Childhood maltreatment disrupts HPA-axis activity under basal and stress conditions in a dose-response relationship in children and adolescents.

BACKGROUND: This study investigates the impact of childhood maltreatment (CM) on hypothalamic-pituitary-adrenal (HPA)-axis functioning and on anxiety perception. Moreover, the influence of CM severity and frequency was also explored. METHODS: In total, 187 participants aged 7-17 were assessed for CM history using validated questionnaires and ad hoc interviews to be classified according to the criteria of the Tool for Assessing the Severity of Situations in which Children are Vulnerable (TASSCV). Psychopathology was ascertained using the K-SADS-PL5. To assess HPA-axis functioning, salivary cortisol samples were collected throughout a normal day and during an acute psychosocial stressor, the Trier Social Stress Test for children (TSST-C). Subjective anxiety was evaluated using STAI/-C. RESULTS: Youth with a CM history had higher overall diurnal cortisol levels (p = 0.001), blunted cortisol response to acute psychosocial stress (p = 0.002) and greater perceived anxiety (p = 0.003), than those without CM. Specifically, participants exposed to moderate/severe or often/frequent CM showed the greater diurnal cortisol output (pseverity = 0.002; pfrequency = 0.003), and blunted cortisol response during the TSST-C (pseverity = 0.006; pfrequency = 0.008). Meanwhile, youth with low CM severity/frequency exhibited a similar cortisol response to those without CM. However, perceived anxiety was higher in those exposed to CM (p < 0.001), regardless of its severity/frequency. CONCLUSIONS: Disturbances in HPA-axis functioning are already evident early after CM exposure, while psychological and physiological responses to an acute stressor are dissociated in youth exposed to CM. The dose-response relationship described in this paper highlights the need to comprehensively evaluate CM so that vulnerable children can be identified and assigned to proper interventions.

Secretory immunoglobulin A (s-IgA) reactivity to acute psychosocial stress in children and adolescents: The influence of pubertal development and history of maltreatment.

BACKGROUND: Mucosal secretory immunoglobulin A (s-IgA) is an antibody protein-complex that plays a crucial role in immune first defense against infection. Although different immune biomarkers have been associated with stress-related psychopathology, s-IgA remains poorly studied, especially in youth. OBJECTIVES: The present study investigated how s-IgA behaves in front of acute psychosocial stress in children and adolescents, including possible variability associated with developmental stage and history of childhood maltreatment (CM). METHODS: 94 children and adolescents from 7 to 17 years (54 with a current psychiatric diagnostic and 40 healthy controls) drawn from a larger Spanish study were explored (EPI-Young Stress Project). To assess biological reactivity, participants provided five saliva samples during an acute laboratory-based psychosocial stressor, the Trier Social Stress Test for Children (TSST-C). Samples were assayed for s-IgA, as well as for cortisol. Pubertal development was ascertained by Tanner stage and CM following TASSCV criteria. RESULTS: We observed s-IgA fluctuations throughout the stressor, indicating the validity of TSST-C to stimulate s-IgA secretion (F(4,199) = 6.200, p <.001). Although s-IgA trajectories followed a reactivity and recovery pattern in adolescents, children exhibited no s-IgA response when faced with stress (F(4,197) = 3.406, p =.010). An interaction was found between s-IgA and CM (F(4,203) = 2.643, p =.035). Interestingly, an interaction between developmental stage, CM history and s-IgA reactivity was identified (F(12,343) = 2.036, p =.017); while children non-exposed to maltreatment exhibited no s-IgA changes to acute stress, children with a history of CM showed a similar response to adolescents, increasing their s-IgA levels after the psychosocial stressor. CONCLUSION: Acute psychosocial stress stimulates s-IgA secretion, but only after puberty. However, children with a history of maltreatment exhibited a response resembling that of adolescents, suggesting an early maturation of the immune system. Further studies are needed to clarify the validity of s-IgA as an acute stress biomarker, including additional measures during stress exposure.

Stressful life events during adolescence and risk for externalizing and internalizing psychopathology: a meta-analysis.

The main objective of the present research was to analyze the relations between stressful life events and the externalizing and internalizing spectra of psychopathology using meta-analytical procedures. After removing the duplicates, a total of 373 papers were found in a literature search using several bibliographic databases, such as the PsycINFO, Medline, Scopus, and Web of Science. Twenty-seven studies were selected for the meta-analytical analysis after applying different inclusion and exclusion criteria in different phases. The statistical procedure was performed using a random/mixed-effects model based on the correlations found in the studies. Significant positive correlations were found in cross-sectional and longitudinal studies. A transactional effect was then found in the present study. Stressful life events could be a cause, but also a consequence, of psychopathological spectra. The level of controllability of the life events did not affect the results. Special attention should be given to the usage of stressful life events in gene-environment interaction and correlation studies, and also for clinical purposes.

Intergenerational effects of maternal childhood maltreatment on newborns' stress regulation: The role of maternal depressive symptoms.

BACKGROUND: Maternal childhood maltreatment (CM) has been repeatedly associated with negative offspring's emotional outcomes. The dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis has emerged as the main underlying physiological mechanism. OBJECTIVE: To explore the association between maternal CM and newborns' physiological and neurobehavioral stress responses, considering the role of perinatal maternal depression and bonding. PARTICIPANTS AND SETTING: 150 healthy women were followed throughout pregnancy. 79 mother-infant dyads were included in the final analyses. Maternal CM was evaluated using the Childhood Trauma Questionnaire and depressive symptoms by the Edinburgh Postnatal Depression Scale (EPDS) at each trimester. At 7 weeks postpartum, the EPDS and the Postpartum Bonding Questionnaire were administered. Newborns' behavioral responses were assessed using "States Organization" (SO) and "States Regulation" (SR) subdomains of the Neonatal Behavioral Assessment Scale (NBAS). Newborns' salivary samples were collected before and after the NBAS to study cortisol reactivity. METHODS: A cross-lagged panel model was employed. RESULTS: Infants born to mothers with higher CM presented more optimal scores on SO (ß (0.635) = 0.216, p ã€ˆ001) and SR (ß (0.273) = 0.195, p = .006), and a higher cortisol reactivity after NBAS handling (ß(0.019) = 0.217, p = .009). Moreover, newborns of mothers with higher CM and postpartum depressive symptoms exhibited a poorer performance on SR (ß (0.156 = -0.288,p = .002). Analyses revealed non-significant relationships between mother-infant bonding, newborns' cortisol reactivity and SO. CONCLUSIONS: Newborns from mothers with greater CM present higher cortisol reactivity and more optimal behavioral responses, which may reflect a prenatal HPA axis sensitization. However, those exposed to maternal postnatal depressive symptoms present poorer stress recovery.

Diurnal cortisol throughout pregnancy and its association with maternal depressive symptoms and birth outcomes.

BACKGROUND: Depression during pregnancy is a common complication that can negatively affect fetal health and birth outcomes. Cortisol is believed to be a key mediator of this association. Although pregnancy entails a natural increase in cortisol levels, preclinical depression could alter its circadian rhythm, producing excessively high overall diurnal cortisol levels that might be harmful for the fetus and future offspring development. OBJECTIVES: Using a prospective longitudinal design, we aimed to study (i) trimestral cortisol circadian rhythm and its overall levels throughout pregnancy in healthy women, (ii) the extent to which maternal depressive symptoms influence both cortisol rhythmicity and overall levels, and (iii) the possible adverse consequences of elevated maternal cortisol on the offspring's weight and gestational age at birth. STUDY DESIGN: 112 healthy pregnant women from the general Spanish population were recruited before their first pregnancy. To assess cortisol circadian rhythm, participants provided four saliva samples at each trimester of pregnancy (at awakening, 30 min after awakening, before lunch and before going to bed). Overall cortisol levels were calculated with AUCg approximation. Depressive symptoms were evaluated in each trimester and defined according to EPDS cut-off values (1st trimester, EPDS ≥ 11; 2nd and 3rd trimesters, EPDS ≥ 10). At birth, the risk for low weight, prematurity and weight birth percentile was retrieved for 100 infants. Mixed models and simple effects were employed to study changes of maternal cortisol circadian rhythm and overall levels throughout pregnancy and the possible influence of maternal depressive symptoms. Finally, logistic regressions were performed to assess the associations between maternal overall cortisol levels in each trimester of pregnancy and birth anthropometrics. RESULTS: Although overall diurnal cortisol levels increase throughout pregnancy, cortisol circadian rhythm is preserved in all trimesters [1st (F(3110)= 92.565, p < .001), 2nd (F(3,85)= 46.828, p < .001) and 3rd (F(3,90)= 65.555, p < .001)]. However, women with depressive symptoms showed a flattened cortisol circadian pattern only during the second trimester, characterized by a blunted awakening peak and reduced evening decline (F(3,85)= 4.136, p = .009), but not during the first (F(3,11)= 1.676, p = .176) or the third (F(3,90)= 1.089, p = .358) trimesters. Additionally, they did not show a cortisol increase from second to third trimester (p = .636). Finally, higher maternal cortisol levels in second and third trimesters seemed to be associated with increased risk of prematurity (adjusted OR -0.371, 95% CI 0.490-0.972, p = .034) and low birth weight percentile (adjusted OR -0.612, 95% CI 0.348-0.846, p = .007) respectively. CONCLUSION: Maternal cortisol levels increased throughout pregnancy, although cortisol circadian rhythm was preserved in all trimesters of pregnancy. However, prenatal depressive symptoms were associated with flattened maternal cortisol circadian rhythm in mid-pregnancy. Therefore, it seems that women with depressive symptoms tended to increase less gradually their cortisol levels from mid to late pregnancy. Finally, higher maternal cortisol levels in mid and late-pregnancy seem to be associated with poorer birth anthropometrics Early detection of depressive symptoms in general population could help to prevent putative obstetrical and birth adverse outcomes.

Further evidence for the association between childhood trauma and suicidal ideation in young individuals: A twin based study.

BACKGROUND: Suicide is a major cause of death among youth. Childhood trauma (CT) has emerged as a leading environmental risk factor for suicidal ideation (SI). The present study intends to understand the association between CT and SI in a sample of twins, highlighting the relevance of CT per se, regardless of genetic vulnerability. METHODS: Data were derived from a general population young twin study, the TwinssCan project (N = 796; mean age = 17.4). Different types of CT (physical, emotional and sexual) were explored with CTQ and SI through SCL-90-R. The discordance within twin-pairs was used to dissect the genetic and CT effects in SI. RESULTS: Total CT and all subdomains were associated with an increased risk for SI. The within-pair differences analysis in monozygotic and dizygotic twins suggested that part of this association is not attributable to genetic predisposition, which points out the relevance of CT itself upon the increase of SI. This result converged with CT subdomain analyses of physical abuse and neglect. LIMITATIONS: While within-pair twin analyses control for genetic risk, additional environmental shared and individual characteristics should be controlled for (such as poverty or protective factors). More detailed information on SI would be of great interest to better capture the complexity of this construct. CONCLUSION: CT appears to be an important environmental risk factor for SI and at least partly independent of Gene-Environment correlation (rGE). This study highlights the importance of including the history of CT in psychiatric evaluations of patients. The burden of the psychosocial environment on SI could be disentangled by further research on environmental risk and protective factors.

Maternal respiratory viral infections during pregnancy and offspring's neurodevelopmental outcomes: A systematic review.

Maternal infections during pregnancy, as cytomegalovirus and zika, have been consistently associated with severe newborn neurodevelopmental conditions, mainly related to vertical transmission and congenital infection. However, little is known about the neurodevelopmental consequences of maternal respiratory viral infections, which are the most prevalent infections during pregnancy. The recent COVID-19 pandemic has increased the interest in understanding the consequences of infections in offspring's development. This systematic review explores whether maternal gestational viral respiratory infections are associated with neurodevelopmental deviations in children below 10 years-old. The search was conducted in Pubmed, PsychInfo and Web of Science databases. 13 articles were revised, including information about maternal infection (Influenza, SARS-CoV-2 and unspecified respiratory infections) and offspring's neurodevelopment (global development, specific functions, temperament and behavioral/emotional aspects). Controversial results were reported regarding maternal respiratory infections during pregnancy and infants' neurodevelopment. Maternal infections seem to be associated with subtle alterations in some offspring's developmental subdomains, as early motor development, and attentional, behavioral/emotional minor problems. Further studies are needed to determine the impact of other psychosocial confounding factors.

Complex post-traumatic stress disorder (CPTSD) of ICD-11 in youths with childhood maltreatment: Associations with age of exposure and clinical outcomes.

BACKGROUND: Exposure to childhood maltreatment (CM) increases the risk of psychiatric morbidity in youths. The new Complex Post-Traumatic Stress Disorder (CPTSD) diagnosis captures the heterogeneity and complexity of clinical outcomes observed in youths exposed to CM. This study explores CPTSD symptomatology and its association with clinical outcomes, considering the impact of CM subtypes and age of exposure. METHODS: Exposure to CM and clinical outcomes were evaluated in 187 youths aged 7-17 (116 with psychiatric disorder; 71 healthy controls) following the Tools for Assessing the Severity of Situations in which Children are Vulnerable (TASSCV) structured interview criteria. CPTSD symptomatology was explored by confirmatory factor analysis, considering four subdomains: post-traumatic stress symptoms, emotion dysregulation, negative self-concept and interpersonal problems. RESULTS: Youths exposed to CM (with or without psychiatric disorders) showed greater internalizing, externalizing and other symptomatology, worse premorbid adjustment and poorer overall functioning. Youth with psychiatric disorder and exposed to CM reported more CPTSD symptomatology, psychiatric comorbidity and polypharmacy and earlier onset of cannabis use. Different subtypes of CM and the developmental stage of exposure differentially impact CPTSD subdomains. LIMITATIONS: Small percentage of resilient youths was studied. It was not possible to explore specific interactions between diagnostic categories and CM. Direct inference cannot be assumed. CONCLUSIONS: Gathering information on type and age of exposure to CM is clinically useful to understand the complexity of psychiatric symptoms observed in youths. Inclusion of the CPTSD diagnosis should increase the implementation of early specific interventions, improving youths' functioning and reducing the severity of clinical outcomes.

Stressful Life Events and Distress in Breast Cancer: A 5-Years Follow-Up.

Background/Objective: Environmental factors such as psychosocial stress have demonstrated to have an impact on the breast cancer (BC) course. This study aims to explore the impact of psychotherapy and stressful life events (SLE) on BC survivors' illness trajectories. Method: 68 women with BC underwent Positive Psychotherapy or Cognitive-Behavioral Stress Management and 37 patients were included as a control group. The effects of distress reduction and SLE on their 5-year recurrence were investigated. Additional analyses examined the effect of receiving vs. not receiving psychotherapy and of the type of therapy on survival and disease-free interval, DFI. Results: A one-point decrease of the Hospital Anxiety and Depression Scale (HADS) after psychotherapy predicted a lower risk of 5-year recurrence, OR = 0.84, p = .037, 95% CI = 0.71-0.99). Also, a one point-increase in the number threatening SLE (OR = 1.92; p = .028, 95% CI = 1.07-3.43) was related to higher 5-year recurrence. Conclusions: The findings highlight the necessity of studying not only a given situation (i.e., psychotherapy, SLE) but its specific impact on individuals.

Antecedentes/Objetivo: El estrés psicosocial ha demostrado tener un impacto en la evolución del cáncer de mama (CM). Este estudio tiene como objetivo explorar el impacto de la psicoterapia y de los acontecimientos vitales estresantes (AVE) en la supervivencia de pacientes con CM. Método: 113 mujeres con CM recibieron psicoterapia positiva o terapia cognitivo-conductual para manejar el estrés y 37 se incluyeron como grupo control. Se analizaron los efectos de la reducción de la Escala de Ansiedad y Depresión Hospitalaria (HADS) y de los AVE sobre la recurrencia a los cinco años, así como el efecto de recibir psicoterapia y del tipo de enfoque d esta sobre la supervivencia. Resultados: La reducción de un punto en la HADS después de recibir psicoterapia predijo un menor riesgo de recurrencia, OR = 0,84, p = 0,037, IC 95% = 0,71-0,99. Además, cada aumento en el número de AVE vividos como amenazantes (OR = 1,92; p = 0,028, 95% CI = 1,07-3,43) se relacionó con una mayor recurrencia. Conclusiones: Los resultados indican la necesidad de estudiar no solo la presencia de un evento potencialmente impactante en la conducta (psicoterapia o AVE) sino el efecto especifico que ha tenido en cada individuo.

Risk of Suicidal Behavior in Children and Adolescents Exposed to Maltreatment: The Mediating Role of Borderline Personality Traits and Recent Stressful Life Events.

Childhood maltreatment (CM) is associated with increased non-suicidal self-injury (NSSI) and suicidal behavior (SB), independently of demographic and mental health conditions. Self-Trauma Theory and Linehan's Biopsychosocial Model might explain the emergence of Borderline Personality Disorder (BPD) symptoms as mediators of the association between CM and the risk of SB. However, little is known regarding such relationships when the exposure is recent for young persons. Here, we study 187 youths aged 7-17, with or without mental disorders. We explore CM experiences (considering the severity and frequency of different forms of neglect and abuse), recent stressful life events (SLEs), some BPD traits (emotion dysregulation, intense anger and impulsivity), and the risk of SB (including NSSI, suicide threat, suicide ideation, suicide plan and suicide attempt). We study the direct and mediating relationships between these variables via a structural equation analysis using the statistical software package EQS. Our findings suggest that youths exposed to more severe/frequent CM have more prominent BPD traits, and are more likely to have experienced recent SLEs. In turn, BPD traits increase the risk of SLEs. However, only emotion dysregulation and recent SLEs were found to be correlated with SB. Therefore, targeted interventions on emotion dysregulation are necessary to prevent NSSI or SB in children and adolescents exposed to CM, as is the minimization of further SLEs.

Recent Stressful Life Events (SLE) and Adolescent Mental Health: Initial Validation of the LEIA, a New Checklist for SLE Assessment According to Their Severity, Interpersonal, and Dependent Nature.

The main aim of the present study was to develop and validate a checklist for adolescents, the Life Events Inventory for Adolescents (LEIA), for screening stressful life events (SLEs) of different nature (major-minor, dependent-independent, and personal-interpersonal). The LEIA was administered together with another SLE checklist (Escala de Acontecimientos Vitales [Life Events Scale], EAV), and with measures of life satisfaction and externalizing and internalizing symptoms. The results showed that the kappa and the percentage agreement reliability indices were adequate. Regarding validity evidences, the correlations found between the LEIA and the EAV ranged from .65 to .69, and between the LEIA and the psychopathological symptoms ranged from .26 to .38. Specifically, major dependent noninterpersonal SLEs were the best predictors of externalizing psychopathology; while major independent noninterpersonal SLEs were the best predictors of internalizing symptoms and low life satisfaction. To conclude, the LEIA could be considered an adequate checklist to screen for SLEs in adolescents.

Stressful Life Events and Distress in Breast Cancer: A 5-Years Follow-Up / Acontecimientos vitales estresantes y malestar emocional en cáncer de mama: seguimiento a 5 años

AbstractBackground/Objective: Environmental factors such as psychosocial stress have demonstrated to have an impact on the breast cancer (BC) course. This study aims to explore the impact of psychotherapy and stressful life events (SLE) on BC survivors’ illness trajectories. Method: 68 women with BC underwent Positive Psychotherapy or Cognitive-Behavioral Stress Management and 37 patients were included as a control group. The effects of distress reduction and SLE on their 5-year recurrence were investigated. Additional analyses examined the effect of receiving vs. not receiving psychotherapy and of the type of therapy on survival and disease-free interval, DFI. Results: A one-point decrease of the Hospital Anxiety and Depression Scale (HADS) after psychotherapy predicted a lower risk of 5-year recurrence, OR = 0.84, p = .037, 95% CI = 0.71-0.99). Also, a one point-increase in the number threating SLE (OR = 1.92; p = .028, 95% CI = 1.07-3.43) was related to higher 5-year recurrence. Conclusions: The findings highlight the necessity of studying not only a given situation (i.e., psychotherapy, SLE) but its specific impact on individuals.

ResumenAntecedentes/Objetivo: El estrés psicosocial ha demostrado tener un impacto en la evo-lución del cáncer de mama (CM). Este estudio tiene como objetivo explorar el impacto de la psicoterapia y de los acontecimientos vitales estresantes (AVE) en la supervivencia de pacientes con CM. Método: 113 mujeres con CM recibieron psicoterapia positiva o terapia cognitivo-conductual para controlar el estrés y 37 se incluyeron como grupo con-trol. Se analizaron los efectos de la reducción de la Escala de Ansiedad y Depresión Hos-pitalaria (HADS) y de los AVE sobre la recurrencia a los cinco años, así como el efecto de recibir psicoterapia y del tipo de enfoque sobre la supervivencia. Resultados: La reduc-ción de un punto en la HADS después de recibir psicoterapia predijo un menor riesgo de recurrencia, OR = 0,84, p = 0,037, IC 95% = 0,71-0,99. Además, cada aumento en el nú-mero de AVE vividos como amenazantes (OR = 1,92; p = 0,028, 95% CI = 1,07-3,43) se relacionó con una mayor recurrencia. Conclusiones: Los resultados indican la necesidad de estudiar no solo la presencia de un evento potencialmente impactante en la conducta (psicoterapia o AVE) sino el efecto específico que ha tenido en cada individuo.

Las consecuencias neurobiológicas del maltrato infantil y su impacto en la funcionalidad del eje HHA / The neurobiological consequences of child abuse and its impact on the functionality of the Hypothalamic-Pituitary-Adrenal (HPA) Axis / Les conseqüències neurobiològiques del maltractament infantil I el seu impacte en la funcionalitat de l'eix Hipotàlem-Hipofisiari-Adrenal (HHA)

Este artículo pretende revisar algunos de los mecanismos neurobiológicos afectados por el maltrato infantil, poniendo especial énfasis en la función del eje HHA, el principal mecanismo de regulación del estrés en humanos. Este eje HHA parece estar desregulado en aquellas personas que han sufrido maltrato infantil, mostrándose hiporeactivo frente situaciones de estrés psicosocial medidas mediante el Trier Social Stress Test (TSST). Todas estas alteraciones podrían estar asociadas a cambios epigenéticos que modifican la expresión génica de algunos genes de interés implicados en la regulación del eje HHA, como el gen del receptor de glucocorticoides (NR3C1). Además, se discute la gran relevancia que tienen algunos aspectos como los periodos evolutivos de exposición al maltrato, tiempo de exposición a este, la coexistencia de diferentes tipos de maltrato, la severidad o el sexo del sujeto

This article aims to review some of the neurobiological mechanisms affected by child abuse, emphasizing the function of the HPA axis, the main mechanism for regulating stress in humans. People who have suffered child abuse seem to have a deregulated HPA axis and to be hypo reactive to situations of psychosocial stress, according to the Trier Social Stress Test (TSST). All these alterations could be associated with epigenetic changes that modify the gene expression of the genes of interest involved in the regulation of the HPA axis, such as the glucocorticoid receptor gene (NR3C1). Besides, the great relevance of some aspects such as the evolutionary periods of exposure to mistreatment, the time of exposure, the coexistence of different types of mistreatment, the severity or the sex of the subject is discussed

Aquest article pretén revisar alguns dels mecanismes neurobiològics afectats pel maltractament infantil, posant especial èmfasi en la funció de l'eix HHA, el principal mecanisme de regulació de l'estrès en els éssers humans. Aquest eix HHA sembla estar desregulat en aquelles persones que han patit maltractament infantil; així, es mostra hiporeactiu enfront de situacions d'estrès psicosocial mesurades amb el Trier Social Stress Test (TSST). Totes aquestes alteracions podrien estar associades a canvis epigenètics que modifiquen l'expressió gènica d'alguns gens d'interès implicats en la regulació de l'eix HHA, com el gen del receptor de glucocorticoides (NR3C1). A més, es discuteix la gran rellevància que tenen alguns aspectes com els períodes evolutius d'exposició al maltractament, el temps d'exposició, la coexistència de diferents tipus de maltractament, la severitat o el sexe del subjecte