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A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment
Published on: January 11, 2020
LSD acutely impairs working memory, executive functions, and cognitive flexibility, but not risk-based
Thomas Pokorny1,2, Patricia Duerler1,2, Erich Seifritz3
1Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
Lysergic acid diethylamide (LSD) impairs cognitive functions like working memory and executive flexibility. Blocking the serotonin (5-HT) 2A receptor with ketanserin reversed these LSD-induced deficits in healthy adults.
Area of Science:
- Neuroscience
- Psychopharmacology
Background:
- Cognitive impairments, including deficits in working memory and executive functions, are hallmarks of psychiatric and neurodegenerative diseases.
- The neuropharmacology of these cognitive functions remains poorly understood, with the serotonin (5-HT) 2A receptor being a potential target for modulation.
- While Lysergic acid diethylamide (LSD) is known to act on the 5-HT2A receptor, its specific effects on human cognition using standardized tests are largely unexamined.
Purpose of the Study:
- To investigate the acute effects of LSD on cognitive domains, specifically executive functions, cognitive flexibility, and working memory.
- To determine if the 5-HT2A receptor antagonist ketanserin can counteract LSD-induced cognitive impairments.
- To explore the role of the 5-HT2A receptor system in cognitive processes relevant to psychiatric disorders.
Main Methods:
- A double-blind, randomized, placebo-controlled, within-subject design was employed with 25 healthy participants.
- Participants received LSD (100 µg) alone or in combination with ketanserin (40 mg), or placebo.
- Cognitive functions were assessed using the Intra/Extra-Dimensional shift task (IED), Spatial Working Memory task (SWM), and Cambridge Gambling Task (CGT).
Main Results:
- LSD significantly impaired executive functions, cognitive flexibility, and working memory compared to placebo, as measured by the IED and SWM tasks.
- Decision-making and risk-taking on the Cambridge Gambling Task were not significantly affected by LSD.
- Pretreatment with ketanserin successfully normalized all cognitive deficits induced by LSD.
Conclusions:
- The serotonin (5-HT) 2A receptor system plays a crucial role in executive functions and working memory.
- Targeting 5-HT2A receptors with antagonists may offer a therapeutic strategy for cognitive dysfunction in psychiatric disorders.
- This study provides novel insights into the neuropharmacology of cognition and the specific role of the 5-HT2A receptor.
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