Neuroinflammation and neuroprogression in depression: Effects of alternative drug treatments

Brandon Richardson; Andrew J. Macpherson; Francis Rodriguez Bambico

doi:10.1016/j.bbih.2022.100554

Neuroinflammation and neuroprogression in depression: Effects of alternative drug treatments

Brandon Richardson, Andrew J. Macpherson, Francis Rodriguez Bambico

Brain, Behavior, & Immunity - Health November 7, 2022 DOI: 10.1016/j.bbih.2022.100554 (opens in new tab)

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AI-extracted from the abstract

Characteristics	Theoretical or philosophical paper Peer reviewed
Interventions	Ketamine Cannabinoids Psychedelics
Topics	Depression
Citations	52
Key points	Argues that chronic inflammation is a primary mechanism triggering biological changes that lead to major depressive disorder, rather than monoamine imbalance alone. Proposes that ketamine, cannabinoids, and psychedelics may produce rapid and lasting symptom relief partly via anti-inflammatory effects that reduce proinflammatory cytokines, but contends it is unclear what mechanistically distinguishes these compounds and calls for further investigation.

Abstract

Given that available antidepressant pharmacotherapies are not optimally effective, there is a need for alternative treatment options that are rooted in a comprehensive understanding of the illness's pathophysiology. Major depressive disorder (MDD) has been historically attributed to monoamine, i.e., serotonin (5-hydroxytryptamine, 5-HT) imbalance and some brain morphological pathologies that have directed treatment towards particular medications that are only minimally effective. MDD pathophysiologies have now been regarded as linked to chronic inflammation and MDD can be treated with compounds that have anti-inflammatory properties. Individuals vulnerable to MDD have increased baseline neuroinflammatory response that is exacerbated by psychogenic stress. When pro-inflammatory mechanisms are chronically hyperactive, dysfunction of brain-related processes occur. We propose that inflammation is one of the primary mechanisms that trigger biological changes leading to MDD. Inflammatory resolution occurs when homeostasis is achieved after an inflammatory response. However, cascading biological events are likely to prevent resolution from occurring and worsen both inflammation and MDD. Novel and alternative pharmacotherapies-e.g., ketamine, cannabinoids, and psychedelics-provide a richer mechanistic perspective on the role of neuroinflammation and neuroprogression by means of rapid, short-term, and long-term symptom relief potentially based on their anti-inflammatory properties. These drugs ultimately decrease proinflammatory cytokine levels that correspond with improved symptoms. However, it is unclear what differentiates these compounds from others in their mechanistic efficacy. Thus, a closer investigation into their anti-inflammatory effects is imperative in order to better elucidate the link between MDD and inflammation, as well as uncover the mechanisms involved in long-term symptom reduction of MDD.

Comparable studies

Other theoretical and historical papers on depression, most cited first.

Study	Year	Design
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
Improving cognitive functioning in major depressive disorder with psychedelics: A dimensional approach	2021	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 5

Cites 26

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