Sabine C. Herpertz

Oxytocin Attenuates Amygdala Responses to Emotional Faces Regardless of Valence

BACKGROUND Oxytocin is known to reduce anxiety and stress in social interactions as well as to modulate approach behavior. Recent studies suggest that the amygdala might be the primary neuronal basis for these effects. METHODS In a functional magnetic resonance imaging study using a double-blind, placebo-controlled within-subject design, we measured neural responses to fearful, angry, and happy facial expressions after intranasal application of 24 IU oxytocin compared with placebo. RESULTS Oxytocin reduced right-sided amygdala responses to all three face categories even when the emotional content of the presented face was not evaluated explicitly. Exploratory whole brain analysis revealed modulatory effects in prefrontal and temporal areas as well as in the brainstem. CONCLUSIONS Results suggest a modulatory role of oxytocin on amygdala responses to facial expressions irrespective of their valence. Reduction of amygdala activity to positive and negative stimuli might reflect reduced uncertainty about the predictive value of a social stimulus and thereby facilitates social approach behavior.

Effects of intranasal oxytocin on emotional face processing in women

The neuropeptide oxytocin (OXT) has previously been found to reduce amygdala reactivity to social and emotional stimuli in healthy men. The present study aimed to investigate the effect of intranasally administered OXT on brain activity in response to social emotional stimuli of varying valence in women. In a functional magnetic-resonance imaging study, sixteen women were presented with fearful, angry, happy and neutral facial expressions after a single dose of 24IU OXT or a placebo administration in a within-subject design. Group analysis revealed that the blood-oxygen-level-dependent (BOLD) signal was enhanced in the left amygdala, the fusiform gyrus and the superior temporal gyrus in response to fearful faces and in the inferior frontal gyrus in response to angry and happy faces following OXT treatment. This effect was independent of fixation pattern to specific sections of the facial stimuli as revealed by eye tracking and independent of basal plasma levels of OXT, estradiol, and progesterone. The results are at odds with the previously reported effects found in men. Future studies should include both sexes to determine a possible sexual dimorphism in the neural effects of OXT, considering gonadal steroids and OXT receptor affinity.

Emotion recognition in borderline personality disorder—A review of the literature.

Borderline personality disorder (BPD) is characterized by distinct impairments in emotion regulation, resulting in affective instability especially in the social context. It has been suggested that impaired social cognitive functioning such as impaired facial emotion recognition contributes to the social disturbances in BPD. In accordance with this notion, a number of behavioral studies have revealed a pattern of alterations in facial emotion recognition associated with BPD: subtle impairments in basic emotion recognition, a negativity or anger bias, and a heightened sensitivity to the detection of negative emotions. Furthermore, there is increasing evidence for structural and functional changes in the neural networks underlying affective dysregulation and emotional hyperreactivity in BPD. Merging these lines of evidence, we propose that emotional hyperreactivity interferes with the cognitive processes of facial emotion recognition, thereby contributing to the specific pattern of altered emotion recognition in BPD. Suggestions for future research and clinical implications are discussed.

Impulsivity in self-mutilative behavior: Psychometric and biological findings

This paper examines impulsivity as a central factor in moderate/superficial self-mutilation such as skin-cutting and burning. A sample of 165 subjects were divided into four groups, namely self-mutilators, patients with any modes of impulsive behavior other than self-mutilation, patients without any impulsive behavior, and normal probands. All were administered the 10th version of the Barratt Impulsiveness Scale, the State-Trait Anger Expression Inventory, and the Inventory for the Assessment of Factors of Aggressiveness. They also were interviewed carefully in regards to both impulsive and self-mutilative behavior. A d-fenfluramine challenge test was administered to 36 females and prolactin levels were measured. On the whole results implicate impulsive personality functioning as a major factor in subjects with moderate/superficial self-mutilative behavior whose trait pathology is similar to personality disordered patients with other modes of self-harming impulsive behavior.

Prospective 10‐year Follow‐up in Adolescent Anorexia Nervosa—Course, Outcome, Psychiatric Comorbidity, and Psychosocial Adaptation

The aim of the present study was to follow up the long-term course of adolescent-onset anorexia nervosa by repeated assessment, to analyze the association between the course of the eating disorder and psychiatric comorbidity, and to evaluate psychosocial outcome. The sample consisted of 39 inpatients who were reinvestigated 3, 7, and 10 years after discharge. The patients and 39 controls matched for age, gender, and occupational status were assessed with structured interviews on DSM-III-R eating disorders, additional axis I and axis II psychiatric disorders, and psychosocial functioning. Results showed that 69 % of the original subjects met the criteria for full recovery at the 10-year follow-up. One patient (3%) still exhibited the full syndrome of restrictive anorexia nervosa, two patients (5%) the full syndrome of bulimia nervosa. None of the patients had died. Of the subjects, 51% currently had an axis I psychiatric disorder and 23% met the full criteria for a personality disorder. Apart from the eating disorder, anxiety disorders and avoidant-dependent and obsessive-compulsive personality disorders were the most common psychiatric diagnoses. There was a significant association between psychiatric comorbidity and the outcome of the eating disorder and between outcome and psychosocial adaptation. With regard to psychiatric morbidity and psychosocial functioning, long-term recovered patients did not differ significantly from normal controls. It is concluded that in most patients adolescent anorexia nervosa takes a prolonged course, although it seems to be more favorable than in adult-onset forms. Those who achieve complete recovery from the eating disorder have a good chance of overcoming other psychiatric disorders and to adapt to social requirements.

Morphometric brain abnormalities in boys with conduct disorder.

OBJECTIVE Children with the early-onset type of conduct disorder (CD) are at high risk for developing an antisocial personality disorder. Although there have been several neuroimaging studies on morphometric differences in adults with antisocial personality disorder, little is known about structural brain aberrations in boys with CD. METHOD Magnetic resonance imaging and voxel-based morphometry were used to assess abnormalities in gray matter volumes in 23 boys ages 12 to 17 years with CD (17 comorbid for attention-deficit/hyperactivity disorder) in comparison with age- and IQ-matched controls. RESULTS Compared with healthy controls, mean gray matter volume was 6% smaller in the clinical group. Compared with controls, reduced gray matter volumes were found in the left orbitofrontal region and bilaterally in the temporal lobes, including the amygdala and hippocampus on the left side in the CD group. Regression analyses in the clinical group indicated an inverse association of hyperactive/impulsive symptoms and widespread gray matter abnormalities in the frontoparietal and temporal cortices. By contrast, CD symptoms correlated primarily with gray matter reductions in limbic brain structures. CONCLUSIONS The data suggest that boys with CD and comorbid attention-deficit/hyperactivity disorder show brain abnormalities in frontolimbic areas that resemble structural brain deficits, which are typically observed in adults with antisocial behavior.

The Neural Correlates of Sex Differences in Emotional Reactivity and Emotion Regulation

Sex differences in emotional responding have been repeatedly postulated but less consistently shown in empirical studies. Because emotional reactions are modulated by cognitive appraisal, sex differences in emotional responding might depend on differences in emotion regulation. In this study, we investigated sex differences in emotional reactivity and emotion regulation using a delayed cognitive reappraisal paradigm and measured whole‐brain BOLD signal in 17 men and 16 women. During fMRI, participants were instructed to increase, decrease, or maintain their emotional reactions evoked by negative pictures in terms of cognitive reappraisal. We analyzed BOLD responses to aversive compared to neutral pictures in the initial viewing phase and the effect of cognitive reappraisal in the subsequent regulation phase. Women showed enhanced amygdala responding to aversive stimuli in the initial viewing phase, together with increased activity in small clusters within the prefrontal cortex and the temporal cortex. During cognitively decreasing emotional reactions, women recruited parts of the orbitofrontal cortex, the anterior cingulate, and the dorsolateral prefrontal cortex to a lesser extent than men, while there was no sex effect on amygdala activity. In contrast, compared to women, men showed an increased recruitment of regulatory cortical areas during cognitively increasing initial emotional reactions, which was associated with an increase in amygdala activity. Clinical implications of these findings are discussed. Hum Brain Mapp, 2010.

White matter microstructure underlying default mode network connectivity in the human brain

Resting state functional magnetic resonance imaging (fMRI) reveals a distinct network of correlated brain function representing a default mode state of the human brain. The underlying structural basis of this functional connectivity pattern is still widely unexplored. We combined fractional anisotropy measures of fiber tract integrity derived from diffusion tensor imaging (DTI) and resting state fMRI data obtained at 3 Tesla from 20 healthy elderly subjects (56 to 83 years of age) to determine white matter microstructure underlying default mode connectivity. We hypothesized that the functional connectivity between the posterior cingulate and hippocampus from resting state fMRI data would be associated with the white matter microstructure in the cingulate bundle and fiber tracts connecting posterior cingulate gyrus with lateral temporal lobes, medial temporal lobes, and precuneus. This was demonstrated at the p<0.001 level using a voxel-based multivariate analysis of covariance (MANCOVA) approach. In addition, we used a data-driven technique of joint independent component analysis (ICA) that uncovers spatial pattern that are linked across modalities. It revealed a pattern of white matter tracts including cingulate bundle and associated fiber tracts resembling the findings from the hypothesis-driven analysis and was linked to the pattern of default mode network (DMN) connectivity in the resting state fMRI data. Our findings support the notion that the functional connectivity between the posterior cingulate and hippocampus and the functional connectivity across the entire DMN is based on distinct pattern of anatomical connectivity within the cerebral white matter.

Emotional Processing in Male Adolescents with Childhood-Onset Conduct Disorder.

BACKGROUND Boys with early onset of conduct disorder (CD), most of whom also meet diagnostic criteria of a comorbid attention deficit hyperactivity disorder (ADHD), tend to exhibit high levels of aggression throughout development. While a number of functional neuroimaging studies on emotional processing have been performed in antisocial adults, little is known about how CD children process emotional information. METHOD Functional magnetic resonance imaging data were analyzed in 22 male adolescents aged 12 to 17 years with childhood-onset CD (16 of them with comorbid ADHD) compared to 22 age-matched male healthy controls. In order to consider the likely confounding of results through ADHD comorbidity, we performed a supplementary study including 13 adolescent subjects with pure ADHD who were compared with healthy controls. To challenge emotional processing of stimuli, a passive viewing task was applied, presenting pictures of negative, positive or neutral valence. RESULTS When comparing CD/combined disorder patients with healthy controls, we found enhanced left-sided amygdala activation in response to negative pictures as compared to neutral pictures in the patient group. In addition, these boys exhibited no reduced activation in the orbitofrontal, anterior cingulate and insular cortices. By contrast, children with pure ADHD did not show any abnormalities in amygdala activation but showed decreased neural activity in the insula only in response to negative pictures. CONCLUSIONS Increased rather than reduced amygdala activation found in our study may indicate an enhanced response to environmental cues in adolescents with early-onset CD (most of whom also met the condition of ADHD), and is not consistent with the assumption of a reduced capacity to take note of affective information in the social environment. Further studies with an emphasis on developmental aspects of affect regulation are needed to clarify the relationship between CD and adult personality pathology associated with different modes of persistent antisocial behavior.

Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder

BACKGROUND Autism spectrum disorder (ASD) is associated with altered face processing and decreased activity in brain regions involved in face processing. The neuropeptide oxytocin has been shown to promote face processing and modulate brain activity in healthy adults. The present study examined the effects of oxytocin on the neural basis of face processing in adults with Asperger syndrome (AS). METHODS A group of 14 individuals with AS and a group of 14 neurotypical control participants performed a face-matching and a house-matching task during functional magnetic resonance imaging. The effects of a single dose of 24 IU intranasally administered oxytocin were tested in a randomized, placebo-controlled, within-subject, cross-over design. RESULTS Under placebo, the AS group showed decreased activity in the right amygdala, fusiform gyrus, and inferior occipital gyrus compared with the control group during face processing. After oxytocin treatment, right amygdala activity to facial stimuli increased in the AS group. CONCLUSIONS These findings indicate that oxytocin increases the saliency of social stimuli and in ASD and suggest that oxytocin might promote face processing and eye contact in individuals with ASD as prerequisites for neurotypical social interaction.