Psychometric properties of the Hungarian childhood trauma questionnaire short form and its validity in patients with adult attention-deficit hyperactivity disorder or borderline personality disorder.

BACKGROUND: Compelling evidence supports the role of childhood traumatization in the etiology of psychiatric disorders, including adult attention-deficit hyperactivity disorder (aADHD) and borderline personality disorder (BPD). The aim of this study was to examine the psychometric properties of the Hungarian version of the Childhood Trauma Questionnaire Short Form (H-CTQ-SF) and to investigate the differences between patients diagnosed with aADHD and BPD in terms of early traumatization. METHODS: Altogether 765 (mean age = 32.8 years, 67.7% women) patients and control subjects were enrolled from different areas of Hungary. Principal component analysis and confirmatory factor analysis were carried out to explore the factor structure of H-CTQ-SF and test the validity of the five-factor structure. Discriminative validity was assessed by comparing clinical and non-clinical samples. Subsequently, aADHD and BPD subgroups were compared with healthy controls to test for the role of early trauma in aADHD without comorbid BPD. Convergent validity was explored by measuring correlations with subscales of the Personality Inventory for DSM-5 (PID-5). RESULTS: The five scales of the H-CTQ-SF demonstrated adequate internal consistency and reliability values. The five-factor model fitted the Hungarian version well after exclusion of one item from the physical neglect scale because of its cross-loading onto the emotional neglect subscale. The H-CTQ-SF effectively differentiated between the clinical and non-clinical samples. The BPD, but not the aADHD group showed significant differences in each CTQ domain compared with the healthy control group. All CTQ domains, except for physical abuse, demonstrated medium to high correlations with PID-5 emotional lability, anxiousness, separation insecurity, withdrawal, intimacy avoidance, anhedonia, depressivity, suspiciousness, and hostility subscales. CONCLUSIONS: Our study confirmed the psychometric properties of the H-CTQ-SF, an easy-to-administer, non-invasive, ethically sound questionnaire. In aADHD patients without comorbid BPD, low levels of traumatization in every CTQ domain were comparable to those of healthy control individuals. Thus, the increased level of traumatization found in previous studies of aADHD might be associated with the presence of comorbid BPD. Our findings also support the role of emotional neglect, emotional abuse and sexual abuse in the development of BPD.

Brain activity during emotion perception: the role of attachment representation.

To examine emotional face processing in mothers of different attachment representations, event-related potentials were recorded from 16 mothers during presentation of infant emotion faces with positive, negative or neutral emotional expressions within a three-stimulus oddball paradigm, and frontal asymmetries were assessed. Insecure mothers, as compared to secure ones, showed a more pronounced negativity in the face-sensitive N170 component and a smaller N200 amplitude. Regarding the P300 component, secure mothers showed a stronger response to face stimuli than insecure mothers. No differences were found for frontal asymmetry scores. The results indicate that attachment differences may be related to neuropsychological functioning.

[Screening childhood behavior problems using short questionnaires II.: The Hungarian version of the SWAN-scale (Strength and Weakness of ADHD-symptoms and Normal-behavior) for screening attention deficit/hyperactivity disorder]. / Gyermekkori viselkedési prblémák felismerésének lehetoségei rövid kérdoívekkel II: A SWAN (Strength and Weakness of ADHD-symptoms and Normal-behavior) skála magyar változata a figyelemhiányos/hiperaktivitás zavar szurésére.

INTRODUCTION: The SWAN (Strength and Weakness of ADHD-symptoms and Normal-behavior) Questionnaire is a short instrument suitable for screening attention deficit/hyperactivity disorder. Its completion by parents or teachers requires a few minutes. Positive re-wording of attention- and activity-related behaviors and the extended 7- point rating scale anchored to average behavior make the instrument especially suitable for normal populations. Here, we report the Hungarian version of SWAN and compare its scales with relevant scales of the Child Behavior Checklist (CBCL) and the Strengths and Difficulties Questionnaire (SDQ). METHOD: Questionnaire data were collected from parents of 156 six-year-old children in a community sample. Of the 156 children 89 were participants of the longitudinal Budapest Infant-Parent Study (BIPS). RESULTS: Internal consistency of the Hungarian SWAN scales was excellent (Cronbach alfa: 0.87-0.93), correlations with relevant CBCL and SDQ scales were as expected (0.40-0.49 and 0.67-0.74) showing that the short questionnaire was suitable for detection of attention and hyperactivity problems. SWAN scores in our sample were normally distributed and scale means were also similar to foreign studies. CONCLUSIONS: These initial Hungarian data confirm international experience with the SWAN. Psychometric indices, distribution of scale scores in the sample and across the sexes were consistent with foreign studies. Following collection of normative data, the Hungarian version of SWAN might be suitable for assessing mental health of children and adolescents, and for screening problem cases. Due to the wider range and the normal distribution of scores, SWAN provides a more suitable phenotype for genetic studies, than symptom scales.

Catechol-O-methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children.

Methylphenidate is the most frequently prescribed drug in the treatment of attention deficit hyperactivity disorder (ADHD) but it is not effective in every case. Therefore, identifying genetic and/or biological markers predicting drug-response is increasingly important. Here we present a case-control study and pharmacogenetic association analyses in ADHD investigating three dopaminergic polymorphisms. Previous studies suggested variable number of tandem repeats (VNTR) in the dopamine D4 receptor (DRD4) and the dopamine transporter (DAT1) genes as genetic risk factors for ADHD and as possible markers of methylphenidate response. Our results did not indicate substantial involvement of these two VNTRs in ADHD, however, both the case-control and the pharmacogenetic analyses showed significant role of the high activity Val-allele of cathecol-O-methyltransferase (COMT) Val158Met polymorphism in our ADHD population. The Val-allele was more frequent in the ADHD group (n = 173) compared to the healthy population (P = 0.016). The categorical analysis of 90 responders versus 32 non-responders showed an association between the Val-allele or Val/Val genotype and good methylphenidate response (P = 0.009 and P = 0.034, respectively). Analyzing symptom severity as a continuous trait, significant interaction of COMT genotype and methylphenidate was found on the Hyperactivity-Impulsivity scale (P = 0.044). Symptom severity scores of all three genotype groups decreased following methylphenidate administration (P < 0.001), however Val/Val homozygote children had significantly less severe symptoms than those with Met/Met genotype after treatment (P = 0.015). This interaction might reflect the regulatory effect of COMT dominated prefrontal dopamine transmission on subcortical dopamine systems, which are the actual site of methylphenidate action.

[Screening childhood behavior problems using short questionnaires I.: the Hungarian version of the Strengths and Difficulties Questionnaire]. / Gyermekkori viselkedési problémák felismerésének lehetoégei rövid kérdoívekkel I: a Strengths and Difficulties Questionnaire magyar változata.

INTRODUCTION: The Strengths and Difficulties Questionnaire (SDQ) is a short questionnaire suitable for screening childhood behavior problems. Completing the questionnaire requires 5 minutes of parents' or teachers' time. The scales of the original version showed good agreement with relevant scales of the much longer Child Behavior Checklist (CBCL). In this study, we report the use of the Hungarian version of the SDQ and results of a comparison between the scales of the SDQ and the CBCL. METHODS: Questionnaire data were collected from the parents of 156 six-year-old children from a community sample. Of the 156 children, 89 were participants of the longitudinal Budapest Infant-Parent Study (BIPS). RESULTS: Internal consistency of the Hungarian SDQ scales were moderate-satisfactory (0.43-0.70), correlations between the relevant SDQ and CBCL scales were as expected (0.41-0.65), showing that the short questionnaire was equally suitable for the detection of problems. In our six-year-old age group, the mean of the total problem scores (11.0) was much higher than the means measured in other Western European countries and North-America. However, in developing countries, such as Brazil or China, levels were higher and closer to the Hungarian mean score. CONCLUSIONS: These initial Hungarian data confirm international experience with the SDQ, i.e., psychometric indices and the distribution of scale scores across the sexes are consistent with the results of foreign studies. On the other hand, a cautious generalization of our results indicates a higher level of problems in Hungary than in Western Europe and other developed countries. We think that following further collection of normative data the Hungarian version of the SDQ, which will take only a few minutes to complete, will be suitable for assessing the mental health of children and adolescents, and for the quick screening of problematic cases.

A pilot study of early onset obsessive-compulsive disorder: Symptom dimensions and association analysis with polymorphisms of the serotonin transporter gene.

Our aim was to introduce more homogenous phenotypes for studying genetic variations in the clinically heterogeneous obsessive compulsive disorder (OCD) beside classical case-control analysis. Symptoms were assessed with Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and principle component analysis of the lifetime symptom categories yielded four factors (Cleaning, Obsessive, Compulsive, Sexual). The comparison of serotonin transporter linked polymorphic region (5-HTTLPR) in 102 OCD patients and 223 controls showed an increased L-allele frequency but no difference was observed when rs25531 was included. Intronic variants of the serotonin transporter gene did not show association with either OCD, nor with the obtained factors.

Association analysis of norepinephrine transporter polymorphisms and methylphenidate response in ADHD patients.

AIMS: Methylphenidate (MPH) is the most frequently prescribed drug in Attention Deficit Hyperactivity Disorder (ADHD). Hitherto mostly the dopamine transporter gene has been studied in MPH-response and only a few studies analyzed the norepinephrine transporter (NET, SLC6A2) gene, although MPH is a potent inhibitor of both dopamine and norepinephrine transporters. We aimed to analyze this monoamine transporter gene in relation to ADHD per se and MPH-response in particular to gain further knowledge in ADHD pharmacogenetics using a Caucasian sample. METHODS: Six single nucleotide polymorphisms (rs28386840, rs2242446, rs3785143, rs3785157, rs5569, rs7194256 SNP) were studied across the NET gene in 163 ADHD children (age: 9.3±2.6; 86.5% male) using ADHD-RS hyperactivity-impulsivity and inattention scales. For case-control analysis 486 control subjects were also genotyped. At the MPH-response analysis responders had minimum 25% decrease of ADHD-RS total score after 2months of treatment, and chi-square test compared 90 responders and 32 non-responders, whereas ANOVA was used to assess symptom improvement after the first month among the 122 ADHD patients. RESULTS: The classical case-control analysis did not yield any association with ADHD diagnosis, which was supported by meta-analysis conducted on the available genetic data (combining previously published and the present studies). On the other hand, the intronic rs3785143 showed nominal association with inattention symptoms (p=0.01). The haplotype analysis supported this association, and indicated the importance of the first haploblock encompassing the intronic and 2 promoter SNPs. With MPH-response only the promoter rs28386840 showed nominal association: Those with at least one T-allele were overrepresented in the responder group (42% vs 19%, p=0.08), and they had better improvement on the hyperactivity-impulsivity scale compared to the AA genotype (p=0.04). CONCLUSION: Although none of our single SNP findings remained significant after correcting for multiple testing, our results from the MPH-response analysis indicate the potential importance of promoter variants in the NET gene.

Differential Genetic Effect of the Norepinephrine Transporter Promoter Polymorphisms on Attention Problems in Clinical and Non-clinical Samples.

Among the monoaminergic modulatory neurotransmitters, norepinephrine is involved in task orienting, hence noradrenergic genetic variants have been studied in connection to attentional processes. The role of this catecholamine system is also highlighted by the selective norepinephrine transporter blocking atomoxetine, which has proved to be effective in the pharmacological treatment of Attention Deficit Hyperactivity Disorder (ADHD). In the present genetic association study three single nucleotide polymorphisms (rs28386840, rs2242446, rs3785143 SNPs) were analyzed from the 5' region of the norepinephrine transporter (NET, SLC6A2) gene, which have been linked to ADHD previously. Attention problems scores of the mother-rated Child Behavior Checklist (CBCL) were used in separate analyses of 88 preschoolers (59.1% male, 6 years of age) recruited from the general population and 120 child psychiatry patients with ADHD diagnosis (85.8% male, age: 9.8 ± 2.9). The NET SNPs showed associations with attention problems, but the direction was different in the two groups. Regarding the promoter variant rs28386840, which showed the most consistent association, the T-allele-carrier patients with ADHD had lower CBCL attention problems scores compared to patients with AA genotype (p = 0.023), whereas T-allele-carriers in the community sample had more attention problems (p = 0.042). Based on previous reports of lower NE levels in ADHD children and the inverted-U shape effect of NE on cognitive functions, we propose that rs28386840 (-3081) T-allele, which is associated with lower NET expression (and potentially higher synaptic NE level) would support attention processes among ADHD patients (similarly as atomoxetine increases NE levels), whereas it would hinder cortical functions in healthy children.

Association between dopamine D4 receptor (DRD4) gene polymorphisms and novelty-elicited auditory event-related potentials in preschool children.

We investigated associations of the exon III repeat and the -521 C/T polymorphisms of the DRD4 gene with novelty-elicited auditory ERP components and behavioral resistance to distraction in 57 healthy, typically developing 6-year-old children. Dopamine-related gene polymorphisms have previously been linked to processes directing focused attention. We did not find associations between the 7-repeat allele or the T.7 haplotype and the early ERP responses suggesting that DRD4 polymorphisms did not affect the detection of novelty. However, the same polymorphisms affected the late negative components (LN1 and LN2). Late negativities elicited by deviant and novel sounds have been regarded as reflecting reorientation after distraction or additional processing of new information. Children carrying the T.7 haplotype had significantly smaller LN1 and LN2 amplitudes. The presence of the T.7 haplotype also significantly enhanced behavioral resistance to distraction. We suggest that less distraction in T.7 carriers led to less reorienting activity (reflected by the LN components). We also speculate that activation of less sensitive and fewer D4 receptors (as with the T.7 haplotype) is less effective in modulating GABAergic inhibitory signaling, which in turn is reflected in smaller LN amplitudes.

[Effects of the D4 dopamine receptor gene variation on behavior problems at 6 years of age]. / A D4 dopamin receptor gén hatása a 6 éves kori viselkedési problémákra.

Association of the 7-repeat allele of the D4 dopamine receptor (DRD4) exon 3 polymorphism with attention deficit/hyperactivity disorder is well-established, and a link with mother-reported aggressiveness was also found in healthy pre-schoolers assessed by the quantitative scale of the Child Behavior Checklist. In the present study, we hypothesized that children carrying the 7-repeat allele would show more attention problems and externalizing (aggressive and delinquent) behavior at 6 years of age. Further, we hypothesized a potential mediating role of early temperament in the relationship of DRD4 gene with behavior problems. Mothers filled in the Achenbach Child Behavior Checklist for 88 six-year-old firstborn children (51 boys, 35 girls) followed from birth. Mother-reported temperament for the same children was assessed by the Rothbart Infant Behavior Questionnaire at 12 months. Genotypes of the DRD4 repeat polymorphism were determined using buccal cells. Significant main effects of gender and DRD4 genotype were observed on 6-year behavioral problems. Boys showed more attention problems and externalizing behavior, and children lacking the 7-repeat variant showed more externalizing and internalizing behavior. These effects remained significant after controlling for 1-year temperament. Our results did not confirm the negative effect of the 7-repeat allele on attention problems and externalizing behavior measured on quantitative scales. On the contrary, we found elevated problem scores in the absence of the 7-repeat allele. Further research including environmental risk factors is needed to clarify the role of the DRD4 gene in the development of externalizing behavior.

Infant genotype may moderate sensitivity to maternal affective communications: attachment disorganization, quality of care, and the DRD4 polymorphism.

Disorganized attachment is an early predictor of the development of psychopathology in childhood and adolescence. Lyons-Ruth et al. (1999) developed the AMBIANCE coding scheme to assess disrupted communication between mother and infant, and reported the link between maternal behavior and disorganized attachment. The Hungarian group found an association between a polymorphism of the DRD4 gene and disorganized attachment (Lakatos et al., 2000; 2002; Gervai et al., 2005). The present collaborative work investigated the interplay between genetic and caregiving contributions to disorganized attachment. 138 mother-infant dyads, 96 from a Hungarian low-social-risk sample and 42 from a US high-social-risk sample, were assessed for infant disorganized attachment behavior, for DRD4 gene polymorphisms, and for disrupted forms of maternal affective communication with the infant. In accord with literature reports, we found a robust main effect of maternal AMBIANCE scores on infant disorganization. However, this relation held only for the majority of infants who carried the short form of the DRD4 allele. Among carriers of the 7-repeat DRD4 allele, there was no relation between quality of maternal communication and infant disorganization. This interaction effect was independent of degree of social risk and maternal DRD4 genotype.

Transmission disequilibrium tests confirm the link between DRD4 gene polymorphism and infant attachment.

Following up the results of a previous population association study (Lakatos et al. [2000: Mol Psychiatry 5:633-637; Lakatos et al. [2002: Mol Psychiatry 7:27-31]) by analyses based on parental genetic data confirmed the link between infant attachment and the dopamine D4 receptor (DRD4) gene. Extended transmission disequilibrium tests (ETDT) were performed to determine whether biased transmission of exon III 48 basepair repeat alleles occurred to infants displaying disorganized and secure attachment behavior with their mothers. The overall allele-wise TDTs were significant for both groups (P = 0.038 and 0.020, respectively): a trend for preferential transmission of the seven-repeat allele to disorganized infants was observed (TDT(chi)(2) = 3.27, df = 1, P = 0.071), and there was a significant non-transmission of the same allele to securely attached infants (TDT(chi)(2) = 6.00, df = 1, P = 0.014). Analysis of haplotypes of the exon III repeat and the -521 C/T promoter polymorphisms in family trios showed that the transmission bias in the larger secure group was due to the low-rate transmission of the T.7 haplotype containing both the seven-repeat and the -521 T alleles (TDT(chi)(2) = 4.46, df = 1, P = 0.035). This suggests that not carrying the T.7 haplotype of the DRD4 gene may act as a resilience factor in the optimal development of early attachment.