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N. van Dam

Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome

March 21, 2017 / Depressive Disorders, Ketamine, Papers, Psychiatry & Medicine, Psychology / By / , , , , , ,

Abstract

A subset of patients with depression have elevated levels of inflammatory cytokines, and some studies demonstrate interaction between inflammatory factors and treatment outcome. However, most studies focus on only a narrow subset of factors in a patient sample. In the current study, we analyzed broad immune profiles in blood from patients with treatment-resistant depression (TRD) at baseline and following treatment with the glutamate modulator ketamine. Serum was analyzed from 26 healthy control and 33 actively depressed TRD patients free of antidepressant medication, and matched for age, sex and body mass index. All subjects provided baseline blood samples, and TRD subjects had additional blood draw at 4 and 24 h following intravenous infusion of ketamine (0.5 mg kg−1). Samples underwent multiplex analysis of 41 cytokines, chemokines and growth factors using quantitative immunoassay technology. Our a priori hypothesis was that TRD patients would show elevations in canonical pro-inflammatory cytokines; analyses demonstrated significant elevation of the pro-inflammatory cytokine interleukin-6. Further exploratory analyses revealed significant regulation of four additional soluble factors in patients with TRD. Several cytokines showed transient changes in level after ketamine, but none correlated with treatment response. Low pretreatment levels of fibroblast growth factor 2 were associated with ketamine treatment response. In sum, we found that patients with TRD demonstrate a unique pattern of increased inflammatory mediators, chemokines and colony-stimulating factors, providing support for the immune hypothesis of TRD. These patterns suggest novel treatment targets for the subset of patients with TRD who evidence dysregulated immune functioning.
Kiraly, D. D., Horn, S. R., Van Dam, N. T., Costi, S., Schwartz, J., Kim-Schulze, S., … & Iosifescu, D. V. (2017). Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome. Translational psychiatry, 7(3), e1065. 10.1038/tp.2017.31
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Current Status of Ketamine and Related Therapies for Mood and Anxiety Disorders

October 1, 2015 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

Major depressive disorder (MDD) is a leading cause of disability worldwide. Despite a plethora of established treatments, less than one third of individuals with MDD achieve stable remission of symptoms. Given limited efficacy and significant lag time to onset of therapeutic action among conventional antidepressants, interest has shifted to treatments that act outside of the monoamine neurotransmitter systems (e.g., serotonin, norepinephrine, and dopamine). Preclinical and clinical research on the glutamate system has been particularly promising in this regard. Accumulating evidence shows support for a rapid antidepressant effect of ketamine—a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. The present article reviews the pharmacology, safety, and efficacy of ketamine as a novel therapeutic agent for mood and anxiety disorders. The majority of clinical trials using ketamine have been conducted in patients with treatment-resistant forms of MDD; recent work has begun to examine ketamine in bipolar disorder, post-traumatic stress disorder, and obsessive–compulsive disorder. The impact of ketamine on suicidal ideation is also discussed. The current status and prospects for the identification of human biomarkers of ketamine treatment response and hurdles to treatment development are considered. We conclude by considering modulators of the glutamate system other than ketamine currently in development as potential novel treatment strategies for mood and anxiety disorders.

Costi, S., Van Dam, N. T., & Murrough, J. W. (2015). Current Status of Ketamine and Related Therapies for Mood and Anxiety Disorders. Current Behavioral Neuroscience Reports, 1-10. https://dx.doi.org/10.1007/s40473-015-0052-3
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