Post by Kayla Simanek

What’s the science?

Serotonin is a neurotransmitter (chemical) known to influence learning, executive function, and emotion. Depletion of serotonin is thought to contribute to mood disorders like depression or obsessive-compulsive disorder. Selective serotonin reuptake inhibitors, or SSRIs), are drugs that prevent the breakdown of serotonin. However, studies on the clinical SSRI escitalopram (often a first line of treatment) show that acute doses can actually have effects suggestive of serotonin depletion (possibly due to inhibition of neurotransmission itself). Higher, sub-chronic doses of citalopram, on the other hand, have been shown to improve cognitive flexibility. As SSRIs are the first choice in treatment for people with mood disorders, understanding their effects on cognition is imperative. This week in Neuropsychopharmacology, Skandali and colleagues tested the effects of the clinical SSRI escitalopram in human volunteers, using a battery of tests designed to analyze cognitive functions.

How did they do it?

The authors randomly administered either acute (not chronic) dosage (20mg) of escitalopram or a placebo to sixty-five healthy volunteers. Three hours after drug administration, the authors conducted four tests to assess learning, cognitive flexibility, response control and emotional sensitivity: 1) A reversal learning task to determine ability to overcome misleading information and learn a rule based on positive and negative feedback. Subjects chose between two different patterns on a touchscreen and were provided immediate, sometimes misleading, feedback. After 40 trials, the rules changed and the subject had to re-learn the “correct” answer. 2) A set-shift test to detect symptoms of neurodegenerative disorders, like Alzheimer’s or Parkinson’s Disease (i.e. cognitive flexibility via analysis of visual, spatial and short-term memory functions). This tested their capacity to attend to multiple parameters simultaneously. 3) A response inhibition task in which subjects were required to respond to directional cues. Sometimes a “stop” cue was added, signaling to the subject to refrain from pressing a button, and the time to abort the action was measured (response control). 4) An emotional processing task. For example, one test asked subjects to create a scenario by choosing four of nine stimuli (faces, thoughts or facts) and then judge whether it was connotatively positive or negative.

What did they find?

For the reversal learning test (test #1), it was found that the acute dosage of escitalopram resulted in a deficit in learning by reinforcement and enhanced sensitivity to negative feedback (symptoms observed in people with mood disorders). Together, the set-shift and response inhibition tasks (tests #2 and #3) measured executive function but produced contradictory results. Although cognitive flexibility was impaired in some of the set-shift tasks, response control to a stop cue was surprisingly enhanced in the escitalopram group compared to placebo. Emotional processing (test #4) was largely unaffected. It is possible that different parts of the brain respond differently to serotonin, or more specifically, require different levels of serotonergic neurotransmission for optimal performance. However, the administration of the SSRI in this study was acute, and effects on cognition of chronic escitalopram treatment must also be investigated.