The polymorphisms in serotonin-related genes (5-HT2A and SERT) and the prevalence of depressive symptoms in obese patients.

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The polymorphisms in serotonin-related genes

(5-HT2A and SERT) and the prevalence of

depressive symptoms in obese patients.

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Neuroscience

Letters

j ou rn a l h om ep a g e :w w w . e l s e v i e r . c o m / l o c a t e / n e u l e t

Research

article

The

polymorphisms

in

serotonin-related

genes

(5-HT

2A

and

SERT)

and

the

prevalence

of

depressive

symptoms

in

obese

patients

Maciej

Bieli ´nski

a,d,∗

_,

_Marta

_Tomaszewska

a

_,

_Marcin

_Jaracz

a

_,

_Joanna

_{Pulkowska-Ulfig}

a

_,

Dominika

Długosz

a

_,

_Marcin

_Sikora

b

_,

_Andrzej

_Tretyn

b

_,

_Anna

_{Kami ´nska}

c

_,

Roman

Junik

c

_,

_Alina

_Borkowska

a

a_{CollegiumMedicumofNicolausCopernicusUniversity,DepartmentofClinicalNeuropsychology,Bydgoszcz,Poland} b_{NicolausCopernicusUniversity,DepartmentofBiotechnology,Toru´n,Poland}

c_{CollegiumMedicumofNicolausCopernicusUniversity,DepartmentofEndocrinologyandDiabetology,Bydgoszcz,Poland} d_{JanBiziel’sUniversityHospital,DivisionofVascularDiseasesandInternalMedicine,Bydgoszcz,Poland}

h

i

g

h

l

i

g

h

t

s

•Weexaminetheassociationbetweenserotonin-relatedgenepolymorphismsandtheoccurrenceofdepressivesymptoms.

•Theexperimentalgroupconsistsofobesepatients.

•ForthedepressivesymptomsmeasurementweusetheBeckDepressionInventory(BDI)andHamiltonDepressionScale(HAM-D).

•39%ofpatientsarediagnosedwithdepressivesymptoms.

•Therearenosignificantassociationsbetween5-HT2Aand5-HTTgenepolymorphismsanddepressivesymptoms.

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received18August2014 Receivedinrevisedform 26November2014 Accepted3December2014 Availableonline5December2014 Keywords: Depression Obesity Serotonergicsystem HAM-D BDI Mann-WhitneyUtest R-Spearmantest

a

b

s

t

r

a

c

t

Asoverweightandobesityareagrowingprobleminindustrializedsocieties,theybecomeamainfocus ofmanystudies.Theaimofthisstudywastodeterminewhetherthereisanassociationbetweenthe occurrenceofpolymorphismsinserotonin-relatedgenesandtheprevalenceofdepressivesymptoms inobesepatients.Twopolymorphismsweretested:a44-bpinsertion/deletionintheserotonin trans-porter(SERT)geneandasingle-nucleotidevariation(1438G/A)intheserotonin2Areceptor(5-HT2A)

gene.Thestudyinvolved180patients(41men;139women)previouslydiagnosedasobese.Allpatients weresubjectedtoclinical,biochemical,andneuropsychologicalevaluationandgenotyping. Amplifica-tionofthegenefragmentswasobtainedbythepolymerasechainreaction(PCR)method.Productsof thegenotypingwereseparatedviaelectrophoresis.Theintensityofdepressivesymptomswasmeasured usingtheBeckDepressionInventory(BDI)andHamiltonDepressionScale(HAM-D).Clinicallyrelevant depressivesymptomswerediagnosedin39%ofsubjects.Thelowestintensitiesofdepressivesymptoms wereascertainedinthegroupwiththeleastadvancedobesity,butthistrendwasstatistically insignifi-cant.Smalldifferenceswereobservedinobesityindicatorsamongthreegroupsofpatientswithvarious genotypesoftheSERTgene,butthesedifferenceswerealsostatisticallyinsignificant.Furthermore,in thecontextoftheintensityofdepressivesymptoms,nosignificantassociationswereobservedinthese twogroups.Furthermore,nostatisticallysignificantdifferenceswereobservedamongspecificobesity parametersandintensityofdepressivesymptomsasafunctionofthe5-HT2Agenepolymorphism.To

conclude,depressivesymptomswereprevalentinobeseparticipants:39%ofsubjectsexperienced symp-tomsofclinicalrelevance.However,nosignificantassociationswereobservedbetween5-HT2AandSERT

genepolymorphismsanddepressivesymptomsinthisstudygroup.

©2014ElsevierIrelandLtd.Allrightsreserved.

∗ Correspondingauthorat:DepartmentofClinicalNeuropsychology,Collegium MedicumofNCUul.MariiCurie-Skłodowskiej9,85-094Bydgoszcz,Poland. Tel.:+48525853707;fax:+48525853707.

E-mailaddress:bielinskim@gmail.com(M.Bieli ´nski).

1. Introduction

Thehighestprevalenceofobesityaffectsindustrialized coun-triesandsocieties,inwhichhigh-caloriedietsarewidespread.In Poland,thenumberofpeoplelivingwiththisproblemisincreasing. ResultsobtainedbythePol-MONICAstudyin1984,1988,and1993 http://dx.doi.org/10.1016/j.neulet.2014.12.012

32 M.Bieli´nskietal./NeuroscienceLetters586(2015)31–35

revealedthatthepercentageofobesewomenincreasedfrom28% to29%andthatofobesemenincreasedfrom18.6%to22.4%over thistimeperiod[1].

Overweightandobesityarealsocorrelatedwiththeoccurrence ofdepressivesymptoms.Prospectiveobservationalresearchhas shownthatoccurrenceofdepressionpredictsthedevelopmentof obesity,andalsothattheoccurrenceofobesityisafactorinthe developmentofdepression[2,3].Datacollectedoverthecourseof anationalhealthprogramconductedintheUSAfrom2005to2006 revealedthatBMIpositivelycorrelateswithmildand moderate depressivesymptoms,aswellaswithmajordepression,definedas havingascoreof≥10ormeetingtheDiagnosticandStatistical Man-ualofMentalDisorders,4thedition(DSM-IV)diagnosticcriteria formajordepressiononthenine-itemPatientHealth Question-naire(PHQ-9).Theincreaseindepressivesymptomsasafunction ofweightstartsataBMIof30kg/m[2,4].

A large body of research indicates that serotonergic trans-missionplays a role in eating disorders. In humans, serotonin anditsagonistscausemoderationoffoodingestion,weightloss, andincreasedenergyexpenditure.Theactivityoftheserotonin transporter(SERT) is negatively correlated withBMI [5], possi-blyexplaining theeffectiveness of selective serotoninreuptake inhibitors(SSRI)forthetreatmentofobesity[6,7].

ThegeneencodingSERTislocatedonthelongarmof chromo-some17(17q11.1–17q12).Polymorphismsinthetranscriptional regulatoryregionofthisgene(5-HTTLPR:SERTgene-linked poly-morphicregion)involvearegionofvariablelengththatisrichin guanine–cytosinepairs.Theabsenceorpresenceofa44-bp frag-mentin this region resultsin theshort (S)or long(L) variant, respectively;thesevariants differingene promoteractivity[8]. TheS-alleleislinkedtolowerbaselinetranscriptionalactivityof theSERTgene,resultinginlowerefficiencyofserotoninreuptake

[9,10].Todate,itremainsunclearwhetherthe5-HTTLPR polymor-phismisrelatedtoobesity.

Thegeneencodingtheserotonin2Areceptor(5-HT2A)islocated

on the long arm of chromosome 13 (13q14–q21). The most commonly investigated polymorphism of this gene is a single-nucleotidevariation,1438G/A, inthepromoter. Severalstudies haveinvestigatedthepossibleroleofthispolymorphismin obe-sity,buttheresultsareambiguous.Perez-Cornagoetal.determined thatDNAhypermethylationof5-HT2Aisassociatedwithaworse

responsetoaweightlossinterventioninsubjectswithmetabolic syndrome[11].

Bothof thesepolymorphismshavealsobeeninvestigated in thecontextof theirassociationwithdepressivesymptoms.In a Scottishpopulation,theS-allelepositivelycorrelatedwith unipo-lardisorder[12];however,anotherstudyshowedthattheL-alleleis associatedwiththisdisease[13].Ameta-analysispublishedin2004 revealedastatisticallysignificantassociationbetweentheS-allele andunipolardisorder[14].Analysisofthe1438G/Apolymorphism didnotrevealanysignificantcorrelationwiththeoccurrenceof majordepression[15].However,ina groupof67personswith seasonaldepression,theA-allelewasmoreprevalent[16]. 2. Theaimofthestudy

Wesoughttoassesstheassociationbetweenpolymorphismsin serotonin-relatedgenes(5-HT2AandSERT)andtheoccurrenceof

depressivesymptomsinobesepatients. 3. Methods

Thestudyinvolved180patients(139women)ofPolish nation-alityandCaucasianethnicity,aged18–73years(mean,43.7±7.8). Demographic factors are shown in Table 1. The subjects were

diagnosed as obese (BMI>30kg/m2_{) and they were recruited}

frompopulationhospitalizedinDepartmentofEndocrinologyand DiabetologyofCollegiumMedicumoftheNicolausCopernicus Uni-versity(NCU)duetoobesity.Patientswithaddictionsorsevere somatic,psychiatric,orneurologicaldisorderswereexcluded,as werepatientswithsecondaryobesity.Permissionforthestudywas obtainedfromtheBioethicalCommissionoftheNCU,Collegium MedicuminBydgoszcz(No.533/2008).Thesubjectsdemonstrated their willingness to participate in the project by signing the InformedConsentForm.

3.1. Assessments

Thefirststageofthestudywastheclinicalassessment,which consistedofobtainingamedicalhistoryandperforminga phys-icalexamination.Aspectsofobesityandpsychologicaldisorders mentionedinthemedicalhistorywereemphasized.Metric mea-surementsweretakenofbodyweight,waistcircumference,and hipcircumference;waist-hipratio(WHR)wasalsocalculated.

Thenextstepwasassessment of theintensityofdepressive symptoms.Forthispurpose,TheBeckDepressionInventory(BDI) and theHamiltonDepressionRatingScale (HAM-D)wereused. Accordingtothe BDI, patientsscoring12 or more pointswere diagnosedashavingclinicallyimportantsymptomsofdepression. HAM-Disamultiple-choicequestionnairethatisusefulfor mea-suringlevelsofdepressionamongpatients.Thequestionnaireis filledinbytheclinician;therefore,itisanobjectivetoolfor mea-suringtheintensityofdepressivesymptoms.HAM-D,whichwas designedforadults,definesthelevelofobserveddepressive symp-toms,includinglowmood,insomnia,anxiety,andweightloss. 3.2. Isolationofgeneticmaterial

7–10mlofperipheralbloodwascollectedandmixedwith0.5ml of0.5Methylenediaminetetraaceticacid(EDTA), thenfrozenin liquidnitrogenandstoredat−80◦_{Cuntilisolation.Theisolation}

procedurewasfollowedusingfastisolationprocedurebyLahiri andSchnabel[17]andstoredat−20◦_C.

3.3. Genotypeanalysis

5-HT2AgenepromoterregionandSERTgenefragmentswhere

amplifiedusingthepolymerasechainreaction(PCR)methodwith thefollowingprotocol:initialdenaturationat95◦Cfor5min,30 cyclesofdenaturationat95◦C for1min,annealingat58◦C for 1min,elongationat72◦Cfor1min,andfinal extensionat72◦C for2min.Thereactionmixturecontained0.2UofTaqpolymerase (Fermentas),5pmolofeachprimer,1×(NH4)2SO4buffer,4mmol dNTPmixture,100–200ngofmatrixDNA,1.5mMMgCl2andH2O tofinalvolumeof20␮l.

Primers’ sequences for 5-HT2A were: F

5’-ACGAAGGGACTCCTGGTTTC-3’ and R

5’-CTGGGTGGGATATTTCTGCT-3’ [18]. Amplified product of 515bp length (∼100ng) was digested overnight with 0.2U of HpaII restrictionenzyme(Fermentas)at37◦C.Ampliconswith−1438G allelewerecutinto331bpand184bpfragments,whilethosewith −1438Aremainedundigested.Thefragmentswereseparatedvia electrophoresis in 3%agarose gel containingethidium bromide andvisualizedunderUVilluminationwithO’RangeRulerTM_50bp

DNALadder(Fermentas)asDNAlengthmarker(Fig.1).

Primers’ sequences for SERT were:

5-GGCGTTGCCGCTCTGAATGC-3 and 5

-GAGGGACTGAGCTGGACAACCAC-3 [19]. Amplified products of529and485bp,correspondingtoLand Sallelerespectively, wereseparatedviaelectrophoresisin 2%agarosegelcontaining ethidium bromide and visualized under UV illumination with

Table1

Demographicandclinicalcharacteristicsofthestudyparticipantsundefined.

Group N MedianBMI

(range) [95%CI]

Medianage, years(range) [95%CI]

MedianBDIscore (range) [95%CI]

MedianHAM-Dscore (range)

[95%CI]

Women 139 42.4charndash

(30.1–64.1) [41,8to44,5] 40charndash (18–73) [37,5to42,0] 9charndash (0–34) [9,4to12,5] 4charndash (0–29) [5,0to8,4]

Men 41 47.3charndash

(30.7–59.4) [43,2to48,1] 40charndash (19–63) [37,5to44,7] 11charndash (0–35) [8,5to15,7] 6charndash (0–20) [3,6to10,0] BMI:bodymassindex;BDI:BeckDepressionInventory;HAM-D:HamiltonDepressionScale.

Fig.1.Representativephotoofthedigested5-HT2APCRproductsdependingon thegenotype:AA–only515bpband;G/A–515,331and184bpbands;GG–331and 184bpbands.

Fig.2.RepresentativephotoofseparatedSERTPCRproductsdependingonthe genotype:LL–only529bpband;S/S485bpband;L/S–529and458bpbandsM-DNA ladder.

O’RangeRulerTM _{50bp DNA Ladder (Fermentas) as DNA length}

marker(Fig.2). 3.4. Statisticalanalysis

STATISTICA9.0wasusedforstatisticalanalyses.The distribu-tionofvariableswasanalyzedusingtheShapiro–Wilktest,which indicatedthatthevariableswerenon-parametric.Toassessthe sig-nificanceofthedifferencesbetweengroups,theMann–Whitney Utestwasconductedforcomparisonsbetweentwogroupsand theKruskal–Wallisone-wayanalysisofvariancebyrankstestwas usedforcomparisonsamongthreegroups.TheR-Spearmantest wasusedtodeterminecorrelationsbetweenvariables.The com-puterprogram‘UtilityProgramsforAnalysisofGeneticLinkage’ (Copyright©1988J.Tot)wasutilized totest thegoodnessof fit ofthegenotypestoHardy–Weinbergequilibrium.Ap-value>0.05 indicatesagreementwithHardy–Weinbergequilibrium.

4. Results

TheMann–WhitneyUtestwasperformedtodeterminewhether theBMIparameterdifferedsignificantlybetweenmaleandfemale subjects.ThemeanBMIvaluewasslightlyhigherinthemale pop-ulation,butthisdifferencewasnotstatisticallysignificant.

The intensities of depressive symptoms determined by the BDIandHAM-Dscaleswerehighlypositivelycorrelatedinboth women(p=1E-05)andmen(p=0.0001).Clinicallyrelevant depres-sivesymptomswerediagnosedin39%ofsubjects.Becausethedata werenon-parametricwecalculatedtheR-Spearmanrank correla-tioncoefficienttoinvestigatethecorrelationbetweenageandBMI; thesevalues werepositivelycorrelated (r=0.329;p=0.000022). NorelevantcorrelationsamongageandBDI/HAM-Dscoreswere observed.Thelowestintensitiesofdepressivesymptoms(as mea-suredbytheBDI)wereobservedinthegroupwiththelowestlevel ofobesity,butthistrendwasnotstatisticallysignificant.

RegardingtheL/S(SLC6A4)polymorphismoftheSERTgene,we usedboththeBDIandHAM-Dtomeasuretheintensityof depres-sivesymptomsinL/LandS/ShomozygotesandL/Sheterozygotes insubgroupscomprisingmaleandfemalesubjects(Table2).

Inaddition,weexaminedthecorrelationbetweentheL/S poly-morphismandexcessivebodymass.(Table2)presentsthemean

Table2

BDI,HAM-DandBMIresultsinrelationtopolymorphismL/S(SLC6A4)oftheSERT gene. TOTAL L/L(n=63) L/S(n=89) S/S(n=25) p-value BDI 10.0 (0.0–34.0) [9,6to14,3] 8 (0.0–35.0) [7,6to11,7] 15.5 (0.0–32.0) [9,3to18,0] 0.11 HAM-D 6.0 (0.0–29.0) [5,1to10,7] 4.0 (0.0–25.0) [3,9to7,9] 5.0 (0.0–19.0) [2,11to10,9] 0.66 BMI 43.2 (30.1–61.9) [41,7to45,8] 42.4 (30.1–64.1) [41,8to45,3] 44.3 (33.2–59.4) [41,8to47,6] 0.85 FEMALES L/L(n=50) L/S(n=65) S/S(n=20) p-value BDI 9.0 (0.0–34.0) [9,4to14,8] 6.0 (0.0–25.0) [6,6to10,7] 15.5 (0.0–32.0) [9,2to18,5] 0.054 HAM-D 7.0 (0.0–29.0) [5,4to11,7] 3.0 (0.0–25.0) [2,7to7,0] 8.0 (0.0–19.0) [2,3to14,3] 0.08 BMI 41.5 (30.1–57.1) [40,1to44,6] 41.3 (30.1–64.1) [41,3to45,6] 43.9 (37.2–58.6) [41,2to46,4] 0.55 MALES L/L(n=13) L/S(n=24) S/S(n=5) p-value BDI 11.0 (0.0–27.0) [6,3to17,9] 9.0 (0.0–35.0) [6,9to17,4] 12.0 (3.0–21.0) [0,3to23,7] 0.99 HAM-D 3.5 (0.0–8.0) [-2,4to9,9] 9.5 (0.0–20.0) [4,6to14,4] 1.0 (1.0–5.0) [-3to8,0] 0.13 BMI 48.9 (31.7–59.2) [42,8to52,3] 43.9 (30.7–55.1) [41,1to17,4] 51.5 (33.2–59.4) [30,6to67,2] 0.42

Valuesareexpressedasthemedian(range).[95%CI]–95%confidenceinterval;BDI: BeckDepressionInventory;HAM-D:HamiltonDepressionScale.

34 M.Bieli´nskietal./NeuroscienceLetters586(2015)31–35 Table3

BDI,HAM-DandBMIresultsinrelationtopolymorphism1438G/Aofthe5-HT2A

gene.

TOTAL

A/A(n=25) A/G(n=83) G/G(n=69) p-value BDI 9.0 (0.0–33.0) [6,2to15,6] 8.0 (0.0–35.0) [9,0to13,2] 11.0 (0.0–34.0) [9,5to14,0] 0.69 HAM-D 7.0 (0.0–21.0) [3,5to12,2] 3.0 (0.0–29.0) [3,8to8,6] 7.0 (0.0–21.0) [5,2to9,1] 0.38 BMI 43.2 (30.1–64.1) [40,8to48,6] 43.9 (30.8–61.9) [41,8to45,1] 43.2 (30.1–59.2) [42,1to46,0] 0.82 FEMALES

A/A(n=19) A/G(n=59) G/G(n=57) p-value BDI 8.0 (0.0–33.0) [4,6to16,9] 8.0 (0.0–31.0) [8,0to12,5] 11.0 (0.0–34.0) [9,8to14,5] 0.21 HAM-D 7.0 (0.0–21.0) [3,3to14,9] 3.0 (0.0–29.0) [3,0to8,7] 6.0 (0.0–21.0) [4,7to9,1] 0.32 BMI 45.0 (30.8–61.9) [41,5to50,1] 41.5 (30.1–59.2) [40,7to44,5] 41.9 (30.1–64.1) [40,9to45,3] 0.47 MALES

A/A(n=6) A/G(n=24) G/G(n=12) p-value BDI 11.0 (3.0–21.0) [5,3to17,6] 11.0 (0.0–35.0) [7,5to18,5] 10.0 (0.0–30.0) [4,2to18,2] 0.79 HAM-D 4.5 (0.0–9.0) [-2,9to11,9] 5.0 (0.0–20.00) [1,5to13,6] 7.5 (4.0–11.0) [2,5to12,4] 0.99 BMI 37.4 (31.7–59.4) [30,0to52,6] 47.6 (30.8–59.2) [42,5to49,3] 48.9 (36.6–55.4) [43,7to51,0] 0.99

Valuesareexpressedasthemedian(range).M[95%CI]–95%confidenceinterval; IBDI:BeckDepressionInventory;HAM-D:HamiltonDepressionScale;BMI:Body MassIndex.

valuesoftheparametersdescribingobesityinthreesubgroups: L/LandS/ShomozygotesandL/Sheterozygotes.Analysisofthese resultsindicatedthattherewerenostatisticallysignificant differ-encesamongthethreesubgroups,BMIoscillatedaroundsimilar valuesregardlessofthealleletype.

Amongobesefemales,theassociationsbetweenL-allele car-rierandS-allelehomozygotestatusandtheintensityofdepressive symptoms(measuredwiththeBDI)werelikewisenotsignificant (Table2).InL/LandL/Sfemalestheintensityofdepressive symp-tomswas9.0,andamongS/Sfemalesitwas15.5,withthep-value of0.077.

Themostfrequentlystudiedpolymorphismofthe5-HT2Agene

isthe1438G/Apromoterpolymorphism.Therefore,wenext inves-tigatedwhethertheoccurrenceofobesitydifferedamongA/Aand G/GhomozygotesandG/Aheterozygotes(insubgroupsofwomen andmen) (Table3).However,thedifferenceswere not statisti-callyrelevant;BMIoscillatedaroundsimilarvaluesregardlessof thealleletype.

In addition, we investigated the association between poly-morphismsin the 5-HT2A gene and the intensityof depressive

symptomsasmeasuredbyboth BDIandHAM-D(Table3).This analysisdidnot detectanysignificantdifferences in the inten-sityofdepressioninassociationwiththe5-HT2Agene1438G/A polymorphism.

5. Discussion

Overweight and obesity have become serious problems in recentyears;therefore,identifyingthecausesanddevelopingnew

treatmentsareimportantscientificgoals.Furthermore, psycholog-icalissuesareakeyaspectofeatingdisorders.

Many studies show that the most common problem affect-ingoverweightandobesepeopleisdepression[2–4,20].Here,we confirmedthattheprevalenceofdepressioninacohortofobese patientswas39%.Itisinagreementwithpreviousstudieswhich likewiseindicatedhighprevalenceofdepressioninobesesubjects

[2].Previousstudiesreportacorrelationbetweenperturbationsof theserotoninergicsystem,obesity,anddepression;consistentwith this,serotoninergicantidepressantshavebeenusedsuccessfullyto treatsomecasesofobesity[21].

Onthebasisoftheseearlierfindings,oneofthemaingoalsof thepresentstudywastoassesstheinterplaybetween polymor-phismsingenesrelatedtoneurotransmitteractivity,parametersof obesity,anddepressivesymptoms;certaininterdependenceswere identified.

Previousstudies[8,22,23]ontheassociationbetweentheL/S 5-HTTLPRpolymorphismand obesityyieldedconflictingresults. Similarly,theresultspresentedheredonotdemonstrateaspecific correlationbetweenBMIandL/S5-HTTLPR.Therefore,thisquestion requiresadditionalstudyinothergroupsofobesesubjects.

Studiesconducted nearly20 years ago suggesta correlation betweentheL-alleleandunipolardisease[12,13].However,a sub-sequentmeta-analysisofthreestudiesindicatesthattheS-alleleis associatedwithunipolardisease[24].Theresultspresentedherein aredifferentfromthoseofpreviousstudies,whichsuggestedthat theS-alleleisassociatedwithagreaterpredispositiontodepression

[25].AlsoinrecentstudySchulzetal.observedrelevant correla-tionbetweenS-alleleanddepressionmeasuredbyShortGeriatric DepressionScaleingroupof606individuals[26].

Here,weobservednoassociationsbetween5-HTTLPRgenotype andtheintensityofdepressivesymptoms(asmeasuredbyBDIand HAM-D).Thisfindingsuggeststhatinthesepatientspolymorphism oftheserotonintransportergeneisnotthemostsignificantfactor leadingtodepression.

Astothe1438G/Apolymorphismintheserotonin2A recep-tor,weobservednosignificantdifferenceinobesityindicatorsin subjectscarryingthis allele.Similarly, nosuchdifferenceswere detected in a family study conducted in a Spanish population

[29].

Likewise,wedidnotobserveanassociationbetweentheGand Aallelesandtheintensityofdepressivesymptomsinobese sub-jects.Therefore,itislikelythatpolymorphismofthe5-HT2Agene

doesnotplay asignificantrole intheetiology ofdepression in obesepeople.Similarresultswereobtainedinseveralstudiesof affectivediseasesassessedintwometa-analyses[15,16],inwhich majordepression,unipolarandbipolardisorderswarediagnosed accordingtoastandarddiagnosticcriteria(DSM,ICD).

Thefindingsofglobalstudiesarenotuniform:Japaneseauthors havedemonstratedastatisticallysignificantassociationbetween the 5-HT2A A/G polymorphism and the intensity of depressive

symptoms(asmeasuredbytheMADRSscale)[30].

Thepresentresultssuggest,atleastinthisspecificpopulation, thatitisunlikelythatpolymorphismsintheSERTand5-HT2Agenes

aresignificantlycorrelatedwiththeintensityofdepressive symp-tomsinobesesubjectsorwithobesityitself.Thus,theresultsreflect theenormouscomplexityoftheproblemofobesityanddepression. Wemustcontinuesearchingforthegeneticmechanisms respon-siblefordepressivesymptomsinthesepatients.

Conflictofinterest

Theauthorsdeclarenoconflictsofinterestinassociationwith thismanuscript.

Acknowledgment

ThisresearchwassupportedbyagrantfromthePolishMinistry ofScienceandHigherEducation(GrantNo.NN402053136). References

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