Tackling anxiety and depression in students with a working memory treatment

First we will tell you about depression, then we will focus on anxiety and
finally both disorders will be linked in the part about working memory
training:

Depression:
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 irr













elevant 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?

Anxiety:
An anxiety disorder consists of an ongoing and severe kind of anxiety without
the presence of a realistic threat. There are different kinds of anxiety
disorders, for example panic disorders, agoraphobia, social phobia, generalized
anxiety disorders (GAD) and obsessive compulsive disorders (OCD). Together with
mood disorders and substance use disorders, anxiety disorders are among the
most prevalent mental disorders (Brysbaert, 2006). The World Health
Organisation (WHO; 2010) estimates that around 12% of the population suffers
from clinical anxiety every year. The life of people with an anxiety disorder
changes significantly. Symptoms of anxiety are frequently associated with a
variety of physical symptoms like sweating, heart palpitations and trembling.
Anxiety causes a great deal of distress to the patients and to their families.
In addition, anxiety disorders cause significant economic costs. For example,
these disorders were costing the Netherlands 285,6 million euros in 2005 (Van
Wieren, Schoemaker, & Van Balkom, 2010). Treatment strategies for anxiety
disorders include cognitive therapy, cognitive-behavioral therapy,
psychopharmacology, exposure therapy, relaxation training, biofeedback,
meditation, supportive psychotherapy, psychodynamic psychotherapy, and other
forms of psychotherapy (Miller, Fletcher, & Kabat-Zinn, 1995). The most common
treatment strategies these days are cognitive-behavioral therapy and
psychopharmacology. Past research indicates that both genetics and important
events in a person*s life are playing a significant role in the development of
anxiety disorders. However, because there is still a lot unknown about the
aetiology and maintenance of these disorders, more research is needed to
address these issues and to enhance prevention and treatment. Therefore the
current proposal aims to examine important cognitive processes involved in
anxiety and aspires to set up a new approach to a clinical treatment method
targeting these processes. Over the past three decades cognitive models of
anxiety disorders have demonstrated that selective information processing plays
an important role in the development and maintenance of anxiety (Williams,
Watts, MacLeod, & Mattews, 1988). More specifically, recent studies provide
considerable evidence to state that anxiety is strongly associated with an
attentional bias towards threatening stimuli and biases in interpretation and
memory (Mathews & MacLeod, 1994; Mathews & MacLeod, 2005). Patients with an
anxiety disorder tend to interpret ambiguous information in a negative way.
Several researches demonstrate that individuals reporting high levels of
anxiety display a disproportionate ability to identify or detect emotionally
negative words (e.g. Foa & McNally 1986; as described in Mathews & MacLeod,
1994). For example, during Stroop tasks, anxious individuals display problems
ignoring the emotionally negative content of threat-related stimulus words
(e.g. Mathews & MacLeod 1985; as described in Mathews & MacLeod, 1994).
However, the nature of the relation between anxiety and cognition is far from
clear. Therefore, it is necessary to get more insight in the cognitive
processes behind anxiety. A lot of past research shows that high levels of
anxiety are associated with a reduced ability to perform complex cognitive
tasks (Mueller 1992, Watts & Cooper 1989; as described in Mathews & MacLeod,
1994). A lot of researchers state that these reductions are being caused by a
depletion of capacity-limited cognitive resources, especially working memory
(Eysenck & Calvo 1992, Ellis & Ashbrook 1988; as described in Mathews &
MacLeod, 1994). Therefore, working memory is an important concept in
understanding the cognitive biases associated with anxiety disorders.

Working memory:
Working memory can be described as a limited capacity system for the temporary,
active maintenance and storage of information (Baddeley, 2003). This system is
critical for human thought processes. The ability to retain and manipulate
information in working memory is linked with the prefrontal cortex (Fuster,
1989; Goldman-Rakic, 1987; as described in Klingberg, Forssberg, & Westerberg,
2002) and underlies different executive functions, such as problem solving and
reasoning (Engle, Kane, & Tuholski, 1999; Hulme & Roodenrys, 1995; Klingberg,
2000; as described in Klingberg et al., 2002). The theoretical concept of
working memory argues that working memory is important for human thought
processes because it provides an interface between perception, long-term memory
and action (Andrade, 2001; Miyake & Shah, 1999; Conway, Jarrold, Kane, Miyake,
& Towse, 2007; as described in Klingberg et al., 2002). Reduced working memory
capacity is associated with several neurological and psychiatric disorders like
schizophrenia and ADHD (Goldman- Rakic, 1994; Castellanos & Tannock, 2002; as
described in McNab et al., 2009). Working memory training: Seminal work by
Klingberg and colleagues has demonstrated that training the working memory 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. Recent studies showed that even in schizophrenia (Subramaniam
et al., 2012) and in people with alcohol problems (Houben, Nederkoorn, Wiers &
Jansen, 2011) the complaints decreased after training the working memory.
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.

Study whether a working memory training can decrease anxiety and depression
complaints in a student population. This is measured by means of a fysiological
measure (pupil size with an eyetracker), a working memory task and
questionnaires about depression and anxiety complaints. Besides a comparison
will be made between students without anxiety and depression symptoms and
students with these symptoms. When a relation between complaints and fatigue is
found, measured with the eyetracker (pupil dilation), the variable can be used
as physical measure in working memory research.

126 students are allocated to two groups by means of a double blind RCT:
working memory training or a bogus working memory training.
Students have to fill in the BDI and STAI to determine whether they met the
inclusioncriteria.

Pre-test:
* 2-back task on the eyetracker
* Spanboard task
• BDI-II: depression
• RRS: Rumination
• STAI: anxiety state and trait

Working memory training (half of the students get a bogus training:3 weeks 3
times a week on the computer (25 minutes per session): working memory tasks;
all valid, reliable and often used working memory tasks. The tasks in the
working memory training condition will be adapted to the level of the patient
to train the working memory. Because of the adaption it is never too hard or
easy for the patient. The same tasks will be executed in the bogus training,
but the level will not adapt and will stay at a really easy level.

Post-test (after 3 weeks):
* 2-back task on the eyetracker
* Spanboard task
• BDI-II: depression
• RRS: Rumination
• STAI: anxiety state and trait

The 63 healthy students will only execute the pre-test.

The students execute a 25-minutes working memory training in the lab of the
Erasmus University Rotterdam during 3 weeks, 3 times a week. Student assistants
answer questions of the students and contact students who do not show up. The
training consists of diverse experiments. The level of the experiments in the
experimental group adapts to their working memory capacity. In the placebo
version the experiments are very easy to not train the working memory.
The working memory training consists of 8 different experiments, each training
another aspect of the working memory. The training consists of auditory, visual
and spatial working memory tasks.
Simon task: This task is equal to the famous Simon game and is used in other
studies to measure the working memory capacity (o.a. Gendle & Ransom, 2006). In
the training two versions are used. Version 1: students see a ring existing of
the colors green, red, yellow and blue. The colors lighten in a certain order,
for example: red, blue, green, red. The participant has to repeat the order by
pressing the correct colors. Version 2: The set begins with only one color, for
example, green. The subject has to repeat the set, so presses green.
Subsequently blue lightens and the subject has to press green and blue, and so
on. The length of the series varies between 3 and 9 items and is dependents of
the level (combo-level) of the participant.
Number recall task: The number recall task is a frequently used task to measure
the level of someone*s working memory (o.a. Cowan, 2001; Alloway & Alloway,
2009). In this task two different versions were used. In the first version the
subject hears a set of numbers which has to be repeated in the same order. The
second version is the same but in reverse order. When the subject hears the set
3, 8, 5, he/she has to fill in: 5, 8, 3. The length of the set varies between 3
and 9 items and is dependent of the level.
Letter-span task: In this task the subject sees a set of consonants on the
screen and has to repeat them in the correct order by selecting them. The
length of the set is dependent of the level and varies between 3 and 9.
Figure task: In this tasks different figures (square, circle, star, triangle,
cross, question mark, exclamation mark, @-symbol and percent sign) in different
colors (blue, red, green, purple, yellow, black, orange and white) are shown on
the screen for a couple of seconds. After the figures disappeared the subject
is asked which color a particular sign had. The number of figures and the
presentation time of the figures are dependent on the level of the subject and
varies between 3 and 8 figures and 6 to 13 seconds.
Block-task: In this task the participant sees a grid of 4x4 or 5x5 with
respectively 16 or 25 blocks. A couple of these squares are red while the
others are white. After the squares disappear the subject has to mark the
locations of the red squares. The size of the grid, the number of red squares
and the length of presentation time is dependent of the level and varies
between 5 to 11 squares and 2800 to 4600 ms.

The task will cost the participant 2 hours at the pre- and post-test and 3
weeks 3 times a week 25 minutes. They can execute the training whenever and
where they want. There are no risks linked with this study.