Analytes with overlapping significant interactions between sex and log₂-transformed serum concentration in MDD and (A) CMA and (B) remitted MDD compared to controls.

<p>The natural logarithm of the odds ratio (OR; ratio of the odds of diagnosis associated with a two-fold increase in the untransformed serum concentration of that analyte from the logistic model) is shown for males and females with 95% confidence intervals. <i>P-</i> and <i>q-</i>values (FDR-adjusted <i>p-</i>values) are shown for the interaction tests. Analytes are plotted in the same order as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156624#pone.0156624.g003" target="_blank">Fig 3</a>. <b>Abbreviations:</b> CMA (comorbid MDD and anxiety disorder(s)); OR (odds ratio); Q (<i>q-</i>value, FDR-adjusted <i>p—</i>value); TFF3 (trefoil factor 3); IGFBP (insulin-like growth factor binding protein); B2M (β2-microglobulin); FAS (FASLG receptor); MIP-3B (macrophage inflammatory protein-3β).</p

Sample exclusion for NESDA patient groups and controls after data pre-processing.

<p>Numbers are indicated in brackets. Red boxes = initial data after pre-processing; blue boxes = excluded data; green boxes = data after exclusion. Participants were excluded if they were not fasting or if they had a current/lifetime anxiety disorder or dysthymia only, current minor depression, a depressive and/or anxiety diagnosis within two years of the baseline measurement, or a lifetime bipolar disorder diagnosed at the two-year assessment. <b>Abbreviations:</b> NESDA (Netherlands Study of Depression and Anxiety); MDD (major depressive disorder); CMA (comorbid MDD and anxiety disorder(s)).</p

Study methods overview.

<p>A brief overview of the study methods is shown here, from sample collection to data analysis. <b>Abbreviations:</b> NESDA (Netherlands Study of Depression and Anxiety); MDD (major depressive disorder); CMA (comorbid MDD and anxiety disorder(s)).</p

Analytes with significant interactions between log₂-transformed serum concentration and sex in MDD compared to controls.

<p>The natural logarithm of the odds ratio (OR; the ratio of the odds of MDD diagnosis associated with a two-fold increase in the untransformed serum concentration of that analyte from the logistic model) is shown for males and females with 95% confidence intervals. <i>P-</i> and <i>q-</i>values (FDR-adjusted <i>p-</i>values) are shown for the interaction tests. <b>Abbreviations:</b> OR (odds ratio); Q (<i>q-</i>value, FDR-adjusted <i>p—</i>value); TFF3 (trefoil factor 3); IGFBP (insulin-like growth factor binding protein); B2M (β2-microglobulin); uPAR (urokinase-type plasminogen activator receptor); FABP (fatty acid-binding protein); TBG (thyroxine-binding globulin); HGF (hepatocyte growth factor); vWF (von Willebrand factor); PPP (pancreatic polypeptide); TN-C (tenascin-C); CRP (C-reactive protein); CD5L (CD5 antigen-like); OPG (osteoprotegerin); TNFR2 (tumor necrosis factor receptor 2); VCAM (vascular cell adhesion molecule); FAS (FASLG receptor); MDC (macrophage derived chemokine); PARC (pulmonary and activation-regulated chemokine); MMP (matrix metalloproteinase); MIP-3B (macrophage inflammatory protein-3β); IL-2RA (interleukin-2 receptor α). † Eotaxin-1 was no longer significant when analyzed using multiple imputation (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156624#pone.0156624.s006" target="_blank">S4 Table</a>).</p

Multilingual markers of depression in remotely collected speech samples: a preliminary analysis

BackgroundSpeech contains neuromuscular, physiological and cognitive components, and so is a potential biomarker of mental disorders. Previous studies indicate that speaking rate and pausing are associated with major depressive disorder (MDD). However, results are inconclusive as many studies are small and underpowered and do not include clinical samples. These studies have also been unilingual and use speech collected in controlled settings. If speech markers are to help understand the onset and progress of MDD, we need to uncover markers that are robust to language and establish the strength of associations in real-world data.MethodsWe collected speech data in 585 participants with a history of MDD in the United Kingdom, Spain, and Netherlands as part of the RADAR-MDD study. Participants recorded their speech via smartphones every two weeks for 18 months. Linear mixed models were used to estimate the strength of specific markers of depression from a set of 28 speech features.ResultsIncreased depressive symptoms were associated with speech rate, articulation rate and intensity of speech elicited from a scripted task. These features had consistently stronger effect sizes than pauses.LimitationsOur findings are derived at the cohort level so may have limited impact on identifying intra-individual speech changes associated with changes in symptom severity. The analysis of features averaged over the entire recording may have underestimated the importance of some features.ConclusionsParticipants with more severe depressive symptoms spoke more slowly and quietly. Our findings are from a real-world, multilingual, clinical dataset so represent a step-change in the usefulness of speech as a digital phenotype of MDD.</p

The impact of COVID-19 lockdown on adults with major depressive disorder from Catalonia: a decentralized longitudinal study

The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the "new normality", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them