Between Temperament and Psychopathology: Examples from Neuropharmacological Challenge Tests in Healthy Humans.

Background: This paper tries to demonstrate that the questionnaire-based continuum between temperament traits and psychopathology can also be shown on the biochemical level. A common feature is the incapacity to adapt to external demands, as demonstrated by examples of disturbed hormone cycles as well as neurotransmitter (TM) responses related to affective and impulse control disorders.

Methods: Pharmacological challenge tests performed in placebo-controlled balanced crossover experiments with consecutive challenges by serotonin (5-HT), noradrenaline (NA), and dopamine (DA) agonistic drugs were applied to healthy subjects, and individual responsivities of each TM system assessed by respective cortisol and prolactin responses were related to questionnaire-based facets of depressiveness and impulsivity, respectively.

A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH.

NK cell detachment from target cells is regulated by successful cytotoxicity and influences cytokine production.

Natural killer (NK) cells participate in early immune defenses against pathogens and tumors and play a major role as immune effector and regulatory cells. The NK cell-mediated elimination of an infected or cancerous cell is a highly regulated process that requires the formation of a cell contact, the establishment of an immunological synapse and the polarization and release of lytic granules. Additionally, the detachment of NK cells from target cells is important for NK cells to bind and kill other cells in a process called serial killing.

Diversity in action: exchange of perspectives and reflections on taxonomies of individual differences.

Throughout the last 2500 years, the classification of individual differences in healthy people and their extreme expressions in mental disorders has remained one of the most difficult challenges in science that affects our ability to explore individuals' functioning, underlying psychobiological processes and pathways of development. To facilitate analyses of the principles required for studying individual differences, this theme issue brought together prominent scholars from diverse backgrounds of which many bring unique combinations of cross-disciplinary experiences and perspectives that help establish connections and promote exchange across disciplines. This final paper presents brief commentaries of some of our authors and further scholars exchanging perspectives and reflecting on the contributions of this theme issue.

Benefits and limitations of drug studies in temperament research: biochemical responses as indicators of temperament.

This paper presents a discussion of principles and problems of neurotransmitter challenge tests using examples of experiments, most of which were performed in the author's laboratory. Drugs targeting synthesis, release, receptors or reuptake of dopamine, serotonin and noradrenergic transmitter (TM) systems were used for characterizing or discriminating certain temperament or personality traits and their sub-factors. Any personality or temperament trait is characterized by multiple TM responses, thus constellations of hormone responses to drugs acting on different TM systems or on different sources of TM activity were investigated within individuals in crossover designs.

Termination of the Activating NK Cell Immunological Synapse Is an Active and Regulated Process.

Cellular cytotoxicity is essential for the elimination of virus-infected and cancerous cells by NK cells. It requires a direct cellular contact through the establishment of an immunological synapse (IS) between the NK cell and the target cell. In this article, we show that not only the establishment of the IS, but also its maintenance is a highly regulated process.

Breast cancer survivors` recollection of their quality of life: Identifying determinants of recall bias in a longitudinal population-based trial.

Background: The recollections of survivors of breast cancer are an important source of information about the disease for their family, friends, and newly diagnosed patients. So far, little is known about these memories. This study investigated how accurately survivors of breast cancer remember their past quality of life (QoL) during the disease and if this memory is modified by women`s present QoL and negative affect.

Relapse (number of detoxifications) in abstinent male alcohol-dependent patients as related to personality traits and types of tolerance to frustration.

Background: Personality traits like depression on the one hand and aggression and impulsivity on the other are assumed to be predisposing factors for different types of alcohol dependence. Both types are associated with sensitivity to frustration, but this may be different for the two types of personality according to whether they are confronted with frustrations caused by withdrawal from positive or infliction of negative events. It has not been shown so far if both types of personality factors and the two different sources of frustration are differently relevant for the propensity of relapse.

The impact of coping style on gaze duration.

The understanding of individual differences in response to threat (e.g., attentional bias) is important to better understand the development of anxiety disorders.

A defined serum-free medium useful for monitoring anti-melanoma responses induced by dendritic cell immunotherapy.

Animal sera provide a non-defined source of nutrients and growth factors for mammalian cell culture. Animal serum supplementation may also introduce experimental artefacts, including immune responses against foreign serum proteins. This artefact is particularly apparent in tumour immunotherapy experiments using dendritic cells (DC) and melanoma cells cultured in fetal calf serum (FCS)-replete media.

Aggression--interactions of serotonin and testosterone in healthy men and women.

Serotonin (5-HT) and testosterone (T) have both been implicated in the regulation of aggression. Findings in humans however are very inconclusive, with respect to main effects of either system. Animal models implicate T to modulate 5-HT system activity, and furthermore have shown behaviorally relevant interactions of T and 5-HT with respect to aggression.

Do smoking intensity-related differences in vigilance indicate altered glucocorticoid receptor sensitivity?

The relationship of critical flicker fusion frequency (CFF) and a pharmacologically induced cortisol suppression by means of dexamethasone (DEX) and metyrapone (MET) was investigated during nicotine deprivation in a between-subjects design in 60 male smokers divided into light, medium and heavy smokers. DEX reduced vigilance in medium smokers and improved it in heavy smokers compared to placebo, whereas MET was more detrimental in heavy smokers. The hypothesis was put forward that the intensity of nicotine consumption is related to differences in glucocorticoid and mineralocorticoid receptor sensitivity.

Using Latent Mixed Markov Models for the choice of the best pharmacological treatment.

The choice of the best pharmacological treatment for an individual patient is crucial to optimize convalescence. Due to their effects on pharmacokinetics variables like gender and age are important factors when the pharmacological regimen is planned. By means of an example from anaesthesiology the usefulness of Latent Mixed Markov Models for choosing the optimal anaesthetic considering patient characteristics is demonstrated.

Dopamine agonist and antagonist responders as related to types of nicotine craving and facets of extraversion.

The role of dopamine (DA) in drug seeking behavior has been a matter of debate in the literature: One theory claims that DA triggers incentive motivational behavior, the other one favors the idea that DA itself is the rewarding property induced by the positive stimuli. The present experiment tries to contribute to a solution of the controversy by the approach of relating DA-associated motivational behavior to constellations of hormone response to a DA agonistic and DA antagonistic challenge performed in the same subjects and by relating their responses to different aspects of personality and smoking motivation. DA agonist (lisuride = LIS), DA antagonist (fluphenazine = FLU), and placebo (P) were applied to 36 male smokers who were deprived from smoking for 3.

Blunted ACTH and cortisol responses to systemic injection of corticotropin-releasing hormone (CRH) in fibromyalgia: role of somatostatin and CRH-binding protein.

Thirteen female patients suffering from fibromyalgia (FM) and thirteen female age-matched controls were intravenously injected with a bolus dose of 100 microg corticotropin-releasing hormone (CRH), and the evoked secretion pattern of ACTH, cortisol, somatostatin, and growth hormone (GH) was followed up for two hours, together with the plasma levels of CRH. The increases of ACTH and cortisol following CRH were not significantly different between controls and FM patients. The increase of plasma CRH following its injection was significantly higher in FM patients and lasted about 45 min, paralleled by an increase of somatostatin with a similar time course.

Prenatal stress diminishes the cytokine response of leukocytes to endotoxin stimulation in juvenile rhesus monkeys.

This study investigated whether exposing the fetal primate to repeated episodes of maternal stress would have long-lasting effects on the endotoxin-induced cytokine response and corticosteroid sensitivity of peripheral blood cells in juvenile animals. Pregnant rhesus monkeys were acutely aroused on a daily basis for 6 wk using an acoustical startle protocol, either early or late in the 24-wk pregnancy. To quantify cytokine responses and corticosteroid sensitivity in their offspring at 2 yr of age, whole blood cultures were stimulated with lipopolysaccharide and incubated with dexamethasone (DEX).

Reboxetine in a neuroendocrine challenge paradigm: evidence for high cortisol responses in healthy volunteers scoring high on subclinical depression.

This paper investigates if the highly selective norepinephrine reuptake inhibitor reboxetine leads to a dose-dependent cortisol release and if this response depends on personality dimensions related to clinical depression in healthy volunteers. Twenty-four male subjects received placebo, 2 mg, or 4 mg reboxetine in a balanced, randomized cross-over study. Cortisol was measured in saliva at six different time-points according to the kinetics of the drug.