Categorical Diagnosis Research Articles

A taxometric analysis of panic disorder

ABSTRACT Panic disorder is costly, and while evidence-based interventions for panic disorder are effective, obtaining a diagnosis often precludes access to such treatments. This is problematic because the categorical diagnosis of panic disorder (i.e. “you have it, or you don’t”) supported by modern diagnostic manuals contradicts empirically supported dimensional models of panic disorder. Taxometric analyses, which test the dimensional or categorical latent structure of constructs, have consistently revealed dimensional latent structures when applied to other anxiety disorders and panic-related processes, but taxometric analyses have never been applied to panic disorder. To address this gap in the literature, three nonredundant taxometric procedures were applied to seven theoretically-relevant indicators of panic disorder derived from Panic Disorder Severity Scale data collected from 663 participants recruited via Amazon Mechanical Turk. Simulated comparison plots and objective fit indices were also evaluated. The collective results provided consistent empirical support for a dimensional model of panic disorder, with an overall mean CCFI score of .39. The implications of the present findings for the measurement, assessment, diagnosis, and treatment of panic disorder are discussed.

Clarifying the place of p300 in the empirical structure of psychopathology over development.

Psychophysiology can help elucidate the structure and developmental mechanisms of psychopathology, consistent with the Research Domain Criteria initiative. Cross-sectional research using categorical diagnoses indicates that P300 is an electrocortical endophenotype indexing genetic vulnerability to externalizing problems. However, current diagnostic systems' limitations impede a precise understanding of risk. The Hierarchical Taxonomy of Psychopathology (HiTOP) overcomes these limitations by delineating reliable dimensions ranging in specificity from broad spectra to narrow syndromes. The current study used a HiTOP-aligned approach to clarify P300's associations with a higher-order externalizing factor versus syndrome-specific manifestations within externalizing and internalizing spectra during middle and late adolescence. Participants from the Minnesota Twin Family Study's Enrichment Sample contributed psychophysiological and clinical data at age 14 (N = 930) and follow-up clinical data at age 17 (N = 913). Blunted target P300 at age 14 was selectively associated with externalizing as manifested at age 17 at the superspectrum level (rather than specific externalizing syndromes). Unlike in prior work, target P300 amplitude was positively associated with age 17 depressive symptoms (once controlling for standard stimuli). No association was observed with lifetime symptoms of childhood externalizing or depression evident by age 14. The results indicate that blunted target P300 elucidates specific risk for the development of late-adolescent/young-adult expressions of general externalizing, over and above symptoms evident by middle adolescence. Additionally, the findings speak to the synergistic utility of studying HiTOP-aligned dimensions using multiple measurement modalities to build a more comprehensive understanding of the development of psychopathology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Pathological personality dimensions and neurobiological emotional reactivity.

The Hierarchical Taxonomy of Psychopathology (HiTOP) offers a promising framework to identify the neurobiological mechanisms of psychopathology. Many forms of psychopathology are characterized by dysfunctional emotional reactivity. The late positive potential (LPP) is an event-related potential component that provides an index of neurobiological emotional reactivity. Several categorical disorders have demonstrated a similar association with the emotion-modulated LPP. It is possible that higher-order dimensional representations of psychopathology might explain the comparable results. The present study examined the association between HiTOP-consistent pathological personality dimensions across multiple levels of the hierarchy and neurobiological emotional reactivity. The sample included 215 18-35-year-old adults (86% female) who were oversampled for psychopathology. Participants completed the emotional interrupt task while electroencephalography was recorded to examine the LPP. Participants also completed the Comprehensive Assessment of Traits relevant to Personality Disorders to assess pathological personality. At the spectra level, higher negative emotionality was associated with a larger emotion-modulated LPP, while higher detachment was associated with a smaller emotion-modulated LPP. There were no associations between higher-order psychopathology levels and the emotion-modulated LPP. Compared to categorical diagnoses, spectra-level personality pathology dimensions significantly improved the prediction of the emotion-modulated LPP. The present study indicates that HiTOP spectra levels of negative emotionality and detachment demonstrate unique associations with neurobiological emotional reactivity. The study highlights the utility of examining dimensional and hierarchical, rather than categorical, representations of psychopathology in the attempt to identify the neurobiological origins of psychopathology.

Where do neurodevelopmental conditions fit in transdiagnostic psychiatric frameworks? Incorporating a new neurodevelopmental spectrum.

Features of autism spectrum disorder, attention-deficit/hyperactivity disorder, learning disorders, intellectual disabilities, and communication and motor disorders usually emerge early in life and are associated with atypical neurodevelopment. These "neurodevelopmental conditions" are grouped together in the DSM-5 and ICD-11 to reflect their shared characteristics. Yet, reliance on categorical diagnoses poses significant challenges in both research and clinical settings (e.g., high co-occurrence, arbitrary diagnostic boundaries, high within-disorder heterogeneity). Taking a transdiagnostic dimensional approach provides a useful alternative for addressing these limitations, accounting for shared underpinnings across neurodevelopmental conditions, and characterizing their common co-occurrence and developmental continuity with other psychiatric conditions. Neurodevelopmental features have not been adequately considered in transdiagnostic psychiatric frameworks, although this would have fundamental implications for research and clinical practices. Growing evidence from studies on the structure of neurodevelopmental and other psychiatric conditions indicates that features of neurodevelopmental conditions cluster together, delineating a "neurodevelopmental spectrum" ranging from normative to impairing profiles. Studies on shared genetic underpinnings, overlapping cognitive and neural profiles, and similar developmental course and efficacy of support/treatment strategies indicate the validity of this neurodevelopmental spectrum. Further, characterizing this spectrum alongside other psychiatric dimensions has clinical utility, as it provides a fuller view of an individual's needs and strengths, and greater prognostic utility than diagnostic categories. Based on this compelling body of evidence, we argue that incorporating a new neurodevelopmental spectrum into transdiagnostic frameworks has considerable potential for transforming our understanding, classification, assessment, and clinical practices around neurodevelopmental and other psychiatric conditions.

Prospective prediction of treatment outcomes in adolescents: A head-to-head comparison of alternative model for personality disorder versus borderline personality disorder.

Despite substantial evidence in support of the alternative model for personality disorder (AMPD) that has accumulated over the last decade, a gap remains in terms of head-to-head comparisons of the predictive power of Section II categorical diagnoses versus Section III AMPD diagnoses for clinical outcomes. The current study uses archival data from a naturalistic treatment outcome study in an adolescent psychiatric inpatient sample to compare the predictive power of the Section III AMPD (combined Criterion A and B assessment) versus Section II borderline personality disorder (BPD) in predicting treatment outcomes from admission to discharge. Outcomes in general psychiatric severity and emotion dysregulation were assessed in a sample of 59 adolescents (76.3% female, Mage = 15.27, SD = 1.17) at admission and at discharge on average about a month later. Results showed that, on average, predictive power of both AMPD measures and BPD were relatively modest. However, the AMPD, operationalized through combined measures of identity diffusion and maladaptive traits, was a stronger predictor of reduction in general psychiatric severity than a measure of BPD. The findings of the study add to a growing body of literature pointing to the advantages of Section III AMPD over Section II categorical diagnosis for clinical utility in predicting treatment response. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A transdiagnostic and diagnostic-specific approach on inflammatory biomarkers in eating disorders: A meta-analysis and systematic review

Eating disorders (EDs) are severe mental illnesses with a multifactorial etiology and a chronic course. Among the biological factors related to pathogenesis and maintenance of EDs, inflammation acquired growing scientific interest. This study aimed to assess the inflammatory profile of EDs, focusing on anorexia nervosa, bulimia nervosa, and including for the first time binge eating disorder. A comprehensive research of existing literature identified 51 eligible studies for meta-analysis, comparing levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), osteoprotegerin (OPG), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), interleukin-1β (IL-1β), and interleukin-10 (IL-10) between patients with EDs and healthy controls (HCs). The systematic review explored other inflammatory biomarkers of interest, which did not meet the meta-analysis criteria. Results revealed significantly elevated levels of TNF-α, OPG, sRANKL, and IL-1β in patients with EDs compared to HCs. Additionally, the results highlighted the heterogeneity of inflammatory state among patients with EDs, emphasizing the need for further research into the association between inflammatory biomarkers and psychopathological correlates. This approach should transcend categorical diagnoses, enabling more precise subcategorizations of patients.Overall, this study contributed to the understanding of the inflammatory pathways involved in EDs, emphasizing potential implications for diagnosis, staging, and targeted interventions.

A Secondary Analysis of the Complex Interplay between Psychopathology, Cognitive Functions, Brain Derived Neurotrophic Factor Levels, and Suicide in Psychotic Disorders: Data from a 2-Year Longitudinal Study.

Identifying phenotypes at high risk of suicidal behaviour is a relevant objective of clinical and translational research and can facilitate the identification of possible candidate biomarkers. We probed the potential association and eventual stability of neuropsychological profiles and serum BDNF concentrations with lifetime suicide ideation and attempts (LSI and LSA, respectively) in individuals with schizophrenia (SCZ) and schizoaffective disorder (SCA) in a 2-year follow-up study. A secondary analysis was conducted on a convenience sample of previously recruited subjects from a single outpatient clinic. Retrospectively assessed LSI and LSA were recorded by analysing the available longitudinal clinical health records. LSI + LSA subjects consistently exhibited lower PANSS-defined negative symptoms and better performance in the BACS-letter fluency subtask. There was no significant association between BDNF levels and either LSI or LSA. We found a relatively stable pattern of lower negative symptoms over two years among patients with LSI and LSA. No significant difference in serum BDNF concentrations was detected. The translational viability of using neuropsychological profiles as a possible avenue for the identification of populations at risk for suicide behaviours rather than the categorical diagnosis represents a promising option but requires further confirmation.

Autism Symptom Presentation and Hierarchical Models of Intelligence.

There is a substantial history studying the relationship between general intelligence and the core symptoms of autism. However, a gap in knowledge is how dimensional autism symptomatology associates with different components of clinically-relevant hierarchical models of intelligence. We examined correlations between autism diagnostic symptom magnitude (Autism Diagnostic Observational Schedule; ADOS) and a hierarchical statistical model of intelligence. One autistic cohort was tested on the fourth edition of Wechsler Intelligence Scale for Children (WISC-IV; N = 131), and another on the fifth edition (WISC-V; N = 83). We anticipated a convergent pattern of results between cohorts. On WISC-IV, ADOS scores were correlated significantly with g and three out of four intermediate factor scores, which was a broader pattern of correlations than anticipated from the literature. In the WISC-V cohort, only one intermediate factor correlated significantly with the ADOS; correlations with g and the other intermediate factors were less statistically certain. ADOS-factor correlations were larger in the WISC-IV than WISC-V cohort; this difference was significant at the 90% level. WISC-IV shows dimensional relationships with ADOS at multiple points in the hierarchical model of intelligence. Moreover, the current results provide evidence that relationship between core autism symptomatology and the construct of general intelligence may depend on how intelligence is measured. Known cohort effects in the relationship between categorical autism diagnosis and general intelligence have previously been attributed to changes in autism diagnostic practices. To our knowledge, this is the first evidence that differing versions of IQ tests may be implicated.

Competing Models of Personality Disorder: Relations With Psychosocial Functioning.

The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5; American Psychiatric Association, 2013), includes 10 categorical personality disorders (PD) in Section II (Section II PD) and a dimensional alternative model of PD (AMPD) in Section III. We compared the two models in explaining concurrent psychosocial functioning levels in psychiatric outpatients and community residents screened as at risk for PD pathology (N = 600). The AMPD's fully dimensional form showed stronger associations with psychosocial difficulties and explained more of their variance compared with the categorical Section II PD. AMPD Criterion A (personality functioning impairment) and Criterion B (pathological traits) incrementally predicted psychosocial functioning about equally with some unique predictions. Finally, AMPD's six categorical PD diagnoses did not show stronger associations with psychosocial functioning than the corresponding Section II PD diagnoses. Findings directly comparing the two models remain important and timely for informing future conceptualizations of PD in the diagnostic system.

Association of categorical diagnoses and psychopathologies with quality of life in patients with depression, anxiety, and somatic symptoms: A cross-sectional study

ObjectiveMajor depressive disorder (MDD), anxiety disorders, and somatic symptom disorder (SSD) are associated with quality of life (QoL) reduction. This cross-sectional study investigated the relationship between these conditions as categorical diagnoses and related psychopathologies with QoL, recognizing their frequent overlap. MethodsWe recruited a total of 403 clinical patients and healthy individuals, administering diagnostic interviews based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. QoL and psychopathologies were assessed using the WHO Quality of Life-BREF (WHOQOL-BREF) and several self-administered questionnaires, respectively. Multiple linear regression analyses examined the associations between psychiatric diagnoses, psychopathologies, and QoL. ResultsSSD and MDD were independently associated with impaired global (β = −0.318 and − 0.287) and all QoL domains (β = −0.307, −0.150, −0.125, and − 0.133, in physical, psychological, social, and environmental domains respectively for SSD; β = −0.278, −0.344, −0.275, and − 0.268 for MDD). The Beck Depression Inventory-II score showed pervasive associations with QoL (β = −0.390, −0.408, −0.685, −0.463, and − 0.420, in global, physical, psychological, social, and environmental domains). The Patient Health Questionnaire-15 and Health Anxiety Questionnaire scores were associated with global (β = −0.168 and − 0.181) and physical (β = −0.293 and − 0.121) QoL domain, while the Cognitions About Body and Health Questionnaire score was only associated with environmental QoL domain (β = −0.157). ConclusionSSD and MDD were independently associated with QoL impairment. Depressive symptoms were associated with all QoL domains, whereas somatic symptom burden and health anxiety primarily affected the physical QoL domain. Clinicians should consider concomitant psychopathologies when managing patients with depression, anxiety, or somatic symptoms.

Personality disorders, fact or fiction? The dark future of their diagnosis

The categorical diagnosis of personality disorders (PDs) has been criticized for various reasons, among which are overlapping of symptoms between different disorders, their high comorbidity, and the dichotomous nature of their diagnosis. These criticisms have led to the development of a dimensional approach in the latest versions of the classification systems, DSM-5/DSM-5-TR and ICD-11, considering two substantial aspects for its new diagnosis: personality functioning, and a series of pathological features. Despite the large amount of literature that has been published since the beginning of this century on this dimensional proposal, it is not clear, to date, that this approach enhances clinical utility. The vague, abstract, and inoperative exposition of what constitutes personality functioning and the complex and forced designation of major and minor traits (facets) in the DSM-5/DSM-5-TR, and only major and optional traits in the ICD-11, complicate, in an unusual way, the dimensional diagnosis of PDs. This paper discusses all of these issues in an attempt to shed some light on the potentially dark future of the current PDs panorama.

Comparing the DSM-5 categorical model of personality disorders and the alternative model of personality disorders regarding clinician judgments of risk and outcome.

The goal of this study was to compare the predictive validity of the alternative model for personality disorders (AMPD) versus the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Section II categorical model regarding clinician judgments about mental health outcomes. To do so, we instructed a national sample of 136 mental health professionals to provide clinical judgments on a random subset of four (out of a possible 12) case vignettes. For each case, they made a variety of diagnostic judgments corresponding to each model, as well as clinical outcome judgments (e.g., prognosis). Our analyses included hierarchical and individual regressions to compare the predictive value of each diagnostic system toward these clinical outcome judgments. We found that the AMPD predictors consistently added unique variance beyond the Section II predictors, whereas the Section II predictors were rarely incremental above the AMPD. Further, the AMPD judgments predicted outcome judgments very consistently (98.3% of regressions) compared to the Section II predictors (70% of regressions), and the single Criterion A judgment (level of personality functioning) was the strongest overall predictor. Finally, the categorical borderline personality disorder diagnoses from the two systems performed similarly in predicting clinical outcomes and agreed in 79% of cases. We interpreted our results to suggest that the AMPD is at least as effective, and by some measures more effective, than the DSM-5 categorical model at predicting clinician's judgment of outcomes in clinical cases. We conclude by discussing the value of this evidence in relation to the broader AMPD literature, as well as possible paths forward for the diagnosis of personality disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Personality traits as predictors of depression across the lifespan

BackgroundDepression is a major public health concern. A barrier for research has been the heterogeneous nature of depression, complicated by the categorical diagnosis of depression which is based on a cluster of symptoms, each with its own etiology. To address the multifactorial etiology of depression and its high comorbidity with anxiety, we aimed to examine the relations between personality traits, diverse behavioral, cognitive and physical measures, and depression and anxiety over the lifespan. MethodOur sample was drawn from the NKI-RS, a community-based lifespan sample (N = 1494 participants aged 6 to 85). Analyses included multivariate approach and general linear models for group comparisons and dimensional analyses, respectively. A machine learning model was trained to predict depression using many factors including personality traits. ResultsDepression and anxiety were both characterized by increased neuroticism and introversion, but did not differ between themselves. Comorbidity had an additive effect on personality vulnerability. Dimensionally, depression was only associated with personality in adolescence, where it was positively correlated with neuroticism, and negatively correlated with extraversion, agreeableness, and conscientiousness. The relationship between anxiety and personality changed over time, with neuroticism and conscientiousness being the most salient traits. Our machine learning model predicted depression with 70 % accuracy with neuroticism and extraversion contributing most. LimitationsDue to the cross-sectional design, conclusions cannot be drawn about causal relationships between personality and depression. ConclusionThese results underscore the impact of personality on depressive disorders and provide novel insights on how personality contributes to depression across the lifespan.

The course of borderline personality disorder from adolescence to early adulthood: A 5-year follow-up study

BackgroundStudies of the medium- to long-term clinical and functional course for treatment-seeking adolescents with borderline personality disorder (BPD) are lacking. This study aims to outline the psychopathological and functional status of participants, five years after being diagnosed with BPD during adolescence. MethodsParticipants were originally enrolled in a randomized clinical trial that compared mentalization-based group treatment with treatment as usual for adolescents with BPD. Semi-structured interview assessments at five-year follow-up included the Schedules for Clinical Assessment in Neuropsychiatry and the Structured Clinical Interview for DSM-5 Personality Disorders. Attention deficit hyperactivity disorder (ADHD), alcohol, substance and tobacco use, posttraumatic stress disorder (PTSD), complex PTSD, and general functioning were assessed using self-report instruments. Results97 of the original sample of 111 participants (87%) participated. They were aged 19–23 years. The most prevalent disorders were ADHD (59%), any personality disorder (47%) of which half continued to meet criteria for BPD (24%), anxiety disorders (37%), depressive disorders (32%), PTSD or complex PTSD (20%), schizophrenia (16%), and eating disorders (13%). Only 16% did not meet criteria for any mental disorder. Approximately half of the sample were in psychological and/or psychopharmacological treatment at the time of follow-up. Their general functioning remained impaired, with 36% not engaged in education, employment or training (NEET), which is nearly four times the rate of NEET in the same age group in the general population. ConclusionsAlthough stability of the categorical BPD diagnosis is modest, adolescents meeting diagnostic criteria for BPD show a broad range of poor outcomes at five-year follow-up. BPD appears to be a marker of general maladjustment during adolescence and a harbinger of severe problems during the transition to young adulthood. Early intervention programs for adolescents diagnosed with BPD should focus upon a broad range of functional and psychopathological outcomes, especially social and vocational support, rather than the narrow BPD diagnosis.

Testing Criterion Validity in Hierarchical Models of Psychopathology: Comparison of Latent-Variable and Factor-Score Approaches

The Hierarchical Taxonomy of Psychopathology is a quantitative diagnostic system that is gaining traction as a framework for studying the correlates of mental-health problems. However, it remains unknown how best to operationalize hierarchically related psychopathology dimensions during criterion validity tests. In a series of simulations, we evaluated the performance of latent-variable (i.e., structural equation modeling [SEM]) and factor-score representations of hierarchical psychopathology constructs in criterion validity analyses. In models based on continuously distributed psychopathology indicators (e.g., symptom composites), SEM and factor-score methods both tended to yield unbiased estimates of criterion validity coefficients. In contrast, for models based on dichotomous indicators (e.g., categorical diagnoses), SEM led to more accurate estimates than factor scores in most cases. We offer recommendations for psychopathology researchers based on these results and provide an R function ( https://osf.io/u3j5d/ ) that investigators can use to apply the approaches studied here in real-world data sets.

Shared and unique characteristics of metabolic syndrome in psychotic disorders: a review.

People with psychosis spectrum disorders (PSD) face an elevated risk of metabolic syndrome (MetS), which may reduce their life expectancy by nearly 20%. Pinpointing the shared and specific characteristics and clinical implications of MetS in PSD is crucial for designing interventions to reduce this risk, but an up-to-date review on MetS across the psychosis spectrum is lacking. This narrative review fills this gap by examining the clinical literature on characteristics and implications of MetS in both distinct PSD and transdiagnostically, i.e., across traditional categorical diagnoses, with a focus on psychiatric and cardio-metabolic management. We discuss common and specific characteristics of MetS in PSD, as well as factors contributing to MetS development in PSD patients, including unhealthy lifestyle factors, genetic predisposition, pro-inflammatory state, drugs consumption, antipsychotic medication, and psychotic symptoms. We highlight the importance of early identification and management of cardio-metabolic risk in PSD patients, as well as the existing gaps in the literature, for instance in the screening for MetS in younger PSD patients. We compare hypotheses-generating clinical associations and characteristics of MetS in different PSD, concluding by reviewing the existing recommendations and challenges in screening, monitoring, and managing MetS in PSD. Early identification and management of MetS are crucial to mitigate the long-term cardio-metabolic toll in PSD patients. Interventions should focus on healthy lifestyle and appropriate pharmacological and behavioral interventions. Further translational and clinical research is needed to develop targeted interventions and personalized treatment approaches for this vulnerable population, aiming at improving physical health and overall well-being.

Gender diversity is correlated with dimensional neurodivergent traits but not categorical neurodevelopmental diagnoses in children.

Gender clinic and single-item questionnaire-based data report increased co-occurrence of gender diversity and neurodevelopmental conditions. The nuances of these associations are under-studied. We used a transdiagnostic approach, combining categorical and dimensional characterization of neurodiversity, to further the understanding of its associations with gender diversity in identity and expression in children. Data from 291 children (Autism N = 104, ADHD N = 104, Autism + ADHD N = 17, neurotypical N = 66) aged 4-12 years enrolled in the Province of Ontario Neurodevelopmental Network were analyzed. Gender diversity was measured multi-dimensionally using a well-validated parent-report instrument, the Gender Identity Questionnaire for Children (GIQC). We used gamma regression models to determine the significant correlates of gender diversity among age, puberty, sex-assigned-at-birth, categorical neurodevelopmental diagnoses, and dimensional neurodivergent traits (using the Social Communication Questionnaire and the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scales). Internalizing and externalizing problems were included as covariates. Neither a categorical diagnosis of autism nor ADHD significantly correlated with current GIQC-derived scores. Instead, higher early-childhood dimensional autistic social-communication traits correlated with higher current overall gender incongruence (as defined by GIQC-14 score). This correlation was potentially moderated by sex-assigned-at-birth: greater early-childhood autistic social-communication traits were associated with higher current overall gender incongruence in assigned-males-at-birth, but not assigned-females-at-birth. For fine-grained gender diversity domains, greater autistic restricted-repetitive behavior traits were associated with greater diversity in gender identity across sexes-assigned-at-birth; greater autistic social-communication traits were associated with lower stereotypical male expression across sexes-assigned-at-birth. Dimensional autistic traits, rather than ADHD traits or categorical neurodevelopmental diagnoses, were associated with gender diversity domains across neurodivergent and neurotypical children. The association between early-childhood autistic social-communication traits and overall current gender diversity was most evident in assigned-males-at-birth. Nuanced interrelationships between neurodivergence and gender diversity should be better understood to clarify developmental links and to offer tailored support for neurodivergent and gender-diverse populations.

Link between neurodevelopmental disorders and suicidal risk in children

IntroductionSuicide represents a significant public health issue among children and adolescents. However, in this population, while the literature seems to support a link between suicidal risk and neurodevelopmental disorders, there are still few studies on the subject. The psychopathological description of children who have realized a suicide attempt with a high potential for lethality, which can be defined as “serious”, appears to resemble that of children who have died by suicide. This study aimed to characterize the dimensional aspects of the neurodevelopmental profile of a population of children and adolescents hospitalized at Necker-Enfants–Malades Hospital for a serious suicide attempt. MethodsThis is an observational, prospective, and single-center study. Questionnaires for collecting general information and dimensional scales of neurodevelopment (Autism-Tics, ADHD, and Other Comorbidities Inventory, Social Responsiveness Scale, and Conners-3 for parents) were used. This study included 21 patients aged 9 to 15 years at the time of their hospitalization. ResultsThe results supported the presence of at least one neurodevelopmental disorder (autistic traits, attention-deficit/hyperactivity disorder, learning disorder, or motor disorder) in 70% (n=14) of the subjects, and at least one behavioral disorder (oppositional defiant disorder, conduct disorder) in 65% (n=13) of these subjects. ConclusionThe observed frequency of traits indicative of neurodevelopmental disorders in our population was higher than that observed in the general population, without the presented symptoms being eligible for categorical diagnosis. Considering the dimensional aspects of neurodevelopmental symptoms would therefore enable better identification of children at suicidal risk and more tailored interventions to contribute to the prevention of suicide in children.

Estimating Dementia Onset: AT(N) Profiles and Predictive Modeling in Mild Cognitive Impairment Patients.

Mild Cognitive Impairment (MCI) usually precedes the symptomatic phase of dementia and constitutes a window of opportunities for preventive therapies. The objective of this study was to predict the time an MCI patient has left to reach dementia and obtain the most likely natural history in the progression of MCI towards dementia. This study was conducted on 633 MCI patients and 145 subjects with dementia through 4726 visits over 15 years from Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. A combination of data from AT(N) profiles at baseline and longitudinal predictive modeling was applied. A data-driven approach was proposed for categorical diagnosis prediction and timeline estimation of cognitive decline progression, which combined supervised and unsupervised learning techniques. A reduced vector of only neuropsychological measures was selected for training the models. At baseline, this approach had high performance in detecting subjects at high risk of converting from MCI to dementia in the coming years. Furthermore, a Disease Progression Model (DPM) was built and also verified using three metrics. As a result of the DPM focused on the studied population, it was inferred that amyloid pathology (A+) appears about 7 years before dementia, and tau pathology (T+) and neurodegeneration (N+) occur almost simultaneously, between 3 and 4 years before dementia. In addition, MCI-A+ subjects were shown to progress more rapidly to dementia compared to MCI-A- subjects. Based on proposed natural histories and cross-sectional and longitudinal analysis of AD markers, the results indicated that only a single cerebrospinal fluid sample is necessary during the prodromal phase of AD. Prediction from MCI into dementia and its timeline can be achieved exclusively through neuropsychological measures.

Polygenic risk scores for mood and related disorders and environmental factors: Interaction effects on wellbeing in the UK biobank

Mood disorders have a genetic and environmental component and interactions (GxE) on the risk of psychiatric diseases have been investigated. The same GxE interactions may affect wellbeing measures, which go beyond categorical diagnoses and reflect the health-disease continuum.We evaluated GxE effects in the UK Biobank, considering as outcomes subjective wellbeing (feeling good and functioning well) and objective measures (education and income). We estimated the polygenic risk scores (PRSs) of major depressive disorder, bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. Stressful/traumatic events during adulthood or childhood were considered as E variables, as well as social support. The addition of the PRSxE interaction to PRS and E variables was tested in linear or multinomial regression models, adjusting for confounders.We included 33 k–380 k participants, depending on the variables considered. Most PRSs and E factors showed additive effects on outcomes, with effect sizes generally 3–5 times larger for E variables than PRSs. We found some interaction effects, particularly when considering recent stress, history of a long illness/disability/infirmity, and social support. Higher PRSs increased the negative effects of stress on wellbeing, but they also increased the positive effects of social support, with interaction effects particularly for the outcomes health satisfaction, loneliness, and income (p < Bonferroni corrected threshold of 1.92e-4). PRSxE terms usually added ∼0.01–0.02% variance explained to the corresponding additive model.PRSxE effects on wellbeing involve both positive and negative E factors. Despite small variance explained at the population level, preventive/therapeutic interventions that modify E factors could be beneficial at the individual level.