Over­com­ing Fear: Tough for Teens

Study shows fear is hard to ex­tin­guish from the de­vel­op­ing teenage brain, which may ex­plain why anx­i­ety and de­pres­sion spikes dur­ing ado­les­cence

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As­tudy by Weill Cor­nell Med­i­cal Col­lege re­searchers shows that ado­les­cents’ re­ac­tions to threat re­main high even when the dan­ger is no longer present. Ac­cord­ing to re­searchers, once a teenager’s brain is trig­gered by a threat, the abil­ity to sup­press an emo­tional re­sponse to the threat is di­min­ished which may ex­plain the peak in anx­i­ety and stress-re­lated dis­or­ders dur­ing this de­vel­op­men­tal pe­riod. The study, pub­lished Sept. 17, 2012 in the early online edi­tion of the Pro­ceed­ings of the Na­tional Academy of Sciences (PNAS), is the first to de­code fear ac­qui­si­tion and fear “ex­tinc­tion learn­ing,” down to the synap­tic level in the brains of mice, which mir­ror hu­man neu­ronal net­works. Also, through hu­man and ro­dent ex­per­i­ments, the study finds that ac­quired fear can be dif­fi­cult to ex­tin­guish in some ado­les­cents. By con­trast, the study shows that adults and chil­dren do not have the same trou­ble learn­ing when a threat is no longer present.

“This is the first study to show, in an ex­per­i­ment, that adolescent hu­mans have di­min­ished fear ex­tinc­tion learn­ing,” says the study’s lead au­thor, Dr. Siob­han S. Pat­twell, a post­doc­toral fel­low at the Sack­ler In­sti­tute

for De­vel­op­men­tal Psy­chobi­ol­ogy at Weill Cor­nell. “Our find­ings are im­por­tant be­cause they might ex­plain why epi­demi­ol­o­gists have found that anx­i­ety dis­or­ders seem to spike dur­ing ado­les­cence or just be­fore ado­les­cence. It is es­ti­mated that over 75 per­cent of adults with fear-re­lated dis­or­ders can trace the roots of their anx­i­ety to ear­lier ages.” The study find­ings sug­gest there is al­tered plas­tic­ity in the pre­frontal cor­tex of the brain dur­ing ado­les­cence, with its in­abil­ity to over­come fear, says the study’s se­nior coin­ves­ti­ga­tor, Dr. Fran­cis Lee, pro­fes­sor of phar­ma­col­ogy and psy­chi­a­try at Weill Cor­nell Med­i­cal Col­lege, and an at­tend­ing psy­chi­a­trist at NewYork-Pres­by­te­rian Hos­pi­tal/ Weill Cor­nell Med­i­cal Center. “This study is the first to show ac­tiv­ity, at the synap­tic level, for both fear ac­qui­si­tion and fear ex­tinc­tion — and we find that while th­ese ar­eas func­tion well in both younger and older mice, neu­rons in­volved in fear ex­tinc­tion are not as ac­tive in adolescent mice,”

says Dr. Lee. “If ado­les­cents have a more dif­fi­cult time learn­ing that some­thing that once fright­ened them is no longer a dan­ger, then it is clear that the stan­dard de­sen­si­ti­za­tion tech­niques from fear may not work on them. This new knowl­edge about the teenage brain’s synap­tic con­nec­tions not re­spond­ing op­ti­mally will help clin­i­cians un­der­stand that the brain re­gion used in fear ex­tinc­tion may not be as ef­fi­cient dur­ing this sen­si­tive de­vel­op­men­tal pe­riod in ado­les­cents.”

ADOLESCENT MICE NEVER LOSE THEIR FEAR RE­SPONSE

Fear learn­ing is a highly-adap­tive, evo­lu­tion­ar­ily con­served process that al­lows one to re­spond ap­pro­pri­ately to cues as­so­ci­ated with dan­ger. In the case of psy­chi­atric dis­or­ders, how­ever, fear may per­sist long af­ter a threat has passed, and this un­remit­ting and of­ten de­bil­i­tat­ing form of fear is a core com­po­nent of many anx­i­ety dis­or­ders, in­clud­ing post­trau­matic stress dis­or­ders (PTSD). Ex­ist­ing treat­ments, such as ex­po­sure ther­apy, are de­signed to ex­pose an in­di­vid­ual slowly to the cues as­so­ci­ated with a per­ceived threat. This tech­nique is used for a va­ri­ety of fears, from war­time PTSD to fear of fly­ing, as well as se­ri­ous adolescent anx­i­ety about school, says Dr. Lee, who treats, among oth­ers, pa­tients with PTSD ac­quired dur­ing the World Trade Center col­lapse on Septem­ber 11, 2001.

Anx­i­ety dis­or­ders are in­creas­ingly be­ing di­ag­nosed in chil­dren and ado­les­cents, but the suc­cess rate of fear ex­tinc­tion-based ex­po­sure ther­a­pies are cur­rently not known in this pop­u­la­tion. This study aimed to dis­cover if they could be ef­fec­tive — and why or why not. The hu­man ex­per­i­ment was con­ducted at the Sack­ler In­sti­tute for De­vel­op­men­tal Psy­chobi­ol­ogy at Weill Cor­nell in col­lab­o­ra­tion with its di­rec­tor, Dr. B.J. Casey, a study se­nior co-in­ves­ti­ga­tor, who is the Sack­ler Pro­fes­sor of De­vel­op­men­tal Psy­chobi­ol­ogy and pro­fes­sor of psy­chol­ogy in psy­chi­a­try at Weill Cor­nell. In the ex­per­i­ment, a group of vol­un­teers — chil­dren, ado­les­cents and adults — wore head­phones and skin sweat me­ters and were asked to look at a com­puter screen with a se­quence of blue or yel­low square im­ages. One of the squares was paired with a re­ally un­pleas­ant sound. For ex­am­ple, 50 per­cent of the time the blue square would set off the noise. If the par­tic­i­pants ac­quired a fear of the noise, they showed in­creased sweat when view­ing the im­age that was paired with it, says Dr. Pat­twell. The same group was brought back the next day, and again viewed a se­quence of blue or yel­low squares, but this time there was no as­so­ci­ated noise. “But teenagers didn’t de­crease their fear re­sponse, and main­tained their fear through­out sub­se­quent tri­als when no noise was played,” she says. How­ever, the re­searchers doc­u­mented that, un­like the teens par­tic­i­pat­ing in this study aged 12-17, both chil­dren and adults quickly learned that nei­ther square was linked to a nox­ious sound, and this un­der­stand­ing rapidly de­creased their fear re­sponse. The mouse ex­per­i­ment, which used stan­dard fear con­di­tion­ing com­mon in th­ese types of an­i­mal stud­ies, ob­tained sim­i­lar find­ings. Adolescent mice (29 days old) did not de­crease their fear re­sponse to stim­uli that no longer ex­isted, but younger and older mice did. In­ter­est­ingly, the adolescent mice never lost their fear re­sponse as they aged. The re­search team then mon­i­tored the brains of mice as they par­tic­i­pated in the ex­per­i­ment. With the as­sis­tance of study se­nior co-in­ves­ti­ga­tor, Dr. Ipe Ni­nan, an elec­tro­phys­i­ol­o­gist at NYU Lan­gone Med­i­cal Center who is an as­sis­tant pro­fes­sor of psy­chi­a­try, the re­search team found that the pre­lim­bic re­gion in the pre­frontal cor­tex, the brain re­gion that pro­cesses emo­tion, is ac­ti­vated dur­ing ac­qui­si­tion of fear, and the in­fral­im­bic pre­frontal cor­tex is used to ex­tin­guish this fear as­so­ci­a­tion. While other groups have sug­gested that the pre­frontal cor­tex plays a role in ex­tinc­tion, no one has shown that this ac­tiv­ity is at the level of the sy­napse — the con­nec­tions be­tween the neu­rons. “In young and old mice, we see plas­tic­ity, which is ac­tiv­ity in the in­fral­im­bic cor­tex, which helps the an­i­mals de­crease their fear re­sponse when a threat no longer ap­plies,” says Dr. Pat­twell. “In­ter­est­ingly, we didn’t wit­ness sim­i­lar ac­tiv­ity in adolescent mice.” Ac­cord­ing to re­searchers there is much more to ex­plore about the fear re­sponse and its decoding in hu­man ado­les­cents, such as whether genes con­trib­ute to sus­cep­ti­bil­ity to al­tered fear learn­ing, and most im­por­tantly, what can be done to help the adolescent pop­u­la­tion over­come fear. “We need to in­ves­ti­gate per­son­al­ized ap­proaches to treat­ment of th­ese fear and anx­i­ety dis­or­ders in teens,” says Dr. Lee. “It is es­sen­tial that we find a way to help teenagers be­come more re­silient to the fear they ex­pe­ri­ence dur­ing ado­les­cence to pre­vent it from lead­ing to a life­time of anx­i­ety and de­pres­sion.”

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