Effects of extended-release quetiapine fumarate on long-term functioning and sleep quality in patients with Generalized Anxiety Disorder (GAD): Data from a randomized-withdrawal,placebo-controlled maintenance study

Background

This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD.

Methods

Analysis of patient-reported data from a randomized-withdrawal, double-blind, placebo-controlled study of quetiapine XR monotherapy in GAD. Following open-label run-in (4–8 weeks) and a 12–18-week stabilization phase (quetiapine XR 50, 150, or 300 mg/day), eligible patients were randomized to continue on quetiapine XR or receive placebo for up to 52 weeks. Primary variable was time to an anxiety event. Secondary variables included the Sheehan Disability Scale (SDS) and Pittsburgh Sleep Quality Index (PSQI).

Results

In total, 432 patients were randomized (quetiapine XR, N=216; placebo, N=216). The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo (HR 0.19; 95% CI 0.12, 0.31; p<0.001). Quetiapine XR was more effective than placebo at maintaining SDS total scores (LSM change: −0.19 vs. 1.01; p=0.017) and non-work-related SDS domain score ‘family life/home responsibilities’ (−0.13 vs. 0.32; p=0.011), but not ‘social life’ (0.05 vs. 0.34; p=0.114). Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score ‘days lost’ (−0.05 vs. 0.11; p=0.027), but not ‘work/school’ (−0.10 vs. 0.29; p=0.051) or ‘days underproductive’ (0.06 vs. 0.13; p=0.619). PSQI global scores were reduced from randomization with quetiapine XR vs. placebo (0.39 vs. 1.60; p<0.001).

Limitations

Lack of active-comparator arm, exclusion of patients with comorbid depression.

Conclusions

In patients with GAD, long-term treatment with quetiapine XR (50–300 mg/day) monotherapy was effective at maintaining improvements in functioning and sleep quality.     

Lithium-associated hyperparathyroidism and hypercalcaemia: A case-control cross-sectional study

Background

Lithium is recommended as a first-line treatment for Bipolar Disorder (BD). Thyroid and renal alterations are well known lithium side-effects, while effects on parathyroids are less studied. The aim of this case-control cross-sectional study is to compare parathyroid hormone (PTH) and calcium levels in lithium-exposed bipolar patients and in subjects who had never been exposed to lithium.

Methods

112 BD patients were enrolled, 58 on lithium since at least 1 month (mean exposure 60.8±74.8 months) and 54 in the control group. Blood exams included complete blood count, PTH, total and ionized calcium, TSH, T3 and T4, creatinine, urea, sodium and potassium, and lithium serum levels. The Student's t-test and the Pearson's Chi-square test were used for bivariate analyses. A linear regression model was used to analyze the relationship between the duration of exposure to lithium and PTH and calcium levels.

Results

PTH and ionized calcium levels were significantly higher in lithium-exposed patients; the proportions of subjects with hyperparathyroidism (8.6%) and hypercalcaemia (24.1%) were significantly greater in lithium-exposed patients. The linear regression analyses showed a significant effect of exposure to lithium in months on ionized calcium levels but not on PTH levels.

Limitations

Given the cross-sectional design of the study we could not identify the exact time of occurrence of hyperparathyroidism.

Conclusions

Our results indicate that lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation and during long-term lithium maintenance, calcium (and eventually PTH) should be added.     

Detection and quantitation of two cucurbit criniviruses in mixed infection by real-time RT-PCR

Cucurbit chlorotic yellows virus (CCYV) and Cucurbit yellow stunting disorder virus (CYSDV) are whitefly-transmitted criniviruses infecting cucurbit crops inducing similar symptoms. Single and multiplex RT-PCR protocols were developed and evaluated on cucurbit samples collected from commercial greenhouses. Primers and probes were designed from the highly conserved heat shock protein 70 homolog (Hsp70h) gene. Conventional RT-PCR and multiplex RT-PCR assays showed high specificity and suitability for routine screening. TaqMan-based quantitative real-time RT-PCR (RT-qPCR) protocols were also developed for the detection and quantitation of both viruses occurring in single or mixed infection. The assays proved to be highly specific with no cross amplification. RT-qPCR assays showed a 100–1000 times improved sensitivity over conventional RT-PCR. Virus titers in mixed infections were compared to singly infected plants by RT-qPCR. CYSDV and CCYV titers decreased in double infected plants. This paper reports highly specific conventional RT-PCR and quantitative real-time PCR assays for detection, quantitation and differentiation between two closely related cucurbit-infecting criniviruses.     

Trouble psychotique partagé ou trouble délirant induit ? Étude d’un cas clinique

Can a delusional idea be contagious? This question may seem paradoxical when we know that the very definition of delirium correspond to “an erroneous belief (…) maintained despite the very generally shared opinion” (DSM4) and so implies that peers do not share the beliefs expressed by the subject. However, cases of collective delirium have been described for many years, and have been the subject of numerous scientific publications since the 19th century. Among them, an entity emerged : “folie à deux”, in which a primary active subject could induce his delusions to a secondary subject, more vulnerable, said induced and passive. In 1877, Lasègue and Falret first introduced the term “folie à deux” and proposed the diagnostic criteria. They describe nine essential criteria among which, three would be the sine qua non conditions that can allow the outbreak of a delirium shared by two. They are the presence of an active element of superior intelligence, the existence of a common life between the two individuals, sufficiently long and intimate and a “closed and isolated” environment. These criteria were subsequently supplemented to arrive at the current definitions of induced delusional disorder (ICD10) and shared psychotic disorder (DSM4). This rare disorder has been the subject of numerous publications. However, these publications were often divided over both its epidemiology, its diagnostic criteria, and the specific treatment to be offered. The two recent definitions resulting from current classifications can also illustrate this dichotomy on certain criteria, beyond the very semantics which here oppose the terms “induced delusional” and “shared psychosis”. Moreover, this disorder has the particularity to question its real existence as it is currently challenged in the new classifications of the DSM V and ICD 11. We can therefore see that if the subject fascinates, it divides. What is it really? Can a delirium really be transmitted? Can a psychosis really be shared? And if so, is one of the two definitions more suitable to describe this disorder? What future can we imagine for this pathology? During the hospitalization of a patient for a “délire à deux”, concerning two persons from two different families sharing a delirium of filiation, we observed the current issues around this disorder and we asked ourselves which treatment to administer to these patients. The hospitalization took place over two stages: the first stage to understand the disorder, the second one to treat it. À family interview was conducted in the presence of the dyad of patients, to explore the interactional elements together, and establish the diagnosis. A preliminary step essential to therapeutic work on the question of loyalty and differentiation. This clinical case recalls the value of an integrated approach based on the systemic epistemology, both for the diagnostic phase than during therapeutic support. The objective of this work is to study, through an atypical clinical case and a review of recent literature, the different diagnostic, therapeutic and evolutionary perspectives of this particular pathology.     

Differential diagnosis on the autism spectrum: Theorizing an “Ordinary Autism”

ObjectivesData on the prevalence of Autism Spectrum Disorder (ASD) reveal several clinical evolutions inducing new psychiatric definitions and diagnostic practices. Thus, autism has shifted from being a rare syndrome with severe clinical forms to a new paradigm: the paradigm of “ordinary” or “invisible” autism, in terms of the frequency and the intensity of the disorders. These changes incorporate new populations into our conception of autism, with new phenotypes that pose theoretical and clinical challenges to clinicians. In response, we propose the hypothesis — based on psychoanalytic theories of psychic structures — of an “ordinary autism” as a definition of a non-prototypical autistic psychic functioning that falls outside the DSM diagnostic framework. This idea seems to provide us new theoretical references that nourish our practices as well as fundamental research.MethodFirst, we will review the nosographic mutations of the DSM-5 and their implications for non-prototypical psychic modes of functioning of autistic people that may not be contained within the autism spectrum's blurry boundaries — especially for the adult population without intellectual delay and in the case of complicated differential diagnosis for clinical and societal reasons. Next, we will discuss the definition of “ordinary” or “invisible” autism in a psychoanalytic structural model, as a possible epistemological orientation for identifying and designing practice with the clinical heterogeneity of autism outside the boundaries of psychiatric ASD.ResultsThe autistic population targeted by the DSM-5 criteria is different from that previously defined by DSM-IV. This leads to two consequences: on the one hand, autistic modes of functioning are not limited to individuals who have been diagnosed with Autism Spectrum Disorders as defined by the DSM-5; thus individuals with autism do not have access to the diagnosis of ASD or are given other diagnoses. The alternative diagnoses proposed by the DSM-5 that attempt to correct this diagnostic exclusion — such as Social (Pragmatic) Communication Disorder — are unsatisfactory. Therefore, there is an entire segment of the autistic population that has subclinical, non-prototypic autistic manifestations or more subtle phenomena discernible in the broader autistic phenotype or sub-threshold autism spectrum that does not have access to the ASD diagnosis and raises differential diagnostic issues. On the other hand, it appears that the autism spectrum brings together extremely different entities and false positives such as schizophrenia and schizophrenic spectrum personality disorders under one diagnostic rubric. Then, the differential problem appears central: both at the theoretical level and in diagnostic practices. The recognition of these limits should encourage us to promote research and clinical applications on this subject. One solution that we envisage is to be found in an extension of Maleval's structural psychoanalytical model: we propose the notion of “ordinary autism” — an echo of ordinary psychosis — to define attenuated or compensated non-prototypical autistic phenotypes, increasingly frequent and with fewer “extraordinary” phenomenological expressions than the classic cases of autism which now call into question the relationship between the normal and the pathological.Discussion“Ordinary autism” seems to offer clinicians the opportunity to formalize the new contemporary and extensive clinical reality of autism. This term situates itself within a theoretical model whose current and future developments might help us respond to clinical and diagnostic issues, but also to therapeutic and societal ones. We propose to continue on the path of the operationalization of these theoretical models in order to identify autistic structural constants that could be found throughout the “ordinary” clinic of autism and could serve as differentiating tools for diagnosis as well as a support in developing and refining therapeutic practices.ConclusionWe conclude that there is an urgent need to conceive of “ordinary autism” to provide us with reference points to respond to new clinical issues, but also to reintroduce respect for the autistic person in his or her subjectivity to the center of our therapeutic practices.     

FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability

Chromosome 1q41‐q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41‐q42 microdeletion, WDR26 and FBXO28, have been implicated in monogenic disease. Patients with WDR26 encephalopathy overlap clinically with those with 1q41‐q42 deletion syndrome, whereas only one patient with FBXO28 encephalopathy has been described. Seizures are a prominent feature of 1q41‐q42 deletion syndrome; therefore, we hypothesized that pathogenic FBXO28 variants cause developmental and epileptic encephalopathies (DEEs). We describe nine new patients with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and analyze all 10 known cases to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features, albeit different to those typically seen in 1q41‐q42 deletion syndrome and WDR26 encephalopathy. We distinguish FBXO28 encephalopathy from both of these disorders with more severe intellectual impairment, drug‐resistant epilepsy, and hyperkinetic movement disorders.     

Symptômes reliés au diagnostic du trouble de personnalité limite à l’adolescence : une recension systématique de la littérature

The diagnosis of borderline personality disorder (BPD) in adolescence is controversial among some researchers and clinicians. For many, the symptoms presented in young people with BPD resemble normal functioning in adolescence. The diagnosis is then delayed in adulthood, postponing the treatment. The aim of this systematic review of the literature is to investigate the symptoms that can differentiate an adolescent population with BPD from one with another diagnosis and/or without any psychiatric issues. In all, 17 studies out of the 4789 titles initially identified met the inclusion criteria and were analyzed. This systematic review considers diverse symptoms: internalized and externalized disorders, suicide, mentalization errors, maladaptive schemas and comorbid diagnoses. Several symptoms significantly differentiated adolescents with BPD from three control groups teenagers: non-psychiatric, with another personality disorder and with another diagnosis. Finally, a pattern of symptoms could also be observed between suicidal adolescents with BPD and suicidal youth without it.     

Specificity of psychological treatments for bulimia nervosa and binge eating disorder? A meta-analysis of direct comparisons

Treatment guidelines state that cognitive–behavioral therapy (CBT) and interpersonal therapy are the best-supported psychotherapies for bulimia nervosa (BN) and that CBT is the preferred psychological treatment for binge eating disorder (BED). However, no meta-analysis which both examined direct comparisons between psychological treatments for BN and BED and considered the role of moderating variables, such as the degree to which psychotherapy was bona fide, has previously been conducted Thus, such an analysis was undertaken. We included 77 comparisons reported in 53 studies. The results indicated that: (a) bona fide therapies outperformed non-bona fide treatments, (b) bona fide CBT outperformed bona fide non-CBT interventions by a statistically significant margin (only approaching statistical significance for BN and BED when examined individually), but many of these trials had confounds which limited their internal validity, (c) full CBT treatments offered no benefit over their components, and (d) the distribution of effect size differences between bona fide CBT treatments was homogeneously distributed around zero. These findings provide little support for treatment specificity in psychotherapy for BN and BED.     

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.