What Lab Tests Should Be Checked for Depression?
- Ashley Hughes
- Aug 4
- 5 min read
Written by: Ashley Hughes, PMHNP-FNP
Psychiatric Mental Health Nurse Practitioner and Family Nurse Practitioner
If you've been struggling with low mood, fatigue, lack of motivation, or brain fog, you may wonder if there is a blood test that can diagnose depression.
The short answer is no.

There isn't a lab test that can diagnose depression. Depression is diagnosed through a comprehensive psychiatric evaluation, discussion of your symptoms, medical history, and standardized screening tools when appropriate. However, lab work can be incredibly valuable because many medical conditions can cause symptoms that look almost identical to depression. One of my goals at Aligned Psychiatric Care is to understand why you're feeling the way you do rather than simply treating the symptoms. Sometimes depression is exactly what is going on. Other times, there may be an underlying medical issue that needs to be addressed as well.
Why Do Lab Tests Matter?
While depression is a real medical condition, symptoms like fatigue, poor concentration, low energy, sleep changes, and difficulty thinking clearly can also occur with vitamin deficiencies, thyroid disorders, chronic illness, medication side effects, and other medical conditions.
A thorough evaluation helps ensure we're not missing something important.
For example, I have seen patients convinced they were simply burned out or depressed, only to discover they had a significant vitamin B12 deficiency or untreated hypothyroidism contributing to many of their symptoms. Addressing those medical issues often became an important part of their overall treatment plan.
Common Lab Tests for Depression I May Recommend
Not every patient needs extensive laboratory testing. Recommendations depend on your symptoms, medical history, age, medications, and any underlying health conditions. Some of the most commonly ordered labs include:
Complete Blood Count (CBC)

A CBC evaluates your red and white blood cells.
It can identify anemia, infections, or other blood disorders that may contribute to fatigue, weakness, poor concentration, and low energy.
Comprehensive or Basic Metabolic Panel
This panel looks at several important areas, including: kidney function, electrolytes, blood glucose, liver function
Abnormalities can contribute to fatigue, cognitive changes, and mood symptoms.
Thyroid Function (TSH)
Your thyroid plays an important role in regulating metabolism and energy.
An underactive thyroid (hypothyroidism) commonly causes symptoms that resemble depression, including:
Fatigue
Weight gain
Low motivation
Feeling cold
Slowed thinking
Low mood
Vitamin B12 and Folate
Low vitamin B12 or folate levels can contribute to:
Fatigue
Brain fog
Memory difficulties
Depression
Numbness or tingling
Deficiencies become more common as we age and are particularly important to evaluate in older adults or those with certain dietary restrictions or gastrointestinal conditions.
Additional Testing When Appropriate
Sometimes your history suggests that additional testing would be helpful. Depending on your symptoms, I may also recommend:
Vitamin D
Although research continues to evolve, vitamin D deficiency is common and may contribute to fatigue and low mood in some individuals.

Iron Studies
Iron deficiency can cause profound fatigue, poor concentration, headaches, and decreased exercise tolerance, even before anemia develops.
Testosterone (Men)
Low testosterone may contribute to:
Low mood
Fatigue
Reduced motivation
Decreased libido
Testing is generally reserved for men with symptoms suggestive of testosterone deficiency.
Your Medications Matter Too
One of the most overlooked causes of depressive symptoms is actually something I routinely evaluate... It's your medication list. Several medications have been associated with depression or worsening mood in some individuals, including:
Certain beta blockers
Some hormonal medications
Opioid medications
Certain medications used to treat neurological conditions
Some antibiotics
This doesn't mean these medications should automatically be stopped, but it does mean they deserve careful review during your evaluation.
Do All Patients Need Lab Work?
Not necessarily.
For someone with a long history of depression who has already had a medical evaluation, repeating extensive laboratory testing may not always be necessary.
However, I generally have a lower threshold for recommending lab work if:
This is your first episode of depression.
Symptoms developed suddenly.
You're over age 50 and experiencing new-onset depression.
Your symptoms seem unusual or severe.
You have significant fatigue or unexplained physical symptoms.
You have multiple medical conditions.
You're taking several medications.
There is concern for nutritional deficiencies.
The decision is individualized because every patient is different.
What About Genetic Testing or Special Biomarkers?
You may have seen advertisements for specialized blood tests that claim to diagnose depression or predict the best antidepressant. At this time, there are no laboratory biomarkers that can diagnose depression. Researchers continue to study inflammatory markers, blood sugar control, liver enzymes, growth factors, and other biological markers, but these tests are not currently validated for diagnosing depression or routinely guiding treatment. This is something that I evaluate in my nutritional psychiatry evaluations.
Similarly, while pharmacogenetic tests such as GeneSight may be helpful in select situations, they do not diagnose depression and are only one small piece of the overall clinical picture.
My Approach at Aligned Psychiatric Care
I believe good psychiatric care starts with listening.
During a depression evaluation, I don't simply ask about mood. We discuss your sleep, energy, nutrition, medical history, medications, hormone changes, stress, life events, and any physical symptoms that may be contributing to how you're feeling. I ask your goals both short and long term as a guide to where you want to be.
When appropriate, I recommend evidence-based laboratory testing to help identify medical conditions that could be affecting your mental health. Sometimes the results are completely normal, which can be reassuring. Other times, they reveal an important piece of the puzzle that allows us to create a more comprehensive treatment plan.
Depression is rarely as simple as "just take a medication." My goal is to understand the whole picture so we can develop a treatment plan that fits your individual needs.
Ready to Take the Next Step?
If you've been experiencing persistent sadness, loss of interest, fatigue, anxiety, or difficulty concentrating, you don't have to figure it out alone. A comprehensive psychiatric evaluation can help determine whether depression is present, identify possible contributing medical conditions, and create a personalized treatment plan based on your symptoms and goals.
About the Author

Ashley Hughes, MSN, APRN, FNP-BC, PMHNP-BC is a board-certified Psychiatric Mental Health Nurse Practitioner and Family Nurse Practitioner with over 18 years of healthcare experience. She specializes in comprehensive psychiatric evaluations and medication management for adolescents and adults, taking an evidence-based, patient-centered approach that considers the whole person. Ashley has a special interest in anxiety, depression, ADHD, women's mental health, and integrative psychiatry, including the role of lifestyle, nutrition, sleep, and medical conditions in mental wellness.
Through Aligned Psychiatric Care, she provides both in-person care in the Lake Norman area and telehealth services throughout North Carolina.
Disclaimer: The information provided in this article is for educational purposes only and is not intended to diagnose, treat, or replace individualized medical or mental health care. Every person is unique, and symptoms of depression or other mental health conditions should be evaluated by a qualified healthcare professional. If you are experiencing symptoms of depression or have concerns about your mental health, schedule an appointment with a licensed provider for a comprehensive evaluation.
If you are experiencing thoughts of harming yourself or believe you are in immediate danger, call 911 or go to your nearest emergency department immediately. You can also call or text 988 to reach the Suicide & Crisis Lifeline for free, confidential support available 24 hours a day, 7 days a week.


