More to the Story

Research

Exercise & Mental Health

• BMJ network meta-analysis (2024): Exercise is effective for depression; walking/jogging, strength training, yoga among most helpful. https://www.bmj.com/content/384/bmj-2023-075847 BMJ

• PubMed record of the same study: https://pubmed.ncbi.nlm.nih.gov/38355154/ PubMed

• JAMA summary/commentary (2024): Exercise ≈ CBT/meds for many; combo often best. https://jamanetwork.com/journals/jama/fullarticle/2815858 JAMA Network

Inflammation ↔ Mood

• Review: “Inflamed depression”—interactions between inflammation and depression (2024). https://www.sciencedirect.com/science/article/pii/S1043661824002676 ScienceDirect

• Cohort/meta evidence on cytokines & depression (2024). https://pmc.ncbi.nlm.nih.gov/articles/PMC10924400/ PMC

• Sex differences in inflammatory markers in depression (2024). https://pubmed.ncbi.nlm.nih.gov/39089535/ PubMed

Stress Hormones / HPA Axis

• Review: Cortisol axis & psychiatric disorders (2025). https://link.springer.com/article/10.1007/s43440-025-00782-x SpringerLink

• Frontiers review (2025): HPA axis–gut–brain interplay in depression. https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1541075/full Frontiers

Gut–Brain / Microbiome

• 2025 review: Microbiota–gut–brain axis in depression. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1644160/full Frontiers

• 2025 systematic review: Gut microbiota in depression & anxiety. https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-06871-8 BioMed Central

Omega-3s (adjunct treatment)

• 2024 meta-analysis (anxiety outcomes): https://pmc.ncbi.nlm.nih.gov/articles/PMC11186166/ PMC

• Cochrane-style review (2024) on depression: https://pubmed.ncbi.nlm.nih.gov/39564892/ PubMed

• Narrative research overview (2024): https://www.mdpi.com/1422-0067/25/16/8675 MDPI

Explore innovative testing and treatment options for gut-brain connection and lifestyle changes.

Gut-Brain Axis

• Stool testing (microbiome analysis): Looks at the balance of gut bacteria, yeast, and other microbes. Can identify overgrowths or missing strains linked to inflammation or mood.

• Bloodwork: Includes markers for thyroid, hormones, vitamin levels (like B12, D, folate), and inflammation (CRP, cytokines). These can affect both gut and brain health.

• Food sensitivity testing: Helps identify foods that may be triggering gut inflammation and symptoms.

• Functional lab panels: May check for gut permeability (“leaky gut”), adrenal function, or nutrient absorption issues.

Treatment Options

• Nutrition: Eating more fiber, fermented foods, and plant-based diversity supports a healthy microbiome.

• Probiotics & prebiotics: Supplements or foods that add healthy bacteria or feed them. Evidence shows some strains may reduce anxiety and depression.

• Lifestyle: Stress management, exercise, and good sleep improve both gut balance and brain resilience.

• Medication & integrative care: Antidepressants, anti-anxiety medication, or hormone support may be combined with nutrition and lifestyle changes for a whole-person approach.

• Targeted support: In some cases, doctors may recommend anti-inflammatory supplements (like omega-3s), gut repair nutrients (like zinc or L-glutamine), or tailored probiotic strains.

Inflammation

• hs-CRP (high sensitivity C-reactive protein): sensitive marker for chronic low-grade inflammation, linked to depression and cardiovascular risk.

• ESR (erythrocyte sedimentation rate): shows systemic inflammation, though less specific.

• Ferritin: elevated in chronic inflammation or infection (also iron status marker).

• Fibrinogen: clotting protein that rises with inflammation.

• Homocysteine: high levels indicate oxidative stress and vascular inflammation.

Cytokine & Immune Signaling Panels (specialty labs)

• IL-6 (interleukin-6): strongly linked with depression, fatigue, and chronic illness.

• TNF-α (tumor necrosis factor alpha): pro-inflammatory cytokine associated with mood changes and neuroinflammation.

• IL-1β: another key cytokine in “sickness behavior” (fatigue, low motivation).

• IL-10: anti-inflammatory cytokine; low levels may suggest poor immune regulation.

• IFN-γ (interferon gamma): immune activation marker, sometimes elevated in viral triggers.

Oxidative Stress & Cell Damage

• 8-OHdG (8-hydroxy-2’-deoxyguanosine): marker of oxidative DNA damage.

• Malondialdehyde (MDA): lipid peroxidation marker.

• Glutathione (reduced/oxidized ratio): body’s main antioxidant buffer.

Metabolic & Vascular Inflammation

• Adiponectin & leptin: imbalances linked to insulin resistance and inflammation.

• Lp-PLA2 (lipoprotein-associated phospholipase A2): vascular inflammation marker.

• GlycA (Glycoprotein acetylation): advanced marker of systemic inflammation used in research/clinical labs.

Gut-Immune Markers

• Calprotectin, Lactoferrin: stool markers of gut inflammation.

• Zonulin: marker of gut permeability (“leaky gut”).

• sIgA (secretory IgA): mucosal immunity indicator.

• Short-chain fatty acids (butyrate, acetate, propionate): beneficial anti-inflammatory metabolites (low levels suggest dysbiosis).

• Autoimmune screens

  • ANA (antinuclear antibody)

  • Rheumatoid factor, anti-CCP

  • Thyroid antibodies (TPO, TgAb)

  • HLA typing if autoimmune suspicion (celiac, ankylosing spondylitis)

  • Other disease-specific antibodies (SSA/SSB, dsDNA, etc. as indicated)

  Viral / infectious panels

  • EBV (Epstein–Barr virus) antibodies (IgG, IgM) – linked to fatigue and chronic activation

  • CMV (Cytomegalovirus) antibodies

  • Lyme and co-infections (Borrelia, Babesia, Bartonella – region dependent)

  • HHV-6 (human herpesvirus 6) titers

  • Hepatitis panel (if risk factors present)

  • HIV screen (standard of care in unexplained immune issues)

Hormonal Balance

Testing

• Bloodwork: Measures thyroid hormones, estrogen, progesterone, testosterone, and cortisol to check for imbalances.

• Saliva or urine hormone panels: Sometimes used to track daily hormone fluctuations or adrenal function.

• Vitamin and nutrient testing: Low levels of B12, D, folate, or iron can mimic or worsen mood problems.

• Functional testing: In some cases, providers may check for inflammation markers or gut health, since these interact with hormones.

Treatment

• Lifestyle support: Stress management, exercise, and healthy sleep patterns naturally improve hormone balance.

• Nutrition: Balanced meals with enough protein, healthy fats, and micronutrients support hormone production.

• Medications: Antidepressants, thyroid medication, or other psychiatric/medical treatments may be needed.

• Hormone therapy: Options like thyroid replacement, testosterone therapy for men, or estrogen/progesterone support for women can restore balance when levels are low.

• Integrative care: Supplements (omega-3s, vitamin D, adaptogens, etc.) may be added, guided by lab results and medical advice.