Disentangling the effects of attentional weighting and associative mediation in perceptual learning reveals no evidence for associative mediation.

Learning to categorize perceptually similar stimuli can result in people becoming more sensitive to differences along perceptual dimensions that are relevant to category membership and/or less sensitive to equivalent differences along irrelevant perceptual dimensions. These effects of acquired distinctiveness and acquired equivalence may be caused by changes in the representations of stimuli which come about through adjustment to the relative attentional weighting of perceptual features or dimensions. Alternatively, the development of associations between individual stimuli and category labels could result in those labels being incorporated into the stimulus representation, hence increasing or decreasing generalization between the stimuli. For many categorization tasks, the expected effects of attentional weighting and associative mediation on stimulus similarity are the same. We report 3 experiments using complex category structures, which allowed us to assess the independent influence of each mechanism on stimulus similarity. The results suggest that, in these categorization tasks, attentional weighting affects perceptual similarity but associative mediation does not. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Cardiometabolic risk in young adults with depression and evidence of inflammation: A birth cohort study.

BACKGROUND: Young adults with depression and evidence of inflammation may represent a high-risk group for cardiometabolic disorders, but studies of cardiometabolic risk in this population are scarce. We aimed to examine: (1) the prevalence of low-grade inflammation in young-adults with depression; (2) cross-sectional and longitudinal associations between cardiometabolic risk factors and depression with or without evidence of inflammation. METHOD: The ALSPAC birth cohort participants were assessed for depression and serum high-sensitivity C-Reactive Protein (CRP) levels at age 18, alongside cardiometabolic measures (fasting insulin, fasting plasma glucose, low-density lipoprotein, high-density lipoprotein, triglycerides, smoking, alcohol intake) at age 18 years, and body mass index at ages 9, 13 and 18 years. Low-grade inflammation was defined as CRP>3 mg/L. Multinomial regression was used to examine associations of cardiometabolic markers with depression cases with and without evidence of inflammation. Sensitivity analyses were conducted to examine for interactions between depression, inflammation and cardiometabolic traits. RESULTS: Out of 2932 participants, 215 met ICD-10 criteria for depressive episode at age 18 years; 23 (10.7 %) had CRP>3 mg/L and 57 (26.5 %) had CRP 1-3 mg/L. Depressive episode with raised CRP (>3 mg/L) was associated with higher triglycerides (adjusted OR = 2.09; 95 % C.I., 1.35-3.24), higher BMI (adjusted OR = 1.13; 95 % C.I., 1.05-1.22) and insulin insensitivity (adjusted OR = 1.12; 95 % C.I., 1.01-1.26), and longitudinally with higher BMI at ages 9 (adjusted OR = 1.27; 95 % C.I., 1.10-1.48) and 13 (adjusted OR = 1.23; 95 % C.I., 1.09-1.38). There was evidence for interaction between BMI and CRP for the risk of depression at age 18 (adjusted OR for the interaction term = 1.56; 95 % C.I. 0.98-2.02) and between CRP and depressive symptoms for the risk of increased BMI at age 18 (adjusted ß for the interaction term = 0.05; 95 % C.I. 0.00-0.12). CONCLUSIONS: A notable proportion of young adults with depression have evidence of inflammation. These individuals are at increased risk of cardiometabolic disorders. Management of cardiometabolic risk in depressed individuals with evidence of inflammation should form part of routine clinical practice.

Protocol for the insight study: a randomised controlled trial of single-dose tocilizumab in patients with depression and low-grade inflammation.

INTRODUCTION: Observational studies indicate a potentially causal role for interleukin 6 (IL-6), a proinflammatory cytokine, in pathogenesis of depression, but interventional studies based on patients with depression have not been conducted. Tocilizumab, anti-inflammatory drug, is a humanised monoclonal antibody that inhibits IL-6 signalling and is licensed in the UK for treatment of rheumatoid arthritis. The main objectives of this study are to test whether IL-6 contributes to the pathogenesis of depression and to examine potential mechanisms by which IL-6 affects mood and cognition. A secondary objective is to compare depressed participants with and without evidence of low-grade systemic inflammation. METHODS AND ANALYSIS: This is a proof-of-concept, randomised, parallel-group, double-blind, placebo-controlled clinical trial. Approximately 50 participants with International Classification of Diseases 10th revision (ICD-10) diagnosis of depression who have evidence of low-grade inflammation, defined as serum high-sensitivity C reactive protein (hs-CRP) level ≥3 mg/L, will receive either a single intravenous infusion of tocilizumab or normal saline. Blood samples, behavioural and cognitive measures will be collected at baseline and after infusion around day 7, 14 and 28. The primary outcome is somatic symptoms score around day 14 postinfusion. In addition, approximately, 50 depressed participants without low-grade inflammation (serum hs-CRP level <3 mg/L) will complete the same baseline assessments as the randomised cohort. ETHICS AND DISSEMINATION: The study has been approved by the South Central-Oxford B Research Ethics Committee (REC) (Reference: 18/SC/0118). Study findings will be published in peer-review journals. Findings will be also disseminated by conference/departmental presentations and by social and traditional media. TRIAL REGISTRATION NUMBER: ISRCTN16942542; Pre-results.