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. 2025 May 2:55:e131.
doi: 10.1017/S0033291725001011.

A longitudinal analysis of the relationship between emotional symptoms and cognitive function in patients with major depressive disorder

Jingjing Zhou  1   2 , Jinjie Xu  1   2 , Zizhao Feng  1   2 , Rui Liu  1   2 , Le Xiao  1   2 , Ruinan Li  1   2 , Xiaoya Li  1   2 , Xueshan Zhang  1   2 , Jing Liu  1   2 , Yuan Feng  1   2 , Jia Zhou  1   2 , Gang Wang  1   2
Affiliations

A longitudinal analysis of the relationship between emotional symptoms and cognitive function in patients with major depressive disorder

Jingjing Zhou et al. Psychol Med. .

Abstract

Background: The relationship between emotional symptoms and cognitive impairments in major depressive disorder (MDD) is key to understanding cognitive dysfunction and optimizing recovery strategies. This study investigates the relationship between subjective and objective cognitive functions and emotional symptoms in MDD and evaluates their contributions to social functioning recovery.

Methods: The Prospective Cohort Study of Depression in China (PROUD) involved 1,376 MDD patients, who underwent 8 weeks of antidepressant monotherapy with assessments at baseline, week 8, and week 52. Measures included the Hamilton Depression Rating Scale (HAMD-17), Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16), Chinese Brief Cognitive Test (C-BCT), Perceived Deficits Questionnaire for Depression-5 (PDQ-D5), and Sheehan Disability Scale (SDS). Cross-lagged panel modeling (CLPM) was used to analyze temporal relationships.

Results: Depressive symptoms and cognitive measures demonstrated significant improvement over 8 weeks (p < 0.001). Baseline subjective cognitive dysfunction predicted depressive symptoms at week 8 (HAMD-17: β = 0.190, 95% CI: 0.108-0.271; QIDS-SR16: β = 0.217, 95% CI: 0.126-0.308). Meanwhile, baseline depressive symptoms (QIDS-SR16) also predicted subsequent subjective cognitive dysfunction (β = 0.090, 95% CI: 0.003-0.177). Recovery of social functioning was driven by improvements in depressive symptoms (β = 0.384, p < 0.0001) and subjective cognition (β = 0.551, p < 0.0001), with subjective cognition contributing more substantially (R2 = 0.196 vs. 0.075).

Conclusions: Subjective cognitive dysfunction is more strongly associated with depressive symptoms and plays a significant role in social functioning recovery, highlighting the need for targeted interventions addressing subjective cognitive deficits in MDD.

Keywords: Chinese Brief Cognitive Test (C-BCT); Hamilton Depression Rating Scale (HAMD-17); Perceived Deficits Questionnaire for Depression-5 (PDQ-D5); Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16); Sheehan Disability Scale (SDS); cognitive impairment; cohort study; depressive symptoms; major depressive disorder; objective cognition; social functioning; subjective cognition.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

Figures

Figure 1.
Figure 1.
Cross-lagged panel models depicting the associations of objective cognition with depressive symptoms and with anxiety symptoms. Note: Standardized estimates with 95% confidence intervals are presented. Solid lines in the Cross-Lagged Panel Models indicate statistically significant standardized estimates, while dashed lines represent estimates that are not statistically significant. A total of 504 patients were followed at Week 8.
Figure 2.
Figure 2.
Cross-lagged panel models associations between depressive symptoms and objective cognition stratified by episode groups and treatments. Note: Standardized estimates with 95% confidence intervals are presented. Solid lines in the Cross-Lagged Panel Models indicate statistically significant standardized estimates, while dashed lines represent estimates that are not statistically significant. Patients taking medications other than SSRIs included 141 cases on SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors), 23 cases on Mirtazapine, and 318 cases on other antidepressants, such as Bupropion and Trazodone. Additionally, 518 patients were on other psychiatric medications, including 191 on sedative-hypnotics, 348 on benzodiazepines, and 132 on non-benzodiazepines. Some patients were concurrently taking multiple medications.
Figure 3.
Figure 3.
Cross-lagged panel models associations between depressive symptoms and subjective cognition stratified by episode groups and treatment types. Note: Standardized estimates with 95% confidence intervals are presented. Solid lines in the Cross-Lagged Panel Models indicate statistically significant standardized estimates, while dashed lines represent estimates that are not statistically significant. Patients taking medications other than SSRIs included 141 cases on SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors), 23 cases on Mirtazapine, and 318 cases on other antidepressants, such as Bupropion and Trazodone. Additionally, 518 patients were on other psychiatric medications, including 191 on sedative-hypnotics, 348 on benzodiazepines, and 132 on non-benzodiazepines. Some patients were concurrently taking multiple medications.
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