Science. Awareness.

Clinical Care.

Adolph Meyer envisioned programs “along lines…little-cultivated in this country” when he came to Hopkins in1909 to head America’s first academic inpatient psychiatrycenter. Meyer stood out as a prime figure of early 20thcentury psychiatry. And the “lines” he had in mind meant amore ordered, scientific way to look at mental illness—ideas just short of radical at the time. Meyer’s belief in thatapproach, in addition to his passion for collecting detailedpatient histories, echo to this day.

Separating out mood disorders as a discipline, though,didn’t catch on until Paul McHugh’s tenure as departmenthead (1975–2002). As a revolution surged in molecularbiology worldwide, McHugh wisely reminded Hopkins ofscience’s potential to ease psychiatric illness.Neurobiologists, geneticists, neuroradiologists andbehavioral biologists swelled Hopkins’ faculty. And a first-rate affective (mood) disorders program appeared,shepherded by J. Raymond DePaulo.

DePaulo set up both a consultation service and ahospital unit solely for patients with depression or bipolarillness. In 1986, he sparked large-scale communityeducation through an annual affective disorders symposiumthat today attracts hundreds. He has been a key figure instudies on bipolar genetics. And because DePaulo, nowPsychiatry’s director, has tackled mood disorders on threefronts—sound science, public awareness and finest clinicalcare—those priorities drive the Mood Disorders Center.

Holding the Line:Hopkins’ approach to mood disorders stems from a profound belief in science, awareness and clinical care.

From An Unquiet MindKay Redfield Jamison

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From Our Directors:Nothing Less than

the Conquest of Mood Disorders

More than 20 million Americans suffer from depressionor bipolar disorder. The World Health Organization’smost recent global burden of disease study cites depres-sion as the leading cause of disability worldwide. Socuring these brain diseases in the best way we think possi-ble—by understanding their genetics and biology and bytranslating sound clinical research into good care—is ourconstant goal.

But what might that mean in more practical terms? Should thepace of research keep up, here’s a possible scenario: It beginsordinarily enough, with a man in his s who arrives at Hop-kins, apparently depressed. We ask for a blood sample. But thefirst difference lies in a rapid gene screening and sequencingthat reveal his as a particular subtype of depression, one fairlyresponsive to a new, tailored antidepressant. A printout tells usto titrate it to a dose best for him.

During several visits, after a few sessions of transcranial mag-netic stimulation as additional therapy, his mood lightens. And,as his genes confer a greater susceptibility to environmentalstressors, our patient also enters a program of psychotherapy. With the science of these illnesses becomingclear, societal attitudes have changed. Now our patient feels less stress discussing his illness at his office. Hereadily takes his medication because, as the depression wanes—our functional MRI confirms—he feels muchmore his creative, exuberant self.

We don’t think our vision so unrealistic.

Our Hopkins colleagues in the war on cancer have cut a path to its cure: We’re amazed to watch them type apatient’s tumor markers into a computer and get a printout of options that let them tailor treatment andextend life as never before. That gives us hope as we begin our process. Like our oncology friends, we mustwage our war on three fronts: science, awareness and clinical care. And, like them, we realize that only a stronginfrastructure that fosters collaboration will succeed.

That’s why Hopkins’ Mood Disorders Center is a necessity. It provides a setting for collaboration, superbclinical teaching, a site for clinical trials, a place large enough to attract the creativity and spark the drive thatwill ultimately bring our patients what they need.

J. Raymond DePaulo Kay Redfield JamisonHenry Phipps Professor, ProfessorChairman, Department of Psychiatry Department of Psychiatryand Behavioral Sciences and Behavioral Sciences

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We’re no strangers to mood disorders.

Each year, thousands of patients cometo our clinics with every nuance of moodillness—many with more than one psy-chiatric or physical disease. As membersof one of the top psychiatry depart-ments in this country, our faculty isexperienced and compassionate. More-over, our decades of genetic studies,especially recent ones that allow us todistinguish among the many varieties ofmood disorders, give us sharpened per-ceptions of our patients and of what ailsthem.

We see, daily, the toll that the stigma of hav-ing mental illness and ignorance abouttreatment take on families and society.

At the same time, we’re in an academic insti-tution that, from early days, has heldresearch into the biology of mental illness asfundamental, well before that was standardpractice. Today, Hopkins Psychiatry’s studieson the genetics of mood disorders, for exam-ple, have formed a foundation forworldwide research. The work takes place inwhat peers have rated as the number onehospital in the nation for the last years, inlaboratories that consistently top the list forNIH research funding.

All this gives us the perspective to change thestatus quo. Namely, we understand whatwe’re dealing with in mood disorders; we’reaware of what therapies cannot now but ulti-mately must be able to do. We have the basic

tools—the skills to accomplish fine science,to teach young doctors, the clinical infra-structure to run trials and an awareness ofhow to improve social attitudes.

Our desire for change is strong. The fact thatpresent therapies don’t help everyone is morethan frustrating. And because whole-genomescreening and other new biotech techniquestantalize us with—at last—a real understand-ing of mood disorders’ basic biology, there’s ahope and urgency we haven’t felt before.

Science. Awareness. Clinical Care. They’re allof a piece. Our clinicians alternate patientcare and teaching duties with time in thelaboratory or in running drug or other ther-apy studies. Some of us feel as though welive on airplanes, traveling nationwide toraise awareness about mood disorders.

The Center’s clinician/ researchers, clini-cian/educators, geneticists, data managersand analysts, medical psychologists, post-doctoral fellows, epidemiologists andspecialists in clinical trials form a depart-ment-within-a-department, all working toadvance the master plan outlined on thefacing page:

The Mood Disorders Center

About Us

How the MDC Works

The Johns Hopkins Mood Disorders Center com-prises nearly 50 scientists, clinicians, techniciansand administrators. J. Raymond DePaulo, M.D.,and Kay Redfield Jamison, Ph.D., are co-direc-tors.

James Potash, M.D., heads research endeavorswhile Karen Swartz, M.D., oversees clinicalservices, Mary Beth Beaudry, M.S.N., M.P.H.,is the administrator.

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THE CENTER’S SCIENTIFIC ADVISORY BOARD

Our scientific advisors offer valuable direction and perspective.

They’re known worldwide for their ability to lift researchbeyond the ordinary.

Antonio Damasio, a professor of neuroscience, directsthe Brain and Creativity Institute at the University ofSouthern California. He’s made seminal contributions tounderstanding how the brain processes memory, lan-guage, emotions and decisions.

Robert Gallo heads the Institute of Human Virology atthe University of Maryland’s Biotechnology Institute. Thefirst to identify retroviruses in humans, he’s the co-discov-erer of the AIDS virus. His work sparked major advancesin AIDS and cancer therapy. Gallo holds two LaskerAwards.

Solomon Snyder, a Lasker Award recipient, foundedthe Department of Neuroscience at Johns Hopkins. He’sdiscoverer of the opioid receptor and endorphins. He pio-neered the labeling of neuroreceptors, enabling the abilityto locate all of the brain’s major neurotransmitter sys-tems. Snyder’s work laid a foundation for revealing thebiology of mental illness.

James Watson is best known as co-discoverer of thestructure and function of DNA, work that earned him aNobel Prize. Watson was a driving force behind theHuman Genome Project. He’s been associated with NewYork’s Cold Spring Harbor Laboratory some 40 years, asdirector, president and chancellor.

F I N D C A U S E S O F M O O D D I S O R D E R S

GeneticsFinding genes for mood disorder risk is a priority.

EpigeneticsCould mood disease result, in part, from badly tuned geneexpression?

HormonesHow do hormones affect at-risk patients?

EnvironmentHow does stress trigger mood disorders?

U S E T H AT TO D E V E L O P N E W T H E R A P I E S

Animal ModelsOnce risk genes are found, we use that to create animalmodels for mood disorders, letting us study the neurobiologyand identify targets for therapy.

PharmacologyOur knowledge of mood disorder biology will let us screenhundreds of existing drugs for new therapies.

NeuropsychologyHow does thinking/personality change in illness? With medication?

How can we ensure that patients stay on their medications?

T E S T / F I N E - T U N E N E W T R E AT M E N T S

I N PAT I E N T S

Clinical TrialsTightly designed studies let us test drugs and other therapies.

PharmacogeneticsHow can a patient’s genetic makeup help us tailor medication?

E D U C AT E A B O U T M O O D D I S O R D E R S /

L E A R N B E S T C L I N I C A L A P P R O A C H E S

ADAPOur Adolescent Depression Awareness Program is expandingnationwide.

Outpatient clinicA new clinic to let us follow patients over time will ensurebetter therapy.

Master clinician/educatorThis physician’s physician is a model for students, a resourcefor community doctors, a national educator.

Our Efforts

Improved brain imaging is high on the Center's listas a tactic to improve diagnosis and treatment.

He’s trained leaders inacademic medicine,helped thousands of

patients, made geneticsresearch far sounder.Colleagues call Ray

DePaulo a triple threat.

Shadow Ray DePaulo on the Meyer 4inpatient unit for an hour and it’s clearthat what he does isn’t ordinary.DePaulo co-directs the Mood DisordersCenter; he also heads Hopkins’ psychia-try department, so you’d expectexecutive skills as well as a clinician’seye—the ability to size up illness, chart atherapeutic course.

But several decades of medical students andpatients know there’s more.

When he’s on rounds, it’s not the samephysician who addresses a depressed, tearfulelderly woman, a N.Y. film editor numbedby his new bipolar diagnosis, a youngmother with a ladder of cuts up her arm. Ofcourse, different illnesses and life historiesdemand some adapting. Yet DePaulo’s wholeposture and demeanor shift, as does the tim-bre of his voice, his closeness to the patient:He’s reassuring with one; firm and somberwith another; an advocate against a manipu-lative family member for a third. Words arehonest: “This isn’t quick. You can expect upsand downs for weeks, probably. Monthseven.” His empathy enfolds patients like atherapeutic cloak. Stature and experiencehelp keep it in place.

That same concern drives DePaulo’s research.He began, in the early s, by defininglimits of lithium’s use as therapy for bipolardisorder. But like many, he saw that the real

hope for that illness lay in isolating itsgenes. Understanding the biologywould follow.

Thus began a hunt for bipolar genesthat continues today. DePaulo andHopkins colleagues were quick to seepossibilities in linkage analysis—a sta-tistical approach that tells the likelihoodthat a trait, such as having bipolar dis-order, is linked to a specific stretch ofchromosome. It’s a first step. But thestudies require the pedigrees of hun-dreds of patients and family members,squads of psychiatric interviewers andcostly DNA sequencing—whatDePaulo calls “big science” resources.

So in -, he became a leader of adogged amalgam of the country’s bestpsychiatric geneticists, the NIMHGenetics Initiative Bipolar Group, in aseries of ever-better linkage studiesthat’s continued for years. Surpris-ingly, in several dozen national studies,most involving Hopkins, no masterbipolar gene has surfaced. The ground-work, however, has produced a handfulof suspects.

The Next Phase, then, turns on a newidea: that bipolar illness stems from theway a number of genes—some probablybenign enough on their own—interactwith each other and with environmen-tal triggers. A new approach of tighter,“boutique” studies, as DePaulo callsthem, aimed to flush out those genesfrom small, less diverse family groups,has already begun at Hopkins.

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A Rayof Light

James Potash entered this world at TheJohns Hopkins Hospital, where his fatherwas a psychiatrist. After Yale and thePeace Corps, Potash returned to Hop-kins for a public health degree, medschool, a psychiatry residency. He joinedthe faculty in 1998. Perhaps it’s his easewith the place that’s let him step intouncharted research territory for a psy-chiatrist, even one comfortable withgenetics.

Potash joined the search for genes just as hismentors were starting to clear the under-brush, work beginning to link symptoms ofmood illness with chromosomal areas. Still,areas aren’t genes. And Potash was more thankeen to seek an alternate approach, onebased on mood disorder subtypes—traits likehaving suicidal tendencies or having oddlydistorted thinking—that can accompany thedisorders. Because subtypes tend to bunch infamilies, he’s found that surveying genomesof “purer” family groups can force subtypegenes into the open. That, in turn, narrowsthe search for the “main” genes for bipolar(BP) or major depressive disorder.

Potash had his eye on psychosis, for example.In some BP families, he noticed, most everyone affected also has delusions or halluci-nations. By sampling a whole family’s DNA,he and colleagues narrowed symptoms of psy-chosis to chromosomes and , incidentally

the same areas linked with such abnormalthinking in schizophrenia. The find notonly gives a toehold for the fine-mappingthat will likely yield genes; it also buildsinsight into the closeness of the two dis-orders.

What is most exciting, however, are his studies in epigenetics, a new fieldthat deals with ways to control geneexpression operating outside of thegenetic code, even though it’s still heritable (see box). Epigenetics mayoffer a scientist’s heaven of sorts, themuch-sought tie between mood disor-ders and environmental factors like stressor diet. Also, there’s the exciting sugges-tion that therapies such as lithium andDepakote work, in part, by changes inthe epigenetic control of key genes.

As the Center’s research director, Potashis making epigenetic mood disorderstudies a priority. He’s begun, for exam-ple, by comparing postmortem brains ofpeople with and without major depres-sion for differences in epigeneticpatterns.

The potential of a whole new approachto mental illness waits, untapped.

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Gene Work: A Sample

Center research has shown that:• Bipolar disorder (BP) II is a common,

genetically distinct illness.• Some chronic depression, especially

one beginning in childhood, runs infamilies.

• Certain BP subtypes likely have agenetic basis, with a chromosomal“home.” They include panic disorder(chromosome 18), psychotic symp-toms (chromosomes 13 and 22),suicide attempts (chromosome 2) andearly-age onset (chromosome 21).

• A gene called NTRK3 codes for braincell growth and development.

• A flawed form of that gene, on chro-mosome 15, may raise risk ofdepression.

• The gene FKBP5, which produces aprotein tied to the brain’s stressresponse, likely plays a part in BP sus-ceptibility.

• Two genes, HMG2L1 and NRG1, thatcode for signaling proteins within thenervous system appear tied to the riskof psychosis in BP.

Epi at the Forefront

Now that the genome is sequenced, sci-entists realize it’s but a backbone forunderstanding how genetic programsdirect development. Superimposed onthe human DNA sequence, like so manyPost-it notes, is a layer of heritable epi-genetic information that we’re onlybeginning to appreciate.

It’s sure that added-on epigeneticcontrols play a part in human disease. In1983, Hopkins researchers showed forexample, that in certain cancers,the“post-its” were lost in ways consistentwith each variety. But what of mood dis-orders? “Some connection is likely,” saysthe Center’s James Potash, who headsefforts in the field. “We know, forinstance, that Depakote, the most com-mon bipolar medicine, alters epigeneticpatterns.”

In 2007, Hopkins opened the firstepigenetics center. And its new BrainScience Institute, a group of world-classbasic scientists, confirms epigenetics asa frontier. Prodded by Potash, Hopkinshas set up the Epigenetics MicroarrayLab to uncover epi-effects on the brainin health and disease.

When Impatience

Is a Virtue

“I want to make adifference for mypatients, and for theirfamilies. The thing thatpulls hardest at myheartstrings is theparents. I always seemyself in them andimagine what it would belike if my sons weretortured by depression orbipolar disorder.”

Students at the Baltimore School forthe Arts have been quick to learn thesigns of mood disorders, Karen Swartzsays, as have the other ,+ sheand ADAP colleagues have taught.“We can’t stress it enough: these ill-nesses are treatable.”

Finding at least one gene for suicide is agoal that occupies a fair amount of VirginiaWillour’s time. Recently, she and colleaguestook a new look at earlier data on patientswith problems where suicide risk runs high:in major depression, bipolar disorder andalcoholism. By focusing on people withinthose illnesses who had attempted suicide,the rationale went, her team hoped some-thing would stand out. And it has, almost.

What’s intriguing, says Willour, who has aPh.D. in genetics from Stanford, is that all threedisorders point to the same spot on chromosome. That would suggest that a “suicide gene”within it isn’t solely tied to a specific disease. Itlooks to be something independent, somethingthat may prompt an “impulsive aggression,”Willour says, “that nudges an already depressedperson to act on suicidal thoughts.”

The next step—finding the actual gene—takes expertise andthe researcher’s ability to delay gratification. Willour hasdesigned a large-scale study that acts like a fine sieve in win-nowing out what’s distracting in the broad chromosomaltarget area, to pinpoint where DNA differs between suicide-prone mood disorder patients and healthy controls. It’ll takeseveral years. “But I have incentive,” she says. Her family’saffected by bipolar disorder; her grandfather died of suicide.“Our goal is to bring new logic to therapy, to use anapproach based on understanding the biology. So I’m in itfor the long haul.”

To Stem the Tide

of Suicide

In Peter Zandi’s hands, results of sci-entific research can take on a new life.He has both the intellect and a real giftfor recognizing how data sets from anumber of studies can be pooled todraw new conclusions, saving time,money and, sometimes, years of effort.

Zandi also sees how a study’s outcomesfit into the larger context of psychiatricdisease. All that makes him in demand.

Masses of data are the rule in epidemi-ology—one of Zandi’s fields—and a partof the tools of molecular genetics—another field. The latter uses statisticsto extract trends from hundreds ofpatient families, or to interpret millionsof data points from DNA chips: the sortof demanding efforts that cause lights inthe computer lab to dim.

Data managing, analysis and statisti-cal genetics, then, are Zandi’s strengths.He’s joined national searches for bipolar,autism and panic disorder genes as wellas studies on Alzheimer’s disease thera-pies.

But Zandi’s also aware of context.After the genome project sequencedhuman DNA, laboratories undertookthe next generation of studies tounravel the purpose of specificsequences and to catalogue their smallvariances from person to person. Asscores of different databases beganappearing worldwide, Zandi’s otherskills come in. He’s expert at finding andanalyzing those databases to applywhat’s relevant to Hopkins studies. “Byleveraging what’s learned in the geneticscommunity,” he says, “you make moresense of your own data.”

At Ease with Numbers

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Birth ofa Notion

“When you think about it,pregnancy is a natural

experiment. At no other timecan we predict that a certain

percentage of people will have amood episode and know when.”

“Unlike the women we see with typical postpartummood problems, other women become deeplydepressed literally hours after they deliver a baby,especially if they’ve been depressed before,” Jennifer Payne explains. “They tell me it’s like a curtain falling.”

Since her first encounters as a medical resident, psychia-trist Payne has felt compelled to help women whosemoods slip out of control at hormones’ bidding: thosewith premenstrual, pregnancy, postpartum or peri-menopausal difficulties. “Mood disorders in women areunderstudied, to put it mildly,” she says.

Payne aims to remedy that. First, she and colleagueKaren Swartz created the Women’s Mood DisordersCenter, a much-needed consultation clinic within Hop-kins’ broader mood center. Payne also cites the desperateneed for research. Clinical trials, for example, would tell

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how best to use available therapies—What about lithiumduring pregnancy? Do you taper it during labor? Moredescriptive studies shed light on the biology. Because themood disorders she sees come and go predictably,women can serve as their own experimental controls.“It’s a unique chance to tell what’s broken in majordepression and bipolar disorder.”

Payne begins by collecting data: Following at-riskwomen through pregnancy and after delivery, for exam-ple, yields DNA for gene studies, information on stresslevels and chemistry, on sleep and hormone levels. “I’mhoping to say something like, look, if you have elevatedIL6—an immune protein—you’re at greater risk forpostpartum depression.” IL6, then, could predict disease.And when, at last, patient-testing of a potential therapycomes around, IL6 might tell, early on, if it’s working.“Trials,” she adds, “make sense of what we do.”

“Our mantra is thatdepression is a treatable

medical illness.”

Stopping a simple misperception couldsave the lives of thousands of youngadults on the cusp of life.

That thought entered Karen Swartz’smind and took hold. “The idea out there,”she says, “is that teenage suicide is a responseto extreme stress or pressure and could hap-pen to anyone.” But that’s so far from thetruth as to be shocking, she says. A multi-tude of studies show that roughly percentof teenagers who die that way had a treatablepsychiatric illness. Worse, some of the veryprograms high schools use to prevent sui-cide—about three-fourths of U.S. schoolshave such a curriculum—inadvertently drainthe act of its taboo status and may evenromanticize it.

But Swartz is a resourceful woman with theright background—she’s a psychiatrist spe-cializing in mood disorders. She has publichealth training. And the word can’t justbounces off her. In , Swartz drewtogether a group of concerned Hopkins psy-chiatric nurses and clinicians, promptingcreation of ADAP, the Adolescent Depres-sion Awareness Program, which she nowheads.

ADAP’s aim is to increase basic depres-sion literacy, starting with highschoolers. Now a national program, itteaches the symptoms of depressive andbipolar illnesses, distinguishing themfrom normal adolescent ups and downs.Students—and, in separate programs,their parents and teachers—learn howclinicians diagnose and treat depressionand why ignoring it courts danger.

“Our mantra,” says Swartz, “is thatdepression is a treatable medical illness.”

From the first, Swartz decided not tomake suicide prevention the focus, butto take a public health approach, to cut awider swath. “Many more teenagers willexperience depression throughout theirlives than will ever try to commit sui-cide,” she says. “We focus on the mooddisorders themselves and what to do.”

Reliability marks the program. Using herresearch background, Swartz has beendogged in testing each phase of ADAP.She’s seen, for example, that medical students or high school teachers caninstruct as well as the core group whobegan it. She’s analyzed which tech-niques work best. And it’s paying off.Student pre- and post-tests show they’relearning the truths. “Collaboratorswanted to expand faster than I thoughtwe were ready to,” says Swartz. “No.No,” I said. “We have to do it right.”

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The Myth-Breakers

A Rare, Healing Place

Not to have a place to come for expertcare for an illness that often surfaces atone of the most vulnerable times of lifehas never made sense to psychiatristElizabeth Kastelic. That’s why shedirects one of the few U.S. psychiatricinpatient services for young adults andteens with mood disorders. Kastelicspecializes in diagnosing and treatingdepression and bipolar disorder in thoseon the verge of adulthood.The approach she and staff use hinges

on an exquisite awareness of that stageof human development, on an ability tosort pathology from teenage angst, forexample, or to use an awareness ofpeer pressure to advantage. And withhome environment crucial to therapyfor teenagers, educating parentsbecomes part of that approach.

Kastelic’s clinical questions clearlyguide her research. The shortage ofinformation on mania in adolescence hasprompted her to follow its appearancein children whose parents have bipolardisorder. And she’s part of a nationalquest for better treatments for them.

< Karen Swartz and Elizabeth Kastelicarm students with awareness.

Psychiatrist Irving Reti knows better than most theneed for variety in depression therapies. As thehead of Hopkins ECT (electroconvulsive therapy)service, he sees the steady line of patients from allover the country who’ve come because antidepres-sants haven’t helped or because they find sideeffects intolerable. “Effective as ECT can be,” hesays, “we’ve known for years that we need alterna-tives.”

But now, psychiatry is discovering an exciting new physi-cal approach to therapy. Somatic treatment, as it’sknown, springs from research in which stimulating spe-cific areas of the depressed brain—directly withelectricity or through targeted electromagnetic waves—apparently raises mood and does it well.

For years, Reti, also a neuroscientist, hasstudied molecular changes that follow ECTand other somatic approaches. That worknow informs the new therapies. Furthestalong is transcranial magnetic stimulation(TMS), a use of magnetic waves to rouseareas near the brain surface, like the pre-frontal cortex, that have gone metabolicallysluggish. Remarkably, patients show noapparent side effects so far in thoughtprocesses or memory. “And the early evi-dence says it may be especially effective inyounger patients,” says Reti, “which is goodnews given today’s concerns about teens andantidepressants.”

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The Near FutureDiscovery’s Bright Possibilities

A Bipolar BiomarkerHoly grail” is overworked, the stuff ofbad brochures, but applied to bipolarresearch, the tag seems right. Becausethat disorder almost certainly rests uponmultiple altered genes, as well as onenvironmental cues, creating a labora-tory test—a biomarker—that can verifyit in patients is indeed holy grail-ish. Andpsychiatrist Dean MacKinnon is a seeker.

Recently, MacKinnon devised a prototypetest based on the idea that bipolar disorderstems, in part, from a problem in emotionallearning. Something’s amiss, he believes, in

the learning that shapes a person’s appetitesand motivates appropriate behavior. And justas such flaws may cause patients to cyclebetween having no motivation or too muchof it, the underlying biology may also skew amost basic appetite, that for fresh air. In test-ing patients’ response to breathing air withslightly elevated carbon dioxide, MacKin-non’s noted that they show characteristicdifferences from people without the disorder.

He’s now at work testing his biomarker inlarger groups. If it holds, the benefits topatient treatment, to the search for therapyand to lessening stigma would be huge.

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“

Dean MacKinnon’ssearch for a bipolarmarker goes in unex-pected directions.

The Best Sort of Balancing Act“Call it guilt by association,” says psychi-atrist Francis Mondimore,considering a role for the three B vita-mins—folic acid, B-12 and B-6—indepression. Some studies suggest thatfolic acid lifts mood and that too little B-12 or B-6 does the opposite.

A gifted clinician, Mondimore divideshis time between seeing patients andwriting for them. Reading his Depression:The Mood Disease and Bipolar Disorder: AGuide for Patients and Families is in itselftherapeutic. But Mondimore’s eye is alsosharp for research to translate quicklyto the clinic, as in his study of already-safe B vitamins.

All three, he says, are cogs in brainneurotransmitter machinery. As impor-

tant, however, is that they lower homo-cysteine, an intermediate but vilemolecule in that same chemical cascade.Mondimore says homocysteine’srecently discovered potential to dampnerve function in the hippocampus andother mood areas in the brain makes itsuspect.

A series of studies he’s plannedshould tell if the vitamins, as a trio, offermood relief. The first sees if patients athigh risk of depression are more likelyto have genetically flawed vitaminmetabolism. The second is to learn ifthat flaw’s more common in the chroni-cally depressed. Last come the actualtrials of the vitamins for depressedpatients.

The Near Future On the Way

Patients at Hopkins Hospital who find them-selves on the recovery side of a flight into maniaor a free-fall into depression—especially youngadults hearing they have bipolar disorder—areoften given what should be called bibliotherapy.Kay Jamison’s book An Unquiet Mind is potent fordoing what pills can’t: It lets patients read forthemselves how destructive not taking theirmedicine can be, it tells of the healing power ofstructure, psychotherapy and a social network. Ittells them they’re not alone. And, as critical, itshows, by Jamison’s example, that the diagnosisneedn’t drain all the life from life.

Jamison is perhaps this country’s most famous writerabout manic-depressive illness. Her books and articlesnot only help patients, they have raised society’s con-sciousness. Her public appearances inform Americansabout their millions of fellow citizens who suffer mooddisorders. Her work and life chip away at the stigma ofmental illness.

Jamison, a professor of psychiatry and the recipient of aMacArthur “genius” award, has widely researched med-ication adherence and suicide. She is the co-author ofManic Depressive Illness: Bipolar Disorders and RecurrentDepression, the definitive medical text on the topic.

But within the Mood Disorders Center, Jamison is seenas a tether. She grounds its scientific studies in humanity,giving what she calls, “a broader notion of moods in thehuman perspective.

“I’m interested in the boundaries between normal moodsand abnormal, between normal and abnormal behavior.It’s the overlap that fascinates,” she says. And it’s in thosetenuous states between a normal passion and pathology,she believes, that exuberance and creativity surface. “Thetie between high accomplishment in business, scienceand the arts and mood disorders is far from coinciden-tal.” And understanding the psychology and biologybehind that, she says, “could lead to therapy even betterthan what exists, that doesn’t tamper with a rich, imagi-native life.”

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Kay Redfield Jamison:Tamper-Proof Humanity

From An Unquiet MindKay Redfield Jamison

Like much that’s worthwhile at Hopkins, help formood disorders began with a book and a dona-tion. Clifford Beers was never a patient here;psychotic with bipolar disorder, he was shuttledamong New England institutions. And in a lull inhis illness, Beers detailed his brutal experiences ina memoir. The impact was profound.

In , newly hired as head of Hopkins psychia-try, Adolph Meyer received a preprint copy of AMind that Found Itself. Intrigued by a book thatmirrored his convictions about treatment reform,Meyer offered his copy to Henry Phipps Jr., a hos-pital trustee. Phipps was deeply altruistic. And, asAndrew Carnegie’s right hand, he was also theworld’s second wealthiest man. The resultingHenry Phipps Psychiatric Clinic was completed in. It put a new face on treatment and kindledmajor advances in treating mental illness.

Almost a century later, we’re still indebted toPhipps, and to those whose gifts have enabled thebest of psychiatric research, have raised commu-nity awareness of mood disorders and have helpedmake normal the lives of those who have them.

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The Johns Hopkins Phipps Psychiatric Clinic, 1913.

A Book, a Boon

“More fundamental than any technical reform, cure

or prevention...is a changed spiritual attitude toward

the insane. They are still human: they love and hate

and have a sense of humor.”Clifford Beers,

TO L E A R N H OW YO U C A N M A K E A G I F T TO

T H E J O H N S H O P K I N S M O O D D I S O R D E R S C E N T E R ,

C O N TA C T :

Jessica Preiss LunkenDirector of DevelopmentDepartment of Psychiatry and Behavioral SciencesFund for Johns Hopkins Medicine North Charles Street, Suite

Baltimore,

Phone: --

jlunken1@jhmi.edu

“The future belongs to science.”Sir William Osler

Physician in Chief, The Johns Hopkins Hospital,

-