Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome.
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.
Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
D D
DD
Kiraly
Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
S R
SR
Horn
Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
N T
NT
Van Dam
Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
S
S
Costi
Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J
J
Schwartz
The Immunology Institute, Human Immune Monitoring Core, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
S
S
Kim-Schulze
The Immunology Institute, Human Immune Monitoring Core, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
M
M
Patel
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
G E
GE
Hodes
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
S J
SJ
Russo
The Immunology Institute, Human Immune Monitoring Core, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
M
M
Merad
Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
D V
DV
Iosifescu
Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
D S
DS
Charney
Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J W
JW
Murrough
D000328:Adult; D016022:Case-Control Studies; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000276:immunology*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy / Q000276:immunology*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000276:immunology; D006801:Humans; D007249:Inflammation; D007262:Infusions, Intravenous; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology*; D053582:Interleukin-1alpha / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007649:Ketamine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D018691:Excitatory Amino Acid Antagonists; C508584:IL1A protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D007649:Ketamine