today’s research gives us a clearer, more compassionate, more accurate picture of what depression actually is and what it isn’t.

Before We Go Further, Something Important Needs to Be Said

There’s a harmful myth that people with depression hear over and over:

“If you just exercise and eat healthy, you won’t be depressed.”

Let’s be clear:
No scientific evidence supports the idea that exercise alone cures true major depression.
Yes, movement can help mood - especially in those without biological mental illness
Yes, nutrition matters - but it does not cure. It can treat, but not cure.
For many people, especially those with trauma histories, chronic illness, or neurobiological depression, these things do not erase the condition.

The implication that people with depression aren’t trying,
aren’t eating well enough, moving enough, or thinking positive enough
is not only false, it’s cruel.

You can run miles, lift weights, do yoga, drink green juice, meditate, go outside, call friends, take hikes, and still suffer from depression and anxiety.

You can take care of yourself better than anyone you know and still be sick.

Exercise and nutrition can support healing, but they do not cure:

• trauma-induced nervous system dysregulation

• genetic vulnerabilities

• inflammatory genetic disorders

• mitochondrial dysfunction

• gut-brain disruption

• neurocircuit imbalances

People with real depression are often trying harder than anyone in the room- and still hurting.

Your struggle is not because you’re not doing enough.
Your struggle is because depression is a complex medical and psychological condition, not “simple sadness.”

With that said, here’s what new science is teaching us.

1. Inflammation Can Change the Brain

One of the strongest findings in modern research is that chronic inflammation plays a meaningful role in depression.

Long-term inflammation caused by stress, trauma, illness, autoimmunity, gut issues, or even genetics affects:

• dopamine and serotonin

• motivation

• emotional regulation

• energy and sleep

• neuroplasticity

• stress hormones

This is why people with depression often feel physically ill, exhausted, or inflamed. Your brain is responding to signals coming from your body.

2. Trauma Doesn’t Just Affect Your Mind - It Reshapes Your Biology

Trauma does not stay in your “past.”
It leaves physiological fingerprints.

Research shows trauma alters:

• brain circuits

• immune function

• cortisol patterns

• inflammation

• gut bacteria

• mitochondrial function

This can create:

• emotional overwhelm

• shutdown

• rumination

• anxiety + depression cycles

• difficulty regulating emotions

• feeling unsafe without knowing why

If you’ve ever wondered “Why can’t I just get over it?”
The truth is: your nervous system may still be defending you from something that’s no longer happening.

That’s not a failure.
That’s survival.

3. The Gut–Brain Axis Plays a Central Role in Mood

The gut microbiome regulates inflammation, immune function, and neurotransmitter production.

When gut bacteria are imbalanced, depression can worsen due to:

• disrupted serotonin pathways

• increased inflammation

• nutrient deficiencies

• altered vagus nerve signaling

• stress-sensitivity loops

Your gut literally talks to your brain.
And your brain listens.

4. Depression Is a Brain Circuit Disorder not a Personal Failure

The newest neuroscience models show depression as a network imbalance between the regions involved in:

• emotions

• motivation

• memory

• self-awareness

• threat detection

When these circuits fall out of sync, you may experience:

• intrusive negative thoughts

• emotional numbness

• feeling “stuck”

• difficulty making decisions

• brain fog

• hopelessness

You cannot “think your way out” of this because the circuits needed for flexible thinking are the ones affected.

This is why somatic therapy, trauma-processing methods, and brain-body modalities often help in ways talk therapy alone may not.

5. Depression Has an Energetic Component - Literally

A major scientific development is the link between depression and mitochondrial function.

Mitochondria fuel the brain.
When they struggle, symptoms include:

• severe fatigue

• low motivation

• emotional flatness

• brain fog

• slowed thinking

This explains why depression feels heavy.
Your cells aren’t generating the energy required for a healthy emotional life.

This has nothing to do with “laziness.”
It is a biological depletion.

6. Depression Happens When Multiple Systems Overload at Once

The new model of depression views it as a network condition involving:

• trauma

• biology

• genetics

• inflammation

• gut health

• brain circuits

• unconscious beliefs

• thinking patterns

• stress

• cortisol dysregulation

• hormones

• metabolism

  
  Your system is overwhelmed and trying to survive.

What This Means for Healing

If depression is multi-dimensional, healing must be too.

This doesn’t mean “fix everything at once.”
It means you have multiple valid pathways:

• trauma work

• nervous system regulation

• belief and identity healing

• somatic release

• metabolic support

• gut repair

• emotional processing

• connection and safety

• purpose and meaning

• relationship repair

Many people have heard the phrase “chemical imbalance,” but the truth is more complex. Yes, chemical imbalance is real. But it doesn’t come from one single broken chemical. Depression can involve dysregulation in multiple systems at once, including dopamine, serotonin, cortisol, norepinephrine, adrenaline, and other mood-regulating pathways. Each of these chemicals plays a different role in motivation, energy, focus, pleasure, stress response, and emotional regulation.

This is one reason antidepressants don’t work the same for everyone. You might be prescribed a medication that targets serotonin when the deeper issue involves dopamine, cortisol, inflammation, or a combination of several systems. Depression isn’t one imbalance - it’s often a network of imbalances that interact with trauma, stress, metabolism, and nervous system patterns.

Depression is not your entire identity,
it’s a pattern your amazing body learned under pressure to keep y0u alive under severe stress in multiple body systems,

This whole-person understanding is the foundation of my approach to mental illness: the mind, body, trauma, beliefs, biology and nervous system all need to work together toward healing.

References (APA Style)

Attwells, S., Penninx, B., & Harrison, N. (2024). Inflammation as a treatment target in depression: Biological mechanisms and clinical implications. Nature Reviews Neuroscience.

Barzilay, R., et al. (2025). Childhood maltreatment interacts with genetics to shape brain structure and depression risk.Nature Neuroscience.

Bozdag, S., et al. (2024). Short, low-intensity exercise improves depressive symptoms and stress markers. Nature Mental Health.

Chu, A. L., et al. (2024). Mendelian randomization analysis of the gut microbiome and depression: Evidence of bidirectional causality. Psychological Medicine.

Enache, D., Pariante, C., & Mondelli, V. (2024). Immune system dysfunction in major depressive disorder: A comprehensive review. The Lancet Psychiatry.

Kim, D., et al. (2025). Mitochondrial gene pathways in depression: A multi-omics causal analysis. Nature Genetics.

Kuwano, J., et al. (2025). Postmortem genomic mapping of cell-type changes in depression. Cell.

Liu, Y., et al. (2024). Ultra-processed food consumption and depression: An inflammatory perspective. JAMA Network Open.

Zheng, P., et al. (2024). Trauma-related major depression and gut microbiome alterations: Causal evidence. Translational Psychiatry.