Jobbe Goossens1,2, Manuel Morrens3, Violette Coppens3,4. 1. Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, R3.22, Building R, Campus Drie Eiken, Universiteitsplein 1, 2610, Antwerp, Belgium. jobbe.goossens@uantwerpen.be. 2. University Department of Psychiatry, Campus Duffel, Stationsstraat 22c, 2570, Duffel, Belgium. jobbe.goossens@uantwerpen.be. 3. Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, R3.22, Building R, Campus Drie Eiken, Universiteitsplein 1, 2610, Antwerp, Belgium. 4. University Department of Psychiatry, Campus Duffel, Stationsstraat 22c, 2570, Duffel, Belgium.
Abstract
BACKGROUND: Psychiatric disorders have a major impact on the global burden of disease while therapeutic interventions remain insufficient to adequately treat a large number of patients. Regrettably, the efficacy of several psychopharmacological treatment regimens becomes apparent only after 4-6 weeks, and at this point, a significant number of patients present as non-responsive. As such, many patients go weeks/months without appropriate treatment or symptom management. Adequate biomarkers for treatment success and outcome prediction are thus urgently needed. OBJECTIVE: With this systematic review, we provide an overview of the use of peripheral blood mononuclear cells (PBMCs) and their signaling pathways in evaluating and/or predicting the effectiveness of different treatment regimens in the course of psychiatric illnesses. We highlight PBMC characteristics that (i) reflect treatment presence, (ii) allow differentiation of responders from non-responders, and (iii) prove predictive at baseline with regard to treatment outcome for a broad range of psychiatric intervention strategies. REVIEW METHODS: A PubMed database search was performed to extract papers investigating the relation between any type of PBMC characteristic and treatment presence and/or outcome in patients suffering from severe mental illness. Criteria for eligibility were: written in English; psychiatric diagnosis based on DSM-III-R or newer; PBMC isolation via gradient centrifugation; comparison between treated and untreated patients via PBMC features; sample size ≥ n = 5 per experimental group. Papers not researching in vivo treatment effects between patients and healthy controls, non-clinical trials, and non-hypothesis-/data-driven (e.g., -omics designs) approaches were excluded. DATA SYNTHESIS: Twenty-nine original articles were included and qualitatively summarized. Antidepressant and antipsychotic treatments were mostly reflected by intracellular inflammatory markers while intervention with mood stabilizers was evidenced through cell maturation pathways. Lastly, cell viability parameters mirrored predominantly non-pharmacological therapeutic strategies. As for response prediction, PBMC (subtype) counts and telomerase activity seemed most promising for antidepressant treatment outcome determination; full length brain-derived neurotrophic factor (BDNF)/truncated BDNF were shown to be most apt to prognosticate antipsychotic treatment. CONCLUSIONS: We conclude that, although inherent limitations to and heterogeneity in study designs in combination with the scarce number of original studies hamper unambiguous identification, several PBMC characteristics-mostly related to inflammatory pathways and cell viability-indeed show promise towards establishment as clinically relevant treatment biomarkers.
BACKGROUND: Psychiatric disorders have a major impact on the global burden of disease while therapeutic interventions remain insufficient to adequately treat a large number of patients. Regrettably, the efficacy of several psychopharmacological treatment regimens becomes apparent only after 4-6 weeks, and at this point, a significant number of patients present as non-responsive. As such, many patients go weeks/months without appropriate treatment or symptom management. Adequate biomarkers for treatment success and outcome prediction are thus urgently needed. OBJECTIVE: With this systematic review, we provide an overview of the use of peripheral blood mononuclear cells (PBMCs) and their signaling pathways in evaluating and/or predicting the effectiveness of different treatment regimens in the course of psychiatric illnesses. We highlight PBMC characteristics that (i) reflect treatment presence, (ii) allow differentiation of responders from non-responders, and (iii) prove predictive at baseline with regard to treatment outcome for a broad range of psychiatric intervention strategies. REVIEW METHODS: A PubMed database search was performed to extract papers investigating the relation between any type of PBMC characteristic and treatment presence and/or outcome in patients suffering from severe mental illness. Criteria for eligibility were: written in English; psychiatric diagnosis based on DSM-III-R or newer; PBMC isolation via gradient centrifugation; comparison between treated and untreated patients via PBMC features; sample size ≥ n = 5 per experimental group. Papers not researching in vivo treatment effects between patients and healthy controls, non-clinical trials, and non-hypothesis-/data-driven (e.g., -omics designs) approaches were excluded. DATA SYNTHESIS: Twenty-nine original articles were included and qualitatively summarized. Antidepressant and antipsychotic treatments were mostly reflected by intracellular inflammatory markers while intervention with mood stabilizers was evidenced through cell maturation pathways. Lastly, cell viability parameters mirrored predominantly non-pharmacological therapeutic strategies. As for response prediction, PBMC (subtype) counts and telomerase activity seemed most promising for antidepressant treatment outcome determination; full length brain-derived neurotrophic factor (BDNF)/truncated BDNF were shown to be most apt to prognosticate antipsychotic treatment. CONCLUSIONS: We conclude that, although inherent limitations to and heterogeneity in study designs in combination with the scarce number of original studies hamper unambiguous identification, several PBMC characteristics-mostly related to inflammatory pathways and cell viability-indeed show promise towards establishment as clinically relevant treatment biomarkers.
Authors: Todd P Gilmer; Christian R Dolder; Jonathan P Lacro; David P Folsom; Laurie Lindamer; Piedad Garcia; Dilip V Jeste Journal: Am J Psychiatry Date: 2004-04 Impact factor: 18.112
Authors: A John Rush; Madhukar H Trivedi; Stephen R Wisniewski; Andrew A Nierenberg; Jonathan W Stewart; Diane Warden; George Niederehe; Michael E Thase; Philip W Lavori; Barry D Lebowitz; Patrick J McGrath; Jerrold F Rosenbaum; Harold A Sackeim; David J Kupfer; James Luther; Maurizio Fava Journal: Am J Psychiatry Date: 2006-11 Impact factor: 18.112
Authors: Dietrich van Calker; Ingo Zobel; Petra Dykierek; Christoph Michael Deimel; Sabine Kech; Klaus Lieb; Mathias Berger; Elisabeth Schramm Journal: J Affect Disord Date: 2008-10-11 Impact factor: 4.839