The sleep-enhancing effect of valerian inhalation and sleep-shortening effect of lemon inhalation

We examined the effects of odorant inhalation on the sleep-wake states in rats. Odorants used in the experiment were clove, jasmine, lavender, lemon, peppermint, pine, rose, sandalwood, valerian, and ylang-ylang. Valerian and rose inhalation significantly prolonged the pentobarbital-induced sleeping time, whereas lemon inhalation significantly shortened it. The effect of valerian inhalation was markedly noticeable. In the anosmic rats, a significant effect of odorants on the pentobarbital sleep time was not seen. Electroencephalographic studies on natural sleep revealed that rose inhalation did not exert any significant effect on sleep, but a significant shortening in sleep latency and a significant prolonging in total sleep time were observed with valerian inhalation, whereas a significant prolonging in sleep latency was observed with lemon inhalation. Such effects of valerian and lemon inhalation were not admitted in anosmic rats. gamma-Aminobutyric acid (GABA) transaminase assay indicates that valerian inhalation decreases the activity of the enzyme and enhances GABA activity. Although valerian has been reported to exert a good effect for sleep as a medicine for internal use, the present study is the first medical report suggesting that the inhalation of valerian may enhance the sleep. On the other hand, the present results may suggest the possibility that lemon inhalation may cause a worsening of insomnia symptoms.     

Microduplication 22q11.2: a description of the clinical, developmental and behavioral characteristics during childhood

Microduplication 22q11.2 is a recently discovered genomic disorder. So far, targeted research on the cognitive and behavioral characteristics of individuals with this microduplication is limited. Therefore, 11 Flemish children (3-13 years old) with a microduplication 22q 1.2 were investigated in order to describe their clinical, developmental and behavioral characteristics. We measured their general intelligence, visual-motor capacities, attention, behavioral problems and characteristics of autism. In addition, there was an interview with the parents on developmental history and we reviewed available information from other specialists. The results show that the cognitive and behavioral phenotype of the children with microduplication 22q.11.2 is very wide and heterogeneous. Some of the children have a cognitively nearly normal development whereas others are more severely affected. All children had some degree of developmental delay and some of them have an intellectual disability. The most common clinical features include congenital malformations such as heart defects and cleft lip, feeding problems, hearing impairment and facial dysmorphism. The most common non-medical problems are learning difficulties, motor impairment, attention deficits, social problems and behavioral problems. There is no correlation between the size of the duplication and the phenotype.     

A systematic review of treatment of settling problems and night waking in young children

OBJECTIVE: To assess the efficacy of treatment of settling problems and night waking in young children. DESIGN: A systematic review of randomized controlled trials of interventions. SETTING: Electronic bibliographic databases and references on identified papers, hand searches, and personal contact with specialists. SUBJECTS: Children aged 5 years or younger who had established settling problems or night waking. INTERVENTIONS: Interventions had to be described and a placebo, waiting list, or another intervention needed to have been used as a comparison. Interventions comprised drug trials or nondrug trials. Main outcome measures Number of wakes at night, time to settle, or number of nights in which these problems occurred. RESULTS: Drugs seemed to be effective in treating night waking in the short term, but long-term efficacy was questionable. In contrast, specific behavioral interventions showed both short-term efficacy and possible longer term effects for dealing with settling problems and night walking. CONCLUSIONS: Given the prevalence and persistence of childhood sleep problems and the effects they can have no children and families, treatments that offer long-lasting benefits are more appealing, and these are likely to be behavioral interventions.     

Hyperactivity,concentration difficulties and impulsiveness improve during seven weeks’ treatment with valerian root and lemon balm extracts in primary school children

BackgroundValerian root and lemon balm extracts have previously shown efficacy and excellent tolerability in children < 12 years suffering from restlessness and insomnia. We now examined whether treatment with a fixed combination of both may also improve concentration, hyperactivity and impulsiveness.Methods169 primary school children suffering from hyperactivity and concentration difficulties but not meeting ADHD criteria were treated in an observational study by 27 office based pediatricians with a recommended daily dose of 640 mg valerian root extract WS® 1014 and 320 mg lemon balm extract WS® 1303 (Sandrin®), and evaluated by pediatricians and parents using standardized questionnaires at baseline, weeks 2 and 7.ResultsThe fraction of children having strong/very strong symptoms of poor ability to focus decreased from 75% to 14%, hyperactivity from 61% to 13%, and impulsiveness from 59% to 22%. Parent rated social behavior, sleep and symptom burden showed highly significant improvements. Only in two children mild transient adverse drug reactions were observed.ConclusionIn primary school children with restlessness, concentration difficulties and impulsiveness treatment with WS® 1014 and WS® 1303 (Sandrin®) provides a viable option in addition to counseling and education.     

Supporting the generalist genes hypothesis for intellectual ability/disability: the case of SNAP25

Intellectual disability (ID) is an unresolved health care problem with a worldwide prevalence rate of 2–3%. For many years, research into the genetic causes of ID and related disorders has mainly focused on chromosomal abnormalities or X‐linked genetic deficits. Only a handful of autosomal genes are known to cause ID. At the same time it has been suggested that at least some cases of ID represent an extreme form of normal intellectual ability and therefore that genes important for intellectual ability in the normal range may also play a role in ID. In this study, we tested whether the autosomal SNAP25 gene, which was previously associated with variation in intellectual ability in the normal range, is also associated with ID. The gene product of SNAP25 is an important presynaptic plasma membrane protein, is known to be involved in regulating neurotransmitter release, and has been linked to memory and learning by its effect on long term potentiation in the hippocampus. Allele frequencies of two genetic variants in SNAP25 previously associated with intellectual ability were compared between a group of 636 ID cases (IQ < 70) and a control group of 361 persons of higher than average intellectual ability. We observed a higher frequency of the putative risk allele of rs363050 (P = 0.02; OR = 1.24) in cases as compared to controls. These results are consistent with a role of SNAP25 in ID, and also support the notion that ID reflects the lower extreme of the quantitative distribution of intellectual ability.     

Copy Number Variation Screen Identifies a Rare De Novo Deletion at Chromosome 15q13.1-13.3 in a Child with Language Impairment

A significant proportion of children (up to 7% in the UK) present with pronounced language difficulties that cannot be explained by obvious causes like other neurological and medical conditions. A substantial genetic component is predicted to underlie such language problems. Copy number variants (CNVs) have been implicated in neurodevelopmental and psychiatric conditions, such as autism and schizophrenia, but it is not fully established to what extent they might contribute to language disorders. We conducted a CNV screen in a longitudinal cohort of young children with language-related difficulties (n = 85), focusing on single events at candidate loci. We detected a de novo deletion on chromosome 15q13.1–13.3. The adjacent 15q11-13.1 locus is disrupted in Prader-Willi and Angelman syndromes, while disruptions across the breakpoints (BP1-BP6) have previously been implicated in different neurodevelopmental phenotypes including autism, intellectual disability (ID), seizures and developmental delay (DD). This is the first report of a deletion at BP3-BP5 being linked to a deficit confined to language impairment, in the absence of ID, expanding the range of phenotypes that implicate the chromosome 15q13 locus.     

Conscious Sedation Procedures Using Intravenous Midazolam for Dental Care in Patients with Different Cognitive Profiles: A Prospective Study of Effectiveness and Safety

The use of midazolam for dental care in patients with intellectual disability is poorly documented. This study aimed to evaluate the effectiveness and safety of conscious sedation procedures using intravenous midazolam in adults and children with intellectual disability (ID) compared to dentally anxious patients (DA). Ninety-eight patients with ID and 44 patients with DA programmed for intravenous midazolam participated in the study over 187 and 133 sessions, respectively. Evaluation criteria were success of dental treatment, cooperation level (modified Venham scale), and occurrence of adverse effects. The mean intravenous dose administered was 8.8±4.9 mg and 9.8±4.1 mg in ID and DA sessions respectively (t-test, NS). 50% N₂O/O₂ was administered during cannulation in 51% of ID sessions and 61% of DA sessions (NS, Fisher exact test). Oral or rectal midazolam premedication was administered for cannulation in 31% of ID sessions and 3% of DA sessions (p<0,001, Fisher exact test). Dental treatment was successful in 9 out of 10 sessions for both groups. Minor adverse effects occurred in 16.6% and 6.8% of ID and DA sessions respectively (p = 0.01, Fisher exact test). Patients with ID were more often very disturbed during cannulation (25.4% ID vs. 3.9% DA sessions) and were less often relaxed after induction (58.9% ID vs. 90.3% DA) and during dental treatment (39.5% ID vs. 59.7% DA) (p<0.001, Fisher exact test) than patients with DA. When midazolam sedation was repeated, cooperation improved for both groups. Conscious sedation procedures using intravenous midazolam, with or without premedication and/or inhalation sedation (50% N₂O/O₂), were shown to be safe and effective in patients with intellectual disability when administered by dentists.     

Delayed sleep phase disorder and Attention deficit and hyperactivity symptoms in a teenager

JR is an 18-year-old male with five-year history of going to bed late and waking up late. He gives history of poor frustration tolerance, inattention and fidgetiness in school for which he has been unsuccessfully been treated with stimulant medications for last 3 years. There is history of similar sleep problems in his father who works nights as a mechanic. JR's sleep log shows him going to bed early morning and waking up late morning/afternoon. He shows no sleep maintenance problems and sleeps an average of 8 h per night. He shows no symptoms of depression, anxiety, inattention or hyperactivity during his hospital stay. He does not show any learning, cognitive, attention or intellectual deficits. He is currently not taking any medications. He is discharged home after 3-day hospital stay and is reportedly doing well working in a video rental store at night.     

Adequacy of Maternal Iron Status Protects against Behavioral,Neuroanatomical, and Growth Deficits in Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASD) are the leading non-genetic cause of neurodevelopmental disability in children. Although alcohol is clearly teratogenic, environmental factors such as gravidity and socioeconomic status significantly modify individual FASD risk despite equivalent alcohol intake. An explanation for this variability could inform FASD prevention. Here we show that the most common nutritional deficiency of pregnancy, iron deficiency without anemia (ID), is a potent and synergistic modifier of FASD risk. Using an established rat model of third trimester-equivalent binge drinking, we show that ID significantly interacts with alcohol to impair postnatal somatic growth, associative learning, and white matter formation, as compared with either insult separately. For the associative learning and myelination deficits, the ID-alcohol interaction was synergistic and the deficits persisted even after the offsprings’ iron status had normalized. Importantly, the observed deficits in the ID-alcohol animals comprise key diagnostic criteria of FASD. Other neurobehaviors were normal, showing the ID-alcohol interaction was selective and did not reflect a generalized malnutrition. Importantly ID worsened FASD outcome even though the mothers lacked overt anemia; thus diagnostics that emphasize hematological markers will not identify pregnancies at-risk. This is the first direct demonstration that, as suggested by clinical studies, maternal iron status has a unique influence upon FASD outcome. While alcohol is unquestionably teratogenic, this ID-alcohol interaction likely represents a significant portion of FASD diagnoses because ID is more common in alcohol-abusing pregnancies than generally appreciated. Iron status may also underlie the associations between FASD and parity or socioeconomic status. We propose that increased attention to normalizing maternal iron status will substantially improve FASD outcome, even if maternal alcohol abuse continues. These findings offer novel insights into how alcohol damages the developing brain.     

The nature of social cognitive deficits in children and adults with Klinefelter syndrome (47,XXY)

About 1 in 650 boys are born with an extra X chromosome (47,XXY or Klinefelter syndrome). 47,XXY is associated with vulnerabilities in socio‐emotional development. This study was designed to assess types of cognitive deficits in individuals with 47,XXY that may contribute to social‐emotional dysfunction, and to evaluate the nature of such deficits at various levels: ranging from basic visuospatial processing deficits, impairments in face recognition (FR), to emotion expression impairments. A total of 70 boys and men with 47,XXY, aged 8 to 60 years old, participated in the study. The subtests feature identification, FR and identification of facial emotions of the Amsterdam Neuropsychological Tasks were used. Level of intellectual functioning was assessed with the child and adult versions of the Wechsler Intelligence Scales. Reaction time data showed that in the 47,XXY group, 17% had difficulties in visuospatial processing (no social load), 26% had difficulties with FR (medium social load) and an even higher number of 33% had difficulties with facial expressions of emotions (high‐social load). Information processing impairments increased as a function of “social load” of the stimuli, independent of intellectual functioning. Taken together, our data suggest that on average individuals with XXY may have more difficulties in information processing when “social load” increases, suggesting a specific difficulty in the higher‐order labeling and interpretation of social cues, which cannot be explained by more basic visuospatial perceptual skills. Considering the increased risk for social cognitive impairments, routine assessment of social cognitive functioning as part of neuropsychological screening is warranted.     

Are parents’ working patterns associated with their child’s sleep? An analysis of dualparent families in Australia

Insufficient sleep in children predicts emotional and behavioral problems, poorer school performance, and health problems. Child sleep durations have declined in recent decades, suggesting a need to identify and understand predictors of short sleep. The present study investigated whether aspects of parental employment (i.e. parental work hours, and non-standard work hours) were associated with sleep in children. Data collected from 2477 children aged 6-7 years as part of the Longitudinal Study of Australian Children were used in this paper. Child sleep duration, bedtimes, and wake times were determined from parent self-report using time-use diaries. Parents completed a survey assessing their work patterns as well as a range of other demographic and social factors. The results indicated that long mother work hours were associated with later bedtimes and increased odds of <9.5 h sleep in children. Long father work hours were associated with earlier waketimes, earlier bedtimes, and reduced odds of long sleep. Non-standard work hours were associated with longer sleep and earlier bedtimes. The present results indicate the need to develop strategies to limit any adverse effects of parental work on child sleep, perhaps by promoting earlier and regular bedtimes. These findings warrant further investigation given the importance of sleep in healthy child development.

     

Malondialdehyde,Antioxidant Enzymes,and Renal Tubular Functions in Children with Iron Deficiency or Iron-Deficiency Anemia

We aimed to investigate the effects of iron deficiency (ID) or iron-deficiency anemia (IDA) on oxidative stress and renal tubular functions before and after treatment of children. A total of 30 children with a diagnosis of IDA constituted the IDA group and 32 children with a diagnosis of ID constituted the ID group. Control group consisted 38 age-matched children. Serum ferritin, soluble transferrin receptor (sTfR), serum, and urinary sodium (Na), potassium (K), calcium (Ca), phosphorus (P), creatinine (Cr), uric acid (UA), urinary N-acetyl-β-d-glucosaminidase (NAG) levels, and intra-erythrocyte malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured before and after iron therapy in the IDA and ID groups, whereas it was studied once in the control group. We have divided the study group in groups according to age (infants <2 years, children 3–9 years, and adolescents 10–15 years). Patients with IDA (infant, adolescent) and ID (infant, children, and adolescent) had a significantly high level of MDA in post-treatment period in comparison to those of healthy control. Patients with IDA (children, adolescent) and ID (infant, children) had a significantly high level of pre-treatment GSH-Px than controls. Post-treatment SOD was lower in IDA (children and adolescent) groups than control and post-treatment CAT was lower in IDA and ID (adolescent) groups than control. These findings show that ferrous sulfate used in the treatment of ID or IDA could lead to oxidative stress; however, a marked deterioration of in proximal renal tubular functions was not seen.     

Treatment of atopic eczema in children: clinical trial of 10% sodium cromoglycate ointment.

In a double-blind randomised group-comparative trial 21 children with chronic atopic eczema were treated twice daily for up to 12 weeks with an ointment containing 10% sodium cromoglycate (SCG) in white soft paraffin. A similar group of 21 children was treated for up to 12 weeks with a placebo ointment consisting of the white soft-paraffin base only. The number of patients who withdrew from the trial because treatment was ineffective was significantly greater in the placebo group (16) than in the SCG group (four). Comparison between the two groups also showed significant improvement in inflammation, lichenification, and cracking and the symptoms of itching and sleep disturbance among those on SCG treatment. At the end of treatment significantly more patients in the SCG group (16) had benefited from treatment compared with only two patients in the placebo group. No patients experienced side effects. I conclude that SCG ointment may be a safe alternative to topical steroids in the treatment of atopic eczema in children.     

Language,Reading, and Math Learning Profiles in an Epidemiological Sample of School Age Children

Dyscalculia, dyslexia, and specific language impairment (SLI) are relatively specific developmental learning disabilities in math, reading, and oral language, respectively, that occur in the context of average intellectual capacity and adequate environmental opportunities. Past research has been dominated by studies focused on single impairments despite the widespread recognition that overlapping and comorbid deficits are common. The present study took an epidemiological approach to study the learning profiles of a large school age sample in language, reading, and math. Both general learning profiles reflecting good or poor performance across measures and specific learning profiles involving either weak language, weak reading, weak math, or weak math and reading were observed. These latter four profiles characterized 70% of children with some evidence of a learning disability. Low scores in phonological short-term memory characterized clusters with a language-based weakness whereas low or variable phonological awareness was associated with the reading (but not language-based) weaknesses. The low math only group did not show these phonological deficits. These findings may suggest different etiologies for language-based deficits in language, reading, and math, reading-related impairments in reading and math, and isolated math disabilities.     

A randomized controlled trial with bright light and melatonin for delayed sleep phase disorder: Effects on subjective and objective sleep

Delayed sleep phase disorder (DSPD) is assumed to be common amongst adolescents, with potentially severe consequences in terms of school attendance and daytime functioning. The most common treatment approaches for DSPD are based on the administration of bright light and/or exogenous melatonin with or without adjunct behavioural instructions. Much is generally known about the chronobiological effects of light and melatonin. However, placebo-controlled treatment studies for DSPD are scarce, in particular in adolescents and young adults, and no standardized guidelines exist regarding treatment. The aim of the present study was, therefore, to investigate the short- and long-term effects on sleep of a DSPD treatment protocol involving administration of timed bright light and melatonin alongside gradual advancement of rise time in adolescents and young adults with DSPD in a randomized controlled trial and an open label follow-up study. A total of 40 adolescents and young adults (age range 16–25 years) diagnosed with DSPD were recruited to participate in the study. The participants were randomized to receive treatment for two weeks in one of four treatment conditions: dim light and placebo capsules, bright light and placebo capsules, dim light and melatonin capsules or bright light and melatonin capsules. In a follow-up study, participants were re-randomized to either receive treatment with the combination of bright light and melatonin or no treatment in an open label trial for approximately three months. Light and capsules were administered alongside gradual advancement of rise times. The main end points were sleep as assessed by sleep diaries and actigraphy recordings and circadian phase as assessed by salivary dim light melatonin onset (DLMO). During the two-week intervention, the timing of sleep and DLMO was advanced in all treatment conditions as seen by about 1?h advance of bed time, 2?h advance of rise time and 2?h advance of DLMO in all four groups. Sleep duration was reduced with approximately 1?h. At three-month follow-up, only the treatment group had maintained an advanced sleep phase. Sleep duration had returned to baseline levels in both groups. In conclusion, gradual advancement of rise time produced a phase advance during the two-week intervention, irrespective of treatment condition. Termination of treatment caused relapse into delayed sleep times, whereas long-term treatment with bright light and melatonin (three months) allowed maintenance of the advanced sleep phase.     

Exploring the behavioral and cognitive phenotype of KBG syndrome

KBG syndrome is a neurodevelopmental disorder, caused by dominant mutations in ANKRD11, that is characterized by developmental delay/intellectual disability, mild craniofacial dysmorphisms, and short stature. Behavior and cognition have hardly been studied, but anecdotal evidence suggests higher frequencies of ADHD‐symptoms and social‐emotional impairments. In this study, the behavioral and cognitive profile of KBG syndrome will be investigated in order to examine if and how cognitive deficits contribute to behavioral difficulties. A total of 18 patients with KBG syndrome and a control group consisting of 17 patients with other genetic disorders with comparable intelligence levels, completed neuropsychological assessment. Age‐appropriate tasks were selected, covering overall intelligence, attention, memory, executive functioning, social cognition and visuoconstruction. Results were compared using Cohen's d effect sizes. As to behavior, fewer difficulties in social functioning and slightly more attentional problems, hyperactivity, oppositional defiant behavior and conduct problems were found in the KBG syndrome group. Regarding cognitive functioning, inspection of the observed differences shows that patients with KBG syndrome showed lower scores on sustained attention, cognitive flexibility, and visuoconstruction. In contrast, the KBG syndrome group demonstrated higher scores on visual memory, social cognition and emotion recognition. The cognitive profile of KBG syndrome in this sample indicates problems in attention and executive functioning that may underlie the behavior profile which primarily comprises impulsive behavior. Contrary to expectations based on previous (case) reports, no deficits were found in social cognitive functioning. These findings are important for counseling purposes, for tailored education planning, and for the development of personalized intervention.     

Sleep patterns and sleep problems among Egyptian school children living in urban,suburban, and rural areas

The present study was conducted to determine the prevalence of sleep patterns and sleep problems among Egyptian school-aged children and to compare sleep patterns and sleep problems among school children from urban, suburban, and rural areas. In this cross-sectional survey, parents of 629 school-aged children, aged 6 to 10 years, from 15 elementary schools in five rural, urban, and suburban areas in the Giza governorate, Egypt, completed the Arabic version of the Children’s Sleep Habits Questionnaire (CSHQ) and questions about parents’ level of education and significant medical problems and/or medication for the child. The mean (SD) of total sleep duration for all children was 8.96 h (SD, 1.20). The most prevalent CSHQ subscales were: bedtime resistance, daytime sleepiness, and night wakings. There were significant differences regarding bedtime (P= 0.006) and night-time sleep duration (P < 0.001) among school children from different areas, but there were no significant differences regarding wake-up time, total sleep duration, duration of nap, and the eight CSHQ subscale scores. The percentage of children who took a daytime nap was 52.9% (n= 184) and the mean (SD) duration of a nap was 1.5 h (SD, 0.92). Paternal illiteracy was associated with higher CSHQ total score and many subscales. In conclusion, sleep duration was shorter than that reported in previous studies. Sleep problems are fairly common among elementary school children in the Giza governorate, whether in urban, suburban, or rural areas. Paternal level of education has an impact on the prevalence of sleep problems.

     

Array CGH analysis of a cohort of Russian patients with intellectual disability

The use of array comparative genomic hybridization (array CGH) as a diagnostic tool in molecular genetics has facilitated the identification of many new microdeletion/microduplication syndromes (MMSs). Furthermore, this method has allowed for the identification of copy number variations (CNVs) whose pathogenic role has yet to be uncovered. Here, we report on our application of array CGH for the identification of pathogenic CNVs in 79 Russian children with intellectual disability (ID). Twenty-six pathogenic or likely pathogenic changes in copy number were detected in 22 patients (28%): 8 CNVs corresponded to known MMSs, and 17 were not associated with previously described syndromes. In this report, we describe our findings and comment on genes potentially associated with ID that are located within the CNV regions.     

Extracts of Valeriana officinalis L. s.l. show anxiolytic and antidepressant effects but neither sedative nor myorelaxant properties.

Extracts of Valeriana officinalis L. s.l. are used for treating mild sleep disorders and nervous tension. Despite intensive research efforts, the pharmacological actions accounting for the clinical efficacy of valerian remain unclear. Thus, it was the aim of this study to evaluate CNS-related effects of different valerian extracts using behavioral paradigms (mice and rats). Following oral administration two commercially available preparations (extraction solvents: 45% methanol m/m and 70% ethanol v/v), a 35% ethanolic v/v extract and a refined extract derived from it (patented special extract phytofin Valerian 368) were tested for sedative (locomotor activity, ether-induced anaesthesia) and anxiolytic (elevated plus maze) activity. Using the forced swimming and the horizontal wire test the latter two extracts were additionally tested for antidepressant and myorelaxant properties. Up to maximum dosages of 500 or 1000 mg/kg bw none of the valerian extracts displayed sedative effects. Neither spontaneous activity was reduced nor the duration of ether-induced narcosis was prolonged. In contrast, results obtained in the elevated plus maze test revealed a pronounced anxiolytic effect of the 45% methanolic and 35% ethanolic extract as well as of phyotofin Valerian 368 in a dose range of 100-500 mg/kg bw. Additionally and different from its primary extract (35% ethanolic extract) phytofin Valerian 368 showed antidepressant activity in the forced swimming test after subacute treatment. Myorelaxant effects were not observed in dosages up to 1000 mg/kg bw. Due to these findings it is proposed that not sedative but anxiolytic and antidepressant activity, which was elaborated particularly in the special extract phytofin Valerian 368, considerably contribute to the sleep-enhancing properties of valerian.