MRI predictors of pharmacotherapy response in major depressive disorder

Gerlach, Andrew R.; Karim, Helmet T.; Peciña, Marta; Ajilore, Olusola; Taylor, Warren D.; Butters, Meryl A.; Andreescu, Carmen

doi:10.1016/j.nicl.2022.103157

Cited by 20 publications

(9 citation statements)

References 164 publications

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“…We also showed that in vivo the Th17 and Treg relative frequencies play key roles in myelin maintenance and regeneration, with higher Th17 associated with higher fractional anisotropy in the core WM skeleton of the brain (Poletti et al, 2017). WM integrity predicts antidepressant response both in MDD and in BD (Bollettini et al, 2015; Gerlach et al, 2022). Rapid antidepressant response associates with a rapid improvement in WM integrity (Melloni et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Low-dose interleukin 2 antidepressant potentiation in unipolar and bipolar depression: Safety, efficacy, and immunological biomarkers

Poletti,

Zanardi,

Mandelli

et al. 2023

Preprint

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Immune-inflammatory mechanisms are promising targets for antidepressant pharmacology. Based on reported immune cell abnormalities, we defined an antidepressant potentiation treatment with add-on low-dose interleukin 2 (IL-2), a T-cell growth factor of proven anti-inflammatory efficacy in autoimmune conditions, increasing thymic production of naive CD4+ T cells, and possibly correcting the partial T cell defect observed in mood disorders. We performed a single-center, randomised, double-blind, placebo-controlled phase II trial evaluating the safety, clinical efficacy and biological responses of low-dose IL-2 in depressed patients with MDD or BD. 36 consecutively recruited inpatients at the Mood Disorder Unit were randomised in a 2:1 ratio to receive either aldesleukin (12 MDD and 12 BD) or placebo (6 MDD and 6 BD). Active treatment significantly potentiated antidepressant response to ongoing SSRI/SNRI treatment in both diagnostic groups, and expanded the population of Treg, Th2, and Naive CD4+/CD8+ immune cell counts. Changes in cell counts were rapidly induced in the first five days of treatment, and predicted the later improvement of depression severity. No serious adverse effect was observed. This is the first RCT evidence supporting the hypothesis that treatment to strengthen the T cell system could be a successful way to correct the immuno-inflammatory abnormalities associated with mood disorders, and potentiate antidepressant response.

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Section: Discussionmentioning

confidence: 99%

Low-dose interleukin 2 antidepressant potentiation in unipolar and bipolar depression: Safety, efficacy, and immunological biomarkers

Poletti,

Zanardi,

Mandelli

et al. 2023

Preprint

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“…The CCN is primarily involved in top-down executive functions [ 48 ]. Substantial evidence suggests CCN integrity differentiates healthy controls from depressed individuals [ 42 ] and influences treatment response [ 49 ]. The CCN may be especially relevant in LLD characterized by executive dysfunction [ 50 , 51 ], where aberrant functional connectivity of the CCN (particularly the dorsolateral prefrontal cortex [DLPFC] hub), is associated with executive deficits [ 52 ].…”

Section: Neural Network Implicated In Depressionmentioning

confidence: 99%

“…Individuals with persistent depressive symptoms similarly exhibit greater increases in WMH volume over time [ 163 ]. Greater vascular burden may be associated with poorer response to pharmacological and nonpharmacological treatments [ 158 , 164 – 166 ], although this relationship for medication response is somewhat weak [ 49 , 78 ]. The higher vascular burden is further associated with greater disability [ 167 ], gait and other motor deficits [ 168 ], and frailty [ 169 ].…”

Section: Factors Contributing To Depression Vulnerabilitymentioning

confidence: 99%

Biological factors influencing depression in later life: role of aging processes and treatment implications

Szymkowicz,

Gerlach,

Homiack

et al. 2023

Transl Psychiatry

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Late-life depression occurring in older adults is common, recurrent, and malignant. It is characterized by affective symptoms, but also cognitive decline, medical comorbidity, and physical disability. This behavioral and cognitive presentation results from altered function of discrete functional brain networks and circuits. A wide range of factors across the lifespan contributes to fragility and vulnerability of those networks to dysfunction. In many cases, these factors occur earlier in life and contribute to adolescent or earlier adulthood depressive episodes, where the onset was related to adverse childhood events, maladaptive personality traits, reproductive events, or other factors. Other individuals exhibit a later-life onset characterized by medical comorbidity, pro-inflammatory processes, cerebrovascular disease, or developing neurodegenerative processes. These later-life processes may not only lead to vulnerability to the affective symptoms, but also contribute to the comorbid cognitive and physical symptoms. Importantly, repeated depressive episodes themselves may accelerate the aging process by shifting allostatic processes to dysfunctional states and increasing allostatic load through the hypothalamic–pituitary–adrenal axis and inflammatory processes. Over time, this may accelerate the path of biological aging, leading to greater brain atrophy, cognitive decline, and the development of physical decline and frailty. It is unclear whether successful treatment of depression and avoidance of recurrent episodes would shift biological aging processes back towards a more normative trajectory. However, current antidepressant treatments exhibit good efficacy for older adults, including pharmacotherapy, neuromodulation, and psychotherapy, with recent work in these areas providing new guidance on optimal treatment approaches. Moreover, there is a host of nonpharmacological treatment approaches being examined that take advantage of resiliency factors and decrease vulnerability to depression. Thus, while late-life depression is a recurrent yet highly heterogeneous disorder, better phenotypic characterization provides opportunities to better utilize a range of nonspecific and targeted interventions that can promote recovery, resilience, and maintenance of remission.

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“…Cerebral connectivity, assessed with resting-state functional MRI, can be used to investigate functional impairments in the brain of patients with psychiatric disorders, including depression that has been associated with functional connectivity changes that could be restored with successful treatment [9]. Among the connectivity maps, the anterior cingulate cortex (which is constituted of subgenual, perigenual and supracallosal -or dorsal -regions, respectively labelled as sgACC, pgACC and scACC) has been suggested to constitute a major hub where impairments in this network may contribute to depressive symptoms [10].…”

Section: Introductionmentioning

confidence: 99%

Changes in Cerebral Connectivity and Brain Tissue Pulsations with the Antidepressant Response to an Equimolar Mixture of Oxygen and Nitrous Oxide: an MRI and Ultrasound study

Desmidt

Dujardin²,

Andersson

et al. 2023

Preprint

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Nitrous oxide (N2O) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP). Thirty participants (20 depressed and 10 healthy controls - HC) were exposed to a one-hour single session of EMONO and followed for one week. Cerebral connectivity of the Anterior Cingulate Cortex (ACC, seed based resting state blood oxygen level dependent) and BTP (as assessed with ultrasound Tissue Pulsatility Imaging) were compared before and after exposure (as well as during exposure for BTP) among HC, non-responders and responders. Response was defined as a reduction of at least 50% in the MADRS score one week after exposure. Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we observed a significant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal ACC with the mid-cingulate also significantly decreased after exposure in HC and in non-responders. BTP significantly increased in the 3 groups between baseline and gas exposure, but the increase in BTP within the first ten minutes was only significant in responders. We found that a single session of EMONO can rapidly modify the functional connectivity in the ACC, especially in the subgenual region, which appears to contribute to the antidepressant response. In addition, larger increases in BTP, associated with a significant rise in cerebral blood flow, appear to promote the antidepressant response, possibly by facilitating optimal drug delivery to the brain. Our study identified potential cerebral mechanisms related to the antidepressant response of N2O, as well as potential markers for treatment response with this fast-acting antidepressant.

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MRI predictors of pharmacotherapy response in major depressive disorder

Cited by 20 publications

References 164 publications

Low-dose interleukin 2 antidepressant potentiation in unipolar and bipolar depression: Safety, efficacy, and immunological biomarkers

Low-dose interleukin 2 antidepressant potentiation in unipolar and bipolar depression: Safety, efficacy, and immunological biomarkers

Biological factors influencing depression in later life: role of aging processes and treatment implications

Changes in Cerebral Connectivity and Brain Tissue Pulsations with the Antidepressant Response to an Equimolar Mixture of Oxygen and Nitrous Oxide: an MRI and Ultrasound study

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