REVISTA ROMÂNĂ de PSIHIATRIE - Revista Romana de Psihiatrie

Transcription

COMITET DE REDACŢIE
Redactor şef:
Dan PRELIPCEANU
Redactor-şefi
adjuncți:
Dragoş MARINESCU
Aurel NIREŞTEAN
COLECTIV REDACŢIONAL
Doina COZMAN
Liana DEHELEAN
Marieta GABOŞ GRECU
Maria LADEA
Cristinel ŞTEFĂNESCU
Cătălina TUDOSE
Secretari de redacţie: Elena CĂLINESCU
Valentin MATEI
CONSILIU ŞTIINŢIFIC
Vasile CHIRIŢĂ (membru de onoare
al Academiei de Ştiinţe Medicale,
Iaşi)
Michael DAVIDSON (Professor, Sackler
School of Medicine Tel Aviv Univ.,
Mount Sinai School of Medicine,
New York)
Virgil ENĂTESCU (membru al Academiei de
Ştiinţe Medicale, Satu Mare)
Ioana MICLUŢIA (UMF Cluj-Napoca)
Şerban IONESCU (Universitatea
Paris VIII, Universitatea TroisRivieres, Quebec)
Mircea LĂZĂRESCU (membru de onoare al
Academiei de Ştiinţe Medicale,
Timisoara)
Juan E. MEZZICH (Professor of Psychiatry
and Director, Division of Psychiatric
Epidemiology and International
Center for Mental Health, Mount
Sinai School of Medicine, New York
University)
Teodor T. POSTOLACHE, MD (Director,
Mood and Anxiety Program,
Department of Psychiatry,
University of Maryland School of
Medicine, Baltimore)
Sorin RIGA (cercetător principal gr.I)
Dan RUJESCU (Head of Psychiatric
Genomics and Neurobiology
and of Division of Molecular and
Clinical Neurobiology, Department
of Psychiatry, Ludwig- MaximiliansUniversity, Munchen)
Eliot SOREL (George Washington
University, Washington DC)
Maria GRIGOROIU-ŞERBĂNESCU
(cercetător principal gr.I)
Tudor UDRIŞTOIU (UMF Craiova)
ARPP
ASOCIAŢIA ROMÂNĂ
DE PSIHIATRIE ŞI PSIHOTERAPIE
www.romjpsychiat.ro
REVISTA
ROMÂNĂ
de
PSIHIATRIE
ROMANIAN JOURNAL OF PSYCHIATRY
Vol XVIII
Nr. 1
March 2016
QUARTERLY
CNCSIS B+
p-ISSN: 1454-7848
e-ISSN: 2068-7176
CUPRINS
ARTICOLE SPECIALE
& Dimensiunea spirituală a personalității și rolul său în sănătatea mintală
1
Aurel Nireștean, Emese Lukacs, Gabriela Buicu, Monica Bilcă, Pokorny Vasile
ARTICOLE DE SINTEZĂ
& Modelul integrativ al psihoterapiei cognitiv-comportamentale în tulburările de personalitate
4
Cosmin O. Popa, Mihai Ardelean, Tudor Nireștean, Gabriela Buicu
& Screening-ul depresiei la nivelul asistenței medicale primare - o intervenție cost-eficientă
8
Raluca Ileana Nica, Mihail Cristian Pîrlog
& Ideație, comportament și tulburări de dispoziție în boala Parkinson - studiu clinic
11
Iordan Ganev, Toni Donchev, Krasimir Kostadinov, Velina Mancheva-Ganeva, Lachezar Manchev,
Ivan Manchev, Mihai Pirlog, George L. Paraschiv, Ruxandra C.m. Banu, Traian Purnichi
ARTICOLE ORIGINALE
& Evoluția simptomatologiei și funcționalității la pacienți români cu episod
depresiv major - studiu observațional
15
Valentin P. Matei, Victor Marinescu, Eda M. Ciorabai, Ileana Marinescu, Lavinia Duica, Mihai Pirlog,
George Paraschiv, Ioana G. Pavel, Alexandra Dolfi, Diana A. Mihalache, Iulia A. Mitea, Diana Mihalcea,
Mihnea Manea, Ana Giurgiuca, Mihai Bran, Bogdan Stania, Traian Purnichi, Dan Prelipceanu
& Tulburări psihice în epilepsia copilului
21
Elisabeta Racos – Szabo, Iringó Száva, Anamaria Todoran – Butila
INSTRUCŢIUNI PENTRU AUTORI
Revista Română de Psihiatrie este indexată de Consiliul Naţional al Cercetării Ştiinţifice din
Învăţământul Superior la categoria B+. Apare trimestrial.
Colegiul Medicilor din România acordă abonaţilor la această publicaţie 5 credite EMC/an.
Articolele ştiinţifice publicate în revistă sunt creditate cu 80 credite EMC/articol.
Revista Română de Psihiatrie este editată de Asociaţia Română de Psihiatrie şi Psihoterapie
şi Asociaţia Medicală Română
25
SPECIAL ARTICLES
THE SPIRITUAL DIMENSION OF PERSONALITY
AND ITS ROLE IN MENTAL HEALTH
Aurel Nireștean1, Emese Lukacs2, Gabriela Buicu3, Monica Bilcă4, Pokorny Vasile5
Rezumat:
Conceptul de sănătate mintală este unul global și
complementar psihiatriei. Aceasta și pentru că boala
psihică este adeseori o imagine deformată, caricaturală a
sănătății mintale. Atât sănătatea cât și boala mintală
implică corpul fizic, viața psihică dar și dimensiunea
spirituală a persoanei. Ambele interferează cu datele
biografice individuale și colective, cu tradițiile și
obiceiurile comunitare dar și cu lumea valorilor culturale,
religioase și morale. În abordarea sănătății mintale și a
personalității individuale un rol major îl are perspectiva
dimensională. Conform acesteia dimensiunile
personalității favorizează acele experiențe spirituale care
c re s c c a p a c i t ă ț i l e a d a p t a t i v e , f a v o r i z e a z ă
autodeterminarea și reprezintă o modalitate de cultivare a
acelor virtuți care protejează sănătatea mintală și permit
ființei umane să respecte și lucrurile pe care nu le înțelege
și care nu depind de ea.
Cuvinte cheie: sănătate mintală, personalitate,
dimensiune spirituală
Abstract:
The concept of mental health is a global concept and is
complementary to psychiatry. That is also because
psychiatry disorder is often a deformed and caricatured
image of mental health. Both mental health and
psychiatric disorders implies physical body, psychism, as
well as spiritual dimension of personality. Both of them
interfere with individual and collective biography, with
community traditions and customs, as well as with
cultural, religious, and moral values. In the mental health
and personality approaches the dimensional perspective
plays a major role. According to this perspective,
personality dimensions favor those spiritual experiences
that enhance the coping abilities, self-determination, and
are representing a way of cultivating those virtues which
protect the mental health and allow the human being to
respect also those things and events which don't depend of
it.
Key words: mental health, personality, spiritual
dimension
The term “spirituality” continues to be the subject
of great controversy. The diversity of its definitions
corresponds to its complexity (Cook, Powell, Sims 2009).
No matter the perspective, the spiritual world is a vast
territory which integrates not only existential meanings
and goals and affective and cognitive references, but also
transpersonal beliefs and experiences which lead to a
deeper understanding of the connection between psychic
normality and abnormality and the normality and
abnormality of the personality.
Mental health is a global concept complementary to
psychiatry which incorporates both a public health
objective and a point of reference which is simultaneously
individual and collective (Prelipceanu, Mihailescu,
Teodorescu 2000). Thus, mental health promotes the
totality of objective strategies which aim to protect the
wellness of the community in both mind and spirit. It takes
into account all the favorable factors, as well as the trigger
factors for the diversity of psychic episodes and illnesses.
A second component of mental health is the subjective
individual and collective state of wellness which is a result
of a harmonious personality which integrates and assumes
life experiences in a coherent manner. They insure wellbalanced interpersonal relationships as well as common
access to authentic and liberating existential values.
Knowledge of the governing principles of mental health
becomes a major factor in the prevention of mental
diseases and contributes decisively to eliminating the
stigma associated with mental illness and psychiatry in
general. This is due to the fact that both mental wellness
and mental illness are conditioned by biology, psychology
and social culture, and thus must be discussed taking into
account not only an individual's intentional subjectivity
and ability to reflect, but also one's freedom to decide, act
and transcend one's condition.
Five centuries ago already, the description of a series of
vaguely delineated and fleeting psychiatric entities
showed the connection between psychiatry and the social
and economic environment. Using the health biography
of two brothers from Basel, who upon returning to their
city of residence, recovered from a severe mental
condition, Hofer describes “nostalgia”, a condition which
subsequently became very well known in Western
Europe. A couple of centuries later, several other fleeting
clinical psychiatric conditions such as the hysterical and
epileptic pathological fugues, were identified and
described. They were called “ambulatory automatisms”
in France, and “ambulatory determinisms” in Italy. At the
end of the 20th century, “multiple personality” is
described by Hacking (1995). The list of psychic
disorders directly connected to socio-cultural dynamics
can continue with impulse-control disorders, PTSD, and
Gulf Syndrome which appeared after the Vietnam and
Gulf Wars, as well as pathological post-traumatic states
induced by certain sadistic abuses whose perpetrators
have not been condemned as moral authors of the crime.
1
MD, PhD, Professor, Chief of Psychiatry Department, UMF Targu Mures
MD, PhD, Assistant Professor, Psychiatry Clinic II, UMF Targu Mures
3
MD, PhD, Lecturer, Psychiatry Department, UMF Targu Mures
4
MD Psychiatry Resident, Psychiatry Clinic II, UMF Targu Mures
5
PhD, Manager, Brancovenesti Psychiatry Hospital
Received December 22, 2015, Revised January 13, 2016, Accepted January 21, 2016
2
1
Aurel Nireștean, Emese Lukacs, Gabriela Buicu, Monica Bilcă, Pokorny Vasile: The Spiritual Dimension Of Personality
And Its Role In Mental Health
Mental health and psychic diseases must be discussed in
terms of the self-conscious human being since they both
deal with the biology, psyche, and spiritual values of the
individual. Besides, the role of interpersonal
relationships, autobiography and collective biography,
community traditions and customs, cultural values and
religion must always be discussed and emphasized.
It is well known that contemporary society and culture are
dominated by science, technology, religion, and
community values which all inform, motivate and control
the dynamics of contemporary life. Today's culture is one
of overproduction and excessive consumption of goods
and leisure. It promotes hedonistic living in the present
moment as well as an individual's freedom to organize his
or her life in a strictly subjective way. New models of
success and false values which throw one's aspirations and
motivations into disarray and confusion are constantly
created. People communicate and befriend one-another
through the internet where they are more likely to have
superficial, soulless encounters. Though not everything is
“proper”, everything is permitted, and promoting moral
norms and trust in the law become optional (Nirestean
2009).
Culture is more and more removed from universal
symbols that give it cohesion. It promotes form over
substance and it feeds it to a public who readily digests it
without discernment. In the spirit of the “new
democracy”, everything goes in a world overwhelmed by
individualism, which prefers the winners to those who live
wisely, no matter the means of their success.
In contemporary society, human beings live for
themselves and have a constant and insatiable desire for
more. They make quick attempts at reaching peaks of real
existential meanings, but are disadvantaged by selfishness
and lack of self-control. The individual ego is
hypertrophied but lacks substance. It turns within with an
inauthentic and vulnerable self-esteem which is fed and
sustained by a highly subjective interpretation of events
and life experiences (Lipovetzky, 2007). This is the way
human beings believe they can achieve the state of
subjective wellbeing which is understood as a form of
happiness- a main component of mental health.
One's self-image and self-esteem condition each-other in
the whirlwind of the search for the perfect moment, of
competitiveness and competition, where altruism and
empathy have become undesirable. Individual identity is
thus built on rationality and knowledge, not on
interpersonal harmony, faith, or spiritual experiences. The
contemporary “Homo Democraticus” is very different
from “Homo Spiritualis”. Nevertheless, knowledge can
also bring about wisdom when human beings open up to
spiritual values and espouse - even for narcissistic
reasons- the way of good intentions.
The structure of one's personality influences the somatic
state of health- as is the case with certain cardio-vascular
disease which are significantly affected- as well as one's
psyche, in which it can be a breeding ground for addictions
and a great diversity of psychic diseases. A mature
personality takes coherent charge of its life experiences
and has the ability to adapt to life's events and to its stress
factors.
From a conceptual perspective, mental health must be
defined in connection with the various stages of life and its
critical periods, and from an utilitarian viewpoint, it is
2
important to develop those factors which protect mental
health and mental longevity.
The most appropriate way to understand the connection
between personality and mental health is to consider the
points of reference of the dimensional perspective. The
most commonly used are the ones belonging to the seven
factors. For example, during adolescence, a heightened
search for novelty and childhood sensations can lead to
impulse-control disorders, addictive behavior as well as
impulsivity and aggression. During puberty and
adolescence, heightened levels of nervousness can
facilitate the onset of the metabolic syndrome and of
obesity in the years to follow, while being more
conscientious protects one's health and longevity. Also
during adolescence, having a pleasant, attitude and being
conscientious can positively influence self-control and the
ability to learn, and protect one's health as an adult. The
frequency of negative life events, addictive behavior and
mortality rates also diminish. On the contrary, a low level
of self-control leads to diminished activity, impulsecontrol disorders, hetero-aggressiveness, as well as high
rates of suicide upon reaching adulthood. At the
adolescent stage, the progressive and elaborate access to
human values has a positive effect on mental health, in
contrast with the transitory access to inauthentic and
fleeting values which are so often promoted in
contemporary culture.
In adults, having a high degree of nervousness, being
unpleasant and not being conscientious can favor obesity,
nicotine and alcohol addiction, as well as sustain a
persistent pessimism and low self-esteem. On the
contrary, being an extrovert means being active and
sociable.
The structure of the personality as well as the concept of
mental health integrates biological, psychological, social
and spiritual components. The subjectivity and
intentionality of each individual are constantly completed
and changed by one's spiritual needs which connect the
individual with the world of the senses, of existential
motivations, and self-transcendence.
Spiritual needs reside at the foundation of the
homonymous dimension of the personality. It molds
together a diversity of attributes which are predominantly
conditioned by culture, such as: intellectual abilities,
curiosity, vision, originality, logic and depth, artistic and
esthetic sense, wisdom, common sense, dignity, humor,
but also the ability to control and transcend one's ego.
Other major virtues of a spiritual person are tolerance,
prudence, the ability to communicate, empathy,
gratefulness, the ability to forgive and believe and respect
that which we do not understand and which does not
depend on us. This diversity of attributes of our spiritual
being represents both a source of vitality and motivation,
and a major framework of support for building self-esteem
and a sense of belonging to the energy of the universe.
They can also be said to represent a “divine calling”
(Nirestean, 2011).
In view of the above, the connection with the dominant
attributes of mental wellness becomes evident. Among
them are the self-control, the feeling of personal
detachment, the ability to communicate intelligently and
empathetically with those around you, the adaptability to
stress and resilience or responsible involvement in one's
life roles, accompanied by the ability to manage tasks
Romanian Journal of Psychiatry, vol. XVIII, No.1, 2016
which are seen as positive stimuli instead of sources of
anxiety (Kobassa, Maddi, Zola, 1983). Optimism and selfassertion- which integrates both the ability to choose a
professional option and that of developing feelings of
friendship and love, are to be added to the list of
characteristics of a mentally stable human being.
The complex notion of mental wellness also includes the
capacity to access the traditions and products of culture,
faith and religion- mystical experiences being among
those that confirm the unity of all things... A corollary of
this diverse mental health structure is the state of
subjective wellbeing with its two components, the
cognitive and the affective. This “type of happiness” is
fifty percent dependent on the quality of one's life and
circumstances, but the rest correlates in an obvious
manner to the dimensions of one's personality. Thus, high
levels of neuroticism negatively affect the subjective
wellbeing, while high levels of neuroticism stimulate it.
Low levels of neuroticism allow for the growth of
personal aptitudes and talents, and a rise in self-control.
They also diminish addictive tendencies, stimulate
vigilance, activism, empathy in interpersonal
relationships, and group cohesion due to higher
correctness and cooperation. The individual's moral
stance is also enhanced, as he or she can only become
whole and gain self-worth by being surrounded by others.
In the same context, when one is more pleasant,
conscientious and outgoing, one is more likely to be also
be drawn by meditation, the sacred, and prayer which
often enhances one's ability for self-transcendence. A
variety of spiritual experiences are enhanced, which in
their turn shape and mobilize these dimensions of the
personality.
In general, the growth in spirituality significantly
influences the individual's psyche and behavior. People
with a rich spiritual life can easily decide that God or
Heaven is with them, and thus develop self-confidence
and self-respect.
Supportive, optimistic attitudes, thus sociability sustained
by empathy and confidentiality in interpersonal
relationships, are also influenced positively. The quality
and duration of marriages grows, and in its turn favors
longevity and the quality of life. It is a well known fact that
the latter are clearly affected in people who live alone.
Efficiency and creativity are dominant behaviors, and thus
the conditions necessary to living a purposeful life are
always present. Consequently, periods of personal
satisfaction are more frequent, and existential meanings
and motivations diversify. Under these conditions, selfimage and subjective wellbeing are enhanced and
positively condition each-other and can shape narcissistic
type tendencies. Structured in this manner, they have an
obvious adaptive role to play, and create a protective
framework against various psychic episodes and illnesses
as well as behavioral disorders including suicide.
Nurturing one's talents as well as spiritual practiceincluding religious practice- have an obvious therapeutic
and rehabilitative non-medical role to play in one's
psychological state of being because they contribute to the
awareness of illness and one's attitude towards it, even in
extreme situations. It also enhances one's attitude of
compliance to therapy. This role holds true not only for the
superstitions and beliefs of proto-religions, but also under
the conditions of religious liberalism and syncretism of
contemporary society. All of the above show the
complexity of the concept of mental wellness in which the
physical person, the psyche, society and the supernatural
coalesce.
Mental health is in the end a major attribute of human
beings which is protected by the dimensions of personality
such as, emotional balance, perseverance, imagination,
common sense, wisdom, humor, faith, and the ability to
transcend by accessing the sacred and the supernatural.
This vast concept constitutes a major existential ideal, not
only because "When God wants to punish humans, He first
takes their minds away."
Mature and truly self-aware individuals sometimes ask
questions such as, "What is really important in life?";
What can help us through difficulties?"; "Where and under
what conditions do we feel good about ourselves?" "Are
we capable of true faith or aligning ourselves with spiritual
values?" For those who practice psychiatry, an exchange
of ideas and experiences with priests, monks and spiritual
counselors would certainly be of great value in answering
these types of questions.
From the perspective of spiritual values, the concept of
mental health- like the concept of personality- pleads for
the union of man, society, nature and the universe. It is
confirmed that spiritual beings have both a divine,
contemplative, profound nature, and one that is worldly,
and the union of the two can lead to all that is good,
beautiful, right, emotionally supported and open toward
transcendence in human existence. The harmony between
the two teaches us to live “with something” and not “for
something”, and gives us the freedom and authenticity
which are being so strongly challenged in our world today.
REFERENCES
1.Cook C, Powell A, Sims A. Spirituality and psychiatry.London:
RCPsych Publications, 2009
2.Prelipceanu D, Mihailescu R, Teodorescu R (sub red.).Tratat de
sanatate mintala. Vol.I. Bucuresti: Editura Enciclopedica, 2000
3.Hacking I. Rewriting the Soul: Multiple Personality and the Sciences of
Memory. Princeton: Princeton Univ.Press, 1995
4.Nirestean A (sub red.). Personalitate si deschidere spirituala. Targu
Mures: University Press, 2009
5. Lipovetzky G. Fericirea paradoxala. Iasi: Editura Polirom, 2007
6. Nirestean A (sub red.). Personalitate, credinte si religii. Targu Mures:
University Press, 2011
7. Kobasa SC, Maddi SR, Zola MA. Type A and hardiness. Journal of
Behavioral Medicine 6 (1): 41–51(1983).
***
3
REVIEW ARTICLES
THE INTEGRATIVE MODEL OF COGNITIVEBEHAVIORAL PSYCHOTHERAPY IN
PERSONALITY DISORDERS
Cosmin O. Popa1, Mihai Ardelean2, Tudor Nireștean3, Gabriela Buicu4
Abstract
In their entirety, personality disorders represent specific
clinical nosologies which affect areas of the patient's
functionality, especially in human relations. Cognitivebehavioral psychotherapy involves a number of
guidelines/ strategies, most of them benefiting from a solid
empirical support; thus, this paper deals with personality
disorders from the perspective of the general integrative
model of CBT and not from the perspective of a specific
therapeutic strategy.
Keywords: cold cognitions, hot cognitions, cognitive
restructuring, the ABCDE model, borderline personality
disorder, narcissistic personality disorder
INTRODUCTION
The current cognitive behavioral therapy
(CBT) paradigm starts from an integrative model that is
based on the scientifically proven effectiveness in the
psychological treatment of personality disorder (PD)
treatments, some therapeutic strategies being derived from
other psychotherapeutic guidelines. Thus, CBT is the
integrative framework which could facilitate the
connection between psychological and
pharmacotherapeutic treatments whenever there is
scientific support for this co-association. It however,
requires a revision of these integrative issues but it is wellknown currently that the treatment of choice of PDs is
psychological interventions (1).
Personality disorders can be defined as
sustainable patterns of some inner experiences found at the
behavioral level, which significantly contradict the
expectations of the individual, the culture to which he/ she
belongs, these models being pervasive and inflexible.
They are stable over time and occur in adolescence or early
adulthood, and are responsible for the generation of stress
and impairment (2). In terms of the model of cognitivebehavioral psychotherapy, personality disorders are
associated with a dysfunctional pattern of thinking based
and particularly influenced by dysfunctional beliefs/
cognitive schemas, manifested at the behavioral level by
difficulty in adapting and in relationships (3) (4) (5). The
central beliefs that occur in PD are specific patterns of
thinking derived from the negative interaction of the
patient and their genetic background with the
disadvantaged physical environment in which the
individual has evolved (6). Early maladaptive schemas
(EMSs) are based on the dysfunctions that occur at one or
more levels specific for attachment or development of the
individual's own identity since childhood, and which occur
in adulthood in a latent/ manifested way mainly in PDs,
being biologically determined (by temperament) (7) (8)
(9) (10) (11) (12).
There are several strategies/ therapeutic
guidelines that make up CBT, some representing new
psychological methods, there already being empirical
support that demonstrates effectiveness in the treatment
of PDs (13) (14) (15). In terms of comorbidity between
PD and a disorder from the non-psychotic psychiatric
range, the result of the intervention CBT is as effective as
in the case of the unique non-psychotic psychiatric one,
especially in the case of co-occurrence between PDs and
disorders of anxiety/ depression (16).
Clinically, PDs are worsening and
maintaining factors of disorders from the field of
psychopathology, but this depends on the specificity and
intensity of the PD (17). The complexity of these cases
required finding methods and techniques to complement
the standard intervention intervention of CBT so that
together with psychopharmacotherapy the clinical picture
can be improved by the flexibility of maladaptive
thinking schemas and the change of some maladaptive
behaviors (18).
THE INTEGRATIVE MODEL OF COGNITIVEBEHAVIORAL THERAPY
Most cognitive theories are based on the
assessment of the so-called “cold cognitions”
(descriptions/ inferences – e.g. “They are glaring at me
and want to hurt me”), namely, what a person thinks in a
difficult life situation about that particular situation, and
under that assumption negative feelings arise because of
these cold cognitions. This is only a half-truth, since “hot
cognitions” are actually responsible for generating
negative emotions, more precisely the significance a
patient attaches to “cold cognitions” (e.g. “I need to be
appreciated by people and it is catastrophic if they want to
hurt me”). Thus, if a patient with avoidant personality
1
Lecturer, PhD, Clinical psychologist, CBT Psychotherapist, The Department of Ethics and Social Sciences, The University of Medicine and Pharmacy of
Tîrgu Mureș, Romania.
2
PhD, MD, Senior in psychiatry, Mental Health Center of Tîrgu-Mureș, Romania.
3
Assistant professor, PhD student, MD, resident in psychiatry, The Department of Ethics and Social Sciences, The University of Medicine and Pharmacy of
Tîrgu Mureș, Romania.
4
Lecturer, PhD, MD, Specialist in psychiatry, The Department of Psychiatry, The University of Medicine and Pharmacy of Tîrgu Mureș, Romania.
Corresponding author: Tudor Nireștean, Assistant professor, PhD student, MD, University of Medicine and Pharmacy of Tîrgu Mureș, Str. Gheorghe
Marinescu nr. 38, 540142, Tîrgu-Mureș, Romania, e-mail: tudornirestean@gmail.com
Received January 29, 2016, Revised February 29, 2016, Accepted March 17, 2016
4
disorder has an automatic negative thought in a social
situation, such as: “others will laugh at me” (cold
cognition), it is not the thought that causes anxiety but the
significance that the person gives to the thought: “if they
laugh at me, others will reject me and this is an unbearable
and unacceptable thing” (hot cognition) (19) (20) (4).
Both automatic negative thoughts (surface) and
maladaptive cognitive schemas (depth) refer to/ include
both hot and cold cognitions, which may occur in one of
the two forms (1).
The application of cognitive techniques combined with
behavioral and relaxation one, but mainly the focus of the
therapist on modifying hot cognitions, belonging to
Cluster C in PD, will result in modification and flexibility
of some dysfunctional beliefs, which contributes to
remission of comorbidities and to the change of some
maladaptive behaviors (21) (22). There are cases in which
PDs have a unique, complex, and high intensity specificity
(such as Borderline PDs) so that identifying and changing
dysfunctional cognitions (hot cognitions) requires a
completion through the use of experiential techniques.
This is due to the fact that in severe personality disorders
causality implies traumatic life events such as sexual/
emotional/ physical abuse in childhood (23) (24).
In the case of such PDs, a storage of traumatic
memories in the amygdala is determined by a mechanism
similar to posttraumatic stress syndrome, as well as a
storage of cognitive traumatic memories in the
hippocampus and neocortex (11), these being mediated by
the prefrontal cortex. In such cases, CBT is effective on
the one hand because of the inhibition of the response of
the amygdala that generates negative emotions associated
with trauma and which bypass the cognitive system and
reasoning, and on the other hand because CBT boosts the
response of the prefrontal cortex (PFC), cognitive
restructuring having the purpose of alleviating
dysfunctional cognitions related to trauma, since the
activation of the dorsal prefrontal cortex (DPFC) causes a
decrease in activation of the amygdala. This implicitly
suggests that the cognitive conscious processes have a role
in emotional regulation (25) (26) (27).
As a result, experiential, gestalt, mindfulness
techniques and those which address the relationship of the
object, cognitive-behaviorally conceptualized, may
contribute to increased therapeutic efficacy in PDs,
especially when the patient has a history of a trauma or
psychotrauma in early childhood. The effectiveness of
these techniques is given by the direct approach to early
trauma using imagery and role-play, and by associated
cognitive restructuring in order to increase the flexibility
of dysfunctional beliefs with the aim of determining
phenomena of awareness in these patients (28) (29). The
resulting therapeutic benefits that stem from cognitive
restructuring and awareness are essential in the process of
changing maladaptive behaviors in PDs. Theory and,
primarily, clinical practice indicates that, generally, PDs
are egosyntonic, the patients are not aware of a multitude
of reactions and maladaptive behaviors that they have in
different life situations (30) (31). Due to this egosyntonic
character, in terms of cognitive theory, we might consider
that some of these types of behavior are determined by
unconscious information processing (32). Identifying
unconscious beliefs along with the conscious ones during
the therapeutic process contributes to: 1) determining
cognitions/ beliefs/ dysfunctional cognitive schemas
associated to specific PDs (33), 2) flexibilizing them
through cognitive restructuring techniques, 3) the
assumption of adaptive thought patterns (34).
In designing the treatment plan specific for
CBT, the PD conceptualization of the case has to include a
causal/ inter-determination relationship of the stressors
such as negative life events (triggering stimuli) and
maladaptive cognitive schemas of the patient (which also
include biological vulnerability). This interdependence
determines the cognitive, subjective/ emotional, and
behavioral symptomatic manifestations in these patients
(35).
Conceptualization in PDs is important because
the patient thus understands the causes and manifestation
manner of their psychological problems; this is essential in
establishing the therapeutic goals together with the
patient. Especially in PDs, a correct conceptualization is
done after at least three sessions of clinical psychological
evaluation. From a psychometric point of view, the most
useful instrument to identify the PD is SCID-II, Structured
Clinical Interview, the degree of validity of this instrument
being directly proportionate to the therapist's clinical
experience (21).
A model of conceptualization that can be
applied simply and effectively in PDs (but also in other
psychopathological disorders) is the ABC (DE) model.
Hyland, and Boduszek (2012) citing Ellis (1958, 1962,
1994), David and Freeman (2015), David et al., (2010)
have shown that the ABC model can describe
psychopathology in that cognitions are considered
determinants of emotional, behavioral, and attitudinal
reactions of a patient. In other words, when a person
relates themselves to negative life events (A) through a set
of central irrational beliefs (cognitive B-schemas: “I value
nothing as a human”) he/ she will generate surface
dysfunctional beliefs (B-automatic thoughts: “I will not
succeed”) which then support the dysfunctional negative
emotions and maladaptive behaviors (C). Identifying
these irrational beliefs/ central and surface dysfunctional
thoughts and their debate/ change (D) contributes to
replacing them with rational/ alternative beliefs, which
clinically contributes to the remission of the disorder and
adopting a style of thinking effectively and rationally (E)
(1) (36) (19).
In PDs, this model must be completed and
insisted on more, particularly on the relationship between
B (beliefs) and C (consequences). Due to cognitive and
dysfunctional behavioral patterns, it is necessary to
complete the ABCDE model, where D (discussion/
modification) may be supplemented by cognitive
diffusion techniques and E by changing the relational
framework. Even if diffusion cognitive techniques appear
to some extent in cognitive restructuring specific for
traditional CBT (37), in the case of PDs they should be
applied systematically. This is due, for example, to the
thought-action fusion phenomenon that usually occurs in
obsessive-compulsive disorder (OCD) (38), but also in
several other PDs (31). Hence, a patient with comorbid
OCD may think: what if I am going to hurt children? This
thought (assessed by hot cognitions “I must not hurt them
and it would be catastrophic if I harmed them”) triggers
feelings of anxiety because for the patient thinking is
synonymous with acting. Cognitive diffusion will focus
5
Cosmin O. Popa, Mihai Ardelean, Tudor Nireștean, Gabriela Buicu: The Integrative Model Of Cognitive-behavioral
Psychotherapy In Personality Disorders
on the separation of the thought of event/ the person itself,
the way semantics can influence the development of
dysfunctional negative emotions being already
demonstrated (39) (40), the patient regarding it as a mental
construct, stringing phrases, etc., that is, the patient is
taught not to identify themselves with the thought or the
thinking process.
Also, another effective technique in these patients is
framework changing/ relational context. With its aid, the
patient with PD acquires coping adaptive mechanisms that
help them learn to accept themselves as a person, to realize
that thoughts are just thoughts, to live the present moment
and to define the values of life, all of these being the
attributes that belong to a psychological flexibility (41)
(42).
Generating change in patients with PD is not
achieved by using the therapeutic relationship as a
framework for change, but by applying an ABC
conceptual model in which the autobiography/ life history
of the patient is brought to date “here and now” and faced
with the current issue of the patient's life. For example, a
patient with a narcissistic/ passive-aggressive PD can
develop hostile behavior toward the therapist. In that
particular moment, using the Socratic dialogue technique
(asking questions the answer to which is mostly known by
the therapist) the patient is asked “please let me know
when, in your entire life, you have felt something
identical, how you are feeling toward me/ behaving with
me now (hostile feelings), or more precisely under what
circumstances?” Reference to similar events in the history
of life and reporting to the present with subsequent
extrapolation through the same ABC model to a problem
that is present in the patient's life makes them understand
the source of their problems and thus generate change by
changing irrational beliefs/ dysfunctional thoughts (43).
Another important aspect of CBT intervention
in PDs will be based on the autobiographical versus
semantic cognition model (19). Perhaps more than in any
other psychiatric condition, in PDs cold/ hot cognitions
affect autobiographical memory, which in turn changes
the sense of semantic cognitions. For example, cold
cognition in narcissistic PD: “I am special and others must
respect me” is related to semantic memory and is
interrelated with it. Thus, hot cognition is associated with
semantic cognition and determines: “It is terrible and
unbearable not to be respected” (as cited by David, 2003)
(44). This dysfunctional type of thinking specific to PDs is
determined by maladaptive cognitive schemas which,
through the bio-psycho-social tendencies they
incorporate, influence the behavioral and attitudinal
patterns of the patient. Confronting these schemas in PDs
can be done both in a cognitive way and through
(experiential) imagery with the purpose to change some of
the maladaptive behavioral patterns (45) (46) (47).
Mindfulness techniques can also be used, but caution is
advised in their implementation, particularly because of
excessive detachment of the patient from life events,
which prevents them to confront their own schemas due to
decreased motivation (48).
Since behavioral techniques consist of
exposure to the anxiogenic stimuli and behavioral
experiments, they can be implemented by combining
them with cognitive techniques, first by exposure in the
psychotherapist's office (in-vitro), followed by gradual
6
exposure to real anxiogenic stimuli (in-vivo) (49) (50).
CONCLUSIONS:
CBT interventions in PDs require a holistic approach in
which treatment involves customization depending on the
particularities and specificities of the PD so that the
therapeutic plan for these complex cases be based on a
multimodal approach. The ABC model is defining both in
terms of psychopathological conceptualization, and in
terms of the therapeutic intervention itself, focusing on the
application of a “bridge over time” in which the patient's
past problems are brought to the present, the change thus
being generated by modifying irrational beliefs “here and
now”. It is necessary that the scientific support as known
to date be supplemented with other studies that have
immediate clinical application, this relieving the
pathology associated to PDs and improving the
relationing of these patients.
ACKNOWLEDGEMENTS:
We are thankful to Prof. Daniel David, Babeș-Bolyai
University of Cluj-Napoca, Romania, associate professor
at the Icahn School of Medicine at Mount Sinai, New
York, USA, Research Director of the Albert Ellis Institute,
New York, USA, for his supervision and the papers with
which he provided us in writing this article.
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***
7
REVIEW ARTICLES
DEPRESSION SCREENING AT THE PRIMARY CARE
LEVEL – A COST-EFFICIENT INTERVENTION
Raluca Ileana Nica1, Mihail Cristian Pîrlog2
Abstract:
Over 350 million people worldwide suffer from
depression, and it is one of the leading causes of disability
across the globe (1, 2, 3, 4, 5). In Europe, approximately 21
million people are affected by depression out of a
population of 446 million people. Depression places a
burden not only on individuals but also on the society due
to its impact on health, social and economic systems.
Depression accounts for 1% of the GDP of Europe (8), and
amounted to approximately 118 billion euros, which
translates to approximately EUR 253 per inhabitant (8).
Given the magnitude of the burden of depression, there is a
need for efforts to be directed at early identification to
improve recovery and enhance treatment outcomes and
ideally, to prevent depressive symptoms from developing
into a clinical depressive episode. Depression is
considered as a common mental health disorder (CMHD)
given its high prevalence and many people presenting with
depressive symptoms often seek care from their primary
care physician or general practitioner first, making the
general practitioner an ideal gatekeeper for screening and
detection and management of depression (6, 7, 26).
Screening for depression at the primary care level can
have a significant impact on early recognition and
treatment, prevention of the development of more severe
forms of depression, better adherence to treatment of
chronic conditions, enhancement of recovery outcomes
and consequently on the associated costs. According to the
studies, despite the high prevalence of depression and the
fact that many people experiencing depressive symptoms
first come into contact with the health system through their
primary care physicians, depression is in fact only
identified in 30-50% of instances by primary care
professionals (27,34). Early intervention is key as previous
research shows that 20% of people who committed suicide
visited a primary care physician in the month preceding
the suicide (12, 35). The purpose of this review is to search
based on the existing studies what are the
recommendations regarding depression screening at the
primary care level. At present, at the international level
based on the existing studies is not a uniform opinion about
recommending the screening at the primary care level for
depression and about the criteria to be met for the
depression screening at the primary care level that could
lead to a cost-efficient intervention. It is still incipient the
research regarding the efficiency of this intervention and
the conditions in which it becomes cost-efficient.
Key words: depression, screening, primary care
The prevalence of depression regardless of
severity among the general population ranges between 8%
and 12% (24, 25) depending on the methodological
approach and scales used to classify depression, while the
prevalence of major depression at the primary care level is
5-10% (23, 24, 32). Of the number of people presenting
with depression in primary care, approximately 10-20%
have a comorbidity with another non-communicable
disease such as diabetes mellitus, cardiovascular disease,
or cancer (23, 42). Given the high prevalence of depression
and given that the patient first access the primary care
services, as in most of countries, Romania being one of
them, GP's are the main gatekeeper for a multitude of
health problems, including mental health problems, and as
they often have many tasks and a high caseload, they
require easy to use, quick and effective screening tools that
help them be confident in identifying depression and
taking action on it.
Depression screening usually implies the administration of
questionnaires to people presenting with depressive
symptoms by primary care staff (physicians or primary
care nurses). Questionnaires can either be self-report or
administered by a physician or nurse, having a small or
medium number of questions the can be self-administered
or can be administered by the family doctor both to the
patients with high risk for developing depression such as
patients with chronic illness diagnosis (10, 36) but also to
the other patients. One of the questionnaires that is
frequently used by the primary care physicians to detect
depression is patient health questionnaire 2 (PHQ - 2),
that contain 2 questions namely: Over the last 2 weeks,
how often have you been bothered by any of the following
problems? 1.During the past month, have you often been
bothered by feeling down, depressed, or hopeless?
2.During the past month, have you often been bothered by
little interest or pleasure in doing things? The possible
answers for each of questions are: Not at all (scoring 0),
several days (scoring 1), several days (scoring 1), More
than half the days (scoring 2) and Nearly every day
(scoring 3). The total scoring ranges from 0 to 6, the
authors (44) identified a PHQ-2 score of 3 as the optimal
cut point of the screening purposes and stated that a cut
point of 2 would enhance sensitivity and a cut point of 4
would enhance specificity. These two verbal questions
have also the advantage that are concise and detect the
majority of the depression cases (31). The purpose of the
questionnaire is to enhance routine inquire about the most
prevalent and treatable mental disorder in primary care.
The National Institute for Health and Care Excellence
(NICE) (15) recommended in the depression guideline
that the entire population should be screened for
depression at the primary care level, done with the PHQ -
1
PhD Student, “Carol Davila” University of Medicine and Pharmacy Bucharest
PhD, Lecturer at department of Psychiatry, University of Medicine and Pharmacy of Craiova
Received February 26, 2016, Revised February 29, 2016, Accepted March 17, 2016
2
8
2 questionnaire (15), which has a sensitivity of 97% (95%
CI, 83% to 99%) and a specificity of 67% (95% CI, 62% to
72%) (31,43). A person responding yes to both of the
PHQ-2 items is referred for a more in-depth assessment at
the specialized level services. The probability rate for the
screening to be positive when done with this two questions
was 2.9 (2.5 to 3.4), and the probability rate for the
screening to be negative was 0.05 (0.01 to 0.35) (31).
At present, at the level of European and international
clinical guidelines there is no agreement with regards to
the efficiency of the depression screening at the primary
care level (13,14,15,16,18,20,21,23,27,43,44). This is a
consequence of the fact that there are not enough
randomized control trials that could provide the necessary
evidence regarding its efficiency when done at the general
level of the population as well as when done for high-risk
target groups. In addition, there is a concern regarding the
unjustified increase of the number of patients that due to
the false positives arising from tools, resulting in clients
being sent to specialised care when in fact it is not required
(27). On the other hand, studies of primary care patients
have found that health care costs are higher in depressed
patients than non-depressed in many categories, including
primary care visits, medical specialty visits, lab tests,
pharmacy costs, inpatient medical costs, and mental
health visits (8, 9). To illustrate, one study conducted in
England found that patients diagnosed with depression in
Great Britain show that patients diagnosed with
depression have costs two time higher ($4246 vs $2371, P
< .001) compared with the ones that are not diagnosed, this
situation remaining similar one year after the initiation of
antidepressant treatment ($3971 vs $2644 (28). However,
there is still a need to understand how big this problem is:
is it more of a cost risk that more people get referred to
specialized care when in fact they could be managed in
primary care, or more of a problem if people go undetected
completed in primary care which is more of an ethical and
low quality of life problem.
There are a number of aspects that should be taken into
account when doing depression screening which could
influence the result of screening and its cost-effectiveness.
In order to recommend the screening as a cost-effective
intervention at the primary care level there are some
criteria which need to be met (23):
1)Patients who do not have this diagnosis agree to do the
screening (29)
2)A relatively high number of positive results of screening
are obtained (29)
3)Agreement of patients who screen positively to access
the specialized services for supplementary evaluation that
would validate/invalidate the initial result
4)Reasonable accessibility of the patients to the
specialized services (33), patients from rural and isolated
areas being disadvantaged
5)A relatively high number of false positive results of
screening are obtained (29)
6)Patient agreement for depression treatment one the
depression diagnosis was confirmed (29)
7)For the treatment adherence psycho-education services
are offered (37), knowing that there is an attrition rate
from treatment of 70% in the first three months (38,39),
while clinical guidelines recommend that depression
treatment lasts between 6 months and one year (37)
8)Accessibility to psychological interventions such as
cognitive behavioural therapy (40,41), according to the
recommendation of the NICE clinical guidelines (15).
An overview of the criteria listed above, leads to the
conclusion that a screening program in order to be costeffective has to take into consideration at least three
essential aspects: a relatively high number of positive
results of screening, a relatively low number of false
positive results of screening and the accessibility to
specialized services that can provide evaluation and
comprehensive treatment (medication, psycho-education,
cognitive behaviour psychotherapy) and a possibility for
accomplishing these aspect is the integration of
specialized services in primary care (20).
As a consequence, it is important that randomized
controlled trials focused on screening for depression at the
primary care level specify the criteria for
inclusion/exclusion for screening, patients' randomization
and the patients' accessibility of specialized services after
getting a positive screening result.
Some previous research studies have found that
depressive symptoms do not change much as a result of
screening done at the primary care level. To illustrate, a
2008 Cochrane systematic review (28) evaluated five
randomized controlled trials and found that there is no
evidence of a reduction of depressive symptomatology in
the general population as a result of depression screening
in primary care settings without substantial staff-assisted
depression care supports. In another research study from
the Netherlands depression screening was done on a
sample of 1687 patients with a high risk of developing
depressions through a questionnaire sent by mail. Out of
the 770 patients that returned the questionnaire filled in,
226 (29%) showing a positive result for depression, only
17 (1%) initiated depression treatment (22).
A research study done by a Spanish group of researchers
(19,21), study that respected the randomization criterion
and the cluster of patients screened consisted of patients
with high risk for developing depression such as those
with a depression history, those with somatic symptoms
that are not caused by somatic illness and those with
psychological comorbidities due to somatic illnesses and
those with drug and alcohol abuse, the result showing that
the depression rate 6 month after screening (15%) (21)
was not different to the one in the control group (15,8%),
(average mean difference − 0.02 and confidence interval
95%−0.25 la 0.20) (18). In contrast, the American clinical
guideline for depression (46) reviewed 9 randomised
controlled trials and concluded that screening for
depression is cost-efficient in the context of integrated
primary care and specialized services but inefficient in the
absence of the services' integration (17,30).
In sum, there seems to be mixed results supporting the
notion of screening for depression at the primary care
level. More research is needed for shading light on the
efficiency of recommending the depression screening in
the primary care services (11) and if this should be
recommended to general population or only to indicated
risk groups.
Conclusions:
At present there is insufficient evidence that universal
screening for depression at the primary care level is
beneficial from a cost-effectiveness or detection and
treatment point of view. That being said, primary care
professionals should still be aware of the following two
groups of patients presenting in primary care that should
be screened further for depressive symptoms:
9
Raluca Ileana Nica, Mihail Cristian Pîrlog: Depression Screening At The Primary Care Level – A Cost-efficient
Intervention
1.Group of patients with high risk of developing
depression due to a previous diagnosis of depression,
presence of a chronic illness, a family history of
depression, unexplained somatic symptoms, traumatic
life events and those that have a frequent utilization of
services without a resulting diagnosis.
2.Patients who present with depressive symptoms such as
little pleasure or interest in doing things, feeling hopeless,
chronic fatigue or insomnia.
The RCTs done up to now have inconclusive results with
regards to the reduction of depressive symptoms and
disappointing due to low percentage of people who accept
to initiate the depression treatment, after being screened
and diagnosed with depression at the primary care level.
The absence of the research studies to demonstrate the
cost-efficiency of universal screening for depression at the
primary care level leads to the necessity that more
research need to be developed in this direction, studies that
should include more than the screening itself but also
include the screening instruments, criteria for screening
and treatment.
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***
REVIEW ARTICLES
CLINICAL STUDY OF THE MENTATION,
BEHAVIOR AND MOOD DISORDERS IN
PARKINSON'S DISEASE
Iordan Ganev1, Toni Donchev1, Krasimir Kostadinov1, Velina Mancheva-Ganeva2,
Lachezar Manchev3, Ivan Manchev2, Mihai Pirlog4, George L. Paraschiv4,
Ruxandra C.M. Banu5, Traian Purnichi6
Abstract:
Introduction: Parkinson's disease is a general
invalidating neurodegenerative disease. The impaired
non-motor functions are well recognized as part of the
clinical course of the disease with great impact over the
quality of life of the patients. On the other hand, they are
highly unrecognized by clinicians and pose great
difficulty in detection and measurement. The UPDRS is
widely used to assess and follow up PD patients and
Part I is used to assess non motor functions such as
mentation, behavior and mood disorders. Therefore, we
used it in our study for the assessment of the prevalence
of the non-motor symptoms measured by UPDRS Part I
in PD patients. Objective: To show that there's high
prevalence of mentation, behavior and mood disorders
as measured by UPDRS Part I in PD patients. Methods:
293 patients with Parkinson's disease (129 men and 164
women) aged 58-79, randomly picked for an 8-year
period (2005-2012) were studied. The study used the
following assessment tools: І. Unified Parkinson's
Disease Rating Scale; Modified Hoehn and Yahr scale
for assessment of clinical symptoms; Schwab and
England Activities of Daily Living Scale. Statistical
methods for processing the data received – SPSS
statistics software with analysis of variances and
alternates was used. Results: The mentation, behavior
and mood functions were studied in 293 patients
diagnosed with Parkinson's disease. Lack of
motivation/initiative was most frequently observed – in
245 patients (83.6%), followed by depression – in 200
patients (68.2%)and memory disorders – in 199 patients
(67.9%). Thought disorder was the least frequent
(26.9%). As a result of these disorders all patients had a
considerably reduced quality of life mainly due to the
development of significant cognitive impairment.
Conclusion: This results confirm the observation that
mentation, behavior and mood dysfunctions are a highly
prevalent and important feature of PD. Therefore,
treating physicians should look for them routinely. The
UPDRS showed that it is sensitive and reliable tool for
detecting such symptomatology.Key words: Parkinson's
disease, depression, UPDRS, cognitive impairment
INTRODUCTION
Parkinson's disease (PD) is a complex neurodegenerative
condition manifested by characteristic motor impairment
and a wide array of non-motor symptoms (NMS) (1, 2).
Recently, sleep, fatigue, mood, cognition, pain and
autonomic disorders have been recognized as important
components of the disease, with a consistent impact on
patients' health and quality of life (3, 4, 5, 6, 7). Despite of
these problems and the high burden of NMS in most
patients (4, 8) NMS remain frequently neglected (9) or
undocumented (10). NMS thus present one of the biggest
challenges for management by the clinician and a
comprehensive assessment that includes NMS as well as
motor state of the patient is essential (11). NMS can be
assessed by several tools specifically designed for these
symptoms, including the NMS questionnaire
(NMSQuest)(12), the unified PD rating scale
(UPDRS)(13) and the PD sleep scale (PDSS) (14).
Pathophysiological, NMS may be related to both
dopaminergic and non-dopaminergic alterations. For
example, PET studies reported dopamine dysfunction at
the hypothalamus (15). Degeneration of cholinergic,
adrenergic or serotoninergic pathways could also
contribute to NMS genesis (16). Moreover, NMS can
precede motor symptoms and thus PD diagnosis (17).
Some studies suggest that NMS are common in all stages
of PD and more common as the motor symptoms
progression regardless of age of onset, levodopa dosage
or disease duration. The most prevalent NMS in this study
were highly similar to other previous international studies
using the 30-item NMSQuest (18, 19 and 20). Non-motor
symptoms dominate the clinical picture as PD progresses
and may also contribute to shortened life expectancy (2,
21). Most do not respond to, and may be exacerbated by,
dopamine replacement therapy (22). NMSs also account
for the burden of hidden costs such as sick leave, early
retirement and informal care not only for patients but also
for caregivers in certain instances. The cost burden of
NMSs is significantly high, especially in patients with
advanced PD and increasingly severe symptoms, for
which there is a poorer quality of life, reduced
productivity and a greater need for health-care services,
which in turn have an impact on direct and indirect costs.
Thus, identifying disease-modifying treatments early in
1
Clinic of Psychiatry, Military Medical Academy, 3 Sveti Georgi Sofiiski Street, 1606 Sofia, Bulgaria, Phone: +359898535610, E-mail: bestar@abv.bg
Dep. of Neurology and Psychiatry, Trakia Faculty of Medicine, Stara Zagora, Bulgaria
Dep. of Physics, Biophysics, Roentgenology and Radiology,Faculty of Medicine, Stara Zagora, Bulgaria
4
University of Medicine in Craiova
5
National Institute of Geriatrics and Gerontology of Bucharest
6
Alexandru Obregia Psychiatric Hospital in Bucharest
Received November 19, 2015, Revised January 11, 2016, Accepted January 31, 2016
2
3
11
Iordan Ganev, Toni Donchev, Krasimir Kostadinov, Velina Mancheva-Ganeva, Lachezar Manchev, Ivan Manchev,
Mihai Pirlog, George L. Paraschiv, Ruxandra C.m. Banu, Traian Purnichi: Clinical Study Of The Mentation, Behavior
And Mood Disorders In Parkinson's Disease
the disease, before any functional or motor disability
appears, is critical in reducing costs and preserving quality
of life. Evidence suggests that initial therapy with nonlevodopa agents is cost-effective, prolongs time to
levodopa initiation and delays the onset of dyskinesia
(23).
There is a significant interrelationship of severity of
disease, quality of life, patients and caregiver's burden,
and cost of illness. NMSs contribute to the overall PD
burden, which is a major determinant of quality of life. An
increasing awareness of 'at-risk' individuals, based on
detection of some or a combination of NMSs, is essential
for an early identification of PD patients. Identification of
prodromal patients plays a key factor in preventing the
burden of economic costs and improving quality of life of
patients and caregivers. Keeping this in mind, it becomes
important to optimize the management of all aspects of
NMSs in PD (24). Therefore we conducted our study to
evaluate the high prevalence of non-motor symptoms in
PD patients, particularly those measured by UPDRS Part I
as it is one of the most used clinical scales in PD and thus
with great clinical significance.
OBJECTIVE
To show the high prevalence of mentation, behavior and
mood disorders as measured by UPDRS Part I in PD
patients.
MATERIAL AND METHOD
293 out patients with PD (129 men and 164 women) aged
58-79, all retired due to illness (PD), randomly selected
in terms of different PD stages for an 8-year period (20052012) were investigated after the inform consent was
signed. They were outpatient recruited from a PD center
of Department of Neurology and Psychiatry. The patients
received L-DOPA, dopamine agonists and antioxidants.
The same team member who performed the clinical
diagnosis also applied the scale. The patients have not
been researched for concomitant illnesses. The study used
the following assessment tools:
І. Unified Parkinson's disease Rating Scale (UPDRS) Part I: evaluation of mentation, behavior, and mood.
UPDRS is the most used scale to follow the longitudinal
course of PD. (16, 17)
ІІ. Modified Hoehn and Yahr scale for assessment of
clinical symptoms;
ІІІ. Schwab and England Activities of Daily Living Scale;
Modified Hoehn and Yahr scale for assessment of clinical
symptoms and Schwab and England Activities of Daily
Living Scale are parts of UPDRS, but are mentioned
separately because were used alone in the process of
diagnosing the disease. The complete UPDRS was used
latter for the measurement of the progression of the
disease.
IV. Statistical methods for processing the data received
–SPSS 11 software with analysis of variances and
alternates was used.
RESULTS
MENTATION, BEHAVIOR AND MOOD.
1. Intellectual Impairment. That symptom was observed
in 199 patients (67.9%). No significant gender-related
differences were found. From Part 1 of UPDRS the item 1
- “light consistent forgetfulness with partial recollection
of events” and the item 2 – “moderate memory loss with
disorientation to time and often to place” were
considerably prevalent as compared to the item 4 “severe
memory loss with orientation only to person” (p<0.05%)
(Table 1).
2. Thought disorder. Thought disorder was found in 79
patients (26.9%). The item 2 - “benign hallucinations
“with retained insight was most frequently observed. The
item 3 – “Frequent hallucinations or delusions were
almost equally frequent. Then came the item 1 - “vivid
dreaming”, while persistent hallucinations and delusions
were the least frequent. No significant gender-related
differences were found (Table 2).
3. Depression (depression symptoms) the item 2 –
“sustained depression, lasting more than a week was the
most frequently observed in both genders. It was found in
90 patients (30.7%), followed by the item 1 – “periods of
sadness and guilt”. Their values increased significantly as
compared to the item “long-term depression with
vegetative symptoms and suicidal thoughts or intentions”
(p<0.05%) (Table 3).
12
4. Motivation/Initiative. Lack of motivation and loss of
initiative were most frequent among the PD patients.
Those symptoms were found in 245 patients (83.6%).
They were less assertive and more passive. Complete loss
of motivation was the least frequent, the low results being
statistically significant as compared to the milder
impairment stages (p<0.01%) (Table 4). Apathy was
observed in 54% of the patients diagnosed with mild to
moderate PD related depressive symptoms
CONCLUSIONS:
This study showed moderate to high prevalence of nonmotor neuropsychiatric disturbances in patients with PD
in different stages of the disease as measured by the
UPDRS Part I. This confirms that they are important part
of the disease. Therefore, treating physicians should look
for them routinely in their effort for the improvement of
quality of life in patients with PD. The UPDRS showed
that it is sensitive and reliable tool for detecting such
symptomatology.DISCUSSIONS:
As PD is a multidimensional disorder, the disease
progression and treatment efficacy should be assessed not
only through motor symptoms but also through
psychopathological and autonomic symptoms. The
Unified Parkinson's Disease Rating Scale (UPDRS) was
developed as a brief, valid, and reliable scale for the
assessment of activities and non-motor symptoms in PD
and has replaced many of the older assessment scales. (25,
26) Cognitive disorders in PD consist first of an
intellectual slowing and difficulties to organize and
manage the intellectual capacities, with preservation of
global cognitive efficiency for long time.(27) Eventually,
these disturbances can increase with the time and even
progress to dementia. It is important to distinguish mild
cognitive impairment from dementia, the latter being
present only in a moderate percentage of PD patients. Our
results revealed high prevalence of intellectual
impairment (67.9%) as measured by the UPDRS which
underlines the significance of its early recognition.
Hallucinations occur usually in a normal state of
consciousness, without delirium, and have a chronic
course. (28) The prevalence of complex visual
hallucinations ranges from 22 to 38%.(29) Risk factors for
hallucinations are older age, long duration of the disease,
cognitive impairment, severity of PD symptoms, sleep
disorders (somnolence), and visual disorders. (30) Risk of
psychotic symptoms is increased in late onset PD, in
patients taking high doses of dopaminergic drugs and
suffering of REM sleep behavior disorder (RBD).
Hallucinations must be identified by systematically
questioning the patient.
Visual hallucinations are surprising, but their intensity is
quite variable. Benign hallucinations are limited to
presence sensation, passing lights or visions at periphery
of the visual field, with great tolerance by the patient. (31)
Our results showed moderate frequency of thought
disorder in our study population. Thought disorder was
found in 79 patients (26.9%) and the item “benign
hallucinations “with retained insight was most frequently
observed.
Depression occurs at any stage of the disease, even at the
beginning or sometimes many years before the onset of the
disease. (32) Depression can occur in up to 27.6% of PD
patients during early stages of the disease.(33) Depression
may consist in major depressive disorder (17%), minor
depressive disorder (22%), and dysthymia (13%), and
clinical significant depressive symptoms are present in
35% of PD patients. (34, 35) Our results show that the item
“sustained depression, lasting more than a week” was the
most frequently observed in both genders. It was found in
90 patients (30.7%) in our study sample.
Apathy consists in a loss of motivation, which appears in
emotional, intellectual domains and in the behavior. For
the diagnosis of apathy, the decrease of spontaneous
acting must not be imputable to motor disability, nor to
severe cognitive decline. (36, 37) Indeed, this
neuropsychiatric symptom is frequent, with a prevalence
of 30% to 40% in PD patients. (38, 39) Apathy is one of the
major determinants of a reduced quality of life in PD, (40)
even at early stages. As such, early diagnosis and efficient
therapy are important in order to avoid further
consequences on quality of life and disability. Lack of
motivation and loss of initiative were most frequent
13
Iordan Ganev, Toni Donchev, Krasimir Kostadinov, Velina Mancheva-Ganeva, Lachezar Manchev, Ivan Manchev,
Mihai Pirlog, George L. Paraschiv, Ruxandra C.m. Banu, Traian Purnichi: Clinical Study Of The Mentation, Behavior
And Mood Disorders In Parkinson's Disease
among the PD patients. Those symptoms were with high
prevalence in our study sample and was found in 245
patients (83.6%).
ACKNOWLEDGEMENTS:
All the authors had an equal contribution and have
similar rights. All the authors approved the final version of
this article.
DISCLOSURES:
The authors report no conflict of interest for this
article.
LIST OF ABBREVIATIONS:
PD – Parkinson's disease
UPDRS - Unified Parkinson's disease Rating Scale
MMSE - –MiniMental State Examination
МОСА - Montreal Cognitive Assessment Scale
MCI - Mild Cognitive Impairment
NMS – Non-motor symptoms
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***
ORIGINAL ARTICLES
EVOLUTION OF SYMPTOMATOLOGY AND
FUNCTIONALITY OF ROMANIAN PATIENTS
WITH MAJOR DEPRESSIVE EPISODE IN A
COHORT OBSERVATIONAL STUDY
Valentin P. Matei1, Victor Marinescu, Eda M. Ciorabai, Ileana Marinescu,
Lavinia Duica, Mihai Pirlog3, George Paraschiv3, Ioana G. Pavel, Alexandra Dolfi5,
Diana A. Mihalache5, Iulia A. Mitea, Diana Mihalcea5, Mihnea Manea5,
Ana Giurgiuca5, Mihai Bran5, Bogdan Stania3, Traian Purnichi5, Dan Prelipceanu1
Abstract:
Background: Depression is a common and disabling
psychiatric condition which cause substantial impairment
in daily functioning and increases the risk for both social
and physical disability, and as a result, increases the costs
for other medical services.
Objectives: The study aims at underlining particularities
regarding the evolution and functionality of patients with
major depressive disorder (MDD) under Agomelatine
treatment. The most important objectives were to evaluate
the daily functionality in MDD patients under treatment,
the evolution of the symptomatology and treatment
adherence.
Methods: We included in a prospective, observational and
longitudinal study 1194 patients with depressive episode,
who were assessed with Clinical Global Impressions Scale
(CGI scale) and Quick Inventory of Depressive
Symptomatology Scale (QUIDS-C16), in order to perform
a correlational analysis.
Results: In this study, the target group had a moderate
symptomatology (depressed mood, loss of concentration,
anhedonia) and had a good evolution from the second
week of treatment and a considerable improvement of
anhedonia after 10 weeks of treatment.
Conclusions: The antidepressant treatment with
Agomelatine was considered efficient and safe, with an
important improvement of the symptomatology after 10
weeks of treatment, a good treatment adherence and
improvement in daily functioning.
Key words: CGI scale, anhedonia, antidepressant
treatment.
Rezumat:
Istoric: Depresia este o frecventă tulburare psihică care
determină modificări substanțiale în funcționarea de zi cu
zi, crește riscul pentru handicap social și fizic, și secundar,
cresc costurile și pentru alte servicii medicale.
Obiective: Studiul a avut ca scop evaluarea
particularităților evoluției simptomatologiei,
funcționalitatea si aderența terapeutică la pacienții cu
tulburare depresivă majoră sub tratament cu agomelatină.
Metode: Am inclus într-un studiu prospectiv,
observațional și longitudinal 1194 pacienți cu episod
depresiv sau tulburare depresivă majoră, care au fost
evaluați prin Scala de Impresie Clinică Globală (scala
CGI) și Inventarul Rapid al Simptomatologiei Depresive
(QIDS-C16), în scopul de a realiza o analiză statistică
elocventă.
Rezultate: In acest studiu, grupul de pacienți înrolați au
avut o simptomatologie moderată (dispozitie depresivă,
scaderea capacității de concentrare, anhedonie) și au
prezentat o evoluție bună incă din a doua săptămână de
tratament și o îmbunătățire considerabilă a anhedoniei
după 10 săptămâni de tratament.
Concluzii: Tratamentul antidepresiv cu agomelatină a fost
considerat eficient și sigur, iar după perioada de 10
săptămani de tratament s-a constatat o îmbunătățire
importantă a simptomatologiei, o bună aderență la
tratament și îmbunătățirea funcționării socioocupaționale zilnice.
Cuvinte cheie: scala CGI, anhedonie, tratament
antidepresiv
1. INTRODUCTION
Major Depressive Disorder (MDD) is a
heterogeneous, complex and debilitating disorder that put
a burden not only upon patients but also on their family and
society (1). MDD considerably affects patient's daily
functionality with important effect on their quality of life
because the social functionality decreases as depression's
severity increases. The literature data are showing that
almost 52% of patients with Major Depressive Episode
(MDE) have persistent and important symptomatology
compared to 18% of patients with mild MDE that
experience major difficulties in daily social interactions
(2).
Even if the available antidepressants (AD) help
patients to obtain a good response or remission of
symptoms, there is a period of several weeks until their
entire pharmacological action is perceived by patients and
clinicians.
1
University of Medicine and Pharmacy “Carol Davila” Bucharest
University of Medicine “Ovidius” Constanța
3
University of Medicine in Craiova
4
University of Medicine “Lucian Blaga” Sibiu
5
MD at “Prof. Dr. Alex. Obregia” Psychiatric Hospital in Bucharest; email: tradress@yahoo.com; tel: 0040749156565
Received December 3, 2015, Revised December 11, 2015, Accepted December 22, 2015
2
15
Valentin P. Matei, Victor Marinescu, Eda M. Ciorabai, Ileana Marinescu, Lavinia Duica, Mihai Pirlog, George
Paraschiv, Ioana G. Pavel, Alexandra Dolfi, Diana A. Mihalache, Iulia A. Mitea, Diana Mihalcea, Mihnea Manea,
Ana Giurgiuca, Mihai Bran, Bogdan Stania, Traian Purnichi, Dan Prelipceanu: Evolution Of Symptomatology And
Functionality Of Romanian Patients With Major Depressive Episode In A Cohort Observational Study
Even so many patients have inadequate response,
comorbid symptoms that are not completely controlled or
under a poly-pharmacotherapy that can be associated with
tolerability issues (1).
There are still significant controversies regarding
the moment when the symptomatic amelioration became
significant on the evolution of MDE treated with AD.
Even though several methodological limitations exist
(like the focusing on the clinical response rather than upon
symptomatology remission), the results collected from
randomized clinical trials (RCT), meta-analyses and
observational studies show that: (A). in general AD are
associated with early amelioration of the symptoms which
can be observed in the first 2 weeks since antidepressant
treatment initiation (defined as a reduction ≥ 20% in
depression severity measured by standardized rating
scales); (B) several antidepressants like Agomelatine are
associated with early amelioration of both central
symptomatology (depressed mood and anhedonia) and
specific symptoms like sleep-wake disturbances; (C)
early amelioration is a predictor of symptomatology
remission and early response. Subsequently, the lack of
amelioration could be seen as a predictor of nonresponse
(3).
According to analytical studies on factors and
groups there has been shown that depressive mood
(negative emotions), anhedonia and psychomotor
symptoms are the elements that define major depressive
disorders the best (4). Diverse studies showed that
anhedonia can precede the onset of a depressive episode, it
can influence its severity, can be a predictor of a bad
outcome 12 months later and it is a residual symptom
frequently present. The inclusion of patients in subtypes
according to the type of symptoms and phenomenological
approach could constitute a further step of the future
psychopharmacology in order to prescribe the best
antidepressant according to specific symptoms. There are
articles on this subject in the literature but until now the
results are not yet conclusive (5).
2. METHODS
2.1 Participants
The study population was constituted of in and
outpatients from 59 representative centers in Romania.
The investigators were psychiatrists working in the public
health system (hospital or specialized ambulatory) or in
private practice. The observational study took place
between 1st of February 2012 and 8th of June 2012.
In the study were included 1194 patients with a first
MDE or a recurrent MDE according to the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV-TR) [6],
over 18 years old but under 75 years, whose doctors
recommended Agomelatine before the inclusion in the
study and who accepted in common agreement with their
clinician to be monitored during study. In the final analysis
we also included patients with bipolar disorder (2.68%,
n=32) and patients without specification of MDE (10%,
n=125) due to the fact that this was a naturalistic study and
these diagnostics were modified after baseline.
Out of 1194 MDE patients included in the study,
more than half (645 patients) were with recurrent MDE.
The exclusion criteria referred to the patients that: (A)
went to the doctor in emergency regime, (B) use of
16
psychoactive substances, (C) have an age under 18 years
or above 75 years old and (D) presented serious
comorbidities and/or severe pathology which could affect
their participation in the study (hepatic impairment,
limited cooperation, legal limited capacity, another severe
non-psychiatric disorder, cancer, medication abuse,
severe cardiovascular disease or renal failure).
The main objective of this observational study was
the evaluation of daily functionality in MDD patients
under AD treatment, who were prospectively followed.
The secondary objectives included MDE severity
improvement and MDD symptomatology evolution in
these
patients and the adherence to the AD treatment.
The prospective observation of the patients lasted
for 10 weeks and included 4 visits: V0- baseline, V1- 2
weeks since inclusion, V2 and V3 at 6 respectively 10
weeks since inclusion. At the initial visit (baseline)
depressive mood, anhedonia and focusing
difficulties/decision making were the most prominent
symptoms as measured with Quick Inventory of
Depressive Symptomatology scale.
2.2 Instruments
In order to evaluate the MDE standard instruments
were used: CGI scale (Clinical Global Impressions Scale).
The CGI scale is an instrument through which the
clinician evaluates 3 different global parameters (7):
A. The severity of the disease: global evaluation of
actual severity of patient's symptoms (CGI-S);
B. The global improvement: general comparison
between patient's actual state and the initial (baseline)
state (CGI-I)
C. Efficacy index: general comparison between
patient's initial state and a rapport between the actual
therapeutic benefit and severity of adverse reactions
(CGI-E).
For severity evaluation of MDE Quick Inventory of
Depressive Symptomatology scale (QIDS-C16 - Rush et
al., 2003) was used. The QIDS16 scale includes all the
symptomatology domains, which was developed on the
base of DSM-IV criteria for diagnosis of major depressive
episode [8,9]: 4 items for evaluation of sleep disturbances;
2 items for evaluation of psychomotor disturbances
(agitation or slowing of the psychomotor function); 4 for
appetite/ weight evaluation (increasing/decreasing of
appetite and weight gain/loss) and only one item for
evaluating the other 6 domains (depressed mood, low
interest, decreased level of energy, feelings of inutility/
guilt, concentration/decision making difficulties, suicidal
ideation). Each item is evaluated on a scale from 0 to 3. For
the domains that require the evaluation of least 2 items, the
highest score is considered. For example if at the
beginning of sleep the value of insomnia is 0, the value of
insomnia the middle of the night sleep is 1, for morning
insomnia is 3 and 0 for hypersomnia, then the sleep
disturbances domain gains a total score of 4 points. The
total score varies between 0 and 27. The reference interval
in the evaluation of symptoms severity is the 7 days period
prior to evaluation. QIDS is sensitive to the change of the
clinical state status associated with medical treatment,
psychotherapy or somatic treatment, being a very good
instrument in both research and clinical practice.
The degree of adherence to the treatment throughout study
development was evaluated by the number of pills
declared by the patient as taken from one visit to another.
study was prospective, observational and longitudinal; all
the participants signed an inform consent before being
included into the study.
2.3 The statistical analysis was done by CEGEDIM
Company using Kynos Modalisa software with a
confidence level of 95%, a maximum sampling error for
all patients of ± 2.81% and p-value.
LEVEL
OF
ANALYSES
-
INDICATORS
-
-
-
SIGNIFICANCE
TESTING
-
-
-
OPEN-ENDED
QUESTIONS
-
All CRFs
Splits
on
patient
categories,
e.g.
gender,
age
categories,
diagnosis
Absolute and relative
frequencies
for
categorical variable
Central
tendency
indicators
for
quantitative variables
Confidence
levels
provided in annex
(Excel file)
Fisher’s F test – testing
for significant differences
among pre-defined groups
z-test for means, t-test for
matched samples – testing
for significant differences
between visits
Chi2 test – testing for
association among predefined groups
Similar answers grouped in
categories
Database keeps the original
verbatim as well
3). The evolution of the symptoms severity at each
evaluation (comparing to the initial moment) is
graphically presented in Figure 1.
Characteristics
Women
Diagnosis
Major
depression-new
episode
Major
depression-first
episode
Bipolar disorder
Unspecified
Prior antidepressant treatment
Yes
No
Total medium score QDISC16*
Dominant symptoms (QDISC16):
Depressive mood
Sad mood more than half the
time
Sad mood almost every time
Involvement, interest to other
people or activities
Keeps just one or two
activities of the past ones
There is no interest regarding
past activities
Focusing, decision making
Tries most of the time to focus
attention or make decisions
Cannot focus well enough to
read or cannot take even
minor decisions
46.56
40.28
2.68
10.46
46%
54%
12.25
56
35
51
22
61
19
* n=1186-1189 for each domain evaluated with QIDS-C16
Table 2: Baseline characteristics of the MDD patients
Table 1 – Statistical parameters
QIDS-C16 score
25
3. RESULTS
3.1. Demographic characteristics:
Women represented 68% of the population (n=1190) with
a mean age of 48 years. A higher representation had the
patients included in the 55 to 60 years' age group (18%),
followed by patients in the 50 to 55 age group (17%)
(n=1186). The lowest representation in the group was for
the patients under 25 years (3%). No gender differences
were seen regarding the type of episode and the duration of
anterior affliction in patients with a current major
depressive episode. The characteristics of the study group
are presented in Table 2.
3.2. QIDS-C16 score and symptoms evolution: The average
of QIDS-C16 score at inclusion was 12.25. This is
associated with medium intensity symptoms. The
symptoms were ameliorated by the AD treatment reaching
a final score of 1.77 at V3 (the interval 0-5 is considered in
normal range). The symptoms evolution was statistically
significant between visits and also at the final visit (Table
% of all patients
68
20
12,25
15
8,41
10
4,50
5
1,77
0
V0
V1
V2
V3
Figure 1: Evolution of the MDE severity during study
(QIDS-C16 scale)
Visit
Visit 0
Visit 1
Visit 2
Visit 3
Average QIDSC16value
12,25 [12.05-12.45]
t-value
(vs V0)
-
pvalue
-
8,41 [8.21-8.61]
4,5 [4.33-4.67]
1,77 [1.66-1.88]
46,08
0,00
80,19
96,72
0,00
0,00
Table 3: Evolution of the MDE symptoms evaluated with
QIDS-C16 scale
17
QIDS-C16
Items
V0
(W0)
N=1186
- 1189
Patient Percentage
V1 (W2) V2
N=1187- (W6)
1190
N=1181
- 1184
Depressive mood
Doesn’t
feel 0.2
7
sad
Feels sad in 8
47
less than half
of time
Sad mood more 56
43
than half of
time
Sad
mood 35
3
almost all the
time
Implication
No
change
1
9
from
the
common level
of
interest
toward other
people
or
activities
Decreasing the
26
52
interest
of
current
activities
Keeping only 1
51
35
or 2 activities
from the old
ones
Having
no
22
4
interest from
the
old
activities
Concentration/ making decisions
No change in
1
7
the
daily
capacity
of
concentration
and
making
decisions
Sometimes
20
49
feels undecided
or observe that
attention
is
diminished
Most part of
61
40
the time trying
to concentrate
or
making
decisions
Cannot
19
4
concentrating
enough
for
reading
or
cannot making
minor
decisions
V3
(W10)
N=1169
- 1171
24
67
65
32
11
1
1
0.1
36
76
V 0
V1
19%
7%
1%
0,1%
22%
18%
4%
4%
0,4%
0,3%
3%
0,3%
0%
0%
0%
Concentration/making
decisions
8
23
2
0.1
0
25
60
V3
4%
0,2%
0,1%
3%
0,1%
0%
0%
2%
0,2%
0%
Figure 2: The evolution of the highest score
symptomatology on QIDS-C16 scale
Depressed mood
56
V2
18%
9%
Item
Visit 1
vs 0
17.9
12.0
Visit 2
vs 0
24.7
16.1
Visit 3
vs 0
25,3
16.1
Self-esteem
11.0
15.7
15.7
Suicidal thoughts
5.0
5.2
5.2
Implication
13.4
18.0
18.0
Energy level/fatigue
12.1
16.0
16.0
Psycho-motor
retardation
8.0
10.7
10.7
Z value > 2.56 is meaningful for the interval of
confidence about 99%
Table 5: Z test applied on the QIDS-C16 items
65
39
9
2
0.4
0
Table 4: The evolution of the depressed mood,
anhedonia and impaired concentration/ making
decisions during the study (QIDS-C16)
18
35%
The statistics revealed that while all the patients presented
a significant improvement of the symptomatology, some
categories have registered more progress, as follows
(supplementary details can be obtained on request):
·Age: The elderly patients (age between 65 and 75) have a
slower improvement than other age categories, for all the
visits (p=0.002 at V1, p=0.001 at V2 and V3);
·Major depressive episode (new/recurrent): it has been
noted significant differences between the patients with a
new major depressive episode and recurrent in all that
concerns the total scores (ANOVA), but the items scores
(Chi2). The patients with recurrent MDD had a slowly
recovery.
3.3. Comorbidities of the MDD on the patients of the
study:
The presence of somatic comorbidity was observed in
26% of the patients; the most frequently reported
comorbidities (n=307) were arterial hypertension (82%)
and the ischemic coronary disease (30%).
3.4. Adherence to treatment during the study:
From the patients who had previous AD treatment (n=645,
54%), the main reason for switching/discontinuing was
the loss of therapeutic response, followed by the patients'
choice not to be treated with that AD or considering that he
does not need treatment anymore. Though, there are cases
for which this reason could not be specified.
At the end of the study98.5% of the patients (n1194) continued the AD treatment (7 patients discontinued
the treatment due to economic reasons).During the
observational study there have not been reported any
adverse reactions linked to Agomelatine according to the
investigators clinical judgement.
4. DISCUSSIONS
We noticed a concordance of the results of this
study with the data from the literature regarding the
percent of women with MDD and the low prevalence of
depression in the age category under 25 years (2).
The group of patients enrolled in this study had a
moderate symptomatology and this could be explained by
the fact that patients who were addressing to the
emergency services were excluded. Another explanation
could be the presence of the residual symptoms in patients
with recurrent depression and their treatment was changed
because of the loss of therapeutic response (the main
reason of the changing anterior treatment in this study).
For this group of patients, the symptomatology
domains at the initial moments and who had a
considerable improvement starting with the second week
of treatment have been represented by the depressed
mood, loss of concentration and making decisions and
anhedonia. Of the three domains, after ten weeks of
treatment anhedonia presented a better improvement. (3rd
table). Considering that the medication for the study was
represented exclusively by Agomelatine, it is possible that
this substance plays an important role which can concord
with the results of the recent studies (4, 10).
In this study, the patients recently diagnosed
(<3months) and treated have presented a significant
improvement after ten weeks of treatment compared with
the patients diagnosed with depression more than one year
before. Also, the patients with more than 65 years old
diagnosed with depression more than one year before had
a slow improvement during all the visits. These two
observations sustain the importance of recognizing
depression and the initiation of the treatment from the
beginning, which allow a good improvement of the
functionality.
A good adherence to the treatment is a great
contributor to the improvement of the symptomatology
and thus, to recovering the level of functionality before the
disease episode. No side effects related to the AD
treatment were recorded according to the clinician's
judgement.
Considering that the medication was based almost
exclusively on Agomelatine, the results of the study can be
considered representative for this substance. In the same
time, we cannot make specific correlations, the Chi test
being extremely sensitive in big samples. Another limit
can be represented by the short period of the study – 10
weeks, which can permit an observation of the evolution
and the adherence only for the acute phase of the
treatment. It was observed a good improvement of the
functionality from the self-reported data by the patients.
At the same time, it might be useful to make a correlation
of the functionality with the symptomatology through the
evaluation of the patient's response at a self-administered
scale for functionality.
5. CONCLUSIONS
The AD treatment with
considered efficient and
the MDE patients. After 10 weeks of treatment it has been
noticed a good improvement of MDE patients'
symptomatology, a good adherence to treatment and a
good improvement of the functionality from the selfreported data by the patients.
6. DISCLOSURE
The authors declare that received in the past grants
from Servier Pharma and other speaker fees. In addition,
all the authors received in the past speaker's fees and/or
sponsorship from Servier Pharma and others companies
for scientific research or communication. Dr. Traian
Purnichi also works as a marketing specialist consultant
for Servier Pharma and Dr. George Paraschiv and IuliaAlma Mitea are employees of Servier Pharma.
7. ACKNOWLEDGEMETS
All the authors had an equal contribution and have
similar rights. All the authors approved the final version of
this article.
The authors will like to thank:
-Cegedim Company that did the statistical analysis using a
Kynos Modalisa software.
-MedinteractivPlus for helping on the study draft.
- Servier Pharma for offering the grant that made this study
possible.
- The following doctors for assessing the patients included
in this study: Ramona Baba, , Alexandrina Baloescu,
Ciprian Bacila Magdalena Blaj, RuxandraBloj, Mihaela
Brad, Magdalena Bujor, Ion Burlacu, IeronimBurghelea,
Ana Campeanu, Liliana Chelariu, Angela Chelcea,
RaisaCirlig, Victor Cojocaru, Delia Coltoiu,
MinodoraDumitrescu, Corina-Mihaela Echim,
LiviuGanea, Felicia Giurgi, Carmen Haragus,
AncutaHordoan, CameliaHriban, Ioana Ilea, Sorin Iova,
Bogdana Lazar, MinodoraManea, Auras Margina,
LigiaMincu, Eli Morman, Eugenia ElzaMoruzzi, Eduard
Motoescu, Ildiko Must, VioricaNancu, Laura PacurarCatana, Corina Panzaru, Ioana Papava, Rita Platona, Alina
Pop, Cristian Popa, NeoniliaPopa, Elena Preda, Dan
Prelipceanu, Eugenia Roca, Dan Rusu, HoratiuSalvan,
Iulia Daria Scorei, Daniela Sichitiu, Lia Sonia Simon,
Adina Singalevici, Rodica Stan, Luigya-Claudia Stanci,
JeniStanciu, Izabela Stania, AncaTalasman, Livia Taran,
Andreea Teodorescu, AlexandruTiugan, Mihaela Tranca,
Silvia Trandafir, Corina Tudor, Monica Varlan, Claudiu
Ionut Vasile, AndreiaVasilescu, Nicolae Vlad.
8. FINANCIAL SUPORT
This study was founded by a grant from Servier Pharma.
REFERENCES
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C., Millan MJ.: Agomelatine, the first melatonergic antidepressant:
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August 2010, 628-642
2.Lam R.W., Mok H.: Depression, Oxford University Press, New York,
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3.Lam R.W.: Onset, time course and trajectories of improvement with
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– S498
4.Giannantonio M., Martinotti G.: Anhedonia and major depression: the
role of agomelatine, European Neuropsychopharmacology (2012) 22,
S505 – S510
5.Hasler G., Drevets WC., Manji HK., Charney DS., Discovering
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19
List of abbreviations:
1.
CGI scale - Clinical Global Impressions Scale
2.
QUIDS - Quick Inventory of Depressive
Symptomatology Scale
3.
MDD - Major Depressive disorder
4.
MDE - Major Depressive Episode
5.
AD - Antidepressant
6.
RCT - Randomized Clinical Trials
7.
DSM-IV-TR - Diagnostic and Statistical
Manual of Mental Disorders
20
ORIGINAL ARTICLES
MENTAL DISORDERS IN CHILD EPILEPSY
Elisabeta Racos – Szabo1, Iringó Száva2, Anamaria Todoran – Butila3
Abstract
Introduction
Epilepsy is a chronic condition characterized by the
presence of recurrent paroxysmal brain seizures (epileptic
seizures), as a result of an excessive discharge of neurons.
The prevalence of mental disorders in epilepsy is of 3040%, and those of psychoses of
1-3%, being
higher in patients with temporal lobe epilepsy. Psychoses
and personality disorders are 3 times more frequent in
those with temporal lobe seizures. Among the mental
disorders in child epilepsy we care to mention: cognitive
impairment, behaviour disorders with aggressiveness and
psychomotor agitation, learning disorders, depression,
anxiety.
Material and methods
There have been evaluated 24 children with epilepsy,
admitted in 2014 in the Clinic of Pediatric Neurology and
Psychiatry Tg-Mures, with ages between 12 and 18. There
have been applied Raven's Matrices, various scales for
depression and anxiety (MASC, Hamilton, Beck, Bender).
The diagnosis of mental disorders has been established
based on the criteria DSM-V and ICD 10.
Results
The prevalence of mental disorders in child epilepsy was of
12%, with the highest incidence in the group age between
10 and 12. These mental disorders have been: cognitive
disorders (79%), behaviour disorders (37,5%),
disharmonic personality developments (33%), anxiety
(20,8%), psychosis (8,3%), depression (4,2%).
Discussions
Child epilepsy evolves having a high risk for the
occurrence of cognitive impairment, behaviour disorders,
language or mood disorders all the more so as the
underlying structural disorders are higher. The early onset
of the epileptic seizures under the age of 3, in a child with a
psychic under development represents a vulnerability
factor. Patients with temporal lobe epilepsy present a risk
for psychoses, also 1/3 of the epileptics develop
personality disorders.
Conclusions
The onset of epileptic seizures under the age of 3
constitutes a risk factor for the occurrence of language
disorders, cognitive or behaviour disorders.
The prognostic in mental disorders in the epileptic child is
influenced by the underlying structural brain anomalies
responsible for the occurrence of epileptic seizures.
Key words : epilepsy, mental disorders, child.
Rezumat
Introducere
Epilepsia este o afectiune cronica caracterizata prin
prezenta crizelor cerebrale paroxistice recurente (crize
epileptice),ca urmare unei descarcari excesive a
neuronilor .
Prevalenta tulburarilor psihice in epilepsie este de 3040%,iar cea a psihozelor de 1-3%,fiind mai mare la
pacientii cu epilepsie de lob temporal.Psihozele si
tulburarile de personalitate sunt de 3 ori mai frecvente la
cei cu crize de lob temporal.Dintre tulburarile psihice in
epilepsia copilului amintim:deficitul cognitiv,tulburarile
de comportament cu agresivitate si agitatie psihomotorie,tulburarile de invatare,depresia,anxietatea.
Material si metode
Au fost evaluati 24 copii cu epilepsie, internati in 2014 in
Clinica de Neurologie si Psihiatrie pediatrica TgMures,avind virsta cuprinsa intre 12 si 18 ani.S-au aplicat
matricea Raven,diferite
scale pentru depresie si
anxietate(MASC, Hamilton,Beck,Bender).Diagnosticul
tulburarilor psihice s-a stabilit pe baza criteriilor DSM-V
si ICD 10.
Rezultate
Prevalenta tulburarilor psihice in epilepsie a fost de
0,14%,cu incidenta cea mai mare la grupa de virsta intre
10 si 12 ani(33%).Acestea au fost: tulburari
c o g n i t i v e ( 8 3 % ) , t u l b u r a r i d e
comportament(37,5%),dezvoltari dizarmonice de
personalitate(33%),anxietatea(20,8%),psihoza(8,3%),de
presia(4,2%).
Discutii
Epilepsia copilului evolueaza cu risc crescut de aparitie a
deficitului cognitiv,a tulburarilor de comportament, a
celor de limbaj sau de dispozitie cu atit mai mult cu cit
tulburarile structurale subiacente sunt mai mari.Debutul
precoce al crizelor epileptice sub virsta de 3 ani, la un
copil cu un psihic in dezvoltare reprezinta un factor de
vulnerabilitate.Pacientii cu epilepsie de lob temporal
perzinta risc pentru psihoze, de asemenea 1/3 dintre
epileptici dezvolta tulburari de personalitate.
Concluzii
Debutul crizelor epileptice sub virsta de 3 ani constitue
factor de risc pentru aparitia tulburarilor de limbaj,a
celor cognitive sau de comportament.
Prognosticul in tulburarile psihice la copilul epileptic este
influentat de anomaliile structurale cerebrale subiacente
responsabile de aparitia crizelor epileptice.
Cuvinte cheie : epilepsie,tulburari psihice,copil.
1
Senior lecturer, University of Medicine and Pharmacy Tg-Mures, Clinic of Pediatric Neurology and Psychiatry, Tg-Mures, Panselutelor 5., tel.0365882662, elisabetaracos@yahoo.com
2
Resident Physician Pediatric Psychiatry, Clinic of Pediatric Neurology and Psychiatry Tg-Mures, Tg-Mures, Panselutelor 5,
3
Junior Lecturer, University of Medicine and Pharmacy Tg-Mures - Subject Medical Genetics:, Specialist Physician Pediatric Neurology
Received November 1, 2015, Revised November 16, 2015, Accepted January 8, 2016
21
Elisabeta Racos – Szabo, Iringó Száva, Anamaria Todoran – Butila: Mental Disorders In Child Epilepsy
Introduction
Epilepsy is a chronic condition characterized by the
presence of recurrent paroxysmal brain seizures (epileptic
seizure), as a result of an excessive discharge of the
neurons within a structural or biochemical epileptogenic
brain injuries (according to the International League
Against Epilepsy approved by World Health
Organization).(1,2)
The association of epilepsy with mental disorders is
already known from antiquity(8). Later Kraepelin
affirmed that patients with epilepsy present personality
disorders and predisposition for psychoses.(9)
The prevalence of mental disorders in epilepsy is of 3040%, being able to exceed even 60% in those with
different neurological impairments, and the psychoses one
is of 1-3%, being higher in patients with temporal lobe
epilepsy(5,7). Kaplan mentions that epileptics present
mental disorders, depression being present in 7.5 up to
34% of them. At the same it is to be mentioned that
psychoses and personality disorders are 3 times more
frequent in patients with complex partial seizures. (9) The
most frequent comorbidity in epilepsy is depression, the
estimated prevalence of it vary between 50-55% in
patients attending hospital, or ambulatory system, 20-30%
in those with reccurent seizures, and 6-9% in those in
remission. Depression can appear after epilepsy surgery
too.(4) The suicide rate in population suffering of epilepsy
is 5% (in the whole population 1,4%).(11) The epilepsy
treatment can also lead to depression, nervousness,
abnormal thinking (Topiramate, vigabatrin) (4,6).
The mental disorders in the epileptic child are different
depending on age(10). Thus, we care to mention
behaviour disorders with instability and psychomotor
agitation, cognitive impairment, personality disorders
(with viscosity, aggressiveness, irritability, egocentrism),
learning disorders, attention deficit, hyperactivity
disorder, anxiety, depression, psychosis. (12)
old 13% (3 patients).
Figure 1: Mental disorders prevalence in child epilepsy
Figure 2 : Distribution of cases on genders
Material and methods
A study has been performed within the Clinic of Pediatric
Neurology and Psychiatry from Tg-Mures during 2014,
being monitored 24 children with various forms of
epilepsy, aged between 10 and 18, who presented
neurological disorder as well. The patients have been
examined neurologically, paraclinically by EEG, brain
imaging (CT scan and brain MRI), also psychiatrically by
Raven's Matrices, projective tests, depression and anxiety
scales (MASC, Hamilton, Beck, Bender).
Figure 3 : Distribution of cases on age groups
Results
Out of the 171 cases of epilepsy diagnosed in our Clinic of
Pediatric Neurology and Psychiatry from Tg-Mures in
2014, the prevalence of epilepsy associated with mental
disorders was of 12%.
The specialized literature mentions a higher incidence of
epilepsy in male gender, in the studied cases this being of
71%.
The maximum incidence of mental disorders in epileptic
children has been in the group with ages between 10 and
12, namely 33% (6 cases), 12-14 years old 29% (7
patients), 14-16 years old 25% (6 patients), 16-18 years
22
Figure 4 : Incidence of mental disorders in child epilepsy
The incidence of mental disorders in epileptic children
according to their background has been equal between the
urban and rural environment, namely 50%.
The mental disorders encountered in the child diagnosed
and treated for epilepsy have been:
- cognitive disorders: (37%);
- behaviour disorders: (17%)
- disharmonic personality developments: (15%)
- attention deficit hyperactivity disorder: ( 9%)
- anxiety: ( 9%)
- learning disorders: (7%)
- psychosis: (4%)
- mood disorders of depressive nature: (2%)
schooling in aided school in 25% of cases, moderate
mental retardation in 17% of cases and severe mental
retardation in 37% of cases, and 21 % of the patients had a
normal cognitive level.
Behaviour disorders have been encountered in 11 patients
consisting in irascibility (2 cases), disobedience and
stubbornness (4 cases), auto- and hetero-aggressive
manifestations (5 cases).
Figure 7: Incidence of psychotic disorder, of learning and
mood disorders in child epilepsy
Figure 5: Incidence of behavior disorders in child epilepsy
Personality disorders have been encountered in 8 cases,
consisting in withdrawal (1 case), viscosity (1 case),
impulsiveness (4 cases), antisocial manifestations as theft
and consumption of alcohol (2 cases).
Figure 8 : Incidence of cognitive impairment in child
epilepsy
The severity of the cognitive impairment has been
correlated with the age at the epilepsy onset, thus in 45.8%
of cases the onset of the epileptic seizures has occurred
before the age of 3.
17% of the epileptic children have not been schooled, due
to the seizures frequency and lack of favourable response
to the antiepileptic treatment, at the same time due to the
associated cognitive impairment.
Figure 6: Incidence of personality disorders in child
epilepsy
The psychotic type of disorder has been the most severe
mental disorder in the epileptic child, consisting in
mystical and paranoid delirious ideas, in 2 cases (8%).
Language disorders were also present consisting in
dyslalia, stuttering, dysarthria in 13 children. Also there
have been encountered affective and mood disorders
namely: 1 case of depressive disorder, and also 1 case of
anxiety.
The associated cognitive impairment in the children
patients with epilepsy under treatment, has consisted in
mild mental retardation (intellectual disability) with
Discussions
Recent studies point out the fact that child epilepsy
evolves with a high risk for the occurrence of cognitive
impairment, behaviour disorders, emotional disorders,
language or mood disorders. This risk is all the more
higher as the structural underlying disorders to the
epileptic process are more pregnant(2). The monitored
patients presented a cognitive impairment in most of the
cases (79%), only 21 % of them having a normal cognitive
level. At the same time the behavioural disorder consisting
in disobedience, irascibility, impulsiveness with auto- and
hetero-aggressiveness has been present in 11 patients.(12)
In most of the epileptic children within the study (45.8%)
the onset of the epileptic seizures occurred before the age
of 3, when the child's psychic is at its peak of development,
therefore the psychic vulnerability is higher, aspect
mentioned also in the specialized literature (1,2,6)
Personality disorders appear in a 1/3 of the epileptic
23
Elisabeta Racos – Szabo, Iringó Száva, Anamaria Todoran – Butila: Mental Disorders In Child Epilepsy
patients , fact emphasized also in the children within the
study, namely in 33% of them, under the form of viscosity,
adhesiveness, antisocial type of elements, instability,
impulsiveness, consistent with the specialized literature
data.(9,12)
It is mentioned the occurrence of psychosis in patients
with temporal lobe seizures (5).
Epileptic children with psychotic decompensation within
our study (2 cases) have presented seizures of complex
absence type, complex focal seizures secondarily
generalized, the structural lesion being in the temporal
lobe.(5,7)
Some of the antiepileptic medications may cause reactions
of behavioral or cognitive type (12). Within the study
performed it could not be established if cognitive or
behavioral disorders had a bearing on the antiepileptic
medication treatment.(6)
Conclusions
Among the mental disorders in epileptic children, the
most frequently emphasized was the cognitive
impairment (79%).
The maximum incidence of mental disorders was in the
age group between 10 and 12.
The early onset of epileptic seizures under the age of 3
constitutes an unfavourable prognostic factor for the
occurrence of mental disorders as language disorders,
24
cognitive impairment, behavioral disorders.
The prognostic of mental disorders in child epilepsy is
influenced by brain structural anomalies responsible for
the epileptic seizures, also the therapeutic response at
specialized medication.
Bibliography
1. Popescu V, Arion C., Dragomir D.: Convulsions and epilepsy in child,
Medicala Publishing, Bucharest, 1989, 298-301.
2. Benga I: Epilepsy and non-epileptic seizures, Medical University
Publishing „Iuliu Hatieganu”, Cluj-Napoca, 2003, 271-275.
3. Kaplan HI:Synopsis of Psychiatry, Seventh Edition, Williams and
Wilkins, Baltimore, 1994.
4. M J Jackson1,D Turkington2: Depression and anxiety in epilepsy,
Neurol Neurosurg Psychiatry 2005;76:i45-i47
doi:10.1136/jnnp.2004.060467
5. Trimble MR, Schmitz B: Schizophrenia and other psychoses, in
Aicardi J: Epilepsy: a comprehensive text book, 2007, 204:2113-21
6. Rogozea R, Magureanu S, Constantin D: Updates in epilepsy, Tehnica
Publishing, Bucharest, 1998, 108-110
7. Sander JW: Epilepsy, Questions and answers, 2000
8. Popescu V: Pediatric neurology, Teora Publishing, 2001, 619-622,
627-634, 893-900
9. Dome L: Szemelyiseg zavarok, Filum Publishing, 2001
10. David A.S, Fleminger S,: Lishman's Organic Psychiatry, WileyBlackwell, 2009, 333-354
11. Barnhill I, Hurley A: Mood disorders and epilepsy, Ment. Health
Aspects Dev. Disabil., 2003, 6:36-39.
12. Leung LS, Mc Lachan RS: Behaviours induced or disrupted by
complex partial seizures, Neurosciences and behaviour reviews, 2000,
24:762-775.
***
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ROMANIAN JOURNAL
OF PSYCHIATRY
CONTENTS
EDITOR-IN-CHIEF:
CO-EDITORS:
SPECIAL ARTICLES
& The Spiritual Dimension of Personality and its Role in Mental Health
Aurel Nireștean, Emese Lukacs, Gabriela Buicu, Monica Bilcă,
Pokorny Vasile
1
ASSOCIATE EDITORS:
Doina COZMAN
Liana DEHELEAN
Marieta GABOŞ GRECU
Maria LADEA
Cristinel ŞTEFĂNESCU
Cătălina TUDOSE
REVIEW ARTICLES
&
&
&
The Integrative Model of Cognitive-behavioral Psychotherapy in
Personality Disorders
Cosmin O. Popa, Mihai Ardelean, Tudor Nireștean, Gabriela Buicu
4
Depression Screening at The Primary Care Level – a Cost-efficient
Intervention
Raluca Ileana Nica, Mihail Cristian Pîrlog
8
Clinical Study of The Mentation, Behavior and Mood Disorders
in Parkinson's Disease
Iordan Ganev, Toni Donchev, Krasimir Kostadinov, Velina ManchevaGaneva, Lachezar Manchev, Ivan Manchev, Mihai Pirlog, George L.
Paraschiv, Ruxandra C.m. Banu, Traian Purnichi
Executive editors: Elena CĂLINESCU
Valentin MATEI
11
ORIGINAL ARTICLES
&
Evolution of Symptomatology and Functionality of Romanian
Patients with Major Depressive Episode in a Cohort
Observational Study
15
Valentin P. Matei, Victor Marinescu, Eda M. Ciorabai, Ileana Marinescu,
Lavinia Duica, Mihai Pirlog, George Paraschiv, Ioana G. Pavel,
Alexandra Dolfi, Diana A. Mihalache, Iulia A. Mitea, Diana Mihalcea,
Mihnea Manea, Ana Giurgiuca, Mihai Bran, Bogdan Stania, Traian
Purnichi, Dan Prelipceanu
&
Mental Disorders in Child Epilepsy
Elisabeta Racos – Szabo, Iringó Száva, Anamaria Todoran – Butila
INSTRUCTIONS FOR AUTHORS
21
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Dan PRELIPCEANU
Dragoş MARINESCU
Aurel NIREŞTEAN
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Vasile CHIRIŢĂ (Honorary Member
of the Romanian Academy of
Medical Sciences, Iaşi)
Michael DAVIDSON (Professor, Sackler
School of Medicine Tel Aviv Univ.,
Mount Sinai School of Medicine,
New York)
Virgil ENĂTESCU (Member of the Romanian
Academy of Medical Sciences, Satu
Mare)
Ioana MICLUŢIA (UMF Cluj-Napoca)
Şerban IONESCU (Paris VIII Universiy, TroisRivieres University, Quebec)
Mircea LĂZĂRESCU (Honorary Member of the
Romanian Academy
of Medical Sciences, Timişoara)
Juan E. MEZZICH (Professor of Psychiatry
and Director, Division of Psychiatric
Epidemiology and International
Center for Mental Health, Mount
Sinai School of Medicine, New York
University)
Teodor T. POSTOLACHE, MD (Director,
Mood and Anxiety Program,
Department of Psychiatry,
University of Maryland School of
Medicine, Baltimore)
Sorin RIGA (senior researcher)
Dan RUJESCU (Head of Psychiatric Genomics
and Neurobiology
and of Division of Molecular and
Clinical Neurobiology,
Department of Psychiatry, LudwigMaximilians-University, Munchen)
Eliot SOREL (George Washington University,
Washington DC)
Maria GRIGOROIU-ŞERBĂNESCU
(senior researcher)
Tudor UDRIŞTOIU (UMF Craiova)
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REVISTA ROMÂNĂ de PSIHIATRIE - Revista Romana de Psihiatrie

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Pediatric Ophthalmology and Eye Center

The global economic crisis

Margaret Bates

October - Postpartum Support Virginia

BOYS ROCK Homemade Bubbles

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