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.     

Effects of mirtazapine on dehydroepiandrosterone-sulfate and cortisol plasma concentrations in depressed patients

Background

Among the neuroactive steroids, dehydroepiandrosterone sulfate (DHEA-S) is at least in part produced in the adrenal gland and is therefore under the control of the hypothalamic-pituitary-adrenocortical (HPA)-system. In the present study, the impact of mirtazapine on DHEA-S and cortisol (COR) levels was investigated in relation to clinical response in depressed patients.

Methods

A total of 23 inpatients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 0800 h and quantified for COR and DHEA-S levels.

Results

Mirtazapine significantly reduced both COR and DHEA-S concentrations, but had no impact on the COR/DHEA-S ratio. The percentage decrease of DHEA-S, but not that of COR was significantly and positively correlated with the percentage reduction in the sum score of the Hamilton Depression Rating Scale at week 5, suggesting a relationship between DHEA-S reduction and clinical efficacy of mirtazapine. There was a significant positive correlation between the decline in COR and DHEA-S levels.

Conclusions

Apparently, the decrease in COR and DHEA-S concentrations conjointly reflects an attenuating impact of mirtazapine on HPA axis activity, thereby decreasing the adrenal secretion of COR and DHEA-S.     

Psychological and behavioral factors in patients with comorbid obstructive sleep apnea and insomnia

Objective

Insomnia symptoms in patients with obstructive sleep apnea (OSA) are commonly assumed to be secondary to respiratory disturbances. Previous studies, however, showed that insomnia might persist after treatment for OSA. Higher levels of emotional disturbances were reported in OSA patients with insomnia than those without insomnia, which suggests that psychological factors may play an important role for their sleep difficulties. This study aimed to further explore sleep-related psychological/behavioral factors that may contribute to insomnia in OSA patients.

Methods

This study included 88 men, of which 33 had OSA (OSA group); 29, primary insomnia; (Insomnia group); and 26, both OSA and insomnia (OSA+Insomnia group). All subjects underwent polysomnography (PSG) overnight and completed a package of questionnaires, including the Insomnia Severity Index (ISI), Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), Sleep Hygiene Practice Scale (SHPS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Pre-Sleep Arousal Scale (PSAS).

Results

The OSA+Insomnia and Insomnia groups had significantly more dysfunctional sleep beliefs, more arousal-inducing sleep-related behaviors, and higher levels of pre-sleep arousal, anxiety, and depression than did the OSA group. The respiratory indices and arousal index were higher for OSA and OSA+Insomnia groups than for the Insomnia group.

Conclusion

Although OSA patients with insomnia showed a similar degree of respiratory disturbances as patients with OSA only, their psychological and behavioral profiles resembled the features of primary insomnia patients. The results support the concept of comorbid insomnia and suggest the importance of evaluating and treating both physiological and psychological factors in these patients.     

Interactions between sleep normative data and sociocultural characteristics in the elderly

Objective

To present sleep patterns in elderly individuals and factors associated with short sleep and long daytime and nighttime sleep.

Methods

A total of 8091 subjects aged between 55 and 101 years representative of the noninstitutionalized general population of seven European countries (France, Finland, Italy, Germany, Portugal, Spain, and UK) were interviewed by telephone about their sleep habits and sleep disorders.

Results

The average sleep duration was 6 h and 57 min. Sleep duration was longer in men than in women. Five percent of the sample slept 5 h or less and 5% slept 9 h or more per night. Factors associated with short sleep (lower fifth percentile) were age, living in UK, no physical exercise, drinking six cups of coffee or more per day, taking a medication for sleep, difficulty initiating sleep, disrupted sleep, early morning awakening, and presence of an anxiety disorder. Factors associated with long sleep (≥95th percentile) were age, living in France, Portugal, or Spain, being underweight, no physical exercise, disrupted sleep, taking a medication for sleep, and presence of an anxiety disorder. Long daytime sleep (54 min or more) were age, being a man, being overweight or obese, physical disease, being dissatisfied with one's social life, smoking, drinking alcohol, and having a major depressive disorder.

Conclusion

Sleep patterns considerably varied among the countries in the elderly population. Extreme values of sleep duration (short and long sleep) were associated with several sleep and mental health problems.     

The Brazilian database on pregnancy in multiple sclerosis

Objectives

To report the results from the Brazilian database on multiple sclerosis (MS) and pregnancy.

Methods

Retrospective data from MS patients who became pregnant at any time of their disease were sent to a Brazilian database, using a specific file for this purpose.

Results

Data on 128 women (142 pregnancies) from 30 neurologists working in 21 cities in Brazil were collected. Patients’ average age at pregnancy was 29.8 years (range 16-42). EDSS at start of pregnancy was 1.5 ± 1.4; and the relapse rate in the year preceding pregnancy was 1.2 ± 1.5. Exposure to medication at any time during pregnancy was high (69.7%): 48.6% to interferon beta; 14.1% to glatiramer acetate; and 7% to other immunomodulatory and immunosuppressive drugs. There was a significant decrease in relapse rate during pregnancy. The prevalence of complications was relatively low, with 4.9% of obstetric and 1.4% neonatal unfavorable outcomes.

Conclusions

Our patients had low degrees of disability, short histories of disease, high drug exposure, and relatively high relapse rate in the year previous to pregnancy. Obstetric and neonatal outcomes were successful in over 90% of our patients.     

Are personality dimensions associated with sleep length in a large nationally representative sample?

Objectives

The purpose of this hypothesis-generating study was to determine whether personality domains and specific personality traits are uniquely associated with sleep duration using data obtained from the National Comorbidity Survey (NCS).

Methods

Using trained interviewers, we administered to the 5877 noninstitutionalized adults living in the United States the Composite International Diagnostic Interview (World Health Organization. Composite International Diagnostic Interview. Geneva, Switzerland: WHO, 1990) to assess for any DSM-III-R psychiatric diagnoses, and they completed self-report measures of personality and sleep. This was a secondary data analysis using information from a large existing public use data set (NCS-part II). The NCS-part II was an epidemiologic survey based on a stratified multistage area probability method with a response rate of 82.4%.

Results

Using a multivariate logistic regression technique, we found significant and positive associations between short sleep (defined as ≤6 hours of sleep per 24-hour period) and self-criticism (odds ratio [OR] = 1.36), the presence of a medical condition (OR = 1.35), neuroticism (OR = 1.30), and the use of sedating medication in the past 12 months (OR = 1.26). Significant and positive associations were found for long sleep (defined as ≥9 hours per 24 hour period) and a diagnosis of dysthymia (OR = 1.52), the use of a sedating medication in the past 12 months (OR = 1.52), emotional reliance on another person (OR = 1.37), employment status (OR = 1.31), and marital status (OR = 1.20).

Conclusions

Findings suggest that personality, even after controlling for psychiatric and medical conditions, is associated with sleep length and may be an additional factor to consider when assessing any individual patient.     

Amours et neurologie

Introduction

Love is a complex emotional state which is difficult to define. Considering anthropological studies, this feeling can now be divided into three distinct behaviors: lust, attraction for a specific partner and conjugal or filial attachment.

State of art

For each, recent findings have contributed to identify specific neuronal networks which are interconnected as shown by common activation of limbic and paralimbic systems. A major role of arginine/vasopressin and oxytocin has also been pointed out for mate choice and attachment promotion. In the field of neurology, studies about pathologies of love are sparse and mainly focused on sexual disorders. Pathologies of attachment like autism and borderline personality are beginning to be identified.

Perspectives

Future investigations would yield a better understanding of this complex emotional state and a better detection of new pathologies related to a major affective disability.

Conclusion

Neurosciences have contributed to highlight mechanisms involved in love.     

An experimental exploration of behavioral and cognitive-emotional aspects of intolerance of uncertainty in eating disorder patients

Objective

Intolerance of uncertainty (IU) is an important concept in eating disorders (ED). Cognitive, emotional, and behavioral features of IU amongst individuals with and without ED were investigated.

Method

Participants completed the intolerance of uncertainty scale (IUS) and four versions of a data-gathering task varying in difficulty/uncertainty, and rated their Beads task experience.

Results

ED groups had significantly higher IUS scores than healthy controls (HC). Bulimia Nervosa (BN) participants requested more cues than HC and Anorexia Nervosa (AN) participants before making decisions. ED groups found the task more distressing than HC participants, with those with BN feeling more uncertain and less confident in their decisions, and those with AN attributing greater importance in making the correct decision.

Discussion

While both ED groups reported raised IUS scores only BN participants engaged in an elevated evidence requirement data gathering style. Future research might benefit from further exploration of the role of perseverative processes in BN.     

Effort-reward imbalance at work and risk of sleep disturbances. Cross-sectional and prospective results from the Danish Work Environment Cohort Study

Objectives

This study aimed to analyze if adverse psychosocial working conditions, defined by the model of effort-reward imbalance (ERI), increase the risk of sleep disturbances in the Danish workforce.

Methods

Analyses were conducted both cross-sectionally and prospectively in a representative sample of Danish employees. The cross-sectional sample included 2614 participants (50% women) aged 18-59 years, of whom 263 had sleep disturbances. Of the 2351 participants initially free of sleep disturbances, 304 (12.9%) developed sleep disturbances during the 5-year follow-up. Data were analyzed with gender-stratified, multivariate logistic and linear regression analyses, adjusted for numerous covariates.

Results

Cross-sectionally, a 1 S.D. increase in the ERI ratio was associated with sleep disturbances among both men [odds ratio (OR)=1.65, 95% confidence interval (CI)=1.20-2.27] and women (OR=1.82, 95% CI=1.46-2.28). In the prospective analysis, a 1 S.D. increase of the ERI ratio at baseline predicted the onset of sleep disturbances among men (OR=1.39, 95% CI=1.03-1.87) but not among women (OR=0.97, 95% CI=0.76-1.24).

Conclusion

Among men, ERI is a risk factor for the development of sleep disturbances in the Danish workforce. Among women, an association between ERI and sleep disturbances was restricted to the cross-sectional sample. Improving psychosocial working conditions might reduce the risk of sleep disturbances and subsequently also help to prevent clinical disorders related to sleep disturbances.     

Inaccuracy and misjudged factors of Glasgow Coma Scale scores when assessed by inexperienced physicians

Objectives

Appropriate triage of a large number of patients with head injury is crucial in the emergency department (ED) as well as in the field. Traumatic brain injury (TBI) is primarily assessed using the Glasgow Coma Scale (GCS) to evaluate consciousness. However, GCS score assignment is far from sufficiently reliable for correct assessment, especially with inexperienced users. The purpose of this study was to reveal what factors are misjudged when assessed by inexperienced medical personnel.

Methods

We analyzed GCS eye, verbal, and motor response (EVM) scoring profiles conducted by postgraduate year 1 junior residents (n = 94) before they began residency in specific departments. GCS assessment was tested using a video simulation that portrayed mock patients with eight different levels of consciousness that are frequently encountered in trauma patients.

Results

On average, 26 ± 18% of examinees failed to provide the correct EVM profiles for the eight selected consciousness levels. Primary misjudged GCS factors belonged to two categories: the assessment of “confused conversation (V4)”, and the assessment of “withdrawal motor response (M4)”.

Conclusion

Additional instruction regarding the specific misjudged factors identified in this study may help inexperienced medical personnel improve the reliability of GCS score assignment to casualties with TBI.     

Adoption, adolescence et difficultés de comportement : quels facteurs de risque ?

Objective

To explore the impact of the age at adoption, gender and country from origin in developing problem behaviours for adopted adolescents.

Patients

Three hundred and fifty-eight adolescents adopted in Quebec from 1985 aged from 12- to 18-year-old.

Methods

Parents-reported and self-reported questionnaires on problem behaviours, and information about adoption (date and country).

Results

We found that adolescents that have been adopted lately and from Eastern Europe were the most vulnerable to problem behaviours. We identify problems related to adoption in itself and problems related to age at adoption and country from origin. But if children are adopted before 6 months or between 12 and 24 months, the country of origin has no impact on problem behaviours.

Conclusion

It appears that there are two critical periods in which children are more vulnerable for change related to adoption. The first is between 6 to 12 months, when differentiated relationships are created, and the second one appears to be after 24 months, during the stabilization of attachment processes.     

Attentional bias for emotional faces in paediatric anxiety disorders: An investigation using the emotional go/no go task

Background

The present study examined contextual modulation of attentional control processes in paediatric anxiety disorders.

Method

Anxious children (N = 20) and non-anxious controls (N = 20) completed an emotional Go/No Go task in which they responded on some trials (i.e., Go trials) when neutral faces were presented amongst either angry or happy faces to which children avoided responding (i.e., No Go trials) or when angry and happy faces were presented as Go trials and children avoided responding to neutral faces.

Results

Anxious girls were slower responding to neutral faces with embedded angry compared with happy face No Go trials whereas non-anxious girls were slower responding to neutral faces with embedded happy versus angry face No Go trials. Anxious and non-anxious boys showed the same basic pattern as non-anxious girls. There were no significant group differences on No Go trials or when the emotional faces were presented as Go trials.

Conclusions

Results are discussed in terms of selective interference by angry faces in the control of attention in anxious girls.     

Association of FKBP5 gene haplotypes with completed suicide in the Japanese population

Background

The hypothalamus-pituitary-adrenal (HPA) axis is known to have a role in suicidal behaviors in patients with affective disorders. However, the incomplete overlapping of the genetic factors of suicidal behaviors and the genetic factors of affective disorders suggest that the genes associated with predisposition to suicidal behaviors and affective disorders are different. There is increasing evidence that genes regulating the HPA axis have effects on suicidal behaviors. To test this idea, we examined the association of three HPA axis-related genes (glucocorticoid receptor (NR3C1), mineralocorticoid receptors (NR3C2), and FK506 binding protein 5 (FKBP5)) with suicide.

Methods

We selected 3 SNPs of the FKBP5 (rs3800373, rs1360780, and rs2395635), 2 SNPs of the NR3C1 (rs6196 and rs10052957), and 3 SNPs of the NR3C2 genes (rs5525, rs5522, and rs2070951) based on their frequency in the Japanese population. Using TaqMan probe assays, we determined these SNPs in 219 completed suicide victims and 228 age- and gender-matched healthy control subjects.

Results

No significant differences in genotypic distribution or allelic frequency of any single SNPs between the completed suicide and control groups were observed. The distributions of TT, TC, and GT haplotypes of the FKBP5 gene (comprised of rs3800373 and rs1360780) between the completed suicide and control groups were significantly different (p < 0.05 for each haplotype). The TC haplotype withstood correction for multiple comparisons (corrected p = 0.034).

Conclusion

Our results suggest that haplotypes in FKBP5 gene are associated with completed suicide. This finding needs to be confirmed using rigorous SNPs selection in a larger sample.     

Expansion of the phenotypic spectrum of SPG6 caused by mutation in NIPA1

Background

Hereditary spastic paraplegia type 6 (SPG6) is caused by mutations in the NIPA1 gene, this is a rare cause of HSP, until now, all the affected individuals reported displayed “pure” spastic paraplegia.

Objectives

To analyze the genotype/phenotype correlation of mutations so far described in NIPA1.

Methods

Eighty-six Chinese Han HSP patients were investigated for SPG6 mutations by direct sequencing of the NIPA1 gene.

Results

One heterozygous missense mutation c.316G > C/p.G106R was identified in a complicated form of ADHSP family with peripheral nerves disease, and SPG6 mutation in our sample accounted for 3.6% (1/28) of ADHSP families and 1.1% (1/86) of non-ARHSP patients who were negative for SPG4, SPG3A and SPG31 mutations.

Conclusions

We report the first complicated case of SPG6 in the world by the presence of peripheral neuropathy, which extends the phenotype initially described.     

Un tremblement d’attitude révélant une maladie de Huntington

Introduction

Initial manifestations of Huntington's disease (HD) are varied and chorea is not always the first motor symptom.

Case report

We report the case of a 44-year-old woman, with a family history of HD, who presented isolated head and upper limbs tremor for 4 years. Genetic testing confirmed the diagnosis of HD and no cause of secondary postural tremor was found. Propanolol was introduced with success.

Conclusion

This kind of presentation is unusual and has mostly been reported in the juvenile form of HD.     

Sleep spindles in chronic psychophysiological insomnia

Objective

A sleep spindle is an electroencephalographic feature that is unique to sleep. It has been suggested that this phasic event has a sleep-protective function. The objective of the present study was to document one aspect of sleep protection in chronic insomnia sufferers: the number and density of sleep spindles in Stage 2 sleep.

Methods

Sleep spindles were scored during Stage 2 sleep on the second and third nights of a protocol of polysomnographic recordings that lasted for four consecutive nights. The sample included 16 participants suffering from insomnia (INS group; mean age=43.4 years) and 14 good sleepers (GS group; mean age=38.1 years). Participants underwent sleep and psychological evaluations. The INS group participants met the diagnostic criteria for primary psychophysiological insomnia (mean duration of insomnia=9.6 years).

Results

The total number of sleep spindles in Stage 2 sleep and the density (sleep spindles per minute) according to the total time spent in Stage 2 sleep were compiled. Repeated-measures analyses of variance showed no significant difference in the number and in the density of sleep spindles between the INS group (68.46 and 0.60, respectively) and the GS group (56.28 and 0.46, respectively).

Conclusion

These results suggest no deficiency in the sleep-protection mechanism of psychophysiological insomnia sufferers in comparison with good sleeper controls, as measured by the number and density of sleep spindles.     

Hierarchy of insomnia criteria based on daytime consequences

Objectives

To explore how insomnia symptoms are hierarchically organized in individuals reporting daytime consequences of their sleep disturbances.

Methods

This is a cross-sectional study conducted in the general population of the states of California, New York, and Texas. The sample included 8937 individuals aged 18 years or older representative of the general population. Telephone interviews on sleep habits and disorders were managed with the Sleep-EVAL expert system and using DSM-IV and ICSD classifications. Insomnia symptoms and global sleep dissatisfaction (GSD) had to occur at least three times per week for at least three months.

Results

A total of 26.2% of the sample had a GSD. Individuals with GSD reported at least one insomnia symptom in 73.1% of the cases. The presence of GSD in addition to insomnia symptoms considerably increased the proportion of individuals with daytime consequences related to insomnia. In the classification trees performed, GSD arrived as the first predictor for daytime consequences related to insomnia. The second predictor was nonrestorative sleep followed by difficulty resuming sleep and difficulty initiating sleep.

Conclusions

Classification trees are a useful way to hierarchically organize symptoms and to help diagnostic classifications. In this study, GSD was found to be the foremost symptom in identifying individuals with daytime consequences related to insomnia.     

Measuring disability in patients with chronic fatigue syndrome: reliability and validity of the Work and Social Adjustment Scale

Background

Disability is a defining feature of chronic conditions, and it is an increasingly used measure of therapy effectiveness. The Work and Social Adjustment Scale (WSAS) is a simple and clear measure of disability. Although the scale is widely used, no study has yet investigated its psychometric properties in patients with chronic fatigue syndrome (CFS).

Methods

Data from two samples of patients were used, one from a multicenter randomized controlled clinical trial of treatments for CFS (n =639) and the other from a clinic that specializes in CFS (n=384). All patients completed the WSAS as well as other measures.

Results

Internal consistency and the Spearman-Brown split-half coefficient values indicated that the scale is reliable. CFS patients who had comorbid diagnoses of depression, anxiety or fibromyalgia had higher WSAS scores. High levels of disability were associated with high number of physical symptoms, severe fatigue, depression, anxiety, poor sleep quality and poor physical fitness, with correlation coefficients ranging between 0.41 and 0.11. Lower scores on the WSAS were modestly associated with better physical functioning as well as higher levels of physical capacity as assessed by a walking test. Sensitivity to change was evaluated in a subgroup of patients who had undergone a course of cognitive behavioral therapy. Disability significantly decreased after therapy and remained stable at follow-ups.

Conclusion

The WSAS is a reliable and valid assessment tool for disability in patients with CFS.     

Impact of loudness dependency of auditory evoked potentials on the panic response to CCK-4

Rationale

Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) has been established as a model to study the pathophysiology of panic disorder. In line with the serotonin (5-HT)-hypothesis of panic disorder it has been suggested that the panicogenic effects of CCK-4 are mediated in part through the 5-HT system. The analysis of the loudness dependency of the auditory evoked potentials (LDAEP) is a valid non-invasive indicator of central serotonergic activity.

Methods

We investigated the correlation between LDAEP and behavioral, cardiovascular and neuroendocrine panic responses to CCK-4 in 77 healthy volunteers and explored whether differences in LDAEP paralleled subjective panic severity. Behavioral panic responses were measured with the panic symptom scale (PSS). Heart rate and ACTH/cortisol plasma concentrations were assessed concomitantly.

Results

LDAEP did not differ between panickers and nonpanickers. Furthermore, LDAEP did not correlate with the behavioral panic response. However, a significant positive correlation between LDAEP and CCK-4 induced HPA-axis activation, which was uniform in panickers and nonpanickers, could be detected.

Conclusions

The psychological effects of CCK-4 rather are mediated by neurotransmitters others than the endogenous 5-HT system. However, the extent of the neuroendocrine activation related to the CCK-4 panic provocation was correlated with the LDAEP, thereby suggesting that central 5-HT mechanisms are involved in the HPA-axis activation during this challenge paradigm.