Thomas Plieger

On the molecular genetics of flexibility: The case of task-switching, inhibitory control and genetic variants

The adjustment of behavior to changing goals and environmental constraints requires the flexible switching between different task sets. Cognitive flexibility is an endophenotype of executive functioning and is highly heritable, as indicated by twin studies. Individual differences in global flexibility as assessed by reaction-time measurement in a task-switching paradigm were recently related to a single nucleotide polymorphism in the vicinity of the dopamine d2 receptor gene DRD2. In the present study, we assessed whether the DRD2 gene is related to backward inhibition, a control mechanism that contributes to cognitive flexibility by reducing proactive interference by no longer relevant task sets. We found that carriers of the DRD2 A1+ variant who have a lower striatal dopamine d2 receptor density than A1– carriers show a larger backward inhibition effect. This is in line with previous results demonstrating increased behavioral flexibility in carriers of this genetic variant. The discussion relates the present finding to those of previous studies assessing the neurogenetic foundations of inhibitory control.

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.

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.

The impact of acute stress on cognitive functioning: a matter of cognitive demands?

ABSTRACT Introduction: There is a controversy in the literature whether stress and related cortisol responses are beneficial or impairing for cognitive functioning. Conflicting results might be due to individual differences in stress reactivity and cognitive load of the applied tasks. Methods: N = 48 participants underwent the Socially Evaluated Cold Pressor Test and were confronted with the Frankfurter Aufmerksamkeits-Inventar-2 (FAIR-2) which is a low-load attention task and two subscales of the Intelligenz-Struktur-Test 2000 R (I-S-T 2000R) as a high-load reasoning task before and after the stressor. Participants were post hoc divided into high (stress induced cortisol increase of ≥1.5 nmol/l) vs. low-cortisol responders. Results: Cortisol responders showed an increased attentional performance in the post-stress condition (η2 > .14). However, there were neither stress or responder main effects nor an interaction effect on reasoning abilities. Conclusions: Results of the present study show that stress related changes in cognitive performance are due to individual differences in cortisol response and the cognitive load of the performed task. Future studies will show if these results are also valid for alternative cognitive tasks and if they can be replicated in female participants.

The role of genetic variation in the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) in the association between cortisol response and cognition under acute stress

Although HPA - axis reactivity has repeatedly been related to cognitive functioning, ambiguity remains regarding the direction of the effect, i.e. whether it benefits or impairs functioning. Genetic factors that contribute to HPA - axis reactivity on the one hand and to cognitive functioning on the other could therefore help clarify the association between stress and cognition. We genotyped 10 single nucleotide polymorphisms (SNPs) on the NR3C1 gene (rs10482682, rs33389, rs10482633, rs10515522, rs2963156, rs4128428, rs9324918, rs41423247, rs6189, rs10052957) coding for the glucocorticoid receptor (GR) and 4 SNPs on the NR3C2 gene (rs6810951, rs4635799, rs11099695, rs2070950) coding for the mineralocorticoid receptor (MR) and required N=126 healthy males to perform tasks assessing attention and reasoning before and after experiencing an acute laboratory stressor (the Socially Evaluated Cold Pressor Test, SECPT). Haplotype analyses revealed significant effects of NR3C1 (p=0.011) and NR3C2 (p=0.034) on cortisol stress response. NR3C2 also influenced attentional performance via an interaction with stress-induced cortisol response (p<0.001). Neither NR3C1 haplotype nor NR3C2 haplotype was associated with reasoning abilities. Results suggest that the association between stress induced cortisol reactivity and cognition strongly depends on genetic variation. The idea of an optimal arousal level depending on stress reactivity and genetic disposition is discussed.

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.