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☆
processingtaskswasassociatedwithanincreasedriskofdevelopingPDwithin5years.
In 2007, Haehner et al
24
 published data on a clinical follow-up of 30 patients diagnosed with
idiopathic olfactory loss. Four years from baseline, 7% (n = 2) of the individuals with idiopathic
olfactorylosswhowereavailableforfollow-upexamination(n=24)hadnewlydevelopedclinicalPD
symptoms.Altogether,13%(n=4)ofthepatientspresentedwithPD-relevantabnormalitiesofthemotor
system.Theresultsindicatedthatunexplainedolfactorylossmaybeassociatedwithanincreasedriskof
developingPD-relevantmotorsymptoms.
Bycontrast,authorsofatwinstudy
25
concludedthatsmellidentificationabilitymaynotbeasensitive
indicatoroffuturePD,eveninatheoreticallyat-riskpopulation.Thiswasbasedonthefactthatpatients
whosubsequentlydevelopedPDhadnoevidenceofsignificantsmelllosswhentheywereinitiallytested.
However,as pointedout bytheauthors themselves,the reasonforthisnegative findingmight lieinthe
verylong delayof7 years betweenbaselineassessmentand follow-up visit.Theinitial testmayhave
beentooearlyfortheirsubjectstohavedevelopedsignsofsmelldysfunction.
This is in accordancewith the resultsof a largelongitudinal study byRossandcolleagues.
26
 They
assessedolfactoryfunctionin2,267elderlymenintheHonoluluHeartProgramandfoundanassociation
betweensmelllossand future developmentofPD.Theycametotheconclusion thatimpairedolfaction
canpredatePDbyatleast4 years and maybe a usefulscreeningtooltodetectthose athigh riskfor
developmentofPDinlaterlife.However,thisrelationshipappearstoweakenbeyondthe4-yearperiod.
Along with quantitative smell loss, idiopathic phantosmia has also been proposed to herald PD.
Severalcasereportsshowthatsomepatientshaveexperiencedphantosmiaveryearlyinthecourseofthe
disease.
27,28
According toarecentstudybyLandisetal,
29
however,idiopathic phantosmiaas an early
signofPDprobablyremainsaratherexceptionalpresentationandtheoverwhelmingmajorityofpeople
withidiopathicphantosmiawillnotdevelopPD.
RecentdataonolfactorylossasanearlyPDsymptomarecompatiblewithpredictionsmade onthe
basis of neuropathological investigations. Braak et al
30
 (Fig. 11.2) describe involvement of olfactory
pathways and lower brainstem regions before nigrostriatal pathways are affected, which might cause
early nonmotor symptoms. Documented pathological alterations in the olfactory bulb (OB) include
neuronallossandtheaccumulationofLewybodiesandLewyneuriteswithintheintrabulbarportionsof
the anterior olfactory nucleus (Fig. 11.3). Other layers of the OB also exhibit accumulation of Lewy
bodiesandLewyneuritestoalesserdegree.Indeed,ithasbeensuggestedthattheolfactorysystemisan
ideal locationto try tobetterunderstand the pathophysiology ofLewyneurodegeneration.
31
 Inanother
attempttounderstandtheetiologyofolfactorydysfunctioninPD,Huismanetal
32
foundanincreaseof
periglomerulardopaminergicneuronsintheOBinpatients withPD(Fig. 11.3).They interpreted their
findingwithinthecontextofapossiblecompensatorymechanisminresponsetothelossofdopaminergic
neuronsinthebasal ganglia. Thisconcurswiththeirobservationthat dopaminergicneurogenesisinthe
glomerularlayertripledafternigrostriatallesioningand,consistentwiththisfinding,thetotalnumberof
tyrosine hydroxylase positive cells increased.
33
 However, results of a follow-up study
34
 indicated a
gender-relatedchange,namelythatthenumberofdopaminergiccellsintheOBofbothmaleandfemale
patientswithPDequalsthatofhealthymalesofthesameagegroup.Theauthorsthereforeconcludedthat
thehyposmiainpatientswithPDcannotsimplybeascribedtodopamineintheOB.Inanotherattemptto
explainthemechanismofolfactorydysfunctioninPD,Sobelandcolleaguesdemonstratedadeficitinthe
magnitude of sniffing in patients with PD and reported small improvements in odor identification
performancewithforcedvigoroussniffing.
35
Severalprospectivestudiescurrentlyunderwaywillhelptodetermineifolfactorylossmaybecomea
useful biomarker of PD development within populations at risk for PD. For instance, the current
Parkinson-associated risk syndrome study,
36
 which is examining the use of olfactory dysfunction and
dopaminergicfunctionalimagingaspredictorsofriskinfirst-degreerelativesofpatientswithPD,will
advanceourunderstandingofearlyPDpresentation.
OlfactoryDysfunctionintheDifferentialDiagnosisofParkinsonianSyndromes
Numerous studies suggest that olfactory disturbances in PD may have diagnostic utility for the
differentiation of PD from other movement disorders. Wenning et al
37
 presented data suggesting that
olfactory function is differentially impaired in distinct parkinsonian syndromes. They reported a
preserved or mildly impaired olfactory function to be more likely in atypical parkinsonism such as
multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal degeneration
(CBD), whereas pronounced olfactory loss appeared to suggest PD. In a study on 50 patients with
parkinsoniansyndromes, Müller etal
21
also foundevidenceforolfactory loss inMSA, butlittleorno
olfactory loss in (the few investigated) patientswith PSP andCBD. With regardto the differentiation
betweenMSAandPD,acombined odor thresholds,odordiscrimination,andodoridentification(TDI)
scorecut-offof19.5hadasensitivityof78%andaspecificityof100%.WhentheTDIscorecut-offwas
increased to 24.8, sensitivity in this sample was 100% while specificity fell to 63%. This moderate
specificity seems tobethe limitingparameterfor diagnosticpurposes. Arecent AmericanAcademyof
Neurology practice parameter on the diagnosis and prognosis of PD concluded that olfactory testing
“shouldbeconsidered”todifferentiatePDfromPSPandCBDbutnotfromMSA.
38
Furthermore,Liberini
etal
39
reportedasignificant olfactoryimpairment inLewybodydisease (LBD),whichdoesnot allow
differentiation from PD. In a sample of 116 patients with mild LBD, mild AD, and mild cognitive
impairmentandcontrols,Williams etal
40
describe evenmore markedolfactory impairmentinpatients
withmilddementiawithLewybodiesthaninthosewithmildAD.Thislendssignificancetotheroleof
Lewybodypathologyinolfactorydysfunction,whichwouldbeinlinewiththeobservationthatpatients
withnondegenerativecausesofparkinsonism, such asvascular parkinsonism,
41
present with preserved
smellfunction.Thereisalsoevidenceforlessolfactorydisturbanceinfamilialparkinsonism.InPARK2
PD,theolfactorysenseisrelativelywellpreserved,whereasPARK1PDsubjectsarehyposmic(Table
11.1;reviewedinref.4).TwostudiesexaminedolfactorydysfunctioninautosomalrecessivePARK6PD
and found impaired olfactory function in symptomatic homozygotes as well as asymptomatic
heterozygotes.
42,43
Recent data
44
 suggestthat patientswith PARK8PDpresentwithimpaired olfactory
identificationwhileasymptomaticcarriersshownormalolfactoryperformance,althoughthestudieshave
includedrelativelyfewsubjects(reviewedinref.45).
Results from studies of secondary parkinsonism also indicate a relationship between parkinsonian
symptoms and olfactory dysfunction. Krüger et al
46
 found an association between medication-induced
parkinsonismandolfactorydysfunctioninpatientswithpsychoticdepressiontreatedwithdopamineD2
receptor–blockingneurolepticdrugs.Here,theseverityofmotorsymptomspositivelycorrelatedwiththe
degree of olfactorydysfunction,whichmightindicate patientswith latent basal ganglia dysfunction of
neurodegenerativeetiology.Similar totheresultsseenindrug-inducedparkinsonism,a recentstudyof
patientswithWilsondiseaserevealedthatthosewithneurologicalsymptomsshowedsignificantolfactory
dysfunction compared with those with hepatic symptoms.
47
 Individuals who were more severely
neurologically affected also presented with more pronounced olfactory deficits. Based on these
observations,olfactorytestingshouldnotbeconsideredtodifferentiatePDfromthesespecificconditions
byitself.However,olfactorytestingcaninformthedifferentialdiagnosisofparkinsonisminthesameway
that many other examinations, including deep tendon reflex, extraocular movement, and cerebellar
functionassessments, cannot distinguish parkinsonian disorders in isolation,but can be helpful in the
contextofa complete historyandphysical examination. In particular,olfactorydysfunctionassessment
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
canbeimportantincaseswherepatientspresentwithparkinsonianfeaturesbutpreservedolfaction,when
itappearstobevalidtoquestionadiagnosisofPD.
Conclusions
RecentdatasuggestthatinexpensiveolfactoryprobesimprovethediagnosticprocessinpatientswithPD.
Incontrasttoimagingprocedures,olfactory testingisquickandeasytoperform.Validatedtestscanbe
usedasreliablediagnostictoolseveninnonspecializedcenters.Deebetal
22
foundthatabasicsmelltest
isassensitiveasadopaminetransporterscan(DaTSCAN).Accordingtothisstudy,thesensitivitiesof
the University of Pennsylvania Smell Identification Test and DaTSCAN are high at 86% and 92%,
respectively.AlthoughDaTSCANissuperiorfor“localization,”asmelltestisconsiderablycheaper,and
neitherisdiseasespecific.Inarecentbiopsystudy,
48
itwasshownthatsubjectswithPDdidnotpresent
specific histomorphological abnormalities of the olfactory mucosa compared with younger hyposmic
controls. Consequently,structuredandvalidatedtestsofolfactoryfunction should be consideredinthe
diagnosisofearlyPDandindifferentiatingPDfromothersecondaryandatypicalformsofparkinsonism.
Fig. 11.2a–c Six stages ofbrain pathology inParkinsondisease. Whereas firstlesions appear in stage one inthe olfactorybulb, anterior
olfactory nucleus,anddorsalnucleusofthevagusnerve(a), lesionsin thesubstantianigraarenotpresentbeforestagethree(b). Atstage
fourthepresymptomaticphaseyieldstothesymptomaticphaseofthedisorder.Eventually, associateareasoftheneocortexpresymptomatic
phase become involved (c). (From Hummel T, Welge-Lüssen A. Riech- und Schmeckstorungen: Physiologie, Pathophysiologie und
TherapeutischeAnsatze.Stuttgart:Thieme;2009.)
Fig.11.3a–eOlfactorybulbanatomyandpathology.
aThehumanolfactorybulb(OB)restsontheinferiorsurfaceofthefrontallobes,adjacenttothegyrusrectus(GR).
bTheolfactory bulbconsists ofsixlayers(enlargedviewrepresentativeofboxedportionofa), whicharenotalwayswellpreservedin the
elderly.Theseincludetheolfactory nervelayer, whereaxonsofolfactory receptorneuronstraversethe bulbenroutetoodorant-specific
glomeruliintheglomerularlevel(GL),wheretheysynapsewithdendritesofmitralandtuftedneurons;theexternalplexiformlayer(EPL);
themitralcelllayer(asterisks);theinternalplexiformlayer(IPL);andthegranularlayer(GrL).
cTyrosinehydroxylase immunostainingofthe olfactory bulbrevealsdopaminergicperiglomerularneurons(cellbodies surroundingglomeruli
andprocesseswithinglomeruli)thatmodulatetransmissionbetweenolfactoryreceptorneuronsandmitralandtuftedneurons.
d In Parkinson disease, Lewy bodies and Lewy neurites (identified by α-synuclein immunostaining) are concentrated within the anterior
olfactorynucleus(asterisks).
e At higher power magnification, the anterior olfactory nucleus (AON) in Parkinson disease is characterized by neuronal loss and
accumulationofLewybodies(roundinclusionswithincells)andLewyneurites(curvilinearinclusionswithincellprocesses).
Table 11.1Relativedegreeofolfactorydysfunctioninneurologicaldisorders
Disease
Relativeolfactory
dysfunction
Parkinsondisease,Alzheimerdementia,Lewybodydementia,PARK1Parkinsondisease,PARK8
Parkinsondisease
Severe
Multiplesystematrophy,Huntingtondisease,Multiplesclerosis,PARK6Parkinsondisease Moderate
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Motorneurondisease,Friedreichataxia,spinocerebellarataxiatype2,progressivesupranuclearpalsy Mild
Corticobasaldegeneration,spinocerebellarataxiatype3,PARK2Parkinsondisease,essentialtremor,
restlesslegssyndrome
Slighttonormal
ImpairmentofolfactionisacharacteristicandearlyfeatureofPD.Recentdataindicatethat>95%
ofpatientswithPDdevelopsignificant olfactoryloss.Deficitsinthe senseofsmellmayprecede
clinicalmotorsymptomsbyyearsandcanbeusedtoassesstheriskfordevelopingPDinotherwise
asymptomatic individuals. Numerous studies suggest that olfactory disturbances in PD may have
diagnosticutilityforthedifferentiationofPDfromothermovementdisorders.
AlzheimerDementia
Similar olfactory deficits have been shown in AD as inPD. Ina meta-analysis,
6
 defects in olfactory
functioninpatientswithADandPDwere relativelyuniform,althoughtherewasatrendtoward better
performance in patients with AD on threshold tests than on odor identification tests. Therefore, no
measure candistinguishthe twoconditions.As inPD,olfactory impairmentisanearlyfeatureofAD.
Postmortem studies have demonstrated that olfactoryand transentorhinal regions are the earliesttobe
affectedinthecourseofthedisease.
49
ImpairedolfactioninADmaybeduetothedepositionofamyloid
plaquesandneurofibrillarytanglesintheOBandtheentorhinalcortex,astructurewhichisalsomainly
involvedincognitiveprocessing.IncontrasttoPD,acorrelationbetweendementiaseverityandanosmia
canbeseeninAD.Furthermore,ithasbeenfoundthatthevolumeoftheOBsignificantlycorrelateswith
global cognitive performance in AD patients. OB atrophy appears very early in the course of the
disease,
50
whichmay contribute toearlydiagnosis. Thisiscontrarytothe findingsofasmall studyof
OBsinpatientswithPD,
51
whichdemonstratedlittleornodifferenceinbulbsizebetweenpatientswith
PDandhealthycontrols.
Patientswithmildcognitive impairmentwhoareconsidered atriskfordeveloping ADdemonstrate
significantolfactoryimpairmentcomparedwithcontrols.
52
Thisassociationbetweensmelllossandlater
conversiontodementiaalsoappliestohealthyelderlypeople.Inalongitudinalstudyof471cognitively
normalelderlypeoplebyWilsonetal,
53
olfactorydysfunctionwasastrongpredictorofpostmortemAD
pathology.
In addition to LBD, which was discussed previously, other forms of dementia, including
frontotemporaldementia,havebeenassociatedwithvaryingdegreesofolfactorydysfunction.
54
AsinPD,olfactoryimpairmentisanearlyfeatureofADandcanbeobservedinpatientswithmild
cognitiveimpairment.Otherformsofdementiahavealsobeenassociatedwitholfactorydysfunction.
HuntingtonDisease
PatientswithHuntingtondiseasepresentwithmoderatehyposmiaaffectingolfactorydetectionthreshold,
odordiscrimination,andodoridentification.
7
Subsequentstudiesusingdiscriminationandidentification
tests have not shown abnormalities in presymptomatic relatives of unknown genotype (e.g., ref. 55),
implyingthatolfactoryabnormalitiesdonotoccurbeforetheonsetofcognitiveormotorsymptoms.This
is in contrasttotheresultsofLarssonetal,
56
whoreportedimpairmentofodor discrimination, butnot
otherolfactoryassessments,inat-riskpersons.
OtherNeurodegenerativeDiseases
Olfactory function has been assessed in patients with cerebellar ataxia due to Friedreich ataxia and
spinocerebellarataxias(SCA)type2and3.PatientswithSCA2presentwithslightolfactoryabnormality
involving olfactory detection threshold, odor discrimination, and odor identification.
57
 Patients with
SCA3,however,havenormalsmell function,
58
whichmighthavediagnostic utility,astheycanpresent
withparkinsonianfeatures.InFriedreichataxia,slightolfactorydysfunctionwasobserved.
59
Mild olfactory impairment has also been demonstrated in motor neuron disease. However, study
resultsvaryconsiderably,
60,61
possiblybecauseofthefactthatmainlypatientswithbulbardysfunctionare
affected.SimilartoolfactorydysfunctioninPD,thereisprobablyasmalleffectfromreducedsniffing.
35
Olfactory dysfunction has also been demonstrated in some forms of inherited ataxia and motor
neurondisease.
TherapyofSmellLoss
To date, no therapeutic interventions for olfactory loss in neurodegenerative disorders are available.
Several studies indicate that pharmacological treatment of PD, including levodopa and the dopamine
agonist apomorphine, fails to restore olfactory function in patients with PD.
1
 However, recent
experiments indicate that deep-brain stimulation of the subthalamic nucleus in patients with PD may
improve odor discrimination, but not odor detection thresholds.
62
 In addition, it is possible that
improvementofolfactoryfunctionmaybeachievedwithimprovementsinsniffing,whichhasbeenshown
tobedysfunctionalinpatientswithPDandmotorneurondisease.Despitethelackoftherapeuticoptions,
patientsshouldbeadvisedofpotentialrisksofsmellloss,includinginabilitytosmellsmoke,naturalgas,
and spoiled food products, and offered follow-up examinations of their sense of smell. In addition,
regardlessofthepresenceofneurologicaldisease,othercommoncausesofolfactoryimpairmentshould
alwaysbeconsidered.
Althoughtherearenoproventreatmentsforolfactorydysfunctioninmostneurologicaldiseases,itis
importanttocounselpatientswitholfactorydysfunctionaboutthepossiblerisksthatthisimpairment
posestotheirwellbeing.
Ourexperiencesuggeststhatittakeslittletimetofollowuppatientswithadiagnosisofidiopathicsmell
lossneurologicallyasanessentialpartoftheirregularlyscheduledvisittothesmellandtasteClinic.In
addition,elderlypatientswithidiopathicsmelllossshouldbeconsideredforreferraltoaneurologistas
theyhaveanincreasedriskofdevelopingPDorAD.Suchacomprehensive,multidisciplinaryapproach
mightenablethe physiciantodetectslightmotororcognitive abnormalities inanat-riskpopulation as
early as possible. This may give rise to clinical studies that allow administration of neuroprotective
substancesinindividualswithunexplainedsmellloss.Therapeuticstudieswithneuroprotectiveagentsin
patientswithhyposmiaand PDarecurrentlyunderway andmayhelpustoevolvepreventivestrategies
forneurodegenerativediseasesinthefuture.
CaseReport:UnexplainedSmellLoss
A63-year-oldmanwasreferredbecauseofsevereolfactorydysfunctionholdinghimbackfromhis
passiontocook.Fouryearsearlier,hehadnoticedunpleasantolfactorysensationsforthefirsttime.
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During the following months, these sensations became less troublesome in terms ofintensityand
unpleasantness.Finally,theunpleasantsensationsdisappeared.Henoticed,however,thathissense
ofsmelldeterioratedgradually.
Psychiatric, neurological, and ear, nose, and throat examinations were normal. Detailed
chemosensorytestingrevealedfunctionalanosmia.Inaddition,thepatient'shistoryshowedelements
ofphantosmia:theywerenottriggeredbyodors,theyweredifficulttoexplainverbally,andodors
wereunfamiliartothepatient.Tastewasnormal.Thediagnosisof“idiopathic”olfactorylosswas
basedon(1) negativemagneticresonanceimagingandcomputedtomography;(2)nohistoryofan
associationbetweenolfactorylossandheadtraumaorinfectionsoftheupperrespiratorytract;(3)
gradualonsetofolfactoryloss overmonths oryears;(4)absenceofsigns ofsinonasaldiseaseon
detailednasalendoscopy;(5)lackofresponsetoshort-termsystemictreatmentwithcorticosteroids;
(6)nocomplaintofParkinson-likemotorsymptomsorhistoryofneurologicaldisorders;and(7)no
historyofexposuretotoxinsordrugspotentiallyleadingtoolfactorydisturbances.
Atafollow-upvisittotheclinic12monthslater,thepatientreportedleftshoulderpainandsubtle
slownessofmovement. Hissenseofsmell had notimproved.Neurological examinationrevealed
reduced left-sided arm-swing and slight bradykinesia of the left hand that improved markedly
followingapositivetestwithlevodopa200mg.Consequently,thepatientwassuspectedofsuffering
fromParkinsondisease.Thediagnosiswasconfirmedby18-fluoro-dihydroxyphenylalaninepositron
emissiontomography,whichshoweddecreasedlevelsoftheneurotransmitterdopamineinthebasal
ganglia.
Conclusion
We reporta case ofidiopathicphantosmia andanosmia with eventual manifestation ofParkinson
disease.Thiscaseillustratesthesignificanceofneurologicalexaminationinpatientswithidiopathic
olfactory loss. Unexplained smell loss should be considered a first sign of neurodegenerative
disorders.
Non-neurodegenerativeDisorders
MultipleSclerosis
Thedataontheprevalenceofolfactoryimpairmentinmultiplesclerosis(MS)varybetween15and45%,
although smell changesare rarelyreported by patients with MS.Correlations havebeendemonstrated
between plaque activity within olfactory-related central brain regions (e.g., the inferior frontal and
temporal lobes) and the olfactory deficit (Fig. 11.4).
63
 Recent studies report that the frequency of
olfactoryimpairmentishigherinpatientswithsecondaryprogressiveMSthan in thosewithrelapsing–
remitting or primary progressive courses. The observed association between decreased odor
identificationabilityandsymptomsofanxietyanddepressioninpatientswithMSsuggeststhatmoodand
anxietydisorders should be considered in assessing olfaction in patientswith MS.
64
 There are a few
anecdotal case reports onolfactory impairmentas anearlyfeature of MSevenbeforeoptical neuritis
occurs.
InpatientswithMS,smelllosshasbeencorrelatedwiththelesionloadinbrainregionsinvolvedin
olfaction.
Epilepsy
It is generally accepted that temporal lobe epilepsy (TLE) may cause a brief olfactory aura prior to
seizures. Olfactory assessment revealed that patients with TLE do not show abnormalities of odor
thresholds compared with healthy controls.
65
 They do, however, show impairment of higher level
olfactory functions such as odor identification and discrimination.
65,66
 Furthermore, latencies of
chemosensoryevokedpotentialsinthesepatientsareprolonged.
67
Fig. 11.4 Fluid-attenuated inversion–recovery sequence in a 29-year-old patient with temporal multiple sclerosis lesions and concomitant
hyposmia.(FigurecourtesyofDr.HagenKitzler.)
Migraine
Similartoanepilepticaura,migraineauramaypresentwitholfactoryhallucinations,butthesearemuch
less common than visual auras. Migraine patients often report intolerance to odors in terms of
hypersensitivity.
68
 This applies during migraine attacks as well as in the time in between attacks.
Consequently, odorsmaytrigger attacks.
69
Some patientsexperienceosmophobia duringattacks, which
mightbeimportantindistinguishingmigrainefromtensionheadache.
Meningioma
Meningiomas can present with olfactory disturbances. Unilateral or bilateral olfactory dysfunction is
thought to be a very earlysymptom of olfactorygroovemeningioma.According to a study byWelge-
Luessenetal,
70
however,olfactorytestingseemstobeoflittlehelpindetectingolfactorymeningioma,as
fewpatientscomplainofolfactorydysfunction.Thelikelihoodofnormalpostoperativeolfactoryfunction
contralateral to the tumor was high when the tumor was less than 3 cm in diameter and preoperative
normosmiahadbeenestablished.Further,preservationofolfactoryfunctionipsilateraltothetumorseems
tobeextremelydifficult,irrespectiveoftumorsizeorsurgicalapproach.
IschemicLesions
Olfactorydysfunctionshavebeeninfrequentlyreportedinpatientsfollowingstroke.
71
Systematicstudies
ofpatientswithcerebralischemiahavenotbeenperformedtodate.Mainlandetal
72
examinedolfactory
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functioninpatientswith unilateral cerebellar lesionsdue to ischemia or tumors. Testingrevealed that
patientshadacontralesionalimpairmentinolfactoryfunction.Findingsofthisstudystronglyimplicatean
olfactocerebellar pathway in odor identification and detection that functionally connects each nostril
primarilytothecontralateralcerebellum.
PsychiatricDiseases
Compared with healthy controls, the prevalence of olfactory dysfunction is higher in patients with
accompanying schizophrenia or acutedepression.Patients with acute major depressive disorder show
significantly lower olfactory sensitivity,
73
 but there is no difference in olfactory performance after
successfultherapywithantidepressants.Patientswithacutemajordepressivedisorderalsopresentwith
smallerOBvolumesthanhealthycontrols,andasignificantnegativecorrelationbetweenOBvolumeand
depression score.
74
 In schizophrenia, impairment of olfactory sensitivity, identification, and
discrimination abilities were observed in patients and first-degree relatives,
74
 suggesting a genetic
vulnerabilityforchemosensorydeficits.
In addition to neurological diseases, several psychiatric conditions have been associated with
olfactorydysfunction,includingschizophreniaandacutedepression.
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