Subgroup Of Disorders Research Articles

The clinical and genetic spectrum of paediatric speech and language disorders.

Speech and language disorders are known to have a substantial genetic contribution. Although frequently examined as components of other conditions, research on the genetic basis of linguistic differences as separate phenotypic subgroups has been limited so far. Here, we performed an in-depth characterization of speech and language disorders in 52 143 individuals, reconstructing clinical histories using a large-scale data-mining approach of the electronic medical records from an entire large paediatric healthcare network. The reported frequency of these disorders was the highest between 2 and 5 years old and spanned a spectrum of 26 broad speech and language diagnoses. We used natural language processing to assess the degree to which clinical diagnoses in full-text notes were reflected in ICD-10 diagnosis codes. We found that aphasia and speech apraxia could be retrieved easily through ICD-10 diagnosis codes, whereas stuttering as a speech phenotype was coded in only 12% of individuals through appropriate ICD-10 codes. We found significant comorbidity of speech and language disorders in neurodevelopmental conditions (30.31%) and, to a lesser degree, with epilepsies (6.07%) and movement disorders (2.05%). The most common genetic disorders retrievable in our analysis of electronic medical records were STXBP1 (n = 21), PTEN (n = 20) and CACNA1A (n = 18). When assessing associations of genetic diagnoses with specific linguistic phenotypes, we observed associations of STXBP1 and aphasia (P = 8.57 × 10-7, 95% confidence interval = 18.62-130.39) and MYO7A with speech and language development delay attributable to hearing loss (P = 1.24 × 10-5, 95% confidence interval = 17.46-infinity). Finally, in a sub-cohort of 726 individuals with whole-exome sequencing data, we identified an enrichment of rare variants in neuronal receptor pathways, in addition to associations of UQCRC1 and KIF17 with expressive aphasia, MROH8 and BCHE with poor speech, and USP37, SLC22A9 and UMODL1 with aphasia. In summary, our study outlines the landscape of paediatric speech and language disorders, confirming the phenotypic complexity of linguistic traits and novel genotype-phenotype associations. Subgroups of paediatric speech and language disorders differ significantly with respect to the composition of monogenic aetiologies.

DIFFERENCES IN PARENTS' ATTITUDES TOWARDS THE CAUSES OF NEURODEVELOPMENTAL DISORDERS

Neurodevelopmental disorders are a heterogeneous group of clinical conditions characterized by deficits in one or more aspects of development, with the most prevalent subgroups being autism spectrum disorders and intellectual developmental disorders. Longitudinal studies have shown a significant increase in the number of children with autism spectrum disorders over the past few decades compared to the stable prevalence of intellectual developmental disorders. The aim of this study was to examine and compare the attitudes of parents of children with autism spectrum disorders and parents of children with intellectual developmental disorders regarding genetics, vaccination, and stress as causes of these disorders. The sample consisted of 80 parents, with 40 parents of children with intellectual developmental disorders and 40 parents of children with autism spectrum disorders. The study used a survey as the instrument, employing content analysis, interviewing, and scaling techniques. Data were statistically analyzed using quantitative methods in the JASP program. The results showed that parents' attitudes towards genetics as a cause did not statistically differ, with the most of parents not considering genetics as a cause of neurodevelopmental disorders (40%). There was a notable difference between these two subgroups of neurodevelopmental disorders in the number of children who had undergone genetic testing. A third of the participants expressed a negative attitude towards genetic testing in the future. A statistically significant difference was confirmed in attitudes towards vaccination as a cause of disorders. While most parents did not believe that stress caused their child's disorder, a higher number of parents with children who have intellectual developmental disorders cited stress as a contributing factor. Well-informed parents about the origins of neurodevelopmental disorders influence the lives of entire families, reducing the risk of unnecessary exposure of children to various interventions and treatments.

Development of hepatic fibrosis in common variable immunodeficiency-related porto-sinusoidal vascular disorder.

Liver involvement is an increasingly recognised complication of common variable immunodeficiency (CVID). Nodular regenerative hyperplasia (NRH), a subgroup of porto-sinusoidal vascular disorder, and manifestations of portal hypertension (PH) unrelated to cirrhosis are the most common findings. Nonetheless, the evolution of liver disease over time remains unknown. Retrospective review of patients followed at the National Institutes of Health with CVID-related liver disease and liver biopsy from 1990 to 2020. Clinical, imaging and histological follow-up were recorded as part of clinical research protocols. Forty patients were included, with a median age of 37.5 years at initial biopsy, 73% presenting with clear evidence of NRH, and a median fibrosis stage of 1. At biopsy, median platelet count was 100 × 109/L, spleen size 19.5 cm, hepatic venous pressure gradient 9.5 mmHg and 37.5% of patients had signs of PH. Cumulative incidence of PH was 65% at 5 years. In a subgroup of 16 patients, a follow-up liver biopsy, performed at a median time of 3 years after the index biopsy, revealed an increase in fibrosis by ≥2 stages in 31% of cases and an increase to an overall stage of 2.2 (p = 0.001). No clinical or histological factors were associated with progression of fibrosis. In this CVID cohort, NRH is the most common initial histological finding; however, unexpectedly fibrosis progresses over time in a subgroup of patients. A better understanding of the underlying causal process of liver disease CVID might lead to improved outcomes.

Efficiency of fluoxetine and alprazolam in the treatment of panic disorder

Panic disorder, a mental illness that causes panic attacks as the main symptom, is an important subgroup of anxiety and fear disorders, but it has received little attention and research until recent decades. After it was included in the DSM-II in 1980, researchers began studying drug treatments for the disorder. Among the many drugs, the two most effective are 5-HT reuptake inhibitors and benzodiazepines, and the two most representative drugs are fluoxetine and alprazolam. The purpose of this study was to analyze the effectiveness of fluoxetine and alprazolam in the treatment of panic disorder by studying the structure, synthesis, pharmacology and economic benefits of the two drugs, as well as to analyze the methods of clinical use of the drugs.

Incidence Rates and Predictors of Recurrent Long-Term Mental Sickness Absence Due to Common Mental Disorders.

Several predictors have been identified for mental sickness absence, but those for recurrences are not well-understood. This study assesses recurrence rates for long-term mental sickness absence (LTMSA) within subgroups of common mental disorders (CMDs) and identifies predictors of recurrent LTMSA. This historical prospective cohort study used routinely collected data from 16,310 employees obtained from a nationally operating Dutch occupational health service (ArboNed). Total follow-up duration was 23,334 person-years. Overall recurrence rates were assessed using Kaplan-Meier estimators. Recurrence rates within subgroups of CMDs were calculated using person-years. Univariable and multivariable Cox proportional hazards models were used to identify predictors. 15.6% of employees experienced a recurrent LTMSA episode within three years after fully returning to work after a previous LTMSA episode. Highest recurrence rates for LTMSA were observed after a previous LTMSA episode due to mood or anxiety disorders. Mood or anxiety disorders and shorter previous episode duration were predictors of recurrent LTMSA. No associations were found for age, gender, company size, full-time equivalent and job tenure. Employees should be monitored adequately after they fully returned to work after LTMSA. It is recommended to monitor high-risk employees (i.e. employees with mood or anxiety disorders and short LTMSA episode) more intensively, also beyond full return to work. Moreover, diagnosis of anxiety and depressive symptoms should be given a higher priority in occupational healthcare.

STM-Suite, an Online Platform for the Assessment of Memory Functions Discriminates among Subgroups of Children with Different Types of Specific Learning Disorders

A deficit in short-term memory (STM) functions characterizes many neurodevelopmental disorders, in particular, specific learning disorders. Hence, there is a need to develop a web-based platform capable of testing specific variables and administration conditions in a controlled manner. The platform herein presented allows for the assessment of short-term memory (STM) items and order components in a series of different conditions. Stimulus types, presentation, and response modalities were appropriately selected to assess the impact of those variables on memory performances. The usefulness of such a systematic, fine-grained analysis of STM functions was tested by applying the complete assessment in a group of 100 school-age children (47 Typically Developing children and 53 children with learning disorders) and evaluating the capacity of the software to highlight different specific memory processes activated during reading, writing, and calculation. A cluster analysis was applied to the learning performances of the whole group, and a four-cluster solution representing the best division into subgroups of learning disorders (affecting reading, writing, and mathematical skills, variously combined) also showed clear-cut differences in the children’s STM profiles. This confirms the potential and the usefulness of the tool for the characterization of STM in school-age children.

Relationship Between Ankylosing Spondylitis and Cerebrovascular Disorders: A Systematic Review.

Cerebrovascular events are linked to ankylosing spondylitis. Accelerated atherosclerosis and endothelial dysfunction against a backdrop of inflammation have been widely blamed for the increased cerebrovascular risk in ankylosing spondylitis. The absence of a comprehensive review encouraged us to consider the link between ankylosing spondylitis and cerebrovascular diseases. Web of Science, PubMed, Medline, Scopus, and EMBASE were searched to identify studies published from 2000 to June 10, 2023. All observational and cohort studies reporting myocardial infarction or stroke and considering classic cerebrovascular risk in ankylosing spondylitis patients and healthy controls were included. Most of the included studies reported that the risk of cerebrovascular disorders was greater in ankylosing spondylitis than in the general population. Also, most studies showed that for both sexes, the prevalence of cardiovascular illnesses rose with age, and this trend was consistent across all subgroups of cardiovascular disorders. Also, most studies reported that the rate of cerebrovascular accidents in ankylosing spondylitis patients was higher than in control groups. Some studies reported that the risk of developing an ischemic stroke was higher in young patients with ankylosing spondylitis, while others did not. Our systematic analysis found that most studies agreed that ankylosing spondylitis patients had a higher risk of cerebrovascular diseases than the general population. Still, this increased risk was influenced by several factors that need further research exploration.

Frequency, clinical, and laboratory findings of platelet secretion disorders in patients referred to the specialized coagulation laboratory of the Iranian Blood Transfusion Organization.

Platelet secretion disorders (PSDs) are a subgroup of platelet function disorders (PFDs) caused by defects in the content or release of platelet granules. These patients have a variable degree of mucocutaneous bleeding tendency. The diagnostic facilities of PSDs are imitated in Iran, even in specialized coagulation laboratories. The present study aims to estimate the frequency of PSDs among patients referred to the Iranian Blood Transfusion Organization (IBTO). The research population includes all patients referred to the specialized coagulation laboratory of IBTO and requested platelet function and von Willebrand testing by their physicians. They were recruited between May 2022 and October 2022 if they were not diagnosed as having procoagulant defects, von Willebrand disease (VWD), Glanzmann thrombasthenia (GT), Bernard-Soulier syndrome (BSS), and platelet count <100 × 10 9 (except in the syndromic forms). Patients with a defect in response to at least two agonists in Light transmission aggregometry (LTA), one agonist in the ATP-secretion study, and/or impairment in the expression of CD62P are considered PSDs. Among 121 cases referred to our center over 6 months, 40 patients fulfilled the inclusion and exclusion criteria. Ten patients were diagnosed with PSDs. Six were classified as δ-platelet secretion disorders (δ-PSD), two α-platelet secretion disorders (α-PSD), and two αδ-platelet secretion disorders (αδ-PSD). The prevalence of PSDs in our population study was 25% (10/40), which seems highly prevalent. Therefore, expanding laboratory approaches to platelet function defects is necessary as a routine in our country.

Neurocognitive correlates of metabolic dysregulation in individuals with mood disorders: a systematic review and meta-analysis.

Individuals with mood disorders are predisposed to metabolic dysfunction, while those with metabolic dysregulation such as diabetes and obesity experience more severe depressive symptoms. Both metabolic dysfunction and mood disorders are independently associated with cognitive deficits. Therefore, given their close association, this study aimed to explore the association between metabolic dysfunction in individuals with mood disorders in relation to cognitive outcomes. A comprehensive search comprised of these three domains was carried out; a random-effects meta-analysis pooling mean cognitive outcomes was conducted (PROSPERO ID: CRD42022295765). Sixty-three studies were included in this review; 26 were synthesized in a quantitative meta-analysis. Comorbid metabolic dysregulation was associated with significantly lower global cognition among individuals with mood disorders. These trends were significant within each mood disorder subgroup, including major depressive disorder, bipolar disorder, and self-report depression/depressive symptoms. Type 2 diabetes was associated with the lowest cognitive performance in individuals with mood disorders, followed by peripheral insulin resistance, body mass index ⩾25 kg/m2, and metabolic syndrome. Significant reduction in scores was also observed among individual cognitive domains (in descending order) of working memory, attention, executive function, processing speed, verbal memory, and visual memory. These findings demonstrate the detrimental effects of comorbid metabolic dysfunction in individuals with mood disorders. Further research is required to understand the underlying mechanisms connecting mood disorders, metabolism, and cognition.

Arginine metabolomics in mood disorders

Alterations of nitric oxide (NO) homeostasis have been described in mood disorders. However, the analytical challenges associated with the direct measurement of NO have prompted the search for alternative biomarkers of NO synthesis. We investigated the published evidence of the association between these alternative biomarkers and mood disorders (depressive disorder or bipolar disorder). Electronic databases were searched from inception to the June 30, 2023. In 20 studies, there was a trend towards significantly higher asymmetric dimethylarginine (ADMA) in mood disorders vs. controls (p = 0.072), and non-significant differences in arginine (p = 0.29), citrulline (p = 0.35), symmetric dimethylarginine (SDMA; p = 0.23), and ornithine (p = 0.42). In subgroup analyses, the SMD for ADMA was significant in bipolar disorder (p < 0.001) and European studies (p = 0.02), the SMDs for SDMA (p = 0.001) and citrulline (p = 0.038) in European studies, and the SMD for ornithine in bipolar disorder (p = 0.007), Asian (p = 0.001) and American studies (p = 0.005), and patients treated with antidepressants (p = 0.029). The abnormal concentrations of ADMA, SDMA, citrulline, and ornithine in subgroups of mood disorders, particularly bipolar disorder, warrant further research to unravel their pathophysiological role and identify novel treatments in this group (The protocol was registered in PROSPERO: CRD42023445962)

Searching for diagnoses and subgroups: a suggestion for criteria.

New subgroups of psychiatric disorders are often claimed. In contrast, classification systems have repeatedly had to abandon established subgroups such as paranoid vs. disorganised and catatonic schizophrenia due to lack of empirical evidence. Four criteria are proposed that should be met to claim valid subgroups: 1. distinct distribution of the defining characteristic between groups; 2. significant differences in variables other than those defining the subgroups cross-sectionally and longitudinally; 3. long-term stability; 4. significant differences between groups in aetiology, pathophysiology, and evidence-based therapy. In contrast to examples from somatic medicine, such as type 1 and type 2 diabetes, few psychiatric disorders meet these requirements.

Variability of Maximum Glottal Angle on Clinical Sniff Task Differs in Patients With Functional and Organic Laryngeal Pathologies Compared to Healthy Controls

ObjectivesPractitioners rely heavily on flexible endoscopic visualization of the true vocal folds during a repeated “sniff-ee” maneuver to assess vocal fold mobility. However, the human eye lacks the temporal and spatial precision required to accurately gauge fine differences in maximal glottal angle. This study compared differences in maximal glottal angle variables during “sniff-ee” maneuvers across patients with various voice and laryngeal breathing disorders. MethodsWe retrospectively measured glottal angle from flexible laryngoscopy exams in six groups of patients with voice and upper airway disorders: laryngeal dystonia/essential tremor (LD/ET), vocal fold lesions, vocal fold atrophy, paradoxical vocal fold motion disorder (PVFMD), muscle tension dysphonia (MTD), and healthy controls. Maximum glottal angle (GAMAX) and average glottal angle (GAAVG) were calculated during three serial “sniff-ee” maneuvers for all participants. Individual disorder groups (MTD, PVFMD, LD/ET, atrophy, lesion) and broader disorder types (functional and organic) were compared to healthy controls using simple linear regression analyses. ResultsNo significant difference in either GAMAX or GAAVG was found between controls and the disorder subgroups or broader disorder type (function and organic). However, there were statistically significant differences in the variability of GAMAX in both PVFMD (6.2° more variability; p<0.001) and LD/ET (5.8° more variability; p<0.001) compared to healthy controls. ConclusionPatients diagnosed with LD/ET and PVFMD both demonstrated significantly more variability in their GAMAX compared to healthy controls, suggesting that movement consistency or coordination may be relatively compromised in these patient groups. Further research is warranted to investigate the sensitivity and specificity of glottal angle variability in diagnosing PVFMD and LD in clinical or research settings. Level of Evidence4 Short SummaryLaryngeal exams from five patient groups were compared to those from healthy controls. Patients with paradoxical vocal fold motion disorder and laryngeal movement disorders exhibited significantly greater variability of glottal angle during sniff maneuver compared to healthy controls.

Risk factors of reattempt among suicide attempters in South Korea: A nationwide retrospective cohort study.

This study aimed to identify underlying demographic and clinical characteristics among individuals who had previously attempted suicide, utilizing the comprehensive Health Insurance Review and Assessment Service (HIRA) database. Data of patients aged 18 and above who had attempted suicide between January 1 and December 31, 2014, recorded in HIRA, were extracted. The index date was identified when a suicide attempt was made within the year 2014. The medical history of the three years before the index date and seven years of follow-up data after the index date were analyzed. Kaplan-Meier estimate was used to infer reattempt of the suicide attempters, and Cox-proportional hazard analysis was used to investigate risk factors associated with suicide reattempts. A total of 17,026 suicide attempters were identified, of which 1,853 (10.9%) reattempted suicide; 4,925 (28.9%) patients had been diagnosed with depressive disorder. Of the reattempters, 391 (21.1%) demonstrated a history of suicide attempts in the three years before the index date, and the mean number of prior attempts was higher compared to that of the non-reattempters (1.7 vs.1.3, p-value < 0.01). Prior psychiatric medication, polypharmacy, and an increase in the number of psychotropics were associated with suicide reattempt in overall suicide attempters. (Hazard ratio (HR) = 3.20, 95% confidence interval [CI] = 2.56-4.00; HR = 2.42, 95% CI = 1.87-3.14; HR = 19.66, 95% CI = 15.22-25.39 respectively). The risk of reattempt decreased in individuals receiving antidepressant prescriptions compared to those unmedicated, showing a reduction of 78% when prescribed by non-psychiatrists and 89% when prescribed by psychiatrists. Similar risk factors for suicide reattempts were observed in the depressive disorder subgroup, but the median time to reattempt was shorter (556.5 days) for this group compared to that for the overall attempters (578 days). Various risk factors including demographics, clinical characteristics, and medications should be considered to prevent suicide reattempts among suicide attempters, and patients with depressive disorder should be monitored more closely.

Digital and Clinical evaluation of temporomandibular disorders in full dentition and free end extension patients.

Background: Temporomandibular disorders (TMD) Which are a subgroup of craniofacial pain disorders involving chronic pain, dysfunction of the temporomandibular joint (TMJ), masticatory muscles and associated musculoskeletal structures of the head and neck. Pain is one of the most frequent clinical features for these TMD in addition to the clicking, limitation of mouth opening and deviation. This study aimed to evaluate Digital evaluation of the occlusal instability parameters (Disclusion Time, Occlusion Time, trajectory of force Index and Occlusal Interferences). Method: the study including 180 patients with free end extension and full dentition (kennedy classification class I and II) their age was between (20-50) years old .they had either disc displacement or myofascial pain dysfunction syndrome according to shiffman criteria.and also examined by digital T scan. Result: the result showed significant pain difference between free end extension and full dentition patients. Conclusion: The trajectory of force distribution is highly variable between the two major groups, the full dentition exhibit more posterior force while The free end patients tend to establish more anterior force which lead to a series of temporomandibular disorders.

Digital Phenotyping for Mood Disorders: Methodology-Oriented Pilot Feasibility Study.

In the burgeoning area of clinical digital phenotyping research, there is a dearth of literature that details methodology, including the key challenges and dilemmas in developing and implementing a successful architecture for technological infrastructure, patient engagement, longitudinal study participation, and successful reporting and analysis of diverse passive and active digital data streams. This article provides a narrative rationale for our study design in the context of the current evidence base and best practices, with an emphasis on our initial lessons learned from the implementation challenges and successes of this digital phenotyping study. We describe the design and implementation approach for a digital phenotyping pilot feasibility study with attention to synthesizing key literature and the reasoning for pragmatic adaptations in implementing a multisite study encompassing distinct geographic and population settings. This methodology was used to recruit patients as study participants with a clinician-validated diagnostic history of unipolar depression, bipolar I disorder, or bipolar II disorder, or healthy controls in 2 geographically distinct health care systems for a longitudinal digital phenotyping study of mood disorders. We describe the feasibility of a multisite digital phenotyping pilot study for patients with mood disorders in terms of passively and actively collected phenotyping data quality and enrollment of patients. Overall data quality (assessed as the amount of sensor data obtained vs expected) was high compared to that in related studies. Results were reported on the relevant demographic features of study participants, revealing recruitment properties of age (mean subgroup age ranged from 31 years in the healthy control subgroup to 38 years in the bipolar I disorder subgroup), sex (predominance of female participants, with 7/11, 64% females in the bipolar II disorder subgroup), and smartphone operating system (iOS vs Android; iOS ranged from 7/11, 64% in the bipolar II disorder subgroup to 29/32, 91% in the healthy control subgroup). We also described implementation considerations around digital phenotyping research for mood disorders and other psychiatric conditions. Digital phenotyping in affective disorders is feasible on both Android and iOS smartphones, and the resulting data quality using an open-source platform is higher than that in comparable studies. While the digital phenotyping data quality was independent of gender and race, the reported demographic features of study participants revealed important information on possible selection biases that may result from naturalistic research in this domain. We believe that the methodology described will be readily reproducible and generalizable to other study settings and patient populations given our data on deployment at 2 unique sites.

Inborn errors of immunity underlying defective T-cell memory.

T-cell memory is a complex process not well understood involving specific steps, pathways and different T-cell subpopulations. Inborn errors of immunity (IEIs) represent unique models to decipher some of these requirements in humans. More than 500 different IEIs have been reported to date, and recently a subgroup of monogenic disorders characterized by memory T-cell defects has emerged, providing novel insights into the pathways of T-cell memory generation and maintenance, although this new knowledge is mostly restricted to peripheral blood T-cell memory populations. This review draws up an inventory of the main and recent IEIs associated with T-cell memory defects and their mice models, with a particular focus on the nuclear factor kappa B (NF-κB) signalling pathway, including the scaffold protein capping protein regulator and myosin 1 linker 2 (CARMIL2) and the T-cell co-stimulatory molecules CD28 and OX-40. Besides NF-κB, IKZF1 (IKAROS), a key transcription factor of haematopoiesis and STAT3-dependent interleukin-6 signals involving the transcription factor ZNF341 also appear to be important for the generation of T cell memory. Somatic reversion mosaicism in memory T cells is documented for several gene defects supporting the critical role of these factors in the development of memory T cells with a potential clinical benefit. Systematic examination of T-cell memory subsets could be helpful in the diagnosis of IEIs.

GPI-anchoring disorders and the heart: Is cardiomyopathy an overlooked feature?

Glycosylphosphatidylinositol anchoring disorders (GPI-ADs) are a subgroup of congenital disorders of glycosylation. GPI biosynthesis requires proteins encoded by over 30 genes of which 24 genes are linked to neurodevelopmental disorders. Patients, especially those with PIGA-encephalopathy, have a high risk of premature mortality which sometimes is attributed to cardiomyopathy. We aimed to explore the occurrence of cardiomyopathy among patients with GPI-ADs and to raise awareness about this potentially lethal feature. Unpublished patients with genetically proven GPI-ADs and cardiomyopathy were identified through an international collaboration and recruited through the respective clinicians. We also reviewed the literature for published patients with cardiomyopathy and GPI-AD and contacted the corresponding authors for additional information. We identified four novel and unrelated patients with GPI-AD and cardiomyopathy. Cardiomyopathy was diagnosed before adulthood and was the cause of early demise in two patients. Only one patients underwent cardiac workup after being diagnosed with a GPI-AD. All were diagnosed with PIGA-encephalopathy and three had a disease-causing variant at the same residue. The literature reports five additional children with GPI-AD related cardiomyopathy, three of which died before adulthood. We have shown that patients with GPI-ADs are at risk of developing cardiomyopathy and that regular cardiac workup with echocardiography is necessary.

Older age bipolar disorder.

Older age bipolar disorder (OABD) refers to patients with bipolar disorder aged 50 years and over. There is a paucity of evidence-based guidelines specific to OABD, but in recent years, several studies have been published on OABD. The current review synthesizes previous literature (up to January 1, 2021) as well as most recent literature on OABD (since January 1, 2021). This review covers the following themes: diagnosis and specifiers, clinical course, psychosocial functioning, cognition, physical comorbidities, and pharmacotherapy. On the basis of the latest data, specific clinical recommendations are proposed for each theme. OABD forms a more complex subgroup of bipolar disorder, with an increased risk of cognitive deficits, physical comorbidities, impaired psychosocial functioning, and premature death. The distinctions between BD-I and BD-II and between EOBD and LOBD do not clinically represent relevant subtypes for OABD patients. Mental healthcare professionals should treat all OABD patients with an integrative care model that takes into account cognitive and physical comorbidities and that contains elements aimed at improvement of psychosocial functioning and quality of life. Older age itself should not be a reason to withhold lithium treatment. Future research should collect data on essential data domains using validated measurement scales.

Performance validity of the Dot Counting Test in a dementia clinic setting

Objective This study examined the utility of a performance validity test (PVT), the Dot Counting Test (DCT), in individuals undergoing neuropsychological evaluations for dementia. We investigated specificity rates of the DCT Effort Index score (E-Score) and various individual DCT scores (based on completion time/errors) to further establish appropriate cutoff scores. Method This cross-sectional study included 56 non-litigating, validly performing older adults with no/minimal, mild, or major cognitive impairment. Cutoffs associated with ≥90% specificity were established for 7 DCT scoring methods across impairment severity subgroups. Results Performance on 5 of 7 DCT scoring methods significantly differed based on impairment severity. Overall, more severely impaired participants had significantly higher E-Scores and longer completion times but demonstrated comparable errors to their less impaired counterparts. Contrary to the previously established E-Score cutoff of ≥17, a cutoff of ≥22 was required to maintain adequate specificity in our total sample, with significantly higher adjustments required in the Mild and Major Neurocognitive Disorder subgroups (≥27 and ≥40, respectively). A cutoff of >3 errors achieved adequate specificity in our sample, suggesting that error scores may produce lower false positive rates than E-Scores and completion time scores, both of which overemphasize speed and could inadvertently penalize more severely impaired individuals. Conclusions In a dementia clinic setting, error scores on the DCT may have greater utility in detecting non-credible performance than E-Scores and completion time scores, particularly among more severely impaired individuals. Future research should establish and cross-validate the sensitivity and specificity of the DCT for assessing performance validity.

Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing.

Background: Lysosomal storage disorders (LSDs) are a group of inherited metabolic diseases, which encompass more than 50 different subtypes of pathologies. These disorders are caused by defects in lysosomal enzymes, transporters, and other non-lysosomal proteins. Mucopolysaccharidosis (MPS) is the most common subgroup of lysosomal storage disorders in which the body is unable to properly breakdown mucopolysaccharides. The aim of the present study was to identify novel genes and pathogenic variants in families from diverse regions of Pakistan with clinically diagnosed mucopolysaccharidosis type I and mucopolysaccharidosis type II. Methods: Clinical diagnosis identified 12 with mucopolysaccharidosis I and 2 with mucopolysaccharidosis II in 14 families and whole genome sequencing (WGS) was performed to identify the causative variations in 15 affected individuals. Twenty-two unaffected individuals including parents or normal siblings of patients were also sequenced. Putative causal variants were identified by co-segregation and functional annotation. Results: Analysis of whole genome sequencing data revealed ten novel and six previously reported variants in lysosomal storage disorders-associated genes (IDUA, GALNS, SGSH, GAA, IDS, ALDOB, TRAPPC4, MASP1, SMARCAL, KIAA1109, HERC1, RRAS2) and a novel candidate gene (ABCA5) for lysosomal storage disorder-like phenotypes, which has previously been associated with symptoms strongly related with lysosomal storage disorder in animal models. Conclusion: Multigenic inheritance was found in several families highlighting the importance of searching for homozygous pathogenic variants in several genes also in families with a high degree of consanguinity.