Longitudinal study of peer victimization, social support, and mental health during early adolescence.

BACKGROUND: Peer victimization predicts the development of mental health symptoms in the transition to adolescence, but it is unclear whether and how parents and school environments can buffer this link. METHODS: We analyzed two-year longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study, involving a diverse sample of 11 844 children across the United States (average at baseline = 9.91 years; standard deviation = 0.63; range = 8.92-11.08; complete case sample = 8385). Longitudinal associations between peer victimization and two-year changes in mental health symptoms of major depression disorder (MDD), separation anxiety (SA), prodromal psychosis (PP), and attention-deficit/hyperactivity disorder (ADHD) were examined including a wide range of covariates. Mixed linear models were used to test for the moderating effects of parental warmth and prosocial school environment. RESULTS: 20% of children experienced peer victimization. Higher exposure to peer victimization was associated with increases in MDD, SA, and ADHD symptoms. Parental warmth was associated with decreases in MDD symptoms but did not robustly buffer the link between peer victimization and mental health symptoms. Prosocial school environment predicted decreases in PP symptoms and buffered the link between peer victimization and MDD symptoms but amplified the link between peer victimization and SA and ADHD symptoms. CONCLUSIONS: Peer victimization is associated with increases in mental health symptoms during the transition to adolescence. Parental warmth and prosocial school environments might not be enough to counter the negative consequences of peer victimization on all mental health outcomes.

Separation anxiety disorder, perceived overprotection and quality of life in epilepsy patients.

OBJECTIVE: People with epilepsy suffer from the stress of living with a chronic, unpredictable disease that can lead to discrimination, misunderstanding, social stigma, and loss of autonomy in activities of daily life, elevating anxiety. Within the scope of this research, we aimed to elucidate the frequency of separation anxiety disorder in adult people with epilepsy and to examine the relationship between separation anxiety symptoms, perceived overprotection, and quality of life in comparison to the control group. MATERIAL AND METHODS: This prospective study was conducted with 105 people with epilepsy and 115 healthy volunteers. All participants were evaluated by a psychiatrist in this study using a DSM-5-based clinical interview. Sociodemographic Data Questionnaire, Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), Separation Anxiety Symptom Inventory (SASI), Adult Separation Anxiety Questionnaire (ASA-27), Beck Depression Inventory (BDI) were administered to both groups, and Overprotection Scale, Quality of Life in Epilepsy Inventory (QOLIE-31) to only epilepsy group. Hierarchical regression analysis was used to explain the quality of life in epilepsy. Multivariate linear regression analysis was used to explain separation anxiety symptom scores. RESULTS: The rates of education, employment, and living alone were lower in the epilepsy group (p < 0.001, p < 0.001 and p < 0.001). Separation anxiety disorder of adulthood and other psychiatric comorbidities were significantly higher in the epilepsy group (p = 0.029 and p = 0.003). There was a significant negative correlation between the quality of life in epilepsy and separation anxiety symptom level, overprotection, and depression scores (p < 0.001, p = 0.01 and p < 0.01). In the logistic regression analysis, adult separation anxiety symptom level and depression scores were found to be independent factors for quality of life in epilepsy (p = 0.029 and p < 0.01). In patients with epilepsy, depression and quality of life scores were predictors for adult separation anxiety symptoms severity (p = 0.02 and p = 0.01). CONCLUSION: The frequency of diagnosis of separation anxiety disorder in adulthood was significantly higher in people with epilepsy. Overprotective attitudes of families and low quality of life were associated with high levels of separation anxiety.

A LONGITUDINAL STUDY OF CHILDHOOD SEPARATION ANXIETY DISORDER AND ITS IMPLICATIONS FOR ADOLESCENT PSYCHOPATHOLOGY.

A prevalent psychiatric disorder called Child Separation Anxiety Disorder (SAD) is characterized by extreme discomfort when a child gets separated from their primary carers. While SAD's quick consequences on kids are well-researched, its long-term implications for teenage psychopathology have received less attention. This longitudinal study aims to ascertain the connection between child SAD and future psychopathological consequences in adolescents. 500 adolescents were chosen as part of the adolescent depression project, and at the age of 17, we retrospectively evaluated past and present mental disorders. At ages 25 and 32, they conducted diagnostic evaluations of these people during adolescence while they continued to monitor them. Based on childhood/adolescent assessments, the participants were split into different groups: SAD (n=34), other forms of Anxiety (n=76), a control group with combined psychiatric conditions (n=205), and mentally sound control group (n=185). Statistics were evaluated by hierarchical multiple logistic regression after various illnesses and pertinent demographic variables were considered. It implies that SAD has a high risk (80.2%) of being a significant risk indicator for the emergence of mental illnesses in young adults. This study highlights the importance of early SAD management and therapy and the possible advantages of treating SAD in lowering the likelihood of developing other mental health problems in adolescence. It also emphasizes the value of continuous studies to comprehend these connections and enhance the effects on SAD sufferers' psychological well-being.

Relationship of behavioral inhibition to separation anxiety in a sample (N = 377) of adult individuals with mood and anxiety disorders.

BACKGROUND: Behavioral Inhibition (BI) is an early temperamental trait characterized by shyness, withdrawal, avoidance, uneasiness, and fear of unfamiliar situations, people, objects, and events. The DSM-5 refers to behavioral inhibition as a temperamental factor related to neurodevelopmental conditions in childhood, including attention deficit hyperactivity disorder, selective mutism, and specific phobias; and to its influence on adult anxiety disorders including social anxiety disorder, agoraphobia, and generalized anxiety disorder, but, interestingly, not separation anxiety disorder (SAD). However, there are phenomenological overlaps between BI and SAD. We aimed to explore whether there is a correlation between BI as an early temperamental trait and childhood or adult separation anxiety disorder. METHODS: The study was conducted in 377 consecutive adults (mean age 40.2±12.4 years) outpatients with anxiety and mood disorders as the principal diagnosis, grouped on the presence/absence of a DSM-5 diagnosis of childhood or adult separation anxiety disorder. Separation anxiety was assessed by the Structured Clinical Interview for Separation Anxiety (SCI-SAS) and the Adult Separation Anxiety Checklist (ASA27). Behavioral inhibition was assessed by the Retrospective Self-Report of Inhibition (RSRI). RESULTS: The four comparison groups included: 1) 168 patients without childhood or adult SAD, 2) 81 with adult SAD, 3) 97 with both adult SAD and childhood SAD, and 4) 31 with childhood SAD only. The group with both adult and childhood SAD had the highest scores on RSRI total and sub-scale scores. Both groups with adult SAD had significantly higher RSRI scores than the group with only childhood SAD or without SAD. Significant bivariate correlations were found between ASA-27 scores and RSRI scores. Correlations between RSRI scores and measures of anxiety and depressive symptoms were significantly weaker than those on the ASA-27. Regression analyses showed a significant predictive value of RSRI scores on ASA-27 total score, but not of age of onset of SAD. CONCLUSIONS: BI has an onset in the very first years of life and may represent a potential developmental endophenotype for later anxiety disorders. Our findings indicate that BI and separation anxiety are connected in individuals with affective and anxiety disorders. This may have important clinical and therapeutic implications for preventive interventions.

Hypothalamus-pituitary-adrenal axis imbalance and inflammation contribute to sex differences in separation- and restraint-induced depression.

Whether social contact contributes to the underlying mechanisms of depression and the observed sex differences is unclear. In this study, we subjected young male and female mice to separation- and restraint-induced stress for 4 weeks and assessed behaviors, neurotransmitter levels, hormones, and inflammatory cytokines. Results showed that, compared with controls, male mice exposed to stress displayed significant decreases in body weight and sucrose preference after 1 week. In the fourth week, they exhibited a higher degree of anxiety (open field test) and depressive-like behavior (forced swim test). Moreover, the males showed significant decreases in monoamine neurotransmitters, including norepinephrine and dopamine in striatum, and an increase in pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1ß in serum. In contrast, females showed persistent loss of weight during stress and displayed significant decreases in sucrose preference after stress. Importantly, the females but not males showed activation of the hypothalamus-pituitary-adrenal (HPA) axis, with significantly higher levels adrenocorticotropic hormone. Additionally, mRNA level of c-fos and AVP showed there was significant interaction between stress and sex. Finally, we conclude that an imbalance of the HPA axis and inflammation might be important contributors to sex differences in separation/restraint-induced depressive behavior and that changes might be mediated by c-fos and AVP.

Internet-delivered cognitive behavior therapy with minimal therapist support for anxious children and adolescents: predictors of response.

BACKGROUND: In general, Internet-delivered cognitive behavior therapy (iCBT) produces significant reductions in child and adolescent anxiety, but a proportion of participants continue to show clinical levels of anxiety after treatment. It is important to identify demographic, clinical, and family factors that predict who is most likely to benefit from iCBT in order to better tailor treatment to individual needs. METHODS: Participants were 175 young people (7-18 years) with an anxiety disorder, and at least one of their parents, who completed an iCBT intervention with minimal therapist support. Multilevel modeling (MLM) examined predictors of response to iCBT as measured by the slope for changes in the primary outcome measures of child- and parent-reported anxiety scores, from pretreatment, to 12-weeks, 6-month, and 12-month follow-ups, controlling for pretreatment total clinician severity ratings of all anxiety diagnoses. RESULTS: Child age, gender, father age, parental education, parental mental health, parenting style, and family adaptability and cohesion did not significantly predict changes in anxiety in the multivariate analyses. For child-reported anxiety, greater reductions were predicted by a separation anxiety disorder diagnosis (SEP) and elevated depression, with lower reductions predicted by poor couple relationship quality. For parent-reported child anxiety, greater reductions were predicted by higher pretreatment total CSRs, SEP, and lower family income, with lower reductions for children of older mothers. Irrespective of these predictors of change, children in general showed reductions in anxiety to within the normal range. CONCLUSIONS: Overall, children responded well to iCBT irrespective of the demographic, clinical, and family factors examined here. Poor couple relationship quality and older mother age were risk factors for less positive response to iCBT in terms of reductions in anxiety symptoms although still to within the normal range.

Ambiguous Loss in Transnational Families' Adolescents: An Exploratory Study in Ecuador.

In psychosocial migration literature, the perspective of ambiguous loss has been relevant to articulate personal and relational experiences in the context of transnational families and ongoing separation. Most studies have focused on adult members' experiences of transnational families, but research exploring ambiguous loss in adolescents whose parents have migrated is still lacking. The present study aimed to explore adolescents' lived experiences of parental migration. In a pilot explorative study, 14 adolescents with at least one parent who migrated were interviewed about their lived experiences of transnational parent-child relationships and ongoing parent-child separation. Data analysis identified four themes in participants' accounts: practices of separation creating confusion; current relationship with migrant parents permeated by ambiguity; distrustful representations of migrant parents; and family and social dynamics reactivating the pain of loss. The findings reveal how in the context of parental migration, patterns of separation and ongoing relational processes, compounded by the uncertainty of reunification and an exclusionary social fabric, constitute core elements that shape adolescents' lived experiences of parent-child relationships characterized by ambiguity.

En la bibliografía sobre las consecuencias psicosociales de la migración, la perspectiva de la pérdida ambigua ha sido relevante para expresar las experiencias personales y relacionales en el contexto de las familias transnacionales y la separación constante. La mayoría de los estudios se han centrado en las experiencias de los miembros adultos de las familias transnacionales, pero aun faltan investigaciones que analicen la pérdida ambigua en los adolescentes cuyos padres han emigrado. El presente estudio tiene como finalidad analizar las vivencias de los adolescentes de padres migrantes. En un estudio piloto exploratorio, se entrevistó a 14 adolescentes con al menos un padre que emigró acerca de sus vivencias con respecto a las relaciones transnacionales entre padre e hijo y la separación constante entre padre e hijo. Los análisis de datos identificaron cuatro temas en los informes de los participantes: las prácticas de separación que generan confusión; la relación actual con los padres emigrantes impregnada por la ambigüedad; las representaciones desconfiadas de los padres emigrantes; y la dinámica familiar y social que reactiva el dolor de la pérdida. Los resultados revelan cómo, en el contexto de la migración parental, los patrones de separación y los procesos relacionales constantes, agravados por la incertidumbre de la reunificación y una estructura social exclusivista, constituyen elementos fundamentales que moldean las vivencias de los adolescentes en las relaciones entre padres e hijos caracterizadas por la ambigüedad.

Infant Attachment Insecurity and Baseline Physiological Activity and Physiological Reactivity to Interpersonal Stress: A Meta-Analytic Review.

This meta-analytic review (k = 5-10; N = 258-895) examined links between attachment insecurity and physiological activity at baseline and in response to interpersonal stress elicited by separation-reunion procedures in the early life course (1-5 years). Insecurity was trivially, nonsignificantly associated with baseline physiological activity (heart rate [HR]: g = -.06; respiratory sinus arrhythmia [RSA]: g = -.06; cortisol: g = .01) and nonsignificantly associated with physiological reactivity to separation from parents (HR: g = -.001; RSA: g = .24). However, insecurity was moderately associated with heightened RSA (g = .26) and cortisol (g = .27) reactivity upon reunion with parents. Findings provide insight into the biobehavioral organization of attachment, suggesting that early insecurity is associated with heightened physiological reactivity to interpersonal stress.

Working memory moderates the association between early institutional care and separation anxiety symptoms in late childhood and adolescence.

Adverse caregiving, for example, previous institutionalization (PI), is often associated with emotion dysregulation that increases anxiety risk. However, the concept of developmental multifinality predicts heterogeneity in anxiety outcomes. Despite this well-known heterogeneity, more work is needed to identify sources of this heterogeneity and how these sources interact with environmental risk to influence mental health. Here, working memory (WM) was examined during late childhood/adolescence as an intra-individual factor to mitigate the risk for separation anxiety, which is particularly susceptible to caregiving adversities. A modified "object-in-place" task was administered to 110 youths (10-17 years old), with or without a history of PI. The PI youths had elevated separation anxiety scores, which were anticorrelated with morning cortisol levels, yet there were no group differences in WM. PI youths showed significant heterogeneity in separation anxiety symptoms and morning cortisol levels, and WM moderated the link between caregiving and separation anxiety and mediated the association between separation anxiety and morning cortisol in PI youth. Findings suggest that (a) institutional care exerts divergent developmental consequences on separation anxiety versus WM, (b) WM interacts with adversity-related emotion dysregulation, and (c) WM may be a therapeutic target for separation anxiety following early caregiving adversity.

Separation anxiety and gender variance in a community sample of children.

In clinical child and retrospective adult samples, childhood gender variance (GV; i.e., cross-gender behaviour) has been associated with separation anxiety (SA; i.e., distress related to separation from attachment figures) in males. This study examined GV and SA in a nonclinical sample of 892 boys and 933 girls aged 6-12 years via parent-reports. Parental factors (i.e., parenting style, parent-child relationship, willingness to serve as an attachment figure, attitudes towards gender stereotypes in children) were examined as potential moderators. GV predicted SA in boys, even when statistically controlling for general psychopathology and demographic variables. Authoritative parenting, closeness in the parent-child relationship, willingness to serve as an attachment figure, and liberal attitudes towards gender stereotypes in children moderated the association between GV and SA in both boys and girls. Thus, SA may be a unique internalizing problem related to GV in boys in nonclinical samples and influenced by a variety of parental factors.

Mind and mourning: The primacy of "we" in complicated grief.

Standard models of complicated grief rely on a self-other divided mind that reflects the physical separateness of individuals. In these models, grief persists for those mourners who cannot reorganize self-and-other mental representations or adapt to identity changes after loss. However, advances in cognitive science indicate that relationships are often processed via distributed social-cognitive coding whereby individuals together form a psychologically extended common mind. I propose a novel "we" hypothesis in which shared representations, rather than self-other distinctions, shape the mind for a subgroup of mourners with complicated grief. Recognition of "we-experiences" in mourning can enhance grief theory, research, and practice.

Persistent complex bereavement symptoms explain impairments above depression, posttraumatic stress, and separation anxiety: an incremental validity study.

The present study examined the incremental validity of persistent complex bereavement disorder (PCBD) symptoms using an on-line survey of 255 bereaved college students. A series of hierarchical multiple regression analyses examined the extent to which PCBD symptoms explained unique variance in different domains of life impairment, beyond symptoms of depression, posttraumatic stress, and separation anxiety. The results supported the incremental validity of PCBD symptoms for fear of future losses, sleep impairment, and work/social impairment. However, PCBD symptoms did not account for loneliness scores. These findings collectively support the validity and clinical utility of the DSM-5's PCBD construct.

The characteristics of the comorbidity between social anxiety and separation anxiety disorders in adult patients.

Objective: In the present study, we compared social anxiety disorder (SAD) patients with (n = 31) and without childhood and adulthood separation anxiety disorder (SeAD) (n = 50) with respect to suicidal behavior, avoidant personality disorder (AvPD), other anxiety disorders (ADs), and major depression as well as some sociodemographic variables. Methods: In assessment of patients, we used Structured Clinical Interview for Separation Anxiety Symptoms, childhood and adulthood Separation Anxiety Symptom Inventories, Liebowitz Social Anxiety Scale, The SCID-II Avoidant Personality Disorder Module, Beck Depression Inventory, and Beck Scale for Suicidal Ideation. Results: SAD patients with SeAD had higher comorbidity rates of AvPD, other lifetime ADs and panic disorder, and current major depression than those without SeAD. The current scores of SAD, depression, and suicide ideation and the mean number of AvPD symptoms were significantly higher in comorbid group compared to pure SAD subjects. The SAD and SeAD scores had significant associations with current depression, suicide ideations, and AvPD. The mean number of AvPD criteria and the current severity of depression were significantly associated with the comorbidity between SAD and SeAD. Conclusion: Our findings might indicate that the comorbidity of SeAD with SAD may increase the risk of the severity of AvPD and current depression.

Content-Specific Interpretation Bias in Children with Varying Levels of Anxiety: The Role of Gender and Age.

The current study examined whether children varying in their levels of social anxiety, separation anxiety and spider fear exhibit a negative interpretation bias specific for their fears. Furthermore, age and gender were assessed as moderators of this relation. Children (N = 603) of the age of 7-12 years were asked to solve ambiguous scenarios reflecting social threat, separation threat or spider threat. Children's levels of anxiety were assessed with self-report questionnaires. Results indicated that children scoring higher on self-reported social anxiety, separation anxiety or spider fear, displayed a negative interpretation bias for the threat-scenarios pertaining to their specific anxiety or fear, even after controlling for comorbidity with other anxiety subtypes. Contrary to our hypotheses, we did not find moderating effects of age or gender. These results indicate that even in a community sample, content-specificity of negative interpretation biases is present.

Investigation of the Fear of 7-18-Year-Old Hospitalized Children for Illness and Hospital.

Illness and hospitalization are conditions leading to negative effects in children's lives regardless of their age. This study was performed descriptively in order to examine the fears of hospitalized children for illness and hospital. The study was descriptive and sectional and performed in Karabük University (Turkey) Training and Research Hospital between February 1 and May 1, 2015. Sample of the study was composed of 144 children who were hospitalized due to an acute illness and their parents who approved to participate in the study. Participant information form and an information form that was prepared to evaluate the fears of children for illness and hospital were used as data collection tools. Data were collected by face-to-face interview technique. Statistical analyses were used to assess data. It was found that 56.2% of children in the study were males and were between 7 and 10 years of age; 42.4% were scared of getting illness. 39.5% of 86 children who were previously hospitalized have stated that they experienced fear due to hospitalization; injections were in the first place among causes of fear by 64.7%. When the causes of children's fear for illness and hospital were examined, it was determined that "undergoing an operation (3.21 ± 1.13)," "staying away from the family during hospitalization (3.11 ± 0.96)" and "worrying the family when he/she gets an illness (3.02 ± 1.05)" were in the first three ones. When the relationship between some characteristics of the children and their parents and children's status of fear for illness was investigated, it was detected that there was a significant difference between their previous fear of hospitalization and their current status of fear for getting illness (p = 0.003). It was observed that children in the study experienced fear for illness and hospitalization and the percentage of children with fears was found to be high. It was also determined that undergoing an operation, staying away from the family during hospitalization and worrying the family when he/she gets an illness were among the first causes of their fears.

Early life voiding dysfunction leads to lower urinary tract dysfunction through alteration of muscarinic and purinergic signaling in the bladder.

Lower urinary tract dysfunction (LUTD) is a common problem in children and constitutes up to 40% of pediatric urology clinic visits. Improved diagnosis and interventions have been leading to better outcomes in many patients, whereas some children are left untreated or do not respond to the treatment successfully. In addition, many of these patients are lost by the pediatric urologists during their teenage years, and the outcome in later life largely remains unidentified. Studies suggest childhood LUTD is associated with subsequent adult urinary tract symptoms. However, whether and how early life LUTD attributes to urinary symptoms in those patients later in life remains to be elucidated. In the current study, we investigated the effects of early life voiding perturbation on bladder function using a neonatal maternal separation (NMS) protocol in mice. The NMS group displayed a delayed development of voluntary voiding behavior, a significant reduction of functional bladder capacity, and bladder overactivity compared with control mice later in life. In vitro evaluation of detrusor smooth muscle and molecular study showed a decrease in muscarinic contribution alongside an increase in purinergic contribution in detrusor contractility in NMS mice compared with control group. These results suggest that early life bladder dysfunction interfered with the normal maturation of the voluntary micturition control and facilitated LUTD in a later stage, which is at least partly attributed to an alteration of muscarinic and purinergic signaling in the urinary bladder.

Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats.

BACKGROUND & AIMS: Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity. METHODS: We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity). We also compared the mycobiomes of Long-Evans rats separated from their mothers (hypersensitive) with non-handled (normally sensitive) rats. We investigated whether fungi can cause visceral hypersensitivity using rats exposed to fungicide (fluconazole and nystatin). The functional relevance of the gut mycobiome was confirmed in fecal transplantation experiments: adult maternally separated rats were subjected to water avoidance stress (to induce visceral hypersensitivity), then given fungicide and donor cecum content via oral gavage. Other rats subjected to water avoidance stress were given soluble ß-glucans, which antagonize C-type lectin domain family 7 member A (CLEC7A or DECTIN1) signaling via spleen-associated tyrosine kinase (SYK), a SYK inhibitor to reduce visceral hypersensitivity, or vehicle (control). The sensitivity of mast cells to fungi was tested with mesenteric windows (ex vivo) and the human mast cell line HMC-1. RESULTS: α diversity (Shannon index) and mycobiome signature (stability selection) of both groups of IBS patients differed from healthy volunteers, and the mycobiome signature of hypersensitive patients differed from that of normally sensitive patients. We observed mycobiome dysbiosis in rats that had been separated from their mothers compared with non-handled rats. Administration of fungicide to hypersensitive rats reduced their visceral hypersensitivity to normal levels of sensitivity. Administration of cecal mycobiomes from rats that had been separated from their mothers (but not non-handled mycobiome) restored hypersensitivity to distension. Administration of soluble ß-glucans or a SYK inhibitor reduced visceral hypersensitivity, compared with controls. Particulate ß-glucan (a DECTIN-1 agonist) induced mast cell degranulation in mesenteric windows and HMC-1 cells responded to fungal antigens by release of histamine. CONCLUSIONS: In an analysis of patients with IBS and controls, we associated fungal dysbiosis with IBS. In studies of rats, we found fungi to promote visceral hypersensitivity, which could be reduced by administration of fungicides, soluble ß-glucans, or a SYK inhibitor. The intestinal fungi might therefore be manipulated for treatment of IBS-related visceral hypersensitivity.

Insulin sensitivity, leptin, adiponectin, resistin, and testosterone in adult male and female rats after maternal-neonatal separation and environmental stress.

Care of premature infants often requires parental and caregiver separation, particularly during hypoxic and hypothermic episodes. We have established a neonatal rat model of human prematurity involving maternal-neonatal separation and hypoxia with spontaneous hypothermia prevented by external heat. Adults previously exposed to these neonatal stressors show a sex difference in the insulin and glucose response to arginine stimulation suggesting a state of insulin resistance. The current study used this cohort of adult rats to evaluate insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], plasma adipokines (reflecting insulin resistance states), and testosterone. The major findings were that daily maternal-neonatal separation led to an increase in body weight and HOMA-IR in adult male and female rats and increased plasma leptin in adult male rats only; neither prior neonatal hypoxia (without or with body temperature control) nor neonatal hypothermia altered subsequent adult HOMA-IR or plasma adiponectin. Adult male-female differences in plasma leptin were lost with prior exposure to neonatal hypoxia or hypothermia; male-female differences in resistin were lost in the adults that were exposed to hypoxia and spontaneous hypothermia as neonates. Exposure of neonates to daily hypoxia without spontaneous hypothermia led to a decrease in plasma testosterone in adult male rats. We conclude that neonatal stressors result in subsequent adult sex-dependent increases in insulin resistance and adipokines and that our rat model of prematurity with hypoxia without hypothermia alters adult testosterone dynamics.

Postnatal stress is associated with impaired fear conditioning and extinction, and heightened hippocampal fibroblast growth factor 2, in mother rats.

Rats exposed to early-life maternal separation (MS) exhibit later alterations in fear conditioning and impairments in fear extinction. As MS creates long-lasting anxiety in the mother, the present study assessed the influence of MS on fear conditioning and extinction in mother rats. It also examined whether estrous cycle effects on extinction, which are robust in nulliparous rats, but abolished in primiparous rats, re-emerge after MS. Following parturition, pups were removed from their mothers for 3 h daily from postpartum day 2-14 (MS), or remained housed with their mothers (standard reared condition, SR). Pups were weaned at postpartum day 24, and three months later, mothers received fear conditioning, extinction training, and test for extinction recall over three days. Extinction training took place during Proestrus (high estradiol and progesterone) or Metestrus (low estradiol and progesterone). Similar to past findings in non-stressed mothers, estrous cycle was not associated with conditioned fear expression (indexed by fear responses at the start of extinction training) or extinction recall in either MS or SR mothers. However, MS mothers exhibited weaker conditioned fear expression and impaired extinction recall, relative to SR mothers. Hippocampal fibroblast growth factor-2, a neurotrophin involved in stress regulation and fear expression, was elevated in MS relative to SR mothers. These results indicate that postnatal stress has long-lasting consequences for neural and behavioral systems involved in fear learning and inhibition without altering the involvement of ovarian hormones in these processes.

Comparison of nebulised dexmedetomidine, ketamine, or midazolam for premedication in preschool children undergoing bone marrow biopsy.

BACKGROUND: The aim of our study was to compare the efficacy of dexmedetomidine, ketamine, and midazolam for sedative premedication administered by nebuliser 30 min before general anaesthesia in preschool children undergoing bone marrow biopsy and aspiration. METHODS: Ninety children aged 3-7 yr were randomly allocated into three equal groups to be premedicated with either nebulised ketamine 2 mg kg-1 (Group K), dexmedetomidine 2 µg kg-1 (Group D), or midazolam 0.2 mg kg-1 (Group M). The primary endpoint was a five-point sedation score on arrival in the operating room 30 min after end of study drug administration. Secondary outcomes included: parental separation anxiety scale; medication and mask acceptance scales; haemodynamic variables; recovery time; postoperative face, legs, activity, cry, and consolability scale; emergence agitation scale; and adverse effects. RESULTS: The median (range) sedation score on arrival in the operating room was 3.5 (1-4), 2.0 (2-3) and 2.0 (1-3) in Groups M, D, and K, respectively (P=0.000). Subjects in Group D showed higher medication (P<0.03) and mask acceptance scores (P<0.015) and more satisfactory parental separation anxiety scale (P<0.044). The median (range) recovery time was significantly shorter in Group D [5.5 (4-8) min] compared with Group K [10.0 (5-15) min, P=0.000] and M [8.0 (6-15) min, P=0.000]. The incidence of emergence agitation was lower in Group D (P<0.008). CONCLUSIONS: Preschool children premedicated with nebulised dexmedetomidine had more satisfactory sedation, shorter recovery time, and less postoperative agitation than those who received nebulised ketamine or midazolam. CLINICAL TRIAL REGISTRATION: NCT02935959.