BDNF promoter methylation and suicidal behavior in depressive patients

Introduction

Suicide is a major health problem, and depression is a major psychiatric cause of suicide. Suicide is influenced by the multifactorial interaction of many risk factors. Therefore, epigenetic research may lead to understandings that are applicable to suicide. This study investigated whether epigenetic changes are associated with suicidal behavior and evaluated the treatment outcome of suicidal ideation in depressive patients.

Methods

In 108 patients with major depression, the promoter methylation of the gene encoding brain-derived neurotrophic factor (BDNF) was measured. Sociodemographic and clinical characteristics including a history of previous depressive episodes, age at onset, duration of illnesses, family history of depression, and number of stressful life events as well as subjective perception of stress and assessment scales for depression (HAMD), anxiety (HAMA), function (SOFAS), disability (WHODAS-12), and quality of life (WHOQOL-BREF) were evaluated at baseline. Suicidal behavior was ascertained using a semistructured clinical interview with questions about severity and intent. Beck Scale for Suicide Ideation (BSS) was administered during 12 weeks of treatment with antidepressants.

Results

A higher BDNF promoter methylation status was significantly associated with a previous suicidal attempt history, suicidal ideation during treatment, and suicidal ideation at last evaluation as well as with higher BSS scores and poor treatment outcomes for suicidal ideation.

Limitations

Methylation status was investigated with limited area of the BDNF gene and sample size was relatively small.

Conclusions

BDNF methylation status could be a proxy marker for previous suicidal attempts and a clinical biomarker for poor treatment outcomes of suicidal ideation in depression.     

Patients réfractaires aux soins : quelle évolution après le suivi intensif d’une équipe mobile de psychiatrie ?

ObjectivesBeneficial effects of Assertive Community Treatment (ACT) programs on patients with severe mental disorders are well established over short or medium term. However, studies that investigate long term clinical and psychosocial outcomes are remarkably scarce, and it is not known whether the support and intensive care delivered by these programs maintain their benefits over time, especially after discharge. Thus, the present study sought further understanding on this issue by evaluating long term clinical and psychosocial evolution of patients who had been treated by an ACT team in 2007. We investigated the nature of treatment interventions and the level of care since discharge from ACT, especially in terms of adherence to care and number of psychiatric hospitalizations. We also examined factors, at inclusion in the ACT program and after six months of treatment, that could predict better long-term outcomes.MethodsTwenty-nine patients with severe mental disorders, characterized by the heavy use of inpatient facilities and refusal of care, were treated by an ACT team which was implmented between 2007 and 2009. They participated at that time in an initial study on the effect of the program and were therefore assessed at inclusion and again after six months of treatment. Between 2016 and 2017, the present follow up took place and patients were assessed again on their current psychosocial functioning, quality of life and intensity of symptoms, using the same scales as those administered in the initial study. This design allowed us to compare baseline with “early” (after six months) and “late” (after a mean of 8.7 years) effects of ACT program on patients. In order to assess adherence to care since discharge from ACT, data on nature and level of psychiatric treatment was systematically reviewed, including all public and private inpatient and outpatient treatments since the end of the ACT program.ResultsDetailed tables on hospitalizations before, during and after ACT treatment are reported, as well as tables summarizing the level of care and nature of treatment since discharge from ACT. During the mean of 8.7 years of evolution and 6.3 years after discharge from ACT, these patients, characterized by severe mental disorders, heavy use of inpatient facilities and refusal of care, sustained a reduced rate of hospitalizations and a minor rate of disengagement from outpatient care (6.9 %). Both severity of symptoms, poorer quality of life and worst functioning in the community at inclusion (baseline) as well as early improvements (after six month of ACT treatment) of the same outcomes were significantly associated with long term improvements. Results also show other baseline predictors of long term improvement: fewer years since disorder onset was associated with improvement of functioning in the community; further advancement in the recovery process predicted better enhancement in quality of life, and a better initial functioning in the community was associated with a better improvement of symptomatology.ConclusionsThis study provides insight on the sustainability of the benefits of ACT programs, suggesting that these interventions can help patients who are refractory to care to gain clinical and psychosocial improvement in the long term. Our results also suggest that baseline severity as well as early improvements after six months of treatment were associated with larger improvement at follow up. These clinical predictors provide some help to distinguish which patients are more likely to benefit from an ACT approach.     

Kétamine,psilocybine, et antidépresseurs d'action rapide : de nouvelles promesses pour la psychiatrie?

The hypothesis of monoaminergic deficiency has long dominated the conceptual framework for the development of new antidepressant strategies, but the limits of conventional antidepressant treatments targeting monoaminergic signaling have motivated the search for new antidepressant pathways. The success of ketamine in the management of depressive disorders has provoked a renewed interest in hallucinogenic substances such as psilocybin targeting the serotonergic signaling 5HT^2A and neurosteroid allosteric modulator of γ-aminobutyric acid (GABAA) receptors such as brexanolone. Unlike conventional treatments, these modulators of glutamatergic, serotonergic and GABAergic systems exert a rapid antidepressant effect ranging from 24 hours to a week. Apart from their clinical interest and the fantasized search for a “miracle” molecule that jointly meets the expectations of patients and clinicians, these new targets could lead to the identification of potential new biomarkers for the development of rapid-acting antidepressants and redefine therapeutic strategies in mood disorders.     

Spinal cord injury pain

Spinal cord injury pain encompasses musculoskeletal and neuropathic pain. Its management is often multidisciplinary and involves specific drugs such as antidepressants and antiepileptics, and nonpharmacological treatment including psychotherapy, physical therapy and neuromodulation techniques. Recent progress in the diagnosis, assessment, and understanding of its mechanisms offers the perspective of a more rational therapeutic management, which should result in better therapeutic outcome.     

Medication overuse headache: Updating of the French recommendations regarding the treatment strategies

Regular and frequent use of analgesics and acute antimigraine drugs can increase the frequency of headache, and induce the transition from episodic to chronic migraine or medication-overuse headache (MOH). The one-year prevalence of this condition is between 1% and 2% in Europe, provoking substantial burden. MOH is more prevalent in people with comorbid depression, anxiety, and other chronic pain conditions. This paper aims at presenting an updating of French recommendations regarding treatments strategies. Prior French recommendations, published in 2014, were written in French. A literature search in the major medical databases including the terms “medication overuse headache”, “symptomatic medication overuse”, published between 2010 and 2020 was carried out. Three main strategies can be recommended and conducted in parallel: education and explanations about the negative consequences of overusing acute antimigraine drugs, discontinuation of the overused medication, and finally, preventive drug therapy and non-pharmacological prevention. Medication overuse headache remains a debated problem and evidence for the most effective treatment strategy is needed.     

Inhibition of Lupus by Genetic Alteration of the Interferon-α/β Receptor

Type I interferons (IFN-αβ) are immunoregulatory cytokines that promote both innate and adaptive immune responses. Although they have been implicated in human SLE, recent studies in mice have helped solidify this connection. By using lupus-prone mice with knockout of the IFN-αβ receptor, we and others have documented that lack of IFN-αβ leads to a marked reduction in disease manifestations, including autoantibody production, target organ damage and mortality. Furthermore, IFN-αβ was found to potentially contribute to several levels of disease pathogenesis. These included the differentiation and activation of dendritic cells, the activation and proliferation of T cells, T cell survival and the activation and survival of autoantibody-producing B cells. These findings strongly support the targeting of IFN-αβ in SLE and suggest that definition of the specific pathways critical for disease induction will be important for optimal intervention.     

Prophylactic Insulin Treatment of Diabetes-prone BB/OK Rats by Application of a Sustained Release Insulin Implant

Normoglycemic diabetes-prone BB/OK rats aged 33, 45 or 75 days were subjected to prophylactic insulin treatment by means of a single subcutaneous application of a sustained release insulin implant. The single application of a sustained release insulin implant decreased the incidence of diabetes or delayed the onset of the disease in BB/OK rats of all treatment groups. Prophylactic insulin administration caused a transient hypoglycemic period accompanied by an inhibition of glucose stimulated insulin secretion and a decrease of the insulin content of Langerhans' islets as detectable in vitro . Compared to islets of normoglycemic controls pancreatic islets isolated from hypoglycemic BB/OK rats within 7-21 days after the insulin application at 45 days of age displayed a decreased susceptibility of the cells to complement-dependent cytotoxicity of the monoclonal islet cell surface antibody (ICSA) K14D10 but not to the cytotoxic effect of the ICSA M3aG8. The appearance of complement-dependent antibody-mediated cytotoxicity to islet cells and pancreatic exocrine cells in serum regarded as a sign of immune dysregulation in BB/OK rats seems not to be affected by insulin prophylaxis and was detectable during hypoglycemia as well as in the subsequent normoglycemic state. In conclusion, BB/OK rats of different age can be protected from diabetes by a single application of a sustained release insulin implant. Insulin and/or hypoglycemia seem to influence the expression of cell surface antigens, thus render the islets of Langerhans less vulnerable to immune cytolysis, whereas the appearance of humoral immunological abnormalites is not affected.     

Is choroidal vascularity index a useful marker in different stages of idiopathic epiretinal membranes?

BackgroundThis study aims to evaluate the choroidal vascularity index in patients with idiopathic epiretinal membrane at different stages.MethodsThis prospective study included 125 eyes of 125 patients with idiopathic epiretinal membrane and 62 eyes of 62 healthy control subjects. In this study, epiretinal membrane stages were defined based on the spectral-domain optical coherence tomography staging system. The choroidal vascularity index was measured as the ratio of the luminal area to the stromal area in the central 1500 μm after binarization on enhanced depth imaging optical coherence tomography images. Data on epiretinal membrane stages, choroidal vascularity index, and best-corrected visual acuity were noted.ResultsOf 125 eyes with epiretinal membrane, 38 (30.4 %) had stage 1, 32 (25.6 %) had stage 2, and 55 (44 %) had stage 3 disease. Visual acuity was better in eyes with stage 1 or 2 epiretinal membrane than those with stage 3 epiretinal membrane (p < 0.001). The mean choroidal vascularity index was 2.29 ± 1.02 in the control, 2.23 ± 0.98 in the stage 1 epiretinal membrane, 2.22 ± 0.91 in the stage 2 epiretinal membrane, and 2.23 ± 1.11 in the stage 3 epiretinal membrane group. There was no significant difference between epiretinal membrane subgroups and the control group regarding the choroidal vascularity index (p = 0.81).ConclusionFrom the results obtained in the present study, the choroidal vascularity index was not effected by either the development or the progression of idiopathic epiretinal membrane.     

A comparison of treatment planning techniques for low-dose-rate (LDR) prostate brachytherapy

PurposeThe purpose of this study was to compare low-dose-rate prostate brachytherapy treatment plans created using three retrospectively applied planning techniques with plans delivered to patients.Methods and MaterialsTreatment plans were created retrospectively on transrectal ultrasound (TRUS) scans for 26 patients. The technique dubbed 4D Brachytherapy was applied, using TRUS and MRI to obtain prostatic measurements required for the associated webBXT online nomogram. Using a patient's MRI scan to create a treatment plan involving loose seeds was also explored. Plans delivered to patients were made using an intraoperative loose seed TRUS-based planning technique. Prostate V₁₀₀ (%), prostate V₁₅₀ (%), prostate D₉₀ (Gy), rectum D_0.1cc (Gy), rectum D_2cc (Gy), urethra D₁₀ (%), urethra D₃₀ (%), and prostate volumes were measured for each patient. Statistical analysis was used to assess and compare plans.ResultsProstate volumes measured by TRUS and MRI were significantly different. Prostate volumes calculated by the webBXT online nomogram using TRUS- and MRI-based measurements were not significantly different. Compared with delivered plans, TRUS-based 4D Brachytherapy plans showed significantly lower rectum D_0.1cc (Gy) values, MRI-based 4D Brachytherapy plans showed significantly higher prostate V₁₀₀ (%) values and significantly lower rectum D_0.1cc (Gy), urethra D₁₀ (%), and urethra D₃₀ (%) values, and loose seed MRI-based plans showed significantly lower prostate V₁₀₀ (%), prostate D₉₀ (Gy), rectum D_0.1cc (Gy), rectum D_2cc (Gy), urethra D₁₀ (%), and urethra D₃₀ (%) values.ConclusionsTRUS-based 4D Brachytherapy plans showed similar dosimetry to delivered plans; rectal dosimetry was superior. MRI can be integrated into the 4D Brachytherapy workflow. The webBXT online nomogram overestimates the required number of seeds.