Perez-Cornago et al. Nutrition Journal 2014, 13:36

Transcription

1 RESEARCH Open Access A decline in inflmmtion is ssocited with less depressive symptoms fter dietry intervention in metolic syndrome ptients: longitudinl study Auror Perez-Corngo 1, Rocio de l Iglesi 1, Ptrici Lopez-Legrre 1,2, Itzir Aete 3, Sntigo Nvs-Crretero 1,4, Clr I Lcunz 5, Frncisc Lhortig 5, Miguel A Mrtinez-Gonzlez 6, J Alfredo Mrtinez 1,4* nd M Angeles Zulet 1,4 Astrct Bckground: Metolic syndrome (MetS) nd depression hve ecome two prevlent diseses worldwide, whose interction needs further investigtion. Dietry tretment for weight loss in ptients with MetS my improve depressive mnifesttions, however, the precise interctive pthwys remin uncertin. Therefore, the im of this study ws to exmine the effects of hypocloric diet designed to reduce MetS fetures on self-perceived depression nd the possile underlying fctors. Methods: Sixty sujects (Age: 50 ± 1 y; BMI: 36.1 ± 0.6 kg/m 2 ) with MetS were selected from the RESMENA study (control nd intervention) fter they completed the 6-months hypocloric tretment nd rted for depressive symptoms using the Beck Depression Inventory (BDI). Anthropometric nd iochemicl mesurements including leptin, C-rective protein (CRP) nd insulin levels were evluted. Results: Depressive symptoms decresed during the weight loss intervention, with no differences etween oth dietry groups (control group 4.2 ± 0.8 vs RESMENA group 3.2 ± 0.6, P = 0.490). The numer of criteri of the MetS ws higher mong sujects with more somtic-relted depressive symptoms t seline (B = 1.032, P-trend = 0.017). After six months of dietry tretment, ody weight decresed in ll sujects ( 8.7%; confidence intervl (95% CI) = ) nd lso self-perceived depression ( 37.9%; 95% CI = ), s well s circulting leptin ( 20.1%; 95% CI = ), CRP ( 42.8%; 95% CI = ) nd insulin ( 37.7%; 95% CI = ) concentrtions. The decrese in BDI ws significntly ssocited with declines in ody ft mss (B = 0.34, 95% CI = ) nd lso with the decrese in leptin (B = 0.16, 95% CI = ) nd CRP (B = 0.24, 95% CI = ) concentrtions. Conclusions: The decrese in depressive mnifesttions fter weight loss intervention ws relted with diposity, CRP nd leptin in sujects with MetS. Tril registrtion: CliniclTrils.gov: NCT Keywords: Metolic syndrome, Depression, Inflmmtion, Leptin, Hypocloric diet, Adiposity * Correspondence: jlfmtz@unv.es 1 Deprtment of Nutrition, Food Science nd Physiology, University of Nvrr, Irunlrre 1, Pmplon 31008, Spin 4 Crlos III Helth Reserch Institute, CIBERon, Physiopthology of Oesity nd Nutrition, Mdrid, Spin Full list of uthor informtion is ville t the end of the rticle 2014 Perez-Corngo et l.; licensee BioMed Centrl Ltd. This is n Open Access rticle distriuted under the terms of the Cretive Commons Attriution License ( which permits unrestricted use, distriution, nd reproduction in ny medium, provided the originl work is properly credited. The Cretive Commons Pulic Domin Dediction wiver ( pplies to the dt mde ville in this rticle, unless otherwise stted.

2 Bckground The metolic Syndrome (MetS) is defined s cluster of mjor crdiovsculr risk fctors including centrl oesity, glucose intolernce, hypertension nd serum lipid disorders, whose prevlence is rpidly incresing worldwide [1,2]. Similrly, certin MetS fetures such s excessive diposity, glucose intolernce nd dyslipidemi, hve een ssocited with depression [3], which is considered the fourth leding cuse of disese urden in the world [4]. Becuse of the high prevlence nd pulic helth implictions of oth depression nd MetS, the potentil ssocition etween them hs recently received much ttention [5,6]. However, the exct interctive pthwys etween these diseses still remin uncertin, lthough they seem to e idirectionl nd predisposed y oth iochemicl nd ehviorl meditors [6]. Depression involves dysregultion of the drenocorticl nd utonomic nervous systems, which could increse MetS risk y fvoring dominl ft ccumultion nd insulin resistnce [6]. Furthermore, sujects with MetS present incresed levels of inflmmtory cytokines nd leptin resistnce. Thus, C-rective protein (CRP), serum mrker of systemic inflmmtion, hs een frequently investigted inflmmtory mrker in sujects with MetS [7]. Also, chronic inflmmtion could e involved in mood disorders, s positive reltionship etween depression nd CRP hs een reported [8]. Regrding the ssocition etween depression nd leptin, n dipokine minly secreted y dipocytes with key role in energy regultion, it seems tht resistnce to this hormone my contriute to higher depression rtes in oese sujects [9]. Vrious strtegies hve een proposed to counterct MetS mnifesttions, including lifestyle (diet nd exercise) modifiction nd drug therpy sed on ntihypertensives, insulin sensitizers or therpies for dyslipidemi [10]. One of the most prescried lifestyle chnges is dietry tretment for weight loss, where the Mediterrnen diet hs een proven to e useful tool to improve oth MetS nd depression symptoms [11,12]. Also, the psychologicl effects of weight loss pproches hve een mtter of controversy, minly regrding how chnges in ody weight correlte with depressive symptoms [13]. This reserch is sed on susmple of the RESMENA-S study [14-17], rndomized, controlled intervention study tht ims to reduce MetS fetures using hypocloric diet during six months. In this rticle, we hypothesized tht hypocloric tretment designed to reduce MetS fetures produces positive effect on depressive symptoms, nd we sought to explore the possile underlying mechnisms nd interctions of this effect. Pge 2 of 9 Sujects nd methods Sujects A totl of ninety-three sujects (52 M/41 F) with ody mss index (BMI) of 36.1 ± 0.6 kg/m2 ged 50 ± 1 yers dignosed with MetS ccording to the IDF cut-offs [18] strted the weight loss tretment. The inclusion nd exclusion criteri hve een previously reported [14-17], ut it should e pointed out tht sujects following ntidepressnt tretment were excluded s well s those with pst mood disorders, including eting disorders. Also, vitmin or minerl supplements were not llowed. After six months of weight loss intervention there were twenty-six dropouts due to loss to follow-up or consent withdrwl. Seven of the sixty-seven prticipnts tht finished the study did not complete ll the Beck Depression Inventories (BDI). Therefore the present longitudinl study ssessed the dt from those 60 sujects (ge: 50 ± 1 y.; 38 M/22 F), who completed the BDI in the three min visits (seline, fter two months nd t the end of the study), s descried in the study flowchrt (Figure 1). In the RESMENA study, the CONSORT 2010 guidelines [19] were followed, nd ll the volunteers signed written informed consent efore prticipting in the intervention study. The study protocol ws performed in ccordnce with the ethicl guidelines of the Declrtion of Helsinki, nd ws pproved y the Reserch Ethics Committee of the University of Nvrr (ref. 065/2009). Study protocol The current study is sed on susmple of the RESMENA-S study, rndomized controlled intervention study iming to improve clinicl criteri nd iomrkers ssocited with MetS through dietry strtegy for weight loss during six months. Briefly, prticipnts were rndomly ssigned to follow one of the two energy-restricted diets, the control diet [20] or the RESMENA diet [14-17], oth with the sme energy restriction ( 30% energy of the clculted requirements) y using the rndom etween 1 nd 2 function in the Microsoft Office Excel 2003 softwre (Microsoft Ieric, Spin). The diets composition, s well s the different 48-h dietry records, were nlyzed y the DIAL (Alce Ingenieri, Mdrid, Spin) softwre nd descried elsewhere [16,17]. The volunteers were sked to mintin their usul physicl ctivity, which ws controlled y 24-h physicl ctivity questionnire t the eginning nd t the end of the study [21]. A psychologicl control using the BDI questionnire ws crried out t the min time points previously mentioned. More spects of this intervention study hve een previously detiled [14-17].

3 Pge 3 of 9 Figure 1 Flowchrt of the rndomized nd controlled dietry intervention for dults with MetS. The 26 volunteers tht dropped out did so for personl resons not relted to the study. Arevitions: BDI, Beck Depression Inventory; IDF, Interntionl Dietes Federtion; MetS, Metolic Syndrome. Anthropometric nd iochemicl mesurements Assessment of depressive symptoms Anthropometric nd ody composition mesurements were tken following stndrdized procedures previously descried [15-17]. Serum glucose, totl cholesterol, HDL-cholesterol, triglycerides nd free ftty cids serum concentrtions were mesured in n utonlyser Pentr C-200 (HORIBA ABX, Mdrid, Spin) with specific kits. Insulin concentrtions were determined y n enzyme-linked immunosorent ssy (ELISA) kit (Mercodi, Uppsl, Sweden) using n utomted nlyser system (Triturus, Grifols, Brcelon). Serum insulin resistnce ws estimted y the Homeostsis Model Assessment Index (HOMA-IR) clculted with the following formul: HOMA-IR = fsting glucose (mmol/l)xfsting insulin (mu/l)]/22.5 [22]. Plsm concentrtions of CRP ws ssessed y n Immunodignostic AG kit (Bensheim, Germny) using n utomted nlyser system (Triturus, Grifols, Brcelon). Serum concentrtions of leptin were mesured using RIA-sed method (Dignostic Products Corp., Los Angeles, CA). Symptoms of depression were ssessed t the min three time points of the study (seline, fter two months nd t the end of the study) using the Spnish version of the BDI [23], which is considered vlidted nd relile mesure of depressive symptoms [24,25]. A score 10 reflects moderte depressive symptoms. The BDI questionnire ws divided into two suscles: the cognitive nd the somtic symptom components. Question numer 19 of the test, relting to weight loss, ws discrded in some of the nlyses given tht losing weight is considered depressive symptom, ut our volunteers estimted it positive spect ecuse they were enrolled in weight loss tretment progrm [17]. Sttisticl nlyses The smple size for the min study (the RESMENA study) ws clculted sed on previous findings [26], where the men difference in the wist circumference ws 4.3 cm nd the stndrd devition (SD) ws 6.8 cm. To test the hypothesis of the present sustudy nd tking into ccount previous studies [27], smple size of

4 29 sujects would e enough to otin sttisticlly significnt difference in the reduction of BDI score (2.2 ± 2.5 units), with n lph error of 5% nd power of 90%. The min results were summrized s men ± SEM. Following pulished studies, the BDI score ws nlyzed s continuous vrile [9]. The Kolmogorow-Smirnov nd the Shpiro Wilk test were used to nlyze the normlity of the mesured vriles. Anlysis of covrince (ANCOVA) ws used to ssess chnges etween dietry tretments for the min dietry vriles of the study, with sex nd ge s covrites. Chnges in nthropometric nd iochemicl vriles, s well s chnges in the BDI questionnire nd physicl ctivity level, were evluted y repeted-mesures ANOVA (three time points) or y using the nonprmetric Friedmn test when vriles followed non-norml distriution. Also, the effect of diet on these vriles s well s the time-diet interction ws tken in considertion. A Bonferroni post hoc multiple comprison nlysis ws used when pproprite. Tests of liner trend y incresing MetS criteri were conducted y ssigning the men vlue of BDI (somtic nd cognitive questions seprtely) nd modeling these vlues s continuous vrile. The chnges in the cognitive nd somtic questions (6 months seline) were ssessed y ANCOVA with sex, ge nd dietry group s covrites. The ssocition etween chnges (6 months seline) in BDI questionnire nd chnges (6 months seline) totl ft mss (kg) ws nlyzed using multivrile liner regression nlysis djusted y sex, ge nd dietry group. For the ssocition etween chnges in CRP, leptin nd insulin with chnges in BDI score three models were constructed: Model 1 included sex, ge nd dietry group vriles. Model 2 included model 1 dditionlly djusted for chnges in ctivity level, nd model 3 consisted of model 1 plus chnges in totl ft mss (kg). All sttisticl nlyses were crried out using SPSS 15.0 softwre for Windows (SPSS Iéric, Mdrid, Spin). Differences were considered sttisticlly significnt t P < Results The min dietry chrcteristics of the two prescried diets were compred showing tht, s expected, the RESMENA group consumed more protein thn the Control group during the dietry tretment. Moreover, the RESMENA group showed greter decrese in lipid intke, ut lower intke of ω3 PUFA (Tle 1). After six months of dietry tretment, sujects nthropometric nd iochemicl vriles improved significntly, oserving men weight loss of 8.4 ± 1.2 kg (P ). However, there were no differences (P 0.10) etween oth dietry intervention groups in neither nthropometric nor iochemicl vriles, s well s ctivity level of the volunteers. Also, oth Control nd RESMENA diets proved to Pge 4 of 9 e eqully effective on improving the BDI score (Tle 2). Therefore, s no significnt differences etween dietry groups were found in ny of the vriles nlyzed in this study, henceforth the two groups were merged nd nlyzed together s unique experimentl group. The comprtive nlysis etween completers (n = 62) nd dropouts (n = 25) concerning BDI score ville t seline, showed no significnt differences (P = 0.255). Nonetheless, completers evidenced lower men vlue of BDI score t seline (7.6 ± 0.7) in reltion to those who did not finish the dietry tretment (9.3 ± 1.0). The totl numer of sujects presenting BDI score 10 units t seline ws 25% (9 M/6 F). After two months of weight loss tretment, this numer decresed to 8.3% of the volunteers (3 M/2 F). At the end of the study (6 months lter), only 6.6% of the sujects reported BDI score 10 (2 M/2 F). A test of liner trend reveled tht the higher the numer of components of MetS ccording to IDF criteri (3, 4 or 5 components), the higher somtic BDI score t seline. Interestingly, this ssocition ws not oserved in the cognitive questions of the questionnire (Figure 2). In turn, losing more weight led to greter reductions (P < 0.013) in depressive symptoms (more weight loss ΔBDI = 5.2 ± 0.9; vs less weight loss ΔBDI = 2.5 ± 0.6). As expected, when we compred ll the somtic-relted questions seprtely etween oth groups (more weight loss vs less weight loss), significnt differences were oserved in the weight loss question, ut lso in the ftigility nd loss of liido questions. Sujects reported losing more weight t 6 months thn t seline in the BDI questionnire, hence the score of this question ws higher t the end of the study. However, sujects who lost more weight did not show greter reduction in the cognitive-relted questions compred to individuls with lower ody weight chnge (Figure 3). Additionlly, positive ssocition etween chnges in depressive symptoms nd chnges in kg of totl ft mss ws oserved (Figure 4). We lso found n ssocition etween chnges in BDI score during the intervention period nd chnges in CRP, leptin nd insulin levels. Further djustment for ody ft chnge eliminted the reltion etween depressive symptoms nd insulin levels, however, the ssocition of BDI with CRP nd leptin remined sttisticlly significnt (Tle 3). Discussion The present study reports n ssocition of the reduction in depressive mnifesttions with the decrese in CRP nd leptin fter dietry tretment for weight loss in sujects with MetS. Moreover, the reduction in ft mss ws lso involved in the decrese of depressive symptoms, ut it ws not implicted in the ssocition of this vrile with CRP nd leptin. Previous investigtions hve reported

5 Pge 5 of 9 Tle 1 Comprison of the two dietry tretments, control diet nd RESMENA diet Control group (n = 32) P vlue RESMENA group (n = 28) Dietry intke Bseline 6 months Bseline 6 months Totl energy intke, Kcl/d 2108 ± ± 54* 2279 ± ± 72* Proteins, g/d 95.9 ± ± 3.4* 95.6 ± ± 3.4* Crohydrtes, g /d ± ± 8.1* ± ± 6.2* Lipids, g/d 94.7 ± ± 2.9* ± ± 3.8* Fier, g/d 21.4 ± ± ± ± Glycemic lod ± ± 5.8* ± ± 5.1* ω3 PUFAs, g/d 0.28 ± ± ± ± 0.02* ± ± ± ± Mel frequency, mels/d Dt re men ± SEM, n = 60. *Different from seline in ech dietry group, P <0.05; P vlue: comprison etween dietry group differences (6 months-seline). Arevitions: ω3 PUFAs, omeg-3 polyunsturted ftty cids. decrese in depressive mnifesttions fter weight loss tretment [13,28], however, this study specificlly demonstrtes reltionship of the decrese in CRP nd leptin with the reduction in self-perceived depression in sujects suffering MetS. The domins of self-perceived depression were divided in cognitive nd somtic questions in order to etter interpret the primry cuse of ptient depression [29]. At seline, there ws rnked reltionship etween incresing numer of MetS components nd higher rte of somtic questions ut not of cognitive components. These findings were similr to those oserved in previous study lso sed on self-reported BDI questionnire [30]. Question numer 19 of the BDI test, relted to weight loss, ws pprently distorting the totl BDI score. This oservtion ws confirmed ecuse the weight loss ws ssocited with the decrese in ody weight t the end of the dietry tretment, showing tht those sujects who lost most weight, hd higher score on the weight loss question of the test. Therefore, the weight loss question Tle 2 Anthropometric nd iochemicl vriles in dults with MetS P vlue Vriles Bseline 2 months 6 months Time Diet TimexDiet Weight, kg ± ± ± BMI, kg/m ± ± ± WC, cm ± ± ± ± ± ± 1.2c 1 DXA mesurements Ft mss, kg Muscle mss, kg ± ± ± ± ± ± Biochemicl vriles Cholesterol, mg/dl 1 Glucose, mg/dl 128 ± ± ± 4 TG, mg/dl 195 ± ± ± 12 FFA, mmol/l CRP, mg/l 0.56 ± ± 0.7 HOMA index, mm/l 4.9 ± 0.4 Leptin, ng/ml 21.5 ± 2.1, 0.52 ± ± 0.4, ± ± ± ± ± 1.5c 17.2 ± Insulin, μu/ml 15.4 ± ± ± BDI questionnire 7.6 ± ± ± 0.7c Activity level2 1.6 ± ± ± Vlues re men ± SEM n = Effects of time, diet (control diet vs RESMENA diet) nd time-diet interctions were nlysed with repeted-mesures ANOVA or Friedmn test. Vlues in row with different superscript letters (,, c) re significntly different, P < 0.05 y Bonferroni post hoc test, eing > > c. Arevitions: BDI, Beck Depression Inventory; BMI, ody mss index; CRP, C-rective protein; DXA, dul-energy X-ry sorptiometry; FFA, free ftty cids; MetS, Metolic Syndrome; TG, triglycerides; WC, wist circumference. 1 P-vlue sed on non-prmetric Friedmn test compred the three time points of the study. 2 Averge dily exercise clculted y twenty-four physicl ctivity questionnire.

6 Pge 6 of 9 Figure 2 Assocition etween the numer of MetS components ssessed y IDF criteri nd the BDI score t seline. Vlues re men ± SEM, n = 60. BDI score divided y somtic nd cognitive questions Arevitions: BDI, Beck Depression Inventory; IDF, Interntionl Dietes Federtion. Figure 3 Chnges in BDI cognitive nd somtic questions scores (6 months seline). n = 60. Rnge from 3 to 3. Sujects with MetS were divided into more ( medin = 7.6 kg) or less (<the medin = 7.6 kg) ody weight chnge fter the dietry tretment. Arevitions: BDI, Beck Depression Inventory; MetS, Metolic Syndrome. *p < **p <

7 Pge 7 of 9 Figure 4 Assocition etween chnges in BDI score nd chnges in ody ft (kg). Arevitions: BDI, Beck Depression Inventory. Adjusted y sex, ge nd dietry group. Chnges (6 months seline), n = 60. ws removed from the totl BDI score in some nlyses. Moreover, the improvement in the ftigility nd loss of liido questions (somtic-relted questions) might e considered s enefits of the weight loss. Noteworthy, positive ssocition etween decreses in CRP vlues nd reductions in depressive symptoms ws oserved s hs een reported in previous studies [8]. Inflmmtion seems to e, in prt, responsile for the link Tle 3 Assocition etween chnges in BDI score nd chnges in CRP, leptin nd insulin Chnge in BDI score Chnges in: B 95% CI p Undjusted model to Model to Model to Model to CRP mg/l Leptin ng/ml Undjusted model to Model to Model to Model to Undjusted model to Model to Model to Model to Insulin μu/ml The tle shows B coefficients (95% CI) nd p-vlue. Chnges (6 months-seline), n = 60. Arevition: BDI, Beck Depression Inventory; CRP, C-rective protein. Model 1: Adjusted y sex, ge nd dietry group. Model 2: Model 1 dditionlly djusted for chnges in ctivity level. Model 3: Model 1 dditionlly djusted for chnges in ody ft (kg). etween depressive symptoms nd MetS. However, the precise nture of this reltionship is not cler [8]. Theoreticlly, the ssocition of leptin with depression my e relted oth to its metolic properties nd neuroiologicl ctivities [9]. Leptin ffects cognition nd mood in the hippocmpus, the cortex nd other rin res ssocited with cognition [9,31]. Oesity is relted to higher levels of circulting leptin reflecting, in prt, n incresed formtion of dipocytes, nd cusing leptin resistnce in some oese sujects. A positive ssocition etween the decline in BDI score nd the drop in leptin vlues ws found, in line with results from previous studies [9,32]. Furthermore, in n undjusted model, positive ssocition ws noted etween insulin nd depressive symptoms, eing this link well-estlished [33,34]. However, this ssocition ws no longer sttisticlly significnt when chnge in ody ft ws introduced in the model. A previous weight loss intervention study showed tht depression scores t seline predicted dherence to dietry tretment [28]. In ccordnce with this outcome, higher BDI score in drop-outs t seline ws oserved, lthough this vlue did not rech sttisticl significnce. A positive ssocition etween lower BDI score nd decreses in ody weight ws found, which is in greement with previous studies [13]. In ddition, there is some evidence suggesting tht diposity is directly relted with depression [3]. In this study, the higher decrese in depressive symptoms ws noticele in those prticipnts with greter decline in totl ft mss. Since dipose tissue is known to secrete inflmmtory cytokines nd leptin [35], it might e hypothesized tht the decrese in ody ft mss my hve contriuted to reduce CRP nd leptin nd susequently decrese depressive symptoms. Furthermore, the Mediterrnen diet hs een ssocited with reduced prevlence nd incidence of MetS nd depressive symptoms [11,12]. A helthy dietry pttern hs een ssocited with etter mood [36] nd diets rich in ω3 PUFA my decrese serum cytokine production nd depressive signs [37]. Also, n inverse ssocition etween oth vitmin D nd vitmin C levels with depressive symptoms hs een oserved [38,39]. In this context, we hve previously shown tht folte intke during this dietry intervention ws well correlted with the decrese in depressive symptoms [17]. Becuse oth MetS nd depressive mnifesttions seem to shre severl common mechnisms, it hs een suggested tht the dietry recommendtions for MetS might e helpful for depression tretment [5]. The present study strengthens this hypothesis, s the dietry tretment for MetS mnifesttions lso reduced depressive symptoms. Moreover, severl unhelthy lifestyle hits hve een relted with depressive symptoms, such s fst food consumption, high ft intke or low physicl ctivity [5,40]. In this study, physicl ctivity ws not directly ssocited

8 with depressive symptoms, eing in greement with previous investigtions [41]. The control diet sed on the AHA guidelines is well-design strtegy for weight loss [20], wht my explin tht no differences etween dietry groups were oserved in the vriles nlyzed in this study. As oth dietry groups proved to e effective in reducing depressive symptoms nd no differences etween them were found, oth groups were merged nd nlyzed together s unique experimentl group. A longitudinl oservtionl nlysis compring the BDI scores efore nd fter intervention ws conducted, serving the volunteers s their own control. The cler differences etween the eginning nd the end of the study lend support to the soundness of the nlysis. One of the strengths of withinsujects (pired) nlyses is the reduction in error vrince ssocited with individul differences, which increses sttisticl power. Moreover, in order to control the possile confounding role of the intervention group, this vrile ws included in the multiple-djusted models investigting the ssocition of nthropometric nd iochemicl vriles with depressive mnifesttions in the complete smple [17]. The study hs some limittions. Firstly, depressive symptoms were evluted using self-report questionnire, the Beck Depression Inventory, which is not designed s dignostic tool ut s screening method [24]. However, this test ws chosen s it is widely recognized, it hs een shown to e vlid for clinicl ssessment [25] nd it hs previously een used to record depressive symptoms in weight loss studies [13,28]. Secondly, this study only imed to evlute the ssocition etween the vriles included nd it cnnot e determined ny conclusions on cuslity etween chnges in ody weight, ft mss, leptin nd CRP nd chnges in depressive symptoms. In ddition, the prevlence of depressive symptoms in our smple ws low, which cn e explined with the fct tht sujects presenting psychitric disorders t enrollment were not llowed to prticipte in the study. Also, the numer of prticipnts in this study is not very high, ut it my e proposed tht type-ii errors were overcome since importnt sttisticl differences were found. Conclusions In conclusion, this study shows n ssocition of the reduction in depressive mnifesttions with CRP nd leptin in sujects with MetS fter following weight loss tretment. Interestingly, the decrese in ft mss ws lso relted with the reduction of depressive symptoms. More studies re needed to explore the mechnisms underlying the MetS-depression reltionship, which my e decisive for the prevention nd tretment of oth conditions. Pge 8 of 9 Competing interests The uthors declred tht they hve no competing interests. Authors contriutions The uthors contriutions were s follows: APC performed the reserch, nlysed dt nd wrote the mnuscript; RI, PLL, IA nd SNC conducted reserch; FL nd CIL selected nd contriuted to the interprettion of the psychologicl test; MAM contriuted to the sttisticl nlysis. JAM nd MAZ designed nd mnged the reserch, nd hd primry responsiility for finl content. All the uthors red nd pproved the finl version of the mnuscript. Acknowledgements We wish to thnk the volunteers of this study nd Blnc E. Mrtínez de Morentín, Slomé Pérez, s well s Verónic Ciurriz for excellent technicl ssistnce in the University of Nvrr. We would like to thnk Dr Pul W. Miller from the Institute of Modern Lnguges of the University of Nvrr for creful reding the mnuscript. Author detils 1 Deprtment of Nutrition, Food Science nd Physiology, University of Nvrr, Irunlrre 1, Pmplon 31008, Spin. 2Fculty of Helth Science, Universidd Autonom de Chile, Sntigo, Chile. 3Biodonosti Helth Reserch Institute, Doctor Begiristin (no numer), 20014, Sn Sestin, Spin. 4Crlos III Helth Reserch Institute, CIBERon, Physiopthology of Oesity nd Nutrition, Mdrid, Spin. 5Deprtment of Psychitry nd Medicl Psychology, University Clinic of Nvrr, Pio XII 36, Pmplon 31008, Spin. 6 Deprtment of Preventive Medicine nd Pulic Helth, University of Nvrr, Irunlrre 1, Pmplon 31008, Spin. Received: 2 Mrch 2014 Accepted: 15 April 2014 Pulished: 24 April 2014 References 1. Ymok K, Tngo T: Effects of lifestyle modifiction on metolic syndrome: systemtic review nd met-nlysis. BMC Med 2012, 10: Yni H, Tomono Y, Ito K, Furutni N, Yoshid H, Td N: The underlying mechnisms for development of hypertension in the metolic syndrome. Nutr J 2008, 7: Murito JM, Mssro JM, Clifford B, Hoffmnn U, Fox CS: Depressive symptoms re ssocited with viscerl diposity in community-sed smple of middle-ged women nd men. Oesity 2013, 21: Ustun TB, Ayuso-Mteos JL, Chtterji S, Mthers C, Murry CJ: Glol urden of depressive disorders in the yer Br J Psychitry 2004, 184: Snchez-Villegs A, Mrtinez-Gonzlez MA: Diet, new trget to prevent depression? BMC Med 2013, 11:3. 6. Pn A, Keum N, Okereke OI, Sun Q, Kivimki M, Ruin RR, Hu FB: Bidirectionl ssocition etween depression nd metolic syndrome: systemtic review nd met-nlysis of epidemiologicl studies. Dietes Cre 2012, 35: Krj AT, Province MA, Arnett D, Wgenknecht L, Tng W, Hopkins PN, Djousse L, Borecki IB: Do inflmmtion nd procogultion iomrkers contriute to the metolic syndrome cluster? Nut Met 2007, 4: Dly M: The reltionship of C-rective protein to oesity-relted depressive symptoms: longitudinl study. Oesity 2013, 21: Morris AA, Ahmed Y, Stoynov N, Hooper WC, De Sterke C, Gions G, Quyyumi A, Vccrino V: The ssocition etween depression nd leptin is medited y diposity. Psychosom Med 2012, 74: Swislocki AL, Siegel D, Jill I: Phrmcotherpy for the metolic syndrome. Curr Vsc Phrmcol 2012, 10: Sls-Slvdo J, Bullo M, Bio N, Mrtinez-Gonzlez MA, Irrol-Jurdo N, Bsor J, Estruch R, Covs MI, Corell D, Aros F, Ruiz-Gutierrez V, Ros E: Reduction in the incidence of type 2 dietes with the Mediterrnen diet: results of the PREDIMED-Reus nutrition intervention rndomized tril. Dietes Cre 2011, 34: Snchez-Villegs A, Delgdo-Rodriguez M, Alonso A, Schltter J, Lhortig F, Serr Mjem L, Mrtinez-Gonzlez MA: Assocition of the Mediterrnen dietry pttern with the incidence of depression: the Seguimiento Universidd de Nvrr/University of Nvrr follow-up (SUN) cohort. Arch Gen Psychitry 2009, 66: Frictore AN, Wdden TA, Higginothm AJ, Fulconridge LF, Nguyen AM, Heymsfield SB, Fith MS: Intentionl weight loss nd chnges in symptoms

9 Pge 9 of 9 of depression: systemtic review nd met-nlysis. Int J Oes 2011, 35: de l Iglesi R, Lopez-Legrre P, Aete I, Bondi-Pons I, Nvs-Crretero S, Forg L, Mrtinez JA, Zulet MA: A new dietry strtegy for long-term tretment of the metolic syndrome is compred with the Americn hert ssocition (AHA) guidelines: the MEtolic syndrome REduction in NAvrr (RESMENA) project. Bri J Nutr 2014, 111: Lopez-Legrre P, de l Iglesi R, Aete I, Bondi-Pons I, Nvs-Crretero S, Forg L, Mrtinez JA, Zulet MA: Short-term role of the dietry totl ntioxidnt cpcity in two hypocloric regimes on oese with metolic syndrome symptoms: the RESMENA rndomized controlled tril. Nutr Met 2013, 10: de l Iglesi R, Lopez-Legrre P, Celd P, Snchez-Muniz FJ, Mrtinez JA, Zulet MA: Beneficil effects of the RESMENA dietry pttern on oxidtive stress in ptients suffering from metolic syndrome with hyperglycemi re ssocited to dietry TAC nd fruit consumption. Int J Mol Sci 2013, 14: Perez-Corngo A, Lopez-Legrre P, de l Iglesi R, Lhortig F, Mrtinez JA, Zulet MA: Longitudinl reltionship of diet nd oxidtive stress with depressive symptoms in ptients with metolic syndrome fter following weight loss tretment: the RESMENA project. Clin Nutr 2013, Alerti KG, Zimmet P, Shw J: The metolic syndrome new worldwide definition. Lncet 2005, 366: Schulz KF, Altmn DG, Moher D: CONSORT 2010 sttement: updted guidelines for reporting prllel group rndomised trils. BMJ 2010, 340:c Grundy SM, Cleemn JI, Dniels SR, Donto KA, Eckel RH, Frnklin BA, Gordon DJ, Kruss RM, Svge PJ, Smith SC Jr, Spertus JA, Cost F: Dignosis nd mngement of the metolic syndrome: n Americn hert ssocition/ntionl hert, lung, nd lood institute scientific sttement. Circultion 2005, 112: Food nd Nutrition Bord NRC: Recommended dietry llownces. 10th edition. Wshington, DC: The Ntionl Acdemy Press; Mtthews DR, Hosker JP, Rudenski AS, Nylor BA, Trecher DF, Turner RC: Homeostsis model ssessment: insulin resistnce nd et-cell function from fsting plsm glucose nd insulin concentrtions in mn. Dietologi 1985, 28: Conde C, Useros E: Adptción cstelln de l escl de evlución conductul pr l depresión de Beck. Rev Psiqit Psicol Med 1975, 12: Beck AT, Wrd CH, Mendelson M, Mock J, Erugh J: An inventory for mesuring depression. Arch Gen Psychitry 1961, 4: Dvidson KW, Kupfer DJ, Bigger JT, Cliff RM, Crney RM, Coyne JC, Czjkowski SM, Frnk E, Frsure-Smith N, Freedlnd KE, Froelicher ES, Glssmn AH, Kton WJ, Kufmnn PG, Kessler RC, Kremer HC, Krishnn KR, Lespernce F, Rieckmnn N, Sheps DS, Suls JM: Assessment nd tretment of depression in ptients with crdiovsculr disese: ntionl hert, lung, nd lood institute working group report. Ann Behv Med 2006, 32: Ktcher HI, Legro RS, Kunselmn AR, Gillies PJ, Demers LM, Bgshw DM, Kris-Etherton PM: The effects of whole grin-enriched hypocloric diet on crdiovsculr disese risk fctors in men nd women with metolic syndrome. Am J Clin Nutr 2008, 87: Brinkworth GD, Buckley JD, Nokes M, Clifton PM, Wilson CJ: Long-term effects of very low-crohydrte diet nd low-ft diet on mood nd cognitive function. Arch Intern Med 2009, 169: Somerset SM, Grhm L, Mrkwell K: Depression scores predict dherence in dietry weight loss intervention tril. Clin Nutr 2011, 30: Kupper N, Widdershoven JW, Pedersen SS: Cognitive/ffective nd somtic/ffective symptom dimensions of depression re ssocited with current nd future inflmmtion in hert filure ptients. J Affect Disord 2012, 136: Skilton MR, Moulin P, Terr JL, Bonnet F: Associtions etween nxiety, depression, nd the metolic syndrome. Biol Psychitry 2007, 62: Morrison CD: Leptin signling in rin: link etween nutrition nd cognition? Biochim Biophys Act 2009, 1792: Milneschi Y, Simonsick EM, Vogelzngs N, Strotmeyer ES, Yffe K, Hrris TB, Tole MI, Ferrucci L, Penninx BW: Leptin, dominl oesity, nd onset of depression in older men nd women. J Clin Psychitry 2012, 73: Kullmnn S, Heni M, Veit R, Ketterer C, Schick F, Hring HU, Fritsche A, Preissl H: The oese rin: ssocition of ody mss index nd insulin sensitivity with resting stte network functionl connectivity. Hum Brin Mpp 2012, 33: Silv N, Atlntis E, Ismil K: A review of the ssocition etween depression nd insulin resistnce: pitflls of secondry nlyses or promising new pproch to prevention of type 2 dietes? Curr Psychitry Rep 2012, 14: Clement K, Viguerie N, Poitou C, Crette C, Pelloux V, Curt CA, Sicrd A, Rome S, Benis A, Zucker JD, Vidl H, Lville M, Brsh GS, Bsdevnt A, Stich V, Cncello R, Lngin D: Weight loss regultes inflmmtion-relted genes in white dipose tissue of oese sujects. FASEB J 2004, 18: Perez-Corngo A, Zulet MA, Mrtinez JA: Assocition etween mood nd diet qulity in sujects with metolic syndrome prticipting in ehviourl weight-loss progrm; cross-sectionl ssessment. Nutr Neurosci 2014, Swenne I, Rosling A, Tengld S, Vessy B: Omeg-3 polyunsturted essentil ftty cids re ssocited with depression in dolescents with eting disorders nd weight loss. Act Peditr 2011, 100: Bertone-Johnson ER, Powers SI, Spngler L, Brunner RL, Michel YL, Lrson JC, Millen AE, Bueche MN, Slmoirgo-Blotcher E, Liu S, Wssertheil-Smoller S, Ockene JK, Ockene I, Mnson JE: Vitmin D intke from foods nd supplements nd depressive symptoms in diverse popultion of older women. Am J Clin Nutr 2011, 94: Amr M, El-Mogy A, Shms T, Vieir K, Lkhn SE: Efficcy of vitmin C s n djunct to fluoxetine therpy in peditric mjor depressive disorder: rndomized, doule-lind, plceo-controlled pilot study. Nutr J 2013, 12: Rosenerg DE, Bomrdier CH, Artherholt S, Jensen MP, Motl RW: Selfreported depression nd physicl ctivity in dults with moility impirments. Arch Phys Med Rehil 2013, 94: Appelhns BM, Whited MC, Schneider KL, M Y, Oleski JL, Merrim PA, Wring ME, Olendzki BC, Mnn DM, Ockene IS, Pgoto SL: Depression severity, diet qulity, nd physicl ctivity in women with oesity nd depression. J Acd Nutr Diet 2012, 112: doi: / Cite this rticle s: Perez-Corngo et l.: A decline in inflmmtion is ssocited with less depressive symptoms fter dietry intervention in metolic syndrome ptients: longitudinl study. Nutrition Journl :36. Sumit your next mnuscript to BioMed Centrl nd tke full dvntge of: Convenient online sumission Thorough peer review No spce constrints or color figure chrges Immedite puliction on cceptnce Inclusion in PuMed, CAS, Scopus nd Google Scholr Reserch which is freely ville for redistriution Sumit your mnuscript t

10 Reproduced with permission of the copyright owner. Further reproduction prohiited without permission.