Platelet-Derived Growth Factor as an Antidepressant Treatment Selection Biomarker: Higher Levels Selectively Predict Better Outcomes with Bupropion-SSRI Combination

Abstract Background Platelet derived growth factor is integral to maintenance of blood brain barrier, increases in response to blood brain barrier disruption, and may reflect neuroinflammation. Based on previous reports of better outcomes with dopaminergic antidepressants in depressed patients with elevated inflammatory biomarkers, we hypothesize that elevated peripheral platelet derived growth factor levels can serve as a powerful biomarker for selecting dopaminergic antidepressants. Methods Platelet derived growth factor, basic fibroblast growth factor, and granulocyte colony stimulating factor were measured as part of Bioplex Pro human cytokine 27-plex kit in participants of the Combining Medications to Enhance Depression Outcomes trial who provided baseline plasma (n=166) and were treated with either bupropion-plus-escitalopram, escitalopram-plus-placebo, or venlafaxine-plus-mirtazapine. Differential changes in overall symptom severity and anhedonia as well as side effects were tested with a treatment-arm-by-biomarker interaction in mixed model analyses. Effect of biomarkers with significant interaction was calculated in subsequent analyses stratified by treatment arm. Results There was a significant treatment-arm-by-platelet derived growth factor interaction for depression severity (P=.03) and anhedonia (P=.008) but not for side effects (P=.44). Higher baseline platelet derived growth factor level was associated with greater reduction in depression severity (effect size=0.71, P=.015) and anhedonia (effect size=0.66, P=.02) in the bupropion- selective serotonin reuptake inhibitor but not the other two treatment arms. There was no significant treatment-arm-by-biomarker interaction for both depression severity and side effects with the other two biomarkers. Conclusion As compared with selective serotonin reuptake inhibitor monotherapy or venlafaxine-plus-mirtazapine, bupropion-plus-escitalopram selectively improves anhedonia, which in turn results in improved overall depression severity in depressed patients with elevated platelet derived growth factor levels.

• Publication year

  2017

• Venue

  International Journal of Neuropsychopharmacology

• Publication date

  2017-07-23

• Fields of study

  Medicine

• Identifiers
  DOI 10.1093/ijnp/pyx060PMID 29016822PMCID 5737519
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

  2017cited by this paper
• Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial.

  2017cited by this paper
• The acute‐phase mediator serum amyloid A is associated with symptoms of depression and fatigue

  2017cited by this paper
• Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: Novel T cell biomarker for antidepressant medication selection.

  2017cited by this paper
• Distinct Subtypes of Apathy Revealed by the Apathy Motivation Index

  2017cited by this paper
• Association between C-reactive protein (CRP) with depression symptom severity and specific depressive symptoms in major depression.

  2017cited by this paper
• Is C-reactive protein ready for prime time in the selection of antidepressant medications?

  2017cited by this paper
• Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

  2017cited by this paper
• The role of day-to-day emotions, sleep, and social interactions in pediatric anxiety treatment.

  2017influential reference
• Clinical Experience With High-Dosage Pramipexole in Patients With Treatment-Resistant Depressive Episodes in Unipolar and Bipolar Depression.

  2016cited by this paper
• Right patient, right treatment, right time: biosignatures and precision medicine in depression

  2016cited by this paper
• Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions

  2016cited by this paper
• Inflammatory cytokines influence measures of white matter integrity in Bipolar Disorder.

  2016cited by this paper
• Mapping inflammation onto mood: Inflammatory mediators of anhedonia.

  2016cited by this paper
• Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design.

  2016cited by this paper
• The Role of Dopamine in Inflammation-Associated Depression: Mechanisms and Therapeutic Implications.

  2016cited by this paper
• ABCB1 Genetic Effects on Antidepressant Outcomes: A Report From the iSPOT-D Trial.

  2015influential reference
• Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior

  2015influential reference
• The pro-inflammatory profile of depressed patients is (partly) related to obesity.

  2015cited by this paper
• Depression Subtypes in Predicting Antidepressant Response: A Report From the iSPOT-D Trial.

  2015cited by this paper
• Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder

  2015cited by this paper
• Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression

  2015cited by this paper
• An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline.

  2014cited by this paper
• Lipopolysaccharide Reduces Incentive Motivation While Boosting Preference for High Reward in Mice

  2014cited by this paper
• A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers.

  2013cited by this paper
• A novel approach for developing and interpreting treatment moderator profiles in randomized clinical trials.

  2013influential reference
• Modeling predictors, moderators and mediators of treatment outcome and resistance in depression.

  2013cited by this paper
• Association of depressive symptoms with inflammatory biomarkers among pregnant African-American women.

  2012cited by this paper
• Biomarkers and the Future of Treatment for Depression

  2012cited by this paper
• PDGF receptor β signaling in pericytes following ischemic brain injury.

  2012cited by this paper
• The Effect of Antidepressant Medication Treatment on Serum Levels of Inflammatory Cytokines: A Meta-Analysis

  2011cited by this paper
• Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans

  2011cited by this paper
• Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study.

  2011cited by this paper
• A meta-analysis of cytokines in major depression.

  2010cited by this paper
• Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward.

  2010cited by this paper
• Cellular mechanisms of IL‐17‐induced blood‐brain barrier disruption

  2010cited by this paper
• Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis

  2009cited by this paper
• TH17 cells in development: an updated view of their molecular identity and genetic programming

  2008influential reference
• Functional Interleukin-17 Receptor A is Expressed in the Central Nervous System and Upregulated in Experimental Autoimmune Encephalomyelitisa

  2008cited by this paper
• Production and functions of IL-17 in microglia.

  2008cited by this paper
• Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation

  2007cited by this paper
• Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts.

  2006cited by this paper
• Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice.

  2006cited by this paper
• An evaluation of the quick inventory of depressive symptomatology and the hamilton rating scale for depression: a sequenced treatment alternatives to relieve depression trial report.

  2006cited by this paper
• A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice.

  2006cited by this paper
• Medication augmentation after the failure of SSRIs for depression.

  2006cited by this paper
• Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.

  2006cited by this paper
• Self-Rated Global Measure of the Frequency, Intensity, and Burden of Side Effects

  2006cited by this paper
• Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.

  2006cited by this paper
• Bupropion in the management of apathy

  2004cited by this paper
• The Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) and Self-Report (IDS-SR), and the Quick Inventory of Depressive Symptomatology, Clinician Rating (QIDS-C) and Self-Report (QIDS-SR) in public sector patients with mood disorders: a psychometric evaluation

  2004cited by this paper
• The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression.

  2003cited by this paper
• The Inventory of Depressive Symptomatology (IDS): psychometric properties

  1996influential reference
• A Scale for the Assessment of Hedonic Tone the Snaith–Hamilton Pleasure Scale

  1995cited by this paper
• Bupropion: a review of its mechanism of antidepressant activity.

  1995cited by this paper
• Differential diagnosis and classification of apathy.

  1990cited by this paper
• Cumulative meta-analysis of interleukins 6 and 1 beta , tumour necrosis factor alpha and C-reactive protein in patients with major depressive disorder

  year unknowncited by this paper

• Development and Validation of a Multivariate Diagnostic Model for Major Depressive Disorder With Comorbid Insomnia Based on Lymphocyte Subsets and Resting-State Functional MRI

  2025cites this paper
• Baseline circulating biomarkers, their changes, and subsequent suicidal ideation and depression severity at 6 months: A prospective analysis in patients with mood disorders.

  2024cites this paper
• Plasma cytokine and growth factor response to acute psychosocial stress in major depressive disorder.

  2023cites this paper
• Associations of potential plasma biomarkers with suicide attempt history, current suicidal ideation and subsequent suicidal events in patients with depression: A discovery study.

  2023cites this paper
• Platelets bridging the gap between gut dysbiosis and neuroinflammation in stress-linked disorders: A narrative review.

  2023influential citation
• PDGF‐BB‐Dependent Neurogenesis Buffers Depressive‐Like Behaviors by Inhibition of GABAergic Projection from Medial Septum to Dentate Gyrus

  2023cites this paper
• Transcriptome Analysis Identifies Biomarkers for the Diagnosis and Management of Psoriasis Complicated with Depression

  2023cites this paper
• Biomarkers in Psychiatric Drug Development: From Precision Medicine to Novel Therapeutics.

  2023cites this paper
• Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles

  2022cites this paper
• In Vitro Effects of Cannabidiol on Activated Immune–Inflammatory Pathways in Major Depressive Patients and Healthy Controls

  2022cites this paper
• The Immune Profile of Major Dysmood Disorder: Proof of Concept and Mechanism Using the Precision Nomothetic Psychiatry Approach

  2022cites this paper
• Effects of cannabidiol on activated immune-inflammatory pathways in major depressive patients and healthy controls.

  2022cites this paper
• Comparison of inflammatory markers as moderators of depression outcomes: A CO-MED study.

  2021cites this paper
• Development and Internal Validation of a Novel Model to Identify Inflammatory Biomarkers of a Response to Escitalopram in Patients With Major Depressive Disorder

  2021cites this paper
• Chaperone Sigma1R and Antidepressant Effect

  2020cites this paper
• Excess body weight as a predictor of response to treatment with antidepressants in patients with depressive disorder.

  2020cites this paper
• Positive and negative valence systems in major depression have distinct clinical features, response to antidepressants, and relationships with immunomarkers.

  2020cites this paper
• Pretreatment Reward Sensitivity and Frontostriatal Resting-State Functional Connectivity Are Associated With Response to Bupropion After Sertraline Nonresponse.

  2020cites this paper
• Platelet-derived growth factor BB: A potential diagnostic blood biomarker for differentiating bipolar disorder from major depressive disorder.

  2020cites this paper
• Higher S100B Levels Predict Persistently Elevated Anhedonia with Escitalopram Monotherapy Versus Antidepressant Combinations: Findings from CO-MED Trial

  2019cites this paper
• Pharmacogenomics and Biomarkers of Depression.

  2019cites this paper
• Good, better, best: clinical scenarios for the use of L-methylfolate in patients with MDD

  2019cites this paper
• Potential Adverse Cardiovascular Effects of Treatment With Fluoxetine and Other Selective Serotonin Reuptake Inhibitors (SSRIs) in Patients With Geriatric Depression: Implications for Atherogenesis and Cerebromicrovascular Dysregulation

  2019cites this paper
• Major depressive disorders accompanying autoimmune diseases - Response to treatment.

  2019cites this paper
• Exploring Links between Melatonin, Inflammation and Depression

  2019cites this paper
• Biomarker-Based Treatment Selection: A Precision Medicine Approach for Depression

  2019cites this paper
• Validating pre-treatment body mass index as moderator of antidepressant treatment outcomes: Findings from CO-MED trial.

  2018cites this paper
• Adiponectin Moderates Antidepressant Treatment Outcome in the Combining Medications to Enhance Depression Outcomes Randomized Clinical Trial.

  2018cites this paper
• Experimental Therapies for Treatment-Resistant Depression: "How do you decide when to go to an unproven or experimental therapy with patients that are treatment-resistant depression?"

  2018cites this paper
• Personalized Antidepressant Selection and Pathway to Novel Treatments: Clinical Utility of Targeting Inflammation

  2018cites this paper
• Association of T and non-T cell cytokines with anhedonia: Role of gender differences.

  2018cites this paper
• Accurately identifying patients who are excellent candidates or unsuitable for a medication: a novel approach

  2017cites this paper