Subgroup Of Disorders Research Articles

Functional constipation: A commonand often overlooked cause for abdominal pain in children.

The most common causes for chronic pain abdomen in pediatric practice are functional abdominal pain disorders, a subgroup of functional gastrointestinal disorders under the Rome IV classification. Constipation is usually associated with painful defecation, but abdominal pain as a predominant or presenting symptom of functional constipation (FC) is not very well recognized. We conducted this study to ascertain the prevalence of FC in chronic pain abdomen and proportion of FC children presenting with predominant complaints of pain abdomen. Prevalence of FC and functional abdominal pain was ascertained separately over a1-year in children > 4 years of age in our hospital. The number of children with FC presenting with abdominal pain was noted. Abdominal pain site and duration werenoted in the FC group and werecompared with those in the functional abdominal pain group to find out any significance. Diagnosis was based on Rome IV criteria, but relevant investigations to rule out organic pathology were done whenever clinically indicated. The prevalence of abdominal pain was 22% in our gastroenterology service and that of FC was 27%. Among the children presenting with chronic abdominal pain, FC was seen in 10% of the patients and functional abdominal pain disorders in 34%. Among children presenting with constipation, 12% had pain as the sole complaint. However, some form of pain or pain as one of the symptoms was seen in 47.5%. FC is a major cause for abdomen pain in children and is often overlooked. Not attributing pain to constipation may delay the diagnosis, which may have poor prognosis.

Neighbourhood characteristics and the treated incidence rate of borderline personality pathology among young people.

The impact of the wider social environment, such as neighbourhood characteristics, has not been examined in the development of borderline personality disorder. This study aimed to determine whether the treated incidence rate of full-threshold borderline personality disorder and sub-threshold borderline personality disorder, collectively termed borderline personality pathology, was associated with the specific neighbourhood characteristics of social deprivation and social fragmentation. This study included young people, aged 15-24 years, who attended Orygen's Helping Young People Early programme, a specialist early intervention service for young people with borderline personality pathology, from 1 August 2000-1 February 2008. Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Personality Disorders, and census data from 2006 were used to determine the at-risk population and to obtain measures of social deprivation and fragmentation. The study included 282 young people, of these 78.0% (n = 220) were female and the mean age was 18.3 years (SD = ±2.7). A total of 42.9% (n = 121) met criteria for full-threshold borderline personality disorder, and 57.1% (n = 161) had sub-threshold borderline personality disorder, defined as having three or four of the nine Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) borderline personality disorder criteria. There was more than a sixfold increase in the treated incidence rate of borderline personality pathology in the neighbourhoods of above average deprivation (Quartile 3) (incidence rate ratio = 6.45, 95% confidence interval: [4.62, 8.98], p < 0.001), and this was consistent in the borderline personality disorder sub-groups. This association was also present in the most socially deprived neighbourhood (Quartile 4) (incidence rate ratio = 1.63, 95% confidence interval: [1.10, 2.44]), however, only for those with sub-threshold borderline personality disorder. The treated incidence of borderline personality pathology increased incrementally with the level of social fragmentation (Quartile 3: incidence rate ratio = 1.93, 95% confidence interval: [1.37, 2.72], Quartile 4: incidence rate ratio = 2.38, 95% confidence interval: [1.77, 3.21]). Borderline personality pathology has a higher treated incidence in the more socially deprived and fragmented neighbourhoods. These findings have implications for funding and location of clinical services for young people with borderline personality pathology. Prospective, longitudinal studies should examine neighbourhood characteristics as potential aetiological factors for borderline personality pathology.

New-Onset Bipolar Disorder in Late Life: a case report and review of literature

IntroductionThe elderly represents the fastest growing group of the population. It is fair to assume that the portion of old age patients suffering from bipolar disorder will grow in a similar manner. Elderly patients represent approximately 25% of the bipolar population. Summarizing, 5–10% of patients were 50 years of age when they experienced their first manic episode, constituting the subgroup of late onset bipolar disorder (LOBD).ObjectivesThe purpose of this case report and literature review is to emphasise the importance of LOBD in old population and to highlight its still sparse-knowledge.MethodsDescriptive case study and review of literature (Arnold,I. et al. Old Age Bipolar Disorder—Epidemiology, Aetiology and Treatment. Medicina 2021,57,587; Baldessarini et al. Onset-age of bipolar disorders at six international sites. J Affect Disord 2010;121(1-2):143-6).ResultsA 60-year-old woman is brought to the emergency department for evaluation by her family. Over the past 7 days, the patient has become increasingly irritable and argumentative, is sleeping less, is talking faster than usual and has begun to express paranoid concerns about her students “stealing my exam”. The patient is a university professor.In the assessment interview she is hyperverbal, expansive, and grandiose. The family has also just recently discovered that she has spent a large sum of money on the Internet.She has no history of psychiatric contact or substance use disorders; however, she has a family history of severe depression.In the absence of any plausible non-psychiatric condition that could mimic or induce mania, the working diagnosis is bipolar I disorder, most recent episode (MRE) manic with psychotic features.Image:Image 2:ConclusionsThe share of older age bipolar disorder will grow constantly in the next decades and further research on this neglected patient group is urgently required.Disclosure of InterestNone Declared

Definition of early age at onset in bipolar disorder according to distinctive neurodevelopmental pathways: insights from the FACE-BD study.

Converging evidence suggests that a subgroup of bipolar disorder (BD) with an early age at onset (AAO) may develop from aberrant neurodevelopment. However, the definition of early AAO remains unprecise. We thus tested which age cut-off for early AAO best corresponds to distinguishable neurodevelopmental pathways. We analyzed data from the FondaMental Advanced Center of Expertise-Bipolar Disorder cohort, a naturalistic sample of 4421 patients. First, a supervised learning framework was applied in binary classification experiments using neurodevelopmental history to predict early AAO, defined either with Gaussian mixture models (GMM) clustering or with each of the different cut-offs in the range 14 to 25 years. Second, an unsupervised learning approach was used to find clusters based on neurodevelopmental factors and to examine the overlap between such data-driven groups and definitions of early AAO used for supervised learning. A young cut-off, i.e. 14 up to 16 years, induced higher separability [mean nested cross-validation test AUROC = 0.7327 (± 0.0169) for ⩽16 years]. Predictive performance deteriorated increasing the cut-off or setting early AAO with GMM. Similarly, defining early AAO below 17 years was associated with a higher degree of overlap with data-driven clusters (Normalized Mutual Information = 0.41 for ⩽17 years) relatively to other definitions. Early AAO best captures distinctive neurodevelopmental patterns when defined as ⩽17 years. GMM-based definition of early AAO falls short of mapping to highly distinguishable neurodevelopmental pathways. These results should be used to improve patients' stratification in future studies of BD pathophysiology and biomarkers.

Antenatal Corticosteroid Exposure is Associated with Childhood Mental Disorders in Late Preterm and Term Infants.

To study the association between antenatal corticosteroids treatment and childhood mental disorders in infants born at different gestational ages, and to investigate the effect of different administration timing. This population-based cohort study used data from the Taiwan National Health Insurance Research Database. All singleton live births born between 2004 and 2010 were enrolled and followed up for at least 6years. The primary outcome was any childhood mental disorder. Secondary outcomes included 7 specific subgroups of mental disorders. A total of 1 163 443 singleton infants were included in the analysis, and 16 847 (1.45%) infants were exposed to antenatal corticosteroid treatment. Children exposed to antenatal corticosteroids were found to have a higher risk of developing childhood mental disorders in the entire cohort (hazard ratio [HR], 1.13; 95% CI, 1.08-1.18), the term group (HR, 1.11; 95% CI, 1.05-1.16), and the late-preterm group (HR, 1.15; 95% CI, 1.06-1.25). The administration of corticosteroids in the early stage of pregnancy (<28weeks of gestation) significantly increased the risk of childhood mental disorders (HR, 1.22; 95% CI, 1.14-1.31). Exposure to antenatal corticosteroid treatment increases the cumulative risk of childhood mental disorders and attention deficit hyperactivity disorders, both in term and late preterm infants. The administration of corticosteroids in the early stage of pregnancy tends to increase the risk of mental disorders.

The efficacy of lumateperone on symptoms of depression in bipolar I and bipolar II disorder: Secondary and post hoc analyses

A recent Phase 3, randomized, double-blind, placebo-controlled study established that lumateperone 42-mg monotherapy significantly improved symptoms of depression in patients with bipolar depression. This manuscript reports prespecified secondary and post hoc efficacy analyses. Patients with bipolar I or bipolar II disorder experiencing a major depressive episode were randomized 1:1 to lumateperone 42 mg or placebo, administered orally once daily for 6 weeks. Prespecified analyses evaluated change from baseline to Day 43 in individual Montgomery-Åsberg Depression Rating Scale (MADRS) item scores in the modified intent-to-treat population (mITT) and bipolar I and bipolar II disorder subgroups. Post hoc analyses investigated the MADRS anhedonia factor and categorical shifts in MADRS item scores. In the mITT, there was significant improvement from baseline to Day 43 with lumateperone 42 mg compared with placebo for all 10 MADRS items; most MADRS items significantly improved in subgroups with bipolar I (9 items) and bipolar II disorder (8 items). A significantly higher proportion of patients receiving lumateperone compared with placebo shifted from baseline MADRS item score ≥4 to ≤2 at end of treatment in Reported Sadness, Reduced Sleep, Concentration Difficulties, Lassitude, Inability to Feel, and Pessimistic Thoughts. Lumateperone significantly improved the MADRS anhedonia factor from baseline to Day 43 compared with placebo in the mITT (effect size, −0.47) and subgroups with bipolar I (−0.36) and bipolar II disorder (−0.90). Lumateperone 42 mg treatment significantly improved depression symptoms compared with placebo, with consistent efficacy across a broad range of symptoms in people with bipolar I and bipolar II disorder.

Catecholaminergic and cholinergic neuromodulation in autism spectrum disorder: A comparison to attention-deficit hyperactivity disorder.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social impairments and restricted, repetitive behaviors. Treatment of ASD is notoriously difficult and might benefit from identification of underlying mechanisms that overlap with those disturbed in other developmental disorders, for which treatment options are more obvious. One example of the latter is attention-deficit hyperactivity disorder (ADHD), given the efficacy of especially stimulants in treatment of ADHD. Deficiencies in catecholaminergic systems [dopamine (DA), norepinephrine (NE)] in ADHD are obvious targets for stimulant treatment. Recent findings suggest that dysfunction in catecholaminergic systems may also be a factor in at least a subgroup of ASD. In this review we scrutinize the evidence for catecholaminergic mechanisms underlying ASD symptoms, and also include in this analysis a third classic ascending arousing system, the acetylcholinergic (ACh) network. We complement this with a comprehensive review of DA-, NE-, and ACh-targeted interventions in ASD, and an exploratory search for potential treatment-response predictors (biomarkers) in ASD, genetically or otherwise. Based on this review and analysis we propose that (1) stimulant treatment may be a viable option for an ASD subcategory, possibly defined by genetic subtyping; (2) cerebellar dysfunction is pronounced for a relatively small ADHD subgroup but much more common in ASD and in both cases may point toward NE- or ACh-directed intervention; (3) deficiency of the cortical salience network is sizable in subgroups of both disorders, and biomarkers such as eye blink rate and pupillometric data may predict the efficacy of targeting this underlying deficiency via DA, NE, or ACh in both ASD and ADHD.

New-Onset Sleep Disorders before Cardiac Surgery May Indicate an Increased Risk of Postoperative Atrial Fibrillation.

We aimed to determine if sleep disorders before cardiac surgery indicate an increased risk of postoperative atrial fibrillation (POAF). In this study, 238 patients undergoing coronary artery bypass grafting in our center were included. Patients were separated into the preoperative sleep disorder group and the control group. The primary endpoint was the incidence of POAF, and the secondary endpoints were the incidence of postoperative stroke, duration of invasive ventilation, length of intensive care unit, and hospitalization stay. Propensity score matching and multivariable logistic regression were used for adjusting potential confounders. A total of 165 (69.3%) patients had sleep disorders before surgery, and 73 well-matched pairs were generated. A higher incidence of POAF was found in the preoperative sleep disorder group (16.4% versus 5.5%, p = 0.034). In multivariable logistic regression, preoperative sleep disorders were correlated to a higher risk of POAF (odds ratio = 4.627, 95% confidence interval: 1.181-18.123, p = 0.028). In the subgroup of patients without long-term sleep disorders, those who experienced preoperative sleep disorders had a higher incidence of POAF (16.1% versus 4.3%, p = 0.024), meanwhile, no difference was found in the subgroup of long-term sleep disorders. New-onset sleep disorders before cardiac surgery may indicate a higher incidence of POAF.

DRDs and Brain-Derived Neurotrophic Factor Share a Common Therapeutic Ground: A Novel Bioinformatic Approach Sheds New Light Toward Pharmacological Treatment of Cognitive and Behavioral Disorders.

Cognitive and behavioral disorders are subgroups of mental health disorders. Both cognitive and behavioral disorders can occur in people of different ages, genders, and social backgrounds, and they can cause serious physical, mental, or social problems. The risk factors for these diseases are numerous, with a range from genetic and epigenetic factors to physical factors. In most cases, the appearance of such a disorder in an individual is a combination of his genetic profile and environmental stimuli. To date, researchers have not been able to identify the specific causes of these disorders, and as such, there is urgent need for innovative study approaches. The aim of the present study was to identify the genetic factors which seem to be more directly responsible for the occurrence of a cognitive and/or behavioral disorder. More specifically, through bioinformatics tools and software as well as analytical methods such as systemic data and text mining, semantic analysis, and scoring functions, we extracted the most relevant single nucleotide polymorphisms (SNPs) and genes connected to these disorders. All the extracted SNPs were filtered, annotated, classified, and evaluated in order to create the "genomic grammar" of these diseases. The identified SNPs guided the search for top suspected genetic factors, dopamine receptors D and neurotrophic factor BDNF, for which regulatory networks were built. The identification of the "genomic grammar" and underlying factors connected to cognitive and behavioral disorders can aid in the successful disease profiling and the establishment of novel pharmacological targets and provide the basis for personalized medicine, which takes into account the patient's genetic background as well as epigenetic factors.

LGMDR1 with Prominent Limb–Joint Contractures and Inflammatory Changes Misdiagnosed as Scleromyositis with a Novel CAPN3 Mutation: A Case Report

Muscle diseases with prominent limb–joint contractures (LJCs) are a subgroup of rare neuromuscular disorders. Prominent LJCs are not specific to genetic myopathies. Myositis can also induce severe contractures, especially in the late stages. We report the case of a 12-year-old girl with a 3-year history of painful muscular weakness with generalized LJCs. The inflammatory pattern associated with positive anti-PM/ Scl antibodies on muscle biopsy allowed us to initially retain the diagnosis of scleromyositis. After 12 months of corticosteroids and immunosuppressive treatment, there was no clinical improvement, and creatine kinase levels remained high (over 10 times the normal value). A second muscle biopsy showed persistent inflammatory infiltrate with the appearance of dystrophic features. Immunohistochemical analysis showed the absence of class 1 major histocompatibility complex expression on muscle fibres, raising the possibility of the diagnosis of muscular dystrophy. Whole-exome sequencing revealed a missense homozygous novel mutation c.386G&gt;T (p.Arg129Ile) on the calpain 3 gene, finally confirming the diagnosis of autosomal recessive limb–girdle muscular dystrophy recessive type 1 (or calpainopathy). This case report highlights the diagnostic challenges and the importance of a comprehensive evaluation in cases of muscle diseases with prominent LJCs.

Phenomenology, quality of life, and predictors of reversibility in patients with drug-induced movement disorders: a prospective study.

Drug-induced movement disorders (DIMDs) form an important subgroup of secondary movement disorders, which despite conferring a significant iatrogenic burden, tend to be under-recognized and inappropriately managed. We aimed to look into phenomenology, predictors of reversibility, and its impact on the quality of life of DIMD patients. We conducted the study in the Department of Neurology at a tertiary-care centre in India. The institutional ethics-committee approved the study. We assessed 55-consecutive DIMD patients at presentation to our movement disorder clinic. Subsequently, they followed up to evaluate improvement in severity-scales (UPDRS, UDRS, BARS, AIMS) and quality of life (EuroQol-5D-5L). Wilcoxan-signed-rank test compared the scales at presentation and follow-up. Binary-logistic-regrerssion revealed the independent predictors of reversibility. Fourteen patients (25.45%) had acute-subacute DIMD and 41 (74.55%) had tardive DIMD. Tardive-DIMD occurred more commonly in the elderly (age 50.73±16.92 years, p<0.001). Drug-induced-Parkinsonism (DIP) was the most common MD, followed by tardivedyskinesia. Risperidone and levosulpiride were the commonest culprit drugs. Patients in both the groups showed a statistically significant response to drug-dose reduction /withdrawal based on follow-up assessment on clinical-rating-scales and quality of life scores (EQ-5D-5L). DIMD was reversible in 71.42% of acute-subacute DIMD and 24.40% of patients with chronic DIMD (p=0.001). Binary-logistic-regression analysis showed acute-subacute DIMDs and DIP as independent predictors of reversibility. DIP is the commonest and often reversible drug-induced movement disorder. Levosulpiride is notorious for causing DIMD in the elderly, requiring strict pharmacovigilance.

The Incidence of Post-infectious Irritable Bowel Syndrome, Anxiety, and Depression in Iranian Patients with Coronavirus Disease 2019 Pandemic: A Cross-Sectional Study.

Irritable bowel syndrome refers to a subgroup of disorders of gut-brain interaction associated with stress-related symptoms, but gastrointestinal infection can also be considered the leading risk factor. It is well reported that coronavirus disease 2019 can also result in gastroenteritis. Therefore, this study aimed to evaluate the incidence of post-infectious irritable bowel syndrome and stressful status among coronavirus disease 2019 patients. This cross-sectional study was conducted on adults with coronavirus disease 2019 referred to the Infectious Disease Clinic in Iran from November 2020 to February 2021. Patients who met all eligibility criteria were included in the study. The data were collected using a demographic questionnaire, Rome IV criteria questionnaire, and Hospital Anxiety and Depression Scale. Totally, the data obtained from 233 eligible patients (136 women, 97 men; mean age 38.41) 11.52 (years) were collected and analyzed, and 53.2% of the cases had a moderate coronavirus disease 2019. The analysis showed that 27 (11.6%) patients suffered from irritable bowel syndrome symptoms based on Rome IV criteria after the recovery from the infection. Also, Hospital Anxiety and Depression Scale-based symptoms of depression and anxiety that occurred with coronavirus disease 2019 were reported in 27.4% and 36.9%, respectively. Our finding illustrated that irritable bowel syndrome symptoms based on Rome IV could occur in post-infected coronavirus disease 2019 patients. Also, Hospital Anxiety and Depression Scale-based symptoms of depression and anxiety were more common in females and coronavirus disease 2019 infected patients with clinical symptoms including cough, shortness of breath, and sore throat.

Troubles de la régulation sensorielle en pédopsychiatrie

IntroductionThe processing of sensory information determines the development and growth of a child's abilities. Dysfunction in the processing of sensory stimuli can affect a child's behavior and can disrupt development. Sensory Regulation Disorders are frequently associated with Autism Spectrum Disorder (ASD), with the DSM-5 even including it as a diagnostic criterion. However, they are also observed in other neurodevelopmental disorders. At present, the frequency of Sensory Regulation Disorders in children consulting child psychiatry has never been evaluated, although it seems to be a population at risk. ObjectivesTo evaluate the frequency of sensory regulation disorders in children between 3 and 6 years old who first consult a child psychiatrist in Marseille. To determine whether certain reasons for consultation are correlated with the presence of sensory regulation disorders. MethodsA multicenter cross-sectional study was conducted for four months in Marseille. Sensory regulation disorders were assessed by the second version of Dunn's short sensory profile. ResultsFifty-eight patients were included. A significant difference was found between the frequency of SRT in our primary child psychiatry population and the general population. Subgroup analyses according to the reason for consultation showed that there would be more SRT in the Motor Instability/Inattention, Conduct Disorder and Socialization Disorder subgroups. ConclusionWe observed a higher frequency of SRT in the child psychiatry consultation population. SRT could explain, or at least partly participate in, the children's symptomatology. The results are in favor of an early detection of SRT in the population of children consulting child psychiatry. The evaluation of the sensory profiles of these children allows a better understanding of the child's functioning and an adjustment of the intervention and support strategies proposed to the family.

Editorial introductions.

Editorial introductions.

Clinical correlates of late-onset versus early-onset bipolar disorder in a global sample of older adults.

Late-onset bipolar disorder (LOBD) represents a significant subgroup of bipolar disorder (BD). However, knowledge for this group is mostly extrapolated from small studies in subjects with early/mixed age of illness onset. In this global sample of older adults with BD (OABD: ≥50years old) we aim to characterize the sociodemographic and clinical presentation of LOBD (≥40years at BD onset) compared to early-onset BD (EOBD: <40years at BD onset). The Global Aging and Geriatric Experiments in Bipolar Disorder consortium provided international data on 437 older age bipolar disorder participants. We compared LOBD versus EOBD on depression, mania, functionality, and physical comorbidities. Exploratory analyses were performed on participants with BD onset ≥50years old. LOBD (n=105) did not differ from EOBD (n=332) on depression, mania, global functioning, nor employment status (p>0.05). Late-onset bipolar disorder was associated with higher endocrine comorbidities (odds ratio=1.48, [95%CI=1.0,12.1], p=0.03). This difference did not remain significant when subjects with BD onset ≥50years old were analyzed. This study is limited by the retrospective nature of the variable age of onset and the differences in evaluation methods across studies (partially overcame by harmonization processes). The present analysis is in favor of the hypothesis that LOBD might represent a similar clinical phenotype as classic EOBD with respect to core BD symptomatology, functionality, and comorbid physical conditions. Large-scale global collaboration to improve our understanding of BD across the lifespan is needed.

Using single molecule Molecular Inversion Probes as a cost-effective, high-throughput sequencing approach to target all genes and loci associated with macular diseases.

Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age-related MD (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing the ABCA4 gene in patients with Stargardt disease to identify associated coding and noncoding variation, however many MD patients still remain genetically unexplained. We hypothesized that the missing heritability of MDs may be revealed by smMIPs-based sequencing of all MD-associated genes and risk factors. Using 17,394 smMIPs, we sequenced the coding regions of 105 iMD and AMD-associated genes and noncoding or regulatory loci, known pseudo-exons, and the mitochondrial genome in two test cohorts that were previously screened for variants in ABCA4. Following detailed sequencing analysis of 110 probands, a diagnostic yield of 38% was observed. This established an ''MD-smMIPs panel,"enabling a genotype-first approach in a high-throughput and cost-effective manner, whilst achieving uniform and high coverage across targets. Further analysis will identify known and novel variants in MD-associated genes to offer an accurate clinical diagnosis to patients. Furthermore, this will reveal new genetic associations for MD and potential genetic overlaps between iMD and AMD.

Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events.

Neuroinflammation is discussed to play a role in specific subgroups of different psychiatric disorders, including anxiety disorders. We have previously shown that a mouse model of trait anxiety (HAB) displays enhanced microglial density and phagocytic activity in key regions of anxiety circuits compared to normal-anxiety controls (NAB). Using minocycline, we provided causal evidence that reducing microglial activation within the dentate gyrus (DG) attenuated enhanced anxiety in HABs. Besides pharmacological intervention, "positive environmental stimuli", which have the advantage of exerting no side-effects, have been shown to modulate inflammation-related markers in human beings. Therefore, we now investigated whether environmental enrichment (EE) would be sufficient to modulate upregulated neuroinflammation in high-anxiety HABs. We show for the first time that EE can indeed attenuate enhanced trait anxiety, even when presented as late as adulthood. We further found that EE-induced anxiolysis was associated with the attenuation of enhanced microglial density (using Iba-1 as the marker) in the DG and medial prefrontal cortex. Additionally, EE reduced Iba1 + CD68+ microglia density within the anterior DG. Hence, the successful attenuation of trait anxiety by EE was associated in part with the normalization of neuro-inflammatory imbalances. These results suggest that pharmacological and/or positive behavioral therapies triggering microglia-targeted anti-inflammatory effects could be promising as novel alternatives or complimentary anxiolytic therapeutic approaches in specific subgroups of individuals predisposed to trait anxiety.

Cluster Analysis of Short Sensory Profile Data Reveals Sensory-Based Subgroups in Autism Spectrum Disorder.

Autism spectrum disorder is a common, heterogeneous neurodevelopmental disorder lacking targeted treatments. Additional features include restricted, repetitive patterns of behaviors and differences in sensory processing. We hypothesized that detailed sensory features including modality specific hyper- and hypo-sensitivity could be used to identify clinically recognizable subgroups with unique underlying gene variants. Participants included 378 individuals with a clinical diagnosis of autism spectrum disorder who contributed Short Sensory Profile data assessing the frequency of sensory behaviors and whole genome sequencing results to the Autism Speaks' MSSNG database. Sensory phenotypes in this cohort were not randomly distributed with 10 patterns describing 43% (162/378) of participants. Cross comparison of two independent cluster analyses on sensory responses identified six distinct sensory-based subgroups. We then characterized subgroups by calculating the percent of patients in each subgroup who had variants with a Combined Annotation Dependent Depletion (CADD) score of 15 or greater in each of 24,896 genes. Each subgroup exhibited a unique pattern of genes with a high frequency of variants. These results support the use of sensory features to identify autism spectrum disorder subgroups with shared genetic variants.

Susceptibility and resilience to maternal immune activation are associated with differential expression of endogenous retroviral elements

Endogenous retroviruses (ERVs) are ancestorial retroviral elements that were integrated into the mammalian genome through germline infections and insertions during evolution. While increased ERV expression has been repeatedly implicated in psychiatric and neurodevelopmental disorders, recent evidence suggests that aberrant endogenous retroviral activity may contribute to biologically defined subgroups of psychotic disorders with persisting immunological dysfunctions. Here, we explored whether ERV expression is altered in a mouse model of maternal immune activation (MIA), a transdiagnostic environmental risk factor of psychiatric and neurodevelopmental disorders. MIA was induced by maternal administration of poly(I:C) on gestation day 12 in C57BL/6N mice. Murine ERV transcripts were quantified in the placentae and fetal brains shortly after poly(I:C)-induced MIA, as well as in adult offspring that were stratified according to their behavioral profiles. We found that MIA increased and reduced levels of class II ERVs and syncytins, respectively, in placentae and fetal brain tissue. We also revealed abnormal ERV expression in MIA-exposed offspring depending on whether they displayed overt behavioral anomalies or not. Taken together, our findings provide a proof of concept that an inflammatory stimulus, even when initiated in prenatal life, has the potential of altering ERV expression across fetal to adult stages of development. Moreover, our data highlight that susceptibility and resilience to MIA are associated with differential ERV expression, suggesting that early-life exposure to inflammatory factors may play a role in determining disease susceptibility by inducing persistent alterations in the expression of endogenous retroviral elements.

Language Ability to Predict Subtypes of Speech Sound Disorder

Objectives: The purpose of this study is to investigate whether there are differences in vocabulary, grammar, pragmatics, and early literacy skills according to subgroups of speech sound disorders (SSDs). Additionally, this study attempted to examine whether language ability could predict the subtype of SSDs suggested by Dodd’s model for differential diagnosis. Methods: Sixty-two children with SSDs aged 3-9 years were classified into groups with articulation disorders (AD), phonological delays (PD), and consistent/inconsistent phonological disorders (CPD/IPD). Vocabulary and grammar skills were evaluated, and pragmatics and early literacy skills was evaluated based on parental reports. Results: Children with SSDs exhibited significant differences in receptive/expressive vocabulary, receptive/expressive grammar, and early reading performance; but no significant differences were found in pragmatics and early writing. In general, children with AD showed significantly better performance in language than children within the other SSD subgroups, and the children with IPD showed lowest performance. This study showed that grammar was the best predictor of the subtypes of children with SSDs and was most vulnerable to children with SSDs. Conclusion: This study is significant in investigating and examining all aspects of language - vocabulary, grammar, pragmatics, and early literacy - of children with SSDs. This study suggests that the reception and expression of the grammar skills of children with SSDs should be evaluated in the clinical field.