Translational psychiatry: cognitive impairment as a predictor of antidepressant drug targets for major depressive disorder

Major depressive disorder (MDD) is a highly heterogeneous disorder
.
Despite decades of efforts, we still don't fully understand the causes behind MDD, and it has been suggested that the diagnosis describes several brain pathological changes
.
This may explain why 30-50% of patients do not respond adequately to selective serotonin uptake inhibitors (SSRIs), which are the standard first-line therapy
for moderate to severe MDD.

Cognitive impairment of MDD constitutes a key therapeutic target and is expected to be an early predictor of antidepressant response; However, its clinical relevance has not been fully established
.
Therefore, some scholars have investigated here whether (1) cognitive performance is improved in the course of antidepressant treatment; (2) whether baseline cognitive performance predicts response
to antidepressant treatment.
In the NeuroPharm study, 92 patients with moderate to severe depression without antidepressants underwent comprehensive cognitive tests
.
Tests
were conducted on patients before and after 12 weeks of standard antidepressant therapy with escitalopram in flexible doses of 10-20 mg.

Performance improved in most cognitive domains during antidepressant therapy
.
Notably, these improvements were not associated with improvements in mood symptoms, emphasizing that cognitive impairment is a unique symptom and therefore a therapeutic target
for MDD.
The results showed that the performance of any single cognitive measure at baseline was associated with
later clinical response to antidepressant treatment.
However, a small group of patients with global cognitive impairment at baseline (N = 28) showed a poorer clinical response after 8 weeks rather than 12 weeks of antidepressant treatment, suggesting that severe cognitive impairment may delay treatment response
.

Therefore, while cognitive performance from a single test prior to treatment may not be a clinical marker of treatment response, documenting profiles of performance in different cognitive domains may be useful for stratification of patients with MDD and useful
for future intervention trials.

References:

Evaluating cognitive disturbances as treatment target and predictor of antidepressant action in major depressive disorder: A NeuroPharm study.
Transl Psychiatry 12, 468 (2022).
https://doi.
org/10.
1038/s41398-022-02240-1