Moderator Effects of Life Stress on the Association between MAOA-uVNTR, Depression, and Burnout.

BACKGROUND: The serotonergic and noradrenergic systems have a strong impact on several affective disorders and are key targets for psychopharmacological therapy. With respect to pathogenesis, there is a growing body of evidence showing an influence of a promoter repeat polymorphism (MAOA-uVNTR) altering the expression rate of monoamine oxidase A. However, only a few studies investigate its influence on depression with only 2 of them considering the moderating effects of life stress. For burnout, there are no studies so far investigating the genetic basis. OBJECTIVES: The aim of the present study was to replicate an interaction effect of MAOA-uVNTR and life stress on depression, and extend these possible findings to the burnout syndrome. Especially, the latter one might help in understanding the underlying mechanisms of burnout and its association to depression. METHOD: A total of n = 1,541 participants (n = 1,099 healthy controls, n = 442 inpatients with affective disorders) provided genetic samples and filled in self-report questionnaires measuring depression, burnout, and the extent of experienced stressful life events (SLEs). RESULTS: A life stress x MAOA-uVNTR interaction on depression and burnout was observed in women suggesting that carriers of the high expressing allele (MAO-H) with many SLEs had the highest scores in both burnout and depression. In men, there was only a weak effect of MAOA-uVNTR on depression. CONCLUSIONS: The results suggest a more pronounced reactivity to adverse environmental factors in carriers of the MAO-H allele. Especially the effect of life stress and MAOA-uVNTR on burnout should be independently replicated in the future as this is the first study showing this association.

A functional polymorphism of the OXTR gene is associated with autistic traits in Caucasian and Asian populations.

There is increasing evidence for associations between polymorphisms of the oxytocin receptor (OXTR) gene and autism spectrum disorder, but to date no study has established links with autistic traits in healthy subjects and potential cultural differences. The present research firstly investigated associations between three widely studied OXTR SNPs and autistic and empathic traits (rs53576 (G/A); rs2254298 (G/A); rs2268498 (T/C)) in two independent studies on male and female Caucasian (n = 537) and Chinese students (n = 280). Autistic and empathic traits were measured in all subjects in the two independent groups using the Autism -Spectrum Quotient (AQ) and the Interpersonal Reactivity Index (IRI) respectively, together with their sub-scales. For both sites, genotyping of the OXTR SNPs was conducted on buccal swab samples using a Cobas Z 480 Light Cycler following automated DNA extraction. Associations at the genotype level with autism trait scores were found in Caucasian subjects for rs2268498 only, with TT carriers having the lowest AQ scores compared with those carrying at least one C-allele. This finding was independently replicated in the Chinese sample although a smaller proportion carried the C-allele compared with the Caucasian sample. Some minor associations were found between empathy trait scores and the three SNPs but were not consistent between the samples. These findings show for the first time that the rs2268498 SNP localized in the promoter flanking region of the OXTR gene is associated with autistic traits in different ethnic/cultural groups. This provides further support for the role of the OXTR gene in relation to autism.

Anxious personality and functional efficiency of the insular-opercular network: A graph-analytic approach to resting-state fMRI.

The brain is an intricate network, not only structurally but also functionally. On the functional level, connectivity in the brain is organized in separable yet interacting networks that support information processing by maintaining a ready state, even in the absence of external stimulation. It has been hypothesized that an insular-opercular network underlies the processing of emotionally salient information and that individual differences in functional connectivity within this network correspond to individual differences in trait anxiety. Here, we tested this relationship by applying graph analysis to multiple regions of interests delineating the insular-opercular network to estimate the characteristic path length that quantifies the overall information exchange efficiency within a given network. We found that people scoring high on the anxiety-related temperament-dimension harm avoidance had decreased insular-opercular network efficiency in the resting state, as indicated by a higher characteristic path length. Furthermore, people scoring high on harm avoidance showed generally reduced functional connectivity between brain regions; the relationship between harm avoidance and insular-opercular network efficiency remained significant when controlling for mean connectivity within this network. No such results were found for other resting-state networks. The results provide insights into how personality is organized in the human brain and point toward clinically relevant endophenotypes for affective and mood disorders.

Reality TV and vicarious embarrassment: an fMRI study.

BACKGROUND: Vicarious embarrassment (VE) is an emotion triggered by the observation of others' pratfalls or social norm violations. Several explanatory approaches have been suggested to explain the source of this phenomenon, including perspective taking abilities or ingroup identification. Knowledge about its biological bases, however, is scarce. To gain a better understanding, the present study investigated neural activation patterns in response to video clips from reality TV shows. Reality TV is well known for presenting social norm violations, flaws and pratfalls of its protagonists in real life situations thereby qualifying as an ecological valid trigger for VE. METHODS: N = 60 healthy participants viewed stand stills from previously watched video clips taken from German reality TV-shows while undergoing functional magnetic resonance imaging. The clips were preselected for high versus low VE content in a pilot study. Besides the investigation of differences in brain activation elicited by VE versus control stand stills (blocked design contrast), we performed additional exploratory functional connectivity analyses (psychophysiological interaction; PPI) to detect VE related brain networks. RESULTS: Compared to the low VE condition, participants in the high VE condition showed a higher activation in the middle temporal gyrus, the supramarginal gyrus, the right inferior frontal gyrus and the gyrus rectus. Functional connectivity analyses confirmed increased connectivity of these regions with the anterior cingulate in the VE condition. Moreover, self-ratings of VE and brain activity were correlated positively. CONCLUSION: Reality TV formats with high VE content activate brain regions associated with Theory of Mind, but also with empathic concern and social identity. Therefore, our results support the idea that the ability to put oneself in other person's shoes is a major prerequisite for VE.

Assessment of empathy via self-report and behavioural paradigms: data on convergent and discriminant validity.

INTRODUCTION: Research on empathy has a long tradition in clinical research, as deficits in empathy have been found in many mental disorders. Over decades, a large amount of measures for empathy have been developed, but in many cases these have not been analysed with respect to validity. Therefore, this paper aims to relate various assessment methods for empathy, schizotypy and autistic traits to gain knowledge on their convergent and discriminant validity. METHODS: A total of N = 108 participants were tested with two of the most widespread empathy questionnaires (Interpersonal Reactivity Index, Empathy Quotient), two behavioural paradigms (Reading the Mind in the Eyes Test, Cambridge Face-Voice Battery) and a rotation task. Furthermore, questionnaires assessing schizotypal and autistic traits were administered. RESULTS: Results indicate convergent validity of the applied empathy self-report measures, although their association with measures of schizotypal and autistic traits is inconsistent. However, results of the behavioural testing barely correlate either with the self-report measures or among each other. CONCLUSIONS: The questionnaire measures of empathy seem valid and exchangeable, and therefore suitable for capturing self-reported empathy in clinical research. The behavioural paradigms cover distinct endophenotypes of empathy and should only be used for very specific research questions.

Insecticidal heterolignans--tubuline polymerization inhibitors with activity against chewing pests.

Starting from natural product podophyllotoxin 1 substituted heterolignans were identified with promising insecticidal in vivo activity. The impact of substitution in each segment of the core structure was investigated in a detailed SAR study, and variation of substituents in both aromatic moieties afforded derivatives 5 and 43 with broad insecticidal activity against lepidopteran and coleopteran species. In vitro measurements supported by modeling studies indicate that heterolignans 3-134 act as tubuline polymerization inhibitors interacting with the colchicine-binding site. Insect specific structure-activity effects were observed showing that the insecticidal SAR described herein differs from reported cytotoxicity studies.

The Role of Empathy and Life Satisfaction in Internet and Smartphone Use Disorder.

Recent studies have yielded initial evidence for an association between Internet Use Disorder (IUD), empathy, and life satisfaction. In the present study we sought to replicate these previous findings, and then to extend this research by also examining the relationship between empathy, life satisfaction, and the related phenomenon of Smartphone Use Disorder (SUD). The present study included independent samples from China (N = 612, 162 females) and Germany (N = 304, 207 females), with the same set of questionnaires administered to both samples. IUD was measured with Pawlikowski's s-IAT and SUD was assessed with the short version of Kwon's Smartphone Addiction Scale. The Interpersonal Reactivity Index (IRI) was used to assess individual differences in empathy. Please note that for the German sample data on the empathy quotient (EQ) are also available. Life satisfaction data were collected using items from the SOEP-Questionnaire (Socio-Economic Panel, Germany). In both of our samples we replicated previous findings showing the association between higher IUD, lower empathy, and lower life satisfaction scores. In addition, individuals with higher SUD showed higher scores on the IRI Personal Distress scale in China and Germany, while further associations between IRI dimensions and SUD were only found in the Chinese sample. Personal Distress is known to be highly correlated with the personality trait of Neuroticism, hence higher stress/negative emotionality in tense social situations is related to SUD. In the present study we confirm earlier findings showing the relationship between empathy, life satisfaction, and IUD, and extend some of these findings to SUD. We also emphasize the importance of cross-cultural studies when investigating IUD/SUD in the context of empathy and life satisfaction.

The serotonin transporter polymorphism (5-HTTLPR) and coping strategies influence successful emotion regulation in an acute stress situation: Physiological evidence.

INTRODUCTION: Emotion regulation is an important everyday-life skill to reduce harm and stress. Consequently, research shows associations between psychopathologies and emotional dysregulation. The serotonin transporter polymorphism (5-HTTLPR) has repeatedly been associated to phenotypes and syndromes related to emotional dysregulation. However, there is no study showing any direct effects of 5-HTTLPR genotype and emotion regulation. Hence, the aim of the present study was to draw a link between 5-HTTLPR to emotion regulation. METHOD: N=91 healthy participants filled in a coping questionnaire, provided gene samples and participated in an emotion regulation experiment. In a within-subject design they viewed emotional pictures and were either instructed to suppress their emotions or not. During the emotion regulation task, skin conductance responses (SCR) were recorded. RESULTS: Emotion regulation abilities measured by SCR were influenced by 5-HTTLPR and coping strategies, together explaining 30% of variance. S-allele carriers showed increased SCRs when watching aversive stimuli in the uninstructed condition. However, when receiving an emotion regulation instruction, they were able to downregulate their arousal resulting in comparable SCRs as observed in LL-carriers. DISCUSSION: This is the first study showing an impact of 5-HTTLPR on physiological emotion regulation. Results show that S-allele carriers have the same emotional arousal as L-allele carriers, when they get a supportive instruction to suppress unwanted feelings. These findings have implications for psychotherapeutic treatments.

The OXTR gene, implicit learning and social processing: Does empathy evolve from perceptual skills for details?

Oxytocin is an important messenger in the brain that has been linked to a variety of social functions in pharmacological studies. Besides, functional genetic variations on the oxytocin receptor gene have been repeatedly associated with social processing and functioning. Despite this knowledge, there are very few studies investigating the mechanisms that may explain the link between oxytocin and social functions. In the endeavor to fill this gap in the literature, the current study searches for associations between the prominent rs2268498 polymorphism on the oxytocin receptor gene and participants' ability to perceive and store implicit social information, which is a fundamental function in social information processing. N=121 healthy participants were experimentally tested with an implicit learning paradigm, answered questionnaires assessing empathy and autistic traits, and were genotyped for the rs2268498 polymorphism. T-allele carriers (TT and TC genotypes) exhibited significantly better implicit learning performance than carriers of the CC-genotype, and learning performance was positively associated with self-reported empathy and negatively with self-reported autistic traits. Results indicate that differences in implicit perception and storing of environmental details while watching social interactions could be an important mechanism to explain the association between differences in endogenous oxytocin activity and social functioning.

Similar Personality Patterns Are Associated with Empathy in Four Different Countries.

Empathy is an important human ability associated with successful social interaction. It is currently unclear how to optimally measure individual differences in empathic processing. Although the Big Five model of personality is an effective model to explain individual differences in human experience and behavior, its relation to measures of empathy is currently not well understood. Therefore, the present study was designed to investigate the relationship between the Big Five personality concept and two commonly used measures for empathy [Empathy Quotient (EQ), Interpersonal Reactivity Index (IRI)] in four samples from China, Germany, Spain, and the United States of America. This approach was designed to advance the way the Big Five personality model can be used to measure empathy. We found evidence of medium effect sizes for associations between personality and empathy, with agreeableness and conscientiousness as the most important predictors of affective and cognitive empathy (measured by the respective IRI subscales) as well as for a one-dimensional empathy score (measured by the EQ). Empathy in a fictional context was most closely related to openness to experience while personal distress was first of all related to neuroticism. In terms of culture, we did not observe any distinct pattern concerning cultural differences. These results support the cross-cultural applicability of the EQ and the IRI and indicate structurally similar associations between personality and empathy across cultures.

The oxytocin receptor gene and social perception.

Social perception is an important prerequisite for successful social interaction, because it helps to gain information about behaviors, thoughts, and feelings of interaction partners. Previous pharmacological studies have emphasized the relevance of the oxytocin system for social perception abilities, while knowledge on genetic contributions is still scarce. In the endeavor to fill this gap in the literature, the current study searches for associations between participants' social perception abilities as measured by the interpersonal perception task (IPT) and the rs2268498 polymorphism on the OXTR-gene, which has repeatedly been linked to processes relevant to social functioning. N = 105 healthy participants were experimentally tested with the IPT and genotyped for the rs2268498 polymorphism. T-allele carriers (TT and TC genotypes) exhibited significantly better performance in the IPT than carriers of the CC-genotype. This difference was also significant for the subscales measuring the strength of social bonding (kinship and intimacy). As in previous studies, T-allele carriers exhibited better performance in measures of social processing indicating that the rs2268498 polymorphism is an important candidate for understanding the genetic basis of social functioning.

Differentiating Burnout from Depression: Personality Matters!

Stress-related affective disorders have been identified as a core health problem of the twenty-first century. In the endeavor to identify vulnerability factors, personality has been discussed as a major factor explaining and predicting disorders like depression or burnout. An unsolved question is whether there are specific personality factors allowing differentiation of burnout from depression. The present study tested the relation between one of the most prominent, biological personality theories, Cloninger's Temperament and Character Inventory, and common measures of burnout (Maslach Burnout Inventory General) and depression (Beck Depression Inventory 2) in a sample of German employees (N = 944) and a sample of inpatients (N = 425). Although the same personality traits (harm avoidance and self-directedness) were predominantly associated with burnout and depression, there was a much stronger association to depression than to burnout in both samples. Besides, we observed specific associations between personality traits and subcomponents of burnout. Our results underline differences in the association of burnout vs. depression to personality, which may mirror differences in scope. While symptoms of depression affect all aspects of life, burnout is supposed to be specifically related to the workplace and its requirements. The much stronger association of personality to depression can be important to select appropriate therapy methods and to develop a more specified treatment for burnout in comparison to depression.

Low empathy is associated with problematic use of the Internet: Empirical evidence from China and Germany.

As empathy has not been investigated in the context of problematic use of the Internet, we conducted a study to test for a potential link. In samples from China (N=438) and Germany (N=202), two self-report measures for empathic behavior and one self-report measure for problematic Internet use (PIU) were administered in adolescents/students. Across both cultures lower empathy was associated with more PIU. The present study underlines the importance to take into account empathy related questionnaires for a better understanding of Internet overuse in the future.

Relationship between oxytocin receptor genotype and recognition of facial emotion.

The ability to understand thoughts and feelings of another person is an important prerequisite for successful social interaction. One part of this ability is the recognition of emotions in the face of the counterpart. Knowledge on genetic contributions to emotion recognition is still scarce. In the present study, 105 healthy participants were experimentally tested for their ability to recognize complex emotions in faces. As prior studies outlined the importance of the oxytocin system for emotion recognition, the functional rs2268498 polymorphism on the OXTR-gene was investigated. Although there were no differences in reaction times between genotype groups, carriers of the T-allele exhibited more accurate recognition skills than subjects carrying the CC-genotype. There was no influence of gender or age. Results support recent findings, demonstrating the importance of the oxytocin system for affect processing and related social behavior.

An interaction of a NR3C1 polymorphism and antenatal solar activity impacts both hippocampus volume and neuroticism in adulthood.

The investigation of the interaction of genes and environment in the context of mental health and personality yields important new insights for a better understanding of human nature. Both antenatal and postnatal environmental factors have been considered as potential modulators of genetic activity. Antenatally, especially smoking or alcohol drinking habits of the mother dramatically influence the health of the child during pregnancy and even later on in life. In the present study we would like to introduce a more "distant" factor that is not under the control of the becoming mother but that nevertheless plays a potential role for the health of the unborn child later on in adulthood. Here, we retrospectively investigate the influence of solar activity (while the child is still in the uterus of the becoming mother) on brain structure (with a focus on hippocampus and amygdala volume) and personality in adulthood. We observe an interaction of a genetic variant (rs41423247) of the glucocorticoid receptor gene (NR3C1) and solar activity in the first trimester after conception on both hippocampal volume and the personality trait neuroticism in adulthood in N = 254 participants. The NR3C1 gene is the focus of interest, because of its influence on the hypothalamic-pituitary-adrenal (HPA) axis and negative emotionality. Carriers of the CC variant of rs41423247 grown in the womb under the influence of high sun radiation (high solar activity) show both the highest hippocampal volume in the left hemisphere and lowest neuroticism scores. The present findings should encourage researchers in psychology and psychiatry to include also environmental influences such as solar activity besides genetics to better understand the etiogenesis of psychiatric disorders.

Interaction of the cholinergic system and the hypothalamic-pituitary-adrenal axis as a risk factor for depression: evidence from a genetic association study.

Chronic stress and related disruption of hypothalamic-pituitary-adrenal axis reactivity is a known risk factor for depression. Besides its effects on glucocorticoids, stress also impacts the cholinergic system. Therefore, the interaction of two polymorphisms, one on the cholinergic CHRNA4 receptor gene and one on the glucocorticoid receptor gene (NR3C1), on depression was investigated. In a sample of 800 healthy participants, we genotyped for the BCL1 rs41423247 and the CHRNA4 rs1044396 single-nucleotide polymorphisms and assessed depressiveness by means of the Beck Depression Inventory. We identified a significant epistasis effect BCL1 by CHRNA4 showing that carriers of the CC genotype at the BCL1 locus who were also homozygous for the T allele at the CHRNA4 locus had the highest depression scores. This is the first evidence from molecular genetics to show that the hypothalamic-pituitary-adrenal axis and the cholinergic system--both involved in stress reactivity--represent a combined risk factor for depression.