Stressful life events in anxious and depressed children

OBJECTIVE: The aim of this study was to examine the occurrence of stressful life events in anxious and depressed children. METHOD: Children (6-12 years of age) with an anxiety disorder (n = 20), depression (n = 45), and normal controls (n = 11) were assessed using the Life Events Record. Cortisol was assessed from plasma samples collected every 20 minutes from an indwelling catheter in the one and two hour window around sleep onset. RESULTS: Depressed children had significantly more events and events that were most likely independent of the child's behavior, compared to both the anxious and normal control children. Independent loss events were significantly more prevalent among the depressed children in the preceding year, compared to anxious children, with a trend toward more loss events compared to the normal controls. For both overall events and independent events, depressed females were significantly more likely to be exposed to stressful environments compared to anxious and normal control females. There were no effects of stress on cortisol secretion around sleep onset. CONCLUSIONS: The results of this study suggest that stressful life events are significantly more likely to occur in depressed children, particularly females, compared to anxious children, and that these events are predominantly characterized by independent events outside of the child's control. The results also suggest that loss events may be specific for depression in children. Interestingly, stress does not appear to impact the HPA axis in children, which is true for anxious, depressed, and normal control children. The temporal occurrence and severity, as well as the type of stressful life events as they relate to the onset and maintenance of anxiety and depression in children, need to be more fully explored.     

Objective sleep in pediatric anxiety disorders and major depressive disorder

OBJECTIVE: To examine objective and subjective sleep problems in early-onset anxiety and depression. METHOD: Children and adolescents (46% female, ages 7 to 17 years) with anxiety disorders (n = 24), major depressive disorder (MDD) without comorbid anxiety disorders (n = 128), or no history of psychiatric disorder (n = 101) spent two consecutive nights in a sleep laboratory and completed self-reports of sleep quality. RESULTS: On objective measures, the anxiety group exhibited more awakenings than the MDD group, less slow-wave sleep than the control or MDD group, and greater night 2 sleep latency than the MDD or control group. The anxiety group exhibited no decrease in rapid eye movement latency from the first night to the second. The MDD group exhibited less time awake than the control group and less stage 1 sleep than the anxiety or control group. On subjective measures, young people with anxiety reported greater sleep latency on the second night and no decrease in sleep latency. Age was covaried in analyses. CONCLUSIONS: Findings provide objective and subjective evidence of sleep disturbance in children and adolescents with anxiety disorders and replicate findings of limited objective sleep disturbance in those with MDD. Sleep problems are an important consideration when treating young people with anxiety.     

Factors associated with the development of substance use disorder in depressed adolescents.

OBJECTIVE: To document rates of substance use disorders (SUD) in adolescents with unipolar major depressive disorder and to examine demographic, clinical, and biological factors associated with the development of SUD. METHOD: Twenty-eight adolescents with unipolar major depression and no SUD history and 35 group-matched normal controls who participated in a cross-sectional sleep polysomnography and neuroendocrine study were reassessed clinically 7 years later. RESULTS: The risk for SUD was high in both groups (34.6% in the depressed group and 24.2% in the controls). Depressed adolescents had earlier onset of SUD than controls. Depressed adolescents who developed SUD had more significant psychosocial impairment than depressed adolescents who did not develop SUD. More anxiety traits and elevated cortisol secretion near sleep onset were associated with SUD in depressed teenagers, whereas less emotional responsiveness to exciting stimuli and higher density of eye movements during REM sleep were related to depression without SUD. CONCLUSIONS: Depressed adolescents who have anxiety traits and whose hypothalamic-pituitary-adrenal axis is active when the system is normally quiescent may be at risk for developing SUD. Co-occurrence of depression and SUD is associated with serious psychosocial morbidity. Identification of risk factors for SUD in depressed teenagers may be helpful in developing more effective treatment and prevention programs.     

Associations between HPA axis functioning and level of anxiety in children and adolescents with an anxiety disorder

The hypothalamus-pituitary-adrenal (HPA) axis becomes active in response to stress. Hence, increased levels of anxiety in children and adolescents may be associated with changes in HPA-axis functioning. The aim of this study was to test if level of anxiety or specific anxiety disorders were associated with basal HPA axis activity in children and adolescents with an anxiety disorder. In 99 8- to 16-year-olds with an anxiety disorder, basal cortisol levels were assessed. It was tested if (1) cortisol levels correlated with the level of self-reported anxiety and (2) if cortisol levels were different for individuals with different anxiety disorders. In girls, low levels of anxiety were associated with a stronger rise in early morning cortisol concentrations. In both boys and girls, harm avoidance predicted low cortisol concentrations after awakening. Separation anxiety and physical anxiety symptoms predicted cortisol concentrations at noon. Differences between individuals with different anxiety disorders were not found. More research is needed regarding mechanisms that explain the associations that were found, and to investigate if treatment may influence HPA axis functioning in children and adolescents with an anxiety disorder.     

Effect of comorbid anxiety disorders on the hypothalamic-pituitary-adrenal axis response to a social stressor in major depression.

BACKGROUND: Major depressive disorder (MDD) is often complicated by anxiety symptoms, and anxiety disorders occur in approximately 30% of mood cases. This study examined the influence of anxiety comorbidity on the hypothalamic-pituitary-adrenal (HPA) axis response to stress in patients with MDD. METHODS: Untreated subjects with pure MDD (n = 15), MDD with comorbid anxiety disorders (n = 18), and pure anxiety disorders (n = 15) were recruited by advertising. Age- and gender-matched control subjects were recruited for each subject with a psychiatric diagnosis (n = 48). All subjects underwent a social stressor, the Trier Social Stress Test (TSST), and blood was collected for adrenocorticotropic hormone (ACTH) and cortisol assay. RESULTS: When all depressed patients (n = 33) were compared with their matched control subjects (n = 33), they showed a significantly greater ACTH response to the stressor; however, this exaggerated ACTH response was exclusively due to the depressed group with comorbid anxiety disorders. A similar but nonsignificant effect was observed in the cortisol response. Subjects with pure mood or pure anxiety disorders showed normal ACTH and cortisol responses to the TSST. All patient groups showed similar levels of TSST-induced anxiety. CONCLUSIONS: Comorbid anxiety disorders might play a role in the increased activation of the HPA axis observed in patients with major depression.     

Salivary cortisol and psychopathology in children bereaved by the september 11, 2001 terror attacks.

BACKGROUND: Studies suggest that stressful events increase risk for childhood anxiety and depression and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This prospective longitudinal study evaluated relationships among severe psychosocial stress, psychiatric morbidity, and HPA axis function in children. METHODS: Forty-five children (mean age: 8.9 +/- 2.9 years) suffering parent death from September 11, 2001 terror attacks and 34 nonbereaved children (mean age: 9.3 +/- 2.5 years) were evaluated prospectively at 6-month intervals in this 2-year study. Assessments involved diagnostic interviews (Child Schedule for Affective Disorders and Schizophrenia [K-SADS]) for psychopathology and 3 days of baseline salivary cortisol and a salivary dexamethasone suppression test for HPA axis function. RESULTS: Bereaved children, but not nonbereaved children, had significantly increased rates of psychiatric disorders involving anxiety disorders, especially posttraumatic stress disorder (PTSD), after September 11, 2001 compared with retrospective assessments before September 11, 2001. Morning (AM) and 4:00 pm baseline cortisol were significantly and persistently higher for bereaved than nonbereaved children. Compared with bereaved children without psychopathology, bereaved children with PTSD had significantly lower 4:00 pm baseline cortisol and significantly greater 4:00 pm cortisol suppression. Children with generalized anxiety disorder had significantly less AM cortisol suppression than children without psychopathology. CONCLUSIONS: Children bereaved by sudden, unexpected parent death had persistent psychological dysfunction and HPA axis dysregulation in this study.     

Preliminary evidence for sleep complaints among children referred for anxiety

BACKGROUND AND PURPOSE: Clinical observation suggests that sleep complaints are common among youth with anxiety disorders though empirical data documenting this co-occurrence of symptoms are generally unavailable. PATIENTS AND METHODS: Based on retrospective chart reviews, the current study examined rates of several types of parent-reported sleep complaints among a sample of (n=35) purely anxious children and adolescents (ANX). Sleep complaints were examined in terms of age (children versus adolescents) and type of anxiety diagnosis (generalized anxiety versus other anxious diagnoses). Rates of sleep complaints among anxious youth also were compared to those among (n=38) healthy control children and (n=33) children referred for sleep problems. RESULTS: The presence of at least one intermittent sleep complaint was reported by 83% of parents of ANX, with almost half reporting at least one frequent sleep complaint. Rates of sleep complaints among anxious children versus adolescents were similar. Children with generalized anxiety disorder (GAD) had a significantly greater number of sleep complaints than children with other types of anxiety disorders, though rates for specific items varied. Although parents of sleep-referred children reported the highest rates of sleep complaints overall, the frequency of several specific types of sleep complaints was highly similar among ANX and sleep-referred children. CONCLUSIONS: Findings indicate that certain sleep complaints are common among ANX. The need for appropriate assessment practices is discussed.     

Twenty-four-hour cortisol secretion patterns in prepubertal children with anxiety or depressive disorders.

BACKGROUND: Previous studies found few abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function in prepubertal children with anxiety or depressive disorders. In this study, we combined data from two independent, consecutive studies to achieve a larger sample size. Our goal was to identify potential alterations in the circadian pattern of cortisol secretion in anxious or depressed children. METHODS: A total of 124 prepubertal subjects from two independent samples (76 with major depressive disorder, 31 with anxiety disorders, and 17 healthy control subjects) were studied. Blood samples collected for cortisol at hourly intervals over a 24-hour period were examined. Analyses were performed aligning cortisol samples by clock-time. Additional analyses aligning samples by sleep-onset time were performed with a subsample of subjects. RESULTS: In the combined sample, significant findings emerged that were previously undetected. Anxious children exhibited significantly lower nighttime cortisol levels and an initially sluggish rise in cortisol during the nighttime when compared with depressed and healthy control children. In contrast, depressed children did not show a clear-cut pattern of differences compared with healthy control children. CONCLUSIONS: Anxious children seem to exhibit an altered pattern of nighttime cortisol secretion, with an initially sluggish or delayed nocturnal rise before reaching similar peak levels of cortisol near the time of awakening. These findings suggest subtle alterations in HPA axis function in prepubertal children with anxiety disorders.     

Childhood-onset bipolar disorder: Evidence for increased familial loading of psychiatric illness

OBJECTIVE: To determine whether childhood-onset bipolar disorder (BP) is associated with an increased psychiatric family history compared with adolescent-onset BP. METHOD: Semistructured psychiatric interviews were conducted for 438 youth with BP spectrum disorders. To evaluate the effects of age at onset and psychiatric family history, the sample was divided into childhood-onset BP (age and BP onset <12 years; n = 192), adolescents with early-onset BP (age > or =12 years and BP onset <12 years; n = 136), and adolescents with late-onset BP (age and BP onset > or =12 years; n = 110). Lifetime family history of psychiatric illness was ascertained for first- and second-degree relatives through both direct interview of caretakers and the Family History Screen. RESULTS: After significant demographic and clinical factors were controlled for, children and adolescents with childhood-onset BP showed higher percentages of positive first-degree family history for depression, anxiety, attention-deficit/hyperactivity, conduct, and substance dependence disorders and suicidal behaviors compared with adolescents with late onset. Subjects with childhood-onset BP also showed elevated familial loading for depression and attention-deficit/hyperactive disorder in second-degree relatives. CONCLUSIONS: These data support a model that postulates a higher density of familial risk for a broad range of psychopathology in childhood-onset BP.     

24-hour cortisol measures in adolescents with major depression: a controlled study

Plasma cortisol levels were determined every 20 min for 24 hr in depressed adolescents (n = 27) meeting research diagnostic criteria (RDC) for major depressive disorder (MDD) and normal controls (n = 32). All subjects were between 12 and 18 years of age, at least Tanner Stage III of sexual development, medically healthy, and medication free at the time of the studies. The results showed that cortisol secretory patterns were very similar between the two groups with the exception that the depressed adolescents showed significantly elevated cortisol levels around sleep onset (a period when cortisol is usually suppressed). Subgroup analyses showed that most of these differences were contributed by the suicidal/inpatient depressed adolescents. The cause of the elevated cortisol during the normally quiescent period warrants further investigation and may be related to other biological disturbances around sleep onset (difficulty initiating sleep, reduced rapid eye movement (REM) latency, and alterations in sleep-stimulated growth hormone secretion).     

Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children.

BACKGROUND: Animal studies suggest that prenatal stress is associated with long-term disturbance in hypothalamic-pituitary-adrenal (HPA) axis function, but evidence in humans is lacking. This study examined the long-term association between prenatal anxiety and measures of diurnal cortisol at age 10 years. METHODS: Measures of cortisol were collected at awakening, 30 min after awakening, and at 4 pm and 9 pm on 3 consecutive days in a sample of 10-year-olds (n = 74) from the Avon Longitudinal Study of Parents and Children, a prospective longitudinal cohort study of mothers and children on whom measures of anxiety and depression were collected in pregnancy and the postpartum period. Analyses examined the links between symptoms of prenatal anxiety and multiple indicators of cortisol, an index of HPA axis functioning. RESULTS: Prenatal anxiety was significantly associated with individual differences in awakening and afternoon cortisol after accounting for obstetric and sociodemographic risk (partial correlations were .32 and .25, p < .05). The effect for awakening cortisol remained significant after controlling for multiple postnatal assessments of maternal anxiety and depression. CONCLUSIONS: This study provides the first human evidence that prenatal anxiety might have lasting effects on HPA axis functioning in the child and that prenatal anxiety might constitute a mechanism for an increased vulnerability to psychopathology in children and adolescents.     

High levels of cortisol among adolescent offspring of parents with bipolar disorder: a pilot study

The hypothalamic-pituitary-adrenal (HPA) axis is compromised at several levels in major depressive and bipolar disorder (BD). However, it is not known whether HPA abnormalities predate the onset of these disorders. We conducted a pilot study comparing salivary cortisol levels of 10 adolescent offspring of parents with BD and 10 offspring of parents with no mental disorder (NMD). For two days, samples were collected at awakening and during the day in the adolescents' natural environment. The offspring of parents with BD had higher mean cortisol levels in the mornings and afternoons than the offspring of parents with NMD. When controlling for age, group differences in cortisol persisted in the afternoon, but not morning samples. None of the adolescents met diagnostic criteria for anxiety, affective, attention-deficit, or conduct disorders. Although preliminary, the results suggest that there is an early abnormality in the HPA system of the offspring of parents with BD.     

Pre-schoolers suffering from psychiatric disorders show increased cortisol secretion and poor sleep compared to healthy controls

BackgroundVarious studies of child cortisol secretion and sleep show a close association between poor sleep, deterioration of the HPA axis and unfavorable psychological functioning. However, there is little evidence as to whether these associations are clearly present in pre-school children suffering from psychiatric disorders.MethodA total of 30 pre-schoolers suffering from psychiatric disorders (anxiety, adjustment disorders, emotional and attachment disorder; hyperactivity or oppositional disorder) and 35 healthy controls took part in the study. Saliva cortisol secretion was assessed both at baseline and under challenge conditions. Sleep was assessed via activity monitoring for seven consecutive days and nights, using a digital movement-measuring instrument. Parents and teachers completed questionnaires assessing children's cognitive, emotional and social functioning. The Berkeley Puppet Interview provided child-based reports of cognitive–emotional processes.ResultsCompared to healthy controls, children suffering from psychiatric disorders had much higher cortisol secretion both at baseline and under challenge conditions. Sleep was also more disturbed, and parents and teachers rated children suffering from psychiatric disorders as cognitively, emotionally and behaviorally more impaired, relative to healthy controls. Children with psychiatric disorders reported being more bullied and victimized.ConclusionsIn five-year old children the presence of psychiatric disorders is reflected not only at psychological, social and behavioral, but also at neuroendocrine and sleep-related levels. It is likely that these children remain at increased risk for suffering from psychiatric difficulties later in life.     

Psychological comorbidity and stress reactivity in children and adolescents with recurrent abdominal pain and anxiety disorders

OBJECTIVE: To compare clinical symptoms, diagnoses, and physiological measures in children and adolescents with recurrent abdominal pain (RAP) (n = 14), to a group with anxiety disorders (ANX) (n = 14) and a physically and psychiatrically healthy control group (HC) (n = 14). METHOD: The cross-sectional study examined group differences in clinical symptoms of anxiety, somatic complaints, depression, and behavior problems. Physiological measures included heart rate, systolic and diastolic blood pressure, and salivary cortisol in response to the Trier Social Stress Test for Children (TSST-C). Subjects were between the ages of 8 and 16 years. RESULTS: RAP and ANX subjects had comparable scores on most psychological measures, and their scores were higher (n < .05) than those of the HC. The ANX and RAP groups exhibited physiological findings that had more shared similarities than either group with the HC group. Few statistically significant group differences were noted in physiological measures, yet the pattern of findings in blood pressure and cortisol supported the use of the TSST-C and the direction of the findings was consistent with expectations. CONCLUSIONS: Understanding more about comorbidity between RAP and anxiety could have important management implications, with observed congruities between the disorders suggesting treatments already demonstrated to be efficacious for pediatric anxiety and depression might be applied productively to RAP.     

Children suffering from separation anxiety disorder (SAD) show increased HPA axis activity compared to healthy controls

Research questions

Separation anxiety disorder (SAD) is one of the most common mental disorders in childhood, and one of the earliest emerging. Little is known about the association between SAD and the hypothalamic-pituitary-adrenocortical (HPA) axis activity. Therefore, the present study aimed at investigating this association in children suffering from separation anxiety compared to healthy controls.

Methods

A total of 31 children with diagnosed SAD (mean age: 8.45; 17 females, 14 males) and 25 healthy controls (HC; mean age: 9.74; 12 females, 13 males) took part in the study. All participants underwent psycho-physiological testing for HPA axis challenge. Testing consisted of a separation and a social exposure paradigm. Saliva samples to assess HPA axis-related cortisol secretion were gathered in parallel.

Results

Compared to healthy controls, children with SAD showed greatly increased HPA axis activity, as reflected by an increased cortisol secretion throughout the entire period of investigation. The rise of cortisol was already observed in anticipation of, but not following the separation paradigm. No gender-related differences of cortisol secretion were observed.

Conclusions

Separation anxiety disorder (SAD) in children is reflected in greatly increased HPA axis activity. Compared to healthy controls, children with SAD showed increased cortisol values from the beginning of, and throughout, the entire investigation. This pattern of results suggests that both the anticipation of a separation and a persistent hyperactivity of the HPA axis system leads to an increased cortisol secretion.     

Behavioural disorders in adolescents with early-treated congenital hypothyroidism

This study analyses the possible risk factors for the on-set of behavioural disorders and psychiatric disturbances in a group of 30 early-treated congenital hypothyroidism (CH) subjects (12 children and 18 adolescents) compared with a control group of 116 age-matched normal subjects (58 children and 58 adolescents). The study also allowed us to evaluate the possible age at onset of behavioural disorders. Both the sample's and the controls' behaviours were assessed using a specific diagnostic instrument: Achenbach's and Edelbrock's Child Behaviour Checklist (CBCL). A clinical structured interview, the Diagnostic Interview for Children and Adolescents--Revised (DICA-R) was also administered to 18 adolescents with early-treated CH, in order to determine the presence of psychopathological disturbances. In accordance with literature data, the children and adolescents with early-treated CH showed more behavioural problems than age-matched, normal controls. In the children, a statistically significant difference versus the controls emerged only in their higher delinquent behaviour score, while the adolescents gave, on the CBCL, significantly higher scores compared with controls in the withdrawal, anxiety/depression, thought problems, attention problems and aggressive behaviour scales. In the DICA-R, 44% of adolescents with early-treated CH showed symptoms of anxiety disorder, in particular, separation anxiety disorder with phobic components; 16% showed mood disorder and depression and 11% showed behavioural disorders with attention deficit.     

Disturbances in morning cortisol secretion in association with maternal postnatal depression predict subsequent depressive symptomatology in adolescents.

BACKGROUND: We have previously reported higher and more variable salivary morning cortisol in 13-year-old adolescents whose mothers were depressed in the postnatal period, compared with control group adolescents whose mothers did not develop postnatal depression (PND). This observation suggested a biological mechanism by which intrafamilial risk for depressive disorder may be transmitted. In the current article, we examined whether the cortisol disturbances observed at 13 years could predict depressive symptomatology in adolescents at 16 years of age. METHODS: We measured self-reported depressive symptoms in 16-year-old adolescents who had (n = 48) or had not (n = 39) been exposed to postnatal maternal depression and examined their prediction by morning and evening cortisol indices obtained via 10 days of salivary collections at 13 years. RESULTS: Elevated morning cortisol secretion at 13 years, and particularly the maximum level recorded over 10 days of collection, predicted elevated depressive symptoms at 16 years over and above 13-year depressive symptom levels and other possible confounding factors. Morning cortisol secretion mediated an association between maternal PND and symptomatology in 16-year-old offspring. CONCLUSIONS: Alterations in steroid secretion observed in association with maternal PND may provide a mechanism by which risk for depression is transmitted from mother to offspring.     

Conduct disorder subtype and comorbidity.

BACKGROUND: Conduct disorder is considered difficult to treat, but comorbid psychiatric disorders may be a basis for treating some youths with conduct disorder. We sought to identify patterns of comorbid psychiatric diagnoses and psychopathology associated with conduct disorder by reported age-of-onset. METHODS: Referred children and adolescents, aged 4-17 years old, were clinically evaluated. Ages of onset of CD symptoms (N=53) were ascertained and divided according to DSM-IV criteria as childhood onset (<10 years old) or adolescent onset (>or=10 years old). RESULTS: Childhood-onset conduct disorder was associated with higher rates of ADHD and anxiety disorders, male gender, and perceived and total hostility scores than adolescent-onset conduct disorder. Adolescent-onset was associated with higher rates of PTSD, alcohol and substance use disorders, complex comorbidity (i.e., 6+ diagnoses lifetime), and female gender. CONCLUSIONS: Understanding age-of-onset-related patterns of comorbidity may facilitate psychiatric treatment planning in children and adolescents with conduct disorder.     

Orexin A in adolescents with anxiety disorders

Abstract

Objectives: The relationships between orexins and stress-related conditions have been well documented in animal studies. However, human studies confirming this relationship are limited. The aim of this study was to investigate the association between orexin-A and anxiety disorders in adolescents. Additionally, we aimed to examine the relationship between orexin-A and cortisol levels in those with anxiety disorders.

Methods: A total of 56 medication-free adolescents diagnosed with any anxiety disorder, except for specific phobias, and 32 healthy controls were included in this study. Depression, state and trait anxiety levels of the participants were measured using self-report scales. Orexin-A and cortisol levels were measured by an enzyme-linked immunosorbent assay (ELISA).

Results: Analysis of covariance (ANCOVA) indicated that serum orexin-A levels were significantly higher in the anxiety disorder group than in the control group while controlling for age, sex and depression levels. After controlling for age and sex, orexin-A levels were positively and negatively correlated to depression and cortisol levels, respectively. In addition, a positive correlation trend between trait anxiety and orexin-A was found.

Conclusions: Orexin-A levels are higher in adolescents with anxiety disorder; however, depressive symptoms should be considered when investigating this relationship.     

A controlled study of alexithymia in adolescent patients with persistent somatoform pain disorder.

OBJECTIVE: To study the differences in levels of alexithymia, depression, and anxiety between a sample of adolescents diagnosed with ICD-10 persistent somatoform pain disorder (defined by the DSM-IV as a pain disorder associated with psychological factors) and healthy adolescent control subjects. METHOD: Using the Toronto Alexithymia Scale and the Hospital Anxiety and Depression Scale, we investigated the point prevalence of alexithymia, anxiety, and depression among adolescents aged 12 to 17 years, with somatoform disorder, who were hospitalized in Kaunas Medical University Hospital, Lithuania (n =120), and a healthy control group (n = 60) of adolescents aged 12 to 17 years, who were randomly selected from 6 schools in Kaunas, Lithuania. RESULTS: The rate of alexithymia in adolescents with somatoform disorder was 59%, which was significantly higher than that in healthy control subjects (1%, P < 0.001). Similarly, the rate of anxiety was significantly higher in the patient group (62%), compared with control subjects (15%, P < 0.001). The rate of depression was low in both groups and did not differ significantly between groups. CONCLUSIONS: Adolescents with somatoform disorder have higher levels of alexithymia and anxiety than healthy adolescent control subjects, but adolescents with somatoform disorder and adolescent control subjects do not have significantly different levels of depression.