Table Of ContentAdvances in Biological Psychiatry
Editors: W.P. Kaschka, W.F. Gattaz
Vol. 30
Biological Aspects
of Suicidal Behavior
Editors
W.P. Kaschka
D. Rujescu
Biological Aspects of Suicidal Behavior
Advances in Biological Psychiatry
Vol. 30
Series Editors
W.P. Kaschka
Ulm/Ravensburg
W.F. Gattaz
São Paulo
Biological Aspects of
Suicidal Behavior
Volume Editors
W.P. Kaschka
Ulm/Ravensburg
D. Rujescu
Halle
4 figures, 4 in color, and 6 tables, 2016
Basel · Freiburg · Paris · London · New York · Chennai · New Delhi ·
Bangkok · Beijing · Shanghai · Tokyo · Kuala Lumpur · Singapore · Sydney
Advances in Biological Psychiatry
Prof. Dr. Wolfgang P. Kaschka Prof. Dr. Dan Rujescu
Department of Psychiatry I Klinik und Poliklinik für Psychiatrie,
University of Ulm Psychotherapie und Psychosomatik
ZfP Südwürttemberg der Martin-Luther Universität
Weingartshofer Strasse 2 Halle-Wittenberg
DE–88190 Ravensburg (Germany) Julius-Kühn-Strasse 7
DE–06112 Halle/Saale (Germany)
Library of Congress Cataloging-in-Publication Data
Biological aspects of suicidal behavior / volume editors, W.P. Kaschka, D.
Rujescu.
p. ; cm. -- (Advances in biological psychiatry, ISSN 0378-7354 ;
vol. 30)
Includes bibliographical references and index.
ISBN 978-3-318-05583-2 (hard cover : alk. paper) -- ISBN 978-3-318-05584-9
(electronic version)
I. Kaschka, Wolfgang P., editor. II. Rujescu, D. (Dan), editor. III.
Series: Advances in biological psychiatry ; v. 30. 0378-7354
[DNLM: 1. Depression--drug therapy. 2. Suicide--psychology. 3.
Adrenergic Neurons--physiology. 4. Mental Disorders--genetics. W1 AD44
v.30 2016 / WM 165]
RC569
362.28--dc23
2015032176
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents® and Index Medicus.
Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and
contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty,
endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the
editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products
referred to in the content or advertisements.
Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this
text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research,
changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader
is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and
precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by
any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and
retrieval system, without permission in writing from the publisher.
© Copyright 2016 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland)
www.karger.com
Printed in Germany on acid-free and non-aging paper (ISO9706) by Kraft Druck, Ettlingen
ISSN 0378–7354
e-ISSN 1662–2774
ISBN 978–3–318–05583–2
e-ISBN 978–3–318–05584–9
Contents
VII Preface
Kaschka, W.P. (Ulm/Ravensburg); Rujescu, D. (Halle)
Epidemiology
1 Global Suicide
Värnik, P. (Tallinn); Wasserman, D. (Stockholm/Strasbourg)
Neurotransmitters
11 Suicidal Ideation, Suicide Attempts and Completed Suicide in Adolescents:
Neurobiological Aspects
Sarchiapone, M.; D’Aulerio, M.; Iosue, M. (Campobasso)
21 Serotonergic and Noradrenergic Neurotransmitter Systems in Suicide
Dwivedi, Y. (Birmingham, Ala.)
37 GABA, Depression and Suicide
Pabba, M.; Sibille, E. (Toronto, Ont.)
Genetics
51 Genetics of Suicidal Behavior
Giegling, I.; Rujescu, D. (Halle)
63 Gene-Environment Interaction Studies in Suicidal Behaviour
Mandelli, L.; Serretti, A. (Bologna)
75 Epigenetics of Suicidal Behaviour
Turecki, G. (Montreal, Que.)
N europsychology/Physiology/Imaging
88 Neurocognitive Processes and Decision Making in Suicidal Behaviour
Richard-Devantoy, S. (Montreal, Que./Angers); Courtet, P. (Montpellier/Créteil)
101 Electroencephalographic Risk Markers of Suicidal Behaviour
Hodgkinson, S.; Steyer, J.; Kaschka, W.P. (Ulm/Ravensburg); Jandl, M. (Bern)
110 Neuroimaging of Suicidal Behavior
Jollant, F. (Montreal, Que./Nîmes)
V
Immunology
123 Inflammation and Suicidal Behavior
Postolache, T.T. (Baltimore, Md./Denver, Colo.); Manalai, P. (Washington, D.C.);
Brenner, L.A. (Aurora, Colo.); Brundin, L. (Grand Rapids, Mich.)
Treatment
145 The Contributions of Lithium and Clozapine for the Prophylaxis and Treatment
of Suicidal Behavior
Müller-Oerlinghausen, B. (Berlin); Lewitzka, U. (Dresden)
Outlook
161 Challenges for Future Research and Closing Remarks
Rujescu, D. (Halle); Kaschka, I.N. (Erlangen); Kaschka, W.P. (Ulm/Ravensburg)
164 Author Index
165 Subject Index
VI Contents
Preface
According to a definition of the Institute of Medicine of the National Academies of
the USA [1] , suicide is ‘a fatal self-inflicted destructive act with explicit or inferred
intent to die’. Globally, year by year, approximately one million people die by suicide,
which corresponds to a rate of 16 per 100,000. In the year 2012, suicide accounted for
1.4% of all deaths worldwide, making it the fifteenth leading cause of death through-
out the lifespan and the second leading cause of death among 15- to 29-year-olds [2] .
In Germany, the suicide rate as of 2013 is almost twice as high as the death rate from
traffic accidents [3] . Therefore, effective and evidence-based interventions should be
implemented at population, subpopulation, and individual levels to prevent suicides
and suicide attempts. However, the reliable assessment of suicide risk in an individu-
al person is a major scientific challenge. Although apparently relevant, psychological,
psychosocial, and cultural factors offer merely weak predictive power with regard to
suicidal behaviour, and even the clinical history of a patient, though extremely valu-
able, can be non-specific. It is generally accepted that mental disorders per se repre-
sent a risk factor for suicidal behaviour, but there appear to exist other causative fac-
tors – environmental as well as dispositional – which are independent of psychiatric
diseases. During recent years, an increasing amount of research has been dedicated
to the analysis of the neurobiological basis of suicide, enabling the development of
neuro-psycho-biological models which may help to improve our understanding of
this complex behaviour. This book provides a comprehensive overview on the epide-
miological, neurobiological, and psychopharmacological aspects of suicide and sui-
cide attempts throughout the lifespan.
Värnik and Wasserman present a meticulous review of the worldwide epidemiol-
ogy of completed and attempted suicide. Mainly based on data from the World Health
Organization, they draw our attention to the broad spectrum of factors influencing
suicide rates, among which age and gender are only the most prominent ones. In ad-
dition, among others, societal, cultural, socioeconomic, and geographic effects have
been identified. Methodological problems involved in the recording of suicide and
attempted suicide rates are also discussed.
The important issue of suicidal ideation, suicide attempts, and completed suicide
in adolescents is dealt with in the chapter by Sarchiapone, D’Aulerio and Iosue, with
VII
special emphasis on neurobiological aspects. The authors review alterations in major
neurotransmitter and signalling systems found to be related to suicidal behaviour.
Most interestingly, different results have been obtained in a number of parameters
when groups of adolescents and adults were compared. In many cases, the biological
significance of these differences has yet to be revealed.
A great number of clinical as well as post-mortem brain studies have shown neu-
robiological abnormalities associated with suicidal behaviour. Many of these were
pointed out to be related to the serotonergic and noradrenergic neurotransmitter sys-
tems. The role of these systems, their intracellular signalling pathways and down-
stream effector molecules and their effects on the regulation of target genes in sui-
cidal behaviour are discussed in the chapter by Dwivedi.
Among neurotransmitter systems, special attention has focused on the role of
GABA in depression and suicide. Pabba and Sibille review the current evidence –
mainly from post-mortem studies – suggesting a dysfunction of GABAergic systems
in suicide victims having suffered from major depressive disorder (MDD-related sui-
cides) compared to those not having suffered from major depression (MDD-unrelat-
ed suicides).
Giegling and Rujescu focus on the genetic part of suicidal behaviour. Beside medical,
psychological, psychosocial, social, cultural, and socioeconomic parameters, biological
factors, especially genetic variants, were also shown to be risk factors for suicidal behav-
iour. The heritability is about 55% assuming a polygenic risk model. The chapter gives
an overview on first-candidate gene studies focusing mainly on the serotonergic sys-
tem. Additionally, newly started genome-wide association studies are discussed.
The relative contributions of heritable versus environmental risk factors to sui-
cidal behaviour have become a more and more challenging question. In their chapter,
Mandelli and Serretti provide a comprehensive overview on studies regarding the
interaction between genes modulating brain functions and stressful life events in the
aetiology of suicide.
A great number of studies have confirmed an association between early-life adver-
sity and increased suicide risk. Turecki describes how epigenetic mechanisms in-
duced by early-life adversity are able to mediate altered behavioural development,
resulting in increased vulnerability toward psychopathology in general and suicidal
behaviour in particular.
In an analysis of what might predispose individuals to make a suicide attempt or
completed suicide, neurocognitive processes appear to play a crucial role. Richard-
Devantoy and Courtet review evidence from the current literature showing that, in
addition to impulsive aggression and persistent hopelessness, impairments in cogni-
tive domains may increase the vulnerability to suicidal behaviour.
Clinical electrophysiology, although mostly neglected in earlier reviews, has also
contributed to our knowledge on the neurobiological basis of suicide. For example, it
was shown that the habituation of P300, an event-related potential, differed between
patients with MDD and a history of suicidal behaviour and MDD patients without
VIII Kaschka · Rujescu
such a history. Hodgkinson, Steyer, Kaschka, and Jandl summarize recent electro-
physiological studies and discuss their implications for suicide risk assessment and
suicide prophylaxis.
The rapid development of neuroimaging techniques during the last decades has
provided us with tools that allow the investigation of suicidal behaviour in vivo. Re-
sults obtained using the different methods of structural and functional neuroimaging
are reviewed by Jollant. Derived from the data presented in the context of the current
literature, the author proposes a neurocognitive model of suicidal behaviour which
could stimulate the development of interventions for the prevention of suicide.
In recent years, evidence has accumulated indicating that inflammatory processes
and alterations within the immune system may contribute to the pathophysiology not
only of depression but also of suicidal behaviour. Postolache, Manalai, Brenner, and
Brundin give a comprehensive overview of the available data and delineate novel
strategies of intervention, targeting immune dysregulation and aiming at the im-
provement of suicide risk assessment and suicide prevention.
The topic of pharmacological influences on suicidal ideation and behaviour is ad-
dressed by Müller-Oerlinghausen and Lewitzka. Whereas a large variety of pharmaco-
logically different compounds is able to induce depressive states, suicidal ideation and
suicidal behaviour, pharmaceutical agents that effectively counteract suicidality are
surprisingly rare. Over the years, satisfactory evidence of an antisuicidal efficacy has
been presented for lithium salts and clozapine only. The authors provide a comprehen-
sive review of the literature, also covering the question of possible mechanisms of ac-
tion. As for lithium, in addition to studies based on the use of lithium salts as pharma-
ceutical drugs, some studies have been published on the potential antisuicidal effects of
lithium as a trace element in drinking water. These are also critically discussed.
Rujescu, Kaschka and Kaschka outline possible further directions of research
which might be promising to improve our understanding of the neurobiological foun-
dations of suicidal behaviour. It is suggested that biological parameters should be in-
tegrated into algorithms for the assessment of suicide risk in individual persons.
Thereby, neurobiological research can be expected to make a significant contribution
to personalized medicine in general and to suicide prevention in particular.
Wolfgang P. Kaschka, Ulm/Ravensburg
Dan Rujescu, Halle
References
1 The Institute of Medicine of the National Acade- 3 Statistisches Bundesamt: Todesursachenstatistik.
mies of the USA. http://www.nap.edu/author/IOM/ http://www.gbe-bund.de (Suizid-Tabellen-Sterbe-
institute-of-medicine (accessed March 10, 2015). fälle; accessed March 10, 2015).
2 World Health Organization: Suicide Prevention
(SUPRE). http://www.who.int/mental_health/
prevention/suicide/suicideprevent/en/ (accessed
March 10, 2015).
Preface IX
