Depression: Symptoms, Causes, Lab Tests, Treatment

Depression, or major depressive disorder (MDD), is a common mental health condition characterized by persistent feelings of sadness, hopelessness, and a lack of interest or pleasure in previously enjoyable activities. It significantly impacts a person's emotional, physical, and cognitive well-being, influencing how they think, feel, and function daily.

Epidemiological Data

Depression is a prevalent mental health condition affecting individuals worldwide, with significant variations across different regions and demographics.

Global Prevalence: According to the World Health Organization (WHO), approximately 280 million people globally experience depression, accounting for about 3.8% of the population. This includes 5% of adults, with a higher prevalence among women (6%) than men (4%).

Age and Gender Disparities: Depression affects individuals across all age groups, but specific populations are more vulnerable:

• Gender: Women are approximately 50% more likely to experience depression than men.
• Age: Older adults, particularly those over 60, have a higher prevalence rate of 5.7%.

Economic and Social Factors: Depression is more common in urban populations and among individuals facing adverse socio-economic conditions, including unemployment and low income. These factors contribute to increased stress and reduced access to mental health resources.

Depression symptoms

Symptoms of depression can vary from person to person, but common signs include:

Emotional Symptoms

• Persistent sadness or low mood.
• Feelings of hopelessness or helplessness.
• Irritability, frustration, or anger outbursts over minor matters.
• Loss of interest or pleasure in activities once enjoyed (anhedonia).
• Feelings of worthlessness, guilt, or excessive self-criticism.
• Difficulty in making decisions or concentrating.

Physical Symptoms

• Fatigue or lack of energy, even for small tasks.
• Changes in appetite (eating too much or too little) or weight.
• Sleep disturbances (insomnia or sleeping too much).
• Aches, pains, or physical complaints without a clear cause.
• Psychomotor changes, such as restlessness or slowed movements.

Behavioral Symptoms

• Withdrawal from social activities and interactions.
• Reduced productivity or performance at work or school.
• Neglect of personal hygiene or responsibilities.
• Increased use of alcohol, drugs, or other coping mechanisms.

Cognitive Symptoms

• Negative or intrusive thoughts.
• Difficulty focusing or making decisions.
• Rumination about failures, mistakes, or negative experiences.
• Thoughts of death or suicide (in severe cases).

Depression causes

The causes of depression are complex and can vary among individuals. They often result from biological, psychological, environmental, and social factors. Here are some common causes and contributing factors:

1. Biological Factors

• Brain Chemistry: Imbalances in neurotransmitters like serotonin, dopamine, and norepinephrine can affect mood regulation.
• Hormonal Changes: Hormonal fluctuations, such as those during pregnancy, postpartum, menopause, or thyroid disorders, can contribute to depression.
• Genetics: A family history of depression or other mood disorders can increase the risk.
• Chronic Illness: Conditions such as diabetes, heart disease, cancer, or chronic pain can lead to depression.

2. Psychological Factors

• Personality Traits: Certain personality traits, such as low self-esteem, perfectionism, or high sensitivity to criticism, may increase vulnerability.
• Trauma: Emotional, physical, or sexual abuse or other traumatic experiences in childhood or adulthood can contribute to depression.
• Negative Thinking Patterns: Persistent pessimism, self-criticism, or catastrophizing can worsen depressive symptoms.

3. Environmental Factors

• Stressful Life Events: Loss of a loved one, financial difficulties, job loss, divorce, or other major stressors can trigger depression.
• Lack of Social Support: Loneliness, isolation, or lack of meaningful relationships can contribute to feelings of despair.
• Substance Abuse: Alcohol or drug abuse can lead to or exacerbate depression.

4. Medical and Physiological Factors

• Gut-Brain Axis: Imbalances in gut microbiota, as seen in gut dysbiosis or conditions like SIBO, may influence mood and depression.
• Chronic Inflammation: Persistent low-grade inflammation in the body is increasingly recognized as a factor in depression.
• Medications: Some medications, such as certain blood pressure drugs or corticosteroids, can cause depressive symptoms as a side effect.

5. Social and Cultural Factors

• Cultural Expectations: Social pressures, stigma, or unrealistic societal standards can contribute to feelings of inadequacy or hopelessness.
• Economic Hardships: Poverty, unemployment, or lack of access to healthcare can increase stress and vulnerability to depression.

6. Combination of Factors

Often, depression results from an interplay of multiple factors rather than a single cause. For example, someone with a genetic predisposition to depression might develop symptoms after a stressful event or due to chronic illness.

Depression functional medicine root causes

Functional medicine views depression as a systemic condition with potential root causes stemming from imbalances in the body. Here are some key functional medicine perspectives on the root causes of depression:

1. Chronic Inflammation

• Mechanism: Chronic, low-grade inflammation can interfere with neurotransmitter production and brain function.
• Potential Sources:
  • Gut dysbiosis or leaky gut (increased intestinal permeability).
  • Autoimmune diseases (e.g., Hashimoto's thyroiditis).
  • Diets high in processed foods, refined sugar, and trans fats.
  • Chronic infections or hidden viral/bacterial load.

2. Gut-Brain Axis Dysregulation

• Mechanism: The gut microbiome produces neurotransmitters like serotonin and dopamine and communicates with the brain via the vagus nerve.
• Contributors:
  • Small Intestinal Bacterial Overgrowth (SIBO) or gut dysbiosis.
  • Nutrient malabsorption (e.g., B vitamins, magnesium, zinc).
  • Imbalances in gut bacteria (low Bifidobacteria or Firmicutes).
  • Food intolerances or sensitivities (e.g., gluten, dairy).

3. Neurotransmitter Imbalances

• Mechanism: Dysregulated production of neurotransmitters like serotonin, dopamine, and norepinephrine can affect mood and cognition.
• Contributors:
  • Nutritional deficiencies (e.g., tryptophan, B6, omega-3s).
  • Genetic variations (e.g., MTHFR gene affecting folate metabolism).
  • Chronic stress depleting neurotransmitter reserves.

4. Hormonal Imbalances

• Mechanism: Hormones regulate brain function, mood, and energy levels.
• Contributors:
  • Thyroid dysfunction (e.g., hypothyroidism or Hashimoto’s thyroiditis).
  • Adrenal dysregulation (e.g., chronic stress leading to HPA axis dysfunction).
  • Sex hormone imbalances (e.g., low estrogen, progesterone, or testosterone).
  • Insulin resistance or blood sugar dysregulation.

5. Nutrient Deficiencies

• Mechanism: Deficiencies in key nutrients impair neurotransmitter synthesis, energy metabolism, and brain function.
• Key Nutrients:
  • B Vitamins: Folate (B9), B12, and B6 are critical for neurotransmitter production.
  • Omega-3 Fatty Acids: Essential for brain health and inflammation control.
  • Magnesium and Zinc: Support neurotransmitter function and stress resilience.
  • Vitamin D: Plays a role in mood regulation and immune health.
  • Iron: Deficiency can lead to fatigue and impaired brain function.

6. Toxin Exposure

• Mechanism: Environmental toxins can disrupt brain chemistry and inflammation pathways.
• Contributors:
  • Heavy metals (e.g., mercury, lead).
  • Mold or biotoxins (e.g., mycotoxins from water-damaged buildings).
  • Pesticides and chemicals in food or the environment.

7. Mitochondrial Dysfunction

• Mechanism: Impaired energy production in cells affects brain function and resilience.
• Contributors:
  • Chronic oxidative stress.
  • Nutrient deficiencies impacting mitochondrial health (e.g., CoQ10, L-carnitine).
  • Poor diet and lack of physical activity.

8. Stress and HPA Axis Dysfunction

• Mechanism: Chronic stress dysregulates cortisol and other stress hormones, impacting mood and brain health.
• Contributors:
  • Persistent high or low cortisol levels.
  • Lack of recovery from stress (e.g., poor sleep, overwork).
  • Trauma and unresolved emotional stressors.

9. Sleep Dysregulation

• Mechanism: Poor sleep disrupts neurotransmitter balance, brain detoxification, and emotional regulation.
• Contributors:
  • Sleep apnea or other sleep disorders.
  • Insomnia from stress, poor sleep hygiene, or circadian rhythm disruption.

10. Food Sensitivities and Allergies

• Mechanism: Inflammatory responses to food can contribute to systemic inflammation and mood changes.
• Common Triggers:
  • Gluten.
  • Dairy.
  • Processed foods with additives or artificial ingredients.

11. Genetic Predispositions

• Mechanism: Genetic variations can affect neurotransmitter production and detoxification pathways.
• Key Variants:
  • MTHFR (affecting folate metabolism and methylation).
  • COMT (involved in dopamine regulation).
  • SLC6A4 (serotonin transporter gene affecting serotonin reuptake).

Depression laboratory tests

In conventional medicine, laboratory tests for depression are primarily used to rule out physical conditions or biochemical imbalances that may mimic or contribute to depressive symptoms. These tests help ensure that the depression is not secondary to an underlying medical issue. Commonly ordered tests include:

1. Thyroid Function Tests

• Thyroid-Stimulating Hormone (TSH): Evaluates overall thyroid function; hypothyroidism is a common cause of depressive symptoms.
• Free T4 and Free T3: Measures active thyroid hormones to detect underactive or overactive thyroid.
• Thyroid Antibodies: To identify autoimmune thyroid conditions like Hashimoto’s thyroiditis.

2. Complete Blood Count (CBC)

• Screens for anemia, infections, or other conditions that can cause fatigue, which may mimic depression.
• Hemoglobin and Hematocrit: Low levels can indicate anemia.

3. Comprehensive Metabolic Panel (CMP)

• Assesses overall metabolic health, including:
  • Liver function: Abnormalities may cause mood symptoms.
  • Kidney function: Chronic kidney issues can lead to depressive symptoms.
  • Electrolyte imbalances: Sodium, potassium, or calcium levels can influence mood.

4. Vitamin and Nutrient Deficiency Tests

• Vitamin B12 and Folate: Deficiencies are linked to mood disorders and cognitive symptoms.
• Vitamin D: Low levels are commonly associated with depression, especially in regions with less sunlight exposure.

5. Blood Glucose and Diabetes Testing

• Fasting Blood Glucose and Hemoglobin A1C: Detects diabetes or prediabetes, which can contribute to fatigue and depressive symptoms.

6. Lipid Panel

• Evaluates cholesterol levels, as very low cholesterol may affect brain function and mood.

7. Inflammatory Markers

• C-Reactive Protein (CRP): Elevated levels may suggest systemic inflammation, which is increasingly linked to depression.
• Erythrocyte Sedimentation Rate (ESR): General marker of inflammation.

8. Hormone Testing

• Testosterone (in men): Low levels are associated with depression.
• Estrogen and Progesterone: Imbalances in women, particularly during menopause or postpartum, can cause depressive symptoms.
• Cortisol: To check for abnormal stress hormone levels, as seen in chronic stress or Cushing's syndrome.

9. Tests for Chronic Illnesses

• Autoimmune Disorders:
  • Antinuclear Antibodies (ANA): Screens for autoimmune conditions like lupus that may cause mood changes.

10. Other Tests

• Electrolyte Panel: Calcium, magnesium, or sodium imbalances can cause mood disturbances.
• Iron Studies/Ferritin: Iron deficiency anemia can lead to fatigue and depression-like symptoms.

Approach in Conventional Medicine

While these tests help identify or rule out underlying medical conditions, conventional medicine typically relies on clinical interviews and standardized diagnostic criteria (e.g., DSM-5) for diagnosing depression. Treatment is often centered around psychotherapy, medication, or a combination of both once organic causes are ruled out.

Depression functional medicine lab tests

Functional medicine takes a root-cause approach to depression, focusing on uncovering underlying physiological, biochemical, and lifestyle factors contributing to mood disorders. Functional medicine lab tests are comprehensive and aim to identify imbalances or dysfunctions that may lead to depression.

Like conventional medicine, functional medicine recommends tests for vitamins and other nutrients (vitamin D, B12, folic acid, magnesium, zinc, iron), thyroid function tests, hormone tests, and inflammatory markers. Let’s look at some additional tests recommended by functional medicine:

1. Gut Health Testing

• Comprehensive Stool Analysis (EnteroScan®)
  • Identifies gut dysbiosis, parasites, and inflammation.
  • Assesses digestive enzyme function and short-chain fatty acid production.
• SIBO Breath Test: To detect Small Intestinal Bacterial Overgrowth, which can contribute to depression via gut-brain axis dysregulation.
• Zonulin: To assess gut permeability (leaky gut), which can drive systemic inflammation.
• FABP2: Measures intestinal permeability.

2. Neurotransmitter and Methylation Pathway Tests

• Homocysteine: Elevated levels can indicate impaired methylation, critical for neurotransmitter production.
• Methylation Markers:
  • Genetic testing for MTHFR mutations can impair folate metabolism.
  • SAMe/SAH ratio (to evaluate methylation status).
• Neurotransmitter Testing (Urine): Measures levels of serotonin, dopamine, norepinephrine, and GABA.

3. Toxin and Heavy Metal Testing

• Heavy Metal Panel: This panel measures exposure to mercury, lead, cadmium, and other toxic metals, which can impair brain function.

4. Oxidative Stress and Mitochondrial Function

• Glutathione Levels: Low levels may indicate oxidative stress.
• Markers of Oxidative Damage: Assesses DNA damage from oxidative stress.
• Coenzyme Q10 (CoQ10): Essential for mitochondrial energy production; low levels are linked to fatigue and depression.
• ATP Intracellular: Εvaluation of mitochondrial function

5. Food Sensitivity and Allergy Testing (TrophoScan®)

• IgG Food Sensitivity Testing: Identifies delayed food reactions that may cause systemic inflammation.
• Celiac Panel (Anti-Gliadin, Anti-tTG Antibodies): This panel screens for gluten sensitivity or celiac disease, which can cause neurological symptoms.

6. Fatty Acid Testing

• Omega-3 to Omega-6 Ratio: Imbalances can drive inflammation.

7. Amino Acid Profile

• Tryptophan: A precursor to serotonin.
• Phenylalanine and Tyrosine: Precursors to dopamine and norepinephrine.

8. Genetic Testing

• MTHFR Gene Variants: To evaluate folate metabolism and methylation issues.
• COMT Gene: Impacts dopamine breakdown.
• SLC6A4: Serotonin transporter gene linked to mood disorders.

Functional Medicine Approach

By identifying and addressing these underlying factors, a functional medicine practitioner creates a personalized treatment plan, often involving dietary changes, targeted supplements, gut healing protocols, stress management, and lifestyle interventions, to support optimal brain function and emotional health.

Depression conventional therapies

Conventional therapies for depression focus on alleviating symptoms and improving quality of life through a combination of medication, psychotherapy, and sometimes physical interventions. These approaches are based on well-established clinical guidelines and research. Here’s an overview of the main conventional therapies:

1. Psychotherapy (Talk Therapy)

Psychotherapy is one of the primary treatments for depression. There are various forms of psychotherapy.

2. Medications

a. Antidepressants

• Selective Serotonin Reuptake Inhibitors (SSRIs): Fluoxetine, Sertraline, and Citalopram. These medications increase serotonin availability in the brain. Common Side Effects: nausea, headache, and sexual dysfunction.
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Venlafaxine, Duloxetine. Boosts serotonin and norepinephrine levels. Often prescribed for depression with pain symptoms.
• Tricyclic Antidepressants (TCAs): Amitriptyline, Nortriptyline. Effective but with more side effects; used less frequently. Side Effects: Sedation, weight gain, dry mouth.
• Monoamine Oxidase Inhibitors (MAOIs): Phenelzine, Tranylcypromine. For treatment-resistant depression requires dietary restrictions.
• Atypical Antidepressants: Bupropion and Mirtazapine. Different mechanisms are often chosen for specific side effects or benefits (e.g., Bupropion for low energy).

b. Mood Stabilizers: For individuals with depression as part of bipolar disorder. Lithium, Lamotrigine.

c. Antipsychotic Medications: For treatment-resistant depression or severe symptoms. Aripiprazole, Quetiapine.

3. Lifestyle Interventions

• Exercise: Regular physical activity can improve mood by boosting endorphins and neurotransmitters.
• Sleep Hygiene: Addressing sleep disorders can reduce depressive symptoms.
• Dietary Changes: Nutritional counseling may be recommended (e.g., avoiding high-sugar diets).

Combination Therapy

• Often, a combination of medication and psychotherapy yields the best results. Regular follow-ups with healthcare providers are essential to monitor progress and adjust treatments as needed.

Depression natural therapies

Natural therapies for depression focus on improving mood and overall well-being by addressing lifestyle, nutrition, and environmental factors. These approaches are often complementary to conventional treatments and can be effective for mild to moderate depression. Here are some commonly recommended natural therapies:

1. Nutritional Support

Omega-3 Fatty Acids

• Reduces inflammation and supports brain health.
• Fatty fish (salmon, mackerel), flaxseeds, walnuts, or supplements.

Vitamin D

• Low levels are associated with depression, especially in winter months.
• Sunlight, fortified foods, fatty fish, or supplements.

B Vitamins

• B12, B6, and Folate are essential for neurotransmitter production.
• Found in Leafy greens, whole grains, meat, eggs, and supplements.

Magnesium

• It calms the nervous system and alleviates mood swings.
• Nuts, seeds, dark leafy greens, and supplements.

Zinc:

• It supports brain function and reduces inflammation.
• Shellfish, pumpkin seeds, and supplements.

Probiotics and Prebiotics:

• Improve gut health, which influences the gut-brain axis.
• Fermented foods (yogurt, kimchi, sauerkraut) and fiber-rich foods.

2. Herbal Remedies

• St. John’s Wort: Popular for mild to moderate depression. Caution: Can interact with medications, including antidepressants and birth control.
• Saffron: Studies show its mood-enhancing properties.
• Ashwagandha: Adaptogen that reduces stress and anxiety.
• Rhodiola Rosea: Improves energy, focus, and mood; beneficial for stress-related depression.
• Chamomile: Calming and can aid sleep, reducing symptoms of depression.
• Lavender: Aromatherapy or tea for relaxation and mood support.

3. Mind-Body Practices

• Meditation and Mindfulness: Reduces stress and promotes emotional regulation.
• Deep Breathing Exercises: Calms the nervous system and reduces anxiety.
• Acupuncture: Stimulates specific points to balance energy and improve mood.

4. Dietary Approaches

• Anti-inflammatory diet: Focus on whole foods: fruits, vegetables, whole grains, lean protein, and healthy fats. Avoid processed foods, refined sugar, and trans fats.
• Mediterranean Diet: Rich in omega-3s, antioxidants, and fiber; associated with reduced depression risk.

5. Supplements

• SAMe (S-Adenosylmethionine): Supports neurotransmitter synthesis. Caution: Should be used under medical supervision, especially if on antidepressants.
• 5-HTP (5-Hydroxytryptophan): Precursor to serotonin; supports mood. Caution: It should not be taken with antidepressants.
• L-Theanine: Found in green tea; promotes relaxation without sedation.
• GABA: Supports calming neurotransmitter activity.