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Subcortical functioning in obsessive-compulsive disorder: An exploratory EEG coherence study

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Subcortical functioning in obsessive-compulsive disorder: An exploratory EEG coherence study
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  The World Journal of Biological Psychiatry VOLUME 8 Number 3, 2007  T  h  e W o r  l   d  J   o u r  n a l   o f   B  i   o l   o  g i   c  a l   P  s   y c  h  i   a t   r   y V o l   u m e 8  N u m b  e r  3  2  0  0  7  P  a  g e s  1  3  7 – 2  0  8  The Official Journal of the World Federation of Societies of Biological Psychiatry www.tandf.no/wjbpISSN 1562–2975 SWBP_8_3_cover.qxp 7/10/07 7:50 AM Page 1  Founding Editors Hans-Jürgen Möller ( Germany )Carlos Roberto Hojaij (  Australia ) Joseph Zohar ( Israel ) Chief Editor Hans-Jürgen MöllerDepartment of PsychiatryLudwig-Maximilians-UniversityNussbaumstrasse 780336 MunichGermanyTel: + 49 89 5160 5501Fax: + 49 89 5160 5522E-mail:hans-juergen.moeller@med.uni-muenchen.de Assistant Chief Editor Rainer RupprechtDepartment of PsychiatryLudwig-Maximilians-UniversityNussbaumstrasse 780336 MunichGermanyTel: + 49 89 5160 2770Fax: + 49 89 5160 5524E-mail: rainer.rupprecht@med.uni-muenchen.de Associate Editors Carlos Roberto HojaijThe Melbourne Institute of BiologicalPsychiatry511 Whitehorse RoadSurrey Hills 3127MelbourneAustraliaTel: + 61 3 9836 0088Fax: + 61 3 9836 0644 Joseph ZoharChaim Sheba Medical CenterDivision of PsychiatryTel-Hashomer, 52621IsraelTel: + 972 3 530 3300Fax: + 972 3 535 2788 Editorial Board Hagop Akiskal ( USA )Michael Bauer ( Germany )Robert H. Belmaker ( Israel )Graham Burrows (  Australia )Arvid Carlsson ( Sweden )Giovanni B Cassano ( Italy )Marcelo Cetkovich-Bakmas (  Argentina )Delcir da Costa ( Brazil )Frederick Goodwin ( USA ) Jose Luis Ayuso Gutierrez ( Spain )Ralf PHemmingsen ( Denmark  )Eric Hollander ( USA )Florian Holsboer ( Germany )Lewis LJudd ( USA )Nobumasa Kato (  Japan )Martin B Keller ( USA )Yves Lecrubier ( France )Brian Leonard ( Ireland )Odd Lingjaerde ( Norway ) Henri Loo ( France ) Juan J Lopez-Ibor ( Spain )Mario Maj ( Italy )Herbert YMeltzer ( USA ) Julien Mendlewicz ( Belgium )Stuart Montgomery ( UK  )David Nutt ( UK  )Tatsuro Ohta (  Japan )Ahmed Okasha ( Egypt )Antonio Pacheco Palha ( Portugal )Stanislaw Puzynski ( Poland )Giorgio Racagni ( Italy )Americo Reyes-Tucas (  Honduras )Philippe H Robert ( France )Bernd Saletu (  Austria )Norman Sartorius ( Switzerland ) Jan Sikora ( Czech Republic )Hernan Silva-Ibarra ( Chile )Constantin Soldatos ( Greece )Costas Stefanis ( Greece )Dan J Stein ( South Africa )Saburo Takahashi (  Japan )Marcio Versiani ( Brazil ) Jerzy Vetulani ( Poland )Daniel Weinberger ( USA ) Regional EditorsAfrica Driss Moussaoui (  Morocco ) Asia Takuya Kojima (  Japan ) Europe Birte Glenthøj ( Denmark  )Siegfried Kasper (  Austria ) Latin-America Wagner Gattaz ( Brazil ) North America Charles Nemeroff ( USA )Owen M. Wolkowitz ( USA ) Editorial Assistant  Jacqueline KlesingDepartment of PsychiatryLudwig-Maximilians-UniversityNussbaumstrasse 780336 MunichGermanyTel: + 49 89 5160 5531Fax: + 49 89 5160 5530E-mail:  jacqueline.klesing@med.uni-muenchen.de Publisher Taylor & FrancisBox 12 PosthusetBiskop Gunnerusgt. 14ANO-0051 OsloNorwayTel: +47 23 10 34 60Fax: +47 23 10 34 61E-mail: post@tandf.no Printers Typeset by Datapage International Ltd., Dublin,IrelandPrinted by Hobbs the Printers, Hampshire, UK The World Journal of Biological Psychiatry is one of the numerous benefits available to World Federation of Societies of Biological Psychiatry registered members, to whom the journal is sent free of charge and isaccessible on-line in the members only section of the Federation’s website www.wfsbp.org. Please contact the WFSBPGlobal Headquartersat info@wfsbp.org for more information. Subscription Information The World Journal of Biological Psychiatry, ISSN print edition 1562-2975, online edition 1814-1412, is published four times a year.Visit our webpage for more information: www.tandf.no/wjbpAnnual subscription rates for volume 8, 2007: Institutions (print &online): $360, institutions (online only): $342, individuals (print &online) $150. Air speed postage included. Supplements are suppliedfree of charge to all subscribers. Orders for subscription, back issues and change of address should be sent to: Taylor & Francis Customer Services, T&F InformaUK Ltd, Sheepen Place, Colchester, Essex CO3 3LP, UnitedKingdom. Tel: +44 (0) 20 7017 5544. Fax: +44 (0) 20 7017 5198. E-mail:tf.enquiries@tfinforma.comTaylor & Francis retains a three year back issue stock of journals. Older volumes are held by our official stockists: Periodicals ServiceCompany (http://www.periodicals.com/tandf.html) 11 MainStreet, Germantown, NY12526, USA, to whom all orders andenquiries should be addressed. Tel:  1 518 537 4700. Fax:  1 518 5375899. E-mail: psc@periodicals.comCorrespondence concerning publishing matters, copyright, permissions and reprints should be addressed to: Taylor & Francis,PO Box 12 Posthuset, NO-0051 Oslo, Norway. Tel:  47 23 10 34 60.Fax:  47 23 10 34 61. E-mail: post@tandf.no The World Journal of Biological Psychiatry (USPS permit pending) is published in March, May, August and November. The 2007 institutional subscription price is $360. Application to mail atperiodicals postage rate is pending at Jamaica, NYby US MailingAgent Air Business Ltd. c/o Priority Airfreight NYLtd. 147-29182nd Street, Jamaica, NY11413, USA. USPostmaster: Please send address changes to sWBP, Air BusinessLtd. c/o Priority Airfreight NYLtd. 147-29 182nd Street, Jamaica,NY11413, USA.Copyright © 2007 Taylor & FrancisAll articles are protected by copyright, which covers exclusiverights to reproduce and distribute the article. No material in this journal may be reproduced photographically or stored on micro-film, in electronic databases, video or compact disks etc. withoutprior written permission from Taylor & Francis. Special regula-tions for photocopies in the USA: Authorization to photocopyitems for internal or personal use, or the internal or personal useof specific clients, is granted by Taylor & Francis for libraries andother users registered with the Copyright Clearance Center(CCC), Transactional Reporting Service, provided the fee of $32per article is article paid to CCC, 222 Rosewood Drive, Danvers,MA01923, USA. This authorization does not include copying forgeneral distribution, promotion, new works, or resale. In thesecases, specific written permission must be obtained from Taylor &Francis. Indexed in: Index Medicus/MEDLINE, Science Citation Index Expanded, ISIAlerting Services, Current Contents/Clinical Medicine, CurrentContents/Life Sciences, NeuroScience Citation Index Impact Factor: 2.800 (Source: 2005 JCR Science Edition) The World Journal of Biological Psychiatry The World Journal of Biological Psychiatry Instructions to Authors The aim of   The World Journal of Biological Psychiatry  is to increase theworldwide communication of knowledge in clinical and basic research onbiological psychiatry. The composition of   The World Journal of Biological Psychiatry , with its diverse categories that allow communication of a greatvariety of information, ensures that it is of interest to a wide range of readers. It offers the opportunity to educate (through critical reviewpapers), to publish srcinal work and observations (srcinal papers andcase reports), and to express personal opinions (Viewpoints/Letters to theEditor).  The World Journal of Biological Psychiatry  is thus an extremelyimportant medium in the field of biological psychiatry all over the world.Manuscripts must be written in standard and grammatical English andshould present new results as well as be of scientific value. Contributionswill be considered for the following categories: /   Editorial /   Reviews/Mini-reviews /   Original investigations/Summaries of srcinal research /   Brief reports /   Viewpoints /   Case reports/Case series /   Letters to the editors /   Book reviews /   Invitations/AnnouncementsThe World Journal of Biological Psychiatry’s Manuscript Central, web-based manuscript submission and handling system, is now available. Please submit all manuscripts online via the Journal’s ManuscriptCentral site that is accessible via the Journal’s home page:www.tandf.no/wjbp Click on ‘‘online submission’’ which directs you to Manuscript Central’slog in page. Here either create an account or enter an existing account tolog in to your ‘‘author centre’’ to upload manuscripts.If you have difficulties in submitting your manuscript electronically, contactThe World Journal of Biological Psychiatry’s Editorial Office.The receipt of the manuscript will be acknowledged by an e-mail whichincludes a manuscript ID number. Each manuscript will be assigned to atleast two reviewers. The manuscript ID number should be quoted in allcorrespondence with the Chief Editor and Editorial Office.Submit manuscript text as a Word file and Figures as separate TIFF or EPSformat files. Use Times New Roman 12 point and double spacingthroughout the manuscript. Use a clear system of headings to divide upand clarify the text, with not more than three grades of headings. Thedesired position of figures and tables should be indicated in the manuscript.Submission of a manuscript implies: that the work described has not beenpublished before (except in the form of an abstract or as part of a publishedlecture, review or thesis); that it is not under consideration for publicationanywhere else; that its publication has been approved by all co-authors, if any, as well as by responsible authorities     tacitly or explicitly     at theinstitute where the work has been carried out.Manuscripts submitted for publication must contain a statement to theeffect that all human studies have been approved by the appropriate ethicscommittee and have therefore been performed in accordance with theethical standards laid down in the 1964 Declaration of Helsinki. It shouldalso be stated clearly in the text that all persons gave their informed consentprior to their inclusion in the study. Details that might disclose the identityof the subjects under study should be omitted.Reports of animal experiments must state that the  Principles of laboratoryanimal care  (NIH publication No. 86-23, revised 1985) were followed, aswell as specific national laws (e.g., the current version of the German Lawon the Protection of Animals) where applicable.The editors reserve the right to reject manuscripts that do not comply withthe above-mentioned requirements. The author will be held responsible forfalse statements or for failure to fulfill the above-mentioned requirements.  Manuscript specifications 1. The manuscript text file shall contain a title page. On the title page thefollowing shall be stated: The title of the article, which should beconcise but informative. A short title not exceeding 40 letters andspaces. The full names, affiliations and addresses of all the contribu-tors, and e-mail address, telephone number and fax number for thecorresponding author. The title page should also include details of thenumber of words, figures, and tables.2. Each article must include a short Abstract of the essential results (notexceeding 200 words).3. Key words. Up to five key words should be inserted below the abstract.Use terms from the Medical Subject Headings list from  Index Medicus. 4. References. All references cited in the text are to be listed (double-spaced) at the end of the paper in alphabetical order under the name of the first author. If there are more than six authors, list the first sixauthors and use ‘et al.’ Articles ‘in press’ may be included, but muststate the journal that has accepted them. Personal communicationsshould be avoided. Journal titles should be abbreviated according to Index Medicus. Citations in the text should be by author and date in parentheses. 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All tables should include a brief descriptivecaption.6. Figures. All illustrations, whether photographs, graphs or diagrams,should be numbered consecutively with Arabic numerals and sub-mitted on separate sheets. Each illustration should be referred to in thetext as ‘Figure 1’, ‘Figures 1    4’, etc. The figures should have a shorttitle followed by a concise description. All abbreviations and symbolsappearing in the figure must be explained in the legend. Remarks suchas ‘for explanation (or details) see text’ should be avoided. Each figureshould have a legend containing sufficient information to render thefigure intelligible without reference to the text. If a figure has beenpublished previously, acknowledge the srcinal source and submitwritten permission from the copyright holder to reproduce it. If photographs of persons are used, either the subjects must not beidentifiable or their written permission to use the photographs mustaccompany the manuscript. Figures can be sent electronically asseparate files in EPS or TIFF format.7. Copyright. It is a condition of publication that authors vest copyrightin their articles, including abstracts, in Taylor & Francis GroupLtd. This enables us to ensure full copyright protection and todisseminate the article, and the journal, to the widest possiblereadership in print and electronic formats as appropriate. Authorsmay, of course, use the material elsewhere after publication providingthat prior permission is obtained from Taylor & Francis GroupLtd. Authors are themselves responsible for obtaining permission toreproduce copyright material from other sources. To view the ‘Copy-right Transfer Frequently Asked Questions’ please visit http://www.tandf.co.uk/joumals/copyright.asp8. Proofs and offprints. Proofs will be sent as a PDF file to thecorresponding author’s e-mail address unless otherwise requested.The corrected proof must be returned to the publisher within 3 days.Authors will be liable to pay for excessive alterations in the proof.Offprints can be ordered by filling out the form accompanying theproofs. The corresponding authors will be supplied with a free copy of the relevant issue.9. For further information about the journal, including links to the onlinesample copy and contents pages, visit the journal homepage:www.tandf.no/wjbp or contact the Editorial Office at the followingaddress: Jacqueline Klesing, Editorial Assistant, Department of Psychiatry,Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich,Germany. Tel: +49 89 5160 5531 Fax: +49 89 5160 5530. E-mail:jacqueline.klesing@med.uni-muenchen.de SWBP_8_3_cover.qxp 7/9/07 8:59 AM Page 2  Editorial Do effectiveness studies tell us the real truth? Hans-Ju¨rgen Mo¨ller  ................................................................................................................................ 138 Reviews Consensus paper of the WFSBP Task Force on Biological Markers: Biological Markersin Depression Rainald Mo¨ssner, Olya Mikova, Eleni Koutsilieri, Mohamed Saoud, Ann-Christine Ehlis,Norbert Mu¨ller, Andreas J. Fallgatter, Peter Riederer  ........................................................................ 141 Meta-analysis of randomized controlled comparisons of psychopharmacological andpsychological treatments for anxiety disorders Borwin Bandelow, Ulrich Seidler-Brandler, Andreas Becker, Dirk Wedekind, Eckart Ru¨ ther  ............... 175 Original Investigation Association study of the norepinephrine transporter gene polymorphisms and bipolardisorder in Han Chinese population Chuan-Chia Chang, Ru-Band Lu, Kuo-Hsing Ma, Hsin-An Chang, Chih-Lun Chen,Cheng-Chang Huang, Wei-Wen Lin, San-Yuan Huang  ...................................................................... 188 Brief Report Subcortical functioning in obsessive-compulsive disorder: An exploratory EEG coherence study Pushpal Desarkar, Vinod Kumar Sinha, Karuppiah Jagadheesan, Shamshul Haque Nizamie  ............. 196 Case Report Chain reaction or time bomb: A neuropsychiatric-developmental/neurodevelopmentalformulation of tourettisms, pervasive developmental disorder, and schizophreniformsymptomatology associated with PANDAS  Jacob Kerbeshian, Larry Burd, Alison Tait  ............................................................................................. 201 The World Journal of Biological Psychiatry Volume 8, No 3, 2007 Contents  EDITORIAL Do effectiveness studies tell us the real truth? What are effectiveness studies? ‘Effectiveness studiesare intended to fill the gap between methodologicallyrigorous RCTs (randomized clinical trials) andnaturalistic observational studies. As such, theyare hybrids of RCTs and naturalistic or quasi-experimental designs and are termed ‘practicalclinical trials’ (Tunis et al. 2003). They are inten-tionally designed to evaluate the effectiveness of thetreatments under real-world conditions and in re-presentative patient samples’ (Lieberman 2006,p. 1070).The actual advantage of these ‘effectiveness’studies, which are often very costly to perform,remains questionable. Do they do justice to theirclaim of treating less selective samples of patientsthan phase III studies? At least some of them give theimpression that they also included a very selectiveclientele. For example, a study on the effectivenessof adjunctive antidepressant treatment in bipolardisorder (Sachs et al. 2007), the Systematic Treat-ment Enhancement Program for Bipolar Disorder(STEP-BD), enrolled only 366 of the 4360 patientsinitially screened (only 2689 of the 4360 patientshad at least one major depressive episode, and 2323of these patients were then ineligible or declined toparticipate). The situation was similar in the study of the effectiveness of olanzapine and haloperidol in thetreatment of schizophrenia (Rosenheck et al. 2003):of the 4386 patients assessed for eligibility, only 309were randomized (7.0%). This rate is even some-what lower than the usual rate of 10    15% in phaseIII studies (Hofer et al. 2000). Thus, effectivenessstudies appear also to have a considerable degree of selection of patients, although the selection may beof a different kind than in phase III trials. Often,patients with milder and more chronic symptomsmay be selected than is the case in phase III studies,thus making it more difficult  per se  to demonstratedrug effects and particularly differences betweeneffects of drugs because a relevant subgroup of patients might be partially unresponsive to drugeffects. Furthermore, in contrast to phase III studies,the ‘real world’ approach allows comorbidity, come-dication (also to a greater degree), etc., so that abroader range of information may be obtained thanfrom phase III studies. However, this results in areduced signal-to-noise ratio and increases the riskof beta error, again making it more difficult to finddifferences between two groups, even if these factorsare adequately considered in the statistical analysis.In order to demonstrate some of the problems of such studies, the Cost Utility of the Latest Anti-psychotic Drugs in Schizophrenia Study (CUtLASSI), an effectiveness study performed in the UK (Jones et al. 2006), will be discussed here. Patients(  N   227) were enrolled who required a change intreatment because of inadequate response to theircurrent treatment or adverse effects, and wererandomly prescribed either FGAs or SGAs (otherthan clozapine), with the choice of individual drugmade by the managing psychiatrist. The sample wascharacterized by symptomatically stabilized, rela-tively chronic, partially non-responsive patients of community psychiatric services with a mean illnessduration of   14 years. The reasons for referral wereas follows: inadequate drug response to pretreatmentalone in 44% (FGA arm) and 54% (SGA arm) of patients; adverse effects alone in 30% (FGA arm)and 12% (SGA arm); presence of both reasons in26% (FGA arm) and 34% (SGA arm).Beside testing the hypothesis that SGAs areassociated with improved quality of life across oneyear compared with FGAs, main outcome measureswere symptoms, adverse effects, participant satisfac-tion and costs of care. The study found no advantageof SGAs over FGAs on Quality of Life Scale scoresor discontinuation rates; costs were similar. After 52weeks, the average pre-post difference in scores onthe PANSS positive subscale was   2 points in theFGA arm and  1.5 points in the SGA arm; changesin the PANSS negative subscale were also small:  3.3 in the FGA arm and   1.8 in the SGA arm.The authors concluded that in people with schizo-phrenia whose medication is changed for clinicalreasons, there is no disadvantage across one year interms of quality of life, symptoms or associated costsof care in using FGAs rather than non-clozapineSGAs. According to the authors, neither inadequatepower nor patterns of drug discontinuation ac-counted for the result (Jones et al. 2006).Many features of CUtLASS 1 are open to criti-cism. The sample size was too small (  N   227randomized;  N   185 after one year) to allow com-parison of active drug regimes (beta-error problem The World Journal of Biological Psychiatry , 2007; 8(3): 138    140 ISSN 1562-2975 print/ISSN 1814-1412 online # 2007 Taylor & FrancisDOI: 10.1080/15622970701534935  as the study was underpowered). The small changes(in a 1-year study!) in the symptom scales areindicative of a drug-insensitive sample, meaningthat a placebo control would have been necessaryto allow efficacy to be evaluated. Adjunctive medica-tion was allowed (although antipsychotic polyphar-macy was discouraged) but not taken into account inthe analysis as a possible confounder or consideredin the interpretation of the results. The main out-come criterion, quality of life, is not very sensitive tochange. Furthermore, so-called ‘blind assessments’are not equivalent to double-blind conditions: Thedoctor responsible for the patient’s care selected thedrug and patients were informed which drug theywere receiving; randomization was only used toassign patients to the FGA or SGA arm. The studythus compared the choice of any SGA to choice of any FGA and not specific agents. The selectionof drugs in the FGA arm was apparently biased: 58of 118 patients in the FGA arm (49%) receivedsulpiride. Of great interest in this context is that in2005, for example, the average defined daily dose(DDD) prescription rate for sulpiride in the UK was1.25% (IMS/Midas[Sergeant] database). Sulpirideis a low-potency FGA that is a more selective D2antagonist than haloperidol and has strong chemicalsimilarities to the SGA amisulpride.A commentary on the study claimed that some of its design features may be viewed as strengths: thenovel design is closer to ‘real-world practice’ thantypical monotherapy trials because treatments arealways unblinded and numerous drugs are availableinreal practice; althoughresearchershavefocused ondifferentiating the SGAs from one another, bothpractice guidelines and physician behaviour suggestthat they are treated as a class in clinical practicewhichjustifiesevaluatingthemasaclass,asisthecaseinCUtLASS1(Rosenheck2006).However,thelargerange of drugs in each treatment arm complicates theinterpretation of the results. It also makes it impos-sibletodrawanyconclusionsaboutcosteffectiveness,efficacy or side effects of a specific drug.CUtLASS applied arange of sophisticated analyticmethods, including multiple imputation to addressmissing data,andtestedminimallysignificant clinicaldifferences to properly support the conclusion that atleast in this study FGAs are not inferior to SGAs. Inhis commentary on the study, Rosenheck writes thatthese methods might represent an advance for thefield in contrast to the potentially biased analyticstrategies (most notably, use of last observationcarried forward) used in many earlier studies(Rosenheck 2006). However, on the other side, thisexcessive statistical computation of the data couldalso be seen as too far-reaching an abstraction fromreality.It can be seen as a serious limitation of the studythat only 59% of patients continued taking theirsrcinally assigned medication for the full year: 55patients in the FGA arm (46.6%) switched to SGA(whereby four switched back to FGA), and 36patients in the SGA arm (33%) switched to FGA(with one changing back to SGA). However, overalldifferences in completion rates taking the initialdrug were not significantly different between FGAsand SGAs, and a 12-week analysis of ‘on protocol’cases showed the same pattern of results as the trialoverall.The methodology of the largest Clinical Antipsy-chotic Trials of Intervention Effectiveness (CATIE)study (Lieberman et al. 2005), currently perhaps theforemost effectiveness study in the field of neurolep-tics, has also been subject to criticism (Mo¨ller 2005;Kasper and Winkler 2006; Ragins 2005; Delisi andNasrallah 2005). Interestingly, neither CATIE norCUtLASS 1 were funded by the pharmaceuticalindustry but by the public domain.Without going into further details of CATIE andother effectiveness studies in the field of neuroleptictreatment of schizophrenia, it can be summarisedthat several methodological pitfalls make it difficultto interpret their results. The findings of thesestudies definitely cannot form the basis for challen-ging the results of methodologically stricter phase IIIstudies. It can even be questioned whether theyreally do come closer to the real conditions of routine clinical care than acute and long-term phaseIII studies as they obviously also enrol a selectivegroup of patients, even though the selection para-meters are different. They therefore give a comple-mentary and not better picture of reality. Althoughthese studies are currently attracting a lot of atten-tion, we should not allow them to make us feelinsecure about earlier findings but should continueto consider the complete array of evidence and use itto guide an evidence-based approach to treatment.Hans-Ju¨rgen Mo¨llerDepartment of Psychiatry, Ludwig-Maximilians-University, Munich, Germany Correspondence: Prof. Dr. med. Hans-Ju¨rgen Mo¨llerChairman, Department of PsychiatryLudwig-Maximilians-UniversityNussbaumstr. 780336 MunichGermanyTel:  49 89 5160 5501Fax:  49 89 5160 5522E-mail:hans-juergen.moeller@med.uni-muenchen.de Editorial   139
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