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Improving cognitive functioning in major depressive disorder with psychedelics
- Source :
- Neurobiology of Learning and Memory, 183:107467. Elsevier Science
- Publication Year :
- 2021
-
Abstract
- The high symptomatic and biological heterogeneity of major depressive disorder (MDD) makes it very difficult to find broadly efficacious treatments that work against all symptoms. Concentrating on single core symptoms that are biologically well understood might consist of a more viable approach. The Research Domain Criteria (RDoC) framework is a trans-diagnostic dimensional approach that focuses on symptoms and their underlying neurobiology. Evidence is accumulating that psychedelics may possess antidepressant activity, and this can potentially be explained through a multi-level (psychobiological, circuitry, (sub)cellular and molecular) analysis of the cognitive systems RDoC domain. Cognitive deficits, such as negative emotional processing and negativity bias, often lead to depressive rumination. Psychedelics can increase long-term cognitive flexibility, leading to normalization of negativity bias and reduction in rumination. We propose a theoretical model that explains how psychedelics can reduce the negativity bias in depressed patients. At the psychobiological level, we hypothesize that the negativity bias in MDD is due to impaired pattern separation and that psychedelics such as psilocybin help in depression because they enhance pattern separation and hence reduce negativity bias. Pattern separation is a mnemonic process that relies on adult hippocampal neurogenesis, where similar inputs are made more distinct, which is essential for optimal encoding of contextual information. Impairment in this process may underlie the negative cognitive bias in MDD by, for example, increased pattern separation of cues with a negative valence that can lead to excessive deliberation on aversive outcomes. On the (sub) cellular level, psychedelics stimulate hippocampal neurogenesis as well as synaptogenesis, spinogenesis and dendritogenesis in the prefrontal cortex. Together, these effects help restoring resilience to chronic stress and lead to modulation of the major connectivity hubs of the prefrontal cortex, hippocampus, and amygdala. Based on these observations, we propose a new translational framework to guide the development of a novel generation of therapeutics to treat the cognitive symptoms in MDD.
- Subjects :
- Hippocampal neurogenesis
Anhedonia
Cognitive Neuroscience
Prefrontal Cortex
Experimental and Cognitive Psychology
Cognitive flexibility
Hippocampus
AUTOBIOGRAPHICAL MEMORY
050105 experimental psychology
ASSISTED PSYCHOTHERAPY
03 medical and health sciences
Behavioral Neuroscience
0302 clinical medicine
Negativity bias
medicine
Humans
VOLUMETRIC-ANALYSIS
Cognitive Dysfunction
0501 psychology and cognitive sciences
Research Domain Criteria
Prefrontal cortex
Depressive Disorder, Major
Neuronal Plasticity
05 social sciences
Cognition
LYSERGIC-ACID DIETHYLAMIDE
medicine.disease
Cognitive bias
Psilocybin
ADULT HIPPOCAMPAL NEUROGENESIS
LIFE-THREATENING CANCER
Pattern separation
RESTING-STATE CONNECTIVITY
PSILOCYBIN TREATMENT
DEFAULT-MODE NETWORK
Rumination
Hallucinogens
Major depressive disorder
medicine.symptom
Psychology
Neuroscience
030217 neurology & neurosurgery
NEUROTROPHIC FACTOR
Subjects
Details
- Language :
- English
- ISSN :
- 10747427
- Volume :
- 183
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Learning and Memory
- Accession number :
- edsair.doi.dedup.....0d97f740a398acebcb55daf7ee8e164b