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/lp/springer-journals/the-role-of-the-brain-derived-neurotrophic-factor-genotype-and-ws4X3BXtpv
- Publisher
- Springer Journals
- Copyright
- Copyright © 2014 by Park et al.; licensee BioMed Central Ltd.
- Subject
- Biomedicine; Neurosciences; Neurology; Behavioral Therapy; Psychiatry
- eISSN
- 1744-9081
- DOI
- 10.1186/1744-9081-10-43
- pmid
- 25425456
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- See Article on Publisher Site
Abstract
Background: We aimed to determine whether early parenting is associated with externalizing and internalizing symptoms in children with attention-deficit hyperactivity disorder (ADHD) and whether such an association is affected by the brain-derived neurotrophic factor (BDNF) val66met polymorphism. Methods: The participants included 92 patients with ADHD aged 6–15 years. Measures of parenting in early life and externalizing and internalizing symptoms and the genotype of the BDNF Val66Met polymorphism were obtained. Results: The degree to which the baby’s autonomy was allowed was significantly and negatively correlated with the CDI scores in ADHD children (r = −0.38, p = 0.005). After adjusting for the child’s gender, the child’s age, the family’s gross annual income, and the maternal education level, there was a significant interaction for the BDNF genotype and mother’s positive feelings about caring in relation to the development of childhood anxiety/depression in ADHD children (F = 2.51, p = 0.011). Conclusions: Our results provide evidence of an interaction between the BDNF met allele and early parenting on the development of depression/anxiety symptoms. Keywords: BDNF, Parenting, ADHD Background environmental factors and gene-environmental interactions Attention-deficit hyperactivity disorder (ADHD) affects 8% (G X E) are essential for a broad understanding of ADHD to 12% of school-aged children [1]. ADHD is characterized pathophysiology. by symptoms of inattention and/or hyperactivity/impulsiv- Given the wide heterogeneity and complex manifesta- ity. With an estimated heritability of approximately 75%, tions of the disorder, recent theoretical work has suggested ADHD is generally regarded as having a genetic basis [2]. the importance of a developmental perspective that views However, the remaining phenotypic variance (25%) in ADHD as a multi-factorial disorder with multiple, causal ADHD has been largely attributed to environmental factors processes and pathways through development [5,6]. Given [3]. From the epigenetic perspective, environmental factors the strong evidence in support of a biological basis of can also modulate gene expression and protein function in ADHD symptoms, there has been relatively little research the brain [4]. Therefore, comprehensive investigations of exploring contextual variables within the family that may contribute to different outcomes for children with ADHD. Indeed, much of the research literature has focused on * Correspondence: soochurl@snu.ac.kr Deparment of Psychiatry and Behavioral Science, Seoul National University the association between family factors and ADHD symp- College of Medicine, Seoul, Republic of Korea tomatology [7-9], rather than on examining the broad Full list of author information is available at the end of the article © 2014 Park et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Park et al. Behavioral and Brain Functions 2014, 10:43 Page 2 of 9 http://www.behavioralandbrainfunctions.com/content/10/1/43 spectrum of difficulties that children with ADHD often The BDNF gene, located on human chromosome 11p13, experience in development; these difficulties include ex- has a guanine-to-adenine single-nucleotide polymorphism ternalizing problems (i.e., oppositional defiant disorder (SNP) at nucleotide 196 (rs6265) that results in an amino and conduct disorder) and internalizing problems (i.e., acid substitution of methionine (Met) for valine (Val) at depression and anxiety). codon 66. This substitution changes the 5-prime prore- A recent review focused on family characteristics associ- gion of the human BDNF protein and appears to lower ated with ADHD [10] provided a thorough examination of depolarization-induced secretion of BDNF in the brain, parenting variables in relation to the development of co- leading to a decrease in available BDNF and a possible im- morbidities and functional impairments in children with pairment of the central nervous system [27,28]. The Met ADHD. The conclusions drawn from Deault’sreviewwere allele of the BDNF gene is associated with depression in that ADHD is associated with problematic family function- the context of childhood adversity and genetic risk [29,30]. ing, including higher rates of parental psychopathology In this study, we investigated the effect of early par- and conflicted parent–child relationships; these relation- enting on the development of ADHD and the relation- ship issues were exacerbated in children with comorbid ship between parenting in early life and externalizing oppositional and conduct problems. However, that review (i.e., oppositional defiant disorder and conduct disorder) also revealed the paucity of studies that consider the role or internalizing (i.e., social problems and depression/ parents play in contributing to their children’s develop- anxiety) symptoms during childhood among children with ment in areas such as social and academic development, ADHD. Based on previous studies in general population as well as the development of internalizing difficulties. [14,15,18,19], we hypothesized that psychological auton- Although there is a paucity of studies that examined omy granting and acceptance by parent might be associ- family factors contributing to the development of comor- ated with less depressive and anxiety symptoms and low bid symptoms of ADHD (i.e., oppositional defiant dis- behavioral control and permissive parenting might be as- order, conduct disorder, depression, and anxiety), many sociated with more oppositional defiant disorder and con- studies conducted in general population found that dys- duct disorder symptoms in children with ADHD. The functional parenting was shown to their offspring’sexter- interaction of parenting variables with the BDNF Val66- nalizing and internalizing problems. For example, high Met polymorphism was also examined in relation to exter- level of behavioral control by parent is related to low levels nalizing and internalizing symptoms. of externalizing problems [11,12] and low behavioral con- trol and permissive parenting, and negative intrusive par- Methods enting behaviors linking to externalizing symptoms during Participants early childhood [13] and also related to various kinds of Children and adolescents with ADHD were recruited maladjustment and conduct disorders [14,15]. High level from the Department of Psychiatry at the Seoul National of psychological control(e.g., love withdrawal, guilt in- University Hospital in Korea. The recruited children duction) and authoritarian parenting are associated with were between 6 and 15 years old and had been diag- internalizing problems [15]. A high level of parental affec- nosed with ADHD according to the DSM-IV criteria as tion would decrease internal and external child problem ascertained by a child psychiatrist and a semi-structured behaviors [16], also sensitive parenting was associated with interview. To diagnose ADHD and comorbid disorders, lower levels of child internalizing symptoms. [13] Psycho- we used the Korean Kiddie-Schedule for Affective Dis- logical autonomy granting and acceptance by parent are orders and Schizophrenia—Present and Lifetime Version associated with less depression and anxiety [17-19]. (K-SADS-PL). The Korean version of K-SADS-PL was Brain-derived neurotrophic factor (BDNF) is a mem- standardized by Kim et al. [31]. The Korean version of ber of the neurotrophin superfamily, which includes K-SADS-PL was reported to be valid and reliable for diag- growth factors that promote cell survival, differentiation nosing major child psychiatric disorders in Korean chil- and death. BDNF has key effects on the serotonergic dren (consensual validity, kappa value = 0.695; test-retest [20], glutamatergic [21] and dopaminergic [22] neuro- reliability, kappa value = 0.755; sensitivity = 0.774; specifi- transmitter systems. BDNF is also involved in hippocam- city = 0.947 for ADHD). The exclusion criteria for ADHD pal long-term potentiation, which is related to learning patients included the following: 1) a history of pervasive and memory efficiency [23]. Given the large amount of developmental disorder, mental retardation, bipolar dis- BDNF protein in the central nervous system and its role order, psychotic disorder, obsessive compulsive disorder, in neurotransmission, a number of researchers have or Tourette’s syndrome; 2) a history of organic brain dis- postulated the existence of a role for the BDNF gene ease, seizure disorder, or other neurological disorder; 3) an (BDNF) in the pathogenesis and treatment response of IQ below 70; 4) the presence of learning disabilities or different neuropsychiatric conditions, including depres- language disorders; 5) the presence of major depressive sion, anxiety, and ADHD [24-26]. disorder, anxiety disorder, or tic disorder requiring drug Park et al. Behavioral and Brain Functions 2014, 10:43 Page 3 of 9 http://www.behavioralandbrainfunctions.com/content/10/1/43 therapy; and 6) any previous course of stimulants or ato- after birth (“Caring for baby is satisfying”; “Feel so angry moxetine treatment lasting more than 1 year or occurring sometimes I could smack my baby”; “My baby makes me within the last 4 weeks. Exclusion of children who were too tired”; “My baby is so good”; “Sometimes I feel like hit- on stimulants or atomoxetine is because these medications ting my baby”; “I feel fed up looking after my baby”). These could alleviate externalizing and internalizing symptoms items were assessed using a 5-point Likert-type scale (1 = of ADHD, which might confound the results. To investi- strongly disagree to 5 = strongly agree). Scores of some gate the effect of early parenting on the development of items were reversed, and high scores represented positive ADHD, we enrolled healthy children and adolescents feelings about caring for the baby. The scale produced a without ADHD between 6 and 15 years old as a control good reliability coefficient (Cronbach α =0.75) [35]. group. The exclusion criteria for the control group were the same as above, except for additionally excluding those Time spent teaching baby with a past or an ongoing history of ADHD. For the con- Mothers were asked a series of 4 items about the time trol group, the K-SADS-PL and questionnaires on parent- spent teaching their babies during the first year after birth ing variables were implemented, but comorbid symptom (“Try to encourage baby to be interested in what going measurements and genotyping of the BDNF Val66Met on”, “My baby likes me talking to him/her”, “Spend a lot polymorphism were not. The study protocol was approved of time teaching baby to recognize things”,and “Love to by the institutional review board for human subjects at play with my baby”). These items were assessed using a the Seoul National University Hospital. Detailed informa- 5-point Likert-type scale (1 = strongly disagree to 5 = tion about the study was given to parents and children, strongly agree). The scores for all of the items were re- and written informed consent was obtained prior to study versed, and high scores represented high involvement in entry. teaching the baby. The scale showed acceptable reliability (Cronbach α =0.65) [35]. Parenting variables We evaluated mother-child interactions and maternal par- Maternal parenting style: the baby is dominant enting style during infancy or toddlerhood using the self- Mothers were asked a series of 3 items about their parent- report questionnaires developed by the Mater University ing styles with regard to their babies’ dominance during Study of Pregnancy and its Outcomes (MUSP) group [32]. the first year after birth (“Always pick up baby as soon as The MUSP is a prospective study of women, and their off- he/she starts to cry”, “Think my baby should get his/her spring, who received antenatal care at a major public hos- own way”,and “Don't allow my baby to rule my life”). pital (Mater Misericordiae Hospital) in South Brisbane Items were assessed using a 5-point Likert-type scale (1 = between 1981 and 1984. The mothers and children have strongly disagree to 5 = strongly agree). Some items were been followed up prospectively with maternal question- reversed, and high scores represented a highly dominant naires, covering a wide range of psychosocial and health baby. characteristics of themselves, their partners and their children. When the children were 6 months, 5 years, and Maternal authoritarian parenting style: degree of autonomy 14 years of age, the mothers were asked about the degree allowed to which they agreed with statements about their subject- Mothers were asked a series of 3 items about their par- ive feelings towards care of the infant. The MUSP group enting styles with regard to their babies’ autonomy dur- found several findings regarding the effect of maternal ing toddlerhood (“Encourage child to go outside and attitudes or parenting practices on child’spsychopatho- play with other children”, “Expect child to disagree with logical outcomes. For example, low maternal control at me if he/she thinks I'm wrong”, and “Encourage child to child age 5 has been reported to predict problematic pat- do his/her own thing"). Items were assessed using a 5- terns of adolescent alcohol consumption at age 14 [33], point Likert-type scale (1 = strongly disagree to 5 = and maternal negative attitude towards the infant at strongly agree). All of the items were reversed, and high 6 months has been shown to be an independent predictor scores represented high autonomy/low control. The of child behavioral outcomes at 5 years, especially the case scale showed a Cronbach’s α value of 0.48 [34]. for externalizing behavior [34]. The four domains of par- enting attitudes or practices included in this study are ADHD and comorbid symptom measurements listed below. The four domains included in this study are Children with ADHD completed the Korean version of listed below. the Children’s Depression Inventory [36]. The mothers completed Korean version of the ADHD Rating Scale-IV Positive feeling about caring for the baby (ADHD-RS) [37] to assess the severity of ADHD symp- Mothers were asked a series of 6 items about their feel- toms and the Disruptive Behavioral Disorder Rating ings toward caring for their babies during the first year Scale according to the DSM-IV (DBDS) [38] to evaluate Park et al. Behavioral and Brain Functions 2014, 10:43 Page 4 of 9 http://www.behavioralandbrainfunctions.com/content/10/1/43 Table 1 Characteristics of participants oppositional defiant disorder (ODD) and conduct dis- order (CD) symptoms and the CBCL [39] to evaluate in- Variable ADHD Controls X /t p (N = 92) (N = 41) ternalizing problems that commonly present in children Sex, male, n (%) 72 (78.3) 27 (65.9) 2.29 0.130 with ADHD. Among the subdomains included in the CBCL, social problems and depression/anxiety were Age, mean (SD), years 9.26 (2.67) 9.68 (2.83) −0.82 0.414 measured for this study. Maternal education, n (%) 0.97 0.324 College degree or more 56 (66.7) 23 (57.5) Genotyping of the BDNF Val66Met polymorphism High school degree or less 28 (33.3) 17 (42.5) Genomic DNA was extracted from the blood (stored Income > $25,000, n (%) 65 (74.7) 25 (62.5) 1.94 0.164 frozen) using a G-DEX II Genomic DNA Extraction Kit Maternal age at pregnancy, 30.06 (4.26) 31.46 (3.45) −1.81 0.072 (Intron, Korea). The detection of a single nucleotide mean (SD) polymorphism was based on the analysis of primer ex- Parenting variables, tension products generated from the genomic DNA that mean (SD) was previously amplified using a chip-based MALDITOF Positive feeling about caring 18.66 (4.49) 20.73 (4.09) −2.53 0.013 mass spectrometry platform (Sequenom, Inc., California, for the baby USA). All primers in the PCR and homogenous mass ex- Spending time teaching the 12.98 (2.73) 12.80 (3.57) 0.31 0.159 tension reactions were designed using Assay Designer baby 3.1 (Sequenom, Inc.) (F: 5’- ACG TTG GAT GCA TCA Parenting style: baby is 10.47 (1.52) 9.80 (2.10) 2.08 0.039 TTG GCT GAC ACT TTC; R: 5’-ACG TTG GAT GCT dominant TCA TTG GGC CGA ACT TTC) [40]. Authoritarian parenting 9.76 (1.94) 10.55 (1.95) −2.15 0.034 style: degree of autonomy Data analysis allowed Pearson correlation analyses were conducted to elucidate ARS, mean (SD) 24.80 (10.48) 4.87 (5.99) 13.40 <0.001 the relationships between parenting variables in toddler- DBDS, mean (SD) hood and the ADHD and comorbid symptom manifest- ODD 4.91 (5.44) ation in children with ADHD. We then performed linear CD 1.29 (2.24) regression analyses in which all parenting variables were CBCL, mean (SD) concurrently entered along with the child’s gender, age, the family’s gross annual income, and the maternal education Social problems 59.65 (9.64) level. Next, we conducted multivariate modeling to exam- Anxiety/depression 57.08 (8.90) ine the relationships among the parenting variables, the CDI 10.77 (7.26) BDNF Val66Met genotypes, and the ADHD and comorbid Abbreviations: ADHD, Attention-Deficit Hyperactivity Disorder; ARS, ADHD Rating symptoms; the child’s gender, the child’s age, the family’s Scale; DBDS, Disruptive Behavioral Disorder Rating Scale according to the DSM-IV; ODD, oppositional defiant disorder; CD, conduct disorder; CBCL,Child Behavior gross annual income, and the maternal education level Checklist; CDI,Children’s Depression Inventory. were included as covariates. A genotype-by-parenting vari- Bold: p <0.013. ables interaction term was also included in the model. In these models, the genotype variable dichotomized subjects distributions were not significantly different between into two groups - children with the BDNF Val/Val geno- ADHD and control subjects. Compared to control sub- type and children with another genotype, because several jects, ADHD subjects showed lower scores on the positive previous studies found that there were some differences in feeling about caring for her baby (p = 0.013) and the de- availability of BDNF protein [41] and clinical characteris- gree of autonomy allowed (p = 0.034) and higher scores on tics [42] between ADHD patients with Met allele and the degree of the baby’s dominance (p = 0.039), but these without Met allele. SPSS (version 21.0; SPSS Inc., Chicago, differences were not statistically significant when adjusted IL) was used to perform all statistical analyses, and a with Bonferroni correction. p-value less than 0.013 (=0.05/4 parenting variables) was Table 2 shows the correlations between parenting vari- considered to be significant. We also noted any finding ables in toddlerhood and the ADHD and comorbid symp- with a p-value less than 0.05. tom manifestation in children with ADHD. The degree to which the baby’s autonomy was allowed was significantly Results and negatively correlated with the CDI scores (r = −0.38, A total of 92 children with ADHD (72 males, 20 females, p = 0.005). A mother’s positive feeling about caring for her mean age 9.26 ± 2.67 years) and 41 healthy controls (27 baby and the degree to which the baby’s autonomy was males and 14 females, mean age 9.68 ± 2.83 years) partic- allowed were negatively, but not significantly, correlated ipated in the study. Table 1 shows group-specific demo- with the child’s anxiety/depression scores on the CBCL graphic and clinical characteristics. The age and gender (r = −0.26, p = 0.019, each). The degree of the baby’s Park et al. Behavioral and Brain Functions 2014, 10:43 Page 5 of 9 http://www.behavioralandbrainfunctions.com/content/10/1/43 Table 2 Correlations between parenting variables and externalizing or internalizing symptoms in children with ADHD ARS scores DBDS, ODD DBDS, CD CBCL, social CBCL, CDI scores scores scores problem depression/ scores anxiety scores rprprp r p r p r p Positive feeling about caring for the baby −0.01 0.928 −0.03 0.780 −0.13 0.231 −0.18 0.107 −0.26 0.019 0.18 0.211 Spending time teaching the Baby 0.14 0.213 0.08 0.493 −0.04 0.696 −0.09 0.412 −0.11 0.318 −0.03 0.855 Parenting style: baby is dominant 0.26 0.018 0.26 0.016 0.10 0.355 0.11 0.316 <0.01 0.997 −0.05 0.743 Authoritarian parenting style: degree of autonomy allowed −0.07 0.506 −0.09 0.424 <0.01 0.992 −0.16 0.164 −0.26 0.019 −0.38 0.005 Abbreviations: ADHD, Attention-Deficit Hyperactivity Disorder; ARS, ADHD Rating Scale; DBDS, Disruptive Behavioral Disorder Rating Scale according to the DSM-IV; ODD, oppositional defiant disorder; CD, conduct disorder; CBCL, Child Behavior Checklist; CDI, Children’s Depression Inventory. Bold: p <0.013. dominance was positively, but not significantly, correlated Discussion with the child’s ARS (r = 0.26, p = 0.018) and ODD (r = The major findings of this study are that the degree to 0.26, p = 0.016) scores. These correlations remained even which the baby’s autonomy is allowed was associated with after adjusting for the child’s gender, the child’sage, the fewer depressive symptoms of ADHD children, and there family’s gross annual income, the maternal education level, was evidence of a G X E interaction for the BDNF Val66- and other parenting variables (Table 3). Met polymorphism and the mother’s positive feelings Among the children with ADHD, the Val/Met genotype about caring for the baby in relation to the development (50.6%) showed the highest frequency among the BDNF of childhood anxiety/depression in ADHD children. Val66Met polymorphism. The Val/Val genotype (27.1%) Children with ADHD experience significant difficulties showed the next highest frequency and the remaining with emotional regulation and are at greater risk for de- 22.3% of children had the Met/Met genotype. The genetic pression and anxiety [43]. However, relatively few studies distributions of the Val66Met polymorphism of BDNF co- have addressed the parenting factors associated with the incided with the expected values of the Hardy-Weinberg depressive and anxious symptoms in children with ADHD Equilibrium (p >0.05). There were no significant differ- [10]. Parental depression or anxiety symptoms, less warmth ences in comorbid symptom severity between ADHD chil- and more power assertiveness in parents, and an inconsist- dren with the BDNF Val/Val genotype and those with the ent parenting style were associated with children’sdepres- Val/Met or Met/Met genotypes (p >0.05). sive symptoms, suggesting an interaction between parental After adjusting for the child’s gender, the child’sage, the psychopathology and parent–child relations [44-46]. With family’s gross annual income, and the maternal education respect to children’s anxiety, maternal anxiety, over- level, the interaction between the mother’spositivefeel- protectiveness, and a lack of positive parenting were re- ings about caring for her baby and the BDNF genotype ported to be independent predictors of anxiety in children was statistically significant only in the anxiety/depression with ADHD [9]. Furthermore, anxious ADHD families variable model (F = 2.51, p = 0.011) (Table 4). The interac- have been described as more controlling, dependent, and tions of the other parenting variables with the BDNF discouraging of autonomy compared to non-anxious genotype were not statistically significant in any of the co- ADHD families [47]. These previous studies used a cross- morbidity variable models (Data available on request). sectional design to compare family characteristics or par- Next, we conducted linear regression analyses using enting variables between an ADHD group with depression the anxiety/depression variable as the outcome and the or anxiety and an ADHD-only group. Such a cross- mother’s positive feelings about caring for her baby as the sectional design makes it impossible to identify a causal predictor within each genotype; thus, separate models were relationship between parenting variables and depression created for subjects with the BDNF Val/Val and other ge- or anxiety problems. Although the notion that parents notypes. For the subjects with the BDNF Val/Met or Met/ have an enduring influence on their children has intuitive Met genotype, there was an association between the appeal, the behavior and temperament of the child can mother’s positive feelings about caring for her baby with also affect the parent–child interaction or the parenting the anxiety/depression scores on the CBCL (B = −0.59, 95% style [48]. To overcome this limitation, a prospective lon- CI = −1.15 to −0.04, p = 0.035), although this association gitudinal study is ideal. Although we did not use a pro- was not significant when adjusted with Bonferroni cor- spective study and we gathered information on parenting rection. However, for the subjects with the BDNF Val/ and the children’s internalizing problems at a single time Val genotype, no associations were found (B = −0.25, point, we could infer a casual relation between parenting 95% CI = −1.55 to 1.06, p =0.676) (Table 5). variables and the children’s internalizing problems by Park et al. Behavioral and Brain Functions 2014, 10:43 Page 6 of 9 http://www.behavioralandbrainfunctions.com/content/10/1/43 Table 3 Associations between parenting variables and externalizing or internalizing symptoms in children with ADHD ARS scores DBDS, ODD scores DBDS, CD scores CBCL, social CBCL, depression/ CDI scores problem scores anxiety scores 2 2 2 2 2 2 B (95% CI) f p B (95% CI) f p B (95% CI) f p B (95% CI) f p B (95% CI) f p B (95% CI) f p Positive feeling about −0.21 0.05 0.490 −0.05 0.01 0.724 −0.09 0.51 0.190 −0.56 0.78 0.052 −0.60 0.71 0.019 0.46 0.19 0.096 caring for the baby (−0.78, 0.36) (−0.34, 0.24) (−0.22, 0.05) (−1.13, 0.01) (−1.09, −0.10) (−0.09, 1.00) Spend time teaching 0.62 0.13 0.242 0.39 0.21 0.141 0.02 0.00 0.885 0.06 0.00 0.917 −0.05 0.00 0.910 0.27 0.02 0.614 the baby (−0.43, 1.66) (−0.13, 0.92) (−0.23, 0.26) (−1.02, 1.14) (−1.00, 0.89) (−0.82, 1.36) Parenting style: baby 1.55 0.43 0.060 0.83 0.45 0.049 0.18 0.20 0.361 0.89 0.16 0.264 0.00 0.00 0.998 0.09 0.00 0.898 is dominant (−0.07, 3.17) (0.01, 1.66) (−0.21, 0.56) (−0.69, 2.47) (−1.39, 1.38) (−1.33, 1.51) Authoritarian parenting −0.34 0.02 0.613 −0.31 0.06 0.405 0.09 0.06 0.591 −0.59 0.08 0.414 −1.20 0.31 0.062 −1.99 1.39 0.002 style: degree of (−1.69, 1.01) (−1.05, 0.43) (−0.20, 0.43) (−2.04, 0.85) (−2.47, 0.06) (−3.21, −0.77) autonomy allowed Associations (B coefficients) are with 1-unit increase in parenting variable scores. In the linear regression analyses, all parenting variables were concurrently entered, along with child’s sex, age, maternal education level, and family’s gross annual income. Abbreviations: ADHD, Attention-Deficit Hyperactivity Disorder; ARS, ADHD Rating Scale; DBDS, Disruptive Behavioral Disorder Rating Scale according to the DSM-IV; ODD, oppositional defiant disorder; CD, conduct disorder; CBCL, Child Behavior Checklist; CDI, Children’s Depression Inventory. Bold: p <0.013. Park et al. Behavioral and Brain Functions 2014, 10:43 Page 7 of 9 http://www.behavioralandbrainfunctions.com/content/10/1/43 Table 4 ANCOVA models examining the main and Several studies have explored the role of family context- interaction effects of a mother’s positive feeling about ual factors in the development of oppositional or conduct caring for her baby and the BDNF genotype on the problems in children with ADHD. These studies suggest depression/anxiety scores in children with ADHD that parental psychopathology and family conflict tend to CBCL, depression/anxiety be more strongly associated with oppositional and conduct Fp symptoms than with inattentive or hyperactive symptoms. Positive feeling about caring for the baby 2.51 0.011 [10] Both parental psychopathology and parenting during early childhood (i.e., observed praise and positive affect) BDNF genotype 1.73 0.198 were predictors of the developmental course of oppos- Positive feeling about caring for the baby X 2.54 0.024 itional or conduct problems [49,50]. In the present study, BDNF genotype we found one unique possible predictor of childhood op- Sex 5.94 0.020 positional behaviors, namely, the allowance of the baby’s Age 0.59 0.446 dominance. It is notable that this factor was not associated Maternal educational level 4.20 0.048 with depression or anxiety but was only associated with Family’s gross annual income 0.55 0.462 the oppositional behaviors. In contrast, less positive feel- Abbreviations: ANCOVA, full analysis of covariance; BDNF, drain-derived neurotrophic ings about caring for the baby and the discouragement of factor; ADHD, attention-deficit hyperactivity disorder; CBCL, Child Behavior Checklist. autonomy were not associated with externalizing problems Bold: p <0.013. but were associated with internalizing problems. This dis- asking questions focused on parenting in early life rather tinction between parenting factors that are associated with than current parenting practices. Consistent with previous either internalizing or externalizing symptoms in ADHD cross-sectional studies [44,46], we found that the encour- suggests there are distinct developmental pathways for agement of autonomy were associated with fewer depres- each comorbid disorder (i.e., depression, anxiety disorder, sive symptoms in children with ADHD. or ODD) in ADHD. Previous studies have found an interaction between This study has several limitations. First, because the data the BDNF Met allele and early adversity on the develop- on parenting variables in early life were based on the rec- ment of depression symptoms in adulthood [27,28]. ollection of the mothers of the children, there is a poten- However, it was not known whether such G X E effects tial for recall bias. In addition, the measures of parenting exist in ADHD. We found that the BDNF Met allele variables were drawn from the mother’s report only, with- moderated the association between less positive parent- out questioning the father or other informants. Second, it ing in early life and the development of depressive symp- is not clear whether the child’s temperament influences toms in children with ADHD, suggesting that individuals the negative parenting attitude or whether the negative with this allele may be more susceptible to early envir- parenting contributes to the development of externalizing onmental influences. It is notable that the G X E inter- or internalizing problems. Third, data on the family his- action was significant only for the anxiety/depression tory of psychiatric disorders and the psychopathology of scale of the CBCL and not for the CDI. Different raters mothers were lacking. Thus, the potentially confounding (i.e. a child for the CDI and a parent for the CBCL) and effects of genetic influences (i.e., heritability of depression) different contents measured (i.e. the severity of depres- or maternal psychopathology (i.e., the effects of over- sive symptoms for the CDI and broader spectrum of de- protectiveness in an anxious mother on the child’s anxiety) pression and anxiety for the CBCL) may partially explain could not be examined. Fourth, there was no control the different results between two scales. group. To determine whether the influence of the BDNF Table 5 Associations between a mother’s positive feeling about caring for her baby and the depression/anxiety scores by BDNF genotype in children with ADHD BDNF Val/Val BDNF Met/Val or Met/Met 2 2 B (95% CI) f p B (95% CI) f p Positive feeling about caring for the baby −0.25(−1.55, 1.06) 0.02 0.676 −0.59(−1.15, −0.04) 0.80 0.035 Spend time teaching the baby −1.17(−4.22, 1.88) 0.04 0.401 0.07(−0.89, 1.04) 0.00 0.877 Parenting style: baby is dominant −1.17(−5.16, 2.81) 0.03 0.516 0.39(−0.97, 1.74) 0.04 0.567 Authoritarian parenting style: degree of autonomy allowed −1.38(−4.52, 1.76) 0.08 0.340 −0.26(−1.73, 1.20) 0.01 0.718 Associations (B coefficients) are with 1-unit increase in parenting variable scores. In the linear regression analyses, all parenting variables were concurrently entered, along with child’s sex, age, maternal education level, and family’s gross annual income. Abbreviations: BDNF, drain-derived neurotrophic factor; ADHD, attention-deficit hyperactivity disorder. Park et al. Behavioral and Brain Functions 2014, 10:43 Page 8 of 9 http://www.behavioralandbrainfunctions.com/content/10/1/43 genotype-parenting variable interaction on the child’sco- hyperacti vity disorder. J Am Acad Child & Adolesc Psychiatry 2003, 42:1424–1432. morbid symptoms is specific to ADHD patients, we 9. Pfiffner L, McBurnett K: Family correlates of comorbid anxiety disorders in should have obtained parenting, symptomatic, and genetic children with attention deficit/hyperactivity disorder. J Abnorm Child data from healthy controls. Finally, the sample size of the Psychol 2006, 34:719–729. 10. 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Cunningham C: A family-centered approach to planning and measuring and take full advantage of: the outcome of interventions for children with attention-deficit/ hyperactivity disorder. J Pediatr Psychol 2007, 32:676–694. • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit
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Published: Nov 25, 2014