The Relationship Between Neurocognitive Functioning and Occupational Functioning in Bipolar Disorder: A Literature Review

Neurocognitive impairment in Bipolar Disorder (BD) has been widely reported, even during remission. Neurocognitive impairment has been identified as a contributing factor towards unfavourable psychosocial functioning within this population. The objective of this review was to investigate the association between neurocognitive impairment and occupational functioning in BD. A literature review of English-language journal articles from January 1990 to November 2013 was undertaken utilising the PsychINFO, Scopus and Web of Knowledge databases. Studies that made specific reference to occupational outcomes were included, and those that reported on global psychosocial measures were excluded. Majority of the papers reviewed (20 out of 23) identified an association between neurocognitive impairment (particularly in executive functioning, verbal learning and memory, processing speed and attention) and occupational functioning. Several methodological issues were identified. There was a discrepancy in the measures used to assess neurocognitive function across studies and also the definition and measurement of occupational functioning. The clinical features of the samples varied across studies, and confounding variables were intermittently controlled. The review focused on English-language papers only and hence there is a bias toward the Western labour market. These limitations therefore influence the generalizability of the interpreted findings and the reliability of comparisons across studies. Neurocognitive impairment in BD appears to play a role in occupational outcomes. The findings of this review highlight the challenges for future research in this area, particularly in the measurement of neurocognitive and occupational functioning. Incorporating neurocognitive interventions in the treatment of BD, which has traditionally focussed solely on symptomatic recovery, may advance the vocational rehabilitation of these patients.

It is reasonable to suggest that neurocognitive functioning subserves not only complex, abstract processing but also daily basis processing; therefore deficits in this area would have ramifications for occupational functioning.
For example, memory is utilised in skill acquisition, and attention is required for job performance. This suggests that a substantial component of successful occupational outcomes rest upon satisfactory neurocognitive performance.
Reviews to date have looked at the relationship between neurocognitive impairment and psychosocial functioning in general, incorporating research articles that have primarily utilised global measures of functioning (Depp et al., 2012a;Wingo et al., 2009). Two recent reviews focussed on the predictors of employment in BD. Gilbert and Marwaha (2013) identified cognitive deficits, depression and level of education as predictors of employment in BD. A meta-analysis conducted by (Tse, Chan, Ng, & Yatham, 2014) identified a relationship between cognitive performance and favourable employment outcomes in BD, and mediating effects of years of education, course of illness, and symptomatology. Executive functioning and verbal memory were highlighted as particularly relevant cognitive domains underlying occupational functioning (Gilbert & Marwaha, 2013;Tse et al., 2014).
The following literature review will focus exclusively on the association between neurocognitive impairment in BD and occupational functioning, incorporating a larger body of literature on this topic. The term occupational functioning has been used so as to not only include studies that focus on employment, but also other related functions that contribute to employment, such as work skills and pre-employment activities. It is expected that by examining occupational outcomes this will provide a broader perspective in this area of functioning in BD.
Employment has been identified as a vital contributor for the wellbeing and quality of life for those with BD (Eklund, Hansson, & Ahlqvist, 2004;Nordt, Müller, Rössler, & Lauber, 2007). This highlights the importance of occupational activity for individuals living with BD, and highlights the potential for occupational functioning as a target for intervention. It is anticipated that the findings from this review will contribute to the knowledge in this field, and inform practitioners working directly in the rehabilitation of BD patients.

Methods
A search of the PsychINFO, Scopus and ISI Web of Sciences databases was conducted for relevant Englishlanguage, peer-reviewed original journal articles, dating from January 1990 to November 2013. Research into neurocognitive functioning within the BD population appears to have received more rigorous attention over the last 10-15 years (Kurtz & Gerraty, 2009) and therefore the aforementioned time frame was selected.
These 46 articles were then examined for specific reference to the relationship between neurocognitive factors and occupational functioning. Twenty-one articles were excluded, mainly as a result of the use of global measures of functioning (for example; Global Assessment of Function and the Social Adjustment Scale) and also a result of failure to specifically identify occupational functioning.
The effect sizes for significant results are reported in Table A1. For studies where effect size data were not available, effect sizes were calculated and converted to Cohen's d or f 2 (for regression

Results
Twenty-three articles were selected for inclusion in the current review (see Table A1). With no papers published before 2004, and 17 since 2010, it is clear that research into the association between neurocognitive functioning and occupational functioning in BD is a relatively new field that is gaining increasingly more interest.
The majority of studies (16) utilised outpatient participants and were primarily conducted in the USA (12) and Spain (9), with single representations from England, Canada, Ireland and Norway. The following section will examine the assessment of neurocognitive functioning, the measurement of occupational functioning, and then the relationship between these two factors.
A variety of formal assessment measures were also employed among studies to assess occupational functioning,  -Arán et al., 2007;Tabarés-Seisdedos et al., 2008;Torrent et al., 2006), these researchers measured occupational outcomes by way of occupational adaptation. They divided participants into "good" or "poor" occupational adaptation groups, determined by a good/acceptable level of functioning most of the time, versus those not working or exhibiting difficulties in their jobs.
Six papers employed other means of assessing occupational outcomes. Burdick, Goldberg, and Harrow ( considered participants work history for the last three years to create two groups -those that had worked for at least six months during that time and those that had not.

The Relationship Between Neurocognitive Functioning and Occupational Functioning
Twenty studies identified a relationship between neurocognitive functioning and occupational functioning in BD.
The major finding reported among these studies was that neurocognitive impairment was associated with diminished occupational functioning.
Just over half (12) of these studies utilised euthymic participants, and the same number of studies also excluded individuals with recent substance abuse or dependence. Eight studies controlled for the effects of medication.
Nineteen of these studies incorporated solely BD populations (with or without healthy controls), whilst four included other diagnostic categories such as schizophrenia (Bowie et al., 2010;Godard et al., 2011;Murtagh et al., 2010;Tabarés-Seisdedos et al., 2008). Only Torrent et al. (2006)  ing/memory (8), processing speed (5) and attention (5). Depp et al. (2012b) and Bowie et al. (2010) did not identify specific domains, instead reporting on overall neurocognitive functioning. Bowie et al. (2010) noted that the relationship between neurocognitive functioning and work skills in BD was indirect and was mediated by adaptive and social competence. The authors defined adaptive competence as the instrumental skills important for functioning independently, and social competence as the linguistic and verbal behaviours essential for communication.
Of the three papers that did not find an association between neurocognitive functioning and occupational functioning, Dickerson et al. (2010) noted that the processing speed domain approached significance for work adjustment in their study, whilst Wingo et al. (2010) reported that their participants differed on various neurocognitive measures, though not to a significant level. Schoeyen et al. (2013) failed to find a relationship between overall neurocognitive functioning, as measured by IQ, and receipt of a disability benefit.

Discussion
The aim of this paper was to investigate the association between neurocognitive and occupational functioning in BD. Of the papers reviewed, most (20) identified a relationship between impaired neurocognitive functioning and reduced occupational functioning in BD. This is consistent with the findings of a recent systematic review and a meta-analysis which considered predictors of employment in BD (Gilbert & Marwaha, 2013;Tse et al., 2014). The current review identified a number of neurocognitive domains that appear to be particularly sensitive to changes in occupational functioning including: executive functioning, verbal memory, processing speed and attention. Although over half (14) of these papers were cross-sectional, seven longitudinal studies identified that the relationship between neurocognitive impairment and reduced occupational functioning was stable over time, and that neurocognitive assessment may provide prognostic information regarding occupational functioning in BD.
Although the relationship between neurocognitive impairment and reduced occupational functioning appears to be stable over time, the current review indentified that certain cognitive domains are more sensitive to changes in occupational functioning in longitudinal studies compared to cross-sectional studies. For example, reduced performance on measures of verbal and working memory were found to be more strongly associated with reduced occupational functioning overtime, and the strength of these effects were considered to be medium to large for both verbal and working memory. Reduced performance on measures of verbal memory were also implicated in reduced occupational functioning in cross-sectional studies suggesting that verbal memory is an important cognitive domain over both short and long periods. Although working memory appeared to be an aspect of executive function implicated in longitudinal studies, measures of executive function associated with cross-sectional studies were somewhat variable. For example, verbal fluency and inhibition were more sensitive to changes in occupational functioning among follow-up studies and the strength of the effect varied substantially. One study reported a small to medium effect size for verbal fluency (Ryan et al., 2013), whereas another study reported a large effect size (Godard et al., 2011). Differences in methodology may underlie such discrepancies, and further information regarding the strength of the relationship between measures of executive function and occupational functioning is required, given that effect sizes could not be calculated for a number of studies.

Clinical Variables
A number of studied identified residual depression as an important predictive factor of employment among BD populations (Gilbert & Marwaha, 2013;Tse et al., 2014). Out of the studies reviewed, approximately half (12) utilised euthymic participants in an attempt to control for the effects of depression. It should be noted though that studies varied in how euthymic populations were defined. Generally (in 8 instances), a Hamilton Depression Rating Scale score below 8 and a Young Mania Rating Scale (YMRS) score below 6 were used to characterise euthymic states, usually stipulated over the last 3-6 months (7). There were variations from this, for example, in two cases a YMRS score below 8 was used, and in another two cases euthymia was prospectively verified over a period of 6 months. Although establishing a standard definition of euthymia remains a challenge ( , 2007). Given the heterogonous nature of BD, medication regimes will vary widely, therefore attempts to control for the effects of medication will ensure that the potential for neurocognitive side-effects are minimised.
Another factor which has the potential to impact on cognitive function, and hence the relationship between neurocognitive and occupational functioning, is comorbid substance abuse. Balanzá-Martínez et al. (2010) noted in their review that neurocognitive functioning in BD is not only impaired by current and recent alcohol use, but even following a period of abstinence from alcohol. In the current review, those studies that excluded participants based on drug and alcohol dependence or abuse (13) varied in their defined periods of abstinence, with periods ranging from 12 months to no current substance abuse/dependence issues (3). The longer participants can abstain from alcohol and illicit drugs, the less likely these substances will have an effect on neurocognitive functioning. However, it is noted that there is a high level of comorbidity between BD and substance abuse and/or dependence, alcohol in particular (American Psychiatric Association, 2013) and excluding or controlling for current substance use may influence the generalizability of research findings in the area. Future research in the area may benefit from reporting the results with and without statistically correcting for substance use in order to examine the impact of comorbid substance abuse more closely. Wingo et al. (2009) identified other factors known to influence neurocognitive functioning in BD including age, education, premorbid IQ, and course of illness or chronicity factors. History of psychosis was identified as factor contributing to poor neurocognitive function (Wingo et al., 2009) and also poor occupational functioning (Levy et al., 2013). There appears to be a complex relationship between these mediating factors and the outcome variables for neurocognitive and occupational functioning. For example, Wingo et al. (2010) reported that the relationship between neurocognitive and functional outcomes was reduced after adjusting for education and residual mood symptoms. Similarly, Schoeyen et al. (2013)

Methodological Issues and Limitations
Neurocognitive Assessment The first methodological issue relates to the assessment of neurocognitive functioning. The domains of cognitive functioning assessed varied across studies, for example executive functioning (16 studies), verbal learning/memory (16), attention (15) and processing speed (11) were the most commonly measured domains. Six studies included a measure of visual memory, and two included a measure of motor control and co-ordination.
The majority (21)  A potential bias regarding occupational functioning is noted with regards to the inclusion criteria for this review.
Limiting the search to English-language studies restricts cross-cultural comparisons, and also tends to reflect Western labour markets. This may pose different consequences for occupational functioning (e.g. employment opportunities) to other economies.

Methodological Limitations
Sample size and therefore statistical power varied across studies, with only 12 papers involving samples greater than 100 participants. Differences in sample size and characteristics make it difficult to generalize interpretations across studies. The clinical samples comprising each study also carried widely. Some studies did not distinguish between BD I and BD I and others incorporated other diagnoses such as schizophrenia. It is therefore difficult to generalise across studies given the heterogeneous nature of BD. The majority of the studies reviewed were cross- sectional, and this also limits the long term generalisations and inferences regarding causal directions for the relationship between cognitive and occupational functioning in BD.

Future Directions and Implications
Despite these limitations the research at hand does seem to suggest that neurocognitive impairment is associated with (and may predict) diminished occupational functioning in BD, and this has important implications for rehabilitation practitioners. Given that most jobs require a degree of memory and attention, it follows that interventions There were a number of methodological limitations associated with the variety of neuropsychological assessments employed across studies and the definition and measurement of occupational status that make it difficult to generalise across studies. In lights of these limitations, assessment of neuropsychological function among BD populations is argued to provide important information with regards to occupational functioning, and information for clinicians with regards to rehabilitation options for improving functional outcomes including occupational functioning.

Funding
The authors have no funding to report.

Competing Interests
The authors have declared that no competing interests exist.