Effects of stand-alone polar residue on membrane protein stability and structure.

Helical membrane proteins generally have a hydrophobic nature, with apolar side chains comprising the majority of the transmembrane (TM) helices. However, whenever polar side chains are present in the TM domain, they often exert a crucial role in structural interactions with other polar residues, such as TM helix associations and oligomerization. Moreover, polar residues in the TM region also often participate in protein functions, such as the Schiff base bonding between Lys residues and retinal in rhodopsin-like membrane proteins. Although many studies have focused on these functional polar residues, our understanding of stand-alone polar residues that are energetically unfavored in TM helixes is limited. Here, we adopted bacteriorhodopsin (bR) as a model system and systematically mutated 17 of its apolar Leu or Phe residues to polar Asn. Stability measurements of the resulting mutants revealed that all of these polar substitutions reduced bR stability to various extents, and the extent of destabilization of each mutant bR is also correlated to different structural factors, such as the relative accessible surface area and membrane depth of the mutation site. Structural analyses of these Asn residues revealed that they form sidechain-to-backbone hydrogen bonds that alleviate the unfavorable energetics in hydrophobic and apolar surroundings. Our results indicate that membrane proteins are able to accommodate certain stand-alone polar residues in the TM region without disrupting overall structures.

Acetic acid as a protic solvent for reducing sulphuric acid concentrations in the production of cellulose nanocrystals alongside transition metal co-catalysts.

Cellulose nanocrystals (CNC) conventionally involve highly concentrated sulphuric acid, which typically resulted in the formation of undesirable by-products. Although less corrosive mineral acids have been explored as alternatives, high concentrations are still required. In this study, CNC was successfully isolated from Leucaena leucocephala wood using mild sulphuric acid with acetic acid as protic solvent, and it was further studied with the addition of Lewis acids in the form of multivalent transition metal salts as co-catalyst. Selected divalent and trivalent transition metal salts including (Cr(NO3)3, Fe(NO3)3, Co(NO3)2, and Ni(NO3)2) were investigated. The morphology, chemical structure, particle size, and physicochemical properties of the CNCs were determined. Controlled depolymerization of cellulose was observed using transmission electron microscopy (TEM). Rod-like morphology for all CNCs was obtained during the hydrolysis process with the smallest CNC particles found at an average length of 278.1 ± 35.1 nm and a diameter of 13.4 ± 3.0 nm. The results showed that higher valence state metal ions resulted in better cellulose hydrolysis efficiency. In addition, the use of transition metal salt as a co-catalyst improved production efficiency and minimised carbonization of CNC while maintaining desired crystallinity and thermal properties.

Daily prediction of inpatient suicide attempts using routinely collected theory-driven data.

We lack knowledge about the short-term predictors of suicide attempts (SAs) among treatment-seeking individuals. The current study evaluated whether (a) interpersonal difficulties, hopelessness, and affective states are associated with an increased risk of SAs on the same and the next day; (b) these daily states are interconnected differently over time among inpatients who attempt suicide compared to those who do not. In total, 110 psychiatric inpatients who attempted suicide during their stay at a psychiatric hospital self-reported their suicidal ideation, negative affect, positive affect, wish to live, interpersonal needs, and hopelessness each day (3,018 daily reports). Multilevel structural equation modeling was used to examine same-day and next-day predictors of SAs. Multilevel temporal network models assessed interconnectedness between daily predictors and were compared to network models from a matched sample of 110 psychiatric inpatients who did not attempt suicide. In multivariate models, increases in perceived burdensomeness were significantly associated with same-day SAs, whereas increased hopelessness was associated with next-day SAs. Network models for patients who attempted suicide indicated that hopelessness and suicidal ideation were central to change, leading to next-day deteriorations in mental health. In subsequent models, feeling calm and relaxed, and feeling fresh and rested were centrally connected to other variables. The centrality of these metrics tended to be higher than in the network models for patients who did not attempt suicide, suggesting differences in the interplay between risk and protective factors. This study suggests routinely monitoring interpersonal factors and hopelessness may help identify increased short-term risk of SAs among psychiatric inpatients. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The trajectory of maternal perinatal depressive symptoms predicts executive function in early childhood.

BACKGROUND: Perinatal maternal depression may affect fetal neurodevelopment directly or indirectly via exposures such as smoking, alcohol, or antidepressant use. The relative contribution of these risk factors on child executive function (EF) has not been explored systematically. METHODS: A prospective pregnancy cohort of 197 women and their children was studied to determine whether maternal depression diagnosis and the trajectory of maternal depressive symptoms (MDSs) from early pregnancy to 12 months postpartum predicts child EF at age 4 (measured using the preschool age psychiatric assessment, NEPSY-II, and Shape School task) using latent growth curve modeling. Indirect effects of smoking, alcohol, and antidepressant use were also formally tested. RESULTS: Increasing maternal perinatal depressive symptoms over time predicted more inattentive symptoms, poorer switching, and motor inhibition, but not cognitive inhibition. When adjusted for multiple comparison, and after accounting for maternal cognition and education, the association with child inattentive symptoms remained significant. However, diagnosed depression did not predict child EF outcomes. Prenatal exposure to smoking, alcohol, and antidepressants also did not mediate pathways from depressive symptoms to EF outcomes. Our findings were limited by sample size and statistical power to detect outcome effects of smaller effect size. CONCLUSIONS: This study suggests that increasing MDSs over the perinatal period is associated with poorer EF outcomes in children at age 4 - independent of prenatal smoking, drinking, or antidepressant use. Depressive chronicity, severity, and postpartum influences may play crucial roles in determining childhood outcomes of EF.

Interventions to reduce wait times for adolescents seeking mental health services: a scoping review protocol.

INTRODUCTION: The demand for adolescent mental health services has increased significantly in recent years, leading to excessive wait times for adolescents seeking mental health services and poor mental health outcomes. Timely access to mental health services is critical to reducing the risk of symptom chronicity and progression to mental disorder. A better understanding of whether and how interventions to reduce wait times impact mental health outcomes is needed to guide mental health policymakers and service planners in their approach to reducing wait times. METHODS AND ANALYSIS: The scoping review will use Arksey and O'Malley's six-stage framework for scoping reviews and Rayyan to support screening, data extraction and evidence synthesis. The review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. We will search the Cochrane Library, EBSCOhost, MEDLINE (Ovid), PsycArticles (Ovid), PsycINFO (Ovid), EMBASE (Ovid), Web of Science, ProQuest and Scopus databases for peer-reviewed texts published in English between 1 January 2000 and 28 February 2023. We will also search Google Scholar for additional grey literature. To be eligible for inclusion, studies must focus on adolescent populations aged 13-18 years and report on interventions to reduce wait times for any mental health service except crisis and emergency services. Title, abstract and full-text screening will be done by two reviewers. We will extract data describing the interventions and their effects on wait times and adolescent mental health outcomes, and we will identify strengths and limitations in the evidence base to inform recommendations for future research. A youth advisory group with lived experience of mental health difficulties will be consulted throughout the review process. ETHICS AND DISSEMINATION: Ethics approval is not required. Findings will be disseminated via peer-reviewed publications and presented at conferences. STUDY REGISTRATION: The protocol was registered with the Open Science Framework on 20 February 2023 (https://osf.io/qt4zy).

Salmonella YqiC exerts its function through an oligomeric state.

Protein oligomerization occurs frequently both in vitro and in vivo, with specific functionalities associated with different oligomeric states. The YqiC protein from Salmonella Typhimurium forms a homotrimer through its C-terminal coiled-coil domain, and the protein is closely linked to the colonization and invasion of the bacteria to the host cells. To elucidate the importance of the oligomeric state of YqiC in vivo and its relation with bacterial infection, we mutated crucial residues in YqiC's coiled-coil region and confirmed the loss of trimer formation using chemical crosslinking and size exclusion chromatography coupled with multiple angle light scattering (SEC-MALS) techniques. The yqiC-knockout strain complemented with mutant YqiC showed significantly reduced colonization and invasion of Salmonella to host cells, demonstrating the critical role of YqiC oligomerization in bacterial pathogenesis. Furthermore, we conducted a protein-protein interaction study of YqiC using a pulled-down assay coupled with mass spectrometry analysis to investigate the protein's role in bacterial virulence. The results reveal that YqiC interacts with subunits of Complex II of the electron transport chain (SdhA and SdhB) and the ß-subunit of F0 F1 -ATP synthase. These interactions suggest that YqiC may modulate the energy production of Salmonella and subsequently affect the assembly of crucial virulence factors, such as flagella. Overall, our findings provide new insights into the molecular mechanisms of YqiC's role in S. Typhimurium pathogenesis and suggest potential therapeutic targets for bacterial infections.

An Artificial Therapist (Manage Your Life Online) to Support the Mental Health of Youth: Co-Design and Case Series.

BACKGROUND: The prevalence of child and adolescent mental health issues is increasing faster than the number of services available, leading to a shortfall. Mental health chatbots are a highly scalable method to address this gap. Manage Your Life Online (MYLO) is an artificially intelligent chatbot that emulates the method of levels therapy. Method of levels is a therapy that uses curious questioning to support the sustained awareness and exploration of current problems. OBJECTIVE: This study aimed to assess the feasibility and acceptability of a co-designed interface for MYLO in young people aged 16 to 24 years with mental health problems. METHODS: An iterative co-design phase occurred over 4 months, in which feedback was elicited from a group of young people (n=7) with lived experiences of mental health issues. This resulted in the development of a progressive web application version of MYLO that could be used on mobile phones. We conducted a case series to assess the feasibility and acceptability of MYLO in 13 young people over 2 weeks. During this time, the participants tested MYLO and completed surveys including clinical outcomes and acceptability measures. We then conducted focus groups and interviews and used thematic analysis to obtain feedback on MYLO and identify recommendations for further improvements. RESULTS: Most participants were positive about their experience of using MYLO and would recommend MYLO to others. The participants enjoyed the simplicity of the interface, found it easy to use, and rated it as acceptable using the System Usability Scale. Inspection of the use data found evidence that MYLO can learn and adapt its questioning in response to user input. We found a large effect size for the decrease in participants' problem-related distress and a medium effect size for the increase in their self-reported tendency to resolve goal conflicts (the proposed mechanism of change) in the testing phase. Some patients also experienced a reliable change in their clinical outcome measures over the 2 weeks. CONCLUSIONS: We established the feasibility and acceptability of MYLO. The initial outcomes suggest that MYLO has the potential to support the mental health of young people and help them resolve their own problems. We aim to establish whether the use of MYLO leads to a meaningful reduction in participants' symptoms of depression and anxiety and whether these are maintained over time by conducting a randomized controlled evaluation trial.

Differences between DSM-5-TR and ICD-11 revisions of attention deficit/hyperactivity disorder: A commentary on implications and opportunities.

Current ICD-11 descriptions for attention deficit hyperactivity disorder (ADHD) were recently published online, in the same year as the DSM-5-TR (text revised edition) was released. In this commentary, we compare and contrast the DSM-5/DSM-5-TR and ICD-11 diagnostic criteria, summarize important differences, and underscore their clinical and research implications. Overall, three major differences emerge: (1) The number of diagnostic criteria for inattention (IA), hyperactivity (HY) and impulsivity (IM) symptoms (i.e., DSM-5-TR has nine IA and nine HY/IM symptoms, whereas ICD-11 has 11 IA and 11 HY/IM sym-ptoms); (2) the clarity and standardization of diagnostic thresholds (i.e., the diagnostic thresholds for symptom count in IA and HY/IM domains are explicitly specified in DSM-5-TR, whereas in ICD-11 they are not); and (3) the partitioning of HY and IM symptoms into sub-dimensions (i.e., difference in partitioning HY and IM symptom domains relates to the differences between the current and previous editions of DSM and ICD, and this has important research implications). Currently, no ICD-11 based ADHD rating scales exist and while this absence represents an obstacle for respective research and clinical practice, it also presents opportunities for research development. This article highlights these challenges, possible remedies and novel research opportunities.

Daily prediction of nonsuicidal self-injury among inpatients: The roles of suicidal thoughts, interpersonal difficulties, hopelessness, and affect.

OBJECTIVE: Nonsuicidal self-injury (NSSI) is a major public health issue. Despite increased research efforts in clinical samples, we still have little understanding of the short-term correlates, predictors, and targets of NSSI among treatment-seeking individuals. The present study was designed to (a) evaluate how suicidal thoughts, interpersonal difficulties, hopelessness, and affective states are associated with same-day and next-day NSSI; (b) identify which factors may be effective targets in treatment through network modeling. METHOD: Data from 1,265 psychiatric inpatients who self-injured throughout their visit to a psychiatric hospital self-reported their suicidal ideation, negative affect, and positive affect on a daily basis (in total 36,345 prospective reports). An additional 632 patients were also surveyed regarding feelings of hopelessness, wish to live, and interpersonal difficulties. Using multilevel structural equation modeling, we examined contemporaneous and time-lagged associations with NSSI. Multilevel network analyses assessed interconnectedness of daily predictors and were compared with a matched sample of 1,265 patients who did not self-injure during their stay. RESULTS: Increases in suicidal ideation were associated with increased probability of same-day and next-day self-injury, and an inverse relationship was observed for wish to live. Increases in positive affect were also significantly associated with decreased probability of next-day self-injury. Perceived burdensomeness had high centrality in network models, particularly among patients who self-injured, indicating it is susceptible to activation and directly associated with all predictors. CONCLUSIONS: Routine monitoring may improve prediction of when a patient is at short-term risk to self-injure and provides person-specific data that can assist in targeting risk and protective factors during treatment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Perth Alexithymia Questionnaire-Short Form (PAQ-S): A 6-item measure of alexithymia.

BACKGROUND: Alexithymia is a trait characterized by difficulties identifying feelings, difficulties describing feelings, and externally orientated thinking. It is widely regarded as an important transdiagnostic risk factor for a range of psychopathologies, including depressive and anxiety disorders. Whilst several well-validated psychometric measures of alexithymia exist, these are relatively lengthy, thus limiting their utility in time-pressured settings. In this paper, we address this gap by introducing and validating a brief 6-item version of the Perth Alexithymia Questionnaire, called the Perth Alexithymia Questionnaire-Short Form (PAQ-S). METHOD: Across two studies with adult samples (Study 1 N = 508 United States community; Study 2 = 378 Australian college students), we examined the psychometric properties of the PAQ-S in terms of its factor structure, reliability, and concurrent/criterion validity. RESULTS: In exploratory and confirmatory factor analyses, all PAQ-S items loaded well on a single general alexithymia factor. The PAQ-S total score had high reliability, and correlated as expected with the long-form of the PAQ, as well as other established markers of alexithymia, emotion regulation, and affective disorder symptoms. LIMITATIONS: Our samples were general community or college student samples from two Western countries; future validation work in clinical samples and more diverse cultural groups is thus needed. CONCLUSIONS: The PAQ-S retains the psychometric strengths of the PAQ. As such, the PAQ-S can be used as a quick, robust measure of overall alexithymia levels. The introduction of the PAQ-S hence enables valid assessments of alexithymia in a more diverse range of settings and research designs.

Enhancement of temperature-modulated NbO2-based relaxation oscillator via interfacial and bulk treatments.

This work demonstrates oscillation frequency modulation in a NbO2-based relaxation oscillator device, in which the oscillation frequency increases with operating temperature and source voltage, and decreases with load resistance. An annealing-induced oxygen diffusion at 373 K was carried out to optimize the stoichiometry of the bulk NbO2to achieve consistent oscillation frequency shift with device temperature. The device exhibits stable self-sustained oscillation in which the frequency can be modulated between 2 and 33 MHz, and a wider operating voltage range can be obtained. An additional surface treatment step was employed during fabrication to reduce the surface roughness of the bottom electrode and to remove surface contaminants that affect the interfacial properties of the device. The device frequency tunability coupled with high oscillating frequency and high endurance capability of more than 1.5 × 108cycles indicates that the Pt/NbO2/Pt device is particularly suitable for applications in an oscillatory neural network.

Sertraline-Induced Tics: A Case Report and Narrative Review.

This brief report describes the case of a 16-year-old girl who was commenced on sertraline for anxiety and depression, and subsequently developed severe and debilitating motor tics. Cessation of sertraline was associated with the resolution of tics; after this, paroxetine was trialled and well tolerated with good response of targeted symptoms and without re-emergence of tics. A narrative literature review yielded a retrospective observational study and eight single case reports on selective serotonin receptor inhibitor-induced motor tics (three in adolescents and five in adults). Tics are not commonly considered as a side-effect of SSRIs. This case report is novel is several aspects: the tics emergence was immediate whereas previous cases were delayed; the tics symptoms were measured and quantified by a validated scale; a dose-response relationship was observed; to our knowledge, our case was the first adolescent female reported; and finally, paroxetine was well-tolerated as a substitute, although it is unclear whether the observed tics-sparing effect is co-incidental, ideocratic or can be replicated.

Enabling successful life engagement in young people with ADHD: new components beyond adult models of recovery.

PURPOSE: To examine the lived experiences of young people successfully managing life with ADHD and investigate the applicability of adult models of Recovery to these individuals. METHODS: Twenty-seven young people aged 15-31 years participated in qualitative interviews. Participants' success was indicated by employment, school attendance, absence of acute mental health episodes, or absence of chronic alcohol or drug use. Thematic analysis identified specific components of their life successes and challenges. RESULTS: The emergent framework comprised four elements: (i) Recovernance (RE) (a portmanteau merging 'Recovery' and 'Maintenance'; ongoing adjustment to maintain one's personal best without an end point); (ii) Personal Optimization (PO) (continuously striving to maximize function and adjust one's goals given fluctuating impairments and internal resources); (iii) Self (S) (facing internal challenges and developing internal resilience); and (iv) Environment (E) (facing external challenges and fostering external resilience). These four elements yielded the acronym 'REPOSE'. CONCLUSIONS: Recovery in young people with ADHD was not a linear journey, with many missteps leading to greater self-knowledge, life skills and mastery. Progress was leveraged on securely anchored internal and external resilience factors against the prospect of setbacks. Findings provide new concepts and novel lexicons to extend existing concepts in Recovery. Implications for rehabilitationCounselling and therapy for young people with ADHD should foster self-understanding, goal setting and self-vigilance as an ongoing process to build their capacity to tackle setbacks and adversities.Counselling and therapy for young people with ADHD focus on a strengths-based approach building internal and external resources, such as developing skills and establishing social connections that build infrastructure in the environment for meaningful participation.

Network analysis of 18 attention-deficit/hyperactivity disorder symptoms suggests the importance of "Distracted" and "Fidget" as central symptoms: Invariance across age, gender, and subtype presentations.

The network theory of mental disorders conceptualizes psychiatric symptoms as networks of symptoms that causally interact with each other. Our present study aimed to explore the symptomatic structure in children with attention-deficit/hyperactivity disorder (ADHD) using network analyses. Symptom network based on 18 items of ADHD Rating Scale-IV was evaluated in 4,033 children and adolescents with ADHD. The importance of nodes was evaluated quantitatively by examining centrality indices, including Strength, Betweenness and Closeness, as well as Predictability and Expected Influence (EI). In addition, we compared the network structure across different subgroups, as characterized by ADHD subtypes, gender and age groups to evaluate its invariance. A three-factor-community structure was identified including inattentive, hyperactive and impulsive clusters. For the centrality indices, the nodes of "Distracted" and "Fidget" showed high closeness and betweenness, and represented a bridge linking the inattentive and hyperactive/impulsive domains. "Details" and "Fidget" were the most common endorsed symptoms in inattentive and hyperactive/impulsive domains respectively. On the contrary, the "Listen" item formed a peripheral node showing weak links with all other items within the inattentive cluster, and the "Loss" item as the least central node by all measures of centrality and with low predictability value. The network structure was relatively invariant across gender, age and ADHD subtypes/presentations. The 18 items of ADHD core symptoms appear not equivalent and interchangeable. "Distracted" and "Fidget" should be considered as central, or core, symptoms for further evaluation and intervention. The network-informed differentiation of these symptoms has the potentials to refine the phenotype and reduce heterogeneity.

A rare case of pancreatic macrocystic serous cystadenoma in an adolescent: a case report and literature review.

While serous cystadenomas of the pancreas usually consist of small cysts, one rare variant has been reported to be composed of macrocysts. Herein, we present the case of the youngest patient with macrocystic serous cystadenoma (MSC) to be reported in the literature. The patient was a 17-year-old girl who presented with the major symptoms of a palpable abdominal mass accompanied by epigastric pain and vomiting for several months. A potential malignancy could not be excluded on the basis of imaging studies, which showed a large macrocystic pancreatic tumor that was 7 cm in diameter. Owing to the patient's symptoms, after diagnosing the mass as a pancreatic cystic tumor with potential malignancy and large tumor size, surgical intervention was arranged. Pathological analysis of the biopsy sample suggested MSC. By reviewing the literature, we found several unique characters of MSCs that cause them to be frequently misdiagnosed as potential malignancies. Additionally, the age of MSC occurrence was found to be lower than of general serous cystadenomas. The potential of MSC should be kept in mind by clinicians when diagnosing young people with pancreatic macrocystic lesions.

Inter-relationships between ADHD, ODD and impulsivity dimensions in emerging adults revealed by network analysis: extending the 'trait impulsivity hypothesis'.

Background: The trait-impulsivity hypothesis posits impulsivity as the underlying substrate of Attention-deficit/hyperactivity disorder (ADHD) and Oppositional defiant disorder (ODD) symptom expressions. The current study applied network analysis to evaluate the inter-relationships of dimensions within ADHD (inattention and hyperactivity/impulsivity) and ODD (anger/irritable, vindictiveness, and argumentative/defiant behavior) with components of impulsivity as captured by the UPPS-P model (negative urgency, lack of premeditation, lack of perseverance, sensation seeking, and positive urgency). Method: A total of 324 emerging adults (women = 246) from the general community completed questionnaires covering these dimensions. Results: Our findings showed that the ADHD and ODD dimensions were associated differentially with different types of impulsivity, in their unique patterns of network connectivities, a possibility that has had little attention in the trait-impulsivity hypothesis literature. Conclusions: This study is the first to tease out the unique associations of the ADHD and ODD dimensions with different types of impulsivity, and in that way provide new contributions to our understanding of the existing trait impulsivity theory. Our findings would be especially relevant to those interested in understanding how different dimensions of trait impulsivity underly the ADHD and ODD dimensions.

Emotion dysregulation in adults with ADHD: The role of cognitive reappraisal and expressive suppression.

BACKGROUND: Emotion dysregulation (ED) is a common clinical feature of attention-deficit/hyperactivity disorder (ADHD). The present study examined the role of cognitive reappraisal (CR) and expressive suppression (ES) in adults with ADHD. In addition, resting-state fMRI (rs-fMRI) data were analyzed to identify neural substrates of CR/ES-ED relationships. METHODS: A total of 309 adults with ADHD and 163 healthy controls were recruited. ED was assessed using the 'emotional control' (EC) subscale from Behavior Rating Inventory of Executive Function-Adult Version. The Emotion Regulation Questionnaire was used to measure CR and ES. The functional connectivities (FCs) with the amygdala as Region of Interest, were analyzed in a subsample to explore their association with CR, ES and EC, respectively. RESULTS: Higher EC scores (indicative of lesser emotional control), as well as lower CR and higher ES utilization were detected in adults with ADHD compared with healthy controls. CR and ES were both negatively correlated with EC in adults with ADHD. Mediation analysis detected a potential effect of ADHD diagnosis on EC via CR. In addition, a unique significant mediation effect was found between ES-related FC of the right amygdala-prefrontal cortex and ED expression in adults with ADHD, confirming the '↑ES → ↓FCs [amygR-PFC] →↓EC' relationship. LIMITATIONS: Only self-reported scales and rs-fMRI data were included in these analyses. CONCLUSIONS: Our findings provide preliminary evidence that in adults with ADHD, less frequent use of CR accounts for ED expression, while more frequent use of ES may play a unique compensatory role in emotion regulation.

Affective-cognitive-behavioral heterogeneity of Attention-Deficit/Hyperactivity Disorder (ADHD): Emotional dysregulation as a sentinel symptom differentiating "ADHD-simplex" and "ADHD-complex" syndromes?

BACKGROUND: Current DSM and ICD classifications of Attention-Deficit/Hyperactivity Disorder (ADHD) exclude emotional dysregulation (ED) in their diagnostic criteria, despite ED symptoms frequently co-occurring in ADHD and likely sharing common neurobiological substrates. In this study, we examined whether consideration of ED symptoms could delineate more informative "ADHD+ED" subphenotypes. METHOD: 4106 children with ADHD were recruited. ED and inattentive (IA) and hyperactive/impulsive (HI) symptoms were profiled using latent class analyses (LCA). The derived latent class (LC) subphenotypes were evaluated and validated in relation to comorbidity patterns, executive functions, and functional impairments. RESULTS: Five LC subphenotypes with ED symptoms were identified: IA/HI + ED profile (LC1); HI + ED profile (LC2); IA + ED profile (LC3); IA/HI profile (LC4); and IA profile (LC5). Cross-validation of the LCA model using support vector machine analysis confirmed 83% accuracy. ED positive (ED+ve) subphenotypes were associated with higher rates of oppositional defiant disorder, mood disorders, anxiety disorders, as well as more severe autistic traits and sluggish cognitive tempo symptoms. Higher rates of ecological executive functioning impairments (BRIEF ratings) were found among ED+ve subphenotypes (though no differences were detected by laboratory-based measures). Functional impairments were also more severe among participants with ED+ve subphenotypes. LIMITATIONS: The data for our LCA were cross-sectional and based primarily on parent ratings. CONCLUSION: Our classification model has parcellated IA, HI, and ED symptoms into novel informative subphenotypes. These classifications provide preliminary evidence that ED symptoms could serve as sentinel features to identify a potential "ADHD-complex" syndrome, which demarcates a more pervasive condition of greater severity, complexity, and impairment.

Daytime sleepiness and emotional and behavioral disturbances in Prader-Willi syndrome.

Individuals with Prader-Willi syndrome (PWS) often have excessive daytime sleepiness and emotional/behavioral disturbances. The objective of this study was to examine whether daytime sleepiness was associated with these emotional/behavioral problems, independent of nighttime sleep-disordered breathing, or the duration of sleep. Caregivers of individuals with PWS (aged 3 to 25 years) completed the Pediatric Sleep Questionnaire (PSQ), Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), and the parent version of the Developmental Behavior Checklist (DBC-P). Sleep adequacy was adjusted for age by computing sleep duration against age-specific recommendations. The associations between ESS-CHAD and the total DBC and its subscale scores were evaluated by linear regression, adjusted for sleep-related breathing difficulties, sleep adequacy, and body mass index (BMI). There were 54 responses for individuals with PWS (including 22 males) aged 4.4-24.0 (mean 12.5) years. Daytime sleepiness predicted a substantial proportion of the variance in total DBC-P scores in the unadjusted model (28%; ß = 0.028; p < 0.001) and when adjusted for sleep adequacy, BMI, and sleep-related breathing difficulties (29%; ß = 0.023; p = 0.007). This relationship was not moderated by BMI Z-scores, but the relationship was more prominent for children younger than 12 years than for children older than 12 years.Conclusions: These findings provide preliminary novel evidence that daytime sleepiness may drive the expression of emotional/behavioral disturbances, and should be explored as a potential modifiable risk factor for these disturbances in PWS, particularly pre-adolescent children.