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Hopkins
THE NEWSLETTER
SPRING 2013
O F T H E J O H N S H O P K I N S D E PA RT M E N T O F P S Y C H I AT RY A N D B E H AV I O R A L S C I E N C E S
?
“Because psychiatrists
examine mental life,
we’re often more
quickly able to detect
delirium,” says Karin
Neufeld, who’s also
president-elect of
the American
Delirium Society.
A humbling
experience
John Crowder,* 77,
a retired architect,
was his bright, goodnatured self, even
entering a Pennsylvania
hospital for an hour’s
back surgery under
standard general anesthesia. He did well
in recovery and was
wheeled to his hospital
room, dozing until
morning. Then things
unraveled. Crowder
didn’t know where
he was. He told his
wife to feed the rabbit
in the room. He was
anxious, convinced his
roommate was a terrorist. Later transferred
to inpatient rehab,
Crowder remained
confused for several
weeks. Once home
again, he refused to
walk. He was uncharacteristically unfocused
and glum for the six
months it took to
resemble his presurgery
self. He calls the experience “one of the most
humbling of my life.”
From a recent Psychiatry
Grand Rounds
* name and details changed
for privacy.
Demystifying Delirium
R
“
oughly 40 percent of inpatients
at major medical centers will be
delirious at some point in their
stay,” Karin Neufeld told a recent
gathering of fellow Johns Hopkins
psychiatry faculty. “If they’re on ventilators in the ICU, that can jump to 85
percent.”
Delirium is a hospital bane, an unwelcome visitor calling reliably on the very
ill or frail. And it can harm. In adults,
the syndrome is tied to higher mortality and longer time in the hospital (see
box, left). Yet common and damaging as
it can sometimes be, “delirium remains
under-recognized and understudied,”
Neufeld says.
So she and colleagues are among a
band of nationwide movers and shakers
bent on correcting that.
Neufeld, who directs general hospital psychiatry, visits bedsides of three
medical or psychiatric patients a day, on
average, to assess suspected delirium and
consult on therapy. That puts her well
in position to see where the clinical gaps
lie. It’s not uncommon in hospitals, for
example, for staff to overlook “quiet”
or hypoactive delirium or mistake it for
depression, she says, or to find agitated
delirium simply called psychosis.
Neufeld’s most recent work sheds
light on the condition’s nature and its
impact. In a new study, researchers followed about 100 fairly robust patients
over age 70 undergoing hip surgery,
assessing them before it, just afterward
and at hospital discharge. Two results
stood out. One was in the recovery
room, where staff typically don’t look
for delirium, since—the thinking
goes—general anesthesia makes everyone
unfocused and disoriented. But the study
showed that nearly half of patients had
frank, DSM-matching delirium. It faded
quickly in some, but lasted three days in
an equal number later moved to hospital
beds.
The other result confirms others’
findings: Delirium increases the burden
of frailty in older people. “Our elders
who were delirious in recovery,” she says,
“were nine times as likely to go to rehab
or a nursing home.”
What’s the culprit in all this? Is it
length of surgery? Anesthesia? Surgical
sedatives? “Our work suggests the depth
of sedation plays a part, but that needs
more study,” says Neufeld. “We have a
lot to learn.” n
For information: 410-502-1169
A Different
Delirium
“I wanted to see how we stand, clinically, at spotting delirium in children,”
says child psychiatrist Patrick Kelly.
“And the answer is, really bad.”
While the necessity of treating delirium in adults is catching on
(story, left), that hasn’t yet hit home
in pediatrics nationwide, Kelly says.
As in adults, there are problems
of recognition. “We’ll get hospital
calls to evaluate kids who suddenly
become atypically anxious or aggressive,” he says. It’s fairly easy to spot
a child in the PICU who says—this
is an actual case—there’s a purple
watermelon on my bed. But he and
colleague Emily Frosh note that
usually, the phenomenon is more
subtle in kids than adults.
“They come across as quiet and
cute, when, in fact, they have no idea
what’s going on around them. The
delirium is missed entirely,” says Kelly.
So he and Frosh began documenting suspected instances when delirium
was missed. A just-published study
describes their review of records
of 515 children referred, over eight
years, for inpatient psychiatric consultation in The Johns Hopkins Hospital.
Attention was paid to records with a
diagnosis of delirium—or something
close to it. Also, the two sifted computerized pediatric discharge records
of roughly 64,000 kids during the
same period.
The results? Pediatricians listed
delirium only a tiny fraction of the
time as a reason for sending children
for a consult. And for the thousands
of kids who’d passed through the hospital apparently without needing any
such evaluation, the records say that
only 0.1 percent of them had spent
some time delirious. “We know that’s
way out of line,” says Kelly.
What accounts most for the dramatic shortfall, he believes, “is not
realizing how serious delirium is.”
Not infrequently, it carries lingering
cognitive effects and more serious
implications for overall health. It isn’t
a benign process “that just happens
and is done with,” Kelly says.
“What hospitals need
most right now is
consciousnessraising.” n
For information:
410-955-7874
FROM THE LAB
Stress: Can It
Bring More Than
Teen Angst?
T
here’s a reason that Minae Niwa and
Hanna Jaaro-Peled picked mice age 5 to 8
weeks old for their recent study: The rodents
are teenagers. It’s a tender age for mice or humans
and one increasingly eyed by researchers as key to
pathology that schizophrenia, major depression and
bipolar disorder likely have in common.
Recently, a mouse study by Niwa and JaaroPeled’s team, under mentor Akira Sawa, modeled
current thought on triggers of those illnesses—mostly young adult-onset neuropsychiatric disorders. The
results offer a way that stress, at a certain age and
vulnerability, may trip major psychiatric disease.
A body of science confirms that teenage mice and
humans respond similarly to stress. The HPA axis,
the brain’s key stress pathway, goes into overdrive,
releasing cortisol. And at puberty, some studies say,
that hormone’s effect in man and mouse appears
more potent; brains stay longer in “red alert” mode
after each stressor du jour has faded.
Still other research suggests some link between
cortisol and brain levels of dopamine, a neurotransmitter active in cognition, learning, mood and
reward. Dopamine goes awry in schizophrenia, bipolar disorder and depression.
But how, asked the Johns Hopkins group, to tie
the threads together?
Niwa and Jaaro-Peled’s new study simulated
the proposed human risks for illness: Test mice
(and controls) were teenagers. The mice also had
moderate gene-based chances for a troubled brain:
They carried a mutation from a human family
with depression tinged with psychosis. Finally, test
mice in the study lived three weeks on their own,
a situation exposing each animal to stress roughly
as intense, say, as what teens face the first days of
For neuroscientists Hanna Jaaro-Peled and Minae Niwa, finely tailoring mouse models of psychiatric disease helps
show how small shifts in brain chemistry change the very circuits that oversee thinking and behavior.
high school—a “suboptimal” stressor, says Sawa.
The results were telling. Carrying the abnormal
gene had little effect on the mice unless they were
also stressed. Then they became more readily hyperactive or displayed other behaviors that signal brain
disorder.
On a biological level, there was more. The
stress-plus mutation mice showed high cortisol
levels and a significant drop in dopamine. Was
cortisol at work in the drop? An added experimental step said yes. Injecting mice with an agent that
blocks cortisol activity righted dopamine levels. It
also corrected mouse behavior.
The “take-home” from this, Sawa says, “seems
to be that during adolescence, if there’s adequate
genetic risk, stress can change biology and behavior
in ways that we associate with neuropsychiatric
disease.”
Perhaps more important in the long run were
results that suggest therapy targets. The team
found that cortisol affects key, dopamine-rich
nerve paths between the midbrain and the prefrontal cortex. The “ventral tegmental area” is a
vulnerable brain tract that rules concentration, for
example, and other things cognitive that neuropsychiatric disease harms.
The second find suggests that cortisol’s effect at
puberty may last. Mice returned to group life still
behaved abnormally months later. The underlying
biology suggests why: High cortisol clamps epigenetic “governors” on key dopamine genes.
“This study made me think prevention. It’s
certainly not foolish to be more vigilant with our
teenagers who are genetically vulnerable to psychiatric disorders,” says Sawa. “My gut feeling is that
environmental stressors—social ones especially—are
more important than the genetic in letting mental
illness appear.” n
For information: 410-955-4726
CLINICAL RESEARCH
Seeking a Stimulating Solution for Alzheimer’s
T
his past November, Johns
Hopkins surgeons eased a fine
electrode into the brain of a
patient in early-stage Alzheimer’s disease, down to the fornix, a site hard-hit
by the illness.
Far from being routine therapy, the
operation was the first in this country to
explore deep brain stimulation (DBS)
for Alzheimer’s. Its outcome shores up
work to see if the technique might stop
or slow patients’ decline into dementia.
This new trial follows a preliminary
study in Toronto, Canada, in which
surgeons implanted the stimulating
devices in six AD patients. Researchers
then found that under the pulsed
mild current that DBS creates, those
in the study—all in early stages of the
disorder—showed increases in glucose
metabolism that mark heightened
activity in known memory circuits.
The effect lasted over the 13-month test
period. Most patients with AD would
normally see decreases in that length
of time.
“Recent failures of the large trials
of drugs that target beta-amyloid
plaques, a prime AD suspect in the
brain, have sharpened our need for
alternative strategies,” says psychiatrist
Paul Rosenberg, site director of
the new work at Johns Hopkins.
“Trying to enhance brain function
by mechanical means is a whole new
avenue to explore.”
Patients undergoing DBS carry a
pacemaker-like stimulator implanted
just under the skin. An electrode
extends from it, painlessly, to the brain.
The arrangement isn’t new: DBS is
well-established for Parkinson’s disease.
And it’s under study for depression and
chronic pain.
In this newest work, some 40
Alzheimer’s patients will receive DBS
over the next year or so at Hopkins and
four other North American medical
centers—all part of the ADvance Study
co-led by Johns Hopkins psychiatrist
Constantine Lyketsos and neurologist Andres Lozano at the University
of Toronto. Only those impaired
mildly enough to still be able to make
informed decisions can participate. n
For information: 410-550-4258
INSIGHT: Q & A with ROBERT FINDLING
Pediatric Bipolar Disorders: Seeking the Right Child, the Right Time
“You’ve got this vague, fuzzy thing
behind an opaque screen. How do you
figure out what to do with it?” That’s
child psychiatrist Robert Findling’s
take on what clinicians face in pediatric
bipolar disorders.
As new director of Child and Adolescent Psychiatry, Findling brings
broad expertise on those illnesses and
others to Johns Hopkins. His Clinical
Manual of Child and Adolescent Psychopharmacology is in its second edition.
Cognitive-Behavior Therapy for Children
and Adolescents—he’s a co-author—is
just out. He’s published on pediatric
psychotic disorders and juvenile schizophrenia.
But Findling’s prime area is pediatric bipolar illness, a condition whose
unspecific symptoms hamper diagnosis,
especially in young children. That alone
encourages controversy—sometimes
from clinicians, but more from a public
a bit too ready to blame symptoms on
bad parenting or kids being kids. “There’s
been too much heat, not enough light,”
Findling says. So he takes refuge in
sound research.
For the past seven years, he has coheaded the Longitudinal Assessment of
Manic Symptoms (LAMS), a NIMHfunded study that’s followed some 700
children whose elevated irritability,
sudden mood changes and periods of
more than kid-typical giddiness suggest
bipolarity. The research—Findling now
directs it from Johns Hopkins—aims to
sort out what the symptoms mean. Do
they mark a distinct childhood illness?
Who comes out OK?
symptoms. So we follow the children
and, ideally, the study clarifies the disorder, tells us who has it—and where it’s
going—and who doesn’t.
We also have the youngsters undergo
neuroimaging and cognitive testing,
seeing if biological measures help us
improve diagnosis. Are there clear differences in brain structure? In processing of
information?
Where are you headed?
Here’s what he says:
We know you were set on becoming a neurosurgeon until a child
psych rotation in med school
turned that around, but what
sparked your pediatric bipolar
interest?
Early on, a colleague in Cleveland with
adult patients with bipolar disorder
didn’t know where to turn to help their
troubled children—some as young as 6
or 7. The patients would say: I’m terrified for my son. How can I keep him from
suffering as I have? So the youngsters
came to my office. With their cluster
of symptoms—often compounded by
ADHD or oppositional defiance disorder—they didn’t look quite like kids I’d
seen in training.
You quickly saw a pressing need
both for the LAMS study and a different approach, yes?
Correct. Most studies of pediatric bipolar start with the adult disease in mind.
Then they look at symptoms in children
to see whether they match that better
than other childhood disorders.
Sort of like trying on Cinderella’s
glass slipper?
Yes. But that can wrongly presume that
the “bipolaresque” kids are the only ones
who suffer from bipolar disorder. Perhaps worse, it assumes that youth who
are “bipolaresque” indeed have bipolar
illness and are likely to suffer from it as
adults. And we now know that many do
not. LAMS, however, started without
presumptions, with only this cluster of
SUPPORTING THE CAUSE
A Double Dose of Help
W
hen Charles Ellzey worked some
30 years as a ship’s engineer for the
Alcoa and then the Central Gulf
Steamship Lines, Johns Hopkins never crossed
his path. It wasn’t until the sister of his wife
Helen showed signs of dementia that Ellzey
found himself in East Baltimore regularly in
1983, “for diagnosis and whatever help Hopkins
could give us.”
Of course, no cure exists for Alzheimer’s
disease (AD). “But,” says Ellzey, “the moral support alone that we got during the hard job of
caring for my wife’s sister made us feel that we
weren’t out in the forest by ourselves.” During
one later visit, a grateful Ellzey asked how he
might help the cause. It wasn’t long before he’d
signed on as a healthy control in a long-term
study, the Alzheimer’s Disease Research Center’s
Longitudinal Evaluation.
Over the next 30 years, this helpful, “resilient man” as the study’s director, Constantine
Lyketsos, dubs him, has come to Johns Hopkins
annually for a battery of tests—part of the
research. Those at risk of AD are followed to
shed light on the illness’s course and biology.
And controls like Ellzey allow crucial comparisons with normal aging. “I always get a kick out
of coming,” he says.
But Ellzey didn’t stop there. When Helen
passed away in 2007, a generous bequest soon
after her death honored his beloved wife while it
advanced research. And this year, with a charitable gift annuity, Ellzey—now 85—extends both
the support and honor. n
The long-term reports from LAMS are
almost out—what happens to these children with time. That’s where the rubber
meets the road. Then, immediately, we
should start translating that into prevention, change the course of things. We
know that for bipolarity, the earlier the
onset, the worse the adult outcomes. So
if LAMS tells us who’s at risk, there’s a
real opportunity to intervene before the
most pernicious effects take hold.
Nip it in the bud, then.
We hope. Nip at buds too early and you
risk not getting the right bud. And if
you’re a long time away, age-wise, from
a condition’s most extreme expression,
you’re more likely to be imprecise. These
are vulnerable, vulnerable children:
Misdiagnose and treat too early and you
expose kids to medicines with real side
effects, not to mention label them for
life. Fail to catch it early enough and you
add to human suffering. We struggle with
this. Is there any better justification for
research?
Alcohol Withdrawal Screening Questions
New Way for Withdrawal
I
s it a dream? I can’t distinguish things.
I was sure I was back in a bar. I had
no idea I was in a hospital.
Being in a major U.S. medical
center while in the midst of alcohol
withdrawal, as this actual patient was,
isn’t rare. A surprising 17 percent of
patients on general medical wards,
says one hospital survey that psychiatrist Jeffrey Hsu cites, are caught up in
some stage of alcohol withdrawal. That
can jump to 50 percent in emergency
or intensive care settings, he says—
even more in specialized, smaller inpatient units for the very ill with known
substance abuse.
What’s also unexpected is that many
hospitals lack a standard, updated
approach to the problem. Without that,
diagnosis can be tricky. Patients’ earlyon withdrawal symptoms of insomnia,
racing heartbeat, sweating or fever can
be attributed to anxiety or infection,
even overzealous coffee-drinking.
And treatment is less likely patienttailored. “At a suspicion of alcoholism,
it’s not unusual for patients to routinely get high-dose benzodiazepines
followed by a multi-day tapering,”
Hsu says. “That can lengthen hospital
stays, not to mention hitting patients
with higher sedation.”
So a few years back, Hsu helped
start a cross-hospital group to explore
change. It came first from tactics to
raise safety on Johns Hopkins psychia-
Serum blood
alcohol level
is positive
NO
Have you consumed any beer or other alcohol
containing drinks within the last seven days?
YES
In the past week how
1 drink =12 oz beer
8.5 oz malt liquor
many alcohol containing
try wards. “We
5 oz wine
drinks have you had in
1.5 oz spirits
If > 4
NO
a single sitting?
wanted to idenYES
tify and manIf < 4
age patients
Do you drink every day?
YES
early in alcohol
NO
withdrawal,
Do not start
Start patient YES Have you ever had symptoms of NO
alcohol withdrawal such as tremor,
patient on alcohol
on alcohol
before the
seizures, or delirium tremens?
withdrawal
withdrawal
complication of
protocol
protocol
seizures set in,”
he says.
and monitor therapy. And last,
In 2011, the group designed a flow
says Hsu, there’s every sign that the
chart (above) to assess patients’ risk
group’s new treatment protocol—
of being in withdrawal. It’s now an
it’s evidence-based and guided by
online part of inpatient interviews.
the severity of a patient’s withThere’s more: Psychiatric nurse Gigi
drawal—will become the norm. n
Rosenblatt headed a move to update
nursing staff, and now a new computer
course teaches nurses to recognize stages For information: 410-614-3618
Hopkins
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Hopkins
T H E N EW S L ET T ER
Deliriously
(Un)happy
Tackling the problem
of hospital delirium.
PAGE 1
O F T H E J O H N S H O P K I N S D E PA RT M E N T O F P S Y C H I AT RY A N D B E H AV I O R A L S C I E N C E S
SPRING 2013
Stress in Teens
Circuit-Pretty
Bipolar and Kids
Mouse study suggests
it’s a psychiatric hazard.
Brain Stimulation for
Alzheimer’s?
Bringing it into
sharper focus.
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