NEUROENDOCRINE

NEUROENDOCRINEDr dr Anwar Wardy W, SpS, DFM (K)Dept.Neurology FK.UMJanwar wardy wdept.neurology fk.umjWhat is Response NeuroEndocrine?A physiologic response to a demand for changeFight or Flight responseGeneral Adaptation SyndromeSympathetic Nervous system Dominance anwar wardy wdept.neurology fk.umjSTRESS PHYSIOLOGY

Without stress, there would be no lifeStress = nonspecific response of the body to any demand.anwar wardy wdept.neurology fk.umjHOW CAN STRESS CAUSE SO MUCH DAMAGE?Selyes General Adaptation SyndromeThe 3 Stages of StressArousal Rapid increases in catecholamines (alarm molecules) Slower increases of corticosteroids (stress steroids)AdaptationCharacterized by sustained increased levels of corticosteroids and alarm moleculesAltered glucose tolerance, blood pressure, thyroid hormone and sex hormone metabolismExhaustionDegenerative diseases characterized by the adverse influence of corticosteroids and alarm moleculesanwar wardy wdept.neurology fk.umjSTRESS versus THERELAXATION RESPONSEFIGHT OR FLIGHT RESPONSESympathetic StateInc. Heart RateInc. Blood PressureInc. Respiratory RateDilated PupilsMuscle TensionInhibits Digestionanwar wardy wdept.neurology fk.umjRELAXATION RESPONSEParasympathetic StateDec. Heart RateDec. Blood PressureDec. Respiratory RateConstricted PupilsMuscle RelaxationEnhances DigestionSTRESS and NEUROLOGIC DiseaseThe basis for human stress related disease is the high percentage of time spent in the sympathetic dominant state.anwar wardy wdept.neurology fk.umjSYMPATHETIC DOMINANCE:LONG-TERM EFFECTS OF ELEVATED CORTISOL & CATECHOLAMINESGI distress: IBS, ulcersCardiovascular symptoms: rapid pulse, pounding heart, weakness, dizziness, chest pain, high BPMood changes: general irritability, floating anxiety, depression, impulsive behavior, nervous laughter, increase startle responseHyper-kinesis or excitationSleep disturbances: nightmares, insomniaBrain architecture changes: Lower hippocampal volume (inc cortisol)anwar wardy wdept.neurology fk.umjCognitive impairment: inability to concentrate, poor memoryNeuromusculoskeletal complaints: TMJ, bruxism, trembling, nervous ticks, back and muscle acheEnergy level: Fatigue of unknown originAdrenal architecture changes: Adrenal hyperplasia burnout: dryness of mouth, sweating, salt cravingsImmune impairment: increased susceptibility to viral infections, autoimmune disorders STRESSAND ADRENAL PROBLEMStress triggers psycho-neuroendocrine-immune imbalancesanwar wardy wdept.neurology fk.umjEmotional trauma Limbic system HypothalumsLocus Coenuleus Primary Afferent Nociceptor Noxious Stimulusanwar wardy wdept.neurology fk.umj

Emotional trauma Limbic system Hypothalums

Norepinephine (NE) Sympathetic Nervous Systemanwar wardy wdept.neurology fk.umj Corticotrophin Releasing Hormone (CRH) Anterior Pitutiary AdrenocorticotrophinAdrenal cortexCortisolCortisolIncreases with age and can elevate blood glucose by up to 50%, contributing to insulin resistance and inflammation.anwar wardy wdept.neurology fk.umjCORTISOL INFLUENCES NEUROENDOCRINE FUNCTIONInc. Epinephrine (E) & NorepinephrineInc. CortisolInc. Insulin (due to inc. glucose)Inc. visceral fat depositionDec. TSH, T4, T3Dec. estrogen, Testosterone, ProgesteroneAltered neurotransmitter balanceanwar wardy wdept.neurology fk.umjInc. oxidative stressInc. inflammationInc. need for detoxificationImpaired immunityDec. Secretory IgAInc. Antigen penetrationInc. IgGDec. NK cell activityDec. IL-2Inc. bone lossSympathetic Dominance Can TriggerHPA HypoactivationGlucocorticoid receptor insensitivity or under production of cortisol (adrenal insufficiency)Symptoms and conditionsFatigue/malaiseRisk of inflammatory conditionsRisk of autoimmune diseaseMyocardial infarctionUnable to perform routine tasksInability to copeApathyAnorexiaWeight lossRestless sleepWeaknessChronic painReduced libidoanwar wardy wdept.neurology fk.umjSympathetic Dominance Can TriggerHPA HyperactivationCortisol and catecholamine excess and imbalanceSymptoms and conditionsAnxietyAgitation/irritabilityRestless sleepIncreased cholesterolIncreased triglyeridesIncreased blood pressureInsulin resistanceReduced libidoFatigueDepression

anwar wardy wdept.neurology fk.umjImpaired memory learningGastrointestinal disordersCentral obesityNeurologic disordersLoss of muscle toneDecreased growthProtein wastingBone lossSkin disordersReduced immune defensePoor injury/illness recoveryReduced sex hormone levelsReduced reproductive functionFunctional renal problemsSympathetic Dominance Can TriggerHPA HypoactivationHPA hyperactivationAdrenal Exhaustion adrenal gland hyperplasia and failure to respond.anwar wardy wdept.neurology fk.umjStress Neuro_PhysiologyConditions Linked with Overproduction & Underproduction of Cortisol

OverproductionCushings SyndromeDepression & OCDDiabetesSleep deprivationAnorexia nervosaExcessive exerciseChildhood abuseHyperthyroidismanwar wardy wdept.neurology fk.umjUnderproductionSeasonal depressionCFIDSFibromyalgiaHypothyroidismTobacco withdrawalAllergies/AsthmaRheumatoid arthritisB. McEwen. The End of Stress as We Know It. 2002, p.64RECOGNIZE SIGNS OF PHYSICAL AND MENTAL STRESSAnxietyBack painConstipationDiarrheaDepressionExhaustionFatigueHeadachesHigh blood pressureanwar wardy wdept.neurology fk.umjInsomnia (disturbed sleep)Relationship problems (i.e. loss of sexual desire)Shortness of breathStiff neckUpset stomachWeight gainWeight lossWorryingIDENTIFY NEURO_STRESS AROUSAL TRIGGERSPSYCHOLOGICAL STRESSORS-Divorce-Unemployment -Death-Children, etc.-Self-esteem Environmental Stressors-Chemical/toxic-Infection-Endobiosis-Noise-Light-Vibrationanwar wardy wdept.neurology fk.umjMETABOLIC STRESSORS-Nutritional (need beyond supply, supply beyond need)-Oxidative-InflammatoryPhysiological stressors-Structural-Traumatic-Pain-Excess exercise-Poor sleepSUBCLINICAL HYPOTHYROIDISMSubclinical hypothyroidism is more common than overt hypothyroid in elderly, especially womenSubclinical hypothyroidism (inc. TSH in the presence or normal T concentrations)Increasing evidence to suggest a predisposing factor for depression, cognitive impairment and dementiaDavis JD et al: Current Psychiatry Reports (2003)S:384-390anwar wardy wdept.neurology fk.umjNeuro-Stress & ImmunityDynamic Balance = HealthTh1 dominance = tissue/organ specific autoimmune disorders, delayed hypersensitivity reactionsTh2 dominance = allergic & atopic conditions, systemic autoimmune disordersTh3 imbalance = immunosuppression in allergies and autoimmunityanwar wardy wdept.neurology fk.umjOBESITY AND MOODSObesity is associated with an approximately 25% increase in odds of mood and anxiety disorders and an approximately 25% decrease in odds of substance use disorders. Variation across demographic groups suggests that social or cultural factors may moderate or mediate the association between obesity and mood disorder.

Arch Gen Psychiatry. 2006;63:824-830

anwar wardy wdept.neurology fk.umjManage Stress Naturally-Core Functional ApproachEating habitsDietSpecific nutrientsPlant adaptogensCognitive techniques to alter stress perceptionExercise

anwar wardy wdept.neurology fk.umjFood Improves Mood by Buffering the Stress ResponseSkipping meals, GI Dietlow blood sugarHungry brain=inc. Cortisolinc. hepatic glucagon, inc. muscle breakdowninc. sugar, inc. insulin, inc. fatsanwar wardy wdept.neurology fk.umjOmega-3 fatty Acids and Neuropsychiatric Disordersdecreased blood levels of omega-3 fatty acids have been associated with several neuropsychiatric conditions, including Attention Deficit (Hyperactivity) disorder, Alzheimers Disease, Schizophrenia and Depression

Young, G et al: Reprod Nutr Dev. 2005 Jan-Feb:454(1);1-28anwar wardy wdept.neurology fk.umjHow Adaptogenic Herbs Buffer Stress Molecules and Protect the Nervous SystemNon-toxic no change in normal physiologyHelps the body adapt to stressNormalizes body functionanwar wardy wdept.neurology fk.umjDISTURBED SLEEP & MOOD60 million Americans suffer from disturbed sleep, characterized by functional impairments during the day.Today, the widespread practice of burning the candle at both ends in western industrialized societies has created so much sleep deprivation that what is really abnormal sleep is now almost the normanwar wardy wdept.neurology fk.umjNATURAL SLEEP CYCLELight sleep: Body movement decreases. Spontaneous awakening may occur.Stage 1: dec. serotoninIntermediate sleep: Most of the night is spent in this stage. Helps refresh the body.Stage 2: dec. MelatoninDeep sleep: Difficult to arouse. Most restorative stage, lasting 30-40 minutes in first few cycles, less in later cycles.Stage 3 & 4: dec. SerotoninREM: Dreaming occurs. Heart rate increases. Lasts about 10 minutes in first cycle, 20-30 minutes in later cyclesStage 5: inc.Acetycholine, dec. GABA, dec. Dopamineanwar wardy wdept.neurology fk.umj27During a full nights sleep, you repeat the sleep cycle 4 6 times, moving from one stage of sleep to anotherREM-NREM BalanceREM=ErgotrophicOn-line, engagedExternalizedHypermetabolicCholinergic

anwar wardy wdept.neurology fk.umjNREM=RestorativeOff line, AutisticInternalizedHypometabolicSerotonergic and GABAergicNeurotransmitters Involved in SleepSerotonin-NREMAcetylcholine-REMGABA-inhibits brain arousal centers, reduces REMHistamine-stimulates brain arousal centers, wake promoting neurotransmitteranwar wardy wdept.neurology fk.umjHEALTHY SLEEP HYGIENECreate A Relaxing Bedtime Routine:Read a bookListen to musicPractice a relaxation techniqueTake a warm bathKeep the temperature in your bedroom at a comfortable level: extremes can disrupt your sleepGo to sleep and wake at the same time each day helps to develop a sleep-wake rhythm that encourages better sleepanwar wardy wdept.neurology fk.umjMELATONINReduced sleep onsetIncreased REM sleep compared to placeboEffective in children and adolescents with ADHD and insomniaImproves tinnitusImprovement in behavioral symptoms in dementia patientsCluster headachesanwar wardy wdept.neurology fk.umjMELATONINShort half life (approx 1 hour)Metabolized by P450 cytochromesPhysiologic range between 8 to 3 mgModest decrease in sleep latencyMelatonin has thermoregulatory effects that assist in its sophoric effects, reduces core body temperatureanwar wardy wdept.neurology fk.umjSTRESS & RELAXATIONEVERYTHING to do with healthWorry is the most common effectType II stress is exhausting80% serious illnesses preceded by high stress levels in previous yearAnimal research (Vernon Riley)anwar wardy wdept.neurology fk.umjBreath & Back PainPatients suffering from chronic low back pain improved significantly with breath therapy. Changes in standard low back pain measures of pain and disability were comparable to those resulting from high quality, extended physical therapy. Qualitative data suggested improved coping skills and new insight into the effect of stress on the body as a result of breath therapy.Mehling WE, et al. RCT of Breath Therapy for Patients with chronic low back pain. Altern Ther Health Med. 2005;11(4)44-52.anwar wardy wdept.neurology fk.umjJAMA 2005:294;2010-2011what we do agree on is reduction of risk factors for heart disease and diabetes through lifestyle changes first, is an appropriate treatment.anwar wardy wdept.neurology fk.umjWassalam, Maret 2015Anwar Wardy WDept.Neurology FK UMJanwar wardy wdept.neurology fk.umj