Association of Obesity and Inflammatory Marker Levels on Treatment Outcome

Shelton, Richard C.; Pencina, Michael J.; Barrentine, Lori W.; Ruiz, Juan; Fava, Maurizio; Zajecka, John; Papakostas, George I.

doi:10.4088/jcp.14m09587

Cited by 47 publications

(12 citation statements)

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“…Conventional antidepressants (e.g., fluoxetine) have been found to reduce both central and peripheral levels of the pro-inflammatory cytokine interleukin-1 beta (IL-β) in the alleviation of depressive symptoms [ 32 ]. Other treatments with antidepressant properties have also been reported with mechanistically dissimilar treatments (e.g., omega 3 fatty acids, L-methylfolate) [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder

Rong

Park

Rosenblat

et al. 2018

IJERPH

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Objectives: Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD) symptoms as a part of major depressive disorder (MDD) and bipolar disorder (BD). The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to identify the pretreatment predictors of response to ketamine in TRD as part of MDD and BD. Method: Electronic search engines PubMed/MEDLINE, , and Scopus were searched for relevant articles from inception to January 2018. The search term ketamine was cross-referenced with the terms depression, major depressive disorder, bipolar disorder, predictors, and response and/or remission. Results: Multiple baseline pretreatment predictors of response were identified, including clinical (i.e., Body Mass Index (BMI), history of suicide, family history of alcohol use disorder), peripheral biochemistry (i.e., adiponectin levels, vitamin B12 levels), polysomnography (abnormalities in delta sleep ratio), neurochemistry (i.e., glutamine/glutamate ratio), neuroimaging (i.e., anterior cingulate cortex activity), genetic variation (i.e., Val66Met BDNF allele), and cognitive functioning (i.e., processing speed). High BMI and a positive family history of alcohol use disorder were the most replicated predictors. Conclusions: A pheno-biotype of depression more, or less likely, to benefit with ketamine treatment is far from complete. Notwithstanding, metabolic-inflammatory alterations are emerging as possible pretreatment response predictors of depressive symptom improvement, most notably being cognitive impairment. Sophisticated data-driven computational methods that are iterative and agnostic are more likely to provide actionable baseline pretreatment predictive information.

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Section: Resultsmentioning

confidence: 99%

Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder

Rong

Park

Rosenblat

et al. 2018

IJERPH

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“…These include administration of BH4 itself [ 269 ], which is currently approved in a synthetic form to treat phenylketonuria [ 270 - 272 ], and folic acid or S-adenosyl-methionine (SAMe), which have a role in the synthesis and/or regeneration of BH4 [ 3 , 273 , 274 ]. Although effects of BH4 administration on behavioral symptoms have not been reported outside of case reports [ 275 , 276 ], folic acid (in the form of L-methylfolate) and SAMe have demonstrated efficacy as adjuvants in depression trials [ 277 - 281 ]. Administration of L-methylfolate (marketed as Deplin and Zervalx) to patients with MDD has been shown to augment the efficacy of standard antidepressant therapy in two studies [ 278 , 279 ], however mixed results were reported in two parallel-sequential trials with only one trial finding efficacy over placebo [ 280 ].…”

Section: Mechanisms Of Inflammation Affects On Threat and Reward Circmentioning

confidence: 99%

Imaging the Role of Inflammation in Mood and Anxiety-related Disorders

Felger

2018

332

215

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BackgroundStudies investigating the impact of a variety of inflammatory stimuli on the brain and behavior have reported evidence that inflammation and release of inflammatory cytokines affect circuitry relevant to both reward and threat sensitivity to contribute to behavioral change. Of relevance to mood and anxiety-related disorders, biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of patients with major depressive disorder (MDD), bipolar disorder, anxiety disorders and post-traumatic stress disorder (PTSD).MethodsThis review summarized clinical and translational work demonstrating the impact of peripheral inflammation on brain regions and neurotransmitter systems relevant to both reward and threat sensitivity, with a focus on neuroimaging studies involving administration of inflammatory stimuli. Recent translation of these findings to further understand the role of inflammation in mood and anxiety-related disorders is also discussed.ResultsInflammation was consistently found to affect basal ganglia and cortical reward and motor circuits to drive reduced motivation and motor activity, as well as anxiety-related brain regions including amygdala, insula and anterior cingulate cortex, which may result from cytokine effects on monoamines and glutamate. Similar relationships between inflammation and altered neurocircuitry have been observed in MDD patients with increased peripheral inflammatory markers, and such work is on the horizon for anxiety disorders and PTSD.ConclusionNeuroimaging effects of inflammation on reward and threat circuitry may be used as biomarkers of inflammation for future development of novel therapeutic strategies to better treat mood and anxiety-related disorders in patients with high inflammation.

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“…DNA hypomethylation can be corrected by methyl donors. l -Methylfolate has been tested as an adjunctive therapy in many clinical trials, 123 , 124 , 125 , 126 , 127 proving to be safe and effective in MDD patients. Another methyl donor, S -adenosyl methionine ((2 S )-2-amino-4-[[(2 S ,3 S ,4 R ,5 R )-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-methylsulfonio]butanoate), has been shown to restore normal gene expression in neuroblastoma cells.…”

Section: Psychosis In Bd As a Shared Traitmentioning

confidence: 99%

Dissecting bipolar disorder complexity through epigenomic approach

Ludwig

Dwivedi

2016

Mol Psychiatry

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In recent years, numerous studies of gene regulation mechanisms have emerged in neuroscience. Epigenetic modifications, described as heritable but reversible changes, include DNA methylation, DNA hydroxymethylation, histone modifications and noncoding RNAs. The pathogenesis of psychiatric disorders, such as bipolar disorder, may be ascribed to a complex gene–environment interaction (G × E) model, linking the genome, environmental factors and epigenetic marks. Both the high complexity and the high heritability of bipolar disorder make it a compelling candidate for neurobiological analyses beyond DNA sequencing. Questions that are being raised in this review are the precise phenotype of the disorder in question, and also the trait versus state debate and how these concepts are being implemented in a variety of study designs.

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Association of Obesity and Inflammatory Marker Levels on Treatment Outcome

Abstract: ClinicalTrials.gov identifier: NCT00955955.

Cited by 47 publications

References 0 publications

Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder

Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder

Imaging the Role of Inflammation in Mood and Anxiety-related Disorders

Dissecting bipolar disorder complexity through epigenomic approach

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