Homogeneous Disorder Research Articles

Is postpartum depression a homogenous disorder: time of onset, severity, symptoms and hopelessness in relation to the course of depression

Postpartum depression (PPD) is a common illness, but due to the underlying processes and the diversity of symptoms, some variability is exhibited. The risk of postpartum depression is great if the mother has previously suffered from depression, but there is some evidence that a certain subgroup of women only experience depression during the postpartum period. The study group consisted of 104 mothers with postpartum major depression and a control group of 104 postpartum mothers without depression. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) was used for data collection. The severity of depression and other mental symptoms were assessed using several validated rating scales. A history of past depression (82%), including depression during pregnancy (42%) and during the postpartum period (53%), was very common in those with current PPD. Eighteen per cent of mothers with current PPD had previously not had any depressive episodes and four per cent had experienced depression only during the postpartum period. Therefore, pure PPD was rare. The onset of PPD was usually (84%) within six weeks of childbirth. Obsessive-compulsive symptoms, phobic anxiety, paranoid ideation, depressed mood, diminished pleasure/interest, decreased energy, and psychomotor agitation/retardation were common with all kinds of depression histories. Pure PPD was the most similar to the first depressive episode. Nevertheless, the severity of depression, the level of hopelessness, somatisation, interpersonal sensitivity, anxiety, hostility, psychoticism, sleep disturbance, and suicidal ideation were lower, appetite changed less, and concentration was better than in other recurrent depressions. According to this study, PPD is not a homogenous disorder. The time of onset, severity, symptoms, level of hopelessness, and the course of depression vary. Recurrent depression is common. All mothers must be screened during the sixth week postpartum at the latest. Screening alone is not effective; it is also important to give mothers information about PPD and to discuss the symptoms with them in order for them to recognise this disorder and possible new episodes in the future.

Characteristics and stability of empirically derived anorexia nervosa subtypes: Towards the identification of homogeneous low-weight eating disorder phenotypes.

Anorexia nervosa (AN) is characterized by within-group heterogeneity in symptom presentation, which poses problems for research on etiology and treatment. This study sought to identify homogeneous subtypes of AN, and examine their short-term stability, using empirical methods. A treatment-seeking sample with AN (n = 194) was assessed at baseline and 6- and 12-month follow-ups. Latent class analysis was used to identify homogeneous AN subgroups, and latent transition analysis was used to examine the stability of latent classes. Three low-weight eating disorder classes were identified: 1) fat-phobic restricting (AN-R-FP); 2) fat-phobic binge-eating/purging (AN-BP-FP); and 3) non-fat-phobic restricting (AN-R-NFP). Subtype membership was stable over follow-up, with .68 to .88 probabilities of remaining in the same class from baseline to 6 months, and .87 to 1.00 from 6 months to 12 months. The most common transition pattern was between AN-R-FP and AN-R-NFP (56.8% of transitions); the majority of these participants transitioned from AN-R-FP to AN-R-NFP (n = 20/21). Predictors of latent class membership included lifetime mood and substance use disorder comorbidities, negative temperament, illness duration, and body mass index at treatment presentation. Disinhibition (vs. constraint), history of overweight or obesity, and illness duration decreased the probability of latent transition. Findings support the presence of 3 low-weight eating disorder phenotypes that are highly stable over short-term follow-up. Identification of a stable non-fat-phobic AN phenotype is intriguing and highlights the importance of studying mechanisms that differentiate fat-phobic and non-fat-phobic eating disorders.

Emergence of nanoscale inhomogeneity in the superconducting state of a homogeneously disordered conventional superconductor

The notion of spontaneous formation of an inhomogeneous superconducting state is at the heart of most theories attempting to understand the superconducting state in the presence of strong disorder. Using scanning tunneling spectroscopy and high resolution scanning transmission electron microscopy, we experimentally demonstrate that under the competing effects of strong homogeneous disorder and superconducting correlations, the superconducting state of a conventional superconductor, NbN, spontaneously segregates into domains. Tracking these domains as a function of temperature we observe that the superconducting domains persist across the bulk superconducting transition, Tc, and disappear close to the pseudogap temperature, T*, where signatures of superconducting correlations disappear from the tunneling spectrum and the superfluid response of the system.

Preliminary Results of the ARUBA Study

Preliminary Results of the ARUBA Study

Kiwifruit as a food allergen source

Since its first appearance on the market kiwifruit has become very popular in the human diet due to its pleasant taste, low caloric value and high content of vitamin C. However, kiwifruit allergy has become a frequent cause of type I hypersensitivity in the western society. Molecular basis for kiwifruit allergy has been ascribed to up-to-now 11 identified IgE reactive molecules. They are proteins and glycoproteins with a molecular mass between 50 and 10 kDa. The major kiwifruit allergen is a cysteine protease denoted as Act d 1, which represents 50% of the soluble protein extract. Due to a difference in the abundance of protein components and biological activity, the quality of kiwifruit extracts intended for allergy diagnosis can vary in content and amount of IgE reactive molecules. In addition, the quality of allergen extracts for allergy diagnosis depends on the fruit ripening stage and storage conditions. In terms of clinical reactivity it has become evident that kiwifruit allergy is not a homogeneous disorder. Different patterns of IgE reactivity accompany several clinical subgroups that have been identified in different geographical regions. In the last decade an enormous progress has been made in isolation and characterization of kiwifruit allergens. This paper will give an overview of the structural features of kiwifruit allergens.

Dyscalculia from a developmental and differential perspective

Developmental dyscalculia (DD) and its treatment are receiving increasing research attention. A PsychInfo search for peer-reviewed articles with dyscalculia as a title word reveals 31 papers published from 1991–2001, versus 74 papers published from 2002–2012. Still, these small counts reflect the paucity of research on DD compared to dyslexia, despite the prevalence of mathematical difficulties. In the UK, 22% of adults have mathematical difficulties sufficient to impose severe practical and occupational restrictions (Bynner and Parsons, 1997; National Center for Education Statistics, 2011). It is unlikely that all of these individuals with mathematical difficulties have DD, but criteria for defining and diagnosing dyscalculia remain ambiguous (Mazzocco and Myers, 2003). What is treated as DD in one study may be conceptualized as another form of mathematical impairment in another study. Furthermore, DD is frequently—but, we believe, mistakenly- considered a largely homogeneous disorder. Here we advocate a differential and developmental perspective on DD focused on identifying behavioral, cognitive, and neural sources of individual differences that contribute to our understanding of what DD is and what it is not.

Twenty patients including 7 probands with autosomal dominant cutis laxa confirm clinical and molecular homogeneity

BackgroundElastin gene mutations have been associated with a variety of phenotypes. Autosomal dominant cutis laxa (ADCL) is a rare disorder that presents with lax skin, typical facial characteristics, inguinal hernias, aortic root dilatation and pulmonary emphysema. In most patients, frameshift mutations are found in the 3’ region of the elastin gene (exons 30-34) which result in a C-terminally extended protein, though exceptions have been reported.MethodsWe clinically and molecularly characterized the thus far largest cohort of ADCL patients, consisting of 19 patients from six families and one sporadic patient.ResultsMolecular analysis showed C-terminal frameshift mutations in exon 30, 32, and 34 of the elastin gene and identified a mutational hotspot in exon 32 (c.2262delA). This cohort confirms the previously reported clinical constellation of skin laxity (100%), inguinal hernias (51%), aortic root dilatation (55%) and emphysema (37%).ConclusionADCL is a clinically and molecularly homogeneous disorder, but intra- and interfamilial variability in the severity of organ involvement needs to be taken into account. Regular cardiovascular and pulmonary evaluations are imperative in the clinical follow-up of these patients.

A novel synonymous mutation causing complete skipping of exon 16 in the SLC26A4 gene in a Korean family with hearing loss

IntroductionMutations in PDS (or SLC26A4) cause both Pendred syndrome (PS) and DFNB4, two autosomal recessive disorders that share hearing loss as a common feature. PS and DFNB4 are genetically homogeneous disorders caused by bi-allelic SLC26A4 mutations. Here, we report a novel synonymous mutation (c.1803G>A, p.Lys601Lys), that caused aberrant splicing in two Korean family members who were clinically considered to have DFNB4, along with congenital hearing loss and dilated vestibular aqueducts (DVA). MethodsAfter extracting DNA from whole blood using standard procedures, the 21 exons and flanking introns of SLC26A4 were amplified with PCR. To evaluate the implication of a novel synonymous mutation (c.1803G>A), we used The Berkeley Drosophila Genome Project (BDGP) (http://www.fruitfly.org/) as a splice site prediction program and performed exon trapping analysis. ResultsIn molecular analysis of the 21 exons of SCL26A4, we detected a known splicing mutation (c.919-2A>G, heterozygote) and a novel variant (c.1803G>A, heterozygote) in the patients (II-1 and II-2). According to in silico analysis, the novel variant (c.1803G>A) affects canonical splice donor nucleotide positioning. To define the transcript level effects of this novel 1803G>A variant, we performed exon trapping and confirmed that exon 16 is completely skipped in this variant type. ConclusionWe report a novel synonymous mutation (c.1803G>A) causing complete exon 16 skipping in the SLC26A4 gene in two Korean family members with hearing loss. This is the first case of a synonymous SNP (c.1803G>A) affecting vestibulocochlear organs through altering splicing accuracy by causing a complete skipping of exon 16. An important issue raised by this study is that synonymous mutations that have been previously ignored in clinical diagnoses must now be considered as potential pathogenic mutations.

Outcomes of adults with restrictive cardiomyopathy after heart transplantation

Restrictive cardiomyopathy (RCM) represents a spectrum of disorders with a common physiology but divergent etiologies. RCM commonly leads to progressive heart failure and the need for heart transplantation (HTx). Pediatric RCM is a more homogeneous disorder with post-HTx outcomes comparable to those for non-RCM patients. However, post-HTx outcomes in adult RCM patients have not been studied to date. Demographic, clinical and survival outcomes of 38,190 adult HTx-only recipients from 1987 to 2010 were acquired from the registry of the United Network of Organ Sharing. The study population included 544 RCM patients (1.4%) and 37,646 non-RCM patients (98.6%). RCM diagnoses included idiopathic (n = 227, 42%), amyloid (n = 142, 26%), sarcoid (n = 81, 15%), radiation/chemotherapy (XRT) (n = 35, 6%) and other (n = 59, 11%). Follow-up began at the time of HTx (74±64 months). During the follow-up period, 224 (41%) patients in the RCM group died, whereas 18,791 (50%) in the non-RCM group died. Crude 1-, 5- and 10-year survival for RCM patients was 84%, 66% and 45%, and for non-RCM patients was 85%, 70% and 50%, respectively. The overall unadjusted hazard ratio of RCM vs non-RCM for all-cause mortality was 1.07 (confidence interval [CI] 0.93 to 1.22). Multivariate Cox proportional hazards regression analysis yielded a hazard ratio of 1.06 (CI 0.91 to 1.25). RCM subgroup analysis showed decreased survival at 1, 5 and 10 years in the XRT (71%, 47% and 32%) and amyloid (79%, 47% and 28%) patient groups. The unadjusted hazard ratio for the XRT and amyloid subgroups vs RCM for all-cause mortality was 1.81 (p = 0.002) and 1.85 (p = 0.0004), respectively. Outcomes for RCM patients post-HTx are comparable to those of non-RCM patients. However, RCM subgroup analysis suggests increased mortality for XRT and amyloid subgroups. Further analysis is warranted to understand the contributing factors.

Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings

Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder, progressive spastic gait, and peripheral neuropathy. Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency. To improve clinical diagnosis and enable future evaluation of therapeutic strategies, we conducted a multinational study of the natural history and imaging features of APBD. We gathered clinical, biochemical, and molecular findings in 50 APBD patients with GBE deficiency from Israel, the United States, France, and the Netherlands. Brain and spine magnetic resonance images were reviewed in 44 patients. The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%). The median age was 51 years for the onset of neurogenic bladder symptoms, 63 years for wheelchair dependence, and 70 years for death. As the disease progressed, mild cognitive decline may have affected up to half of the patients. Neuroimaging showed hyperintense white matter abnormalities on T2 and fluid attenuated inversion recovery sequences predominantly in the periventricular regions, the posterior limb of the internal capsule, the external capsule, and the pyramidal tracts and medial lemniscus of the pons and medulla. Atrophy of the medulla and spine was universal. p.Y329S was the most common GBE1 mutation, present as a single heterozygous (28%) or homozygous (48%) mutation. APBD with GBE deficiency, with occasional exceptions, is a clinically homogenous disorder that should be suspected in patients with adult onset leukodystrophy or spastic paraplegia with early onset of urinary symptoms and spinal atrophy.

Group-based trajectory modeling: A novel approach to examining symptom trajectories in acute bipolar episodes

BackgroundPattern analysis can aid understanding of trajectories of symptom evolution. However, most studies focus on relatively homogeneous disorders with a restricted range of outcomes, prescribed a limited number of classes of medication. We explored the utility of pattern analysis in defining short-term outcomes in a heterogeneous clinical sample with acute bipolar disorders. MethodIn a naturalistic observational study, we used Group-based trajectory modeling (GBTM) to define trajectories of symptom change in 118 bipolar cases recruited during an acute DSM IV episode: major depression (56%), (hypo)mania (26%), and mixed states (18%). Symptoms were assessed weekly for a month using the MATHYS, which measures symptoms independent of episode polarity. ResultsFour trajectories of symptom change were identified: Persistent Inhibition, Transient Inhibition, Transient Activation and Over-activation. However, counter to traditional predictions, we observed that bipolar depression shows a heterogeneous response pattern with cases being distributed approximately equally across trajectories that commenced with inhibition and activation. LimitationsThe observational period focuses on acute outcomes and so we cannot use the findings to predict whether the trajectories lead to stable improvement or whether the clinical course for some clusters is cyclical. As in all GBTM, the terms used for each trajectory are subjective, also the modeling programme we used assumes dropouts are random, which is clearly not always the case. ConclusionThis paper highlights the potential importance of techniques such as GBTM in distinguishing the different response trajectories for acutely ill bipolar cases. The use of the MATHYS provides further critical insights, demonstrating that clustering of cases with similar response patterns may be independent of episodes defined by mood state.

Multi-Scale Motility Amplitude Associated with Suicidal Thoughts in Major Depression

Major depression occurs at high prevalence in the general population, often starts in juvenile years, recurs over a lifetime, and is strongly associated with disability and suicide. Searches for biological markers in depression may have been hindered by assuming that depression is a unitary and relatively homogeneous disorder, mainly of mood, rather than addressing particular, clinically crucial features or diagnostic subtypes. Many studies have implicated quantitative alterations of motility rhythms in depressed human subjects. Since a candidate feature of great public-health significance is the unusually high risk of suicidal behavior in depressive disorders, we studied correlations between a measure (vulnerability index [VI]) derived from multi-scale characteristics of daily-motility rhythms in depressed subjects (n = 36) monitored with noninvasive, wrist-worn, electronic actigraphs and their self-assessed level of suicidal thinking operationalized as a wish to die. Patient-subjects had a stable clinical diagnosis of bipolar-I, bipolar-II, or unipolar major depression (n = 12 of each type). VI was associated inversely with suicidal thinking (r = –0.61 with all subjects and r = –0.73 with bipolar disorder subjects; both p<0.0001) and distinguished patients with bipolar versus unipolar major depression with a sensitivity of 91.7% and a specificity of 79.2%. VI may be a useful biomarker of characteristic features of major depression, contribute to differentiating bipolar and unipolar depression, and help to detect risk of suicide. An objective biomarker of suicide-risk could be advantageous when patients are unwilling or unable to share suicidal thinking with clinicians.

382 Outcomes of Adults with Restrictive Cardiomyopathy (RCM) Post Heart Transplant (HT): UNOS Registry Analysis

RCM represents multiple disorders with common physiology but divergent etiologies progressing to heart failure & HT need. Pediatric RCM is a more homogeneous disorder with post HT outcomes comparable to non-RCM (NRCM). However, adult RCM post-HT outcomes have not been studied to date.

The Interdependence of Subtype and Severity: Contributions of Clinical and Neuropsychological Features to Melancholia and Non-melancholia in an Outpatient Sample

Major depressive disorder is often considered to be a homogenous disorder that changes in terms of severity; however, the presence of distinct subtypes and a variety of presenting symptoms suggests much heterogeneity. Aiming to better understand the relationship between heterogeneity and diagnosis we used an exploratory approach to identify subtypes of depression on the basis of clinical symptoms and neuropsychological performance. Cluster analysis identified two groups of patients distinguished by level of cognitive dysfunction with the more severe cluster being associated with melancholic depression. While the relationship between cluster and subtype was significant, only 58% of melancholic patients were assigned to cluster 1 (the more severe cluster) and 66% of non-melancholic patients assigned to cluster 2. Subtypes also displayed a distinctive profile of impairment such that melancholic patients (n = 65) displayed more variability in attention while non-melancholic patients (n = 59) displayed memory recall impairment. While melancholia and non-melancholia are associated with a more severe and less severe form of depression respectively, findings indicate that differences between melancholia and non-melancholia are more than simple variation on severity. In summary, findings provide support for the heterogeneity of depression.

A homemade MLPA assay detects known CTNS mutations and identifies a novel deletion in a previously unresolved cystinosis family

Infantile nephropatic cystinosis is a rare, recessive, and genetically homogeneous disorder impairing renal function. It is caused by mutations in CTNS. Several large copy number aberrations have been identified but, for the majority of these, heterozygous patients and carriers can not easily be identified. We therefore developed a multiplex ligation-dependent probe amplification assay targeting eight of the twelve CTNS exons. We show that this assay is valid in detecting known deletions in both the homozygous and heterozygous state. The application to a family previously found mutation-negative by conventional screening revealed a novel large deletion which, as the first of its kind, does not involve the coding region. We conclude that our assay represents a valid tool for further completing the CTNS mutation spectrum and for simplified carrier testing in cystinosis families harboring copy number mutations. More generally, our study exemplifies the use of synthetic, homemade MLPA probesets as cheap, efficient, and rapidly available screening tools for small genes and/or very rare diseases.

Asthma: a simple concept but in reality a complex disease

Asthma is a disorder of the conducting airways that contract too easily and too much to cause variable airflow obstruction with symptoms of wheeze, cough, chest tightness and shortness of breath. Based on this knowledge, initial treatments were directed to dilating the contracted airways with anticholinergic and adrenergic drugs. The recognition that allergic-type inflammation underlay the hyperresponsive airways in asthma led to the introduction of anti-inflammatory drugs such as sodium cromoglicate and corticosteroids. Over the 2 decades that followed, these drugs have been progressively improved by increasing their therapeutic index and duration of action. A review of the recent literature indicates that since the 1980s, the explosive increase in knowledge of the cell and mediator mechanisms of asthma has only led to modest improvements in therapy including the introduction of leukotriene modifiers and a blocking monoclonal antibody against IgE. Indeed, biologics targeting allergic cytokines and effector cells have on the whole proven disappointing despite initial promise being shown in animal models. Part of the difficulty lies in the oversimplified concept that asthma is only driven by allergic processes when in reality there are many environmental causes and triggers and the view that it is a homogeneous disorder only varying in severity. The more recent views that asthma is a complex disorder made up of different subtypes with differing causes, treatment responses and natural histories creates a new opportunity for stratified medicine in which therapies acting upstream selectively target specific disease subtypes identified by specific diagnostic biomarkers.

Fronto-temporal lobar degeneration: neuropathology in 60 cases

Sixty cases of frontotemporal lobar degeneration (FTLD) were collected over 22 years. Brain weight was negatively correlated with disease duration. The neuronal and/or glial inclusions were labeled by anti-TDP, anti-FUS or anti-TAU antibodies, respectively, in 40, 3 and 12 cases. In the FTLD-TDP group, mutation of the progranulin gene was found in four cases (FTD-GRN), with nuclear, cat eye inclusions and severe neuronal loss in CA1 and subiculum. The motor neurons were involved in 27 cases (fronto-temporal dementia with amyotrophic lateral sclerosis = FTD-ALS). Familial FTD-ALS cases lived longer than sporadic ones. In nine cases, there was no ALS, no GRN mutation (FTD-NAP). The cases in the FTD-ALS and FTD-NAP subgroups were of Sampathu type 2 (TDP-positive inclusions located mostly in cell bodies and short neurites) with the exception of five cases which belonged to type 1 (long TDP-positive neurites in the superficial layers of the cortex). All of the FTLD-FUS of this series cases were affected by neuronal intermediate filament inclusion disease (NIFID). They were young. The survival was short. In the FTLD-tau group, mutations P301P (previously not recognized as pathogenic), P301L and S305N were identified. Pick disease (n = 5) appeared as a homogeneous sporadic disorder. The current nomenclature allows the neuropathological classification of nearly all the cases of FTD. The prevalence of the different types of FTD is tightly linked to the recruitment. This series was enriched in motor neuron disease (explaining the overall predominance of type 2 TDP inclusions).

New structural features of non-crystalline tetrahedrally bonded networks: A modeling approach

A large model of amorphous silicon (2052 atoms) with 0.5% dangling bonds has been built and investigated. The refinement of the coordinates evidenced the presence of small domains with advanced ordering. These domains preclude the formation of crystallization nuclei and play an essential role in the redistribution of the defects in the material with homogenization of the free energy and stabilization against aging. An effect of amorphization of the ordered nuclei due to free energy redistribution is assessed. The glass relaxation of a-Si (a-Ge) occurring during heating below T g receives a natural explanation as a structural change from local quasi-ordering to homogeneous disordering.

Disgust in contamination-based obsessive–compulsive disorder: a review and model

Obsessive–compulsive disorder (OCD) is characterized by the presence of unwanted, intrusive thoughts coupled with ritualized behaviors intended to reduce subjective anxiety. Although once considered a homogeneous disorder, recent findings support a view of OCD as consisting of symptom subtypes. Additionally, there has been increased interest in the contribution of disgust to various forms of psychopathology. The present article summarizes the available literature on contamination-based OCD with an emphasis on the role of disgust as it pertains to the etiology and maintenance of this form of OCD. We propose an updated model of contamination-based OCD that accounts for the elevated disgust response observed in individuals with this form of OCD. Treatment implications of a disgust-based model of the disorder are discussed in the context of cognitive–behavioral therapy.

Theoretical and Observed Subtypes of DSM-IV Alcohol-and Cannabis-Use Disorders in the Australian Population

Using a polythetic combinatorial approach to diagnosing substance-use disorders according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria inevitably leads to substantial clinical heterogeneity in the manifestation of these disorders. Not all theoretically possible combinations of symptoms are found in reports from North American samples. Cross-cultural differences in substance use and dependence make it important to consider patterns of problematic use in other countries. The heterogeneity of DSM-IV alcohol- and cannabis-use disorders in Australia was explored by calculating the number of theoretically possible subtypes for these disorders based on the DSM-IV diagnostic criteria and identifying which of these subtypes are observed in the 1997 National Survey on Mental Health and Wellbeing. Of the theoretically possible subtypes, 55.6% were observed for alcohol dependence, 73.3% for alcohol abuse, 61.9% for cannabis dependence, and 53.3% for cannabis abuse. Four subtypes, containing only one criterion each, accounted for 87.5% of individuals with alcohol abuse. Fourteen subtypes characterized 70% of participants with alcohol dependence. One subtype, use in physically hazardous situations, accounted for 75.7% of individuals with cannabis abuse. Eight subtypes represented 72.3% of individuals with cannabis dependence. Alcohol and cannabis abuse appear to be homogeneous disorders, whereas alcohol and cannabis dependence are heterogeneous disorders, in Australia. All of the DSM-IV diagnostic criteria for substance dependence contributed to understanding the symptoms associated with these disorders among Australians. The importance of not making major decisions regarding the type and number of diagnostic criteria for a given disorder based on analysis of data from a single country was highlighted.