Our results demonstrate that cognitive measures at the time of symptomatic recovery, particularly in the domains of working memory/attention and speed of processing, are strongly associated with concurrent occupational recovery, even after accounting for the effects of age and depression severity. There was also a trend toward better episodic memory at baseline predicting three-month functional recovery. Most notably, cognitive improvements across multiple domains over this same time period were also highly predictive of functional recovery three months later.
Few studies have been performed to date examining either cross-sectional or longitudinal neuropsychological predictors of occupational outcome in bipolar disorder. In the current study, even after controlling for subsyndromal symptoms, neurocognitive impairments in the domains of episodic memory, visual scanning, working memory/attention, and speed of processing were independently associated with concurrent occupational impairment. Similarly, in a cross-sectional study Wingo et al. (13
) found that among euthymic or mildly depressed bipolar disorder patients, fewer years of education, not being married, and greater duration of illness were independently associated with poorer functional recovery (defined as regaining individual premorbid residential and vocational status), even after controlling for residual depressive symptoms, diagnostic subtype, and psychiatric comorbidity. Additionally, Wingo and colleagues observed a trend for functionally unrecovered bipolar disorder patients to have poorer verbal fluency performance than recovered patients. Other cross-sectional studies have also observed a relationship between verbal memory deficits and poor psychosocial functioning in euthymic bipolar disorder patients (20
While we found that baseline cognitive impairment across multiple domains was significantly associated with concurrent functional (occupational) impairment, we did not find evidence of a significant relationship between baseline cognitive performance and subsequent functional recovery. In contrast, Jaeger et al. (27
) found that baseline neurocognitive functioning in the attentional and speed of processing domains (specifically, Trail Making A and Stroop word reading and color naming tests) predicted functional outcome, as assessed by the Multidimensional Scale of Independent Functioning (43
), over a longer (12-month) follow-up period. Similarly, Martino et al. (12
) in a study of 35 subjects found that both baseline cognitive impairment (in the domains of attention, executive function, and verbal memory) and length of time spent with subsyndromal depressive symptomatology were independently associated with poorer long-term functional outcome over a 12-month period. There were some key methodological differences that could account for these discrepant findings: (i) our follow-up analysis included only
those study participants who had not occupationally recovered at baseline; (ii) unlike our study, the prior investigations did not specifically enroll patients who had previously been employed.
We could only identify one other study in the literature that conducted repeated cognitive assessments in bipolar disorder patients, in order to examine change in cognitive functioning over time in relationship to functional outcome (28
). In this study, global neurocognitive function at baseline–or improvement in this score over one year–predicted changes in functioning as assessed by the GAF. While we did not find a significant relationship between baseline cognitive performance and subsequent functional recovery, our finding of robust associations between cognitive improvement over time and functional recovery is consistent with these findings.
A strength of our study is that we employed data reduction methods (factor analysis) in order to allow greater specification of the cognitive domains most associated with occupational recovery. We did not find that a single cognitive domain was clearly superior to the others in its predictive power; rather, multiple domains, i.e., episodic memory, visual scanning, attention/working memory, executive function, and speed of processing, all uniquely contributed to cross-sectional and longitudinal prediction of functional recovery. Improvements over time, particularly in the domains of episodic memory, attention/working memory, and executive function, were extremely robust predictors of occupational recovery over this time period. Although it is possible that our analyses were underpowered to detect baseline predictors of subsequent recovery, the highly significant relationships detected between neurocognitive improvement and occupational recovery suggest that even if baseline scores were predictive, the relationship is much weaker than the relationship between neurocognitive change over time and recovery.
These findings have potentially important clinical implications. Despite achieving symptomatic recovery from mania, a substantial proportion of patients nevertheless continue to experience functional impairment. Given that cognitive deficits across multiple domains emerged as independent predictors of occupational outcome, cognitive rehabilitation is a rational treatment target in bipolar disorder. Cognitive remediation has been associated with significant, though modest, improvements in cognitive performance and psychosocial functioning in schizophrenia patients (44
). However, surprisingly few studies on the prevention or remediation of cognitive impairments in bipolar disorder have been conducted to date (45
). The development of treatments that target cognitive impairment may have an impact on the ultimate functional status of patients with bipolar disorder. Recently, two small studies have reported that rehabilitative interventions, such as cognitive remediation and supported employment, may improve vocational outcomes for bipolar disorder patients (46
). This will require replication in larger investigations, but is an important area of future investigation in bipolar disorder.
Several studies have found that subsyndromal depressive symptoms are associated with both cognitive impairment and functional disability (40
). For this reason, we controlled for depressive symptoms in our analyses and still found multiple domains of neurocognitive function uniquely contributing to occupational impairment. This suggests that neurocognitive impairment impacts one’s ability to return to work, independent of the effects of residual depressive symptoms. These results are consistent with the findings of at least two other studies, which assessed clinical (subsyndromal depressive) symptoms and neurocognitive symptoms and their impact on functional outcome (12
Slightly over half (57%) of the bipolar disorder patients in our sample were functionally recovered at the time of symptomatic recovery, but a substantial minority of patients (43%) were not. These findings comport with prior literature indicating that for a large percentage of bipolar disorder patients, functionally recovery lags behind symptomatic recovery. However, by the six-month follow-up timepoint after symptomatic recovery was obtained, a high rate of subjects in our sample had achieved occupational recovery (71%). This rate is higher than others reported in the literature, which have found that less than half of bipolar disorder patients are employed by six months following hospitalization (5
). These findings could be due to careful physician follow-up to ensure medication adherence and, again, the fact that the patients followed all had a history of employment prior to the manic episode. Thus, it may be that the poor outcome
reported as percentages of employed persons for many bipolar disorder patients in the literature is a reflection of over-enrollment in the beginning of the study of persons who were not working to begin with. We also excluded patients with alcohol or substance use abuse/dependence within the past three months; given that comorbid substance use clearly contributes to occupational disability, as well as neurocognitive impairment in patients with bipolar disorder (e.g., 51
), the exclusion of patients with this acute co-morbidity may also contribute to the relatively high rates of occupational recovery we observed. Similarly, recurrent depressive episodes, including subsyndromal depression, are associated with occupational impairment (12
), and we maintained strict criteria for euthymia over the follow-up period. Most follow-up studies do not include this information, but results previously reported on unemployment rates in subjects with bipolar disorder after recovery from a manic episode or hospitalization may be a misrepresentation of the percentage of persons in the bipolar disorder community who have a poor outcome following a manic episode by not accounting for such factors.
Several limitations of this study should be noted. In particular, 26% of our sample was lost to follow-up following the initial assessment. Retaining patients with bipolar disorder in longitudinal protocols is challenging; nevertheless, we were able to follow 75% of the subjects who had attained symptomatic but not occupational recovery. In addition, our high rate of occupational recovery over the follow-up period led to an unexpectedly small number of subjects remaining in the protocol after the three-month visit. However, despite the relatively small ratio of subjects to variables, we were able to demonstrate, using a bootstrap resampling technique, that the results of our longitudinal analyses were very stable, particularly for the three strongest predictor variables (i.e., working memory/attention, episodic memory, and executive function). Another limitation is that our measure of occupational function, although completed at multiple timepoints, did not specifically assess for occupational stability (i.e., how long one remained in the same job). Although not assessed systematically, none of the patients in our sample changed jobs frequently throughout the study. Most subjects, when returning to employment, returned to work with their previous employers and maintained that job throughout the follow-up. Nevertheless, occupational stability is an important aspect of functioning that has not yet been well-addressed in the literature and warrants further investigation. In addition, other aspects of illness history, in particular, a history of psychotic symptoms, were not investigated here. The presence of psychotic symptoms during mood episodes may be associated with poorer neurocognitive function (54
) and possibly worse occupational outcome. This issue requires further study in longitudinal investigations. Finally, most patients in our study were taking psychotropic medications; given that medication status did not differ between patients who were occupationally recovered and unrecovered at baseline, we do not believe that medication presents a significant confound.