Objective neuropsychological tests can be used to subclassify the cognitive symptoms present in patients with major depression into three patterns having implications for treatment responsiveness, Gitte Moos Knudsen, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.
“Our data highlight the importance of assessing and targeting cognitive symptoms,” said Dr. Knudsen, the ECNP president and professor of neurology at the University of Copenhagen.
She was a coauthor of the Danish NeuroPharm study, in which 92 antidepressant-free patients with moderate or severe major depressive disorder and 103 healthy controls completed a comprehensive neuropsychological test battery. The testing included a validation study of the EMOTICOM test battery, a novel neuropsychological test battery developed specifically to assess what has been called “hot” cognition, such as emotion processing, social cognition, and affective verbal memory.
Overall, the depressed patients collectively showed moderate increases in measures of guilt and shame, moderate deficits in working and verbal memory, moderately slowed reaction time, and mild to moderate negative affective bias, compared with controls. No correlation was found between performance on any of the individual cognitive domains and depression severity as measured using the Hamilton Depression Rating Scale, underscoring the concept that cognitive impairment is a distinct component of depressive pathology rather than an extension of the classic mood and somatic symptoms of major depression.
Cluster analysis revealed three distinct patterns of cognitive impairment in the study population. Unlike the individual cognitive domains, these cognitive clusters did correlate with depression severity. The implication is that as they become available.
Investigators classified 38 of the 92 patients with major depressive disorder as falling within Cluster A. That is, they exhibited marked deficits in hot cognition expressed in a greatly impaired ability to accurately identify facial emotions on photographs, with resultant high scores for emotion recognition bias and emotion misattribution bias. This impairment in hot cognition was accompanied by minimal guilt and shame and little or no deficits in the cold cognitive domains of verbal and working memory.
Cluster B, composed of 28 patients, was characterized by generally good cognitive function, with positive biases in emotion processing, near-normal guilt and shame ratings, but moderate deficits across the cold cognition domains, making for a mirror image of Cluster A.
The 26 patients in Cluster C demonstrated large deficits in both the hot and cold cognition domains, with particularly pronounced guilt and shame scores.
The three clusters didn’t differ in terms of age or sex. However, patients in Cluster C had significantly more severe core depressive symptoms as measured by Hamilton scores than in Clusters A and B.
This analysis from the NeuroPharm study was cross-sectional. Dr. Knudsen cited a recent large Chinese longitudinal study to underscore how the prevalence of patient-reported cognitive deficits in major depressive disorder is high. And while those deficits decrease over time, they nonetheless remain substantial after 6 months on antidepressant therapy.
That study included 598 Chinese outpatients with major depressive disorder. At baseline, 77% had cognitive symptoms as evidenced by a total score of 21 or more on the self-rated Perceived Deficits Questionnaire–Depression (PDQ-D). One month after going on antidepressant monotherapy, the prevalence of cognitive symptoms had dropped to 59%. At 2 months, the rate was 45%. And at month 6, a PDQ-D score of 21 or greater was still present in 32.4% of patients. High baseline PDQ-D scores were associated with worse clinical outcomes, including a lower treatment response rate at 1 month and a lower remission rate at 2 months. Moreover, high PDQ-D scores at 2 months were associated with lower remission and higher relapse rates at 6 months.
Dr. Knudsen reported having no financial conflicts regarding the NeuroPharm study, which was conducted free of commercial support. She serves as an adviser to Sage Therapeutics and Sanos.