Blood-based immune-endocrine biomarkers of treatment response in depression

Antidepressant treatment for major depressive disorder remains suboptimal with response rates of just over 50%. Although treatment guidelines, algorithms and clinical keys are available to assist the clinician, the process of finding an effective pharmacotherapy to maximise benefit for the individual patient is largely by "trial and error" and remains challenging. This highlights a clear need to identify biomarkers of treatment response to help guide personalised treatment strategies. We have carried out the largest multiplex immunoassay based longitudinal study to date, examining up to 258 serum markers involved in immune, endocrine and metabolic processes as potential biomarkers associated with treatment response in 332 depression patients recruited from four independent clinical centres. We demonstrated for the first time that circulating Apolipoprotein A-IV, Endoglin, Intercellular Adhesion Molecule 1, Tissue Inhibitor of Metalloproteinases 1, Plasminogen Activator Inhibitor 1, Thrombopoietin, Complement C3, Hepatocyte Growth Factor and Insulin-like Growth Factor-Binding Protein 2 were associated with response to different antidepressants. In addition, we showed that specific sets of immune-endocrine proteins were associated with response to Venlafaxine (serotonin-norepinephrine reuptake inhibitor), Imipramine (tricyclic antidepressant) and other antidepressant drugs. However, we were not able to reproduce the literature findings on BDNF and TNF-$\alpha$, two of the most commonly reported candidate treatment response markers. Despite the need for extensive validation studies, our preliminary findings suggest that a pre-treatment immune-endocrine profile may help to determine a patient's likelihood to respond to specific antidepressant and/or alternative treatments such as anti-inflammatory drugs, providing hope for future personalised treatment approaches.Drs Chan, Cooper and Prof. Bahn were supported by grants from the Stanley Medical Research Institute (no. 07R-1888). The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10- 000-1002) and is supported by participating universities (VU University Medical Center, Arkin, Leiden University Medical Center, University Medical Center Groningen

The Rotterdam Study: 2012 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods

A new concept of maternity blues: Is there a subgroup of women with rapid cycling mood symptoms?

Background: Rapid cycling mood symptoms during the first postpartum week are an important aspect of maternity blues. The aim of this study is to identify women with these rapid cycling mood symptoms in the general population and to investigate possible risk factors of these symptoms. Methods: The Maternity Blues Scale (MBS) was validated in The Netherlands in 949 women at one week postpartum. Personal and family history of mood disorders and obstetric demographics were collected and the Edinburgh Postnatal Depression Scale (EPDS) was completed. A 16 item three factor NIBS solution was found: depression, negative arid positive affect. The latter two were used to define a rapid cycling mood symptoms group. Results: Using the 75th percentile cut-off, 20(2%) women reported high negative/high positive affect (rapid cycling mood group) and 65 (7%) women were depressed (EPDS >= 11). A previous episode of depression, major life events and instrumental delivery were independently related to depression (OR 3.5, 2.5 and 23, respectively) while only a history of depression in first-degree relatives was independently related to rapid cycling mood (OR 3.4, 95% CI 1.2-93). Limitations First, no syndromal diagnoses were obtained for depression and rapid cycling mood disorder. Second, history of depression was self-reported (not based on structural psychiatric interviews). Third, our study was not designed to study the longitudinal follow-up of women with rapid cycling mood symptoms. Conclusion the 16-item MBS could be useful in screening programs in detecting postpartum women at risk for (severe) mood disorders. Postpartum women with 'rapid cycling mood symptoms' can be identified with a possible more familiar form of mood disorder. (C) 2015 Elsevier B.V. All rights reserved

Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock

Maintenance of epigenetic modifiers is of utmost importance to preserve the epigenome and consequently appropriate cellular functioning. Here, we analyzed Polycomb group protein (PcG) complex integrity in response to heat shock (HS). Upon HS, various Polycomb Repressive Complex (PRC)1 and PRC2 subunits, including CBX proteins, but also other chromatin regulators, are found to accumulate in the nucleolus. In parallel, binding of PRC1/2 to target genes is strongly reduced, coinciding with a dramatic loss of H2AK119ub and H3K27me3 marks. Nucleolar-accumulated CBX proteins are immobile, but remarkably both CBX protein accumulation and loss of PRC1/2 epigenetic marks are reversible. This post-heat shock recovery of pan-nuclear CBX protein localization and reinstallation of epigenetic marks is HSP70 dependent. Our findings demonstrate that the nucleolus is an essential protein quality control center, which is indispensable for recovery of epigenetic regulators and maintenance of the epigenome after heat shock