Effect of childhood emotional abuse on depression and anxiety in adulthood is partially mediated by neuroticism: Evidence from a large online sample.

Childhood trauma is widely recognized as a potential risk factor for psychiatric illness in adulthood, yet the precise mechanisms underlying this relationship remain incompletely understood. One proposed mechanism involves the impact of childhood trauma on personality development, particularly in relation to neuroticism, which may subsequently heighten susceptibility to psychiatric disorders. In this study, we aimed to investigate this hypothesis through an online survey involving 1116 participants (232 male, 21 %). Participants completed the Childhood Trauma Questionnaire (CTQ), assessing emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect, along with the Trait Self-Description Inventory (TSDI) for personality assessment and the PHQ-9 and GAD-7 clinical questionnaires for depression and anxiety symptoms evaluation, respectively. Our analyses revealed significant positive correlations between all facets of childhood trauma and neuroticism (all p < .01). Linear regression analysis demonstrated that emotional abuse significantly contributed to neuroticism (ß = 0.267, p < .05), openness (ß = 0.142, p < .05), and agreeableness (ß = 0.089, p < .05), while sexual abuse was associated with agreeableness (ß = 0.137, p < .01) Emotional neglect was negatively correlated with conscientiousness (ß = -0.090, p < .01), extroversion (ß = -0.109, p < .01) and agreeableness (ß = -0.154, p < .01). Furthermore, linear regression analysis revealed that emotional abuse was positively and significantly correlated with PHQ-9 and GAD-7 scores (r = 0.330, p < .01 and r = 0.327, p < .01, respectively). Mediation analysis supported a significant mediating role of neuroticism in the association between childhood emotional abuse and both depression (PHQ-9) (z = 8.681, p < .01) and anxiety (GAD-7) (z = 9.206, p < .01). Notably, the correlation between childhood emotional abuse and psychiatric symptoms was attenuated but not eliminated after controlling for neuroticism, suggesting partial mediation. While our cross-sectional design precludes causal inference, our findings support the notion that childhood emotional abuse may contribute to increased neuroticism, thereby elevating vulnerability to affective disorders in adulthood. These results underscore the importance of considering personality factors in understanding the long-term consequences of childhood trauma on mental health outcomes.

The Fake IQ Test: a novel measure of self-reflection in major depressive disorder.

BACKGROUND: Excessive negative self-referential processing plays an important role in the development and maintenance of major depressive disorder (MDD). Current measures of self-reflection are limited to self-report questionnaires and invoking imagined states, which may not be suitable for all populations. AIMS: The current study aimed to pilot a new measure of self-reflection, the Fake IQ Test (FIQT). METHOD: Participants with MDD and unaffected controls completed a behavioural (experiment 1, n = 50) and functional magnetic resonance imaging version (experiment 2, n = 35) of the FIQT. RESULTS: Behaviourally, those with MDD showed elevated negative self-comparison with others, higher self-dissatisfaction and lower perceived success on the task, compared with controls; however, FIQT scores were not related to existing self-report measures of self-reflection. In the functional magnetic resonance imaging version, greater activation in self-reflection versus control conditions was found bilaterally in the inferior frontal cortex, insula, dorsolateral prefrontal cortex, motor cortex and dorsal anterior cingulate cortex. No differences in neural activation were found between participants with MDD and controls, nor were there any associations between neural activity, FIQT scores or self-report measures of self-reflection. CONCLUSIONS: Our results suggest the FIQT is sensitive to affective psychopathology, but a lack of association with other measures of self-reflection may indicate that the task is measuring a different construct. Alternatively, the FIQT may measure aspects of self-reflection inaccessible to current questionnaires. Future work should explore relationships with alternative measures of self-reflection likely to be involved in perception of task performance, such as perfectionism.

BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disorders.

INTRODUCTION: Anxiety disorders are common, disabling psychiatric conditions associated with excessive worry, irritability, and physiological symptoms of stress. Following insufficient response to psychological therapies, first-line pharmacological treatments for anxiety disorders suffer from inconsistent efficacy, addiction, and intolerable side-effect profiles (e.g. sedation), especially when used inappropriately or contrary to evidence-based guidelines. Developing anxiolytics acting via cholinergic modulation may provide novel options for the treatment of anxiety disorders, without the drawbacks of existing anxiolytics. AREAS COVERED: We review pharmacological treatment of anxiety disorders and proposed mechanisms of action in relation to the associated neural circuitry. We then consider the mechanism of action, pharmacodynamics, and pharmacokinetics of the negative-allosteric modulator of the alpha7 nicotinic receptor BNC210, an investigational anxiolytic so far employed in studies of those with social anxiety disorder, post-traumatic stress disorder, and agitation in hospitalized elderly. Lastly, we consider the environment of competitor compounds for this indication, and BNC210's place within it, in both the present and near-future. EXPERT OPINION: : There is a relative paucity of data regarding BNC210, albeit the small amount of mostly non-peer reviewed data indicate it is a well-tolerated, effective anxiolytic. Phase III trials are required for proper appraisal of its utility.

Objective measures of reward sensitivity and motivation in people with high v. low anhedonia.

BACKGROUND: Anhedonia - a diminished interest or pleasure in activities - is a core self-reported symptom of depression which is poorly understood and often resistant to conventional antidepressants. This symptom may occur due to dysfunction in one or more sub-components of reward processing: motivation, consummatory experience and/or learning. However, the precise impairments remain elusive. Dissociating these components (ideally, using cross-species measures) and relating them to the subjective experience of anhedonia is critical as it may benefit fundamental biology research and novel drug development. METHODS: Using a battery of behavioural tasks based on rodent assays, we examined reward motivation (Joystick-Operated Runway Task, JORT; and Effort-Expenditure for Rewards Task, EEfRT) and reward sensitivity (Sweet Taste Test) in a non-clinical population who scored high (N = 32) or low (N = 34) on an anhedonia questionnaire (Snaith-Hamilton Pleasure Scale). RESULTS: Compared to the low anhedonia group, the high anhedonia group displayed marginal impairments in effort-based decision-making (EEfRT) and reduced reward sensitivity (Sweet Taste Test). However, we found no evidence of a difference between groups in physical effort exerted for reward (JORT). Interestingly, whilst the EEfRT and Sweet Taste Test correlated with anhedonia measures, they did not correlate with each other. This poses the question of whether there are subgroups within anhedonia; however, further work is required to directly test this hypothesis. CONCLUSIONS: Our findings suggest that anhedonia is a heterogeneous symptom associated with impairments in reward sensitivity and effort-based decision-making.

Brain activity during pursuit and goal-conflict threat avoidance in major depressive disorder.

Threat avoidance is a prominent symptom of affective disorders, yet its biological basis remains poorly understood. Here, we used a validated task, the Joystick Operated Runway Task (JORT), combined with fMRI, to explore whether abnormal function in neural circuits responsible for avoidance underlies these symptoms. Eighteen individuals with major depressive disorder (MDD) and 17 unaffected controls underwent the task, which involved using physical effort to avoid threatening stimuli, paired with mild electric shocks on certain trials. Activity during anticipation and avoidance of threats was explored and compared between groups. Anticipation of aversive stimuli was associated with significant activation in the dorsal anterior cingulate cortex, superior frontal gyrus, and striatum, while active avoidance of aversive stimuli was associated with activity in dorsal anterior cingulate cortex, insula, and prefrontal cortex. There were no significant group differences in neural activity or behavioral performance on the JORT; however, participants with depression reported more dread while being chased on the task. The JORT effectively identified neural systems involved in avoidance and anticipation of aversive stimuli. However, the absence of significant differences in behavioral performance and activation between depressed and non-depressed groups suggests that MDD is not associated with abnormal function in these networks. Future research should investigate the basis of passive avoidance in major depression. Further, the JORT should be explored in patients with anxiety disorders, where threat avoidance may be a more prominent characteristic of the disorder.

Cholinergic modulation of disorder-relevant human defensive behaviour in generalised anxiety disorder.

Drugs that are clinically effective against anxiety disorders modulate the innate defensive behaviour of rodents, suggesting these illnesses reflect altered functioning in brain systems that process threat. This hypothesis is supported in humans by the discovery that the intensity of threat-avoidance behaviour is altered by the benzodiazepine anxiolytic lorazepam. However, these studies used healthy human participants, raising questions as to their validity in anxiety disorder patients, as well as their generalisability beyond GABAergic benzodiazepine drugs. BNC210 is a novel negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor and we recently used functional Magnetic Resonance Imaging to show it reduced amygdala responses to fearful faces in generalised anxiety disorder patients. Here we report the effect of BNC210 on the intensity of threat-avoidance behaviour in 21 female GAD patients from the same cohort. We used the Joystick Operated Runway Task as our behavioural measure, which is a computerised human translation of the Mouse Defense Test Battery, and the Spielberger state anxiety inventory as our measure of state affect. Using a repeated-measures, within-subjects design we assessed the effect of BNC210 at two dose levels versus placebo (300 mg and 2000 mg) upon two types of threat-avoidance behaviour (Flight Intensity and Risk Assessment Intensity). We also tested the effects of 1.5 mg of the benzodiazepine lorazepam as an active control. BNC210 significantly reduced Flight Intensity relative to placebo and the low dose of BNC210 also significantly reduced self-reported state anxiety. Risk Assessment Intensity was not significantly affected. Results show both human defensive behaviour and state anxiety are influenced by cholinergic neurotransmission and there provide converging evidence that this system has potential as a novel target for anxiolytic pharmacotherapy.

Relationship of a big five personality questionnaire to the symptoms of affective disorders.

Online assessments allow cost-effective, large-scale screening for psychiatric vulnerability (e.g., university undergraduates or military recruits). However, conventional psychiatric questionnaires may worsen mental health outcomes due to overmedicalizing normal emotional reactions. Personality questionnaires designed for occupational applications could circumvent this problem as they utilise non-clinical wording and it is well-established that personality traits influence susceptibility to psychiatric illness. Here we present a brief, free-to-use occupational personality questionnaire, and test its sensitivity to symptoms of Bipolar Disorder (BD) and Major Depressive Disorder (MDD) in an online sample. Our study used a cross-sectional, self-report design to assess the relationship between self-reported symptoms of affective disorders and scores on the personality dimensions of openness, conscientiousness, extraversion, agreeableness and neuroticism. We used SEM to compare affective symptoms in 8,470 individuals (mean age 25.6 ± 7.0 years; 4,717 male) with scores on an online adaption of the TSDI, a public-domain 'Big Five' personality questionnaire. ROC curve analyses assessed cut off scores for the best predictors of overall vulnerability to affective disorders (represented by a composite screening score). Neuroticism was the most robust predictor of QIDS-16 depression symptoms and MDQ Hypomania symptoms (ß = 0.68 and 0.39 respectively, p < .0001). Extraversion was the most robust predictor of HCL-16 Hypomania symptoms (ß = 0.34, p < .0001). ROC curve analyses suggest if the TSDI was used for screening in this sample, neuroticism cut offs of approximately 58 for men and 70 for women would provide the most useful classification of overall vulnerability to affective disorders.

Differentiating anxiety from fear: an experimental-pharmacological approach.

Gray's theory of personality postulates that fear and anxiety are distinct emotional systems with only the latter being sensitive to anxiolytic drugs. His work was mainly based on animal research, and translational studies validating his theory are scarce. Previous work in humans showed an influence of the benzodiazepine lorazepam on both systems, however, dependent on dosage (1 and 2 mg) and personality differences in negative emotionality. The present study aims to replicate these findings, and in addition tests the drug threshold effect by introducing a lower dosage of 0.5 mg lorazepam. Fifty healthy adults (23 males, agemean 22.40, SD ± 3.68) participated in an experimental threat-avoidance paradigm designed to dissociate risk assessment intensity (RAI, reflecting anxiety) and flight intensity (FI, reflecting fear) and completed two self-report questionnaires assessing facets of negative emotionality (Spielberger State Trait Anxiety Inventory and Fear Survey Schedule). In a randomized placebo-controlled within-subjects design, 0.5 and 1 mg of lorazepam were applied per os. Saccadic peak velocity was assessed by means of eye-tracking in order to control for sedating drug effects. Results showed the expected and specific anxiolytic effect of lorazepam on RAI, however, only in the 0.5 mg condition. FI was not influenced by lorazepam, and previous findings of interaction effects of lorazepam with self-reported negative emotionality could not be corroborated. Overall, this study demonstrates anxiolytic effects of lorazepam in dosages ≤1 mg in the absence of a drug effect on fear using a translational behavioural task. However, a putative moderating role of personality on defensive behaviour has to be clarified in future research.

Threat-sensitivity in affective disorders: A case-control study.

BACKGROUND: Anxiety disorders are highly comorbid with major depression but differ in their symptom profiles and pharmacological responses. Threat-sensitivity may explain such differences, yet research on its relationship to specific disorders is lacking. METHODS: One-hundred patients (71 women) and 35 healthy controls (23 women) were recruited. Thirty-five had Panic Disorder (PD), 32 had Generalized Anxiety Disorder (GAD) and 33 Major Depressive Disorder (MDD). Threat-sensitivity was measured via behaviour (Joystick Operated Runway Task; JORT) and self-report (Fear Survey Schedule; FSS). RESULTS: Behavioural sensitivity to simple threat was higher in females compared to males (p = .03). Self-reported sensitivity to simple threat (FSS Tissue Damage Fear) was higher in PD patients compared to other groups (p ≤ .007) and in GAD patients compared to controls (p = .02). Behavioural sensitivity to complex threat was higher in females than males (p = .03) and a group by sex interaction (p = .01) indicated that this difference was largest in PD patients. Self-reported sensitivity to complex threat (FSS Social Fear) was higher in all patients compared to controls (p ≤ .001). Females scored higher than males on FSS Tissue Damage Fear and FSS Social Fear). CONCLUSIONS: Our findings oppose the simple/complex threat dichotomy, instead suggesting elevated sensitivity to physical threat differentiates anxiety disorders from MDD, whereas elevated sensitivity to social threat is associated with both anxiety disorders and MDD.

Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety Disorder.

BACKGROUND: Generalized anxiety disorder is associated with hyperactivity in the amygdala-prefrontal networks, and normalization of this aberrant function is thought to be critical for successful treatment. Preclinical evidence implicates cholinergic neurotransmission in the function of these systems and suggests that cholinergic modulation may have anxiolytic effects. However, the effects of cholinergic modulators on the function of anxiety-related networks in humans have not been investigated. METHODS: We administered a novel α7 nicotinic acetylcholine receptor-negative allosteric modulator, BNC210, to 24 individuals (3 male subjects) with generalized anxiety disorder and assessed its effects on neural responses to fearful face stimuli. RESULTS: BNC210 reduced amygdala reactivity to fearful faces relative to placebo and similarly to lorazepam and also reduced connectivity between the amygdala and the anterior cingulate cortex, a network involved in regulating anxious responses to aversive stimuli. CONCLUSIONS: These results demonstrate for the first time that the function of disorder-relevant neural circuits in generalized anxiety disorder can be beneficially altered through modulation of cholinergic neurotransmission and suggest potential for this system as a novel target for anxiolytic pharmacotherapy.

Brain activation during human defensive behaviour: A systematic review and preliminary meta-analysis.

The neural underpinnings of defensive behaviour have implications for both basic research and clinical translation. This review systematically collates published research on neural response during simple avoidance of threat and approach-avoidance behaviour during goal-conflicting situations and presents an exploratory meta-analysis of available whole-brain data. Scopus, PsychInfo and Web of Science databases were searched for the period up to March 2018. 1348 simple avoidance and 1910 goal-conflict publications were initially identified; following review, 8 simple avoidance and 11 goal-conflict studies were included, with 5 datasets used in a preliminary meta-analysis. A move from forebrain-to-midbrain activation as threat becomes more pertinent was noted, indicating support for the Reinforcement Sensitivity Theory of behaviour and general compatibility with animal work. However, these findings were not reflected in the subsequent preliminary meta-analysis. This review highlights the considerable heterogeneity in currently available defensive behaviour paradigms and the lack of research in clinically relevant populations.

Towards a neuroscience-based theory of personality: within-subjects dissociation of human brain activity during pursuit and goal conflict.

As demonstrated by neuroimaging data, the human brain contains systems that control responses to threat. The revised Reinforcement Sensitivity Theory of personality predicts that individual differences in the reactivity of these brain systems produce anxiety and fear-related personality traits. Here we discuss some of the challenges in testing this theory and, as an example, present a pilot study that aimed to dissociate brain activity during pursuit by threat and goal conflict. We did this by translating the Mouse Defense Test Battery for human fMRI use. In this version, dubbed the Joystick Operated Runway Task (JORT), we repeatedly exposed 24 participants to pursuit and goal conflict, with and without threat of electric shock. The runway design of JORT allowed the effect of threat distance on brain activation to be evaluated independently of context. Goal conflict plus threat of electric shock caused deactivation in a network of brain areas that included the fusiform and middle temporal gyri, as well as the default mode network core, including medial frontal regions, precuneus and posterior cingulate gyrus, and laterally the inferior parietal and angular gyri. Consistent with earlier research, we also found that imminent threat activated the midbrain and that this effect was significantly stronger during the simple pursuit condition than during goal conflict. Also consistent with earlier research, we found significantly greater hippocampal activation during goal conflict than pursuit by imminent threat. In conclusion, our results contribute knowledge to theories linking anxiety disorders to altered functioning in defensive brain systems and also highlight challenges in this research domain.

Meta-analyses of the neural mechanisms and predictors of response to psychotherapy in depression and anxiety.

Understanding the neural mechanisms underlying psychological therapy could aid understanding of recovery processes and help target treatments. The dual-process model hypothesises that psychological therapy is associated with increased emotional-regulation in prefrontal brain regions and decreased implicit emotional-reactivity in limbic regions; however, research has yielded inconsistent findings. Meta-analyses of brain activity changes accompanying psychological therapy (22 studies, n = 352) and neural predictors of symptomatic improvement (11 studies, n = 293) in depression and anxiety were conducted using seed-based d mapping. Both resting-state and task-based studies were included, and analysed together and separately. The most robust findings were significant decreases in anterior cingulate/paracingulate gyrus, inferior frontal gyrus and insula activation after therapy. Cuneus activation was predictive of subsequent symptom change. The results are in agreement with neural models of improved emotional-reactivity following therapy as evidenced by decreased activity within the anterior cingulate and insula. We propose compensatory as well as corrective neural mechanisms of action underlie therapeutic efficacy, and suggest the dual-process model may be too simplistic to account fully for treatment mechanisms. More research on predictors of psychotherapeutic response is required to provide reliable predictors of response.

Prescreening clinical trial volunteers using an online personality questionnaire.

BACKGROUND: The cost of a clinical trial is affected by the efficiency of participant recruitment. It would be desirable to create a prescreening method that identifies appropriate candidates for full screening, in order to prevent inconvenience for both trial and volunteers. This study presents an online prescreening tool for this purpose. METHODS: In order to facilitate recruitment of 24 individuals meeting the criteria for generalized anxiety disorder to a pharmacological functional magnetic resonance imaging trial, we created an online personality questionnaire that generated a personality profile for each respondent and screened for the trial's basic criteria. RESULTS: Our online platform screened 6,293 people for anxious personality traits in 1 year. A total of 862 eligible individuals were identified through this route, each of whom automatically received an email invitation to contact the study team for further telephone screening, if interested. Of those, 266 individuals contacted the team and 173 were telephone screened, with 53 attending the study site for medical checks. Twenty-eight individuals were fully eligible, and 24 completed the trial. This permitted completion on time and on budget. CONCLUSION: Our online prescreening personality questionnaire platform did not remove the need for telephone screening or onsite medical checks, but increased the efficiency of recruitment through noninvasive identification of those meeting key requirements. Thus, our platform is a useful recruitment technique for clinical trials and is time-saving for both the trial and potential participants.

Effects of lorazepam on saccadic eye movements: the role of sex, task characteristics and baseline traits.

BACKGROUND: Saccadic eye movements are controlled by a network of parietal, frontal, striatal, cerebellar and brainstem regions. The saccadic peak velocity is an established biomarker of benzodiazepine effects, with benzodiazepines reliably reducing the peak velocity. AIMS: In this study, we aimed to replicate the effects of benzodiazepines on peak velocity and we investigated effects on previously less studied measures of saccades. We also explored the roles of sex, task characteristics and the baseline variables age, intelligence and trait anxiety in these effects. METHOD: Healthy adults ( N = 34) performed a horizontal step prosaccade task under 1 mg lorazepam, 2 mg lorazepam and placebo in a double-blind, within-subjects design. RESULTS: We replicated the dose-dependent reduction in peak velocity with lorazepam and showed that this effect is stronger for saccades to targets at smaller eccentricities. We also demonstrated that this effect is independent of sex and other baseline variables. Lorazepam effects were widespread, however, occurring on mean and variability measures of most saccadic variables. Additionally, there were sex-dependent lorazepam effects on spatial consistency of saccades, indicating more adverse effects in females. CONCLUSIONS: We conclude that saccadic peak velocity is a sensitive and robust biomarker of benzodiazepine effects. However, lorazepam has pronounced effects also on other parameters of horizontal saccades. Sex-dependent drug effects on spatial consistency may reflect cerebellar mechanisms, given the role of the cerebellum in saccadic spatial accuracy.

Thinking too much: self-generated thought as the engine of neuroticism.

Neuroticism is a dimension of personality that captures trait individual differences in the tendency to experience negative thoughts and feelings. Established theories explain neuroticism in terms of threat sensitivity, but have limited heuristic value since they cannot account for features of neuroticism that are unrelated to threat, such as creativity and negative psychological states experienced in benign, threat-free environments. We address this issue by proposing that neuroticism stems from trait individual differences in activity in brain circuits that govern the nature of self-generated thought (SGT). We argue our theory explains not only the association of neuroticism with threat sensitivity but also the prominence within the neurotic mind of representations of information that are unrelated to the way the world is right now, such as creativity and nonsituational 'angst'.

Buprenorphine and medication management in a community corrections population: a pilot study.

AIMS: This project sought to demonstrate the feasibility and acceptability of providing on-site buprenorphine treatment to individuals under community corrections supervision. METHODS: Seventeen women and 13 men were enrolled on-site over a 2-week period at a community corrections location. Study participants received open-label study medication dispensed weekly over 12 weeks, weekly medication management therapy, and returned for a 1-month follow-up. RESULTS: Participants were predominantly female (56%) and white (90%) with an average age of 31.7 ± 7.4 years. More than half (53%) had hepatitis C virus infection and 75.9% reported intravenous use of opioids in the 30 days before treatment. Rates of illicit substance use was high, as 37.9% of urines were positive for benzodiazepines, 31.7% were positive for cocaine, and 13.7% were positive for alcohol across the time in the study. Although rates of positive urines for opiate use and sex with multiple partners did not change during treatment, rates of injection drug use significantly decreased during treatment. Overall, 86.7% of participants were retained through the 1-month follow-up with low rates of adverse events. CONCLUSIONS: Acceptability and feasibility of this approach were demonstrated by the ability to enroll and randomize the target sample of participants over 2 weeks with high retention and low rates of adverse events through 1-month follow-up. This pilot study demonstrated that this population could be successfully engaged in treatment and show reductions in risky behaviors. However, more intensive interventions may be needed to reduce opiate use to reach this vulnerable population at their point of contact with the criminal justice system.

Gender and racial differences for suicide attempters and ideators in a high-risk community corrections population.

BACKGROUND: Community corrections populations are a high-risk group who carry multiple suicide risk factors. AIMS: To identify factors correlated with historical suicide attempts and ideation among African-American men, African-American women, White men, and White women in a community corrections population. METHOD: Self-report data from 18,753 enrollees in community corrections were analyzed. Multinomial logistic regression analyses were conducted to determine associations between historical suicidal ideation and attempts among the four demographic groups. RESULTS: Participants with historical suicide attempts tended to be younger, White, female, be taking psychotropic medication, have a history of physical or sexual abuse, and meet criteria for dependence on alcohol, amphetamines, cocaine, opioids, or sedatives. Five variables were commonly associated with suicide attempts for all four race/gender groups: younger age, being on disability or retirement, taking psychotropic medication, history of sexual or physical abuse, and cocaine dependence. Other demographic variables had race or gender specificities as risk factors for suicide attempts. CONCLUSIONS: Participants had high rates of historical suicide attempts with unique correlates differentiating attempters from ideators among different racial and gender groups. Cocaine dependence was universal predictor of suicide attempts, while other substance dependencies show specific racial and gender profiles associated with suicide attempts.

A dose of ruthlessness: interpersonal moral judgment is hardened by the anti-anxiety drug lorazepam.

Neuroimaging data suggest that emotional brain systems are more strongly engaged by moral dilemmas in which innocent people are directly harmed than by dilemmas in which harm is remotely inflicted. In order to test the possibility that this emotional engagement involves anxiety, we investigated the effects of 1 mg and 2 mg of the anti-anxiety drug lorazepam on the response choices of 40 healthy volunteers (20 male) in moral-personal, moral-impersonal, and nonmoral dilemmas. We found that lorazepam caused a dose-dependent increase in participants' willingness to endorse responses that directly harm other humans in moral-personal dilemmas but did not significantly affect response choices in moral-impersonal dilemmas or nonmoral dilemmas. Within the set of moral-personal dilemmas that we administered, lorazepam increased the willingness to harm others in dilemmas where harm was inflicted for selfish reasons (dubbed low-conflict dilemmas) as well as responses to dilemmas where others were harmed for utilitarian reasons (i.e., for the greater good, dubbed high-conflict dilemmas). This suggests that anxiety exerts a general inhibitory effect on harmful acts toward other humans regardless of whether the motivation for those harmful acts is selfish or utilitarian. Lorazepam is also a sedative drug, but we found that lorazepam slowed decision times equally in all 3 dilemma types. This finding implies that its specific capacity to increase ruthlessness in moral-personal dilemmas was not a confound caused by sedation.