Stresul: Perspective interdisciplinare - partea a 2-a -

MPS 2012

Clarificri...
Stimularea eliberrii de ACTH hipofizar i cortizol corticosuprarenalian prin administrarea de CRF sau dexametazon (GC sintetic): REACTIVITATEA ADENOHIPOFIZEI LA CRF i REGLAREA AXEI HPA Stres psihosocial (de ex., TSST): rspuns care presupune procesare cognitiv i emoional i IMPLIC STRUCTURI SUPRAHIPOTALAMICE I MAI MULI NEUROTRANSMITORI
VERSUS

Axa HPA n depresie

Cortizolul plasmatic este mai mare (Board et al., 1956) Nivel mare de CRF n LCR (Nemeroff et al., 1984), dar necorelate cu severitatea simptomelor Se corecteaz la 24h dup o serie de ECT (Nemeroff et al., 1991) sau tratament cu fluoxetin (De Bellis et al., 1993) Lipsa normalizrii cortizolului n LCR prezice recderea Hipertrofie hipofizar i suprarenal (Krishnan et al., 1991)

Arborelius et al., 1999

Axa HPA n depresie

Administrare de CRF: eliberare redus de ACTH, dar sintez i secreie de cortizol normale prima se corecteaz dup recuperarea pacientului Testul de supresie cu dexametazon: supresia ACTH i cortizolului este mai mic sau mai scurt (engl., escape from suppression/non-suppression) Tipar: DMX: cort = CRF: ACTH Mecanism: hipersecreie de CRF (!!! extrahipotalamic: hipocamp, cortex cerebral, amigdal) care reduce receptorii pentru CRF (CRF1) n hipofiz Cortizol normal la TSST (Young et al., 2000)

Charles Nemeroff

TTST n depresie + anxietate

Young et al., 2004

TTST n depresie + anxietate

Young et al., 2004

The elevated ACTH response to challenge seems to be associated with the interactive presence of both depression and an anxiety disorder, and not merely with the presence of specific symptoms

Axa HPA n anxietate

Cortizol redus i supersupresie a cortizolului la testul cu dexametazon (Yehuda, 2002) CRF n LCR este crescut n PTSD (veterani din Vietnam) (Nemeroff et al., 1997) Acelai mecanism ca la depresie: hipersecreie extrahipotalamic de CRF (de ex., hipocamp) Volum hipocampic mai redus n PTSD (Bremner et al., 1995)
Rachel Yehuda

Axa HPA n anxietate

Atacuri de panic fr hipersecreie de cortizol, n studiu de laborator (Abelson et al., 2005), dar nu i n mediul natural (Bandelow et al., 2000) Hipersecreie de ACTH? Din cauza hipersensibilitii la context (laborator): rspund la fel i la placebo, dispare efectul dac faci debriefing sau i lai s se habitueze cu intervenia HPA abnormalities n panic are due to dysregulation in suprahypothalamic circuits and may involve a specific hypersensitivity to novelty cues (Abelson et al., 2007) Medial prefrontal cortex is a strong candidate for inclusion in such a modulatory circuit, since it is known to process emotional salience and to provide inhibitory input to the HPA axis (idem)

Bandelow et al., 2000

However, elevations were already present in the first sample taken, immediately after attack onset, and may have been present even beforehand. In this naturalistic model, a cortisol response may not have beenseen if levels during the attack were compared to those immediately before, as is done in laboratory model. In the laboratory models, elevations would likely also be seen if the baseline used was cortisol measured 24 hours later at home. (Abelson et al., 2007)

Perspective
Thus, the clinical data provide some evidence for a role of central CRF neuronal system in anxiety disorders but not to the extent observed in depression. (Arborelius et al., 1999) These data suggest that depression is more robustly linked to HPA axis dysregulation than is anxiety and dominates the neuroendocrine picture when the disorders are comorbid. (Young, Abelson, & Cameron, 2004)

Dezvoltarea axei HPA

Nou-nscui: creteri de cortizol i ACTH la examinri medicale sau vaccinuri Pn la un an, scad aceste rspunsuri, chiar dac semnele de distres comportamental rmn Stress hyporesponsive period ine pn n perioada precolar DAC li se ofer un mediu securizant n condiii de stres (de ex., prini, educatoare) Copiii mici (engl., toddler) cu o istorie de neglijare/abuz, prezint creteri de cortizol n condiii de stres i tipar conflictual de comportamente de abordare i evitare fa de figura de ataament De ex.: copii crescui n orfelinate din Europa de est, n perioada comunist, afieaz niveluri de cortizol reduse diminea, far modificri pe parcursul zilei Dezvoltare tipic: nivelul de cortizol, mai ales cel de diminea, crete n copilrie i adolescen, n legtur cu pubertatea E posibil ca funcia HPA s fie influenat social pn la pubertate Pubertatea semnalizeaz sfritul perioadei de hiporeactivitate la stres i maturarea complet a ritmului circadian

(Tarullo & Gunnar, 2006)

Abuz n copilrie i HPA

La injectare de CRF, femeile cu istorie de abuz n copilrie, dar fr depresie au hiperreactivitatea ACTH La cele cu abuz, dar i cu depresie, reactivitatea este redus, ca la cele cu depresie fr istoric de abuz Heim et al., 2001

Abuz n copilrie i HPA (cont.)

TSST la persoane abuzate emoional nainte de 15 ani: eliberare de cortizol redus, ceea ce predispune la tulburri de externalizare i tendine impulsive, iniiere mai timpurie a ctivitii sexuale, abuz de substane We have argued elsewhere that stress responses should be viewed as aving a normative range and that deviations from the norm in either direction might signal a systems dysregulation with potential health consequences. (Lovallo et al., 2012)

Lovallo et al., 2012

Anxietate matern, HPA i depresia la progenituri

Anxietatea matern la 12-22 sptmni de sarcin sunt asociate cu alterarea secreiei circadiene de cortizol la progenituri de 14-15 ani (niveluri mai mici dimineaa i mai mari dup-amiaz) Doar la progenituri femei: profilul circardian aplatizat al cortizolului mediaz efectul anxietii materne la 12-22 spc asupra depresiei

Van den Bergh et al., 2008