Matti Gärtner

Oxytocin improves mentalizing – Pronounced effects for individuals with attenuated ability to empathize

The ability to predict the behavior of others based on their mental states is crucial for social functioning. Previous studies have provided evidence for the role of Oxytocin (OXT) in enhancing the ability to mentalize. It has also been demonstrated that the effect of OXT seems to strongly depend on socio-cognitive skills with more pronounced effects in individuals with lower socio-cognitive skills. Although recent studies indicate that mentalizing is related to empathy, no study has yet examined whether the effects of OXT on mentalizing depend on the ability to empathize. 71 male participants participated in a double-blind, between-subjects, placebo-controlled experiment. The Reading the Mind in the Eye Test (RMET) was used to investigate mentalizing abilities. We analyzed the effect of OXT on easy and difficult items of the RMET depending on differential empathy scores of the participants as assessed with the Empathy Quotient (EQ). Our results showed that OXT improves mentalizing for difficult but not for easy items. We generally observed increased mentalizing accuracy in participants with higher empathy scores. Importantly, however, whereas the performance in participants with higher empathy scores was comparable in both OXT and placebo condition, OXT specifically enhanced mentalizing accuracy in participants with lower empathy scores. Our findings suggest that OXT enhances mentalizing abilities. However, we also demonstrate that not all participants benefited from OXT application. It seems that the effects of OXT strongly depend on baseline social-cognitive skills such as empathy.

Working memory-related frontal theta activity is decreased under acute stress

Acute stress impairs prefrontal cortex (PFC) function and has detrimental effects on working memory (WM) performance. Converging evidence from electrophysiological studies suggests a close link between WM processes and frontal theta (FT) activity (4-8 Hz). However, the effect of stress on WM-related FT activity has not been investigated yet. To shed light on this topic we acquired EEG data from 31 healthy male subjects who underwent a stressful and a neutral control condition. In both conditions, they performed an n-back WM task at two different difficulty levels. Our results showed that WM-related FT activity was decreased under stress. Behaviorally, we found performance impairments under stress in the difficult task condition that were related to FT decreases. Increased cortisol levels indicated a successful moderate stress induction. These findings indicate that FT is a potential neurobiological marker for intact PFC functioning during WM and further supports the recently made assumption that FT acts in the PFC to optimize performance.

Interaction of Early Life Stress and Corticotropin-Releasing Hormone Receptor Gene: Effects on Working Memory

BACKGROUND Early life stress (ELS) experience is associated with persisting working memory (WM) deficits; changes to the corticotropin-releasing hormone (CRH) system; and structural, functional, and epigenetic changes in the hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS experience to predict depression as well as neuroendocrine and neuronal reactivity. Although these findings indicate that vulnerable genotypes might also show impaired WM performance after ELS experience, no previous study investigated whether there is an interaction effect of CRHR1 polymorphisms and ELS experience on WM performance. METHODS Subjects (N = 451) were genotyped for rs110402 and rs242924 within the CRHR1 gene. We used an n-back task to investigate the hypothesis that WM performance in healthy subjects may be subtly influenced by functional differences in CRHR1 and represents an early marker of increased vulnerability after exposure to ELS. RESULTS Exposure to ELS had a particularly strong impact on WM performance in subjects with the common homozygous GG GG genotype, whereas only severe exposure to ELS interfered with WM accuracy in AT carriers. CONCLUSIONS Our data indicate that specific CRHR1 polymorphisms moderate the effect of ELS experience on WM performance. Exposure to ELS in combination with a vulnerable genotype results in subtle memory deficits in adulthood, which might develop before psychopathological symptoms.

The beneficial effect of oxytocin on avoidance-related facial emotion recognition depends on early life stress experience

RationalePrevious studies have shown that oxytocin (OXT) enhances social cognitive processes. It has also been demonstrated that OXT does not uniformly facilitate social cognition. The effects of OXT administration strongly depend on the exposure to stressful experiences in early life. Emotional facial recognition is crucial for social cognition. However, no study has yet examined how the effects of OXT on the ability to identify emotional faces are altered by early life stress (ELS) experiences. Given the role of OXT in modulating social motivational processes, we specifically aimed to investigate its effects on the recognition of approach- and avoidance-related facial emotions.MethodsIn a double-blind, between-subjects, placebo-controlled design, 82 male participants performed an emotion recognition task with faces taken from the “Karolinska Directed Emotional Faces” set. We clustered the six basic emotions along the dimensions approach (happy, surprise, anger) and avoidance (fear, sadness, disgust). ELS was assessed with the Childhood Trauma Questionnaire (CTQ).ResultsOur results showed that OXT improved the ability to recognize avoidance-related emotional faces as compared to approach-related emotional faces. Whereas the performance for avoidance-related emotions in participants with higher ELS scores was comparable in both OXT and placebo condition, OXT enhanced emotion recognition in participants with lower ELS scores. Independent of OXT administration, we observed increased emotion recognition for avoidance-related faces in participants with high ELS scores.ConclusionsOur findings suggest that the investigation of OXT on social recognition requires a broad approach that takes ELS experiences as well as motivational processes into account.

Empathy in depression: Egocentric and altercentric biases and the role of alexithymia

BACKGROUND Major depressive disorder (MDD) has been associated with empathy deficits. The exact nature of these deficits and their relation to concurrent alexithymia remain unknown. Here we tested under which conditions MDD patients with high and low alexithymia show deficient empathy, particularly investigating empathic abilities when inhibition of self-related emotional states is needed and when it is not. METHODS Healthy controls (low: n=28, high: n=14) and currently depressed MDD patients (low: n=11, high: n=18) with low or high alexithymia performed an emotional egocentricity paradigm based on tactile stimulation. This task measures empathic judgements, when emotional states of self and other differ and inhibition of self-related emotional states is needed, and when they do not and thus empathic judgments can be based on simple projection mechanisms. RESULTS Only alexithymia but not depression decreased empathy, in situations when simple projection sufficed. However, when inhibition of self-related emotional states was needed, MDD patients showed an egocentric bias during empathic judgments and an altercentric bias during self emotion judgments, the latter suggesting heightened emotional contagion, both independent of alexithymia. Across the entire sample, alexithymia decreased the size of the egocentric bias. LIMITATIONS This study was based on a relatively sample size. CONCLUSIONS These results suggest that MDD patients show intact empathic judgments, when simple projection is required and no concurrent alexithymia is present. In situations when incongruent emotional states of self and other have to be resolved, MDD patients are prone to egocentric and altercentric biases.

Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach

The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognitive functions across the lifespan in a sample of 378 healthy subjects (age range 18-89 years). Consistent with previous findings we found an age-related cognitive decline across a wide range of neuropsychological domains (memory, attention, executive functions), thereby proving the usability of our tablet-based application. Regardless of prior computer experience, subjects of all age groups were able to perform the tasks without instruction or feedback from an experimenter. Increased motivation and compliance proved to be beneficial for task performance, thereby potentially increasing the validity of the results. Our promising findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction.

Frontal midline theta oscillations during mental arithmetic: effects of stress

Complex cognitive tasks such as mental arithmetic heavily rely on intact, well-coordinated prefrontal cortex (PFC) function. Converging evidence suggests that frontal midline theta (FMT) oscillations play an important role during the execution of such PFC-dependent tasks. Additionally, it is well-established that acute stress impairs PFC function, and recent evidence suggests that FMT is decreased under stress. In this EEG study, we investigated FMT oscillations during a mental arithmetic task that was carried out in a stressful and a neutral control condition. Our results show late-onset, sustained FMT increases during mental arithmetic. In the neutral condition FMT started to increase earlier than in the stress condition. Direct comparison of the conditions quantified this difference by showing stronger FMT increases in the neutral condition in an early time window. Between-subject correlation analysis showed that attenuated FMT under stress was related to slowed reaction times. Our results suggest that FMT is associated with stimulus independent mental processes during the natural and complex PFC-dependent task of mental arithmetic, and is a possible marker for intact PFC function that is disrupted under stress.

Variation in the corticotropin-releasing hormone receptor 1 (CRHR1) gene modulates age effects on working memory

Decline in working memory (WM) functions during aging has been associated with hippocampal dysfunction mediated by age-related changes to the corticotropin-releasing hormone (CRH) system. Recent reports suggest that GG-homozygous individuals of single nucleotide polymorphisms (rs110402 and rs242924) in the CRH receptor 1 (CRHR1) gene show increased stress vulnerability and decreased BOLD responses in WM relevant regions. However, until now, no study investigated the interaction effects of variation in the CRHR1 gene and age on individual differences in WM. Here, young, middle-aged and old subjects (N = 466) were genotyped for rs110402 and rs242924 within the CRHR1 gene and an n-back task was used to investigate the hypothesis that vulnerable genotypes (GG-homozygotes) would show impaired WM functions that might be magnified by increased CRH production with advancing age. Our results show an impact of genotype already in middle-age with significantly better performance in AT-carriers. Working memory performance in AT-carriers did not differ between young and middle-aged subjects, but was significantly impaired in old age. In GG-homozygotes, severe working memory dysfunction occurred already in middle age. Our data indicate that GG-homozygotes of CRHR1 rs110402 and rs242924 represent a genetically driven subtype of early WM impairments due to alterations in hippocampal CRHR1 activation. Early interventions that have proven effective in delaying cognitive decline appear to be particularly important for these subjects at risk for premature memory decline, who are in the prime of their personal and professional lives.

Encoding-related EEG oscillations during memory formation are modulated by mood state

Mood states have a strong impact on how we process incoming information. It has been proposed that positive mood facilitates elaborative, relational encoding, whereas negative mood promotes a more careful, stimulus-driven encoding style. Previous electrophysiological studies have linked successful information encoding to power increases in slow (<8 Hz) delta/theta and fast (>30 Hz) gamma oscillations, as well as to power decreases in midrange (8-30 Hz) alpha/beta oscillations. Whether different mood states modulate encoding-related oscillations has not been investigated yet. In order to address this question, we used an experimental mood induction procedure and recorded electroencephalograms from 20 healthy participants while they performed a free recall memory task after positive and negative mood induction. We found distinct oscillatory patterns in positive and negative mood. Successful encoding in positive mood was accompanied by widespread power increases in the delta band, whereas encoding success in negative mood was specifically accompanied by frontal power decreases in the beta band. On the behavioral level, memory performance was enhanced in positive mood. Our findings show that mood differentially modulates the neural correlates of successful information encoding and thus contribute to an understanding of how mood shapes different processing styles.

The interaction of corticotropin-releasing hormone receptor gene and early life stress on emotional empathy

&NA; Early life stress (ELS) is associated with increased vulnerability for depression, changes to the corticotropin‐releasing hormone (CRH) system and structural and functional changes in hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS to predict depression, cognitive functions and hippocampal activity. Social cognition has been related to hippocampal function and might be crucial for maintaining mental health. However, the interaction of CRHR1 gene variation and ELS on social cognition has not been investigated yet. We assessed social cognition in 502 healthy subjects to test effects of ELS and the CRHR1 gene. Participants were genotyped for rs110402 and rs242924. ELS was assessed by Childhood Trauma Questionnaire, social cognition was measured via Multifaceted Empathy Test and Empathy Quotient. Severity of ELS was associated with decreased emotional, but not cognitive empathy. Subjects with the common homozygous GG GG genotype showed decreased implicit emotional empathy after ELS exposure regardless of its severity. The results reveal that specific CRHR1 polymorphisms moderate the effect of ELS on emotional empathy. Exposure to ELS in combination with a vulnerable genotype results in impaired emotional empathy in adulthood, which might represent an early marker of increased vulnerability after ELS.