ecnp matters NEWSLETTER NO. 7, June 2004

Stockholm is the location of the next ECNP Congress. From October 9 - 13, 2004 improvement. The presentation of the scientists in the field of neuropsychopharmacology will be attending some of the hyperbolic function by Lars Farde, i.e. 28 symposia, educational meetings and more. Although these will take place the relationship between dose/concen- between the walls of the congress centre, ecnp matters would like to give you a tration and receptor occupancy has had view of neuropsychopharmacology in Sweden. a substantial impact on clinical psy- chopharmacology. It can be questioned if not the main advantages of atypicals in comparison with the classical neu- Neuropsychopharma- roleptics are dose related.

cology traditionally Increasing gap Jan Milders In the past decade molecular genetics strong position in has been successfully applied in phar- macology. However, psychopharmacol- cological research has been hampered Sweden ogy is also dependent on understanding by decreased resources during the past complex interactions among different decade. Psychiatrists have very little Frits-Axel Wiesel, Uppsala University Hospital transmission systems and effects on time for research, which is largely due behaviour in developing and evaluating to cuts in the health care budget Among Swedish psychiatrists the interest in neuropsychopharmacology animal models in human psychophar- together with decreasing grants. was evident even before the introduction of the neuroleptics and antide- macology. One outstanding researcher Furthermore, there is an increasing gap pressants in the 1950s. Psychopharmacology at that time was of greater in this respect is Torgny Svensson who, between clinical and basic research. interest to Swedish psychiatrists than psychoanalytical theories. There was among other things, has demonstrated Although there are several young scien- a close connection between basic and clinical research and therefore new that not only the firing but also the pat- tists in neurobiology and pharmacol- ideas were easily transmitted to clinical psychiatry. terns are of importance in the commu- ogy, most of them are not medical stu- nication among neurons. Arvid Carlsson dents. During the successful years in he basic neuropsychopharmacologi- The discovery of the endorphins by also represents this research tradition, psychopharmacology research, several Tcal research in Sweden started with Lars Terenius has had an impact on the which is behind the development of the clinical researchers were trained in Ulf von Euler who discovered nora- view of addiction as a brain disease. third generation of antipsychotics, i.e. basic science before becoming clinical drenaline and defining it as a transmit- Jörgen Engel has worked with behav- the dopamine stabilizers. researchers. The importance of this ter in the sympathetic nervous system. iour and central neurotransmission and The basis for successful psychopharma- change is unclear, however. Later Arvid Carlsson demonstrated that how pharmacology could intervene in dopamine was not just an intermediate the mechanisms underlying addiction. in noradrenaline synthesis but an inde- Closer to the brain pendent transmitter in the brain. These Clinical pharmacology was developed Hot Topics Session two Nobel laureates have meant a great during the 1960s and 1970s. Folke deal for the interest in and development Sjöquist had a major role in this devel- The presenters of the sixteen best posters of the 2004 ECNP Workshop for young scien- The 17 th ECNP Congress is organ- of neuropsychopharmacology in opment. There was a hope to find rela- tists have been selected to present the two Hot Topics Sessions at the Stockholm ised under the patronage of Her Sweden. Arvid Carlsson is still very tionships between clinical effects and Congress. Majesty Queen Silvia from Sweden. influential in both basic and clinical sci- drug concentrations in the blood. ence. Another person of great impor- Although research interest in pharmaco- The sessions are: tance was Nils-Åke Hillarp who collab- kinetics was intense, results were rather S.04 Hot topics in preclinical neuropsychopharmacology orated with Arvid Carlsson. It was meagre. Correlations with side effects Sunday October 10, 2004 (09.00 – 11.05 hours) Hillarp who developed the technique to were found but for the therapeutic • Diverse psychotomimetics act through a common signalling pathway visualise the monoamine neurons. This effects only ranges of plasma concen- Per Svenningsson, Sweden technique attracted several young trations could be defined. The determi- • Neurobiological and behavioural effects of chronic mild stress in glucocorticoid researchers to his laboratory at the nation of drug concentrations is helpful receptor-impaired transgenic mice Karolinska Institute. Kjell Fuxe and to individualise drug treatment and con- Nicolas Froger, France Annica Dahlström mapped the trol for adherence. One has analysed • Leptin treatment in activity-based anorexia monoamine neurons in the rat brain drug concentrations in CSF to come Jaquelien Hillebrand, the Netherlands and Urban Ungerstedt mapped in detail closer to the brain, though that has not • Temporal and anatomical characterization of stress-related changes on the dopamine neurons. Another break- improved the value of drug analysis in BDNF expression in the rat central nervous system through was Thomas Hökfelt’s discov- understanding clinical effects in the Raffaella Molteni, Italy ery that a neuron operated with more patients. Obviously one has to come • Changes in subunit composition of N-methyl-D-aspartate receptor in animal than one transmitter (i.e. different kinds closer to the brain. model of schizophrenia: effect of subunit selective antagonist of neuropeptides). During the 1970s the first positron cam- Iryna Skuba, Czech Republic era was built in the USA. Lars Ericsson • Prefrontal cortex dysfunction in an animal model for neurodevelopmental psy- Still present took part in this development and, chopathological disorders The find by Arvid Carlsson that anti- when he returned to Sweden he built a Leontien Diergaarde, the Netherlands psychotics blocked catecholamine/ camera in Stockholm. The introduction • Neuroimaging changes in an animal model of schizophrenia dopamine receptors and that antidepres- of positron emission tomography (PET) Céline Risterucci, Switzerland sant inhibited reuptake of serotonin and in clinical research was the accomplish- • Hypothalamic histochemistry in different genetic models of anorexia noradrenaline was fundamental in psy- ment of David Ingvar. In the first stud- Serguei Fetissov, Sweden chopharmacology. In fact the hypothe- ies patients with schizophrenia were Page 2 ses formulated at that time are still pres- investigated with 11C-glucose as the S.07 Hot topics in interface neuropsychopharmacology Educational Team Bulgaria ent today. During the 1960s new analyt- tracer. However, it was soon clear that Sunday, October 10, 2004 (14.00 – 16.05 hours) ical methods were introduced into phar- the glucose technique was not very use- • Anxiogenic drugs act selectively on topgraphically distinct midbrain, pontine, Page 3 macology, including masspectrometry, a ful in psychopharmacological research. and medullary serotonergic neurones Jan K. Buitelaar: “Children are development led by Bo Holmstedt Pharmacological principals to deter- Jolane Abrams, United Kingdom not simply small adults!” whose main interest was in toxicology mine receptor numbers, binding and • Identification of GABAA receptor subtypes involved in tolerance against the and the cholinergic system. Göran affinity could be used in vivo with PET sedative action of diazepam Sedvall together with Frits-Axel Wiesel as shown by Lars Farde, Göran Sedvall Carolien van Rijnsoever, Switzerland Page 5 and Leif Bertilsson together with Marie and Frits-Axel Wiesel. In the first phar- • GABAB receptors play a key role in the modulation of anxiety and antidepres- The history of HCNP Åsberg developed massfragmento- macological studies of patients with sant-related behaviour: genetic and pharmacological evidence graphic methods to analyse monoamine schizophrenia it was demonstrated that Cedric Mombereau, Switzerland metabolites in body tissues. By analysis D2-dopamine receptors were occupied • Association between serotonin-related genetic polymorphisms and cholecys- of monoamine metabolites in CSF from by different kinds of neuroleptic drugs. tokinin tetrapeptide induced panic attacks in healthy volunteers patients, it was shown that different The clinical relevance of the PET tech- Eduard Maron, Estonia types of neuroleptics increased nique in dosage was obvious. One of • Rivastigmine therapy for memory deficits in patients with schizophrenia dopamine turnover as postulated by the first patients investigated with PET receiving electroconvulsive treatment Arvid Carlssson. Moreover Marie Åsberg, was severely agitated; thus the ward Dana Ophir, Israel in collaboration with Lil Träskman- staff wanted to increase her dose from • Brain volume changes in patients with schizophrenia: a 5-year longitudinal Bendz found that patients who commit- 4mg Haloperidol to the double level. MRI study across the age range ted suicide had lower levels of the sero- However, the patient accepted to be Neeltje van Haren, the Netherlands tonin metabolite 5-HIAA in CSF. investigated with PET and we found • Stimulation of α1-adrenergic and AMPA receptors in rat medial prefrontal Research in addiction has also been that her receptor occupancy was 85%, cortex increases local in vivo serotonin release: reversal by antipsychotic drugs fruitful in Sweden. The first centre of i.e. too high. The patient’s dose was Mercé Amargós-Bosch, Spain methadone treatment for heroin addicts adjusted to 2mg Haloperidol, which • Brain networks in sleep as revealed by combined EEG and fMRI in Europe was started by Lars Gunne resulted in the agitation disappearing Renate Wehrle, Germany after a visit at Rockefeller University. and her condition showing signs of

1 sented on stage to an audience of In each 'guided tour' eight people will get all you can out of the posters. By around thirty people who can just sit present their posters. The short presen- means of this initiative the SPC hopes to down and watch the posters 'tour' by. tations are followed by five-minute dis- give both presenters and congress par- The selection of the posters takes cussions. The poster presentations at ticipants the opportunity to explore the place at the 17th ECNP Congress in ECNP Congresses have always been posters a bit more in depth. Stockholm during the poster presenta- lively - indeed maybe a bit too busy to tions of the relevant topics. The reason for this initiative according to David Nutt chair of the Scientific Programme Committee (SPC) is: "... to try ECNP Brainstorming Session a new format of poster presentations that has been successfully utilised in other ECNP members received an e-mail last •Child and adolescent neuropsy- meetings. The background is that individ- March, informing them of an exciting chopharmacology uals will get an opportunity to talk about initiative at the 17th ECNP Congress at (Celso Arango,Spain) their poster contents rather than simply Stockholm, Sweden. From Sunday • Getting rid of mal performing EPS be passive recipients for questions. In October 10 to Tuesday October 12 they rating scales some countries such a presentation is have been given the opportunity to (Anton Loonen, the Netherlands) helpful or even necessary in order to get organise a brainstorming session on a • Glucocorticoid signalling: A novel funding to attend a meeting. Moreover, topic of their choice. At the end of April pathway for antidepressant drug we thought we could develop a theme nine brainstorm sessions were selected discovery from a group of posters which would be out of the 32 proposals received. (Ulrike Schmidt & Marcus cohesive and perhaps give greater value In the proposals the members were Rosenhagen, Germany) than the sum of its parts. The selection of asked to name two other experts on the • Pharmacological treatment of stimu- posters is based on an attempt to develop topic in question. The registration fee is lant dependence – preclinical and one of the key scientific areas of the con- waived for up to three experts and clinical aspects gress. The plan is not to seek controversy ECNP provides a room for a maximum (Ulrich Tacke, Finland) but to look for a group of posters which, of thirty people, including facilities for •Treatment of women with depres- when taken together, will give an inter- presentation. The brainstorm sessions sion esting and perhaps challenging overview and the chairs are: (Peter Gaszner, Hungary) of the scientific hot topics." • ADHD in Adults •Tryptophan depletion and loading Two of such presentations will be held (Johanna Krause, Germany) techniques: reappraisal and recent Jan Milders on the following dates and topics: •Aβ protofibril formation in developments Guided poster tour • Sunday, October 10 2004, 12.30 - Alzheimer’s disease (Abdullah Badawy, UK) 13.30 hours (Room K2) (Lars Lannfelt, Sweden) A new element in the ECNP Congresses Affective disorders and antidepressants • Bipolar disorder: can we extrapolate is the guided poster tour. The 'tour' is • Monday, October 11 2004, 11.15 - from registration studies to guide- Full details of the location and other metaphorical as in this case tour means 12.15 hours (Room K2) lines and clinical practice? experts will be published in the pro- that the selected posters will be pre- Psychotic disorders and antipsychotics. (Willem Nolen, the Netherlands) gramme.

“I have been long wondering whether the questions inside your head. The Educational Team Bulgaria I was working properly and whether I answers will be found sometime.” Three ECNP experts met a group of 27 young Bulgarian psychiatrists at the had been attending the right meetings. complex ‘Fenerite’ bordering upon a renowned Bulgarian architectural and I have been sitting at those endless cor- Georgi Vishev porative presentations of incredibly Forth year of specialization in psychiatry ethnographic reserve. It was a temporally concise meeting, yet providing good drugs as well as at reviews of Sofia University Hospital ‘Alexandrovska’, ample opportunity for discussions on March 25 to 27 2004. absolutely unbiased internationally psychiatric clinic, Bulgaria. acquired data. At the same time I have been living in a very different reality, “For the first time in my professional Luchezar G. Hranov, local coordinator Educational Team Bulgaria treating people with old medications as biography I was formally asked to pres- the new ones proved ineffective. ent a CV and project summary so I Trapped in a double professional stan- could attend a meeting. I was intrigued dard, I began to ask myself where to find which ‘wonders’ awaited me things get distorted and I even arrived there… A conspiring group gathered far to some definite conclusions. from the farsighted reach of the phar- On the way to this meeting I had maceutical industry in a Bulgarian ren- already organised my thinking around aissance village with the only ‘mes- the concept that I would participate in sianic’ idea to hear, to ask and to learn the same sort of event. However when I what happens with psychiatric SCIENCE joined the discussion and acquainted and how the results of serious and myself with the ideas, projects and REAL research should be obtained and visions of Joseph Zohar, René Kahn, and presented. Jean-Pierre Lépine I told myself that I On the first day the visiting experts for- had simply not mingled with the right mally presented their topics and in the people. My bewilderment was complete following discussions I felt proud of the when during the whole educational fact that I am a psychiatrist and I can course at ‘Fenerite’ I was gently but per- grasp the manner in which psychiatry is sistently led to the same conclusions ‘made’ to be strict, honest, and not in and solutions to which I had arrived the conditional inclination. During the before. The whole experience enriched second and last day of the event the my general view on evidence-based experts consulted the research projects medicine as I could look at it from the of the participants. This brought the perspective of three impartial and com- inevitable disappointments. All of us petent experts. Our conversation ran lack good tutors and try to compensate smoothly and was completely unpre- by reading thick volumes. But when tending. Moreover, I found it awfully you encounter a professional who is stimulating to share my personal experi- not only giving a structure to your ideas he topics chosen: interface of anxi- The whole event was completely inter- ence, no matter how unevidential it was but also is generating ideas that fit per- Tety and depression (Joseph Zohar), active and the exchange of information and to exchange opinions with people fectly into your ‘revelations’, you just contemporary long-term treatment of and ideas was free and unbiased. The who had fresh ideas about how to make want to go on discussing every issue in schizophrenia (René Kahn), and psychi- participants gained valuable knowledge medicine and psychiatry effective and depth and in no hurry. Unfortunately atric epidemiology (Jean Pierre Lépine) on how “to pose questions that advance useful in the real world. the time limitations did not allow such were not only of high practical interest the field”, in the words of Prof. Zohar. There were bad things too: all was over comprehensive reviewing of the really to the participants, but also gave them Altogether a very satisfactory event, in a jiffy, one could hardly take one’s interesting projects of my colleagues the opportunity to touch upon diverse well-worth the time and effort invested, breath and above all a lot of issues and it made me feel abstinent and ask issues related to their own experience as illustrated on this page by the were left outside the discussions but and research. impressions of some participants. anyway, the important thing is to have continued on page 4

2 A has been fascinated by the versatility and different anglesinthetherapy. has beenfascinatedbytheversatilityanddifferent Buitelaar gotinvolvedwithchildpsychiatryduringhisstudiesandsincethen developmentofADHDandautism. he willconcentrateontheneurobiological nary lecture* atthe17 nary lecture* try atUMCSintRadboudinNijmegen,theNetherlands,willbegivingaple- Jan Buitelaar, inadultpsychiatryandchildadolescentpsychia- professor adults!” “Children arenotsimplysmall Jan K.Buitelaar: problems canoccur?Which things ADHD? Whataretheriskfactors? Which significance ofeducation: What is There aretwoaspects.Thefirst isthe in thesamewayastreating children. Tr treatment. require atotallydifferent behavioural disorder. Assuchthey a personalitydisorderandADHDis Borderlineis one importantdifference; "Although therearesimilaritiesis Education Disorder hadADHDasachild." fromBorderline all adultssuffering adults. Researchshowsusthathalfof ADHD inadultsandBorderline tionship betweenADHDinchildren, fact itisinterestingtodiscusstherela- ness, andachaoticjobenvironment.In there: manyconflicts,majorforgetful- but thelimitationsarestillverymuch might havebecomesomewhatmilder still havethediseaseasanadult;it About athirdofchildrenwithADHD the otherpossibleproblems. with theillnessassuchandtodeal well shouldhaveadoubleaim:todeal lems. Thismeansthatthetreatmentas and, inshort,encountermajorprob- of school,getinvolvedwithdrugabuse W the disorderisarealriskforthem. ADHD simplyneedtreatmentbecause diagnose thisdisorder. Childrenwith dangerous nottodiagnosethanmis- ADHD rathertooquickly,itisfarmore denied thatsomedoctorsdiagnose and parents.Althoughitcannotbe giventoyoubyteachers information especially asyoualsodependonthe ficult toknowwheredrawtheline, or isachildjustbeingnaughty?Itdif- ADHD: Isittrulyhyperactivebehaviour dilemma oflabellingachildwith of MedicineinwhichIdiscussedthe cle onthisissuefortheDutchJournal ADHD. AfewyearsagoIwroteanarti- public thatisprimarilyfocussedon rily focussedonADHD;rather, itisthe However, itisnottruethatIamprima- creative anduseallkindsoftechniques. child intherapy.You havetobevery treatment andyoucannotjusttalktoa ronment playanimportantroleinthe not onlythechildbuthisorherenvi- try; Iamfascinatedbytheversatility- ferred childpsychiatrytoadultpsychia- outIpre- atric disorders.Asitturned more aboutthedevelopmentofpsychi- child psychiatryasIwantedtofindout drome. Inthe80sIstartedstudying with depressionandTourette syn- lesser degreeyouwillalsofindchildren ADHD andautism;inasomewhat “The maindisordersinchildrenare withthisimpression? agree marily dealwithADHD?Would you thatyoupri- came totheimpression I andmore andmore information eating ADHDinadultscantakeplace ithout treatmenttheymightdropout searched Internet forbackground Internet searched forthisinterviewI s Iprepared interview th ECNP Congress inStockholm,Sweden.Inthislecture ECNP Congress December 12-16,2004 San Juan-PuertoRico, Brain GABA 2004 atACNP ECNP - 25yearsofprogress but itistakingalongtime. Inthe tion. Thereissomechange going on research resultsforchildren's medica- “I thinkitisverybadnot tohave tion? How doyoufeelaboutthissitua- while. populations tomakeitworththeir tively notenoughchildreninthose groups theyhavetotestonandrela- tive forthemasthereareseveralage just toomuchfussandalsonotaslucra- which group.Researchinchildrenis drugs theyshouldberesearchingin ceutical companiestodecidewhich research isthatituptothepharma- cal practice.Thereasonforthelackof questions thangivinganswersforclini- unpublished data,generatingmore ever withabiasbetweenpublishedand been someresearchwithSSRIs,how- been testedonchildren.Therehas However, hardly anyantipsychotichas EMEA. tested onchildrenandapprovedby few moregeneraldrugsthathavebeen EMEA, see on by EMEA(Formoreinformation on 6–18yearsoldsandacknowledged exception isRitalinthathasbeentested ical andpsychiatricdisorders.Anotable neurolog- dren’s medicationconcerning below eighteen.Thesamegoesforchil- has beendoneontheagegroups olds. Thereasonbeingthatnoresearch ing thedrugtoundereighteenyear children usuallyadviseagainstprescrib- instruction leafletsofmedicinegivento label’asmanyofthe atrics is‘off “Most medicationforchildreninpaedi- medication? children's of What abouttheprescription antipsychotics." standard wetreatBorderlinewith good resultswecannotsaythatasa for thisgroupandalthoughwebooked Radboud wehavetriedantipsychotics Borderline though.AttheUMCSint is nostandardmedicationtreatmentfor fering fromBorderlineDisorder. There cation isalsoimportantforpeoplesuf- step, alsoforchildren!Ofcourse,edu- Understanding theillnessisfirst emphasise theroleofeducation. themedicinaltreatment,Imust cerning in abitmorerelaxedmanner. Alsocon- enables patientstoorganise theirlives regulating andplanningso,inshort,it lates thefrontalcortexthatcontrols phetamine. Thisparticulardrugstimu- Methylphenidate (Ritalin)anddexam- ment withstimulantsas Secondly, thereisthemedicinaltreat- bit tooversatileforme! for childrenwithADHDbutthatwasa best. Iactuallyoncedidagroupsession that theindividualisticapproachworks dren Iquicklycametotheconclusion tion takesplaceingroupsbutwithchil- should theyfocusonfirst?Theeduca- ecnp matters A receptors 5). Therearea T ropsychiatric disorderstochildren. comes toprescribingdrugsforneu- United Kingdomisfairlyantiwhenit approach. Ontheotherhand, Scandinavia followtheAmerican and The Netherlands,France,Germany psychiatric andneurologicaldisorders. medication, especiallythoseconcerning tries inlinewithregardtochildren’s togetallcoun- It appearstobedifficult istration) matters has itsowntraditions.(Alsosee Authority (EMEA)nearlyeverycountry there isacentralEuropeanMedication lem withEuropeisthateventhough believe weneedachange.Theprob- that istheidealsituationbutIdo exchange forlicensing.Idon’tknowif industry toconductacertainresearchin Administration canstronglyrequestthe United StatestheFoodandDrugs Kirsten Bett,editor workedwell. The generalconsensuswasthattheformat beingselectedonthe basisofanopensubmissionpapers. with therest institutes viaEuropean registered about halfoftheyoungscientistswere 2004 AtthelastmeetinginMarch scientists givingshortpresentations. certainthemesfollowedbyjunior that twodistinguishedscientistsaddress Y works well New formatworkshopNice neuropsychopharmacology, behavioural neuropsychopharmacology, three recurringtopics(molecular Each yeartheworkshopfocusses on the nextworkshopisOctober 152004. The deadlineforsubmittingabstracts for work!" that makestheformat for thediscussion.Itisinteraction tinguished speakerstoremainpresent sider, suchasthenecessityfordis- There aresomeminorpointstocon- everybody thinksitisworkingwell. menting anychangesasatthemoment to waitanothertwoyearsbeforeimple- "The Workshop Committeehasdecided tists participatinginthe2004workshop. see theenthusiasmofyoungscien- Wo • Stress andbenzodiazepinereceptorfunction • Imaging benzodiazepinesubtypesandreceptorfunction • Subtypes asdrugtargets • From bindingsitetomolecularfunction Chair: DavidJ.Nutt,UK oung scientists are the target group oftheECNPWorkshop. group thetarget oung scientistsare is Theformat Giovanni Biggio,Italy Anne Lingford-Hughes,UK UK Ruth McKernan, Hanns Möhler, Switzerland rkshop Committee,waspleasedto high. DavidNutt,chairofthe he qualityoftheworkshopwas 5 for more information onreg- 5 formoreinformation ecnp matters ecnp on www.ecnp.nl. or programme found inthepreliminary detailscanbe (11.15 -12.00)More onMondayOctober11,2004 Congress try' willtakeplaceatthe17 ofpsychia- and Adolescents:thefuture * doing well!” tive: Ifajobisworthdoing,it the treatmentcouldbefarmoreeffec- ing couldbeimprovedaswell.Then of inaccuracyinthedose.Themonitor- not oftenenoughbutratheraquestion for children-prescribingtoooftenor because theydomostoftheprescribing question ofgeneralpractitioners- medicinal treatment.Itisnotsomucha Dosingisessentialin the efficacy. on without sayingthathaseffect concentration intheblood.Itgoes significanceisthe real pharmacokinetic this hasconsequencesforthedose.Of than thatofanadult'sliver. Ofcourse capacity ofachild'sliverismuchbigger fromadults,forexamplethe differ they developing. Pharmacodynamically still growingandtheirbrainis are notsimplysmalladults.They best dosesare,forexample.Children theyareandwhatthe just howeffective on need tohavescientificinformation results specificallyforchildren.We is necessarytogetsomeresearch it “Although theyseemtobeeffective, effective? children to prescribed label) thatare oroff- thedrugs(registered Are research." be financingpharmaceutical cal companiesaretheoneswhoshould justify thisbystatingthatpharmaceuti- finance researchofmedication.They case intheNetherlands–donot of scientificresearch-atleastthisisthe institutions responsibleforthefinancing reservation. Anotheraspectisthatthe Spain, PortugalandItalyshowthesame place fromMarch4-6inNice, France. the 2005ECNPWorkshop thatwilltake Please visitwww.ecnp.nlforupdates on phrenia. For2005itwillbedepression. variable topic.For2004thiswasschizo- Thereisalsoone chopharmacology). andclinicalneuropsy- pharmacology, Jan Buitelaar's plenary lecture 'Children Jan Buitelaar'splenarylecture ecnp th ECNP All thebestforfuture! ation ofeverynewnewsletter. cation andoptimisminthecre- like tothankherfordedi- ing anewcareer. We would Our editorKirstenBettisstart- Breaking News matters 3

interview Kirsten Bett, editor ecnp matters and get to know each other, listen to, plenary lectures and group discussions. consult and help each other in a realis- The Bulgarian participants were greatly tically convenient time frame.” impressed by the unique possibility to receive creative stimulus through in- Tony Donchev depth analysis of their individual proj- Department of Psychiatry, Military ects based on personal experience and Medical Institute aiming at future research. All the activ- Sofia, Bulgaria ity was superbly moderated by the vis- iting experts. The two-day event was “I had the pleasure to be one of the imperceptibly over leaving the general continued from page 2 group of psychiatrists invited to partici- impression that a meeting of well-edu- atric research in Bulgaria and is the first pate in the unique interactive event cated and inquisitive young psychiatrist step on the road to a future fruitful col- myself in a childishly naïve manner if ECNP Educational Team Bulgaria 2004. lacking experience in the field of scien- laboration with our colleagues in united there isn’t a possibility to find me such The local organisation was carried tific standards with leading scientists Europe.” a consultant at least for a single week. through in a responsible and selfless who are ready to help the realization of Two more things seem worth mention- manner by Luchezar Hranov. The any original idea relying on the author- Svetlozar Georgiev ing: the perfect organisation of the event world-famous experts openly and ity of ECNP is exceptionally useful. Department of Psychiatry, Medical and my suggestion to the Bulgarian psy- enthusiastically shared their enormous I find that this event creates new possi- University

Educational Team Bulgaria Educational Team chiatric researchers to meet annually professional experience in the format of bilities for the development of psychi- Plovdiv, Bulgaria

In ecnp matters 5 Anne Lingford-Hughes was the first to appear in ‘What mice), selective agents are indispensa- ery, it is unrealistic to expect that novel matters to…’. In this feature members of the Scientific Advisory Panels ble in the experimental characterisation solutions to the treatment of depression share their concerns and expectations of neuropsychopharmacology. of novel targets. However, it may be will rapidly cascade from the human Which items do they find important? In what lies their specific interest? questioned whether drugs with highly- genome. Rather, it provides a point of Is there anything they would like to see changed? This issue we asked these discrete actions are well-adapted to the departure, a structural and informa- questions to Mark J. Millan, member of the Scientific Advisory Panel on treatment of a disorder as complex as tional foundation, which, assuming its psychotic disorders and antipsychotics. Dr. Millan obtained his qualifica- depression which entails a widespread rational exploitation within the frame- tions from the University of Cambridge, England, and spent nearly 10 years perturbation of cerebral function. For work outlined above, offers long-term at the Max Planck Institut for Psychiatry in Munich, Germany. He is Director novel targets, it may be wise to incor- hope of genuine improvement in the of the Psychopharmacology Division at the Institute de recherche Servier, porate activity into molecules possess- management of depression, if not for Croissy-sur-Seine, Paris, France. In this capacity, he is confronted on a daily ing other (established) modes of action. our generation then for those that will basis with the challenge of discovering improved drugs for the treatment of That is, multi-target agents should be follow us. It is critical that this notion of depression and other CNS disorders, a lengthy and complex undertaking. prioritised for the improved treatment ‘time’ be more generally understood not of depression. only by those - like this writer - daily confronted with the challenge of drug The key notion of ‘time’ discovery, but also the medical commu- What matters to.... Partly for reasons outlined above and in nity, agencies, governments and, no view of the intrinsically difficult and less importantly, depressed patients, Mark J. Millan time-consuming nature of drug discov- their families and the general public.

Despite the improved tolerance of necks in drug discovery have not newer antidepressants as compared to changed: rigorous, pre-clinical target 2003 ECNP-ACNP Exchange Award older tricyclic agents, we urgently need validation, transformation of chemical more rapidly-acting drugs (or other leads into genuine drugs respecting Winner Monica M. Marcus reports... treatments) of greater efficacy. If possi- stringent pharmacological, pharmacoki- ble, with complementary properties netic and toxicological criteria (the first "As one of the winners of the 2003 permitting control of co-morbid anxious five years of high-throughput screening ECNP-ACNP Exchange Award I was and cognitive symptoms. There has and allied technologies have proven invited to participate in the ACNP been spectacular progress in experi- hugely disappointing) and imaginative, Congress in Puerto Rico, USA, mental research over the past decade. well-controlled clinical trials. December 2003. I was also invited to However, the difficulty remains of send in my abstract that was presented translating these gains in knowledge Second, monoamines fulfil a pivotal and awarded at the 2003 ECNP into tangible benefits for patients. In ris- role in the control of mood, and in Congress in Prague. The title of this ing to this challenge it is important to the pathogenesis and treatment of abstract is Addition of nicotine to the remember that depression is a hetero- depressive states D2 antagonist raclopride or the weak D4 geneous disorder with a complex and All currently available antidepressants antagonist L-745,870 augments NMDA- the opportunity to discuss my results multifactorial aetiology involving act by a broad-based reinforcement of induced currents in pyramidal cells with many other scientists. I must admit genetic (hereditary), developmental corticolimbic monoaminergic transmis- from the rat medial prefrontal cortex. that I have rarely encountered such a (neonatal) and environmental (life sion. One may, then, enquire whether Since I had previously heard about the positive response to a poster presenta- events) factors. Within this light, several depressive states can be improved via ACNP meeting from my supervisor, pro- tion. It was most encouraging. interrelated and fundamental issues mechanisms acting independently of fessor Torgny H. Svensson, I had high At the ACNP meeting I was also invited must be addressed. monoaminergic networks. Certain novel expectations. I had been told that within to two social events, The Travel Award agents may act upstream of, and modu- the field of neuropsychopharmacology Breakfast and The Travel Award First, the impact of the human late, monoaminergic transmission - as the ACNP meeting is one of the best Luncheon, arranged for all Travel genome illustrated by neurokinin1 receptor meetings in the world and for me, work- Awardees (about 40) who had received Its sequencing has fuelled hopes of dis- antagonists which were initially pro- ing with the mechanisms of action of their Awards from various organisations. covering hitherto-unknown targets for claimed to work by an entirely new antipsychotic drugs, it would give me Both events were very pleasant indeed. improved symptomatic control of mechanism of action. Other classes of the opportunity to learn more about My general impression of the ACNP depressive states, and even their pre- drug may act downstream of both preclinical and clinical research at meeting is that the quality of the pre- vention in predisposed individuals pre- monoaminergic pathways, perhaps con- the frontier of the field. sentations was high, generally present- senting genetic, endocrine or neurolog- verging onto common cellular sub- My expectations were indeed fulfilled ing state of the art science, and that the ical markers. Further, though it is strates. However, clinical proof that and there were several highlights at the participants were genuinely interested unlikely that a ‘gene for depression’ will depressive states can be alleviated by meeting. If I should mention some, it in discussing the results. Since it is nec- be found, subpopulations of patients agents not involving monoaminergic would be two panel sessions. The first essary to be an ACNP member to partic- may express genes rendering them vul- mechanisms is awaited. It is crucial, one was From NMDA to D1 dysfunction ipate in the meeting, or to have an invi- nerable to other genetic, developmental therefore, to pursue monoaminergic, and back: Models of prefrontal pathol- tation for attendance, and since my and/or environmental factors. However, non-monoaminergic and combined ogy in schizophrenia with presentations ECNP-ACNP Exchange Award also identification of novel genes (targets) strategies in the search for novel anti- by H. Tsukada, A. Abi-Dargham, J. includes invitations to attend the next potentially implicated in depressive depressants. Seamans and J.Krystal. Secondly, The two years meetings, I sincerely hope states is by no means the end of the language of dopamine neurons: What that I will find funds so I can participate story, it is just the beginning. There is Third, for genome-derived, novel spike activity tells us about function, in these meetings as well. no pre-programmed and straightfor- targets “specificity” of drugs actions included presentations by S. Floresco, Finally, I would like to thank the ECNP ward sequence from the genome to is invariably emphasized M. Marinelli, M. Diana and W. Schultz. Award Committee for giving me this improved treatment of disease: That is, priority is afforded to drugs Both sessions were very interesting and great Award." genome-derived drugs are not inher- interacting exclusively with a single site relevant to my own work. ently better than any others, and they hypothesised to be implicated in The poster sessions were also of high Monica M. Marcus are certainly not quicker or easier to depressive states. Together with genetic quality and presented many interesting Med Lic, PhD student discover and develop. The real bottle- research strategies (such as knock-out studies. At my poster presentation, I had Karolinska Institutet, Sweden

4 University MedicalSchoolin Szeged, professor andchairattheSzent-Gyorgy Neurology inBudapest.Zoltan Janka, National InstituteofPsychiatry and renowned clinicianandteacheratthe papersanda ical psychopharmacology Zoltan Rihmer, aprolificauthorofclin- retary; laterthisdutywastakenoverby 55), chosetoservefirstasgeneralsec- edly diedonJuly272003attheageof College, MihalyArato(whounexpect- decade. Thetrueoriginatorofthe tition forboardpositionsinthepast HCNP membershavehadlittlecompe- group, Being alooselyformalised tual activity:exactlywhatweintended. pureintellec- its owncouldonlyafford ous downsidethattheorganisation on pendence has,ofcourse,hadtheobvi- no directfinancialties.Thisproudinde- remained anindependentCollegewith support fromseveralparties,ithas enjoyed fullandunreservedprofessional 1993. AlthoughtheCollegehasalways inauguratedinMay HCNP wasformally Little competition cology research. andpsychopharma- chopharmacology monise viewsaboutclinicalpsy- exchange experienceaswellhar- together andtoletthemregularly objective wastobringtheexperts group ofopinionleaders.Ourmodest mitment toECNP-butratherasmall head andalogoemphasisingourcom- though wedidcreateasimpleletter- andbusyaccountants- showy offices membership lists,stamps,secretaries, associationwith just anotherformal ing theHCNPwedidnotseektocreate socialfreedom.Byform- western-style of savouring thelong-awaitedreturn this inanatmosphereofconstantflux, ganising practicallyeverything–andall andreor- tious enterprises,reforming simmering withnewendeavours,ambi- Rihmer andI.AtthattimeHungarywas Arato, IstvanBitter, ZoltanJanka, Those 'foundingfathers'wereMihaly 1992. Duringthe5 exceptionswasinOctober Oneoftherare inEurope. est, sunniestregions Spain,isamongthedri- The MediterraneancoastlineofAndalusia,southern HCNP Csaba M.Banki,president catalysing progress Exchanging informationand The historyofHCNP: in Hungary: the Hungarian College of NeuroPsychopharmacology (HCNP). in Hungary:theHungarianCollegeofNeuroPsychopharmacology exchange andinformation thinking,research, of psychopharmacological forthepromotion noons, decidedtoestablishanewnationalorganisation Hungarian psychiatrists,whileunwillinglystayingindoorsinthelateafter- thewholeweek.Itwasduringthosedampdaysthatfive throughout intermittently withdarkcloudsandheavyrainsshowered ally covered

interview th ECNP Congress heldinMarbella,theskywascontinu- ECNP Congress official journal ofthesectionandcreatingawebsite. journal official wPsychiatriiiNeurologii",an ing aquarterly"Farmakoterapia May 2004.Amongtheactivitiesinnearfutureispublish- SectionofthePolishPsychiatricAssociationin pharmacology Janusz RybakowskiwaselectedpresidentofthePsycho- News PolishPsychiatric Association Founding fathers. always beenactiveinpromotingand clinical practiceandresearch.Ithas exchange andconsensusseekingin forinformation serve asaplatform The primeaimofHCNPhasbeento dedicated neuropsychopharmacologists. dred psychiatristsandonlyafewdozen small countrywithlessthaneighthun- more thanfiftymembers.Hungaryisa a membershipfee,HCNPhasneverhad meetings repeatedlyrejectedtheideaof Despite thefactthatinitialboard journals. published ininternational ogy andwithoriginalresearchpapers cant activityinneuropsychopharmacol- academic degree,demonstratingsignifi- Membership isfreetoanyonewithan A platform untilnow. (to mysurprise)ineffect leged appointmentthathasremained 1993. Iconsiderthisagenuinelyprivi- unanimously electedHCNPPresidentin currently asscientificdirectorIwas border), institution closetotheeastern Nagykallo (thesecondlargest specialist the RegionalPsychiatricHospitalin years (whichattimesfeelslike300) Having faithfullyservedalmostthirty ing thepositionsofvice-presidents. Medical SchoolinBudapest,keephold- chiatry attheSemmelweisUniversity and IstvanBitter, nowprofessorofpsy- ECNP andafteronlytwoyears, we the immediateintellectualsupport of cooperation aswell.We startedoutwith HCNP isanadvocateofinternational Dedicated cooperation Diagnosis andTreatment?'. Psychiatric Neuroscience Affect provocative title:'DoRecentResultsin November 2003,withasomewhat pants. Thelastconferencetookplacein ters andaboutthreehundredpartici- always attractedtheverybestpresen- year. Thesethematicconferenceshave Nagykallo inlateNovembereveryother tific meetings,customarilyheldin temptation tointroduceitsownscien- mind, HCNPcouldnotlongresistthe Though originallywedidnothaveitin papers'. HCNP documentstrue'consensus ward theircomments).Thismakes attend thesemeetings(oratleastfor- are ableandwillingtopersonally already knoweachotherandthatthey all thepotentialparticipantsinafield small country’sadvantagethatalmost at leastonceeverythreeyears.Itisa vened nationalconsensusconferences guidelines; wehavesincethencon- taining andregularlyupdatingthese HCNP assumedresponsibilityformain- Hungarian CollegeofPsychiatrists. proposals inpsychiatry,issuedbythe apy sectionofthegeneraltherapeutic was reproducedinthepharmacother- held in1996,andtheresultingmaterial HCNP consensusconferenceswere options inHungary.Thefirstfour the availablepharmacotherapeutical lines, possiblyevidence-basedviewsof andpublishingguide- of formulating consensus meetingswiththeobjective priority toorganise aseriesofnational 1990. HCNPthereforeconsidereditfirst chiatry wereabsentinHungarybefore Clinical therapeuticguidelinesinpsy- The verybest Society. the HungarianPsychopharmacological and 1999,co-organised byHCNPand in Budapesteachyearbetween1995 Semmelweis UniversityMedicalSchool tookplaceatthe psychopharmacology courses inbiologicalpsychiatryand CMEtraining 1999. Thefirstofficial existencein which cametoformal medical educationschemeinHungary, continuing nents ofadoptingauniform structure. HCNPwasamongthepropo- slowly progressingintoanationwide also startedasavoluntarymovement, wait decadesuntilbecomingreality.It was anotherimportantissuethathadto Continuous MedicalEducation(CME) courses fortheresidents. shops andlocalorregionalthematic continues toprovideeducationalwork- was dejureadoptedin1998.HCNP lum. Thistrainingsysteminpsychiatry partofthecurricu- chopharmacology HCNP hascontributedtothepsy- countrywide (withregionalcentres). network hasbeengraduallydeveloped sity-based postgraduateeducational all itsalliedorganisations, thisuniver- Hungarian PsychiatricAssociationand programme. Incooperationwiththe shaping apsychiatricresidencytraining Hungarian CollegeofNeuroPsychopharmacology e-mail: [email protected] Secretariat: H–4321Nagykallo,P.O.Box 18.Phone:(36-42)563-810;Fax:263-128, Tr President: CsabaM.Banki;Secretary:ZoltanRihmer;Vice-presidents: IstvanBitter, ZoltanJanka; easurer: ErikaSzadoczky. activity inyearstocome. renewed scientificinterestand research period andstilllookforward toa nitely hopethatthisisjusta transient professional organisations. We defi- unwillingness toevennegotiatewith ment interventionsandtheirfirm been severelyhamperedbygovern- has ofpharmacotherapy ernisation to thefewexceptions)andmod- younger generation(withduerespect seems tobelessattractivethe researchnow psychopharmacological slowed downsignificantly.Neuro- quality. Morerecentlythisprogress was remarkablebothinquantityand years. ThescientificoutputinHungary more than30%withinless15 utably highsuicideratedecreasedby improved spectacularlyandthedisrep- Diagnosis andpharmacotherapy practice inHungarywasontherise. researchand ropsychopharmacology mixed feelings.Ten yearsagoneu- We tions. Union, didnotsurvivethe2002elec- tosimilarboardsintheEuropean form but thisinitiative,althoughfullycon- committee wassetupforthispurpose bursement regulation.Ashort-lived ability, prescriptionrulesandreim- macotherapy relatedissueslikeavail- decisions about,amongothers,phar- through theirColleges–ingovernment ment ofthehealthprofessionals– initiative calledforthedirectinvolve- parties. Afewyearsagoapromising paign foropennegotiationsamongall andcam- is topromulgateinformation best aprofessionalorganisation cando etatism inhealthadministration.The low-income populationandstrong sensitivities inthisfieldduetotheir European democracieshaveparticular industry isdelicate.ThenewCentral authorities andthepharmaceutical between theclinicians,health T and anyrelevantnews. the guidelines,conferenceabstracts, all theconsensusconferencepapers, have anHCNPNewsletterthatcontains existing Hungarianones.Moreoverwe orinanyofthe journals in international cited authorsintheirfield.Theypublish among themostproductiveand élan. TheboardmembersofHCNPare tion withACNPisanothersourceof butnolessdedicatedcoopera- formal most encouraging.Thesomewhatless of CINP, amarkofrespectweconsider became aCorrespondentOrganisation rying tofacilitatecommunication

look tothefuturewithsomewhat ecnp 5 Founding meetingin1993. matters 2004 ECNP Neuropsychophar- ecnp matters Calendar of ECNP Events macology Award ecnp matters is a publication of the Printing ECNP Congresses: European College of Neuropsychopharma- Teewes Textpresse Grafische Bedrijven Julien Mendlewicz cology (ECNP). October 9 - 13, 2004 17th ECNP Congress, Stockholm - Sweden chair ECNP Illustrations October 22 - 26, 2005 18th ECNP Congress, Amsterdam - the Netherlands Neuropsychopharma- Edited by cartoons: Jan Milders September 16 - 20, 2006 19th ECNP Congress, Paris - France cology Award, 2004 Kirsten Bett, editor October 13 - 17, 2007 20th ECNP Congress, Vienna - Austria Jocelyn K. Koole-Krusemeijer, adviser Call for copy September 20 -24, 2008 21st ECNP Congress, Istanbul - Turkey The jury of the 2004 ECNP Jan M. van Ree, adviser Deadline next issue: November 1, 2004 Neuropsychopharmacology Award has voted to recog- Editorial Committee Copy (600 words maximum) can be sent to: For further information: nise the contributions of David J. Nutt (chair) ECNP-Office Organising Secretariat Scientific Secretariat: Michael Davidson to the Filippo Drago PO Box 85410 17th ECNP Congress ECNP-Office field of neuropsychophar- Joseph Zohar 3508 AK Utrecht Congrex Holland BV PO Box 85410 macology. Because of his The Netherlands PO Box 302 3508 AK Utrecht many scientific achieve- Executive Committee ECNP phone: +31 30 253 8567 1000 AH Amsterdam The Netherlands ments Michael Davidson is Yves Lecrubier (France), president [email protected] The Netherlands phone: +31 30 253 8567 one of the pre-eminent Christer Köhler (Sweden), vice-president phone: + 31 20 50 40 207 fax: +31 30 253 8568 researchers in the field of Julien Mendlewicz (Belgium), president-elect fax: + 31 20 50 40 225 e-mail: [email protected] schizophrenia. Jan M. van Ree (the Netherlands), past president e-mail: [email protected] website: www.ecnp.nl His studies on HVA and on Joseph Zohar (Israel), secretary biological mechanisms of René S. Kahn (the Netherlands), treasurer action of antipsychotic Celso Arango, (Spain) ECNP Workshop on Neuropsychopharma- drugs in schizophrenia and Filippo Drago (Italy) his subsequent post-mortem Siegfried Kasper (Austria) cology for young scientists in Europe: studies on schizophrenia Hans-Jürgen Möller (Germany) March 4 - 6, 2005 and Alzheimer's disease David J. Nutt (United Kingdom) Nice - France have significantly con- Sven O. Ögren (Sweden) • Molecular Neuropsychopharmacology tributed to our scientific Jean-Charles Schwartz (France) Copyright for all published material is held • Behavioural Pharmacology knowledge. Alexandra Eva Sulcova (Czech Republic) by ECNP unless specifically stated otherwise. • Clinical neuropsychopharmacology: Focus on Depression Michael Davidson has also Hans-Ulrich Wittchen (Germany) ecnp matters is carefully prepared and pub- • Depression: Towards New Drug Targets contributed to move the lished. The expressed views are not neces- field forward through his Contributors sarily those of ECNP or the editorial staff. continuous efforts to Csaba M. Banki They are the responsibility of the writer of establish a unique schizo- Kirsten Bett the article. The editorial staff, however, does ECNP Consensus Meeting: phrenia brain bank with Luchezar Hranov have the right to refuse or shorten copy. The March 6 - 9, 2005 ante-mortem assessment. Liedewij J. Jepsen writers are consulted about major changes in Finally, his epidemiological Mark Millan the copy. For information: studies have greatly con- David Nutt ECNP-Office tributed to the recognition Frits-Axel Wiesel Permission is given to reproduce the text of PO Box 85410 of predictive factors in the any information found in this newsletter as 3508 AK Utrecht early diagnosis of schizo- Graphic Design long as the sense is not distorted by omis- The Netherlands phrenia. Pieter Hoogeveen sion or addition and the original place of phone: +31 30 253 8567 Design and Art Direction publication is cited. fax: +31 30 253 8568 e-mail: [email protected] website:www.ecnp.nl

Events national societies 8th ECNP Regional Meeting, Moscow - Russia April 14 - 16, 2005

• Depression EUROPEAN COLLEGE OF • Anxiety NEUROPSYCHOPHARMACOLOGY British Association for Psychopharmacology • Aging • Alcohol, Drugs and Tobacco Addiction • July 25-28, 2004: Summer Meeting, Harrogate International Centre The annual meeting contains an excellent programme of invited symposia, short For information: orals, poster presentations and satellite symposia. The 2004 Guest Lecture will be ECNP-Office presented by Professor Pierre Blier, University of Ottawa PO Box 85410 3508 AK Utrecht The Netherlands • September 9, 2004: Refresher Course for Psychiatrists, London phone: +31 30 253 8567 Launched in March 2004, the Refresher Course includes updates of the treatment 8th ECNP REGIONAL MEETING fax: +31 30 253 8568 April 14 - 16, 2005 and management of depression, anxiety, schizophrenia and bipolar disorder, with Moscow, Russia e-mail: [email protected] First announcement emphasis on pharmacological aspects. The programme is compiled for those who website:www.ecnp.nl have an understanding of the pharmacology of the drugs and disorders reviewed, to allow maximum time for questions and discussion during the day.

• September 10, 2004: Psychopharmacology Course for Psychiatrists in Russian Scientific Society of Pharmacology Training, London th This one-day course in Psychopharmacology and Basic Neuroscience focusses • April 14 -16, 2005: 8 ECNP Regional Meeting, Moscow specifically on aiding preparation for the MRCPsych Part 1 and Part 2 examinations. • October 2005: XIth International Summer School on Behavioural Neuro- • October 1-2, 2004: Affective Disorders, Newcastle genetics, Suzdal A core module within the BAP Clinical Certificate in Psychopharmacology Course For more information: Elena Valdman: [email protected] • December 3-4, 2004: Old Age Psychiatry, Manchester A specialist module within the BAP Clinical Certificate in Psychopharmacology Course Swiss Society of Biological Psychiatry

• January 21-22, 2005: Anxiety Disorders, Bristol • October 21 -24, 2004: 6. Dreiländer-Symposium für Biologische Psychia- A core module within the BAP Clinical Certificate in Psychopharmacology Course trie, Bern

For more information: [email protected] or [email protected] For more information: www.ssbp.ch/dreilaender

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