Reverse translation of major depressive disorder symptoms: A framework for the behavioural phenotyping of putative biomarkers

Daniels, Stephen; Horman, Thomas; Lapointe, Thomas; Melanson, Brett; Storace, Alexandra; Kennedy, Sidney H.; Frey, Benício N.; Rizvi, Sakina J.; Hassel, Stephanie; Müller, Daniel J.; Parikh, Sagar V.; Lam, Raymond W.; Blier, Pierre; Farzan, Faranak; Giacobbe, Peter; Milev, Roumen; Placenza, Franca; Soares, Cláudio N.; Turecki, Gustavo; Uher, Rudolf; Leri, Francesco

doi:10.1016/j.jad.2019.11.108

Cited by 6 publications

(4 citation statements)

References 245 publications

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“…Therefore, the objective of this study was to establish whether high and low n -6/ n -3 (LA:ALA) ratio diets could alter fatty acid content in different regions of the rat brain. Adult male Sprague Dawley rats were selected because of their widespread use in animal models of human psychopathology [ 18 ]. The diets employed in this study were selected to explore the impact of different LA:ALA ratios using isocaloric diets, rather than supplementation studies that are more commonly used, in order to capture the biological interactions of these essential fats [ 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Dietary n-6/n-3 Ratio Influences Brain Fatty Acid Composition in Adult Rats

et al. 2020

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There is mounting evidence that diets supplemented with polyunsaturated fatty acids (PUFA) can impact brain biology and functions. This study investigated whether moderately high-fat diets differing in n-6/n-3 fatty acid ratio could impact fatty acid composition in regions of the brain linked to various psychopathologies. Adult male Sprague Dawley rats consumed isocaloric diets (35% kcal from fat) containing different ratios of linoleic acid (n-6) and alpha-linolenic acid (n-3) for 2 months. It was found that the profiles of PUFA in the prefrontal cortex, hippocampus, and hypothalamus reflected the fatty acid composition of the diet. In addition, region-specific changes in saturated fatty acids and monounsaturated fatty acids were detected in the hypothalamus, but not in the hippocampus or prefrontal cortex. This study in adult rats demonstrates that fatty acid remodeling in the brain by diet can occur within months and provides additional evidence for the suggestion that diet could impact mental health.

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Section: Introductionmentioning

confidence: 99%

Dietary n-6/n-3 Ratio Influences Brain Fatty Acid Composition in Adult Rats

et al. 2020

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“…An intriguing interpretation of the current findings in rats is that the KET-paired CS+ acquired some of the psychoactive properties of KET linked to mechanisms implicated in the regulation of mood (Mkrtchian et al, 2021; Rincón-Cortés & Grace, 2020), and that a conditioned mood response contrasted the expression of “behavioral despair” (Daniels et al, 2020) experienced during exposure to the inescapable stressor. In support of this interpretation, it is known that KET alleviates impairments in reward processing, such as stress-induced deficits in sucrose (Zhang et al, 2016) and saccharin preference (Melanson et al, 2021), and that it increases dopamine release within the mesolimbic dopamine system (Kokkinou et al, 2018).…”

Section: Discussionmentioning

confidence: 80%

“…Therefore, although it appears that rats in this study may have avoided the compartment paired with KET, their behavioral response in the FST was not consistent with the expected behaviors that would coincide with a conditioned aversive state. An intriguing interpretation of the current findings in rats is that the KET-paired CS+ acquired some of the psychoactive properties of KET linked to mechanisms implicated in the regulation of mood (Mkrtchian et al, 2021;Rinco ´n-Cortés & Grace, 2020), and that a conditioned mood response contrasted the expression of "behavioral despair" (Daniels et al, 2020) experienced during exposure to the inescapable stressor. In support of this interpretation, it is known that KET alleviates impairments in reward processing, such as stressinduced deficits in sucrose (Zhang et al, 2016) and saccharin preference , and that it increases dopamine This document is copyrighted by the American Psychological Association or one of its allied This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.…”

Section: Discussionmentioning

confidence: 81%

Conditioned anti-immobility by ketamine: A comparison to escitalopram and bupropion.

Melanson¹,

Wolter²,

Leatham³

et al. 2023

Experimental and Clinical Psychopharmacology

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This study was designed to explore the clinical belief that “set and setting” play an important role in favorable responses to psychedelic agents such as ketamine (KET). In fact, there is evidence in animals that the antidepressant effect of this drug may involve drug–environment interactions in which a context paired with its effects acquires the ability to influence behavior. Therefore, it was investigated in male Sprague–Dawley rats whether exposure to a context paired with the effects of KET, or with the effects of the common antidepressant medications bupropion (BUP) and escitalopram (ESC), could produce an antidepressant-like conditioned response. In Experiment 1, subjects received saline in a vehicle-paired context (denoted as CS−), and 0, 10, or 20 mg/kg KET, 10 mg/kg ESC, or 10 mg/kg BUP in a drug-paired context (denoted as CS+), on 10 alternating days (5 pairings with each context). The rats were then exposed drug free to the CS− and CS+ prior to the assessment of immobility in the forced-swimming test. Experiment 2 assessed approach/avoidance responses induced by the CS− and CS+ in a place-conditioning test. It was found that exposure to the KET CS+ significantly reduced immobility without affecting general locomotor activity in comparison to the SAL CS+ and the BUP CS+, but not the ESC CS+. Moreover, no group differences were observed in the place-conditioning test, indicating that the anti-immobility effect of the KET CS+ was likely not influenced by a conditioned incentive or aversive state. Together, these data suggest that a KET-paired context can elicit a conditioned antidepressant-like response, which may be a mechanism involved in its sustained antidepressant clinical action.

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“…As such, we cannot make strong empirical claims as to the validity of our conjectures. The "bedside-to-bench" trajectory of discovery has a history of advancing medical science (Moore, 2008;Shakhnovich, 2018;Wagner, 2018), including psychiatry (Malkesman et al, 2009;Daniels et al, 2020), but this depends on subsequent empirical investigation of the treatment targets and therapeutic techniques proposed. The clinical utility of the ideas presented here thus remains to be empirically tested.…”

Section: Limitationsmentioning

confidence: 99%

Extinction and beyond: an expanded framework for exposure and response prevention for obsessive-compulsive disorder

Berg,

Webler,

Klein

et al. 2024

Front. Psychol.

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Exposure therapy is a first-line, empirically validated treatment for anxiety, obsessive-compulsive, and trauma-related disorders. Extinction learning is the predominant theoretical framework for exposure therapy, whereby repeated disconfirmation of a feared outcome yields fear reduction over time. Although this framework has strong empirical support and substantial translational utility, extinction learning is unlikely to be the sole process underlying the therapeutic effects of exposure therapy. In our clinic, we commonly treat obsessive-compulsive disorder (OCD) patients successfully with exposure therapy even when some or all of their feared outcomes are not amenable to disconfirmation and, by extension, to extinction learning. Herein, we present a generic clinical vignette illustrating a commonly encountered feared outcome in OCD that cannot be disconfirmed through exposure (damnation resulting from blasphemous thoughts). We describe two specific non-extinction-based strategies we commonly employ in such cases, and we associate these strategies with known change mechanisms that might account for their effectiveness: (1) non-associative habituation to aversive stimuli, and (2) fear-memory elicitation and subsequent reconsolidation. We discuss the limitations inherent in the reverse-translational approach taken and its opportunities for expanding the framework of exposure therapy.

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Reverse translation of major depressive disorder symptoms: A framework for the behavioural phenotyping of putative biomarkers

Cited by 6 publications

References 245 publications

Dietary n-6/n-3 Ratio Influences Brain Fatty Acid Composition in Adult Rats

Dietary n-6/n-3 Ratio Influences Brain Fatty Acid Composition in Adult Rats

Conditioned anti-immobility by ketamine: A comparison to escitalopram and bupropion.

Extinction and beyond: an expanded framework for exposure and response prevention for obsessive-compulsive disorder

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