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31 Pages·2013·0.52 MB·English

Title: The Role of Oxytocin in Psychiatric Disorders: A Review of Biological and Therapeutic Research
Findings
Activity Date: This activity will be available as an online learning module starting August 30, 2013, and
will be available for one year.
Activity Location: Online
Target Audience Statement: This CME activity is intended for psychiatrists.
Accreditation: Lippincott Continuing Medical Education Institute, Inc. is accredited by the Accreditation
Council for Continuing Medical Education to provide continuing medical education for physicians.
Credit Designation: Lippincott Continuing Medical Education Institute, Inc. designates this enduring
material for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should only claim credit
commensurate with the extent of their participation in the activity.
Learning Objectives: After completing this activity, the learner should be better able to:
 Identify the biological role of oxytocin in forming attachments.
 Evaluate the relationship between various neuropsychiatric disorders and oxytocin.
 Identify clinical implications of using oxytocin to treat various neuropsychiatric disorders.
Faculty Credentials and Disclosure Information
Shelly F. Greenfield, MD, MPH David M. Cochran, MD, PhD
Editor in Chief Assistant Professor
Harvard Review of Psychiatry University of Massachusetts Medical School
Harvard Medical School Department of Psychiatry
Boston, MA Worcester, MA

Joshua L. Roffman, MD, MMSc Daniel Fallon, MD
Deputy Editor Assistant Professor
Harvard Review of Psychiatry University of South Florida
Harvard Medical School Department of Psychiatry and Behavioral
Boston, MA Neurosciences
Tampa, FL
Stephen Scher, PhD, JD
Senior Editor Michael Hill, BS
Harvard Review of Psychiatry Research Coordinator
Harvard Medical School University of Massachusetts Medical School
Boston, MA Department of Psychiatry
Worcester, MA
Dawn E. Sugarman, PhD
Communications Editor Jean A. Frazier, MD
Harvard Review of Psychiatry Professor
Harvard Medical School Robert M. and Shirley S. Siff Endowed Chair in
Boston, MA Autism
Vice Chair and Director, Division of Child and
Adolescent Psychiatry
University of Massachusetts Medical School
Department of Psychiatry
Worcester, MA

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R
EVIEW
The Role of Oxytocin in Psychiatric Disorders:
A Review of Biological and Therapeutic
Research Findings
David M. Cochran, MD, PhD, Daniel Fallon, MD, Michael Hill, BS, and Jean A. Frazier, MD
LearningObjectives:Afterparticipatinginthiseducationalactivity,thephysicianshouldbebetterableto
1.Identifythebiologicalroleofoxytocininformingattachments.
2.Evaluatetherelationshipbetweenvariousneuropsychiatricdisordersandoxytocin.
3.Identifyclinicalimplicationsofusingoxytocintotreatvariousneuropsychiatricdisorders.
Oxytocinisapeptidehormoneintegralinparturition, milkletdown,andmaternalbehaviorsthat hasbeendemon-
stratedinanimalstudiestobeimportantintheformationofpairbondsandinsocialbehaviors.Thishormoneisin-
creasingly recognized as an important regulator of human social behaviors, including social decision making,
evaluatingandrespondingtosocialstimuli,mediatingsocialinteractions,andformingsocialmemories.Inaddition,
oxytocinisintricatelyinvolvedinabroadarrayofneuropsychiatricfunctionsandmaybeacommonfactorimportant
inmultiplepsychiatricdisorderssuchasautism,schizophrenia,andmoodandanxietydisorders.Thisreviewarticle
examines the extant literature on the evidence for oxytocin dysfunction in a variety of psychiatric disorders and
highlightstheneedforfurtherresearchtounderstandthecomplexroleoftheoxytocinsysteminpsychiatricdisease
and thus pave the way for developing new therapeutic modalities. Articles were selected that involved human
participantswithvariouspsychiatricdisordersandthateithercomparedoxytocinbiologytohealthycontrolsorexam-
inedtheeffectsofexogenousoxytocinadministration.
Keywords:anxiety,anxietydisorders,autism,humans,mooddisorders,oxytocin,schizophrenia
Oxytocin is a peptide hormone that is synthesized confirmedoxytocin’sroleasasocialhormonethatmediates
in the supraoptic and paraventricular nuclei of the many social behaviors involved in forming attachments.4
hypothalamus and is directly projected into other In healthy controls, oxytocin decreases both cortisol release
brain areas, where it acts as a neurotransmitter. It is also re- and anxiety in response to social stress,5 reduces amygdala
leasedintothebloodstream,viatheposteriorpituitarygland, activity in response to fearful or threatening visual images6
to peripheral targets.1,2 Animal studies highlight the impor- or emotional faces,7 increases trust behavior in a money-
tance of oxytocin in parturition, milk letdown, protective transferring game,8 increases the ability to interpret mental
aggression, socialbehaviors,and bonding between mothers states,9andincreasestheamountoftimespentgazingatthe
and infants and in mating pairs.3 Human studies have eyes when viewing faces.10 Van Ijzendorn and Bakermans-
Kranenburg11provideameta-analysissupportingthenotion
FromtheDivisionofChildandAdolescentPsychiatry,DepartmentofPsy- that intranasal oxytocin in healthy individuals enhances the
chiatry, University of Massachusetts Medical School (Drs. Cochran and
recognition of emotion and elevates the level of trust in es-
Frazier,andMr.Hill);DepartmentofPsychiatry,UniversityofSouthFlorida
(Dr.Fallon). tablished relationships. In addition to its prosocial effects, it
Original manuscript received 15 August 2012; revised manuscript re- hasalsobeenshowntobeinvolvedinjealousy,gloating,and
ceived1March2013,acceptedforpublication25March2013. out-groupdiscrimination.12–15Giventheeffectofoxytocinon
Correspondence:DavidCochran,MD,PhD,DivisionofChildPsychiatry, these basic interpersonal interactions, a growing body of re-
UniversityofMassachusettsMedicalSchool,55LakeAve.N.,Worcester,
search has investigated the possible involvement of oxytocin
MA01655.Email:[email protected]
HarvardReviewofPsychiatryoffersCMEforreaderswhocomplete inthepathophysiologyofneuropsychiatricdisordersthataffect
questions about featured articles. Questions can be accessed from the socialfunctioning,suchasautism,schizophrenia,anddepression.
HarvardReviewofPsychiatrywebsite(www.harvardreviewofpsychiatry.org) Many studies have examined the relationship between
byclickingtheCMEtab.Pleasereadthefeaturedarticleandthenlogintothe oxytocinandparent-childinteractions.16–20(Foradetailed
websiteforthiseducationaloffering.Ifyouarealreadyonline,clickheretogo
directlytotheCMEpageforfurtherinformation. review see Galbally et al.)21 For example, studies have
©2013PresidentandFellowsofHarvardCollege demonstrateddecreasedurinaryoxytocinlevelsinchildren
DOI:10.1097/HRP.0b013e3182a75b7d placed in orphanages shortly after birth22 and decreased
HarvardReviewofPsychiatry www.harvardreviewofpsychiatry.org 219
D. M. Cochran etal.
Table1
Human Studies of Oxytocin in Psychiatric Disorders
Authors Subjects Methodofstudy Mainfindings
Autismspectrumdisorders
Plasmalevels
Modahletal. 59males: PlasmalevelsofOT& SignificantlylowerOTlevelsinautistic
(1998)27 29autism unprocessedprecursor disorder(range=0–2.48pg/mL;
Greenetal. toOT mean=0.64±0.58pg/mL)thanin
(2001)28 30healthycontrols healthycontrols(range=0–2.72pg/mL;
Agerange=6–11 mean=1.16±0.77pg/mL;p<.004)
ElevatedOTlevelswereassociatedwith
lowerVABSscoresinautisticchildren
HigherlevelsofOTprecursorpeptidein
autisticdisorderthaninhealthycontrols
Jansenetal. 24subjects: PlasmalevelsofOTbefore NodifferenceinOTresponsetostress
(2006)29 10ASD(9M,1F; &afterpsychosocial IncreasedbasalOTlevelsinadults
meanage=21.8±2.0) stressor(publicspeaking) withASD(F=6.70;p<.05)
14healthycontrols(13M,1F; OTlevelswerenotcorrelatedwith
meanage=21.0±3.4) impairmentsinsocialinteractionor
communication,orwithstereotypedbehavior
Geneticstudies
Wuetal. 195ChineseHan FBATof4SNPswithin Significantassociationbetweenautism
(2005)30 autismproband-parenttrios OXTR;haplotype-specific &2SNPs:rs2254298A(Z=2.287;
FBAT p=.022)&rs53576A(Z=2.573;p=.01)
Numberofhaplotypes(inparticular,
involvingrs53576)weresignificantly
associatedwithautism
Jacobetal. 57Caucasianautism FBATof4SNPswithin Significantassociation
(2007)31 proband-parenttrios OXTR;haplotype-specific betweenautism&1SNP,
FBAT rs2254298G(χ2=4.80;p=.03)
Nohaplotypesweresignificantly
associatedwithautism
Lereretal. 152IsraeliASDprobands FBATof18SNPs Significantassociationbetweenthe
(2008)32 &theirfamilies withinOXTR; following:
haplotype-specificFBAT ASD&2SNPs:rs2268494(p=.01)
&rs1042778(p=.01)
IQ&2SNPs:rs4686301(p=.003)
&rs1042778(p=.01)
VABStotalscore&2SNPs:
rs4686301(p=.05)&rs6770632(p=.03)
VABSsubdomainscores&8SNPs:
communication(rs2254298[p=.02],
rs4686301[p=.04],rs2268490
[p=.02],rs237887[p=.04]&
rs6770362[p=.002]);dailyliving
skills(rs4564970[p=.04],
rs13316193[p=.02],rs2254298
[p=.03],rs237888[p=.05],rs237887
[p=.02]&rs6770632[p=.02]);
socialization(rs6770362[p=.02])
Multiplehaplotypesweresignificantly
associatedwithASDdiagnosis
Continuedonnextpage
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Role of Oxytocinin Psychiatric Disorders
Table 1
Continued
Authors Subjects Methodofstudy Mainfindings
Autismspectrumdisorders
Geneticstudies
Yrigollenetal. 177(93%Caucasian)ASD FBATof2SNPs Significantassociationbetweenthe
(2008)33 probands&theirfamilies withinOXT& following:
3SNPswithinOXTR ASD&1SNPwithinOXTR,rs2268493
(p=0.008)
Stereotypedbehaviors&1SNPwithin
OXT,rs2740204(p=.016)
Noassociationsremainedsignificant
aftercorrectionformultipletesting
Liuetal. Japanesesubjects: FBATof11SNPswithin NoassociationfoundinFBATanalysis
(2010)34 223ASDprobands& OXTR Significantdifferencesinallelic
theirfamilies(FBAT) Population-based, frequenciesof4SNPsin
65unrelatedASD case-control case-controlanalysis:
patients comparison rs237887G(p=.023),
rs2268491T(p=.004),
440unrelatedhealthy
rs2254298A(p=.001)
controls
&rs2268495G(p=.032)
Tanseyetal. 436CaucasianASD FBATof18SNPswithin Nominalassociationof3SNPswith
(2010)35 probands&theirfamilies OXTR ASDdiagnosisin1samplethatdid
(Irish,Portuguese&UK notwithstandcorrectionfor
samples) multiplecomparisons:
rs11720238G(p=.03),
rs7632287G(p=.008)
&rs4564970C(p=.009)
Wermteretal. 100GermanASDprobands& FBATof22SNPs Nominallysignificantassociationof
(2010)36 theirfamilies withinOXTR; 1SNP&1haplotypewithASDthat
haplotype-specificFBAT didnotwithstandcorrectionfor
multiplecomparisons:rs2270465G
(p=.02),rs237851-rs6791619-
rs53576-rs237884T-G-T-T(p=.007)
Patientscarryingthishaplotypeshowed
nominallysignificantimpairmentsin
socialinteraction&communication
comparedtononcarriers
Campbelletal. 2333(95%Caucasian)ASD FBATof25SNPswithin SignificantassociationbetweenASD
(2011)37 probands&theirfamilies OXTR &3SNPsthatwerealsoassociated
withmeasuresofsocial-
communicationdysfunction
(pvaluesforASDdiagnosison
AutismDiagnosticObservation
Schedule):rs2268493T(p=.04),
rs1042778G(p=.04)&rs7632287G
(p=.007)
Continuedonnextpage
HarvardReviewofPsychiatry www.harvardreviewofpsychiatry.org 221
D. M. Cochran etal.
Table1
Continued
Authors Subjects Methodofstudy Mainfindings
Autismspectrumdisorders
Epigeneticstudies
Gregoryetal. Singlemaleprobandand BSSofOXTRinperipheral AutisticbrotherofpatientwithOXTR
(2009)38 brother,bothwithautism bloodcellstodetermine deletionhadhypermethylation
butonlyformerwith methylationstatus ofOXTR
deletionin3p25.3
containingOXTR
20patientswithautism BSSofOXTRinperipheral SignificanthypermethylationofOXTR
(10M,10F) bloodcellstodetermine regionsinindividualswithautism
20healthycontrols methylationstatus comparedtocontrols
(10M,10F)
Postmortemtissuefrom BSSofOXTRintemporal Significanthypermethylationof
8autismpatients& cortextissuetodetermine OXTRregionsinautismcasescompared
8healthycontrols methylationstatus tocontrols
ResponsetoexogenousOT
Hollanderetal. 15subjects: Randomized,double-blind, Significantlygreaterreductionin
(2003)39 6autism placebo-controlled,crossover repetitivebehaviorsovertime
Hollanderetal. 9Asperger’ssyndrome challengeofcontinuous followingOT(drug×time
(2007)40 intravenousinfusionof interaction:F=3.487;p=.027)
14M,1F OT(10–15IU)orplacebo Increasedretentionofability
Meanage=32.9 over4hours betweentrialstoaccuratelyidentify
(range=19.4–55.6) effectofspeechinauditory
MeanIQ=90.3±9.9 comprehensiontaskifOTwas
(range=74–110) receivedfirstcomparedtoplacebo
beingreceivedfirst(time×treatment×
orderinteraction:Z=−2.134;
p=.033)
Guastellaetal. 16maleswithautistic Randomized,double-blind, OTimprovedperformanceonRMET
(2010)41 disorderorAsperger’s placebo-controlled,crossover for60%ofparticipants(t(14)=2.43;
syndrome challengeofintranasalOT p=.03)
Meanage=14.9±2.4 (18IUforages12–15,24IU Highlysignificantdifferenceon
(range=12–19) forages16–19)orplacebo easieritemsintheRMET
(t(14)=4.39;p=.001);
nosignificantdifferencefor
harderitems
Bartzetal. 27malehealthycontrols Randomized,double-blind, OTincreasedaccuracyofempathic
(2010)42 Meanage=26.8±7.0 placebo-controlled,crossover ratingofothers’emotionsonlyin
challengeofintranasal thosewithhighAQscores(drug
OT(24IU)orplacebo condition×AQinteraction:
b=0.11;t(232)=2.01;p<.05)
Andarietal. 26subjects: Randomized,double-blind, OTincreasedparticipants’
(2010)43 10Asperger’ssyndrome placebo-controlled,crossover interactionswithacooperative
challengeofintranasal playerinacomputerized
3high-functioningautism
OT(24IU)orplacebo ball-throwinggamecompared
11M,2F tononcooperativeplayers(Z=2.04;
Meanage=26(range=17–39) p<.04)
MeanIQ=99±23.5) OTsignificantlyincreased
timespentgazingatthefacein
13healthycontrols
eye-trackingexperiment,with
(age-&sex-matched)
significantlyincreasedfixationtimeon
theeyeregion(Z=2.12;p<.04)
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Role of Oxytocinin Psychiatric Disorders
Table 1
Continued
Authors Subjects Methodofstudy Mainfindings
Autismspectrumdisorders
ResponsetoexogenousOT
Kosakaetal. 116-year-oldfemalewith Casereportofadministration Improvementinsocial
(2012)44 autisticdisorder ofintranasalOT(8IUonce behaviorsnoted:
dailyfor2months) AberrantBehaviorChecklistscore
droppedfrom69to15,withmarked
decreasesinirritability&
hyperactivitysubscores
CGI-Severityscoreimprovedfrom
6(“severelyill”)to3(“mildlyill”)
CGI-Improvement=1(“verymuch
improved”)
Anagnostouetal. 19adultswith Randomized,double-blind, OTgroup:
(2012)45 high-functioningautism placebo-controlledtrialof Significantimprovementinability
orAsperger’ssyndrome intranasalOT(24IUtwice toidentifyemotionscomparedto
16M,3F dailyfor6weeks;n=10)or placebo(p=.002)
placebo(n=9)
Meanage=33.2±13.3 SignificantimprovementinWorld
MeanIQ=107±24 HealthOrganizationQualityofLife
Questionnaireemotional/social
subscale(p=.031)
Trendtowardimprovementon
RepetitiveBehaviorScale(p=.065)
Nonsignificantimprovementin
DiagnosticAnalysisofNonverbal
Accuracy,Social
ResponsivenessScale,Yale-Brown
Obsessive-CompulsiveScale&CGI
Schizophrenia
Plasma/CSFlevels
Linkowskietal. 24subjects: CSFhNPIIlevels hNPIIwashigherinpatientswith
(1984)46 12schizophrenia(9M,3F) schizophrenia(4.5±1.2ng/mL)than
incontrols(3.05±1.4ng/mL;
12age-matched t=2.82;p<.01)
neurologicalcontrols
(8hydrocephalus,1acoustic
neuroma,3cerebral
atrophy;8M,4F)
Agerange=29–65
Beckmannetal. 43subjects: CSFOTlevels OTwashigherinpatientswith
(1985)47 28maleswithschizophrenia, schizophreniaafterhaloperidoltreatment
paranoidtype(meanage= (13.46±5.96pg/mL;p<.01)&in
30.6±8.0) patientswithoutneuroleptic
treatment(10.03±4.03pg/mL;
15healthycontrols(13M,2F; p<.05)thaninhealthycontrols
meanage=35.0±15.7)
(7.11±4.03pg/mL)
Continuedonnextpage
HarvardReviewofPsychiatry www.harvardreviewofpsychiatry.org 223
D. M. Cochran etal.
Table1
Continued
Authors Subjects Methodofstudy Mainfindings
Schizophrenia
Plasma/CSFlevels
Legrosetal. 23subjects: SerumhNPIIlevels BasallevelsofhNPIIwerehigherin
(1992)48 9malepatientswith before&after schizophrenia(3.34±0.04ng/mL)
schizophrenia apomorphinechallenge thaninhealthycontrols
(0.92±0.21ng/mL;p=.001)
14healthycontrols
Nosignificantchangein
schizophreniaafterapomorphine
challengecomparedto2-fold
increaseinhealthycontrols
Basallevelswerehigherinparanoid
subgroup(5.15±0.99ng/mL;
n=4)thaninnonparanoidsubgroup
(1.92±0.61ng/mL;n=4;p<.03)
Glovinskyetal. 66subjects: CSFOTlevels Nosignificantdifferencesbetween
(1994)49 20neuroleptic-treatedpatients groups(p=.11)
31neuroeptic-withdrawn
patients
15healthycontrols
Goldmanetal. 22subjects: PlasmaOTlevelsbefore& OTwasnonsignificantlylowerin
(2008)50 6polydipsic, afterstressinduction hyponatremicpatients(100±35pg/mL)
hyponatremicpatients thaninotherthreegroups
(266±309pg/mL,301±338pg/mL&
4polydipsic,
240±224pg/mL,respectively;p=.07)
normonatremicpatients
OTlevelswereinversely
5nonpolydipsic,
correlatedwithanteriorhippocampal
normonatremicpatients
volumesinstructuralMRI
7healthycontrols
OTlevelswerecorrelatedwith
patients’abilitytocorrectlyidentify
facialemotions(r=0.62;p=.02)
Kerietal. 100subjects: PlasmaOTlevels NosignificantdifferencesinOT
(2009)51 50withschizophrenia levelsafterneutralinteractions
withexaminer
50healthycontrols
OTlevelsincreasedsignificantly
inhealthycontrolsaftertrust-related
interactions(p<.001)butnotin
patientswithschizophrenia(p>.5)
SignificantlylowerOTlevelsin
patientsaftertrust-relatedinteractions
(p<.0001)
LowOTlevelsaftertrust-related
interactionssignificantly
correlatedwithnegativesymptoms
asmeasuredbyPANSSscore
(F(1,48)=35.03,p<.0001;β=−0.65;
R2=0.42)
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Role of Oxytocinin Psychiatric Disorders
Table 1
Continued
Authors Subjects Methodofstudy Mainfindings
Schizophrenia
Plasma/CSFlevels
Rubinetal. 108subjects: PlasmaOTlevels Nosignificantdifferencebetween
(2010)52 50patientswith patients&controls,oracross
schizophrenia phasesofmenstrualcycleinfemales
(27M,23F) Femalepatients:higherOTlevels
58healthycontrols associatedwithlowerPANSStotal
(27M,31F) symptom,positivesymptom&
generalpsychopathologysubscores
(p<.01forall);trendtoward
associationwithlowernegative
symptomsubscore(p=.06)
Allpatients:higherOTlevels
associatedwithbetterprosocial
scoresonPANSS(p<.01for
females;p<.05formales)
Sasayamaetal. 48subjects: CSFOTlevels CSFlevelsdidnotdiffersignificantly
(2012)53 27patientswith betweenpatients&controls
schizophrenia OTlevelsweresignificantlynegatively
21healthycontrols correlatedwithsecondgeneration
antipsychoticdose(r=−0.49;
p=.010)&negativesymptom
PANSSsubscore(r=−0.47;p=.016)
Geneticstudies
Souzaetal. 358subjects(case-control): Case-controlcomparison FBATanalysis:OXT,rs2740204
(2010)54 179patientswith of7SNPswithinOXT T(p=.027)
schizophrenia &13SNPsinOXTR; Case-controlstudy:OXTRrs4813625
FBATofsameSNPs
179healthycontrols C(p=.036)&rs3761248C(p=.030)
FBAT: Noneremainedsignificantafter
correctionformultipletesting
49probands&their
healthyparents
Souzaetal. 140patientswith AssociationofOXT OXTrs2740204G:significantly
(2010)55 schizophrenia &OXTRvariantswith associatedwithtreatmentresponse
treatedwithclozapine symptomseverity& (p=.042aftercorrectionformultiple
responsetoclozapine testing);nominallysignificant
associationwithnegativesymptoms
(p=.01priortocorrection)
OXTRrs237885T&rs237887A:
nominallysignificantassociationwith
severityofoverallsymptoms(p=.014&
.033,respectively,priortocorrection)
OXTRrs11706648A,rs4686301C
&rs237899G:nominallysignificant
associationwithimprovementofpositive
symptomsonclozapine(p=.0002,
.0002&.039,respectively,priorto
correction)
Continuedonnextpage
HarvardReviewofPsychiatry www.harvardreviewofpsychiatry.org 225
D. M. Cochran etal.
Table1
Continued
Authors Subjects Methodofstudy Mainfindings
Schizophrenia
Geneticstudies
Teltshetal. Clanof56Arab-Israeli Identifiedgenevariants TwovariantsofOXTweresignificantly
(2011)56 individuals inOXTinindividuals associatedwithschizophreniain
52Arab-Israelinuclear inclanwithschizophrenia; initialclanstudied:rs4813626G
families(n=276) thensoughtassociation (p=.002)&rs2740204A(p=.00059)
Jewishcase-controlsample withschizophreniainthis Oppositealleleofonevariant
(n=545) pedigreeandin2larger (rs4813626A)wassignificantly
populationsamples associatedwithschizophreniain
nuclearfamilysample(p=.0055)&in
menonlyintheJewishcase-control
sample(p=.0006)
Montagetal. 812subjects: Case-controlcomparison Significantassociationof2OXTR
(2012)57 406patientswithschizophrenia of2SNPswithinOXT& variantswithdiagnosisofschizophrenia:
4SNPSwithinOXTR rs53576A(p=.008)&
406healthycontrols
rs237885T(p=.025)(posthoc
analysisrevealedassociationwith
GeneralPsychopathology
PANSSsubscores)
Montagetal. 290subjects: Case-controlcomparison Nosignificantassociationof
(2012)58 145patientswith of2SNPswithinOXTR rs2254298orrs53576with
schizophrenia diagnosis
145healthycontrols Withinschizophreniagroup,
rs2254298Awasassociatedwith
higherlevelsofempathicconcernin
theInterpersonalReactivityIndex
Watanabeetal. 1218subjects: Case-controlcomparison Nosignificantassociationsbetween
(2012)59 544patientswith of14SNPswithinOXTR; anyof14SNPsexamined&
schizophrenia FBATofsameSNPs thediagnosis
674healthycontrols
FBAT:
105triosofpatientswith
schizophrenia&theirparents
ResponsetoexogenousOT
Bakharevetal. 45malesubjects Placebo-controlledstudyof Nocomplicationsorsideeffects
(1986)60 withschizophrenia OTfor2nonconsecutive Positiveresultsbutmethodological
weeks(5IUbid;n=27)vs. limitations;“bestresultsachievedin
placebo(n=18) personswhosepredominantsymptoms
wereanergy,asthenia,andapathy
combinedwithdepressedmood”
Feifeletal. 19patientswithschizophrenia Randomized,double-blind, SignificantreductioninPANSS
(2010)61 crossoverstudy;3weeksof &CGI-Improvementat3-week
OT(titratedto40IUbid)or endpointcomparedtoplacebo
placeboasadjunctive (p<.001)
treatmenttostable Significantreductioninpositive
antipsychoticregimen symptomsubscore(p=.006)
&negativesymptomsubscore
(p=.023)atweek3
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