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Keywords:

  • cognitive deficits;
  • major depression;
  • neurocognitive functions;
  • Taiwanese Depression Questionnaire

Abstract

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Aims:  Although cognitive deficits are a common and potentially debilitating feature of major depressive disorder (MDD), such subjective declines in cognitive function are seldom validated by objective methods as a clinical routine. The aim of this study was to validate the Taiwanese Depression Questionnaire (TDQ) for detecting cognitive deficits in a sample of drug-free patients with MDD.

Methods:  The subjects consisted of 40 well-characterized medication-free patients with MDD and 40 healthy controls. Clinical and neuropsychological assessments, including the Wisconsin Card Sorting Test, the Wechsler Memory Scale–Revised, the Continuous Performance Test, and the Finger-Tapping Test, were administered at the time of recruitment.

Results:  Factor analyses of the TDQ yielded three factors. Memory, attention and psychomotor performance were significantly poorer in patients with MDD. The performances of verbal and delayed memory of the Wechsler Memory Scale–Revised were correlated with the cognitive domains of the TDQ. Generalization of our results must be undertaken with caution considering the relatively small sample size, which could lead to increased β-error.

Conclusion:  Cognitive subdomains might be considered important for including in patient-administered questionnaires used to measure symptoms of MDD when developing a new scale.

THE INCLUSION OF cognitive symptoms in the DSM-IV criteria for major depressive episodes highlights the importance of cognition. For example, the criteria for the diagnosis of this condition include a diminished ability to concentrate, indecisiveness, and psychomotor retardation or agitation. There is a growing body of evidence of a significant reduction in neurocognitive functions in major depressive disorder (MDD),1 and depression-related disturbances of cognitive function have been demonstrated in a range of domains, including attention,2–4 memory,5,6 executive functions,7–10 and psychomotor functions.11 However, findings to date are varied,12 with many factors potentially contributing to inconsistencies between studies, including age, hospitalization duration, severity and subtype of depression, and the effect of psychotropic medication.13,14

Although cognitive deficits are a common and potentially debilitating feature of MDD, subjective cognitive decline is seldom validated by objective methods. Only a limited number of items pertain to neurocognitive decline in the most widely used depression rating scales, for example, the Hamilton Depression Rating Scale (HDRS)15 and the Beck Depression Inventory (BDI).16 However, in a recently developed patient-administered depression questionnaire, more comprehensive incorporation of cognitive items was attempted,17,18 although the validity concerning the neurocognitive domain of depression has not yet been confirmed.

The aims of this study were to: (i) validate the Taiwanese Depression Questionnaire (TDQ) for cognitive deficits in a sample of patients with MDD; and (ii) compare the cognitive function of depressed patients with that of their controls.

METHODS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Subjects

We recruited 40 patients with a mean age of 38.72 ± 13.02 years (11 men and 29 women), who were evaluated with the Mini-International Neuropsychiatric Interview19 and were diagnosed as having MDD according to the criteria of the DSM-IV at the outpatient clinic of the Department of Psychiatry, National Cheng Kung University, Tainan, Taiwan. Before any procedure was performed, informed consent was obtained from patients and healthy controls. The Ethical Committee for Human Research of the hospital approved the study protocol. Patients were included if they had not received any psychotropic medication for more than 3 months; and we excluded patients with: (i) a current diagnosis of dysthymia or other mental disorders; (ii) serious suicidal risk; or (iii) any acute or unstable medical condition. We also excluded patients who had undergone electroconvulsive therapy. Healthy controls (11 men and 29 women) who had been recruited from the community by advertisement for various studies were also enrolled in this study (Table 1). All participants confirmed that they were not taking antidepressants at the time of recruitment.

Table 1.  Clinical data of the patients with major depressive disorder and the controls
 Patients with MDD (n = 40)Controls (n = 40)t / x2P-value
Mean(SD)Mean(SD)
  1. CPT, Continuous Performance Test; FTT, Finger-Tapping Test; HDRS, Hamilton Depression Rating Scale; MDD, major depression disorder; SD, standard deviation; TDQ, Taiwanese Depression Questionnaire; WCST, Wisconsin Card Sorting Test; WMS-R, Wechsler Memory Scale–Revised.

Age (years)39.37(13.96)39.01(12.77)0.120.90
Sex      
 Male11110.001.00  
 Female2929    
Educational level (years)11.27(3.69)12.98(3.58)−1.950.06
Duration of illness (years)1.27(2.24)    
HDRS21.47(5.07)3.95(1.89)20.04<0.0005
TDQ      
 Affective domain12.54(5.45)2.40(3.25)10.01<0.0005
 Cognitive domain5.90(2.31)2.03(1.85)8.23<0.0005
 Somatic domain17.03(5.90)3.78(3.83)11.82<0.0005
 Sum35.46(12.08)8.20(8.18)11.71<0.0005
WMS-R      
 Verbal memory index85.21(19.12)97.03(17.22)−2.780.01
 Visual memory index93.82(22.74)107.25(17.15)−2.880.01
 General memory index85.15(21.70)100.15(17.69)−3.25<0.0005
 Attention/concentration98.76(20.91)108.63(15.14)−2.290.03
 Delayed-recall memory index92.32(21.60)106.78(14.79)−3.40<0.0005
WCST      
 Perseverative errors11.05(5.52)12.93(9.66)−1.050.29
 Category completed2.36(1.44)2.35(1.58)0.030.98
CPT      
 CPT unmasked d'3.89(1.17)4.39(0.58)−2.100.04
 CPT masked d'3.33(1.22)3.52(1.16)−0.580.56
FTT      
 Dominant hand34.93(12.61)43.75(8.66)−3.390.00

Measurements

All participants completed the TDQ.17 This questionnaire contains 18 items for depression symptoms; it is a culturally relevant and subjective questionnaire in which patients are asked to indicate, on a 4-point Likert scale, whether and how often each item is experienced. The TDQ total score ranges from 0 to 54, and the higher the score, the more severe the level of depression. A cut-off score of 19 has a good validity (sensitivity = 0.89, specificity = 0.92). On examination of the internal consistency, Cronbach's α coefficient of the questionnaire was 0.94. Three factors, somatic, affective and cognitive factors, were reported when the TDQ was developed; however, no detailed descriptions were included in the original article.17 Furthermore, the 17-item HDRS is an itemized questionnaire providing information on the affective and somatic symptoms of depression and was rated by a senior psychiatrist (Y.K.Y.) in this study.15

Wisconsin Card Sorting Test20

The Wisconsin Card Sorting Test (WCST) was conducted by an experienced clinical neuropsychologist. All definitions of the indices were as described in the WCST manual.20 We chose to analyze the most commonly used indices, ‘perseverative errors’ and ‘completed categories’, among the many indices of the WCST.21,22

Wechsler Memory Scale–Revised version23

The Wechsler Memory Scale–Revised version (WMS-R) test was administered by trained psychologists with masters' degrees. This test comprises a series of 13 brief subtests that include assessment of: (1) information and orientation; (2) mental control; (3) figure memory; (4) logical memory I; (5) visual paired associates I; (6) verbal paired associates I; (7) visual reproduction I; (8) digit span; (9) visual memory span; (10) logical memory II; (11) visual paired associates II; (12) verbal paired associates II; and (13) visual reproduction II, each measuring a different facet of memory. Subtests 3–9 measure immediate learning, while the latter four subtests measure recall of the material learned in the previous subtests. All subtests except the information and mental control tests measure episodic learning of both verbal and figural materials.

Continuous Performance Test24,25

The Continuous Performance Test (CPT) is a vigilance task requiring the monitoring of rapid information processing and the detection of briefly presented target stimuli. Subject responses were recorded automatically on a diskette using a CPT machine (Sunrise Systems V2.20, Pembroke, MA, USA). Each subject undertook two forms of the CPT: the unmasked task and the masked task. The attention test index (d') is a measurement of a subject's ability to differentiate a signal from background noise, and a higher d' indicates a better processing capability. In general, the distribution of the attention test index (d') should be normal.

Finger-Tapping Test

The Finger-Tapping Test (FTT) measures the motor speed of the index finger of each hand. The finger-tapping score is defined as the mean number of taps per 10 s collected over five trials. Using a specially adapted tapper, the subject tapped as fast as possible using the index finger of each hand. In this study, only dominant hand data were analyzed.

Statistical analysis

Estimates of internal reliability were computed using Cronbach's α. Because sample size in this study (n = 40) was too small to perform factor analysis, we used all MDD patients from our previous studies (n = 140) in order to examine whether we would be able to obtain three factors, as was suggested by Lee et al.17 The correlations between the TDQ subdomains and neurocognitive performances in the patient group were computed. Demographic data and the results of clinical assessments were analyzed using Pearson's correlation for continuous data. The level of significance was set at P < 0.05 (two-tailed). Because seven patients were not able to complete the WMS-R test, only 33 depressed patients were included in the subsequent analysis of the correlations between TDQ subscores and WMS-R indices. In addition, only 28 depressed patients completed the CPT and 27 completed the FTT. Compared with the controls, no significant differences in basic characteristics (e.g. age or sex) were found after the missing data of depressed patients were removed. All analyses were performed using the spss 15.0 computer package (spss, Chicago, IL, USA).

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Three subdomains of the TDQ, the cognitive, affective, and somatic domains, were indeed confirmed from factor analysis (Table 2). The reliability of the overall TDQ was good (Cronbach's α = 0.93), and the reliabilities of the TDQ subdomains (the somatic, affective and cognitive domains) are shown in Table 2. A significant correlation between TDQ score and HDRS score was noted in this study (r = 0.56, P < 0.0001). Cognitive declines in patients with MDD were observed from their performance in the WMS-R, CPT and FTT (Table 1). In the patients group, there was a significant negative correlation between the TDQ cognition subscale and the WCST index of the number of categories completed (r = −0.33, P = 0.038); significant negative correlations between the TDQ cognition subscale and the WMS-R indices of verbal memory (r = −0.36, P = 0.04) and delayed recall memory (r = −0.37, P = 0.035) were also observed. In addition, the correlation between the TDQ cognition subscale score and the general memory index was marginally negative (r = −0.34, P = 0.057). The unmasked d' obtained from the CPT was also correlated with the cognitive domain of the TDQ (Table 3).

Table 2.  Cronbach's α for the Taiwanese Depression Questionnaire subdomains (n = 140)
 Factor loading
123
Factor 1: Cognitive subdomain Cronbach's α = 0.87
 10. I had poor memory0.710.170.34
 11. I could not concentrate when doing things0.770.230.36
 12. I was slower in thinking and doing things than before0.790.250.16
Factor 2: Affective subdomain Cronbach's α = 0.95
  1. I often felt like crying0.060.540.32
  3. I felt more agitated than before0.200.410.39
 13. I felt less confident than before0.480.610.26
 14. I tended to look at the dark side of everything0.150.780.24
 15. I felt miserable and even wanted to die0.250.740.19
 16. I lost interest in everything0.340.560.43
 18. I felt worthless0.290.680.25
Factor 3: Somatic subdomain Cronbach's α = 0.96
  2. I felt blue and depressed0.140.560.64
  4. I had trouble sleeping0.230.210.52
  5. I had poor appetite0.250.430.47
  6. I frequently had chest tightness ('sim-guan-tau-bang-bang')0.260.350.64
  7. I felt uneasy, uncomfortable0.270.370.67
  8. I felt tired and weak (‘Xu’, ‘mo wan qi’)0.350.360.62
  9. I felt upset0.280.460.64
 17. I felt sick (headache, dizziness, palpitations, or abdominal distress)0.180.100.72
Table 3.  Relationship between TDQ subscale scores and scores for various cognitive tests in patients with major depressive disorder
 TDQ
SomaticAffectiveCognitiveTotal score
  • *

    P < 0.05;

  • **

    P < 0.01.

  • CPT, Continuous Performance Test; FTT, Finger-Tapping Test; TDQ, Taiwanese Depression Questionnaire; WCST, Wisconsin Card Sorting Test; WMS-R, Wechsler Memory Scale–Revised.

WCST (n = 40)    
 Preservative errorsr = −0.05r = −0.01r = 0.12r = −0.01
P = 0.76P = 0.93P = 0.47P = 0.96
Number of categories completedr = 0.01r = −0.10r = −0.33r = −0.10
P = 0.94P = 0.55P = 0.04*P = 0.54
WMS-R (n = 33)    
 Verbal memory indexr = −0.16r = −0.24r = −0.36r = −0.26
P = 0.39P = 0.18P = 0.04*P = 0.15
 Visual memory indexr = 0.19r = 0.08r = −0.24r = −0.09
P = 0.28P = 0.66P = 0.19P = 0.63
 General memory indexr = −0.03r = −0.13r = −0.34r = − 0.14
P = 0.88P = 0.46P = 0.057P = 0.44
 Attention/concentration indexr = −0.09r = −0.03r = −0.22r = −0.10
P = 0.60P = 0.89P = 0.21P = 0.58
 Delayed recall memory indexr = −0.13r = −0.29r = −0.37r = −0.27
P = 0.46P = 0.10P = 0.04*P = 0.13
CPT (n = 28)    
 CPT unmasked d'R = −0.35R = −0.39r = −0.45r = −0.44
P = 0.06P = 0.04*P = 0.02*P = 0.02*
 CPT masked d'R = −0.57R = −0.43r = −0.42r = −0.54
P = 0.01**P = 0.05P = 0.06P = 0.01*
FTT (n = 27)    
 Dominant handR = −0.01r = 0.02r = −0.28r = −0.04
P = 0.95P = 0.90P = 0.16P = 0.83

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

The results of poorer cognitive performance in drug-free patients with MDD in this study were similar to those of previous studies.26 The findings of significant memory decline in patients with MDD supported the review by Buchanan et al.,27 which reported that memory decline was more profound than executive function decline in patients with MDD. Additionally, it is known that the hippocampus plays a key role in the regulation of mood and cognition. Hickie et al. showed that reduction in hippocampal volumes was associated with declines in visual and verbal memory functions in older people with depression,28 while Taylor Tavares et al. also found that unmedicated MDD patients experienced a significant reduction in executive function as compared with healthy subjects and bipolar II depressed patients.29

In this study, neuropsychological measures in depressed patients were found to be correlated with the cognitive domain of a depression questionnaire; in other words, cognitive symptoms perceived by depressed patients are correlated with objective measures of neurocognitive performance. Antikainen et al. reported that patients complaining of memory disturbance had higher BDI and HDRS scores than patients who did not, and that they also performed poorly in objective memory tests but not in tests of other cognitive functions.30 Even in the context of suspected cognitive disorder, the discrepancy between memory complaints and memory performance in patients is a subject of debate.31,32 A few studies have examined the association between subjective cognitive symptoms and objective neurocognitive measurements in patients. As such, Crane et al. found that depressive symptoms were independently associated with subjective memory complaints in non-demented older adults.33 Another example is the study of Bruce et al.,34 which demonstrated that BDI scores were positively correlated with mini-mental status and memory impairment. However, Bruce et al. did not identify which of the subdomains of the BDI are correlated with objective neuropsychological assessments.34 In contrast to these results, some studies have shown that memory complaints are associated with depressive symptoms35–37 but not with all domains of neuropsychological measurements, particularly psychomotor speed measures.38 These inconsistent results may be due to the use of different symptom checklists or different subdomains in the different studies.

In this study it was demonstrated that the cognitive subdomain of the validated depression questionnaire, the TDQ, is correlated with objectively measured cognitive functions in patients with MDD. Lee et al.39 also demonstrated that mild cognitive decline is highly prevalent among geriatric depressed patients in the course of the acute phase. It might therefore be important to include cognitive symptoms of major depression when developing a depression questionnaire.

No significant correlation was found in this study between self-rated cognitive domain scores of the TDQ and psychomotor speed, as measured by the FTT, as with the study of Naismith et al.;38 however, self-rating of cognitive deficits by depressed patients is still important. The discrepancy between objective and subjective measurements of cognitive performance still exists,38 as demonstrated by the large unexplained variance, and clinicians cannot rely solely on subjective reports of cognitive decline to assess cognitive function in depressed patients.

The results of the current study need to be interpreted with caution due to the following limitations. First, this study only recruited a small sample. Second, no significant correlations were observed between TDQ cognitive subdomain scores and some indexes of cognitive performance. Third, MDD patients can be subgrouped into non-psychotic or psychotic, single episode or multiple episodes, and other grouping variations; however, only non-psychotic and unipolar MDD patients were recruited to this study. Finally, the lack of inter-rater reliability of MDD diagnosis, detailed clinical assessment by psychiatrists and the short disease duration could confound the results.

ACKNOWLEDGMENTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

This study was supported by a grant from Zuoying Armed Forces General Hospital (9715). The authors gratefully acknowledge Yun-Hsuan Chang, Tsai-Hua Chang, Szu-ting Hsu and Linda J. Chang for their statistical, administrative and editorial assistance.

REFERENCES

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES
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