Are neuroticism and extraversion associated with the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS)? An exploratory 4-week trial

Depressive Disorders Program, Douglas Mental Health University Institute and McGill University, Montréal, Québec, Canada
Neuroscience Letters (Impact Factor: 2.03). 01/2013; 534(1). DOI: 10.1016/j.neulet.2012.12.029
Source: PubMed
ABSTRACT
Several randomized, controlled trials have found high frequency repetitive transcranial magnetic stimulation (HF-rTMS) to be effective for treating major depressive disorder (MDD), but its antidepressant mechanisms have yet to be firmly understood. In this context, pre-treatment personality traits and subsequent changes in personality concomitant to treatment may be relevant for our understanding of these mechanisms. To investigate this issue we conducted a naturalistic trial in which 14 subjects with moderate to severe depression were treated with daily HF-rTMS over the left dorsolateral prefrontal cortex for 4 weeks. Objective depressive symptoms (as assessed by the HAM-D(21)) and the major personality dimensions of neuroticism and extraversion were measured pre-post HF-rTMS. Pre-rTMS levels of extraversion predicted subsequent decrease in depressive symptoms. Also, HF-rTMS treatment resulted in a decrease in neuroticism scores, and this relative decrease was associated with the relative decrease in depression. Our results suggest that HF-rTMS may positively affect the personality dimension of neuroticism. Also, pre-treatment levels of extraversion may predict the subsequent antidepressant response to HF-rTMS. However, further studies with larger samples and controlled designs are needed to better clarify these preliminary findings.

Full-text

Available from: Marcelo Berlim, Mar 07, 2014
Please
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article
in
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as:
M.T.
Berlim,
et
al.,
Are
neuroticism
and
extraversion
associated
with
the
antidepressant
effects
of
repetitive
transcranial
magnetic
stimulation
(rTMS)?
An
exploratory
4-week
trial,
Neurosci.
Lett.
(2013),
http://dx.doi.org/10.1016/j.neulet.2012.12.029
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at
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Neuroscience
Letters
jou
rn
al
h
om
epage:
www.elsevier.com/locate/neulet
Are
neuroticism
and
extraversion
associated
with
the
antidepressant
effects
of
repetitive
transcranial
magnetic
stimulation
(rTMS)?
An
exploratory
4-week
trial
1
2
Marcelo
T.
Berlim
a,b,
,
Alexander
McGirr
a
,
Marie-Martine
Beaulieu
a
,
Frederique
Van
den
Eynde
b
,
Q1
Gustavo
Turecki
a,b
3
4
a
Depressive
Disorders
Program,
Douglas
Mental
Health
University
Institute
and
McGill
University,
Montréal,
Québec,
Canada5
b
Neuromodulation
Research
Clinic,
Douglas
Mental
Health
University
Institute,
Montréal,
Québec,
Canada6
7
h
i
g
h
l
i
g
h
t
s8
9
Pre-rTMS
levels
of
extraversion
predicted
subsequent
improvements
in
depressive
symptoms.10
HF-rTMS
resulted
in
a
decrease
in
neuroticism
scores.11
Measures
of
personality
traits
and
depressive
symptoms
do
not
appear
to
be
redundant
content-wise.12
13
a
r
t
i
c
l
e
i
n
f
o14
15
Article
history:16
Received
15
October
201217
Received
in
revised
form
4
December
201218
Accepted
19
December
201219
20
Keywords:21
Transcranial
magnetic
stimulation22
Major
depression23
Neuroticism24
Extraversion
25
a
b
s
t
r
a
c
t
Several
randomized,
controlled
trials
have
found
high
frequency
repetitive
transcranial
magnetic
stim-
ulation
(HF-rTMS)
to
be
effective
for
treating
major
depressive
disorder
(MDD),
but
its
antidepressant
mechanisms
have
yet
to
be
firmly
understood.
In
this
context,
pre-treatment
personality
traits
and
sub-
sequent
changes
in
personality
concomitant
to
treatment
may
be
relevant
for
our
understanding
of
these
mechanisms.
To
investigate
this
issue
we
conducted
a
naturalistic
trial
in
which
14
subjects
with
moder-
ate
to
severe
depression
were
treated
with
daily
HF-rTMS
over
the
left
dorsolateral
prefrontal
cortex
for
4
weeks.
Objective
depressive
symptoms
(as
assessed
by
the
HAM-D
21
)
and
the
major
personality
dimen-
sions
of
neuroticism
and
extraversion
were
measured
pre-post
HF-rTMS.
Pre-rTMS
levels
of
extraversion
predicted
subsequent
decrease
in
depressive
symptoms.
Also,
HF-rTMS
treatment
resulted
in
a
decrease
in
neuroticism
scores,
and
this
relative
decrease
was
associated
with
the
relative
decrease
in
depression.
Our
results
suggest
that
HF-rTMS
may
positively
affect
the
personality
dimension
of
neuroticism.
Also,
pre-treatment
levels
of
extraversion
may
predict
the
subsequent
antidepressant
response
to
HF-rTMS.
However,
further
studies
with
larger
samples
and
controlled
designs
are
needed
to
better
clarify
these
preliminary
findings.
© 2012 Elsevier Ireland Ltd. All rights reserved.
High
frequency
repetitive
transcranial
magnetic
stimulation
(HF-26
rTMS)
is
a
non-invasive
neuromodulation
technique
in
which27
rapidly
changing
magnetic
fields
are
used
to
focally
depolarize
cor-28
tical
neurons
[18].
Several
randomized
controlled
trials
[1,14,19,31]29
and
meta-analyses
[21,26,37]
have
shown
HF-rTMS
to
be
effective30
and
safe
for
treating
major
depressive
disorder
(MDD).
However,
31
its
antidepressant
mechanism
is
still
largely
unknown
[18].
One
32
hypothesis
proposes
that
at
least
part
of
this
mechanism
might33
result
from
common,
underlying
therapeutic
effects
of
rTMS
on34
Corresponding
author
at:
Douglas
Mental
Health
University
Institute,
6875
LaSalle
Blvd.,
FBC-3
Pavilion,
Rm.
F-3131-2,
Montréal,
Québec
H4H
1R3,
Canada.
Tel.:
+1
514
761
6131;
fax:
+1
514
888
4466.
E-mail
addresses:
nrc.douglas@me.com,
marcelo.berlim@mcgill.ca,
mberlim@me.com (M.T.
Berlim).
psychological
processes
that
are
linked
to
personality
dimensions
35
[36].
36
Currently,
a
prominent
dimensional
model
of
personality
struc-
37
ture
is
the
five-factor
model
(FFM)
[40].
The
FFM
is
divided
in
five
38
broad
personality
domains
that
have
been
identified
and
validated
39
across
multiple
languages
and
cultures
[4],
and
have
been
shown
40
to
be
at
least
moderately
heritable
[24]
and
biologically
based
[6].
41
These
include
extraversion,
agreeableness,
conscientiousness,
neu-
42
roticism
and
openness
[41].
43
Of
the
FFM
dimensions,
extraversion
and
neuroticism
are
espe-
44
cially
relevant
to
MDD
[2].
Extraversion
characterizes
individuals
45
described
in
terms
such
as
excitement,
engagement,
and
enthu-
46
siasm
(i.e.,
positive
affectivity/emotionality),
whereas
neuroticism
47
characterizes
individuals
described
in
terms
such
as
fear,
anxiety,
48
anger,
and
distress
(i.e.,
negative
emotionality)
[40].
Neuroticism
49
seems
to
be
a
significant
risk
factor
for
MDD
[5,10,24].
Extraver-
50
sion,
in
turn,
has
been
shown
in
some
(but
not
all)
longitudinal
51
0304-3940/$
see
front
matter ©
2012 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.neulet.2012.12.029
Page 1
Please
cite
this
article
in
press
as:
M.T.
Berlim,
et
al.,
Are
neuroticism
and
extraversion
associated
with
the
antidepressant
effects
of
repetitive
transcranial
magnetic
stimulation
(rTMS)?
An
exploratory
4-week
trial,
Neurosci.
Lett.
(2013),
http://dx.doi.org/10.1016/j.neulet.2012.12.029
ARTICLE IN PRESS
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Model
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xxx
investigations
to
predict
the
onset
of
MDD
[24].
Of
note,
changes52
in
personality
dimensions
may
independently
contribute
to
acute53
and
long-term
treatment
outcomes
following
trials
of
antidepres-54
sants
and/or
cognitive-behavioral
therapy
[9,35,39].
Furthermore,55
changes
in
neuroticism
and
extraversion
following
treatment
for56
MDD
have
been
found
not
to
be
completely
accounted
for,
or
redun-57
dant
with,
MDD
improvement
[7,8].58
However,
despite
the
accumulating
evidence
associating59
extraversion
and
neuroticism
with
a
causal
path
to
MDD,
little60
research
exists
on
the
putative
association
between
these
person-61
ality
domains
and
the
antidepressant
effects
of
HF-rTMS.62
Thus,
in
the
current
clinical
trial
of
HF-rTMS
over
the
left63
dorsolateral
prefrontal
cortex
(DLPFC)
in
depressed
subjects,
we64
analyzed
the
association
between
extraversion
and
neuroticism65
with
treatment
outcome.
In
agreement
with
the
current
literature66
on
the
impact
of
antidepressant
medications
on
personality
traits67
[9,17,33,35,39],
we
hypothesized
that
(a)
measures
of
personality68
traits
and
depression
would
not
be
redundant
contents-wise,
that69
(b)
four
weeks
of
daily
HF-rTMS
would
reduce
and
increase
the70
levels
of
neuroticism
and
extraversion,
respectively,
and
that
(c)71
baseline
neuroticism
and
extraversion
levels
would
independently
72
predict
the
improvements
in
depressive
symptoms
post-rTMS.73
1.
Participants
and
methods74
1.1.
Depressed
patients75
The
present
study
was
approved
by
the
Douglas
Mental
Health76
University
Institute’s
(DMHUI)
Research
Ethics
Board,
and
written77
informed
consent
was
obtained
from
all
participants.
A
sample
of78
15
depressed
subjects
(7
males,
8
females)
were
recruited
between
79
September
2008
and
2009
from
the
Depressive
Disorders
Program80
at
the
DMHUI.
All
participants
had
a
primary
diagnosis
of
at
least81
a
moderate
current
major
depressive
episode
(MDE)
as
assessed
82
by
the
Structured
Clinical
Interview
for
DSM-IV
Axis
I
Disorders
83
(SCID-I)
[13]
and
the
21-item
Hamilton
Depression
Rating
Scale84
(HAM-D
21
)
[20].85
Patients
were
not
withdrawn
from
psychotropics,
but
their
86
doses
were
required
to
remain
stable
in
the
8
weeks
preceding
the87
trial
and
for
its
entire
duration.88
Exclusionary
criteria
consisted
of
the
presence
of
current
89
psychotic
features,
lifetime
history
of
any
non-mood
psychotic
dis-90
order
or
bipolar
disorder
type
I
or
II,
current
substance
or
alcohol
91
abuse/dependence
(within
the
past
6
months),
current
neurolog-92
ical
disease,
pregnancy,
and
presence
of
any
contraindication
for
93
HF-rTMS
(e.g.,
personal
history
of
epilepsy,
metallic
head
implants).
94
1.2.
Evaluation
and
outcome
measurements
95
A
psychiatrist
(M.T.B.)
performed
baseline
medical
and
psychi-96
atric
history
assessments
and
safety
screenings.
Data
were
gathered97
at
baseline
and
at
week
4
by
a
trained
mental
health
researcher98
(M.-M.B.).99
The
HAM-D
21
[20]
was
used
as
a
clinician-rated
measure
of100
depressive
symptoms.
Extraversion
and
neuroticism
were
assessed101
using
the
Big
Five
Inventory
(BFI)
[4],
a
self-report
measure
based102
on
the
FFM
[40].
Reliability
analyses
revealed
very
good
internal
103
consistency
for
both
pre-
and
post-rTMS
measures
of
extraversion104
(pre-
=
0.88;
post-
=
0.87),
and
neuroticism
(pre-
=
0.77;
post-105
=
0.88).106
1.3.
rTMS
treatment
107
HF-rTMS
was
administered
using
a
Magstim
Rapid
2®
magnetic108
stimulator
with
a
focal
70-mm
figure-of-eight
coil.
The
resting109
motor
threshold
was
determined
over
the
left
primary
motor
cortex110
using
the
visualization
method
[32]
and
the
maximum
likelihood
111
strategy
[29].
Coil
positioning
was
determined
by
the
10–20
EEG
112
system,
such
that
F3
corresponds
to
the
left
DLPFC
[22].
113
The
coil
was
set
flat
against
the
scalp
with
the
handle
pointing
114
45
away
from
the
midline.
Stimulation
at
10
Hz
was
applied
at
115
120%
resting
motor
threshold
in
75
trains
of
4
s
duration
with
26
s
116
intertrain
interval,
totaling
3000
pulses
per
session
[31].
Patients
117
received
daily
rTMS
sessions,
excluding
weekends,
for
a
period
of
118
four
weeks.
119
1.4.
Statistical
analyses 120
Statistical
analyses
were
performed
with
IBM
SPSS
20.
Pre-post
121
rTMS
comparisons
were
analyzed
with
repeated
measures
ANOVA 122
and
correlations
with
Spearman
coefficients. 123
We
tested
the
ability
of
baseline
extraversion
and
neuroticism
124
levels
to
predict
decreases
in
depressive
symptoms
after
HF-rTMS
125
treatment
using
repeated
measures
ANOVA
(by
including
these
126
personality
traits
as
covariates
in
the
model).
Linear
regression
was
127
then
used
to
confirm
the
relationship
between
baseline
personality
128
traits
and
change
in
depressive
symptoms
after
HF-rTMS
treatment.
129
We
aimed
to
determine
how
identified
changes
in
depressive
130
symptoms
as
a
function
of
HF-rTMS
treatment
were
related
to
131
changes
in
personality
traits
as
a
function
of
the
same
treatment.
132
To
this
end,
we
used
linear
regressions
to
examine
the
relationship 133
between
percent
change
in
depressive
symptoms
and
%
change
in
134
personality
traits
affected
by
HF-rTMS
treatment.
135
To
test
the
role
of
neuroticism
as
a
mediator
of
the
HF-
136
rTMS-induced
changes
in
depressive
symptoms,
we
used
repeated
137
measures
ANOVA
to
re-examine
changes
in
depressive
symptoms
138
including
the
relative
change
in
neuroticism
as
a
covariate.
A
pri-
139
ori,
mediation
was
defined
as
a
significant
interaction
between
the
140
relative
change
in
neuroticism
and
depressive
symptoms.
A
simple
141
decrease
in
the
strength
of
the
main
effect
of
depressive
symptoms
142
was
deemed
insufficient
to
demonstrate
mediation
due
to
the
sam-
143
ple’s
limited
statistical
power
and
resulting
instability
as
a
result
of
144
including
an
additional
covariate
in
the
model.
145
p
<
0.05
was
taken
as
indicating
statistically
significant
differ-
146
ences.
147
2.
Results
148
2.1.
Sample
characteristics
149
One
subject
(male,
37
years-old)
was
excluded
from
the
analyses
150
because
he
did
not
complete
post-rTMS
measures.
151
Subjects’
ages
ranged
from
33
to
61
years,
with
a
mean
age
of
152
47.6
years
±
8.44.
Most
of
them
(n
=
13)
were
Caucasians
and
had
153
a
high
school
or
university
degree.
Mean
baseline
and
endpoint
154
HAM-D
21
scores
were,
respectively,
30.2
±
7.23
and
24.21
±
8.34,
155
indicating
a
significant
improvement
in
depressive
symptoms
156
(d.f.
=
13;
t
=
4.03;
p
=
0.001).
Current
MDEs
were
chronic,
ranging
157
from
18
to
120
months
in
length
(mean
=
64.4
±
32.4
months).
All
158
participants
had
at
least
one
comorbid
Axis
I
disorder.
159
2.2.
Correlation
between
personality
traits
and
depressive 160
symptoms
161
Analyses
showed
that
both
neuroticism
and
extraversion
levels
162
were
not
significantly
correlated
with
HAM-D
21
scores
at
baseline
163
(i.e.,
r
=
0.4,
p
=
0.16
and
r
=
0.09,
p
=
0.75,
respectively)
or
at
endpoint
164
(i.e.,
r
=
0.46,
p
=
0.1
and
r
=
0.35,
p
=
0.22,
respectively).
165
Page 2
Please
cite
this
article
in
press
as:
M.T.
Berlim,
et
al.,
Are
neuroticism
and
extraversion
associated
with
the
antidepressant
effects
of
repetitive
transcranial
magnetic
stimulation
(rTMS)?
An
exploratory
4-week
trial,
Neurosci.
Lett.
(2013),
http://dx.doi.org/10.1016/j.neulet.2012.12.029
ARTICLE IN PRESS
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Model
NSL
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xxx (2013) xxx–
xxx 3
Table
1
Pre-intervention
extraversion
and
neuroticism
levels
predicting
depressive
symptom
improvement.
Mean
square
d.f.
a
F
p
Extraversion
Depressive
symptoms 7.55
(1,
12) 0.74
0.404
Depressive
symptoms
extraversion
b
80.99
(1,
12)
8.03
0.015
b
Neuroticism
Depressive
symptoms 0.00
(1,
12)
0.00
0.982
Depressive
symptoms
neuroticism
b
6.05
(1,
12)
0.37
0.554
a
Degrees
of
freedom.
b
Statistically
significant.
2.3.
Pre-post
rTMS
comparisons166
HF-rTMS
significantly
decreased
neuroticism
levels167
(pre
=
32.93
±
5.49
vs.
post
=
30.57
±
6.75;
F(1,13)
=
6.04,
p
=
0.03).168
However,
no
change
was
observed
in
extraversion
levels169
(pre
=
17.9
±
7.07
vs.
post
=
19.07
±
6.35;
F(1,13)
=
2.29,
p
=
0.15).170
2.4.
Pre-treatment
personality
and
subsequent
HF-rTMS
171
treatment
outcome172
Pre-rTMS
assessments
of
neuroticism
and
extraversion
predict-173
ing
depressive
symptoms
reduction
are
summarized
in
Table
1.
174
Pre-rTMS
intervention
assessment
of
extraversion
significantly175
predicted
the
subsequent
change
in
depressive
symptoms.
This176
relationship
was
further
explored
using
linear
regression
where177
change
in
depressive
symptoms
as
measured
by
the
HAM-D
21
178
was
predicted
by
pre-rTMS
assessment
of
extraversion.
This
anal-179
ysis
revealed
a
significant
relationship
between
pre-intervention180
extraversion
and
subsequent
response
to
HF-rTMS
(B
=
0.54,
181
F(1,13)
=
8.03,
p
=
0.015)
which
is
illustrated
in
Fig.
1.Q2182
2.5.
Change
in
personality
dimensions
and
antidepressant183
outcome184
We
sought
to
determine
whether
the
changes
in
neuroticism185
and
depressive
symptoms
induced
by
HF-rTMS
were
related.
Linear186
regressions
testing
the
ability
of
the
relative
change
in
neuroticism
187
to
predict
the
relative
change
in
depressive
symptoms
revealed
a188
significant
relationship
(B
=
1.16,
F(1,13)
=
6.82,
p
=
0.023)
which
is189
summarized
in
Fig.
2.190
Fig.
1.
As
the
changes
in
depressive
symptoms
and
neuroticism
were
191
significantly
associated,
we
aimed
to
test
the
mediating
effect
192
of
changes
in
neuroticism
on
depressive
symptoms.
These
anal-
193
yses
found
no
evidence
for
mediation,
as
they
did
not
reveal
a 194
significant
DEPRESSIVE
SYMPTOM
× RELATIVE
CHANGE
NEUROTI-
195
CISM
interaction
(mean
square
=
28.88;
F(1,12)
=
2;
p
=
0.18),
yet
the
196
main
effect
of
DEPRESSIVE
SYMPTOMS
remained
significant
(mean 197
square
=
129.46;
F(1,12)
=
8.97;
p
=
0.011).
198
3.
Discussion
199
This
prospective
exploratory
study
assessed,
in
a
sample
of
200
subjects
with
moderate
to
severe
MDD,
whether
the
personality
201
dimensions
of
extraversion
and
neuroticism
were
associated
with
202
the
antidepressant
effects
of
HF-rTMS.
Briefly,
we
have
shown
that
203
extraversion
levels
significantly
predicted
the
subsequent
changes
204
in
depressive
symptoms
following
HF-rTMS,
and
that
HF-rTMS
205
resulted
in
changes
in
neuroticism
that
were
related,
but
per-
206
haps
independent,
from
improvements
in
depression.
Previously,
207
Spronk
et
al.
[38]
have
shown
a
decrease
in
neuroticism
and
an
208
increase
in
extraversion
levels
following
21
sessions
of
HF-rTMS
209
over
the
left
DLPFC
in
a
smaller
sample
of
patients
with
uncompli-
210
cated
MDD
(n
=
8).
211
Overall,
our
findings
suggest
that
the
relationship
between
the
212
antidepressant
response
to
HF-rTMS
and
its
effects
on
person-
213
ality
variables,
such
as
neuroticism,
may
occur
via
independent
214
mechanisms,
and
that
changes
in
neuroticism
may
accompany
215
clinical
response.
Indeed,
recent
studies
support
these
possibil-
216
ities.
For
example,
Quilty
et
al.
[35]
conducted
a
study
on
93
217
depressed
patients
who
were
treated,
among
other
medications,
218
with
selective
serotonin
reuptake
inhibitors
(SSRIs),
and
have
219
Fig.
2.
Page 3
Please
cite
this
article
in
press
as:
M.T.
Berlim,
et
al.,
Are
neuroticism
and
extraversion
associated
with
the
antidepressant
effects
of
repetitive
transcranial
magnetic
stimulation
(rTMS)?
An
exploratory
4-week
trial,
Neurosci.
Lett.
(2013),
http://dx.doi.org/10.1016/j.neulet.2012.12.029
ARTICLE IN PRESS
G
Model
NSL
29466
1–5
4 M.T.
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et
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/
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xxx (2013) xxx–
xxx
shown
that
those
receiving
SSRIs
exhibited
greater
neuroticism220
change
than
those
receiving
noradrenergic/dopaminergic
antide-221
pressants,
and
that
greater
neuroticism
change
was
associated
with222
greater
depressive
symptom
change,
suggesting
that
any
treat-223
ment
effect
of
SSRIs
occurred
through
neuroticism
reduction.
More224
recently,
the
same
research
group
[34]
has
shown,
in
a
8-week225
randomized
controlled
trial
with
93
outpatients
with
MDD,
that226
subjects
receiving
the
tricyclic
antidepressant
clomipramine
had227
significantly
lower
post-treatment
scores
on
harm
avoidance
(HA;228
conceptually
similar
to
and
highly
correlated
with
neuroticism229
[28])
compared
to
those
in
the
control
group
(receiving
either230
placebo
or
sub-therapeutic
doses
of
duloxetine)
(d
=
0.53),
that
HA231
was
associated
with
depression
reduction
(r
=
0.48,
p
<
0.01),
and232
that
greater
HA
reduction
was
associated
with
greater
depression233
reduction.
Furthermore,
Tang
et
al.
[39]
have
reported,
in
a
8-week234
randomized
controlled
trial
with
240
depressed
patients
assigned235
to
receive
either
cognitive-behavioral
therapy
(CBT),
the
SSRI236
paroxetine
or
placebo,
that
those
who
took
paroxetine
reported237
6.8
and
3.5
times
as
much
change
in
neuroticism
(p
<
0.001)
and238
extraversion
(p
=
0.002),
respectively,
than
those
who
took
placebo,239
even
after
controlling
for
depression
improvement,
and
that
the
240
advantage
of
paroxetine
over
placebo
in
antidepressant
efficacy241
was
no
longer
significant
after
controlling
for
change
in
these
two242
personality
traits.
CBT,
in
turn,
produced
greater
personality
change243
than
placebo
(p
0.01),
but
its
advantage
on
neuroticism
was
no244
longer
significant
after
controlling
for
depression.
Nevertheless,245
Knorr
et
al.
[25]
have
recently
shown
no
significant
difference
in
the246
change
in
reported
neuroticism
or
extraversion
scores
among
80247
healthy
first-degree
relatives
of
patients
with
MDD
who
were
ran-248
domized
to
receive
either
the
SSRI
escitalopram
or
placebo.
Finally,249
a
recent
meta-analysis
[23]
has
shown
that
HA
scores
markedly
250
and
negatively
change
from
baseline
to
endpoint
among
patients251
treated
for
MDD
(p
<
0.0001).252
In
addition,
our
study
suggests
that
certain
personality
traits253
(in
this
case
extraversion)
are
more
likely
to
predict
response
to254
treatment
after
HF-rTMS.
Interestingly,
previous
studies
have
also255
supported
this
finding.
For
example,
Bagby
et
al.
[3]
have
shown,256
in
a
sample
of
280
depressed
subjects
randomized
to
receive
SSRIs257
or
CBT,
that
higher
scores
on
openness
at
baseline
were
associated
258
with
lower
depression
severity
at
treatment
completion
regard-
259
less
of
the
therapeutic
intervention
received
(ˇ
=
0.26,
t
=
3.61,260
p
<
0.001),
whereas
higher
neuroticism
scores
at
baseline
were261
associated
with
lower
post-treatment
depression
severity
only262
for
those
receiving
SSRIs
(ˇ
=
0.9,
t
=
2.12,
p
<
0.04).
Furthermore,263
Fiedorowicz
et
al.
[12]
reported
that
neuroticism
was
inversely264
correlated
with
depressive
symptoms
improvement
over
a
4-
265
week
open-label
trial
with
the
SSRI
escitalopram
(n
=
21;
r
=
0.57,266
p
=
0.007).267
One
possible
explanation
for
our
findings
might
be
that
MDD268
and
neuroticism/extraversion
share
part
of
their
neurobiological269
substrates
and
may
thus
respond
to
similar
therapeutic
interven-270
tions
[6,11,15].
Interestingly,
neuroimaging
studies
have
generally271
indicated
that
functional
and
structural
variability
in
brain
regions
272
known
to
be
related
to
affective
processing
and
ultimately
to273
mood
disorders
are
also
associated
with
individual
differences274
in
neuroticism
and
extraversion
[43].
Furthermore,
neuroen-275
docrine
studies
have
linked
high
neuroticism
with
exaggerated
276
hypothalamic–pituitary–adrenal
activation
(a
hallmark
of
melan-277
cholic
depression
[30])
[44],
while
molecular
studies
have
shown,278
for
example,
that
lower
brain-derived
neurotrophic
factor
(BDNF)
279
serum
levels
in
healthy
participants
were
related
to
high
neuroti-
280
cism
(which
might
explain,
at
least
partially,
the
vulnerability
of
281
individuals
with
high
neuroticism
to
MDD)
[27].282
However,
a
number
of
limitations
of
our
study
deserve
con-283
sideration.
Firstly,
a
certain
degree
of
skepticism
is
warranted
284
when
considering
the
self-reported
validity
of
personality
variables285
during
a
MDE.
Nevertheless,
studies
investigating
the
psychometric
286
properties
of
FFM-related
scales
pursuant
to
antidepressant
ther-
287
apy
suggest
that
self-reported
personality
is
valid
[7].
Moreover,
288
studies
on
self-reported
personality
support
decreases
in
neuroti-
289
cism
and
increases
in
extraversion
with
response
to
antidepressant
290
therapy
in
MDD
[7].
Also,
the
possibility
that
the
measures
of
per-
291
sonality
traits
and
depressive
symptoms
employed
in
this
study
292
are
circular/redundant
content-wise
is
not
supported
by
our
results
293
(i.e.,
their
common
variances
ranged
from
only
1%
to
21%).
Secondly,
294
this
was
a
small
open-label
trial
as
opposed
to
a
blinded
study,
and
295
this
might
have
inflated
its
results
[42].
Thirdly,
since
we
did
not
296
employ
a
control
group,
an
estimation
of
the
placebo
effect
was
297
not
possible.
There
is,
however,
strong
evidence
to
suggest
that
298
the
placebo
response
rates
are
much
lower
in
subjects
with
mod-
299
erate
to
severe
MDD
[16].
Finally,
the
assessment
of
personality
300
and
depressive
symptoms
before
and
after
HF-rTMS
prohibited
a 301
detailed
analysis
of
the
course
of
change
during
treatment. 302
In
summary,
the
present
study
provides
preliminary
evidence 303
that
neuroticism
and
extraversion
are
likely
associated
with
the
304
antidepressant
effects
of
HF-rTMS
over
the
left
DLPFC.
However, 305
further
randomized,
sham-controlled
and
double-blind
trials
in
306
larger
samples
and
using
more
robust
statistic
approaches
(e.g.,
307
structure
equation
modeling)
should
be
carried
out
to
better
under-
308
stand
this
relationship.
309
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Page 4
Please
cite
this
article
in
press
as:
M.T.
Berlim,
et
al.,
Are
neuroticism
and
extraversion
associated
with
the
antidepressant
effects
of
repetitive
transcranial
magnetic
stimulation
(rTMS)?
An
exploratory
4-week
trial,
Neurosci.
Lett.
(2013),
http://dx.doi.org/10.1016/j.neulet.2012.12.029
ARTICLE IN PRESS
G
Model
NSL
29466
1–5
M.T.
Berlim
et
al.
/
Neuroscience
Letters
xxx (2013) xxx–
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  • Source
    • "predicting outcome. Previous authors have identified a variety of DLPFC-rTMS outcome predictors: age and number of previous failed medication trials [30], episode duration [31], extraversion [32], sleep disturbance [33], apathy symptomatology [34], and HamD 17 items for depressed mood and guilt [35]. A prospective study with more rigidly defined inclusion criteria, and more structured assessment of medication resistance, could reveal whether these predictors apply to DMPFC-rTMS as well. "
    Full-text · Article · Mar 2015 · Brain Stimulation
  • Source
    • "predicting outcome. Previous authors have identified a variety of DLPFC-rTMS outcome predictors: age and number of previous failed medication trials [30], episode duration [31], extraversion [32], sleep disturbance [33], apathy symptomatology [34], and HamD 17 items for depressed mood and guilt [35]. A prospective study with more rigidly defined inclusion criteria, and more structured assessment of medication resistance, could reveal whether these predictors apply to DMPFC-rTMS as well. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Conventional rTMS protocols for major depression commonly employ stimulation sessions lasting >30 min. However, recent studies have sought to improve costs, capacities, and outcomes by employing briefer protocols such as theta burst stimulation (iTBS). Objective: To compare safety, effectiveness, and outcome predictors for DMPFC-rTMS with 10 Hz (30 min) versus iTBS (6 min) protocols, in a large, naturalistic, retrospective case series. Methods: A chart review identified 185 patients with a medication-resistant major depressive episode who underwent 20-30 sessions of DMPFC-rTMS (10 Hz, n = 98; iTBS, n = 87) at a single Canadian clinic from 2011 to 2014. Results: Clinical characteristics of 10 Hz and iTBS patients did not differ prior to treatment, aside from significantly higher age in iTBS patients. A total 7912 runs of DMPFC-rTMS (10 Hz, 4274; iTBS, 3638) were administered, without any seizures or other serious adverse events, and no significant differences in rates of premature discontinuation between groups. Dichotomous outcomes did not differ significantly between groups (Response/remission rates: Beck Depression Inventory-II: 10 Hz, 40.6%/29.2%; iTBS, 43.0%/31.0%. 17-item Hamilton Rating Scale for Depression: 10 Hz, 50.6%/38.5%; iTBS, 48.5%/27.9%). On continuous outcomes, there was no significant difference between groups in pre-treatment or post-treatment scores, or percent improvement on either measure. Mixed-effects modeling revealed no significant group-by-time interaction on either measure. Conclusions: Both 10 Hz and iTBS DMPFC-rTMS appear safe and tolerable at 120% resting motor threshold. The effectiveness of 6 min iTBS and 30 min 10 Hz protocols appears comparable. Randomized trials comparing 10 Hz to iTBS may be warranted. (C) 2015 The Authors. Published by Elsevier Inc.
    Full-text · Article · Nov 2014 · Brain Stimulation
  • Source
    • "nts scoring lower on SD had also comorbid personality disorder is mainly speculative at this point. Of note, two recent studies from the same research group recently examined the predictive value of the Big Five Inventory ( Martínez and John, 1998 ), based on the NEO-V model of personality (McCrae and Costa, 1987), on rTMS outcomes on MDD patients. Berlim et al. (2013) reported in their 4-week exploratory open trial that only high scores on extraversion predicted the clinical outcome of left DLPFC HF-rTMS treatment. McGirr et al. (2014) found that higher baseline levels of agreeableness and conscientiousness predicted remission after 4 weeks of deep HFrTMS delivered on the left DLPFC and the levels of"
    [Show abstract] [Hide abstract] ABSTRACT: Although well-defined predictors of response are still unclear, clinicians refer a variety of depressed patients for a repetitive Transcranial Magnetic Stimulation (rTMS) treatment. It has been suggested that personality features such as Harm Avoidance (HA) and self-directedness (SD) might provide some guidance for a classical antidepressant treatment outcome. However, to date no such research has been performed in rTMS treatment paradigms. In this open study, we wanted to examine whether these temperament and character scores in particular would predict clinical outcome in refractory unipolar depressed patients when a typical high-frequency (HF)-rTMS treatment protocol is applied. Thirty six unipolar right-handed antidepressant-free treatment resistant depressed (TRD) patients, all of the melancholic subtype, received 10 HF-rTMS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). All patients were classified as at least stage III TRD and were assessed with the Temperament and Character Inventory (TCI) before a HF-rTMS treatment. Only the individual scores on SD predicted clinical outcome. No other personality scales were found to be a predictor of this kind of application. Our results suggest that refractory MDD patients who score higher on the character scale SD may be more responsive to the HF-rTMS treatment.
    Full-text · Article · Aug 2014 · Psychiatry Research
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