Conceptual endophenotypes: A strategy to advance the impact of psychoneuroendocrinology in precision medicine.

Psychobiological research has generated a tremendous amount of findings on the psychological, neuroendocrine, molecular and environmental processes that are directly relevant for mental and physical health, but have overwhelmed our capacity to meaningfully absorb, integrate, and utilize this knowledge base. Here, we reflect about suitable strategies to improve the translational success of psychoneuroendocrinological research in the era of precision medicine. Following a strategy advocated by the National Research Council and the tradition of endophenotype-based research, we advance here a new approach, termed "conceptual endophenotypes".

The role of early adversity and recent life stress in depression severity in an outpatient sample.

Pre-, peri-, and postnatal stress have frequently been reported to be associated with negative health outcomes during adult life. However, it is unclear, if these factors independently predict mental health in adulthood. We estimated potential associations between reports of pre-, peri-, and postnatal stress and depression severity in outpatients (N = 473) diagnosed with depression, anxiety or somatoform disorders by their family physician.

Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation.

The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N = 100) conducted in Basel, Switzerland (2007-10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1-3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY).

Frequency of Perceived Poststress Symptoms in Inpatients, Outpatients and Healthy Controls: The Role of Perceived Exhaustion and Stress.

Background: Poststress symptoms occur as a consequence of stress, most commonly during leisure periods such as weekends and vacations. However, the prevalence and the pathological mechanisms of poststress symptoms are poorly understood.

Methods: Here, we compared the frequency of poststress symptoms in healthy controls (n = 984), outpatients (n = 420), and inpatients (n = 101).

Assessment of the cortisol awakening response: Expert consensus guidelines.

The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30-45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening.

Lack of Breastfeeding: A Potential Risk Factor in the Multifactorial Genesis of Borderline Personality Disorder and Impaired Maternal Bonding.

Borderline personality disorder (BPD) is characterized by a pattern of intense but unstable interpersonal relationships. These interpersonal dysfunctions may originate from impaired bonding and attachment that is determined during early life. Remarkably, it has been reported that the quality of mother-infant relationship is influenced by the feeding mode.

Trier social stress test in Indian adolescents.

Objective: To test the Trier Social Stress Test for children (TSST-C) in a cohort of Indian adolescents.

Design: Cohort study.

Setting: Holdsworth Memorial Hospital, Mysore, India.

Prenatal programming of emotion regulation: neonatal reactivity as a differential susceptibility factor moderating the outcome of prenatal cortisol levels.

Objective: Hypothalamic-pituitary-adrenal (HPA) activation during pregnancy is linked to dysfunctional behavioral outcomes in the offspring. According to Belsky's differential susceptibility hypothesis, individuals vary regarding their developmental plasticity. Translating the differential susceptibility hypothesis to the field of fetal programming, we hypothesize that infants' temperament, as the constitutionally based reactivity to stimulation, moderates prenatal environmental effects on postnatal emotion regulation.

Stress-induced allodynia--evidence of increased pain sensitivity in healthy humans and patients with chronic pain after experimentally induced psychosocial stress.

Background: Experimental stress has been shown to have analgesic as well as allodynic effect in animals. Despite the obvious negative influence of stress in clinical pain conditions, stress-induced alteration of pain sensitivity has not been tested in humans so far. Therefore, we tested changes of pain sensitivity using an experimental stressor in ten female healthy subjects and 13 female patients with fibromyalgia.

How to measure prenatal stress? A systematic review of psychometric instruments to assess psychosocial stress during pregnancy.

Background: A growing body of literature documents associations of maternal psychosocial stress during pregnancy with fetal, infant and child behaviour and development. However, findings across studies are often inconsistent, which may in part be due to differences in stress definitions and assessments.

Methods: We systematically reviewed methods applied to assess maternal psychosocial stress during pregnancy in studies looking at associations with biobehavioural outcomes in the offspring.

Adult cognitive ability and socioeconomic status as mediators of the effects of childhood disadvantage on salivary cortisol in aging adults.

In this longitudinal study we investigate the influence of childhood disadvantage on midlife hypothalamic-pituitary-adrenal (HPA) axis regulation. Two mechanisms by which early life stress may affect later pathophysiology are through its influence on cognitive functioning or later socioeconomic (SES) disadvantage. We predicted that individual differences in young adult cognitive ability and midlife SES would mediate the influence of childhood disadvantage on midlife cortisol.

Prenatal adversity: a risk factor in borderline personality disorder?

Background: Patients with borderline personality disorder (BPD) show a high prevalence of early adversity, such as childhood trauma. It has also been reported that prenatal adverse conditions, such as prenatal maternal stress, drug taking, tobacco smoking or medical complications, may be associated with an increased risk of mental disorders in the offspring. Prenatal adversity is investigated here for the first time as a potential risk factor in the diagnosis of BPD.

Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF ) after acute psychosocial stress.

Environmentally induced epigenetic alterations are related to mental health. We investigated quantitative DNA methylation status before and after an acute psychosocial stressor in two stress-related genes: oxytocin receptor (OXTR) and brain-derived neurotrophic factor (BDNF ). The cross sectional study took place at the Division of Theoretical and Clinical Psychobiology, University of Trier, Germany and was conducted from February to August 2009.

Salivary cortisol in ambulatory assessment--some dos, some don'ts, and some open questions.

The impact of stress on health and disease is an important research topic in psychosomatic medicine. Because research on hypothalamic-pituitary-adrenal (HPA) axis regulation under controlled laboratory studies lacks ecological validity, it needs to be complemented by a research program that includes momentary ambulatory assessment. The measurement of salivary cortisol offers the possibility to trace the free steroid hormone concentrations in ambulant settings.

A multivariate twin study of hippocampal volume, self-esteem and well-being in middle-aged men.

Self-esteem and well-being are important for successful aging, and some evidence suggests that self-esteem and well-being are associated with hippocampal volume, cognition and stress responsivity. Whereas most of this evidence is based on studies on older adults, we investigated self-esteem, well-being and hippocampal volume in 474 male middle-aged twins. Self-esteem was significantly positively correlated with hippocampal volume (0.

Positive life events predict salivary cortisol in pregnant women.

Maternal stress during pregnancy has been repeatedly associated with problematic child development. According to the fetal programming hypothesis adverse experiences during pregnancy increase maternal cortisol, which is then assumed to exert a negative effect on fetal development. Recent studies in non-pregnant women report significant associations between positive emotionality and low cortisol levels.

No evidence of increased cortisol stress response in obese women with binge eating disorder.

Increased cortisol levels after stress have been associated with excessive food intake during binges in obese women with binge eating disorder (BED). The present study tried to replicate these findings in a sample of obese women with BED compared to obese women without BED. Twenty women with a mean BMI of 37.

Neuropattern: a new translational tool to detect and treat stress pathology. II. The Teltow study.

The present study was designed to test the clinical utility of Neuropattern (NP), a newly developed translational diagnostic tool. NP consists of biological and psychological measures that facilitate the identification of functional changes (called "neuropatterns") in patients with stress-related health problems. In this prospective, randomized control trial, we expected NP to improve therapeutic efficacy, as compared with the usual treatment.

Neuropattern: a new translational tool to detect and treat stress pathology I. Strategical consideration.

Translational research is most prominently represented by the search for biomarkers and preclinical research. Aside from generating such new measures and methodologies, translational research additionally refers to translation of integrated knowledge. This strategy involves synthesis, exchange, and dissemination of available knowledge, with the goal of improving health services and health care systems.

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood.

Leukocyte telomere length (LTL) is a predictor of age-related disease onset and mortality. The association in adults of psychosocial stress or stress biomarkers with LTL suggests telomere biology may represent a possible underlying mechanism linking stress and health outcomes. It is, however, unknown whether stress exposure in intrauterine life can produce variations in LTL, thereby potentially setting up a long-term trajectory for disease susceptibility.

Increased peripheral NF-κB pathway activity in women with childhood abuse-related posttraumatic stress disorder.

In addition to neuroendocrine changes PTSD pathophysiology may also involve dysfunction of the innate immune inflammatory system. PTSD patients have been found to exhibit increased concentrations of circulating inflammatory markers such as C-reactive protein and interleukin-6, suggesting dysfunction of the innate immune inflammatory system. However, few studies have investigated molecular signaling pathways known to critically regulate inflammation.

Negative emotionality, depressive symptoms and cortisol diurnal rhythms: analysis of a community sample of middle-aged males.

Prior research suggests that individuals with particular personality traits, like negative emotionality, are at greater risk for adverse health outcomes. Despite bivariate associations between negative emotionality, depressive symptoms and the hypothalamic pituitary adrenal axis (HPA axis), few studies have sought to understand the biological pathways through which negative emotionality, depressive symptomatology and cortisol-one of the primary hormonal products of the HPA axis--are associated. The present study explored whether negative emotionality influenced cortisol dysregulation through current depressive symptomatology and whether negative emotionality served as a moderator of the relationship between depressive symptoms and cortisol.

Genetic and environmental effects on diurnal dehydroepiandrosterone sulfate concentrations in middle-aged men.

Background: Dehydroepiandrosterone sulfate (DHEAS) is important for its association with immune system function and health outcomes. The characterization of the genetic and environmental contributions to daily DHEAS concentrations is thus important for understanding the genetics of health and aging.

Methods: Saliva was collected from 783 middle-aged men (389 complete pairs and 5 unpaired twins) as part of the Vietnam Era Twin Study of Aging.

Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression.

Postpartum depression (PPD) affects up to 19% of all women after parturition. The non-apeptide oxytocin (OXT) is involved in adjustment to pregnancy, maternal behavior, and bonding. Our aim was to examine the possible association between plasma OXT during pregnancy and the development of PPD symptoms.

Cross-sectional and 35-year longitudinal assessment of salivary cortisol and cognitive functioning: the Vietnam Era twin study of aging.

High levels of cortisol, a sign of potential hypothalamic-pituitary-adrenal (HPA) axis dysregulation, have been associated with poor cognitive outcomes in older adults. Most cortisol research has focused on hippocampal-related abilities such as episodic memory; however, the presence of glucocorticoid receptors in the human prefrontal cortex suggests that cortisol regulation is likely to be associated with prefrontally-mediated executive function abilities. We hypothesized that elevated cortisol levels would be associated with poorer frontal-executive function in addition to episodic memory.