Ceramide levels in blood plasma correlate with major depressive disorder severity and its neutralization abrogates depressive behavior in mice.

Major depressive disorder (MDD) is a severe disease of unknown pathogenesis that will affect ∼10% of people during their lifetime. Therapy for MDD requires prolonged treatment and often fails, predicating a need for novel treatment strategies. Here, we report increased ceramide levels in the blood plasma of MDD patients and in murine stress-induced models of MDD. These blood plasma ceramide levels correlated with the severity of MDD in human patients and were independent of age, sex, or body mass index. In addition, intravenous injection of anti-ceramide antibodies or neutral ceramidase rapidly abrogated stress-induced MDD, and intravenous injection of blood plasma from mice with MDD induced depression-like behavior in untreated mice, which was abrogated by ex vivo preincubation of the plasma with anti-ceramide antibodies or ceramidase. Mechanistically, we demonstrate that ceramide accumulated in endothelial cells of the hippocampus of stressed mice, evidenced by the quantitative measurement of ceramide in purified hippocampus endothelial cells. We found ceramide inhibited the activity of phospholipase D (PLD) in endothelial cells in vitro and in the hippocampus in vivo and thereby decreased phosphatidic acid in the hippocampus. Finally, we show intravenous injection of PLD or phosphatidic acid abrogated MDD, indicating the significance of this pathway in MDD pathogenesis. Our data indicate that ceramide controls PLD activity and phosphatidic acid formation in hippocampal endothelial cells and thereby mediates MDD. We propose that neutralization of plasma ceramide could represent a rapid-acting targeted treatment for MDD.

Gravitational Waves from a Core g Mode in Supernovae as Probes of the High-Density Equation of State.

Using relativistic supernova simulations of massive progenitor stars with a quark-hadron equation of state (EOS) and a purely hadronic EOS, we identify a distinctive feature in the gravitational-wave signal that originates from a buoyancy-driven mode (g mode) below the proto-neutron star convection zone. The mode frequency lies in the range 200≲f≲800 Hz and decreases with time. As the mode lives in the core of the proto-neutron star, its frequency and power are highly sensitive to the EOS, in particular the sound speed around twice saturation density.

Cancer Patients' Age-Related Benefits from Mobile Neurofeedback-Therapy in Quality of Life and Self-efficacy: A Clinical Waitlist Control Study.

Electroencephalographic neurofeedback (EEG NF) can improve quality of life (QoL) and reduce distress by modifying the amplitude of selected brain frequencies. This study aims to investigate the effects of NF therapy on QoL and self-efficacy in cancer patients and to explore age-related reactions. In a waitlist control paradigm, psychometric data (EORTC QLQ-C30, General Self-Efficacy Scale) of 20 patients were collected at three different time points, each five weeks apart. An outpatient 10-session NF intervention (mobile) was conducted between the second and third measurement point. QoL and self-efficacy changed significantly over time (QoL: F(2,36) = 5.294, p < .05, η2 = .227; Self-efficacy: F(2,26) = 8.178, p < .05, η2 = .386). While QoL increased in younger patients, older patients initially showed a decrease in QoL, which then increased during intervention. Younger patients did not differ from older patients in QoL in both waitlist control (T0-T1) and intervention phase (T1-T2). QoL in older patients significantly differed between waitlist control and intervention phase (Z = - 2.023, p < .05, d = 1.085). Self-efficacy increased in both age categories. Younger and older patients did not differ in self-efficacy in waitlist control, but in intervention phase (F(1,16) = 7.014, p < .05, η2 = .319). The current findings suggest that NF therapy is a promising treatment modality for improving QoL in cancer patients. Our study reveals NF being a tool to influence self-efficacy, which should receive more appreciation in clinical care. However, the effect of NF in different age groups as well as the influence on further cancer-related symptoms should be investigated in future research.

Erratum: Universal Relations for Gravitational-Wave Asteroseismology of Protoneutron Stars [Phys. Rev. Lett. 123, 051102 (2019)].

This corrects the article DOI: 10.1103/PhysRevLett.123.051102.

Reduced Jumping to Conclusion Bias after Experimentally Induced Enhancement of Subjective Body Boundaries in Psychosis.

INTRODUCTION: A disturbed sense of self is frequently discussed as an etiological factor for delusion symptoms in psychosis. Phenomenological approaches to psychopathology posit that lacking the sense that the self is localized within one's bodily boundaries (disembodiment) is one of the core features of the disturbed self in psychosis. The present study examines this idea by experimentally manipulating the sense of bodily boundaries. METHODS: Seventy-three patients with psychosis were randomly assigned to either a 10-min, guided self-massage in the experimental group (EG) to enhance the sense of bodily boundaries or a control group (CG), which massaged a fabric ring. Effects on an implicit measure (jumping to conclusion bias; JTC) and an explicit measure (Brief State Paranoia Checklist; BSPC) of delusion processes were assessed. The JTC measures the tendency to make a decision with little evidence available, and the BSPC explicitly measures the approval of paranoid beliefs. RESULTS: Patients in the EG showed a lower JTC (M = 4.11 draws before decision) than the CG (M = 2.43; Cohen's d = 0.64). No significant difference in the BSPC was observed. DISCUSSION/CONCLUSION: Our results indicate that enhancing the sense of body boundaries through a self-massage can reduce an implicit bias associated with delusional ideation and correspondingly support the idea that disembodiment might be a relevant factor in the formation of psychotic symptoms.

Amygdalar nuclei and hippocampal subfields on MRI: Test-retest reliability of automated volumetry across different MRI sites and vendors.

BACKGROUND: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. METHODS: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. RESULTS: Significant MRI site and vendor effects (p â€‹< â€‹.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman's r correlations >0.43, p â€‹< â€‹1.39E-36). In particular, volumes larger than 200 â€‹mm3 (for amygdalar nuclei) and 300 â€‹mm3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε â€‹< â€‹5% and DICE â€‹> â€‹0.80). CONCLUSION: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.

Theory of mind, emotion recognition, delusions and the quality of the therapeutic relationship in patients with psychosis - a secondary analysis of a randomized-controlled therapy trial.

BACKGROUND: Cognitive models of psychosis postulate an important role of Theory of mind (ToM) in the formation and maintenance of delusions, but research on this plausible conjecture has gathered conflicting findings. In addition, it is still an open question whether problems in emotion recognition (ER) are associated with delusions. We examined the association of problems in ToM and ER with different aspects of delusions in a large sample of patients with psychosis enrolled in a therapy trial. This also enabled us to explore the possible impact of ToM and ER on one part of patients' social life: the quality of their therapeutic relationship. METHODS: Patients with psychotic disorders and delusions and/or hallucinations (n = 185) and healthy controls (n = 48) completed a ToM picture sequencing task and an ER task. Subsequently, patients were enrolled in a randomized-controlled Cognitive Behavior Therapy (CBT) trial (ISRCTN29242879). Patients and therapists rated the quality of the therapeutic relationship during the first five sessions of therapy. RESULTS: In comparison to controls, patients were impaired in both ToM and ER. Patients with deficits in ER experienced more severe delusional distress, whereas ToM problems were not related to delusions. In addition, deficits in ER predicted a less favorable therapeutic relationship and interactional problems viewed by the therapist. Impaired ER also moderated (increased) the negative influence of delusions on the therapeutic relationship and interactional difficulties viewed by the therapist. CONCLUSIONS: Cognitive models on the formation and maintenance of delusions should consider ER as a potential candidate that might be related to the formation and maintenance of delusional distress, whereas problems in ToM might not be directly related to delusions and secondary dimensions of delusions. In addition, problems in ER in patients with psychosis might have an impact on the quality of the therapeutic relationship and patients with problems in ER are more likely to be viewed as problematic by their therapists. Nevertheless, training ER might be a way to improve the quality of the therapeutic relationship and potentially the effectiveness of CBT or other interventions for patients with psychosis.

Problems in measuring the JTC-bias in patients with psychotic disorders with the fish task: a secondary analysis of a baseline assessment of a randomized controlled trial.

BACKGROUND: The jumping to conclusions bias (JTC) is considered to be an important causal factor in theoretical models for the formation and maintenance of delusions. However, recent meta-analytic findings show a rather equivocal pattern of results regarding associations between JTC and delusions. Thus, the present study aims to investigate in a large sample whether the JTC-bias is more pronounced in patients with psychotic disorders in comparison to controls and whether the JTC bias is associated with a more severe delusional conviction, persecutory delusions, and positive symptoms in general. METHODS: Patients with psychotic disorders (n = 300) enrolled in a therapy trial and healthy controls (n = 51) conducted a variant of the beads task (fish task) as a measure for the JTC-bias at the start of the trial. Further, clinical interviews were used to assess patients' delusional severity and delusional conviction. RESULTS: There were no statistically significant differences between patients with psychotic disorders (with 53% displaying the JTC-bias) and controls (41%). Furthermore, there were no statistically significant correlations between JTC measures and persecutory delusions, delusional conviction, and positive symptoms. CONCLUSIONS: We found no differences in JTC between patients with psychotic disorders and healthy controls, which is in part in line with meta-analytic findings using a wide range of JTC task variants. Interestingly, patients with psychotic disorders displayed JTC rates commonly found in the literature, while healthy control subjects showed an unexpectedly high level of JTC. The task variant we used in the present study (fish task) is discussed as a potential reason for our results, as it may induce a more deliberative reasoning style in controls as compared to the traditional beads task. Furthermore, possible implications for the measurement of the JTC-bias, in general, are discussed. TRIAL REGISTRATION: ISRCTN29242879 ( isrctn.com ), date of registration: April 12th 2006, retrospectively registered.

Universal Relations for Gravitational-Wave Asteroseismology of Protoneutron Stars.

State-of-the-art numerical simulations of core-collapse supernovae reveal that the main source of gravitational waves is the excitation of protoneutron star modes during postbounce evolution. In this work we derive universal relations that relate the frequencies of the most common oscillation modes observed, i.e., g modes, p modes, and the f mode, with fundamental properties of the system, such as the surface gravity of the protoneutron star or the mean density in the region enclosed by the shock. These relations are independent of the equation of state, the neutrino treatment, and the progenitor mass and, hence, can be used to build methods to infer protoneutron star properties from gravitational-wave observations alone. We outline how these measurements could be done and the constraints that could be placed on the protoneutron star properties.

Sodium-Selective Fluoroionophore-Based Optodes for Seawater Salinity Measurement.

A new fluorescent sensor for Na+ is presented. The sensor relies on a Na+ selective fluoroionophore based on a bright red-emitting BODIPY chromophore. The fluorescence of the fluoroionophore is enhanced upon binding of Na+-ions to the highly selective aza-crown ether receptor due to reduction of the photoinduced electron transfer (PET) quenching. Solid state sensing materials were prepared by physically embedding the fluoroionophore into water-swellable biocompatible polymer matrices (polyurethane hydrogels), thus enabling continuous measurements of aqueous samples. Despite the simple design, the sensor showed no leaching of the indicator and featured fast and reversible response. Among different polyurethane hydrogels investigated, the hydrogel D1 featuring the highest water uptake was found to be the most suitable due to the highest dynamics between "off" and "on" states. Due to little or no cross sensitivity to other ions (e.g., Mg2+, Ca2+, K+) and its insensitivity to potential changes in pH, this sensor is promising for use in clinical diagnostics and for biological and marine applications. Fiber-optic sensors based on referenced read-out with a compact phase fluorimeter were prepared. To demonstrate their practical applicability, the sensors were used to determine the salinity in the seawater and brackish water of the Baltic Sea.

Free water elimination improves test-retest reproducibility of diffusion tensor imaging indices in the brain: A longitudinal multisite study of healthy elderly subjects.

Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test-retest reproducibility. This study compares a bi-tensor model for FWE with DTI by extending a previous longitudinal-reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55-80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white-matter regions of the JHU-ICBM-DTI-81 white-matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12-26, 2017. © 2016 Wiley Periodicals, Inc.

Test-retest reliability of the default mode network in a multi-centric fMRI study of healthy elderly: Effects of data-driven physiological noise correction techniques.

Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test-retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z-scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. © 2016 Wiley Periodicals, Inc.

Occipital event-related potentials to addiction-related stimuli in detoxified patients with alcohol dependence, and their association with three-month relapse.

BACKGROUND: Understanding the biological underpinnings of relapse in alcohol dependency is a major issue in addiction research. Based on recent evidence regarding the relevance of occipital visual evoked response potentials (ERPs) in addiction research, and its significance for relapse research, we assessed occipital ERPs to alcohol- and non-alcohol-related stimuli in recently detoxified patients and controls. METHODS: Thirty recently detoxified patients with alcohol addiction, and 31 healthy control subjects, were assessed in a Go and a NoGo condition, each using three visual stimuli: tea, juice and beer. In the "Go" condition, subjects had to respond to the juice (12.5 %) and the beer stimulus (12.5 %), and ignore the tea picture (75 %). In the "NoGo" condition, subjects had to respond to the tea picture (75 %) and ignore the juice and the beer picture (12.5 % each). The subjects' EEGs were analyzed with regard to the occipital P100 and N170 ERP components. Patients were then evaluated for relapse 3 months after this initial assessment. RESULTS: P100 amplitudes differed between conditions and between stimuli, and we found a condition x electrode interaction. However, none of these P100 results involved group or relapse-status effects. N170 amplitudes in patients were elevated as compared to controls. Additionally, patients' heightened N170 amplitudes in response to the alcohol-related (beer) stimulus were found only under the NoGo condition, where subjects had to react to the frequent tea stimulus and ignore the beer and the juice stimuli, thus resulting in a condition x stimulus x group interaction. Patients reporting relapse in a 3-month follow-up assessment showed larger NoGo N170 alcohol cue-related ERP amplitudes and increased depression scores as compared to patients who stayed abstinent. Depression was related to shortened P100 latencies in patients, but unrelated to the N170 NoGo cue-reactivity effect. CONCLUSIONS: Our results indicate a sensitivity of occipital ERPs to addiction-related stimuli when these act as non-targets. Recently detoxified patients may be vulnerable to addiction-related cues when these occur outside the focus of directed attention, thereby circumventing intentional control processes. Furthermore, ERPs to addiction-related stimuli may be useful as a predictor of abstinence success in recently detoxified patients.

Longitudinal reproducibility of automatically segmented hippocampal subfields: A multisite European 3T study on healthy elderly.

Recently, there has been an increased interest in the use of automatically segmented subfields of the human hippocampal formation derived from magnetic resonance imaging (MRI). However, little is known about the test-retest reproducibility of such measures, particularly in the context of multisite studies. Here, we report the reproducibility of automated Freesurfer hippocampal subfields segmentations in 65 healthy elderly enrolled in a consortium of 13 3T MRI sites (five subjects per site). Participants were scanned in two sessions (test and retest) at least one week apart. Each session included two anatomical 3D T1 MRI acquisitions harmonized in the consortium. We evaluated the test-retest reproducibility of subfields segmentation (i) to assess the effects of averaging two within-session T1 images and (ii) to compare subfields with whole hippocampus volume and spatial reliability. We found that within-session averaging of two T1 images significantly improved the reproducibility of all hippocampal subfields but not that of the whole hippocampus. Volumetric and spatial reproducibility across MRI sites were very good for the whole hippocampus, CA2-3, CA4-dentate gyrus (DG), subiculum (reproducibility error∼2% and DICE > 0.90), good for CA1 and presubiculum (reproducibility error ∼ 5% and DICE ∼ 0.90), and poorer for fimbria and hippocampal fissure (reproducibility error ∼ 15% and DICE < 0.80). Spearman's correlations confirmed that test-retest reproducibility improved with volume size. Despite considerable differences of MRI scanner configurations, we found consistent hippocampal subfields volumes estimation. CA2-3, CA4-DG, and sub-CA1 (subiculum, presubiculum, and CA1 pooled together) gave test-retest reproducibility similar to the whole hippocampus. Our findings suggest that the larger hippocampal subfields volume may be reliable longitudinal markers in multisite studies.

Concise synthesis of C-1-cyano-iminosugars via a new Staudinger/aza Wittig/Strecker multicomponent reaction strategy.

A new Staudinger/aza Wittig/Strecker multicomponent reaction sequence to C-1-cyano iminoalditols has been developed. When applied to 5-azidodeoxy-d-xylose and -d-glucose as substrates the method leads smoothly in good yield and with excellent stereoselectivity to respectively, 1,5-dideoxy-1,5-imino-d-idurono nitrile and 2,6-didesoxy-2,6-imino-d-glycero-d-ido-heptononitrile.

The precuneus and the insula in self-attributional processes.

Attributions are constantly assigned in everyday life. A well-known phenomenon is the self-serving bias: that is, people's tendency to attribute positive events to internal causes (themselves) and negative events to external causes (other persons/circumstances). Here, we investigated the neural correlates of the cognitive processes implicated in self-serving attributions using social situations that differed in their emotional saliences. We administered an attributional bias task during fMRI scanning in a large sample of healthy subjects (n = 71). Eighty sentences describing positive or negative social situations were presented, and subjects decided via buttonpress whether the situation had been caused by themselves or by the other person involved. Comparing positive with negative sentences revealed activations of the bilateral posterior cingulate cortex (PCC). Self-attribution correlated with activation of the posterior portion of the precuneus. However, self-attributed positive versus negative sentences showed activation of the anterior portion of the precuneus, and self-attributed negative versus positive sentences demonstrated activation of the bilateral insular cortex. All significant activations were reported with a statistical threshold of p ≤ .001, uncorrected. In addition, a comparison of our fMRI task with data from the Internal, Personal and Situational Attributions Questionnaire, Revised German Version, demonstrated convergent validity. Our findings suggest that the precuneus and the PCC are involved in the evaluation of social events with particular regional specificities: The PCC is activated during emotional evaluation, the posterior precuneus during attributional evaluation, and the anterior precuneus during self-serving processes. Furthermore, we assume that insula activation is a correlate of awareness of personal agency in negative situations.

Neutrino signature of supernova hydrodynamical instabilities in three dimensions.

The first full-scale three-dimensional core-collapse supernova (SN) simulations with sophisticated neutrino transport show pronounced effects of the standing accretion shock instability (SASI) for two high-mass progenitors (20 and 27 M([Symbol: see text])). In a low-mass progenitor (11.2 M([Symbol: see text])), large-scale convection is the dominant nonradial hydrodynamic instability in the postshock accretion layer. The SASI-associated modulation of the neutrino signal (80 Hz in our two examples) will be clearly detectable in IceCube or the future Hyper-Kamiokande detector, depending on progenitor properties, distance, and observer location relative to the main SASI sloshing direction. The neutrino signal from the next galactic SN can, therefore, diagnose the nature of the hydrodynamic instability.

The impact of alcohol dependence on social brain function.

The impact of alcoholism (ALC) or alcohol dependence on the neural mechanisms underlying cognitive and affective empathy (i.e. the different routes to understanding other people's minds) in schizophrenic patients and non-schizophrenic subjects is still poorly understood. We therefore aimed at determining the extent to which the ability to infer other people's mental states and underlying neural mechanisms were affected by ALC. We examined 48 men, who suffered either from ALC, schizophrenia, both disorders or none of these disorders, using functional magnetic resonance imaging while performing on a mind reading task that involves both cognitive and affective aspects of empathy. Using voxel-based morphometry, we additionally examined whether between-group differences in functional activity were associated with deficits in brain structural integrity. During mental state attribution, all clinical groups as compared with healthy controls exhibited poor performance as well as reduced right-hemispheric insular function with the highest error rate and insular dysfunction seen in the schizophrenic patients without ALC. Accordingly, both behavioral performance and insular functioning revealed schizophrenia × ALC interaction effects. In addition, schizophrenic patients relative to non-schizophrenic subjects (regardless of ALC) exhibited deficits in structural integrity and task-related recruitment of the left ventrolateral prefrontal cortex (vlPFC). Our data suggest that ALC-related impairment in the ability to infer other people's mental states is limited to insular dysfunction and thus deficits in affective empathy. By contrast, mentalizing in schizophrenia (regardless of ALC) may be associated with insular dysfunction as well as a combination of structural and functional deficits in the left vlPFC.

Networks of Neuropsychological Functions in the Clinical Evaluation of Adult ADHD.

This study applied network analysis to explore the relations between neuropsychological functions of individuals in the clinical evaluation of attention-deficit/hyperactivity disorder (ADHD) in adulthood. A total of 319 participants from an outpatient referral context, that is, 173 individuals with ADHD (ADHD group) and 146 individuals without ADHD (n-ADHD group), took part in this study and completed a comprehensive neuropsychological assessment. A denser network with stronger global connectivity was observed in the ADHD group compared to the n-ADHD group. The strongest connections were consistent in both networks, that is, the connections between selective attention and vigilance, and connections between processing speed, fluency, and flexibility. Further centrality estimation revealed attention-related variables to have the highest expected influence in both networks. The observed relationships between neuropsychological functions, and the high centrality of attention, may help identify neuropsychological profiles that are specific to ADHD and optimize neuropsychological assessment and treatment planning of individuals with cognitive impairment.

Cognitive Underperformance in a Mixed Neuropsychiatric Sample at Diagnostic Evaluation of Adult ADHD.

(1) Background: The clinical assessment of attention-deficit/hyperactivity disorder (ADHD) in adulthood is known to show non-trivial base rates of noncredible performance and requires thorough validity assessment. (2) Objectives: The present study estimated base rates of noncredible performance in clinical evaluations of adult ADHD on one or more of 17 embedded validity indicators (EVIs). This study further examines the effect of the order of test administration on EVI failure rates, the association between cognitive underperformance and symptom overreporting, and the prediction of cognitive underperformance by clinical information. (3) Methods: A mixed neuropsychiatric sample (N = 464, ADHD = 227) completed a comprehensive neuropsychological assessment battery on the Vienna Test System (VTS; CFADHD). Test performance allows the computation of 17 embedded performance validity indicators (PVTs) derived from eight different neuropsychological tests. Further, all participants completed several self- and other-report symptom rating scales assessing depressive symptoms and cognitive functioning. The Conners' Adult ADHD Rating Scale and the Beck Depression Inventory-II were administered to derive embedded symptom validity measures (SVTs). (4) Results and conclusion: Noncredible performance occurs in a sizeable proportion of about 10% up to 30% of individuals throughout the entire battery. Tests for attention and concentration appear to be the most adequate and sensitive for detecting underperformance. Cognitive underperformance represents a coherent construct and seems dissociable from symptom overreporting. These results emphasize the importance of performing multiple PVTs, at different time points, and promote more accurate calculation of the positive and negative predictive values of a given validity measure for noncredible performance during clinical assessments. Future studies should further examine whether and how the present results stand in other clinical populations, by implementing rigorous reference standards of noncredible performance, characterizing those failing PVT assessments, and differentiating between underlying motivations.