Anxiety-associated and separation distress-associated behaviours in Angelman syndrome.

BACKGROUND: Anxiety is considered a 'frequent' feature in the clinical criteria for Angelman syndrome; however, the nature and severity of anxiety symptoms have not been well characterised in this population. Anxiety behaviours, especially in response to separation from a preferred caregiver, have been described clinically but have not yet been explored empirically. METHOD: This study used a combination of standardised and clinician-derived survey items to assess the frequency, nature and severity of behaviours associated with anxiety and separation distress in 100 individuals with Angelman syndrome. Family (e.g. income and maternal education) and individual (e.g. age, sex, genetic subtype, sleep difficulties and aggressive behaviours) variables were also gathered to assess possible predictors of higher anxiety levels. Approximately half of the sample was seen in clinic and assessed with standardised measures of development and daily functioning, allowing for an additional exploration of the association between anxiety symptoms and extent of cognitive impairment. RESULTS: Anxiety concerns were reported in 40% of the sample, almost 70% were reported to have a preferred caregiver and over half displayed distress when separated from that caregiver. Individuals with the deletion subtype and individuals who are younger were less likely to have anxiety behaviours. Sleep difficulties and aggressive behaviour consistently significantly predicted total anxiety, the latter suggesting a need for future studies to tease apart differences between anxiety and aggression or anger in this population. CONCLUSIONS: Anxiety concerns, especially separation distress, are common in individuals with Angelman syndrome and represent an area of unmet need for this population.

Childhood trauma and the enduring consequences of forcibly separating children from parents at the United States border.

Forcible separation and detention of children from parents seeking asylum in the United States has been decried as immoral and halted by court order. Babies and children have been separated and transported to facilities sometimes many miles away. Limited data on forced detention of unaccompanied minors reveal high incidence of posttraumatic stress, anxiety disorders, depression, aggression, and suicidal ideation. These consequences will be magnified in youths forcibly separated from their parents, particularly younger children who depend on attachment bonds for self-regulation and resilience. Studies exploring the neuropsychiatric consequences of traumatic stress have revealed consistent effects of early life stress on brain structure, function and connectivity, and the identification of sensitive periods, which occur throughout childhood when specific regions and pathways are strongly influenced by adversity. Studies of epigenetics, inflammation and allostatic load are similarly enhancing our awareness of the molecular mechanisms underpinning the long-term consequences of traumatic stress. We must consider effects on the developing brain, mind and body to appreciate the long-term consequences of policies that force separation and detention of children.

Is surgery a risk factor for separation anxiety in children?

OBJECTIVE: Postoperative anxiety symptoms are distressing for both family and child. The aim of this study was to examine the prevalence of postoperative anxiety symptoms in children. METHODS: 60 children aged 6-12 undergoing surgery were included in the study group. The study group was assessed three times in terms of separation anxiety disorder (SAD), at the time of presentation, 1 and 3 months postoperatively. A personal information form and the SAD section of the K-SADS-PL on the basis of DSM-IV diagnostic criteria for screening SAD symptoms were used. RESULTS: Study group consisted of 19 girls (31.7%) and 41 boys (68.3%) (mean age 8.9 ± 2.3). Four (6.6%) of the cases at the time of presentation and 13 (21.6%) in the study group met SAD diagnostic criteria in 1 month and 21 (35.0%) in 3 months. Anxiety disorder symptoms were significantly higher in the study group at 3 months postoperatively (p < 0.05). There is significant correlation between both SAD symptoms and duration of hospitalization. There was also a positive correlation between duration of hospitalization and parental education and SAD symptoms. CONCLUSION: Greater SAD was observed in children undergoing surgical procedures. It will be useful to physicians to consider SAD after surgery in pediatric patients especially when the level of parental education and duration of hospitalization increase. Since SAD may persist long after surgery, it may cause constant fear in personality disorders and lead to psychological problems by significantly lowering quality of life.

The interaction of Matrix Reasoning and Social Motivation as predictors of Separation anxiety in boys with Autism Spectrum Disorder.

BACKGROUND: It has been suggested that higher cognitive functioning based in the pre-frontal cortex is implicated in the ability of people with Autism Spectrum Disorder (ASD) to understand and communicate in social situations. Low motivation to engage in social interaction may also be influential in this process. Although both of these factors have been argued to influence the levels of comorbid anxiety in young people with ASD, no detailed examination of those relationships has been reported to date. METHODS: A sample of 90 boys with ASD (aged 6 to 12 yr) and 29 of their non-ASD peers, matched for age and IQ, completed tests of cognitive function and anxiety. RESULTS: Only one form of anxiety-fear of being separated from their parents- was significantly associated with cognitive function, at the Full Scale IQ and Matrix Reasoning levels, plus motivation to engage in social interactions, and only for the ASD boys. CONCLUSION: These data represent a complex interaction between the neurobiological aspects of ASD, fluid reasoning, social motivation, and Separation Anxiety in boys with ASD. As such, they bring a new perspective to understanding and treating anxious behaviour in these boys.

Temporal dynamics and longitudinal co-occurrence of depression and different anxiety syndromes in youth: Evidence for reciprocal patterns in a 3-year prospective study.

BACKGROUND: Depression is highly comorbid with anxiety in youth. It is frequently reported that anxiety precedes depression; however, evidence surrounding the temporal precedence of anxiety over depression is mixed. Many studies of anxiety-depression co-occurrence lump distinct forms of anxiety, obscuring information regarding trajectories of specific anxiety syndromes. This study sought to more accurately describe the development of anxiety and depression over time by moving beyond the question of temporal precedence to investigate a developmentally dynamic model of anxiety-depression co-occurrence. METHODS: A community sample of 665 youth (M= 11.8, SD= 2.4; 55% female) completed repeated self-report measures of depression and anxiety (social, physical, and separation anxiety) over a 3-year longitudinal study. Prospective associations between distinct syndromes of anxiety with depression were analyzed using an autoregressive cross-lagged path model over four time points. RESULTS: Physical symptoms and depression symptoms reciprocally predicted each other, above and beyond the stability of either domain. Social anxiety and depression symptoms similarly predicted each other in a systematic pattern. LIMITATIONS: Our study is limited in its generalizability to other forms of anxiety, like worry. Additional research is needed to determine whether similar patterns exist in clinical populations, and whether these processes maintain symptoms once they reach diagnostic levels. CONCLUSIONS: The development of syndromes of depression, physical, and social anxiety during childhood and adolescence occurs in a predictable, systematic reciprocal pattern, rather than sequentially and unidirectionally (i.e., anxiety syndromes precede depression). Results are clinically useful for predicting risk for disorder, and demonstrate the necessity of tracking symptom levels across domains.

Adolescent escitalopram prevents the effects of maternal separation on depression- and anxiety-like behaviours and regulates the levels of inflammatory cytokines in adult male mice.

There is little research on the effects of adolescent administration of antidepressants on behavioural function and inflammation in early-life stressed adult mice. Using maternal separation (MS), a paradigm of early adversity, we investigated the effects of adolescent (PND 33-54) escitalopram (ES; 10mg/kg) exposure on depression- and anxiety-like behaviours and the levels of inflammatory cytokines (interleukin [IL]-1ß, tumor necrosis factor [TNF]-α, and IL-10) in the ventral hippocampus (HPV), prefrontal cortex (PFC), and serum in adult (PND 61) male offspring mice. The results showed that MS has no effect on locomotor activity, but increased depression-like behaviours in the saccharin preference test and increased anxiety-like behaviours in the social preference and elevated plus maze tests. MS increased the levels of IL-1ß in the HPV, PFC, and serum, while decreasing the level of IL-10 in the HPV. Furthermore, adolescent ES treatment inhibited these depression- and anxiety-like behaviours, decreased the levels of IL-1ß, and increased the level of IL-10 in the HPV. The results also showed that there are no effects of chronic escitalopram administration on normal behaviour in control mice. Taken together, the current data provide experimental evidence that MS increases depression and anxiety levels in adult male offspring. Additionally, the findings support the idea that early pharmacological intervention with ES may be an effective treatment for reducing the behavioral abnormalities induced by early adversity and regulating the underlying inflammatory mechanisms involved.

Infant stranger fear trajectories predict anxious behaviors and diurnal cortisol rhythm during childhood.

Although a robust literature has linked stable, high levels of fear across childhood to increased risk for anxiety problems, less is known about alternative pathways to anxiety. We tested two putatively normative developmental pathways of early fearfulness for their distinct associations with behavioral (anxiety-related behaviors and symptoms) and biological (diurnal cortisol) markers of anxiety risk in middle childhood in a community-based sample (n = 107). Steeper increases in fear from 6 to 36 months predicted more parent-reported anxiety symptoms at age 8 years. In addition, children who exhibited steep increases in fear during infancy were overrepresented among children with diagnoses of separation anxiety disorder at age 8 years. Finally, we showed that steeper increases in fearfulness in infancy predicted flatter slopes of diurnal cortisol at age 8 years for girls. Thus, differences in stranger fear across infancy may indicate varying degrees of risk for anxious behaviors in later childhood.

Psychiatric outcomes of bullying victimization: a study of discordant monozygotic twins.

BACKGROUND: Bullying victimization in childhood is associated with a broad array of serious mental health disturbances, including anxiety, depression, and suicidal ideation and behavior. The key goal of this study was to evaluate whether bullying victimization is a true environmental risk factor for psychiatric disturbance using data from 145 bully-discordant monozygotic (MZ) juvenile twin pairs from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and their follow-up into young adulthood. METHOD: Since MZ twins share an identical genotype and familial environment, a higher rate of psychiatric disturbance in a bullied MZ twin compared to their non-bullied MZ co-twin would be evidence of an environmental impact of bullying victimization. Environmental correlations between being bullied and the different psychiatric traits were estimated by fitting structural equation models to the full sample of MZ and DZ twins (N = 2824). Environmental associations were further explored using the longitudinal data on the bullying-discordant MZ twins. RESULTS: Being bullied was associated with a wide range of psychiatric disorders in both children and young adults. The analysis of data on the MZ-discordant twins supports a genuine environmental impact of bullying victimization on childhood social anxiety [odds ratio (OR) 1.7], separation anxiety (OR 1.9), and young adult suicidal ideation (OR 1.3). There was a shared genetic influence on social anxiety and bullying victimization, consistent with social anxiety being both an antecedent and consequence of being bullied. CONCLUSION: Bullying victimization in childhood is a significant environmental trauma and should be included in any mental health assessment of children and young adults.

The stability and change of etiological influences on depression, anxiety symptoms and their co-occurrence across adolescence and young adulthood.

BACKGROUND: Depression and anxiety persist within and across diagnostic boundaries. The manner in which common v. disorder-specific genetic and environmental influences operate across development to maintain internalizing disorders and their co-morbidity is unclear. This paper investigates the stability and change of etiological influences on depression, panic, generalized, separation and social anxiety symptoms, and their co-occurrence, across adolescence and young adulthood. METHOD: A total of 2619 twins/siblings prospectively reported symptoms of depression and anxiety at mean ages 15, 17 and 20 years. RESULTS: Each symptom scale showed a similar pattern of moderate continuity across development, largely underpinned by genetic stability. New genetic influences contributing to change in the developmental course of the symptoms emerged at each time point. All symptom scales correlated moderately with one another over time. Genetic influences, both stable and time-specific, overlapped considerably between the scales. Non-shared environmental influences were largely time- and symptom-specific, but some contributed moderately to the stability of depression and anxiety symptom scales. These stable, longitudinal environmental influences were highly correlated between the symptoms. CONCLUSIONS: The results highlight both stable and dynamic etiology of depression and anxiety symptom scales. They provide preliminary evidence that stable as well as newly emerging genes contribute to the co-morbidity between depression and anxiety across adolescence and young adulthood. Conversely, environmental influences are largely time-specific and contribute to change in symptoms over time. The results inform molecular genetics research and transdiagnostic treatment and prevention approaches.

[Welcoming a child of a parent hospitalized in intensive care]. / L'accueil d'un enfant auprès d'un parent hospitalisé en réanimation.

For a child, the hospitalisation of one of their parents in intensive care has a huge impact on family dynamics. The neurosurgical intensive care team at Rouen general hospital has consequently developed specific ways of enabling children in these situations to visit their parent.

Early-life stress increases the survival of midbrain neurons during postnatal development and enhances reward-related and anxiolytic-like behaviors in a sex-dependent fashion.

Clinical studies have suggested that early-life stress (ELS) increases the risk of psychopathologies that are strongly associated with dysfunction of dopaminergic neurotransmission. Thus, ELS may interfere with the development and maturation of the dopaminergic system; however, the mechanisms involved in such interference are poorly understood. In the present study, we investigated the effect of ELS on the survival of specific populations of neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) during postnatal development. First, we injected bromodeoxyuridine (BrdU) into pregnant rat dams on embryonic days 12, 13 and 14 to permanently label midbrain neurons. Then, after birth, the dams and litters were subjected to a maternal separation (MS) procedure to model ELS conditions. The number of BrdU+ neurons and the total number of neurons (cresyl violet+, CV+) were estimated in both male and female juvenile, adolescent, and adult rats. Moreover, sucrose preference and anxiety-like behaviors were studied during adulthood. We found that MS permanently increased the number of BrdU+ and CV+ neurons in the VTA of males. In the SNc, a temporary increase in the number of BrdU+ neurons was observed in juvenile MS males; however, only adult MS males displayed an increase in the number of CV+ neurons. Immunofluorescence analysis implied that MS affected the fate of non-dopaminergic neurons. MS males displayed anxiolytic-like behavior and an increase in sucrose preference. These results suggest that ELS induces distinct dysregulation in the midbrain circuitry of males, which may lead to sex-specific psychopathology of the reward system.

Involvement of the strychnine-sensitive glycine receptor in the anxiolytic effects of GlyT1 inhibitors on maternal separation-induced ultrasonic vocalization in rat pups.

Several studies have shown that glycine transporter 1 (GlyT1) inhibitors have anxiolytic actions. There are two types of glycine receptor: the strychnine-sensitive glycine receptor (GlyA) and the strychnine-insensitive glycine receptor (GlyB); however, which receptor is the main contributor to the anxiolytic actions of GlyT1 inhibitors is yet to be determined. Here, we clarified which glycine receptor is the main contributor to the anxiolytic effects of GlyT1 inhibitors by using maternal separation-induced ultrasonic vocalization (USV) by rat pups as an index of anxiety. We confirmed that administration of the benzodiazepine diazepam or the selective serotonin reuptake inhibitor escitaloplam, which are both clinically proven anxiolytics, or the GlyT1 inhibitor SSR504734 (2-chloro-N-[(S)-phenyl[(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide), decreases USV in rat pups. In addition, we showed that another GlyT1 inhibitor, ALX5407 ((R)-N-[3-(4'-fluorophenyl)-3(4'-phenylphenoxy)propyl]sarcosine) also decreases USV in rat pups. SSR504734- or ALX5407-induced decreases in USV were dose-dependently reversed by administration of the GlyA antagonist strychnine, whereas the diazepam- or escitalopram-induced decreases in USV were not. Furthermore, GlyT1-induced decreases in USV were not reversed by administration of the GlyB antagonist L-687,414. Together, these results suggest that GlyA activation is the main contributor to the anxiolytic actions of GlyT1 inhibitors and that the anxiolytic actions of diazepam and escitalopram cannot be attributed to GlyA activation. Our findings provide new insights into the importance of the activation of GlyA in the anxiolytic effects of GlyT1 inhibitors.

The right amygdalar tumor presenting with symptoms of separation anxiety disorder (SAD): a case report.

A patient with an astrocytoma of the right-sided amygdala developed symptoms of separation anxiety disorders (SADs). These symptoms significantly subsided after tumor resection. The temporal relationship suggested that the amygdalar tumor could result in the specific symptoms. To our knowledge, this is the first report of SAD as one manifestation of the amygdalar tumor. The tumorigenesis of amygdala resulted in impaired regulation and abnormal activity associated with anticipating anxiety and conditioning. It deserves clinical attention to early detection and intervention.

Dysfunctional family environments and childhood psychopathology: the role of psychiatric comorbidity / Ambientes de famílias disfuncionais e psicopatologia infantil: o papel da comorbidade psiquiátrica

Introduction: The study of the association between specific characteristics of family environments and different types of psychopathology may contribute to our understanding of these complex disorders and ultimately inform therapeutics. Objective: To compare the family characteristics of four groups: typically developing children; children with anxiety disorders only; children with externalizing disorders only; and children with both anxiety and externalizing disorders. Methods: This study enrolled 115 individuals from the community. Child psychiatrists made psychiatric diagnoses using a structured clinical interview. The Family Environment scale was used to evaluate six domains of family function. Results: The group with both anxiety and externalizing disorders had higher levels of conflict in family environment and lower levels of organization when compared with typically developing children. In addition, internalizing and externalizing symptoms were positively associated with conflict and negatively with organization. Maternal depressive and anxious symptoms were also associated with higher conflict and lower organization scores. Conclusion: An important between-group difference in comorbid cases of anxiety and behavioral disorders suggests that children with this comorbidity are potential candidates for family interventions to address family conflicts and organizational aspects (AU)

Introdução: O estudo da relação entre características específicas do ambiente familiar e os diferentes tipos de psicopatologias pode contribuir para o nosso entendimento desses complexos transtornos e possivelmente gerar informações para seu tratamento. Objetivo: Comparar as características familiares de quatro grupos: Crianças com desenvolvimento típico; crianças com transtornos de ansiedade apenas; crianças com transtornos de externalização apenas; e crianças com transtornos de ansiedade e de externalização. Métodos: Cento e quinze indivíduos foram recrutados na comunidade. Psiquiatras pediátricos usaram uma entrevista clínica estruturada para estabelecer os diagnósticos psiquiátricos. A Escala do Ambiente Familiar (Family Environment) foi usada para avaliar os seis domínios de funcionamento da família. Resultados: O grupo que apresentava tanto transtornos de ansiedade quanto de externalização apresentou níveis mais altos de conflito e níveis mais baixos de organização quando comparados com as crianças com desenvolvimento típico. Além disso, os sintomas de externalização e internalização estavam positivamente relacionados a conflitos e negativamente a organização. Sintomas depressivos e de ansiedade da mãe também se mostraram relacionados a resultados mais altos para conflito e mais baixos para organização. Conclusão: Uma importante diferença entre grupos em casos de comorbidades de transtornos de ansiedade e de comportamento sugerem que as crianças com esta comorbidades são candidatos em potencial para intervenções familiares que abordem conflitos familiares e aspectos organizacionais (AU)

Early-life risk factors for panic and separation anxiety disorder: insights and outstanding questions arising from human and animal studies of CO2 sensitivity.

Genetically informative studies showed that genetic and environmental risk factors act and interact to influence liability to (a) panic disorder, (b) its childhood precursor separation anxiety disorder, and (c) heightened sensitivity to CO2, an endophenotype common to both disorders. Childhood adversities including parental loss influence both panic disorder and CO2 hypersensitivity. However, childhood parental loss and separation anxiety disorder are weakly correlated in humans, suggesting the presence of alternative pathways of risk. The transferability of tests that assess CO2 sensitivity - an interspecific quantitative trait common to all mammals - to the animal laboratory setting allowed for environmentally controlled studies of early parental separation. Animal findings paralleled those of human studies, in that different forms of early maternal separation in mice and rats evoked heightened CO2 sensitivity; in mice, this could be explained by gene-by-environment interactional mechanisms. While several questions and issues (including obvious divergences between humans and rodents) remain open, parallel investigations by contemporary molecular genetic tools of (1) human longitudinal cohorts and (2) animals in controlled laboratory settings, can help elucidate the mechanisms beyond these phenomena.

Infant cardiac surgery: mothers tell their story: a therapeutic experience.

BACKGROUND: Serious congenital heart disease frequently requires major congenital heart surgery. It causes much distress for parents, which may not always be recognized and treated appropriately. PATIENTS AND METHODS: As part of a larger study, 26 mothers of two-month-old infants subjected to recent cardiac surgery were interviewed in depth. Each mother was invited to describe her own and what she perceived were her infant's experiences and to comment on the interview process. A systematic content analysis of the interviews was performed using qualitative research methodology. RESULTS: Almost all participants described acute stress symptoms relating to the diagnosis and the infant's surgery. In addition, most mothers reported that the interview helped them to think about and integrate what had happened to them and their infant, suggesting a probable therapeutic value to the interview. CONCLUSIONS: A suitably qualified and experienced mental health professional, assisting the mother to tell her story about the diagnosis and her infant's cardiac surgery, may provide a valuable, brief, and very cost-effective therapeutic intervention for these mothers and infants. It has the potential to alleviate maternal distress, with associated gains for the developing mother-infant relationship, reducing infant morbidity, and enhancing the quality of life for both infant and mother.

Behavior changes after minor emergency procedures.

OBJECTIVES: Procedures are common in pediatric emergency departments and frequently cause distress from pain and/or anxiety. The objective of this study was to describe the incidence, types, and magnitude of long-term behavior changes after procedures in the emergency setting. METHODS: This is a descriptive pilot study to determine if children display negative behavioral changes after a minor emergency department procedure (abscess drainage or laceration repair). Behavior change was measured at 1 week by telephone follow-up using the 27-item Post Hospitalization Behavior Questionnaire, a well-validated instrument that measures behavior changes across 6 categories: general anxiety, separation anxiety, anxiety about sleep, eating disturbances, aggression toward authority, and apathy/withdrawal. Significant behavior change was defined as 5 or more negative behavior changes on the 27-item questionnaire. RESULTS: Twenty percent of children who underwent abscess drainage (n = 30) and 20% who underwent laceration repair (n = 30) displayed significant negative behavior change at 1 week. Children who displayed significant negative behavior change tended to be younger (3.6 vs 5.9 years) and trended toward being more likely to have received anxiolysis or sedation (16.7% vs 8.3%). Separation anxiety, sleep difficulties, and aggression toward authority were the most common behavior changes. CONCLUSIONS: In this pilot study, a significant percentage of children undergoing common emergency procedures exhibited an appreciable burden of negative behavior change at 1 week; these results demonstrate the need for further rigorous investigation of predictors of these changes and interventions, which can ameliorate these changes.

Psychodynamic approaches to medically ill children and their traumatically stressed parents.

This article describes the authors' clinical experience of integrating psychodynamic therapeutic approaches in the care of medically ill children and their families. A case report of a boy with severe, chronic liver disease requiring a double organ transplant is described as an illustration of how such approaches cannot only improve quality of life and functioning but may also be life saving. The authors describe original research investigating how parents' traumatic stress and related interference with children's emotional regulation can compromise their ability to make meaning of their experience, thus posing a risk for adherence to the prescribed medical regimen.