9 Root Causes of Depression: Why Your Symptoms May Have Been Missed

9 Root Causes of Depression Your Doctor Probably Hasn't Tested For

Most people who come to see me for depression have already tried antidepressants. Some felt better. Many didn't. A few felt worse. What they hadn't done was look at why their brain chemistry was off in the first place. Depression is not a Prozac deficiency. In clinical practice, it rarely has a single cause — what I find consistently, across 25 years, is a cluster of biological imbalances that, when addressed together, shift mood more reliably than any medication alone.

Standard psychiatric treatment targets neurotransmitters directly — raising serotonin pharmacologically without asking why it dropped. That's not wrong. For some people, it's necessary. But it misses the biological context that drove the imbalance in the first place. The patients I see who've struggled most are those with unaddressed underlying drivers: gut dysfunction, hormonal disruption, toxic load, nutrient depletion. Often several at once.

According to Beyond Blue, depression affects around one in seven Australians in their lifetime. Women are diagnosed at approximately twice the rate of men. The standard treatment pathway — GP, antidepressant prescription, psychology referral — addresses the symptom. It rarely investigates the biology underneath it.

What follows are the nine root causes I assess in every patient presenting with depression, anxiety, or mood disorders. Most of them are measurable. All of them are treatable.

1. Chronic Inflammation

Persistent inflammation changes the way your brain operates. When inflammatory cytokines — signalling proteins produced during immune activation — are chronically elevated, they interfere with serotonin and dopamine production, disrupt sleep architecture, impair cognitive function, and directly contribute to low mood.

Research published in JAMA Psychiatry has found that people with depression have measurably higher levels of inflammatory markers compared to non-depressed controls.¹ The relationship appears bidirectional: depression amplifies inflammatory signalling, and inflammation worsens depression. Breaking that cycle requires addressing the inflammatory drivers directly.

If you have ongoing pain, chronic fatigue, autoimmune conditions, skin problems, or joint symptoms alongside your mood disorder, inflammation is very likely part of the picture. Standard blood tests often miss this — high-sensitivity CRP and specific cytokine panels tell a different story.

2. Food Sensitivities and Poor Gut Absorption

The gut-brain connection is not metaphorical. The gut produces over 90% of the body's serotonin and communicates directly with the brain via the vagus nerve. When the gut lining is compromised — through undiagnosed food sensitivities, dysbiosis, or increased intestinal permeability — inflammatory compounds enter the bloodstream and cross the blood-brain barrier, directly disrupting mood regulation and cognition.

In clinical practice, the gut connection is one of the first things I assess in patients with depression. Common signs that this is a contributing factor: bloating, reflux, irregular bowel habits, blood sugar swings after eating, and a history of antibiotic use. Many patients have no obvious digestive complaint — but functional testing reveals significant dysbiosis or permeability issues that correlate directly with their mood symptoms.

Gluten and dairy are the most common dietary triggers I see. Functional food sensitivity testing through NutriPath provides far more actionable clinical information than standard allergy panels — which test IgE-mediated reactions and miss the delayed IgG responses that drive most gut-mood presentations.

3. Liver Dysfunction and Neurotransmitter Production

Your liver is directly involved in the production and clearance of neurotransmitters. It activates B vitamins — particularly B6, B12, and folate — that are essential cofactors in serotonin and dopamine synthesis. It also clears excess oestrogen, which when elevated, suppresses progesterone and drives anxiety and mood instability. When liver function is impaired, these pathways slow down or fail.

What does this look like clinically? Low mood that doesn't respond to supplements or antidepressants. Irritability that seems disproportionate. Difficulty concentrating. Heightened sensitivity to alcohol, medications, or perfumes. Fatty liver, sluggish bile flow, or high toxic load — common in people eating a Western diet with regular alcohol — can all create this pattern.

Liver support is a component of almost every depression protocol I run. Nutrients that support liver phase I and II detoxification — including B vitamins, NAC, and specific botanical medicines — often produce noticeable mood improvements within four to six weeks.

4. Heavy Metal and Chemical Toxicity

Heavy metals — mercury, lead, cadmium, arsenic — are neurotoxic. They disrupt enzyme function, interfere with neurotransmitter signalling, deplete antioxidants, and create direct oxidative damage in brain tissue. The mood picture with heavy metal toxicity typically includes depression that doesn't respond to conventional treatment, combined with irritability, aggression, memory problems, headaches, and difficulty concentrating.

Exposure is more common than most people realise: mercury from amalgam dental fillings and regular fish consumption; lead from older housing stock and certain occupational exposures; cadmium from cigarette smoke and some fertilised soils. Individual susceptibility varies — genetic polymorphisms in detoxification enzymes (particularly MTHFR and COMT) affect how efficiently different people clear toxic metals.

Urine or hair mineral analysis identifies which metals are elevated and guides a targeted detoxification protocol. This is not an area to self-treat — mobilising heavy metals without adequate drainage support can worsen symptoms temporarily.

5. Oxidative Stress — "Your Body is Rusting"

Every cell in your body runs on oxygen. As a by-product of that metabolic process, free radicals are produced — unstable molecules that damage cell membranes, proteins, and DNA. Antioxidants neutralise them. When the antioxidant system is overwhelmed, oxidative stress accumulates — and the brain is particularly vulnerable, given its high oxygen demand and relatively modest antioxidant defences compared to other organs.

Oxidative stress is a documented contributor to depression, cognitive decline, chronic fatigue, cardiovascular disease, and autoimmune conditions. Research has identified elevated oxidative stress markers in people with major depressive disorder, and antioxidant interventions — including N-acetyl cysteine (NAC), which supports glutathione production — have shown clinical benefit in mood disorders in several controlled trials.²

Key antioxidants that are commonly depleted in complex chronic presentations include glutathione, CoQ10, zinc, selenium, and vitamins C and E. Identifying which are depleted requires testing — not guesswork supplementation.

6. Blood Sugar Dysregulation

Blood sugar instability is one of the most underappreciated drivers of mood disorders. When glucose spikes sharply after eating and then crashes, the brain experiences that drop as a physiological stress event — triggering cortisol release, lowering serotonin, and producing anxiety, irritability, and low mood. Repeat this cycle across three meals and two snacks per day, and you have a structural driver of mood dysregulation that no antidepressant will fix.

The clinical picture is recognisable: mood or irritability that worsens before meals, energy crashes in the mid-afternoon, difficulty concentrating when hungry, cravings for sugar or carbohydrates, waking at 2–3am. A high-carbohydrate, low-protein diet — common in Australian women eating "reasonably" — makes all of this worse.

Fasting glucose, HbA1c, and fasting insulin together give a functional picture of metabolic health. Fasting insulin in particular is a more sensitive early marker of dysregulation than glucose alone, and is rarely ordered on standard Medicare panels.

7. Hormonal Imbalance

The hormonal system and the brain are inseparable. Oestrogen, progesterone, testosterone, cortisol, and thyroid hormones all have direct effects on mood, motivation, and emotional regulation — and all of them can be disrupted by stress, gut dysfunction, poor liver clearance, or subclinical thyroid disease.

In women, the oestrogen-progesterone ratio is particularly important. Oestrogen dominance — driven by chronic stress, gut dysbiosis reducing enterohepatic oestrogen recycling, or impaired liver clearance — is associated with anxiety, depression, irritability, migraines, and premenstrual mood changes. Many women experience their worst psychological symptoms in the luteal phase, which is a direct reflection of this hormonal pattern.

Low testosterone in both men and women presents as flat affect, low motivation, anhedonia, and social withdrawal — often misdiagnosed as straightforward depression. Subclinical hypothyroidism — where TSH sits within the "normal" range but Free T3 is low — is one of the most consistently missed causes of depression I see in clinic. A full thyroid panel is non-negotiable in any thorough mood assessment.

8. Nutrient Deficiencies

The brain is metabolically expensive. It requires a steady supply of specific nutrients to manufacture neurotransmitters, maintain myelin integrity, regulate neuroinflammation, and manage the physiological stress response. When those nutrients are depleted — which is common in people eating a processed Western diet, under chronic stress, or taking medications that deplete micronutrients — mood suffers.

The deficiencies I find most consistently in patients with depression and anxiety:

Supplementation without testing is guesswork. I run a full micronutrient panel before prescribing anything — what looks clinically like a magnesium picture may actually be a B12 deficiency, and treating the wrong deficiency produces no improvement. All supplement prescribing through Vital Health and Natural Medicine uses practitioner-grade formulations from BioCeuticals, Metagenics, and Orthoplex.

9. Neurotransmitter Imbalance

Serotonin, dopamine, GABA, and noradrenaline are the primary mood-regulating neurotransmitters. They don't exist in isolation — they depend on the raw materials (amino acids, vitamins, minerals) covered above, and they're disrupted by all eight of the factors listed in this article. Treating neurotransmitter imbalance without addressing the upstream drivers is like filling a bucket with a hole in it.

That said, identifying which neurotransmitters are specifically depleted guides treatment. Low serotonin presents as low mood, poor sleep, sugar cravings, and heightened pain sensitivity. Low dopamine looks like flat affect, lack of motivation, and difficulty experiencing pleasure — anhedonia. Low GABA drives anxiety, restlessness, an inability to wind down, and poor stress tolerance. High noradrenaline or glutamate drives hyperarousal, racing thoughts, and emotional reactivity.

Neurotransmitter testing via first-morning urine through NutriPath gives a functional picture of where the imbalances sit, and allows for targeted amino acid therapy — using 5-HTP, tyrosine, taurine, or GABA precursors in appropriate doses — alongside the dietary and lifestyle foundations that support lasting rebalance.

How the ROOT Method™ Addresses These Systematically

Each of these nine root causes is measurable. Each is treatable. The challenge is that most people with depression have several operating simultaneously — and treating one in isolation, while the others continue unchecked, produces partial improvement at best.

The ROOT Method™ — Review, Order, Observe, Treat — is the framework I use to work through these layers systematically. We begin with a thorough clinical review of your history, symptom timeline, and any existing test results. We then order the appropriate functional pathology — which varies by patient but typically includes inflammation markers, full thyroid panel, nutrient status, hormone profile, and gut assessment. We observe the results in clinical context, identifying the primary and secondary drivers. Then we treat in the right sequence, addressing root causes rather than suppressing symptoms.

This doesn't replace your GP or psychiatrist. I work alongside them. If your existing medication is working, we build on it. If it isn't, we look at what the biology shows and address the missing pieces. The goal is a brain and body environment where mood can stabilise — not because we've overridden it chemically, but because the underlying conditions for healthy neurochemistry are actually present.

Should You See a Naturopath for Depression in Australia?

Standard Medicare blood panels typically include a basic metabolic screen. What they don't include is fasting insulin, neurotransmitter testing, a four-point salivary cortisol profile, full thyroid panel beyond TSH, or gut microbiome assessment — all of which may be clinically relevant in depression that hasn't responded to standard treatment.

Working with an ATMS-registered naturopath means access to functional pathology through providers like NutriPath, and a treatment approach built around what your individual biology shows. You don't need a referral to book. Private health fund rebates for naturopathy were removed by the Australian Government in 2019 — consult your fund for current extras coverage, which varies by provider.

Initial consultations at Vital Health and Natural Medicine are available in-clinic at 195A Sunshine Ave, Kealba VIC 3021, or via telehealth nationally. A free 20-minute discovery call is available for anyone who wants to understand whether a naturopathic approach is appropriate for their situation before committing to a full consultation.