Post on 20-Apr-2020
Attentional Bias Training, Antidepressant Drugs and their Combination
Can the Neurocognitive Effects of the Treatments for Anxiety
be Used to Guide the Development of Novel Combination Regimes?
Michael Browning
FMRIB Centre, University of Oxford
ADAA April 2012
Cognition in anxiety
• Anxious patients tend to attend to and interpret environmental information in a negative manner
• These “negative cognitive biases” are believed to by causally related to anxious symptoms
Mathews & MacLeod 2005
Antidepressant Medication– Behavioural Effects
Attention to emotional stimuli
.
..
• Are one or two dots presented?
..
Anti-depressant effect
Murphy et al . 2009
-25
0
25
50
Citalopram
Placebo
Vig
ilan
ce (
ms)
•Decreased attention to negative stimuli
*
FEAR HAPPY
Left Right
% S
ign
al C
han
ge
Placebo
Citalopram -0.2
-0.1
0
0.1
0.2
0.3
** *
Harmer et al. 2006
Murphy et al. 2009
Fu et al. 2004
-0.2
-0.1
0
0.1
0.2
0.3
• Citalopram reduced amygdala responses to fearful but not happy facial expressions
Amygdala responses
Antidepressant Medication– Neural Effects
Cognitive Bias Modification
• Learn a different cognitive bias
MacLeod et al. 2002
Attention to emotional stimuli
.
..
• Are one or two dots presented?
..
Avoid-threat
Attend-threat
CBM– Behavioural Effects
- 30
- 20
- 10
0
10
20
30
40
50
60
70
80
Vig
ila
nc
e (
ms
)
**
Browning et al. 2010
•CBM does what it says on the tin
Attention to emotional stimuli
.
..
• Are one or two dots presented?
..
CBM– Neural Effects
-0.15
-0.1
-0.05
0
0.05
0.1
0.15
0.2
0.25
Look at
emotional faces
Look away from
emotional faces
Avoid-threat Attend-threat
% s
ign
al c
ha
ng
e f
or
fea
r-n
eu
tra
l fa
ce
s *
Browning et al. 2010
•Following CBM prefrontal control systems react to violations of the training rule
Question
• The effects of antidepressant medication and CBM appear to be mediated by different neural systems
• What happens when the two interventions are combined?
Testing Treatment Interaction
• 62 non-clinical volunteers
• Cognitive bias (memory, categorisation) measured after one week of treatment
Citalopram Placebo
Positive CBM 16 15
Neutral CBM 15 16
Browning et al. 2012
Interaction Between Antidepressants and CBM
15
16
17
18
19
20
21
22
23
24
Placebo, no CBM
Placebo, Positive CBM
Citalopram, No CBM
Citalopram, Positive CBM
Nu
mb
er N
ega
tive
Wo
rds
Rec
ogn
ise
d
* *
* ^
Combining antidepressants and CBM produces interference on emotional
memory (and categorisation) Browning et al. 2012
Summary
• Cognitive biases can be altered in the laboratory using antidepressant drugs and CBM
• The effects of the interventions appear to be mediated by different neural systems
• When combined they produce an interference effect on measures of cognitive bias
Outstanding Questions
• Can these cognitive effects account for the mixed clinical picture when CBT and antidepressants are combined?
• What drug would enhance the effect of CBM?
• What psychological intervention would enhance the effect of antidepressant drugs?