7 Lab Tests Your Psychiatrist Should Order But Probably Won’t

Conventional psychiatry rarely includes laboratory testing — a patient sees a psychiatrist, describes symptoms, receives a DSM diagnosis, and is prescribed medication, all without a single blood test. Yet multiple common and correctable medical conditions directly cause psychiatric symptoms: thyroid disease, nutrient deficiencies, hormonal imbalances, and gut dysfunction, to name a few. Here are seven lab tests I consider essential in any comprehensive psychiatric evaluation.

1. Complete Thyroid Panel (TSH, Free T3, Free T4, Reverse T3, Antibodies)

A standard TSH alone is entirely insufficient for ruling out thyroid contribution to psychiatric symptoms. TSH can be technically ‘normal’ while Free T3 (the active thyroid hormone) is suboptimal, while Reverse T3 is blocking cellular thyroid function, or while Hashimoto’s thyroiditis is causing an autoimmune attack on the thyroid with fluctuating symptoms. I routinely find that patients with treatment-resistant depression, anxiety, brain fog, or fatigue have thyroid dysfunction that was missed by basic testing. A complete thyroid panel — TSH, Free T3, Free T4, Reverse T3, anti-TPO antibodies, and anti-thyroglobulin antibodies — provides the full picture. Hashimoto’s thyroiditis, in particular, produces episodic psychiatric symptoms as antibodies flare that can mimic anxiety, panic disorder, bipolar cycling, and depression.

2. Vitamin D (25-Hydroxyvitamin D)

Vitamin D deficiency is epidemic — affecting an estimated 40% of American adults and far higher rates in those living in northern latitudes, with darker skin tones, or with limited sun exposure. Vitamin D is not just a bone mineral — it is a neuroactive hormone with receptors in virtually every area of the brain involved in mood regulation. Low Vitamin D is associated with increased rates of depression, seasonal mood changes, anxiety, cognitive decline, and poor antidepressant response. Most laboratory reference ranges (typically >20 ng/mL) are based on bone health minimums rather than optimal brain function; I typically aim for levels of 50–70 ng/mL in patients with psychiatric symptoms. Testing 25-hydroxyvitamin D (not 1,25-dihydroxyvitamin D) is the appropriate clinical measure. Supplementing without testing leads to under- or over-replacement.

3. B12 and Folate (with Homocysteine)

Vitamin B12 and folate are essential for methylation — the biochemical process that produces serotonin, dopamine, norepinephrine, and melatonin. B12 deficiency can present with depression, anxiety, psychosis, cognitive decline, peripheral neuropathy, and fatigue, and is easily missed because standard serum B12 testing has poor sensitivity for functional deficiency. Active B12 (holotranscobalamin) and methylmalonic acid provide better functional assessment. Folate, particularly in the methylated form (5-MTHF), is critical for the synthesis of SAMe (the brain’s primary methyl donor) and neurotransmitter production. MTHFR gene variants — present in approximately 40% of the population — impair folate conversion and are associated with depression, anxiety, and antidepressant non-response. Homocysteine is an excellent functional marker for B12/folate status: elevated homocysteine signals inadequate methylation and is independently associated with depression and cognitive decline.

4. Comprehensive Metabolic Panel and CBC

A comprehensive metabolic panel (CMP) assesses liver function, kidney function, electrolytes, blood glucose, and albumin — providing a broad view of physical health that contextualizes psychiatric symptoms. Blood sugar abnormalities (high fasting glucose, insulin resistance) can drive anxiety, mood instability, and cognitive impairment. Liver function testing is important before starting certain psychiatric medications and can reveal dysfunction that drives neurological symptoms. Electrolyte imbalances (particularly sodium, potassium, and magnesium) affect neurological function. A complete blood count (CBC) can identify iron deficiency anemia (low hemoglobin, low MCV) — a common and commonly missed driver of fatigue, brain fog, depression, anxiety, and restlessness. Iron deficiency without anemia can also cause significant neurological symptoms and should be assessed with ferritin testing (below).

5. Iron and Ferritin

Iron deficiency — including iron deficiency without frank anemia — is significantly underdiagnosed as a driver of psychiatric symptoms. Iron is required for dopamine synthesis (as a cofactor for the enzyme tyrosine hydroxylase), for the production of myelin sheaths on nerve fibers, and for optimal mitochondrial energy production in neurons. Low ferritin (the iron storage protein) — even with technically ‘normal’ hemoglobin — causes fatigue, brain fog, depression, anxiety, restless legs, impaired cognitive function, and poor ADHD medication response. I typically aim for ferritin levels above 50–70 ng/mL in patients with psychiatric symptoms (standard lab references often show ‘normal’ as low as 12 ng/mL). Iron deficiency is particularly common in premenopausal women with heavy periods, vegetarians and vegans, frequent blood donors, and those with gut malabsorption conditions.

6. Inflammatory Markers (CRP, Homocysteine)

Chronic, low-grade inflammation is increasingly recognized as a primary biological driver of depression, anxiety, and cognitive impairment. High-sensitivity C-reactive protein (hsCRP) is the most clinically accessible inflammatory marker; levels above 1 mg/L are associated with increased depression risk, and levels above 3 mg/L are associated with poor antidepressant response and significantly higher depression risk. Homocysteine — an amino acid that accumulates when methylation is impaired — is both an inflammatory marker and a direct neurotoxin at elevated levels, associated with depression, cognitive decline, and cardiovascular disease. Elevated homocysteine responds to B12, B6, and folate supplementation. Additional inflammatory markers worth considering in complex cases include ESR, fibrinogen, ferritin, and specific cytokines through specialized testing.

7. Stool Microbiome Testing (Advanced Functional Testing)

Comprehensive stool testing — through functional labs like Genova Diagnostics, Doctor’s Data, or Viome — can identify microbiome imbalances (dysbiosis), pathogenic organisms (bacterial, fungal, parasitic), markers of intestinal inflammation, gut permeability markers (zonulin), and digestive enzyme sufficiency. Given the well-established gut-brain axis connection and the role of the microbiome in serotonin synthesis, inflammation, and neurotransmitter metabolism, gut assessment is a valuable piece of the psychiatric puzzle — especially for patients with both gut symptoms and treatment-resistant psychiatric conditions. Organic acids testing (OAT) through Great Plains Laboratory provides complementary information about nutrient status, mitochondrial function, neurotransmitter metabolism, and the presence of fungal (Candida) or bacterial overgrowth, and can reveal biochemical patterns not captured by standard labs.

Comprehensive functional lab testing is the foundation of my integrative psychiatric evaluations at drlewis.com. Understanding your unique biology — not just your symptoms — is how we find and address root causes rather than just managing symptoms. Brooklyn and telehealth available.