Download Folie 1 - Universitätsklinikum Ulm

Neural correlates of successful psychotherapy of
depression in adolescents
Joana Straub1, Paul L. Plener1, Nina Spröber1, Linda Sprenger3, Michael G. Kölch1, Georg Grön2, Birgit Abler2
Kinder- und JugendPsychiatrie/Psychotherapie
Universitätsklinikum Ulm
1
Dept. of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Ulm, Ulm, Germany; 2Dept. of Psychiatry and Psychotherapy III, University
Hospital Ulm, Ulm, Germany; 3 Dept. of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Philipps-University Marburg, Marburg, Germany
Introduction
Results
Adolescence is a vulnerable period for the development of psychiatric
disorders such as depression which often shows a chronic course with
relapses in adulthood (Patton et al. 2014). Investigating the neural correlates
of psychiatric disorders early in life offers the opportunity to bypass effects of
previous medication and/or by changes in neural processing due to a chronic
course of a disorder (Cullen, 2012). Research on regional brain activity
showed a particularly consistent pattern of involvement of the amygdala,
hippocampus and subgenual anterior cingulate cortex (sgACC) in depressed
adolescents and adults. Pharmacological treatment led to altered pre-to-post
signal changes in those brain areas in adults and adolescents (Tao et al.
2012). While psychotherapeutic treatment effects were only sparsely
investigated in adults (Fu et al. 2008) they await empirical investigation in
adolescents. Aim of the present study was to investigate neural correlates of
depression in depressed adolescents after a brief cognitive behavioral group
therapy.
Clinical symptoms Significant reduction of depressive symptoms (BDI-II and
CDRS-R) for PAT-I complete (N=18) from pre-to-post and pre-to-follow-up.
Symptoms stayed constant from post-to-follow-up (s. Figure 3). Significant
interaction effects (group: PAT-I subgroup (N = 10) / PAT-W (N = 12) * time point:
pre / post) were found for BDI-II (p = .04) and CDRS-R (p = .03).
Figure 3 Symptom reduction for the complete PAT-I group (N=18) from pre-to-post, post-to-follow-up and pre-to-follow-up
BDI-II = Beck Depression Inventory Revision; CDRS-R = Children’s Depression Rating Scale Revised; n.s. = not significant (p>.05)
fMRI whole brain analysis were done across all depressed adolescents prior
to waiting or intervention (N=22).
Methods
Ziel der vorliegenden Untersuchung war es, neuronale Korrelate des Effekts der
Design
Teilnahme an einer KVT in der Gruppe in depressionsrelevanten Arealen zu
untersuchen.
Figure 4 Differential activation within amygdala, nucleus accumbens (NAcc), subgenual anterior cingulate cortex (sgACC) and
hippocampus; thresholded at p<.001 at the voxel level, extent threshold of 60 contiguously significant voxels per cluster, significant at
p<.05, family-wise corrected for multiple comparisons the left side of the image corresponds to the left side of the brain.
Figure 1 Study design MICHI = Manualized Intervention to Cope with depressive symptoms, Help strenghten ressources and
Improve emotion regulation; TAU = treatment as usual; PAT-W = patients of waiting group; PAT-I = patients of intervention group;
CDRS-R = Children‘s Depression Rating Scale Revised; BDI-II = Beck Depression Inventory- Revision.
Inclusion criteria CDRS-R sumscore ≥ 36; Diagnosis of a Major Depressive
Disorder according to DSM-IV; comorbidities were allowed (except for
schizophrenia, bipolar disorder and substance abuse); no contradictions to
fMRI scans
Subjects
Age (years)
PAT-I complete (N=18)
M ± SD
16.66±1.37
PAT-I subgroup(N=10)
M ± SD
16.39±1.58
PAT-W (N=12)
M ± SD
16.54±1.21
Gender
15 females (83.3%)
8 females (80%)
9 females (75%)
Handedness1
17 righthanded (94.4%)
10 righthanded (100%)
10 righthanded (83.3%)
Significance
n.s.a
ROI analyses
In the sgACC, amygdala and hippocampus the PAT-I subgroup (N=10)
showed significant pre-to-post signal reductions (right sgACC p=0.02, left
amygdala p=0.02, left hippocampus p=0.01), while pre-to-post signal
changes were not significantly different from zero in the PAT-W group.
Significant interaction effects (pre-to-post differences between PAT-I
subgroup and PAT-W) were observed for signal changes in the right sgACC
(p=.03), left amygdala (p=.01), and left hippocampus (p=.04).
Association between symptom reduction and signal change
pre-to-post sgACC
Pre-to-post difference BDI-II scores were
signal change
■ pre-to-post BDI-II score change
significantly correlated with pre-to-post Δ pre-to-follow-up BDI-II score change
signal changes in the left (r=.57, p=.01)
and right (r=.54, p=.02) sgACC. Pre-tofollow-up difference BDI-II scores were
even stronger correlated with pre-topre sgACC signal
follow-up changes in the left (r=.69,
p=.002) and right (r=.73, p=.001) sgACC
(s. Figure 5 upper graph).
Pre-treatment activation was correlated
with pre-to-follow-up symptom changes in Δ pre-to-follow-up BDI-II score change
the left (r=-.56, p=.02) and right (r=-.59, p=
Figure 5 Correlation between signal and symptom change
.01) sgACC (s. Figure 5 lower graph.)
3
2
IQ
97.81±7.29
100.00±8.72
99.67±7.55
Depression
subtypes2
Major depression, mild
(N=3); moderate (N=11);
severe (N=4)
Major depression, mild
(N=2); moderate (N=7);
severe (N=1)
Major depression, mild
(N=4); moderate (N=5);
severe (N=3)
n.s. a
1
0
-35
-30
-25
-20
-15
-10
-5
0
5
10
15
0
5
10
15
-1
-2
-3
Smoker
7 ( 38.9%)
5 (50%)
3 (25%)
Table 1 Of 18 PAT-I group patients who received the intervention, eight also participated in the waitlist group (PAT-W
N=12) before treatment while ten patients solely received the intervention without a preceding waiting period (PAT-I
subgroup N=10). 1 Edinburgh Handedness Inventory; 2 Diagnosis according to DSM-IV; significances were calculated
between the reduced PAT-I group (N=10) and PAT-W (N=12). a independent sample t-test; n.s. = not significant
-4
-5
-6
4
3.5
3
Diagnostic instruments: Children´s Depression Rating Scale-Revised (CDRS-R);
2.5
2
Beck-Depression Inventory Revision (BDI-II)
1.5
1
Psychotherapeutic treatment: Cognitive behavioral group therapy (CBT-G)
comprising five sessions á 75-90 minutes and one booster session (Spröber et al. 2012).
0
-35
-30
-25
-20
-15
-10
-5
-0.5
-1
fMRI paradigm: Contrast win versus loose
The monetary incentive delay task compasses
different parametric variations of probabilities (0%,
25%, 50%, 75%, 100%) to win a fixed amount of
money (1€) that are displayed in form of circles.
After an expectation period, in which the
probability circles were demonstrated, subjects
had to correctly react with a button press to one of
two different symbols (triangle or square). When
the target disappeared, the feedback followed
about the amount of money (1€ - win trial or 0 € lose trial) they won in the trial.
0.5
Conclusions
Successful treatment of depression in adolescents after a brief group CBT
was related to signal changes in the sgACC, amygdala and hippocampus,
previously demonstrated to be linked with pharmacological treatment,
particularly in adults.
Figure 2 Monetary incentive delay task (Abler et
al. 2006)
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