Craving Moderates the Effects of Intranasal Oxytocin on Anger in Response to Social Stress Among Veterans With Co-Occurring Posttraumatic Stress Disorder and Alcohol Use Disorder.

PURPOSE/BACKGROUND: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) commonly co-occur among US military veterans. Oxytocin may have therapeutic value in treating both conditions. The potential for oxytocin to augment affective features common to PTSD and AUD, such as anger, is relevant to inform emerging treatments. METHODS/PROCEDURES: We examined the influence of intranasally administered oxytocin on connections between alcohol craving and stress-induced anger in a sample of 73 veterans (91.3% men) with co-occurring PTSD and AUD. Participants self-administered oxytocin (40 IU) or placebo (saline) 45 minutes before completing the Trier Social Stress Task (TSST). Self-reports of alcohol craving and anger were assessed pre- and post-TSST using a modified visual analog scale. Multiple regression analysis, including main effects for group, baseline craving, and their interaction, was used to predict post-TSST anger. FINDINGS/RESULTS: A marginally significant interaction was observed, suggesting a positive association between baseline craving and anger for those in the oxytocin group (B = 0.65, P = 0.01). Among those reporting low craving, participants in the oxytocin group reported significantly lower post-TSST anger than those in the placebo group. IMPLICATIONS/CONCLUSIONS: The current study is among the first to examine relevant psychosocial moderators that may influence the effects of oxytocin among veterans with comorbid PTSD and AUD. Although oxytocin attenuated ratings of anger after a stress task among those with low baseline craving, findings suggest that oxytocin may not be as effective at reducing anger, a highly salient factor in PTSD, for individuals experiencing high levels of craving. Findings are consistent with the social salience hypothesis and suggest that individual differences in alcohol craving should be considered when evaluating oxytocin as a potential treatment for individuals with comorbid PTSD and AUD.

Reduction of fatigue and anger-hostility by the oral administration of 5-aminolevulinic acid phosphate: a randomized, double-blind, placebo-controlled, parallel study.

Although large populations feel fatigue, the standardized medicinal therapy is currently absent. In this study, we determined whether 5-aminolevulinic acid (5-ALA) supplementation alleviates the feeling of fatigue in healthy subjects who feel chronic physical tiredness. Males and females between ages of 20 and 64 who felt physical fatigue on a daily basis, with a visual analogue scale (VAS) for fatigue ≥ 40 mm, a T-score of Fatigue-Inertia in the Profile of Mood States-Second Edition-Adult (POMS2-A) ≥ 50, and a T-score of Vigor-Activity in POMS2-A ≤ 60 were recruited. Seventy eligible participants were randomly assigned to either a 5-ALA or a placebo group. During the 8 weeks of consumption, the subjects completed VAS questionnaires for fatigue and POMS2-A at 4-week intervals. The VAS values for overall feeling of fatigue and feeling of work-related fatigue, and the Anger-Hostility subscale of POMS2-A were decreased by 5-ALA with significant time × group interaction effects (p = 0.040, 0.020, and 0.045, respectively). Besides, the 5-ALA group showed significant differences in Fatigue-Inertia, Depression-Dejection and Total Mood Disturbance scores, when compared between pre- and post-intervention, while the placebo group did not. In conclusion, the oral administration of 5-ALA improves fatigue and negative mood in subjects who constantly feel physical fatigue.This clinical trial was registered with University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as UMIN000031528 on 2/3/2018.

The effect of oxytocin on pupil response to naturalistic dynamic facial expressions.

The neuropeptide oxytocin (OT) has been found to play an important role in a variety of social behaviours and social cognition in particular. The social salience hypothesis of OT suggests that OT shifts attention towards socially relevant stimuli, which offers an explanation for improvements on social cognition measures following OT administration. Pupil dilation occurs with increasing attentional resource allocation and previous research has found that OT administration led to an increase in pupil diameter in response to social stimuli relative to placebo (PL), thereby suggesting increased social attention. The current study aimed to investigate the effects of OT on pupillary responses to more naturalistic social stimuli in a larger sample. Ninety-four male participants took part in the double-blind, placebo controlled, mixed-design study, in which they self-administered either an OT or PL nasal spray before viewing naturalistic dynamic facial expressions of emotion (happy, sad, fear and anger). Contrary to prediction, there was no effect of OT administration on pupil diameter. The results are discussed in light of the social salience hypothesis and with reference to the methodological differences between studies.

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

RATIONALE: Stress 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. OBJECTIVES: We pharmacologically suppressed activations of SNS, HPA, or both, prior to stress and investigated how each stress system modulates social threat assessment. METHODS: One 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. RESULTS: With 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. CONCLUSION: Our 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.

2,3-Dimethylpyrazine (3DP) and 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) generated by the Maillard reaction in foods affect autonomic nervous activity and central nervous activity in human.

This study investigated the effect of the odors generated by the glycine/glucose Maillard reaction and the potent odorants 2,3-dimethylpyrazine (3DP) and 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) on the human mood and integrative physiological activity. The score of certain subjective moods, especially anger-hostility, and tension-anxiety were decreased significantly after inhalation of the Maillard reaction sample and DMHF, and fatigue-inertia mood was also significantly decreased by DMHF, suggesting a sedative effect of these odors on mood, while 3DP had no effect. Miosis rate and fingertip temperature increased significantly following inhalation of the odor from the Maillard reaction sample and both potent odorants, suggesting that the parasympathetic nervous system dominates through suppression of the sympathetic activity. The physiological relaxing effect of these odors was also confirmed by decreased flicker frequency value and decreased oxyhemoglobin in the prefrontal cortex.

Emotions after stroke: A narrative update.

AIM: In this narrative review we aimed to describe how stroke affects emotions and update the readers on the emotional disturbances that occur after stroke. METHODS: We searched Medline from 1.1.2013 to 1.7.2019, personal files and references of selected publications. All retrieved systematic reviews and randomized controlled trials were included. Other references were selected by relevance. SUMMARY OF REVIEW: The emotional response includes a reactive behavior with arousal, somatic, motivational and motor components, and a distinctive cognitive and subjective affective experience. Emotional category responses and experiences after stroke can show dissociations between the behavioral response and the cognitive and affective experiences. Emotional disturbances that often occur after stroke include fear, anger, emotional indifference, lack of understanding of other emotions, and lack of control of emotional expression. Emotional disturbances limit social reintegration of the persons with stroke and are a source of caregiver burnout. The evidence to support the management of the majority of emotional disorders in stroke survivors is currently weak and of low or very low methodologic quality. An exception are the disorders of emotional expression control where antidepressants can have a strong beneficial effect, by reducing the number and duration of the uncontrollable episodes of crying or laughing. CONCLUSION: Our current knowledge of the emotional disorders that occurs in acute stroke patients and in stroke survivors is heterogeneous and limited. Joint efforts of different research approaches, methodologies and disciplines will improve our current understanding on emotional disorder after stroke and indicate rational pathways to manage them.

The role of oxytocin in the facial mimicry of affiliative vs. non-affiliative emotions.

The present paper builds upon a growing body of work documenting oxytocin's role in social functioning, to test whether this hormone facilitates spontaneous mimicry of others' emotional expressions. In a double-blind, randomized trial, adult Caucasian males (n = 145) received a nasal spray of either oxytocin or placebo before completing a facial mimicry task. Facial expressions were coded using automated face analysis. Oxytocin increased mimicry of facial features of sadness (lips and chin, but not areas around the eyes), an affiliative reaction that facilitates social bonding. Oxytocin also increased mimicry of happiness, but only for individuals who expressed low levels of happiness in response to neutral faces. Overall, participants did not reliably mimic expressions of fear and anger, echoing recent theoretical accounts of emotional mimicry as dependent on the social context. In sum, our findings suggest that oxytocin facilitates emotional mimicry in ways that are conducive to affiliation, pointing to a possible pathway through which oxytocin promotes social bonding.

Effect of brivaracetam on the anger levels of epilepsy patients. A prospective open-labelled controlled study.

PURPOSE: The rate of brivaracetam-related behavioural adverse events is a current focus of discussion. This study aims to assess the effect of brivaracetam on anger levels in patients with epilepsy, adjusted by mood symptoms, history of psychiatric disorders and seizure response. METHOD: Prospective analysis of 37 patients assessed for anger levels (STAXI-2), depression-anxiety (HADS) and quality of life (QOLIE-10) before adjunctive brivaracetam treatment and reassessed 3-6 months later. A control group following the same protocol of assessment was used for 1:1 comparison. A high percentage of mood stabilisers were included in this control group. RESULTS: Brivaracetam was indicated for patients including focal onset (79%) and generalised epilepsies (21%). Nearly 60% of responders and no psychiatric adverse events were found. This was similar to controls. The overall results revealed that brivaracetam was assoiciated with better in anger levels, mood scores and quality of life at baseline. Prior use of levetiracetam or the presence of a psychiatric background did not influence the results. However, improvements in anger levels were seen in the brivaracetam responders. CONCLUSION: This study shows that brivaracetam is not associated with an increased level of anger in patients with either focal or generalised epilepsies in the absence of psychiatric comorbidity. However, an improvement in anger levels is possibly influenced by a good seizure response.

Levels of anger in epilepsy patients treated with eslicarbazepine acetate.

INTRODUCTION: Aggressive behavior is commonly associated with epilepsy and can be influenced by the antiepileptic drugs (AEDs) taken. Sodium channel blockers, specifically the carboxamides derivatives such as carbamazepine and oxcarbazepine, are some of the AEDs considered to have a favorable psychiatric effect profile. OBJECTIVES: We aimed to assess whether the carboxamide analogue eslicarbazepine acetate (ESL) has any effect on the levels of anger in patients with epilepsy. MATERIAL AND METHODS: We prospectively recruited adult patients with epilepsy on treatment with ≦2 active AEDs, who required AED addition or substitution, excluding patients with active psychiatric disorders. All patients completed anger level (STAXI-2), depression-anxiety (HADS), and quality of life (QOLIE-10) assessments, and were evaluated at baseline and within 3-6 months after treatment initiation. RESULTS: Of 78 patients receiving ESL, as add-on therapy or in substitution of a previous AED, were recruited into the ESL group, with an average age of 48 years and 54% men. We used a control group of 58 patients receiving AEDs other than carboxamides. CONCLUSIONS: Patients overall showed improvements in anger levels, mood, and quality of life during the follow-up. A history of psychiatric disorders was a limiting factor to improve anger levels. As compared to controls, anger levels improved in ESL patients independently from seizure control. Therefore, ESL seems to exert a favorable influence on the anger levels of otherwise healthy patients with epilepsy, including those unresponsive to seizure control. The potential ESL anti-aggressive effect should be studied in patients with epilepsy and active psychiatric disorders.

A single dose of fluoxetine reduces neural limbic responses to anger in depressed adolescents.

Depression in adolescence is frequently characterised by symptoms of irritability. Fluoxetine is the antidepressant with the most favourable benefit:risk ratio profile to treat adolescent depression, but the neural mechanisms underlying antidepressant drugs in the young brain are still poorly understood. Previous studies have characterised the neural effects of long-term fluoxetine treatment in depressed adolescents, but these are limited by concurrent mood changes and a lack of placebo control. There is also recent evidence suggesting that fluoxetine reduces the processing of anger in young healthy volunteers, which is consistent with its effect for the treatment of irritability in this age group, but this remains to be investigated in depressed adolescents. Here we assessed the effects of a single, first dose of 10 mg fluoxetine vs. placebo on neural response to anger cues using fMRI in a sample of adolescents with Major Depressive Disorder (MDD) who had been recently prescribed fluoxetine. As predicted, adolescents receiving fluoxetine showed reduced activity in response to angry facial expressions in the amygdala-hippocampal region relative to placebo. Activity in the dorsal anterior cingulate cortex (dACC) was also increased. No changes in symptoms were observed. These results demonstrate, for the first time in depressed adolescents, that fluoxetine has immediate neural effects on core components of the cortico-limbic circuitry prior to clinical changes in mood. The effect on anger is consistent with our previous work and could represent a key mechanism through which fluoxetine may act to alleviate irritability symptoms in adolescent depression.

Neuroticism predicts the impact of serotonin challenges on fear processing in subgenual anterior cingulate cortex.

The personality trait neuroticism is associated with increased vulnerability to anxiety and mood disorders, conditions linked with abnormal serotonin neurotransmission and emotional processing. The interaction between neuroticism and serotonin during emotional processing is however not understood. Here we investigate how individual neuroticism scores influence the neural response to negative emotional faces and their sensitivity to serotonergic tone. Twenty healthy participants performed an emotional face task under functional MRI on three occasions: increased serotonin tone following infusion of a selective serotonin reuptake inhibitor (SSRI), decreased serotonin tone following acute tryptophan depletion (ATD) protocol, and no serotonin challenge (control). During the task, participants performed a gender-discrimination task of neutral, fearful or angry facial expressions. Individual variations in neuroticism scores were associated with neural response of subgenual anterior cingulate cortex to fearful facial expressions. The association was however opposite under the two serotoninergic challenges. The fear-related response in this region and individual neuroticism scores correlated negatively during citalopram challenge and positively during ATD. Thus, neuroticism scores were associated with the relative impact of serotonin challenges on fear processing in subgenual anterior cingulate cortex. This finding may link to a neural mechanism for the variable therapeutic effect of SSRI treatment observed in clinical populations.

Affect and cannabis use in daily life: a review and recommendations for future research.

BACKGROUND: Although cannabis is often used for the purposes of relieving negative affective states such as anxiety and depression, the associations between cannabis use and affect in daily life are unclear. Ecological momentary assessment (EMA) has been used to study these associations in individuals' natural environments, providing more ecological validity, minimizing retrospective bias, and allowing for the analysis of within-individual processes over time. This review focuses on studies that utilized EMA to examine daily-life associations of cannabis use and negative and positive affective states. METHODS: We review the findings of the 19 articles that met inclusion criteria, including clinical and community samples. RESULTS: Results provide equivocal evidence regarding relations between cannabis use and affect for community samples. Findings are mixed for clinical samples as well, but more consistent patterns emerge for general negative affect (NA) and anger/hostility at the momentary level; cannabis use may be more likely following increased NA and lead to decreases in NA and anger/hostility in psychiatric populations. CONCLUSIONS: Findings support a negative reinforcement hypothesis for clinical samples in terms of general NA and anger/hostility. However, discrepancies among studies point to a need to thoroughly characterize samples, consider motives for and expectancies of use, improve quantification of cannabis use, and consider co-use with other substances. Additional design recommendations are also offered for future studies.

Levetiracetam efficacy on frontal lobe dysfunctions and anger rumination in patients with epilepsy.

This study compared the frontal lobe functioning and anger rumination between patients with epilepsy and healthy individuals. The second objective was to examine the efficacy of levetiracetam therapy on frontal lobe dysfunctions and anger rumination in patients with epilepsy. Participants (50 patients with epilepsy and 50 healthy individuals) completed the Frontal Assessment Battery (FAB) and Anger Rumination Scale (ARS). The patients had two testing sessions: pre- and post-levetiracetam therapies. The results showed that patients with epilepsy had frontal lobe dysfunctions in contrast with healthy individuals. Patients with epilepsy had higher anger rumination than healthy individuals. Compared with baseline performance, frontal lobe dysfunctions and anger rumination were significantly reduced after three months of levetiracetam therapy in patients with epilepsy. It is concluded that levetiracetam therapy may be beneficial in improving frontal lobe functioning and anger rumination thought pattern in patients with epilepsy. However, further studies are required to confirm this evidence.

Morphine reduced perceived anger from neutral and implicit emotional expressions.

The µ-opioid system modulates responses to pain and psychosocial stress and mediates non-social and social reward. In humans, the µ-opioid agonist morphine can increase overt attention to the eye-region and visual exploration of faces with neutral expressions. However, little is known about how the human µ-opioid system influences sensitivity to and appraisal of subtle and explicit cues of social threats and reward. Here, we examined the effects of selective µ-opioid stimulation on perception of anger and happiness in faces with explicit, neutral or implicit emotion expressions. Sixty-three healthy adults (32 females) attended two sessions where they received either placebo or 10 mg per oral morphine in randomised order under double-blind conditions. Based on the known µ-opioid reduction of pain and discomfort, as well as reports suggesting that the non-specific partial agonist buprenorphine or the non-specific antagonist naltrexone affect appraisal of social emotional stimuli, we hypothesised that morphine would reduce threat sensitivity and enhance perception of happy facial expressions. While overall perception of others' happiness was unaffected by morphine treatment, morphine reduced perception of anger in stimuli with neutral and implicit expressions without affecting perception of explicit anger. This effect was statistically unrelated to gender, subjective drug effects, mood and autism trait measures. The finding that a low dose of µ-agonist reduced the propensity to perceive anger in photos with subtle facial expressions is consistent with the notion that µ-opioids mediate social confidence and reduce sensitivity to threat cues.

Effects of intranasal oxytocin on the attentional bias to emotional stimuli in patients with bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN) is characterized by binge eating and emotional dysregulation including increased negative affectivity (anger, anxiety). The aim of this study was to examine the effect of oxytocin on attentional processes towards anger in patients with BN. METHOD: The study design consisted of a double-blind, placebo-controlled within-subject crossover, single dose experiment. Sixty-four women (31 patients with BN and 33 healthy comparisons) completed self-reported measures to evaluate emotional difficulties and were administered a single dose of intranasal oxytocin (40IU) or placebo followed by a visual probe detection task to examine attentional orienting to angry or happy faces. RESULTS: Patients with BN reported higher emotional dysregulation and more difficulties in controlling anger compared to the healthy comparison group. Patients with BN and the healthy women exhibited similar attentional bias to angry faces in the placebo condition. Intranasal oxytocin reduced the attentional bias towards angry faces in both the BN patients and the healthy women. CONCLUSIONS: We found that a single dose of oxytocin reduced vigilance towards angry faces in patients with BN as well as healthy women. The results showed that patients with BN are not different from healthy women in terms of vigilance towards threat.

Anger Assessment in Patients Treated With Brivaracetam.

OBJECTIVES: To assess state and trait anger, adjusted by epilepsy type, seizure control, anxiety-depression status and quality of life, in patients treated with brivaracetam (BRV) from an open study. METHODS: We evaluated prospectively consecutive patients with partial onset seizures in an open-label study. Patients had 5 years or longer of epilepsy and were taking between 1 and 3 antiepileptic drugs. They were treated with BRV and compared with a control group selected from outpatients attending our epilepsy unit who met the following criteria: age ≥16 years and diagnosis of epilepsy with focal-onset seizures at least 1 year before inclusion in the study. The following tests were assessed: State-Trait Anger with the Expression Inventory-2, Hospital Anxiety and Depression Scale, and Quality of Life in Epilepsy Inventory. RESULTS: We recruited 39 patients, 17 treated with BRV and 22 with other drugs, including 13 with levetiracetam (LEV). Mean age was 47.3 years, 43.6% were men. Symptomatic cases, 66% and 52% temporal lobe epilepsy. Antiepileptic drug polytherapy was present in 82.1% of the cases (100% BRV vs 68.2% control group). Demographic and clinical characteristics, as well as Quality of Life in Epilepsy Inventory and Hospital Anxiety and Depression Scale scores were similar in both groups. When compared with the subgroup of LEV groups did not differ significantly on their Hospital Anxiety and Depression Scale scores. CONCLUSIONS: This small, open study suggests that BRV increases anger measures less than LEV in epilepsy patients. However, larger, blinded control studies are required to establish whether this apparent difference can be confirmed.

Does Testosterone Treatment Increase Anger Expression in a Population of Transgender Men?

BACKGROUND: The acquisition of phenotypic male features in transmen with gender dysphoria requires testosterone treatment. The suppression of menses is 1 of the most desired effects. The relation between testosterone levels and human aggressive behavior has been described. However, the effects of testosterone on anger expression have been poorly investigated in trans-persons. AIM: To assess the effects of testosterone treatment on anger expression in transmen using a validated self-report questionnaire (Spielberger's State-Trait Anger Expression Inventory-2 [STAXI-2]). METHODS: 52 transmen diagnosed with gender dysphoria were evaluated before (T0) and at least 7 months after (T1) initiation of continuous gender-affirming testosterone treatment. Sociodemographic characteristics, anthropometric parameters, diagnosis of psychiatric disorders, current psychopharmacologic treatments, and life events were investigated at T0. OUTCOMES: STAXI-2 scores, serum testosterone, and estradiol levels at T0 and T1 were compared. RESULTS: Most of the sample (61.5%, n = 32) had no Axis I or II comorbidity. All subjects at T1 achieved significantly higher serum testosterone levels (5.67 ± 3.88 ng/mL), whereas no significant difference in estradiol levels was observed from T0 to T1. At T1 only 46.2% (n = 24) of the sample achieved iatrogenic amenorrhea, whereas most of the sample had persistent regular bleedings. A significant increase in STAXI anger expression and anger control scores from T0 to T1 was recorded. Patients with persistent bleedings and Axis I disorders seemed to have higher odds of expressing anger. However, circulating testosterone levels at T1 did not influence anger expression. CLINICAL IMPLICATIONS: Interestingly, despite the increase of anger expression scores, during continuous testosterone treatment, there were no reports of aggressive behavior, self-harm, or psychiatric hospitalization. STRENGTHS AND LIMITATIONS: A limitation to this study is that although the STAXI-2 is a well-validated instrument measuring anger expression, it is a self-report psychometric measure. CONCLUSION: This study demonstrates that during 7 months of continuous gender-affirming hormonal treatment, anger expression and anger arousal control increased in transmen. Persistence of menstrual bleedings and Axis I disorders, but not circulating testosterone levels, were predictive of the increase in anger expression score. Continuous psychological support to transmen during gender-affirming hormonal treatment was useful to prevent angry behaviors and decrease the level of dysphoria. Motta G, Crespi C, Mineccia V, et al. Does Testosterone Treatment Increase Anger Expression in a Population of Transgender Men? J Sex Med 2018;15:94-101.

Exogenous testosterone in a non-social provocation paradigm potentiates anger but not behavioral aggression.

Animal studies suggest a causal link between testosterone and aggression. However, in human research the exact role of this hormone is still unclear, having been linked to dominance and approach behavior rather than to aggression per se. In a social context, the induction of aggression might be confounded with dominance or status changes, which potentially influence the association between aggression and testosterone. The objective of the current study was to investigate the influence of testosterone on non-social aggression in a double-blind, placebo-controlled experiment including 90 healthy male participants. To this end, we developed an innovative paradigm in which participants were provoked by a malfunctioning joystick restraining them from a promised reward. As measures for aggression throughout the task the joystick amplitude was recorded and anger was assessed via emotional self-ratings. Participants reacted to the provocation with a significant shift to more negative emotions and increased implicit aggressive behavior, reflected in the force exerted to pull the joystick following provocation. Importantly, the study demonstrated first evidence for a modulating influence of testosterone on non-social aggression in males: Self-rated anger was significantly elevated in the testosterone group compared to the placebo group as a function of provocation. Testosterone administration did not significantly influence the implicit aggressive response. These findings demonstrate a potentiating effect of testosterone on provocation-related anger in a non-social context. Furthermore, the results highlight the importance of disentangling different components of aggression and characterizing different influencing factors when inferring on hormonal effects.

Lurasidone for the treatment of irritability and anger in autism spectrum disorders.

INTRODUCTION: Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by deficits in social interaction and communication as well as restricted patterns of behaviors and interests. Irritability marked by tantrums, self-injury and aggression occurs frequently in youth with ASD, causing significant parent and caregiver distress. Atypical antipsychotics have been the most studied drug class targeting irritability in ASD. Risperidone and aripiprazole are Food and Drug Administration (FDA)-approved atypical antipsychotics for treatment of irritability in youth with ASD. However, other atypical antipsychotics, such as lurasidone, are often considered for off-label use in the treatment of irritability, whether because of tolerability issues with risperidone and aripiprazole or because of the drug-refractory nature of this symptom cluster. Areas covered: Following a comprehensive review of the literature this article summarizes information on the efficacy and tolerability of lurasidone as a potential off label treatment of irritability in children and adolescents with ASD. Available data included a 6 week randomized, blind, fixed dose, placebo-controlled study and a case study. Expert opinion: To date the safety and tolerability of lurasidone in treating irritability in youth with ASD has yet to be established with, lurasidone being the only antipsychotic with published negative placebo-controlled results.

Exogenous testosterone decreases men's personal distance in a social threat context.

BACKGROUND: Testosterone can motivate human approach and avoidance behavior. Specifically, the conscious recognition of and implicit reaction to angry facial expressions is influenced by testosterone. The study tested whether exogenous testosterone modulates the personal distance (PD) humans prefer in a social threat context. METHODS: 82 healthy male participants underwent either transdermal testosterone (testosterone group) or placebo application (placebo group). Each participant performed a computerized stop-distance task before (T1) and 3.5h after (T2) treatment, during which they indicated how closely they would approach a human, animal or virtual character with varying emotional expression. RESULTS: Men's PD towards humans and animals varied as a function of their emotional expression. In the testosterone group, a pre-post comparison indicated that the administration of 50mg testosterone was associated with a small but significant reduction of men's PD towards aggressive individuals. Men in the placebo group did not change the initially chosen PD after placebo application independent of the condition. However comparing the testosterone and placebo group after testosterone administration did not reveal significant differences. While the behavioral effect was small and only observed as within-group effect it was repeatedly and selectively shown for men's PD choices towards an angry woman, angry man and angry dog in the testosterone group. In line with the literature, our findings in young men support the influential role of exogenous testosterone on male's approach behavior during social confrontations.