Psychomotor Retardation and Agitation in Clinical Depression

Psychology Research Progress

P sychopathology T h e o r y , P e r s p e c t iv e s and

F uture A pproaches

Drozdstoj Stoyanov E d it o r

Complimentary Contributor Copy

Copyright © 2013 by Nova Science Publishers, Inc. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. For permission to use material from this book please contact us: Telephone 631 -231 -7269; Fax 631-231-8175 Web Site: http://www.novapublishers.com NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers’ use of, or reliance upon, this material. Any parts of this book based on government reports are so indicated and copyright is claimed for those parts to the extent applicable to compilations of such works. Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book. Library of Congress Cataloging-in-Publication Data Psychopathology: theory, perspectives and future approaches / editor, Drozdstoj Stoyanov, Department of Psychiatry, Faculty of Medicine, Medical University of Plovdiv, Bulgaria, pages cm Includes index. ISBN: 978-1-62618-507-4 (eBook)

1. Psychology, Pathological. 2. Clinical psychology—Methodology. 3. Psychotherapy. 4. Mental illness. I. Stoyanov, Drozdstoj, editor of compilation. RC454.P7872 2013 616.89T4—dc23 2013009427

Published by Nova Science Publishers, Inc. f New York


Contents Preface

vii

Section I: Theory and Phenomenology of Psychopathology Chapter 1

Chapter 2

Chapter 3

On Persons and Structures: Phenomenology’s Contribution to Psychopathological Investigations Cristian Muscelli

1 3

The Concepts o f ‘Depressive Pathogenic Situation’ and ‘Melancholic Type of Personality’ as Applied in the Case of Postpartum Depression Alessandra Ambrosini and Giovanni Stanghellini

23

The Psychopathology of Everyday Life as a Problem Before Socioanalysis Deyan Deyanov, Svetlana Sabeva and Todor Petkov

51

Section II: Epistemology, Methodology and Mental Disorder

79

Chapter 4

Classification, Validity and Psychiatric Kinds Somogy Varga

81

Chapter 5

Emotional States and Emotional Disorders: A Case Study for Indeterminacy of Definitions and Criteria in Mental Health George Nikolaidis

Chapter 6

Chapter 7

97

Neuroscience and Psychopathology: The Significance of Translational Validation Drozdstoj St. Stoyanov

125

Subthreshold Symptoms in Affective Disorders: Methodological Challenges Georgi Popov and Rayna Mandova

137


VI

Contents

Section III: Explanations in Psychopathology: Neuroscience and Psychological Approaches Chapter 8

Chapter 9

Empathy: The Crosstalk between Humanistic Disciplines and Neuroscience Massimiliano Aragona, Giorgio Kotzalidis and Antonella Puzella Self-Esteem and Psychopathology: The Connections Between Feelings of Self-Worth and Psychological Adjustment Virgil Zeigler-Hill and Christopher J. Holden

Chapter 10

Appraising Neuroscience Research in the Field of Mental Disorders Luis Madeira and Maria Luisa Figueira

Chapter 11

Neurobiological and Philosophical Perspectives of the Psychiatric Patient Jakob K orf

Section IV: Empirical Perspectives in Psychopathology Chapter 12

Potential Risk Biomarkers in Psychopathology: An Update and Critical Reappraisal Valentin Akabaliev, Zlatoslav Arabadjiev, Katherina Akabalieva and Sevdalina Kandilarova

Chapter 13

Psychomotor Retardation and Agitation in Clinical Depression Petya Terziivanova and Svetlozar Haralanov

Chapter 14

Affective Computing Applied in Elderly with Depression and Alzheimer’s Disease Rayito Rivera-Hernandez, Drozdstoj Stoyanov, Magda Tsolaki and Gines Llorca Ramon

Chapter 15

Psychopathology Associated with Motor Vehicle Crashes Ashley Craig, Yvonne Tran and Jan D. Cameron

Chapter 16

The Place of Chronobiology in the Pathogenesis and Diagnostic of Psychiatry Nadejda Petrova Madjirova

Index

149 151

181 201

227 251 253

283

299

323

343 363


In: Psychopathology Editor: Drozdstoj Stoyanov

ISBN: 978-1-62618-470-1 © 2013 Nova Science Publishers, Inc.

Chapter 13

Psychomotor Retardation and A gitation in Clinical Depression Petya Terziivanova 1’2 and Svetlozar Haralanov3 4 *

’

'Psychiatry in Medical University, Sofia, Bulgaria, 2Multiprofile Hospital for Active Treatment in Neurology and Psychiatry “Sveti Naum,” Sofia, Bulgaria 3Psychiatry in Medical University, Sofia, Bulgaria 4Psychiatric Department in Multiprofile Hospital for Active Treatment in Neurology and Psychiatry “Sveti Naum,” Sofia, Bulgaria

A bstract Major depressive disorder is a severe, chronic and etiologically complex psychiatric illness. There is growing evidence that the diagnosis “depression”, as defined by the main world classification systems, the Diagnostic and Statistical Manual (DSM-IV-TR) and the International Classification of Diseases (ICD-10), is heterogeneous in nature and includes different subgroups. The diagnosis of depression relies more on the course of the illness (unipolar-bipolar) than on the current clinical presentation and the specificity of the psychopathological symptoms. It seems that the widespread approach, e.g. “5 from 9” symptoms, tends to substitute thorough clinical evaluation, cautious observation and description of the psychopathology of depressive syndrome. For centuries, psychomotor disturbances have been regarded as cardinal symptoms of depression. Their objective assessment may have predictive value with respect to the severity of clinical depression, treatment outcome, and prognosis of affective illness. Psychomotor symptoms may have pathophysiological significance as psychomotor disturbances, caused by motor dysregulation, go along with affective dysregulation. It is supposed that common neurotransmitter pathology in the brain structures causes simultaneously psychomotor and affective dysregulation that underlie the pathophysiology of depressive disorder. Also, psychomotor retardation is thought to be a cardinal depressive symptom in endogenous depressions - unipolar and bipolar. On the other hand, psychomotor agitation may be considered as latent bipolarity, although the presence of manic symptoms within *

E-mail: [email protected].


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Petya Terziivanova and Svetlozar Haralanov a depressive state and the role of psychomotor agitation in depressive patients are still disputable.

In t r o d u c t io n The lifetime prevalence of major depressive disorder is approximately 16 % (Kessler, et al., 2003). Recurrent by nature, depression is associated with a great number of years of life lost due to disability and premature death. It is not surprising that the world-spread difficulties in clinical identification of depressive syndrome (underdiagnosis), the delays of psychiatric consultation and treatment initiation, the poor management of patients with clinical depression, are all expected to make depression the second leading cause of disability by the year 2020 (Lopez, et al., 2006). In Europe nine out of a thousand people suffer from depression (Ayuso-Mateos, et al., 2001). In other words, depression is a disease with an enormous social significance. The origin of the word “depression” comes from the Latin verb “deprimo”, which means press, suppress, oppress. It is assumed that depression, as a mental illness, mainly affects the emotions. Depression is associated with prevalence of negative (asthenic) emotions such as sadness, grief, and worry. Emotional disturbances are biologically related to disturbances in motility which is supported by the fact that the origin of the word “emotion” comes from the Latin verb for movement - "movere". The strong correlation between emotion and movement is often reflected in the language. In English for example, we speak of “spring in one’s step” when someone is in a bright mood and of “heavy steps” when someone is in a sad mood. Psychomotor disturbances within the depressive syndrome in patients with unipolar and bipolar depression may develop in two opposite directions from the norm. Clinically observed disturbances in psychomotility are the so-called psychomotor retardation and psychomotor agitation. In psychomotor retardation, the depressive mood corresponds to an overall reduction in volitional activity and emotional reactivity. On the other hand, in psychomotor agitation, the depressive mood is associated with a raise in volitional activity and emotional reactivity. Therefore, in terms of clinical manifestation and pathophysiology, psychomotor retardation and agitation are different conditions which require different diagnostic and treatment approaches (Haralanov and Terziivanova, 2010; 2011). Kraepelin was the first to conclude that over the years recurrent depression could become a bipolar one. It is considered that latent bipolarity leads to poor treatment outcomes and causes therapy-resistant depressions. The bipolar predictors by themselves are not sufficient to make the difference between unipolar and bipolar depression. The absence of clear clinical boundaries for “depression” seems to turn the bipolar predictors into useless and unpractical instruments. In spite of the considerable progress in neuroscience, the diagnosis of depression remains mainly descriptive. The heterogeneity in depressive syndromes increases the risk for its over-diagnosis, as well as for its under-diagnosis, and impedes the correct diagnosis of the illness and the achievement of a favorable treatment response (Parker, 2005). The validity and specificity of diagnostic criteria in clinical depression are still a subject of dispute in psychiatry. According to different authors, patients with recurrent depression, as well as those suffering from normal sorrow, receive the same diagnosis of “clinical depression” (Helmchen and Linden, 2000; Clarke and Kissane, 2002; Wakefield, 2007). Since there are no acurate disease-specific symptoms, it is still being debated in the scientific


Psychomotor Retardation and Agitation in Clinical Depression

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community which approach is more useful - the dimentional or the categorial one. In recent years, scientific research is directed towards the identification of specific subgroups within the heterogeneous group of depressive patients. The establishment of specific depressive subgroups is expected to facilitate the study of genetic and biochemical changes that underlie the observed clinical differences. This approach would improve the treatment and the prediction of the illness course.

Objectives Psychomotor disturbances are recognized by many authors as psychopathological specific symptoms with predictive value in respect to the severity of clinical depression, the treatment outcome and the prognosis of the illness (Sobin and Sackeim, 1997; Mitchell and Malhi, 2004; Mitchell, et al., 2008; Parker, 2011; Haralanov and Terziivanova, 2010; 2011; Terziivanova and Haralanov in press). In this paper we will demonstrate the clinical and theoretical significance of the psychomotor symptoms in the psychopathology and pathophysiology of depression.

A rgum ent

1. Definitions and Operational Constructs: Psychomotor Behavior, Depression, Emotion Psychomotor behavior (from the Greek word “psyche” - soul and the Latin word “motorius” - motor) includes the complex movements of the muscles of the face and the whole body that reflect the personality and the overall mental experiences. Psychomotor performance includes two basic components - volitional activity and emotional reactivity (Stoimenov, et al., 2004). Psychomotor changes are visible components of human behavior. Due to the control which the central nervous system exerts over all human movements, each movement is a single behavioral act, which can be segmented into a number of motor units, each lasting for a few seconds. Performance of movements and maintenance of balance both require intact peripheral and central brain structures with good integration of the information between them. The cognitive and emotional disturbances in different psychiatric disorders affect the time and the spatial structure of movements. Psychomotor disturbances are basic symptoms of unipolar and bipolar depression. Table 1 presents the psychopathological symptoms included in the diagnostic criteria of DSM-IV-TR and ICD-10. According to the ICD-10 and DSM-IV-TR criteria, psychomotor disturbances in depressive patients could be directed in the two opposite directions from the norm - towards psychomotor retardation (motility slowdown) or towards psychomotor agitation (motility activation).


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Table 1. DSM-IV-TR and ICD-10 diagnostic criteria for major depressive disorder DSM-IV-TR Five (or more) of the following symptoms are present during the same 2-week period and represent a change from the previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. 1. Depressed mood most of the day, nearly every day as indicated by either a subjective report (e.g. feels sad or empty) or an observation by others (e.g. appears tearful) 2. Marked diminished interest or pleasure in all or almost all,activities for most of the day, nearly every day (as indicated by either a subjective report or an observation by others) Additional symptoms 3. Significant weight loss when not on a diet or weight gain (e.g. change of more than 5 % of the body weight in a month), or decreased or increased appetite nearly every day 4. Insomnia or hypersomnia nearly every day 5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or of being slow) Fatigue or loss of energy nearly every 6. day 7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day 8. Diminished ability to think or concentrate, or indecisiveness nearly every day (either by subjective account or as observed by others) 9. Recurrent thoughts about death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicidal attempt or a specific plan for committing a suicide

ICD-10 Three are the basic, typical symptoms:

1.

Depressed mood

2. 3.

Loss of interests and loss of ability to feel pleasure and joy Increased fatigue and reduced activity

4.

Psychomotor retardation and agitation

5.

Concentration difficulties

6

Loss of appetite or increased appetite

7

Sleep disturbances - increase or reduction of the total sleep time Low self-esteem and loss of self confidence

8

9

Feelings of guilt and self-accusation

10

Pessimistic thoughts for the future

11 12

Suicidal thoughts and intentions Loss of libido



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Psychopathological symptoms that are considered typical for patients with depression are the loss of facial expressions and gestures, as well as the reduction of volitional activity, emotional reactivity, and gross motor activity. Depressed patients present themselves with bradyphrenia (slowed thinking), hypokinesia (reduction in spontaneous movement), bradykinesia (slowed activity), poor coordination, postural abnormalities. Their gait is slowed down and less stable than in euthymic state. Patients rarely establish eye contact. In severely depressed patients, the personal hygiene is neglected. Patients experience difficulties in performing “usual tasks”. They complain of constant fatigue and feeling of weakness. Psychomotor retardation is considered as a core symptom of depression. (Sadock, Sadock and Ruiz, 2009b). In the case of psychomotor agitation, the basic symptoms include severe tension and anxiety. Depressed patients are tense, anxious, restless. They experience intense inner tension, and therefore difficulty to stay in one place. Agitated patients constantly touch different parts of their body (usually head, hair, knees) and nearby objects such as handbags or clothing (an edge of garment or buttons). They may appear at a clinical interview with handwringing, tapping fingers and stamping feet. Agitated patients tend to complain constantly, repeating the same phrases. They are inclined to exaggerate their emotional experience and bodily complaints. Irritability and hypochondriac symptoms also dominate. All these psychopathological symptoms occur along with depressed mood and/or loss of interest or pleasure. Depressed patients describe themselves as being sad, depressed, dominated by feelings of sorrow, regret, disappointment, uncertainty. Some patients describe their sadness and grief as an experience of "body pain." From a certain point of view, there is a reciprocal relationship between the body and the emotions. The emotional reaction influences various somatovisceral and motor systems while at the same time the state of the body as a whole determines how certain emotional information will be apprehended and analyzed. Damasio’s definition of emotion includes “all changes occurring in the body and the brain as a result of various internal and external stimuli”. He concludes that “emotion” is a consequence of the bodily perceptions entering the central nervous system from various organs, and that the emotion itself participates in maintaining the balance with the environment and in the process of adaptation. Damasio considers three types of emotions: primary (basic), secondary (complex) and main (background). Basic or primary emotions engage phylogenetically ancient structures of the cortex and provide protection in critical and hazardous environments. They are fast, short lived, highly automated and in case of emergency could cause rapid motor response. Complex or secondary emotions are slower, they include the basic emotions and are result of the interaction between the limbic structures and the different structures of the neocortex. They are evolutionarily newer and allow implementation of more accurate motor responses to internal homeostasis changes and to external environmental factors. Background emotions reflect the feelings of our own body - hunger, thirst, pleasure, pain (Damassio, 1999). In fact, Damasio revived the theory of James-Lange about emotions. James and Lange postulated that primarily the internal and external stimuli cause specific changes in the body sensations and these specific changes are experienced as an emotion - "I am sad because I’m crying, I'm angry because I’m fighting, I'm afraid because I’m trembling". If we apply the same logic to the psychomotor disturbances in patients with depression, it would lead us to the possible conclusion that "I am depressed because my psychomotorics is slowed down".


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James-Lange summarized that in the course of evolution and struggle for existence it was really important and life-saving first to respond to the situation, and only then to interpret the actions that were performed in the context of the emotions generated by the motor response. Emotions have cognitive functions - they enable us to organize and explain our human actions, interpersonal relationships and everyday communication (Stickland, 2001). The sustained disturbances in emotions and affect lead to disturbances in social functioning. On the other hand, emotional and affective disturbances are the primary features of the underlying affective disorders. Kraepelin used the term “affective dysregulation” to explain the occurrence of manic-depressive illness. He supposed that “affective dysregulation” is the cause that generated the episodes of depression and mania.

2. Descriptive Phenomenology: Melancholia and Mania, Unipolar and Bipolar Depression The symptoms of the current depressive episode could define the depression as being of melancholic or non-melancholic type. The classical description of melancholia includes: 1) depressed mood (dysthymia); 2) changes in psychomotor activity towards retardation; 3) slowed thinking. The criteria of ICD-10 for the diagnosis “melancholic depression” are: 1) 2) 3) 4) 5) 6) 7) 8)

loss of interest or pleasure in activities that normally bring pleasure; lack of emotional response to normally pleasant environment and events; waking up in the morning two hours or more before the usual time; deeper depression in the morning hours; objective evidence of psychomotor disturbances - described by others; loss of appetite; weight loss more than 5% of body weight for the last month; loss of libido.

Patients with melancholic depression are often found to have psychomotor retardation and to respond better to treatment with tricyclic antidepressants (TCA) and serotonin and noradrenaline reuptake inhibitors (SNRI) compared to treatment with antidepressants of the group of serotonin reuptake inhibitors (SSRI) (Malhi, et al., 2009). The term "melancholia" has a Greek origin (from Greek “melas” - black and “chole” bile) and was first introduced by Hippocrates in the 5th-4th century BC. He described the disease melancholia as a state of hopelessness, rejection of food intake, insomnia, irritability and restlessness. He explained the state of fear or depression with an accumulated excess of "black bile" in the patient body. The accumulation of the so-called "yellow bile" leads to the development of a syndrome opposite to depression - mania (from Greek “mania” - passion, madness, desire). The clinic manifestation of manic syndrome includes totally contrast psychopathological symptoms:



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1) elevated mood (hyperthymia); 2) changes in psychomotor activity towards activation (hyperactivity); 3) accelerated thinking. Aretaeus of Cappadocia is supposed to be the first to combine melancholia and mania within the same mental disease. According to him "melancholia is the beginning and part of the mania .... The development of mania is in fact worsening of the disease (melancholia) rather than a change into another disease..." (Goodwin and Jamison, 2007a). Despite the polarity of the disease, scientists, especially Kraepelin, studied, described, followed up, and tried to explain and cure manic-depressive illness as a whole for centuries. The contrasting psychopathology of the manic-depressive phases during the course of the disease forced the scientists to search for a new type of classification system for depression. So the new terms “unipolar” and “bipolar” depression were proposed by Leonhard in 1957 (Goodwin and Jamison, 2007b). He summarised, that there is a group of patients whose course of affective illness includes only episodes with depressive symptoms and termed these forms as “monopolar” or “unipolar” depressions. These are the Kraepelin’s periodic depressions within the manic-depressive illness. The other patients’ group illness course includes both depressive and manic episodes - the Kraepelin’s manic-depressive illness of circular type. This group was termed by Leonhard as “bipolar” depressions. The unipolarbipolar separation of depression puts an emphasis only on the course of the disease and not on the severity and the specificity of the current depressive symptoms. Division, based only on the polarity of the symptoms, does not emphasize or put into consideration the clinical manifestation of the current depressive psychopathology. The findings of Leonhard were supported by the results of research independently conducted in 1966 by Angst and Perris on family history of patients with depression (Goodwin and Jamison, 2007b). The unipolar-bipolar distinction replaced Kraepelin’s unitary concept of manic-depressive illness and was incorporated into the classification systems - in DSM-III in 1980 and in ICD-10 in 1994. According to both classification systems, a depressive episode could be either within the recurrent depressive disorder, know as unipolar depression, or within the bipolar affective disorder, known as bipolar depression. Therefore, the current classification systems focus more on the course of the disease over time rather than on the clinical description of the current depressive episode. This approach is associated with the term "latent bipolarity," as it is known that the first manic or hypomanic episode usually occurs years after the clinical manifestation of the first depressive episode. According to the diagnostic criteria of ICD-10 and DSM-IV-TR, we could conclude that unipolar patients or patients with recurrent depression are all depressive patients with no history of mania or hypomania. Thus, unipolar are all depressive patients who are not bipolar, and the diagnosis “depression” includes a heterogeneous group of depressed patients, including patients with endogenous, neurotic and reactive depression (Goodwin and Jamison, 2007b). The unipolar-bipolar distinction seems to be important for the clinical practice, mainly because of the established significant differences in unipolar and bipolar depression treatment (Benazzi, Koukopoulos and Akiskal, 2004; Akiskal, et al., 2005; Benazzi, 2008). In recent years, large-scale retrospective and prospective studies prove that while antidepressants remain the major therapeutic agent during the acute and maintenance phase of unipolar depression and act as a successful monotherapy, in bipolar depression they often have a paradoxical effect. The usage and efficacy of antidepressants in bipolar depression remain


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controversial. It is shown that antidepressants often worsen the course of the disease and contrary to mood stabilizers act as "mood destabilizers” (Akiskal, et al., 2005). Therefore, many experts recommend that in the presence of even discrete symptoms or a short state of hypomania in depressed patients, the role of antidepressants has to be immediately reassessed and their exclusion from the maintenance therapy or at least their combination with mood stabilizers and/or atypical antipsychotics has to be considered (Akiskal, et al., 2005; Hantouche, et al., 2005; Koukopoulos, et al., 2005). The main problem is that in clinical practice the detection of bipolarity is very difficult because in half of the cases bipolar affective disorder manifests itself with a series of depressive episodes before the onset of the first manic or hypomanic episode. It should be noted though that Kraepelin was again the first to conclude that most of the recurrent depressions over the years could become bipolar. Therefore, often bipolar depression is seen as "unipolar" for years and is incorrectly treated with antidepressants (Benazzi, Koukopoulos and Akiskal, 2004; Akiskal, et al., 2005; Hantouche, et al., 2005; Koukopoulos, et al., 2005; Benazzi, 2008). To avoid this practice that harms patients, research efforts are directed towards early identification of latent bipolarity in apparently unipolar (recurrent) endogenous depressions, without waiting for the occurrence of hypomanic or manic episode (Koukopoulos and Koukopoulos, 1999; Goldberg, Harrow and Whiteside, 2001; Benazzi, Koukopoulos and Akiskal, 2004; Cassano, et al., 2004; Akiskal, et al., 2005; Koukopoulos, et al., 2005; Benazzi, 2007b; Benazzi, 2008; Angst, 2007; Angst, et al., 2009; Zimmermann, et al., 2009). The main “predictors of bipolarity” found in the scientific literature are: family history of bipolar disorder, hyperthymic and cyclothymic personality, early onset of the depression, single psychotic symptoms and antidepressant treatment resistance (Koukopoulos and Koukopoulos, 1999; Goldberg, Harrow and Whiteside, 2001; Cassano, et al., 2004; Benazzi, Koukopoulos and Akiskal, 2004; Benazzi, 2005; Akiskal, et al., 2005; Hantouche, et al., 2005; Benazzi, 2007a; Benazzi, 2008; Angst, et al., 2009). There are also episodic (subthreshold) psychopathological symptoms of bipolarity: racing thoughts, irritability, anxiety, impulsiveness, talkativeness, easy-going in social contacts, unusual familiarity with strangers, sudden bursts of high energy and willingness to work, unjustified optimism, reduced need for sleep and lack of fatigue during the day, gambling behavior, increased appetite, and unusual hypersexuality. The listed symptoms could be both inter- and intra- the current depressive episode, i.e. exist not only outside but also during the depressive phase. As mentioned above, Kraepelin defined the term “affective dysregulation” as the basic pathophysiological disturbances that cause the clinical occurrence of affective disorders (Akiskal, 2008). Patients with affective disorders are presented clinically with affective, as well as with psychomotor disturbances, so the affective disorders occur simultaneously with motor and emotional dysregulation (Haralanov and Terziivanova, 2010; 2011). As it was mentioned, psychomotor disturbances include psychomotor retardation and agitation.

3. The Significance of Psychomotor Retardation and Agitation Psychomotor retardation includes reduction of movements and bradyphrenia within the depressive episode (DSM-IV-TR). The significance of psychomotor retardation and agitation in patients with unipolar and bipolar depression is still debated in the scientific literature.



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Psychomotor retardation is one of the major features of endogenous depression (Nelson and Chamey, 1981). Bipolar depression is most often characterized with psychomotor retardation. According to Sobin and Sackeim (1997), psychomotor retardation is more likely to occur at patients with bipolar depression compared to unipolar depression patients. After reviewing the literature on the phenomenology of bipolar disorder, Goodwin and Jamison (1990) stated that "activity and behavior are almost always slowed in bipolar depression". Parker, et al. (2000) recognized psychomotor retardation as the main manifestation of melancholic depression. Mitchell, et al. (2001; 2008), Mitchell and Malhi (2004), Beigel and Murphy (1971) also found that bipolar depression patients were more likely to have psychomotor retardation. The clinical significance of psychomotor retardation remains controversial. Some authors suggest that psychomotor retardation is more likely to occur in patients with melancholic type of endogenous depression, while other scientists argue that psychomotor retardation is a specific feature for patients who suffer from the more severe forms of depression (Parker, et al., 2000; Cassano, et al., 2004; Pier, Hulstijn and Sabbe, 2004; Buyukdura, McClintock and Croarkin, 2011; Calugi, et al., 2011). According to Kupfer, et al. (1974), psychomotor retardation precedes the onset of the other depressive symptoms such as hopelessness, helplessness and suicidal behavior, and remains even after the initial remission is achieved. Kupfer concluded that the "hypokinesia" dynamics during the course of the depressive episode could have a prognostic value and could give an essential information about the course of the depressive illness as a whole. A research of Beigel and Murphy (1971) shows that patients with unipolar depression are more active and hostile than those with bipolar depression. In 1997, Sobin and Sackheim after a review on the topic concluded that patients with unipolar depression had increased psychomotor activity compared to bipolar patients. Agitated depression meets the criteria for major depressive episode (DSM-IV-TR) and includes at least two of the following symptoms: 1) motor agitation; 2) psychic agitation (intense inner tension); 3) intense thought engagement. According to the international classification systems, a depressive episode with psychomotor agitation could be presented in patients with unipolar and bipolar depression, without any subtyping. There is no distinction between disturbances in psychomotor activity towards retardation and agitation neither in DSM-IV-TR (2000), nor in ICD-10 (1992). Only in The Research Diagnostic Criteria established by Spitzer (1978), agitated depression is plit in a different subtype of depression. Agitated depression as a clinical syndrome was first described by Richarz in 1858. He used the term "melancholia agitans" to emphasize the “aimless restlessness” of these depressive patients (Mameros and Goodwin, 2005b). The term "agitated depression" was introduced by Weygandt and entered Kraepelin’s classification system in 1899 as a "depressive state with excitation". Kraepelin and Weygandt consider agitated depression as one of the six types of mixed states in which symptoms of the two opposite poles of the manic-depressive illness - depression and mania - are presented simultaneously. They assume that during an episode of agitated depression the two basic depressive symptoms -


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depressive mood and thought inhibition coexist with the manic symptom - psychomotor activity. Both Kraepelin and Weygandt conclude that instability in the domain of mood, psychomotor activity (psychomotility) and thinking are main clinical manifestations of manic-depressive illness (insanity) (Mameros and Goodwin, 2005a). The studies of Koukopoulos and Koukopoulos (1999), Perugi, et al. (2001), Maj, et al. (2003), Akiskal and Bennazzi (2005) support Kraepelin’s conclusions for the existence of an overlap between the two opposite clinical categories, depression and mania, within the mixed states. These studies confirm that within agitated depression the depressive symptoms overlap with manic symptoms such as irritability, intense inner tension, talkativeness, distractibility and psychosis. Recent perspectives recognize agitated depression as part of the “bipolar spectrum”, which includes the different types of bipolar affective disorder and the recurrent (unipolar) depressions with predictors or subthreshold manifestations of bipolarity (Benazzi, Koukopoulos and Akiskal, 2004; Cassano, et al., 2004; Benazzi, 2005; Benazzi, 2007a; Benazzi, 2007b; Haralanov and Terziivanova, 2011). According to the authors quoted above, psychomotor agitation and its detection within an ongoing depressive episode has a great practical significance. Patients with agitated depression have a higher rate of relapse and recurrence. They are at greater risk for suicidal tendencies and antidepressant monotherapy could worsen the course and the prognosis of their illness (Anderson, 2001; Anderson, et al., 2008; Baldessarini, et al., 2005; Fawcett, et al., 2009). The choice of medication strategy should be different in depressive patients with psychomotor retardation and agitation. It is considered that antidepressant monotherapy increases the agitation, acts as a “mood destabilizer”, worsens the course of the illness, increases the duration of the episodes, and causes persistence of the residual depressive symptoms between the episodes. Consiquently, many authors recommend the usage of mood stabilizers and/or low doses of antipsychotics along with antidepressants in cases of patients with agitated depression. On the other hand, some studies support the antidepressant monotherapy usage in cases of patients with agitated depression (Fawcett, et al., 1995; Fava, et al., 2000; Serretti, et al., 2007). It is supposed that depressive patients with psychomotor retardation would respond better to therapy with TCA, SNRI, NaSSA, NRI, and sertraline, while patients with psychomotor agitation would respond better to therapy with SSRI. Obviously, the therapy schemes in agitated and retarded depression remain controversial (Flament, et al., 1999; Anderson, 2001; Flament and Lane, 2001; Joyce, et al., 2002; Sechter, et al., 2004; Taylor, et al., 2006; Serretti, et al., 2007).

4. Beyond Mood, Psychomotor Activity (Psychomotility) and Thinking Dysregulation Berk, et al. (2007) published an interesting hypothesis about the cycling dysregulation of dopamine neurotransmission in patients with bipolar affective disorder (manic-depressive illness). They supposed that the depressive phase generated the manic phase and vice versa, because of changes in the dopamine receptors. During the manic episode, the increased dopamine activity leads to reduction in the number and the sensitivity of the dopamine receptors (down-regulation), which could cause a depressive state. On the other hand, the depressive episode is associated with reduction in dopamine activity, which leads to an increase in the number and the sensitivity of the dopamine receptors (up-regulation) and the amount of dopamine in the synaptic cleft. The excess of the dopamine neurotransmission



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could also generate a new manic or hypomanic state. The poor synchronization between different brain structures during the up- and down- regulations explains the appearance of mixed states. Presumably, patients with latent bipolarity are more likely to exhibit a mixture of symptoms from both opposite poles of the disease. Psychomotor agitation in depressive patients could be a clinical representation of the deficiency in the dopamine brain regulation systems. Psychomotor retardation is well-known to be associated with hypodopaminergia in the mesocortical and mesolimbic structures. Different authors compare the dopamine dysregulation in depression with those observed in patients with Parkinson disease and negative symptoms in schizophrenia (Mackay, 1980; Andreasen, 1982; Schmidt, et al., 2001; Tandon and Jibso, 2002; Berk, et al. 2007; Malhi and Berk, 2007; MacDonald, et al., 2011). Psychomotor agitation is supposed to be a result of disturbances in the serotonin prefrontal brain structures and subcortical dopamine structures, and to be a result of the disturbances in the amygdala and the hypothalamic-pituitary-adrenal axis (Swann, et al., 1994; Brus, et al., 2004; Hellweg, et al., 2007; Sadock, B., Sadock, V. and Ruiz, 2009a; Homberg, 2012). Psychomotor activation in agitated depression is in fact manic hyperactivity during the dominant depressive mood. It is presumed that the increased psychomotor activity is linked to dopamine changes opposite to those observed in psychomotor retardation. Psychomotor activation is supposed to be a consequence from the hyperdopaminergia similar to that observed in patients with mania and positive symptoms of schizophrenia. It is known that amphetamine and cocaine can cause mania, and an overdose of antiparkinsonian drugs (dopamine agonists) leads to agitation, akathisia and psychotic symptoms (Nutt, 2006; Berk, et al., 2007). The mood stabilizers - lithium, carbamazepine and valproate - change the activity of D2-receptors in substantia nigra, nucleus accumbens, and the prefrontal cortex, as well as the activity of NMDA-receptors. These brain structures are responsible for the motor and emotional control. The specific pharmacodynamic profile of the mood stabilizers explains their therapeutic effect in patients with mania and resistant depression. In patients with bipolar affective disorder, depression is three times more common than mania and often the latent bipolar depression is inadequately treated. Therefore, the dopamine instability in patients with bipolar depression, discussed above, and specifically in patients with agitated depression, explains why antidepressants worsen the course of the illness, as well as the need of treatment with mood stabilizers and antipsychotics (Rapoport, et al., 2009).

C o n c l u s io n The diagnosis “depression” comprises of an array of clinical syndromes which manifest themselves with different psychopathological symptoms. Psychomotor disturbances retardation and agitation - as key aspects of the depressive psychopathology could be regarded as equivalent to the emotional symptoms. As a clinical syndrome depression remains puzzling and paradoxical probably due to the affective and motor dysregulation in different brain structures and the complex interactions between them. Despite the rapid development of neuroscience and genetics, as Beck and Alford (2009) comment, there are still unresolved issues regarding the nature, classification and etiology of depression. Therefore, a revision of the present diagnostic standards, taxonomies and treatment guidelines


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is needed and may be achieved by more in-depth studies aimed at understanding the underlying mechanisms of these mental disorders. One possible approach would be to place a greater emphasis on the criteria of objective psychomotor agitation and retardation within the phenomenological rationale of depression. Although neuroscience has developed very rapidly in recent years, psychopathology remains the main method in the clinical practice in the field of psychiatric diseases. As a science, psychiatry should integrate the ancient and modem knowledge in order to be more successful in curing the human psyche.

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