The high prevalence of obstructive sleep apnea among patients with bipolar disorders

Introduction: Sleep plays an important role in maintaining stability in bipolar disorders, and sleep disturbances can trigger mood episodes. Obstructive sleep apnea (OSA) is a common sleep disorder, yet the co-occurrence with bipolar disorder has not been methodically studied. Methods: This is a chart review of 482 consecutively seen patients with a bipolar disorder who underwent routine screening for OSA using a self-report sleep apnea questionnaire. Positive screens were referred for a sleep study. Results: A positive screen was found in 214 (44.4%) patients. Sleep studies were obtained on 114 patients, and 101, were diagnosed with OSA: point prevalence 21%. Discussion: The 21% prevalence fails to consider the false negative rate of the questionnaire, or the exclusion of patients who screened positive but failed to get a sleep study. Taking these into consideration it is estimated that the true prevalence of OSA in this study may be as high as 47.5%. The co-occurrence of OSA and bipolar disorders is markedly higher than previously thought. Of note, OSA may play a role in refractory bipolar, disorders, and carries significant mortality and morbidity that overlap, with the mortality and morbidity found with bipolar disorders. Limitations: This was a retrospective study based on a self-report questionnaire. Polysomnographic confirmation was performed in only a subgroup of subjects. Conclusions: The data suggest that unrecognized OSA may play a major role in the mortality and morbidity of bipolar disorders. All patients diagnosed with a bipolar disorder should be screened with an OSA questionnaire.     

Heritability and linkage analysis of personality in bipolar disorder

Background

The many attempts that have been made to identify genes for bipolar disorder (BD) have met with limited success, which may reflect an inadequacy of diagnosis as an informative and biologically relevant phenotype for genetic studies. Here we have explored aspects of personality as quantitative phenotypes for bipolar disorder through the use of the Temperament and Character Inventory (TCI), which assesses personality in seven dimensions. Four temperament dimensions are assessed: novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (PS). Three character dimensions are also included: self-directedness (SD), cooperativeness (CO), and self-transcendence (ST).

Methods

We compared personality scores between diagnostic groups and assessed heritability in a sample of 101 families collected for genetic studies of BD. A genome-wide SNP linkage analysis was then performed in the subset of 51 families for which genetic data was available.

Results

Significant group differences were observed between BD subjects, their first-degree relatives, and independent controls for all but RD and PS, and all but HA and RD were found to be significantly heritable in this sample. Linkage analysis of the heritable dimensions produced several suggestive linkage peaks for NS (chromosomes 7q21 and 10p15), PS (chromosomes 6q16, 12p13, and 19p13), and SD (chromosomes 4q35, 8q24, and 18q12).

Limitations

The relatively small size of our linkage sample likely limited our ability to reach genome-wide significance in this study.

Conclusions

While not genome-wide significant, these results suggest that aspects of personality may prove useful in the identification of genes underlying BD susceptibility.     

Dimensional endophenotypes in bipolar disorder: Affective dysregulation and psychosis proneness

Background

The clinical phenotype of bipolar disorder (BPD) is heterogeneous and the genetic architecture of the disorder is complex and not well understood. Given these complications, it is possible that the identification of intermediate phenotypes (“endophenotypes”) will be useful in elucidating the complex genetic mechanisms that result in the disorder. The examination of unaffected relatives is critical in determining whether a particular trait is genetically-relevant to BPD. However, few dimensional traits related to BPD have been assessed in unaffected relatives of patients.

Methods

We assessed affective temperament and schizotypy in 55 discordant sibling pairs and 113 healthy controls (HCs) using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego, Auto-questionnaire version (TEMPS-A) to assess affective temperament and the Schizotypal Personality Questionnaire (SPQ) to assess schizotypy.

Results

BPD patients scored significantly higher than HCs on all subscales of the SPQ and on all but one subscale (hyperthymic) of the TEMPS-A (all p<0.01). Siblings demonstrated scores that were significantly intermediate to patients and HCs on the anxious subscale of the TEMPS-A and on the interpersonal deficits and disorganized subscales of the SPQ.

Limitations

We did not investigate the BPD spectrum as most patients were diagnosed with BPD I (n=47). Most of the patients had experienced psychosis (n=42) and so we were unable to examine whether psychosis status impacted upon affective temperament or schizotypy in patients or their siblings.

Conclusion

These data suggest that schizotypy and affective temperament represent dimensional traits that are likely to underlie the genetic risk for BPD.     

When aspiration fails: A study of its effect on mental disorder and suicide risk

Background

The Strain Theory of Suicide postulates that psychological strains usually precede suicide mental disorders including suicidal behavior. The four sources of strain are basically (1) differential value conflicts, (2) discrepancies between aspiration and reality, (3) relative deprivation, and (4) lack of coping skills. This paper focuses on the effect of perceived failed life aspiration on the individual's mental disorder and suicide risk.

Method

Data for this study were from a large psychological autopsy study conducted in rural China, where 392 suicides and 416 community living controls were consecutively recruited. Two informants (a family member and a close friend) were interviewed for each suicide and each control. Major depression was assessed with HAM-D and the diagnosis of mental disorder was made with SCID.

Results

It was found that individuals having experienced failed aspiration were significantly more likely than those having not experienced a failed aspiration to be diagnosed with at least one disorder measured by the SCID and major depression measured by HAM-D, and to be a suicide victim, which is true of both suicides and controls.

Conclusion

This study supports the hypothesis that the discrepancies between an individual's aspiration and the reality is likely to lead to mental disorder including major depression and suicidal behavior. Lowering a patient's unrealistic aspiration can be part of the of psychological strains reduction strategies in cognitive therapies by clinicians' and mental health professionals.     

Meta-analytic evidence for neuroimaging models of depression: State or trait?

Background

Major Depressive Disorder (MDD) is a leading cause of disease burden worldwide. With the rapid growth of neuroimaging research on relatively small samples, meta-analytic techniques are becoming increasingly important. Here, we aim to clarify the support in fMRI literature for three leading neurobiological models of MDD: limbic–cortical, cortico–striatal and the default mode network.

Methods

Searches of PubMed and Web of Knowledge, and manual searches, were undertaken in early 2011. Data from 34 case-control comparisons (n=1165) and 6 treatment studies (n=105) were analysed separately with two meta-analytic methods for imaging data: Activation Likelihood Estimation and Gaussian-Process Regression.

Results

There was broad support for limbic–cortical and cortico–striatal models in the case-control data. Evidence for the role of the default mode network was weaker. Treatment-sensitive regions were primarily in lateral frontal areas.

Limitations

In any meta-analysis, the increase in the statistical power of the inference comes with the risk of aggregating heterogeneous study pools. While we believe that this wide range of paradigms allows identification of key regions of dysfunction in MDD (regardless of task), we attempted to minimise such risks by employing GPR, which models such heterogeneity.

Conclusions

The focus of treatment effects in frontal areas indicates that dysregulation here may represent a biomarker of treatment response. Since the dysregulation in many subcortical regions in the case-control comparisons appeared insensitive to treatment, we propose that these act as trait vulnerability markers, or perhaps treatment insensitivity. Our findings allow these models of MDD to be applied to fMRI literature with some confidence.     

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.