Tackling depressive disorder: A working memory intervention

The life of individuals with a depressive disorder changes significantly. A
depression changes the way people feel and how they perceive themselves as well
as the world around them. According to the World Health Organisation (WHO),
around 12% of the population is suffering from clinical depression, making it
among the most prevalent psychiatric disorders. The WHO estimates that this
number is increasing, and that by the year 2020, depression will be the most
prevalent disorder causing disability for all ages in men and women. In
addition to the distress depression causes to individuals and their families,
this emotional disorder also incurs extensively direct and indirect economic
costs, which for instance in the Netherlands exceeds one billion Euros annually
and in the United States of America 65 billion dollars. Clearly, more research
is needed to increase the understanding of the causes and maintenance of this
disorder, and to enhance prevention and treatment. Therefore the current
proposal is aimed at examining crucial underpinnings of depression and also
aspires to yield a novel approach of clinical treatment by targeting these
deficits.

Apart from important neurobiological research examining the onset and
maintenance of depression, a dominant focus in the past 30 years has been on
cognitive models of depression. These posit that selective information
processing plays a crucial role in the development and maintenance of this
disorder (for a review, see Williams, Watts, MacLeod, & Mathews, 1988, 1997).
That is, how people think, make inferences, approach certain situations, attend
to certain events, and how they recall these events determine their emotional
responses and, as a consequence, whether or not they are likely to incur a
depression. Clearly, cognitive processes play a crucial role in how much people
are affected by negative experiences and determine whether these events will be
followed by quick recovery or by recurring depressive episodes. These models,
therefore, make the important assumption that investigating the content of
cognition and the nature of cognitive processes in depression is essential for
our understanding of the onset and maintenance of this disorder.

The extensive research programs generated by these cognitive models have shown
that depressed individuals are characterised by preferential processing of
negative material, difficulties in disengaging attention from negative
information, interpreting ambiguous information in a negative way and recalling
events in a more negative and more general fashion than they originally were
(Mathews & MacLeod, 2005). Recently, new procedures (i.e., cognitive bias
modification; CBM) have been developed and studied to manipulate these biases
and the first steps have now been made to experimentally employ these CBM
procedures for improving cognitive deficits in depression. For instance,
Watkins, Baeyens, and Read (2009) administered a concreteness training that
successfully overcame the depression-related cognitive bias to process
self-relevant information in an overgeneralised manner. In a similar vein,
Holmes and colleagues demonstrated that modifying maladaptive interpretations
reduces depressive intrusions (e.g., Holmes, Lang, & Shah, 2009).

An important concept in understanding these dysfunctional cognitive processes
is working memory. Working memory is commonly described as a system for the
active maintenance and manipulation of information in memory and for the
control of attention (Baddeley & Hitch, 1974). The capacity of this system is
limited; therefore it is important that its contents are updated efficiently,
which is controlled by executive processes (e.g., Friedman & Miyake, 2004).
Executive processes direct the access to working memory, by removing
information that is no longer relevant, as well as protecting it from
intrusions. If these processes perform poorly, cognitive and emotional
functioning are likely to be affected. For example, poor interference
resolution may lead to more intrusive thoughts. In fact, increased interference
from irrelevant intrusions has been suggested as a source of low working memory
capacity (Geraerts, Merckelbach, Jelicic, & Habets, 2007). Irrelevant negative
intrusions are an important characteristic of depression. Indeed, such
deficient executive functioning has been linked to depression (Joormann, 2010).
Emerging evidence now shows that depression is characterized by difficulties in
the inhibition of mood-congruent material, resulting in prolonged processing of
negative, goal-irrelevant aspects of presented information. This in turn
hinders recovery from negative mood and leads to sustained negative affect,
which is typical for depressive episodes.

Accordingly, theorists have suggested that deficits in executive functioning
lie at the heart of biases in attention, interpretation, and memory in
depression. They are said to lead to ruminative responses to negative events
and, consequently, negative mood states. Indeed, a study by Joormann and Gotlib
(2008) has shown that interference control was decreased in depressive
patients. This means that they experienced difficulty from removing irrelevant
material from working memory. Noticeably, this increased interference was
linked to rumination, one of the hallmark symptoms of depression. This
association was still evident after a 6-month period (Zetsche & Joormann, in
press). Similarly, Goeleven, de Raedt, Baert, and Koster (2006) found that
depressed patients showed strongly impaired inhibition of negative affect.
These findings of executive deficits in depression have been backed up by
neuroscientific work, which indicated abnormalities in neural function
underlying difficulties in inhibition of negative thoughts in depressed
individuals (Koster, De Lissnyder, Derakshan, & De Raedt, in press).

One wonders whether such executive deficits can be trained in the same manner
as those deficits targeted in cognitive bias modification procedures. Is it
possible to improve executive processes, which then in turn influence
higher-order cognitive abilities and even overt behaviour? Seminal work by
Klingberg and colleagues has demonstrated that this is possible. These
researchers showed that training of working memory in both children and adults
improved their executive functioning and higher-order abilities such as
reasoning (Klingberg, Forssberg, & Westerberg, 2002). This improvement was
related with changes in cortical activity (McNab et al., 2009). Interestingly,
in a sample of children with attention deficit/hyperactivity disorder (ADHD) a
working memory training improved executive functioning but also led to a
significant reduction in the severity of ADHD symptoms (Klingberg et al.,
2005). Likewise, Jaeggi, Buschkuehl, Jonides, and Perriq (2008) showed that a
working memory training improved participants* reasoning and problem solving
skills.

Noticeably, these different lines of research all point towards one conclusion:
individual differences in the ability to control the contents of working memory
may be related to the onset and maintenance of depressive disorder. Improving
working memory abilities could therefore tackle what may be at the root of
depression.

The present study is aimed at investigating cognitive underpinnings of
depression, by focusing on working memory abilities in both depressed and
non-depressed individuals. These findings will be employed to design and test a
therapeutic intervention targeting working memory deficits in depressed
patients, both on a short and longer term. In doing so, this project ought to
yield novel approaches of clinical treatment by targeting cognitive deficits
related to depression, in that way bridging the gap between basic cognitive
science and clinical psychological treatments for depression.

This study will focus on the outcome of a working memory intervention in a
large sample of individuals with major depressive disorder. Additionally, it
will be studied whether the outcome effects are resistant to a mood provocation
test.

A randomised controlled trial (RCT) will be used in people diagnosed with major
depressive disorder: 120 individuals will be randomly allocated to either a
working memory training or a bogus working memory training (i.e., simple
arithmetic tasks that do not significantly load working memory ability). All
participants will be recruited from mental health care centres in which they
are waiting for a treatment after having had a diagnostic intake for depression
. During an initial session (i.e., Pretest), the researcher -blind to
condition- will use the Structured Clinical Interview for DSM-IV disorders
(SCID) to confirm the diagnosis of major depressive disorder. Also, the BDI-II
and the Hamilton Rating Scale will be used as self-report measures of the
severity of individuals* depressive symptomatology. The RRS and AMT will be
performed in order to examine whether the effects of the intervention transfer
to other important depression-related cognitive characteristics (i.e.,
rumination and overgeneral memory, respectively).

In the four weeks following this pretest, participants will receive the working
memory intervention three times a week. This intervention will take about half
an hour and is easily accessible via a website that participants can access
from their computer at home. The researcher monitors whether participants have
performed the training and will alert participants in case they have missed a
session. The training will systematically teach individuals to utilize their
working memory on a variety of domains. The tasks will target the specific
working memory abilities that are poor in depression.

After the four-week intervention, the researcher and the participant meet again
(i.e., Posttest). In this posttest, the same measures will be performed as
during the pretest (i.e., SCID, BDI-II, Hamilton Rating Scale, RRS, AMT, and
appropriate working memory tests). It is predicted that participants who
received the working memory training will show an increased performance on
working memory tests and a decrease in depressive symptoms (SCID, BDI-II,
Hamilton Rating Scale), relative to pretest and to control participants. As
deficits in executive functioning have been linked to rumination and
overgeneral memory deficits in depression, it is expected that individuals who
underwent the working memory intervention will show transfer effects by having
a lessened ruminative thinking style (RRS) as well as overgeneral memory (AMT).

One of the essential questions is whether this pattern of reduced
symptomatology holds when confronted with stressors. Would our participants
still react with increased working memory performance and reduced depressive
symptomatology when they are temporarily brought into a dysphoric state? To
examine this issue, a sad mood provocation (i.e., Velten mood procedure;
Velten, 1968) will be used. Indeed, recent research has shown that relapse can
best be predicted by performance on such a mood induction procedure (Segal et
al., 2006). If the working memory training appears to be successful, one would
expect that compared to controls, individuals in the intervention condition are
more resistant to the mood induction and still show increased working memory
performance (hypothesized to be similar as in the posttest), indicating that
relapse is unlikely.

A follow-up test (Follow-up I) after two months will be the final step.
Assuming that individuals in the training condition have benefited from the
working memory intervention, one would assume that their depressive symptoms
(SCID, BDI-II, Hamilton Rating Scale) and depression-related characteristics
(RRS and AMT) would still be lower after such a time interval, relative to
individuals in the control condition. Additionally, one would assume that their
working memory ability is still improved, indicated by a better performance on
the working memory tasks.

Workingmemory tasks at pre- and posttests and at home:
- AB-AC-AD taak
- Number-letter taak

Workingmemory task only at pre- and posttests:
Sternberg taak

Moodinduction

No risks are associated with participation. The benefit is an earlier treatment
and a possible effective treatment.