Anja Riesel

Responses to unpredictable threat have been proposed as a candidate mechanism in anxiety-related psychopathology, but clinical findings remain heterogeneous and often rely on single physiological outcomes. The present study examined whether physiological responses during threat anticipation map onto categorical and dimensional conceptualizations of psychopathology across the anxiety and obsessive-compulsive spectrum. In a transdiagnostic sample of N = 163 participants, patients with specific phobia, social anxiety disorder (SAD), and obsessive-compulsive disorder (OCD), as well as unaffected controls completed the NPU-threat test in order to measure responses to predictable and unpredictable threat. Physiological responding was assessed using startle reflex, skin conductance responses (SCR), and event-related potentials indexing early sensory processing (N1) and later attentional allocation (P3). Results indicated a group-based effect for SCR, such that patients with OCD showed enhanced autonomic responding during unpredictable threat anticipation. Dimensionally, anxious arousal was associated with reduced SCR during unpredictable threat and lower P3 amplitudes across conditions. Intolerance of uncertainty modulated startle particularly in controls, and anxious apprehension was associated with increased N1 amplitudes in OCD. Exploratory latent profile analysis identified three multisystem physiological response profiles. A threat-reactive profile characterized by increased N1 and both increased SCR and startle to unpredictable threat was particularly clinically enriched, showing higher clinical severity, greater representation of SAD and OCD, and elevated anxious apprehension and social anxiety symptoms. Together, findings suggest that threat anticipation in anxiety-related psychopathology is best understood as a multisystem and partly transdiagnostic process rather than as a single physiological marker of diagnostic status or unpredictable-threat sensitivity.

This commentary was submitted to Psychotherapy and Psychosomatics on 9February 2026 and was declined on 9 March 2026 on the basis of one anonymous externalreview. The manuscript is made publicly available here as a preprint in its original submittedform to support transparent scholarly exchange and ongoing discussion.

Fear learning processes are often considered underlying mechanisms in the development and maintenance of anxiety‐ and stress‐related disorders. However, limited attention has been paid to whether these changes are shared across disorders or certain symptoms. In this context, transdiagnostic research on symptom dimensions is especially relevant, as it addresses the significant symptom overlap and heterogeneity observed in these disorders. In the current study, we investigated the late positive potential, fear‐potentiated startle, and subjective ratings (US‐expectancy) in a transdiagnostic sample ( N = 156) including participants with obsessive‐compulsive disorder (OCD; n = 38), social anxiety disorder (SAD; n = 39), specific phobia (SP; n = 40), and control participants ( n = 39). Anxious arousal, anxious apprehension, and depressive symptoms were examined as relevant core symptom dimensions to these disorders. A differential fear learning paradigm using geometrical forms was employed, including a habituation, acquisition, generalization, and extinction phase. We observed successful fear acquisition across all outcomes, which generalized to the stimulus most similar to the CS+, the GS+. During extinction, fear responses to the CS+ remained significantly elevated compared to the CS−. Group comparison revealed that patients with SAD rated US‐expectancy for the CS− higher during acquisition. On a dimensional level, anxious arousal was associated with increased US‐expectancy and startle response for the CS+ during acquisition and increased US‐expectancy for the GS+ during generalization. Depressive symptoms were linked to an overall higher US‐expectancy during extinction. These findings suggest that individual differences in symptom dimensions, particularly anxious arousal and depressive symptoms, appear to influence fear learning and extinction processes across disorders. This underscores the potential of adopting transdiagnostic approaches in future research and clinical interventions and highlights that the frequently co‐occurring comorbid depressive symptoms impact fear extinction, and therefore, should be considered in the treatment of anxiety disorders to enhance therapeutic outcomes.

Adverse childhood experiences (ACEs) are well established and strong risk factors for mental health challenges later in life, but the underlying mechanisms remain largely unclear. Associative learning, which shapes emotional and cognitive responses to environmental cues, may play a critical role in this relationship. However, the neural underpinnings linking ACEs and ACE load to alterations in associative threat and safety learning remain poorly understood. In this multimodal fMRI study, 171 participants (97 with ACEs, 74 without ACEs) underwent a one-day fear conditioning paradigm, which included fear acquisition, generalization, extinction, and a return of fear test (ROF) after reinstatement. During fear acquisition, generalization and the ROF test, higher ACE load was associated with reduced discrimination between threat and safety cues, primarily driven by blunted responses to the threat cue across arousal ratings and central nodes of the fear network key brain regions (striatal regions and the vmPFC). During fear generalization, individuals with ACEs showed reduced activation in key brain regions to the CS+ (and GS+) but no differences in generalization gradients. In contrast, ACEs were neither related to expectancy ratings for nor aversiveness ratings for the unconditioned aversive event. These findings indicate a striking dissociation between cognitive and affective threat processing - putatively originating from a reduced transfer of US-related arousal to the CS+ as a mechanistic pathway through which ACEs become physiologically and neurobiologically embedded, thereby increasing the risk for mental health challenges.

Background: By studying how individuals in an "at-risk" state of psychosis learn about threat and safety cues – specifically, how they develop and unlearn fear responses to neutral cues - we might better understand the mechanisms leading to heightened arousal and fear that are characteristic of acute psychotic episodes.Methods: At-risk individuals (N = 88; of which 28 fulfilled ultra-high-risk criteria on the Comprehensive Assessment of At-Risk Mental States interview and 60 scored above a predefined threshold in the Community assessment of Psychic Experiences questionnaire) and healthy controls (N = 44) underwent a standardized and validated differential fear conditioning paradigm including an acquisition, generalization, and extinction phase. The main outcomes of interest were the late positive potential, fear-potentiated startle, and self-reported ratings of valence, arousal, fear, and expectancy elicited by the conditioned stimuli (CS).Results: The at-risk group exhibited diminished fear learning, evident in significantly reduced differentiation between the CS+ vs. CS- in the valence ratings, compared to controls. Additionally, they demonstrated impaired fear extinction, evident in valence and arousal ratings, in which their CS differentiation showed a slower reduction than the controls. There were no group differences in late positive potential responses.Conclusion: At risk mental states appear to be associated with problems in distinguishing dangerous from safe stimuli and a diminished ability to adjust affective responses to conditioned stimuli based on new information, while the late-positive potential and fear-potentiated startle are unaltered. Early interventions could focus on recalibrating subjective emotional evaluations of fear-associated events.

Background: Although mental disorders are highly prevalent among older adults, evidence suggests that they underutilize psychotherapy. However, formal estimates of their actual representation in routine clinical settings are scarce. This study applied a representation quotient approach to identify and quantify age-related disparities in outpatient psychotherapy utilization in Germany. Methods: We analyzed data from 13,635 adult patients who initiated cognitive-behavioral therapy between 2018 and 2023 at 29 university outpatient clinics. Using a representation quotient approach, we compared the observed proportions of young-old adults (65–74 years) and old-old adults (≥75 years) with prevalence-stratified population age distributions. The robustness of the results was investigated by extensive sensitivity analyses, including alternative prevalence assumptions and adjustments for long-term care needs. Results: Even under conservative assumptions, young-old adults only accounted for about 25% and old-old adults for about 13% of their expected proportion. In contrast, young working-age adults (18–34 years) were particularly overrepresented in the sample. Underrepresentation of older adults was most pronounced among patients with post-traumatic stress disorder, eating disorders, and dysthymia, less pronounced among patients with generalized anxiety disorder, and not significant among patients with pain disorders. Conclusion: This study demonstrates the utility of representation quotients for systematically identifying and quantifying age-related disparities in psychotherapy utilization based on routine care data. Our analyses of large-scale data from university outpatient clinics in Germany revealed a marked underrepresentation of older adults in this setting. These findings highlight the need to improve access to, and utilization of, psychotherapeutic services for older adults.

This meta-analysis integrates data from 139 studies involving 10,084 participants, identified through a systematic literature search, to examine neural error processing across various mental disorders—including obsessive-compulsive disorder (OCD), anxiety disorders, depressive disorders (MDD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), substance-related and addictive disorders (SUD), and psychotic disorders. Using pairwise and network meta-analyses, we identified robust alterations in error-related brain responses measured by the error-related negativity (ERN). OCD (g = -0.43) and anxiety disorders (g = -0.23) exhibited heightened error-related neural responses (larger ERN), whereas ADHD (g = 0.26), ASD (g = 0.30), and psychotic disorders (g = 0.67) demonstrated blunted responses (smaller ERN). No significant differences in ERN were detected in MDD (g = 0.00) or SUD (g = 0.00) overall. Patients with psychotic disorders exhibited the greatest blunting of error processing, while those with OCD showed the strongest amplification—both significantly differing from healthy participants and all other clinical groups. These findings support the transdiagnostic potential of the ERN as a reliable neurocognitive marker. ERN alterations in anxiety disorders, OCD, and psychotic disorders may serve as endophenotypes or neural risk markers that precede symptom onset and offer predictive validity, aligning with established endophenotype criteria. Increased ERN signals may reflect amplified prediction errors, leading to over-control and risk-avoidant behaviors, while decreased ERN responses indicate hypoactive error processing, impairing adaptive responses to errors and feedback. Overall, ERN alterations hold promise as biomarkers of cognitive control dysregulation, with important implications for personalized interventions and early risk detection.