Improving cognitive functioning in major depressive disorder with psychedelics: A dimensional approach
Igor Magaraggia, Zilla Kuiperes, Rudy Schreiber
Neurobiology of Learning and Memory May 25, 2021 DOI: 10.1016/j.nlm.2021.107467 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Intervention | Psilocybin |
| Topics | Depression |
| Keywords | Cognition Rumination Cognitive psychology |
| Citations | 49 |
| Key points | Proposes that psychedelics reduce negativity bias in major depressive disorder by enhancing pattern separation, a hippocampal-dependent mnemonic process. |
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.
Comparable studies
Other theoretical and historical papers on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Mindfulness-based cognitive therapy for depression | 2006 | Theoretical or philosophical paper | |
| Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame | 2020 | Theoretical or philosophical paper | |
| The Yale Manual for Psilocybin-Assisted Therapy of Depression (using Acceptance and Commitment Therapy as a Therapeutic Frame) | 2020 | Theoretical or philosophical paper | |
| Neuroinflammation and neuroprogression in depression: Effects of alternative drug treatments | 2022 | Theoretical or philosophical paper | |
| An Integrative Approach to Ketamine Therapy May Enhance Multiple Dimensions of Efficacy: Improving Therapeutic Outcomes With Treatment Resistant Depression. | 2021 | Theoretical or philosophical paper |
Citations in the library
Cited by 34
- Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. Journal of Psychopharmacology February 2, 2022
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics TIPS - Trends in Pharmacological Sciences September 24, 2021
- Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes JAMA Psychiatry December 6, 2023
- The costs and benefits of psychedelics on cognition and mood Neuron January 20, 2023
and 29 more in the library
Cites 67
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
and 62 more in the library