Transcript
Page 1: Alcat Test_Food Allergy and Chemical Sensitivity Tests

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Anxiety and Your PatientA holistic, integrative approach for the general practitioner-

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EpidemiologyJournal Clinical Psychiatry- most

common psych disorder15.7 million in the US 30% seek treatmentPresent to general practitioners

more than psychiatrist

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What is AnxietyPersistent fear response without

identifiable specific trigger orProlonged responseStarts fight or flight response Anxiety increases risk of

inflammatory diseasesMore prone to mistakes, less

productive

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Genetic? Studies show may be genetic

susceptibility with variants of retinoid-related orphan receptor alpha (RORA) gene to PTSD

Gene primary function to protect brain from stress

Gene Variant of BDNF gene Met66Met- smaller hippocampus on imaging and higher response amygdala to emotional stimuli with fMRI (Val66Val calmer)

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Mediators- B.I.GBrain (neuroendocrine)Immune System- surveillance, Gut Vagus nerve 2 way

communication system between brain and gut

All interact to form super information highway

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Brain-Theories and Substances

TriggerArrives amygdala To Locus CereleusActivation of sympathetic systemPrefrontal lobeResponse

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Brain Connection- Pathway r

Trigger

Amygdala

Locus Cereleu

sNE

CRH

ACTHAdrenal

Stimulation

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Theories and SubstanceAmygdala stores fear memoriesUsed Pavlovian conditioned and

unconditioned stimulus Substances affect amygdala can

escalate or ameliorate anxiety

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Brain ConnectionLocus Cereleus primary NE

center in brainLC can be affected by other NTLC connects to all parts of brain

including hypothalamusNE play role in HTN, behavioral

changes and modulates HPA axisIncreased cytokines increase NE

in hypothalamus via LC neurons

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Brain ConnectionSeveral factors seem to play a

role hereNT such as GABA, Serotonin and

Norepinephrine and glutamate have been assigned significant roles

The HPA with CRF axis gets activated as well

Cytokines can form de novo in the brain and trigger responses

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Brain Connection The major neurotransmitters

implicated in the anxiety response

GABANESerotoninGlutamate

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Brain ConnectionSerotonin is known as inhibitory

NTDerived from trytophanMajority found in gut (90%)Rest brain and plateletsFoods that irritate gut can caused

excess release of serotonin leading to diarrhea (goal is to expel substance causing issue)

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Brain ConnectionSerotonin depletion in prefrontal

cortex leads to anxiety symptomsSerotonin has 7 subtype

receptors5HT1a- related to anxiety5HT3 in the chemoreceptor

center brain can be stimulated by excess serotonin and cause nausea and vomiting

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Brain Connection GABA major inhibitory in the

brainAlso found in GutRegulation of GABA system in

amygdala important part of anxiety pathology

Pathway conversion excitatory Glutamate to GABA via enzyme glutamate decarboxylase

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Brain Connection- GABA 3 types GABA receptors- A, B. CDeficiency in GABA receptors (A)-

led to hyper activation of HPA axis

GABA-A (fast)– binding increase cl conductance so hyperpolarize post synaptic neurons to decrease excitation

GABA-B- inhibit Ca channels to reduce NT release, and K channels to decrease excitability

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Glutamate

Excitatory NT (most abundant)Several studies indicate that

modulating glutamate receptors can improve anxiety

Mechanism not fully elucidatedGlial cells responsible removal of

glutamate Dysfunction or reduction leads to

glutamate toxicity

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GlutamateThought to be mediated through

NDMA receptorNeeds glutamate, glycine and

voltage for activation and opening channels

Open- Calcium influxExcess calcium- neuronal injuryFine line because activation

NDMA needed for memory and learning

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NorepinephrineIncreases symptoms of anxietyWhen administered symptoms of

anxiety- HR, diaphoresis, etc.Controversy if NE from LC

causative

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Brain Connection- Other substances CCK 4- provokes anxiety BDNF- responsible for health,

growth and plasticity of nerves (adaptability)

BNDF protects neurons from glutamate toxicity

Oxytocin- role in social phobias

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Brain Connection- BDNF Human study showed depressed

individuals with lower BDNFThose with lowest BDNF levels

did not respond as well to anti-depressant treatment

Several studies show BDNF facilitates function of anti-depressant esp. SSRI

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Immune ConnectionThe immune system is thought to be

trigger Chronic GI inflammation increases

inflammatory cytokines and anxiety behavior

Immune system and neuroendocrine share many receptor sites and ligands

Cytokines (produced by immune system and also by brain) can regulate stress response in brain as well as endocrine system and behavior

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Immune connectionImmune system when triggered

produce cytokinesEx. IL-6, IL-1, IL-2, IFN-gamma, TNF,Peripheral cytokines can cross BBBStimulate HPA axis as well as cause

brain (glial Cells) to produce de novo cytokines

Excess IL-6 act on neurons increase anxiety and cognitive deficits

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Immune ConnectionCytokine can activate HPA axisIncrease CRHCRH sensitize cells and facilitate

effect of cytokines like TNFTNF alpha injected in amygdala

facilitated ETOH withdrawal anxiety

Inhibitor of CRH receptor decreased magnitude of anxiety response

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Immune ConnectionInterferon gamma stimulates

enzyme indoleamine2,3 dioxygenase (IDO). This degrades Tryptophan (responsible for serotonin formation) to other inflammatory substances such as Kynurenine

17 B-estradiol could increases INF gamma thereby potentially increasing inflammation

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Immune ConnectionAging increases Cytokines such as

INF gamma, TNF alphaDysregulates HPA feedback

mechanism thereby increasing cortisol levels

Cortisol affects metabolism of tryptophan towards inflammatory along with direct effect hippocampus

Theorized one of reasons elderly more prone to depression/anxiety

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Immune ConnectionStudies show that TCA like

imipramine and SSRI have anti-inflammatory effect

Decreases levels of IL-2, IL-1, TNF, IL-6, INF gamma

These substances have immediate effect on NE and Serotonin but takes longer for clinical benefits (about time that it takes to have effect on cytokines

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Gut ConnectionGut has over 100 million neurons90% visceral neurons have

connection with brain95% all serotonin found in gut

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Gut ConnectionStudies showed that changing

bacterial flora in mice changed behavior

Colonized germ free mice with gut flora from active or passive mice would change behavior accordingly

Mice treated with antibiotics- anxiety reduction.

Stopped antibiotics flora and anxiety returned to baseline

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Gut ConnectionChanges seem to be associated with

change in BDNF (linked to anxiety and depression)

Stressor exposure changed bacterial flora in gut (decrease genus Bacteroides and increase Clostridium)

Stressor also increased inflammatory cytokines (IL-6, MCP-1) further affected other bacterial flora

IL-6 inflammatory cytokine

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Gut ConnectionEvidence that Lactobacillus

Rhamnosus augments GABA function in brain via vagus nerve from gut (results lost with vagotomy)

Also lowered corticosterone levels

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Gut ConnectionInfectious colitis induces anxiety

Bifidobacterium longum NCC3001 improved anxiety (results lost with vagotomy)

Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels

Enbrel- decreased cytokines and improved anxiety but did not affect BDNF

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Gut ConnectionSince inflammation can directly

affect flora of gut and flora can affect behavior

Could anything such as food sensitivities cause inflammation in gut and thereby exacerbate anxiety symptoms

Personal food sensitivity such as ALCAT may be an important adjunct as testing looks at immune response to foods

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Gut ConnectionStudy showed stress contributed

to development of food allergies by increasing gut permeability therefore increased uptake of food antigen

Bacteria like H. Pylori has been shown to do the same in gastric mucosa, also increasing food sensitivity

Activation of immune system and cytokines

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Gut Connection Food sensitivities trigger gut

permeabilityPart treatment remove triggersHeal gutBifidobacterium Animalis Lactis

LKM 512 found to help to keep tight junction gut and decrease permeability

Decreased inflammation in elderly

Seems to suppress inflammatory bacteria

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What to do?When and if possible identify triggerGut symptoms- know can be variety

of things from food sensitivity, to infectious or inflammatory trigger such as IBD to emotional stress (remember changes flora)

ALCAT may be helpfulRemove and or treat triggerConsider probiotics with

neuromodulatory effect

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What to doConsider other substances to

decrease inflammatory cytokines while treatment is on going (curcumin, fish oil, and resveratrol, andrographis)- ?medical food

Tea Tree Oil (inhalation)- decreases TNF alpha, IL 1

If over weight start weight lossRemember Adipocytes can

generate cytokines as well

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What to doGerman Chamomille- inhibited

release lipopolysaccharide which induce macrophage prostaglandin E2 (LOX-2 inhibitor

Maybe possess some anti-microbial properties (gut dysbiosis)

Contains Apigenin flavonoid- study show mild sedative via inhibition NDMA-R

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What to doI have found neurotransmitter testing

helpfulEven though no info on receptors,

etc. I find it helps me to chose supplements or meds

Check for easy nutrient deficiencies B12, folate, red blood cell magnesium (easier than loading test)

Check cortisol/ACTH levels - helps in choosing tx

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What to do- herbalValerian- blocks glutamate

receptorJujube (Ziziphysis Spinosa)-

inhibits glutamate receptor to decrease excitability

Kava- shown to improve anxietyConcern with liver issues due to

quality of Kava, parts used and inappropriate dosage

Passion Flower extract – thought to have GABA agonist properties

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What to doTryptophan- just remember that

inflammation can turn a good AA bad

Studies do not support St. Johns Wort for anxiety

Magnesium- modulates NDMA-R slow influx calcium- protecting neurons

Vitamin B12 studies show protects neurons NDMA-R glutamate toxicity

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What to doL-Theanine- studies suggests works

thru GABA- A receptorsOther studies show affect on

serotonin and dopamine NTPersonally noted that if dopamine

on NT test high, theanine may have slightly anxiogenic affect

Good news- neuroprotective by decreasing formation glutamine to glutamate

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What to do- HPA AxisLavender Essential oil stimulates

PNS to decrease excitabilityLemon Balm- inhibitor of GABA

transaminase (enzyme clears GABA)

Address HPA axisStress managementCognitive therapy (enhanced with

D-cycloserine for specific phobias)

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What to do-HPA Magnolia officianlis (honokiol and

magnolol)- decrease corticosterone, increase 5HT in hippocampus, antimicrobial, decrease TNF alpha

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What to doIf menopausal consider there

may be a hormonal componentChanges in hormones such as

estrogen, progesterone and testosterone can contribute to anxiety symptoms

I could correct other issues first to optimize results

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What to do- Hormones Several studies suggest estradiol

can be anxiolyticEstrogen increases the mRNA for

trytophan hydroxylase enzyme (rate limiting step in production of serotonin

Effects in dorsal raphe and seems to occur binding ER beta

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What to do- hormones Can increase proinflammatory

cytokines Avoid with autoimmunity? One study suggest this effect

may be at least in part influenced by presence of hydroxylated estrogens (2,4,16) and cortisol

Personal approach r/o autoimmunity, correct inflammation if present before this step

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What to do- Hormones Progesterone- anxiolytic or

anxiogenicSeveral studies suggest that

effect on GABA receptorsConversion to allopregnanelone

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What to do- Pharmacological SSRI, 5HT1a-R agonist- decrease

inflammation, increase serotonin (E.g. Lexapro, Buspar)

Also seem to modulate NDMA-RBenzodiazepene- GABAB-Blocker (Inderal)- performance

anxiety (stage fright, exams, etc.)Block sympathetic symptoms, also

acutely decrease endorphin levels

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Some ConcernsProlonged use SSRI can lead to

osteoporosisShown eventual decrease in

serotonin levels below baseline with chronic use

Benzodiazepenes addictive potential

Long term effect of beta blocker- depression, memory loss etc.

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What to AvoidSpirulina- increases, TNF alphaEchinaccea- can potentially increase

IL-6, TNF alpha?? Honey- works by increasing TNF

alpha, IL 6, IL 1Remember cytokines can stimulate

HPA axis as well as activate amygdala and LC =NE anxiety

Caffeine blocks its receptors adenosine that slows HR and calms-

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THANK YOU

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