Impact of pubertal timing and depression on error-related brain activity in anxious youth.

Anxiety disorders are associated with enhanced error-related negativity (ERN) across development but it remains unclear whether alterations in brain electrophysiology are linked to the timing of puberty. Pubertal timing and alterations of prefrontal and limbic development are implicated in risk for depression, but the interplay of these factors on the ERN-anxiety association has not been assessed. We examined the unique and interactive effects of pubertal timing and depression on the ERN in a sample of youth 10-19 years old with anxiety disorders (n = 30) or no history of psychopathology (n = 30). Earlier pubertal maturation was associated with an enhanced ERN. Among early, but not late maturing youth, higher depressive symptoms were associated with a reduced ERN. The magnitude of neural reactivity to errors is sensitive to anxiety, depression, and development. Early physical maturation and anxiety may heighten neural sensitivity to errors yet predict opposing effects in the context of depression.

Error-related brain activity and internalizing disorder symptom dimensions in depression and anxiety.

BACKGROUND: Research suggests that enhanced neural reactivity to errors, measured via the error-related negativity (ERN), is relatively unique to internalizing psychopathologies (IPs) and symptom clusters characterized by excessive worry and apprehension. However, no prior study has tested the association between the ERN and IP symptom dimensions in a heterogeneous, clinically representative patient population. The current study was designed to address this gap in the literature and clarify the role of the ERN in an adult IP treatment-seeking patient sample. METHOD: Eighty-five participants completed a well-validated flanker task known to robustly elicit the ERN and a battery of questionnaires assessing a range of IP symptoms. All participants had at least one IP diagnosis and over 75% had co-occurring IPs. A principal components analysis (PCA) was performed on the questionnaire data indicating two distinct factors that characterized the IP sample: affective distress/misery and fear-based anxiety. RESULTS: Analyses indicated that within this sample, an enhanced ERN, but not CRN, was associated with greater fear-based anxiety symptoms but had no relation with distress/misery symptoms. CONCLUSIONS: Together, these findings indicate that an enhanced ERN may not be specific to worry/apprehension and may extend to the IP fear dimension. The results also converge with a broader literature suggesting that fear-based psychopathology is characterized by an exaggerated reactivity to threat and this objective, psychophysiological response tendency may distinguish fear disorders from distress.

Biological sex and hormonal contraceptive associations with drug cue reactivity in cannabis use disorder.

Biological sex differences in Cannabis Use Disorder (CUD) progression, cannabis withdrawal severity, and pharmacotherapy response have been reported, suggesting that CUD mechanisms may differ by sex. Drug cue reactivity is an established predictor of drug use behavior, but the literature on sex differences in drug cue reactivity is mixed, including in CUD. One possible moderator of sex differences in drug cue reactivity is hormonal contraceptive (HC) use. The aim of the present study was to test whether sex differences in neural cannabis cue reactivity and craving varied by female HC use in a CUD sample. As part of a larger study, 152 adults reporting frequent cannabis use completed a drug cue reactivity task during electrocenphalogram recording. Late positive potential (LPP) amplitude modulation by cannabis cues was used to measure neural cue reactivity. Craving after the cue reactivity task was also assessed. Males (n = 74) and naturally-cycling females (n = 26), who did not differ from each other, showed significantly greater LPP enhancement to cannabis vs. neutral cues compared to HC-using females (n = 52), an effect mostly driven by neutral cues. Craving was significantly higher in naturally-cycling but not HC-using females compared to males, but only in covariate-unadjusted analyses. Exploratory analyses of HC and menstrual phase characteristics indicate a progesterone-related mechanism may underlie HC effects on cannabis cue reactivity. The present study's results suggest that mixed findings on drug cue reactivity sex differences may be due to variability in HC use, which has implications for sex-specific models of CUD progression and treatment.

Impact of a brief distress intolerance intervention on acute stress modulation of response inhibition neurophysiology in cannabis use disorder.

BACKGROUND: The prevalence of cannabis use in the US has increased within the past two decades. Moreover, cannabis use disorder (CUD) is associated with significant disability, but the underlying neural mechanisms of CUD are unclear. Distress intolerance (DI), a psychological risk factor for CUD, may confer risk in part via impaired inhibitory control (IC) capacity during acute stress. DI and cannabis use problems have been associated with altered N2 amplitude, an IC-related event-related potential, in prior cross-sectional studies, but whether altered N2 is a state marker of CUD severity, a pathoplastic factor responsive to intervention and predictive of CUD symptom change over time, or an enduring trait-like vulnerability is unclear. In this secondary analysis, we tested the impact of a DI-targeted intervention on acute stress-related modulation of the N2 and whether pre-intervention N2 predicted CUD symptom change through follow-up. METHOD: Sixty participants were randomly assigned to a DI-targeted or control intervention. Participants completed an IC task before and after a stress induction at pre- and post-intervention lab visits while EEG activity was recorded. RESULTS: The DI intervention did not alter the N2 compared to a control intervention. Pre-intervention post-stress IC-related N2 was associated with worse CUD severity but did not predict changeover time. CONCLUSION: Findings are consistent with blunted N2 after acute stress acting as a stable marker of CUD severity rather than a pathoplastic factor predictive of CUD trajectory. Future research should investigate whether stress-related blunting of N2 is a consequence of severe CUD or a pre-existing vulnerability.

Physiological stress modulation of neural drug cue reactivity in cannabis use disorder.

OBJECTIVE: Rates of daily cannabis use and cannabis use disorder (CUD) are increasing in the United States. Prominent addiction theories suggest that stress potentiation of drug cue incentive salience is a central feature of disordered versus recreational drug use, which has been corroborated using a neurophysiological index of drug cue incentive salience (i.e., the late positive potential [LPP]) in adults who regularly use cannabis. However, the mechanism through which acute stress potentiates the cannabis LPP in CUD is unclear. METHOD: To address this gap, cannabis LPPs were measured before and after a stress induction in 95 adults who regularly use cannabis. Physiological (hypothalamic-pituitary-adrenal [HPA] axis, heart rate, skin conductance) and subjective stress reactivity were also measured. RESULTS: Based on prior work, we hypothesized that cortisol stress reactivity would predict poststress cannabis LPP enhancement in more severe CUD. The hypothesis was supported and specific to HPA-axis versus autonomic or subjective stress reactivity. CONCLUSIONS: Acute stress potentiation of the cannabis LPP, likely via HPA-axis activation, may be a biomarker of heavy/disordered cannabis use in adults who regularly use cannabis. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Temporal stability of neurophysiological drug cue reactivity before and after acute stress in cannabis users: A test of incentive sensitization.

BACKGROUND: Given increasing rates of Cannabis Use Disorder (CUD), objective measures are needed that can reliably index risk and track cannabis use progression. Based on incentive sensitization models, neurophysiological reactivity to cannabis cues, measured with the electroencephalography-recorded late positive potential (LPP), may be a candidate biomarker. To serve as such, the cannabis cue-elicited LPP must demonstrate adequate retest reliability and sensitivity to cannabis use change. Moreover, incentive sensitization theory suggests that state-level contextual variables, such as acute stress, can impact drug cue reactivity. Therefore, the present study evaluated the three-month retest reliability of the cannabis cue-elicited LPP, recorded before and after a laboratory stress induction, as well as its sensitivity to cannabis use change. METHOD: Cannabis and neutral cue-elicited LPPs were measured in 102 adults reporting frequent cannabis use (86 % with current CUD) before and after an acute stress induction at two lab visits three-months apart. Physiological and subjective stress reactivity were also measured. RESULTS: Manipulation checks confirmed expected cannabis cue and acute stress effects. Cannabis cue-elicited LPP amplitudes showed significant three-month retest reliability of poor-to-fair through moderate-to-good size. Change in cannabis use frequency significantly predicted change in cannabis cue-elicited LPP amplitudes, particularly at post-stress. CONCLUSION: Consistent with incentive sensitization models of addiction, the cannabis cue-elicited LPP demonstrated trait-like, moderate three-month stability and responsivity to change in cannabis use behavior. Greater predictive validity of the post-stress LPP may arise through kindling effects of acute stress on incentive salience-related neural activity, which should be explored in future studies.

Neurophysiological error processing and addiction self-awareness correlates of reduced insight in cannabis use disorder.

BACKGROUND AND AIMS: Cannabis use disorder (CUD) prevalence has increased, while perceived risks of cannabis use and CUD treatment need have decreased. Chronic cannabis use may also impair the neural and behavioral mechanisms of insight, further hampering treatment-seeking. This study aimed to measure whether CUD is characterized by reduced self-monitoring in drug-related contexts (objectively-assessed insight), subserved by functional neural abnormalities in error-processing and manifested clinically as decreased awareness of the need to change. DESIGN: Case-control laboratory study was used. SETTING: University setting was in Alabama, USA. PARTICIPANTS: There were 42 CUD participants and 47 age-, sex-, and nicotine use-matched controls. MEASUREMENTS: Participants completed a probabilistic choice task, adapted for the first time for CUD, in which they selected pleasant, unpleasant, neutral, and cannabis-related images according to their preference. Reduced versus accurate insight was operationalized as the correspondence between self-reported and actual most chosen image type. Neurophysiological error-processing during an inhibitory control task was recorded using electroencephalography. Participants with CUD completed measures of cannabis problem recognition and motivation to change. FINDINGS: Compared with controls, the CUD group made significantly more cannabis selections on the choice task (mean difference [MD] = 8.11, 95% confidence interval [CI] [4.88 11.35], p < 0.001) and had significantly reduced insight into cannabis choice (odds ratio [OR] = 9.69, 95% CI [1.06 88.65], p = 0.04). CUD participants with reduced insight on the choice task had significantly decreased neurophysiological reactivity to errors on the inhibitory control task (error-related negativity) compared with CUD participants with accurate insight (MD = 2.64 µV, 95% CI [0.74 µV 4.54 µV], p = 0.008) and controls (MD = 4.05 µV, 95% CI [1.29 µV 6.80 µV], p = 0.005). Compared with CUD participants with accurate insight on the choice task, CUD participants with reduced insight reported significantly less agreement that they had a cannabis problem (MD = -5.06, 95% CI [-8.49-1.62], p = 0.003). CONCLUSIONS: People with CUD who show reduced insight on a drug-related choice task may also have decreased early neural error-processing and less cannabis problem recognition.

Impact of a computerized distress intolerance intervention on electrocortical reactivity to cannabis and threat cues: A randomized controlled trial.

OBJECTIVE: Given increasing rates of daily cannabis use and Cannabis Use Disorder (CUD) in the United States, it is imperative to understand CUD mechanisms in high-risk groups. Cannabis users with high distress intolerance (DI) are at elevated risk for severe and chronic CUD, but neural mechanisms linking CUD and DI are unknown. Cross-sectional data suggests that acute stress modulation of the cannabis and threat cue-elicited late positive potential (LPP), a neurophysiological marker of motivated attention, are possible mechanisms. However, longitudinal research is needed to clarify the roles of these elicited LPPs in CUD maintenance. METHOD: Sixty cannabis users with high DI were randomized a brief computerized intervention targeting DI or a control intervention. Elicited LPPs were measured before and after a stressor at baseline and postintervention. Intervention effects on stress modulation of the cannabis and threat LPPs, as well as their prospective associations with CUD, were assessed. RESULTS: Elicited LPPs did not significantly change in either intervention group. Acute stress enhancement of the cannabis LPP predicted more severe CUD and greater chronicity at 4-month follow-up. CONCLUSIONS: Cannabis and threat LPPs were not altered by a brief DI intervention despite improvement in DI and cannabis use outcomes. Given that acute stress enhancement of the cannabis LPP predicted poorer CUD outcome, it may be a fruitful intervention target in distress intolerant cannabis users. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Development and validation of a cannabis cue stimulus set.

Regular cannabis use and cannabis use disorder (CUD) have become increasingly prevalent in the United States over the past two decades. Theory and empirical data suggest that the incentive salience of cannabis cues is important to the development and chronicity of CUD. Cannabis cue incentive salience is often assessed with a cannabis cue reactivity paradigm wherein cannabis-related and neutral images are presented. However, prior cannabis cue reactivity studies have been limited by the use of heterogeneous stimuli that were not properly characterized across motivational/affective characteristics, physical image attributes, or non-cannabis-related salient image features (e.g., human presence, face visibility). In order to increase standardization and flexibility of future cannabis cue reactivity tasks, the aim of the present study was to develop and validate a cannabis cue and matched neutral image database comprised of motivational/affective ratings as well as physical image attributes. 234 regular cannabis users varying in primary use method (i.e., bowl, blunt/joint, bong, vaporizer) made motivational (i.e., urge to smoke cannabis) and affective (i.e., arousal, valence) ratings of cannabis-related and neutral images matched on salient, non-cannabis-related features. Physical features (hue, saturation, value) of each image were also analyzed. Motivational/affective ratings of cannabis-related and neutral images differed as expected, and cannabis use frequency and cannabis craving correlations with cannabis image ratings generally supported stimulus validity. Motivational/affective ratings did not significantly differ across cannabis use method-specific images. This database may be a useful tool for future behavioral and neuroscience research on cannabis cue reactivity.

Impact of a computerized intervention for high distress intolerance on cannabis use outcomes: A randomized controlled trial.

OBJECTIVE: Prevalence of regular cannabis use and cannabis use disorder (CUD) have increased in the past two decades, but treatment-seeking is low and extant brief interventions do not target causal risk factors implicated in etiological models of addiction. Elevated distress intolerance (DI) is one risk factor that has been empirically linked with greater CUD severity and maintenance in regular users, but, to our knowledge, research has never targeted it in a brief intervention among cannabis users with CUD or at high risk. The current RCT evaluated the impact of a DI intervention (i.e., Distress Tolerance Intervention [DTI]) compared to a healthy habits control intervention (i.e., Healthy Video Control [HVC]) on DI and cannabis use outcomes. METHOD: We randomized cannabis users with high DI (N = 60) to the DTI or HVC condition and they received two computerized intervention sessions. We assessed relief cannabis craving at pre- and post-treatment; and we assessed DI, cannabis use coping motives, use-related problems, and use frequency at pre- and post-treatment as well as one- and four-month follow-ups. We assessed CUD symptoms via interviews at pre-treatment and four-month follow-up. RESULTS: Significant, durable reductions in DI and all cannabis use outcomes occurred in both conditions. Compared to the HVC condition, the DTI led to greater reductions in use frequency during the treatment period. Reductions in self-reported DI were correlated with reductions in coping motives and CUD symptoms. CONCLUSION: The DTI's impact on all outcomes was largely comparable to the control condition, though it may have utility as an adjunctive intervention.

Psychometric properties of the late positive potential in combat-exposed veterans.

Trauma exposure is prevalent, associated with multiple forms of psychopathology, and thought to alter the neurobiological substrates of threat processing. The late positive potential (LPP) is an event-related potential (ERP) that may be a clinically useful probe of the neurobiology of threat processing. Despite evidence that combat-exposed veterans exhibit aberrant threat modulation of the LPP, no studies to date have tested the psychometric properties of the LPP in combat trauma-exposed, symptomatic veterans. The primary aim of the current study was to evaluate the reliability (internal consistency, retest reliability) and convergent validity of LPP modulation by threatening faces and scenes in two common tasks among combat-exposed veterans. Participants included 82 combat-exposed veterans who completed face-matching and emotion regulation tasks during EEG recording at baseline and twelve weeks. Internal consistencies of the early LPP time windows (<1000 ms) were acceptable in both tasks, whereas they were poor in late time windows (>1000 ms). Twelve-week retest reliabilities were fair for the early window LPPs to threatening scenes and fear faces, as well as in the late time window for fear faces. Reliabilities were better for individual condition compared to difference scores. Finally, LPPs modulated by threatening scenes and faces were unrelated. Together, these results suggest that the LPPs to threatening scenes and faces reflect distinct forms of threat processing in combat-exposed veterans, and their reliabilities for the early window indicate potential clinical utility in this population.

Nonlinear relations between post-traumatic stress symptoms and electrocortical reactivity during emotional face processing in combat-exposed veterans.

Combat-related post-traumatic stress symptoms (PTSS) are prevalent among recently deployed veterans, making identification of biomarkers of PTSS in this population a public health priority. Given the link between threat processing neurobiology and PTSS, the threat-related late positive potential (LPP), an ERP reflective of attentional processing sensitive to emotion and its regulation, may have utility as a cost-effective biomarker. Existing PTSS/threat-related LPP findings are mixed, possibly due to variability in PTSS across samples, but this has never been explicitly tested. To address this gap, LPP amplitudes to angry, fearful, and happy emotional face stimuli were recorded among 81 combat-exposed veterans at a VA hospital. A quadratic relationship between self-reported PTSS and LPP amplitude modulation by angry faces emerged such that greater PTSS was related to a decreased LPP response to angry faces among veterans with subthreshold PTSD and an enhanced LPP response to angry faces among veterans with probable PTSD. These results suggest that prior mixed findings may be due to variability in PTSS severity. In addition, exploratory moderation analysis revealed that PTSS was positively associated with late LPP modulation for veterans reporting low cognitive reappraisal use and negatively associated with late LPP modulation for veterans reporting high cognitive reappraisal use. All results were specific to the 1,000-3,000 ms LPP time window. Thus, the functional nature of LPP modulation by direct threat cues may depend upon PTSS severity and/or related variables (e.g., cognitive reappraisal utilization).

Differential impact of post-deployment stress and PTSD on neural reactivity to emotional stimuli in Iraq and Afghanistan veterans.

For many veterans returning from combat in Iraq and Afghanistan, the transition from military to civilian life is complicated by an array of postdeployment stressors. In addition to significant stress associated with reintegration after deployment, many returning veterans also contend with the added burden conferred by PTSD symptoms. While the relationship between PTSD symptoms and the neurobiological substrates of emotion dysregulation has begun to be studied, even less is known about the effects of postdeployment stress on neural function. In order to assess the relationship among a neural measure of attention to emotion (i.e. the late positive potential; LPP), PTSD symptoms and postdeployment stressors, EEG was recorded and examined in a linear mixed model of 81 OEF/OIF/OND veterans. Results revealed a main effect for postdeployment stressors such that increased postdeployment stress was associated with a relatively enhanced LPP across all emotion types. There was also a main effect for PTSD symptoms such that greater symptoms were related to a relatively blunted LPP across all emotion types. Findings may have important implications for understanding how both current stress and PTSD symptoms affect motivated attention as measured by the LPP. Moreover, this work highlights the need to consider the effects of current stress, in addition to PTSD symptoms, on the functioning of returning veterans.

Error-related Brain Activity as a Treatment Moderator and Index of Symptom Change during Cognitive-Behavioral Therapy or Selective Serotonin Reuptake Inhibitors.

Increased neural error monitoring, as measured by the error-related negativity (ERN), is a transdiagnostic neurobiological marker of anxiety. To date, little is known about whether the ERN can inform the choice between first-line anxiety disorder treatments and whether the ERN changes following treatment completion. The aim of the study was to therefore assess whether the ERN is a treatment moderator and index of symptom change during cognitive-behavioral therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs). Participants included adult volunteers (M age=25.8±8.5; 67% female) with principal anxiety disorders (n=60) or no lifetime history of Axis I psychopathology (ie, healthy controls; n=26). A flanker task was used to elicit the ERN at baseline and 12 weeks later, following either CBT or SSRIs in the patient sample. Results indicated that baseline ERN was a significant treatment moderator such that a more enhanced baseline ERN was associated with greater reduction in anxiety symptoms within individuals who received CBT but not SSRIs. Results also revealed that the ERN increased pre- to post-treatment among patients randomized to SSRIs, but remained stable among patients randomized to CBT and healthy controls. Together, these novel findings highlight that ERN may help guide treatment decisions regarding engagement in CBT or SSRIs, especially among individuals with an enhanced ERN. The findings also suggest that SSRIs have the capacity to alter individual differences in the ERN, providing evidence that the ERN is not entirely static in patients with anxiety disorders.

Neural response to errors is associated with problematic alcohol use over time in combat-exposed returning veterans: An event-related potential study.

BACKGROUND: Currently, we do not have biomarkers to help identify individuals at-risk for chronic, problematic alcohol use, especially among veteran populations, who have notoriously high rates of alcohol use. One biomarker that may predict individuals at risk for chronic, problematic alcohol use is error-related brain activity. We examined longitudinal associations between the error-related negativity (ERN), an event-related potential observed following the commission of errors, and problematic alcohol use among U.S. military veterans returning from recent conflicts in Iraq and Afghanistan. METHODS: Forty-six military veterans, aged 18-55 years, completed a well-validated flanker task known to elicit the ERN at baseline. Problematic alcohol use and other clinically relevant variables were assessed at baseline, 3-, 6-, 9-, 12-, 15-, 18-, 21-months, and 2 years. RESULTS: Results indicated that the ERN magnitude was associated with problematic alcohol use over time, even after controlling for relevant clinical variables. Specifically, veterans with a smaller ERN magnitude evidenced a decline in problematic alcohol use over time, while veterans with a larger ERN magnitude had no change in their problematic alcohol use across the follow-up. In addition, exploratory analyses found that treatment engagement during the study did not moderate these relationships. CONCLUSIONS: Our findings provide preliminary evidence that ERN can be used as a predictor of problematic alcohol use over time. Therefore, neural response to errors could help to identify individuals at risk for continued problematic alcohol use for intervention efforts and suggests that error processing may be an important therapeutic target within Alcohol Use Disorder intervention efforts.

Neural indices of emotional reactivity and regulation predict course of PTSD symptoms in combat-exposed veterans.

After diagnosis, veterans with posttraumatic stress disorder (PTSD) display significant variability in the natural course of illness (Bonanno et al., 2012)). Cross-sectional work reveals that abnormal neural response during emotion reactivity-measured using the late positive potential (LPP)-correlates with PTSD symptom severity; however, whether the LPP during emotional reactivity and regulation predicts symptoms over time is unknown. The current study examined the LPP during emotion reactivity and regulation as predictors of PTSD symptoms over one year in OEF/OIF/OND combat-exposed veterans. At baseline, participants completed an Emotion Regulation Task (ERT) during electroencephalogram recording. The Clinician Administered PTSD Scale (CAPS) was completed at baseline (N=86), 6-months (N=54) and 1-year (N=49) later. During ERT, participants viewed negative pictures; partway through they were instructed to "reappraise" (i.e., reduce negative affect/regulate) or "look" (i.e., passively react). Change in LPP during emotional reactivity (ΔLPP-E) and reappraisal (ΔLPP-R) were calculated and used in multilevel mixed modeling to predict CAPS over time. Findings demonstrated that deficiency in reappraisal (ΔLPP-R) predicted more overall symptoms over time, while greater neural responses to emotion (ΔLPP-E) and greater change in neural response as a function of reappraisal (ΔLPP-R) predicted a decline in avoidance symptoms over time. Together, results support the utility of neural markers of emotional reactivity and regulation as predictors of PTSD symptoms-and change in symptoms-across one year.

Neural reactivity to reward and internalizing symptom dimensions.

BACKGROUND: Reduced reward responsiveness, measured via the event-related potential (ERP) component the reward positivity (RewP), has been linked to several internalizing psychopathologies (IPs). Specifically, prior studies suggest that a reduced RewP is robustly related to depression and to a lesser extent anxiety. No studies to date, however, have examined the relation between the RewP and IP symptom dimensions in a heterogeneous, clinically representative patient population that includes both depressed and/or anxious subjects. The primary aim of the current study was to examine the relation between the RewP and specific internalizing symptom dimensions among patients with a variety of IP diagnoses and symptoms. METHODS: A total of 80 treatment seeking adults from the community completed a battery of questionnaires assessing a range of IP symptoms and a well-validated reward processing task known to robustly elicit the RewP. RESULTS: A principal components analysis (PCA) on clinical assessments revealed two distinct factors that characterized the patient sample: affective distress/misery and fear-based anxiety. Results showed that within this sample, an attenuated RewP was associated with greater affective distress/misery based symptoms; however, the RewP was unrelated to fear-based anxiety symptoms. CONCLUSIONS: The current findings suggest that patients with higher distress/misery symptoms are characterized by decreased responsivity to rewards at the physiological level, and that this response tendency distinguishes distress/misery symptoms from fear-based symptoms. The RewP may be one promising transdiagnostic biological target for intervention efforts for individuals with distress-based symptoms of psychopathology.

Impact of alcohol use disorder comorbidity on defensive reactivity to errors in veterans with posttraumatic stress disorder.

Converging lines of evidence suggest that individuals with comorbid posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) may be characterized by heightened defensive reactivity, which serves to maintain drinking behaviors and anxiety/hyperarousal symptoms. However, it is important to note that very few studies have directly tested whether individuals with PTSD and AUD exhibit greater defensive reactivity compared with individuals with PTSD without AUD. Therefore, the aim of the current study was to test this emerging hypothesis by examining individual differences in error-related negativity (ERN), an event-related component that is larger among anxious individuals and is thought to reflect defensive reactivity to errors. Participants were 66 military veterans who completed a well-validated flanker task known to robustly elicit the ERN. Veterans were comprised of 3 groups: controls (i.e., no PTSD or AUD), PTSD-AUD (i.e., current PTSD but no AUD), and PTSD + AUD (i.e., current comorbid PTSD and AUD). Results indicated that individuals with PTSD and controls generally did not differ in ERN amplitude. However, among individuals with PTSD, those with comorbid AUD had significantly larger ERNs than those without AUD. These findings suggest that PTSD + AUD is a neurobiologically unique subtype of PTSD, and the comorbidity of AUD may enhance defensive reactivity to errors in individuals with PTSD. (PsycINFO Database Record