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. Thyroid Testing (TSH, Free T4, Antibodies)

TSH is the standard first test for thyroid disease. When results are borderline or symptoms point to the thyroid, free T4 and thyroid antibodies add useful information, and antibody testing can pick up Hashimoto’s thyroiditis, an autoimmune thyroid condition. For patients with treatment-resistant depression, anxiety, brain fog, or fatigue, it is worth making sure thyroid dysfunction has been properly checked. A thyroid evaluation can include TSH, free T4, free T3, anti-TPO antibodies and anti-thyroglobulin antibodies; reverse T3 is not recommended for routine testing. Thyroid disease, including Hashimoto’s, can cause symptoms that resemble anxiety, panic, mood cycling and depression.

2. Vitamin D (25-Hydroxyvitamin D)

Vitamin D deficiency is common, especially in people 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 labs consider below 20 ng/mL deficient and 20–30 ng/mL insufficient; your clinician sets a target based on your results and health. There is no proven mood benefit from pushing levels well above that range, and the NIH upper limit for adults is 4,000 IU a day; higher doses should only be taken under a clinician with blood monitoring. Testing 25-hydroxyvitamin D (not 1,25-dihydroxyvitamin D) is the appropriate clinical measure. Testing before supplementing helps avoid both under- and 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 are common and can modestly reduce folate conversion, but routine MTHFR testing is not recommended by the American College of Medical Genetics and Genomics, and a variant does not diagnose any condition. Homocysteine can be a useful supporting 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 an often-missed contributor to 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 normal hemoglobin — can contribute to fatigue, brain fog, depression, anxiety, restless legs, impaired cognitive function, and poor ADHD medication response. Ferritin is interpreted with your lab’s range, your blood count and your symptoms; low-normal results are worth discussing with your clinician, and iron should only be supplemented when testing shows it is needed, because too much iron is harmful. 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 linked to depression, anxiety and cognitive problems in some people, and research on its role is ongoing. High-sensitivity C-reactive protein (hsCRP) is the most clinically accessible inflammatory marker; higher levels have been associated in studies with depression and poorer antidepressant response, but there is no validated cut-off for psychiatric use. 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 often responds to B12, B6, and folate supplementation. B6 above 100 mg/day for long periods can cause nerve damage, so check with your clinician before starting, especially if you take psychiatric medication, are pregnant or breastfeeding. 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 assays are unreliable), and digestive enzyme sufficiency. Given the research on the gut-brain axis connection and the role of the microbiome in serotonin synthesis, inflammation, and neurotransmitter metabolism, some clinicians consider gut assessment, although these commercial stool panels are not validated for psychiatric diagnosis — 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, but it is investigational, with no validated cut-offs for psychiatric use.

Selected lab testing is one part 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.