Veterans are at increased risk for exposure to trauma, developing serious mental illnesses, and death by suicide. History of trauma correlates with worsening outcomes in patients with bipolar ...disorder. This study investigated associations between trauma exposure (type and timing) and suicide attempt in Veterans with bipolar disorder.
One hundred six Veterans with a diagnosis of bipolar disorder and 815 Veterans with no psychiatric history (age rage = 20–72 years old) completed a clinical questionnaire, the Beck Scale for Suicide Ideation, and the Traumatic Live Events Questionnaire. Multinomial logistic regressions investigated correlations between diagnosis, time of trauma (before, during, or after the military), trauma type (attack, illness, accident, child violence, child sexual abuse, and adult sexual abuse), and suicide attempt.
Seventy-five Veterans with bipolar disorder had comorbid PTSD. Controlling for PTSD, Veterans with bipolar disorder had a higher prevalence of trauma including physical assault odds ratio (OR) = 2.85; 95% confidence interval (CI) = 1.39–5.86 and child sexual trauma (OR = 2.89; CI = 1.38–6.05). Veterans with bipolar disorder who endorsed previous suicide attempts (n = 42) had significantly higher levels of exposure to childhood trauma (OR = 5.69; CI = 1.84–17.62).
Results support incorporating history of previous trauma exposure when assessing Veterans at risk for bipolar disorder. Especially, trauma characterized as attack and childhood sexual abuse. Particular attention should be given to Veterans with bipolar disorder and exposure to trauma during childhood, which may be associated with increased risk of suicidality.
•Veterans with bipolar disorder had a higher prevalence of all types of trauma.•Bipolar disorder subjects had more trauma exposure pre, during, and post-deployment.•Bipolar disorder was associated with exposure to sexual trauma during childhood.•Exposure to physical assault was correlated with a diagnosis of bipolar disorder.•Childhood trauma correlates with suicide attempts in Veterans with bipolar disorder.
Background:
Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder ...(BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients.
Methods:
Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR).
Results:
Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels.
Conclusions:
Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness.
•Early onset MDD may be a particular subset of patients with a particular inflammatory profile.•Higher TNFα and IL-1β levels are associated with the early-onset of the MDD.•Changes in inflammatory ...balance may be implicated in the severity of MDD and maybe progression.
Major depressive disorder (MDD) is a common condition that affects the general population over a wide range of ages, regardless of gender and social background. Early-onset of MDD in adulthood, between ages of 18 and 30 years, is associated with worse outcomes and increased years of disability. Stress load and physical health have been associated with age of onset in MDD. We aim to investigate whether early onset MDD might be associated with changes in systemic inflammatory markers. We examined levels of following cytokines: IL-1β, IL-6, IL-10 and TNFα in 234 patients with MDD. Higher serum levels of TNFα and IL-1β are associated with the early onset of the disorder in patients with MDD. IL-6 levels were also higher in the early onset group and IL-10 levels were higher in the late onset group, but with no significant difference. Changes in the anti-inflammatory/pro-inflammatory balance have been described in mood disorders and may be implicated in its severity and pattern of progression. Our findings reinforce that higher serum levels of IL-1β and TNFα may be associated with the earlier onset subgroup of MDD patients. Future research that target inflammatory markers of immune modulation may be, key in the search for novel preventative therapeutics.
Studies investigating inflammatory markers in post-traumatic stress disorder (PTSD) have yielded mixed results. The aim of our study was to compare concentrations of inflammatory markers in patients ...with PTSD compared with healthy controls.
We did a meta-analysis and meta-regression of studies comparing inflammatory markers between patients with PTSD and healthy controls by searching PubMed, Embase, Scopus, Web of Science, and PsycINFO for articles published between Jan 1, 1960, and April 7, 2015. From eligible studies (ie, cross-sectional studies or baseline data from longitudinal studies of peripheral blood cytokine concentrations that compared adults with PTSD with healthy controls), we extracted outcomes of interest, such as mean and SD of peripheral blood cytokines, the time of day blood was collected, whether the study allowed patients with comorbid major depressive disorder in the PTSD group, whether patients were medication free, and severity of PTSD symptoms. We undertook meta-analyses whenever values of inflammatory markers were available in two or more studies. A random-effects model with restricted maximum-likelihood estimator was used to synthesise the effect size (assessed by standardised mean difference SMD) across studies.
8057 abstracts were identified and 20 studies were included. Interleukin 6 (SMD 0.88; p=0.0003), interleukin 1β (SMD 1.42; p=0.045), and interferon γ (SMD 0.49; p=0.002) levels were higher in the PTSD group than in healthy controls. Subgroup meta-analysis of patients who were not given medication showed higher tumour necrosis factor α (TNFα; SMD 0.69, 95% CI 0.35-1.02; p<0.0001) in the PTSD group than the control group in addition to the aforementioned cytokines. TNFα (SMD 1.32, 0.13-2.50; p=0.003), interleukin 1β (SMD 2.35, 0.01-4.68; p=0.048), and interleukin 6 (SMD 1.75, 0.97-2.53; p<0.0001) levels remained increased in the PTSD group in a subgroup meta-analysis of studies that excluded comorbid major depressive disorder. Illness duration was positively associated with interleukin 1β levels (b=0.33, p<0.0001) and severity with interleukin 6 (b=0.02, p=0.042). A model composed of several variables-presence of comorbid major depressive disorder, use of psychotropic medications, assay used, and time of day blood was collected-explained the large amount of heterogeneity between interleukin 1β, interleukin 6, and C-reactive protein studies. Egger's linear regression test revealed a potential publication bias for interleukin 1β. Additionally, for most inflammatory markers, study heterogeneity was reported to be high (I(2)>75%).
PTSD is associated with increased interleukin 6, interleukin 1β, TNFα, and interferon γ levels. This information might be useful for consideration of chronic low-grade inflammation as a potential target or biomarker in PTSD treatment. Use of psychotropic medication and presence of comorbid major depressive disorder were important moderators that might explain the inconsistency between results of previous studies. Our search strategy used a range of databases and we made exhaustive effort to acquire data by contacting the authors. Notably, high levels of between-study heterogeneity were recorded for most cytokine variables measured in our analysis. However, meta-regression analysis could explain a large amount of this heterogeneity.
None.
Initial descriptions of bipolar disorder (BD) emphasized that patients returned to a baseline condition after acute episodes. Such definitions were operational in teasing bipolar disorder apart from ...schizophrenia, where patients were described to be permanently impaired after the initial episodes. However, this view of BD as a disorder where cognition and overall functioning was spared has been changing after the scrutiny of new research. Currently, the cognitive impairment and neuroanatomical changes related to cumulative mood episodes, particularly manic episodes, are well described. In terms of neuropathological findings, recent data suggest that changes in neuronal plasticity, particularly in cell resilience and connectivity, are the main findings in BD. Data from differential lines of research converge to BDNF as an important contributor to the pathophysiology of BD. Serum BDNF levels have been shown to be decreased in depressive and manic episodes, returning to normal levels in euthymia. Moreover, factors that negatively influence the course of BD, such as life stress and trauma, have been shown to be associated with a decrease in serum BDNF levels among bipolar patients. These findings suggest that BDNF plays a central role in the transduction of psychosocial stress and recurrent episodes into the neurobiology of bipolar disorder. The present review discusses the role of BDNF as a mediator of the neuroplastic changes that occur in portion with mood episodes and the potential use of serum BDNF as a biomarker in BD.
A model of staging in the field of bipolar disorder (BD) should offer a means for clinicians to predict response to treatment and more general outcome measures, such as the level of functioning and ...autonomy. The present staging model emphasizes the assessment of patients in the interepisodic period and includes: latent phase: individuals who present mood and anxiety symptoms and increased risk for developing threshold BD; Stage I--patients with BD who present well established periods of euthymia and absence of overt psychiatric morbidity between episodes; Stage II--patients who present rapid cycling or current axis I or II comorbidities; Stage III--patients who present a clinically relevant pattern of cognitive and functioning deterioration, as well as altered biomarkers; and Stage IV--patients who are unable to live autonomously and present altered brain scans and biomarkers. Such a model implies a longitudinal appraisal of clinical variables, as well as assessment of neurocognition and biomarkers in the interepisodic period. Staging facilitates understanding of the mechanisms underlying progression of the disorder, assists in treatment planning and prognosis and, finally, underscores the imperative for early intervention.
Objective:To review the current evidence for efficacy of cannabidiol in the treatment of mood disorders.Methods:We systematically searched PubMed, Embase, Web of Science, PsychInfo, Scielo, ...ClinicalTrials.gov, and The Cochrane Central Register of Controlled Trials for studies published up to July 31, 2019. The inclusion criteria were clinical trials, observational studies, or case reports evaluating the effect of pure cannabidiol or cannabidiol mixed with other cannabinoids on mood symptoms related to either mood disorders or other health conditions. The review was reported in accordance with guidelines from Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol.Results:Of the 924 records initially yielded by the search, 16 were included in the final sample. Among them, six were clinical studies that used cannabidiol to treat other health conditions but assessed mood symptoms as an additional outcome. Similarly, four tested cannabidiol blended with Δ-9-tetrahydrocannabinol in the treatment of general health conditions and assessed affective symptoms as secondary outcomes. Two were case reports testing cannabidiol. Four studies were observational studies that evaluated the cannabidiol use and its clinical correlates. However, there were no clinical trials investigating the efficacy of cannabidiol, specifically in mood disorders or assessing affective symptoms as the primary outcome. Although some articles point in the direction of benefits of cannabidiol to treat depressive symptoms, the methodology varied in several aspects and the level of evidence is not enough to support its indication as a treatment for mood disorders.Conclusions:There is a lack of evidence to recommend cannabidiol as a treatment for mood disorders. However, considering the preclinical and clinical evidence related to other diseases, cannabidiol might have a role as a treatment for mood disorders. Therefore, there is an urgent need for well-designed clinical trials investigating the efficacy of cannabidiol in mood disorders.
Accumulating evidence suggests that reduced levels of brain-derived neurotrophic factor (BDNF) in acute mood episodes may play an important role in the pathophysiology of bipolar disorder (BD). In ...order to assess changes in BDNF serum levels in BD patients before and after treatment for acute mania, ten bipolar patients were prospectively examined at inpatient unit admission and discharge. Diagnoses were made using the Structured Clinical Interview for DSM-IV, SCID-I. Serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were decreased in BD patients during mania when compared to controls (p=0.013) but this difference was no longer significant after treatment (p=0.126). A sharp increase in BDNF levels was found after treatment of the episode of acute mania (p=0.010). These findings suggest that the changes in BDNF serum levels may be associated with treatment response in acute mania. Further studies designed to validate the use of BDNF as a marker of treatment response in bipolar disorder are warranted.
Human survival depends on care received early in life. Infants need to capture adults' attention to have their basic needs met. Therefore, infant stimuli are prioritized by the attention system in ...adults, resulting in an attentional bias toward infant faces. We conducted a systematic review of the literature on behavioral measures of attentional bias toward infant faces. PubMed, PsycINFO, and ISI Web of Knowledge databases were used. The review suggests the existence of a measurable attentional bias toward infant faces and a positive correlation between attentional bias toward infant distress and the quality of mother-infant relationship. Depressive symptoms and breastfeeding modulate this behavior in women. Parental status and sex also influence the attentional prioritization of infant faces. Evidence indicates that differences in attentional bias are associated with clinical symptoms and variations in maternal behavior, reinforcing the potential use of attentional bias as a behavioral marker of clinical outcomes.
Display omitted
•This is a systematic review on measures of attentional bias (AB) toward infant faces.•AB to infant distress correlates with the quality of the mother-infant relationship.•Depressive symptoms and breastfeeding modulate this behavior in women.•Parental status and sex also influence this behavior.
Objectives
Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. ...To facilitate future research in bipolar disorders (BD), a well‐defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking.
Methods
Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders.
Results
Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at‐risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed.
Conclusion
The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light.
PDF
