Promoting independence in bipolar disorder. Does cognitive remediation training of executive functioning lead to an improvement in wellbeing and personal goals of daily functioning?

Bipolar disorder is a chronic and severe mood disorder marked by one or more
manic or hypomanic episodes, which can be accompanied by major depressive
episodes. These symptoms interfere strongly with psychosocial functioning (APA,
2013). Most recent epidemiological research in the Netherlands, NEMESIS-2 (De
Graaf et al., 2010), has shown that the lifetime prevalence in the adult
population (18 to 64 years of age) of the bipolar I and bipolar II disorder as
described by the DSM-IV-TR (APA, 2000) is 1,2% for men and 1,4% for women.
About 45 million people worldwide are affected by a bipolar disorder, according
to a systematic analysis for the Global Burden of Disease Study 2013 (James, S.
et al., 2018; Ferrari et al, 2016). This study also shows that bipolar disorder
rank as the 16th leading cause of years lost due to disability (YLDs) among the
total of (mental and physical) diseases and injuries. Among the mental and
substance abuse disorders, bipolar disorder is even ranked as the fifth leading
cause of healthy life years lost as measured by disability adjusted life years
(DALYs). This can be understood from the fact that between episodes functional
recovery takes considerably longer than symptomatic recovery. Often people with
bipolar disorder achieve a lower socioeconomic status in life than people with
comparable education (APA, 2013). Nearly half of the people with bipolar
disorder continue to experience difficulties in their functioning, including
work impairment, family disturbances, marital and, in general, interpersonal
difficulties, even after symptomatic recovery (Sanchez-Moreno et al., 2009).
Considering all the above, it becomes clear that it is of high importance to
keep searching for possible improvements in mental health care to ameliorate
functional recovery for people with bipolar disorder.

Neurocognitive impairments that accompany bipolar disorder, have been a topic
of interest in research in the past two decades. A systematic review (Tsitsipa
et al., 2015) concluded that a little under half of bipolar patients suffer
from significant neurocognitive deficits. The profile of these neurocognitive
deficits is similar to the profile seen in schizophrenia but less severe. The
presence of neurocognitive problems is seen in both the bipolar I as well as
the bipolar II disorder. The literature does not support a clear difference in
neurocognitive functioning between these subtypes in quantitative terms
(Tsitsipa et al., 2015; Bora, 2018; King et al., 2019). The main cognitive
problems are attention, executive function and verbal memory deficits. These
cannot be explained by medication, as the overall negative impact of medication
on neurocognitive functioning has shown to be small (Goswami et al., 2009;
Tsitsipa et al., 2015). The cognitive problems more likely seem to portray
endophenotypes of bipolar disorder and presumably add to the experience of
overall disease burden.

Persistent neurocognitive impairment has indeed repeatedly been identified as a
contributing factor for impaired psychosocial and occupational functioning in
bipolar disorder (Gitlin and Miklowitz, 2017; Duarte et al., 2016; APA, 2013;
Harvey et al., 2010). Moreover, studies have shown associations between
neurocognitive impairment, impaired psychosocial functioning and low quality of
life in mood disorders (Cotrena et al., 2016; Mackala et al., 2014; Sierra et
al., 2005). From these findings one could argue that treatment for bipolar
disorder also should target neurocognitive functioning, as to accomplish
improvement in psychosocial outcome and overall wellbeing. This is in line with
the Dutch guidelines for treatment of bipolar disorder (Kupka et al., 2015),
which mentions neurocognitive problems as a focus of interest. An approach
directed at neurocognitive functioning would be a way of endorsing patient
empowerment, self-management and participation in society, a vision that is
gaining popularity in mental health care. Abraham et al. (2014) have in fact
associated self-efficacy (i.e. the ability of someone to self-manage his/her
problems) in bipolar patients with a higher general wellbeing. Nevertheless,
as of yet treatment of bipolar disorder in institutes of specialized mental
healthcare in the Netherlands is mostly focussed on symptomatic recovery. The
treatment often is of long duration and mostly consists of pharmacotherapy,
psycho-education and supportive care.

Treatment targeting neurocognitive functioning is known as cognitive
remediation. For schizophrenia, cognitive remediation has already been
identified as a means to ameliorate cognitive performance and functional
outcomes (Best & Bowie, 2017; Wykes et al., 2011; Harvey et al., 2010).
Research focussing on cognitive remediation for bipolar disorder is scarcer but
has been of growing interest in the past years. In these studies, a
differentiation is made between cognitive remediation and functional
remediation, but these are not strictly defined and operationalised. The
interventions always for the better part consist of cognitive enhancement, but
in some cases are combined with other interventions (e.g., social cognitive
training). Reviews (Tsapekos et al, 2019; Kim et al, 2018; Solé et al, 2017;
Miskowiak et al, 2016) show positive outcomes on cognitive and functional
measures. However, findings are described as not robust and only preliminary,
because of methodological difficulties (i.e., differences in selection criteria
for participants, in interventions and in outcome measures). In the
Netherlands, up to now, there has only been one pilot study by Zyto et al.
(2016). In that study a brief intervention was applied consisting of 6 group
sessions and 6 individual sessions. The intervention targeted the different
aspects of cognitive dysfunction. Sample size was small (n=12) and there was no
control group, but there was found to be an improvement of functioning in
patients with bipolar I disorder.

In present study the intervention will encompass cognitive remediation aimed at
executive dysfunctions. As mentioned earlier, these are known problems in
bipolar disorder. Executive functions are a set of higher order cognitive
capacities required for planning, initiation, regulation, and verification of
complex, goal-directed behaviour (Lezak et al., 2012). These functions play an
important role in a person*s ability to adapt to situations that arise in daily
life (Burgess, 2000; Fasotti & Spikman, 2002; Royall et al., 2007; Shallice,
1988). On the whole, persons with executive dysfunction encounter more
difficulties in carrying out instrumental activities of daily living (IADL)
(e.g., shopping, managing their accounts, preparing meals) (Maeir, Krauss, &
Katz, 2011). So, it can be reasoned that an improvement in executive
functioning will lead an improvement in daily functioning. A study by Penadés
et al (2010) has shown that in schizophrenia improvement in executive
functioning indeed predicted improved functioning in everyday life.

In the Netherlands, a multifaceted cognitive remediation treatment for
executive dysfunction has been developed by Boelen et al (2012). This treatment
is originally developed to treat executive problems following acquired brain
injury. For that population the treatment resulted in significant improvements
of executive functioning in daily life, lasting at least 6 months
post-treatment (Spikman et al., 2010). Furthermore, Scholtissen-In de Braek et
al. (2012) developed a Goal Management Training for adults with ADHD, which
also targets executive functioning. A small but significant effect of this
intervention was found in a first study (Scholtissen-In de Braek, 2009). Both
interventions aim to provide insight in how cognitive problems affect daily
functioning and teach the participants strategies how to deal with these
impairments in everyday life. Present study will in

Goal of the study is to find out if cognitive remediation focused on executive
functioning for patients with bipolar disorder improves (1) functioning on
personal goals in everyday life? And (2) improves general wellbeing?

Hypotheses:
Cognitive remediation focused on executive functioning for patients with
bipolar disorder improves executive functioning on (1) personal goals in daily
life. And (2) general wellbeing.

Exploratory hypotheses:
- Cognitive remediation focused on executive functioning for patients with
bipolar disorder improves subjective cognitive functioning in daily life.
- Cognitive remediation focused on executive functioning for patients with
bipolar disorder improves psychosocial functioning and self-sustainability.
- Cognitive remediation focused on executive functioning for patients with
bipolar disorder improves quality of life.
- Cognitive remediation focused on executive functioning for patients with
bipolar disorder improves symptomatology

Expectations are that the intervention will lead to a positive outcome on these
different aspects.

Repeated measures randomised cross-over experimental study.
Duration: 42 weeks, this includes a 6 week baseline period and the follow-up
after 12 weeks.
Setting: GGZ Delfland.

After selection 20 participants will randomly be placed in group A or group B.
Both groups will start with a 6-week baseline period, in which weekly measures
of functioning on personal goals in everyday life and wellbeing will be
measured. Subsequently group A will start with the 12 week cognitive
remediation program, while group B will continue treatment as usual. Hereafter
the groups interchange: group B will also follow the cognitive remediation
program. All this time, both groups will continue the weekly measurements of
personal functioning goals and wellbeing and on 8 moments some additional
questionnaires will be added. 12 weeks after group B has ended the
intervention, a follow-up measurement will take place.
Note: Due to rules and regulations concerning COVID-19, a group size of 10
participants might not be possible. To accommodate to this, it will be an
option to reduce group size by dividing the group in two groups of 5
participants each.

The experimental treatment will consist of a 12-week cognitive remediation
program focussed on enhancing executive functioning. There will be weekly
sessions of 2 hours and the treatment will take place in a group consisting of
10 participants. The treatment will be given by two experienced
neuropsychologists or an experienced neuropsychologist and a
trainee-neuropsychologist.
The cognitive remediation will be based on both a treatment protocol for
patients with acquired brain injury and problems in executive functioning
(Boelen et al., 2012) and a treatment protocol for patients with ADHD
(Scholtissen-In de Braek et al., 2012). Both protocols rely heavily on Goal
Management Training (GMT, Levine et al., 2000). The treatment protocol for
acquired brain injury also relies on Problem Solving Training (PST, von Cramon
& Matthes von Cramon 1994). Both protocols encompass compensatory remediation,
whereby participants learn new skills to better manage cognitive impairment.
Themes in the protocol will be (1) Information and Awareness, (2) Goal Setting
and Planning, and (3) Initiation, Execution, and Regulation. The protocol will
be revised for the bipolar group and submitted for expert review by two
experienced neuropsychologists.
There will be weekly homework assignments, that will be discussed in the
following group session.

Treatment as usual consisting of pharmacotherapy and supportive care will
continue during the cognitive remediation treatment.

Participation in this study requires an additional investment of time and
effort. Nevertheless, the experimental intervention is similar in duration and
patient-investment to other psychological interventions applied in regular
mental health care. Also, application of a neuropsychological examination and
carrying out measurements with questionnaires, fall within the boundaries of
the regular mental health care. Considering this, together with the fact that
participants need to be stable for some time to participate, leads us to expect
no additional risks in participating, outside the regular scope. Furthermore,
it is expected that the intervention will lead to an improvement in functioning
and wellbeing.