Dimensional Measures Of Psychopathology Research Articles

Dimensional Measures of Psychopathology in Children and Adolescents Using Large Language Models

BackgroundTo enable greater use of National Institute of Mental Health Research Domain Criteria (RDoC) in real-world settings, we applied large language models (LLMs) to estimate dimensional psychopathology from narrative clinical notes. MethodsWe conducted a cohort study using health records from individuals age ≤18 years evaluated in the psychiatric emergency department of a large academic medical center between November 2008 and March 2015. Outcomes were hospital admission and length of emergency department stay. RDoC domains were estimated using a Health Insurance Portability and Accountability Act–compliant LLM (gpt-4-1106-preview) and compared with a previously validated token-based approach. ResultsThe cohort included 3059 individuals (median age 16 years [interquartile range, 13–18]; 1580 [52%] female, 1479 [48%] male; 105 [3.4%] identified as Asian, 329 [11%] as Black, 288 [9.4%] as Hispanic, 474 [15%] as other race, and 1863 [61%] as White), of whom 1695 (55%) were admitted. Correlation between LLM-extracted RDoC scores and the token-based scores ranged from small to medium as assessed by Kendall’s tau (0.14–0.22). In logistic regression models adjusting for sociodemographic and clinical features, admission likelihood was associated with greater scores on all domains, with the exception of the sensorimotor domain, which was inversely associated (p < .001 for all adjusted associations). Tests for bias suggested modest but statistically significant differences in positive valence scores by race (p < .05 for Asian, Black, and Hispanic individuals). ConclusionsAn LLM extracted estimates of 6 RDoC domains in an explainable manner, which were associated with clinical outcomes. This approach can contribute to a new generation of prediction models or biological investigations based on dimensional psychopathology.

Identifying internalizing transdiagnostic profiles through motivational and cognitive control systems: Relations with symptoms, functionality, and quality of life

BackgroundThe diversity of patients' symptomatology among people seeking treatment on community-based mental health services poses significant challenges to traditional models of care. Recent approaches favor identifying transdiagnostic factors that allow a better understanding of patient heterogeneity and designing more effective and quality interventions. This study examines the heterogeneity of patients with internalizing symptoms based on profiles identified with cognitive and motivational control variables. Differences between these profiles on dimensional measures of psychopathology and quality of life are examined. Methods263 patients were selected by non-probabilistic sampling procedures on mental health services in the province of Huelva (Spain). A latent class analysis on the standardized scale scores of The Behavioral Inhibition/Behavioral Activation System Scales and the Effortful Control Scale of the Adult Temperament Questionnaire Short-Form was conducted. Profiles were compared on the scores of the Inventory of Depression and Anxiety Symptoms-II, the WHO Disability Assessment Schedule II, and the Health Assessment Questionnaire SF-36. ResultsThe four latent profile solution is the one that showed the best fit indicators and substantive interpretability, with a kappa of 0.94 in the cross-validation procedure with 75% of the sample. No sex differences were found between the profiles (χ32 5.17, p = .160). Profiles #1 and #3, both characterized by an imbalance between low activation and high inhibition, had lower well-being, lower functionality, and quality of life. When comparing profile #2 (featuring the highest inhibitory control) lower scores on most internalizing scales are observed, specially claustrophobia, social anxiety, panic mania. Profile #4 (low control, high activation, and high inhibition) showed greater scores on both mania and euphoria and lower scores on emotional role. ConclusionsWe identified four distinctive profiles that had overly increased behavioral inhibition (as expected in internalizing disorders) and differed in the degree of imbalance between inhibition and activation systems, and between motivational systems and top-down cognitive control. The profile characterized by high activation and reduced cognitive (inhibitory) control was the one showing greater mood-related symptoms and lower levels of quality of life. These profiles could be generated by treatment providers to guide clinical management in an evidence-based manner.

Transdiagnostic psychopathology in the light of robust single-trial event-related potentials.

Recent evidence indicates that event-related potentials (ERPs) as measured on the electroencephalogram (EEG) are more closely related to transdiagnostic, dimensional measures of psychopathology (TDP) than to diagnostic categories. A comprehensive examination of correlations between well-studied ERPs and measures of TDP is called for. In this study, we recruited 50 patients with emotional disorders undergoing 14 weeks of transdiagnostic group psychotherapy as well as 37 healthy comparison subjects (HC) matched in age and sex. HCs were assessed once and patients three times throughout treatment (N = 172 data sets) with a battery of well-studied ERPs and psychopathology measures consistent with the TDP framework The Hierarchical Taxonomy of Psychopathology (HiTOP). ERPs were quantified using robust single-trial analysis (RSTA) methods and TDP correlations with linear regression models as implemented in the EEGLAB toolbox LIMO EEG. We found correlations at several levels of the HiTOP hierarchy. Among these, a reduced P3b was associated with the general p-factor. A reduced error-related negativity correlated strongly with worse symptomatology across the Internalizing spectrum. Increases in the correct-related negativity correlated with symptoms loading unto the Distress subfactor in the HiTOP. The Flanker N2 was related to specific symptoms of Intrusive Cognitions and Traumatic Re-experiencing and the mismatch negativity to maladaptive personality traits at the lowest levels of the HiTOP hierarchy. Our study highlights the advantages of RSTA methods and of using validated TDP constructs within a consistent framework. Future studies could utilize machine learning methods to predict TDP from a set of ERP features at the subject level.

ADHD symptoms and diurnal cortisol in adolescents: The importance of comorbidities

BackgroundAltered regulation of diurnal cortisol has been associated with both dimensional symptoms and clinical diagnoses of attention deficit-hyperactivity disorder (ADHD). Indeed, a recent meta-analysis suggests that lower diurnal cortisol output may be a biomarker of attention deficit-hyperactivity disorder (ADHD); importantly, however, the influence of psychiatric comorbidities on this association has not been characterized. Approximately two-thirds of children with ADHD have at least one co-occurring neuropsychiatric condition, and altered HPA-axis function has been implicated in many of these conditions. Using dimensional measures of psychopathology, we examined whether comorbid symptoms influence the association of ADHD symptoms with daily cortisol output. Methods138 adolescents (ages 11–15 years) completed measures of symptoms of psychopathology and provided saliva samples over two days. We analyzed whether ADHD symptoms were related to morning, afternoon, and evening cortisol, the cortisol awakening response (CAR) and cumulative daily cortisol (area under the curve with respect to ground [AUCg]) while accounting for symptoms of three psychiatric disorders that are commonly comorbid with ADHD: conduct disorder (CD), anxiety, and depression. In sensitivity analyses, we included symptoms of oppositional defiant disorder (ODD) in place of CD symptoms. FindingsAfter controlling for symptoms of CD, anxiety, and depression, ADHD symptoms were associated significantly with higher cumulative diurnal cortisol (AUCg), morning cortisol, and afternoon cortisol. Symptoms of CD, anxiety and depression were not associated significantly with any cortisol metrics; however, in sensitivity analyses, ODD symptoms were associated with lower AUCg and morning cortisol. DiscussionOur findings highlight the distinct influence of ADHD and externalizing symptoms on cortisol output. Further work is needed to examine the specificity of altered HPA-axis activity as a biomarker of ADHD and to elucidate whether symptoms of ADHD differ in their association with diurnal cortisol as a function of their severity.

An Exploratory Study of MMPI-2-RF Personality and Psychopathology Profiles of Adults with Autism Spectrum Disorder without Intellectual Disability.

More empirical research is needed to disentangle the phenotypes of autism spectrum disorder (ASD) and cluster C personality symptomatology (CCPD), as both show similarities in their clinical presentation. We explored personality and psychopathology dimensions as conceptualized in contemporary dimensional taxonomies (i.e., hierarchical taxonomy of psychopathology; HiTOP) in adults with ASD without intellectual disability operationalized by the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). Applying secondary analytic processes using clinical data, we cross-examined the MMPI-2-RF profiles of adults with ASD (n = 28) compared to adults with Cluster C personality disorders (CCPD; n = 28) and a control group (n = 28) by conducting nonparametric tests and assessing effect sizes. The profiles of the ASD and CCPD groups evidenced to be similar, and both average clinical profiles diverged from the average control group profiles by elevated levels of demoralization, internalizing, and somatization symptomatology. There were small differences between the average profiles of adults with ASD and adults with CCPD. Additional research using dimensional measures of psychopathology could elucidate the dimensional phenotypes of ASD and CCPD. Based on the results in this study, the MMPI-2-RF may not meaningfully discriminate between the two clinical presentations, with the exception of various externalizing scales.

Fear-potentiated startle predicts longitudinal change in transdiagnostic symptom dimensions of anxiety and depression

BackgroundElevated defensive responding, through startle reflex (SR) and skin conductance response (SCR), may contribute to onset and maintenance of depression and anxiety. Most work examining SR and SCR has predicted psychiatric diagnoses. There is a paucity of research examining links between SR or SCR and dimensional measures of psychopathology. MethodsWe used latent growth curve modeling to predict longitudinal change in three symptom factors (i.e., General Distress, Fears, Anhedonia-Apprehension) from SR and SCR measured during a fear-potentiated startle paradigm among adolescents oversampled for neuroticism (N = 129). ResultsElevated SCR in danger phases before and after an unpleasant muscle contraction predicted increasing Fears over time. Elevated SR in safe phases post-contraction also predicted increasing Fears over time. Attenuated SR in safe phases post-contraction predicted elevated General Distress longitudinally. Attenuated SCR pre-contraction in danger phases predicted elevated Anhedonia-Apprehension over time. LimitationsOur non-clinical sample may limit generalizability of results. Additionally, we did not assess change in SR and SCR over time. ConclusionsThe present study demonstrates that SR and SCR during a fear-potentiated startle paradigm predict longitudinal change in dimensional anxiety and depression symptom factors and relatedly, that SR and SCR may represent risk factors for the exacerbation of symptomatology.

Examining the neural correlates of error awareness in a large fMRI study.

Goal-directed behavior is dependent upon the ability to detect errors and implement appropriate posterror adjustments. Accordingly, several studies have explored the neural activity underlying error-monitoring processes, identifying the insula cortex as crucial for error awareness and reporting mixed findings with respect to the anterior cingulate cortex (ACC). Variable patterns of activation have previously been attributed to insufficient statistical power. We therefore sought to clarify the neural correlates of error awareness in a large event-related functional magnetic resonance imaging (fMRI) study. Four hundred and two healthy participants undertook the error awareness task, a motor Go/No-Go response inhibition paradigm in which participants were required to indicate their awareness of commission errors. Compared to unaware errors, aware errors were accompanied by significantly greater activity in a network of regions, including the insula cortex, supramarginal gyrus (SMG), and midline structures, such as the ACC and supplementary motor area (SMA). Error awareness activity was related to indices of task performance and dimensional measures of psychopathology in selected regions, including the insula, SMG, and SMA. Taken together, we identified a robust and reliable neural network associated with error awareness.

Psychopathology and Adaptive Functioning in Children, Adolescents, and Young Adults with Noonan Syndrome.

The objective of this study was to examine psychopathology and its impact on adaptive functioning in a sample of patients affected by Noonan syndrome (NS), a genetically heterogeneous condition with systemic manifestations. Forty-two subjects affected by NS (23 males and 19 females), aged 5 to 21 years (mean 12.6 ± SD 5.1), were assessed for nonverbal cognitive abilities, with dimensional measures of psychopathology, adaptive functioning, and family quality of life. The nonverbal intelligence quotient (IQ) mean was 99.4 ± SD 22.2, with 3 subjects (8%, 95% confidence interval [CI], 1.6%-20.9%) showing cognitive impairment (IQ<70). The Parent Child Behavior Checklist (CBCL) total psychopathology score was in the clinical range in 10% of sample and borderline in another 10%. On the Conners' Parent Rating Scales, scores suggestive of attention-deficit/hyperactivity disorder (ADHD) were in the clinical range in 20%. On the autism quotient, autism spectrum disorder symptoms were reported in 10%. Higher scores on the Adaptive Behavioral Assessment System-Second Edition and on the World Health Organization Quality of Life (26 items) were associated with lower problems on the CBCL (r = -0.63, 95% CI, -0.78 to -0.40 and r = -0.48, 95% CI, -0.69 to -0.20, respectively). Psychopathology was common in patients with NS and negatively correlated with global functioning and family quality of life. Treatable psychopathology, such as ADHD, may constitute a treatment target for improving adaptive functioning.

“Children Aren't Just Small Adults”: Non-Specific Mapping of Polygenic Risk Scores Onto Dimensional Psychopathology at Age 9-10 in the ABCD Study

Genome wide association studies (GWAS) in psychiatry, and polygenic risk score (PRS) analyses, have focused primarily on disorders that emerge in adulthood and have enrolled adult participants. Effects of polygenic loading for these disorders on psychopathology in children remain largely unexplored. Dimensional measures of psychopathology in children may index risk for emergence of full-blown disorders later in life. As such, an understanding of how genetic loading for these disorders maps onto dimensional symptoms in children may have value for prognosis and early intervention. Leveraging baseline data from the Adolescent Brain Cognitive Development (ABCD) Study, we examined how indices of polygenic risk track with dimensional psychopathology at age 9-10.

Sub-millimeter variation in human locus coeruleus is associated with dimensional measures of psychopathology: An in vivoultra-high field 7-Tesla MRI study.

The locus coeruleus (LC) has a long-established role in the attentional and arousal response to threat, and in the emergence of pathological anxiety in pre-clinical models. However, human evidence of links between LC function and pathological anxiety has been restricted by limitations in discerning LC with current neuroimaging techniques. We combined ultra-high field 7-Tesla and 0.4×0.4×0.5mm quantitative MR imaging with a computational LC localization and segmentation algorithm to delineate the LC in 29 human subjects including subjects with and without an anxiety or stress-related disorder. Our automated, data-driven LC segmentation algorithm provided LC delineations that corresponded well with postmortem anatomic definitions of the LC. There was variation of LC size in healthy subjects (125.7 +/- 59.3mm3), which recapitulates histological reports. Patients with an anxiety or stress-related disorder had larger LC compared to controls (Cohen's d=1.08, p=0.024). Larger LC was additionally associated with poorer attentional and inhibitory control and higher anxious arousal (FDR-corrected p's<0.025), trans-diagnostically across the full sample. This study combined high-resolution and quantitative MR with a mixture of supervised and unsupervised computational techniques to provide robust, sub-millimeter measurements of the LC in vivo, which were additionally related to common psychopathology. This work has wide-reaching applications for a range of neurological and psychiatric disorders characterized by expected LC dysfunction.

Homo- and Heterotypic Trajectories in a Preschool to Primary-School Clinical Sample: A Prospective Study Related to Maternal Psychopathology.

Background: Most longitudinal or follow-up mental health studies describe developmental pathways using dimensional measures of psychopathology, but seldom using pathways described by clinical disorders.Objective: We aim to describe diagnostic pathways by homotypic (within the disorder continuity) and heterotypic development (between the disorder continuity), with maternal psychopathology as moderator for both trajectories.Methods: Clinically referred children (0–7 years; N = 83) were assessed at preschool age and at primary-school age through a clinical interview. We built a disorder cluster of emotional disorders (ED; F32, F40, F42, F43, F93.0, F93.1, F93.2, F93.8, F95), behavioral disorders (BD; F68.8, F90, F91, F91.3, F93.3, F93.9, F94), and specific early onset disorders (SEO; F50, F51, F70, F98.0, F98.1, F98.2, F98.8, F98.9). We describe the prevalence, comorbidity, and clinical trajectories of various types of homotypic and heterotypic development.Results: We observed a high rate of comorbidity throughout the study (62.6% at admission and 67.5% at follow-up) and in general, a high continuity of mental health problems from preschool to primary-school age children (69.9% of the sample showed continuity), with 50.6% of the sample showing homotypic and 44.6% showing heterotypic development. Hierarchical multiple regression analyses suggest that heterotypic development may be influenced by maternal psychopathology.Conclusion: Currently, evidence-based mental health guidelines for preschool populations are designed and evaluated assuming a homotypic development. However, our findings indicate that treatment interventions and outcome measures should also be designed and evaluated for heterotypic development especially in case of increased maternal psychopathology.

53 - TRANSLATING DISCOVERIES IN ADHD GENOMICS TO THE CLINIC

Background A recent genome-wide association analysis has identified specific susceptibility variants and a substantial polygenic component for Attention-Deficit/Hyperactivity Disorder (ADHD). Given that emerging risk variants are unlikely to track precisely with conventional diagnoses, whether these discoveries will have utility in clinical settings for improved diagnostics and risk stratification requires further study. Our overall goal is to establish the relevance of emerging psychiatric genetics findings to youth clinical samples. In the current study, we aimed to 1) confirm the convergent validity of ADHD polygenic risk with ADHD-related phenotypes in youth presenting for neuropsychiatric evaluation; and 2) determine the extent to which ADHD polygenic risk associates with phenotypes beyond ADHD that putatively share its underlying liability and have implications for functional outcome. Methods Participants were 470 youth, ages 7 to 18, consecutively referred for neuropsychiatric evaluation and genotyped on the Illumina Infinium PsychArray Beadchip. Diagnoses made subsequent to study enrollment reflected a range of psychopathology and comorbidity. We determined the burden of ADHD-related common variants in these patients at different significance thresholds from the ADHD PGC-iPSYCH meta-analysis. We then associated this polygenic risk with clinical phenotypes. First, we conducted univariate analyses relating ADHD polygenic risks scores (PRSs) to ADHD diagnoses (none/borderline/full) and symptoms, cognition, and dimensional ratings of aggression and mania. Second, we stratified youth by low, medium, and high ADHD polygenic burden and used a mixed modeling approach to determine whether risk strata associated with distinct multivariate clinical profiles. Third, we determined phenotypically distinct latent classes in these and other youth (N~900) based on eight dimensional measures of psychopathology and examined whether the ADHD-PRS discriminated among them. Results The ADHD-PRS predicted the ADHD diagnosis at seven discovery sample thresholds after correction for potential confounds and multiple testing. The strongest association occurred at discovery sample p Discussion In a multi-diagnostic clinical sample, ADHD polygenic risk showed convergent validity with ADHD phenotypes. Genotype- and phenotype-first analyses also indicated that ADHD polygenic burden associates with traits reflecting cognition and behavioral and emotional dysregulation that extend beyond ADHD and that have implications for functional outcome.

S109. SYMPTOM NETWORK MODELS OF PSYCHOSIS

BackgroundDisorders within the psychosis spectrum are highly heterogeneous and multifactorial (Weinberger & Harrison, 2010). However, in spite of decades of research, causes of psychosis are still uncertain (e.g., Tandon et al., 2008). In an attempt to overcome these shortcomings, recent years have seen a rise in the modeling of psychotic disorders as networks of interacting symptoms (Borsboom, 2017). The centerpiece of network modeling lies in the idea that symptoms are active causal agents in producing disorder states, and that the study of their causal interaction is central to progress in understanding and treating mental disorders (Isvoranu et al., submitted). This presentation aims to introduce the network approach to mental disorders in the context of psychotic symptomatology.MethodsThe network approach is a novel psychometric framework based on a dynamical systems perspective. In network models, mental disorders such as schizophrenia are no longer conceptualized as common causes of symptoms, but as conditions that arise from the interaction between symptoms. The pattern on interactions can be visualized in a network structure, in which variables (e.g., symptoms, environmental factors, genetic factors) are represented as nodes and the presence of an edge between any two nodes implies the existence of a statistical association, which does not vanish upon controlling for all of the other nodes in the network (Isvoranu et al., 2016). This talk will include two examples of network models. First, using general population data a network model for the relation between three environmental risk factors (cannabis use, developmental trauma, and urban environment), dimensional measures of psychopathology and a composite measure of psychosis is constructed (Isvoranu et al., 2016). Second, using the GROUP dataset (Korver et al., 2012) which includes patients, siblings of patients, parents and controls, a network model is constructed for the relation between a polygenic risk score for psychosis liability and symptoms of psychotic disorders.ResultsThe results of the first study indicate specific paths between environmental factors and symptoms, most often involving cannabis use (Isvoranu et al., 2016). In addition, the analysis suggests that symptom networks are more strongly connected for people exposed to environmental risk factors, indicating that environmental exposure may lead to less resilient symptom networks. The second study indicates that genetic vulnerability assessed via a polygenic risk score is associated with several individual psychotic symptoms – especially positive psychotic symptoms – suggesting that part of the missing heritability problem may be lie in the psychometric conceptualization of psychosis.DiscussionPsychotic disorders feature a multitude of symptoms and problems, which lead to an inherent heterogeneity of psychosis. Current (psychometric) conceptualizations of pathology cannot fully encompass the complexity of these problems – this yields to the need of developing tools that could aid our understanding of psychiatric disorders and could ultimately be implemented in clinical practice. Network modeling may provide such a tool. It is unlikely that there is such a thing as “one-size fits all treatment” for psychosis spectrum disorders, and intervention planning may require personalized network modelling (Isvoranu et al., submitted). In the coming years we are likely to learn the extent to which the network approach could aid research and clinicians.

A Network Approach to Environmental Impact in Psychotic Disorder: Brief Theoretical Framework.

The spectrum of psychotic disorder represents a multifactorial and heterogeneous condition and is thought to result from a complex interplay between genetic and environmental factors. In the current paper, we analyze this interplay using network analysis, which has been recently proposed as a novel psychometric framework for the study of mental disorders. Using general population data, we construct network models for the relation between 3 environmental risk factors (cannabis use, developmental trauma, and urban environment), dimensional measures of psychopathology (anxiety, depression, interpersonal sensitivity, obsessive-compulsive disorder, phobic anxiety, somatizations, and hostility), and a composite measure of psychosis expression. Results indicate the existence of specific paths between environmental factors and symptoms. These paths most often involve cannabis use. In addition, the analyses suggest that symptom networks are more strongly connected for people exposed to environmental risk factors, implying that environmental exposure may lead to less resilient symptom networks.

Cognitive and affective components of Theory of Mind in preschoolers with oppositional defiance disorder: Clinical evidence

The goal of the study was to examine the affective-cognitive components of Theory of Mind (ToM), in a community sample of 538 preschoolers, and more specifically in a subsample of 40 children diagnosed with ODD. The relationship between affective and cognitive ToM and some ODD clinical characteristics was examined. Children were assessed with structured diagnostic interviews and dimensional measures of psychopathology, impairment and unemotional traits. A measure based on eye-gaze was used to assess ToM. Mixed analysis of variance compared the mean cognitive versus affective scale scores and the between-subjects factor ODD. The association between ToM-scores and clinical measures was assessed through correlation models. Execution and reaction time to emotional and cognitive components of ToM tasks are different at age 5 in normally developing children. Oppositional Defiant children had slower response time when performing the affective mentalizing condition than children without the disorder. The correlation matrix between ToM-scores and clinical measures showed specific associations depending on the impaired ToM aspect and the psychological domain. Results may have clinical implications for the prevention and management of ODD.

The Alcohol Use Disorder and Associated Disabilities Interview Schedule-5 (AUDADIS-5): Procedural validity of substance use disorders modules through clinical re-appraisal in a general population sample

BackgroundThe purpose of this study was to assess the procedural validity of the substance disorder modules of the lay-administered Alcohol Use Disorder and Associated Disabilities Interview Schedule, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Version (AUDADIS-5) through clinician re-appraisal re-interviews. MethodsThe study employed a test–retest design among 712 respondents from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III). A clinician-administered, semi-structured interview, the Psychiatric Research Interview for Substance and Mental Disorders, DSM-5 version (PRISM-5) was used as the re-appraisal. Kappa coeffients indicated concordance of the AUDADIS-5 and PRISM-5 for DSM-5 substance use disorder diagnoses, while intraclass correlation coefficients (ICC) indicated concordance on dimensional scales indicating the DSM-5 criteria count for each disorder. ResultsWith few exceptions, concordance of the AUDADIS-5 and the PRISM-5 for DSM-5 diagnoses of substance use disorders ranged from fair to good (κ=0.40–0.72). Concordance on dimensional scales was excellent (ICC≥0.75) for the majority of DSM-5 SUD diagnoses, and fair to good (ICC=0.43–0.72) for most of the rest. ConclusionsAs indicated by concordance with a semi-structured clinician-administered re-appraisal, the procedural validity of the AUDADIS-5 DSM-5 substance use disorder diagnoses found in this study indicates that these AUDADIS-5 diagnoses are useful tools in epidemiologic studies. The considerably stronger concordance of the AUDADIS-5 and PRISM-5 dimensional DSM-5 SUD measures supports a current movement to place more emphasis on dimensional measures of psychopathology, and suggests that such measures may be more informative than binary diagnoses for research, and possibly for clinical purposes as well.

Elevation discrepancies between MMPI-2 clinical and MMPI-2-RF restructured clinical (RC) scales in people with seizure disorders

PurposePeople with seizure disorders experience elevated rates of psychopathology, often undiagnosed and untreated. Accurate diagnosis of psychopathology remains an important goal of quality health care for people with seizure disorders. One of the most widely used dimensional measures of psychopathology is the Minnesota Multiphasic Personality Inventory—Second Edition (MMPI-2). Research in heterogeneous mental health samples suggests that the 2008 revision of this measure, the Minnesota Multiphasic Personality Inventory—Second Edition—Restructured Form (MMPI-2-RF), offers better construct fidelity and more cost-effective administration. This study seeks to extend research on MMPI-2-RF scale elevations to a sample of people with seizure disorders. MethodsIn a consecutive, heterogeneous sample of people with seizure disorders, MMPI-2 and MMPI-2-RF scores were compared in terms of categorical classification agreement (clinically elevated versus not clinically elevated). Scores were also compared in terms of variance attributable to diagnosis-specific items, general demoralization, subtle items, social desirability, and demographic factors. Key findingsScores on MMPI-2 and MMPI-2-RF provided a statistically significant level of agreement between corresponding clinical diagnostic scales ranging from 68% to 84%. Most classification disagreement was attributable to MMPI-2 clinical scale elevations when MMPI-2-RF scales were not elevated. Regression analysis supported the interpretation that general demoralization, subtle items, social desirability, and demographic factors led to MMPI-2 clinical scale elevations. SignificanceThe results provide evidence that in the context of strong psychopathology classification agreement, the MMPI-2-RF restructured clinical scales provide better construct fidelity compared with the more trait heterogeneous MMPI-2 clinical scales. These results should encourage clinicians to use the MMPI-2 Restructured Form (MMPI-2-RF) for improved psychopathology assessment compared with the MMPI-2 in patients with seizure disorders.

Prescribing ANtiDepressants Appropriately (PANDA): a cluster randomized controlled trial in primary care

BackgroundInappropriate use of antidepressants (AD), defined as either continuation in the absence of a proper indication or continuation despite the lack of therapeutic efficacy, applies to approximately half of all long term AD users.Methods/designWe have designed a cluster randomized controlled clinical trial to assess the (cost-) effectiveness of an antidepressant cessation advice in the absence of a proper indication for maintenance treatment with antidepressants in primary care.We will select all patients using antidepressants for over 9 months from 45 general practices. Patients will be diagnosed using the Composite International Diagnostic Interview (CIDI) version 3.0, extended with questions about the psychiatric history and previous treatment strategies. General practices will be randomized to either the intervention or the control group. In case of overtreatment, defined as the absence of a proper indication according to current guidelines, a cessation advice is given to the general practitioner. In the control groups no specific information is given. The primary outcome measure will be the proportion of patients that successfully discontinue their antidepressants at one-year follow-up. Secondary outcomes are dimensional measures of psychopathology and costs.DiscussionThis study protocol provides a detailed overview of the design of the trial. Study results will be of importance for refining current guidelines. If the intervention is effective it can be used in managed care programs.Trial registrationNTR2032

The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence

BackgroundThe International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with ADHD and 1446 unselected siblings. The aim was to describe and analyse questionnaire data and IQ measures from all probands and siblings. In particular, to investigate the influence of age, gender, family status (proband vs. sibling), informant, and centres on sample homogeneity in psychopathological measures.MethodsConners' Questionnaires, Strengths and Difficulties Questionnaires, and Wechsler Intelligence Scores were used to describe the phenotype of the sample. Data were analysed by use of robust statistical multi-way procedures.ResultsBesides main effects of age, gender, informant, and centre, there were considerable interaction effects on questionnaire data. The larger differences between probands and siblings at home than at school may reflect contrast effects in the parents. Furthermore, there were marked gender by status effects on the ADHD symptom ratings with girls scoring one standard deviation higher than boys in the proband sample but lower than boys in the siblings sample. The multi-centre design is another important source of heterogeneity, particularly in the interaction with the family status. To a large extent the centres differed from each other with regard to differences between proband and sibling scores.ConclusionsWhen ADHD probands are diagnosed by use of fixed symptom counts, the severity of the disorder in the proband sample may markedly differ between boys and girls and across age, particularly in samples with a large age range. A multi-centre design carries the risk of considerable phenotypic differences between centres and, consequently, of additional heterogeneity of the sample even if standardized diagnostic procedures are used. These possible sources of variance should be counteracted in genetic analyses either by using age and gender adjusted diagnostic procedures and regional normative data or by adjusting for design artefacts by use of covariate statistics, by eliminating outliers, or by other methods suitable for reducing heterogeneity.

Serum glutamine, set-shifting ability and anorexia nervosa

BackgroundSet-shifting is impaired in people with anorexia nervosa (AN), but the underlying physiological and biochemical processes are unclear. Animal studies have established that glutamatergic pathways in the prefrontal cortex play an important role in set-shifting ability. However, it is not yet understood whether levels of serum glutamatergic amino acids are associated with set-shifting performance in humans. The aim of this study was to determine whether serum concentrations of amino acids related to glutamatergic neurotransmission (glutamine, glutamate, glycine, l-serine, d-serine) are associated with set-shifting ability in people with acute AN and those after recovery.MethodsSerum concentrations of glutamatergic amino acids were measured in 27 women with current AN (AN group), 18 women recovered from AN (ANRec group) and 28 age-matched healthy controls (HC group). Set-shifting was measured using the Wisconsin Card Sorting Test (WCST) and the Trail Making Task (TMT). Dimensional measures of psychopathology were used, including the Eating Disorder Examination Questionnaire (EDEQ), the Maudsley Obsessive-Compulsive Inventory (MOCI) and the Hospital Anxiety and Depression Scale (HADS).ResultsSerum glutamine concentrations in the AN group (1,310.2 ± 265.6 μM, mean ± SD) were significantly higher (by approximately 20%) than those in the HC group (1,102.9 ± 152.7 μM, mean ± SD) (F(2, 70) = 6.3, P = 0.003, 95% CI 61.2 to 353.4). Concentrations of serum glutamine were positively associated with markers of the illness severity: a negative correlation was present between serum glutamine concentrations and body mass index (BMI) and lowest BMI and a positive correlation was found between duration of illness and EDEQ. The AN group showed significantly impaired set shifting in the WCST, both total errors, and perseverative errors. In the AN group, there were no correlations between serum glutamine concentrations and set shifting.ConclusionsSerum concentrations of glutamine may be a biomarker of illness severity in people with AN. It does not appear to be directly associated with changes in executive function.