Explore the vast range of titles available.

Maternal depression is one of the most common prenatal complications, and prenatal maternal depression predicts many child psychopathologies. Here, we apply the fetal programming hypothesis as an organizational framework to address the possibility that fetal exposure to maternal depressive symptoms during pregnancy affects fetal development of vulnerabilities and risk mechanisms, which enhance risk for subsequent psychopathology. We consider four candidate pathways through which maternal prenatal depression may affect the propensity of offspring to develop later psychopathology across the life span: brain development, physiological stress regulation (hypothalamic–pituitary–adrenocortical axis), negative emotionality, and cognitive (effortful) control. The majority of past research has been correlational, so potential causal conclusions have been limited. We describe an ongoing experimental test of the fetal programming influence of prenatal maternal depressive symptoms using a randomized controlled trial design. In this randomized controlled trial, interpersonal psychotherapy is compared to enhanced usual care among distressed pregnant women to evaluate whether reducing prenatal maternal depressive symptoms has a salutary impact on child ontogenetic vulnerabilities and thereby reduces offspring's risk for emergence of later psychopathology.

Corticosteroids, released in high amounts after stress, exert their effects via two different receptors in the brain: glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs). GRs have a role in normalizing stress-induced effects and promoting consolidation, while MRs are thought to be important in determining the threshold for activation of the hypothalamic–pituitary–adrenal (HPA) axis. We investigated the effects of MR blockade on HPA axis responses to stress and stress-induced changes in cognitive function. In a double-blind, placebo-controlled study, 64 healthy young men received 400 mg of the MR antagonist spironolactone or placebo. After 1.5 h, they were exposed to either a Trier Social Stress Test or a non-stressful control task. Responses to stress were evaluated by hormonal, subjective, and physiological measurements. Afterwards, selective attention, working memory, and long-term memory performance were assessed. Spironolactone increased basal salivary cortisol levels as well as cortisol levels in response to stress. Furthermore, spironolactone significantly impaired selective attention, but only in the control group. The stress group receiving spironolactone showed impaired working memory performance. By contrast, long-term memory was enhanced in this group. These data support a role of MRs in the regulation of the HPA axis under basal conditions as well as in response to stress. The increased availability of cortisol after spironolactone treatment implies enhanced GR activation, which, in combination with MR blockade, presumably resulted in a decreased MR/GR activation ratio. This condition influences both selective attention and performance in various memory tasks.

Pediatric major depressive disorder (MDD) represents a leading cause of disability worldwide in children and adolescents, while its underlying pathophysiology remains largely elusive. The endocannabinoid system (ECS) and the hypothalamus-pituitary-adrenal (HPA) axis are considered intertwined regulatory systems crucially implicated in the pathophysiology of depressive disorders. This study explores the cross-sectional and longitudinal association between the ECS, specifically anandamide (AEA), and the HPA axis with its main effector cortisol and MDD status and severity in children and adolescents. Utilizing data from the omega-3-pMDD trial, a phase III Randomized Clinical Trial assessing the efficacy and safety of omega-3 fatty acid supplementation in pediatric MDD, we examined hair AEA and cortisol concentrations in 110 children and adolescents aged 8-17 years, with MDD. Associations between MDD, symptom severity and hair AEA and cortisol concentrations were explored across four measurement time points (baseline, week 6, 24 and 36). Additionally, 127 healthy children and adolescents were examined once to enable cross-sectional comparisons between MDD cases and healthy controls. Baseline comparisons for the 237 children and adolescents showed lower cortisol and AEA levels in hair of children and adolescents with MDD compared to healthy controls. Longitudinal multi-level analysis over all time-points further corroborated negative longitudinal associations between hair cortisol and depressive symptoms in children and adolescents with MDD. Taken together, reduced baseline AEA and cortisol levels emerge as robust biomarker in depressed youth, while the negative longitudinal association between hair cortisol and depression symptoms might provide useful for therapy monitoring purposes. These results hold implications for early detection, diagnosis, and therapeutic response prediction in pediatric MDD.

Schizophrenia is a multifactorial disorder with a range of risk factors. Dysregulation in the systems involved in the stress response is a key component of its pathophysiology. Individuals at risk of developing schizophrenia exhibit hyperreactivity to stress and altered cognitive performance, both known as vulnerability markers. This study aims to determine whether stimulation of the prefrontal cortex can reduce reactivity to stress in unaffected siblings of patients with schizophrenia. In a randomized, sham-controlled trial, 27 participants were assigned to receive either active (  = 14) or sham (  = 13) transcranial direct current stimulation (tDCS) over the prefrontal cortex for 30 min during exposure to an acute stressor. The stress response was measured biologically, via salivary cortisol levels, and cognitively, through a reality monitoring task, which serves as an intermediate cognitive vulnerability marker. In contrast to the sham condition, active stimulation significantly reduced cortisol release in response to stress (  = 1.972;  = 0.04) and prevented stress-induced impairment in reality monitoring (  = 9.954;  = 0.004). These findings suggest that tDCS should be a promising tool for reducing stress-induced biological and cognitive reactivity in a population at risk of schizophrenia.

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus–pituitary–adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress.

Adverse experiences superseding a child’s capacity to sustain regulation of emotion and adaptive function are theorized to constitute “toxic stressors” when they induce a deleterious biological response within an individual. We ascertained presumptive parameters of toxic stress among 164 low-income infants and toddlers (ages 4–48 months) from 132 families enrolled in Early Head Start (EHS). We randomized a subset of these families into a pilot intervention arm of parenting education (the Incredible Years, TIY), which supplemented the EHS curriculum. Official report child abuse and neglect (CAN) and child behavior were serially ascertained over the course of the study. We observed relatively low associations among maternal depression, CAN, caregiver-child relationship quality, hair cortisol, and adverse child behavioral outcomes. Moreover, despite poverty and the high prevalence (51%) of CAN in this sample, the frequency of clinical-level internalizing and externalizing behavior among the children did not exceed that of the general population, by their parents’ report. The pilot supplementation of EHS with TIY improved attendance in group meetings but did not significantly reduce adverse behavioral outcomes or CAN. This study revealed marked independence of standard indices of toxic stress (child maltreatment, maternal depression, caregiver emotional unavailability) which have been presumed to be risk factors for the development of psychopathology. That they were weakly inter-correlated, and only modestly predictive of child behavioral outcomes in this EHS sample, caution against presumptions about the toxicity of individual stressors, highlight the importance of ascertaining risk (and compensatory influences) comprehensively, suggest buffering effects of programs like EHS, and demonstrate the need for greater understanding of what parameterizes resilience in early childhood.

Generalized anxiety disorder (GAD) is a common disorder in older adults, which has been linked to hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in this age group. The authors examined whether treatment of GAD in older adults with a selective serotonin reuptake inhibitor (SSRI) corrects this HPA axis hyperactivity. The authors examined adults aged 60 years and older with GAD in a 12-week randomized controlled trial comparing the SSRI escitalopram with placebo. The authors collected salivary cortisol at six daily time points for 2 consecutive days to assess peak and total (area under the curve) cortisol, both at baseline and posttreatment. Compared with placebo-treated patients, SSRI-treated patients had a significantly greater reduction in both peak and total cortisol. This reduction in cortisol was limited to patients with elevated (above the median) baseline cortisol, in whom SSRI-treated patients showed substantially greater reduction in cortisol than did placebo-treated patients. Reductions in cortisol were associated with improvements in anxiety. Additionally, genetic variability at the serotonin transporter promoter predicted cortisol changes. SSRI treatment of GAD in older adults reduces HPA axis hyperactivity. Further research should determine whether these treatment-attributable changes are sustained and beneficial.

Osteopathic treatments regulate the neurovegetative system through joint mobilizations and manipulations, and myofascial and craniosacral techniques. Despite the growing body of research, the precise impact of osteopathic medicine on the autonomic nervous system (ANS) is not yet fully elucidated. As to Kuchera's techniques, the stimulation of the sympathetic trunk and prevertebral ganglia contributed to harmonization of the sympathetic activity. However, potential relationships between the harmonization of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis largely remain uncertain and warrant further exploration. This study was designed to evaluate the effectiveness of the osteopathic sympathetic harmonization (OSH) on the SNS and the HPA axis in youth with major depressive disorder (MDD). The study included 39 youths aged 15-21 years and diagnosed with MDD. The participants were randomly assigned into either the OSH or the placebo group. Stimulation was performed on the sympathetic truncus and prevertebral ganglia in the OSH group. The stimulation of the placebo group was performed with a lighter touch and a shorter duration in similar areas. Each participant completed the Beck Depression Inventory (BDI) and the State and Trait Anxiety Inventory (SAI and TAI) before the application. Blood pressure (BP) and pulse measurements were made, and saliva samples were taken before, immediately after, and 20 min after application. The baseline BDI (p=0.617) and TAI (p=0.322) scores were similar in both groups. Although the SAI scores decreased in both groups postintervention, no statistically significant difference was found between the two groups. Subjects who received OSH had a decrease in α-amylase level (p=0.028) and an increase in cortisol level (p=0.009) 20 min after the procedure. Following OSH application in depressed youth, SNS activity may decrease, whereas HPA axis activity may increase. Future studies may examine the therapeutic efficacy of repeated OSH applications in depressed individuals.

Upon perception of a stimulus as stressful, the human brain reacts with the activation of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), to mobilize energy resources to better cope with the stressor. Since the perception of the stressor is the initial stimulus, a synchronicity between the subjective perception of stress and the physiological stress reactivity should be expected. However, according to a recent meta-analysis, these associations are weak and inconsistent. The goal of the current study was to investigate the interaction between the SNS, HPA and subjective stress perceptions, by introducing an experimental manipulation of this interaction. For this purpose, we combined the SNS inhibitor propranolol with the Trier Social Stress Test, and measured endocrinological and psychological responses to the stressor. Thirty healthy male participants were recruited and randomly assigned to either a propranolol (PROP; n = 15) or placebo (PLC; n = 15) group. All subjects were administered 80 mg of propranolol 60 minutes prior to exposure to psychosocial stress. Salivary cortisol and alpha amylase (sAA), heart rate, blood pressure and subjective stress responses were assessed throughout the study. We observed significantly reduced sAA levels and heart rate increases in the PROP group in response to stress, with no effects of the drug on systolic or diastolic blood pressure changes. In line with previous studies, a significant increase in cortisol was seen in response to the stress exposure. Importantly, the cortisol increase was significantly higher in the PROP group. A typical increase in subjective stress could be seen in both groups, with no significant group differences emerging. Complementing previous work, this study further demonstrates a significant interaction between the HPA and the SNS during acute stress. The HPA activity was found to be elevated in the presence of a suppressed SNS in reactivity to the TSST.

Studies with nonhuman primates and rodents, as well as with human children, have suggested that early separations from caregivers are often associated with changes in the functioning of the hypothalamus–pituitary–adrenal (HPA) axis. On the basis of these findings, we designed a relational intervention that was intended to normalize HPA functioning among children in foster care. This paper presents findings from a randomized clinical trial that assessed the effectiveness of a relational intervention (Attachment and Biobehavioral Catch-up [ABC]) with regard to HPA functioning. The ABC intervention was intended to enhance children's ability to regulate physiology and behavior. The control intervention (Developmental Education for Families) was intended to enhance children's cognitive skills. A comparison group of children who had never been in foster care was also included. Children's cortisol production was assessed upon arrival at the lab, and 15 and 30 min following the Strange Situation. Random effects analyses of variance were performed to assess differences in initial values and change between children in the two intervention groups. Children in the ABC intervention and comparison group children showed lower initial values of cortisol than children in the treatment control group, considering arrival at lab as initial values (p < .05). Groups did not differ significantly in change over time. These results suggest that the ABC intervention is effective in helping children regulate biology in ways more characteristic of children who have not experienced early adversity.