Symptomdimensionsinanxietydisorders

Wheni sanxiet ya nanxiet ydisorder ?

Anxietyi sanormalemotio nunde rcircumstancesofthrea tandi sthough tt obepar tofth e

evolutionary"fightorflight"reactionofsurvival.Whereasi tmayb enorma lorevenadaptive

t obeanxiouswhenasaber-toot htige r(oritsmodern-dayequivalent)i sattacking ,ther e

aremanycircumstancesinwhichth epresenceofanxietyi smaladaptiveandconstitute s

apsychiatricdisorder.Th eideaofanxietyasapsychiatricdisorderi sevolvingrapidly.It

i scharacterizedbyth econcep tofcoresymptom sofexcessivefearan dworry(symptom s

atth ecenterofanxietydisordersi nFigure14-1)comparedt omajordepression,whichi s

characterizedb ycoresymptom so fdepressedmoo do rlosso finteres t(symptom sa tth e

centerofmajordepressivedisorderinFigure14-1) .

Anxietydisordershaveconsiderablesymptomoverlapwithmajordepression(seethos e

symptom ssurroundin gcorefeaturesshowni nFigure14-1) ,particularlysleepdisturbance,

problemsconcentrating ,fatigue,andpsychomotor/arousalsymptoms .Eachanxietydisorder

alsohasagreatdealofsympto moverlapwithothe ranxietydisorders(Figure s14- 2throug h

14-6) .Anxietydisordersarealsoextensivelycomorbid ,no tonl ywit hmajordepression

bu talsowitheachother,sincemanypatient squalifyovertim eforasecondoreventhir d

concomitan tanxietydisorder(Figures14- 2throug h14-6) .Finally,anxietydisordersare

frequentlycomorbi dwithmanyothe rcondition ssuchassubstanceabuse,attentio ndeficit

FIGURE14-2Generalize danxiet ydisorde r(GAD) .ThesymptomstypicallyassociatedwithGA Dar

eshown

here.Thes eincludethecoresymptomsofgeneralizedanxietyandworryaswellasincrease
darousal,fatigue,

difficultyconcentrating,slee pproblems,irritability,andmuscletension.Manyofthes
esymptoms,includingthe

cor esymptoms,ar epresenti notheranxietydisordersaswell.

FIGUR E14-3Pani cdisorder.Thecharacteristicsymptomsofpanicdisorderar eshownher eandincludethe

cor esymptomsofanticipatoryanxietyaswellasworryaboutpanicattacks;associatedsymptomsarethe

unexpecte dpanicattacksthemselve sandphobicavoidanceorotherbehavioralchange

sassociatedwithconcern

ove rpanicattacks.

FIGURE14-4Socialanxietydisorder.Symptomsofsocialanxietydisorder,shownhere,includethecor e

symptomsanxietyorfearove
rsocialperformanceplusworryaboutsocialexposure.Associatedsymptomsar e

panicattacksthatar epredictableandexpecte di
ncertainsocialsituationsaswellasphobicavoidanceofthos e

situations.

FIGURE14-5Posttraumaticstressdisorder(PTSD) .ThecharacteristicsymptomsofPTS Dareshownhere.

Thes eincludethecoresymptomsofanxietywhilethetraumaticeventi sbeingreexperience

daswellasworry

abouthavingtheothersymptomsofPTSD ,suchasincrease darousalandstartleresponses ,slee

pdifficulties

includingnightmares,andavoidancebehaviors.

FIGUR E14-6Obsessiv ecompulsiv edisorde r(OCD)

.SymptomsofOCD,shownhere,includethecoresymptom

ofanxiety ,whichtrigger sobsession sandcompulsionsinattemptstoreduc

ethatworryaswellastheobsession s

themselves ,whichcanbesee nasatypeofworry.Compulsionsar eake yassociatedfeature.

FIGURE14- 7Anxiety:thephenotype.

Anxietycanbedeconstructed,orbroke n

down,intothetwocoresymptomsof

fea randworry.Thes esymptomsar e

presentinallanxietydisorders,

althoughwhattriggersthemmaydiffer

fromon edisordertothenext.

hyperactivitydisorder,bipolardisorder,paindisorders,sleepdisorders,andmore,jus tasi n
majordepression(discussedi nChapte r12andillustratedi nFigur e12-127 )an dbipolar

disorder(discussedi nChapte r13andillustratedi nFigure13-42) .

What ,therefore ,i sananxietydisorder?Thes edisordersallseemt omaintainth ecore

featuresofsom eformofanxietyorfearcoupledwithsom eformofworry(Figur e14-7) ,bu t

thei rnatura lhistor yovertim eshowsthe mt omorphfromon eint oanother ,t oevolveint o

full-syndromeexpressionofanxietydisordersymptom s(Figur e14-1)an dthe nt orecede int

osubsyndromallevelsonlytoreappea ragainasth eoriginalanxietydisorder,adifferent

anxietydisorder(Figures14- 2throug h14-6) ,ormajordepression(Figur e14-1) .I fanxiety

disordersallsharecoresymptom soffearandworry(Figur e14-7)and ,asdiscussedlate ri n

thi schapter,areallbasicallytreate dwithth esamedrugs ,includin gmanyofth esam edrugs

tha ttrea tmajordepression,th equestionnowarises:Wha ti sth edifferencebetweenone

anxietydisorderandanother?Also,onecouldask:Wha ti sth edifferencebetweenmajor

depressionandanxietydisorders?Areallthes eentitiesreallydifferentdisordersorarethe y

jus tdifferentaspectsofth esameillness?*

Overlappingsymptom sofmajordepressio nandanxietydisorder s

Althoughth ecoresymptom sofmajordepression(depressedmoodorlossofinterest )differ

fromth ecoresymptom sofanxietydisorders(anxiety/fearandworry),ther eisagreatdealof

overlapwithth eothersymptom sconsidereddiagnosticforbot hamajordepressiveepisode

andseveraldifferentanxietydisorders(Figure14-1) .Thes eoverlappingsymptom sinclud e

problemswithsleep,concentration ,andfatigueaswellaspsychomotor/arousalsymptom s

(Figur e14-1) .I ti sthu seasyt oseeho wth egainorlossofjus tafewadditionalsymptom s

canmorphamajordepressiveepisodeint oananxietydisorder(Figur e14-1)oron eanxiety

disorderint oanothe r(Figures14- 2throug h14-6) .

Fromatherapeuti cpoin tofview,i tmaymatterlittl ewhatth especificdiagnosisi s

acrossthi sspectrumo fdisorders(Figure s14- 1throug h14-6) .Tha tis ,psychopharmaco

logicaltreatment smayno tbemuchdifferentforapatien twh ocurrentlyqualifiesfora
majordepressiveepisodeplusth esymptomofanxiety(bu tno tananxietydisorder)versus

apatien twhocurrentlyqualifiesforamajordepressiveepisodeplusacomorbi danxiety

disorderwithfull-criteriaanxietysymptoms .Althoug hi tcanbeusefult omakespecific

diagnosesforfollowingpatientsovertim eandfordocumentin gth eevolutionofsymp toms ,th

eemphasisfromapsychopharmacologicalpoin tofviewisincreasinglytotak ea

symptom-base dtherapeuti cstrategyt opatientswithanyofthes edisorders.Tha tis,specific

treatment scanbetailoredt oth eindividua lpatien tbydeconstructin gwhateverdisorderth e

patien thasint oalistofth especificsymptom sagivenpatien ti sexperiencing(seeFigures

14- 2throug h14-6)andthe nmatchingthes esymptom st ohypotheticallymalfunctioning

braincircuitsregulatedbyspecificneurotransmitter sinordertorationallyselectandcom
binepsychopharmacologicaltreatment st oeliminateallsymptom san dgetth epatientt o

remission.

Discussionofthi sstrategyfortreatin gth esymptom sofamajordepressiveepisodet o

attainremissioni sprovidedi nChapte r12andillustratedi nFigures12-120t o12-126 .

Specificdiscussionofhowtoapproachth eoverlappingsymptom sofproblemswithsleep,

concentration ,andfatigueareillustratedi nFigures12-12 1t o12-123 .

Overlappingsymptom so fanxietydisorde rsubtype s

Althoughther earedifferentdiagnosticcriteriafordifferentanxietydisorders(Figure s14-2

thoug h14-6),the ycanallbeconsideredt ohaveoverlappingsymptom sofanxiety/fear

coupledwithworry(Figur e14-7) .Remarkableprogresshasbeenmadei nunderstandin gth e

circuitryunderlyingth ecoresymptomofanxiety/fear(Figur e14-7)basedonanexplosionof

neurobiologicalresearcho nth eamygdala(Figure s14- 8throug h14-42) .Th elinksbetween

th eamygdala,fearcircuits,andtreatment sforth esympto mofanxiety/fearacrossth e

spectrumofanxietydisordersarediscussedthroughou tth eres tofthi schapter.

Worryi sth esecondcoresymptomsharedacrossth espectrumofanxietydisorders

(Figure14-8) .Thi ssymptomi shypotheticallylinke dt oth efunctionin gofcortico-striatal –

FIGUR E14-8Linkinganxietysymptomstocircuits.Anxietyandfearsymptoms(e.g.,panic,phobias)ar e

regulate dbyanamygdala-centeredcircuit.Worry,ontheotherhand,i sregulatedbyacortico-

striatalthalamic-cortical(CSTC )loop .Thes
ecircuitsmaybeinvolvedinallanxietydisorders,withthedifferent

phenotype sreflectingno tuniquecircuitrybutratherdivergentmalfunctioningwithinthosecircuits.

FIGURE14-9Amygdala.Theamygdala,whichplaysacentralrol eintheexperienceofanxietyandfear ,ha s

reciproca lconnectionswithawiderang eofotherbrainregions .Thes econnectionsallowtheamygdalato

integrat ebothsensor yandcognitiveinformationandthenus ethatinformationtotrigger(o

rnot)afearresponse .

thalamo-cortica l(CSTC )loops .CST Cloop swereintroduce di nChapte r7an dareillus tratedi nFigures7-
16throug h7-21 .Th elinksbetwee nth eCST Ccircuits,"worryand

obsessionloops, "andtreatment sforth esymptomofworryacrossth espectru mofanxiety

disordersarediscussedlate ri nthi schapte r(seealsoFigures14-4 3throug h14-45) .Weshall

seetha twha tdifferentiatesoneanxietydisorderfromanothe rmayno tbeth eanatomica l

localizationorneurotransmitter sregulatin gfearandworry(Figur e14- 7andFigure14-8)

bu trathe rth especificnatureofmalfunctioningwithinthes esam ecircuitsi nvariousanxiety

disorders.

FIGURE14-1 0Affectoffear.Feelings

offearareregulatedbyreciprocal

connectionsbetweentheamygdalaand

th eanteriorcingulatecortex(ACC )and

th eamygdalaandth eorbitofrontal

cortex(OFC).Specifically,itmaybe

tha toveractivationofthesecircuits

producesfeelingsoffear .
FIGURE14-1 1Avoidance.Feelingsof

fearmaybeexpressedthrough

behaviorssuchasavoidance,whichis

partlyregulatedbyreciprocal

connectionsbetweenth eamygdalaand

th eperiaqueductalgray(PAG).

Avoidanceinthi ssenseisamotor

responseandmaybeanalogousto

freezingunderthreat.Othermotor

responsesaretofigh tortorunaway

(flight)inordertosurvivethreatsfrom

theenvironment.

Tha tis,i ngeneralizedanxietydisorder,malfunctioningi nth eamygdalaandCST C

loopsmaybepersistentan dunremittin gyetno tsevere(Figur e14-2) ,whereasmalfunctionin

gmaybeintermitten tbu tcatastrophici nanunexpectedmannerforpani cdisorder

(Figure14-3)ori nanexpectedmannerforsocialanxiety(Figur e14-4) .Circuitmalfunctionin gmayb

etraumati ci norigini nposttraumati cstressdisorder(PTSD )(Figur e14-5)

ortrappe di naredundant ,repetitiveloo pforobsessivecompulsivedisorder(OCD )(Figur e

14-6) .

FIGURE14-1 2Endocrineoutputof

fear .Thefearresponsemaybe

characterizedinpartbyendocrine

effectssuchasincreasesinCortisol,

whichoccurbecauseofamygdala

activationofthehypothalamic-pituitaryadrenal(HPA )axis.ProlongedHP A

activationandCortisolreleasecanhave
significanthealthimplications ,suchas

increasedriskofcoronaryartery

disease,type2diabetes,andstroke.

FIGURE14-1 3Breathingoutput.

Changesinrespirationmayoccur

duringafearresponse;thesechanges

areregulatedbyactivationofth e

parabrachialnucleus(PBN)viathe

amygdala.Inappropriateorexcessive

activationofth ePBNcanleadnotonly

toincreasesintherateofrespiration

butalsotosymptomssuchasshortness

ofbreath,exacerbationofasthma,ora

senseofbeingsmothered.

Theamygdalaandtheneurobiologyoffear

Th eamygdala,analmond-shape dbraincenterlocatednearth ehippocampu s(seeFigure

9-63),hasimportan tanatomicalconnectionstha tallowi tt ointegrat esensoryandcognitive

informationandthe nt odetermin ewhetherther ewillbeafearresponse(seeFigures9-6 4

and9-65aswellasFigures7-12,7-13 ,and7-19throug h7-20) .Figures14-9throug h14-1 5

illustratehowth eamygdala'sconnectionsrelatetoth esignsandsymptom sassociatedAvit h

th efearresponse.Specifically,th eaffectorfeelingoffearmayberegulatedviath ereciprocal

connectionsth eamygdalashareswithkeyareasofprefrontalcortextha tregulateemotions ,

FIGURE14-14Autonomi coutpu tof

fear .Autonomicresponse sar etypically

associatedwithfeelingsoffear .Thes e

includeincrease sinheartrate(HR )and

bloodpressur e(BP),whichare•

regulatedbyreciproca lconnections

betweentheamygdalaandthelocu s

coeruleus(LC).Long-termactivationof

thiscircuitmaylea dtoincrease driskof

atherosclerosis,cardiacischemia,

changei nBP,decrease dHRvariability,

myocardialinfarction(Ml) ,oreve n

suddendeath.

FIGURE14-15Reexperiencing .

Anxietycanbetriggeredno tonlybyan

externalstimulusbutalsobyan

individual'smemories.Traumatic

memoriesstoredinthehippocampus

canactivatetheamygdala,causingthe

amygdala,inturn,toactivateother

brainregion sandgenerateafea r

response .Thisi stermedreexperiencin g

andisaparticularfeatureof

posttraumaticstres sdisorder .

namelyth eorbitofrontalcortexandth eanteriorcingulatecortex(Figur e14-10) .However,

feari sno tjus tafeeling.Th efearresponsecanalsoinclud emotorresponses .Depending

onth ecircumstancesandone'stemperament ,thos emotorresponsescouldbefight ,flight ,

orfreezingi nplace.Moto rresponsesoffearareregulatedi npartbyconnection sbetween

th eamygdalaandth eperiaqueductalgrayareaofth ebrainstem(Figur e14-11) .

Ther earealsoendocrin ereactionstha taccompanyfear,i npar tdu et oconnection s

betweenth eamygdalaandth ehypothalamus ,causingchangesi nth ehypothalamic pituitary-

adrenal(HPA )axisandthu sofCortisollevels.Aquickboos tofCortisolmay

enhanc esurvivalwhe napersoni sencounterin garealbu tshort-ter mthreat .However,

chronican dpersistentactivationofthi saspectofth efearrespons ecanleadt oincreased

medicalcomorbidity,includin gincreasedrate sofcoronar yarterydisease,typ e2diabetes,

andstroke(Figur e14-12) .Breathingcanalsochang edurin gafearresponse ,regulatedi n

par tb yth econnectionsbetweenamygdalaandth eparabrachialnucleusi nth ebrainste m

FIGURE14-16Linkin ganxiet ysymptom st ocircuit st oneurotransmitters .Symptomsofanxiety/fearare

associatedwithmalfunctioningofamygdala-centeredcircuits;theneurotransmittersthatregulatethes
ecircuits

includeserotonin(5HT),gamma-aminobutyricacid(GABA)
,glutamate,corticotrophinreleasingfactor(CRF) ,and

norepinephrine(NE),amongothers.Inaddition,voltage-gatedio nchannelsareinvolve
dinneurotransmission

withinthes ecircuits.

(Figur e14-13) .Anadaptiveresponset ofeari st oacceleraterespiratoryrat ei nth ecourse

ofafight/fligh treactiontoenhanc esurvival;inexcess,however,thi scanleadtounwante d

symptom sofshortnessofbreath ,exacerbationofasthma ,orafalsesenseofbein gsmothere d

(Figure14-13)—allofwhicharecommo ndurin ganxietyandespeciallydurin gattacksof

anxietysuchaspanicattacks.

Th eautonomi cnervoussystemi sattune dtofearandi sabletotrigge

rresponsessuchasincreasedpulseandbloodpressureforfight/flightreaction sandsurvivaldurin greal

threat s-fromth ecardiovascularsystem.Thes eautonomi candcardiovascularresponses

aremediatedbyconnectionsbetweenth eamygdalaandth elocuscoeruleus,hom eofth e

noradrenergiccellbodies(Figur e14-14 )(noradrenergi cneuron sarediscussedi nChap

ters7and11andnoradrenergicpathwaysareillustratedi nFigure7-9) .Whe nautonomi c

responsesarerepetitive—tha tis ,whenthe yareinappropriatel yorchronicallytriggere das

par tofananxietydisorder—thi scaneventuallyleadtoincreasesinatherosclerosis,car

diacischemia,hypertension,myocardialinfarction ,andevensudde ndeat h(Figur e14-15) .

"Scaredt odeath "mayno talwaysbeanexaggerationorafigureofspeech!Finally,anxiety

canbetriggere dinternall yfromtraumati cmemoriesstoredi nth ehippocampu sandacti

vatedbyconnectionswithth eamygdala(Figur e14-15) ,especiallyi ncondition ssuchas

posttraumaticstressdisorder.

Processingofth efearresponsei sregulatedbyth enumerou sneuronalconnection s

flowin gint oandou tofth eamygdala.Eac hconnectio nutilizesspecificneurotransmitter s

actinga tspecificreceptor s(Figur e14-16) .Someofth ekeyneurotransmitter sactin ga tth e

amygdalaareshowni nFigure14-16 ,althoug hth eexactanatomica lconnection swithinth e

amygdalaandth especificrecepto rsubtypesforthes evariouscircuitsarestillbein gclarified.

Wha ti sknownabou tthes econnectionsi stha tseveralneurotransmitter sareinvolvedi nth e

productionofsymptom sofanxietya tth elevelofth eamygdalaandtha tnumerou sanxiolytic

drugshaveactionsonthes especificneurotransmitte rsystemst orelieveth esymptom sof

anxietyandfear(Figur e14-16) .