Psychosis superspectrum II: neurobiology, treatment, and implications.

Alternatives to traditional categorical diagnoses have been proposed to improve the validity and utility of psychiatric nosology. This paper continues the companion review of an alternative model, the psychosis superspectrum of the Hierarchical Taxonomy of Psychopathology (HiTOP). The superspectrum model aims to describe psychosis-related psychopathology according to data on distributions and associations among signs and symptoms. The superspectrum includes psychoticism and detachment spectra as well as narrow subdimensions within them. Auxiliary domains of cognitive deficit and functional impairment complete the psychopathology profile. The current paper reviews evidence on this model from neurobiology, treatment response, clinical utility, and measure development. Neurobiology research suggests that psychopathology included in the superspectrum shows similar patterns of neural alterations. Treatment response often mirrors the hierarchy of the superspectrum with some treatments being efficacious for psychoticism, others for detachment, and others for a specific subdimension. Compared to traditional diagnostic systems, the quantitative nosology shows an approximately 2-fold increase in reliability, explanatory power, and prognostic accuracy. Clinicians consistently report that the quantitative nosology has more utility than traditional diagnoses, but studies of patients with frank psychosis are currently lacking. Validated measures are available to implement the superspectrum model in practice. The dimensional conceptualization of psychosis-related psychopathology has implications for research, clinical practice, and public health programs. For example, it encourages use of the cohort study design (rather than case-control), transdiagnostic treatment strategies, and selective prevention based on subclinical symptoms. These approaches are already used in the field, and the superspectrum provides further impetus and guidance for their implementation. Existing knowledge on this model is substantial, but significant gaps remain. We identify outstanding questions and propose testable hypotheses to guide further research. Overall, we predict that the more informative, reliable, and valid characterization of psychopathology offered by the superspectrum model will facilitate progress in research and clinical care.

Adult age-related differences in susceptibility to social conformity pressures in self-control over daily desires.

Developmental literature suggests that susceptibility to social conformity pressure peaks in adolescence and disappears with maturity into early adulthood. Predictions about these behaviors are less clear for middle-aged and older adults. On the one hand, while age-related increases in prioritization of socioemotional goals might predict greater susceptibility to social conformity pressures, aging is also associated with enhanced emotion regulation that could support resistance to conformity pressures. In this exploratory research study, we used mobile experience sampling surveys to naturalistically track how 157 healthy adults between the ages of 18 and 80 practice self-control over spontaneous desires in daily life. Many of these desires were experienced in the presence of others enacting that desire. Results showed that middle-aged and older adults were better at controlling their desires than younger adults when desires were experienced in the presence of others enacting that desire. Consistent with the literature on improved emotion regulation with age, these results provide evidence that the ability to resist social conformity pressure is enhanced across the adult life span. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The influence of dopamine autoreceptors on temperament and addiction risk.

As a major regulator of dopamine (DA), DA autoreceptors (DAARs) exert substantial influence over DA-mediated behaviors. This paper reviews the physiological and behavioral impact of DAARs. Individual differences in DAAR functioning influences temperamental traits such as novelty responsivity and impulsivity, both of which are associated with vulnerability to addictive behavior in animal models and a broad array of externalizing behaviors in humans. DAARs additionally impact the response to psychostimulants and other drugs of abuse. Human PET studies of D2-like receptors in the midbrain provide evidence for parallels to the animal literature. These data lead to the proposal that weak DAAR regulation is a risk factor for addiction and externalizing problems. The review highlights the potential to build translational models of the functional role of DAARs in behavior. It also draws attention to key limitations in the current literature that would need to be addressed to further advance a weak DAAR regulation model of addiction and externalizing risk.

Accentuated Paralimbic and Reduced Mesolimbic D2/3-Impulsivity Associations in Parkinson's Disease.

Impulsivity is a behavioral trait that is elevated in many neuropsychiatric disorders. Parkinson's disease (PD) patients can exhibit a specific pattern of reward-seeking impulsive-compulsive behaviors (ICBs), as well as more subtle changes to generalized trait impulsivity. Prior studies in healthy controls (HCs) suggest that trait impulsivity is regulated by D2/3 autoreceptors in mesocorticolimbic circuits. While altered D2/3 binding is noted in ICB+ PD patients, there is limited prior assessment of the trait impulsivity-D2/3 relationship in PD, and no prior direct comparison with patterns in HCs. We examined 54 PD (36 M; 18 F) and 31 sex- and age-matched HC (21 M; 10 F) subjects using [18F]fallypride, a high-affinity D2/3 receptor ligand, to measure striatal and extrastriatal D2/3 nondisplaceable binding potential (BPND). Subcortical and cortical assessment exclusively used ROI or exploratory-voxelwise methods, respectively. All completed the Barratt Impulsiveness Scale, a measure of trait impulsivity. Subcortical ROI analyses indicated a negative relationship between trait impulsivity and D2/3 BPND in the ventral striatum and amygdala of HCs but not in PD. By contrast, voxelwise methods demonstrated a positive trait impulsivity-D2/3 BPND correlation in ventral frontal olfactocentric-paralimbic cortex of subjects with PD but not HCs. Subscale analysis also highlighted different aspects of impulsivity, with significant interactions between group and motor impulsivity in the ventral striatum, and attentional impulsivity in the amygdala and frontal paralimbic cortex. These results suggest that dopamine functioning in distinct regions of the mesocorticolimbic circuit influence aspects of impulsivity, with the relative importance of regional dopamine functions shifting in the neuropharmacological context of PD.SIGNIFICANCE STATEMENT The biological determinants of impulsivity have broad clinical relevance, from addiction to neurodegenerative disorders. Here, we address biomolecular distinctions in Parkinson's disease. This is the first study to evaluate a large cohort of Parkinson's disease patients and age-matched healthy controls with a measure of trait impulsivity and concurrent [18F]fallypride PET, a method that allows quantification of D2/3 receptors throughout the mesocorticolimbic network. We demonstrate widespread differences in the trait impulsivity-dopamine relationship, including (1) loss of subcortical relationships present in the healthy brain and (2) emergence of a new relationship in a limbic cortical area. This illustrates the loss of mechanisms of behavioral regulation present in the healthy brain while suggesting a potential compensatory response and target for future investigation.

Measuring Antisocial Behaviors in Behavioral Variant Frontotemporal Dementia With a Novel Informant-Based Questionnaire.

OBJECTIVE: Antisocial behaviors are common and problematic among patients with behavioral variant frontotemporal dementia (bvFTD). In the present study, the investigators aimed to validate an informant-based questionnaire developed to measure the extent and severity of antisocial behaviors among patients with dementia. METHODS: The Social Behavior Questionnaire (SBQ) was developed to measure 26 antisocial behaviors on a scale from absent (0) to very severe (5). It was administered to 23 patients with bvFTD, 19 patients with Alzheimer's disease, and 14 patients with other frontotemporal lobar degeneration syndromes. Group-level differences in the presence and severity of antisocial behaviors were measured. Psychometric properties of the SBQ were assessed by using Cronbach's alpha, exploratory factor analysis, and comparisons with a psychopathy questionnaire. Cluster analysis was used to determine whether the SBQ identifies different subgroups of patients. RESULTS: Antisocial behaviors identified by using the SBQ were common and severe among patients with bvFTD, with at least one such behavior endorsed for 21 of 23 (91%) patients. Antisocial behaviors were more severe among patients with bvFTD, including the subsets of patients with milder cognitive impairment and milder disease severity, than among patients in the other groups. The SBQ was internally consistent (Cronbach's α=0.81). Exploratory factor analysis supported separate factors for aggressive and nonaggressive behaviors. Among the patients with bvFTD, the factor scores for aggressive behavior on the SBQ were correlated with those for antisocial behavior measured on the psychopathy scale, but the nonaggressive scores were not correlated with psychopathy scale measures. The k-means clustering analysis identified a subset of patients with severe antisocial behaviors. CONCLUSIONS: The SBQ is a useful tool to identify, characterize, and measure the severity of antisocial behaviors among patients with dementia.

Rapid Interactions of Widespread Brain Networks Characterize Semantic Cognition.

Language comprehension requires the rapid retrieval and integration of contextually appropriate concepts ("semantic cognition"). Current neurobiological models of semantic cognition are limited by the spatial and temporal restrictions of single-modality neuroimaging and lesion approaches. This is a major impediment given the rapid sequence of processing steps that have to be coordinated to accurately comprehend language. Through the use of fused functional magnetic resonance imaging and electroencephalography analysis in humans (n = 26 adults; 15 females), we elucidate a temporally and spatially specific neurobiological model for real-time semantic cognition. We find that semantic cognition in the context of language comprehension is supported by trade-offs between widespread neural networks over the course of milliseconds. Incorporation of spatial and temporal characteristics, as well as behavioral measures, provide convergent evidence for the following progression: a hippocampal/anterior temporal phonological semantic retrieval network (peaking at ∼300 ms after the sentence final word); a frontotemporal thematic semantic network (∼400 ms); a hippocampal memory update network (∼500 ms); an inferior frontal semantic syntactic reappraisal network (∼600 ms); and nodes of the default mode network associated with conceptual coherence (∼750 ms). Additionally, in typical adults, mediatory relationships among these networks are significantly predictive of language comprehension ability. These findings provide a conceptual and methodological framework for the examination of speech and language disorders, with additional implications for the characterization of cognitive processes and clinical populations in other cognitive domains.SIGNIFICANCE STATEMENT The present study identifies a real-time neurobiological model of the meaning processes required during language comprehension (i.e., "semantic cognition"). Using a novel application of fused magnetic resonance imaging and electroencephalography in humans, we found that semantic cognition during language comprehension is supported by a rapid progression of widespread neural networks related to meaning, meaning integration, memory, reappraisal, and conceptual cohesion. Relationships among these systems were predictive of individuals' language comprehension efficiency. Our findings are the first to use fused neuroimaging analysis to elucidate language processes. In so doing, this study provides a new conceptual and methodological framework in which to characterize language processes and guide the treatment of speech and language deficits/disorders.

New approaches to deep phenotyping in addictions.

OBJECTIVE: The causes of substance use disorders (SUDs) are largely unknown and the effectiveness of their treatments is limited. One crucial impediment to research and treatment progress surrounds how SUDs are classified and diagnosed. Given the substantial heterogeneity among individuals diagnosed with a given SUD (e.g., alcohol use disorder [AUD]), identifying novel research and treatment targets and developing new study designs is daunting. METHOD: In this article, we review and integrate two recently developed frameworks, the National Institute on Drug Abuse's Phenotyping Assessment Battery (NIDA PhAB) and the Hierarchical Taxonomy of Psychopathology (HiTOP), that hope to accelerate progress in understanding the causes and consequences of psychopathology by means of deep phenotyping, or finer-grained analysis of phenotypes. RESULTS AND CONCLUSIONS: NIDA PhAB focuses on addiction-related processes across multiple units of analysis, whereas HiTOP focuses on clinical phenotypes and covers a broader range of psychopathology. We highlight that NIDA PhAB and HiTOP together provide deep and broad characterizations of people diagnosed with SUDs and complement each other in their efforts to address widely known limitations of traditional classification systems and their diagnostic categories. Next, we show how NIDA PhAB and HiTOP can be integrated to facilitate optimal rich phenotyping of addiction-related phenomena. Finally, we argue that such deep phenotyping promises to advance our understanding of the neurobiology of SUD and addiction, which will guide the development of personalized medicine and interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Integrating the BIDS Neuroimaging Data Format and Workflow Optimization for Large-Scale Medical Image Analysis.

A robust medical image computing infrastructure must host massive multimodal archives, perform extensive analysis pipelines, and execute scalable job management. An emerging data format standard, the Brain Imaging Data Structure (BIDS), introduces complexities for interfacing with XNAT archives. Moreover, workflow integration is combinatorically problematic when matching large amount of processing to large datasets. Historically, workflow engines have been focused on refining workflows themselves instead of actual job generation. However, such an approach is incompatible with data centric architecture that hosts heterogeneous medical image computing. Distributed automation for XNAT toolkit (DAX) provides large-scale image storage and analysis pipelines with an optimized job management tool. Herein, we describe developments for DAX that allows for integration of XNAT and BIDS standards. We also improve DAX's efficiencies of diverse containerized workflows in a high-performance computing (HPC) environment. Briefly, we integrate YAML configuration processor scripts to abstract workflow data inputs, data outputs, commands, and job attributes. Finally, we propose an online database-driven mechanism for DAX to efficiently identify the most recent updated sessions, thereby improving job building efficiency on large projects. We refer the proposed overall DAX development in this work as DAX-1 (DAX version 1). To validate the effectiveness of the new features, we verified (1) the efficiency of converting XNAT data to BIDS format and the correctness of the conversion using a collection of BIDS standard containerized neuroimaging workflows, (2) how YAML-based processor simplified configuration setup via a sequence of application pipelines, and (3) the productivity of DAX-1 on generating actual HPC processing jobs compared with earlier DAX baseline method. The empirical results show that (1) DAX-1 converting XNAT data to BIDS has similar speed as accessing XNAT data only; (2) YAML can integrate to the DAX-1 with shallow learning curve for users, and (3) DAX-1 reduced the job/assessor generation latency by finding recent modified sessions. Herein, we present approaches for efficiently integrating XNAT and modern image formats with a scalable workflow engine for the large-scale dataset access and processing.

"Emotional distractor images disrupt target processing in a graded manner": Correction.

Reports an error in "Emotional distractor images disrupt target processing in a graded manner" by Jonathan M. Keefe and David H. Zald (Emotion, Advanced Online Publication, Aug 27, 2020, np). In the article "Emotional Distractor Images Disrupt Target Processing in a Graded Manner" by Jonathan M. Keefe and David H. Zald (Emotion, advance online publication, August 27, 2020, https://doi.org/10.1037/emo0000893), there were errors in the reporting of nonresponse rate and accuracy data. Nonresponse rate was underreported for the data in the Lag 2 condition, resulting in incorrect analysis of variance values for this portion of the Results section as well as incorrect Lag 2 t-test values in Table 1 and incorrect Lag 2 values in Figure 2A. Additionally, error bars for the accuracy data in Figure 2B were mistakenly calculated with data including excluded trials, resulting in larger estimates of standard error of the mean. These corrections do not affect the interpretation of any inferential statistics and in fact increased the effect of lag and distractor valence upon both of these measures. Therefore, no conclusions of the study are altered. All versions of this article have been corrected. (The following abstract of the original article appeared in record 2020-63434-001). The emotional attentional blink (EAB), also referred to as emotion-induced blindness, refers to a transient impairment in the ability to discriminate a single target when it is presented closely in time to an emotional distractor. Although the EAB has typically been characterized as representing a complete loss of target information due to attentional capture by the emotional distractors, it is unclear whether the impact of the emotional distractor is in fact discrete or graded. Here, we tested whether the emotional distractor of the EAB interfered with target processing in a continuous or all-or-none manner by measuring changes in both reaction time (RT) and target-vividness ratings in addition to target-discrimination accuracy. Rapid sequences of landscape images were presented centrally, and participants reported the orientation of a ± 90° rotated target as quickly and accurately as possible. Replicating the classic EAB phenomenon, we found a strong impairment in target discrimination when an emotional distractor shortly preceded the target, and we also found a moderate impairment when the target preceded an emotional distractor. This decrement in accuracy at short lags was accompanied by increases in RT to the target as well as lower ratings of subjective target vividness even when the target was detected, indicating that emotional distractors impacted target processing in a lag-dependent, graded manner. We argue that these results are consistent with an interactive race model of the competition between stimulus representations in the conflict between top-down and bottom-up attentional mechanisms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Emotional induced attentional blink in trauma-exposed veterans: associations with trauma specific and nonspecific symptoms.

Although theoretical models suggest that an attentional bias for threat contributes to the development of post-traumatic stress disorder (PTSD) symptoms, this bias has not been consistently observed in the literature. In the present study, trauma exposed veterans (N = 114) performed an emotional attentional blink task in which task-irrelevant combat-related, disgust, positive, or neutral distractor images appeared 200 ms, 400 ms, 600 ms, or 800 ms (i.e., lag 2, 4, 6, and 8, respectively) before the target. Relative to neutral distractors, impaired target detection was observed following combat distractors and disgust distractors, but not positive distractors. However, veterans were less accurate following disgust distractors compared to combat distractors. As predicted, combat distractors and disgust distractors were also associated with a stronger linear increase in trial accuracy reflecting task improvement with increasing lag before the target. However, the linear trend in trial accuracy for combat distractors and disgust distractors did not significantly differ from each other. Contrary to predictions, trauma specific (i.e., PTSD symptoms and diagnosis) and nonspecific processes (i.e., attentional control) were unrelated to trial accuracy. These data suggest that while initial attentional capture by cues of war is observed among trauma exposed veterans independent of individual differences in trauma specific and nonspecific symptoms, this attentional capture is less robust compared to attentional capture by disgust-eliciting stimuli. The implications of these findings for the theorized role of attentional biases for threat in the development and maintenance of PTSD are discussed.

Emotional distractor images disrupt target processing in a graded manner.

[Correction Notice: An Erratum for this article was reported online in Emotion on May 16 2022 (see record 2022-64181-001). In the article "Emotional Distractor Images Disrupt Target Processing in a Graded Manner" by Jonathan M. Keefe and David H. Zald (Emotion, advance online publication, August 27, 2020, https://doi.org/10.1037/emo0000893), there were errors in the reporting of nonresponse rate and accuracy data. Nonresponse rate was underreported for the data in the Lag 2 condition, resulting in incorrect analysis of variance values for this portion of the Results section as well as incorrect Lag 2 t-test values in Table 1 and incorrect Lag 2 values in Figure 2A. Additionally, error bars for the accuracy data in Figure 2B were mistakenly calculated with data including excluded trials, resulting in larger estimates of standard error of the mean. These corrections do not affect the interpretation of any inferential statistics and in fact increased the effect of lag and distractor valence upon both of these measures. Therefore, no conclusions of the study are altered. All versions of this article have been corrected.] The emotional attentional blink (EAB), also referred to as emotion-induced blindness, refers to a transient impairment in the ability to discriminate a single target when it is presented closely in time to an emotional distractor. Although the EAB has typically been characterized as representing a complete loss of target information due to attentional capture by the emotional distractors, it is unclear whether the impact of the emotional distractor is in fact discrete or graded. Here, we tested whether the emotional distractor of the EAB interfered with target processing in a continuous or all-or-none manner by measuring changes in both reaction time (RT) and target-vividness ratings in addition to target-discrimination accuracy. Rapid sequences of landscape images were presented centrally, and participants reported the orientation of a ± 90° rotated target as quickly and accurately as possible. Replicating the classic EAB phenomenon, we found a strong impairment in target discrimination when an emotional distractor shortly preceded the target, and we also found a moderate impairment when the target preceded an emotional distractor. This decrement in accuracy at short lags was accompanied by increases in RT to the target as well as lower ratings of subjective target vividness even when the target was detected, indicating that emotional distractors impacted target processing in a lag-dependent, graded manner. We argue that these results are consistent with an interactive race model of the competition between stimulus representations in the conflict between top-down and bottom-up attentional mechanisms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Influences of dopaminergic system dysfunction on late-life depression.

Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflammatory burden, the role of dopamine may be particularly salient for late-life depression. We review the literature examining the role of dopamine in the pathogenesis of depression, as well as how dopamine function changes with aging and is influenced by inflammation. Applying a Research Domain Criteria (RDoC) Initiative perspective, we then review work examining how dopaminergic signaling affects these domains, specifically focusing on Cognitive, Positive Valence, and Sensorimotor Systems. We propose a unified model incorporating the effects of aging and low-grade inflammation on dopaminergic functioning, with a resulting negative effect on cognition, reward processing, and motor function. Interplay between these systems may influence development of a depressive phenotype, with an initial deficit in one domain reinforcing decline in others. This model extends RDoC concepts into late-life depression while also providing opportunities for novel and personalized interventions.

Amphetamine-induced dopamine release and impulsivity in Parkinson's disease.

Impulsive-compulsive behaviours manifest in a substantial proportion of subjects with Parkinson's disease. Reduced ventral striatum dopamine receptor availability, and increased dopamine release is noted in patients with these symptoms. Prior studies of impulsivity suggest that midbrain D2 autoreceptors regulate striatal dopamine release in a feedback inhibitory manner, and in healthy populations, greater impulsivity is linked to poor proficiency of this inhibition. This has not been assessed in a Parkinson's disease population. Here, we applied 18F-fallypride PET studies to assess striatal and extrastriatal D2-like receptor uptake in a placebo-controlled oral dextroamphetamine sequence. We hypothesized that Parkinson's disease patients with impulsive-compulsive behaviours would have greater ventral striatal dopaminergic response to dextroamphetamine, and that an inability to attenuate ventral striatal dopamine release via midbrain D2 autoreceptors would underlie this response. Twenty patients with Parkinson's disease (mean age = 64.1 ± 5.8 years) both with (n = 10) and without (n = 10) impulsive-compulsive behaviours, participated in a single-blind dextroamphetamine challenge (oral; 0.43 mg/kg) in an OFF dopamine state. All completed PET imaging with 18F-fallypride, a high-affinity D2-like receptor ligand, in the placebo and dextroamphetamine state. Both voxelwise and region of interest analyses revealed dextroamphetamine-induced endogenous dopamine release localized to the ventral striatum, and the caudal-medial orbitofrontal cortex. The endogenous dopamine release observed in the ventral striatum correlated positively with patient-reported participation in reward-based behaviours, as quantified by the self-reported Questionnaire for Impulsivity in Parkinson's disease Rating Scale. In participants without impulsive-compulsive behaviours, baseline midbrain D2 receptor availability negatively correlated with ventral striatal dopamine release; however, this relationship was absent in those with impulsive-compulsive behaviours. These findings emphasize that reward-based behaviours in Parkinson's disease are regulated by ventral striatal dopamine release, and suggest that loss of inhibitory feedback from midbrain autoreceptors may underlie the manifestation of impulsive-compulsive behaviours.

D2-Like Receptor Expression in the Hippocampus and Amygdala Informs Performance on the Stop-Signal Task in Parkinson's Disease.

The stop-signal task is a well-established assessment of response inhibition, and in humans, proficiency is linked to dorsal striatum D2 receptor availability. Parkinson's disease (PD) is characterized by changes to efficiency of response inhibition. Here, we studied 17 PD patients (6 female and 11 male) using the stop-signal paradigm in a single-blinded d-amphetamine (dAMPH) study. Participants completed [18F]fallypride positron emission topography (PET) imaging in both placebo and dAMPH conditions. A voxel-wise analysis of the relationship between binding potential (BPND) and stop-signal reaction time (SSRT) revealed that faster SSRT is associated with greater D2-like BPND in the amygdala and hippocampus (right cluster qFDR-corr = 0.026, left cluster qFDR-corr = 0.002). A region of interest (ROI) examination confirmed this association in both the amygdala (coefficient = -48.26, p = 0.005) and hippocampus (coefficient = -104.94, p = 0.007). As healthy dopaminergic systems in the dorsal striatum appear to regulate response inhibition, we interpret our findings in PD to indicate either nigrostriatal damage unmasking a mesolimbic contribution to response inhibition, or a compensatory adaptation from the limbic and mesial temporal dopamine systems. These novel results expand the conceptualization of action-control networks, whereby limbic and motor loops may be functionally connected.SIGNIFICANCE STATEMENT While Parkinson's disease (PD) is characteristically recognized for its motor symptoms, some patients develop impulsive and compulsive behaviors (ICBs), manifested as repetitive and excessive participation in reward-driven activities, including sex, gambling, shopping, eating, and hobbyism. Such cognitive alterations compel a consideration of response inhibition in PD. To investigate inhibitory control and assess the brain regions that may participate, we assessed PD patients using a single-blinded d-amphetamine (dAMPH) study, with [18F]fallypride positron emission topography (PET) imaging, and stop-signal task performance. We find a negative relationship between D2-like binding in the mesial temporal region and top-signal reaction time (SSRT), with greater BPND associated with a faster SSRT. These discoveries indicate a novel role for mesolimbic dopamine in response inhibition, and advocate for limbic regulation of action control in this clinical population.

Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): II. Externalizing superspectrum.

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical effort to address limitations of traditional mental disorder diagnoses. These include arbitrary boundaries between disorder and normality, disorder co-occurrence in the modal case, heterogeneity of presentation within dis-orders, and instability of diagnosis within patients. This paper reviews the evidence on the validity and utility of the disinhibited externalizing and antagonistic externalizing spectra of HiTOP, which together constitute a broad externalizing superspectrum. These spectra are composed of elements subsumed within a variety of mental disorders described in recent DSM nosologies, including most notably substance use disorders and "Cluster B" personality disorders. The externalizing superspectrum ranges from normative levels of impulse control and self-assertion, to maladaptive disinhibition and antagonism, to extensive polysubstance involvement and personality psychopathology. A rich literature supports the validity of the externalizing superspectrum, and the disinhibited and antagonistic spectra. This evidence encompasses common genetic influences, environmental risk factors, childhood antecedents, cognitive abnormalities, neural alterations, and treatment response. The structure of these validators mirrors the structure of the phenotypic externalizing superspectrum, with some correlates more specific to disinhibited or antagonistic spectra, and others relevant to the entire externalizing superspectrum, underlining the hierarchical structure of the domain. Compared with traditional diagnostic categories, the externalizing superspectrum conceptualization shows improved utility, reliability, explanatory capacity, and clinical applicability. The externalizing superspectrum is one aspect of the general approach to psychopathology offered by HiTOP and can make diagnostic classification more useful in both research and the clinic.

Dispositional Negative Emotionality in Childhood and Adolescence Predicts Structural Variation in the Amygdala and Caudal Anterior Cingulate During Early Adulthood: Theoretically and Empirically Based Tests.

Substantial evidence implicates the amygdala and related structures in the processing of negative emotions. Furthermore, neuroimaging evidence suggests that variations in amygdala volumes are related to trait-like individual differences in neuroticism/negative emotionality, although many questions remain about the nature of such associations. We conducted planned tests of the directional prediction that dispositional negative emotionality measured at 10-17 years using parent and youth ratings on the Child and Adolescent Dispositions Scale (CADS) would predict larger volumes of the amygdala in adulthood and conducted exploratory tests of associations with other regions implicated in emotion processing. Participants were 433 twins strategically selected for neuroimaging during wave 2 from wave 1 of the Tennessee Twins Study (TTS) by oversampling on internalizing and/or externalizing psychopathology risk. Controlling for age, sex, race-ethnicity, handedness, scanner, and total brain volume, youth-rated negative emotionality positively predicted bilateral amygdala volumes after correction for multiple testing. Each unit difference of one standard deviation (SD) in negative emotionality was associated with a .12 SD unit difference in larger volumes of both amygdalae. Parent-rated negative emotionality predicted greater thickness of the left caudal/dorsal anterior cingulate cortex (ß = 0.28). Associations of brain structure with negative emotionality were not moderated by sex. These results are striking because dispositions assessed at 10-17 years of age were predictive of grey matter volumes measured 12-13 years later in adulthood. Future longitudinal studies should examine the timing of amygdala/cingulate associations with dispositional negative emotionality to determine when these associations emerge during development.

Hierarchical models of psychopathology: empirical support, implications, and remaining issues.

There is an ongoing revolution in psychology and psychiatry that will likely change how we conceptualize, study and treat psychological problems.- Many theorists now support viewing psychopathology as consisting of continuous dimensions rather than discrete diagnostic categories. Indeed, recent papers have proposed comprehensive taxonomies of psychopathology dimensions to replace the DSM and ICD taxonomies of categories. The proposed dimensional taxonomies, which portray psychopathology as hierarchically organized correlated dimensions, are now well supported at phenotypic levels. Multiple studies show that both a general factor of psychopathology at the top of the hierarchy and specific factors at lower levels predict different functional outcomes. Our analyses of data on a large representative sample of child and adolescent twins suggested the causal hypothesis that phenotypic correlations among dimensions of psychopathology are the result of many familial influences being pleiotropic. That is, most genetic variants and shared environmental factors are hypothesized to non-specifically influence risk for multiple rather than individual dimensions of psychopathology. In contrast, person-specific experiences tend to be related to individual dimensions. This hierarchical causal hypothesis has been supported by both large-scale family and molecular genetic studies. Current research focuses on three issues. First, the field has not settled on a preferred statistical model for studying the hierarchy of causes and phenotypes. Second, in spite of encouraging progress, the neurobiological correlates of the hierarchy of dimensions of psychopathology are only partially described. Third, although there are potentially important clinical implications of the hierarchical model, insufficient research has been conducted to date to rec-ommend evidence-based clinical practices.

Pandora: 4-D White Matter Bundle Population-Based Atlases Derived from Diffusion MRI Fiber Tractography.

Brain atlases have proven to be valuable neuroscience tools for localizing regions of interest and performing statistical inferences on populations. Although many human brain atlases exist, most do not contain information about white matter structures, often neglecting them completely or labelling all white matter as a single homogenous substrate. While few white matter atlases do exist based on diffusion MRI fiber tractography, they are often limited to descriptions of white matter as spatially separate "regions" rather than as white matter "bundles" or fascicles, which are well-known to overlap throughout the brain. Additional limitations include small sample sizes, few white matter pathways, and the use of outdated diffusion models and techniques. Here, we present a new population-based collection of white matter atlases represented in both volumetric and surface coordinates in a standard space. These atlases are based on 2443 subjects, and include 216 white matter bundles derived from 6 different automated state-of-the-art tractography techniques. This atlas is freely available and will be a useful resource for parcellation and segmentation.

Emotion dynamics across adulthood in everyday life: Older adults are more emotionally stable and better at regulating desires.

Older adults report experiencing improved emotional health, such as more intense positive affect and less intense negative affect. However, there are mixed findings on whether older adults are better at regulating emotion-a hallmark feature of emotional health-and most research is based on laboratory studies that may not capture how people regulate their emotions in everyday life. We used experience sampling to examine how multiple measures of emotional health, including mean affect, dynamic fluctuations between affective states and the ability to resist desires-a common form of emotion regulation-differ in daily life across adulthood. Participants (N = 122, ages 20-80) reported how they were feeling and responding to desire temptations for 10 days. Older adults experienced more intense positive affect, less intense negative affect, and were more emotionally stable, even after controlling for individual differences in global life satisfaction. Older adults were more successful at regulating desires, even though they experienced more intense desires than younger adults. In addition, adults in general experiencing more intense affect were less successful at resisting desires. These results demonstrate how emotional experience is related to more successful desire regulation in everyday life and provide unique evidence that emotional health and regulation improve with age. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Sluggish Cognitive Tempo and Depressive Symptoms in Children and Adolescents Predict Adulthood Psychopathology.

Sluggish cognitive tempo (SCT) is characterized by behavioral symptoms reflecting slowness and lethargy (e.g., sluggishness, appearing sleepy) and inconsistent alertness/mental confusion (e.g., daydreaming, fogginess). SCT is substantially correlated with the inattentive symptoms of attention-deficit/hyperactivity disorder (ADHD) and may be part of that domain, but in cross-sectional data, SCT is also strongly associated with both inattention and depression. To date, no study has examined the prospective associations of SCT symptoms in childhood/adolescence with symptoms of ADHD and internalizing problems in adulthood. Using a sample of 449 twin children and adolescent pairs, prospective multiple regression analyses examined whether self- and parent-reported SCT, depression, and parent-reported symptoms of ADHD predicted symptoms in adulthood 12 years later. SCT and depression at time one were strongly correlated (self-reported SCT and depression r = 0.84; parent-reported SCT and depression r = 0.78). When adult outcomes were separately regressed on each youth symptom dimension, self-reported SCT (ß = 0.26, p < 0.0001) and depression (ß = 0.13, p < 0.0001) each predicted adult symptoms of depression and self-reported SCT predicted inattention (ß = 0.12, p = 0.0026). Parent-reported depression, but not parent-reported SCT, predicted self-reported adult depression symptoms (ß = 0.17, p = 0.0003). In contrast, when each adult outcome was regressed simultaneously on youth self-reported SCT and depression, neither predicted adulthood inattention or depression. These findings indicate that SCT in childhood and adolescence is strongly associated concurrently and predictively with both inattention and depression. Theoretical and clinical applications of the construct of SCT must take its robust association with both inattention and depression into account.