Overview.
Depression, anxiety, brain fog, and cognitive decline are often treated as purely psychological — managed with therapy and medication without ever checking blood work. Yet thyroid dysfunction, vitamin deficiencies, iron depletion, blood sugar instability, and chronic inflammation all directly impair mood, cognition, and emotional resilience through well-characterised biochemical mechanisms. A targeted blood panel identifies these treatable contributors. Finding a medical cause doesn't invalidate psychological factors — it means you can address BOTH, and often the blood work explains why standard psychiatric treatment isn't working as expected.
Ranked biomarkers.
#1 TSH (Thyroid-Stimulating Hormone)
Thyroid hormones regulate neurotransmitter synthesis (serotonin, dopamine, norepinephrine), brain energy metabolism, and myelination. Hypothyroidism is one of the most common medical mimics of depression — causing low mood, cognitive slowing, fatigue, and apathy that is indistinguishable from major depressive disorder until TSH is checked. Hyperthyroidism mimics anxiety and panic disorder.
Optimal range: 0.5-2.0 mIU/L (functional optimal for mood). Standard 'normal' extends to 4.5, but subclinical hypothyroidism (TSH 3.0-4.5) frequently causes mood symptoms.
Key insight: If you've been diagnosed with depression and SSRIs aren't working well — check TSH. Treating an underlying thyroid condition can be transformative when it's been masquerading as depression for years. Every psychiatric guideline recommends thyroid screening before diagnosing depression, yet it's frequently skipped.
#2 Vitamin D (25-OH)
Vitamin D receptors are dense in brain regions governing mood (prefrontal cortex, hippocampus, cingulate cortex, amygdala). Deficiency is associated with a 2-3x increased risk of depression in meta-analyses. Seasonal affective disorder (SAD) correlates directly with seasonal vitamin D decline. Supplementation improves depression scores in deficient individuals.
Optimal range: 40-60 ng/mL (optimal for mood). <20 ng/mL = deficient. Affects ~40% of adults, more in winter and northern latitudes.
Key insight: If your mood reliably worsens in autumn/winter and improves in spring/summer, vitamin D deficiency is the most likely contributor. Test in late winter (when levels are lowest) and supplement proactively from October through March at higher latitudes.
#3 Vitamin B12
B12 is a cofactor for neurotransmitter synthesis (serotonin, dopamine, norepinephrine) and myelin maintenance. Deficiency causes depression, anxiety, cognitive impairment, psychosis (in severe cases), and peripheral neuropathy. Neuropsychiatric symptoms can occur at B12 levels of 200-400 pg/mL — well within the 'normal' lab range.
Optimal range: >400 pg/mL (functional optimal). Standard 'normal' starts at 200 pg/mL, but mood and cognitive symptoms occur in the 200-400 range.
Key insight: B12 deficiency-induced depression is one of the most satisfying diagnoses in medicine — because it's fully reversible with supplementation. But if missed for years, neuropsychiatric damage becomes permanent. At-risk groups (vegans, metformin users, elderly) should test proactively.
#4 Ferritin (Iron Stores)
Iron is a cofactor for tyrosine hydroxylase (dopamine synthesis) and tryptophan hydroxylase (serotonin synthesis). Low iron directly impairs the neurotransmitters that regulate mood, motivation, and anxiety. Iron deficiency also causes restless legs, insomnia, and poor stress tolerance — all of which compound mood disorders.
Optimal range: >50 ng/mL (functional optimal for brain chemistry). Standard lab 'normal' starts at 12-15 ng/mL. Many women with ferritin 15-30 have significant anxiety and mood symptoms that resolve with supplementation.
Key insight: The connection between iron and anxiety is dramatically underappreciated. Low ferritin impairs dopamine function (motivation, pleasure, focus) and contributes to restless legs (which destroys sleep, which worsens everything). If you have anxiety + fatigue + poor sleep, check ferritin — not just haemoglobin.
#5 Fasting Insulin / HbA1c
The brain uses 20% of the body's glucose despite being 2% of body weight. Blood sugar instability — driven by insulin resistance — causes mood swings, irritability, anxiety, difficulty concentrating, and the mid-afternoon 'crash'. Hyperinsulinaemia is also associated with increased Alzheimer's risk (sometimes called 'Type 3 diabetes').
Optimal range: Fasting insulin <5 μIU/mL. HbA1c <5.3%. HOMA-IR <2.0.
Key insight: If your mood and concentration crash 2-3 hours after meals, blood sugar instability from insulin resistance is a primary suspect. This pattern — anxiety/irritability that resolves with eating — is reactive hypoglycaemia. Dietary change (lower glycaemic index, more protein/fat, fewer refined carbs) often improves mood within DAYS.
#6 Magnesium
Magnesium is a natural GABA receptor agonist (the brain's primary calming neurotransmitter) and modulates the HPA stress axis. Deficiency — present in ~20% of adults — is associated with anxiety, insomnia, irritability, and depression. Multiple RCTs show magnesium supplementation improves anxiety and depression scores.
Optimal range: Serum: >2.0 mg/dL. RBC magnesium: >5.0 mg/dL (more accurate). Serum magnesium only drops when depletion is severe — RBC level is preferred.
Key insight: Magnesium is depleted by stress, alcohol, caffeine, and processed food diets. If you're anxious and can't sleep, a 4-week trial of magnesium glycinate (400mg before bed) is low-risk and often surprisingly effective — even if serum magnesium looks 'normal'.
#7 Omega-3 Index
EPA and DHA (omega-3 fatty acids) are structural components of brain cell membranes and regulate neuroinflammation. Low omega-3 index (<4%) is associated with increased depression and anxiety risk. Meta-analyses of RCTs show omega-3 supplementation (especially EPA-dominant formulas) improves depression scores, with effect sizes comparable to antidepressants in mild-moderate depression.
Optimal range: >8% (cardioprotective and neuroprotective). Most Western adults score 4-6% without supplementation.
Key insight: EPA (eicosapentaenoic acid) is the omega-3 fraction with the strongest antidepressant evidence — choose supplements with EPA:DHA ratio of at least 2:1 for mood. Dose: 1-2g EPA/day. The omega-3 index takes 2-3 months to respond to supplementation.
#8 Testosterone
Testosterone affects mood, motivation, confidence, and cognitive function in BOTH sexes. In men, age-related testosterone decline (1-2%/year after 30) contributes to depression, irritability, low motivation, and cognitive fog. In women, low testosterone (often from oral contraceptives or adrenal suppression) causes similar symptoms. Both hypo- and hyperandrogenism affect mood.
Optimal range: Men: 400-700 ng/dL (morning draw). Women: 15-50 ng/dL. Always test with SHBG to assess free testosterone.
Key insight: In men over 40 with new-onset depression, irritability, and low motivation — testosterone should be checked before starting antidepressants. Low testosterone is a treatable cause of mood symptoms that won't respond to SSRIs. The same applies to women on OCPs with flattened mood — OCP-induced SHBG elevation reduces free testosterone.
How to test.
Request a fasting morning blood draw (7-9 AM): TSH, vitamin D (25-OH), B12, ferritin, fasting insulin + glucose, HbA1c, magnesium (RBC if available), and testosterone + SHBG. Add omega-3 index if your lab offers it (not universally available). Most can be ordered by your GP. Frame it as: 'I'd like to rule out medical causes of my mood symptoms before/alongside psychiatric treatment.'
FAQs.
Should I get blood work before starting antidepressants?
Yes — every major psychiatric guideline recommends thyroid screening and basic blood work before diagnosing depression. In practice, this is frequently skipped. At minimum, check TSH, vitamin D, B12, and ferritin. Finding a treatable medical cause saves you from unnecessary medication and explains why treatment might not be working.
Can fixing a deficiency replace therapy or medication?
Sometimes, but not always. If hypothyroidism or severe B12 deficiency is the primary cause, treating it may resolve mood symptoms entirely. For most people, deficiencies contribute to but don't solely cause mental health conditions. Addressing them alongside therapy and/or medication improves outcomes — think of it as clearing biochemical barriers so psychological treatments can work better.
My blood work is normal but I'm still depressed — does that mean it's 'all in my head'?
No. Normal blood work rules out common medical contributors but doesn't invalidate your experience. Depression and anxiety have neurological, psychological, and social components beyond what blood tests measure. Normal blood work means you can proceed with evidence-based psychiatric treatment (therapy, medication) with confidence that medical causes have been excluded — which is valuable information.
How quickly do mood symptoms improve after treating a deficiency?
Thyroid medication: 2-6 weeks. Iron supplementation: 2-4 weeks for anxiety/energy, 3-6 months for full repletion. B12 injections: days to weeks. Vitamin D: 4-8 weeks. Magnesium: 1-4 weeks. Blood sugar stabilisation (dietary change): days. If a deficiency is the primary driver, the speed and completeness of improvement is often remarkable.
Verdict.
Mental health and physical health are the same system viewed from different angles. These 8 biomarkers cover the most common biochemical contributors to mood, anxiety, and cognitive symptoms: thyroid function (TSH), neuroactive nutrients (vitamin D, B12, ferritin, magnesium), metabolic stability (fasting insulin), neuroinflammation (omega-3 index), and hormonal drive (testosterone). Testing doesn't replace therapy — it ensures you're not fighting biochemistry with willpower alone.