Behavioral Neurobiology of Anxiety and Its Treatment

546 Pages·2010·4.78 MB·English

Current Topics in Behavioral Neurosciences
Series Editors:
Mark Geyer, La Jolla, CA, USA
Bart Ellenbroek, Hamburg, Germany
Charles Marsden, Nottingham, UK
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Murray B. Stein Thomas Steckler
l
Editors
Behavioral Neurobiology
of Anxiety and Its Treatment
Editors
Dr.MurrayB.Stein Dr.ThomasSteckler
DepartmentsofPsychiatryand Johnson&JohnsonPharmaceuticals
Family&PreventiveMedicine Research&Development
UniversityofCaliforniaSanDiego CNSDrugDiscovery
9500GilmanDrive(0855) 2340Beerse
LaJolla,CA92093-0855 Belgium
[email protected] [email protected]
ISSN1866-3370 e-ISSN1866-3389
ISBN978-3-642-02911-0 e-ISBN978-3-642-02912-7
DOI10.1007/978-3-642-02912-7
SpringerHeidelbergDordrechtLondonNewYork
LibraryofCongressControlNumber:2010929746
#Springer-VerlagBerlinHeidelberg2010
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Preface
ThebookispartofaseriesonCurrentTopicsinBehavioralNeurosciences,which
hasasitsfocusanxietyanditstreatment.Wehavebroughttogetheradistinguished
cadreofauthorswiththeaimofcoveringabroadarrayoftopicsrelatedtoanxiety
disorders,rangingfromclinicaldiagnosis,epidemiology,preclinicalneuroscience,
andanimalmodelstoestablishedandinnovativetherapeuticapproaches.Thebook
aims at bridging these disciplines to provide an update of literature relevant to
understandinganxiety,itsconsequences,anditsmanagement.Followingisabrief
overviewofthechaptersandtheircontent,meanttoserveasaguidetonavigating
thebook.
Thefirst sectioncoversclinical aspects ofanxiety disorders. Joe Bienvenuand
colleaguesprovideanincisiveoverviewofdiagnosticconsiderationsintheanxiety
disorders in which they emphasize the strengths and shortcomings of our current
nosologicsystems.Thisisfollowedbyareviewandupdateoftheepidemiologyof
anxiety disorders by Ron Kessler and colleagues, which provides an authoritative
surveyofanxietydisorderincidence,prevalence,andriskfactors.Thisiscomple-
mentedbyacomprehensivereviewoftheliteratureondisordersthatco-occurwith
anxiety disorders by Kathleen Merikangas and Sonja Alsemgeest Swanson. Their
review highlights the tremendous comorbidity that occurs not only within the
anxietydisorders,butalsowithothermentalandphysicalhealthconditions.
Thesecondsectionisdevotedtoclinicalneurosciencetopicsthataregermaneto
anxietydisorders.KatharinaDomschkeandJu¨rgenDeckertprovideasummaryof
genetic findings in the anxiety disorders. Newton Sabino Canteras and colleagues
describe neuroanatomical structures and circuits relevant to anxiety and anxiety
disorders. This section is concluded by Jose´ Miguel Peˆgo and colleagues with a
criticaloverviewoftheneuroendocrinologyofanxietyandstress,tyingthistogeth-
erwithfindingsinanxietyandstressdisorders.
Thethirdsectionfocusesonanimalmodels.DallasTreitandcolleaguesprovide
anoverviewonpreclinicaltestsofanxiety-relatedbehavioranddiscussthevalidity
ofthesetestsandtheirsensitivitytopharmacologicalintervention.Thisisfollowed
by a review by Laura Jacobson and John Cryan on genetic animal models of
anxiety, a discussion of the strengths and weaknesses of such models, and their
v
vi Preface
contribution to our understanding of the neurobiological and genetic basis of
anxietydisorders.
The fourth section is devoted to translational science that can inform our
understandingofanxietydisorders.VictoriaRisbroughdiscussesbehavioralcorre-
latesofanxietydisorderswithaspecial emphasisonworkthathasused emotion-
(usuallyfear-)potentiatedstartletotesttheintegrityofparticularanxiety-relevant
circuitsinhumans.MarliesvanDuinenandcolleaguesprovideareviewoftheso-
called challenge studies in anxiety, in which subjects are exposed to substances
(e.g., pharmacologicalagents)intendedto evoke anxiety asa test oftheir specific
properties. Their particular emphasis in this chapter is on challenges to and
responsesoftherespiratorysystemwhich,arguably,havebeenbeststudiedinthe
anxiety disorders, particularlypanicdisorder.AmitEtkinsubsequentlyprovidesa
comprehensive review of the functional neuroimaging literature in anxiety disor-
ders.Heexaminesthesimilaritiesanddifferencesacrossanxietydisordersthathave
emerged from this literature, much of it using functional magnetic resonance
imaging(fMRI). Finally, ina tourde force ofthe merits oftranslational research,
Dennis Choi and colleagues provide a rationale for the pharmacological enhance-
mentofbehaviortherapyforanxietydisorders.
The fifth section covers the preclinical pharmacology of systems that are rele-
vant to anxiety, as well as some of the molecular targets for potential anxiolytics
withnovelmechanismofaction.ClaireDurantandcolleaguessetthescenewitha
reviewoftheclinicalneurochemistryofanxietydisorders,emphasizingthediffer-
entneurochemicalsystemsthataretargetedbycurrentlyusedandnewlydeveloped
anxiolytic drugs. This is followed by an authoritative overview by John Atack on
GABAergic approaches, delineating the potential of GABA-A subunit-specific
compoundstotreatanxietydisorders.AntonBespalovandcolleaguesthendiscuss
theimportance ofantidepressantdrugs inthetreatmentof anxiety disorders, espe-
ciallytheconundrumthatpreclinicalanimalmodelsoftenfailtodetectanxiolytic-
likeeffectsofantidepressantsdespitetheirclinicalutility.Theirinterestingproposal
istoalsoconsidercognitivecomponentsofanxiety-relatedbehaviorandtoexpand
thearmamentariumofpreclinicalmodelsrelevanttoanxietytomorereadilydetect
the efficacy of antidepressant drugs. Will Spooren and colleagues subsequently
review the emerging field of compounds acting at the different metabotropic
glutamate receptors as an innovative avenue for the development of novel anxio-
lyticdrugs,followedbyasummarybyThomasSteckleronthestatusofneuropep-
tidergic approaches to the treatment of anxiety disorders, especially focusing on
clinicalproof-of-conceptstudieswithsmall-molecule,nonpeptidergicantagonistsof
the CRF1, NK1 and 3, and CCK2 receptors, but also on the atrial natriuretic and
oxytocinsystems.Thissectionconcludeswithastate-of-the-artoverviewbyFabricio
Moreira and Carsten Wotjak on cannabinoids and anxiety, and modulation of the
endogenouscannabinoidsystemasyetanotherpromisingtherapeuticapproachinthe
questfornovel,moreefficaciousandbettertoleratedanxiolyticdrugs.
The sixth and final section of the book reviews the clinical pharmacology of
anxiety disorders. This section is organized such that each chapter provides an
authoritative review of the literature on the pharmacological management of the
Preface vii
most common anxiety disorders. David Baldwin and colleagues review the phar-
macotherapyofgeneralizedanxietydisorder(GAD)andthenJeffreyLightfootand
colleaguesdothesameforpanicdisorder.KeithGanasenandDanSteinsummarize
theevidencebasefor thepharmacotherapyofsocialphobia(alsoknownassocial
anxiety disorder), highlighting areas where knowledge is strong and where it is
especially sparse. Lakshmi Ravindran and Murray Stein review the evidence for
pharmacologicaltreatmentofposttraumaticstressdisorder(PTSD),atopicthathas
beenespeciallycontroversialandinthenewsoflate,givenrecentmilitaryconflicts
aroundtheworldandtheincreasedawarenessoftheirimpactonhealthofcomba-
tants and civilians alike. Blair Simpson closes this section with a summary of the
pharmacotherapy of obsessive compulsive disorder (OCD), a particularly chronic
anddifficult-to-treatanxietydisorderforwhichnewtreatmentsaresorelyneeded,
buthavebeenslowincoming.
These chapters, individually and in their aggregate, provide a broad summary
andsynthesisofbehavioralneurosciencefindingsinanxietyandadetailedupdate
on its treatment. As we look forward to the future – as many of the authors have
done in their chapters – we are particularly excited about recent advances in the
translationalneuroscienceofanxietywhichpromisetoleadtothedevelopmentof
morepotenttherapiesforthepatientswhoneedthem.
MurrayB.Stein ThomasSteckler
LaJolla,CA,USA Beerse,Belgium
.
Contents
PartI AnxietyDisorders-Clinical
AnxietyDisordersDiagnosis:SomeHistoryandControversies ............. 3
O.JosephBienvenu,LisaA.Wuyek,andMurrayB.Stein
EpidemiologyofAnxietyDisorders ............................................ 21
RonaldC.Kessler,AyeletMeronRuscio,KatherineShear,
andHans-UlrichWittchen
ComorbidityinAnxietyDisorders ............................................. 37
KathleenRiesMerikangasandSonjaAlsemgeestSwanson
PartII AnxietyDisorders-ClinicalNeuroscience
Genetics .......................................................................... 63
KatharinaDomschkeandJu¨rgenDeckert
NeuroanatomyofAnxiety ...................................................... 77
NewtonSabinoCanteras,LeonardoBarbosaResstel,LeandroJose´ Bertoglio,
AntoniodePa´duaCarobrez,andFranciscoSilveiraGuimara˜es
StressandtheNeuroendocrinologyofAnxietyDisorders ................... 97
J.M.Peˆgo,J.C.Sousa,O.F.X.Almeida,andN.Sousa
PartIII AnimalModels
AnimalModelsofAnxietyandAnxiolyticDrugAction ................... 121
DallasTreit,ElifEngin,andKrisMcEown
ix