for Adolescents, forgetting fears
May pave the Way to Adulthood
“What’s too painful to remember, we simply choose to forget.” this poignant lyric
from “the Way We Were” not only offers insight into the human psyche, but ac-
cording to researchers at nyu langone Medical center, may also explain why young-
sters tend to suppress the fears of childhood as they transition from adolescence to
adulthood. “if the brain of an adolescent fails to forget a frightening situation,” ex-
plains ipe ninan, phd, assistant professor of psychiatry, “abnormal circuitry may form
and perhaps cause certain psychological disorders during teen years or later in life.”
using mouse models to gain insight into the workings of the human brain, dr.
ninan is seeking to understand how early life events may lead to mental illness in
humans, particularly anxiety, depression, and obsessive-compulsive disorder. “We
can follow mice over their lifetime,” he explains, “and systematically study the rela-
tionship between the animals’ altered behaviors and the corresponding molecular
pathways that change in the brain.”
dr. ninan and his team used electric shocks to condition healthy male mice to
fear a particular environment. When a conditioned mouse returns to the environment,
it momentarily freezes—a measure of its learned fear response. An untreated mouse,
however, readily explores the area. the researchers found that adolescent mice be-
tween 29 and 33 days old had a temporary suppression of the acquired fear memory
and did not freeze when they were returned to the threatening environment, but
younger and older mice did freeze. developmentally, mice between 29 and 49 days
old are comparable to teenagers. the brains of the adolescent mice during the sup-
pressed period differed biochemically in the amygdala, the brain’s emotional center,
and in the hippocampus, a region associated with memory of facts and events, sug-
gesting that these regions play a role in the process.
Nipping Lung Cancer in the Bud
forgetting fearful memories is beneficial, dr. ninan suggests, because it enables adolescent mice to leave the nest and explore their environment, much like
teenagers who yearn to leave home so that they can forge their own identities. dr.
ninan is now studying other regions of the brain that may be involved and the molecules that may be responsible for a loss of memory. understanding the role these
molecules play in getting adult animals to forget fears and anxiety, he explains, may
in time help researchers to develop new treatments for debilitating anxiety disorders.
dr. ninan was a senior author of the study, published in Proceedings of the National
Academy of Sciences.
despite all the advances made in diagnosing and treating cancer over the last
half-century, the overall survival rate for lung cancer—the world’s leading cancer
killer—remains 15%, virtually unchanged since 1960. that’s because about 84%
of all cases of lung cancer aren’t diagnosed until they’ve reached an advanced
stage. but when lung cancer is detected early, survival rates are dramatically
better: about 86% of early-stage lung cancer patients survive at least five years.
the question is: how can it be detected earlier?
in 2010, a landmark clinical trial found that low-dose ct scanning—an
approach originally developed by david naidich, Md, professor of radiology—can
detect lung cancer at such an early stage that patients who receive such scans are
at least 20% less likely to die than people who get chest X-rays. but, of course, it’s
not feasible to perform annual ct scans on everyone who smokes. so how do you
decide who should be scanned? investigators at nyu langone Medical center’s
lung cancer biomarker center, now in its 11th year of funding from the national
cancer institute (nci), are trying to find the answer. over the past decade, they
have screened more than 1,300 heavy smokers (as well as age-matched “control”
individuals who never smoked, since lung cancer can also develop in nonsmokers)
as part of the nci’s early detection research network.
“At least half of the smokers we screen have noncalcified nodules in their
lungs, but these nodules don’t necessarily tell us what we need to know,” says
William rom, Md, the sol and Judith bergstein professor of Medicine, professor of
environmental medicine, and director of the division of pulmonary, critical care,
and sleep Medicine. “sometimes they’re a precursor to cancer, and sometimes
they’re nothing. in careful screening of these patients over a decade, we’ve found
approximately 27 lung cancers.”
using blood samples from patients whose nodules turned out to be
cancerous and those whose nodules were benign, as well as smokers who did
not develop nodules at all, dr. rom and his team are working to develop tests for
biomarkers that could identify cases of lung cancer at their earliest stages—when
survival rates are highest. “Working with a biotech company, we’ve screened 850
proteins that might indicate lung cancer against 1,200 samples from our patients,”
explains dr. rom. “out of that group of 850, we’ve identified 40 that seemed to
be suggestive of lung cancer, and then reduced those down to 12 that were very
strong predictors of the disease.” studies are under way in collaboration with
harvey pass, Md, professor of cardiothoracic surgery and surgery, to validate
whether this set of biomarkers can accurately pinpoint patients in the very early
stages of lung cancer.
in another study, conducted with scientists at the university of
pennsylvania, dr. rom and his team found a panel of 29 genes that, together, act
as a strong predictor for lung cancer. they’ve enrolled more than 700 smokers in a
prospective study of gene expression, using that gene panel to try to predict which
lung nodules will become cancerous. “ideally,” says dr. rom, “these biomarker
tests will help us accurately determine which patients should continue to receive
regular ct scans, which ones can comfortably get less aggressive monitoring, and
which ones should undergo surgery right away.”
At Rusk, Young Stroke Survivors Learn That Just About Anything Is Possible
it’s the evening rush hour, and the Manhattan sidewalks are jammed with people
striding briskly from work. but for members of the young stroke survivors support
group, meeting inside nyu langone Medical center’s rusk institute of
rehabilitation Medicine, the world moves at a very different pace.
“how have you been?” asks dina pagnotta, Mpt, a physical
therapist. she suffered a mild stroke herself at 30, one that
thankfully caused no lasting physical damage, although its
emotional impact still resonates. pagnotta, director of the
Musculoskeletal rehabilitation network at the Medical
center, founded this support group four years ago. her
co-leader is pamela singer, Ms W, the primary social
worker for rusk’s inpatient stroke unit and traumatic
brain injury unit.
“i . . . have my . . . ups and downs,” says Ava (not
her real name). “i . . . try to be . . . positive, but my stroke
took away everything.” she starts to cry softly. “My job,
my ability to have a child, my right arm . . . and my speech. i
used to talk beautifully.” Ava’s delivery is halting—the legacy
of the stroke she suffered a year earlier. previously, she’d been
an editor. now, in her 30s, her life centers around speech and
physical therapy. “people engage me,” she adds, “but never for
long. they don’t have the patience.”
“you’ve made real improvement,” says renee gross, Ms W, a
social worker who helps run the group. “your speech flows much more
easily,” agrees ron, whose own stroke occurred a year and a half ago. turning to him,
gross asks, “how are you doing?”
“i was thinking about the dynamic where i used to
work,” says ron. “how it’s survival of the fittest.”
“have you been back to the office?” asks gross.
“once, to a holiday party,” he says. “it was fine, but
it wasn’t the same because, you know, ‘there’s ron,
he’s special now.’ ” ron was in a wheelchair then, but
today he walks with a cane.
the hour passes swiftly as the group touches
on the benefits of hyperbaric oxygen, a website
offering adaptive devices, and people who mistakenly
attribute the slowed speech of stroke survivors to
drunkenness. While strokes are devastating at any age,
younger survivors bear a unique burden. frequently in
midcareer, they’ve lost more than most and must spend a
lifetime dealing with their deficits. At the same time, notes ira
rashbaum, Md, clinical professor of rehabilitation medicine and
director of rusk’s William randolph hearst stroke rehabilitation
unit, “they have reason to be optimistic. younger brains are more
plastic and better able to heal. the recovery process is likely to be
gradual, but it can continue for many years.”
near meeting’s end, pagnotta mentions a guitarist who
suffered a stroke onstage. five years later, he’s playing again.
ron, a musician himself, saw him perform.
“he recovered?” asks Ava.
“he’s recovering,” says pagnotta. “it’s an ongoing process.
so anything is possible. As difficult as that is to imagine, it’s true.
Anything is possible.”
research & clinical spotlight
page 6 | news & views
Illustrations by Wes Bedrosian