Transdiagnostic Phenotype Research Articles

Anhedonia as a Potential Transdiagnostic Phenotype With Immune-Related Changes in Recent-Onset Mental Health Disorders

BackgroundChronic low-grade inflammation is observed across mental disorders and is associated with difficult-to-treat-symptoms of anhedonia and functional brain changes, reflecting a potential transdiagnostic dimension. Previous investigations have focused on distinct illness categories in people with enduring illness, but few have explored inflammatory changes. We sought to identify an inflammatory signal and the associated brain function underlying anhedonia among young people with recent-onset psychosis and recent-onset depression. MethodsResting-state functional magnetic resonance imaging, inflammatory markers, and anhedonia symptoms were collected from 108 (mean [SD] age = 26.2 [6.2] years; female = 50) participants with recent-onset psychosis (n = 53) and recent-onset depression (n = 55) from the European Union/Seventh Framework Programme–funded PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Time series were extracted using the Schaefer atlas, defining 100 cortical regions of interest. Using advanced multimodal machine learning, an inflammatory marker model and a functional connectivity model were developed to classify participants into an anhedonic group or a normal hedonic group. ResultsA repeated nested cross-validation model using inflammatory markers classified normal hedonic and anhedonic recent-onset psychosis/recent-onset depression groups with a balanced accuracy of 63.9% and an area under the curve of 0.61. The functional connectivity model produced a balanced accuracy of 55.2% and an area under the curve of 0.57. Anhedonic group assignment was driven by higher levels of interleukin 6, S100B, and interleukin 1 receptor antagonist and lower levels of interferon gamma, in addition to connectivity within the precuneus and posterior cingulate. ConclusionsWe identified a potential transdiagnostic anhedonic subtype that was accounted for by an inflammatory profile and functional connectivity. Results have implications for anhedonia as an emerging transdiagnostic target across emerging mental disorders.

286. The Emergent Transdiagnostic Phenotype of Attention and Executive Function Delay in Neurodevelopmental Conditions

286. The Emergent Transdiagnostic Phenotype of Attention and Executive Function Delay in Neurodevelopmental Conditions

MAPping affective dimensions of behavior: Methodologic and pragmatic advancement of the Multidimensional Assessment Profiles scales.

Rigorous validation of the full developmentally sensitive normal:abnormal spectrum, including evaluating the incremental value of age-specific behaviors, is necessary for nuanced characterization of dimensional features of psychopathology. To maximize the clinical utility of transdiagnostic approaches to risk identification, derivation of psychometrically sound, pragmatic versions with empirically derived cutoffs is also key. This special section has a central focus on rigorous, developmentally-based measurement of irritability as an exemplar of this theory- and pragmatically-based approach. Elevated irritability is a robust transdiagnostic predictor of the common psychopathologies of childhood. The Multidimensional Assessment Profiles Temper Loss (MAPS-TL) Scales are the only irritability tool specifically designed to capture the normal:abnormal dimensional spectrum. These have been extensively investigated in preschool age but lack rigorous modeling at older and younger ages. In this special issue, (with three independent-and one longitudinal-set of samples), we test and improve measurement of irritability as a transdiagnostic phenotype of psychopathology risk as it unfolds across development, expanding the MAPS-TL scale in three important ways: (1) extending irritability dimensional modeling and the developmental specification approach to older ages, (2) advancing science to practice translation by generating pragmatic irritability screening tools across ages, and (3) extending the dimensional, developmental specification approach to other dimensions of behavior, that is, internalizing. Collectively, the special issue operationalizes and advances application of a neurodevelopmental, dimensional and transdiagnostic approach to psychopathology.

Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies.

Genome-wide association studies (GWAS) provide biological insights into disease onset and progression and have potential to produce clinically useful biomarkers. A growing body of GWAS focuses on quantitative and transdiagnostic phenotypic targets, such as symptom severity or biological markers, to enhance gene discovery and the translational utility of genetic findings. The current review discusses such phenotypic approaches in GWAS across major psychiatric disorders. We identify themes and recommendations that emerge from the literature to date, including issues of sample size, reliability, convergent validity, sources of phenotypic information, phenotypes based on biological and behavioral markers such as neuroimaging and chronotype, and longitudinal phenotypes. We also discuss insights from multi-trait methods such as genomic structural equation modelling. These provide insight into how hierarchical 'splitting' and 'lumping' approaches can be applied to both diagnostic and dimensional phenotypes to model clinical heterogeneity and comorbidity. Overall, dimensional and transdiagnostic phenotypes have enhanced gene discovery in many psychiatric conditions and promises to yield fruitful GWAS targets in the years to come.

Development and validation of the ambiguous scenario task for perfectionistic concerns for university students

Background and objectivesInterpretation biases (IBs) are found in a range of psychological disorders, and the transdiagnostic role of IBs has gained increasing attention. Among the variants, IBs of perfectionism (e.g., interpreting a trivial error as equivalent to complete failure) are understood to be a central transdiagnostic phenotype. Perfectionism is a multidimensional construct and the dimension of perfectionistic concerns has been found to be most closely related to psychopathology. Therefore, capturing IBs that are specifically related to perfectionistic concerns (not perfectionism in general) is of particular importance in studying pathological IBs. Thus, we developed and validated the Ambiguous Scenario Task for Perfectionistic Concerns (AST-PC) to be used in university students. MethodsWe created two versions of the AST-PC and administered each version to one of two independent student samples (i.e., Version A to n = 108 and Version B to n = 110). We then examined the factor structure and associations with established questionnaires of perfectionism, depression, and anxiety. ResultsThe AST-PC showed good factorial validity, confirming the hypothesized three-factor structure: perfectionistic concerns, adaptive, and maladaptive (but not perfectionistic) interpretations. The interpretations related to perfectionistic concerns showed good correlations with questionnaires of perfectionistic concerns, depressive symptoms, and trait anxiety. LimitationsAdditional validation studies are required to establish the temporal stability of the task scores and their sensitivity to experimental induction and clinical intervention. Additionally, IBs of perfectionism should be investigated within a broader transdiagnostic context. ConclusionsThe AST-PC demonstrated good psychometric properties. Future applications of the task are discussed.

An evaluation of the construct validity of the Adult Rejection Sensitivity Questionnaire.

Rejection sensitivity (RS), the predisposition to defensively expect, readily perceive, and react strongly to interpersonal rejection (Downey & Feldman, 1996; Feldman & Downey, 1994), may be a transdiagnostic trait associated with a range of psychiatric symptoms and psychosocial dysfunction. Valid and reliable assessment of vulnerability factors is essential for individualized treatment and improving clinical outcomes. Limited research has examined the factor structure of the predominantly used self-report measure of RS, the Adult Rejection Sensitivity Questionnaire (A-RSQ; Berenson et al., 2009). Across two studies (Study 1: N = 346, 57.2% female, 76.6% White; 16.8% Hispanic/Latinx; Study 2: N = 540; 43.7% female, 80.2% White; 16.7% Hispanic/Latinx), we examined the factor structure of the A-RSQ in samples of adult U.S. residents and investigated associations with mental health correlates, including neuroticism, social anxiety, anxiety, depression, anhedonia, somatic arousal, and psychological distress. Study 2 also evaluated relations with interpersonal correlates, including introversion, submissiveness, and anxious and avoidant attachment. A two-factor solution with rejection expectancy and rejection concern representing separate factors consistently fit the data best. Distinct patterns of associations emerged suggesting that concern was more strongly associated with indicators of negative affect while expectancy was uniquely associated with diminished positive affect. Both concern and expectancy were associated with indicators of interpersonal dysfunction. Findings suggest that the current operationalization, and perhaps conceptualization, of RS as measured by the A-RSQ requires revision. Additionally, RS may be a clinically relevant transdiagnostic phenotype that influences symptom manifestation and psychosocial functioning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Developmental patterning of irritability enhances prediction of psychopathology in preadolescence: Improving RDoC with developmental science.

The transdiagnostic importance of irritability in psychopathology has been demonstrated. However, the contribution of developmentally unfolding irritability patterns to specific clinical and neural outcomes remains an important and unanswered question. To address this gap in the literature, irritability patterns of 110 youth from a large, diverse cohort were assessed at preschool age and again at early school age (∼2.5 years later) with a dimensional irritability scale designed to capture the normal:abnormal spectrum. At preadolescence (∼6 years later), clinical outcomes (internalizing/externalizing symptoms) derived from a semistructured clinical interview and neural outcomes (characterized as gray-matter-volume abnormalities) were assessed. For clinical outcomes, preschool-age irritability alone was a transdiagnostic predictor of internalizing and externalizing symptoms at preadolescence. However, in a model including both preschool and early school age, irritability provided greater specificity, suggesting that higher irritability at early school age related to elevated preadolescent externalizing but not internalizing symptoms. In terms of neural outcomes, elevated preschool irritability did not predict preadolescent gray-matter-volume abnormality; however, irritability at early school age demonstrated an interactive effect among regions, with reduced volume in preadolescence emotional regions (e.g., amygdala, medial orbitofrontal cortex) and increased volume in other regions (e.g., cerebellum). These complex patterns highlight the contribution of a developmentally informed approach, the National Institute of Mental Health's Research Domain Criteria (RDoC) approach, to yield transdiagnostic phenotypes and multiple units of analysis. Capturing these individual differences and developmental heterogeneity can provide critical insight into the unfolding of mechanisms underlying emerging psychopathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neurobiologically Based Stratification of Recent-Onset Depression and Psychosis: Identification of Two Distinct Transdiagnostic Phenotypes

BackgroundIdentifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity and provide better candidates for predictive modeling. We aimed to identify clusters across patients with recent-onset depression (ROD) and recent-onset psychosis (ROP) based on structural neuroimaging data. We hypothesized that these transdiagnostic clusters would identify patients with poor outcome and allow more accurate prediction of symptomatic remission than traditional diagnostic structures. MethodsHYDRA (Heterogeneity through Discriminant Analysis) was trained on whole-brain volumetric measures from 577 participants from the discovery sample of the multisite PRONIA study to identify neurobiologically driven clusters, which were then externally validated in the PRONIA replication sample (n = 404) and three datasets of chronic samples (Centre for Biomedical Research Excellence, n = 146; Mind Clinical Imaging Consortium, n = 202; Munich, n = 470). ResultsThe optimal clustering solution was two transdiagnostic clusters (cluster 1: n = 153, 67 ROP, 86 ROD; cluster 2: n = 149, 88 ROP, 61 ROD; adjusted Rand index = 0.618). The two clusters contained both patients with ROP and patients with ROD. One cluster had widespread gray matter volume deficits and more positive, negative, and functional deficits (impaired cluster), and one cluster revealed a more preserved neuroanatomical signature and more core depressive symptomatology (preserved cluster). The clustering solution was internally and externally validated and assessed for clinical utility in predicting 9-month symptomatic remission, outperforming traditional diagnostic structures. ConclusionsWe identified two transdiagnostic neuroanatomically informed clusters that are clinically and biologically distinct, challenging current diagnostic boundaries in recent-onset mental health disorders. These results may aid understanding of the etiology of poor outcome patients transdiagnostically and improve development of stratified treatments.

Disorder of Selfhood in Schizophrenia: A Symptom or a Gestalt?

Introduction: The concept of schizophrenia (SCZ) was originally associated with a disorder of formal strata of the self. During the last two decades, empirical studies have demonstrated a selective hyper-aggregation of self-disorders in the SCZ spectrum. As with other scientific research areas, the role of self-disturbances in SCZ has been up for debate in various disciplines including cognitive sciences, philosophy of mind, and psychopathology. Several philosophical papers have used the psychopathological phenomena of “thought insertion” as an alleged example of a complete loss of minimal selfhood. In the field of psychopathology, it has been claimed that self-disorders may comprise a transdiagnostic phenotype. Common to these approaches is the underlying assumption that self-disorders reflect well-delineated and isolated symptoms akin to the notion of symptom in the medical model. The aim of this paper was to argue that the clinical manifestation of self-disturbances is to be seen as aspects of a Gestalt of disturbed experiential selfhood. Methods: Seven videotaped interviews of patients with SCZ who were emblematic of very diverse symptomatological constellations were selected and jointly watched and discussed by the authors, who reached a consensus assessment. The interviews were semi-structured and narrative in nature in order to obtain faithful self-descriptions according to the standards of phenomenologically oriented interviews. For the purpose of this article, we chose 4 videos from which excerpts were verbatim transcribed and translated from Danish into English. Results: The patients describe unique combinations of various psychopathological phenomena such as diminished sense of embodied self-presence, loss of ego boundaries, diminished sense of self, alienation and objectification of the experiential processes, mirror-phenomena, and Schneiderian passivity phenomena. Discussion: Through an interweaving of the four vignettes and their subsequent psychopathological discussions, we argue that the invariant commonality across the different symptomatic expressions in these patients resides in a Gestalt of pervasive disturbance of self-experience. From a phenomenological perspective, these self-disturbances target a basic structure of phenomenal consciousness, namely, the first-person givenness of experience. We conclude that self-disorders reflect a trait-instability in the most basic structures of consciousness in SCZ and that its clinical manifestations are to be seen as aspects of a particular Gestalt rather than appearing as separate and well-delineated symptoms.

Transdiagnostic phenotypes of compulsive behavior and associations with psychological, cognitive, and neurobiological affective processing

Compulsivity is a poorly understood transdiagnostic construct thought to underlie multiple disorders, including obsessive-compulsive disorder, addictions, and binge eating. Our current understanding of the causes of compulsive behavior remains primarily based on investigations into specific diagnostic categories or findings relying on one or two laboratory measures to explain complex phenotypic variance. This proof-of-concept study drew on a heterogeneous sample of community-based individuals (N = 45; 18–45 years; 25 female) exhibiting compulsive behavioral patterns in alcohol use, eating, cleaning, checking, or symmetry. Data-driven statistical modeling of multidimensional markers was utilized to identify homogeneous subtypes that were independent of traditional clinical phenomenology. Markers were based on well-defined measures of affective processing and included psychological assessment of compulsivity, behavioral avoidance, and stress, neurocognitive assessment of reward vs. punishment learning, and biological assessment of the cortisol awakening response. The neurobiological validity of the subtypes was assessed using functional magnetic resonance imaging. Statistical modeling identified three stable, distinct subtypes of compulsivity and affective processing, which we labeled “Compulsive Non-Avoidant”, “Compulsive Reactive” and “Compulsive Stressed”. They differed meaningfully on validation measures of mood, intolerance of uncertainty, and urgency. Most importantly, subtypes captured neurobiological variance on amygdala-based resting-state functional connectivity, suggesting they were valid representations of underlying neurobiology and highlighting the relevance of emotion-related brain networks in compulsive behavior. Although independent larger samples are needed to confirm the stability of subtypes, these data offer an integrated understanding of how different systems may interact in compulsive behavior and provide new considerations for guiding tailored intervention decisions.

Transdiagnostic neurocognitive deficits in patients with type 2 diabetes mellitus, major depressive disorder, bipolar disorder, and schizophrenia: A 1-year follow-up study

BackgroundNeurocognition impairments are critical factors in patients with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), and also in those with somatic diseases such as type 2 diabetes mellitus (T2DM). Intriguingly, these severe mental illnesses are associated with an increased co-occurrence of diabetes (direct comorbidity). This study sought to investigate the neurocognition and social functioning across T2DM, MDD, BD, and SZ using a transdiagnostic and longitudinal approach. MethodsA total of 165 participants, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HC), were assessed twice at a 1-year interval using a comprehensive, integrated test battery on neuropsychological and social functioning. ResultsCommon neurocognitive impairments in somatic and psychiatric disorders were identified, including deficits in short-term memory and cognitive reserve (p < 0.01, η²p=0.08–0.31). Social functioning impairments were observed in almost all the disorders (p < 0.0001; η²p=0.29–0.49). Transdiagnostic deficits remained stable across the 1-year follow-up (p < 0.001; η²p=0.13–0.43) and could accurately differentiate individuals with somatic and psychiatric disorders (χ² = 48.0, p < 0.0001). LimitationsThe initial sample size was small, and high experimental mortality was observed after follow-up for one year. ConclusionsThis longitudinal study provides evidence of some possible overlap in neurocognition deficits across somatic and psychiatric diagnostic categories, such as T2DM, MDD, BD, and SZ, which have high comorbidity. This overlap may be a result of shared genetic and environmental etiological factors. The findings open promising avenues for research on transdiagnostic phenotypes of neurocognition in these disorders, in addition to their biological bases.

The role of psychological distress in the relationship between lifestyle and compulsivity: An analysis of independent, bi-national samples.

Poor mental health is a state of psychological distress that is influenced by lifestyle factors such as sleep, diet, and physical activity. Compulsivity is a transdiagnostic phenotype cutting across a range of mental illnesses including obsessive-compulsive disorder, substance-related and addictive disorders, and is also influenced by lifestyle. Yet, how lifestyle relates to compulsivity is presently unknown, but important to understand to gain insights into individual differences in mental health. We assessed (a) the relationships between compulsivity and diet quality, sleep quality, and physical activity, and (b) whether psychological distress statistically contributes to these relationships. We collected harmonized data on compulsivity, psychological distress, and lifestyle from two independent samples (Australian n=880 and US n=829). We used mediation analyses to investigate bidirectional relationships between compulsivity and lifestyle factors, and the role of psychological distress. Higher compulsivity was significantly related to poorer diet and sleep. Psychological distress statistically mediated the relationship between poorer sleep quality and higher compulsivity, and partially statistically mediated the relationship between poorer diet and higher compulsivity. Lifestyle interventions in compulsivity may target psychological distress in the first instance, followed by sleep and diet quality. As psychological distress links aspects of lifestyle and compulsivity, focusing on mitigating and managing distress may offer a useful therapeutic approach to improve physical and mental health. Future research may focus on the specific sleep and diet patterns which may alter compulsivity over time to inform lifestyle targets for prevention and treatment of functionally impairing compulsive behaviors.

Effects of a Novel, Transdiagnostic, Hybrid Ecological Momentary Intervention for Improving Resilience in Youth (EMIcompass): Protocol for an Exploratory Randomized Controlled Trial.

BackgroundMost mental disorders first emerge in youth and, in their early stages, surface as subthreshold expressions of symptoms comprising a transdiagnostic phenotype of psychosis, mania, depression, and anxiety. Elevated stress reactivity is one of the most widely studied mechanisms underlying psychotic and affective mental health problems. Thus, targeting stress reactivity in youth is a promising indicated and translational preventive strategy for adverse mental health outcomes that could develop later in life and for improving resilience. Compassion-focused interventions offer a wide range of innovative therapeutic techniques that are particularly amenable to being implemented as ecological momentary interventions (EMIs), a specific type of mobile health intervention, to enable youth to access interventions in a given moment and context in daily life. This approach may bridge the current gap in youth mental health care.ObjectiveThis study aims to investigate the clinical feasibility, candidate underlying mechanisms, and initial signals of the efficacy of a novel, transdiagnostic, hybrid EMI for improving resilience to stress in youth—EMIcompass.MethodsIn an exploratory randomized controlled trial, youth aged between 14 and 25 years with current distress, a broad Clinical High At-Risk Mental State, or the first episode of a severe mental disorder will be randomly allocated to the EMIcompass intervention (ie, EMI plus face-to-face training sessions) in addition to treatment as usual or a control condition of treatment as usual only. Primary (stress reactivity) and secondary candidate mechanisms (resilience, interpersonal sensitivity, threat anticipation, negative affective appraisals, and momentary physiological markers of stress reactivity), as well as primary (psychological distress) and secondary outcomes (primary psychiatric symptoms and general psychopathology), will be assessed at baseline, postintervention, and at the 4-week follow-up.ResultsThe first enrollment was in August 2019, and as of May 2021, enrollment and randomization was completed (N=92). We expect data collection to be completed by August 2021.ConclusionsThis study is the first to establish feasibility, evidence on underlying mechanisms, and preliminary signals of the efficacy of a compassion-focused EMI in youth. If successful, a confirmatory randomized controlled trial will be warranted. Overall, our approach has the potential to significantly advance preventive interventions in youth mental health provision.Trial RegistrationGerman Clinical Trials Register DRKS00017265; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017265International Registered Report Identifier (IRRID)DERR1-10.2196/27462

Networks of worry\u2014towards a connectivity-based signature of late-life worry using higher criticism

Severe worry is a complex transdiagnostic phenotype independently associated with increased morbidity, including cognitive impairment and cardiovascular diseases. We investigated the neurobiological basis of worry in older adults by analyzing resting state fMRI using a large-scale network-based approach. We collected resting fMRI on 77 participants (>50 years old) with varying worry severity. We computed region-wise connectivity across the default mode network (DMN), anterior salience network, and left executive control network. All 22,366 correlations were regressed on worry severity and adjusted for age, sex, race, education, disease burden, depression, anxiety, rumination, and neuroticism. We employed higher criticism, a second-level method of significance testing for rare and weak features, to reveal the functional connectivity patterns associated with worry. The analysis suggests that worry has a complex, yet distinct signature associated with resting state functional connectivity. Intra-connectivities and inter-connectivities of the DMN comprise the dominant contribution. The anterior cingulate, temporal lobe, and thalamus are heavily represented with overwhelmingly negative association with worry. The prefrontal regions are also strongly represented with a mix of positive and negative associations with worry. Identifying the most salient connections may be useful for targeted interventions for reducing morbidity associated with severe worry in older adults.

Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications.

Exogenous administration of inflammatory stimuli to humans and laboratory animals and chronic endogenous inflammatory states lead to motivational deficits and ultimately anhedonia, a core and disabling symptom of depression present in multiple other psychiatric disorders. Inflammation impacts neurotransmitter systems and neurocircuits in subcortical brain regions including the ventral striatum, which serves as an integration point for reward processing and motivational decision-making. Many mechanisms contribute to these effects of inflammation, including decreased synthesis, release and reuptake of dopamine, increased synaptic and extrasynaptic glutamate, and activation of kynurenine pathway metabolites including quinolinic acid. Neuroimaging data indicate that these inflammation-induced neurotransmitter effects manifest as decreased activation of ventral striatum and decreased functional connectivity in reward circuitry involving ventral striatum and ventromedial prefrontal cortex. Neurocircuitry changes in turn mediate nuanced effects on motivation that include decreased willingness to expend effort for reward while maintaining the ability to experience reward. Taken together, the data reveal an inflammation-induced pathophysiologic phenotype that is agnostic to diagnosis. Given the many mechanisms involved, this phenotype represents an opportunity for development of novel and/or repurposed pharmacological strategies that target inflammation and associated cellular and systemic immunometabolic changes and their downstream effects on the brain. To date, clinical trials have failed to capitalize on the unique nature of this transdiagnostic phenotype, leaving the field bereft of interpretable data for meaningful clinical application. However, novel trial designs incorporating established targets in the brain and/or periphery using relevant outcome variables (e.g., anhedonia) are the future of targeted therapy in psychiatry. SIGNIFICANCE STATEMENT: Emerging understanding of mechanisms by which peripheral inflammation can affect the brain and behavior has created unprecedented opportunities for development of pharmacological strategies to treat deficits in motivation including anhedonia, a core and disabling symptom of depression well represented in multiple psychiatric disorders. Mechanisms include inflammation and cellular and systemic immunometabolism and alterations in dopamine, glutamate, and kynurenine metabolites, revealing a target-rich environment that nevertheless has yet to be fully exploited by current clinical trial designs and drugs employed.

A Higher Order Internalizing Dimension Predicts Response to Partial Hospitalization Treatment

Mental disorders may be best represented by dimensional constructs that span traditional diagnostic boundaries. There is evidence that empirically derived dimensional phenotypes improve nosology and etiological research, but less is known about their clinical utility. We compared dimensional and categorical representations of anxiety and depression as predictors of response to psychological treatment in a large patient sample ( N = 3,760). Confirmatory factor analysis demonstrated that an internalizing factor—hypothesized to be the substrate of anxiety and depression—explained correlations among interview-based diagnoses at treatment outset. The internalizing factor had consistent, albeit sometimes modest, prospective associations with all treatment outcome measures: global clinical improvement, anxiety and depression symptoms, and need for inpatient hospitalization (standardized effect range = .13–.43). Categorical diagnoses—except major depression—did not reliably predict treatment outcome after adjusting for the higher order internalizing dimension. We conclude that reorienting clinical assessment around transdiagnostic phenotypes might enhance prognosis and other aspects of clinical decision-making.

Behavioural inhibition system sensitivity is no longer associated with psychotic-like experiences after controlling for depression and anxiety symptoms.

Elevated behavioural inhibition system sensitivity has been reported among schizophrenia patients. Yet, no study has investigated the relationship between behavioural inhibition system sensitivity and the occurrence of psychotic-like experiences (subthreshold psychotic symptoms considered to be less severe or impairing), despite evidence that behavioural inhibition system sensitivity is related to other forms of psychopathology known to co-occur with psychotic-like experiences, such as depression and anxiety. Thus, the aim of this study was to assess the relationship between behavioural inhibition system levels and psychotic-like experiences while controlling for depression and anxiety symptoms. We hypothesized that behavioural inhibition system sensitivity would be positively associated with the number of reported psychotic-like experiences, and that this association would be nonsignificant after accounting for depression and anxiety symptoms. Psychotic-like experiences, behavioural inhibition system sensitivity, depression symptoms, and anxiety symptoms were measured in 1162 young adults. Bivariate correlations were calculated and linear regressions performed to measure the relationship between variables of interest. Psychotic-like experiences, behavioural inhibition system sensitivity, and symptoms of depression, and anxiety were all significantly and positively correlated with one another. Behavioural inhibition system sensitivity was no longer related to the number of psychotic-like experiences reported after controlling for anxiety symptoms, with and without controlling for depression symptoms. These findings suggest that the hypersensitivity to threat observed among individuals reporting higher levels of psychotic-like experiences is likely related to co-occurring depression and anxiety symptoms. Thus, behavioural inhibition system sensitivity may be more reflective of a transdiagnostic phenotype of general psychopathology than specifically related to psychosis.

The role of Experiential Avoidance in transdiagnostic compulsive behavior: A structural model analysis

Compulsivity is recognized as a transdiagnostic phenotype, underlying a variety of addictive and obsessive–compulsive behaviors. However, current understanding of how it should be operationalized and the processes contributing to its development and maintenance is limited. The present study investigated if there was a relationship between the affective process Experiential Avoidance (EA), an unwillingness to tolerate negative internal experiences, and the frequency and severity of transdiagnostic compulsive behaviors. A large sample of adults (N = 469) completed online questionnaires measuring EA, psychological distress and the severity of seven obsessive–compulsive and addiction-related behaviors. Using structural equation modelling, results indicated a one-factor model of compulsivity was superior to the two-factor model (addictive- vs OCD-related behaviors). The effect of EA on compulsivity was fully mediated by psychological distress, which in turn had a strong direct effect on compulsivity. This suggests distress is a key mechanism in explaining why people with high EA are more prone to compulsive behaviors. The final model explained 41% of the variance in compulsivity, underscoring the importance of these constructs as likely risk and maintenance factors for compulsive behavior. Implications for designing effective psychological interventions for compulsivity are discussed.

Childhood Adversity and Dimensional Variations in Adult Sustained Attention.

Background and ObjectiveSustained attention is a transdiagnostic phenotype linked with most forms of psychopathology. We sought to understand factors that influence the development of sustained attention, by looking at the relationship between childhood adversity and adult sustained attention.Participants, Setting, and MethodsParticipants were 5,973 TestMyBrain.org visitors from English-speaking countries who completed a continuous performance task (gradCPT) of sustained attention and a childhood adversity questionnaire. We analyzed gradCPT performance using a signal detection approach.ResultsDiscrimination ability (the main metric of performance on the gradCPT) was associated with total childhood adversity load, even when controlling for covariates related to age, gender, parental education, race, country of origin, and relative socioeconomic status (β = −0.079, b = −0.032).ConclusionOur results demonstrate that attention differences related to childhood adversity exposure can (1) be measured using brief, performance-based measures of sustained attention, (2) persist into adulthood, and (3) be detected at the population level. These results, paired with the well-documented associations between sustained attention and psychopathology, indicate that sustained attention may be an important mechanism for understanding early influences on mental health.

Effort-cost computation in a transdiagnostic psychiatric sample: Differences among patients with schizophrenia, bipolar disorder, and major depressive disorder.

Amotivational symptoms are observed in schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Effort-cost computation may be a potential contributor to amotivation transdiagnostically. This study examined effort-cost computation in these three diagnostic groups. This study recruited 141 outpatients (49 SCZ, 52 non-psychotic BD, and 40 non-psychotic MDD) and 57 healthy controls (HCs). We administered the Effort-Expenditure for Reward Task (EEfRT), which manipulated different levels of reward magnitude and probability relating to a high and low physical effort task. There were significant interactions between group and reward magnitude, group and reward probability, and group and expected value on the percentage of high-effort choices. SCZ, BD, and MDD patients made comparably fewer high-effort choices than HCs in the high-reward magnitude, high-reward probability, and high-expected-value conditions. Self-reported amotivation did not correlate with decision-making on the EEfRT. Our findings suggest that reduced effort expenditure for reward is a transdiagnostic phenotype in SCZ, BD, and MDD.