SJEZD PSYCHIATRICKE SPOLECNOSTI CLS JEP

BUDOUCNOST PECE 0 DUSEVNE NEMOCNE V SOUVISLOSTECH

12.-15. CERVNA 2014 HOTEL HARMONY, SPINDLERUV MLYN

Poradatele: Martin Holly, Pavel Doubek, Marek Pav

Pofadatele sborniku

MUDr. Martin Holly MUDr. Pavel Doubek, Ph.D. MUDr. Marek Pav, Ph.D. Psychiatricka lecebna Bohnice, Psychiatricka klinika, L lekarska fakulta UK a Vseobecna fakultni nemocnice, Praha

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ISBN 978-80-263-0702-0

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UvODNi SLOV0 ........................................................................... 16 vEDECKY PROGRAM .................................................................. 18 SYMPOZIA A WORKSHOPY ........................................................ 20

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ETICKA DILEMATA PRENOSU A PROTIPRENOSU V KOGNITIVNE BEHA VIORA.LNJ ........................... ............................ 34 J. Vyskocilova

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· A. Grambal, J. Praska, J. Vyskocilova

EXPERIMENTALNf A NA RATIVNi PPRiSTUPY V KOGNITIVNE BEHA VIORALNJ TERAPII ................................ ..................................... 41 J. Praska, J. Vyskocilova, A. Grambal, M. Ociskova

VARIA I .................................................................................. 44

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BUDOUCNOST PECE O DUSEVNE NEMOCNE

V SOUVISLOSTECH

Sbornik pfispevku X. sjezdu Psychiatricke spolecnosti CLS JEP

s mezinarodni ucasti

Brno 2014

fungovani jedince ve spoleenosti je pak tedy predevsim souhrou vrozenych a ziskanych faktoru - tedy geneticke v:Ybavy a stylu v:Ychovy. UrCita patologie, v nasem pnpade predevsim zv:Ysena tendence k agresivnimu chovani a od ni odvisle nasledne delikventni chovani, nevznika nahle a bez pfi­ciny. Naopak, ma urcicy v}'voj, kter:Y je easto motne zaznamenat jiz v ranem obdobi zivota jedince. Vyzkumy zab}'vajici se timto tematem hovon o mnoha faktorech, ktere pozitivne koreluji prave s budoucim kriminalnim, a potazmo nasiln}'m, chovanim. V tom to ohledu dUlezita oblast vedeckeho zkoumani, tedy v}'vojova psychopatologie, se konkretne zamefoje na evoluci psychiceych po­ruch, na jejich zmenu v ease a pfedevsim pak na jejich dopad na osobnost dane­ho jedince. Varovn:Ym signalem se tak dle fatly studii zda b:Yt napriklad v}'skyt agresivniho chovani a sklon k poru5ovani nastavenych pravidel v ranem detstvi. Zda se totiz, ze prave tyto znaky easto predchazeji porucham chovani a jejich v}'skyt v ranem detstvi je tak velmi spatnou progn6zou do budoucnosti a to pre­devsim tehdy, pokud jsou pfidrufony i dalSi faktory. Predevsim z mnozstvi za­hranicnich v:Yzkumu pak take vypl}'va, ze poruchy chovani u adolescentu jsou mnohem zavaznejsi a signifikantnejsi pro predikci dalSiho v}'voje, pokud mu­zeme jejich pocatek nalezt jiz v detstvi. Zda je motno ta to zjisteni aplikovat i na domaci podminky je otazkou, vzhledem k nedostatecnemu mnozstvi domacich v:Yzkumu z teto oblasti. Cilem prezento­vane pilotni studie je poukazat na tuto problematiku a odhalit faktory, ktere je mozno oznaCit za signifikantni prediktory nasilneho chovani u budoucich pa­chatelU trestnych cinu.

Soubor v prezentovane pilotni studii jsme vysetrui skupinu adolescentu ve veku 16-22 let, kten byli odsouzeni za funyslny trestny Cin nasilneho charakteru (n=30) a kontrolni skupinu studentu SS a VS bez historie protipravniho jednani (n=30). Testova baterie byla slofona z dotazniku zamereneho na anamnesticke udaje o dosavadnim v}'voji, zvl. s ohledem na v}'skyt projevli v}'vojove psychopatolo­gie, socialni adaptaci a vzdelani. V testove baterii byla dale obsazena pilotni verze MMPI-A a HCR-Y. Vtomto pnspevku prezentujeme pouze nalezy v oblas­ti projevli psychopatologie v anamneze.

Vysledky V souboru adolescentu odsouzenych za funyslny nasilny trestny Cin lze v anamneze hodnotit tyto statisticky v:Yznamne rozdily oproti kontrolni skupine (p<0.01) i. Poruchy chovani (43 % vs 6,6 %) 2. ADHD (63 % vs 13 %) 3. Porucha opozicniho vzdoru (16, 6 % vs o %) 4. Aspergeruv syndrom (6,6 % vs o %) Jedna se o v}'vojove poruchy diagnostikovane psychiatrem.

Zuver z prezentovaneho pilotniho v:Yzkumu je patrne, ze v}'vojove poruchy jsou statis­ticky v:Yznamn:Ym prediktorem budouciho kriminalniho chovani. Rozhodne se nejedna o jediny faktor. Na rozvoji kriminalni chovani se dale podili cela fada

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specificeych faktoru. Nicmene prezentovane nalezy, ktere jsou v souladu se zahranicni odbornou literaturou, zcela jasne poukazuji na nutnost dostateene psychiatricke a psychologicke pece deti s projevy v}'vojove psychopatologie.

Fodpofeno projektem FRVOUK FSYCHOLOGIE UK.

Literatura Tremblay ER, Nagin SD, Seguin RJ. Physical Aggression During Early Childho-od: Trajectories and Predictors. Pediatrics 2004; 114: e43 - e48. Moffitt ET. Adolescence-Limited and Life-Course-Persistent Antisocial Behavi­or: A Developmental Taxonomy. Psychological Review 1993; 100: 674-701. Hoffmann PJ. A Life-Course Perspective on Stress, Delinquency, and Young Adult Crime. Am J Crim Just 2010; 35:105-120.

VLIV KOGNITIV NA MITOCHONDRL\LNi RESPIRACI A AKTIVl­TU KOMPLEXlJ ELEKTRONOvEHO TRANSPORTNIHO RETEZCE

N. Singh, J. Hroudova, Z. FiSar Fsychiatricka klinika, 1. lekafskafakulta, Univerzita Karlova v Fraze a Vseo-becnafakultni nemocnice v Fraze, Fraha, Ceska Republika

Summary EFFECT OF COGNITIVE DRUGS ON MITOCHONDRIAL RESPIRA-TION AND ACTIVITY OF ELECTRON TRANSPORT CHAIN COM-PLEXES Drugs like 7-MEOTA (7-methoxytacrine), tacrine, memantine, galanthamine, donepezil, latrepirdine (Dimebon) and piracetam are currently being tested to treat patients suffering from neurodegenerative disorders especially Alzheimer's disease (AD). Most of them show reversible acetylcholinesterase-inhibiting ac­tivity, except for memantine, latrepirdine and piracetam. Defects in mitochon­drial metabolism and particularly of electron transport chain (ETC) may play a significant role in pathogenesis of AD; complex IV of ETC plays a major role in controlling of oxidative phosphorylation. We examined in vitro effects of phar­macologically different cognitive (7-MEOTA, memantine, galanthamine, done­pezil) and nootropic drugs Oatrepirdine, piracetam) on both mitochondrial enzyme activities (citrate synthase and complex IV of ETC) and respiration of isolated brain mitochondria. High-resolution respirometry was used to deter­mine respiratory rate driven by substrates of complex I or II of ETC. Results demonstrated no significant drug-induced changes in the activity of citrate syn­thase. Significantly decreased activity of complex IV was observed for cognitive drugs and increased complex IV activity for nootropic drugs. Slight drug­induced decrease in rate of oxygen consumption was observed for galan­thamine, memantine and donepezil, and slight increase for latrepirdine and memantine. Our results support the view that modulation of mitochondrial functions may participate on therapeutic effects of cognitives and nootropics. Keywords: mitochondria; cognitive drug; nootropic; oxidative phosphoryla-tion; mitochondrial respiration

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Souhrn Ll.tky, jako 7-MEOTA (7-methoxytakrin), takrin, memantin, galanthamin, do­nepezil, latrepirdin (Dimebon) a piracetam jsou pouzivana ci testovana pro leCbu osob trpicich neurodegenerativnimi poruchami, predevsim Alzheimero­vou nemoci (AD). Vetsinou se jedna o reverzibilni inhibitory acetylcholinestera­zy, krome memantinu, latrepirdinu a piracetamu. Vyznamnou ulohu v patoge­nezi AD mohou mit poruchy v mitochondrialnim metabolismu a zvlaste v elek­tronovem transportnim retezci (ETC); napr. komplex IV dychaciho retezce m [1 v.Yznamnou ulohu v kontrole oxidaeni fosforylace. Testovali jsme in vitro ucinky fady farmakologicky odlisnych kognitiv (7-MEOTA, memantin, galanthamin , donepezil) a nootropik Oatrepirdin, piracetam) jak na aktivity jednotliv)rch mi­tochondrialnich enzymu (citratsyntazy a komplexu IV), tak na celkovou respi­racni aktivitu mitochondrii izolovanych ze zvirecich mozku. Pro mereni respi­racni rychlosti se vstupem elektronu pres komplex I, nebo pres komplex II, byla pouzita respirometrie s vysok)rm rozlisenim. Mereni ukazala nev.Yznamny vliv testovanych latek na aktivitu citratsyntazy. Kognitiva zpusobovala sniZeni a pro nootropika zv.Yseni aktivity komplexu IV. Mime sniZeni rychlosti spotfeby kysli­ku mitochondriemi bylo pozorovano vlivem galanthaminu, memantinu a done­pezilu. Naopak zv.Yseni respiraeni rychlosti bylo indukovano latrepirdinem a memantinem. Nase v)rsledky podporuji hypotezu, ze modulace mitochondrial­nich funkci se muze podilet na terapeutickych ucincich kognitiv a nootropik. Klieova slova: mitochondrie; kognitiva; nootropika; oxidaeni fosforylace; mitochondrialni respirace

Aim We aimed at measurement of drug-induced changes in the rate of oxygen con­sumption for cognitive and nootropic drugs and to detect the effects of these drugs on complex IV activity of electron transport chain (ETC).

Method The mitochondria were isolated from pig brain cortex as described previously (Fisar et al., 2010). All chemicals were purchased from Sigma-Aldrich Co. (St. Louis, MO, USA). Mitochondrial respiratory rate was measured at 37°C using a titration-injection high-resolution oxygraph (Oxygraph-2k, Oroboros Instru­ments, Innsbruck, Austria) equipped with two closeable tempered glass cham­bers with Clark-type electrodes. DatLab 4.3 software (Oroboros Instruments, Innsbruck, Austria) was used to collect and analyse respirometric data. Changes in activity of citrate synthase or complex IV was measured spectrophotometri­cally (Hroudova and Fisar, 2010) at 50 µM drug concentration; Uvicon XL spec­trophotometer (SECOMAM, Ales, France) was used for all assays. Results were analyzed by STATISTICA (data analysis software system, version 9.0, StatSoft, Inc., Tulsa, OK, USA).

Results No significant drug-induced change in the activity of citrate synthase was found. Significantly decreased activity of complex IV of respiratory electron transport chain was observed for 7-MEOTA, galanthamine and donepezil; increased com-

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plex IV activity was observed for nootropic drugs Oatrepirdine, piracetam). Memantine did not induce any significant change in complex IV activity. De­crease in rate of oxygen consumption was observed for galanthamine and me­mantine at higher drug concentrations, when mitochondrial respiration was supported through complex I; 7-MEOTA, donepezil, latrepirdine and piracetam showed almost no effect on rate of oxygen consumption. When respiration was supported through complex II, donepezil induced decrease and latrepirdine and memantine showed increase in rate of oxygen consumption; no significant changes were observed for other drugs.

Conclusion Drug-induced changes in cellular energetics characterized by complex IV activ-ity and mitochondrial respiration were analysed. Latrepirdine induced increase in was observed for both complex IV activity and respiratory rate supported through complex II. Memantine showed quite ambiguous behaviour showing decrease in respiration supported through complex I and increase in respiration supported through complex II. The results prove the cognitive enhancers­induced effects related to disturbance in electron transport chain, i.e. in cellular energetics. The results can be useful to gain in-depth understanding of mecha­nisms of action of drugs used in treatment of the cognitive impairment in neu­rodegenerative disorders. Our results support the view that modulation of mito­chondrial functions may participate on therapeutic effects of cognitives and nootropics; however, currently used drugs seem not sufficiently efficient in af­fecting mitochondrial respiration and cellular energetics.

References author

PSYCHIATRICKE KOMPLIKACE PROTINADOROvE LECBY

B. Slovackova1 , L. Slovacek2

1Psychiatricka klinika FN a LF UK Hradec Kralove, Ceska republika 2Klinika onkologie a radioterapie FN a LF UK Hradec Kralove, Ceska republi-

ka

Summary PSYCHIATRIC COMPUCATION OF THE CANCER THERAPY The authors report on two cases of cancer therapy-induced psychiatric compli­cation among female patients with breast carcinoma. The case reports high­lights the potential risk of chemotherapy and premedication causing psychiatric complication (i.e. bipolar disorder and drug-induced halucinatory syndrome). At the same time it indicates the need to cooperate with the psychiatrist. Early symptomatic psychopharmacological intervention enabled the smooth comple-tion of cancer therapy).

Rada literarnich zdroju uvadi, ze cytostatika a leky pouzivane v ramci premedi­kace, jsou latky s psychotropnim ucinkem, tj. mohou navodit u disponovanych

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