The Role of Children's Neurophysiological Functioning in the Links Between Emotion-Parenting Behaviors and Child Anxiety Symptoms: A Biological Sensitivity to Context Framework.

A plethora of data supports links between parenting behaviors and child anxiety, but few studies have examined factors that can contribute to variability in these relations. Adopting a biological sensitivity to context framework, this study explored the role of children's physiological stress reactivity in the links between emotion-parenting and child anxiety symptoms in a group of Chinese families. Sixty-one parent-child dyads (child Mage  = 8.21 years, SD = 1.40, range = 6-12 years) participated in an acute stress protocol, from which children's physiological (cortisol and respiratory sinus arrhythmia) responses to a social speech task were recorded. Participants then completed questionnaires assessing parents' emotion-parenting behaviors and children's anxiety symptoms. Results showed that the relation between supportive emotion-parenting and child anxiety was stronger in the context of greater child RSA suppression to acute stress, such that children higher in RSA suppression exhibited lower anxiety symptoms when supportive emotion-parenting was higher than when it was lower. Thus, these findings supported the biological sensitivity to context model. No significant moderation effect was detected for cortisol reactivity or recovery. Instead, exploratory mediation analyses showed that supportive emotion-parenting was negatively related to child anxiety via greater cortisol recovery. There was also a significant indirect path where unsupportive emotion-parenting was related to blunted cortisol recovery, which in turn was associated with higher child anxiety. The results highlight the importance of coaching parents to respond in supportive ways to children's emotional expressions, particularly in the context of greater child reactivity, to help buffer against childhood anxiety symptoms.

Una plétora de datos respaldan las conexiones entre las conductas de crianza y la ansiedad infantil, pero pocos estudios han analizado los factores que pueden contribuir a la variabilidad en estas relaciones. Mediante la adopción de una sensibilidad biológica al marco del contexto, el presente estudio analizó el papel de la reactividad fisiológica al estrés de los niños en los vínculos entre las conductas de crianza emocional y los síntomas de ansiedad infantil en un grupo de familias chinas. Sesenta y una díadas padre-hijo (edad promedio de los niños = 8.21 años, desviación típica = 1.40, rango = 6-12 años) participaron en un protocolo de estrés agudo, del cual se registraron las respuestas fisiológicas de los niños (el cortisol y la arritmia sinusal respiratoria) a una tarea de habla social. Luego, los participantes contestaron cuestionarios que evaluaban las conductas de crianza emocional de los padres y los síntomas de ansiedad de los niños. Los resultados demostraron que la relación entre la crianza emocional comprensiva y la ansiedad de los niños fue más fuerte en el contexto de una mayor supresión de la arritmia sinusal respiratoria del niño ante el estrés agudo, de manera que los niños con mayor supresión de la arritma sinusal respiratoria demostraron menos síntomas de ansiedad cuando la crianza emocional comprensiva fue mayor que cuando fue menor. Por lo tanto, estos resultados respaldaron la sensibilidad biológica al modelo del contexto. No se detectó ningún efecto de moderación importante para la reactividad o recuperación del cortisol. En cambio, los análisis exploratorios de mediación demostraron que la crianza emocional comprensiva estuvo relacionada negativamente con la ansiedad de los niños mediante una mayor recuperación de cortisol. También hubo una vía indirecta significativa donde la crianza emocional incomprensiva estuvo relacionada con la recuperación disminuida de cortisol, que a su vez estuvo asociada con una mayor ansiedad infantil. Los resultados destacan la importancia de capacitar a los padres para responder de maneras comprensivas a las expresiones emocionales de los niños, particularmente en el contexto de una mayor reactividad infantil, a fin de contribuir a atenuar los síntomas de ansiedad en la niñez.

Exogenous glucocorticoids to improve extinction learning for post-traumatic stress disorder patients with hypothalamic-pituitary-adrenal-axis dysregulation: a study protocol description.

Background: Trauma-focused treatments for post-traumatic stress disorder (PTSD) are effective for many patients. However, relapse may occur when acquired extinction memories fail to generalize beyond treatment contexts. A subgroup of PTSD patients - potentially with substantial exposure to early-life adversity (ELA) - show dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which results in lower cortisol levels. Glucocorticoids, including cortisol, appear to facilitate strength and generalization of emotional memories.Objective: We describe the protocol of an integrated PTSD study. We investigate (A) associations between HPA-axis dysregulation, ELA, epigenetic markers, and PTSD treatment outcome (observational study); and (B) effects of exogenous glucocorticoids on strength and generalization of extinction memories and associated neural mechanisms [pharmacological intervention study with functional magnetic resonance imaging (fMRI)]. The objective is to provide proof of concept that PTSD patients with HPA-axis dysregulation often experienced ELA and may show improved strength and generalization of extinction learning after glucocorticoid administration.Method: The observational study (n = 160 PTSD group, n = 30 control group) assesses ELA, follow-up PTSD symptoms, epigenetic markers, and HPA-axis characteristics (salivary cortisol levels during low-dose dexamethasone suppression test and socially evaluated cold-pressor test). The pharmacological intervention study (n = 80 PTSD group, with and without HPA-axis dysregulation) is a placebo-controlled fMRI study with a crossover design. To investigate strength and generalization of extinction memories, we use a differential fear acquisition, extinction, and extinction recall task with spatial contexts within a virtual environment. Prior to extinction learning, 20 mg hydrocortisone or placebo is administered. During next-day recall, strength of the extinction memory is determined by recovery of skin conductance and pupil dilation differential responding, whereas generalization is assessed by comparing responses between different spatial contexts.Conclusion: The integrated study described in the current protocol paper could inform a personalized treatment approach in which these PTSD patients may receive glucocorticoids as a treatment enhancer in trauma-focused therapies.Trial registration: The research project is registered in the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database, https://eudract.ema.europa.eu/, EudraCT number 2020-000712-30.

This protocol reports a proof-of-concept study for glucocorticoids as an enhancer for PTSD treatment.The study examines whether glucocorticoids enhance the strength and generalization of extinction memory.A further aim is to identify HPA-axis-related PTSD subgroups that may particularly benefit.

Effects of oral contraceptives on intrusive memories: a secondary analysis of two studies using the trauma film paradigm in healthy women.

Background: Women are more likely to develop post-traumatic stress disorder (PTSD) than men. Recent research suggests an impact of oral contraceptive (OC) intake on PTSD and intrusive memories, a hallmark symptom of PTSD. Although a majority of women use OCs at some point in their lives, the effects on PTSD pathogenesis are only poorly understood.Objective: In the current paper, we aimed to investigate the impact of OC intake on the acquisition and consolidation of intrusive memories in healthy women after watching a trauma film paradigm.Methods: We performed a secondary analysis of a pooled dataset (N = 437) of two previously conducted and published studies investigating the effect of oxytocin on the development of intrusive memories.Results: Women taking OCs showed an attenuated decline of intrusive memories over time after having watched the trauma film compared to naturally cycling women (F(2.75, 1167) = 3.79, p = .03, ηp2 = .01).Conclusion: These findings indicate that the intake of OCs is associated with the development of intrusive memories after a trauma film paradigm. This indication emphasizes the need to further investigate the complex impact of OCs and gonadal hormones on fear learning processes and PTSD.

The objective of the current study was to analyze the effect of oral contraceptives on the development of intrusive memories after a trauma film paradigm by conducting a secondary analysis of previously published data.Women taking oral contraceptives show an attenuated decline of intrusive memories after watching a trauma film paradigm compared to naturally cycling women in the luteal phase.Women using oral contraceptives show higher basal saliva cortisol levels.

Effects of prenatal exposure to the 1944-45 Dutch famine and glucocorticoid receptor polymorphisms on later life PTSD susceptibility.

Background: Exposure to adversity in utero is thought to increase susceptibility to develop posttraumatic stress disorder (PTSD) following later life trauma, due to neurobiological programming effects during critical developmental periods. It remains unknown whether effects of prenatal adversity on PTSD susceptibility are modulated by genetic variations in neurobiological pathways implicated in PTSD susceptibility.Objective: We investigated whether genetic variation in the glucocorticoid receptor (GR) modulated effects of prenatal famine exposure on late adulthood PTSD symptom severity after trauma exposure in childhood and mid-to-late adulthood.Method: We included N = 439 term-born singleton adults (mean age: 72 years, 54.2% women) from the Dutch Famine Birth Cohort, born around the time of the Dutch Famine of 1944/1945, divided into exposure and control groups based on timing of the famine during gestation. Participants filled out self-report questionnaires on childhood (Childhood Trauma Questionnaire) and mid-to-late adulthood (Life Events Checklist for DSM-5) trauma, and current PTSD symptom severity (PTSD Checklist for DSM-5). GR haplotypes were determined from four functional GR single nucleotide polymorphisms (ER22/23EK, N363S, BclI and exon 9ß) in previously collected DNA. Linear regression analyses were performed to investigate associations of GR haplotype and prenatal famine exposure in conjunction with later life trauma on PTSD symptom severity.Results: We observed a significant three-way interaction between the GR Bcll haplotype, famine exposure during early gestation, and adulthood trauma exposure on PTSD symptom severity in late adulthood. Only participants exposed to famine during early gestation without the GR Bcll haplotype showed a significantly stronger positive association between adulthood trauma and PTSD symptom severity than non-exposed participants, indicating increased PTSD susceptibility.Conclusions: Our results illustrate the importance of integrated approaches considering genetics and environmental contexts throughout various life periods, including the rarely investigated prenatal environment, to elucidate how PTSD susceptibility evolves throughout life.HIGHLIGHTS Adversity during pregnancy is thought to increase offspring's PTSD risk following later life trauma, but exact neurobiological mechanisms underlying this process remain unknown.We found that effects of prenatal famine exposure on PTSD symptom severity were influenced by genetic variation in the glucocorticoid receptor, which signals effects of the stress hormone cortisol.Integrated approaches considering genetics and environmental contexts throughout both early and later life are important to understand how PTSD risk evolves throughout life.

Sleep, circadian system and traumatic stress.

The human circadian system creates and maintains cellular and systemic rhythmicity essential for the temporal organization of physiological processes promoting homeostasis and environmental adaptation. Sleep disruption and loss of circadian rhythmicity fundamentally affects master homeostasic regulating systems at the crossroads of peripheral and central susceptibility pathways, similar to acute or chronic stress and, thus, may play a central role in the development of stress-related disorders. Direct and indirect human and animal PTSD research accordingly suggests circadian-system-linked sleep, neuroendocrine, immune, metabolic and autonomic dysregulation, linking circadian misalignment to PTSD pathophysiology. Additionally, there is evidence that sleep and circadian disruption may represent a vital pre-existing risk factor in the prediction of PTSD development, while sleep-related symptoms are among the most prominent in trauma-associated disorders. These facts may represent a need for a shift towards a more chronobiological understanding of traumatic sequel and could support better prevention, evaluation and treatment of sleep and circadian disruption as first steps in PTSD management. In this special issue, we highlight and review recent advances from human sleep and chronobiological research that enhances our understanding of the development and maintenance of trauma-related disorders.

El sistema circadiano humano crea y mantiene la ritmicidad celular y sistémica esencial para la organización temporal de los procesos fisiológicos que promueven la homeostasis y la adaptación ambiental. La alteración del sueño y la pérdida del ritmo circadiano afectan fundamentalmente a los sistemas de regulación homeostáticos maestros en la encrucijada de las vías de susceptibilidad periféricas y centrales, similar al estrés agudo o crónico y, por lo tanto, pueden desempeñar un papel central en el desarrollo de trastornos relacionados con el estrés. Investigación directa e indirecta en TEPT en humanos y animales respectivamente, sugiere que el sueño ligado al sistema circadiano, la desregulación neuroendocrina, inmune, metabólica y autónoma vincula la desalineación circadiana con la fisiopatología del TEPT. Además, existe evidencia que el sueño y la alteración circadiana pueden representar un factor de riesgo vital preexistente en predicción del desarrollo de TEPT, mientras que los síntomas relacionados con el sueño se encuentran entre los mas importantes en los trastornos asociados a trauma. Estos hechos pueden representar la necesidad de un cambio hacia una comprensión más cronobiológica de la secuela traumática y podría apoyar una mejor prevención, evaluación y tratamiento del sueño y la alteración circadiana como primeros pasos en el manejo del TEPT. En este número especial, destacamos y revisamos los avances recientes del sueño en el ser humano y la investigación cronobiológica que pueda mejorar nuestra comprensión del desarrollo y mantenimiento de los trastornos relacionados con el trauma.

Optimismo Disposicional Y Estrés: Claves Para Promover El Bienestar Psicológico / Dispositional Optimism And Stress: Keys To Promoting Psychological Well-Being

Numerosos estudios señalan que los factores psicológicos afectan de forma importante al funcionamiento fisiológico del organismo. El optimismo disposicional considerado un rasgo unidimensional de personalidad, se relaciona con las expectativas de éxito futuro según la Self-Regulatory Behavior Theory. En diversos estudios, el optimismo se propone como factor modulador de la respuesta de estrés tanto crónico como agudo ya que altos niveles en la dimensión se asocian con bajos niveles de estrés percibido y cortisol. Además, el optimismo parece ser una variable clave en la regulación del ritmo circadiano del eje Hipotálamo-Hipófiso Adrenal (HHA). Esta influencia se ha estudiado con datos de cortisol en pelo, la respuesta matutina de cortisol y el nivel de cortisol a lo largo del día, encontrando resultados inconsistentes hasta el momento. En el presente trabajo se analiza la relación entre el optimismo y la respuesta de estrés acorde al eje HHA que ha mostrado ser relevante en la promoción del bienestar físico y psicológico. Asimismo, se reflexiona sobre la incorporación del optimismo disposicional en los programas de intervención psicológica como estrategia para promover el bienestar psicológico y prevenir la enfermedad en la población dada su relación con el desarrollo de alteraciones físicas y psicológicas como resultado de estados disfuncionales de estrés. (AU)

Numerous studies indicate that psychological factors significantly affect the physiological functioning of the body. Dispositional optimism, considered a one-dimensional personality trait, is related to expectations of future success according to self-regulatory behavior theory. In various studies, optimism is proposed as a modulating factor of both the chronic and acute stress response, since high levels in optimism have been associated with low levels of perceived stress and cortisol. Furthermore, optimism appearsto be a key variable in the regulation of the circadian rhythm of the hypothalamic-pituitary-adrenal (HPA) axis. This influence has been studied with data on hair cortisol, the awakening cortisol response, and the cortisol level throughout the day, with inconsistent results being found so far. In the present work, the relationship between optimism and the stress response according to the HPA axis is analyzed, which has been shown to be relevant in promoting physical and psychological well-being. Likewise, the incorporation of dispositional optimism in psychological intervention programs is considered as a strategy to promote psychological well-being and prevent disease in the population, given its relationship with the development of physical and psychological alterations as a result of dysfunctional states of stress. (AU)

Subclinical social anxiety in healthy young adults: cortisol and subjective anxiety in response to acute stress / Ansiedad social subclínica en adultos jóvenes sanos: cortisol y ansiedad subjetiva en respuesta a estrés agudo

There is no consensus about the pattern of cortisol release and its relationship with subjective anxiety in situations of stress in the population with social anxiety. Our aim was to determine the cortisol and subjective anxiety response in individuals with social anxiety subjected to an acute psychosocial stressor. 26 college students (58.6% males), mean age = 21.62 ± 0.43, were exposed to the stress or control adaptation of the Maastricht Acute Stress Test. Salivary cortisol and subjective anxiety were measured before, during, and after stress. Participants showed an increase in cortisol levels during the stress and post-stress phases, with a significantly higher response in those with high social anxiety. Participants with high social anxiety also showed, as a tendency, higher levels of subjective anxiety, especially in the post-stress phase. Only in the stress phase, cortisol and subjective anxiety correlated significantly in socially anxious participants. The findings support a cortisol hyperresponsiveness in a young, non-clinical population with high social anxiety. Future research should focus on the factors involved and the effects of this physiological response on health. Furthermore, the need to control social anxiety in experiments using a laboratory psychosocial stressor is highlighted.(AU)

No existe consenso sobre el patrón de liberación de cortisol y su relación con la ansiedad subjetiva en situaciones de estrés en población con ansiedad social. Nuestro objetivo fue determinar la respuesta de cortisol y ansiedad subjetiva en individuos con ansiedad social sometidos a un estresor psicosocial agudo. 26 universitarios (58.6% hombres), edad media = 21.62 ± 0.43, fueron expuestos a la versión estrés o control del Maastricht Acute Stress Test. El cortisol salival y la ansiedad subjetiva fueron medidos antes, durante y post-estrés. Los participantes mostraron un incremento en los niveles de cortisol durante las fases de estrés y post-estrés, con una respuesta significativamente mayor en aquellos con ansiedad social. Los participantes con alta ansiedad social mostraron, a nivel muestral, mayores niveles de ansiedad subjetiva, especialmente post-estrés. Sólo en la fase de estrés, el cortisol y la ansiedad subjetiva correlacionaron significativamente en los participantes socialmente ansiosos. Los hallazgos apoyan una hiperresponsividad de cortisol en población no clínica y joven con alta ansiedad social. Futuras investigaciones deberían estudiar los factores involucrados y efectos de esta respuesta fisiológica en la salud. Asimismo, se resalta la necesidad de controlar la ansiedad social en experimentos que utilicen un estresor psicosocial de laboratorio.(AU)

Reproductive response in offspring male rats exposed to prenatal stress and to early postnatal stimulation / Respuestas reproductivas en ratas estresadas prenatalmente, expuestas a estimulación postnatal

Stress in pregnant rats alters the pattern of secretion of corticosterone (COR) and modifies transplacentally hypothalamic-pituitary-adrenal axis (HPA) fetus. Prenatal stress during the critical hypothalamic differentiation is related to decreased fertility of male offspring by an increase in the basal level of COR. This modification could induce long-term changes in the process of apoptosis in the testis. However, early postnatal handling increases maternal behavior and could reverse the effects caused by increased secretion of COR. The aim of this research was to investigate the effects of early postnatal stimulation of male rats prenatal stressed by chronic immobilization during the last two weeks of pregnancy, on the hypothalamic-pituitary-gonadal axis and their relationship with the activity of the HPA. Male Wistar rats 3 month olds, were separated in four groups: (a) prenatally stressed animals by immobilization (IMO), without postnatal stimulation; (b) prenatally stressed animals with postnatal stimulation; (c) control animals without prenatal stress, without postnatal stimulation and (d) control animals without prenatal stress, with postnatal stimulation. In different animals groups plasmatic levels of COR, Testosterone (T) and Luteinizing Hormone (LH) were analyzed. Gonadosomatic index and testicular apoptosis was determined. In conclusion that prenatal stress by IMO increased levels of COR and inhibits the HHG axis obtaining low values of plasmatic LH and T, testicular weight, and induction of apoptosis in testes. On other hand, early postnatal stimulation results in an increase in maternal care to the offspring reversing the effects of prenatal stress on the HPG axis. This effect could be mediated by a mechanism independent of the HPA axis.

El estrés en ratas preñadas altera el patrón de secreción de corticosterona (COR) materna la cual, por vía transplacentaria, produce una alteración del eje Hipotálamo-Hipófiso-Adrenal (HHA) fetal. El estrés prenatal producido durante la etapa crítica de diferenciación hipotalámica, está relacionado con la disminución de la fertilidad en las crías macho, por un aumento en el nivel de COR basal. Esta modificación podría inducir cambios a largo plazo en el proceso de apoptosis testicular. Sin embargo, la estimulación postnatal temprana mejora el comportamiento materno, revirtiendo las alteraciones producidas por el aumento de COR en las crías adultas. El objetivo fue investigar el efecto de la estimulación postnatal temprana sobre el eje Hipotálamo-Hipófiso-Gonadal (HHG) en ratas macho estresadas prenatalmente (EP), por inmovilización crónica durante las dos últimas semanas de la preñez. Se utilizaron crías de 3 meses de edad, que fueron divididas en 4 grupos: (a) individuos EP y sin estimulación postnatal; (b) individuos EP con estimulación postnatal; (c) individuos controles no estresados prenatalmente (CP) y sin estimulación postnatal; y (d) individuos CP con estimulación postnatal. En todos los grupos se midió COR, Testosterona (T) y Hormona Luteinizante (LH). Se determinaron la apoptosis y la Caspasa 3 testicular y el índice gonadosomático. Se concluye que el estrés prenatal por inmovilización aumenta los niveles de COR del eje HHA e inhibe el eje HHG obteniendo valores bajos de LH y T plasmáticas. Se observa disminución del tamaño testicular y aumento de la apoptosis de las células testiculares. Por otro lado, la estimulación postnatal temprana se traduce en un aumento del cuidado materno hacia la cría, lo que revierte los efectos producidos por el estrés prenatal sobre el eje HHG. Este efecto podría estar mediado por algún mecanismo independiente del eje HHA.