Early life adversity, allostasis, and resilence

Paul Plot­sky, PhD, Glax­o­SmithK­line Pro­fes­sor, Depart­ment of Psy­chi­a­try and Behav­ioral Sci­ences, Emory Uni­ver­sity   Web­site |  Pub­li­ca­tions

Abstract: Early life adver­sity (e.g., mal­treat­ment, neglect, divorce, poverty, chronic ill­ness, etc), whether in rodents, non-human pri­mates, or humans, fre­quently impacts devel­op­ment and func­tion of mul­ti­ple sys­tems across the life span. The sever­ity and direc­tion (i.e., neg­a­tive or pos­i­tive) of these effects is sen­si­tive to numer­ous fac­tors encom­pass­ing gen­der, devel­op­men­tal age, sen­si­tive peri­ods, gene poly­mor­phisms, level of social sup­port, and social con­text. Respond­ing to these insults acti­vates allo­sta­tic processes by which the organ­ism actively attempts to rereg­u­late key phys­i­o­log­i­cal sys­tems to main­tain sta­ble func­tion­ing within a bio­log­i­cally appro­pri­ate dynamic range. In humans, early life adver­sity ini­ti­ates the fol­low­ing cas­cade: (1) increases the phys­i­o­log­i­cal reac­tion to stress; (2) increases the degree to which one per­ceives events as stress­ful in ambigu­ous sit­u­a­tions; (3) poorer stress cop­ing skills due to reduced emo­tional con­trol and worse social skills. The cumu­la­tive cost, or allo­sta­tic load, of this process may lead to seri­ous patho­phys­i­ol­ogy. Depend­ing upon envi­ron­men­tal and other fac­tors, the end result can extend from changes in regional gene methy­la­tion, struc­tural changes in the brain, increased vul­ner­a­bil­ity to sym­pa­thetic ner­vous sys­tem and hypothalamic-pituitary-adrenal axis (HPA) hyper-reactivity, immune sys­tem dys­func­tion, meta­bolic and car­dio­vas­cu­lar dis­eases, learn­ing and mem­ory deficits, to psy­chi­atric dis­ease. Alter­na­tively, in the pres­ence of cer­tain gene poly­mor­phisms that increase sen­si­tiv­ity to the envi­ron­ment and solid social sup­port, early life adver­sity gives rise to an appar­ent resilience. While researchers have yet to estab­lish why and how early adver­sity has such pro­found and long-lasting effects, any model attempt­ing to pre­dict and explain these obser­va­tions must encom­pass mol­e­c­u­lar, bio­log­i­cal, and social-cultural factors.

Bio: Paul M. Plot­sky is Direc­tor of the Stress Neu­ro­bi­ol­ogy Lab­o­ra­tory and is the GSK Pro­fes­sor of Psy­chi­a­try.  His research is focused on the inter­ac­tion between genes and the peri­na­tal envi­ron­ment in shap­ing the devel­op­ing ner­vous sys­tem. Using rodent and non­hu­man pri­mate mod­els in col­lab­o­ra­tion with clin­i­cal researchers, he has devel­oped ani­mal mod­els of vul­ner­a­bil­ity to a vari­ety of psy­chi­atric and med­ical dis­eases. Exten­sive char­ac­ter­i­za­tion of these mod­els rang­ing from behav­ioral assess­ments to gene expres­sion and epi­ge­netic pro­fil­ing, as well as neu­ro­mor­phol­ogy have revealed fun­da­men­tal changes in neu­ro­cir­cuits under­ly­ing per­cep­tion and pro­cess­ing of envi­ron­men­tal stim­uli as well as the respon­sive­ness to these events. These mod­els per­mit a detailed analy­sis of behav­ioral, neu­roen­docrine, cog­ni­tive, struc­tural, neu­ro­chem­i­cal, and mol­e­c­u­lar changes asso­ci­ated with these vul­ner­a­ble states and pro­vide avenues for devel­op­ment of new ther­a­peu­tic inter­ven­tions.  Dr. Plot­sky holds adjunct appoint­ments in the Dept. of Psy­chol­ogy and at the Yerkes National Pri­mate Research Cen­ter. He is also on the fac­ulty of the Grad­u­ate Pro­gram in Neu­ro­science and the under­grad­u­ate Neu­ro­bi­ol­ogy and Behav­ior Program.