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The review of the Italian association of psycho-neuro-endocrine-immunology Edited by Francesco Bottaccioli

PNEI NEWS The new knowledge of science and health PNEIINCLINICALPRACTICETHEFOURTHSIPNEINATIONALCONGRESSFLORENCE20th-22ndMARCH2020

PneiNews–bimonthlyreview–nr2–yearXIII–March-April2019

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PNEINEWSNR2–March–April2019EDITORIALPage3.Pneiinclinicalpractice.Experiencesandmodelsofintegrativecare.EMOTIONSANDDIABETESPage4.Thepsyche-brain-pancreasaxisForthefirsttimeithasbeendocumentedthatamygdalahyperactivitypredictstheonsetofdiabetes,independentlyofobesity.FrancescoBottaccioliCHANGEOFPARADIGMPage6.Sportandphysicalexercise:theneedforanintegrativeapproach.Weare livingaparadox: inthe last40yearsthepercentageofpeoplepracticingaphysicalactivityhasincreasedandyetatthesametimeitoccurredalsoadramaticgrowthinpathologieshavingphysicalinactivityasriskfactor.ElenaCampaniniGENDERMEDICINEPage9.Post–partumdepression:Thequestforhappiness:anintravenousinfusionratherthanapill?FDA has approved a new drug for the treatment of post-partumdepression. Thismedication seems tobe costly and complicated touse.Onceagainadrug therapywas preferred to non-pharmacological treatments, like psychotherapy, whoseeffectivenessandsafetyhasbeenwelldocumented.IlarioMammonePage12.AnintegrativeapproachinthetreatmentofPMSThis article is based on a Master’s Diploma Thesis in “PNEI and Science ofIntegrativeCare-LevelIIdiscussedbytheauthorinJanuary2019.MelaniaMandatoHEARTANDSOCIETYPage16.Cardiovasculardiseases:howimportantarepsycho-socialfactors?This article is based on a Master’s Diploma Thesis in “PNEI and Science ofIntegrativeCare-LevelIIdiscussedbytheauthorinJanuary2019.AnnaritaGiacovelliBOOKREVIEWPage22.Silenceisalive.Theartofmeditation.MonicaMambelliPage23.Psychologyofinequality.FrancescoBottaccioli

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Thepsyche-brain-pancreasaxisFrancescoBottaccioliMasterDirectorofPnei.UniversityofAquilaandUniversityofTurinA US interdisciplinary and inter-university group (Harvard Columbia, New York) haspublishedtwopapers(Psychoneuroendorcinology1andJournalofClinicalEndocrinologyandMetabolism2)clarifyingforthefirsttimewithinstrumentalevidencestherelationbetweenemotional stress and diabetes onset. Such link had already been mentioned since manyyearsbyclinicalpracticeandPNEI.Obesityanddiabetes:alinkthatdoesnotexplainsitallThisrelationhasbeenignoredbythetraditionalmedicalvisionthatfocusedratheronthelink between nutrition (with the resulting overweight, visceral obesity) and diabetes.Undoubtedly this relationhasbeenprovedanddocumentedbyseveralobservationalandexperimentalstudies.Yetthereareanomaliesintheparadigmofthegenesisofdiabetesduetoeatinghabits. Firstof all, luckilynot all obesepeoplearediabetic. It is alsopossible tohave diabetes without being obese. Thus, beside excessive food intake and physicalinactivitytheremustbeotherfactorscontributingtotheonsetofthedisease.ThisargumentwasthestartingpointleadingtheUSresearcherstoinvestigatefurther.They used a sophisticated technology (18F-FDG-PET-CT) combining a 18Ffluorodeoxyglucose positron emission tomography and a computed tomography imaging.Thisallowsasimultaneousmeasurementofregionalbrainmetabolicactivityandvolumeofadipose tissue, the fat layer locatedaround the stomach.Themonitoredbrain area is thesaliencenetwork,asetofinterconnectedstructuresinvolvedincomplexfunctionssuchascognition and emotion of which amygdala is a fundamental component. From previousstudiesweknow that amygdala is the key structure for the alarm systemwhich is at thebaseofanxiety3.Asthenameindicatesthesaliencenetworkisactivatedeachtimethemindperceives a significant, namely salient, stimulus and deactivates the dominance of thecerebral circuitrywhich is basedonour internaldefaultmodenetwork thus favoring theshifttowardstheexecutivenetwork.Amygdalaistheswitchgearbecauseitdoesnotonlyactivates the frontal executive circuits but it also activates the stress systemas shown infig.1PET with 18F radionuclide allows the evaluation of the amygdala metabolic activity andenablesthebiologicalmeasurementoftheemotionalstateofthesubject.

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Fig.1Psychologicalstressorsareconveyedthroughtheprefrontalcortexandalsodirectlyfromamygdalathat activates the stress system. Biological and environmental stressors follow instead the brainstem(solitary nucleus) pathway and the brain structures around the ventricular system (circumventricularorgans).Source:BottaccioliF,BottaccioliAG(2017)Psiconeuroendocrinoimmunology.Edra.Milano.Caption. BNST: bed nucleus of the stria terminalis; GABA: gamma-Aminobutyric acid; CRH Ormone:Corticotropin-releasinghormone;ACTHOrmone:Adrenocorticotropin(orcorticotropin).TheresearchersreviewedandcomparedthecerebralPETscansdatafocusingonamygdalainindividualsnotaffectedbydiabetes,withdiseaseonsetinthefollowing5yearsafterthePETscanning.Theyfoundoutthatpeoplewithahigheramygdalametabolicactivityhadamajordiabetesincidence.

Fig.2.IndividualAshowsalowactivityofamygdalawhereasindividualBshowsahighactivity.Both of them show a similar amount of visceral adiposity, but diabetes will occur only forindividualBbecauseoftheamygdalahighemotionalactivity.Source:OsborneMTetal.quotedinnote1.

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Inparticularthehyperactivityofamygdalaisassociatedtoanincreaseofriskuntil5timeshigherascomparedtothegroupshowingalessactiveamygdala.Agreatlyrelevantpointisalso that the correlation between the amygdala hyperactivity and onset of diabetes isindependentofthevisceraladiposityvolume.More precisely, as Fig. 2 shows, with a similar amount of adipose tissue, the onset ofdiabetesisdeterminedbyamygdalahyperactivity.Obviouslytheriskofdiabetesincreasesif,alongwithamygdalahyperactivity,thereisalsoanincreaseofvisceraladiposity.In fact, in both conditions the inflammation increases due to the fat located especiallyaround the abdomen and the visceral area, where inflammatory adipokines are thenreleased.Atthesametimethehyper-activationofthestresssystemthroughtheamygdalaproducesinflammationwithanexcessofcortisolcausingresistanceintheimmunecellsaswellasmobilizingthesesameimmunecellsinthebonemarrow.Thislastphenomenonhasbeenmentionedinnote2:amygdalaactivityhasbeenassociatedwithbonemarrowactivitywhichinitsturnisassociatedwithvisceralfat.Thesephenomenaareatthebaseofinsulin-resistancethatcauseshyperglycemiaanddiabetes.Theseresearchesindicatethebiologicalmechanismsthatcanexplaintherelationbetweenemotionalstress,depressionanddiabetesonsetandreinforceaconceptthatPNEIstudieshave expressed frequent times: the bidirectionality of such relation: depression favorsdiabetesonsetanddiabetesonsetfavorsdepression.Thereareseveralstudiesonthisregard:forareviewIwouldliketorefertoourManualePNEI4where it is possible to find also indications for prevention and integrative care fordiabetesandothermetabolicdisorders.1.OsborneMT, IshaiA,HammadB,TungB,WangY,BaruchA, FayadZA,Giles JT, Lo J, Shin LM,GrinspoonSK,Koenen KC, Pitman RK, Tawakol A (2019) Amygdalar activity predicts future incident diabetes independently of

adiposity.Psychoneuroendocrinology.100:32-40.doi:10.1016/j.psyneuen.2018.09.024.

2. Ishai A, OsborneMT, Tung B,Wang Y, Hammad B, Patrich T, Oberfeld B, Fayad ZA, Giles JT, Lo J, Shin LM,GrinspoonSK,KoenenKC,PitmanRK,TawakolA(2019)AmygdalarMetabolicActivityIndependentlyAssociatesWith

ProgressionofVisceralAdiposity.JClinEndocrinolMetab.104(4):1029-1038.doi:10.1210/jc.2018-01456.

3.LeDoux J.E. (2012).RethinkingtheEmotionalBrain.Neuron,73(4):653-676.DOI:10.1016/j.neuron.2012.02.004;SeealsoLeDouxJ(2018)Didwemisunderstandanxietyandfear?PneiReview2:5-21

4.BottaccioliF&BottaccioliAG(2017)Psiconeuroendocrinoimmunologiaescienzadellacuraintegrata.IlManuale,Edra,Milano,particularlypages.552-554