The predictive role of proinflammatory and neuroendocrine factors in the acute phases of bipolar disorder: study protocol of a longitudinal controlled trial.

INTRODUCTION AND AIMS: Bipolar disorder (BD) is a severe and recurring mental illness associated with a significant personal and social burden. It has been recently hypothesized that increased levels of pro-inflammatory cytokines and cortisol, which is also associated with a reduced expression of the brain-derived neurotrophic factor (BDNF), may influence affective recurrences in BD. Our study aims to: 1) assess changes in the levels of peripheral cytokines, BDNF and salivary cortisol during acute and euthymic phases of bipolar disorder, compared to that of a sample oh healthy controls; 2) evaluate whether these changes represent a biosignature for the different phases of the illness. MATERIALS AND METHODS: Patients aged 18-65 years old, with a diagnosis of BD I or II types, will be enrolled during an acute episode, according to DSM-5 criteria, together with age- and gender-matched healthy controls. Blood and salivary samples will be collected at baseline and after 3 and 6 months. Validated assessment instruments will be administered to all participants for the evaluation of symptom severity, global functioning, suicidal risk, stress levels and physical comorbidities. EXPECTED RESULTS: We expect changes in inflammatory and neuroendocrine indices to be predictive of the onset of an acute phase of bipolar disorder and that overall levels of cytokines, cortisol and BDNF are overall significantly different between BD patients and healthy controls. CONCLUSIONS: The longitudinal design of the study will allow to assess whether the presence of acute affective symptoms in BD patients correlates with significantly higher levels of cytokines and salivary cortisol and with reduced BDNF levels compared to euthymic phases. Moreover, the comparison with healthy control subjects will allow to understand if inflammatory mediators as well as the hypothalamic-pituitary-adrenal (HPA) axis are chronically elevated in BD patients and are independent from mood swings.

Can Brain-Derived Neurotrophic Factor Be Considered a Biomarker for Bipolar Disorder? An Analysis of the Current Evidence.

Brain-derived neurotrophic factor (BDNF) plays a key role in brain development, contributing to neuronal survival and neuroplasticity. Previous works have found that BDNF is involved in several neurological or psychiatric diseases. In this review, we aimed to collect all available data on BDNF and bipolar disorder (BD) and assess if BDNF could be considered a biomarker for BD. We searched the most relevant medical databases and included studies reporting original data on BDNF circulating levels or Val66Met polymorphism. Only articles including a direct comparison with healthy controls (HC) and patients diagnosed with BD according to international classification systems were included. Of the 2430 identified articles, 29 were included in the present review. Results of the present review show a reduction in BDNF circulating levels during acute phases of BD compared to HC, which increase after effective therapy of the disorders. The Val66Met polymorphism was related to features usually associated with worse outcomes. High heterogeneity has been observed regarding sample size, clinical differences of included patients, and data analysis approaches, reducing comparisons among studies. Although more studies are needed, BDNF seems to be a promising biomarker for BD.

The association between childhood maltreatment and eating disorder psychopathology: A mixed-model investigation.

BACKGROUND: Childhood maltreatment (CM) is recognized as a non-specific risk factor for Eating Disorders (EDs), but the mechanisms explaining this association have been insufficiently assessed. We aim to explore the psychological pathways through which CM experiences promote ED core symptoms. METHODS: Two-hundred-twenty-eight people with EDs, 94 with anorexia nervosa restricting (ANR) type and 134 with binge-purging (BP) symptoms (including 23 with AN purging type and 111 with bulimia nervosa), completed the Eating Disorder Inventory-2, the State-Trait Anxiety Inventory and the Childhood Trauma Questionnaire. The variables provided by these questionnaires were included in a network analysis to identify the shortest pathways between CM nodes and ED core symptoms. Then mediation analysis was performed in order to confirm the mediation role of the nodes included in the shortest pathways from CM to ED core symptoms. RESULTS: All types of CM experiences were connected to the ED psychopathology through emotional abuse. In the ANR group, interoceptive awareness was included in the shortest path between emotional abuse and drive to thinness and mediated this relationship. In the BP group, the shortest routes between CM and ED core symptoms included both ineffectiveness and interoceptive awareness. CONCLUSIONS: Combining the network analysis approach with the mediation analyses provides for the first time a putative hybrid model, which reveals that all CM types converge towards ED symptoms through emotional abuse and that interoceptive awareness and ineffectiveness mediate these connections in people with ANR and BP symptoms, respectively. These findings may have possible implications for both research and treatment of EDs.