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

Conflicts of Interest

• No conflicts of interest to report

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

Rostral ACC

Amygdala

Lateral PFC

Vuilleumier 2006

Bishop 2007

X

. ..

..

Measuring affective processing bias

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?

Acknowledgements

• Money– Wellcome Trust

• Collaborators– Cath Harmer, Emily Holmes, Guy Goodwin