Research and Diagnostic Algorithmic Rules (RADAR) for mood disorders, recurrence of illness, suicidal behaviours, and the patient's lifetime trajectory.

The top-down Diagnostic and Statistical Manual/International Statistical Classification of Diseases categories of mood disorders are inaccurate, and their dogmatic nature precludes both deductive (as indisputable) and inductive (as top-down) remodelling of case definitions. In trials, psychiatric rating scale scores employed as outcome variables are invalid and rely on folk psychology-like narratives. Using machine learning techniques, we developed a new precision nomothetic model of mood disorders with a recurrence of illness (ROI) index, a new endophenotype class, namely Major Dysmood Disorder (MDMD), characterised by increased ROI, a more severe phenome, and more disabilities. Nonetheless, our previous studies did not compute Research and Diagnostic Algorithmic Rules (RADAR) to diagnose MDMD and score ROI, lifetime (LT), and current suicidal behaviours, as well as the phenome of mood disorders. Here, we provide rules to compute bottom-up RADAR scores for MDMD, ROI, LT and current suicidal ideation and attempts, the phenome of mood disorders, and the lifetime trajectory of mood disorder patients from a family history of mood disorders and substance abuse to adverse childhood experiences, ROI, and the phenome. We also demonstrate how to plot the 12 major scores in a single RADAR graph, which displays all features in a two-dimensional plot. These graphs allow the characteristics of a patient to be displayed as an idiomatic fingerprint, allowing one to estimate the key traits and severity of the illness at a glance. Consequently, biomarker research into mood disorders should use our RADAR scores to examine pan-omics data, which should be used to enlarge our precision models and RADAR graph.

Cognitive impairment, childhood trauma, sedentary behaviour, and elevated C-reactive protein levels in major affective disorders.

Elevated C-reactive protein (CRP) levels were associated with cognitive decline, sedentary behaviour, and childhood trauma in patients with major affective disorders. This study aims to examine the association of peripheral CRP levels, cognitive function, childhood trauma, sedentary behaviour, and quality of life in individuals with major affective disorders, including bipolar disorder (BD), major depressive disorder (MDD), and individuals without mood disorders (controls). We included outpatients with BD (n = 42), MDD (n = 27), and healthy controls (n = 40). All participants were assessed by a questionnaire, structured clinical interview, and the following scales: international physical activity questionnaire, childhood trauma questionnaire, 17-item Hamilton Depression Rating Scale (HDRS17), and World Health Organization Quality of Life instrument, brief version (WHOQOL-BREF). Other measures were included: hs-CRP levels, anthropometric measures, and cognitive tests (Trail-making test part A and part B, Stroop test, phonemic verbal fluency test, and semantic verbal fluency test). Our results indicated that BD outpatients were less significantly physically active on leisure domain than controls. Levels of hs-CRP ≥ 5 mg/L were significantly linked with a history of childhood sexual abuse and childhood physical abuse, as well as worse neurocognitive performance in major depressive disorders, mainly in BD. There was a significant negative correlation between Trail-making part B score and WHOQOL-BREF total score. The findings support the hypothesis that levels of hs-CRP ≥ 5 mg/L may be a possible predictor of cognitive dysfunction, childhood sexual abuse and sedentary behaviour in major affective disorders.

Development of a Novel Staging Model for Affective Disorders Using Partial Least Squares Bootstrapping: Effects of Lipid-Associated Antioxidant Defenses and Neuro-Oxidative Stress.

Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder. The aims of this study were to use clinical and biomarker data to construct statistically derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology, and biomarkers. In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers. Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the "recurrence LV"), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL, and impairments in cognitive tests. All those factors could be combined into a reliable "ELT-staging LV" which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities, and HR-QoL. Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course, and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage, a relapse-regression stage, and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.

Early Life Trauma Predicts Affective Phenomenology and the Effects are Partly Mediated by Staging Coupled with Lowered Lipid-Associated Antioxidant Defences.

Background Early life trauma (ELT) may drive mood disorder phenomenology, nitro-oxidative pathways and impairments in semantic memory. There are no data regarding the impact of ELT on affective phenomenology and whether these pathways are mediated by staging or lowered lipid-associated antioxidant defences. Methods This study examined healthy controls (n=54) and patients with affective disorders including major depression, bipolar disorder and anxiety disorders (n=118). ELT was assessed using the Child Trauma Questionnaire. In addition, we measured affective phenomenology and assayed advanced oxidation protein products; malondialdehyde, paraoxonase 1 (CMPAase) activity, high-sensitivity C-reactive protein (hsCRP), and high-density lipoprotein (HDL) cholesterol. Results ELT was associated into with increased risk for mood and comorbid anxiety disorders and a more severe phenomenology, including staging characteristics, depression and anxiety severity, suicidal behaviours, type of treatments, disabilities, body mass index, smoking behaviour and hsCRP, as well as lowered health-related quality of life, antioxidant defences and semantic memory. The number of mood episodes and CMPAase/HDL-cholesterol levels could be reliably combined into a new vulnerability staging-biomarker index, which mediates in part the effects of ELT on affective phenomenology and oxidative stress. Moreover, the effects of female sex on mood disorders and affective phenomenology are mediated by ELT. Discussion The cumulative effects of different ELT drive many aspects of affective phenomenology either directly or indirectly through effects of staging and/or lipid-associated antioxidant defences. The results show that children, especially girls, with ELT are at great risk to develop mood disorders and more severe phenotypes of affective disorders.