Cognitive symptoms in major depressive disorder: associations with clinical and functional outcomes in a 6-month, non-interventional, prospective study in China

Figures & data

Table 1 Participant flow

	Number of patients
Total population^a	1,008
Completed the month 6 visit	666 (66.1%)
Ineligible according to at least one inclusion/exclusion criterion	22 (2.2%)
Missing visit at month 2	385 (38.2%)
Missing baseline DSST assessment	5 (0.5%)
Missing month 2 DSST assessment	16 (1.6%)
Analysis population^b,c	598 (59.3%)
Adverse event	1 (0.2%^d)
Lost to follow-up	50 (8.4%^d)
Completed the 6-month observational study	547 (91.5%^d)

Notes: ^aTotal population: All enrolled patients who gave written informed consent. ^bAnalysis population: All patients in the total population who were eligible according to study inclusion/exclusion criteria, and who had valid DSST assessments at baseline and month 2. ^c18 patients had more than one reason for being excluded from the analysis population. ^dOf the analysis population.

Abbreviation: DSST, Digit Symbol Substitution Test.

Table 2 Study population

Sociodemographic characteristics		Total study population (N=1008)	Analysis population (n=598)
Region in China	North, n (%)	571 (56.6)	357 (59.7)
	South, n (%)	69 (6.8)	48 (8.0)
	East, n (%)	178 (17.7)	83 (13.9)
	West, n (%)	190 (18.8)	110 (18.4)
Age (years), mean ± SD		36.0±12.0	36.5±12.0
Women, n (%)		693 (68.8)	410 (68.6)
Married, n (%)		612 (60.8)	371 (62.0)
Educational level, n (%)
Middle school or lower		240 (23.8)	134 (22.4)
High school or junior college		321 (31.8)	194 (32.4)
University or post-graduate		447 (44.3)	270 (45.2)
Employed, n (%)		570 (56.5)	343 (57.4)
Urban residents, n (%)		827 (82.0)	491 (82.1)
Clinical history
First-time episode, n (%)		610 (60.5)	343 (57.4)
Number of previous episodes, mean ± SD		2.2±2.2	2.0±2.1
Range, n		1–20	1–20
Duration of current episode ≥8 weeks, n (%)		725 (71.9)	430 (71.9)
Switch of antidepressant at baseline, n (%)		219 (21.7)	144 (24.1)
Clinical assessments, mean ± SD
PDQ-D total score		33.6±16.3	33.7±16.2
DSST score		50.4±16.9	50.2±16.5
HAM-D17 total score		23.2±4.4	23.3±4.4
CGI-S score		4.6±0.8	4.5±0.8
SDS total score		17.0±7.2	17.4±7.1
WPAI-SHP absenteeism, %		26.5±35.7	26.5±34.9
WPAI-SHP presenteeism, %		54.8±26.8	55.6±26.4
EQ-5D utility index		0.74±0.14	0.73±0.14

Abbreviations: CGI-S, Clinical Global Impressions – Severity of Illness; DSST, Digit Symbol Substitution Test; EQ-5D, European Quality of Life Questionnaire – 5 Dimensions; HAM-D₁₇, Hamilton Depression Rating Scale – 17 items; PDQ-D, Perceived Deficit Questionnaire-Depression; SD, Standard deviation; SDS, Sheehan Disability Scale; WPAI-SHP, Work Productivity and Activity Impairment Questionnaire – Specific Health Problems Questionnaire.

Figure 1 Prevalence of cognitive symptoms (PDQ-D total score ≥21).

Abbreviations: PDQ-D, Perceived Deficits Questionnaire – Depression.

Figure 2 Study assessment across study months. Error bars represent 95% confidence intervals. Baseline: (A) PDQ-D, n=589; (B) DSST, n=598; (C) HAM-D₁₇, n=598; (D) SDS, n=455; (E) WPAI-SHP absenteeism, n=313; presenteeism, n=278; overall work impairment, n=278; activity impairment, n=597; (F) EQ-5D, n=596. Month 6: PDQ-D, n=524; DSST, n=526; HAM-D₁₇, =530; WPAI-SHP absenteeism, n=286; presenteeism, n=272; overall work impairment, n=271; activity impairment, n=529; SDS, n=434; EQ-5D, n=525.

Abbreviations: DSST, Digit Symbol Substitution Test; EQ-5D, European Quality of Life Questionnaire – 5 Dimensions; HAM-D₁₇, Hamilton Depression Rating Scale – 17 items; PDQ-D, Perceived Deficits Questionnaire-Depression; SDS, Sheehan Disability Scale; WPAI-SHP, Work Productivity and Activity Impairment – Specific Health Problems Questionnaire.

Table 3 Baseline correlations among assessments of cognition, mood, and functioning

	N	Pearson’s r (95% CI)	N	Pearson’s r (95% CI)
		PDQ-D total score		DSST score
DSST score	589	−0.068 [−0.148, 0.013]	-	-
HAM-D17 total score	589	0.212 [0.134, 0.288]*	598	−0.254 [−0.328, −0.178]*
PHQ-9 total score	588	0.562 [0.504; 0.615]*	595	−0.098 [−0.176; −0.017]*
SDS total score	447	0.480 [0.404; 0.548]*	455	−0.023 [−0.115; 0.069]
WPAI-SHP scales
Absenteeism	308	0.063 [−0.049; 0.173]	313	−0.041 [−0.151; 0.070]
Presenteeism	274	0.430 [0.327; 0.521]*	278	−0.056 [−0.173; 0.062]
Overall work impairment	274	0.390 [0.284; 0.486]*	278	−0.044 [−0.160; 0.075]
Activity impairment	588	0.416 [0.347; 0.481]*	597	−0.057 [−0.136; 0.024]
EQ-5D utility index	587	−0.324 [−0.395; −0.250]*	596	0.191 [0.112; 0.267]*
UPSA-B total score^a	103	−0.147 [−0.331; 0.049]	107	0.434 [0.264; 0.575]*

Notes: *p<0.05. ^aUPSA-B assessed in a subsample (n=200).

Abbreviations: DSST, Symbol Digit Substitution Test; EQ-5D, European Quality of Life Questionnaire – 5 Dimensions; HAM-D₁₇, Hamilton Depression Rating Scale – 17 items; PDQ-D, Perceived Deficits Questionnaire – Depression; PHQ-9, Patient Health Questionnaire-9 item; SDS, Sheehan Disability Scale; UPSA-B, University of San Diego Performance-based Skills Assessment – Brief; WPAI-SHP, Work Productivity and Activity Impairment Questionnaire – Specific Health Problems Questionnaire.

Figure 3 Associations between cognitive symptoms (PDQ-D total score)/cognitive performance (DSST score) and clinical outcomes. Reference categories (grey symbols): Lowest PDQ quartile/DSST score within norm. Logistic regression based on stepwise backward model selection with age, gender, region, HAM-D₁₇, and PDQ-D/DSST scores as forced factors. Note that Y-axis displays the log-scale (data have not been log-transformed). Error bars represent 95% confidence intervals. P-values based on tests for global differences. PDQ-D quartiles at baseline: 0–20, n=136; 21–32, n=158; 33–43, n=137; 44–80, n=158. PDQ-D quartiles at month 2: 0–9, n=135; 10–17, n=155; 18–30, n=140; 31–80, n=155. DSST categories at baseline: Within norm, n=265; 1/3 to 2/3 SD below norm, n=80; 2/3 to 1 SD below norm, n=72; ≥1 SD below norm, n=181. DSST categories at month 2: Within norm, n=360; 1/3 to 2/3 SD below norm, n=74; 2/3 to 1 SD below norm, n=53; ≥1 SD below norm, n=111. Response defined as a reduction of >50% from baseline in HAM-D₁₇ total score. Remission defined as HAM-D₁₇ total score ≤7. Relapse: “yes” if patients had a PHQ-9 total score ≤9 points at month 2 but worsened to a PHQ-9 total score ≥10 points at month 6, and “no” if PHQ-9 total score ≤9 points both at month 2 and month 6 [for replacement of missing values, see Supplementary materials].

Abbreviations: DSST, Symbol Digit Substitution Test; HAM-D₁₇, Hamilton Depression Rating Scale – 17 items; PDQ-D, Perceived Deficits Questionnaire – Depression; PHQ-9, Patient Health Questionnaire-9.

Table 4 Associations between PDQ-D total score/DSST score and functional outcomes at month 6

	Adjusted mean (SE)^a
	SDS total score	WPAI-SHP absenteeism	WPAI-SHP presenteeism	WPAI-SHP overall work impairment	WPAI-SHP activity impairment	EQ-5D Utility Index	UPSA-B total score^d
PDQ-D quartiles at month 2^b
0–9	5.21 (0.98)	14.44 (5.07)	5.90 (4.36)	6.92 (4.98)	18.93 (4.20)	0.86 (0.02)	75.04 (5.75)
10–17	7.37 (0.87)	15.38 (4.81)	11.26 (4.22)	13.54 (4.82)	24.60 (4.38)	0.83 (0.02)	81.04 (5.77)
18–30	8.98 (0.86)	17.03 (4.56)	19.31 (3.94)	22.12 (4.49)	27.97 (4.17)	0.81 (0.02)	79.59 (5.41)
31–80	12.38 (0.80)	26.07 (4.28)	31.44 (3.75)	35.72 (4.29)	40.67 (4.28)	0.75 (0.02)	78.22 (5.25)
p-value	<0.001	0.031	<0.001	<0.001	<0.001	<0.001	0.282
DSST score at month 2^c
Within norm	7.35 (1.33)	15.32 (4.01)	12.96 (5.07)	14.53 (5.80)	23.79 (3.61)	0.83 (0.02)	88.98 (2.87)
1/3 to 2/3 SD below norm	8.80 (1.55)	14.86 (5.22)	15.38 (5.85)	17.89 (6.69)	28.01 (4.29)	0.79 (0.03)	83.04 (3.52)
2/3 to 1 SD below norm	6.89 (1.65)	33.91 (6.29)	11.03 (7.22)	14.85 (8.26)	25.37 (4.33)	0.83 (0.03)	93.42 (4.93)
≥1 SD below norm	9.23 (1.44)	19.05 (4.84)	15.14 (5.46)	17.55 (6.28)	27.28 (3.92)	0.80 (0.03)	87.27 (4.77)
p-value	0.108	0.027	0.840	0.810	0.415	0.021	0.108

Notes: ANCOVA based on a stepwise backward model selection with age, gender, region, month 2 HAM-D₁₇, and month 2 PDQ-D total score/DSST score as forced factors. ^aLeast squares mean from the ANCOVA model. ^b0–9, n=135; 10–17, n=155; 18–30, n=140; 31–80, n=155. ^cWithin norm, n=360; 1/3 to 2/3 SD below norm, n=74; 2/3 to 1 SD below norm, n=53; or 1 SD or more below norm, n=111. ^dUPSA-B assessed in a subsample (n=200).

Abbreviations: ANCOVA, analysis of covariance; DSST, Digit Symbol Substitution Test; EQ-5D, European Quality of Life Questionnaire – 5 Dimensions; HAM-D₁₇, Hamilton Depression Rating Scale – 17 items; PDQ-D, Perceived Deficits Questionnaire-Depression; SDS, Sheehan Disability Scale; SE, standard error; UPSA-B, University of San Diego Performance-based Skills Assessment – Brief; WPAI-SHP, Work Productivity and Activity Impairment Questionnaire – Specific Health Problems Questionnaire.

Figure 4 Temporal interdependencies among patient-reported measures of cognitive symptoms, patient-reported depressive symptoms, and functional impairment. Standardized regression coefficients based on the structural equation models (SEM) with p-values <0.05 (n=451). The thickness of arrows is proportional to the strength of association. A solid arrow indicates p-value <0.001; a dot-dashed arrow indicates p-value <0.05.

Abbreviations: PDQ-D, Perceived Deficits Questionnaire – Depression; PHQ-9, Patient Health Questionnaire-9; SDS, Sheehan Disability Scale.

Data availability

The authors declare that the data supporting the findings of this study are available within the article. The authors may be contacted for further data sharing.