isrers, estratig that the relatiship betweehealth a the fctiig f the stress respse sys-te is cplex
27
. I aiti, ehyrepiarstere(DHEA), which is als release i respse t stress, hasatiglccrtici effects i the brai. Higher DHEAslphate/crtisl ratis i iivials ergig rigr-s ilitary srvival traiig were assciate with lwerissciative sypts a better ilitary perfrace,pssibly iicatig higher resiliece t stress
28
. I a sty f ale veteras with PTSD, higher DHEA levels wereassciate with sypt iprveet
29
. DHEA hasaitial cetral effects i the brai, tably theGABA (γ-aibtyric aci)-ergic syste, which clals play a part i resiliece
30
.
Noradrenergic system.
Stress als leas t release f rarealie fr braiste clei, st iprtatly the lcs cerles. The reslt is icrease rare-ergic stilati f ers frebrai areas ipli-cate i etial behavir, sch as the aygala,the cles accbes, the prefrtal crtex (PFC)a the hippcaps (see belw). uchecke, chrichyper-respsiveess f the lcs cerles rare-ergic syste is assciate with axiety isrers acarivasclar prbles, a blckae f β-areergicreceptrs i the aygala ca ppse the evelpet f aversive eries i aials a has
31,32
. This sg-gests that rece respsiveess f the lcs cerlesrareergic syste cl prte resiliece.
Serotonergic and dopaminergic systems.
Serti e-rs prect wiely i the brai. Acte stress is assci-ate with icrease serti trver i several brairegis, iclig the aygala, the cles accbesa the PFC. Serti lates eral respsest stress, with bth axigeic a axilytic effects(epeig the brai regi a receptr sbtypeivlve)
3
. Serti fcti is als clsely like t reglati. Dpaie ers are activate irespse t rewar r the expectati f rewar ageerally are ihibite by aversive stili, as etailebelw. Dpaie sigallig facilitates fear exticti,bt its rle i resiliece
per se
is clear.
Neuropeptide Y (NPY).
nPY, a erpeptie that iswiely istribte i the brai, has axilytic-like effectsi rets a is thght t ehace cgiti erstressfl citis. nPY als cteracts the axi-geic effects f CRH i the aygala, the hippcaps,the hypthalas a the lcs cerles, a resilieceight ivlve aitaiig a balace betwee nPY aCRH levels
rig stress
33
. I a sty f special frcessliers, wh are csiere t be highly stress resiliet,higher nPY levels rig rigrs ilitary traiig wereassciate with better perfrace
34
. Ather sty f higher plasa nPY levels i cbat-expse vet-eras witht PTSD tha i thse with PTSD
35
. Thesefiigs i has are csistet with recet sties irats: cetral aiistrati f nPY i rats ihibits theevelpet, a prtes the exticti, f fear c-itiig, with nPY atagists exertig the ppsiteactis. These effects are eiate at least i part by theaygala
36
. mrever, itra-aygala nPY aiistra-ti prtes resiliet respses t stress, i the frf rece axiety-like behavirs i respse t acterestrait
37
.
Brain-derived neurotrophic factor (BDNF).
BDnF, aiprtat erve grwth factr that is expresse at highlevels i the brai, is best kw fr its rle, i retels, i prtig the fctiig f the alt hip-pcaps, iclig the srvival f ewly br gra-le cell ers thrght alt life. I rets, stressecreases BDnF expressi i the hippcaps, aeffect that is reverse by chric atiepressat treat-et
38
. Siilar fiigs have bee bserve i hahippcaps exaie pst-rte. Hwever, BDnFexerts very ifferet effects i ther brai regis.Chric stress icreases BDnF expressi i the retcles accbes, a this has bee like t pr-epressi-like effects i several behaviral assays
39,40
.Iterestigly, this icti f BDnF is casally relatet the egree t which rets are vlerable verss
Box 2 |
Development of resilience
eay f sss an naby
Early physical and sexual abuse is associated with long-lasting interrelated hormonal,neurotransmitter and CNS changes
20,130,131
that are likely to mediate increasedvulnerability to psychiatric disorders into adulthood.Animal studies have shown that prolonged maternal separation in early life hasenduring adverse effects on stress responsivity
20
.
rsnc o ay f sss
Studies in children adopted away from institutional orphanages in Romania illustratethe capacity of adaptive systems to resist or recover from marked disturbances whenthey are healthy and functional
4,132
.Rodent studies have demonstrated that a positive, or more enriched, environmentduring development makes animals less vulnerable to drugs of abuse and to stress laterin life
133
, and can even reverse some of the behavioural impairments that are inducedby early prolonged maternal separation
134
.
rsnc facos
During development a range of factors are potentially protective, as identified instudies of children. These include a close relationship with a caring adult, socialcompetence and agreeableness, positive emotionality and the capacity for self-regulation
135–137
. In particular, studies have shown that proximity to the caregiver is animportant modulator of a child’s sense of safety when facing trauma, as recognized inthe theory of attachment
122,123
. Rodent studies have shown that high levels of licking,grooming and arched-back nursing produce offspring that are less fearful as adults andthat show attenuated hormonal responses to stress
66
. Cross-fostering experimentshave demonstrated that these effects are transmitted behaviourally, and recentresearch has suggested an epigenetic basis for this phenomenon
(see main text)
66,138
.
It is also likely that exposure to manageable stressors during development isassociated with more adaptive coping with stress during adulthood
139
. In studies of squirrel monkeys and rodents, early exposure to manageable stressors (‘stressinoculation’) was found to be associated with reduced behavioural and hormonalresponses to stress later in life
65,140
. Adaptive responses seem to be associated with thedegree of behavioural control an animal has over stress
141
.Finally, the theory of predictive adaptive responses posits that early life experiencecan programme a certain set of responses that may be adaptive given a particular earlyenvironment, but that may prove maladaptive later on if there is a mismatch betweenthis set of responses and the environment in adulthood
142
. In a recent rodent study, theadult offspring of low- as opposed to high-licking and grooming mothers demonstratedgreater experience-dependent structural plasticity and learning under some contexts,but lesser structural and behavioural plasticity in other contexts
143
.
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