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Keywords:

  • bipolar disorder;
  • cognitive functions;
  • neuropsychological performance;
  • quality of life;
  • India

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

Aim

This study aims to assess the neuropsychological performance, quality of life (QoL) and global functioning in euthymic patients and healthy controls. It also explores the hypothesis that poorer cognitive performance will adversely influence the QoL of patients with bipolar disorder.

Methods

We carried out a cross-sectional assessment of 30 euthymic patients with bipolar disorder type I and compared them to a healthy control group. All the participants were evaluated for IQ, sustained attention, information processing speed, executive functions and memory using the Verbal Adult Intelligence Scale, the Trail Making Test A & B, the Stroop Color and Word Test, the N-Back test and Postgraduate Institute Memory Scale. Patients were also rated on World Health Organization QoL (BREF, Hindi version) and Global Assessment of Functioning.

Results

The patient and control group were comparable in age, sex distribution, education, and verbal IQ. Compared to controls, the patients performed poorly on tests for sustained attention, information processing speed, cognitive flexibility, delayed recall and verbal retention. Patients had significantly lower scores in psychological and social domains of QoL as well as global functioning. The test for sustained attention, executive functions and verbal retention showed a significant correlation to QoL domains. On stepwise multiple regression, cognitive flexibility and set shifting (Trail Making Test Part B) could significantly predict the psychological and social QoL domains, explaining 17% and 32% of the variance, respectively.

Conclusion

Patients with bipolar disorder display cognitive impairments in the euthymic period, which appears to adversely affect their QoL and overall functioning.

IN RECENT DECADES we have witnessed the emergence of a gradual consensus over the presence of cognitive deficits in the active phase as well as during remission of bipolar disorder (BD).[1, 2] Efforts are being directed to ascertain the type and extent of these cognitive deficits. Remitted patients with BD have been shown to have deficits in attention, processing speed, memory and executive functions.[2, 3] The deficits in executive functions and verbal memory appear to be especially marked. At this point, it is unclear whether the observed cognitive deficits reflect a single core impairment or multiple cognitive deficits.

Of particular importance is to know the clinical and functional significance of these cognitive impairments for clinicians and patients. The clinical relevance cannot be fully appreciated without assessing their impact on the day-to-day functioning and quality of the patient's life. It has been observed previously that these deficits could be negatively related to functional outcomes of the disorder.[4, 5]

The concept of quality of life (QoL) has become increasingly relevant in chronic, recurring disorders like BD. The QoL of BD patients has been found to be better than that of schizophrenia patients, but poorer compared to controls; however the results have been mixed.[6, 7] Many studies have shown that there is a definite, unexplained gap in the clinical and functional recovery of some patients with BD.[4, 5, 8] Although residual mood symptoms and a host of other factors have been studied as possible explanations, the role and contribution of cognitive impairments towards suboptimal QoL have not received much attention.

The present study was planned for two reasons. First, we wanted to test the hypothesis that poor cognitive functioning is likely to predict a poor QoL in euthymic BD patients. While cognitive functions and QoL have been independently demonstrated to be poor in several studies on BD, the nature and strength of the correlation between these factors merits a separate investigation. Second, most of the available studies have been conducted in Western settings and the current volume of work is not representative of a large part of the developing world, especially the Indian subcontinent.

Therefore, the present study was planned in order to: (i) assess the neuropsychological performance in euthymic patients and healthy controls from India; (ii) assess QoL and global functioning in patients and controls; and (iii) explore the correlation, if any, among cognitive impairments, QoL and global functioning of patients to support our hypothesis.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

Setting

The study was conducted at the Outpatient Clinic, Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), New Delhi, India. This is a premier medical institute for teaching and tertiary care centre for patient care. Patients pay a nominal amount equivalent to nearly 25 US cents for annual registration and thereafter, can seek consultation throughout the year without any other charges, by means of self-referral. In view of a high medical expertise and easy affordability, it attracts patients from all over India, though most come from Delhi and the surrounding states. The ethical approval for the study was taken from the Institutional Ethics Committee, AIIMS. Written informed consent was taken from all the participants.

Study criteria

The present study was a cross-sectional assessment of 30 patients with BD and 20 healthy controls. Inclusion criteria for all participants included an age range of 18–55 years, minimum 5 years of formal education, right-handedness established by Edinburgh Handedness Inventory,[9] absence of color blindness on testing by Ishihara's isochromatic charts[10] and a score of >24 on Hindi Mental State Examination (HMSE).[11] The participants were included in the patient group if they: (i) met a diagnosis of BD type I based on Structured Clinical Interview for DSM-IV, clinician version (SCID-CV);[12] (ii) were in clinical remission for a minimum of 2 months; (iii) were euthymic, indicated by cut-off scores <7 on the 17-item Hamilton Depression Rating Scale (HDRS);[13] and (iv) scored <4 on the Young Mania Rating Scale (YMRS).[14] Exclusion criteria for the patient group included a current or lifetime diagnosis of a major psychiatric disorder other than BD type I, current or lifetime diagnosis of substance dependence other than nicotine, history of electroconvulsive therapy in the previous year or a history of significant head injury, medical or neurological disorder. The present study did not interfere with the clinical care of the patient and the medication(s) prescribed to the patient were continued as advised by the treating clinician.

The control group included healthy persons with absence of any axis I disorder based on SCID-CV,[12] absence of substance dependence other than nicotine, absence of medical or neurological disorder and a negative family history of psychiatric illness. Controls were recruited after proper screening from amongst the non-related attendants of patients, consenting staff members, hospital employees and persons from the community.

Study procedure

The subjects fulfilling the selection criteria were approached. After due informed consent, the principal author performed the evaluation and assessments for each participant in a single session. The sessions were conducted in the first half of the day in quiet surroundings with minimum distraction. Each session lasted 2.5–3 h and participants were offered a 5-min break after each hour, but were not permitted to smoke or consume caffeinated drinks. The assessor was not blind to the status of the participant.

Assessments

After a careful selection using SCID-CV, HDRS, YMRS, Edinburgh's Handedness Inventory, Ishihara's color charts and HMSE as mentioned above, the participants were assessed by using the following tools.

Semi-structured proforma

A semi-structured proforma was used to gather information demographic characteristics of all participants and clinical profile (age at onset, number and nature of episodes, details of each episode, current and past treatment details, family history) in case of patients. Relevant current and previous medical treatment records of the patients were assessed and collateral information was taken into account.

Verbal Adult Intelligence Scale[15]

This battery for verbal tests of intelligence was developed in India, based on items of the Wechsler Adult Intelligence Scale-Revised.[16] It comprises of four sub-tests for general information, arithmetic, digit span and comprehension. It has been standardized for the Hindi-speaking population and is widely used for clinical and research purposes in India. Test–retest reliability over a period of 1–2 weeks was found to be between 0.87 and 0.98. The correlations of four sub-tests with the Wechsler Adult Intelligence Scale-Revised were 0.81, 1.0, 0.91 and 0.87.

Trail Making Test A & B[17]

The Trail Making Test (TMT) consists of two parts: Part A measures visual attention and psychomotor speed; and Part B measures cognitive flexibility and task switching. The test requires a subject to ‘connect-the-dots’ of 25 consecutive targets on a sheet of paper. In part A, the targets are all numbers (1, 2, 3, etc.) and in part B, the subject alternates between numbers and letters (1, A, 2, B, etc.). The goal is to finish the test as quickly as possible and the completion time is used as the primary performance metric.

Verbal Working Memory N-Back Test[18]

The Verbal Working Memory N-Back Test is based on the theoretical premise that two variables, namely, word length and phonemic similarity, can affect verbal working memory. A total of 30 randomly ordered consonants common to multiple Indian languages were presented verbally at the rate of one per second and the subject was required to respond by tapping the table for phonetically similar sounds. In Back Task 1, the subject responds for consecutively repeated sounds and in Back Task 2, the subject responds if the sound is repeated after an intervening phoneme. The number of hits and errors (both omissions and commissions) comprise the score, which are indicative of the internally guided working memory.

Stroop Color and Word Test[19]

The Stroop Color and Word Test (SCWT) measures the relative speeds of reading the names of colors (word card), naming colors (color card), and identifying color names that are printed in another color (interference card). The last task has an interference component because it requires the subject to override or inhibit a reading response. The Color Interference (CI) score is expressed as the difference between the time taken to read the interference card and the word card. This test measures the ease with which a person can shift his or her perceptual set to conform to changing demands and inhibit usual response from interfering with the unusual one. The test is essentially a measure of cognitive flexibility and response inhibition.

Postgraduate Institute Memory Scale[20]

The Postgraduate Institute (PGI) memory scale is part of the PGI battery of brain dysfunction, and has been developed in India. The battery is administered in Hindi, the national language, and has been validated for use in the Hindi-speaking population. It is a comprehensive scale to measure verbal and non-verbal memory and has been extensively used in Indian studies. It consists of 10 sub-tests: remote memory, recent memory, mental balance, attention and concentration (Digit span), immediate recall, verbal retention for similar pairs, verbal retention for dissimilar pairs, visual retention and recognition. All but the first two were used for this study.

World Health Organization QoL–BREF, Hindi version[21]

The World Health Organization (WHO) QoL–BREF, Hindi version has been developed at AIIMS, New Delhi, especially for use in the Indian setting, as part of the multi-centric WHO-QoL project.[22] Based on pilot field trial data, item reduction was done to develop a 100-item questionnaire. The brief 26-item version was developed later and showed high correlation (0.9) with WHO-QoL-100. There is an item each for ‘overall QoL’ and ‘general health’, while the remaining 24 items generate scores in physical, psychological, social relationships and environmental domains on a five-point Likert scale. The physical domain has questions related to daily activities, treatment compliance, pain and discomfort, sleep and rest, energy and fatigue. The psychological domain assesses positive and negative feelings, self-esteem, body image and physical appearance, personal beliefs, and attention. The social relationship domain covers personal relationships, social support, and sexual activity. The environmental domain explores physical security, financial resources, health and social care and their availability, opportunities for acquiring new information and skills, and participation in and opportunities for recreation and transport. The raw scores are converted to transformed scores for each individual domain.

Global Assessment of Functioning[23, 24]

The Global Assessment of Functioning (GAF) is a numeric scale (0–100) to rate the social, occupational, and psychological functioning of adults. GAF covers the range from positive mental health to severe psychopathology and is an overall measure of how a person is functioning. It is also used in Axis V of DSM-IV, but is intended to be a generic rather than a diagnosis-specific scoring system.

All the Indian tests and adaptations used in this study have been standardized for the Indian, Hindi-speaking population and are commonly used for research purposes in India.

Statistical analysis

The data were analyzed using spss version 13 (spss, Chicago, IL, USA). Initial data exploration was done using the Shapiro–Wilk test. The comparison of variables between patients and controls was done using the Independent samples t-test in case of normally distributed variables and the Mann–Whitney U-test was used wherever appropriate. The Mann–Whitney U-test does not assume the asymptotic distribution of test statistic and is reliable regardless of the distribution or balance of the data. Effect sizes for the Mann–Whitney were derived by using the equation r = Z/√n where Z is the Z-score of the test and n is the study sample.[25] Effect sizes for the t-test were based on Cohen's d,[26] calculated as difference of group means divided by pooled SD. Non-parametric correlation analysis (Spearman's correlation) was used to study the association between clinical parameters, neuropsychological performance, QoL domains and global functioning. A P-value of 0.05 was taken as significant, however a higher emphasis was placed on a P-value below 0.01 in view of multiple tests. In order to explore the significant cognitive predictors for QoL, the stepwise multiple regression analysis was performed with QoL domains as dependent variables. No problem of multicollinearity was detected from tolerance and variance inflation factor. All reported P-values are two-tailed.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

There was no significant difference in the sociodemographic profile (age, sex distribution, education, verbal IQ, HMSE) of patients and controls as shown in Table 1. The illness characteristics of the patient group are also shown in Table 1, along with the nature of current medication(s). The majority of patients were of middle socioeconomic status (76.7%), while the rest were of lower socioeconomic status. Nearly 83.3% were currently employed or working productively at home.

Table 1. Sample characteristics: patients and controls
 PatientsControlstP
Mean ± SDMean ± SD
  1. Statistical analysis by independent samples test and χ2-test.

  2. HMSE, Hindi Mental State Examination.

Age33.53 ± 10.3133.25 ± 10.410.0950.93
Sex    
Male63.3% (19)60% (12)γ (48)= 0.8760.35
Female36.7% (11)40% (8)
Education11.87 ± 2.9313.05 ± 3.79−1.2430.22
Verbal IQ102.37 ± 13.53107.20 ± 10.72−1.3400.19
HMSE27.90 ± 1.9028.60 ± 1.23−1.5600.13
Duration of illness (years)10.27 ± 6.44; Median 9.0 (2–28)
Number of episodes 
Total6.23 ± 5.33; Median 4.0 (2–20)
Depressive1.70 ± 2.81; Median: 0.5 (0–12)
Manic4.57 ± 4.35; Median: 3.0 (1–20)
Euthymic period prior to inclusion (months)16.90 ± 16.23 Median: 12 (2–60)
Family history

Positive : 24% (12)

Negative : 76% (18)

Medication 
Lithium21 (70%), 1085.71 ± 211.63 mg/day
Valproate11 (36.7%), 1204.55 ± 218.47 mg/day
Lamotrigine2 (6.7%), 125.00 ± 35.36 mg/day
Olanzapine5 (17.7%), 4.50 ± 2.09 mg/day

Table 2 shows the performance of patient and control group on the tests of attention (Digit span, TMT-A), psychomotor processing speed (TMT-A, Mental Balance subtest, SCWT word and color cards), executive functions (TMT-B, SCWT) and working memory (N-Back). As seen from the table, there is a significant difference in the TMT-A and TMT-B tasks, with patients performing poorly compared to controls. On average, the patients took more time to complete both the tasks as compared to healthy controls (P < 0.01). The psychomotor processing speed was found to be slow among patients as evident from time taken to read the Stroop color card (P < 0.01), with moderate effect size (0.439). Table 3 shows the results of memory test in patients and controls, in which the patients performed poorly on subtests for delayed recall and verbal retention for similar pairs.

Table 2. Neuropsychological performance in patients and controls: Test for attention, psychomotor processing speed, executive functions and working memory
 PatientsControlsZPEffect size
Mean ± SDMean ± SD
  1. Statistical analysis by Mann–Whitney U-test.

  2. PGI, Postgraduate Institute; TMT, Trail Making Test.

Digit span (PGI memory subtest )     
Digit forward + digit backward9.30 ± 1.789.15 ± 1.31−0.1220.9030.017
Mental balance (PGI memory subtest)     
Psychomotor speed7.43 ± 1.437.75 ± 1.25−0.6690.5040.095
TMT     
TMT-A, time taken (s)62.40 ± 30.9047.70 ± 27.65−2.6560.008**0.376
TMT-B, time taken (s)173.63 ± 99.20120.70 ± 65.12−2.7770.005**0.393
TMT B-A111.23 ± 82.6373.00 ± 59.97−2.2890.022*0.324
Stroop Color and Word Test     
Word card, time taken60.60 ± 15.8453.55 ± 11.52−1.8420.0660.260
Color card, time taken120.73 ± 34.1191.40 ± 29.77−3.1080.002**0.439
Interference score149.93 ± 141.06143.35 ± 80.25−0.5350.5930.076
Verbal Working Memory N-Back Test     
1-Back hits8.00 ± 1.178.45 ± 0.83−1.4040.1600.199
1-Back errors1.23 ± 1.451.10 ± 1.89−1.0480.2950.148
2-Back hits5.70 ± 1.566.15 ± 1.95−0.6990.4850.098
2-Back errors3.87 ± 1.693.00 ± 1.89−1.4220.1550.201
Table 3. Neuropsychological performance in patients and controls: Tests for memory
PGI Memory scale subtestsPatientsControlsZPEffect size
Mean ± SDMean ± SD
  1. PGI, Postgraduate Institute.

Delayed recall8.30 ± 1.629.25 ± 1.16−2.4000.016*0.339
Immediate recall10.20 ± 1.1910.85 ± 1.14−1.8450.0650.261
Verbal retention for similar word pairs4.53 ± 0.684.90 ± 0.312.1460.032*0.479
Verbal retention for dissimilar word pairs11.90 ± 3.3411.85 ± 3.48−0.1300.8960.018
Visual retention10.37 ± 2.7911.00 ± 2.25−1.6680.5040.236
Recognition8.90 ± 2.099.75 ± 0.55−1.7730.0950.251

Table 4 shows the group differences in QoL and global functioning. Patients were found to have a significantly lower QoL in psychological and social domains. The difference in global functioning was highly significant (P < 0.01), with patients having poorer scores compared to controls.

Table 4. Quality of life and global functioning in patients and controls
 PatientsControlstPEffect size
Mean ± SDMean ± SD
  1. Statistical analysis by Independent samples t-test and Mann–Whitney U-test.

  2. GAF, Global Assessment of Functioning.

World Health Organization Quality of Life domains     
Physical12.71 ± 2.9114.50 ± 1.96−1.7180.0900.496
Psychological12.62 ± 2.6814.33 ± 2.52−2.4040.020*0.694
Social18.93 ± 4.0320.70 ± 4.01−2.2630.028*0.653
Environmental13.15 ± 1.9714.10 ± 1.60−1.7890.0800.516
Overall quality3.20 ± 0.763.40 ± 0.59−0.9880.3280.285
Overall health3.17 ± 0.833.40 ± 0.75−1.0060.3190.290
GAF     
GAF score71.53 ± 10.4289.10 ± 3.68Z = −5.454<0.001**0.771

The correlation of cognitive variables of patients to the continuous clinical variables (total duration of illness and number of episodes) was examined using Spearman's correlation, the results of which are shown in Table 5. The correlation among the categorical clinical variables (family history, type of medication, age of onset, duration of euthymic period) was also examined using the Mann–Whitney U-test, none of which were found to be significant (not shown in table). The correlation among various cognitive variables, QoL domains and global functioning was examined and, as shown in Table 5, a moderate correlation was found with psychological and social domains as well as GAF score.

Table 5. Neuropsychological performance: Association among clinical variables, quality of life and global functioning in the patients (n = 30)
rs (p)Illness durationNo. of episodesPhysical domainPsychological domainSocial domainEnvironmental domainGAF
  1. Statistical analysis by Spearman's correlation; rs = Spearman's Rho; P-value in parentheses.

  2. GAF, Global Assessment of Functioning; TMT, Trail Making Test.

Word card, time taken (s)0.110.11−0.210.01−0.04−0.30*−0.25
(0.55)(0.57)(0.15)(0.97)(0.85)(0.033)(0.19)
Color card, time taken (s)−0.020.21−0.230.00−0.35−0.51**−0.23
(0.91)(0.27)(0.11)(0.99)(0.06)(<0.001)(0.22)
Interference score0.030.21−0.25−0.34−0.49**−0.39**−0.28
(0.89)(0.27)(0.09)(0.07)(0.006)(0.005)(0.14)
TMT-A, time taken (s)−0.010.07−0.22−0.22−0.39*−0.49**−0.21
(0.96)(0.73)(0.11)(0.24)(0.033)(<0.001)(0.27)
TMT-B, time taken (s)0.43*0.41*−0.36*−0.46*−0.63**−0.57**−0.14
(0.016)(0.027)(0.011)(0.010)(0.000)(<0.001)(0.46)
1-Back hits0.09−0.01−0.030.090.280.210.23
(0.63)(0.95)(0.83)(0.64)(0.14)(0.14)(0.23)
1-Back errors−0.000.140.01−0.040.32−0.15−0.26
(0.99)(0.46)(0.93)(0.82)(0.69)(0.30)(0.16)
2-Back hits−0.36−0.170.170.040.080.19−0.19
(0.05)(0.36)(0.24)(0.82)(0.72)(0.17)(0.31)
2-Back errors0.48**0.28−0.23−0.17−0.23−0.31*0.18
(0.007)(0.13)(0.11)(0.35)(0.23)(0.032)(0.35)
Mental balance0.01−0.010.170.110.330.170.27
(0.95)(0.95)(0.25)(0.58)(0.07)(0.24)(0.15)
Attention and concentration0.020.050.09−0.03−0.08−0.050.33
(0.91)(0.79)(0.54)(0.89)(0.67)(0.73)(0.07)
Delayed recall−0.12−0.120.110.15−0.030.110.34
(0.51)(0.52)(0.45)(0.44)(0.89)(0.45)(0.07)
Immediate recall−0.14−0.090.200.08−0.060.120.25
(0.46)(0.64)(0.16)(0.68)(0.76)(0.41)(0.19)
Verbal retention for similar pairs0.070.090.10−0.01−0.070.270.14
(0.73)(0.62)(0.48)(0.97)(0.71)(0.06)(0.45)
Verbal retention for dissimilar pairs0.050.150.250.080.030.230.23
(0.81)(0.43)(0.17)(0.68)(0.87)(0.11)(0.21)
Visual retention−0.34−0.300.29*0.44*0.330.320.13
(0.06)(0.11)(0.036)(0.015)(0.07)(0.06)(0.48)
Recognition−0.09−0.040.100.250.060.110.47**
(0.60)(0.82)(0.45)(0.18)(0.76)(0.43)(0.009)

The stepwise multiple regression analysis was used to test for significant predictors for QoL domains. Only the cognitive variables with significant correlation were taken as independent variables. There were two independent variables (Visual Retention and TMT-B) each for physical and psychological domain, three (TMT-A, TMT-B, SCWT-CI) for social domain and six (TMT-A, TMT-B, SCWT-CI, word card, color card, 2-Back errors) for environmental domain. The detailed results for each domain are shown in Table 6. Visual retention accounted for 23% of variance in physical domain. TMT-B, which is indicative of cognitive flexibility and set shifting (executive functions), explained 17% of the variance in psychological domain (R2 = 0.17; F [1, 48] = 9.83, P = 0.003) and 32% of variance in social domain (R2 = 0.32; F [1, 48] = 22.45, P < 0.001). TMT-A, which is indicative of attention and psychomotor processing speed, accounted for nearly 12% of variance in environmental domain.

Table 6. Neuropsychological performance as a predictor for quality of life domains in patients
PredictorsBSEβtP
  1. Stepwise multiple regression; n = 30.

  2. Number of independent variables: 2, 2, 3, 6 for domains 1–4, respectively.

  3. DV, dependent variables; SE, standard error; TMT, Trail Making Test.

Constant10.1680.472 6.090<0.001
Visual retention0.3360.1350.3392.4940.016
R2 = 0.12; F (1, 48) = 6.22, P = 0.016; Physical domain as DV
Constant15.3060.695 22.024<0.001
TMT-B−0.0120.004−0.412−3.1350.003
R2 = 0.17; F (1, 48) = 9.83, P = 0.003; Psychological domain as DV
Constant15.9060.636 25.024<0.001
TMT-B−0.0170.004−0.564−4.738<0.001
R2 = 0.32; F (1, 48) = 22.45, P < 0.001; Social domain as DV
Constant15.2260.503 30.291<0.001
TMT-A−0.0300.008−0.483−3.819<0.001
R2 = 0.23; F (1, 48) = 14.58, P < 0.001; Environmental domain as DV

Regression was also repeated after the addition of the significant clinical variables for each QoL domain (namely, age of patient for psychological domain, number of depressive episodes for social domain, education for environmental domain) in the first block and significant cognitive variables in the second block, however the results were not very different (not tabulated). The significant predictive model remained the same in the case of social domain, while in the case of psychological and environmental domain, the age of the patient and number of years of education were respectively added to the model, slightly increasing variance further to 26% and 32%.

GAF score showed significant correlation to Recognition (P = 0.001) subtest of memory scale, which explained nearly 22% of the variance (rs = 0.47; rs2 = 0.22).

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

To the best of our knowledge, this is the first report from the Indian subcontinent to comprehensively investigate the correlation between cognitive impairments and QoL. To date, very few studies[27-29] in the Western literature have focused on the influence of cognitive impairments on QoL of BD patients.

The findings from this study reveal that euthymic patients with BD have significant impairments in selected cognitive functions compared to healthy controls. These include poor performance in tests for attention, information processing speed and executive function in addition to impairments in verbal memory. Several similarities, as well as contrasts, emerged on comparison with previous literature.[1, 2, 30] The executive functions and verbal memory were found to be the most marked deficits in a recent meta-analysis for the euthymic period.[2] In addition, response inhibition, sustained attention, psychomotor speed and set-shifting were also found to be impaired, though to a lesser degree. These findings are broadly similar to the findings from the current study.

A contrasting feature in our study is the stark preservation of response inhibition (SCWT-CI). It is noteworthy that the results for executive functions show a divide across the two tests used, which reflects in a poor cognitive flexibility and set-shifting ability in the TMT-B and a preserved selective attention and response inhibition in the color interference card of SCWT. A previous study[31] had also found a divide in the results of executive functions, however the findings were the reverse of ours, with preserved cognitive flexibility and impaired response inhibition. In contrast to previous studies,[31, 32] visual memory was preserved in the present study. The observation that memory deficits in euthymic patients are mediated by deficient organizational strategies at encoding or poor retrieval processes[33, 34] rather than deficient retention was confirmed by a largely preserved memory retention or storage in the memory tests.

Most previous studies have reported that patients with a greater number of episodes and longer duration of illness suffer greater cognitive decline.[35-37] In this study, time taken for completion of TMT-B correlated significantly with the duration of illness and number of episodes, while number of errors in the 2-Back test showed significant correlation with duration of illness. These associations may be indicative of a progressive disease process, thereby increasing the degree of cognitive impairments with time.

The patients in the present study had a significantly poorer QoL in the psychological and social domains. The global functioning also differed markedly among the two groups, with patients having an overall poorer social, psychological and occupational functioning. In combination, these measures provide self-rating as well as clinician's judgment regarding patient functioning. This finding is consistent with most previous studies.[27, 38-40]

More importantly, what has emerged from this study is confirmation of the hypothesis that cognitive dysfunction is a predictor of poorer QoL in the stable phase of BD. So far, only the mood symptoms were thought to be related to a poor QoL. In fact, it has been mentioned that sub-depressive symptoms may be the most potent predictors of low QoL, even in remitted patients. We have made a strong effort to rule out the possibility of residual affective symptoms by incorporating the criteria of clinical remission for a minimum of 2 months as per the psychiatrist's assessment, as well as application of standard rating scales to screen for depression or mania just prior to assessment. In this regard, our study is more rigorous than some previous ones.

The cognitive impairments explained 12–32% of the variance for various QoL domains. Given the fact that psychological and social domains differed significantly among patients and controls, there may be a possible role of cognitive impairments in explaining these group differences. Perhaps a better cognitive functioning: (i) makes one more equipped to handle one's feelings and thoughts; (ii) increases psychological adjustment and adaptation to social situations; and (iii) enhances social relationships, resulting in better QoL. This study, however, does not investigate a causal correlation and indicates only association and predictive ability.

Of all the tests, the TMT-B, an indicator of cognitive flexibility and set shifting, was found to be a significant predictor of psychological and social domains of QoL, explaining 17% and 32% of the variance. Previous studies have also indicated that perhaps executive dysfunction represents the central bipolar trait deficit, and this impairment underlies not only the broad cognitive deficit pattern that is observed, but also the psychosocial and functional deficits exhibited by patients.[41-43] Recognition was found to be significantly predictive of GAF score, which is in contrast to a previous study where processing speed was robustly associated with social and global functioning in BD.[44]

The influence of cognitive impairments on QoL has been demonstrated in only a few recent studies.[27-29] Brissos et al.[27] studied the clinical and cognitive variables of QoL of BD patients, schizophrenia patients and controls. To their surprise, they found a negative impact of neurocognitive deficits on QoL, while in the same study there was no impact of cognitive deficits on the QoL of schizophrenia patients. A year later, in a different study,[28] the same researchers reported that a poorer self-reported QoL correlated significantly with worse cognitive performance on tests of executive functioning and verbal abstraction. No significant correlation was found, however, between cognitive dysfunction and QoL in a separate study.[29] The existing evidence base is limited and the area merits further research attention.

The present study has several important clinical implications. Cognitive deficits could be an important marker for future neurobiological and pharmacological research. Neurocognitive rehabilitation strategies and appropriate pharmacological strategies need to be developed with the goal of improving cognition and QoL of patients during the stable phase. Early diagnosis and active treatment potentially could reduce the cognitive morbidity associated with BD. Adequate cognitive functioning is desirable for the achievement of better QoL and special attention needs to be devoted to patients who remain functionally impaired despite the resolution of major affective symptoms.

The study was, however, limited by a small sample size and hospital setting. The findings cannot be generalized to individuals with BD from the community. Moreover, almost all patients were on medication, which could affect the cognitive functions and QoL due to their side-effect profile. The present cross-sectional nature of the assessment does not allow for causal inferences among these variables. Future research needs to better estimate the longitudinal correlation between cognitive function and psychosocial outcome across illness phases in the same patient cohort.

To conclude, it is important to understand the functional significance of cognitive impairments in the everyday lives of the patients. The cognitive assessment of patients with BD cannot, or rather should not, be done in isolation from assessment of its impact on psychosocial functioning and QoL of patients.

Acknowledgment

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

The support of the Council of Scientific and Industrial Research (CSIR), New Delhi, India is duly acknowledged. The first author's current position and research is supported by the CSIR Scientists’ Pool Scheme. There is no external source of funding for the study. There is no conflict of interest to declare for any of the authors.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References