Don't worry, it won't be fine. Contributions of worry and anxious arousal to startle responses and event-related potentials in threat anticipation.

A widely shared framework suggests that anxiety maps onto two dimensions: anxious apprehension and anxious arousal. Previous research linked individual differences in these dimensions to differential neural response patterns in neuropsychological, imaging, and physiological studies. Differential effects of the anxiety dimensions might contribute to inconsistencies in prior studies that examined neural processes underlying anxiety, such as hypersensitivity to unpredictable threat. We investigated the association between trait worry (as a key component of anxious apprehension), anxious arousal, and the neural processing of anticipated threat. From a large online community sample (N = 1,603), we invited 136 participants with converging and diverging worry and anxious arousal profiles into the laboratory. Participants underwent the NPU-threat test with alternating phases of unpredictable threat, predictable threat, and safety, while physiological responses (startle reflex and startle probe locked event-related potential components N1 and P3) were recorded. Worry was associated with increased startle responses to unpredictable threat and increased attentional allocation (P3) to startle probes in predictable threat anticipation. Anxious arousal was associated with increased startle and N1 in unpredictable threat anticipation. These results suggest that trait variations in the anxiety dimensions shape the dynamics of neural processing of threat. Specifically, trait worry seems to simultaneously increase automatic defensive preparation during unpredictable threat and increase attentional responding to threat-irrelevant stimuli during predictable threat anticipation. The current study highlights the utility of anxiety dimensions to understand how physiological responses during threat anticipation are altered in anxiety and supports that worry is associated with hypersensitivity to unpredictable, aversive contexts.

The association of dispositional anxiety with the NoGo N2 under relaxation instruction vs. speed/accuracy instruction.

Prior research suggests that cognitive control, indicated by NoGo N2 amplitudes in Go/NoGo tasks, is associated with dispositional anxiety. This negative association tends to be reduced in anxiety-enhancing experimental conditions. However, anxiety-reducing conditions have not yet been investigated systematically. Thus, the present study compares the effect of a relaxation instruction with the conventional speed/accuracy instruction in a Go/NoGo task on the correlation of the NoGo N2 with two subconstructs of dispositional anxiety, namely anxious apprehension and anxious arousal. As the test of differences between correlations needs considerable statistical power, the present study was included into the multi-lab CoScience Project. The hypotheses, manipulation checks, and the main path of pre-processing and statistical analysis were preregistered. Complete data sets of 777 participants were available for data analysis. Preregistered general linear models revealed that the different instructions of the task (speed/accuracy vs. relaxation) had no effect on the association between dispositional anxiety and the NoGo N2 amplitude in general. This result was supported by Cooperative-Forking-Path analysis. In contrast, a preregistered latent growth model with categorical variables revealed that anxious arousal was a negative predictor of the NoGo N2 intercept and a positive predictor of the NoGo N2 slope. Non-preregistered growth models, allowing for correlations of anxious apprehension with anxious arousal, revealed that higher anxious apprehension scores were associated with more negative NoGo N2 amplitudes with increased relaxation. Results are discussed in the context of the compensatory error monitoring hypothesis and the revised Reinforcement Sensitivity Theory.

The dimensional structure of internalizing psychopathology: Relation to diagnostic categories.

Recent approaches aim to represent the dimensional structure of psychopathology, but relatively little research has rigorously tested sub-dimensions within internalizing psychopathology. This study tests pre-registered models of the dimensional structure of internalizing psychopathology, and their relations with current and lifetime depressive and anxiety disorders diagnostic data, in adult samples harmonized across three sites (n=427). Across S-1 bifactor and hierarchical models, we found converging evidence for both general and specific internalizing dimensions. Depression, generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic attacks were all associated with a general internalizing factor that we posit primarily represents motivational anhedonia. GAD was also associated with a specific anxious apprehension factor, and SAD with specific anxious apprehension and low positive affect factors. We suggest that dimensional approaches capturing shared and specific internalizing symptom facets more accurately describe the structure of internalizing psychopathology and provide useful alternatives to categorical diagnoses to advance clinical science.

Disentangling the effects of trait and state worry on error-related brain activity: Results from a randomized controlled trial using worry manipulations.

Enhanced amplitudes of the error-related negativity (ERN) have been suggested to be a transdiagnostic neural risk marker for internalizing psychopathology. Previous studies propose worry to be an underlying mechanism driving the association between enhanced ERN and anxiety. The present preregistered study focused on disentangling possible effects of trait and state worry on the ERN by utilizing a cross sectional observational and a longitudinal randomized controlled experimental design. To this end, we examined the ERN of n = 90 students during a flanker task (T0), which were then randomly assigned to one of three groups (worry induction, worry reduction, passive control group). Following the intervention, participants performed another flanker task (T1) to determine potential alterations of their ERN. Manipulation checks revealed that compared to the control group, state worry increased in the induction but also in the reduction group. ERN amplitudes did not vary as a function of state worry. An association of trait worry with larger ERN amplitudes was only observed in females. Furthermore, we found larger ERN amplitudes in participants with a current or lifetime diagnosis of internalizing disorders. In summary, our findings suggest that the ERN seems to be insensitive to variations in state worry, but that an elevated ERN is associated with the trait-like tendency to worry and internalizing psychopathology, which is consistent with the notion that the ERN likely represents a trait-like neural risk associated with anxiety.

Predictive utility of symptom measures in classifying anxiety and depression: A machine-learning approach.

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent, co-occurring disorders with significant symptom overlap, posing challenges in accurately distinguishing and diagnosing these disorders. The tripartite model proposes that anxious arousal is specific to anxiety and anhedonia is specific to depression, though anxious apprehension may play a greater role in GAD than anxious arousal. The present study tested the efficacy of the Mood and Anxiety Symptom Questionnaire anhedonic depression (MASQ-AD) and anxious arousal (MASQ-AA) scales and the Penn State Worry Questionnaire (PSWQ) in identifying lifetime or current MDD, current major depressive episode (MDE), and GAD using binary support vector machine learning algorithms in an adult sample (n = 150). The PSWQ and MASQ-AD demonstrated predictive utility in screening for and identification of GAD and current MDE respectively, with the MASQ-AD eight-item subscale outperforming the MASQ-AD 14-item subscale. The MASQ-AA did not predict MDD, current MDE, or GAD, and the MASQ-AD did not predict current or lifetime MDD. The PSWQ and MASQ-AD are efficient and accurate screening tools for GAD and current MDE. Results support the tripartite model in that anhedonia is unique to depression, but inclusion of anxious apprehension as a separate dimension of anxiety is warranted.

Early hypervigilance and later avoidance: Event-related potentials track the processing of threatening stimuli in anxiety.

Avoidance behavior is a core symptom of anxiety disorders that may hinder adaptation. Anxiety disorders are heterogeneous and previous research suggests to decompose anxiety into two dimensions: anxious apprehension and anxious arousal. How these two dimensions are associated with avoidance of and exposure to threatening stimuli, as well as their accompanying neural processes, is barely understood. We examined threat processing using event-related potentials (N1, LPP) from 134 individuals considering the influence of anxiety dimensions. During a two-phase picture-viewing task the participants watched neutral and threatening pictures, which they were instructed to either avoid or attend to during repeated presentations. Results showed that threatening compared to neutral pictures were associated with increased attention allocation (N1) and in-depth processing (LPP), modulated by task-instructions (lower during avoidance). Further, increased anxious apprehension was associated with heightened automatic attention (increased N1), followed by reduced LPP amplitudes for threatening pictures suggesting reduced in-depth processing. During re-exposure, threatening pictures were associated with increased in-depth processing, with no difference between previously avoided and maintained pictures. Together, these results illustrate that avoidance and high anxious apprehension seem to lead to similar neural changes in the processing of aversive images that may conflict with long-term adaptation.

Diverging patterns of EEG alpha asymmetry in anxious apprehension and anxious arousal.

Anxious apprehension and anxious arousal are central transdiagnostic anxiety dimensions and have been linked to divergent patterns of frontal and parietal alpha asymmetry. The present study examined the relationship between alpha asymmetry and anxiety dimensions in 130 individuals whose electroencephalogram (EEG) was recorded at rest. We applied a 2 (anxious apprehension: low vs. high) × 2 (anxious arousal, low vs. high) design to contrast brain lateralization in four groups. Results revealed that anxious apprehension was associated with more left-than-right frontal brain activity in the lower alpha band, an effect driven by decreased right frontal activity. Exploratory analyses showed more left-than-right brain activity at central sites associated with anxious apprehension. Parietal activity was not lateralized as a function of anxiety dimensions. Taken together, the current results support that anxious apprehension is associated with more left-than-right frontal and central activity, and suggest a broader distribution of alpha asymmetries associated with anxious apprehension than previously thought.

Women with Major Depressive Disorder, Irrespective of Comorbid Anxiety Disorders, Show Blunted Bilateral Frontal Responses during Win and Loss Anticipation.

BACKGROUND: Electroencephalography (EEG) studies suggest that major depressive disorder (MDD) is associated with lower left than right frontal brain activity (asymmetry), a pattern appearing stronger in women than men, and when elicited during emotionally-relevant paradigms versus an uncontrolled resting state. However, it is unclear whether this asymmetry pattern generalizes to the common presentation of MDD with co-occurring anxiety. Moreover, asymmetry may differ for anxiety subtypes, wherein anxious apprehension (AnxApp: worry characteristic of generalized anxiety disorder) appears left-lateralized, but anxious arousal (AnxAro: panic characteristic of social anxiety, posttraumatic stress, and panic disorders) may be right-lateralized. METHODS: This analysis attempted to replicate frontal EEG asymmetry patterns using functional magnetic resonance imaging (fMRI). Participants completed clinical interviews and a monetary incentive delay (MID) task during fMRI recording. We compared five groups of right-handed women from the Tulsa 1000 study, MDD (n=40), MDD-AnxApp (n=26), MDD-AnxAro (n=34), MDD-Both (with AnxApp and AnxAro; n=26), and healthy controls (CTL; n=24), as a function of MID anticipation condition (no win/loss, win, loss) and hemisphere on frontal blood oxygen-level-dependent (BOLD) signal. RESULTS: CTL exhibited higher bilateral superior, middle, and inferior middle frontal gyrus BOLD signal than the four MDD groups for high arousal (win and loss) conditions. However, frontal attenuations were unrelated to current depression/anxiety symptoms, suggestive of a trait as opposed to a state marker. LIMITATIONS: This was a cross-sectional analysis restricted to women. CONCLUSIONS: Reduced prefrontal cortex recruitment during processing of both positively and negatively valenced stimuli is consistent with the emotion context insensitivity theory of MDD.

Separate contributions of autistic traits and anxious apprehension, but not alexithymia, to emotion processing in faces.

Reduced eye fixation has been commonly reported in autistic samples but may be at least partially explained by alexithymia (i.e., difficulty understanding and describing one's emotional state). Because anxiety is often elevated in autism, and emotion-processing differences have also been observed in anxious samples, anxiety traits may also influence emotion processing within autism. This study tested the contribution of dimensional traits of autism, anxious apprehension, and alexithymia in mediating eye fixation during face processing. Participants included 105 adults from three samples: autistic adults (AS; n = 30), adults with clinically elevated anxiety and no autism (HI-ANX; n = 29), and neurotypical adults without elevated anxiety (NT; n = 46). Experiment 1 used an emotion identification task with dynamic stimuli, while Experiment 2 used a static luminance change detection task with emotional- and neutral-expression static photos. The emotions of interest were joy, anger, and fear. Dimensional mixed-effects models showed that autism traits, but not alexithymia, predicted reduced eye fixation across both tasks. Anxious apprehension was negatively related to response time in Experiment 1 and positively related to eye fixation in Experiment 2. Attentional avoidance of negative stimuli occurred at lower levels of autism traits and higher levels of worry traits. The results highlight the contribution of autism traits to emotional processing and suggest additional effects of worry-related traits.

Worry-inducing stimuli in an aversive Go/NoGo task enhance reactive control in individuals with lower trait-anxiety.

This study relates predictions on reactive and proactive cognitive control to findings on anxious apprehension/worry and ERN/Ne. We investigated whether worry-inducing stimuli in an aversive performance setting lead to a more pronounced increase of the ERN/Ne in individuals with lower anxious apprehension/worry. We also explored the N2 amplitude in the context of worry-inducing stimuli. Fifty-eight participants performed an extended Go/NoGo task. A neutral or fearful face was presented at the beginning of each trial, with the fearful face as a worry-inducing, distracting stimulus. In an aversive feedback condition, aversive feedback was provided for false or too slow responses. We found a more pronounced decrease of the ERN/Ne after worry-inducing stimuli compared to neutral stimuli in participants with lower anxious apprehension/worry. Moreover, less pronounced N2 amplitudes were associated with shorter reaction times in the aversive feedback condition. Implications for future research on error monitoring and trait-anxiety are discussed.

The history of generalized anxiety disorder as a diagnostic category.

From the 19th century into the 20th century, the terms used to diagnose generalized anxiety included "pantophobia" and "anxiety neurosis." Such terms designated paroxysmal manifestations (panic attacks) as well as interparoxysmal phenomenology (the apprehensive mental state). Also, generalized anxiety was considered one of numerous symptoms of neurasthenia, a vaguely defined illness. Generalized anxiety disorder (GAD) appeared as a diagnostic category in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 1980, when anxiety neurosis was split into GAD and panic disorder. The distinct responses these two disorders had to imipramine therapy was one reason to distinguish between the two. Since the revised DSM-III (DSM-III-R), worry about a number of life circumstances has been gradually emphasized as the distinctive symptom of GAD. Thus, a cognitive aspect of anxiety has become the core criterion of GAD. The validity of GAD as an independent category has been questioned from DSM-III up to preparation of DSM-5. Areas of concern have included the difficulty to establish clear boundaries between GAD and (i) personality dimensions, (ii) other anxiety-spectrum disorders, and (iii) nonbipolar depression. The National Institute of Mental Health has recently proposed the Research Domain Criteria (RDoC), a framework destined to facilitate biological research into the etiology of mental symptoms. Within the RDoC framework, generalized anxiety might be studied as a dimension denominated "anxious apprehension" that would typically fit into the research domain called "negative valence systems" and the more specific construct termed "potential threat."

Desde el sigh XIX y hasta el siglo XX, los términos empleados para diagnosticar la ansiedad generalizada incluyeron la "pantofobia" y la "neurosis de ansiedad". Tales términos designaron manifestaciones paroxísticas (ataques de pánico) como también fenomenología interparoxística (el estado mental de aprensión). También la ansiedad generalizada fue considerada uno de Ios numerosos síntomas de la neurastenia, una enfermedad definida vagamente. El trastorno de ansiedad generalizada (TAG) apareció como una categoría diagnóstica en la tercera edición del Manual Diagnóstico y Estadístico de Ios Trastornos Mentales (DSM-III) en 1980, cuando la neurosis de ansiedad fue dividida entre el TAG y el trastorno de pánico. Una de las razones para distínguir estos dos trastornos fue la respuesta diferente que tuvieron a la terapia con imipramina. A partir de la edición revisada del DSM-III (DSM-III-R), la preocupación People Like Us - situaciones de vida se ha enfatizado gradualmente como el síntoma distintivo del TAG. En consecuencia, un aspecto cognitivo de la ansiedad ha llegado a ser el criterio central del TAG. La validez del TAG como una categoría independiente ha sido cuestionada desde el DSM-III hasta la preparación del DSM-5. Algunos aspectos tornados en cuenta han incluido la dificultad para establecer límites claros entre el TAG y 1) dimensiones de la personalidad, 2) otros trastornos del espectro ansioso y 3) la depresión no bipolar. Recientemente, el Instituto National de Salud Mental de EE.UU. propuso Ios Research Domain Criteria (RDoC), un sistema destinado a facilitar la investigación biológica acerca de la etiología de Ios síntomas mentales. Dentro del sistema RDoC, la ansiedad generalizada podría ser estudiada como una dimensión denominada "aprensión ansiosa", la cual podría ajustar típicamente con el dominio de investigación llamado "sistemas de valencía negativa" y más específicamente con el constructo llamado "amenaza potencial".

Entre le XIXe et le XXe siècle, plusieurs termes ont été utilisés pour dénommer l'anxiété généralisée, notamment la «pantophobie¼ et la «névrose d'angoisse¼. Ces termes désignaient à la fois des manifestations paroxystiques (les attaques de panique) ainsi que les symptômes intercritiques (l'état mental d'appréhension). D'autre part, l'anxiété généralisée était aussi considérée comme l'un des nombreux symptômes de neurasthénie, une maladie de définition imprécise. Le trouble anxieux généralisé (TAG) est apparu pour la première fois en tant que diagnostic dans la 3e édition du manuel statistique et diagnostique des troubles mentaux (DSM-III) en 1980 quand la névrose d'angoisse a été divisée en TAG et trouble panique. Ces deux troubles ont été distingués sur la base d'une réponse différente au traitement par imipramine. À partir de la révision du DSM-III (DSM-III-R), l'inquiétude face à un certain nombre de situations de la vie courante a été conceptualisée petit à petit comme le symptôme cardinal du TAG. Ainsi, un aspect cognitif de l'anxiété est devenu le critère primordial du TAG. La validité du TAG en tant que catégorie diagnostique indépendante a été mise en doute depuis le DSM-III jusqu'à la préparation du DSM-5. Les questionnements reposaient sur la difficulté à établir des frontières claires entre le TAG et (1) les dimensions de personnalité, (2) les autres troubles du spectre de l'anxiété et (3) la dépression non-bipolaire. L'institut national de la santé mentale aux États-Unis a récemment mis en place le Research Domain Criteria [RDoC], un cadre destiné à faciliter les recherches biologiques dans le domaine de l'étiologie des troubles mentaux. Dans le cadre du RDoC, l'anxiété généralisée pourrait être étudiée comme une dimension appelée «appréhension anxieuse¼, qui appartiendrait typiquement au domaine de recherche dénommé «systèmes de valences négatives¼ et plus spécifiquement au concept dit de «menace potentielle¼.

Transdiagnostic dimensions of anxiety: Neural mechanisms, executive functions, and new directions.

Converging neuroscientific and psychological evidence points to several transdiagnostic factors that cut across DSM-defined disorders, which both affect and are affected by executive dysfunction. Two of these factors, anxious apprehension and anxious arousal, have helped bridge the gap between psychological and neurobiological models of anxiety. The present integration of diverse findings advances an understanding of the relationships between these transdiagnostic anxiety dimensions, their interactions with each other and executive function, and their neural mechanisms. Additionally, a discussion is provided concerning how these constructs fit within the Research Domain Criteria (RDoC) matrix developed by the National Institutes of Mental Health and how they relate to other anxiety constructs studied with different methods and at other units of analysis. Suggestions for future research are offered, including how to (1) improve measurement and delineation of these constructs, (2) use new neuroimaging methods and theoretical approaches of how the brain functions to build neural mechanistic models of these constructs, and (3) advance understanding of the relationships of these constructs to diverse emotional phenomena and executive functions.

Anxiety type modulates immediate versus delayed engagement of attention-related brain regions.

Background Habituation of the fear response, critical for the treatment of anxiety, is inconsistently observed during exposure to threatening stimuli. One potential explanation for this inconsistency is differential attentional engagement with negatively valenced stimuli as a function of anxiety type. Methods The present study tested this hypothesis by examining patterns of neural habituation associated with anxious arousal, characterized by panic symptoms and immediate engagement with negatively valenced stimuli, versus anxious apprehension, characterized by engagement in worry to distract from negatively valenced stimuli. Results As predicted, the two anxiety types evidenced distinct patterns of attentional engagement. Anxious arousal was associated with immediate activation in attention-related brain regions that habituated over time, whereas anxious apprehension was associated with delayed activation in attention-related brain regions that occurred only after habituation in a worry-related brain region. Conclusions Results further elucidate mechanisms involved in attention to negatively valenced stimuli and indicate that anxiety is a heterogeneous construct with regard to attention to such stimuli.