Time course of recovery showing initial prefrontal cortex changes at 16 weeks,extending to subcortical changes by 3 years in pediatric bipolar disorder

Objective

Activation changes at the interface of affective and cognitive systems are examined over a 3 year period in pediatric bipolar disorder (PBD).

Methods

Thirteen participants with PBD and 10 healthy controls (HC) matched on demographics and IQ were scanned at baseline, at 16 weeks, and after 3 years. All patients received pharmacotherapy based on a medication algorithm. A pediatric affective color matching paradigm was used to probe cognitive processing under emotional challenge.

Results

At baseline, in response to emotional vs. neutral words, patients with PBD showed greater activation than HC in the right dorsal lateral prefrontal cortex (DLPFC) and amygdala, ventral lateral prefrontal cortex (VLPFC), bilateral anterior cingulate cortex (ACC), and ventral striatum. Increased activation in DLPFC in the PBD group normalized by 16 weeks. By 3 years, normalization was observed in VLPFC, ACC, amygdala, and striatum.

Limitations

Small sample size renders the present findings preliminary.

Conclusions

Greater activation in fronto-striatal and fronto-limbic circuits were observed in unmedicated patients with PBD. Present findings suggest the possibility that DLPFC is most malleable to pharmacological intervention with systematic pharmacotherapy leading to immediate response, which extended to amygdalostriatal and ventral cortical regions at 3 years. The seminal observation from this study is the prolonged length of recovery time in the normalization of subcortical activity along with their interfacing cortical regions. Findings from this proof of concept study need to be replicated in a larger sample.     

First controlled treatment trial of bipolar II hypomania with mixed symptoms: Quetiapine versus placebo

Objectives

To compare the efficacy and safety of adjunctive quetiapine (QTP) versus placebo (PBO) for patients with bipolar II disorder (BDII) currently experiencing mixed hypomanic symptoms in a 2-site, randomized, placebo-controlled, double-blind, 8-week investigation.

Methods

Participants included 55 adults (age 18–65 years) who met criteria for BDII on the Structured Clinical Interview for DSM-IV-TR (SCID). Entrance criteria included a stable medication regimen for ≥2 weeks and hypomania with mixed symptoms (>12 on the Young Mania Rating Scale [YMRS] and >15 on the Montgomery Asberg Depression Rating Scale [MADRS] at two consecutive visits 1–3 days apart). Participants were randomly assigned to receive adjunctive quetiapine (n=30) or placebo (n=25).

Results

Adjunctive quetiapine demonstrated significantly greater improvement than placebo in Clinical Global Impression for Bipolar Disorder Overall Severity scores (F(1)=10.12, p=.002) and MADRS scores (F(1)=6.93, p=.0138), but no significant differences were observed for YMRS scores (F(1)=3.68, p=.069). Side effects of quetiapine were consistent with those observed in previous clinical trials, with sedation/somnolence being the most common, occurring in 53.3% with QTP and 20.0% with PBO.

Conclusions

While QTP was significantly more effective than PBO for overall and depressive symptoms of BDII, there was no significant difference between groups in reducing symptoms of hypomania. Hypomania improved across both groups throughout the study.     

A systematic review comparing clinical features in early age at onset and late age at onset late-life depression

Background

Although evidence suggests that there are neurobiological differences between unipolar depression in younger versus older adults, conflicting evidence exists about whether these manifest as clinically identifiable differences.

Method

We conducted a systematic review of aetiological, phenomenological and outcome studies to examine the evidence for a distinction between early onset (EOD) and late onset (LOD) depression. A literature search was completed using the computer databases MEDLINE, EMBASE, PSYCHINFO and PUBMED for papers published between January 1982 and December 2012 which compared groups with EOD and LOD. Studies were included if they were of older people and compared symptoms, aetiological factors or outcomes. We conducted a quality assessment of included articles.

Results

We identified 23 articles which met entry criteria. The only clinical feature which was different between the groups was a higher frequency of a family history of mood disorders in EOD.

Limitations

The number of studies identified was low and their quality was generally poor.

Conclusions

Although neurobiological studies have reported differences between EOD and LOD, generally these do not appear to translate into identifiable distinguishing clinical features.     

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.