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Abstract Objective To extend evidence on the short-term variability of passive and active suicidal ideation (SI) and the association with suggested proximal risk factors such as interpersonal variables (perceived burdensomeness [PB], thwarted belongingness [TB], hopelessness, and depression) in real-time. Methods This is an observational study using a prospective design applying ecological momentary assessments (EMA). Eligible for study inclusion were inpatients with unipolar depression, current or lifetime suicidal ideation, and fluent German. Over six days, 74 participants rated their momentary level of passive and active SI, PB, TB, depressiveness, and hopelessness up to 10 times per day on smartphones. Data was collected from August 2015 to July 2017. Compliance was excellent (89.7%). Results Mean squared successive differences supported temporal instability for all variables. According intra-class correlations, between 25% and 47% of variance was accounted for by within-person variability. Multilevel analysis demonstrated significant positive associations between hopelessness, depressiveness, PB, and TB with passive SI. Prospectively, hopelessness and PB remained predictors of passive SI. For active SI, hopelessness, depression, PB, and TB were significantly associated cross-sectionally. Prospectively, hopelessness, PB, and the interaction PBxTB predicted active SI. All models were controlled for previous level of SI. Conclusions This study provides further evidence on the short-term variability of SI in very short time frames implying the need of assessing SI repeatedly in clinical and research settings. The associations between interpersonal variables and passive and active SI were only partial in line with assumptions of the Interpersonal Theory of Suicide. Overall, the effects were small warranting further investigation. [ABSTRACT FROM AUTHOR]

Importance: Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates., Objective: To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates., Design, Setting, and Participants: This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population. Studies in the IPDMA database compared participant PHQ-9 scores with a major depression classification. From the IPDMA population, 1000 studies of 100, 200, 500, and 1000 participants each were resampled., Main Outcomes and Measures: For the full IPDMA population and each simulated study, an optimal cutoff score was selected by maximizing the Youden index. Accuracy estimates for optimal cutoff scores in simulated studies were compared with accuracy in the full population., Results: The IPDMA database included 100 primary studies with 44 503 participants (4541 [10%] cases of major depression). The population-level optimal cutoff score was 8 or higher. Optimal cutoff scores in simulated studies ranged from 2 or higher to 21 or higher in samples of 100 participants and 5 or higher to 11 or higher in samples of 1000 participants. The percentage of simulated studies that identified the true optimal cutoff score of 8 or higher was 17% for samples of 100 participants and 33% for samples of 1000 participants. Compared with estimates for a cutoff score of 8 or higher in the population, sensitivity was overestimated by 6.4 (95% CI, 5.7-7.1) percentage points in samples of 100 participants, 4.9 (95% CI, 4.3-5.5) percentage points in samples of 200 participants, 2.2 (95% CI, 1.8-2.6) percentage points in samples of 500 participants, and 1.8 (95% CI, 1.5-2.1) percentage points in samples of 1000 participants. Specificity was within 1 percentage point across sample sizes., Conclusions and Relevance: This study of cross-sectional data found that optimal cutoff scores and accuracy estimates differed substantially from population values when data-driven methods were used to simultaneously identify an optimal cutoff score and estimate accuracy. Users of diagnostic accuracy evidence should evaluate studies of accuracy with caution and ensure that cutoff score recommendations are based on adequately powered research or well-conducted meta-analyses.

Introduction: Findings on the role of suicide ambivalence, an individual's wish to live (WL), and wish to die (WD) in the development of suicidality have been heterogenous. The main goal of this study was to examine associations of these constructs within the past week with sociodemographic factors and to longitudinally investigate their predictive power for suicidal ideation (SI) and suicide attempts (SA)., Methods: N = 308 patients (54% female; M = 36.92 years, SD = 14.30), admitted to a psychiatric ward due to suicidality, were assessed for all constructs after admission, after six, nine, and 12 months. Data were analyzed with univariate fixed-effect models and lagged mixed-effect regression models., Results: Decreased, WL increased post-baseline. Gender showed no significant link to ambivalence, WD, and WL. Ambivalence and WD correlated negatively with age and positively with depressiveness. More participants in a relationship showed a WL compared with single/divorced/widowed participants. More single participants or those in a relationship showed ambivalence than divorced/widowed participants. More single participants showed a WD than participants in a relationship/divorced/widowed. Longitudinally, ambivalence and WD predicted SI and SA., Conclusion: The findings underscore the importance of taking suicide ambivalence and WD into account in risk assessment and treatment., (© 2024 The Authors. Suicide and Life‐Threatening Behavior published by Wiley Periodicals LLC on behalf of American Association of Suicidology.)

The Interpersonal Psychological Theory of Suicide (IPTS) states that thwarted belongingness (TB), perceived burdensomeness (PB), and hopelessness are risk factors for suicidal ideation. This ecological momentary assessment (EMA) study aimed to (1) demonstrate that there is substantial between-person variability in the association between IPTS predictors and suicidal ideation, (2) identify clusters of patients for which the predictors differently predict suicidal ideation, and (3) examine whether identified clusters are characterized by specific patient characteristics. EMA data were collected ten times per day for six days in 74 psychiatric inpatients and was analyzed with dynamic structural equation modelling. Idiographic associations were obtained and clustered using k-means clustering. We found substantial between-person variability in associations between IPTS predictors and suicidal ideation. Four distinct clusters were identified and different risk factors were relevant for different clusters. In the largest cluster (n = 36), none of the IPTS predictors predicted suicidal ideation. Clusters in which associations between IPTS variables and suicidal ideation were stronger showed higher suicidal ideation, depression, and lower positive affect. These findings suggest that a one-size-fits-all model may not adequately reflect idiosyncratic processes leading to suicidal ideation. A promising avenue might be to use idiographic approaches to personalize prediction and interventions., Competing Interests: Declaration of Competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Relevant implicit markers of suicidal thoughts and behaviors (STBs) have only been studied in isolation with mixed evidence. This is the first study that investigated a suicide attentional bias, a death-identity bias and a deficit in behavioral impulsivity in a high-risk sample and healthy controls., Method: We administered the Death Implicit Association Test, the Modified Suicide Stroop Task, and a Go/No-Go Task to inpatient suicide ideators (n = 42), suicide attempters (n = 40), and community controls (n = 61)., Results: Suicide ideators and attempters showed a suicide attentional bias and a death-identity bias compared to healthy controls. Ideators and attempters did not differ in these implicit information-processing biases. Notably, only attempters were more behaviorally impulsive compared to controls; however, ideators and attempters did not significantly differ in behavioral impulsivity. Moreover, implicit scores were positively intercorrelated in the total sample., Conclusion: In line with the Cognitive Model of Suicide, ideators and attempters display suicide-related information processing biases, which can be considered as implicit cognitive markers of suicide vulnerability. Furthermore, attempters have elevated levels of behavioral impulsiveness. These results are highly relevant in the context of crisis intervention strategies and warrant further research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: While the impact of climate change on mental health, especially in young people, has been acknowledged, underlying mechanisms of this relation remain elusive. Based on research on active coping, we explored effects of agency on anxiety and coping in an experimental design. We further examined the relation between mental health (i.e., psychopathology, depressiveness, trait anxiety), trait factors (i.e., climate distress, intolerance of uncertainty, trait coping), state anxiety and coping with climate distress., Methods: 244 participants (15-25 years) watched a climate anxiety inducing video, followed by an agency manipulation (high agency vs. low agency vs. control). Trait mental health, intolerance of uncertainty, and climate distress and coping were examined as predictors of state anxiety and coping., Results: State anxiety decreased in the high agency and control conditions, but not in the low agency condition. High agency led to increased meaning-focused coping and low agency to decreased meaning- and problem-focused coping. Trait mental health, problem-focused, and meaning-focused coping strategies each predicted their respective state counterparts. Emotion-focused coping was further predicted by all trait measures., Conclusion: The findings suggest a risk of low agency communication due to the lack of arousal decrease and lack of using functional coping in young people.

Introduction: Suicide risk assessment based on self-report questionnaires is considered as problematic because risk states are dynamic and at-risk individuals may conceal suicidal intentions for several reasons. Therefore, recent research efforts increasingly focus on implicit risk markers such as the suicide attentional bias (SAB) measured with the Suicide Stroop Task (SST). However, most SST studies failed to demonstrate a SAB in individuals with suicide risk and repeatedly demonstrated insufficient psychometrics of the SST. This study aimed to investigate a SAB using a modified SST (M-SST) and to test its psychometric properties., Method: We compared n = 61 healthy controls and a high-risk inpatient sample of n = 40 suicide ideators and n = 40 suicide attempters regarding interference scores of positive, negative and suicide-related words. Interference scores were calculated by subtracting the mean reaction time (mean RT) of the neutral words from the mean RT of the suicide-related words (mean RT Suicide -mean RT Neutral), resulting in a suicide-specific interference score. Similarly, interference scores were calculated for the positive and negative words by subtracting the mean RT of neutral words from the mean RT of positive and negative words., Results: A Group × Interference ANOVA showed a significant interaction effect (p <.001, ηp2 = .09), indicating that group effects significantly vary across interference type. Post hoc comparisons revealed that both ideators and attempters demonstrated greater interferences only for suicide-related words compared to healthy controls, indicating a SAB in patients, while a difference between ideators and attempters was lacking. The suicide interference score classified with an AUC = 0.73, 95% CI [0.65 - 0.82], p <.001, between controls and patients with STBs. The M-SST demonstrated good internal consistency and convergent validity., Discussion: The study adds evidence to the assumptions of the Cognitive Model of Suicide, viewing a SAB as a cognitive marker of suicide vulnerability independently of the engagement in suicidal behavior. The results' clinical implications are discussed in the context of recommended intervention strategies during an acute suicidal state. Future studies with the M-SST should include non-suicidal patient controls to investigate whether a SAB is uniquely related to suicidality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Brüdern, Spangenberg, Stein, Gold, Forkmann, Stengler and Glaesmer.)

Introduction: Men have an increased risk to die by suicide compared to women but are underrepresented in suicide research. To improve individual risk prediction for suicide-related thoughts and behaviors (STBs), risk factors are increasingly being studied at an individual level. The possible affect-regulatory function of suicidal ideation has hardly been investigated ideographically and has not yet been tested in a male sample., Methods: We investigated the bidirectional associations between suicidal ideation and negative and positive affect in a sample of n = 21 male inpatients with unipolar depression and a history of suicidal ideation both at the group level and at the individual level. Participants underwent an intensive ecological momentary assessment for 6 days with 10 data points per day., Results: We found no evidence for an affect-regulatory function of suicidal ideation at the group level, neither for effects of affect on subsequent suicidal ideation (antecedent affect-regulatory hypothesis) nor for effects of suicidal ideation on subsequent affect (consequence affect-regulatory hypothesis). Person-specific analyses revealed substantial variability in strength and direction of the considered associations, especially for the associations representing the antecedent hypothesis., Conclusion: The demonstrated between-person heterogeneity points to the necessity to individualize the investigation of risk factors to enhance prediction and prevention of STBs., (© 2024 The Author(s). Suicide and Life‐Threatening Behavior published by Wiley Periodicals LLC on behalf of American Association of Suicidology.)

Obesity poses significant challenges, necessitating comprehensive strategies for effective intervention. Bariatric Surgery (BS) has emerged as a crucial therapeutic approach, demonstrating success in weight loss and comorbidity improvement. This study aimed to evaluate the outcomes of BS in a cohort of 48 Uruguayan patients and investigate the interplay between BS and clinical and metabolic features, with a specific focus on FSTL1, an emerging biomarker associated with obesity and inflammation. We quantitatively analyzed BS outcomes and constructed linear models to identify variables impacting BS success. The study revealed the effectiveness of BS in improving metabolic and clinical parameters. Importantly, variables correlating with BS success were identified, with higher pre-surgical FSTL1 levels associated with an increased effect of BS on BMI reduction. FSTL1 levels were measured from patient plasma using an ELISA kit pre-surgery and six months after. This research, despite limitations of a small sample size and limited follow-up time, contributes valuable insights into understanding and predicting the success of BS, highlighting the potential role of FSTL1 as a useful biomarker in obesity., (© 2024. The Author(s).)

The Cognitive Model of Suicide proposes a suicide attentional bias in individuals with suicidal thoughts and behavior (STBs). The Suicide Stroop Task (SST) was developed as a behavioral measure to assess this attentional bias. However, prior studies demonstrated poor psychometric properties of the SST., Methods: We developed a modified Suicide Stroop Task (M-SST) and tested its psychometric properties in a sample of healthy controls ( n  = 30) and inpatients with STBs ( n  = 24). Participants (50% female, aged 18 to 61 years) completed the M-SST with neutral, positive, negative, suicide-related positive and suicide-related negative words. Interference scores were calculated by subtracting the mean reaction time (mean RT) of the neutral words from the mean RT of the suicide-related positive words (mean RT Suicide-Positive -mean RT Neutral ) and suicide-related negative words (mean RT Suicide-Negative -mean RT Neutral ), resulting in two suicide-specific interference scores. Similarly, interference scores were calculated for the positive and negative words by subtracting the mean RT of neutral words from the mean RT of positive and negative words., Results: When analyzed separately, patients with STBs showed greater interferences for suicide-related positive words ( p  = 0.039), and for suicide-related negative words ( p  = 0.016), however, we found no group differences in interference scores for positive and negative words, suggesting a suicide attentional bias in patients with STBs. Controlling for the repeated measure design, a repeated measure ANOVA failed to detect a significant group × interference interaction effect ( p  = 0.176), which limits the generalizability of the findings. However, the interference score of suicide-related negative words showed an adequate classification accuracy (AUC = 0.72, 95% CI [0.58-0.86], p  = 0.006) for differentiating between healthy controls and patients with STBs. Moreover, the interference scores showed acceptable internal reliability for the total sample and only suicide-related interference scores were correlated with clinical characteristics, thus demonstrating convergent validity., Conclusion: The results provide preliminary evidence for a suicide attentional bias in individuals with STBs compared to healthy controls. The M-SST represents a promising tool for assessing a suicide attentional bias by revealing adequate psychometric properties. Future studies with larger samples are needed to confirm these preliminary findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gold, Stein, Glaesmer, Spangenberg, Strauss, Schomerus, Stengler and Brüdern.)

Objective: The strongest predictor of suicide attempts is a previous suicide attempt. Individuals hospitalized for suicidal ideation and behavior face an increased risk of suicide following discharge. This study investigates the extent to which outpatient treatment services are utilized the first 6 months after discharge and whether men and women differ in this regard., Method: The study examines data of 124 individuals (with suicide attempts (lifetime), 59.7% female) on the use of outpatient treatment services in the 6 months after inpatient treatment., Results: 37.9% (N=47) of individuals reported not having used any treatment services at all. Men were significantly less likely to make use of the services., Conclusion: Members of a group with an increased risk of suicide, to a large extent, fail to make use of outpatient treatment services. Discharge management should increasingly focus on (gender-specific) barriers and pave the way for treatment in outpatient., Competing Interests: Die Autor:innen geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Understanding the intricate molecular mechanisms governing the fate of human adipose-derived stem cells (hASCs) is essential for elucidating the delicate balance between adipogenic and osteogenic differentiation in both healthy and pathological conditions. Long non-coding RNAs (lncRNAs) have emerged as key regulators involved in lineage commitment and differentiation of stem cells, operating at various levels of gene regulation, including transcriptional, post-transcriptional, and post-translational processes. To gain deeper insights into the role of lncRNAs' in hASCs' differentiation, we conducted a comprehensive analysis of the lncRNA transcriptome (RNA-seq) and translatome (polysomal-RNA-seq) during a 24 h period of adipogenesis and osteogenesis. Our findings revealed distinct expression patterns between the transcriptome and translatome during both differentiation processes, highlighting 90 lncRNAs that are exclusively regulated in the polysomal fraction. These findings underscore the significance of investigating lncRNAs associated with ribosomes, considering their unique expression patterns and potential mechanisms of action, such as translational regulation and potential coding capacity for microproteins. Additionally, we identified specific lncRNA gene expression programs associated with adipogenesis and osteogenesis during the early stages of cell differentiation. By shedding light on the expression and potential functions of these polysome-associated lncRNAs, we aim to deepen our understanding of their involvement in the regulation of adipogenic and osteogenic differentiation, ultimately paving the way for novel therapeutic strategies and insights into regenerative medicine.

Alternative polyadenylation (APA) increases transcript diversity through the generation of isoforms with varying 3' untranslated region (3' UTR) lengths. As the 3' UTR harbors regulatory element target sites, such as miRNAs or RNA-binding proteins, changes in this region can impact post-transcriptional regulation and translation. Moreover, the APA landscape can change based on the cell type, cell state, or condition. Given that APA events can impact protein expression, investigating translational control is crucial for comprehending the overall cellular regulation process. Revisiting data from polysome profiling followed by RNA sequencing, we investigated the cardiomyogenic differentiation of pluripotent stem cells by identifying the transcripts that show dynamic 3' UTR lengthening or shortening, which are being actively recruited to ribosome complexes. Our findings indicate that dynamic 3' UTR lengthening is not exclusively associated with differential expression during cardiomyogenesis but rather with recruitment to polysomes. We confirm that the differentiated state of cardiomyocytes shows a preference for shorter 3' UTR in comparison to the pluripotent stage although preferences vary during the days of the differentiation process. The most distinct regulatory changes are seen in day 4 of differentiation, which is the mesoderm commitment time point of cardiomyogenesis. After identifying the miRNAs that would target specifically the alternative 3' UTR region of the isoforms, we constructed a gene regulatory network for the cardiomyogenesis process, in which genes related to the cell cycle were identified. Altogether, our work sheds light on the regulation and dynamic 3' UTR changes of polysome-recruited transcripts that take place during the cardiomyogenic differentiation of pluripotent stem cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hansel-Frose, Allmer, Friedrichs, dos Santos, Dallagiovanna and Spangenberg.)

Introduction: Depression as well as suicidal ideation and behaviours share several precipitating and maintaining factors and are subject to the influence of overlapping constructs. One of these transdiagnostic constructs is rumination. For the treatment of rumination, a variety of interventions are already available. However, not everyone with a need receives psychotherapeutic treatment. And even if they do: implementing learnt strategies alone at home can be challenging for patients. Therefore, this study aims to test the feasibility of delivering microinterventions for the reduction of rumination in a smartphone-based setting with the goal to make these interventions accessible to a larger number of people and support their use in everyday life., Methods and Analysis: The study's design is an uncontrolled-within-group design. Participants with at least mild depressive symptoms and reported rumination will be included and recruited via outpatient clinics as well as in the general population. The aim is to recruit at least N=70 participants. Participants first undergo a short telephone screening, a baseline assessment, a 7-day smartphone-based assessment including microinterventions in case participants report rumination and a postassessment. For feasibility purposes, primary outcomes relate to participants' compliance, their evaluation of the smartphone-based assessment as well as the microinterventions delivered during the assessment. As a secondary goal, clinical utility will be examined. Clinical outcomes (eg, depressive symptoms, rumination) will be measured at baseline and postassessment., Ethics and Dissemination: The ethics committee of the institute of psychology of the university of Duisburg-Essen and University of Leipzig has approved the study. Study results will be disseminated to healthcare communities, in peer-reviewed science journals and at conferences., Trial Registration Number: DRKS00031743., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Identifying various interacting risk factors for suicidality is important to develop preventive measures. The Interpersonal-Psychological Theory of Suicidal Behavior (IPTS) postulates suicidal ideation resulting from the occurrence of Perceived Burdensomeness (PB) and Thwarted Belongingness (TB). Suicidal behavior ultimately occurs if people have a Capability for Suicide. In past studies, the validity of TB was often not empirically confirmed, questioning which of the aspects of TB are central and related to suicidal ideation and whether applied measurement methods adequately capture the construct., Method: Using a sample of 3,404 individuals from different clinical and nonclinical settings, 30% (1,023) of whom reported suicidal ideation, two network analyses were conducted on the Interpersonal Needs Questionnaire (INQ) and a variable mapping suicidal ideation., Results: Analyses revealed that some items of the INQ were not related to suicidal ideation and the most central items did not have the strongest associations to suicidal ideation., Conclusion: Based on these results, a shortened version of the INQ with the four items that showed the strongest associations with suicidal ideation in the network analyses was suggested., Competing Interests: All authors declare that there is no conflict of interest., (Copyright: © 2023 Conrad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To further validate the concept of suicidal subtypes distinguished by indicators of suicidal thinking and behavior with regard to clinical characteristics and past and future suicide attempts., Methods: Psychiatric inpatients were assessed (study 1: ecological momentary assessments in 74 depressed inpatients with suicidal ideation; study 2: clinical assessments in 224 inpatients after a suicide attempt and over a 12-month follow-up period). Subtypes were identified using latent profile analysis (based on indicators of real-time suicide ideation) and latent class analysis (based on features of past suicide ideation and suicide attempt characteristics). Comparisons between subtypes included clinical characteristics (depression, suicidal ideation, trait impulsivity, childhood trauma) as well as past (study 1) and future (study 2) suicide attempts., Results: Suicidal subtypes emerged that are characterized by suicidal ideation means and stability and features of past suicidal behavior (four in study 1, three in study 2). The subtypes differed in terms of depression/suicidal ideation, but not in terms of trait impulsivity/childhood trauma. Although not significant, the subtypes "high-stable" and "low-moderate stable" reported multiple re-attempts more frequently during follow-up than the "low-stable" subtype in study 2., Conclusion: Differences in clinical variables (and by trend in future suicide attempts) clearly point to the clinical relevance of suicidal subtypes (with variability of suicidal thoughts playing a particularly important role)., (© 2022 The Authors. International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.)

The SPATA5 gene encodes a 892 amino-acids long protein that has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Several studies have associated homozygous or compound heterozygous mutations in SPATA5 gene to microcephaly, intellectual disability, seizures and hearing loss. This suggests a role of the SPATA5 gene also in neuronal development. Recently, our group presented results validating the use of blood cells for the assessment of mitochondrial function for diagnosis and follow-up of mitochondrial disease, minimizing the need for invasive procedures such as muscle biopsy. In this study, we were able to diagnose a patient with epileptogenic encephalopathy using next generation sequencing. We found two novel compound heterozygous variants in SPATA5 that are most likely causative. To analyze the impact of SPATA5 mutations on mitochondrial functional studies directly on the patients' mononuclear cells and platelets were undertaken. Oxygen consumption rates in platelets and PBMCs were impaired in the patient when compared to a healthy control. Also, a decrease in mitochondrial mass was observed in the patient monocytes with respect to the control. This suggests a true pathogenic effect of the mutations in mitochondrial function, especially in energy production and possibly biogenesis, leading to the observed phenotype., (© 2023. The Author(s).)

We present the case of a 53-yr-old woman with an inherited bone marrow failure coexisting with uncommon extrahematological symptoms, such as cirrhosis and skin abnormalities. Whole-exome sequencing revealed a diagnosis of Shwachman-Diamond syndrome (SDS) with an atypical presentation. Unexpected was the age of disease expression, normally around the pediatric age, with a predominantly median survival age of 36 yr. To our knowledge, she was the first adult patient with a molecular diagnosis of Shwachman-Diamond in Uruguay. The patient was referred to our service when she was 43-yr-old with a history of bone marrow failure with anemia and thrombocytopenia. All secondary causes of pancytopenia were excluded. Bone marrow aspirate and biopsy specimens were hypocellular for the patient's age. Numerous dysplastic features were observed in the three lineages. She had a normal karyotype and normal chromosomal fragility. A diagnosis of low-risk hypoplastic MDS was made. Dermatological examination revealed reticulate skin pigmentation with hypopigmented macules involving the face, neck, and extremities; nail dystrophy; premature graying; and thin hair. Extrahematological manifestations were present (e.g., learning difficulties, short stature). Last, she was diagnosed with cryptogenic liver cirrhosis CHILD C. This rules out all other possible causes of chronic liver disease. This clinical presentation initially oriented the diagnosis toward telomeropathy, so we did a telomeropathy NGS panel that came up negative. Finally, we did an exome sequencing that confirmed the diagnosis of SDS. Using whole-exome sequencing, we were able to find two compound heterozygous mutations in the SBDS gene that were responsible for the phenotype of a patient that was undiagnosed for 10 years. An earlier genetic diagnosis could have influenced our patient's outcome., (© 2022 Spangenberg et al.; Published by Cold Spring Harbor Laboratory Press.)

Within the ideation-to-action framework, existing theories of suicidal thoughts and behaviors (STBs) primarily focus on the linear progression of suicide risk. This, however, neglects growing evidence that many suicidal individuals do not experience their suicide attempt as a planned action, and in some instances deny even having experienced any suicidal thoughts. Furthermore, recent research has found that risk factors differ substantially between persons and that this is reflected in the variety of suicidal pathways. Considering the strong variability of STBs, new innovative theoretical concepts and assessment methods are needed to advance our understanding of multiple suicidal pathways. In this review, we apply a dual-system framework to suicidality, the Dual-System Model of Suicidality (DSMS), which accounts for two different systems of information processing and behavior. The first of these described is the reflective system, whereby STBs are viewed from a self-regulation perspective and thusly considered as maladaptive coping behavior to perceived discrepancies regarding important goals. Applying a feedback-based view such as this to STBs provides a deeper understanding into underlying psychological processes involved in the development of STBs. The second system described by the DSMS is the impulsive system. Here, STBs are seen as a maladaptive self-organizing pattern that gets activated in high-risk situations of acute stress, negative affect, and when resources of the reflective system are depleted. In this context, the DSMS is informed by a strength model of self-regulation, which assumes that self-regulation resources are limited, an aspect with important theoretical and clinical implications for the development of STBs. In order to demonstrate the theoretical and practical utility of the DSMS, this review draws mainly on studies using ecological momentary assessment (EMA), a technology that allows to investigate moment-to-moment changes in STBs, and is therefore well suited for capturing the complex interplay of self-regulatory and impulsive processes proposed by the DSMS. The application of a dual-system framework to suicide research represents an innovative and integrative approach for expanding our knowledge about fundamental processes and how their dynamics lead to STBs. The usefulness of the DSMS, implications for future suicide research with EMA, and clinical implications are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brüdern, Glaesmer, Berger and Spangenberg.)

Background: Lissencephaly (LIS) is a cortical malformation, characterized by smooth or nearly smooth cerebral surface and a shortage of gyral and sulcal development, which is caused by deficient neuronal migration during embryogenesis. Neuronal migration involves many gene products, among which is the product of the PAFAH1B1 gene, associated with this disease. LIS is a rare disease, characterized by low population frequency, and with non-specific clinical symptoms such as early epilepsy, developmental delay or cerebral palsy-like motor problems. Given that high-throughput sequencing techniques have been improving diagnosis, we have chosen this technique for addressing this patient., Case Presentation: We present the case of a seven years old male patient with an undiagnosed rare disease, with non-specific clinical symptoms possibly compatible with lissencephaly. The patient was enrolled in a study that included the sequencing of his whole genome. Sequence data was analyzed following a bioinformatic pipeline. The variants obtained were annotated and then subjected to different filters for prioritization. Also mitochondrial genome was analyzed. A novel candidate frameshift insertion in known PAFAH1B1 gene was found, explaining the index case phenotype. The assessment through in silico tools reported that it causes nonsense mediated mechanisms and that it is damaging with high confidence scores. The insertion causes a change in the reading frame, and produces a premature stop codon, severely affecting the protein function and probably the silencing of one allele. The healthy mother did not carry the mutation, and the unaffected father was not available for analysis., Conclusions: Through this work we found a novel de novo mutation in LIS1/PAFAH1B1 gene, as a likely cause of a rare disease in a young boy with non-specific clinical symptoms. The mutation found correlates with the phenotype studied since the loss of function in the gene product has already been described in this condition. Since there are no other variants in the PAFAH1B1 gene with low population frequency and due to family history, a de novo disease mechanism is proposed., (© 2022. The Author(s).)

Previous research provided preliminary support of a potential reinforcing effect of suicidal ideation demonstrating reduced negative affect and increased positive affect after thinking about suicide. The present study therefore sought to investigate the role of mood and affect as a proximal risk factor of suicidal ideation in a high-risk sample. Seventy-four psychiatric inpatients (72% female) with unipolar depression and current and/or lifetime suicidal ideation aged 18 to 85 years (M = 37.6, SD = 14.3) took part in an ecological momentary assessment (EMA) over 6 days. Multilevel analyses were calculated. Analyses revealed negative valence of mood and low positive affect to be predictors of subsequent intensity of suicidal ideation (active, passive) as well as predictors of change in suicidal ideation (active, passive) since the last measurement. High negative affect only predicted intensity of passive suicidal ideation. Suicidal ideation (active, passive) was prospectively associated with subsequent negative valence of mood and lower positive affect as well as with higher intensity of negative affect. Suicidal ideation (active, passive) also predicted the change in valence of mood, positive affect and negative affect since the last measurement. Mood and affect should be taken into account as important proximal risk factors of active and passive suicidal ideation. The results do not support the idea of a reinforcing effect of suicidal ideation. In fact, they show a pattern of reduced subsequent positive affect, negative valence of mood and increased negative affect. Replication studies with larger samples and longer EMA follow-ups are needed., (© 2022 The Authors. Clinical Psychology & Psychotherapy published by John Wiley & Sons Ltd.)

The ancestry of each locus of the genome can be estimated (local ancestry) based on sequencing or genotyping information together with reference panels of ancestral source populations. The length of those ancestry-specific genomic segments are commonly used to understand migration waves and admixture events. In short time scales, it is often of interest to determine the existence of the most recent unadmixed ancestor from a specific population t generations ago. We built a hypothesis test to determine if an individual has an ancestor belonging to a target ancestral population t generations ago based on these lengths of the ancestry-specific segments at an individual level. We applied this test on a data set that includes 20 Uruguayan admixed individuals to estimate for each one how many generations ago the most recent indigenous ancestor lived. As this method tests each individual separately, it is particularly suited to small sample sizes, such as our study or ancient genome samples., Competing Interests: The authors have declared that no competing interests exist.

Background: Sleep disturbances are an underestimated risk factor for suicidal ideation and behavior. Previous research provided preliminary support of a temporal relationship between sleep disturbances and suicidal ideation. The present study therefore sought to investigate the prospective association between sleep disturbances, passive and active suicidal ideation, and further psychological risk factors, such as state impulsivity and depression., Methods: Seventy-three psychiatric inpatients (71% female) with unipolar depressive disorder and current or lifetime suicidal ideation took part in an ecological momentary assessment (EMA). Participants filled out a baseline assessment and data were collected via smartphones over a 6-days period. Multilevel analyses with sleep disturbance as predictor for active and passive suicidal ideation, state impulsivity, and depression were carried out., Results: Patients with sleep disturbance experienced more active suicidal ideation, but no passive suicidal ideation, the following day. Of the four state impulsivity items, one item was significantly associated with sleep disturbance. Sleep disturbance had no effect on next-day depression. Limiting factors are the small and homogeneous sample along with the rather short observation period in an inpatient setting., Conclusions: The micro-longitudinal study provides preliminary support for sleep disturbance as a proximal risk factor for next-day active suicidal ideation. Clinically, results indicate to consider the evaluation and treatment of sleep disturbances for an improved risk assessment and prevention of suicide., (© 2022. The Author(s).)