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PSYC 342
Jens C Pruessner

Lecture 11Feb 16The HPA axisHypothal mediate nervous information with endocrine informationoThe median eminence is located next to the hypothalamusone of the 3 entries from the periphery to the CNS no blood brain barrieroHPA HPG HPTNote pituitary is not part of the brain hormones would have to exit via the median eminenceProcessoAnterior pituitary release ACTH binds to membrane receptoroAdrenal gland synthesis andsecretion of glucocorticoid Glucocorticoids increases glucose metabolism glucocorticoid glucosecortexsteroidGoes directly into cellFunctions oIncrease neoglucogenesisoActs on insulin to maintain glucose in the blood vesselsoEffects on brain and cognitive functionsoAffects the immune systemoPrevent overshoot of other systemsThermoregulation HPA activated when immune system goes into overdrive in trying to ght off infections with a high feveroHPA axis needs to be tightly regulated as it prevents overshoot of other systemsFunctional tests for the HPA axisCRH injection test for pituitary and adrenal responseACTH injectionDexamethasone agonist of glucocorticoid receptortest for extent of negative feedback on the pituitary and the adrenaloMuch more potent in activating the receptorsoBinds to pituitary and have huge negative feedback on pituitaryoDoes not cross blood brain barrier no effect on CRH secretion DEXCRH injection oPurpose to send mix signal to the body to test how robust the regulatory system isoIf DEX receptors are good and present pituitary will stop secreting ACTH momentarily due tohuge negative feedbackeven when CRH given after DEX you still should not see any cortisol releaseoIf cortisol release is seen then there must be a problem with the GR glucocorticoid receptorsBaseline testing Testing integrity of HPA axis oCAR cortisol awakening response peaks 30min after you wake upoWhen exposed to chronic stress there can be variation in the circadian rhythmoCAR levels are used in conjunction with stressor test to show the baseline reactivity of the HPA axis some people have naturally lower cortisol response in generalStress testoEcological valid way to access HPA axisoReference paradigm for stress test DSSTgiving speech in front of peoplea cortisol increase should be seen after In front of people who are very critical 5min to prepare for 5min speechMental calculation for 5min with people constantly telling you that youve got it wrongoSocial stress oOther physical stress tests eg bike for an hourTopic for today applying stress tests to better access relation of HPA axis to certain psychopathologiesIssues difcult to establish relation between the pathologies on the HPA axis It would be tempting to induce a causal effect eg high stress response in depressed population so because they are more stressed they are depressedits just an association correlation and not causationPsychopathologies with dysregulation of the HPA axisMajor depressionChildhood abusePosttraumatic stress disorderGlucocorticoid cascade hypothesisMAJOR DEPRESSIONSymptoms both psychological and physiological Insomnia oversleepAnhedoniaLack of energyRuminative thoughtsBrain correlates of depressionEvidences from both human and animals eg rat modelsModel of depression in animalsUnpredictable chronic mild stress over 36 weeksapproach symptoms seen in humanseg anhedonia no longer drink sugar waterNeuroimaging evidencesDifference in brain structures between healthy controls and depressed patientsRegion involved in stress regulationPrefrontal cortexHippocampus amygdalaThalamusHypothalamus and pituitaryPregenus ACC arcuate cingulate cortexhighly associated with depressionMore activated in depressed patients when given an affective taskDepression and CRH overdriveBoosting the HPA axis induces anxiety related activatesDecreased eating sleeping reproductive activitiesIncreased restless activity in familiar envt withdrawal in unfamiliar envtDepressed patients have overdrive of CRH in the cerebral spinal uidWhen they recover from depression CRH levels goes back to normalThere seem to be a link of causation but still ambiguousRole of the amygdala Fear and stress regulationMore activation in depressed populationCHILDHOOD ABUSEEffects of childhood abuse on brains of depressive patientsResearcher from McGilleffects of varying maternal behaviour over the development of the stress systemOrganizational effect Different maternal rat behaviour has inuence over the organizational events in the HPA axis When rats mature they have differing responses to stress Study 1 by Christine Helm in WomenDysregulation of HPA activity in depressed patients is it due to depression or is it early life trauma
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