THE STANFORD MOOD DISORDERS CENTER Pioneering Solutions for and Bipolar Disorders “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 AND BEHAVIORAL SCIENCES

THE STANFORD MOOD DISORDERS CENTER Pioneering Solutions for Depression and Bipolar Disorders

An estimated 21.4 percent of American adults will experience some form of —depression or MARK ESTES a —in their lifetime. The percentage of adolescents and young adults experiencing depression or anxiety in a given year is increasing dramatically. Yet, mood disorders remain one of the most misunderstood and stigmatized health issues we face. Their impact reverberates far beyond an individual’s life. Families, Alan F. Schatzberg, MD, is founder-director friends, communities, economies—all are affected by of the Stanford Mood Disorders Center. His research focuses on the biological bases these diseases. Depression is a leading cause of disability of depressive disorders, identification of biomarkers, and development of novel phar- worldwide and bipolar disorders rank in the top 20. macologic treatments. His team is exploring Tragically, —often triggered by a mood disorder— biomarkers for suicidal behavior, the role of stress hormones in delusional depression, takes more than one million lives worldwide every year. and developing growth factor analogs as antidepressants. His group published seminal Although the incidence and impact of mood disorders are undeniably on the rise, hope for studies demonstrating that the acute anti- solutions has never been higher. Through the Stanford Mood Disorders Center and Research depressant effects of ketamine are due to Program, scientists and physicians are building on Stanford’s traditions of excellence, healing, effects, opening a search for similar and innovation to build a precision mental health approach to mood disorders. agents with less potential risk of abuse. We 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—we are accelerating the process of translating laboratory discoveries into breakthrough treatments. Through the research programs at the center, Stanford is leading the quest for new knowledge and therapies, expanding and mobilizing diverse expertise toward a powerful, shared mission: to overcome mood disorders through innovation and compassion. NORBERT VON DER GROEBEN VON NORBERT COURTESY OF NOLAN WILLIAMS COURTESY COURTESY OF MANPREET SINGH COURTESY

Manpreet K. Singh, MD, MS, investigates the Leanne Williams, PhD, is developing a precision A dually trained psychiatrist and neurologist, origins and pathways for mood disorders in mental health model for understanding mood Nolan Williams, MD, conducts studies that utilize childhood. Her science is anchored in under- disorders and anxiety as disruptions within novel brain stimulation techniques, psychophar- standing how young people adapt to stress in brain circuits. She has described new subtypes macological approaches, and neuroimaging order to protect and preserve brain function. that translate to more precise diagnoses and methods to develop new models and treatments From socially engaged family-focused interven- treatment tailored to a person’s experience. Her for neuropsychiatric disorders. Among these tions to neuroscience-informed rTMS and digital lab is also engaged in developing a wearable to are major depressive disorder, bipolar disorder, therapeutics, her team strives to position youth characterize mental states quantitatively. , obesity, pain, suicide, and obsessive- to become thriving adults. compulsive disorder.

THE STANFORD ADVANTAGE: AN INTERDISCIPLINARY APPROACH STANFORD MOOD DISORDERS Stanford’s comprehensive, interdisciplinary approach to mood disorders integrates ground- CENTER AT A GLANCE breaking basic science to clinical research with innovative clinical care and training for future An estimated 21.4 percent of U.S. adults experi- physician-scientists. ence a mood disorder at some time in their Faculty members from departments across campus, including some of the most respected lives. More than 14.3 percent of adolescents scientists in the world, take part in research, clinical care, and training programs: experience a mood disorder in any given year. • BIOENGINEERING • NEUROSURGERY • Serving more than 8,000 patients of all • BIOLOGY • PSYCHOLOGY • GENETICS • PSYCHIATRY ages annually • NEUROLOGY • RADIOLOGY • 55-plus clinical trials completed since The Mood Disorders Center leverages this interdisciplinary strength to: center launch

• Understand disease mechanisms through genetics, genomics, and proteomics • More than 200 leading-edge research • Improve imaging techniques that enhance understanding of disease by “looking into the projects underway brain” and monitoring and measuring its functions • 250 medical students trained each year • Pioneer approaches that integrate a deeper understanding of the brain with computational • 230 postdoctoral fellows trained strategies, artificial intelligence, big data, and a diversity of diagnostic and treatment techniques • Build, test, and scale evidence-based digital technology solutions • Undergraduate seminars and courses • Understand the interface of pain, depression, and opiates • Mood Disorders Education Day—an annual community event with talks on the • Leverage pharmacologic, pharmacogenetic, and proteomics approaches to improve outcomes latest advances • Create new therapies using innovative techniques including next-generation drugs, targeted brain stimulation, minimally invasive surgery, and computer-based brain training COURTESY OF MICHAEL OSTACHER MARK TUSCHMAN web-based interventions. exploratory therapeutics, anddevice-based and evidence-based mental health practices including is large-scale clinical trials andimplementation of Research Program. research Hisprimary interest director oftheBipolarDisorder andDepression Michael Ostacher, MD,MPH,MSSc use ofpsychedelicsfor mooddisorders. lineofresearchhas initiated anew exploringthe such as anxiety and . She patients withcomplex, exacerbating conditions treatment approaches, includingstrategies for clinical research optimal focuses ondeveloping the biology and treatment of bipolar disorder. Her Trisha Suppes, MD, PhD , isarecognized experton , is medical

ALEX JOHNSON disorders—the first novel,more step precise, indeveloping and more effective treatments. these studies are unraveling whichcircuits andstructures inthebrain playkeyroles inmood specific regions andcircuits of thebrain. Combinedwith similarpreclinical examinations, One Stanford effort enablesscientists to lookatalarge numberof genes simultaneously in maintain cognitive performance. disorders—for example, byaffecting how our brains respond to stress, modulate mood,or may haveanimpact onmanydifferent functions that can all feed into depression orbipolar be responsible. Wenowknowthatthegenetics ofthesedisorders ismore complex. Genes It was once thoughtthatasinglegenetic alteration inasingleneurotransmitter system may fying genes thatcontribute to treatments. thesedisorders ofnew andon thedevelopment Cornell University, investigators andtheUniversity ofCalifornia atIrvine, are focused onidenti orders andschizophrenia to improve treatment. Inpartnership withtheUniversity ofMichigan, Research Consortium,acollaborative forum established to study theroot causes ofmooddis Since 1996,Stanford hasbeenaninstitutional leader inthePritzker Neuropsychiatric Disorders the mappingofhumangenome overthepast decade. the process ofunraveling theseinteractions techniques usingnoveldiscovery madepossibleby biological orgenetic vulnerability intersects withenvironmental stress. Stanford expertsare in What causes mooddisorders? Scientistsnowunderstand thattheseillnessesoccur when TRACING GENETICROOTS children can alsobeaffected. equally. Althoughtheonset ofthedisorders tends to manifest mostclearly inadulthood, Depression ismore common inwomenwhilebipolardisorders affect menandwomen typically characterized intensity byepisodesofmoodhighsandlows ofvarying andduration. self-destructive thoughts,poorconcentration, andchronic pain. Bipolardisorders are weeks orlonger, includinglowered mood,decreased energy, sleepdisturbances, anxiety, by avariety ofpsychological andphysical signsandsymptoms thatpersist overseveral Cutting awideswath across allcommunities andcultures, majordepression ischaracterized DEFINING DEPRESSION ANDBIPOLAR DISORDERS therapeutics. and new personalization andprediction relevant to current This hasrevealed scalable insightsfor treatment how individualsrespond to various treatments. artificial intelligence methods to understand large data sets using advanced custom-built tion causes psychiatricsymptoms. Heintegrates healthy brain worksandhowabnormalbrain func Amit Etkin,MD,PhD , iselucidatinghowthe -

COURTESY OF CAROLYN RODRIGUEZ compulsive disorder anddepression. for mental severe illnesses,includingobsessive- clinical trialspioneerrapid-acting treatments in moodandanxiety disorders. Herlandmark cidal ideation, andotherperseverative thoughts investigating thebrain basis ofruminations,sui Carolyn Rodriguez, MD,PhD , leads studies - - - compounds inthelaboratory before study in humans. These andotherlandmarkstudies andtools enablescientiststo test novelpharmacologic investigation images, precisely andinreal time,thebrain’s response to antidepressants. hormones affect parts ofthebrain associated depression. withsevere Another novel respond to current therapies. Stillothers are lookingathowcertain activation ofneuronal circuits invarious parts ofthebrain. Others are investigating how Several teams are usingfMRIto explore howchanges inemotionare associated withthe affect mightinfluencethey emotional regulation. explorations withgenetic studies to determine howparticular genes andtheneuronal circuits researchers are lookingathigh-riskchildren ofwomenwithdepression andare combining fMRI region—the subgenual cortex—thought to beassociated withdeepdepression. Other resonance imaging (fMRI)technology thatcan monitor activityinadifficult-to-image brain Among theadvanced atStanford technologies developed isaform offunctional magnetic are diagnosedandtreated. reveal mooddisorders promising atthebiological to level, transform theway brain disorders Stanford isinternationally renowned innovative for exploringanddeveloping technologies that brain? To answerthesequestions,scientistsmustbeableto study thelivingbrain inreal time. the brain are affected bydepression andbipolardisorder? Howdoantidepressants affect the Can stress damage thebrain andmake itmore vulnerable to mood disorders? Whatportions of SEEING ANDHEALINGTHEBRAIN oneormore mooddisorders.developing technologies, thesestudies are revealing cluesasto whichgenes connote increased riskfor samples from more than3,000patients and controls. Usingthelatest ingenetic analytic depression orabipolardisorder. TheBiocollaborative Data Baseofthecenter hasgenetic across generations—collecting data onfamilies inwhichbothadultsandchildren have To explore thegenetic originsofmooddisorders, Stanford isalsoinvestigating thesediseases mood disorders, andcognitive health. relationship between reproductive hormones, Women’s Health, where theteam explores the and the Stanford Center for Neuroscience in the Behavioral Neuroendocrinology Program hormones, stress, andbrain function. Shedirects forefront ofefforts to uncover thelinksbetween Natalie Rasgon, MD,PhD , remains at the

MARK TUSCHMAN obsessive-compulsive disorder. brain addiction,, injury, and in manyconditions includingobesity, traumatic disinhibition. Disinhibition is aclinical feature models of human behavior related to behavioral sive neurostimulation in depression and various the effects ofdeep brain stimulationand respon Neurosurgeon Casey Halpern, MD , investigates -

COURTESY OF CASEY HALPERN focused ultrasound, and augmented-reality TMS. stimulation for impulseandfear-related disorders, stress disorder, closed-loopresponsive neuro- of research trials including for post-traumatic across manydisciplines.Heisactiveinanumber Mahendra Bhati,MD neuropsychiatry, As sectionchiefofinterventional through thecenter. experimental psychology—allreceive training data science, physics, endocrinology, and cognitive neuroscience, bioengineering, basicdisciplines—including neuroscience, Postdoctoral fellows representing diverse the inpatient unitandspecialtyclinics. advanced clinical fellows rotate through in psychiatricdisorders. Residents and students, fostering acareer-long interest The mentorship continues withmedical in multiplemajors, includingpsychology. Center facultywork. teach undergraduates Disorders Center’s innovative, collaborative and neuroscientists to continue theMood tomorrow’s psychologists,psychiatrists, Stanford iswellpositionedto prepare graduate, andpostgraduate programs, With itshighlyregarded undergraduate, NEXT-GENERATION TRAINING , isbuildingcollaborations

COURTESY OF MAHENDRA BAHTI MARK ESTES depression andbipolardisorders. both adultandchildoutpatient clinicsfor and outpatient andoperate services, standard ofclinical care, weoffer inpatient programs Deliveringthehighest inpsychiatry. oneofthepremier clinicalhas developed Health Care andStanford Children’s Health and Behavioral Sciences withStanford The Stanford Department ofPsychiatry LEADING CLINICALCARE ity to experience . symptom ofdepression—anhedonia, theinabil identified apotential target for treating amajor use modifythefunction ofbrain synapses.He mechanisms bywhichstressful ordrug events is aworldleader instudying themolecular of mood disorders. a critical andtreatment role inthedevelopment Modifications inthebrain’s play reward circuitry Robert Malenka, MD,PhD - ,

STEVE FISCH PHOTOGRAPHY childhood andtheoptimalstrategy for treating patients atrisk. states. Manpreet Singh,MD,MS, isexploringtherelative riskofconverting to bipolardisorder in a bipolardisorder.developing Antidepressants can be helpful butcan alsoprecipitate excited Children withsignificant depression andwho haveabipolarparent are atparticular riskfor the riskofsideeffects. techniques to explore riskfactors ofthesecomplications for thedevelopment andto reduce Rasgon, MD,PhD,theRasgon team iscombining novelbrain imagingandendocrinology resistance and diabetes. Incollaboration withanationalresearch network ledbyNatalie relief to patients. However, somecommonly usedmedications are associated withinsulin Bipolar disorders often require a combination ofmoodstabilizers andantidepressants to bring markers to guidetreatment selectionfor individualpatients. available genetic tests to selecttreatment. Ourresearchers continue to explore othergenetic responses to specificantidepressants andseveral ofthesehavebeenincorporated into Stanford scientistshavedescribedanumberofgenetic tests that can beusedto predict antidepressants andwhether improvement could bevisualized through brain imaging. based agent nowusedfor restless leg syndrome mightimprove apatient’s response to rapidly actingopioidagents such asketamine. Onenovelstudy looked athowadopamine- depression andto suicide.Other researchers prevent are exploringthepotential properties of One group ofinvestigators isapplyingaform ofpsychotherapy for insomniato improve treatments new developing thatare more effective orbetter tolerated. approaches new as welldevelop to boosttheeffectiveness ofthesetherapies. are also They Stanford scientistsactivelyexplore whichstrategies are mostsuccessful andfor whichperson, brain, andpsychotherapy aloneorincombination to treat patients withmooddisorders. Psychiatrists today rely onpharmacologic agents, devices thatmodulate andstimulate the IMPROVING OUTCOMES FOR TODAY’S PATIENTS foster collaboration. increase of clinical the efficiency research and a powerful pooleddatabase to catalyze and helping to shapethecenter’s BioCollaborative, the identityofneurobiological difference. Heis social processes and biomedical research on ethics, exploringthereciprocal influences of in neurodevelopmental disorders, genetics, and Joachim Hallmayer, MD, PhD , brings expertise , bringsexpertise

STEVE FISCH PHOTOGRAPHY scientists from around the world in these tech are revealing howbrain Hislabtrains circuits work. optogenetics, CLARITY, STARmap, andCOSMOS, molecularandcellular tools,tionary including work andhisresearch innovations. Hisrevolu MD, PhD A psychiatrist and bioengineer, therapies for brain disorders. of theniques, larger in service quest for targeted , bringsbothperspectives to hisclinical Karl Deisseroth, - - MARK ESTES COURTESY OF PO WANG COURTESY COURTESY OF REBECCA BERNERT OF REBECCA COURTESY

Rebecca Bernert, PhD, focuses on the iden- Po Wang, MD, is chief of the Bipolar Clinic where Depression Research Clinic Co-directors Brent tification of rapid, low-risk therapeutic targets he spearheads the clinical and research programs. Solvason, MD, PhD, (L) and Charles DeBattista, for suicide prevention, including sleep, physical The team focuses on the diagnosis and clini- MD, DMH, (R) share research and clinical interests barriers, policy, and education. Her overarching cal management of bipolar disorders and co- that include treatment of refractory depression, goal is to harness new technologies within sui- occurring conditions, and managing a portfolio novel clinical and augmentation strategies, cide prevention, including artificial intelligence of clinical trials and neuroimaging studies that and the neurobiology of mood disorders. They and mobile health applications, to enhance risk include longitudinal monitoring, novel treatments, explore strategies that augment treatment and detection. and comparative effectiveness. apply exploratory therapeutics such as rTMS and psychedelic agents in severe mood disorders where traditional approaches alone are not sufficient. Dr. DeBattista is the Stanford lead investigator on a multi-site international study to assess the safety and efficacy of psilocybin in refractory depression. CREATING NEW THERAPIES Although most people with mood disorders eventually respond to treatment, many must try several therapies before they find one (or a combination) that works, and some therapies are associated with considerable side effects. To usher in a new era of mood disorders care— more effective, faster acting, better tolerated—Stanford is taking the lead in developing groundbreaking treatment approaches. Stanford is a pioneer in the development of repetitive Transcranial Magnetic Brain Stimulation (rTMS) and has both active clinical and research programs. This noninvasive therapy is now being extended to studies in children and adolescents by Stanford researchers. Nolan A NATIONAL NETWORK Williams, MD, has developed a novel, more focused and intense form of accelerated theta OF EXCELLENCE burst rTMS to provide both more efficacy and more rapid response. Amit Etkin, MD, PhD, Advancing faster through breakthrough is exploring brain circuits using rTMS and other techniques to reveal the role specific brain collaborations, our faculty are founders, circuits play in and treatment response. Leanne Williams, PhD, is elucidating how patterns of brain activity, determined by using magnetic resonance imaging, can be used leaders, and contributing members of a to subtype patients in order to guide clinicians in selecting optimal treatment more quickly. number of national networks including the Development of new drugs represents a challenging and important frontier in the treatment of National Network of Depression Centers, mood disorders—an area Stanford is actively pioneering. For example, measurement of gene the Pritzker Consortium, the Mental Health activation in the brain is laying the groundwork for new targets for medications that affect Technology Transfer Center Network, and the specific systems in the brain. A possible innovative drug treatment based on these studies has international Psychopathology and Allostatic been identified and can now be studied in people. Researchers are attempting to understand Load across the Life Span (PALS) Network. ketamine’s mechanism of action to design safer and more durable drug strategies. The Stanford Biocollaborative’s repository of genetic data can help investigators understand how These networks share a commitment genetic variation relates to specific symptoms and provides clues for novel drug development. to propel and disseminate advances in These research examples represent just some of the strategies that Stanford clinicians and treatment, research, and training related to scientists are exploring. depressive, bipolar, and related disorders. “ MARK ESTES treatment interventions, and our our and interventions, treatment from this source of human suffer finest education and policy depression inchildren atrisk. methods withthegoal to ultimately prevent terization withbrain imaging(fMRI)andtesting disorder. Hisstudies combine genetic charac thought to beatincreased the riskofdeveloping in children of mothers with depression, who are Ian Gotlib, PhD solutions, cultivates understanding, understanding, cultivates solutions, knowledge that leads to true ing. Join with us to generate most effective prevention and by mood disorders need our most and transforms lives. transforms and efforts. efforts. We cannot turn away our science, valuable and creative People whose lives are governed whose lives are governed People , explores emotional processing STANLEY MCCORMICK CHAIR, DEPARTMENT OF BEHAVIORAL SCIENCES PSYCHIATRY AND MEMORIAL PROFESSOR MCCORMICK AND KATHARINE DEXTER Laura Roberts, MD,MA ”

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COURTESY OF RACHEL MANBER medicalgiving.stanford.edu 650.725.2504 Stanford Medical Center Development [email protected] Philanthropic Advisorfor andBehavioral Psychiatry Sciences Deborah Stinchfield PHILANTHROPY PATIENT INQUIRIES CREATE IMPACT Make adifference inthe lives ofthosewithmooddisorders. • • • • • understanding, andtransform lives.Joinwithusandaccelerate ourefforts to: ourmissionto deliversolutions,cultivate wewillachieve With yourphilanthropic support, expertise mixed with compassion. knowledge andgroundbreaking ideas, acollaborative andinnovativeproven spirit, Leading era anew in thetreatment ofmooddisorders takes aconstant hunger for new RALLYING THERESOURCES TO LEAD of otherdisorders, includingmooddisorders. experience their sleep difficulties in the context and specializes in treating those who pioneer incognitive behavioral therapy for treating depression andinsomnia.Sheisa the treatment of depression by simultaneously medicine scientistspecializinginimproving Rachel Manber, PhD

Empower patients, families, andthepublicto create abetter worldfor thosewithmood train,Recruit, andfund thenextgeneration ofcliniciansandscientists Fuel novel,potentially high-yieldendeavors through innovation awards Fund boldventures thatlinkbasic, translational, andclinical sciences disciplinesto withnew Secure andretain innovators andcatalysts through endowedprofessorships andproject- or disorders rapidly improve thepatient experience investigator-specific funding | [email protected]

| For questionsorapersonalized conversation, contact:

| Please call 650.498.9111 , isabehavioral sleep | med.stanford.edu/psychiatry.html

COURTESY OF RUTH O’HARA impact ofcognitive impairment inlate-life and sleepdysfunction, inorder to reduce the investigate psychologicandphysiologicstress imaging, stem cell, andgenetic approaches to tive abilitiesanddepression. Sheusesneuro to thestudy oftherelationship between cogni Ruth O’Hara, PhD psychiatric disorders.

, employs a life-span approach - -

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