Thought‐action fusion and inflated responsibility beliefs in obsessive‐compulsive disorder

In obsessive‐compulsive disorder (OCD), inflated responsibility (IR) beliefs and thought‐action fusion (TAF) are two cognitive schema argued to contribute to obsessions and compulsions. We investigated whether IR and TAF are OCD‐specific or whether they occur in other anxiety disorders. Adults diagnosed with OCD (n = 20) or other anxiety disorders (n = 21), and non‐clinical controls (n = 22) completed measures of OCD symptomatology and severity, TAF, appraisals and interpretations of responsibility, and depression. IR was more prominent in those with OCD as compared with those with other anxiety disorders, with correlational analyses confirming that a high sense of personal responsibility was associated with high levels of obsessionality even after controlling for depression. No group differences, however, emerged between the clinical groups on measures of TAF, both groups showing elevated TAF compared with controls. Indeed, TAF and obsessional symptoms were correlated only in the presence of negative affect. These results suggest that although IR may be higher in those with OCD compared with other anxiety disorders, TAF is not specific to OCD. Results are discussed in the context of cognitive appraisal models of OCD.     

Self‐compassion,trauma, and posttraumatic stress disorder: A systematic review

Self‐compassion has emerged as an important construct in the mental health literature. Although conceptual links between self‐compassion and trauma are apparent, a review has not been completed to examine whether this association is supported by empirical research findings. To systematically summarize knowledge on the association between trauma and/or posttraumatic stress disorder (PTSD) and self‐compassion. Searches were conducted in PsycINFO, PubMed, Ovid Medline, Web of Science, Embase, and PILOTS databases, and papers reporting a direct analysis on the relationship between these constructs were identified. The search yielded 35 studies meeting inclusion criteria. Despite considerable heterogeneity in study design, sample, measurement, and trauma type, there was consistent evidence to suggest that increased self‐compassion is associated with less PTSD symptomatology and some evidence to suggest that reduced fear of self‐compassion is associated with less PTSD symptomatology. There was tentative evidence to suggest that interventions based, in part or whole, on a self‐compassion model potentially reduce PTSD symptoms. Although findings are positive for the association between increased self‐compassion and reduced PTSD symptoms, the precise mechanism of these protective effects is unknown. Prospective and longitudinal studies would be beneficial in clarifying this. The review also highlighted the variability in what is and should be referred to as trauma exposure, indicating the need for further research to clarify the concept.     

Sympathetic and hypothalamic‐pituitary‐adrenal asymmetry in generalized anxiety disorder

Physiologic investigations of generalized anxiety disorder (GAD) have skewed toward assessment of the autonomic nervous system, largely neglecting hypothalamic‐pituitary‐adrenal (HPA) axis variables. Although these systems coordinate—suggesting a degree of symmetry—to promote adaptive functioning, most studies opt to monitor either one system or the other. Using a ratio of salivary alpha‐amylase (sAA) over salivary cortisol, the present study examined symmetry between the sympathetic nervous system (SNS) and HPA axis in individuals with GAD (n = 71) and healthy controls (n = 37). Compared to healthy controls, individuals with GAD exhibited greater baseline ratios of sAA/cortisol and smaller ratios of sAA/cortisol following a mental arithmetic challenge. We propose that the present study provides evidence for SNS‐HPA asymmetry in GAD. Further, these results suggest that increased SNS suppression in GAD may be partially mediated by cortisol activity.     

Sleep‐disordered breathing in major depressive disorder

Individuals with major depressive disorder often experience obstructive sleep apnea. However, the relationship between depression and less severe sleep‐disordered breathing is unclear. This study examined the rate of sleep‐disordered breathing in depression after excluding those who had clinically significant sleep apnea (>5 apneas?h^?1). Archival data collected between 1991 and 2005 were used to assess the prevalence of sleep‐disordered breathing events in 60 (31 depressed; 29 healthy controls) unmedicated participants. Respiratory events were automatically detected using a program developed in‐house measuring thermal nasal air‐flow and chest pressure. Results show that even after excluding participants with clinically significant sleep‐disordered breathing, individuals with depression continue to exhibit higher rates of sleep‐disordered breathing compared with healthy controls (depressed group: apnea–hypopnea index mean = 0.524, SE = 0.105; healthy group: apnea–hypopnea index mean = 0.179, SE = 0.108). Exploratory analyses were also conducted to assess for rates of exclusion in depression studies due to sleep‐disordered breathing. Study exclusion of sleep‐disordered breathing was quantified based on self‐report during telephone screening, and via first night polysomnography. Results from phone screening data reveal that individuals reporting depression were 5.86 times more likely to report a diagnosis of obstructive sleep apnea than presumptive control participants. Furthermore, all of the participants excluded for severe sleep‐disordered breathing detected on the first night were participants with depression. These findings illustrate the importance of understanding the relationship between sleep‐disordered breathing and depression, and suggest that screening and quantification of sleep‐disordered breathing should be considered in depression research.     

Fronto‐striato‐limbic hyperactivation in obsessive‐compulsive disorder during individually tailored symptom provocation

Anxiety disorders have been linked to a hyperactivated cortico‐amygdalar circuitry, but the amygdala's role in the pathophysiology of obsessive‐compulsive disorder (OCD) remains unclear. This fMRI study examined the cortico‐limbic correlates of individually tailored symptom provocation in 14 unmedicated OCD patients and 14 controls. In addition to OCD‐relevant pictures, aversive and neutral control stimuli were included. Patients showed increased fronto‐striatal activation to OCD‐relevant stimuli contrasted with both control categories. Briefly presented symptom‐related triggers elicited stronger amygdala engagement in patients than in controls. This effect, however, did also occur to aversive stimuli and was not symptom specific. Augmented amygdala involvement in patients reflects general emotional hyperarousal. Symptom‐specific frontal activation points towards a sustained endeavor to suppress exaggerated emotional responses to OCD triggers.     

Cardiac stability at differing levels of temporal analysis in panic disorder,post‐traumatic stress disorder,and healthy controls

The panic disorder (PD) literature provides evidence for both physiologic rigidity and instability as pathognomonic features of this disorder. This ambiguity may be a result of viewing PD at differential levels of temporal analysis. We assessed cardiac variability across three levels of temporal scale in PD patients, post‐traumatic stress disorder (PTSD) patients, and healthy controls. Sixteen healthy controls, 14 PD patients, 23 PTSD patients, and 16 PTSD + PD patients presented for a polysomnogram. Differences were assessed in respiratory sinus arrhythmia (RSA), autoregressive stability of heart rate (HR), and the number of nonspecific accelerations in HR over the night. No differences in RSA were found between groups; however, PD patients exhibited significantly lower autoregressive HR stability, and all patients had significantly more HR accelerations than controls. These data reinforce prior findings demonstrating physiologic instability in PD and indicate that prior equivocalities regarding physiologic variability in PD may be due to limited temporal scaling of measurements.     

Voxel‐wise brain‐wide functional connectivity abnormalities in first‐episode,drug‐naive patients with major depressive disorder

Due to different foci and single sample across studies, abnormal functional connectivity (FC) has been implicated in the pathophysiology of major depressive disorder (MDD) with inconsistent results. The inconsistency may reflect a combination of clinical and methodological variability, which leads to limited reproducibility of these findings. The samples included 59 patients with MDD and 31 controls from Sample 1, 29 patients with MDD and 24 controls from Sample 2, and 31 patients with schizophrenia and 37 controls from Sample 3. Global‐brain FC (GFC) and an overlapping technique were applied to analyze the imaging data. Compared with healthy controls, patients with MDD in Samples 1 and 2 showed increased GFC in the overlapped brain areas, including the bilateral insula, right inferior parietal lobule (IPL), and right supramarginal gyrus/IPL. By contrast, decreased GFC in the overlapped brain areas, including the bilateral posterior cingulate cortex/presuneus and left calcarine cortex, was found in patients with MDD. In addition, patients with schizophrenia in Sample 3 did not show any GFC abnormalities in the overlapped areas from the results of Samples 1 and 2. The present study is the first to examine voxel‐wise brain‐wide FC in MDD with two independent samples by using an overlapping technique. The results indicate that aberrant FC patterns of insula‐centered sensorimotor circuit may account for the pathophysiology of MDD.     

Haplotype co‐segregation with attention deficit‐hyperactivity disorder in unrelated german multi‐generation families

Complex disorders have proved to be elusive in the search for underlying genetic causes. In the presence of large multi‐generation pedigrees with multiple affected individuals, heritable familial forms of the disorders can be postulated. Observations of particular chromosomal haplotypes shared among all affected individuals within pedigrees may reveal chromosomal regions, in which the disease‐related genes may be located. Hence, the biochemical pathways involved in pathogenesis can be exposed. We have recruited eight large Attention Deficit‐Hyperactivity Disorder (ADHD, OMIM: #143465) families of German descent. Densely spaced informative microsatellite markers with high heterozygosity rates were used to fine‐map and haplotype chromosomal regions of interest in these families. In three subsets and one full family of the eight ADHD families, haplotypes co‐segregating with ADHD‐affected individuals were identified at chromosomes 1q25, 5q11–5q13, 9q31–9q32, and 18q11–18q21. Positive LOD scores supported these co‐segregations. The existence of haplotypes co‐segregating among affected individuals in large ADHD pedigrees suggests the existence of Mendelian forms of the disorder and that ADHD‐related genes are located within these haplotypes. In depth sequencing of these haplotype regions can identify causative genetic mechanisms and will allow further insights into the clinico‐genetics of this complex disorder. © 2013 Wiley Periodicals, Inc.     

Genetic meta‐analysis of obsessive–compulsive disorder and self‐report compulsive symptoms

We investigated whether obsessive–compulsive (OC) symptoms from a population‐based sample could be analyzed to detect genetic variants influencing obsessive–compulsive disorder (OCD). We performed a genome‐wide association studies (GWAS) on the obsession (rumination and impulsions) and compulsion (checking, washing, and ordering/precision) subscales of an abbreviated version of the Padua Inventory (N = 8,267 with genome‐wide genotyping and phenotyping). The compulsion subscale showed a substantial and significant positive genetic correlation with an OCD case–control GWAS (r _G = 0.61, p = .017) previously published by the Psychiatric Genomics Consortium (PGC‐OCD). The obsession subscale and the total Padua score showed no significant genetic correlations (r _G = ?0.02 and r _G = 0.42, respectively). A meta‐analysis of the compulsive symptoms GWAS with the PGC‐OCD revealed no genome‐wide significant Single‐Nucleotide Polymorphisms (SNPs combined N = 17,992, indicating that the power is still low for individual SNP effects). A gene‐based association analysis, however, yielded two novel genes (WDR7 and ADCK1). The top 250 genes in the gene‐based test also showed a significant increase in enrichment for psychiatric and brain‐expressed genes. S‐Predixcan testing showed that for genes expressed in hippocampus, amygdala, and caudate nucleus significance increased in the meta‐analysis with compulsive symptoms compared to the original PGC‐OCD GWAS. Thus, the inclusion of dimensional symptom data in genome‐wide association on clinical case–control GWAS of OCD may be useful to find genes for OCD if the data are based on quantitative indices of compulsive behavior. SNP‐level power increases were limited, but aggregate, gene‐level analyses showed increased enrichment for brain‐expressed genes related to psychiatric disorders, and increased association with gene expression in brain tissues with known emotional, reward processing, memory, and fear‐formation functions.     

Three new cases of ataxia‐telangiectasia‐like disorder: No impairment of the ATM pathway,but S‐phase checkpoint defect

Ataxia‐telangiectasia‐like disorder (ATLD) is a rare genomic instability syndrome caused by biallelic variants of MRE11 (meiotic recombination 11) characterized by progressive cerebellar ataxia and typical karyotype abnormalities. These symptoms are common to those of ataxia‐telangiectasia, which is consistent with the key role of MRE11 in ataxia‐telangiectasia mutated (ATM) activation after DNA double‐strand breaks. Three unrelated French patients were referred with ataxia. Only one had typical karyotype abnormalities. Unreported biallelic MRE11 variants were found in these three cases. Interestingly, one variant (c.424G>A) was present in two cases and haplotype analysis strongly suggested a French founder variant. Variants c.544G>A and c.314+4_314+7del lead to splice defects. The level of MRE11 in lymphoblastoid cell lines was consistently and dramatically reduced. Functional consequences were evaluated on activation of the ATM pathway via phosphorylation of ATM targets (KAP1 and CHK2), but no consistent defect was observed. However, an S‐phase checkpoint activation defect after camptothecin was observed in these patients with ATLD. In conclusion, we report the first three French ATLD patients and a French founder variant, and propose an S‐phase checkpoint activation study to evaluate the pathogenicity of MRE11 variants.     

Expanding the clinical and genetic spectra of NKX6‐2‐related disorder

Hypomyelinating leukodystrophies (HLDs) affect the white matter of the central nervous system and manifest as neurological disorders. They are genetically heterogeneous. Very recently, biallelic variants in NKX6‐2 have been suggested to cause a novel form of autosomal recessive HLD. Using whole‐exome or whole‐genome sequencing, we identified the previously reported c.196delC and c.487C>G variants in NKX6‐2 in 3 and 2 unrelated index cases, respectively; the novel c.608G>A variant was identified in a sixth patient. All variants were homozygous in affected family members only. Our patients share a primary diagnosis of psychomotor delay, and they show spastic quadriparesis, nystagmus and hypotonia. Seizures and dysmorphic features (observed in 2 families each) represent an addition to the phenotype, while developmental regression (observed in 3 families) appears to be a notable and previously underestimated clinical feature. Our findings extend the clinical and mutational spectra associated with this novel form of HLD. Comparative analysis of our 10 patients and the 15 reported previously did, however, not reveal clear evidence for a genotype‐phenotype correlation.     

Three‐dimensional localisation of NANOG,OCT4, and E‐cadherin in porcine pre‐ and peri‐implantation embryos

The expression patterns of NANOG and OCT4 have previously been reported to differ markedly between mammalian species indicating distinct species‐specific roles during development. We investigate the three‐dimensional expression pattern of NANOG and OCT4 in porcine pre‐ and peri‐implantation embryos. The expression of NANOG differed remarkably from that reported in other species. NANOG was not detected in the inner cell mass of hatched porcine blastocysts, but later appeared in the epiblast and hypoblast of spherical blastocysts where Rauber's layer had disintegrated. In pre‐gastrulating, filamentous embryos NANOG was localised to nuclei in a minor portion of the epiblast cells in which E‐CADHERIN seemed to be up‐regulated and OCT4 down‐regulated. Later NANOG was restricted to the potential PGCs. OCT4 was detected in inner cell mass, epiblast, and mesoderm, and we found that OCT4 expression, in contrast to earlier speculations, at least in hatched blastocysts, resembles the expression pattern in the mouse embryo. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.     

Laboratory testing of SARS‐CoV,MERS‐CoV,and SARS‐CoV‐2 (2019‐nCoV): Current status,challenges, and countermeasures

Emerging and reemerging infectious diseases are global public concerns. With the outbreak of unknown pneumonia in Wuhan, China in December 2019, a new coronavirus, SARS‐CoV‐2 has been attracting tremendous attention. Rapid and accurate laboratory testing of SARS‐CoV‐2 is essential for early discovery, early reporting, early quarantine, early treatment, and cutting off epidemic transmission. The genome structure, transmission, and pathogenesis of SARS‐CoV‐2 are basically similar to SARS‐CoV and MERS‐CoV, the other two beta‐CoVs of medical importance. During the SARS‐CoV and MERS‐CoV epidemics, a variety of molecular and serological diagnostic assays were established and should be referred to for SARS‐CoV‐2. In this review, by summarizing the articles and guidelines about specimen collection, nucleic acid tests (NAT) and serological tests for SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2, several suggestions are put forward to improve the laboratory testing of SARS‐CoV‐2. In summary, for NAT: collecting stool and blood samples at later periods of illness to improve the positive rate if lower respiratory tract specimens are unavailable; increasing template volume to raise the sensitivity of detection; putting samples in reagents containing guanidine salt to inactivate virus as well as protect RNA; setting proper positive, negative and inhibition controls to ensure high‐quality results; simultaneously amplifying human RNase P gene to avoid false‐negative results. For antibody test, diverse assays targeting different antigens, and collecting paired samples are needed.