Neurobiology of Depression 1st Edition
Visit the link below to download the full version of this book:
https://medipdf.com/product/neurobiology-of-depression-1st-edition/
Click Download Now
New Concepts in Cerebral Ischemia
Rick C. S. Lin, Ph.D., Professor of Anatomy, University of Mississippi Medical Center,
Jackson, Mississippi
DNA Arrays: Technologies and Experimental Strategies
Elena Grigorenko, Ph.D., Technology Development Group, Millennium Pharmaceuticals,
Cambridge, Massachusetts
Methods for Alcohol-Related Neuroscience Research
Yuan Liu, Ph.D., National Institute of Neurological Disorders and Stroke,
National Institutes of Health, Bethesda, Maryland
David M. Lovinger, Ph.D., Laboratory of Integrative Neuroscience, NIAAA,
Nashville, Tennessee
Primate Audition: Behavior and Neurobiology
Asif A. Ghazanfar, Ph.D., Princeton University, Princeton, New Jersey
Methods in Drug Abuse Research: Cellular and Circuit Level Analyses
Barry D. Waterhouse, Ph.D., MCP-Hahnemann University, Philadelphia, Pennsylvania
Functional and Neural Mechanisms of Interval Timing
Warren H. Meck, Ph.D., Professor of Psychology, Duke University, Durham, North Carolina
Biomedical Imaging in Experimental Neuroscience
Nick Van Bruggen, Ph.D., Department of Neuroscience Genentech, Inc.
Timothy P.L. Roberts, Ph.D., Associate Professor, University of Toronto, Canada
The Primate Visual System
John H. Kaas, Department of Psychology, Vanderbilt University, Nashville, Tennessee
Christine Collins, Department of Psychology, Vanderbilt University, Nashville, Tennessee
Neurosteroid Effects in the Central Nervous System
Sheryl S. Smith, Ph.D., Department of Physiology, SUNY Health Science Center,
Brooklyn, New York
Modern Neurosurgery: Clinical Translation of Neuroscience Advances
Dennis A. Turner, Department of Surgery, Division of Neurosurgery,
Duke University Medical Center, Durham, North Carolina
Sleep: Circuits and Functions
Pierre-Hervé Luppi, Université Claude Bernard, Lyon, France
Methods in Insect Sensory Neuroscience
Thomas A. Christensen, Arizona Research Laboratories, Division of Neurobiology,
University of Arizona, Tuscon, Arizona
Motor Cortex in Voluntary Movements
Alexa Riehle, INCM-CNRS, Marseille, France
Eilon Vaadia, The Hebrew University, Jerusalem, Israel
Neural Plasticity in Adult Somatic Sensory-Motor Systems
Ford F. Ebner, Vanderbilt University, Nashville, Tennessee
Advances in Vagal Afferent Neurobiology
Bradley J. Undem, Johns Hopkins Asthma Center, Baltimore, Maryland
Daniel Weinreich, University of Maryland, Baltimore, Maryland
The Dynamic Synapse: Molecular Methods in Ionotropic Receptor Biology
Josef T. Kittler, University College, London, England
Stephen J. Moss, University College, London, England
Animal Models of Cognitive Impairment
Edward D. Levin, Duke University Medical Center, Durham, North Carolina
Jerry J. Buccafusco, Medical College of Georgia, Augusta, Georgia
The Role of the Nucleus of the Solitary Tract in Gustatory Processing
Robert M. Bradley, University of Michigan, Ann Arbor, Michigan
Brain Aging: Models, Methods, and Mechanisms
David R. Riddle, Wake Forest University, Winston-Salem, North Carolina
Neural Plasticity and Memory: From Genes to Brain Imaging
Frederico Bermudez-Rattoni, National University of Mexico, Mexico City, Mexico
Serotonin Receptors in Neurobiology
Amitabha Chattopadhyay, Center for Cellular and Molecular Biology, Hyderabad, India
TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades
Wolfgang B. Liedtke, M.D., Ph.D., Duke University Medical Center, Durham, North Carolina
Stefan Heller, Ph.D., Stanford University School of Medicine, Stanford, California
Methods for Neural Ensemble Recordings, Second Edition
Miguel A.L. Nicolelis, M.D., Ph.D., Professor of Neurobiology and Biomedical Engineering,
Duke University Medical Center, Durham, North Carolina
Biology of the NMDA Receptor
Antonius M. VanDongen, Duke University Medical Center, Durham, North Carolina
Methods of Behavioral Analysis in Neuroscience
Jerry J. Buccafusco, Ph.D., Alzheimer’s Research Center, Professor of Pharmacology and Toxicology,
Professor of Psychiatry and Health Behavior, Medical College of Georgia,
Augusta, Georgia
In Vivo Optical Imaging of Brain Function, Second Edition
Ron Frostig, Ph.D., Professor, Department of Neurobiology, University of California,
Irvine, California
Fat Detection: Taste, Texture, and Post Ingestive Effects
Jean-Pierre Montmayeur, Ph.D., Centre National de la Recherche Scientifique, Dijon, France
Johannes le Coutre, Ph.D., Nestlé Research Center, Lausanne, Switzerland
The Neurobiology of Olfaction
Anna Menini, Ph.D., Neurobiology Sector International School for Advanced Studies, (S.I.S.S.A.),
Trieste, Italy
Neuroproteomics
Oscar Alzate, Ph.D., Department of Cell and Developmental Biology,
University of North Carolina, Chapel Hill, North Carolina
Translational Pain Research: From Mouse to Man
Lawrence Kruger, Ph.D., Department of Neurobiology, UCLA School of Medicine, Los Angeles,
California
Alan R. Light, Ph.D., Department of Anesthesiology, University of Utah, Salt Lake City, Utah
Advances in the Neuroscience of Addiction
Cynthia M. Kuhn, Duke University Medical Center, Durham, North Carolina
George F. Koob, The Scripps Research Institute, La Jolla, California
Neurobiology of Huntington’s Disease: Applications to Drug Discovery
Donald C. Lo, Duke University Medical Center, Durham, North Carolina
Robert E. Hughes, Buck Institute for Age Research, Novato, California
Neurobiology of Sensation and Reward
Jay A. Gottfried, Northwestern University, Chicago, Illinois
The Neural Bases of Multisensory Processes
Micah M. Murray, CIBM, Lausanne, Switzerland
Mark T. Wallace, Vanderbilt Brain Institute, Nashville, Tennessee
Neurobiology of Depression
Francisco López-Muñoz, University of Alcalá, Madrid, Spain
Cecilio Álamo, University of Alcalá, Madrid, Spain
NEUROBIOLOGY of DEPRESSION
Edited by
Francisco López-Muñoz
University of Alcalá
Spain
Cecilio Álamo
University of Alcalá
Spain
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2012 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Version Date: 20110722
International Standard Book Number-13: 978-1-4398-3850-1 (eBook - PDF)
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to
publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials
or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material repro-
duced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any
copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any
form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming,
and recording, or in any information storage or retrieval system, without written permission from the publishers.
For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copy-
right.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400.
CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been
granted a photocopy license by the CCC, a separate system of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identifica-
tion and explanation without intent to infringe.
Visit the Taylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
This page intentionally left blank.
This page intentionally left blank.
Contents
Series Preface.....................................................................................................................................xi
Foreword......................................................................................................................................... xiii
Introduction......................................................................................................................................xxi
Contributors...................................................................................................................................xxix
Chapter 1 Animal Models of Depression...................................................................................... 1
Damian Refojo and Jan M. Deussing
Chapter 2 Neurophysiological and Neuropsychological Models of Depression.......................... 27
Stephan Moratti, Alberto Fernández, and Gabriel Rubio
Chapter 3 Neural Foundations of Major Depression: Classical Approaches and
New Frontiers.............................................................................................................. 57
J. Paul Hamilton, Daniella J. Furman, and Ian H. Gotlib
Chapter 4 Genetic Regulation of Emotion Brain Circuitries....................................................... 75
Ulrich Rabl, Christian Scharinger, Tina Hofmaier, Michael Freissmuth, and
Lukas Pezawas
Chapter 5 Development of Brain Monoaminergic Systems........................................................97
Marten P. Smidt
Chapter 6 Contribution of Pharmacology to Development of Monoaminergic Hypotheses
of Depression............................................................................................................. 119
Francisco López-Muñoz and Cecilio Álamo
Chapter 7 Serotonergic Pathways in Depression....................................................................... 143
Stefanie C. Altieri, Yogesh S. Singh, Etienne Sibille, and Anne M. Andrews
Chapter 8 Noradrenergic System in Depression........................................................................ 171
J. Javier Meana, Luis F. Callado, and Jesús A. García-Sevilla
Chapter 9 Glutamatergic System and Mood Disorders............................................................. 185
Rodrigo Machado-Vieira and Carlos A. Zarate Jr.
Chapter 10 Role of the Endocannabinoid System in Etiopathology of Major Depression.......... 203
Ryan J. McLaughlin, Francis Rodriguez Bambico, and Gabriella Gobbi
xi
xii Contents
Chapter 11 Opioid System and Depression................................................................................. 223
Cristina Alba-Delgado, Pilar Sánchez-Blázquez, Esther Berrocoso,
Javier Garzón, and Juan Antonio Micó
Chapter 12 Chronobiological Rhythms, Melatonergic System, and Depression......................... 247
Cecilio Álamo and Francisco López-Muñoz
Chapter 13 Corticotropin-Releasing Factor and Hypothalamic–Pituitary–Adrenal Axis
Regulation of Behavioral Stress Response and Depression...................................... 275
Glenn R. Valdez
Chapter 14 Depression and Cytokine-Regulated Pathways........................................................ 293
Bernhard T. Baune
Chapter 15 Tachykinins and Tachykinin Receptor Antagonists in Depression: Therapeutic
Implications............................................................................................................... 317
Tih-Shih Lee and K. Ranga Krishnan
Chapter 16 Role of Neuropeptide Y in Depression: Current Status............................................ 325
Julio César Morales-Medina and Rémi Quirion
Chapter 17 Nitric Oxide Signaling in Depression and Antidepressant Action........................... 341
Gregers Wegener and Aleksander A. Mathé
Chapter 18 Beta-Arrestins in Depression: A Molecular Switch from Signal Desensitization
to Alternative Intracellular Adaptor Functions......................................................... 371
Sofia Avissar and Gabriel Schreiber
Chapter 19 Brain-Derived Neurotrophic Factor and Major Depression...................................... 391
Kazuko Sakata
Chapter 20 Role of Cyclic Nucleotide Phosphodiesterases in Depression and
Antidepressant Activity............................................................................................. 419
Ying Xu, Han-Ting Zhang, and James M. O’Donnell
Chapter 21 Vascular Depression: A Neuropsychological Perspective......................................... 445
Benjamin T. Mast, Brian P. Yochim, Jeremy S. Carmasin, and Sarah V. Rowe
Chapter 22 Neurobiological Basis for Development of New Antidepressant Agents.................. 455
Cecilio Álamo and Francisco López-Muñoz
Series Preface
The Frontiers in Neuroscience Series presents the insights of experts on emerging experimental
technologies and theoretical concepts that are, or will be, at the vanguard of Neuroscience.
The books cover new and exciting multidisciplinary areas of brain research, and describe break-
throughs in fields like visual, gustatory, auditory, olfactory neuroscience, as well as aging biomedi-
cal imaging. Recent books cover the rapidly evolving fields of multisensory processing, depression,
and different aspects of reward.
Each book is edited by experts and consists of chapters written by leaders in a particular field.
Books are richly illustrated and contain comprehensive bibliographies. Chapters provide substantial
background material relevant to the particular subject.
The goal is for these books to be the references every neuroscientist uses in order to acquaint
themselves with new information and methodologies in brain research. We view our task as series
editors to produce outstanding products that contribute to the broad field of Neuroscience. Now that
the chapters are available online, the effort put in by us, the publisher, the book editors, and indi-
vidual authors will contribute to the further development of brain research. To the extent that you
learn from these books we will have succeeded.
Sidney A. Simon, PhD
Miguel A.L. Nicolelis, MD, PhD
Series Editors
xiii
Foreword
Herman M. van Praag
BIOLOGICAL RESEARCH IN PSYCHIATRY; DIAGNOSIS
AS THE RATE-LIMITING FACTOR
1 A Paradigm Shift in Body/Soul Research
In the early days of biological psychiatric research, iproniazid has been a prime mover. This drug
was a close relative of isoniazid, a compound discovered in the early 1950s as a tuberculostatic.
Iproniazid was also tested in severely ill tubercular patients. Although it appeared to have only weak
effects on the tubercular process, it produced a remarkable symptomatic improvement. Appetite
and libido increased, patients became more active, and mood improved dramatically. The drug thus
seemed to possess antidepressant properties and was introduced as such in the late 1950s.
Iproniazid became the most remarkable psychotropic drug of its generation. Why? Because it was the
only one of which, at the time of its introduction, a modicum was known about its actions in the brain.
It had been demonstrated to be an inhibitor of monoamine oxidase (MAO), an enzyme involved in the
degradation of catecholamines and serotonin (5-hydroxytryptamine). Serotonin had just been discovered
as a compound occurring in blood platelets, the yellow cells of the gut, and in the brain, where it seemed
to serve as a neurotransmitter. Being a MAO inhibitor, iproniazid supposedly increased the availability
of monoamines in the brain. These observations raised three intriguing questions:
(1) Does iproniazid behave as a MAO inhibitor in humans too?
(2) Do MAO inhibition and antidepressant effect hang together?
(3) Is central monoamine functioning disturbed in depression, particularly in those patients
who show a favorable response to a MAO inhibitor?
The introduction of iproniazid was a truly revolutionary event. Up until then, the body–soul rela-
tionship was an exclusively philosophical issue. Now, for the first time ever, this most fundamental
enigma of the human existence had opened up to an experimental approach. This prospect I felt to
be truly exciting. From the very first day of my residency in psychiatry, April 1, 1958, I fell upon
the questions mentioned above. They would intrigue me for the rest of my life (see van Praag et al.
2004).
And it was not only me. For many years, monoamines played a major role in biological depres-
sion research. All our antidepressants so far are based on hypotheses assuming depression or certain
features of depression to be related to disturbances in the functioning of monoaminergic neuronal
systems. Monoamine research is still flourishing as far as depression is concerned. However, in
recent years, many other inroads into the biology of depression opened up and are being explored.
This book, edited by Professors Francisco López-Muñoz and Cecilio Álamo, attests to that. So far,
this research has not resulted in new therapeutic agents, but I am optimistic that eventually it will.
2 Roadblocks
However, we have to deal with a serious roadblock on the way ahead, that is, diagnosis. Biological
approaches into the brain became ever more sophisticated and refined. The other side of the
xv
xvi Foreword
coin—definition, classification, and measurement of abnormal behavior, in this case, depressive
behavior—lagged behind. There, stagnation is rife. For almost one and a half centuries now, we
have been the prisoners of a strictly categorical system, introduced by Kraepelin (Hoff 1995). This
system impedes progress in clarifying the biological determinants of abnormal behavior, as well as
the development of new, innovative drugs.
Kraepelin inaugurated a new diagnostic paradigm in the realm of mental disorders, that of the
nosological entity. Mental pathology, Kraepelin proposed, could be divided in discrete disorders,
with one distinguishable from the other. Each has its own symptomatology and course; each has its
own specific pathophysiology. Nosology, according to Kraepelin, should be the principal guideline
in exploring the biological roots of mental pathology.
And so it came to be. The influence of his ideas has been enormous until this very day. Most
biological psychiatric research is predicated upon the nosological presupposition and aspires to
elucidate the biological underpinnings of discrete disease “packages” as presently defined by the
Diagnostic and Statistical Manual of Mental Disorders (DSM) system, a classification system that
heavily leans on Kraepelinean ideas. This approach has not been productive. After half a century
of research, we cannot boast of much progress. Yes, knowledge of the functioning of the brain
advanced tremendously; insight in the pathophysiology of mental disorders, however, hardly did.
The reason for that, I think, is the diagnostic system in use. I will clarify my point of view, restrict-
ing myself to the construct of depression, as defined by the DSM system. The same reasoning holds,
however, for most diagnoses mentioned in the DSM. The following sections are in part adopted
from another paper (van Praag 2008).
The starting point of my reasoning is that refined diagnosing is the very bedrock of biological
psychiatry; it is the precise definition of the psychopathological construct the pathophysiology of
which one wants to elucidate. Hence, two questions have to be addressed. First, does the construct
major depression, as proposed by the DSM, meet that clarity criterion? Second, is nosology the
proper foundation for biological psychiatric research?
3 Clarity of the Major Depression Construct
Symptomatologically, mood lowering is the anchor symptom of major depression, but for the rest,
the symptoms vary considerably. In other words, the term major depression covers a variety of syn-
dromes. Moreover, these syndromes appear more often than not in conjunction with other mental
disorders, particularly with anxiety and personality disorders. Major depression without further
specification is a diagnosis as general and thus as vague as, for instance, that of anemia. It gives
some information about someone’s mental condition, but far too little.
Course and prognosis of this depression type are unpredictable. It may start rather suddenly,
sometimes even overnight, or gradually, in the course of weeks or months. It may last for a few days
up to many months or even years, recurring frequently, with large time intervals or (more seldom)
not at all. The symptoms of depression may be hardly noticeable to the outer world, may cripple the
patient both socially and professionally, or may even reach a psychotic degree. Recovery may be
full or partial—in which the patient remains hampered in his daily activities—or the disorder may
take a chronic course.
The premorbid personality structure and previous living circumstances may be clearly disturbed,
showing, for instance, considerable weaknesses in interpersonal skills and adaptability to changing
living conditions, or may be quite undisturbed, leaving relatives and friends of the patient wonder-
ing how on earth this person could become depressed.
The depression may follow psychotraumatic life events or may occur “out of the blue,” without
any discernable provocation.
A variety of neurobiological disturbances have been reported to occur in depression, most
prominently in the monoaminergic systems, the stress hormone system, and in the production of
some growth factors, such as brain-derived neurotrophic factor. For instance, the concentration
Foreword xvii
of 5-hydroxyindoleacetic acid in cerebrospinal fluid was found to be diminished, the density of
serotonin 5-HT1A receptors in the brain to be decreased, and the synthesis rate of serotonin to be
attenuated—all signs of disturbed serotonergic functioning in the brain (see van Praag et al. 2004).
These disturbances, however, are found in some depressive patients, not in all. Moreover, they are
not specific for depression, found as they are in other diagnostic categories as well.
Response to treatment, biological or psychological in nature, is hard to predict. Patients may
become symptom-free, show residual symptoms, or hardly respond if they do at all.
One can thus hardly avoid the conclusion that the precision and clarity of the diagnosis major
depression leave much to be desired and that the predictive validity of that construct is close to nil.
Studying the pathophysiology of a construct of such heterogeneity is bound to fail, and surely, it has
failed. We are, as said, not much closer to its biological roots than we were several decades ago. That
outcome was predictable. What would one expect from a research program into the pathophysiology
of, say, cardiac disorders? I presume little if anything. The diagnosis major depression I consider of
comparable exactitude. The chance that utterly heterogeneous psychopathological constructs will
be produced by well-defined brain disturbances is negligibly small.
These and similar observations convinced me that biological psychiatric research has been and
still is proceeding toward a dead end, a street called nosological alley. I feel, and have felt for most of
my professional life, that the diagnostic process in psychiatry should change directions, particularly
if the goal is to explore the biological underpinnings of mental pathology. Two strategies I proposed
should direct that effort. I have named them verticalization and functionalization (van Praag et al.
1987, 2004; van Praag 1997, 2000).
4 Functionalization of Psychiatric Diagnosis
The concept of functionalization implies that diagnosing in psychiatry should proceed stepwise.
First, the diagnostic grouping to which the disorder belongs should be determined; that is, a
categorical diagnosis should be made. For instance, the mental state in question is considered to
belong to the basin of depressive disorders. This first diagnostic step provides no more than a global
diagnostic indication. It is no more informative than the statement that a given person complaining
of pain in the chest is possibly suffering from a cardiac disorder. Diagnostic basins are by definition
heterogeneous.
Next, the syndrome is defined. This diagnostic information is also far from precise. Syndromes
often appear in incomplete form, and many patients suffer simultaneously from more than one
complete or incomplete syndrome.
Hence, a third diagnostic step seems to me crucial. It is one I have called functionalization of
diagnosis. Functionalization means defining first of all the psychopathological symptoms consti-
tuting the syndrome and next—most importantly—examining and if possible measuring the psy-
chic dysfunctions underlying the psychopathological symptoms. Psychopathological symptoms and
psychic dysfunctions are not synonyms. The psychopathological symptom is the way the psychic
dysfunction is experienced by the patient and observed by the investigator.
The last step I consider to be quintessential. If no methods are available to measure the assumed
psychic dysfunctions, they should be developed. Functionalization of psychiatric diagnosing, thus,
presupposes close collaboration between psychiatrists and experimental clinical psychologists.
Here are a few examples. In the case of dementia symptoms, the underlying cognitive distur-
bances should be tracked and measured. In the case of hallucinations, the same applies to the under-
lying perceptual disturbances. In the case of anhedonia, the defect in linking a particular perception
with the corresponding emotion should be searched for.
Psychic dysfunctions underlying psychopathological symptoms should be, I propose, the focus of
biological psychiatric research. It seems much more likely that brain dysfunctions correspond with
disturbances in psychological regulatory systems than with largely man-designed categorical enti-
ties, or with symptom complexes rather arbitrarily designated as a syndrome or a dimension.
xviii Foreword
The search for biological determinants of psychic dysfunctions has indeed been proven to be
much more fruitful than the search for the biological cause of a particular nosological entity, such
as depression or schizophrenia (see Section 7).
5 Advantages of Functionalization of Diagnosis
Functionalization will advance scientification of psychiatric diagnosis. It will make this process
more precise, more scientific, and more attuned to goal-directed biological studies and focused
therapeutic interventions.
It is more precise and more scientific, because psychic dysfunctions are much more measurable
than disease categories and syndromes, often even quantitatively.
Second, this approach provides the diagnostician with a detailed chart of those psychic domains
that function abnormally and those functioning within normal limits. Ultimately, this approach will
lead to what I have called a psychiatric physiology, a detailed chart of brain dysfunctions underlying
abnormally functioning psychic systems.
Treatment, too, could benefit from this approach. Drug treatment as well as psychotherapy is
presently pretty much unfocused. We prescribe drugs because someone is psychotic, depressed,
anxious, or otherwise out of balance. Any further specification is generally lacking or deemed to
be unnecessary. This is not the way to further psychopharmacological research, nor the way to
increase the chance of finding new, innovative, and psychopathologically more specific psycho
tropic drugs.
The same reasoning holds for psychological treatment. We may recommend psychotherapy.
For what exactly is seldom clear. What will be its focus? What do we hope to achieve? It is rarely
defined in any detail. This holds in particular for psychodynamically oriented psychotherapies.
Cognitive–behavioral therapists do somewhat better in this respect. Functionalization of diagno-
sis would make systematic detailing of therapeutic goals feasible. In fact, it would be its logical
consequence.
To avoid misunderstanding, I am not pleading to abandon the categorical system (now). One
should not throw away an existing system before a new and better one is available. What I suggest
is to refine and enrich the categorical system by functionalizing it.
6 Verticalization of Psychiatric Diagnosis
Verticalization is the term I have used for the process of prioritizing the symptoms of a given dis-
order (van Praag 1997). Prioritizing means that their relationship to the underlying biological sub-
stratum is hypothesized (to begin with) and, if possible, established. Are they a direct consequence
of the underlying substratum, or associated in a derivate manner? The former symptoms are called
primary, the latter secondary. It seems possible that the secondary symptoms are a consequence of
pathological processes elicited by the primary symptoms. If so, one can say that the primary symp-
toms possess “pacemaker qualities.”
In medicine, verticalization of diagnosis is a common procedure. For example, a patient feels
miserable and tired, is coughing, has a fever, expectorates, and has difficulties breathing. The doc-
tor weighs the symptoms and considers the symptoms fever, coughing, and impaired breathing as
primary, that is, diagnostically decisive. His tentative diagnosis is pneumonia.
In psychiatry, verticalization is not the common procedure. On the contrary, psychiatrists diag-
nose in a horizontal manner. The symptoms observed in a given psychopathological condition are
counted and placed in a horizontal plane as if they all had the same diagnostic weight. This, however,
is quite improbable. It is much more likely that some are the direct consequences of the underlying
cerebral dysfunctions whereas others are of a subsidiary nature. The former (primary) phenomena
are diagnostically the most important. They should be the focus of biological studies and should be
the main target of psychopharmacological interventions.
