On the CPT, the control group had statistically very highly significant fewer total commissions (P=0.000) and fewer total omissions (P=0.003) than did bipolar I patients. The control group had statistically significantly longer median delay (P=0.039) and average delay (P=0.034) than patients with bipolar I disorder (Table 5).
On the WCST, the control group had statistically significant lower percentage of errors, higher percentage of conceptual level responses, more categories completed, fewer failures to maintain set, lower learning to learn category and statistically highly significantly lower percentage of perseverative responses (P=0.001), percentage of perseverative errors (P=0.002), and percentage of nonperseverative errors (P=0.006) (Table 6).
BD is a relatively common disabling illness characterized by recurrent episodes of mania and depression. These pathological mood states have a clear impact on cognitive functions 23.
These cognitive impairment can be transient (state related), occurring during the symptomatic phase of the illness, or may be enduring (trait or scar related), which persists in the euthymic periods and is associated with psychosocial difficulties 24–26 Furthermore, many studies have provided evidence that the cognitive impairment in euthymic bipolar patients is to a large extent comparable with that of symptomatic bipolar patients 27.
Our findings clarified the presence of significant deficits across a range of neurocognitive tests in euthymic patients with bipolar I disorder when compared with a matched healthy controls.
Executive functions encompass a group of higher level cognitive processes including strategic planning, problem solving, working memory, strategy development, ability to shift cognitive strategy, inhibitory control, and cognitive flexibility 21,28.
We assessed the executive function in our study using the CPT and WCST. Data obtained from CPT showed that euthymic patients scored higher in the total errors and perseverative errors, which reflect difficulty in cognitive flexibility, and they also obtained worse scores in the total correct answers than the healthy controls.
Our study showed that there was a statistically significant difference in performance in WCST between bipolar I patients and controls in almost all domains (except on number of trials to complete one category) (%error, %perseverative response, %perseverative error, %conceptual level response).
Differences between bipolar I patients and control participants were supported by some findings from the literature, whereas others did not.
The extent to which executive dysfunction recovers during remission remains controversial. A number of studies, including our research, have suggested that executive function impairment remains during the euthymic phase and may represent an intrinsic factor to BD 29,30.
In a recent investigation, Torralva et al. 31 found a significant difference in the executive function performance between bipolar patients and control using two experimental tasks (the Multiple Errands Test-Hospital Version and the Hotel Task). Other investigators used different assessment tools and showed a trend toward a higher number of WCST perseverative errors compared with healthy controls 32. Similarly, Hsiao et al.33 found that the bipolar I group performed poorly compared with the control group on measures of executive function using the Trail Making Test part B indicating difficulties with set shifting. Also, Dittmann et al.34 found that bipolar patients showed significantly lower scores in tests of executive functions than healthy controls. In their study, they used the Semantic Fluency subtest of the Repeatable Battery for the Assessment of Neuropsychological Status to measure executive functioning.
Similarly, Kolur et al.35, using the WCST for cognitive flexibility, working memory, problem-solving, and set-shifting abilities; the Stroop Color Word Association Test (SCWT) for selective attention and executive function; and the Tower of London test for forward planning and working memory, concluded that euthymic bipolar I patients showed impairment on tasks of executive functioning and concluded that they are possibly trait abnormalities.
In contrast to the above findings, Van Gorp et al.36 assessed executive function using the Controlled Oral Word Association Test (CWAT) and the WCST in a group of euthymic bipolar I patients with alcohol abuse comorbidity. Half of the patients had a history of alcohol abuse. They found that all patients performed similar to the controls on the CWAT. However, those with a history of alcohol abuse showed impairment in the WCST, particularly in the number of categories achieved, whereas those without such a history performed as well as controls. Also, Rubinsztein et al.37 used the CANTAB battery to compare euthymic bipolar I patients with controls. No deficit was observed in the patients’ ability to solve problems correctly but they took much longer than controls to make their decisions.
The contradiction in these results could be attributed to the use of different assessment tools and perhaps different inclusion criteria.
Memory deficits have been suggested to be a core cognitive deficit associated with acute mania 3. However, evidence indicates that functional recovery of all memory symptoms is not completed 38 and persists during the asymptomatic phase of the disease.
Our study indicates that visual memory as examined by the visual memory subscale of WMS was significantly impaired in the group of bipolar patients compared with healthy controls. Our results are in agreement with a previous investigation that consistently found, using a variety of measures, that explicit visual memory is impaired in euthymic bipolar patients 5,27,39,40.
Verbal memory function includes measures of immediate, recall, and recognition 19. Most studies have reported that there are deficits in verbal memory in patients with euthymic BD 8,27,41,42. Similarly, Simonsen et al.42 found that bipolar I patients had poorer verbal memory and recall using WMS and the California Verbal Learning Task compared with the control group.
Reports on the assessment of verbal memory function in bipolar patients across a range of mood states have clarified that recognition and recall are impaired in the symptomatic phase of the illness; however, impaired recall only persists in the euthymic state 1,32.
Our study confirmed that recall memory (which is a subtype of explicit declarative memory) is significantly impaired in euthymic bipolar I patients; thus, our results are in agreement with those of previous investigators in this field 43,44.
Working memory is the ability to temporarily store and simultaneously manipulate information 45. In our study, we used different parameters to assess working memory such as the CPT, digit span backward, and WCST.
Our euthymic patients made more omission and commission errors in the CPT than did the controls and they also scored lower in digit span backwards, which is a presumably a measure of working memory.
Data obtained in the current study confirmed a previous report by Watson et al. 46. In a similar study, Hsiao et al. 33 reported results showing poorer performance by bipolar I patients on working memory compared with the control group.
In contrast to these findings, some reports highlighted that working memory is impaired only in symptomatic patients and not in periods of euthymia 47–49.
The discrepancies in the different reports may be related to the methods of assessment as working memory is a multicomponent system that requires assessment of different tasks.
Impaired sustained attention may represent a trait marker for BP related to vulnerability to the disorder at a structural and/or a neurochemical level 50. Our study found a statistically significant difference in performance between all patients and controls on CPT, with patients showing significantly more total omissions and commissions and shorter median and average delays than controls. This suggests that euthymic bipolar I patients show more deficits in sustained attention than controls.
Our findings were also in agreement with the study carried out by Burdick et al. 27, who concluded that attention is impaired when assessed by MATRICS in a sample of 80 bipolar patients compared with controls. Moreover, Kolur et al.35 carried out a study on 30 euthymic bipolar I patients and 30 matched healthy controls, who were assessed for sustained attention. The tests used were the CPT, the Trail Making Test part A and part B, and the SCWT; the bipolar group showed impairment on tasks of sustained attention. In conclusion, different investigators have reported that observed impairments in sustained attention during mania or depression did not show complete remission during euthymia 3,51.
Attentional and executive functions are critical to academic and professional success and may reflect the disability associated with illness 23.
General intellectual abilities
Our study found a statistically very highly significant difference in performance on all domains of WAIS between the patient and the control groups, with the patient group showing a poorer performance.
Despite the apparent difference between the groups, it is difficult to state whether this difference is a consequence of BD or not as our sample was cross-sectional. It is possible that this difference predated the onset of the illness and that this is a chance association, or that it might be because of confounding factors (e.g. effect of years of education) or that there is a genuine causal association. A more robust method would be a longitudinal study measuring premorbid IQ, for example, using the National Adult Reading Test (NART) and comparing it with current IQ, which would be more accurate in inferring whether this difference was a consequence of BD or not. Unfortunately, there is no Arabic version of the NART.
Similar studies comparing IQ have shown mixed results, and studies comparing bipolar I and control have also differed in their findings.
Simonsen et al.42 used the NART and WAIS for assessment of the patients and controls enrolled in his study. The study groups did not differ significantly on premorbid IQ estimated by the NART. However, current IQ, assessed using the WAIS, differed significantly between the groups. Bipolar I patients group had lower scores compared to the healthy control group.
In the work of Morice 52, a group of 20 bipolar I patients were examined, most of whom had recovered from a manic episode. Bipolar I patients tended to score lower on almost all the performance IQ subtests, although there were no significant differences between their overall IQ scores and that of the controls.
Coffman et al.53 compared controls with bipolar I patients who were in remission according to the authors’ own clinical judgment and had a history of psychosis during episodes. There were no group differences in IQ. Similarly, in the study by Sapin et al.54, no differences were found between bipolar I patients and controls; unfortunately, they used the Altus Brief Intelligence Test (a measure of verbal intelligence) instead of more widely used tests. A number of studies have used the NART to measure premorbid intelligence in bipolar patients. Ferrier et al.55 and Rubinsztein et al. 37 found no differences between euthymic bipolar I patients and controls.
The neurobiological substrates of cognitive dysfunction
Deficits in neuropsychological testing can provide insights into the underlying neurobiological process in BD. The most consistent structural neuroimaging studies showed an abnormal reduction in prefrontal cortical gray matter volume in patients with BD, a finding that is consistent with executive dysfunction 56,57.
Impairments in selective attention and attentional shift were attributed to dysfunction in the dorsolateral prefrontal cortex 56 and anterior cingulated gyrus 58.
Memory dysfunction is suggested to be because of abnormalities in the temporal lobe, amygdala, basal ganglia, and frontostriatal structures 23. However, the structural brain abnormalities observed in BP and their corresponding functional deficits remain unknown 59.
Our findings support the presence of neurocognitive impairments that persist in the euthymic phase and may represent a trait variable independent of mood state.
The persistence of these deficits necessitates including neurocognitive assessment in routine investigation in all stages of the bipolar illness and should receive specific attention in future research to study its impact on social and occupational functioning.
Although our study was one of only a few to compare cognitive functions in euthymic bipolar I and healthy controls, our study was limited by the sample size; thus, caution should be exercised in generalization of the results of this study and more research should be carried out on larger samples to replicate these results.
One of the limitations of this study is the difference in the educational attainment of the case group versus the control group. According to Glahn et al. 60, educational attainment should not be used to match patients and comparison participants, as appropriate matching of patients and controls is complex, given that cognitive aptitude and achievement measures may be affected by the disease process.
Another limitation of our study was that it was cross-sectional in nature and although it helped identify associations, it was difficult to infer causality in relationships. A longitudinal study would help answer many questions in this area.
It is worth noting that all our patients were receiving mood stabilizers, antidepressants, or antipsychotics; thus, the effect of medication on cognitive functioning cannot be discounted.
The authors would like to thank Mostafa Kamel Ismail and Afaf Hamed Khalil professors of psychiatry, Ain Shams University (Cairo, Egypt), for their valuable guidance throughout the work. Also, they are grateful to Dr Suzan Elkholy, consultant clinical psychologist, for her support in interpretation of the results. They are also indebted to the research team at the institute of psychiatry. Last, but never the least, thanks are due to all the participants in this study for their time, effort, and help.
Conflicts of interest
There are no conflicts of interest.
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Keywords:© 2013 Institute of Psychiatry, Ain Shams University
bipolar; cognition; cognitive impairment; euthymic; Wisconsin Card Sorting Test