Cingulate Overexpression of Mitogen-Activated Protein Kinase Phosphatase-1 as a Key Factor for Depression

Barthas, Florent; Humo, Muris; Gilsbach, Ralf; Waltisperger, Elisabeth; Karatas, Meltem; Leman, Samuel; Hein, Lutz; Belzung, Catherine; Boutillier, Anne‐Laurence; Barrot, Michel; Yalçın, İpek

doi:10.1016/j.biopsych.2017.01.019

Cited by 56 publications

(59 citation statements)

References 52 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The involvement of the MAPK pathway in the pathogenesis of MDD has long been suspected 47 , and accumulating evidence seems to support this notion 48 , 49 . For instance, DUSP2 has previously been identified to link stress experience and depression pathogenesis: DUSP1 and DUSP2 expression was increased in response to chronic stress in rodents and in the brain of two separate cohorts of depressed patients 49 , 50 .…”

Section: Discussionmentioning

confidence: 99%

Childhood trauma, suicide risk and inflammatory phenotypes of depression: insights from monocyte gene expression

et al. 2020

View full text Add to dashboard Cite

Circulating monocytes contribute to inflammatory processes. We here validate abnormal expression of inflammation-related genes in monocytes of a large and well-characterised group of MDD patients, and relate the outcomes to pertinent clinical characteristics. Thirty-two genes of a previously established inflammation-related gene signature were assessed in 197 patients with MDD, and 151 controls collected during the EU-MOODINFLAME project. Monocyte gene- expression data were related to age, sex, BMI, depression severity, childhood adversity (CA) and suicide risk (SR). Three distinct gene profiles were identified within the MDD group (downregulated, mixed upregulated and strongly upregulated genes). Patients in the merged upregulated groups had a significantly higher prevalence of CA and high SR. Using hierarchical clustering of the genes, we found a cluster of mainly cytokine (production)-related genes; patients with SR had a significantly higher expression of this cluster than patients without SR (particularly for IL-6, IL1A and IL1B). Such difference did not emerge for patients with and without CA. A downregulated gene profile was found for patients not exposed to CA and without SR (particularly for glucocorticoid-signalling genes NR3C1a and HSPA1/B). No inflammatory changes were observed for healthy controls exposed to CA. Our data show that inflammatory activation in MDD is not uniform, and that immunologically discernible phenotypes of depression can be linked to CA and high SR. The absence of monocyte inflammatory activation in healthy controls exposed to CA suggests an inflammatory involvement in MDD-prone individuals exposed to early stressors, but not healthy controls.

show abstract

Section: Discussionmentioning

confidence: 99%

Childhood trauma, suicide risk and inflammatory phenotypes of depression: insights from monocyte gene expression

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Future circuit-based manipulations will be needed to examine this hypothesis. With specific regard to ERK signaling, chronic pain-induced negative affect is known to be mediated by increased activity of the GR-regulated MAPK-phosphatase (MKP-1) within at least the cingulate cortex ( Barthas et al, 2017 ). As glucocorticoid signaling supports MKP-1 actions to inhibit ERK ( Kassel et al, 2001 ), this mechanism would appear to remain intact as we did not observe tolerance to GR phosphorylation across frontocortical areas ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Chronic inflammatory pain alters alcohol-regulated frontocortical signaling and associations between alcohol drinking and thermal sensitivity

McGinn

Edwards

2020

Neurobiology of Pain

View full text Add to dashboard Cite

show abstract

“…The authors demonstrate that acute photostimulation of deep layer anterior PL projection neurons modulates limbic system oscillatory power and synchrony, and that ~4 hz stimulation, 5 minutes daily for 14 days, reduced anxiety tested 10 days after termination of the stimulation protocol, but did not impact social avoidance after social defeat stress. Interestingly, a pair of studies 107 , 108 using 20 hz photostimulation, 20 minutes per day over 5 days, of neurons in deep layers of the posterior ACC/PL observed pro-depressant and anxiogenic effects for up to 5 days after stimulation. The rationale and design of the latter study was based on evidence that ACC/PL neuronal activity is increased in models of chronic pain that also produce depression-like behavior.…”

Section: Sustained Effects Of Mpfc Circuit Manipulationsmentioning

confidence: 99%

Prefrontal cortex circuits in depression and anxiety: contribution of discrete neuronal populations and target regions

2020

View full text Add to dashboard Cite

Our understanding of depression and its treatment has advanced with the advent of ketamine as a rapid acting antidepressant and the development and refinement of tools capable of selectively altering the activity of populations of neuronal subtypes. This work has resulted in a paradigm shift away from dysregulation of single neurotransmitter systems in depression towards circuit level abnormalities impacting function across multiple brain regions and neurotransmitter systems. Studies on the features of circuit level abnormalities demonstrate structural changes within the prefrontal cortex (PFC) and functional changes in its communication with distal brain structures. Treatments that impact the activity of brain regions, such as transcranial magnetic stimulation or rapid acting antidepressants like ketamine, appear to reverse depression associated circuit abnormalities though the mechanisms underlying the reversal, as well as development of these abnormalities remains unclear. Recently developed optogenetic and chemogenetic tools that allow high fidelity control of neuronal activity in pre-clinical models have begun to elucidate the contributions of the PFC and its circuitry to depression- and anxiety-like behavior. These tools offer unprecedented access to specific circuits and neuronal subpopulations that promise to offer a refined view of the circuit mechanisms surrounding depression and potential mechanistic targets for development and reversal of depression associated circuit abnormalities.

show abstract

Cingulate Overexpression of Mitogen-Activated Protein Kinase Phosphatase-1 as a Key Factor for Depression

Abstract: These data point to ACC MKP-1 as a key factor in the pathophysiology of depression and a potential target for treatment development.

Cited by 56 publications

References 52 publications

Childhood trauma, suicide risk and inflammatory phenotypes of depression: insights from monocyte gene expression

Childhood trauma, suicide risk and inflammatory phenotypes of depression: insights from monocyte gene expression

Chronic inflammatory pain alters alcohol-regulated frontocortical signaling and associations between alcohol drinking and thermal sensitivity

Prefrontal cortex circuits in depression and anxiety: contribution of discrete neuronal populations and target regions

Contact Info

Product

Resources

About