The effect of tumor necrosis factor antagonists on mood and mental health-associated quality of life: Novel hypothesis-driven treatments for bipolar depression?

Soczynska, Joanna K.; Kennedy, Sidney H.; Goldstein, Benjamin I.; Lachowski, A.; Woldeyohannes, Hanna O.; McIntyre, Roger S.

doi:10.1016/j.neuro.2009.03.004

Cited by 83 publications

(62 citation statements)

References 154 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Iatrogenic, genetic, maladaptive behaviors and lower socioeconomic status also moderate the obesity-mood disorder covariation. Anticytokine therapies that target the inflammatory dysregulation implicated in both mood disorders and obesity can potentially have antidepressant and metabolically favorable effects (Soczynska et al 2009;Channual et al 2009). Individuals with rheumatologic conditions treated with tumor necrosis factor antagonists exhibit significant improvement in depressed mood and mental health-associated quality of life.…”

Section: Resultsmentioning

confidence: 99%

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

et al. 2010

Self Cite

View full text Add to dashboard Cite

The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for obesity in mood disorder populations (and vice versa) is a consequence of shared pathophysiological pathways. We conducted a PubMed search of all English-language articles with the following search terms: obesity, inflammation, hypothalamic-pituitary-adrenal axis, insulin, cognition, CNS, and neurotransmitters, cross-referenced with major depressive disorder and bipolar disorder. The frequent co-occurrence of mood disorders and obesity may be characterized by interconnected pathophysiology. Both conditions are marked by structural and functional abnormalities in multiple cortical and subcortical brain regions that subserve cognitive and/or affective processing. Abnormalities in several interacting biological networks (e.g. immuno-inflammatory, insulin signaling, and counterregulatory hormones) contribute to the co-occurence of mood disorders and obesity. Unequivocal evidence now indicates that obesity and mood disorders are chronic low-grade pro-inflammatory states that result in a gradual accumulation of allostatic load. Abnormalities in key effector proteins of the pro-inflammatory cascade include, but are not limited to, cytokines/adipokines such as adiponectin, leptin, and resistin as well as tumor necrosis factor alpha and interleukin-6. Taken together, the bidirectional relationship between obesity and mood disorders may represent an exophenotypic manifestation of aberrant neural and inflammatory networks. The clinical implications of these observations are that, practitioners should screen individuals with obesity for the presence of clinically significant depressive symptoms (and vice versa). This clinical recommendation is amplified in individuals presenting with biochemical indicators of insulin resistance and other concurrent conditions associated with abnormal inflammatory signaling (e.g. cardiovascular disease).

show abstract

Section: Resultsmentioning

confidence: 99%

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…(Soczynska et al, 2009;Yuksel and Ongur, 2010;Leboyer et al, 2012). Unfortunately, however, correlations among glutamate concentrations, behavior, and inflammatory markers have not been conducted (or reported) in bipolar disorder.…”

Section: Discussionmentioning

confidence: 99%

IFN-Alpha-Induced Cortical and Subcortical Glutamate Changes Assessed by Magnetic Resonance Spectroscopy

Haroon

Woolwine

Chen

et al. 2014

Neuropsychopharmacol

137

108

View full text Add to dashboard Cite

Cytokine effects on behavior may be related to alterations in glutamate metabolism. We therefore measured glutamate concentrations in brain regions shown to be affected by inflammatory stimuli including the cytokine interferon (IFN)-alpha. IFN-alpha is known to alter neural activity in the dorsal anterior cingulate cortex (dACC) and basal ganglia in association with symptoms of depression and increases in peripheral cytokines including the tumor necrosis factor (TNF) and its soluble receptor. Single-voxel magnetic resonance spectroscopy (MRS) was employed to measure glutamate concentrations normalized to creatine (Glu/Cr) in dACC and basal ganglia of 31 patients with hepatitis C before and after B1 month of either no treatment (n ¼ 14) or treatment with IFN-alpha (n ¼ 17). Depressive symptoms were measured at each visit using the Inventory of Depressive Symptoms-Clinician Rating (IDS-C) and the Multidimensional Fatigue Inventory. IFN-alpha was associated with a significant increase in Glu/Cr in dACC and left basal ganglia. Increases in dACC Glu/Cr were positively correlated with scores on the IDS-C in the group as a whole, but not in either group alone. Glu/Cr increases in left basal ganglia were correlated with decreased motivation in the group as a whole and in IFN-alpha-treated subjects alone. No Glu/Cr changes were found in the right basal ganglia, and no significant correlations were found between Glu/Cr and the inflammatory markers. IFN-alphainduced increases in glutamate in dACC and basal ganglia are consistent with MRS findings in bipolar depression and suggest that inflammatory cytokines may contribute to glutamate alterations in patients with mood disorders and increased inflammation.

show abstract

“…Cytokines are one of the most obvious targets for treating the impact of peripheral inflammation on the brain. Early case reports indicated that several of the currently available biological response modifiers (or simply 'biologics') that target cytokines were effective in reducing symptoms of depression and fatigue, as well as quality of life (Soczynska et al, 2009). Biologics are compounds derived from biological processes vs medicinal chemistry.…”

Section: Immunological Targetsmentioning

confidence: 99%

Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior

Haroon

Raison

Miller

2011

Neuropsychopharmacol

819

596

View full text Add to dashboard Cite

The potential contribution of chronic inflammation to the development of neuropsychiatric disorders such as major depression has received increasing attention. Elevated biomarkers of inflammation, including inflammatory cytokines and acute-phase proteins, have been found in depressed patients, and administration of inflammatory stimuli has been associated with the development of depressive symptoms. Data also have demonstrated that inflammatory cytokines can interact with multiple pathways known to be involved in the development of depression, including monoamine metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits relevant to mood regulation. Further understanding of mechanisms by which cytokines alter behavior have revealed a host of pharmacologic targets that may be unique to the impact of inflammation on behavior and may be especially relevant to the treatment and prevention of depression in patients with evidence of increased inflammation. Such targets include the inflammatory signaling pathways cyclooxygenase, p38 mitogen-activated protein kinase, and nuclear factor-kB, as well as the metabolic enzyme, indoleamine-2,3-dioxygenase, which breaks down tryptophan into kynurenine. Other targets include the cytokines themselves in addition to chemokines, which attract inflammatory cells from the periphery to the brain. Psychosocial stress, diet, obesity, a leaky gut, and an imbalance between regulatory and pro-inflammatory T cells also contribute to inflammation and may serve as a focus for preventative strategies relevant to both the development of depression and its recurrence. Taken together, identification of mechanisms by which cytokines influence behavior may reveal a panoply of personalized treatment options that target the unique contributions of the immune system to depression.

show abstract

The effect of tumor necrosis factor antagonists on mood and mental health-associated quality of life: Novel hypothesis-driven treatments for bipolar depression?

Cited by 83 publications

References 154 publications

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

IFN-Alpha-Induced Cortical and Subcortical Glutamate Changes Assessed by Magnetic Resonance Spectroscopy

Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior

Contact Info

Product

Resources

About