Severity of borderline personality symptoms in adolescence: relationship with maternal parenting stress, maternal psychopathology, and rearing styles.

The development of borderline personality disorder (BPD) has been associated with parenting styles and parental psychopathology. Only a few studies have examined current parental rearing styles and parental psychopathology in relationship to BPD symptoms in adolescents. Moreover, parenting stress has not been examined in this group. The current study examined 101 adolescents (14-19 years old) with BPD symptoms and their mothers. Assessments were made on severity of BPD symptoms, youth-perceived maternal rearing styles, and psychopathology and parenting stress in mothers. Multiple regression analyses were used to examine potential predictors of borderline severity. No correlation was found between severity of BPD symptoms in adolescents and parenting stress. Only youth-perceived maternal overprotection was significantly related to BPD severity. The combination of perceived maternal rejection with cluster B traits in mothers was significantly related to BPD severity in adolescents. This study provides a contribution to the disentanglement of the developmental pathways that lead to BPD.

Atomoxetine in autism spectrum disorder: no effects on social functioning; some beneficial effects on stereotyped behaviors, inappropriate speech, and fear of change.

UNLABELLED: Abstract Objective: The objective of this study was to investigate the short-term treatment effects of atomoxetine on autism spectrum disorder (ASD) symptoms in children and adolescents with both ASD and attention-deficit/hyperactivity disorder (ADHD). METHODS: A total of 97 patients 6-17 years of age, with ASD and ADHD, were treated with 1.2 mg/kg/day of atomoxetine during an 8 week double-blind placebo-controlled period. Here, we investigated effects on two parent-based secondary outcome measures, the Aberrant Behavior Checklist (ABC) and the Children's Social Behavior Questionnaire (CSBQ). RESULTS: After 8 weeks of double-blind treatment, atomoxetine administration was associated with significant treatment effects on the ABC subscales Hyperactivity, Inappropriate Speech, and Stereotypic Behavior, and on the CSBQ subscale Fear for Changes. CONCLUSIONS: Our study results indicate no beneficial effects of atomoxetine on social functioning. However, atomoxetine may ameliorate restricted and stereotyped behaviors and communication. This study has been registered in ClinicalTrials.gov ( www.clinicaltrials.gov ) under registration number NCT00380692.

Sex differences in orienting to pictures with and without humans: evidence from the cardiac evoked response (ECR) and the cortical long latency parietal positivity (LPP).

OBJECTIVE: This study investigated the effect of social relevance in affective pictures on two orienting responses, i.e. the evoked cardiac response (ECR), and a long latency cortical evoked potential (LPP) and whether this effect would differ between males and females. Assuming that orienting to affective social information is fundamental to experiencing affective empathy, associations between self-report measures of empathy and the two orienting responses were investigated. METHOD: ECRs were obtained from 34 female and 30 male students, and LPPs from 25 female and 27 male students viewing 414 pictures from the International Affective Picture System. Pictures portrayed pleasant, unpleasant and neutral scenes with and without humans. RESULTS: Both the ECR and LPP showed the largest response to pictures with humans in unpleasant situations. For both measures, the responses to pictures with humans correlated with self-report measures of empathy. While we found a greater male than female responsiveness to the pictures without humans in the ECR, a greater female than male responsiveness was observed in the LPP response to pictures with humans. CONCLUSION AND SIGNIFICANCE: The sensitivity of these orienting responses to social relevance and their differential contribution to the prediction of individual differences underline the validity of their combined use in clinical studies investigating individuals with social disabilities.

Paternal influences on treatment outcome of behavioral parent training in children with attention-deficit/hyperactivity disorder.

This study aims to explore the influence of paternal variables on outcome of behavioral parent training (BPT) in children with attention-deficit/hyperactivity disorder (ADHD). 83 referred, school-aged children with ADHD were randomly assigned to BPT plus ongoing routine clinical care (RCC) or RCC alone. Treatment outcome was based on parent-reported ADHD symptoms and behavioral problems. Moderator variables included paternal ADHD symptoms, depressive symptoms, and parenting self-efficacy. We conducted repeated measures analyses of variance (ANOVA) for all variables, and then analyzed the direction of interaction effects by repeated measures ANOVA in high and low scoring subgroups. Paternal ADHD symptoms and parenting self-efficacy played a moderating role in decreasing behavioral problems, but not in decreasing ADHD symptoms. Paternal depressive symptoms did not moderate either treatment outcome. BPT is most beneficial in reducing children's behavioral problems when their fathers have high levels of ADHD symptoms or high-parenting self-efficacy.

Quantitative linkage for autism spectrum disorders symptoms in attention-deficit/hyperactivity disorder: significant locus on chromosome 7q11.

We studied 261 ADHD probands and 354 of their siblings to assess quantitative trait loci associated with autism spectrum disorder symptoms (as measured by the Children's Social Behavior Questionnaire (CSBQ)) using a genome-wide linkage approach, followed by locus-wide association analysis. A genome-wide significant locus for the CSBQ subscale addressing social interaction was found on chromosome 7q11, with suggestive signals supporting this locus on three other CSBQ subscales. We identified two other suggestive loci for the CSBQ total scale and individual subscales on chromosomes 4q35 and 7p12. Fine-mapping the significantly linked locus resulted in interesting candidate genes, although their association was not significant after permutation testing.

Long-term treatment with atomoxetine for attention-deficit/hyperactivity disorder symptoms in children and adolescents with autism spectrum disorder: an open-label extension study.

OBJECTIVE: The efficacy and tolerability of long-term treatment with atomoxetine for symptoms of attention-deficit/hyperactivity disorder (ADHD) in children with autism spectrum disorder (ASD) has not been established. METHODS: In this study, 88 patients 6-17 years of age, with ADHD and ASD, were treated with 1.2 mg/kg/day atomoxetine for 20 weeks as follow-up of an 8 week double-blind placebo-controlled period. Primary endpoint was the ADHD Rating Scale (ADHD-RS). RESULTS: After 8 weeks of initial treatment, the mean total, inattention, and hyperactivity-impulsivity ADHD-RS further decreased significantly from 34.9 to 27.0 for the total ADHD-RS, from 18.3 to 14.5 for the ADHD-RS inattention subscale, and from 16.5 to 12.6 for the hyperactivity-impulsivity subscale. Adverse events were mild and tended to diminish over time during continued treatment, especially regarding nausea and fatigue. There were no serious adverse events. CONCLUSIONS: The results of the present analysis suggest that continued treatment with atomoxetine up to 28 weeks further improve ADHD symptoms in children and adolescents with ASD, while adverse events tend to subside. Future studies investigating the long-term efficacy of atomoxetine in children and adolescents with ASD should be randomized and placebo controlled. This study has been registered in ClinicalTrials.gov ( www.clinicaltrials.gov ) under registration number NCT00380692.

How to use the ADI-R for classifying autism spectrum disorders? Psychometric properties of criteria from the literature in 1,204 Dutch children.

The algorithm of the Autism Diagnostic Interview-Revised provides criteria for autism versus non-autism according to DSM-IV. Criteria for the broader autism spectrum disorders are needed. This study investigated the validity of seven sets of criteria from the literature, in 1,204 Dutch children (aged 3-18 years) with and without mental retardation. The original criteria (Rutter et al. in ADI-R Autism Diagnostic Interview Revised. Manual. Western Psychological Services, Los Angeles, 2003) well discriminated ASD from non-ASD in MR. All other criteria (IMGSAC in Am Soc Hum Genet 69:570-581 2001; Sung et al. in Am J Hum Genet 76: 68-81, 2005; Risi et al. in J Am Acad Child Adolesc Psychiatry 45: 1094-1103, 2006) were sensitive at the cost of specificity, bearing the risk of overinclusiveness. In the group without MR, clinicians should decide whether sensitivity or specificity is aimed for, to choose the appropriate criteria. Including the Autism Diagnostic Observation Schedule revised algorithms in the classification, the specificity increases, at the cost of sensitivity. This study adds to a more valid judgment on which criteria to use for specific objectives.

Empirically based phenotypic profiles of children with pervasive developmental disorders: interpretation in the light of the DSM-5.

This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental disorder (PDD), and (2) how profiles related to diagnoses and co-occurring behavioral and emotional problems. Six classes with distinct profiles were discerned. Three classes showed profiles not completely in line with the proposed DSM-5 conceptualization of autism. These classes included relatively many cognitively able individuals with PDD-not otherwise specified. However, profiles seemed to suit other diagnostic categories, such as social communication disorder. These alternative diagnoses could retain eligibility for services, and might adequately fit more specifically targeted interventions.

Emotion regulation training for adolescents with borderline personality disorder traits: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of Emotion Regulation Training (ERT), a 17-session weekly group training for adolescents with borderline personality disorder (BPD) symptoms. METHOD: One hundred nine adolescents with borderline traits (73% meeting the full criteria for BPD) were randomized to treatment as usual only (TAU) or ERT + TAU. Outcome measurements included severity of BPD symptoms, general psychopathology, and quality of life. Multilevel analyses were conducted on an intent-to-treat basis. Clinical significant change was determined by normative comparisons on a primary outcome measurement. RESULTS: Independent of treatment condition, the two groups improved equally on the severity of BPD symptoms, general psychopathology, and quality of life. Nineteen percent of the ERT group was remitted according to the cutoff score after treatment (at 6 months) versus 12% of the control group. Follow-up assessments in the ERT group at 12 months showed some further improvement (33% remittance). With regard to predictors of outcomes, adolescents with higher levels of depression or attention-deficit/hyperactivity disorder or oppositional-defiant disorder at baseline and who reported a history of abuse had worse outcomes, regardless of treatment condition. The attrition rate for the ERT sessions was remarkably low (19%). CONCLUSIONS: Early interventions for BPD symptoms in adolescence are feasible and necessary. No additional effect of ERT over TAU could be demonstrated in the present study. There is a clear need for developing effective interventions for adolescents with persistent BPD symptomatology. Clinical trial registration information-Evaluation of Group Training for Adolescents (Emotion Regulation Training) with Emotion Regulation Problems: A Randomized Controlled Clinical Trial; http://trailregister.nl/; ISRCTN97589104.

Psychometric evaluation of the Borderline Personality Disorder Severity Index-IV--adolescent version and parent version.

The Borderline Personality Disorder Severity Index-IV-adolescent and parent versions (BPDSI-IV-ado/p) are DSM-IV based semi-structured interviews for the assessment of the severity of symptoms of borderline personality disorder (BPD) in adolescents. The present study evaluates the psychometric properties of the BPDSI-IV-ado/p. The interviews were administered to 122 adolescents, aged 14-19 years and their parents/caretakers who were referred to mental health centres for emotion regulation problems, and to 45 healthy controls. The interrater reliability and internal consistency of all nine subscales (following the nine BPD symptoms in DSM-IV) proved to be good to excellent. Discriminant, concurrent, and construct validity were satisfactory. Cut-off scores that optimize sensitivity and specificity were derived. Informant agreement between adolescents and parents/caretakers was modest. The results of this study suggest that the BPDSI-IV adolescent and parent versions are valid and reliable instruments for the assessment of BPD symptom severity in adolescents.

Parental rearing and psychopathology in mothers of adolescents with and without borderline personality symptoms.

BACKGROUND: A combination of multiple factors, including a strong genetic predisposition and environmental factors, are considered to contribute to the developmental pathways to borderline personality disorder (BPD). However, these factors have mostly been investigated retrospectively, and hardly in adolescents. The current study focuses on maternal factors in BPD features in adolescence. METHODS: Actual parenting was investigated in a group of referred adolescents with BPD features (N = 101) and a healthy control group (N = 44). Self-reports of perceived concurrent parenting were completed by the adolescents. Questionnaires on parental psychopathology (both Axis I and Axis II disorders) were completed by their mothers. RESULTS: Adolescents reported significantly less emotional warmth, more rejection and more overprotection from their mothers in the BPD-group than in the control group. Mothers in the BPD group reported significantly more parenting stress compared to mothers in the control group. Also, these mothers showed significantly more general psychopathology and clusters C personality traits than mothers in the control group. Contrary to expectations, mothers of adolescents with BPD features reported the same level of cluster B personality traits, compared to mothers in the control group. Hierarchical logistic regression revealed that parental rearing styles (less emotional warmth, and more overprotection) and general psychopathology of the mother were the strongest factors differentiating between controls and adolescents with BPD symptoms. CONCLUSIONS: Adolescents with BPD features experience less emotional warmth and more overprotection from their mothers, while the mothers themselves report more symptoms of anxiety and depression. Addition of family interventions to treatment programs for adolescents might increase the effectiveness of such early interventions, and prevent the adverse outcome that is often seen in adult BPD patients.

A randomized double-blind study of atomoxetine versus placebo for attention-deficit/hyperactivity disorder symptoms in children with autism spectrum disorder.

OBJECTIVE: The efficacy of atomoxetine as treatment of symptoms of attention-deficit/hyperactivity disorder (ADHD) in patients with autism spectrum disorder (ASD) has not been established. METHOD: In this study, 97 patients aged 6 to 17 years with ADHD and ASD were randomly assigned to double-blind treatment with 1.2 mg/kg/day atomoxetine or placebo for 8 weeks. The primary endpoint was the ADHD Rating Scale (ADHD-RS) score; secondary endpoints were the Clinical Global Impression of ADHD-Improvement (CGI-I) and the Conners Teacher Rating Scale-Revised: Short Form (CTRS-R:S) score. RESULTS: Baseline mean ADHD-RS scores for atomoxetine versus placebo were 40.7 and 38.6; after 8 weeks, mixed-effect model repeated-measure means were 31.6 (95% confidence interval 29.2-33.9) and 38.3 (36.0-40.6), respectively, with a difference in least square means of -6.7 (-10.0 to -3.4; p < .001). The CTRS-R:S Hyperactivity subscore also improved significantly for atomoxetine compared with placebo, but not the other CTRS-R:S subscores. However, there were not significantly more patients on atomoxetine (20.9%) who improved much, or very much according to the CGI-I, than on placebo (8.7%; p = 0.14). Adverse events (mostly nausea, decrease in appetite, fatigue, and early morning awakening) were reported in 81.3% of atomoxetine patients and 65.3% of placebo patients (p > .1). There were no serious adverse events. CONCLUSIONS: Atomoxetine moderately improved ADHD symptoms in patients with ASD and was generally well tolerated. Adverse events in this study were similar to those in other studies with ADHD patients without ASD. Clinical trial registration information-A Randomized Double-Blind Study of Atomoxetine Versus Placebo for ADHD Symptoms in Children with ASD; www.clinicaltrials.gov; NCT00380692.

Response time variability and response inhibition predict affective problems in adolescent girls, not in boys: the TRAILS study.

The present study examines the relationship between neurocognitive functioning and affective problems through adolescence, in a cross-sectional and longitudinal perspective. Baseline response speed, response speed variability, response inhibition, attentional flexibility and working memory were assessed in a cohort of 2,179 adolescents (age 10-12 years) from the TRacking Adolescents' Individual Lives Survey (TRAILS). Affective problems were measured with the DSM-oriented Affective Problems scale of the Youth Self Report at wave 1 (baseline assessment), wave 2 (after 2.5 years) and wave 3 (after 5 years). Cross-sectionally, baseline response speed, response time variability, response inhibition and working memory were associated with baseline affective problems in girls, but not in boys. Longitudinally, enhanced response time variability predicted affective problems after 2.5 and 5 years in girls, but not in boys. Decreased response inhibition predicted affective problems after 5 years follow-up in girls, and again not in boys. The results are discussed in light of recent insights in gender differences in adolescence and state-trait issues in depression.

The visual rooting reflex in individuals with autism spectrum disorders and co-occurring intellectual disability.

The rooting reflex has long been studied by neurologists and developmentalists and is defined as an orientation toward tactile stimulation in the perioral region or visual stimulation near the face. Nearly, all previous reports of the visual rooting reflex (VRR) concern its presence in adults with neurological dysfunction. Previously, the VRR was reported to be present in a majority of individuals with autism and absent in control subjects. In the present larger study, we examined the presence of the VRR in 155 individuals with ASD and co-occurring Intellectual Disability (ASD + ID: autism, N = 60; Pervasive Developmental Disorder-Not Otherwise Specified (PDD_NOS), N = 95) and in a contrast group of 65 individuals with ID only. The VRR was present significantly more often in the ASD + ID (43.9%) group than in the ID-only group (24.6%; χ(1)(2)= 7.19; P = 0.007). Individuals with autism displayed a VRR more often (55.0%) than individuals with PDD-NOS (36.8%; χ(1)(2)= 4.92; P = 0.026) and individuals with ID only (24.6%; χ(1)(2)= 12.09; P = 0.001). A positive VRR was associated with lower IQ and adaptive functioning; in the ASD + ID group, ADI-R/ADOS domain scores were significantly higher in the VRR-positive subgroup. The results replicate and extend the finding of an increased occurrence of the VRR in autism. Although some association with IQ was observed, the VRR occurred substantially more often in the autism group compared with an intellectually disabled group, indicating some degree of specificity. Additional studies of infants and children with typical development, ASD and ID are needed to determine the utility of the VRR in ASD risk assessment and to elucidate possible specific behavioral associations.

Dopamine transporter gene moderates response to behavioral parent training in children with ADHD: a pilot study.

There is great variability in the degree to which children with attention deficit/hyperactivity disorder (ADHD) improve through behavioral treatments. This study investigates the influence of the dopamine transporter gene (SCL6A3/DAT1) on outcome of behavioral parent training (BPT). Study subjects were a subsample (n = 50, for whom DAT1 genotypes were available) of a randomized controlled BPT effectiveness study (N = 94) comparing BPT plus ongoing routine clinical care (RCC) versus RCC alone in referred children (4-12 years old) with ADHD. Treatment outcome was based on parent-reported ADHD symptoms and behavioral problems. Presence of 2 versus no or 1 DAT1 10-repeat allele served as moderator variable. Time × Treatment × Genotype effect was analyzed with repeated-measures analysis of variance, controlling for baseline medication status. Results indicate that DAT1 moderated treatment response (p = .009). In children with no or 1 DAT1 10-repeat allele, superior treatment effects of BPT + RCC compared with RCC alone were present (p = .005), which was not the case in children with 2 DAT1 10-repeat alleles (p = .57). Our findings suggest that genetic differences in DAT1 in children with ADHD influence their susceptibility to a behavioral intervention directed at shaping their environment through their parents. The role of the dopamine system in motivation and learning and in the aberrant sensitivity to reinforcement in children with ADHD may explain this moderating effect, given that the management of contingencies is typically addressed in BPT.

Minor neurological dysfunction in children with autism spectrum disorder.

AIM: The aim of this study was to improve the understanding of brain function in children with autism spectrum disorder (ASD) in relation to minor neurological dysfunctions (MNDs). METHOD: We studied MNDs in 122 children (93 males, 29 females; mean age 8 y 1 mo, SD 2 y 6 mo) who, among a total cohort of 705 children (513 males, 192 females; mean age 9 y, SD 2 y 0.5 mo) referred to a regional outpatient non-academic psychiatric centre in the Netherlands, were diagnosed with ASD after an extensive multidisciplinary psychiatric assessment. Children with clear neurological abnormalities (e.g. cerebral palsy or spina bifida) were excluded from the study. MNDs were assessed in all 705 children using the Touwen examination method. Special attention was paid to the severity and type of MND. Data of the children with ASD were compared with neurological morbidity data of children with other psychiatric disorders and with children in the general population, who were born at Groningen University Hospital between 1975 and 1978. RESULTS: Seventy-four percent of the children with ASD showed complex MNDs compared with 52% of the children with other psychiatric disorders and 6% of the reference group (χ(2) =18.0, p<0.001; χ(2) =937.5, p<0.001 respectively). Specific dysfunctions frequently encountered in ASD were dysfunctional posture and muscle tone, fine manipulative disability, dyscoordination, and excessive associated movements. CONCLUSION: These findings suggest a contribution of dysfunctional supraspinal networks involving multiple parts of the brain in the pathogenesis of ASD. This is consistent with findings from neuroimaging studies, and highlights the importance of neurological examinations in paediatric psychiatric assessments.

Standardized ADOS scores: measuring severity of autism spectrum disorders in a Dutch sample.

The validity of the calibrated severity scores on the ADOS as reported by Gotham et al. (J Autism Dev Disord 39: 693-705, 2009), was investigated in an independent sample of 1248 Dutch children with 1455 ADOS administrations (modules 1, 2 and 3). The greater comparability between ADOS administrations at different times, ages and in different modules, as reached by Gotham et al. with the calibrated severity measures, seems to be corroborated by the current study for module 1 and to a lesser extent for module 3. For module 2, the calibrated severity scores need to be further investigated within a sample that resembles Gotham's sample in age and level of verbal functioning.

Risperidone-induced weight gain in referred children with autism spectrum disorders is associated with a common polymorphism in the 5-hydroxytryptamine 2C receptor gene.

Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age- and gender-normed body mass index-standardized z scores at baseline and after 8 weeks of open-label, flexible-dose risperidone treatment (mean dose: 1.70 mg/day) in 32 youths with pervasive developmental disorder (mean age = 8.74, range = 5-16 years) in relation to -759C/T 5-hydroxytryptamine 2C receptor (HTR2C) promoter and rs1414334 HTR2C intragenic C/G alleles, along with gender, age, and risperidone dose, using repeated measures analyses of variance. Carriers of the HTR2C promoter T allele gained an average of 0.043 ± 0.017 body mass index-standardized z scores (1.84 ± 1.51 kg) versus 0.64 ± 0.35 z (3.23 ± 1.47 kg) for non-T-allele carriers (p < 0.001). Presence of the rs1414334 C allele played no significant role. Further, weight gain appeared to be associated with younger age and higher doses of risperidone. The current preliminary findings suggest that the variant T allele of the -759C/T HTR2C promoter polymorphism is protective against risperidone-induced weight gain. Younger children and those treated with higher doses of risperidone may be at higher risk for weight gain.