Depression: Cortisol, hs-CRP, and the Inflammatory Mood Connection

REVIEWED BY

William Maish, MD MBA MPH

Clinical Product Lead

Published

Last updated

Key takeaway:

Blood testing for depression uses cortisol, hs-CRP, and NLR to map stress-axis dysregulation, systemic inflammation, and immune imbalance that may amplify mood symptoms. Elevated hs-CRP (above 3 mg/L) and NLR are associated with inflammatory depression subtypes characterized by fatigue and anhedonia. Tracking these markers connects mood biology to endocrine, immune, and metabolic systems, supporting more targeted care choices.

Read more →

Understand what your mental wellness results really mean

See your biomarkers in context with a comprehensive panel.

  • CLIA-certified labs
  • HIPAA compliant
  • Personalized health protocol
Book your test

Depression and the blood systems that shape mood

Depression biomarkers are measurable signals in blood that mirror the brain–body systems shaping mood, motivation, and energy. They capture how the stress response is operating (hypothalamic–pituitary–adrenal, HPA axis), whether the immune system is activated (systemic inflammation, cytokines), how well nerve cells support growth and connectivity (neurotrophic factors such as BDNF), and how the body manages fuel and timing (metabolic and circadian regulation). Blood testing turns these hidden processes into an objective snapshot that complements conversation and symptom scales. It can reveal when biology is pushing mood through specific pathways, help distinguish different biological “flavors” of depression, and provide a baseline to track change as treatment proceeds. By showing which levers are most perturbed for a given person—stress signaling, immune activity, neuroplasticity, or metabolism—biomarkers enable more targeted choices and clearer monitoring of recovery. In short, they translate an internal experience into a measurable profile (biological phenotype) that can inform care while working alongside clinical judgment and personal goals.

Join 150,000+ others building better health

Get the science behind better health, every week.

By clicking “Subscribe” you agree to our Terms of Service and Privacy Policy.

Why a biological read helps frame the clinical picture

Depression is not just a brain state; it’s a whole-body condition shaped by stress hormones, inflammation, and immune balance. Blood biomarkers help map these systems: cortisol reflects the brain–adrenal stress axis, high-sensitivity CRP (hs-CRP) captures systemic inflammatory tone, and the neutrophil-to-lymphocyte ratio (NLR) shows the balance between innate and adaptive immunity. Together, they clarify whether mood symptoms ride on stress reactivity, inflammation, or immune dysregulation. Typical morning cortisol lands around 10–20, with an optimal pattern in the mid-range and a clear drop by evening. When high, people often feel wired-tired, anxious, and sleep-fragmented; when low or flattened, energy, motivation, and stress tolerance sag. hs-CRP under 1 is generally favorable, 1–3 is average, and over 3 suggests heightened inflammation; lower values tend to be optimal. NLR usually sits near 1–3; the lower end of normal often reflects a calm immune set point, while higher values track physiological stress. Women often show slightly higher hs-CRP than men, and pregnancy raises cortisol and hs-CRP as normal adaptations; children typically have lower NLR.When these markers run low, they tell different stories. Low morning cortisol or a blunted rhythm points to underactive HPA signaling (hypocortisolism), seen in some depression subtypes, with fatigue, hypersomnia, pain sensitivity, and cognitive slowing; teens and the postpartum period may feel this as overwhelming tiredness and reduced stress resilience. Very low hs-CRP usually means minimal systemic inflammation; in depression, it suggests symptoms are driven more by neural circuitry or psychosocial load than inflammation. A markedly low NLR—often from neutropenia or relative lymphocytosis—can indicate viral illness, autoimmune activity, or medication effects, showing up as frequent infections or mouth ulcers; mood effects are typically indirect. Big picture, these markers connect mood to endocrine, immune, metabolic, and sleep systems. Persistent inflammation or stress-axis disruption links to cardiometabolic risk, pain amplification, and cognitive change over time. Tracking cortisol, hs-CRP, and NLR alongside thyroid, glucose–insulin, lipids, vitamin D/B12, and sex steroids provides a systems view of depression biology and its long-term health implications.

Test 150+ biomarkers

Two blood draws. A full picture of your health, explained in plain language.

Book your test

What these markers can and can't tell you about depression

Depression blood testing offers a window into how your body’s stress, immune, and inflammatory systems are functioning—key players in energy, metabolism, cardiovascular health, cognition, and even immunity. At Superpower, we focus on three biomarkers: Cortisol, high-sensitivity C-reactive protein (hs-CRP), and the neutrophil-to-lymphocyte ratio (NLR). Together, these markers help reveal the biological patterns that often accompany depression. Cortisol is a hormone released in response to stress, regulating energy, metabolism, and the body’s daily rhythms. In depression, cortisol levels can be higher or more erratic, reflecting chronic stress or disrupted circadian patterns. hs-CRP is a sensitive marker of inflammation; elevated levels suggest the immune system is more active than usual, which is commonly seen in depression and linked to changes in mood and cognition. NLR measures the balance between two types of white blood cells—neutrophils and lymphocytes—offering insight into immune system activity and inflammation, both of which can shift in depressive states. Healthy stability in these biomarkers supports emotional resilience and balanced brain chemistry. When cortisol, hs-CRP, or NLR are outside typical ranges, it may signal that the body’s stress and immune responses are under strain, which can contribute to or reflect depressive symptoms. Interpretation of these results depends on context. Factors like age, pregnancy, acute illness, chronic conditions, medications, and even lab methods can influence levels. Understanding your unique situation is essential for accurate assessment.

Frequently Asked Questions

References

  1. Stetler C, Miller GE (2011). Depression and hypothalamic-pituitary-adrenal activation: A quantitative summary of four decades of research. *Psychosomatic Medicine*, *73*(2), 114-126. https://doi.org/10.1097/PSY.0b013e31820ad12b
  2. Howren MB, Lamkin DM, Suls J (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: A meta-analysis. *Psychosomatic Medicine*, *71*(2), 171-186. https://doi.org/10.1097/PSY.0b013e3181907c1b
  3. Miller AH, Raison CL (2016). The role of inflammation in depression: From evolutionary imperative to modern treatment target. *Nature Reviews Immunology*, *16*(1), 22-34. https://doi.org/10.1038/nri.2015.5
  4. Mazza MG, Lucchi S, Tringali AGM, Rossetti A, Botti ER, Clerici M (2018). Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis. *Progress in Neuro-Psychopharmacology and Biological Psychiatry*, *84*(Pt A), 229-236. https://doi.org/10.1016/j.pnpbp.2018.03.012
  5. Kishi T, Yoshimura R, Ikuta T, Iwata N (2018). Brain-derived neurotrophic factor and major depressive disorder: Evidence from meta-analyses. *Frontiers in Psychiatry*, *8*, 308. https://doi.org/10.3389/fpsyt.2017.00308

Led by doctors with 40 years of health and longevity expertise

Dr. Anant Vinjamoori

Dr. Anant Vinjamoori, MD

Chief Longevity Officer, Superpower

Dr. Leigh Erin Connealy

Dr. Leigh Erin Connealy, MD

Clinician & Founder of The Centre for New Medicine

Dr. Robert Lufkin

Dr. Robert Lufkin, MD

Physician & UCLA Medical School Professor, NYT bestselling author

Dr. Abe Malkin

Dr. Abe Malkin, MD

Founder & Medical Director of Concierge MD

Biological age 32 — a Superpower member portraitA health system built around you — test, understand, optimize150+ biomarkers across 2 blood drawsWhat to expect with Superpower — week 1 to month 3Trusted by 64,000+ customers — member reviewsBetter than the status quo — Superpower vs the old way60% of members found something a doctor missed — member survey
Daniel OSuperpower memberDavid LSuperpower memberRachel DSuperpower memberCamelia VSuperpower member

4.6 · 64,000+ members

Superpower health membership

Find early signs of 1,000+ conditions - then act, retest, and see what changed.

$349

/year*

150+ biomarkers annually across baseline + retest

Personalized plan that turns results into action

Superpower AI and on-demand care team

Results in 10 days or less

At-home or 2,000+ labs nationwide**

Yearly membership$0.96 / dayHSA/FSA eligible

*Pricing may vary for members in New York and New Jersey

**At-home labs for an additional cost

What we test

TestosteroneFree T4Vitamin DApoBHbA1cThyroid (TSH)hs-CRPFerritinCortisolFasting insulin

60%

found something a doctor missed

93%

rated it more useful than their checkup

77%

found something new in their results

Superpower member survey, 90 days post action plan (n=143).

How does the Superpower membership work?

We test 150+ biomarkers annually across two blood draws. Your baseline test paints a comprehensive picture of your health, and your dashboard shows what’s working, what needs attention, and what to do next. Superpower AI and your care team help you take action across lifestyle, supplements, and treatments. Then we retest to track your progress and continue refining your plan.

Can I cancel anytime?

Yes. You can cancel anytime, no fees. Your membership stays active through the end of your paid year.

How often should I test?

Your membership includes two blood tests per year: one to establish your baseline, and one to see whether your plan improved biomarkers that were out of range or not yet optimized. You can add other diagnostics anytime through the app or with help from your care team.

When will I get my results?

Book your draw at any of 2,000+ partner labs or at-home. Results are typically ready in about a week and land in the Superpower app.

What the 100+ panel measures

All 101 markers in your annual baseline draw, organized by system. Nothing here is an upsell.

Heart & Vascular Health

26

  • Apolipoprotein B
  • Atherogenic Coefficient
  • Atherogenic Index of Plasma
  • Castelli Risk Index I
  • Castelli Risk Index II
  • HDL Cholesterol
  • LDL Cholesterol
  • LDL/HDL Ratio
  • Cholesterol, Total
  • Non-HDL Cholesterol
  • Cholesterol/HDL Ratio
  • Carbon Dioxide, Total
  • High-sensitivity CRP
  • hsCRP-to-Albumin Ratio (CAR)
  • GGT-to-HDL Cholesterol Ratio
  • LDL-C to Apolipoprotein B Ratio (LDL-C/ApoB)
  • LDL Cholesterol / Total Cholesterol (Mass Ratio)
  • Monocyte-to-HDL Ratio (MHR)
  • Neutrophil-to-HDL Cholesterol Ratio (NHR)
  • Non-HDL Cholesterol-to-Apolipoprotein B Ratio (Non-HDL-C/ApoB)
  • NON-HDL Total Cholesterol Ratio
  • Triglyceride HDL Molar Ratio
  • Triglycerides
  • Triglyceride-to-Apolipoprotein B Ratio (TG/ApoB)
  • TyG Index
  • Uric Acid

Metabolic Health

4

  • Estim. Avg Glu (eAG)
  • Eag (mmol/l)
  • Glucose
  • Hemoglobin A1c

Energy

1

  • Cortisol

Liver Health

15

  • Albumin/Globulin Ratio
  • Albumin
  • Alkaline Phosphatase (ALP)
  • Alanine Aminotransferase (ALT)
  • Aspartate Aminotransferase (AST)
  • Bilirubin Direct
  • Bilirubin Indirect
  • Bilirubin, Total
  • Bilirubin-to-Albumin Ratio
  • Ferritin
  • Ferritin-to-Albumin Ratio
  • y-Glutamyl Transferase (GGT)
  • Globulin, Total
  • Indirect-to-Direct Bilirubin Ratio
  • Protein, Total

Kidney

11

  • Calcium
  • Chloride
  • Corrected Calcium (Albumin-adjusted)
  • Creatinine
  • Estimated Glomerular Filtration Rate (eGFR)
  • Potassium
  • Sodium
  • BUN/Creatinine Ratio
  • Blood Urea Nitrogen (BUN)
  • Urea-to-Creatinine Ratio
  • Uric Acid-to-HDL Cholesterol Ratio (UHR)

Sex Hormones

7

  • DHEA-Sulfate (DHEA-S)
  • Free Androgen Index
  • Sex Hormone Binding Globulin (SHBG)
  • Free Testosterone
  • Testosterone, Bioavailable
  • Testosterone, Total
  • Testosterone-to-Estradiol Ratio (T/E₂)

Thyroid Health

4

  • Free Thyroxine Index
  • T3 Uptake
  • T4 (thyroxine) Total
  • Thyroid-Stimulating Hormone (TSH)

Nutrients

13

  • Vitamin D
  • Red Cell Dist Width (RDW)
  • Hematocrit
  • Hemoglobin
  • Total Iron Binding Capacity (TIBC)
  • Iron
  • Iron Saturation
  • Mean Cell Hemoglobin (MCH)
  • Mean Corpuscular Hemoglobin Concentration (MCHC)
  • Mean Cell Volume (MCV)
  • Platelet-to-WBC Ratio (PWR)
  • Red Blood Cells
  • RDW MCV Ratio

Immune System

12

  • Basophils
  • Baso (Absolute)
  • Eosinophils
  • Eos (Absolute)
  • Lymphocytes
  • Lymphs (Absolute)
  • Monocytes
  • Monocytes (Absolute)
  • Neutrophils
  • Neutrophils (Absolute)
  • Mean Platelet Volume
  • Platelet Count

Inflammation

8

  • Lymphocyte-to-Monocyte Ratio (LMR)
  • Monocyte-to-Lymphocyte Ratio (MLR)
  • Neutrophil-to-Lymphocyte-Platelet Ratio (NLPR)
  • Neutrophil-to-Lymphocyte Ratio (NLR)
  • Platelet-to-Lymphocyte Ratio (PLR)
  • Systemic Immune-Inflammation Index
  • Systemic Inflammation Response Index (SIRI)
  • White Blood Cells
Get my health baseline

The full list of 100+ markers and 8 specialty add-ons available at superpower.com/what-we-test.