| Vol 7 n°3 - Pharmacology
in mood disorders |
 Alert |
|
To
print this page in good conditions, please select the "Landscape" mode
of your printer.
|
|
1 8 9
I n
t h i s i s s u e . . .
In the State of the art article
of this issue of Dialogues
in Clinical Neuroscience devoted to the pharmacology
of
mood disorders, David K.
Kupfer (page 191) addresses
the
question of the identification, assessment, and phar-
macological
treatment of depression. He reviews the
currently
available medications, describes their mode of
action,
and discusses practical aspects concerning their
prescription.
He underlines the importance of distin-
guishing
the different phases in the treatment of depres-
sion,
eg, acute treatment versus prevention of relapse.
The
author reviews various clinical forms of depression,
eg,
unipolar vs bipolar, which occur in different types of
patients,
such as the young, the elderly, or those with
psychiatric
or physical comorbid disorders. This should
guide
clinicians in the art of treating depression from an
evidence-based
approach.
The
biology of mood disorders has been of interest to clin-
icians
and researchers for more than 50 years.
Many
hypotheses
have been formulated concerning neurotrans-
mitters, neuroplasticity,
and neuronal circuits. In his Basic
research review, Daniel Bertrand (page 207) focuses
on
neuronal
nicotinic receptors and explains the possible rela-
tionship
between cerebral acetylcholine and mood disor-
ders.
The actions of acetylcholine on muscle receptors and
cerebral
and peripheral muscarinic receptors have been
clarified
for decades, while the outcome of stimulation or
inhibition
of central nicotinic receptors remains a challeng-
ing
theme of basic research. Clinical experience indicates
that
nicotinergic receptors play a role in addiction, depres-
sion,
sleep, and epilepsy, and laboratory observations show
the
interaction of these receptors with several neurotrans-
mitter
systems, as well as with neurohormones such as
steroids.
A cholinergic hypothesis of affective disorder
mechanisms
was proposed more than 25 years ago, fol-
lowing
the observation that physostigmine injection could
induce
depression in humans. The article by Daniel Bertrand
shows
how the cholinergic hypothesis of the mechanism of
mood
disorders can be addressed with new scientific tools.
The Basic research article
by Boris Cyrulnik (page 217)
concerns
the domains of behavior, learning, brain plas-
ticity,
and the biological machinery of the neurotrans-
mission
of information. The author explains how the
personal
history of a living being (a rat, a monkey, or a
human)
can imprint itself in the brain and influence
behavior.
He describes how heredity modulates the
imprinting
of short- or long-lasting personal experiences.
Heredity
is among the factors that determine vulnera-
bility
to stress and the impact of stressors on an individ-
ual’s
attachment to others. In his review, Boris Cyrulnik
illustrates
how personal history is shaped by the charac-
teristics
of the individual brain and how this history also
shapes
the plasticity of the brain. In humans, language
plays
an important role in these multidirectional and
complex
relations between molecular events, neurons,
brain
circuits, and ethological observations.
Pharmacogenomics
and pharmacogenetics have become
of relevance to the Pharmacological
aspects of depres-
sion
and antidepressants. Brigitta Bondy (page 223) reviews
how—and
to what extent—the variability of drug response
can
be understood on the basis of hereditary differences in
antidepressant
molecular targets (eg, the serotonin trans-
porter
and the proteins coupled to neurotransmitter recep-
tors)
and in drug distribution and metabolism (eg, the
cytochrome
P450 hepatic enzymes). She also reviews the
polymorphism
of molecules involved in intracellular trans-
duction
of information in stress hormone regulation or
brain plasticity (eg,
the β3 subunit of G-protein, a gluco-
corticoid
receptor regulating element, and brain-derived
neurotrophic
factor, respectively). Results with the gluco-
corticoid
receptor regulating element are particularly inter-
esting
because having a given genotype (eg, TT homozy-
gote
on rs1360780) has been associated with a better
response
to antidepressants after 5 weeks of treatment.
The
difference was about 5 points of the Hamilton Depres-
sion
Rating scale score, ie, a clinically meaningful difference.
Discoveries
in genetics, genomics, and proteomics are lead-
ing
to a new approach to diagnosis and treatment, since it
is
becoming possible to explain part of the variance in drug
response
from genetic information.
The
issue of measuring plasma concentration of antide-
pressants is discussed
in the Pharmacological aspects arti-
cle by Pierre Baumann
et al (page 231), which constitutes
a
consensus statement and guidelines for therapeutic drug
monitoring
prepared by a group of European experts. This
important
report will guide clinicians in their decision to use
drug
monitoring of antidepressants.
Most
prescribers consider that higher doses are better as far
as
efficacy is concerned, but that they are more risky in
terms of side effects.
In a Clinical research paper, Patricia
Berney (page 249) examines
more than 30 clinical trials and
concludes
that there is little argument in favor of positive
