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Research on Depression By James Hunter & NIMH

Depression is a serious mental health concern that will touch most people's lives at some point in their lifetime (either directly or throu h someone close they !now"# $he sufferin endured %y people with depression and the lives lost to suicide attest to the reat %urden of this disorder on individuals& families& and society# Improved reco nition& treatment& and prevention of depression are critical pu%lic health priorities# 'r ani(ations such as the National Institute of Mental Health (NIMH"& one of the world's leadin mental health %iomedical or ani(ations& conducts and supports research on the causes& dia nosis& prevention& and treatment of depression in the )nited *tates#

+vidence from neuroscience& enetics& and clinical investi ation demonstrate that depression is a disorder of the %rain# Modern %rain ima in technolo ies are revealin that in depression& neural circuits responsi%le for the re ulation of moods& thin!in & sleep& appetite& and %ehavior fail to function properly& and that critical neurotransmitters ,, chemicals used %y nerve cells to communicate ,, are perhaps out of %alance# -enetics research indicates that vulnera%ility to depression results from the influence of multiple

enes actin to ether with environmental factors# *tudies of %rain chemistry and of mechanisms of action of antidepressant medications continue to inform the development of new and %etter medical and psychotherapy treatments#

.ant to !eep up,to,date/ *u%scri%e to our R** depression news and research feed or our depression article R** feed today# In the past decade& there have %een si nificant advances in our a%ility to investi ate %rain function at multiple levels# $he NIMH is colla%oratin with various scientific disciplines to effectively utili(e the tools of molecular and cellular %iolo y& enetics& epidemiolo y& and co nitive and %ehavioral science to ain a more thorou h and comprehensive understandin of the factors that influence %rain function and %ehavior& includin mental illness# $his colla%oration reflects the Institute's increasin focus on 0translational research&0 where%y %asic and clinical scientists are involved in 1oint efforts to translate discoveries and !nowled e into clinically relevant 2uestions and tar ets of research opportunity# $ranslational research holds reat promise for disentan lin the comple3 causes of depression and other mental disorders and for advancin the development of more effective treatments#

*ymptoms and $ypes of Depression *ymptoms of depression include a persistent sad mood4 loss of interest or pleasure in activities that were once en1oyed4 si nificant chan e in appetite or %ody wei ht4 difficulty sleepin or oversleepin 4 physical slowin or a itation4 loss of ener y4 feelin s of worthlessness or inappropriate uilt4 difficulty thin!in or concentratin 4 and recurrent thou hts of death or suicide# 5 dia nosis of ma1or depressive disorder (or unipolar ma1or depression" is made if an individual has five or more of these symptoms durin the same two,wee! period# )nipolar ma1or depression typically presents in discrete episodes that recur durin a person's lifetime#

Bipolar disorder (or manic,depressive illness" is characteri(ed %y episodes of ma1or depression as well as episodes of mania ,, periods of a%normally and persistently elevated mood or irrita%ility accompanied %y at least three of the followin symptoms6 overly,inflated self,esteem4 decreased need for sleep4 increased tal!ativeness4 racin thou hts4 distracti%ility4 increased oal,directed activity or physical a itation4 and e3cessive involvement in pleasura%le activities that have a hi h potential for painful conse2uences# .hile sharin some of the features of ma1or depression& %ipolar disorder is a different illness that is discussed in detail in a separate NIMH pu%lication#

Dysthymic disorder (or dysthymia"& a less severe yet typically more chronic form of depression& is dia nosed when depressed mood persists for at least two years in adults (one year in children or adolescents" and is accompanied %y at least two other depressive symptoms# Many people with dysthymic disorder also e3perience ma1or depressive episodes# .hile unipolar ma1or depression and dysthymia are the primary forms of depression& a variety of other su%types e3ist#

In contrast to the normal emotional e3periences of sadness& loss& or passin mood states& depression is e3treme and persistent and can interfere si nificantly with an individual's a%ility to function# In fact& a recent study sponsored %y the .orld Health 'r ani(ation and the .orld Ban! found unipolar ma1or depression to %e the leadin cause of disa%ility in the )nited *tates and worldwide#

$here is a hi h de ree of variation amon people with depression in terms of symptoms& course of illness& and response to treatment& indicatin that depression may have a num%er of comple3 and interactin causes# $his varia%ility poses a ma1or challen e to researchers attemptin to understand and treat the disorder# However& recent advances in research technolo y are %rin in NIMH scientists closer than ever %efore to characteri(in the %iolo y and physiolo y of depression in its different forms and to the possi%ility of identifyin effective treatments for individuals %ased on symptom presentation#

7iew open Research *tudies Recruitin 8eople for Depression Research 'ne of the most challen in pro%lems in depression research and clinical practice is refractory ,, hard to treat ,, depression# .hile appro3imately 9: percent of people with depression respond very positively to treatment& a si nificant num%er of individuals remain treatment refractory# +ven amon treatment responders& many do not have complete or lastin improvement& and adverse side effects are common# $hus& an important oal of NIMH research is to advance the development of more effective treatments for depression ,, especially treatment,refractory depression ,, that also have fewer side effects than currently availa%le treatments#

Research on $reatments for Depression Medication

*tudies on the mechanisms of action of antidepressant medication comprise an important area of NIMH depression research# +3istin antidepressant dru s are !nown to influence the functionin of certain neurotransmitters in the %rain& primarily serotonin and norepinephrine& !nown as monoamines# 'lder medications ,, tricyclic antidepressants ($;5s" and

monoamine o3idase inhi%itors (M5'Is" ,, affect the activity of %oth of these neurotransmitters simultaneously# $heir disadvanta e is that they can %e difficult to tolerate due to side effects or& in the case of M5'Is& dietary restrictions# Newer medications& such as the selective serotonin reupta!e inhi%itors (**RIs"& have fewer side effects than the older dru s& ma!in it easier for patients to adhere to treatment# Both enerations of medications are effective in relievin depression& althou h some people will respond to one type of dru & %ut not another#

5ntidepressant medications ta!e several wee!s to %e clinically effective even thou h they %e in to alter %rain chemistry with the very first dose# Research now indicates that antidepressant effects result from slow,onset adaptive chan es within the %rain cells& or neurons# <urther& it appears that activation of chemical messen er pathways within neurons& and chan es in the way that enes in %rain cells are e3pressed& are the critical events underlyin lon ,term adaptations in neuronal function relevant to antidepressant dru action# 5 current challen e is to understand the mechanisms that mediate& within cells& the lon , term chan es in neuronal function produced %y antidepressants and other psychotropic dru s and to understand how these mechanisms are altered in the presence of illness#

=nowin how and where in the %rain antidepressants wor! can aid the development of more tar eted and potent medications that may help reduce the time %etween first dose and clinical response# <urther& clarifyin the mechanisms of action can reveal how different dru s produce side effects and can uide the desi n of new& more tolera%le& treatments#

5s one route toward learnin a%out the distinct %iolo ical processes that o awry in different forms of depression& NIMH researchers are investi atin the differential effectiveness of various antidepressant medications in people with particular su%types of depression# <or e3ample& this research has revealed that people with atypical depression& a su%type characteri(ed %y reactivity of mood (mood %ri htens in response to positive events" and at least two other symptoms (wei ht ain or increased appetite& oversleepin & intense fati ue& or re1ection sensitivity"& respond %etter to treatment with M5'Is& and perhaps with **RIs than with $;5s#

Many patients and clinicians find that com%inations of different dru s wor! most effectively for treatin depression& either %y enhancin the therapeutic action or reducin side effects# 5lthou h com%ination strate ies are used often in clinical practice& there is little research evidence availa%le to uide psychiatrists in prescri%in appropriate com%ination treatment# NIMH is in the process of revitali(in and e3pandin its pro ram of clinical research& and com%ination therapy will %e %ut one of numerous treatment interventions to %e e3plored and developed#

)ntreated depression often has an acceleratin course& in which episodes %ecome more fre2uent and severe over time# Researchers are now considerin whether early intervention with medications and maintenance treatment durin well periods will prevent recurrence of episodes# $o date& there is no evidence of any adverse effects of lon ,term antidepressant use#

8sychotherapy

>i!e the process of learnin & which involves the formation of new connections %etween nerve cells in the %rain& psychotherapy wor!s %y chan in the way the %rain functions# NIMH research has shown that certain types of psychotherapy& particularly co nitive,%ehavioral therapy (;B$" and interpersonal therapy (I8$"& can help relieve depression# ;B$ helps patients chan e the ne ative styles of thin!in and %ehavin often associated with depression# I8$ focuses on wor!in throu h distur%ed personal relationships that may contri%ute to depression#

Research on children and adolescents with depression supports ;B$ as a useful initial treatment& %ut antidepressant medication is indicated for those with severe& recurrent& or psychotic depression# *tudies of adults have shown that while psychotherapy alone is rarely sufficient to treat moderate to severe depression& it may provide additional relief in com%ination with antidepressant medication# In one recent NIMH,funded study& older adults with recurrent ma1or depression who received I8$ in com%ination with an antidepressant medication durin a three,year period were much less li!ely to e3perience a recurrence of illness than those who received medication only or therapy only# <or mild depression& however& a recent analysis of multiple studies indicated that com%ination treatment is not si nificantly more effective than ;B$ or I8$ alone#

8reliminary evidence from an on oin NIMH,supported study indicates that I8$ may hold promise in the treatment of dysthymia#

+lectroconvulsive $herapy (+;$"

+lectroconvulsive therapy (+;$" remains one of the most effective yet most sti mati(ed treatments for depression# +i hty to ninety percent of people with severe depression improve dramatically with +;$# +;$ involves producin a sei(ure in the %rain of a patient under eneral anesthesia %y applyin electrical stimulation to the %rain throu h electrodes placed on the scalp# Repeated treatments are necessary to achieve the most complete antidepressant response# Memory loss and other co nitive pro%lems are common& yet typically short,lived side effects of +;$# 5lthou h some people report lastin difficulties&

modern advances in +;$ techni2ue have reatly reduced the side effects of this treatment compared to earlier decades# NIMH research on +;$ has found that the dose of electricity applied and the placement of electrodes (unilateral or %ilateral" can influence the de ree of depression relief and the severity of side effects#

5 current research 2uestion is how %est to maintain the %enefits of +;$ over time# 5lthou h +;$ can %e very effective for relievin acute depression& there is a hi h rate of relapse when the treatments are discontinued# NIMH is currently sponsorin two multicenter studies on +;$ follow,up treatment strate ies# 'ne study is comparin different medication treatments& and the other study is comparin maintenance medication to maintenance +;$# Results from these studies will help uide and improve follow,up treatment plans for patients who respond well to +;$#

-enetics Research Research on the enetics of depression and other mental illnesses is a priority of NIMH and constitutes a critical component of the Institute's multi,level research effort# Researchers are increasin ly certain that enes play an important role in vulnera%ility to depression and other severe mental disorders#

In recent years& the search for a sin le& defective ene responsi%le for each mental illness has iven way to the understandin that multiple ene variants& actin to ether with yet un!nown environmental ris! factors or developmental events& account for the e3pression of psychiatric disorders# Identification of these enes& each of which contri%utes only a small effect& has proven e3tremely difficult#

However& new technolo ies& which continue to %e developed and refined& are %e innin to allow researchers to associate enetic variations with disease& such as unravelin the human enome#

*tress and Depression 8sychosocial and environmental stressors are !nown ris! factors for depression# NIMH research has shown that stress in the form of loss& especially death of close family mem%ers or friends& can tri er depression in vulnera%le individuals# -enetics research indicates that environmental stressors interact with depression vulnera%ility enes to increase the ris! of developin depressive illness# *tressful life events may contri%ute to recurrent episodes of depression in some individuals& while in others depression recurrences may develop without identifia%le tri ers#

'ther NIMH research indicates that stressors in the form of social isolation or early,life deprivation may lead to permanent chan es in %rain function that increase suscepti%ility to depressive symptoms#

Brain Ima in Recent advances in %rain ima in technolo ies are allowin scientists to e3amine the %rain in livin people with more clarity than ever %efore# <unctional ma netic resonance ima in (fMRI"& a safe& noninvasive method for viewin %rain structure and function simultaneously& is one new techni2ue that NIMH researchers are usin to study the %rains of individuals with and without mental disorders# $his techni2ue will ena%le scientists to evaluate the effects of a variety of treatments on the %rain and to associate these effects with clinical outcome#

Brain ima in findin s may help direct the search for microscopic a%normalities in %rain structure and function responsi%le for mental disorders# )ltimately& ima in technolo ies may serve as tools for early dia nosis and su%typin of depression and other mental disorders& thus advancin the development of new treatments and evaluation of their effects#

Hormonal 5%normalities $he hormonal system that re ulates the %ody's response to stress& the hypothalamic, pituitary,adrenal (H85" a3is& is overactive in many patients with depression& and NIMH researchers are investi atin whether this phenomenon contri%utes to the development of the illness#

$he hypothalamus& the %rain re ion responsi%le for mana in hormone release from lands throu hout the %ody& increases production of a su%stance called corticotropin releasin factor (;R<" when a threat to physical or psycholo ical well,%ein is detected# +levated levels and effects of ;R< lead to increased hormone secretion %y the pituitary and adrenal lands which prepares the %ody for defensive action# $he %ody's responses include reduced appetite& decreased se3 drive& and hei htened alertness# NIMH research su ests that persistent overactivation of this hormonal system may lay the roundwor! for depression# $he elevated ;R< levels detecta%le in depressed patients are reduced %y treatment with antidepressant dru s or +;$& and this reduction corresponds to improvement in depressive symptoms#

NIMH scientists are investi atin how and whether the hormonal research findin s fit to ether with the discoveries from enetics research and monoamine studies#

;o,occurrence of Depression and 5n3iety Disorders

NIMH research has revealed that depression often co,e3ists with an3iety disorders (panic disorder& o%sessive,compulsive disorder& post,traumatic stress disorder& social pho%ia& or enerali(ed an3iety disorder"# In such cases& it is important that depression and each co, occurrin illness %e dia nosed and treated#

*everal studies have shown an increased ris! of suicide attempts in people with co, occurrin depression and panic disorder ,, the an3iety disorder characteri(ed %y une3pected and repeated episodes of intense fear and physical symptoms& includin chest pain& di((iness& and shortness of %reath#

Rates of depression are especially hi h in people with post,traumatic stress disorder (8$*D"& a de%ilitatin condition that can occur after e3posure to a terrifyin event or ordeal in which rave physical harm occurred or was threatened# In one study supported %y NIMH& more than ?: percent of patients with 8$*D had depression when evaluated %oth at one month and four months followin the traumatic event#

;o,occurrence of Depression and 'ther Illnesses Depression fre2uently co,occurs with a variety of other physical illnesses& includin heart disease& stro!e& cancer& and dia%etes& and also can increase the ris! for su%se2uent physical illness& disa%ility& and premature death# Depression in the conte3t of physical illness& however& is often unreco ni(ed and untreated# <urthermore& depression can impair the a%ility to see! and stay on treatment for other medical illnesses# NIMH research su ests that early dia nosis and treatment of depression in patients with other physical illnesses may help improve overall health outcome#

$he results of a recent NIMH,supported study provide the stron est evidence to date that depression increases the ris! of havin a future heart attac!# 5nalysis of data from a lar e, scale survey revealed that individuals with a history of ma1or depression were more than four times as li!ely to suffer a heart attac! over a @A,@B year follow,up period& compared to people without such a history# +ven people with a history of two or more wee!s of mild depression were more than twice as li!ely to have a heart attac!& compared to those who had had no such episodes# 5lthou h associations were found %etween certain psychotropic medications and heart attac! ris!& the researchers determined that the associations were simply a reflection of the primary relationship %etween depression and heart trou%le# $he 2uestion of whether treatment for depression reduces the e3cess ris! of heart attac! in depressed patients must %e addressed with further research#

NIMH is plannin to present a ma1or conference with other NIH Institutes on depression and co,occurrin illnesses# $he outcomes of this conference will uide NIMH investi ation of depression %oth as a contri%utin factor to other medical illnesses and as a result of these illnesses#

.omen and Depression Nearly twice as many women (@A percent" as men (C percent" are affected %y a depressive illness each year# 5t some point durin their lives& as many as A: percent of women have at least one episode of depression that should %e treated# 5lthou h conventional wisdom holds that depression is most closely associated with menopause& in fact& the child%earin years are mar!ed %y the hi hest rates of depression& followed %y the years prior to menopause#

NIMH researchers are investi atin the causes and treatment of depressive disorders in women# 'ne area of research focuses on life stress and depression# Data from a recent NIMH,supported study su ests that stressful life e3periences may play a lar er role in provo!in recurrent episodes of depression in women than in men#

$he influence of hormones on depression in women has %een an active area of NIMH research# 'ne recent study was the first to demonstrate that the trou%lesome depressive mood swin s and physical symptoms of premenstrual syndrome (8M*"& a disorder affectin three to seven percent of menstruatin women& result from an a%normal response to normal hormone chan es durin the menstrual cycle# 5mon women with normal menstrual cycles& those with a history of 8M* e3perienced relief from mood and physical symptoms when their se3 hormones& estro en and pro esterone& were temporarily 0turned off0 %y administerin a dru that suppresses the function of the ovaries# 8M* symptoms developed within a wee! or two after the hormones were re,introduced# In contrast& women without a history of 8M* reported no effects of the hormonal manipulation# $he study showed that female se3 hormones do not cause 8M*# Rather& they tri er 8M* symptoms in women with a pree3istin vulnera%ility to the disorder# $he researchers currently are attemptin to determine what ma!es some women %ut not others suscepti%le to 8M*# 8ossi%ilities include enetic differences in hormone sensitivity at the cellular level& differences in history of other mood disorders& and individual differences in serotonin function#

NIMH researchers also are currently investi atin the mechanisms that contri%ute to depression after child%irth (postpartum depression"& another serious disorder where a%rupt hormonal shifts in the conte3t of intense psychosocial stress disa%le some women with an apparent underlyin vulnera%ility# In addition& an on oin NIMH clinical trial is evaluatin the use of antidepressant medication followin delivery to prevent postpartum depression in women with a history of this disorder after a previous child%irth#

;hild and 5dolescent Depression >ar e,scale research studies have reported that up to A#D percent of children and up to 9#B percent of adolescents in the )nited *tates suffer from depression# In addition& research has discovered that depression onset is occurrin earlier in individuals %orn in more recent decades# $here is evidence that depression emer in early in life often persists& recurs& and continues into adulthood& and that early onset depression may predict more severe illness in adult life# Dia nosin and treatin children and adolescents with depression is critical to prevent impairment in academic& social& emotional& and %ehavioral functionin and to allow children to live up to their full potential#

Research on the dia nosis and treatment of mental disorders in children and adolescents& however& has la ed %ehind that in adults# Dia nosin depression in these a e roups is often difficult %ecause early symptoms can %e hard to detect or may %e attri%uted to other causes# In addition& treatin depression in children and adolescents remains a challen e& %ecause few studies have esta%lished the safety and efficacy of treatments for depression in youth# ;hildren and adolescents are oin throu h rapid& a e,related chan es in their physiolo ical states& and there remains much to %e learned a%out %rain development durin the early years of life %efore treatments for depression in youn people will %e as successful as they are in older people# NIMH is pursuin %rain,ima in research in children and adolescents to ather information a%out normal %rain development and what oes wron in mental illness#

Depression in children and adolescents is associated with an increased ris! of suicidal %ehaviors# 'ver the last several decades& the suicide rate in youn people has increased dramatically# In A::E& the most recent year for which statistics are availa%le& suicide was the third leadin cause of death in @D,A? year olds and the fourth leadin cause amon @:,@? year olds# NIMH researchers are developin and testin various interventions to prevent suicide in children and adolescents# However& early dia nosis and treatment of depression and other mental disorders& and accurate evaluation of suicidal thin!in & possi%ly hold the reatest suicide prevention value#

)ntil recently& there were limited data on the safety and efficacy of antidepressant medications in children and adolescents# $he use of antidepressants in this a e roup was %ased on adult standards of treatment# 5 recent NIMH,funded study supported fluo3etine& an **RI& as a safe and efficacious medication for child and adolescent depression# $he response rate was not as hi h as in adults& however& emphasi(in the need for continued research on e3istin treatments and for development of more effective treatments& includin psychotherapies desi ned specifically for children# 'ther complementary studies in the field are %e innin to report similar positive findin s in depressed youn people treated with any of several newer antidepressants# In a num%er of studies& $;5s were found to %e ineffective for treatin depression in children and adolescents& %ut limitations of the study desi ns preclude stron conclusions#

'lder 5dults and Depression In a iven year& %etween one and two percent of people over a e FD livin in the community& i#e#& not livin in nursin homes or other institutions& suffer from ma1or depression and a%out two percent have dysthymia# Depression& however& is not a normal part of a in # Research has clearly demonstrated the importance of dia nosin and treatin depression in older persons# Because ma1or depression is typically a recurrent disorder& relapse prevention is a hi h priority for treatment research# 5s noted previously& a recent NIMH,supported study esta%lished the efficacy of com%ined antidepressant medication and interpersonal psychotherapy in reducin depressive relapses in older adults who had recovered from an episode of depression#

5dditionally& recent NIMH studies show that @B to AC percent of older adults have su%clinical depressions that do not meet the dia nostic criteria for ma1or depression or dysthymia %ut are associated with increased ris! of ma1or depression& physical disa%ility& medical illness& and hi h use of health services# *u%clinical depressions cause considera%le sufferin & and some clinicians are now %e innin to reco ni(e and treat them#

*uicide is more common amon the elderly than in any other a e roup# NIMH research has shown that nearly all people who commit suicide have a dia nosa%le mental or su%stance a%use disorder# In studies of older adults who committed suicide& nearly all had ma1or depression& typically a first episode& thou h very few had a su%stance a%use disorder# *uicide amon white males a ed 9D and older was nearly si3 times the national )#*# rate (FD per @::&::: compared with @@ per @::&:::" in A::E& the most recent year for which statistics are availa%le# 8revention of suicide in older adults is a hi h priority area in the NIMH prevention research portfolio#

5lternative Depression $reatments $here is hi h pu%lic interest in her%al remedies for various medical conditions includin depression# 5mon the her%als is hypericum or *t# John's wort& promoted as havin antidepressant effects# 5dverse dru interactions have %een reported %etween *t# John's wort and dru s used to treat HI7 infections as well as those used to reduce the ris! of or an transplant re1ection# In eneral& preparations of *t# John's wort vary si nificantly#

$he National Institutes of Health conducted a clinical trial to determine the effectiveness of treatin adults who have ma1or depression with *t# Johns wort# $he study included B?: people dia nosed with ma1or depression# 'ne,third of the people too! the her%al medicine& one,third too! an **RI& and one,third too! a place%o& or 0su ar pill#0 $he people did not !now what they were ta!in # $he study found that *t# John's wort was no more effective than the place%o in treatin ma1or depression#

Research studies conducted in other +uropean countries have come to completely different conclusions& however# 5 ;ochrane Review ,, considered the old standard in analy(in the outcomes of research ,, found& 0$he availa%le evidence su ests that the hypericum e3tracts tested in the included trials a" are superior to place%o in patients with ma1or depression4 %" are similarly effective as standard antidepressants4 c" and have fewer side effects than standard antidepressants#0 In other words& in their review& they found si nificant evidence to su est that the use of *t# John's wort is appropriate and effective in the treatment of depression#

$he <uture of Depression Research Research on the causes& treatment& and prevention of all forms of depression will remain a hi h NIMH priority for the foreseea%le future# 5reas of interest and opportunity include the followin 6

NIMH researchers will see! to identify distinct su%types of depression characteri(ed %y various features includin enetic ris!& course of illness& and clinical symptoms# $he aims of this research will %e to enhance clinical prediction of onset& recurrence& and co,occurrin illness4 to identify the influence of environmental stressors in people with enetic vulnera%ility for ma1or depression4 and to prevent the development of co,occurrin physical illnesses and su%stance use disorders in people with primary recurrent depression# Because many adult mental disorders ori inate in childhood& studies of development over time that uncover the comple3 interactions amon psycholo ical& social& and %iolo ical events are needed to trac! the persistence& chronicity& and pathways into and out of disorders in childhood and adolescence# Information a%out %ehavioral continuities that may e3ist %etween specific dimensions of child temperament and child mental disorder& includin depression& may ma!e it possi%le to ward off adult psychiatric disorders# Recent research on thou ht processes that has provided insi hts into the nature and causes of mental illness creates opportunities for improvin prevention and treatment# 5mon the important findin s of this research is evidence that points to the role of ne ative attentional and memory %iases ,, selective attention to and memory of ne ative information ,, in producin and sustainin depression and an3iety# <uture studies are needed to o%tain a more precise account of the content and life course development of these %iases& includin their interaction with social and emotional processes& and their neural influences and effects# 5dvances in neuro%iolo y and %rain ima in technolo y now ma!e it possi%le to see clearer lin!a es %etween research findin s from different domains of emotion and mood# *uch 0maps0 of depression will inform understandin of %rain development& effective treatments& and the %asis for depression in children and adults# In adult populations& chartin physiolo ical chan es involved in emotion durin a in will shed li ht on mood disorders in the elderly& as well as the psycholo ical and physiolo ical effects of %ereavement#

5n important lon ,term oal of NIMH depression research is to identify simple %iolo ical mar!ers of depression that& for e3ample& could %e detected in %lood or with %rain ima in # In theory& %iolo ical mar!ers would reveal the specific depression profile of each patient and would allow psychiatrists to select treatments !nown to %e most effective for each profile# 5lthou h such data,driven interventions can only %e ima ined today& NIMH already is investin in multiple research strate ies to lay the roundwor! for tomorrow's discoveries# $he Broad NIMH Research 8ro ram

In addition to studyin depression& NIMH supports and conducts a %road %ased& multidisciplinary pro ram of scientific in2uiry aimed at improvin the dia nosis& prevention& and treatment of other mental disorders# $hese conditions include %ipolar disorder& clinical depression& and schi(ophrenia#

Increasin ly& the pu%lic as well as health care professionals are reco ni(in these disorders as real and treata%le medical illnesses of the %rain# *till& more research is needed to e3amine in reater depth the relationships amon enetic& %ehavioral& developmental& social and other factors to find the causes of these illnesses# NIMH is meetin this need throu h a series of research initiatives#

NIMH Human -enetics Initiative $his pro1ect has compiled the world's lar est re istry of families affected %y schi(ophrenia& %ipolar disorder& and 5l(heimer's disease# *cientists are a%le to e3amine the enetic material of these family mem%ers with the aim of pinpointin enes involved in the diseases#

Human Brain 8ro1ect $his multi,a ency effort is usin state,of,the,art computer science technolo ies to or ani(e the immense amount of data %ein enerated throu h neuroscience and related disciplines& and to ma!e this information readily accessi%le for simultaneous study %y interested researchers#

8revention Research Initiative 8revention efforts see! to understand the development and e3pression of mental illness throu hout life so that appropriate interventions can %e found and applied at multiple points durin the course of illness# Recent advances in %iomedical& %ehavioral& and co nitive sciences have led NIMH to formulate a new plan that marries these sciences to prevention efforts#

.hile the definition of prevention will %roaden& the aims of research will %ecome more precise and tar eted#

In total& NIMH supports more than A&::: research rants and contracts at universities and other institutions across the nation and overseas# It also conducts %asic research and clinical studies involvin E&::: patient visits per year at its own facilities on the National Institutes of Health campus in Bethesda& MD& and elsewhere# $he NIMH %ud et is appro3imately G@#D %illion in <H A:@:#