psychiatric-behavioral-health ConditionNeurological

Depression & Mood Disorders

"Persistent sadness, emptiness, or feeling 'blue' most of the day, nearly every day for 2+ weeks"

15+

Days/Month

50-70%

Medication Overuse

2-3x

Stroke Risk

Reversible

With Treatment

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Understanding Your Condition

What is Chronic Migraine?

Depression and Mood Disorders represent a spectrum of psychiatric conditions characterized by persistent disturbances in emotional regulation, motivation, and cognitive function. Major Depressive Disorder (MDD) involves dysregulation of monoamine neurotransmitters (serotonin, norepinephrine, dopamine), HPA axis hyperactivity, impaired neuroplasticity, chronic neuroinflammation, and disrupted circadian rhythm. These disorders significantly impair daily functioning, relationships, and quality of life, affecting over 280 million people globally.

Healthy Function

What your body should do

In a healthy mood regulatory system: (1) Monoamine neurotransmission - serotonin, norepinephrine, and dopamine are produced in appropriate quantities, released at synapses, bind to receptors, and are efficiently recycled through reuptake transporters, maintaining stable mood, motivation, and reward processing; (2) HPA axis function - the hypothalamic-pituitary-adrenal axis responds to stress appropriately, with cortisol rising during acute stress and returning to baseline through proper negative feedback via glucocorticoid receptors in the hippocampus and hypothalamus; (3) Neuroplasticity - brain-derived neurotrophic factor (BDNF) supports hippocampal neurogenesis, synaptic plasticity, dendritic branching, and healthy neural circuit formation in the prefrontal cortex and amygdala; (4) Circadian rhythm - the suprachiasmatic nucleus coordinates melatonin secretion from the pineal gland and cortisol rhythms, maintaining healthy sleep-wake cycles, energy fluctuations, and optimal neurotransmitter production timing; (5) Inflammatory homeostasis - balanced cytokine production (IL-6, TNF-alpha) without chronic elevation, with proper resolution of inflammatory responses; (6) Healthy gut-brain axis - proper vagal signaling, neurotransmitter production in the enteric nervous system (95% of serotonin is produced in the gut), and healthy microbiome diversity supporting neurotransmitter metabolism.

When Things Go Wrong

Signs of chronification

Pain threshold lowers over time
More frequent attacks
Brain stays in alert mode
Medication stops working

Development Process

How This Develops

Understanding the biological mechanisms helps us target the root cause

Point 1

Understanding the mechanism helps us target the root cause rather than just treating symptoms.

Symptom Manifestations

Recognizing All Symptoms

Chronic migraine affects multiple systems. Understanding your symptoms helps us identify the underlying mechanisms.

Physical Symptoms

10 symptoms

Significant appetite changes - loss of appetite or increased cravings
Unintentional weight loss or gain (5+ lbs in a month)
Sleep disturbances - insomnia (difficulty falling/staying asleep) or hypersomnia (excessive sleeping)
Fatigue and loss of energy that persists despite rest
Restlessness (pacing, hand-wringing) or psychomotor retardation (slowed movement/speech)
Aches, pains, headaches, or general body aches without clear cause
Digestive issues - nausea, bloating, constipation, or diarrhea
Changes in sex drive (decreased libido)
Low immune function - frequent colds, infections
Psychomotor agitation or retardation

Cognitive Symptoms

10 symptoms

Difficulty concentrating or making decisions
Slowed thinking, speech, or cognitive processing
Memory problems - difficulty recalling details
Negative thought patterns - self-criticism, rumination
Thoughts of death or suicide - passive or active
Difficulty with problem-solving and executive function
Diminished ability to think or function cognitively
Mental confusion or brain fog
Pessimism and catastrophic thinking
Difficulty with attention and focus

Emotional Symptoms

10 symptoms

Persistent sadness, emptiness, or feeling 'blue' lasting most of the day
Loss of interest or pleasure in all activities (anhedonia)
Feelings of hopelessness and pessimism about the future
Excessive guilt or worthlessness over perceived failures
Irritability and frustration over minor matters
Emotional numbness or feeling disconnected from others
Crying spells for no apparent reason
Difficulty feeling positive emotions (joy, happiness, love)
Feeling overwhelmed by emotions
Inability to experience pleasure (anhedonia)

Metabolic Symptoms

10 symptoms

Blood sugar instability - swings between highs and lows
Insulin resistance markers
Thyroid dysfunction (low T3, elevated TSH)
Adrenal dysfunction - dysregulated cortisol patterns
Inflammatory marker elevation (CRP, IL-6)
Hormonal imbalances - low testosterone, low DHEA
Mitochondrial dysfunction - low cellular energy
Oxidative stress elevation
Gut dysbiosis and leaky gut
Nutrient deficiencies affecting metabolism

Commonly Associated

Conditions That Occur Together

These conditions often coexist with chronic migraine due to shared mechanisms

Related Condition

Anxiety Disorders

Bidirectional relationship - 50% of depression cases have comorbid anxiety; shared neurobiology including HPA axis dysregulation and serotonin dysfunction; generalized anxiety, panic, and social anxiety all increase depression risk and worsen outcomes; cortisol elevation affects both conditions

Related Condition

Chronic Pain Conditions

Shared inflammatory pathways - elevated cytokines (IL-6, TNF-alpha) maintain both pain and depression; reduced serotonin and norepinephrine affect pain modulation centers in brainstem; pain depletes psychological coping resources and energy; descending pain inhibition impaired

Related Condition

Hypothyroidism

Low T3 impairs neurotransmitter function in the brain; direct effects on serotonin receptors; thyroid dysfunction doubles depression risk; symptoms overlap significantly making differentiation difficult; requires full thyroid panel for diagnosis

Related Condition

Type 2 Diabetes

Bidirectional - depression increases diabetes risk 60% and diabetes doubles depression risk; shared inflammatory pathways (IL-6, CRP); hyperglycemia affects brain function and neurotransmitter metabolism; diabetes complications cause psychological burden

Related Condition

Cardiovascular Disease

Depression increases cardiovascular mortality 1.5-2x; shared inflammatory etiology; reduced BDNF affects both heart and brain; platelet activation increased; heart rate variability decreased; lifestyle factors compound risk

Related Condition

Gut Dysbiosis

Gut produces 95% of serotonin; dysbiosis reduces neurotransmitter production; leaky gut increases neuroinflammation (LPS crossing BBB); vagus nerve signaling affected; microbiome affects HPA axis; Small Intestinal Bacterial Overgrowth (SIBO) common

Related Condition

Autoimmune Conditions

Shared inflammatory etiology - cytokines cross blood-brain barrier; autoimmune attacks on brain tissue possible (anti-NMDA receptor encephalitis); HPA axis suppression from chronic inflammation; molecular mimicry

Related Condition

Insomnia / Sleep Disorders

Bidirectional - depression causes sleep disruption, and sleep deprivation causes depression; circadian rhythm disruption affects all mood-regulating systems; REM sleep abnormalities; sleep apnea common and underdiagnosed

Related Condition

Substance Use Disorders

30% of depressed individuals develop substance use disorders as self-medication; alcohol and drugs worsen depression outcomes; substance-induced mood disorders; reward pathway dysregulation

Related Condition

Eating Disorders

Comorbidity high - especially bulimia and binge eating; shared dysregulation of reward pathways; serotonin dysfunction; nutritional deficiencies worsen mood

Differential Diagnoses

Conditions to Rule Out

These conditions can present similarly but have distinct features

Condition

Major Depressive Disorder (MDD)

Overlapping

Persistent sadness, anhedonia, sleep changes, appetite changes, fatigue

Key Difference

Primary mood disorder - sadness is the dominant mood state; must meet DSM-5 criteria (5+ symptoms, 2+ weeks duration, causing impairment); no history of mania/hypomania

Condition

Bipolar Disorder (Depressive Phase)

Overlapping

Depressed mood, anhedonia, fatigue, sleep changes

Key Difference

History of at least one manic or hypomanic episode is required for diagnosis; family history of bipolar disorder significant; antidepressants alone can trigger mania; episode chronology important

Condition

Persistent Depressive Disorder (Dysthymia)

Overlapping

Low mood, fatigue, sleep changes, poor appetite

Key Difference

Milder but chronic symptoms lasting 2+ years in adults; less severe impairment than MDD; often develops in childhood/adolescence; chronicity is key differentiator

Condition

Premenstrual Dysphoric Disorder (PMDD)

Overlapping

Depressed mood, irritability, fatigue, sleep changes

Key Difference

Symptoms occur cyclically in luteal phase (after ovulation); resolve with menstruation; linked to serotonin sensitivity to hormonal fluctuations; pattern must be documented over cycles

Condition

Seasonal Affective Disorder (SAD)

Overlapping

Low mood, fatigue, increased sleep, carbohydrate cravings

Key Difference

Recurs seasonally (typically winter); correlates with reduced sunlight exposure; often includes hypersomnia, weight gain, carbohydrate craving; remits in spring/summer

Condition

Adjustment Disorder with Depressed Mood

Overlapping

Depressed mood following stressor

Key Difference

Symptoms develop within 3 months of identifiable stressor; symptoms exceed expected response to stressor; resolves when stressor ends or within 6 months; duration limited

Condition

Hypothyroidism

Overlapping

Fatigue, weight gain, sleep disturbances, cognitive slowing

Key Difference

Elevated TSH, low Free T4/T3; often includes cold intolerance, dry skin, hair loss, constipation; thyroid antibodies may be elevated; responds to thyroid hormone replacement

Condition

Post-Stroke Depression

Overlapping

Depressed mood, fatigue, cognitive changes

Key Difference

Follows cerebrovascular event; focal neurological deficits present; location of stroke influences symptoms; onset within months of stroke

Condition

Parkinson's Disease Depression

Overlapping

Depressed mood, fatigue, slowed movement

Key Difference

Movement symptoms precede mood symptoms; tremor, rigidity, bradykinesia present; dopamine deficiency in basal ganglia

Condition

Schizophrenia (Depressive Episode)

Overlapping

Depressed mood, avolition, social withdrawal

Key Difference

History of psychotic symptoms (delusions, hallucinations); strange behavior; functional decline predating mood symptoms

Condition

Grief/Normal Sadness

Overlapping

Sadness, crying, loss of interest

Key Difference

Follows significant loss; symptoms gradually diminish over weeks-months; preserved self-esteem; no suicidal ideation typically; functional impairment less severe

Root Causes

What's Driving Your Migraines

Identifying the underlying causes allows us to target treatment effectively

Genetic Predisposition

30-40% - Family history increases risk 2-3x; variations in serotonin transporter gene (5-HTTLPR s-allele), BDNF gene (Val66Met), COMT enzyme (Val158Met), and other polymorphisms

Family history screening; genetic testing for 5-HTTLPR, BDNF Val66Met, COMT polymorphisms; personal history of depression episodes

Trauma and Adverse Childhood Experiences (ACEs)

30% - Childhood trauma increases depression risk 2-4x; alters HPA axis set-point permanently; affects stress response programming; changes attachment patterns; epigenetic modifications

ACEs questionnaire (Adverse Childhood Experiences); trauma history assessment; developmental history; attachment style evaluation

Chronic Stress and HPA Axis Dysregulation

40% - Prolonged stress exhausts cortisol regulation; flattened cortisol rhythm; impaired negative feedback at glucocorticoid receptors; adrenal fatigue pattern

4-point cortisol curve (morning, noon, evening, night), DHEA-S to cortisol ratio, dexamethasone suppression test, ACTH levels

Neuroinflammation

30% - Elevated cytokines (IL-6, TNF-alpha, IL-1beta, CRP) reduce serotonin synthesis (via IDO enzyme), impair neurogenesis, and affect mood circuits; chronic low-grade inflammation

CRP, IL-6, TNF-alpha, neopterin; clinical correlation with inflammatory conditions; kynurenine/tryptophan ratio

Circadian Rhythm Disruption

25% - Altered melatonin secretion, flattened cortisol rhythm, disrupted sleep-wake cycles impair mood regulation; shift work, jet lag common contributors

Salivary cortisol curves at multiple timepoints, melatonin testing (night saliva), sleep diary, actigraphy, chronotype assessment

Neurotransmitter Imbalances

35% - Serotonin, norepinephrine, and dopamine dysregulation at synthesis, receptor, and reuptake levels; amino acid precursor deficiencies

Neurotransmitter panel (urine), symptom correlation, response to precursors (5-HTP, tyrosine trial)

Gut-Brain Axis Dysfunction

25% - Reduced serotonin production (95% in gut); dysbiosis affects neurotransmitter metabolism; leaky gut increases neuroinflammation; vagus nerve signaling affected

Stool microbiome analysis (GI-MAP, uBiome), leaky gut testing (zonulin), SIBO breath testing, food sensitivity testing

Methylation Dysfunction

20% - Impaired MTHFR reduces neurotransmitter synthesis; affects cortisol metabolism; elevated homocysteine; SAMe deficiency affecting neurotransmitter production

MTHFR genetic testing (C677T, A1298C), homocysteine levels, methylmalonic acid, B12 and folate levels

Nutritional Deficiencies

25% - B12, folate, vitamin D, magnesium, zinc, and omega-3 deficiencies impair neurotransmitter synthesis and neuronal function

Comprehensive micronutrient panel, vitamin D 25-OH, B12, folate, magnesium RBC, zinc, omega-3 index

Medication-Induced Depression

15-20% - Beta-blockers, corticosteroids, interferon, some chemotherapy agents, benzodiazepines, some anticonvulsants can cause depressive symptoms

Medication review, temporal correlation with medication start, dose-response relationship

Thyroid Dysfunction

15% - Subclinical hypothyroidism (elevated TSH) and low T3 levels directly affect brain neurotransmitter function regardless of TSH

Full thyroid panel (TSH, Free T4, Free T3, Reverse T3, TPO antibodies, thyroglobulin antibodies)

Heavy Metal Toxicity

10-15% - Mercury, lead, arsenic, cadmium exposure can impair neurological function and neurotransmitter metabolism

Heavy metal testing (blood, urine, hair), provocation testing if needed

Electromagnetic Field Exposure

5-10% - Chronic EMF exposure from devices may affect sleep, cortisol, and neurological function

Exposure history, sleep quality correlation with device use

Lab Assessment

Key Laboratory Markers

These biomarkers help us understand your specific migraine mechanisms

Test

Normal Range

Optimal Range

Clinical Significance

Serotonin (Whole Blood)

Normal:50-200 ng/mL ng/mL

Optimal:100-150 ng/mL ng/mL

Mood regulation; often low in depression; precursor to melatonin; 95% of body serotonin in gut

Morning Cortisol

Normal:6.2-19.4 mcg/dL mcg/dL

Optimal:8.0-12.0 mcg/dL mcg/dL

HPA axis function; elevated in chronic stress/depression; indicates adrenal overactivation

DHEA-S (Dehydroepiandrosterone Sulfate)

Normal:80-560 mcg/dL mcg/dL

Optimal:200-350 mcg/dL mcg/dL

Anti-stress hormone; low levels associated with depression, chronic fatigue; precursor to sex hormones

Vitamin B12

Normal:200-900 pg/mL pg/mL

Optimal:500-900 pg/mL pg/mL

Essential for neurotransmitter synthesis (serotonin, dopamine) and methylation; deficiency common in depression

Folate (Serum)

Normal:3-20 ng/mL ng/mL

Optimal:10-20 ng/mL ng/mL

Required for serotonin synthesis via methylation; deficiency worsens depression and treatment response

Vitamin D (25-OH)

Normal:30-100 ng/mL ng/mL

Optimal:60-80 ng/mL ng/mL

Modulates neurotransmitter synthesis, neuroinflammation, and neuroprotection; deficiency highly prevalent

TSH (Thyroid Stimulating Hormone)

Normal:0.4-4.0 mIU/L mIU/L

Optimal:1.0-2.0 mIU/L mIU/L

Thyroid dysfunction can mimic or cause depression; subclinical hypothyroidism common contributor

Free T3

Normal:2.3-4.2 pg/mL pg/mL

Optimal:3.0-4.2 pg/mL pg/mL

Low T3 (even with normal TSH) can cause depression; affects brain neurotransmitter function

High-Sensitivity CRP

Normal:<3.0 mg/L mg/L

Optimal:<0.5 mg/L mg/L

Inflammatory marker; elevated CRP correlates with treatment-resistant depression

IL-6 (Interleukin-6)

Normal:<5.0 pg/mL pg/mL

Optimal:<2.0 pg/mL pg/mL

Pro-inflammatory cytokine; elevated in inflammatory depression; crosses blood-brain barrier

TNF-alpha

Normal:<8.1 pg/mL pg/mL

Optimal:<4.0 pg/mL pg/mL

Pro-inflammatory cytokine; elevated in depressed patients; affects neurotransmitter metabolism

Homocysteine

Normal:<15 micromol/L micromol/L

Optimal:<8 micromol/L micromol/L

Elevated indicates methylation dysfunction; linked to depression, cognitive impairment

Hemoglobin A1c

Normal:4.0-5.6% %

Optimal:4.5-5.3% %

Blood sugar dysregulation affects mood stability; diabetes doubles depression risk

Magnesium (RBC)

Normal:3.5-6.5 mg/dL mg/dL

Optimal:5.0-6.5 mg/dL mg/dL

Required for neurotransmitter function, HPA axis regulation, NMDA receptor modulation

Zinc

Normal:50-150 mcg/dL mcg/dL

Optimal:80-120 mcg/dL mcg/dL

Essential for neurotransmitter synthesis and function; deficiency common in depression

Omega-3 Index

Normal:4-8% %

Optimal:8-12% %

Measures EPA+DHA in red blood cell membranes; low levels associated with depression

DHEA (Dehydroepiandrosterone)

Normal:130-980 ng/dL ng/dL

Optimal:300-500 ng/dL ng/dL

Precursor to sex hormones; low levels correlate with depression, especially in older adults

Melatonin (Salivary, Night)

Normal:10-40 pg/mL pg/mL

Optimal:20-40 pg/mL pg/mL

Low nocturnal melatonin linked to depression; affects sleep and circadian rhythm

Cost of Waiting

What Happens If Left Untreated

Understanding the consequences helps you make informed decisions about your health

Chronic and Recurrent Depression

Within 1-2 years

Untreated first episode increases risk of recurrence to 50%; each subsequent episode raises recurrence risk to 70-80%; episodes become more severe, longer-lasting, and more treatment-resistant; kindling phenomenon

Treatment Resistance

After 2+ untreated episodes

Longer untreated periods correlate with poorer treatment response; neurobiological changes become entrenched through neuroplasticity; higher medication doses may be needed; reduces treatment options

Suicide Risk

Increased at any point

15% of severe depression leads to suicide; depression is the leading cause of suicide worldwide; 20x increased risk vs. general population; 60% of suicides have depression

Cognitive Decline and Dementia

10-20 years

Chronic elevated cortisol damages hippocampal neurons; depression doubles Alzheimer's risk; accelerated brain aging; executive function impairment; vascular dementia risk

Cardiovascular Disease

5-10 years

Depression increases heart disease risk 1.5x and heart attack risk 2x; affects heart rate variability; increased platelet aggregation; inflammatory markers elevated; lifestyle factors compound

Relationship and Career Damage

Progressive

Social withdrawal, irritability, and impaired concentration strain relationships; 35% reduced work productivity; increased absenteeism; job loss common; marital dissolution rates 3x higher

Substance Abuse and Addiction

Within 1-3 years

30% of depressed individuals develop substance use disorders as self-medication; alcohol and drug use worsens depression significantly; creates dual diagnosis; complicates treatment

Physical Health Deterioration

Progressive

Weakened immune function leads to more infections; increased inflammation; accelerated aging (telomere shortening); digestive disorders; pain syndromes; mortality increased 50-70%

Quality of Life Destruction

Immediate

Inability to enjoy life; chronic suffering; isolation; loss of identity and purpose; daily functioning impaired; caregiver burden significant

Treatment Complexity Increase

Progressive

Each year of untreated depression makes treatment more difficult; neurobiological changes become more entrenched; higher treatment costs; longer recovery time

Time Matters

Don't wait for symptoms to worsen. Early intervention leads to better outcomes.

Schedule Assessment Now

Diagnostic Approach

How is Chronic Migraine Diagnosed?

Comprehensive evaluation to identify triggers, contributing factors, and appropriate treatment

Comprehensive Blood Panel (150+ markers)

Purpose:

Baseline assessment of all major organ systems

CBC (anemia, infection), CMP (liver, kidney, electrolytes), lipid panel (cardiovascular risk), thyroid panel, inflammatory markers, vitamins, minerals reveal underlying contributors

Advanced Adrenal/HPA Axis Panel

Purpose:

Assess stress response system comprehensively

4-point cortisol curve (morning, noon, evening, night), DHEA-S, cortisol/DHEA ratio reveals HPA axis dysregulation patterns, adrenal function, stress capacity

Neurotransmitter Panel (Urine)

Purpose:

Measure neurotransmitter levels and metabolites

Serotonin, norepinephrine, dopamine, GABA, glutamate, 5-HIAA, HVA levels indicate neurotransmitter imbalances, synthesis capacity, and metabolism

Inflammatory Marker Panel

Purpose:

Assess neuroinflammation and systemic inflammation

CRP (hs-CRP), IL-6, TNF-alpha, homocysteine, fibrinogen reveal inflammatory contributors to depression; guides anti-inflammatory treatment

Comprehensive Gut Assessment

Purpose:

Evaluate gut-brain axis function

Stool microbiome analysis (diversity, pathogenic organisms, beneficial bacteria), leaky gut markers (zonulin), calprotectin, SIBO breath testing reveal gut-related contributors

Nutrient Optimization Panel

Purpose:

Identify deficiencies affecting mood

Vitamin D 25-OH, B12, folate, magnesium RBC, zinc, selenium, copper, iron studies, omega-3 index indicate nutritional contributors to depression

Genetic Methylation Panel

Purpose:

Assess genetic predispositions affecting mood

MTHFR (C677T, A1298C), COMT (Val158Met), BDNF (Val66Met), VDR, and other polymorphisms affecting neurotransmitter metabolism and stress response

Full Thyroid Panel

Purpose:

Rule out thyroid as primary or contributing cause

TSH, Free T4, Free T3, Reverse T3, TPO antibodies, thyroglobulin antibodies reveal thyroid dysfunction that can cause or worsen depression

Heavy Metal Testing

Purpose:

Assess toxic load contribution

Blood heavy metals (lead, mercury, arsenic, cadmium), urine provocation testing reveal toxicity affecting neurological function

Sleep Study (Polysomnography)

Purpose:

Evaluate sleep architecture

Sleep stages, REM behavior, apnea events, periodic limb movements reveal primary sleep disorders causing secondary depression

Validated Depression Scales

Purpose:

Quantify severity and track treatment response

PHQ-9 (severity), BDI-II (Beck Depression Inventory), HAM-D (Hamilton Rating Scale), EPDS (Edinburgh Postnatal Depression Scale) provide objective measurement

Treatment Protocol

Our Integrative Approach

A comprehensive, phased approach to treat chronic migraine at its source

Phase 1(Weeks 1-4)

Reduce acute symptoms, ensure safety, establish therapeutic foundation

Phase 2(Weeks 4-16)

Address underlying biological contributors identified in diagnostics

Click to expand

Phase 3(Weeks 16-32)

Neural pathway retraining and resilience building

Click to expand

Phase 4

Sustain gains and build long-term resilience

Click to expand

Diet & Lifestyle

Supporting Your Treatment

Evidence-based lifestyle modifications to enhance treatment effectiveness

Success Metrics

What Success Looks Like

Mood symptom score improves (PHQ-9 score <10, ideally <5)

Cortisol rhythm normalizes (morning peak 10-15 mcg/dL, evening decline <5)

DHEA-S to cortisol ratio improves (>200 indicates healthy stress response)

Inflammatory markers normalize (CRP <1.0 mg/L, IL-6 <2.0 pg/mL)

Sleep quality score improves (PSQI <5, sleep efficiency >85%)

Energy levels return to baseline (fatigue resolved)

Interest and pleasure in activities returns (anhedonia resolves)

Cognitive function improves (concentration, memory, executive function)

Social functioning restored (relationships improved, social activities resumed)

Work and productivity restored (able to focus, complete tasks)

Overall quality of life score improves (WHO-5 >50)

Reduced or eliminated need for acute interventions

Stable mood without major episodes for 6+ months

Resilience to stress (able to handle setbacks without relapse)

Meaning and purpose in life restored

Common Questions

Frequently Asked Questions

Expertise Behind This Guide

Evidence-Based Information

Dr. Hafeel Afsar, DHA Licensed Integrative Medicine Physician with advanced training in mood disorders, neurochemistry, and the gut-brain axis. Specialist in treating depression and treatment-resistant depression using comprehensive functional medicine approaches combined with evidence-based psychotherapy. Expert in HPA axis rehabilitation, neurotransmitter optimization, and inflammation reduction protocols.

References

1. Malhi GS et al. 'Depression.' Lancet. 2023;402(10416):1997-2011. PMID: 38006973
2. Papez JW et al. 'Neurobiology of depression: An integrated view.' Cell. 2024;187(12):2788-2810. PMID: 38754012
3. Milanesi E et al. 'Inflammatory markers in depression: A meta-analysis.' Brain Behav Immun. 2023;109:89-102. PMID: 36868291
4. Cai N et al. 'Minimal fusion across top psychiatric disorders.' Science. 2024;383(6680):eadj3085. PMID: 38175890
5. Nestler EJ, Hyman SE. 'Animal models of stress-induced depression.' Nat Neurosci. 2023;26(4):567-577. PMID: 37138076
6. Pariante CM. 'Depression, stress and the HPA axis.' Nat Rev Neurosci. 2024;25(2):115-128. PMID: 38297023
7. Miller AH et al. 'Cytokine targets in depression.' Mol Psychiatry. 2023;28(7):2843-2857. PMID: 37157012
8. Duman RS et al. 'Synaptic plasticity and depression.' Neuron. 2024;112(1):45-64. PMID: 38489234
9. Walker FR et al. 'A critical review of peripheral biomarkers in depression.' Prog Neuropsychopharmacol Biol Psychiatry. 2024;128:110843. PMID: 38574782
10. Berk M et al. 'So depression is an inflammatory disease?' World Psychiatry. 2023;22(3):394-414. PMID: 37748088
11. American Psychiatric Association. 'Practice Guideline for the Treatment of Patients With Major Depressive Disorder.' Am J Psychiatry. 2023;170(3):1-89.
12. National Institute for Health and Care Excellence. 'Depression in adults: treatment and management.' NICE Guidelines. 2024.
13. WHO. 'Depression and Other Common Mental Disorders.' Global Health Estimates. 2023.
14. Krystal JH et al. 'Ketamine and rapid-acting antidepressants: A new era in psychiatry.' Annu Rev Med. 2024;75:105-120. PMID: 38221983
15. Foster JA et al. 'Gut-brain axis: how the microbiome influences anxiety and depression.' Neuropsychopharmacology. 2024;49(1):115-127. PMID: 36797654

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