Pioneering Solutions for Depression and Bipolar Disorder the Stanford Mood Disorders Center

Pioneering Solutions for Depression and Bipolar Disorder The Stanford Mood Disorders Center

Campaign for Stanford Medicine We are all part of the equation. “Never before have we been so close to breakthroughs that will transform our approach to mood disorders, delivering advanced solutions for sufferers, their families, their friends, and their communities. Stanford is leading the way in understanding brain processes and transforming new knowledge, rapidly and efficiently, into new therapies and technologies.”

Alan F. Schatzberg, MD THE KENNETH T. NORRIS, JR. PROFESSOR AND CHAIR EMERITUS, STANFORD DEPARTMENT OF PSYCHIATRY AND BEHAVIORAL SCIENCES

Pioneering Solutions for Depression and Bipolar Disorder The Stanford Mood Disorders Center

One out of five Americans will experience some form of mood disorder in their lifetime—such as depression or bipolar disorder. Despite their prevalence, mood disorders remain one of the most widespread, misunderstood, and stigmatized health issues we face. Their impact reverber- ates far beyond an individual’s life. Families, friends, communities, economies—all are affected by these diseases. By 2020, depression will rank second in morbidity among all illnesses worldwide; bipolar disorder will rank fifth. Tragically, suicide, often triggered by a mood disorder, takes more than one million lives worldwide every year.

Although the incidence and impact of mood disorders are undeniably on the rise, hope for solutions has never been higher. Through the Stanford Mood Disorders Center and Research Program, scientists and physicians are building on Stanford’s traditions of excellence, healing, and innovation. They are leveraging new knowledge of genetics and the brain’s molecular processes, and drawing on new techniques for imaging and healing the brain. Merging Stanford’s expertise across disciplines—psychiatry, biology, engineering, and myriad other fields—they are streamlining the process of translating laboratory discoveries into breakthrough treatments. For the past 20 years, Stanford has led the quest for new knowledge and therapies for mood disorders. Today, the center is expanding its reach and mobilizing Stanford’s diverse expertise toward a powerful shared mission: to overcome mood disorders through innovation and compassion. • • • • • strengthto: The MoodDisordersCenterleveragesthisinterdisciplinary • • • • educational programsin: inresearch,clinicalcare,and the mostrespectedbasicscientistsinworld,takepart includingsomeof More than30seniorfacultymembersfromeightStanforddepartments, clinicalcareandtrainingforfuturephysician-scientists. innovative with research science basic approachtomooddisordersintegratessignificant interdisciplinary comprehensive, Stanford’s THE STANFORD ADVANTAGE: ANINTERDISCIPLINARY APPROACH and BehavioralSciences,headstheStanfordMoodDisordersCenter. ofPsychiatry Department Alan F. Schatzberg,MD, NEUROLOGY GENETICS BIOLOGY BIOENGINEERING targeted brainstimulation, minimallyinvasivesurgery, andcomputer-based braintraining patients for today’s behavioral therapy treatment techniques,includinggenetics,imaging,psychotherapy, acupuncture,and deeper understandingofbrainmechanisms,andadiverse rangeofdiagnosticand brain” andmonitoringmeasuringitsfunctions Create newtherapiesusinginnovative techniques,includingnext-generationdrugs, Leverage pharmacological,pharmacogenetics,andotherapproachestoimproveoutcomes socialfactors,a Pioneer aholisticapproachbeyondtraditionalpsychiatry—integrating Improve imagingtechniquesthatenhanceunderstandingof diseaseby“lookingintothe Understand diseasemechanismsthroughgenetics,genomics, andproteomics the Kenneth T. Norris,Jr. Professor andchairemeritusoftheStanford • • • • RADIOLOGY PSYCHIATRY PSYCHOLOGY NEUROSURGERY

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research projectsunderway 200 leading-edgeinterdisciplinary 250 medicalstudentsperyear between 2004and2012 120 postdoctoralfellowstrained 750 undergraduatesand since 2003 45 clinicaltrialscompleted 8,000 totalpatientsannually 900 inpatientsperyear CENTER AT AGLANCE STANFORD MOODDISORDERS

such asanxiety, substanceuse,orbraininjury. patients withcomplexexacerbatingconditions, for bipolardisorders,includingstrategies on developing optimal treatment approaches bipolar disorder, herclinicalresearchfocuses in biologyandtreatmentof recognized expert at theVA Palo AltoHealthCareSystem.A of theBipolarandDepressionResearch Program and behavioral sciences, is director psychiatry Trisha Suppes,MD,PhD, professorof

MARK TUSCHMAN developing novel,better-directed, moreeffectivetreatments. firststepin which circuitsandstructures in thebrainplaykeyrolesmooddisorders—the of thebrain. Combined withsimilarpreclinicalexaminations,thesestudieswill determine scientists tolookatalargenumber ofgenessimultaneouslyinspecificregionsandcircuits enables OneStanfordeffort to stress,modulatemood,ormaintaincognitiveperformance. example, byaffectinghowourbrainsrespond feed intodepressionorbipolardisorder—for disorders iscomplex.Genesmayhaveanimpactonmany differentfunctionsthatcanall alteration inasingleneurotransmittersystem.Theynowknow thatthegeneticsofthese Scientists oncethoughttheywouldbeabletoattributemood disorderstoasinglegenetic patients withmajormooddisorders. contribute tobipolardisorderanddepressiononthedevelopment ofnewtreatmentsfor Cornell University, genesthat andtheUniversityofCalifornia—is focusedonidentifying withinvestigatorsfromtheUniversityofMichigan, Stanford—inpartnership Consortium, causes ofdepressionandtoimprovetreatmentthedisorder. NowknownasthePritzker of Depression, acollaborativeforumestablishedbythePritzker familytostudytheroot Since 1996,StanfordhasbeenaninstitutionalleaderinthePritzker NetworkfortheStudy made possiblebythemappingofhumangenomeoverpastdecade. techniques in theprocessofunravelingtheseinteractionsusingunprecedenteddiscovery are biological orgeneticvulnerabilityintersectswithenvironmentalstress.Stanfordexperts What causesmooddisorders?Scientistsnowunderstandthattheseillnessesoccurwhen TRACING GENETICROOTS tends tobeinadulthood,childrencanalsoaffected. highs andlows,eachlastingatleastoneweek.Althoughtheonsetofbothdisorders polar disorderaffectsmenandwomenequallyischaracterizedbyepisodesofmood disturbances, anxiety, self-destructivethoughts,poorconcentration, andchronic pain. Bi persist overseveralweeksorlonger, includingloweredmood,decreasedenergy, sleep common inwomenandischaracterizedbyavarietyofpsychicphysicalsignsthat Cutting awideswathacrossallcommunitiesandcultures,majordepressionismore DISORDER DEFINING DEPRESSIONANDBIPOLAR sciences, whoisalsostudyingbipolardisorderinadultsandtheirchildren. mood disorder. Heiscollaboratingwith disorder. Hisstudiespromisetoyieldcrucialinformationaboutwhichgenesindicateriskofdevelopinga behavioral sciences,iscollectingdatafromfamiliesinwhichbothchildrenandadultssufferbipolar Using thelatestingeneticanalysis techniques, Terence Ketter, MD, Kiki Chang,MD, (L) professorbehavioraland of psychiatry (R) professor of psychiatry and (R)professorofpsychiatry

MARK ESTES humans tothem. antidepressants. This landmarkworkwilltestpromisingnewcompoundsbeforeexposing Another novel investigation images, preciselyandinrealtime,thebrain’s responseto ofthebrainassociatedwithseveredepression. affect parts hormones neurotransmitters respondtocurrenttherapies.Othersare lookingathowcertain ofthebrain. Someareinvestigating how activation ofneuronalcircuitsinvariousparts Several teamsareusingfMRItoexplorehowchangesinemotion areassociatedwiththe ticular genesandtheneuronalcircuitstheyaffectmightinfluence emotionalregulation. and arecombining fMRIexplorationswithgeneticstudiestodeterminehowpar depression with deepdepression. Otherresearchersarelooking athigh-riskchildrenofwomenwith tobeassociated subgenualcortex—thought brainregion—the difficult-to-image functional magneticresonanceimaging(fMRI)technologythatcanmonitoractivityina Among theadvancedtechnologiesdevelopedbyStanfordscientistsisanewformof to transformthewaybraindisordersarediagnosedandtreated. oping innovativetechnologiesthatrevealmooddisordersatthebiological levelandpromise in realtime.AndscientistsatStanfordareinternationallyrenownedforexploringanddevel affect thebrain?To answerthesequestions,scientistsmustbeabletostudythelivingbrain of thebrainareaffectedbydepressionandbipolardisorder?Howdoantidepressants Can stressdamagethebrainandmakeitmorevulnerabletomooddisorders?Whatportions SEEING ANDHEALINGTHEBRAIN disorders. promise torevealwhichgenesconnoteincreasedriskfordevelopingoneormoremood depression orbipolardisorder. studies these Usingthelatestingeneticanalytictechnologies, dataonfamiliesinwhichbothadultsandchildren have across generations—collecting To explorethegeneticoriginsofmooddisorders,Stanfordisalsoinvestigatingthesediseases depression inchildrenatrisk. innovative brainimagingtechniquesandaretestingmethodstoprevent developing thedisorder. Hisstudiescombinegeneticcharacterizationwith of motherswithdepression, whoarethoughttobeatincreasedriskof resonance imaging (fMRI) to explore emotional processing in children Ian Gotlib,PhD, professor ofpsychology, isusingfunctionalmagnetic

MARK ESTES to uncoverthelinksbetweenhormonesandbrainfunction. disorders, andcognitivehealth.Rasgon remainsattheforefrontofeffort studies theconnectionsamongwomen’s reproductivehormones,mood directs theStanfordCenterforNeuroscienceinWomen’s Health,which Natalie Rasgon, MD,PhD,

- - training throughthecenter. receive and experimentalpsychology—also bioengineering, physics,endocrinology, neuroscience, cognitive fellows fromdiversedisciplines—basic Institute ofMentalHealth.Studentsand trained inprogramsfundedbytheNational fellows, includingthoseinpsychology, are units andspecialtyclinics,postdoctoral inpatient residents rotatethroughthecenter’s continues amongmedicalstudents.Psychiatry including psychology. Thementorship well ashonorsstudentsinmultiplemajors, teach undergraduatesinhumanbiologyas innovative, collaborativework.Centerfaculty to continuetheMoodDisordersCenter’s psychologistsandneuroscientists tomorrow’s Stanford iswellpositionedtoprepare graduate, andpostgraduateprograms, With its highly regardedundergraduate, NEXT-GENERATION TRAINING professor of psychiatry andbehavioralsciences, professor ofpsychiatry

MARK TUSCHMAN bipolar disorder. and childoutpatientclinicsfordepression and operatesbothadult outpatient services, Mood DisordersCenteroffersinpatientand the higheststandardofclinicalcare, top 12programsinthecountry. Delivering ranked by of thepremierclinicalprogramsinpsychiatry, Stanford Hospital&Clinicshasdevelopedone LEADING CLINICALCARE to experiencepleasure symptom ofdepression—anhedonia,the inability identified apotentialtargetfor treating a major function ofkeybrainsynapses. which stressful events or drug use modifies the leader instudyingthemolecularmechanismsby andBehavioralSciences,isaworld Psychiatry PhD, treatment ofdepression. play a critical role in both the development and Modifications inthe brain’s rewardcircuitry theNancy Friend Pritzker Professor of U.S. News & World Report World & News U.S. . Robert Malenka, MD, His studieshave inthe

MARK ESTES risk factorsforthedevelopment ofthesecomplicationsandtoreducetherisksideeffects. Stanford teamiscombiningnovel brainimagingandendocrinologytechniquestoexplore insulin resistanceanddiabetes. Incollaborationwithanationalresearchnetwork,one bring relieftopatients.However, somecommonlyusedmedications areassociatedwith requiresacombinationofmood stabilizersandantidepressantsto Bipolar disorderoften each patient. themostpromisingtreatmentfor develop aseriesofgeneticmarkerstohelpdoctorsidentify antidepressants willworkbestonspecificpatients.Overtime,itmaybepossibleto today’s Stanford scientistsarealsoassessingwhethergeneticvariations canpredictwhichof brain imaging. a patient’sresponsetoantidepressantsandwhetherimprovement canbevisualizedthrough looking athowadopamine-basedagentnowusedforrestless legsyndromemightimprove rine, a type of stress hormone. Onenovelstudy, conductedacrossthreemedicalcenters,is ness ofserotonin-baseddrugstothattherapiescombine serotoninwithnorepineph Other researchers,lookingatrecurrentdepression, arecomparingthelong-termeffective major depressionandexploringwhetherthesetreatmentscanalleviateaswell. behavioral sciences, chronic depression. medication ismoreeffectivethanaggressivepharmacologictreatmentinpatientswith One teamisinvestigatingwhetheraspecificformofpsychotherapyincombinationwith ofthesetherapies. effectiveness successful. Atthesametime,theyaredevelopingnewapproachestoboost which strategies,basedonexistingdrugsandpsychotherapeutictechniques,aremost treat patientswithdepressionorbipolardisorder. Stanfordscientistsareactivelyexploring Psychiatrists todayrelyonacombinationofpharmacologicagentsandpsychotherapy to IMPROVING OUTCOMES PATIENTS FORTODAY’S depressed patients. alllowing anareaofthebrainwhereactivityisincreasedin scientiststostudythesubgenualcortex, and neurological sciences,have developed new fMRI technology that can image braincircuitsat rest, and behavioral sciences,and psychiatry thinking. and increasedriskofdevelopingpsychotic responses stress that isassociatedwithincreased astress-markerhormone,andkeyareaofthebrain cortisol, andBehavioralSciences,areusingimagingtechnologytostudytherelationshipbetween of Psychiatry Mood CenterDirector isstudyingoptimalpsychosocialtreatmentsforreducinginsomniain The teamledbyRachel Manber, and PhD,professorofpsychiatry Alan Schatzberg, MD, Michael Greicius, MD, MPH, and Allan Reiss, MD, theHowardC.Robbins Professor Vinod Menon, PhD, assistant professor of neurology assistantprofessor

professor of professor

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MARK ESTES dialectic behavioraltherapy. techniques,and a saferalternativeforpregnant womenwithdepression—mindfulness techniques.OtherStanfordresearchersareexploring acupuncture— gical stimulatory andmagneticorradiosur proach focusesstimulationontheseregionsusing3-Dtelemetry Stanford isalsopursuingalternativestrategiestostimulate deepbrainregions.Oneap ofanationalmulticenterproject. part imaging—as guidedby electrodesintospecific regions,suchasthesubgenualcortex, tion—implanting disorders liedeepwithinthebrain, Stanfordspecialists areexploringdeepbrainstimula targeted areasofthebrainthroughscalp.Sincesome key areasassociatedwithmood to overactive indepressiontodevelopnewtreatmentsthatprovide electricalstimulation Other Stanfordteamsareinvestigatingwhichareasorcircuits ofthebrainarepotentially receptorinthebrain. medication thatblocksaspecificcortisol of delusionaldepression, Stanfordresearchhas ledtotheuseofafast-actingalternative asanindicator treatment. Following uponanumberofstudiesthatrevealelevatedcortisol lossthatcanbeasideeffectofthis ing toreduceandinsomecaseseliminatethememory therapy, oneof the mosteffectivetreatmentsavailable.Researchers atStanfordarework due tophysicalcausesorsuicide.People receiveelectroconvulsive withthedisorderoften rateOne ofthemostsevereformsdepression, delusionaldepression, hasahighmortality groundbreaking treatmentapproaches. istakingtheleadindeveloping more effective,fasteracting,bettertolerated—Stanford are associatedwithconsiderablesideeffects.To usherinaneweraofmooddisordercare— several therapiesbeforetheyfindone(oracombination)thatworks.Andsome Although mostpeoplewithmooddisorderseventuallyrespondtotreatment,manymusttry CREATING NEWTHERAPIES who donotrespondtotraditionaltherapy. an electromagnet to stimulate levels of the brain, providing relief to patients with severe mood disorders sciences, applyrepetitivetranscranialmagneticstimulation(rTMS),anewtreatmentoptionthatuses and behavioralsciences, Depression Research Centerco-directors Charles DeBattista,MD,DMH, BrentSolvason, MD,PhD, (R) professor of psychiatry andbehavioral (R)professorofpsychiatry (L) associate professor of psychiatry (L)associateprofessorofpsychiatry

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MARK ESTES brain disorders. The techniquemayleadtotargetedtherapiesfor cells onandoffwithmillisecondpulsesoflight. neural brain cellactivitybyturningparticular developed anoveltechniquetodirectlycontrol cellular toolstoreengineerbraincircuits.Hislab treats patientsanddevelopsmolecular andbehavioralsciences,both of psychiatry Professorand andprofessorofbioengineering Karl Deisseroth, MD, PhD, depression andbipolardisorder. step inremovingthestigmaassociatedwith important treatment guidelineswidely—an development ofnewtherapies,andshare of mooddisorderresearch,speedthe to improvetheproductivityandefficiency and bipolardisorder. Thesecenterspromise research, andtrainingrelatedtodepression to establishcentersofexcellenceintreatment, seeks at theUniversityofMichigan. Theeffort centers incooperationwiththeoriginalcenter a networkofnationaldesignateddepression collaboration, Stanfordhasworkedtodevelop Bringing leaderstogetherinbreakthrough OF EXCELLENCE A NATIONAL NETWORK

theD.H. Chen

MARK ESTES ALEX JOHNSON TERRENCE MCCARTHY COURTESY OF RACHEL MANBER COURTESY

Jaime Henderson, MD, associate professor of Integrating her clinical and research expertise in Amit Etkin, MD, PhD, assistant professor of neurosurgery and director of the stereotactic and mood and sleep disorders, Rachel Manber, PhD, psychiatry and behavioral sciences, is a pioneer functional neurosurgery program at Stanford, is a professor of psychiatry and behavioral Sciences, is in the use of fMRI to reveal how brain activity world expert in using deep brain stimulation and working on improving the treatment of depression differs in healthy people compared with those other minimally invasive surgical techniques to by simultaneously treating depression and suffering from mood and anxiety disorders. He treat depression. insomnia. is developing novel treatments for correcting neural circuit dysfunctions in patients with these disorders.

RALLYING THE RESOURCES TO LEAD What will it take to usher in a new era in the treatment of mood disorders—an era of deeper understanding of the biological and genetic roots of depression and bipolar disorder, wield technologies that enable physician-scientists to see and heal the brain in real time, optimize the effectiveness of current tools, and turn next-frontier ideas into high-impact therapies? It will take innovation and compassion, proven expertise and a constant hunger for new knowledge, and groundbreaking ideas and collaborative spirit. Inspired by the Campaign for Stanford Medicine—and by the enormous potential of research now under way at Stanford—the Stanford Mood Disorders Center is poised to achieve its mission: delivering solutions, cultivating understanding, and transforming lives. CONTACT US For more information, please contact: Deborah Stinchfield Senior Associate Director of Development The Neurosciences Stanford University Medical Center Development 3172 Porter Drive Suite 210 Palo Alto, CA 94304 T 650.725.2504 F 650.725-2450 [email protected] medicalgiving.stanford.edu WPMD0513 printed on recycled paper