Susceptibility variants on chromosome 7p21.1 suggest HDAC9 as a new candidate gene for male-pattern baldness.

BACKGROUND: Male-pattern baldness (androgenetic alopecia, AGA) is the most common form of hair loss among humans. Research has shown that it is caused by genetic factors. Numerous studies have unequivocally identified two major genetic risk loci for AGA: the X-chromosomal AR/EDA2R locus, and the PAX1/FOXA2 locus on chromosome 20. OBJECTIVES: To identify further candidate genes for AGA, and thus gain further insights into this phenotype. METHODS: A German sample of 581 severely affected cases and 617 controls was used to perform a genome-wide association study. The identified associated locus was further analysed by fine-mapping, and then independently replicated in an Australian sample. Expression and pathway analyses were performed to characterize the susceptibility gene identified. RESULTS: The most significant association signal was obtained for rs756853 (P = 1·64 × 10(-7) ), which is located intronically in the histone deacetylase 9 (HDAC9) gene. Fine-mapping and a family-based analysis revealed that rs756853 and the 6-kb distal rs2249817 were the most highly associated single nucleotide polymorphisms. The association finding was replicated in an independent Australian sample, when the analysis was restricted to severely affected cases and unaffected controls (P = 0·026). Analysis of rs2249817 in a combined sample of severely affected German and Australian cases and unaffected controls revealed a strong association signal (P = 9·09 × 10(-8) ). Tissue expression studies demonstrated HDAC9 expression in various tissues, including tissues of relevance to AGA. No strong genotypic effects were observed in genotype-specific expression or splice studies. Pathway analyses supported the hypothesis that HDAC9 plays a functional role in AGA via interaction with the AR gene. CONCLUSIONS: The present study suggests that HDAC9 is the third AGA susceptibility gene.

Selecting infants with OM that need referral and further assessment: creating a case-finding instrument.

OBJECTIVE: In the Netherlands, many children are surgically treated for OM. Recent publications question the need for surgical treatment in common uncomplicated OM, although there is certainly a subgroup of infants that do need further assessment and possible treatment. The present study explores the possibility of using known and presumed risk factors for OM as an instrument for selecting and routing an infant with OM to further care. METHODS: Two questionnaires were used. A questionnaire embracing a wide range of OM-related factors was sent to 6531 children aged nine months that were routinely invited for the hearing screen at nine months. In a second stage, a structured history questionnaire regarding ear and/or hearing problems, subsequent referral and/or treatment, was sent to all parents of children at age 21 months, responding to the first questionnaire. Univariate analysis was performed for identification of potential predictors for surgical treatment of OM for the whole sample as well as for 4 different subsets. Multivariable regression analysis with stepwise backward deletion was applied to arrive at a model for optimal prediction of tube insertion. A ROC (receiver operating characteristic) curve and the accompanying sensitivity and specificity values were analyzed to determine cut off values. RESULTS: Univariate analysis found 10 items predicting surgical treatment for OM. Multivariable regression analysis resulted in a model with a ROC curve having an area of 0.801 and estimated coefficients for risk factors which were used to calculate a OM-score for each case. CONCLUSION: The developed scoring sheet, e.g., to be used in combination with physical examinations and/or tympanometry looks promising as a predictor for those children that might benefit from further assessment and eventually surgically treatment for OM.

Psychometric qualities of questionnaires for the assessment of otitis media impact.

BACKGROUND: The assessment of impact and evaluation of treatment effects in chronic otitis media (OM) calls for a much broader approach than just examining the presence of middle ear effusion or hearing loss. It is increasingly recognised that this condition may result in a comprised quality of life. Several studies have used proxy completed questionnaires to objectify the illness experience associated with chronic OM. OBJECTIVE OF REVIEW: To review questionnaires which have been developed to describe the effects of chronic OM on the daily functioning of children. Psychometric properties have been evaluated, in addition to discriminative and evaluative qualities. TYPE OF REVIEW: A systematic review of publications pertaining to developed questionnaires related with chronic OM. SEARCH STRATEGY: Systematic literature searches of PubMed (1966-January 2007) and EMBASE (1989-January 2007) were conducted, supplemented by using free text words to identify publications after January 2005. RESULTS: The included 15 questionnaires were developed for children with recurrent or persistent OM, describing functional health status (FHS), while two questionnaires also evaluate the effect of tympanostomy tubes insertion. The questionnaires generally cover six impact areas (physical symptoms, child development, educational performance, emotional/practical burden and general health status) with physical symptoms being the most prominant. CONCLUSIONS: The OM8-30, OMO-22 and OM-6 adequately reflect the multidimensional aspects of FHS in chronic OM. The OMO-22 and OM8-30 show the best psychometric properties for the discrimination of impact severity between children, while the OM-6 was found to have the best qualities for the evaluation of clinical change. Clinical applicability is crucial for the assessment of FHS in chronic OM, but requires a trade-off with necessary psychometric properties.

What is the Revised Fear Survey Schedule for Children measuring?

The Fear Survey Schedule for Children-Revised (FSSC-R) is a widely used self-report questionnaire that purports to measure the number of fears and the overall level of fearfulness in children. A number of studies have shown that the ten most common childhood fears can be found on the Danger and Death subscale of the FSSC-R, with upwards of 50% of children endorsing such fears. However, some researchers (e.g., H. McCathie & S.H. Spence, 1991; Behaviour Research and Therapy, 29, 495-502) have questioned the validity of these findings, suggesting that these items do not reflect actual childhood fears that children have or experience on a daily or regular basis. Rather, they suggest that children are responding to these fear items as if they were actually occurring to them in the here and now. The current study examined the occurrence of five Danger and Death fears from the FSSC-R (i.e., "Not being able to breathe", "Being hit by a car or truck", "Falling from high places", "Bombing attacks or being invaded", and "Fire or getting burned") in a sample of normal school children aged eight to 12 years (N=102). More specifically, we used three different methods to asses these fears: (1). prevalence as determined by the standard FSSC-R procedure, (2). prevalence as determined by a fear list procedure, and (3). actual occurrence or prevalence of these fears in the past week, as determined by a diary method. Results indicated that while these fears ranked high when using the standard FSSC-R procedure, they were considerably less common when using the fear list procedure, and had a low probability of actual occurrence on a daily basis, as well as possessing a short duration and low intensity. Implications for the assessment of fears and the use of self-report measures like the FSSC-R are briefly discussed.

The relationship between anxiety sensitivity and fear of pain in healthy adolescents.

The present study investigated the relationship between anxiety sensitivity and fear of pain in a large group of healthy adolescents (N=200). Participants completed the childhood anxiety sensitivity index for children-revised, a questionnaire measuring four specific domains of anxiety sensitivity: fear of cardiovascular symptoms, fear of respiratory symptoms, fear of cognitive dyscontrol, and fear of publicly observable anxiety symptoms, and a simplified version of the pain anxiety symptoms scale, a self-report instrument assessing pain-related anxiety and avoidance (i.e. fear of pain). In line with previous research in adult populations, it was found that anxiety sensitivity is substantially and positively related to fear of pain. Even when controlling for other potential predictors of fear of pain (i.e. pain symptoms, other somatization symptoms, trait anxiety, and panic disorder symptoms), anxiety sensitivity appeared to declare a unique proportion of the variance in pain anxiety symptoms.

Thought-action fusion and anxiety disorders symptoms in normal adolescents.

The present study examined thought-action fusion (TAF) in a large sample of normal adolescents (n=427). Participants completed the Thought-Action Fusion Questionnaire for Adolescents (TAFQ-A) and scales measuring trait anxiety, symptoms of obsessive-compulsive disorder, other anxiety disorders, and depression. Results showed that the TAFQ-A is a reliable instrument assessing two dimensions of TAF, viz. Morality (i.e., the belief that unacceptable thoughts are morally equivalent to overt actions) and Likelihood (i.e., the belief that thinking of an unacceptable or disturbing situation will increase the probability that that situation actually occurs). Furthermore, TAF was not only associated with symptoms of OCD, but also with symptoms of other anxiety disorders and depression. However, when controlling for levels of trait anxiety, most connections between TAF and anxiety disorders symptoms disappeared. Symptoms of OCD and generalised anxiety remained significantly related to TAF. Altogether, the data are supportive of the notion that TAF is involved in a broad range of anxiety disorders and in particular OCD.

Protective and vulnerability factors of depression in normal adolescents.

The present study investigated the role of various protective and vulnerability factors in the development of depressive symptoms. A sample of normal adolescents (N=373) completed the Children's Depression Inventory and measures of a negative attributional style, parental rearing behaviour, coping styles, and perceived self-efficacy. In addition to computing the correlations between depression and these protective and vulnerability factors, the present data were also subjected to structural equations modelling to examine the correlational structure of the data. Depression was accompanied by high levels of parental rejection, negative attributions, and passive coping, and by low levels of active coping and self-efficacy. Furthermore, a model in which negative parental rearing behaviour and a negative attributional style featured as the primary sources of depression, while coping styles and self-efficacy played a mediating role in the formation of depressive symptoms, provided a reasonable fit for the data.

Anxiety sensitivity and fear of pain in children.

Associations among scores on scales of anxiety sensitivity and trait anxiety and a fear of pain questionnaire were examined for 118 children. Analysis showed that anxiety sensitivity was positively and substantially related to fear of pain in the children. Furthermore, the data suggested anxiety sensitivity to be a better predictor of fear of pain than trait anxiety.

Reliability, validity, and normative data of the Penn State Worry Questionnaire in 8-12-yr-old children.

The Penn State Worry Questionnaire for Children (PSWQ-C) is a 14-item self-report questionnaire that intends to measure the tendency of children to engage in excessive, generalized, and uncontrollable worry (Chorpita et al., Behav. Res. Ther. 35 (1997) 569-581). The current study further examined the reliability and validity of the PSWQ-C in a large sample of 8-12-yr-old children (N = 486). Psychometric evaluation indicates that it is preferable to discard the three reverse scored items from the PSWQ-C when using the measure in this particular age group. The shortened 11-item PSWQ-C turned out to be reliable in terms of internal consistency and correlated meaningful with a scale measuring anxiety disorders symptoms. That is, PSWQ-C scores were significantly associated with all types of anxiety disorders symptoms but in particular with symptoms of generalized anxiety disorder. Normative data of the PSWQ-C are provided against which scores of individual children in this age range can be compared.

Autobiographical memory and trauma in adolescents.

Several clinicians who work with traumatized children have noted that these children exhibit a poor autobiographical memory. The present study was a first attempt to subject this clinical impression to formal testing. Memory for autobiographical facts (i.e., semantic autobiographical memory) was assessed in 10 adolescents with an alleged history of trauma and 17 adolescents without such a background. Results suggest that traumatized adolescents, indeed, have more difficulty with semantic personal memory than non-traumatized adolescents. Implications of the present findings for future research on trauma and autobiographical memory in children and adolescents are discussed.

Screening for trauma in children and adolescents: the validity of the Traumatic Stress Disorder Scale of the screen for child anxiety related emotional disorders.

Examined the validity of the Traumatic Stress Disorder scale of the Screen for Child Anxiety Related Emotional Disorders (SCARED), a recently developed self-report questionnaire measuring Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) defined anxiety disorders symptoms in children. A large sample of normal schoolchildren (N = 996) ages 7 to 19 years completed the SCARED. Children who scored high on the SCARED Traumatic Stress Disorder scale (i.e., trauma group; n = 43) and children who scored low on this scale (i.e., control group; n = 43) were then interviewed about their most aversive life event. In addition, children completed self-report questionnaires of traumatic experiences and posttraumatic stress disorder (PTSD) symptomatology. Results showed that children in the trauma group more frequently reported life events that independent judges considered to be 'potentially traumatic' than did control children. Furthermore, children in the trauma group reported having experienced more traumatic incidents and had higher scores on PTSD-related questionnaires compared with control children. Moreover, trauma group children more frequently fulfilled DSM-IV criteria for PTSD than did control children. The results of this study support the validity of the Traumatic Stress Disorder scale of the SCARED.

Worry in children is related to perceived parental rearing and attachment.

In a sample of 159 primary school children, the relationship between perceived parental rearing behaviours and self-reported attachment style, on the one hand, and worry, on the other hand, was investigated. Children completed (a) the EMBU, a questionnaire measuring perceptions of parental rearing behaviours, (b) a single-item measure of attachment style, and (c) the Penn State Worry Questionnaire for Children (PSWQ-C), an index of severity of worrying. Results showed that parental rearing behaviours, in particular rejection and anxious rearing, were positively associated with worry. Thus, children who perceived their parents as more rejective and anxious reported higher levels of worry. Furthermore, self-reported attachment style appeared to be related to worry. More specifically, children who classified themselves as avoidantly or ambivalently attached displayed higher levels of worry than did children who classified themselves as securely attached. These findings are consistent with the notion that family environment factors such as parental rearing and attachment style contribute to the severity of anxiety symptoms in children.

The TOM test: a new instrument for assessing theory of mind in normal children and children with pervasive developmental disorders.

This article describes a first attempt to investigate the reliability and validity of the TOM test, a new instrument for assessing theory of mind ability in normal children and children with pervasive developmental disorders (PDDs). In Study 1, TOM test scores of normal children (n = 70) correlated positively with their performance on other theory of mind tasks. Furthermore, young children only succeeded on TOM items that tap the basic domains of theory of mind (e.g., emotion recognition), whereas older children also passed items that measure the more mature areas of theory of mind (e.g., understanding of humor, understanding of second-order beliefs). Taken together, the findings of Study 1 suggest that the TOM test is a valid measure. Study 2 showed for a separate sample of normal children (n = 12) that the TOM test possesses sufficient test-retest stability. Study 3 demonstrated for a sample of children with PDDs (n = 10) that the interrater reliability of the TOM test is good. Study 4 found that children with PDDs (n = 20) had significantly lower TOM test scores than children with other psychiatric disorders (e.g., children with Attention-deficit Hyperactivity Disorder; n = 32), a finding that underlines the discriminant validity of the TOM test. Furthermore, Study 4 showed that intelligence as indexed by the Wechsler Intelligence Scale for Children was positively associated with TOM test scores. Finally, in all studies, the TOM test was found to be reliable in terms of internal consistency. Altogether, results indicate that the TOM test is a reliable and valid instrument that can be employed to measure various aspects of theory of mind.

The initial development of an instrument for the description of "otitis media with effusion specific behavior" in young children.

The objective of this study was a preliminary evaluation of a newly developed questionnaire concerning behavior of young children with recurrent Otitis Media with Effusion (OME) and documenting behavioral change after tympanostomy tube insertion. A sample of 95 parent-child pairs were interviewed using an age specific questionnaire: after diagnosing OME and scheduling for surgery, at the day care theatre a few weeks later, and 6 weeks after the intervention. The levels of internal consistency were varying from still insufficient to fairly good for the different subscales of the construct "OME-specific behavior" and these levels were comparable for both age specific questionnaires. As expected, parental report proved to be stable during time, but behavioral changes were reported after tympanostomy tubes insertion. The questionnaires seem to assess a decline in behavior expected to be specific for OME. Implications for future research are discussed, while considering the influence of parental concerns on behavioral reports.

Factor analyses of WISC-R and K-ABC in a Dutch sample of children referred for learning disabilities.

This study examined correlations between WISC-R and K-ABC subtests in a sample of 101 children referred for learning disabilities. A considerable overlap between the two instruments was found. Separate factor analyses of the WISC-R and K-ABC were conducted. By and large, the WISC-R factor structure was similar to that found for standardization samples. Three factors emerged, namely Verbal Comprehension, Perceptual Organization, and Freedom From Distractibility. In line with earlier findings, the K-ABC factor analysis resulted in two factors: Simultaneous and Sequential Processing. A shorter battery combining subtests from both instruments is discussed.

Comorbid anxiety symptoms in children with pervasive developmental disorders.

The present study examined the prevalence of comorbid anxiety symptoms in 44 children with pervasive developmental disorders. Parents of the children were interviewed using the Anxiety Disorders section of the Diagnostic Interview Schedule for Children. Results indicated that severe anxiety symptoms are highly prevalent in children with pervasive developmental disorders: 84.1% of the children met the full criteria for at least one anxiety disorder. Furthermore, 72.7% of the children displayed ritualistic behaviors. Implications of the findings are discussed.

Worry in normal children.

OBJECTIVE: To investigate worry in a nonclinical sample of children aged 8 to 13 years (N = 193). METHOD: Children were interviewed about the content, characteristics, origins, and severity of their main intense worry. Furthermore, children completed questionnaires to study the relationship between worry, trait anxiety, and depression. RESULTS: Almost 70% of the children reported that they worried every now and then. The content of these worries predominantly pertained to school performance, dying and health, and social contacts. An examination of the characteristics of children's main intense worries revealed that these worries occurred on average 2 to 3 days per week, were accompanied by modest levels of interference and anxiety, elicited relatively high levels of resistance, and were rather difficult to control. A minority of the children were found to exhibit symptoms of worry in the pathological range: the percentages of children who met the DSM-III-R criteria of overanxious disorder and generalized anxiety disorder were 4.7% and 6.2%, respectively. Finally, worry, anxiety, and depression seemed to be strongly related. CONCLUSION: Worry seems to be a common phenomenon in normal children aged between 8 and 13 years.

Coping styles, anxiety, and depression in children.

Associations among scores on scales of anxiety and depression and a coping styles questionnaire were examined for 71 children. In general, correlations were positive, that is, high scores on anxiety and depression were accompanied by more frequent employment of all types of coping strategies.

What do children fear most often?

Following the critical comments of McCathie and Spence (Behaviour Research and Therapy, 29, 495-502, 1991), the present study obtained fear rank orders in children (N = 394) in two different ways. The first fear rank order was based on children's FSSC-R scores. The second fear rank order was based on what children indicated as their most feared object. Each method resulted in a different fear rank order. These results demonstrate that fear rank orders critically depend on the survey method that researchers employ. The theoretical and methodological implications of this finding are discussed.

Psychometric evaluation of the Dutch version of the Aggression Questionnaire.

Confirmatory factor analyses were done in an attempt to replicate the factor structure of the Aggression Questionnaire constructed by Buss and Perry (1992) [Journal of Personality and Social Psychology, 63, 452-459] in a Dutch sample. The findings indicated that the Buss and Perry 4-factor model provided a poor fit to the full 29-item questionnaire. Although generally confirming the 4-factor structure, subsequent analyses revealed that a better fit was obtained by omitting 3 items (1 Verbal Aggression and 2 Hostility items). In general, the present findings are rather similar to previous research and emphasize the importance of assessing not only overall aggression but also its separate components.