Threat Processing Research Articles

Hidden wounds of violence: Abnormal motor oscillatory brain activity is related to posttraumatic stress symptoms

Victims of urban violence are at risk of developing Posttraumatic Stress Disorder (PTSD), one of the most debilitating consequences of violence. Considering that PTSD may be associated with inefficient selection of defensive responses, it is important to understand the relation between motor processing and PTSD. The present study aims to investigate the extent to which the severity of posttraumatic stress symptoms (PTSS) is related to motor preparation against visual threat cues in victims of urban violence. Participants performed a choice reaction time task while ignoring a picture that could be threating or neutral. The EEG indices extracted were the motor-related amplitude asymmetry (MRAA) in the alpha frequency range, and the lateralized readiness potential (LRP). We observed a linear relation between longer LRP latency and a slower reaction time, selectively during threat processing (compared to neutral) in low PTSS, but not in high PTSS participants. Alpha MRAA suppression and the PTSS were also linearly related: the smaller the alpha MRAA suppression in the threat condition relative to neutral, the greater the PTSS. These results provide evidence that threatening cues affect motor processing that is modulated by the severity of PTSS in victims of urban violence.

Salience and default-mode network connectivity during threat and safety processing in older adults.

The appropriate assessment of threat and safety is important for decision‐making but might be altered in old age due to neurobiological changes. The literature on threat and safety processing in older adults is sparse and it is unclear how healthy ageing affects the brain's functional networks associated with affective processing. We measured skin conductance responses as an indicator of sympathetic arousal and used functional magnetic resonance imaging and independent component analysis to compare young and older adults' functional connectivity in the default mode (DMN) and salience networks (SN) during a threat conditioning and extinction task. While our results provided evidence for differential threat processing in both groups, they also showed that functional connectivity within the SN – but not the DMN – was weaker during threat processing in older compared to young adults. This reduction of within‐network connectivity was accompanied by an age‐related decrease in low frequency spectral power in the SN and a reduction in inter‐network connectivity between the SN and DMN during threat and safety processing. Similarly, we found that skin conductance responses were generally lower in older compared to young adults. Our results are the first to demonstrate age‐related changes in brain activation during aversive conditioning and suggest that the ability to adaptively filter affective information is reduced in older adults.

The impact of torture on interpersonal threat and reward neurocircuitry

Torture adversely influences emotional functioning, but the neurophysiological mechanisms underpinning its impact are unknown. This study examined how torture exposure affects the neural substrates of interpersonal threat and reward processing. Male refugees with (N = 31) and without (N = 27) torture exposure completed a clinical interview and functional magnetic resonance imaging scan where they viewed fear, happy and neutral faces. Between-group activations and neural coupling were examined as moderated by posttraumatic stress disorder symptom severity and cumulative trauma load. Posttraumatic stress disorder symptom severity and trauma load significantly moderated group differences in brain activation and connectivity patterns. Torture survivors deactivated the ventral striatum during happy processing compared to non-torture survivor controls as a function of increased posttraumatic stress disorder symptom severity - particularly avoidance symptoms. The ventral striatum was more strongly coupled with the inferior frontal gyrus in torture survivors. Torture survivors also showed left hippocampal deactivation to both fear and happy faces, moderated by trauma load, compared to controls. Stronger coupling between the hippocampus and frontal, temporoparietal and subcortical regions during fear processing was observed, with pathways being predicted by avoidance and hyperarousal symptoms. Torture exposure was associated with distinct brain activity and connectivity patterns during threat and reward processing, dependent on trauma exposure and posttraumatic stress disorder symptom severity. Torture appears to affect emotional brain functioning, and findings have the potential to guide more targeted interventions for torture survivors.

Retraction Note: Cannabinoid type 1 receptor availability in the amygdala mediates threat processing in trauma survivors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Threat appraisal and negative affect under ambiguity in generalised anxiety disorder

Generalised anxiety disorder (GAD) is one of the most common anxiety disorders, yet its mechanisms remain poorly understood. In the current study, we assessed threat processing and negative affect under conditions of uncertainty and ambiguity in a sample of treatment-seeking individuals with GAD (n = 34) and in community controls (n = 34). Participants completed a laboratory aversive learning task based on that used by Grupe and Nitschke (2011). A bias in threat expectancy was observed in GAD participants relative to controls for an ambiguous cue that had not been mentioned in the instructions. GAD participants also overestimated the number of times this ambiguous cue had been followed by an aversive outcome, relative to an instructed uncertain cue (50 %). This covariation bias was not observed in controls. GAD participants also reported significantly stronger negative affect towards the ambiguous cue than the uncertain cue, a pattern that was not observed in controls, although the group interaction did not reach significance. These results provide preliminary evidence that ambiguity – rather than uncertainty per se – may be a particularly powerful trigger for biased threat appraisal and negative affect in GAD.

Motivations for Social Distancing and App Use as Complementary Measures to Combat the COVID-19 Pandemic: Quantitative Survey Study.

BackgroundThe current COVID-19 pandemic is showing negative effects on human health as well as on social and economic life. It is a critical and challenging task to revive public life while minimizing the risk of infection. Reducing interactions between people by social distancing is an effective and prevalent measure to reduce the risk of infection and spread of the virus within a community. Current developments in several countries show that this measure can be technologically accompanied by mobile apps; meanwhile, privacy concerns are being intensively discussed.ObjectiveThe aim of this study was to examine central cognitive variables that may constitute people’s motivations for social distancing, using an app, and providing health-related data requested by two apps that differ in their direct utility for the individual user. The results may increase our understanding of people’s concerns and convictions, which can then be specifically addressed by public-oriented communication strategies and appropriate political decisions.MethodsThis study refers to the protection motivation theory, which is adaptable to both health-related and technology-related motivations. The concept of social trust was added. The quantitative survey included answers from 406 German-speaking participants who provided assessments of data security issues, trust components, and the processes of threat and coping appraisal related to the prevention of SARS-CoV-2 infection by social distancing. With respect to apps, one central focus was on the difference between a contact tracing app and a data donation app.ResultsMultiple regression analyses showed that the present model could explain 55% of the interindividual variance in the participants’ motivation for social distancing, 46% for using a contact tracing app, 42% for providing their own infection status to a contact tracing app, and 34% for using a data donation app. Several cognitive components of threat and coping appraisal were related to motivation measurements. Trust in other people’s social distancing behavior and general trust in official app providers also played important roles; however, the participants’ age and gender did not. Motivations for using and accepting a contact tracing app were higher than those for using and accepting a data donation app.ConclusionsThis study revealed some important cognitive factors that constitute people’s motivation for social distancing and using apps to combat the COVID-19 pandemic. Concrete implications for future research, public-oriented communication strategies, and appropriate political decisions were identified and are discussed.

BNST and amygdala activation to threat: Effects of temporal predictability and threat mode

Recent animal and human studies highlight the uncertainty about the onset of an aversive event as a crucial factor for the involvement of the centromedial amygdala (CM) and bed nucleus of the stria terminalis (BNST) activity. However, studies investigating temporally predictable or unpredictable threat anticipation and confrontation processes are rare. Furthermore, the few existing fMRI studies analyzing temporally predictable and unpredictable threat processes used small sample sizes or limited fMRI paradigms. Therefore, we measured functional brain activity in 109 predominantly female healthy participants during a temporally predictable-unpredictable threat paradigm, which aimed to solve limited aspects of recent studies. Results showed higher BNST activity compared to the CM during the cue indicating that the upcoming confrontation is aversive relative to the cue indicating an upcoming neutral confrontation. Both the CM and BNST showed higher activity during the confrontation with unpredictable and aversive stimuli, but the reaction to aversive confrontation relative to neutral confrontation was stronger in the CM compared to the BNST. Additional modulation analyses by NPSR1 rs324981 genotype revealed higher BNST activity relative to the CM in unpredictable anticipation relative to predictable anticipation in T-carriers compared to AA carriers. Our results indicate that during the confrontation with aversive or neutral stimuli, temporal unpredictability modulates CM and BNST activity. Further, there is a differential activity concerning threat processing, as BNST is more involved when focussing on fear-related anticipation processes and CM is more involved when focussing on threat confrontation.

The Sociopolitical Context of Abortion Bill Authorship in Texas

This study examines abortion bills proposed in the Texas legislature between 1993 and 2015 to explore how legislators respond to the power resources of minorities versus the (supposed) threat that they pose and how these responses vary across partisan lines to hamper or further pro-life interests. To test competing hypotheses about the influences of women’s socioeconomic and political resources, and the representation of poor, Black, and Hispanic constituents, multilevel models analyze a key behavior that strategically demonstrates issue-positions, that is, authorship of abortion bills. The findings largely support power resources accounts but also detect minority threat processes, and they reveal that beyond mean differences in support for restrictions on legal abortions, Democrats and Republicans respond distinctly to their constituent contexts. This detailed look at an early stage of the legislative process in a major battleground state highlights the multifaceted nature of abortion politics and the importance of considering both partisan and minority interests, especially in the face of sociodemographic shifts within the state and beyond.

RETRACTED ARTICLE: Semantic and prosodic threat processing in trait anxiety: is repetitive thinking influencing responses?

We, the Authors, Editors and Publisher of Cognition and Emotion have retracted the following article: Semantic and Prosodic Threat Processing in Trait Anxiety: Is Repetitive Thinking Influencing Responses? By Simon Busch-Moreno, Jyrki Tuomainen & David Vinson, published online: 14 August 2020 https://www.tandfonline.com/doi/full/10.1080/02699931.2020.1804329 Since publication, the Authors discovered two major errors in the statistical analyses. Specifically, (1) the response time data was not standardised before analysis, which resulted in an inflated effect of worry on response time. (2) One of the hyperpriors for the Student t-distribution in the four response time models induced extreme negative values on the distribution's left tail which magnified the artefactual effect. The statistical errors directly impact the validity of the reported results and conclusions. The Authors alerted the issue to the Editor and Publisher and all have agreed to retract the article to ensure the integrity of the scholarly record. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Time course of pupillary response to threat words before and after attention bias modification for transdiagnostic anxiety disorders: A randomized controlled trial.

IntroductionAltered attention to threatening stimuli at initial and sustained stages of processing may be dissociable dimensions that influence the development and maintenance of transdiagnostic symptoms of anxiety, such as vigilance, and possibly require distinct intervention. Attention bias modification (ABM) interventions were created to implicitly train attention away from threatening stimuli and have shown efficacy in treating anxiety. ABM alters neurocognitive functioning during initial stages of threat processing, but less is known regarding effects of ABM on neural indices of threat processing at sustained (i.e., intermediate and late) stages, or if ABM‐related neural changes relate to symptom response. The current study utilized pupillary response as a temporally sensitive and cost‐effective peripheral marker of neurocognitive response to ABM.Materials and MethodsIn a randomized controlled trial, 79 patients with transdiagnostic anxiety provided baseline data, 70 were randomized to receive eight sessions of twice‐weekly ABM (n = 49) or sham training (n = 21), and 65 completed their assigned treatment condition and returned for post‐training assessment.ResultsAmong ABM, but not sham, patients, pupillary response to threat words during initial and intermediate stages decreased from pre‐ to post‐training. Pre‐ to post‐training reductions in intermediate and late pupillary response to threat were positively correlated with reductions in patient‐reported vigilance among ABM, but not sham, patients.ConclusionsAll measured stages of threat processing had relevance in understanding the neural mechanisms of ABM, with overlapping yet dissociable roles exhibited within a single neurophysiological marker across an initial–intermediate–late time continuum. Pupillometry may be well suited to measure both target engagement and treatment outcome following ABM.

The effects of suppressing the biological stress systems on social threat-assessment following acute stress

RationaleStress is associated with increased sensitivity to threat. Previous investigations examining how stress affects threat processing have largely focused on biomarker responses associated with either the sympathetic-nervous-system (SNS) or the hypothalamus-pituitary-adrenal (HPA) axis.ObjectivesWe pharmacologically suppressed activations of SNS, HPA, or both, prior to stress and investigated how each stress system modulates social threat assessment.MethodsOne hundred sixty-one healthy men and women were randomized in a between-subject design, to one of four pharmacological or placebo conditions: dexamethasone–placebo, placebo–propranolol, dexamethasone–propranolol, or placebo–placebo. Participants provided threat assessments for angry and neutral human faces on a baseline day, and immediately after stress induction on a testing day.ResultsWith both systems responding normally to stress (placebo–placebo), threat assessment was higher for neutral faces compared with angry. Compared with placebo, SNS suppression resulted in increased threat assessment for angry faces. HPA suppression resulted in decreased threat assessment for neutral and angry faces. When both systems were suppressed, there was an increase in threat assessment for angry faces, and no difference from placebo for neutral.ConclusionOur findings demonstrated that when intact, the biological stress systems adaptively support organisms during stress by focusing attention towards specific stimuli that are relevant to the threat. Dysregulations of the stress systems result in important system specific consequences on threat evaluation, such that suppression of either stress system alone resulted in reduced threat assessment for contextually relevant threatening stimuli, whereas when both systems were suppressed, individuals appear indiscriminately attentive to all potential threats in the environment, resulting in increased threat processing of both contextually relevant and irrelevant stimuli. Given that stress-related psychopathologies have been associated with dysregulations of the stress systems and biased responses to social threat, a systematic understanding of the mechanisms that underlie how stress systems modulate social threat assessment is needed, and can provide important insights into the cognitive processes that are involved in the development and maintenance of stress-related psychopathologies.

The Differential Effect of Anxiety and ADHD Symptoms on Inhibitory Control and Sustained Attention for Threat Stimuli: A Go/No-Go Eye-Movement Study

Objective: This study examined the synergistic effects of ADHD and anxiety symptoms on attention and inhibitory control depending on the emotional content of the stimuli. Method: Fifty-four typically developing individuals (27 children/adolescents and 27 adults) completed an eye-movement based emotional Go/No-Go task, using centrally presented (happy, angry) faces and neutral/symbolic stimuli. Sustained attention was measured through saccade latencies and saccadic omission errors (Go trials), and inhibitory control through saccadic commission errors (No-Go trials). ADHD and anxiety were assessed dimensionally. Results: Elevated ADHD symptoms were associated with more commission errors and slower saccade latencies for angry (vs. happy) faces. In contrast, angry faces were linked to faster saccade onsets when anxiety symptoms were high, and this effect prevailed when both anxiety and ADHD symptoms were high. Conclusion: Social threat impacted performance in individuals with sub-clinical anxiety and ADHD differently. The effects of anxiety on threat processing prevailed when both symptoms were high.

Transcriptional Profiling of Primate Central Nucleus of the Amygdala Neurons to Understand the Molecular Underpinnings of Early-Life Anxious Temperament

BackgroundChildren exhibiting extreme anxious temperament (AT) are at an increased risk for developing anxiety and depression. Our previous mechanistic and neuroimaging work in young rhesus monkeys linked the central nucleus of the amygdala to AT and its underlying neural circuit. MethodsHere, we used laser capture microscopy and RNA sequencing in 47 young rhesus monkeys to investigate AT’s molecular underpinnings by focusing on neurons from the lateral division of the central nucleus of the amygdala (CeL). RNA sequencing identified numerous AT-related CeL transcripts, and we used immunofluorescence (n = 3) and tract-tracing (n = 2) methods in a different sample of monkeys to examine the expression, distribution, and projection pattern of neurons expressing one of these transcripts. ResultsWe found 555 AT-related transcripts, 14 of which were confirmed with high statistical confidence (false discovery rate < .10), including protein kinase C delta (PKCδ), a CeL microcircuit cell marker implicated in rodent threat processing. We characterized PKCδ neurons in the rhesus CeL, compared its distribution with that of the mouse, and demonstrated that a subset of these neurons project to the laterodorsal bed nucleus of the stria terminalis. ConclusionsThese findings demonstrate that CeL PKCδ is associated with primate anxiety, provides evidence of a CeL to laterodorsal bed nucleus of the stria terminalis circuit that may be relevant to understanding human anxiety, and points to specific molecules within this circuit that could serve as potential treatment targets for anxiety disorders.

Attentional threat biases and their role in anxiety: A neurophysiological perspective

One of the most important function of selective attention is the efficient and accurate detection and identification of cues associated with threat. However, in pathological anxiety, this attentional mechanism seems to be dysfunctional, which leads to an exaggeration of threat processing and significant functional impairment. This attentional threat bias (ATB) has been proposed as a key mechanism in the etiology and maintenance of anxiety disorders. Recently, evidence has accumulated that the behavioral assessment of ATB by means of reaction times is compromised by conceptual and methodological problems. In this review paper we argue that a brain-based assessment of ATB, which includes different mechanistic aspects of biased attention, may provide neuromechanistic knowledge regarding the etiology and maintenance of anxiety, and potentially start identifying different targets for effective treatment. We summarize examples for such an approach, highlighting the strengths of electrophysiological measurements, which include the sensitivity to time dynamics, specificity to specific neurocomputational mechanisms, and the continuous/dimensional nature of the resulting variables. These desirable properties are a prerequisite for developing trans-diagnostic biomarkers of attentional bias, and hence may inform individually tailored treatment approaches.

Parasympathetic cardiac control and attentional focus in trait worry

Trait worry refers to a tendency toward increased vigilance to threat and reduced tolerance of uncertainty. While it has been established as a risk factor of general morbidity, knowledge about autonomic regulation in trait worry remains scarce. This study investigated parasympathetic cardiac control in trait worry, in the context of attentional focus. Healthy groups with high and low worry were selected using the Penn State Worry Questionnaire (n = 40 per group). Heart rate variability (HRV) was recorded in the high frequency (HF) and low frequency (LF) bands while participants performed a breathing focus task. The task included a phase of instructed worry and two phases during which participants´ ability to concentrate on their breathing was assessed. As compared to the low worry group, the high worry group exhibited lower HRV in the LF band during both breathing focus phases and smaller reduction of LF HRV during instructed worry. HF HRV did not differ between groups. High worry was associated with impaired ability to concentrate on breathing and more intrusive thoughts. In the total sample, negative intrusions correlated negatively with LF HRV during the first breathing focus phase and LF HRV reactivity. Instructed worry led to greater perceived stress and deterioration of mood in high worry participants. Reduced LF HRV reflects blunted parasympathetic cardiac control in trait worry, associated with elevated risk of poor health outcomes. In addition, it might represent a psychophysiological correlate of reduced cognitive inhibition, which interferes with attentional focus and impedes control of threat processing and perseverative thinking.

Time Course and Neural Underpinnings of Pupillary Response to Threat Words Before and After Attention Bias Modification for Transdiagnostic Anxiety Disorders: A Randomized Controlled Trial

Altered attention to threatening stimuli at initial and sustained stages of processing are thought to be dissociable dimensions that underlie anxiety disorders and possibly require distinct intervention. Attention Bias Modification (ABM) interventions implicitly train attention away from threatening stimuli and show efficacy in treating anxiety. ABM alters neurocognitive functioning during initial stages of threat processing, but less is known regarding ABM effects at sustained (i.e., intermediate and late) processing stages, or if ABM-related neural changes relate to symptom response.

Neural function during emotion processing and modulation associated with treatment response in a randomized clinical trial for posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) has been associated with exaggerated threat processing and deficits in emotion modulation circuitry. It remains unknown how neural circuits are associated with response to evidence-based treatments for PTSD. We examined associations between PTSD symptoms and indicators of neural response in key emotion processing and modulation regions. Fifty-six military Veterans with PTSD were randomly assigned to one of three evidence-based treatments (prolonged exposure, sertraline, and PE plus sertraline) in a randomized clinical trial ("PROGrESS"; 2018, Contemp Clin Trials, 64, 128-138). Twenty-seven combat-exposed controls (CCs) served as a comparison group at pretreatment. Before and after PTSD treatment, functional magnetic resonance imaging was used to assess brain activation and connectivity during the validated Shifted Attention Emotion Appraisal Task (2003, J Neurosci, 23, 5627-5633; 2013, Biol Psychiatry, 73, 1045-1053). Greater activation in emotion processing (anterior insula) and modulation (prefrontal cortex) regions and increased connectivity between attentional control (dorsolateral prefrontal cortex and superior parietal cortex) and emotion processing (amygdala) regions, at pretreatment, were associated with subsequent PTSD symptom improvement. This study is one of the first to examine task-based activation and functional connectivity in a PTSD treatment trial, and provides evidence to suggest that activation in and connectivity between emotion processing and modulation regions are important predictors of treatment response.

Acute Posttrauma Resting-State Functional Connectivity of Periaqueductal Gray Prospectively Predicts Posttraumatic Stress Disorder Symptoms

BackgroundPosttraumatic stress disorder (PTSD) is characterized by hyperarousal, avoidance, and intrusive/re-experiencing symptoms. The periaqueductal gray (PAG), which generates behavioral responses to physical and psychological stressors, is also implicated in threat processing. Distinct regions of the PAG elicit opposing responses to threatening or stressful stimuli; the ventrolateral PAG evokes passive coping strategies (e.g., analgesia), whereas the dorsolateral PAG (dlPAG) promotes active responses (e.g., fight or flight). We investigated whether altered PAG resting-state functional connectivity (RSFC) prospectively predicted PTSD symptoms. MethodsA total of 48 trauma-exposed individuals underwent an RSFC scan 2 weeks posttraumatic injury. Self-report measures, including the visual analog scale for pain and the Impact of Event Scale, were collected at 2 weeks and 6 months posttrauma. We analyzed whether acute bilateral PAG RSFC was a marker of risk for total 6-month symptom severity and specific symptom clusters. In an exploratory analysis, we investigated whether dlPAG RSFC predicted PTSD symptoms. ResultsAfter adjusting for physical pain ratings, greater acute posttrauma PAG–frontal pole and PAG–posterior cingulate cortex connectivity was positively associated with 6-month total PTSD symptoms. Weaker dlPAG–superior/inferior parietal lobule connectivity predicted both higher hyperarousal and higher intrusive symptoms, while weaker dlPAG–supramarginal gyrus RSFC was associated with only hyperarousal symptoms. ConclusionsAltered connectivity of the PAG 2 weeks posttrauma prospectively predicted PTSD symptoms. These findings suggest that aberrant PAG function may serve as a marker of risk for chronic PTSD symptoms, possibly by driving specific symptom clusters, and more broadly that connectivity of specific brain regions may underlie specific symptom profiles.

Cannabinoid modulation of corticolimbic activation to threat in trauma-exposed adults: a preliminary study.

Excessive fear and anxiety, coupled with corticolimbic dysfunction, are core features of stress- and trauma-related psychopathology, such as posttraumatic stress disorder (PTSD). Interestingly, low doses of ∆9-tetrahydrocannabinol (THC) can produce anxiolytic effects, reduce threat-related amygdala activation, and enhance functional coupling between the amygdala and medial prefrontal cortex and adjacent rostral cingulate cortex (mPFC/rACC) during threat processing in healthy adults. Together, these findings suggest the cannabinoid system as a potential pharmacological target in the treatment of excess fear and anxiety. However, the effects of THC on corticolimbic functioning in response to threat have not be investigated in adults with trauma-related psychopathology. To address this gap, the present study tests the effects of an acute low dose of THC on corticolimbic responses to threat in three groups of adults: (1) non-trauma-exposed healthy controls (HC; n= 25), (2) trauma-exposed adults without PTSD (TEC; n= 27), and (3) trauma-exposed adults with PTSD (n= 19). Using a randomized, double-blind, placebo-controlled, between-subjects design, 71 participants were randomly assigned to receive either THC or placebo (PBO) and subsequently completed a well-established threat processing paradigm during functional magnetic resonance imaging. In adults with PTSD, THC lowered threat-related amygdala reactivity, increased mPFC activation during threat, and increased mPFC-amygdala functional coupling. These preliminary data suggest that THC modulates threat-related processing in trauma-exposed individuals with PTSD, which may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology.

Aberrant Gray Matter Volume and Cortical Surface in Paranoid-Type Delusional Disorder

Introduction: Delusions are core symptoms of schizophrenia-spectrum and related disorders. Despite their clinical relevance, the neural correlates underlying such phenomena are unclear. Recent research suggests that specific delusional content may be associated with distinct neural substrates. Objective: Here, we used structural magnetic resonance imaging to investigate multiple parameters of brain morphology in patients presenting with paranoid type delusional disorder (pt-DD, n = 14) compared to those of healthy controls (HC, n = 25). Methods: Voxel- and surface-based morphometry for structural data was used to investigate gray matter volume (GMV), cortical thickness (CT) and gyrification. Results: Compared to HC, patients with pt-DD showed reduced GMV in bilateral amygdala and right inferior frontal gyrus. Higher GMV in patients was found in bilateral orbitofrontal and in left superior frontal cortices. Patients also had lower CT in frontal and temporal regions. Abnormal gyrification in patients was evident in frontal and temporal areas, as well as in bilateral insula. Conclusions: The data suggest the presence of aberrant GMV in a right prefrontal region associated with belief evaluation, as well as distinct structural abnormalities in areas that essentially subserve processing of fear, anxiety and threat in patients with pt-DD. It is possible that cortical features of distinct evolutionary and genetic origin, i.e. CT and gyrification, contribute differently to the pathogenesis of pt-DD.