• Deficient Emotional Self-Regulation and Adult Attention Deficit Hyperactivity Disorder: A Family Risk Analysis

      Surman, Craig B.H.; Biederman, Joseph; Spencer, Thomas; Yorks, Dayna; Miller, Carolyn A.; Petty, Carter R.; Faraone, Stephen V. (American Psychiatric Association Publishing, 2011-06)
      Objective: A growing body of research suggests that deficient emotional self-regulation (DESR) is prevalent and morbid among patients with attention deficit hyperactivity disorder (ADHD). Family studies provide a method of clarifying the co-occurrence of clinical features, but no family studies have yet addressed ADHD and DESR. Method: Participants were 83 probands with and without ADHD and 128 siblings. All were assessed for axis I DSM-IV conditions with structured diagnostic interviews. The authors defined DESR in adult probands and siblings using items from the Barkley Current Behavior Scale. Analyses tested hypotheses about the familial relationship between ADHD and DESR. Results: Siblings of ADHD probands were at elevated risk of having ADHD, irrespective of the presence or absence of DESR in the proband. The risk for DESR was elevated in siblings of ADHD plus DESR probands but not in siblings of ADHD probands. ADHD and DESR cosegregated in siblings. The risk for other psychiatric disorders was similar in siblings of the ADHD proband groups. Conclusions: The pattern of inheritance of ADHD with DESR preliminarily suggests that DESR may be a familial subtype of ADHD. Our data suggest that DESR is not an expression of other axis I DSM-IV disorders or of nonfamilial environmental factors. The authors cannot exclude contribution of non-axis-I DSM-IV disorders to risk for DESR and cannot determine whether the cosegregation of ADHD in DESR within families is a result of genes or familial environmental risk factors. Further investigation of DESR and its correlates and treatment both in and outside the context of ADHD is warranted.
    • Deletion at the SLC1A1 glutamate transporter gene co-segregates with schizophrenia and bipolar schizoaffective disorder in a 5-generation family

      Myles-Worsley, Marina; Tiobech, Josepha; Browning, Sharon R.; Korn, Jeremy; Goodman, Sarah; Gentile, Karen; Melhem, Nadine; Byerley, William; Faraone, Stephen V.; Middleton, Frank A. (Wiley, 2013-01-22)
      Growing evidence for genetic overlap between schizophrenia (SCZ) and bipolar disorder (BPD) suggests that causal variants of large effect on disease risk may cross traditional diagnostic boundaries. Extended multigenerational families with both SCZ and BPD cases can be a valuable resource for discovery of shared biological pathways because they can reveal the natural evolution of the underlying genetic disruptions and their phenotypic expression. We investigated a deletion at the SLC1A1 glutamate transporter gene originally identified as a copy number variant exclusively carried by members of a 5-generation Palauan family. Using an expanded sample of 21 family members, quantitative PCR confirmed the deletion in all seven individuals with psychosis, three “obligate-carrier” parents and one unaffected sibling, while four marry-in parents were non-carriers. Linkage analysis under an autosomal dominant model generated a LOD-score of 3.64, confirming co-segregation of the deletion with psychosis. For more precise localization, we determined the approximate deletion end points using alignment of next-generation sequencing data for one affected deletion-carrier and then designed PCR amplicons to span the entire deletion locus. These probes established that the deletion spans 84,298 bp, thus eliminating the entire promoter, the transcription start site, and the first 59 amino acids of the protein, including the first transmembrane Na2+/dicarboxylate symporter domain, one of the domains that perform the glutamate transport action. Discovery of this functionally relevant SLC1A1 mutation and its co-segregation with psychosis in an extended multigenerational pedigree provides further support for the important role played by glutamatergic transmission in the pathophysiology of psychotic disorders. © 2013 Wiley Periodicals, Inc.
    • Differential Effect of Environmental Adversity by Gender: Rutter’s Index of Adversity in a Group of Boys and Girls With and Without ADHD

      Biederman, Joseph; Faraone, Stephen V.; Monuteaux, Michael C. (American Psychiatric Association Publishing, 2002-09)
      Objective: This study examined the effect of gender in mediating the association between environmental adversity and the risk of attention deficit hyperactivity disorder (ADHD) and associated impairments. Method: The authors studied 280 ADHD and 242 healthy comparison probands of both genders who were between the ages of 6 and 17 years. They tested the association between Rutter’s indicators of adversity (including family conflict, social class, family size, maternal psychopathology, and paternal criminality) and ADHD, comorbidity, and functioning. Results: Greater levels of environmental adversity were associated with a greater risk for ADHD and other comorbidity in both genders in a dose-dependent fashion. However, learning disability and global functioning were modified by gender, with more detrimental effects observed in boys than in girls. Low social class, maternal psychopathology, and family conflict were significantly associated with psychopathology and functional impairment in the probands, with control for gender, parental ADHD, proband ADHD status, and maternal smoking during pregnancy. Conclusions: Psychosocial adversity in general and low social class, maternal psychopathology, and family conflict in particular increased the risk for ADHD and associated morbidity independently of gender and other risk factors, but gender modified the risk for adverse cognitive and interpersonal outcomes; boys were more vulnerable to the disorder than girls. Because of the difficulties in separating the effects of genetics from environment, these results must be interpreted as provisional until confirmation from twin and adoption studies.
    • Disorder Versus Disability: The Challenge of ADHD in the Context of a High IQ

      Antshel, Kevin M.; Hendricks, Kaitlin; Faraone, Stephen V.; Gordon, Michael (Guilford Publications, 2011-04)
    • Dopamine D4 Gene 7-Repeat Allele and Attention Deficit Hyperactivity Disorder

      Faraone, Stephen V.; Biederman, Joseph; Weiffenbach, Barbara; Keith, Tim; Chu, Monica P.; Weaver, Alix; Spencer, Thomas J.; Wilens, Timothy E.; Frazier, Jean; Cleves, Mario; et al. (American Journal of Psychiatry, 1999-05)
      Objective: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component, and some studies have reported an association between ADHD and the dopamine D4 (DRD4) gene. Method: The authors recruited 27 triads that comprised an ADHD adult, his or her spouse, and their ADHD child. These triads were assessed for ADHD, and their DNA was genotyped for DRD4 alleles. Results: A multiallelic transmission disequilibrium test suggested an association between ADHD and the DRD4 7-repeat allele. Among family members, the number of 7-repeat alleles predicted the diagnosis of ADHD. Conclusions: Prior reports of an association between ADHD and DRD4 generalize to families recruited through clinically referred ADHD adults. However, because there are some conflicting studies, further work is needed to clarify the role of DRD4 in the etiology of the disorder.
    • The dopamine receptor D4 7-repeat allele influences neurocognitive functioning, but this effect is moderated by age and ADHD status: An exploratory study

      Altink, Marieke E.; Rommelse, Nanda N.J.; Slaats-Willemse, Dorine I.E.; Väsquez, Alejandro Arias; Franke, Barbara; Buschgens, Cathelijne J.M.; Fliers, Ellen A.; Faraone, Stephen V.; Sergeant, Joseph A.; Oosterlaan, Jaap; et al. (Informa UK Limited, 2011-11-23)
      Objectives. Evidence suggests the involvement of the dopamine D4 receptor gene ( DRD4 ) in the pathogenesis of ADHD, but the exact mechanism is not well understood. Earlier reports on the effects of DRD4 polymorphisms on neurocognitive and neuroimaging measures are inconsistent. This study investigated the functional consequences of the 7-repeat allele of DRD4 on neurocognitive endophenotypes of ADHD in the Dutch subsample of the International Multicenter ADHD Genetics study. Methods. Participants were 350 children (5 – 11.5 years) and adolescents (11.6 – 19 years) with ADHD and their 195 non-affected siblings. An overall measure of neuropsychological functioning was derived by principal component analysis from five neurocognitive and five motor tasks. The effects of DRD4 and age were examined using Linear Mixed Model analyses. Results. The analyses were stratified for affected and non-affected participants after finding a significant three-way interaction between ADHD status, age and the 7-repeat allele. Apart from a main effect of age, a significant interaction effect of age and DRD4 was found in non-affected but not in affected participants, with non-affected adolescent carriers of the 7-repeat allele showing worse neuropsychological performance. In addition, carrying the 7-repeat allele of DRD4 was related to a significantly worse performance on verbal working memory in non-affected siblings, independent of age. Conclusions. These results might indicate that the effect of the DRD4 7-repeat allele on neuropsychological functioning is dependent on age and ADHD status.
    • Dr. Glatt and Colleagues Reply

      Glatt, Stephen J.; FARAONE, STEPHEN V.; Tsuang, Ming T. (American Psychiatric Association Publishing, 2004-06)
    • DRAMS: A tool to detect and re-align mixed-up samples for integrative studies of multi-omics data

      Jiang, Yi; Giase, Gina; Grennan, Kay; Shieh, Annie W.; Xia, Yan; Han, Lide; Wang, Quan; Wei, Qiang; Chen, Rui; Liu, Sihan; et al. (Public Library of Science (PLoS), 2020-04-13)
    • Effectiveness and Tolerability of Tomoxetine in Adults With Attention Deficit Hyperactivity Disorder

      Spencer, Thomas; Biederman, Joseph; Wilens, Timothy; Prince, Jeffry; Hatch, Mary; Jones, Janice; Harding, Margaret; Faraone, Stephen V.; Seidman, Larry (American Psychiatric Association Publishing, 1998-05)
      Objective: The authors assessed the experimental noradrenergic compound tomoxetine as an alternative treatment for adult attention deficit hyperactivity disorder (ADHD). Method: They conducted a double-blind, placebo-controlled, crossover study of tomoxetine in 22 adults with well-characterized ADHD. Results: Treatment with tomoxetine at an average oral dose of 76 mg/day was well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall and sufficiently robust to be detectable in a parallel-groups comparison restricted to the first 3 weeks of the protocol. Eleven of 21 patients showed improvement after receiving tomoxetine, compared with only two of 21 patients who improved after receiving placebo. Significant tomoxetine-associated improvement was noted on neuropsychological measures of inhibitory capacity from Stroop tests. Conclusions: This preliminary study showed that tomoxetine was effective in treating adult ADHD and was well tolerated. These promising results provide support for further studies of tomoxetine over an extended period of treatment.
    • Environmental risk factors for attention‐deficit hyperactivity disorder

      Banerjee, Tania Das; Middleton, Frank; Faraone, Stephen V. (Wiley, 2007-06-15)
      Attention-deficit hyperactivity disorder (ADHD) is the most common cognitive and behavioural disorder diagnosed among school children. It is characterized by deficient attention and problem solving, along with hyperactivity and difficulty withholding incorrect responses. This highly prevalent disorder is estimated to affect 5–10% of children and in many cases, persists into adulthood, leading to 4% prevalence among adults. Converging evidence from epidemiologic, neuropsychology, neuroimaging, genetic and treatment studies shows that ADHD is a valid medical disorder. The majority of studies performed to assess genetic risk factors in ADHD have supported a strong familial nature of this disorder. Family studies have identified a 2- to 8-fold increase in the risk for ADHD in parents and siblings of children with ADHD. Various twin and adoption studies have also highlighted the highly genetic nature of ADHD. In fact the mean heritability of ADHD was shown to be 0.77, which is comparable to other neuropsychiatric disorders such as schizophrenia or bipolar disorder. However, several biological and environmental factors have also been proposed as risk factors for ADHD, including food additives/diet, lead contamination, cigarette and alcohol exposure, maternal smoking during pregnancy, and low birth weight. Many recent studies have specifically examined the relationships between ADHD and these extraneous factors. This review describes some of these possible risk factors.
    • Evidence for Similar Structural Brain Anomalies in Youth and Adult Attention-Deficit/Hyperactivity Disorder: A Machine Learning Analysis

      Zhang-James, Yanli; Helminen, Emily C; Liu, Jinru; Franke, Barbara; Hoogman, Martine; Faraone, Stephen V (Cold Spring Harbor Laboratory, 2019-02-11)
      Attention-deficit/hyperactivity disorder (ADHD) affects 5% of children world-wide. Of these, two-thirds continue to have impairing symptoms of ADHD into adulthood. Although a large literature implicates structural brain differences of the disorder, it is not clear if adults with ADHD have similar neuroanatomical differences as those seen in children with recent reports from the large ENIGMA-ADHD consortium finding structural differences for children but not for adults. This paper uses deep learning neural network classification models to determine if there are neuroanatomical changes in the brains of children with ADHD that are also observed for adult ADHD, and vice versa. We found that structural MRI data can significantly separate ADHD from control participants for both children and adults. Consistent with the prior reports from ENIGMA-ADHD, prediction performance and effect sizes were better for the child than the adult samples. The model trained on adult samples significantly predicted ADHD in the child sample, suggesting that our model learned anatomical features that are common to ADHD in childhood and adulthood. These results support the continuity of ADHD’s brain differences from childhood to adulthood. In addition, our work demonstrates a novel use of neural network classification models to test hypotheses about developmental continuity.
    • Evidence for the multigenic inheritance of schizophrenia

      Freedman, Robert; Leonard, Sherry; Olincy, Ann; Kaufmann, Charles A.; Malaspina, Dolores; Cloninger, C. Robert; Svrakic, Dragan; Faraone, Stephen V.; Tsuang, Ming T. (Wiley, 2002-08-21)
      Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these ®endings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z ¼ 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the a7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z ¼ 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci.
    • Examining the Comorbidity Between Attention Deficit Hyperactivity Disorder and Bipolar I Disorder: A Meta-Analysis of Family Genetic Studies

      Faraone, Stephen V.; Biederman, Joseph; Wozniak, Janet (American Psychiatric Association Publishing, 2012-12)
      Objective: The existence of comorbidity between attention deficit hyperactivity disorder (ADHD) and bipolar I disorder has been documented in clinical and epidemiological studies, in studies of children and adults, and in diagnosed ADHD and bipolar I patient samples. Yet questions remain about the validity of diagnosing bipolar I disorder in ADHD youth. The authors aim to clarify these issues by reviewing family genetic studies of ADHD and bipolar I disorder. Method: The authors applied randomeffects meta-analysis to family genetic studies of ADHD and bipolar I disorder. Twenty bipolar proband studies provided 37 estimates of the prevalence of ADHD in 4,301 relatives of bipolar probands and 1,937 relatives of comparison probands. Seven ADHD proband studies provided 12 estimates of the prevalence of bipolar I disorder in 1,877 relatives of ADHD probands and 1,601 relatives of comparison probands. Results: These studies found a significantly higher prevalence of ADHD among relatives of bipolar probands and a significantly higher prevalence of bipolar I disorder among relatives of ADHD probands. These results could not be accounted for by publication biases, unusual results from any one observation, sample characteristics, or study design features. The authors found no evidence of heterogeneity in the ADHD or bipolar family studies. Conclusions: The results suggest that ADHD plus bipolar comorbidity cannot be accounted for by misdiagnoses, but additional research is needed to rule out artifactual sources of comorbidity. More research is also needed to determine whether comorbidity of ADHD and bipolar I disorder constitutes a familial subtype distinct from its constituent disorders, which if confirmed would have implications for diagnostic nosology and genetic studies.
    • Familial Risk Analyses of Attention Deficit Hyperactivity Disorder and Substance Use Disorders

      Biederman, Joseph; Petty, Carter R.; Wilens, Timothy E.; Fraire, Maria G.; Purcell, Caitlin A.; Mick, Eric; Monuteaux, Michael C.; Faraone, Stephen V. (American Psychiatric Association Publishing, 2008-01)
      Objective: A robust and bidirectional comorbidity between attention deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (alcohol or drug abuse or dependence) has been consistently reported in the extant literature. Method: First-degree relatives from a large group of pediatrically and psychiatrically referred boys with (112 probands, 385 relatives) and without (105 probands, 358 relatives) ADHD were comprehensively assessed by blind raters with structured diagnostic interviews. Familial risk analysis examined the risks in first-degree relatives for ADHD, psychoactive substance use disorder, alcohol dependence, and drug dependence after stratifying probands by the presence and absence of these disorders. Results: ADHD in the proband was consistently associated with a significant risk for ADHD in relatives. Drug dependence in probands increased the risk for drug dependence in relatives irrespective of ADHD status, whereas alcohol dependence in relatives was predicted only by ADHD probands with comorbid alcohol dependence. In addition, ADHD in the proband predicted drug dependence in relatives, and drug dependence in comparison probands increased the risk for ADHD in relatives. Both alcohol dependence and drug dependence bred true in families without evidence for a common risk between these disorders. Conclusions: Patterns of familial risk analysis suggest that the association between ADHD and drug dependence is most consistent with the hypothesis of variable expressivity of a common risk between these disorders, whereas the association between ADHD and alcohol dependence is most consistent with the hypothesis of independent transmission of these disorders. Findings also suggest specificity for the transmission of alcohol and drug dependence.
    • Family based association analysis of statistically derived quantitative traits for drug use in ADHD and the dopamine transporter gene

      Lasky-Su, Jessica; Biederman, Joseph; Doyle, Alysa E.; Wilens, Timothy; Monuteaux, Michael; Smoller, Jordan W.; Faraone, Stephen (Elsevier BV, 2006-06)
      Objective To determine whether SNPs within the dopamine transporter gene (DAT) are associated with quantitative phenotypes generated from drug frequency variables in an ADHD sample. Method 35 SNPs were genotyped in and around DAT. We developed a quantitative phenotype at each SNP by weighting the drug frequency variables. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, a screening procedure was used to select and test the SNPs with the greatest power to detect an association in DAT. Results No SNPs in DAT were associated with the quantitative phenotypes generated from the drug frequency variables after the multiple comparisons adjustment; however, some SNPs achieved nominal significance. A sliding window of analysis of 3 SNPs also resulted in only nominal associations. Conclusions SNPs in DAT do not appear to be associated with the phenotypes generated from drug frequency variables among individuals with ADHD.
    • Family based association study of pediatric bipolar disorder and the dopamine transporter gene (SLC6A3)

      Mick, Eric; Kim, Jang Woo; Biederman, Joseph; Wozniak, Janet; Wilens, Timothy; Spencer, Thomas; Smoller, Jordan W.; Faraone, Stephen V. (Wiley, 2008-10-05)
      Thedopaminetransportergene(SLC6A3) isacompelling candidate for pediatric bipolar disorder because (a) it has been associated with ADHD, (b) bipolar comorbidity with ADHD has been hypothesized to be an etiologically distinct familial subtype (c) blockade of the dopamine transporter with psychostimulants can induce mania in susceptible individualsand(d) previous studies have implicated the gene in bipolar disorder in adults. We conducted a family-based association study of SLC6A3 in 170 affected offspring trios defined by a child (12.9 5.3 years of age)with DSM-IV Bipolar-I disorder. Twenty-eight tag SNPs were chosen from the CEU (European) population of the International HapMap project (www.hapmap.org). Results indicated nominally positive association for 4 SNPs (rs40184, rs11133767, rs3776512, and rs464049), but only rs40184 survived correction formultiple statistical comparisons (P¼0.038). This is the first examination of the association with SLC6A3 and bipolar disorder in children and, like previous findings in adults with bipolar disorder, we found evidence of association with SNPs in the 30 region of the gene. These data provide suggestive evidence supporting a role for SLC6A3 in the etiology of pediatric bipolar disorder.
    • Family-based and case-control association studies of catechol-O-methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism

      Qian, Qiujin; Wang, Yufeng; Zhou, Rulun; Li, Jun; Wang, Bing; Glatt, Stephen; Faraone, Stephen V. (Wiley, 2003-03-04)
      Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset behavioral disorder. Boys are more often affected than girls. Family, twin, and adoption studies have supported a strong genetic basis. Some studies show that a catechol-O-methyltransferase (COMT) polymorphism affecting enzyme activity was associated with personality characteristics and diseases, such as novelty-seeking personality, substance abuse, and heroin addiction, whose features are similar to ADHD or are associated with ADHD. These findings suggest that the COMT gene may be a candidate gene for ADHD. TDT, HHRR, and case-control association studies were conducted within a sample of 202 nuclear ADHD families, 340 ADHD cases, and 226 controls in the Han Chinese population. Diagnoses and ADHD subtypes were ascertained according to DSM-IV criteria using American Clinical Diagnostic Interviewing Scales. The HHRR analysis suggested that the low enzyme-activity COMT Met allele was preferentially transmitted to ADHD boys (160 trios, χ2 = 3.858, P = 0.05, df = 1) but not girls. This association is particularly pronounced among male ADHD probands without any comorbidity (50 trios, HHRR: χ2 = 5.128, P = 0.024, df = 1; TDT: χ2 = 4.558, P = 0.033, df = 1), especially the ADHD-I subtype (32 trios, HHRR: χ2 = 5.792, P = 0.016, df = 1; TDT: χ2 = 5.333, P = 0.021, df = 1). The case-control study revealed that the Val allele was more frequent in females meeting ICD-10 or DSM-IV criteria for ADHD than in female controls (86 and 79.5%, respectively, χ2 = 4.059, P = 0.044, df = 1). Although these results suggest the COMT gene exerts some influence on the risk for ADHD in the Han Chinese population, given the potential for Type I error, these findings require replication before drawing definitive conclusions. © 2003 Wiley-Liss, Inc.
    • Family-based association study of markers on chromosome 22 in schizophrenia using African-American, European-American, and Chinese families

      Takahashi, Sakae; Cui, Yu-hu; Kojima, Takuya; Han, Yong-hua; Zhou, Ru-lum; Kamioka, Masashi; Yu, Shun-ying; Matsuura, Masato; Matsushima, Eisuyke; Wilcox, Marsha; et al. (Wiley, 2003-06-13)
      Several studies suggest that loci at chromosome 22q11.2-q13 might be linked to susceptibility to schizophrenia. Here we performed family-based association studies on chromosome 22q using 12 DNA microsatellite markers in African-American, European-American, and Chinese pedigrees. The marker D22S683 showed significant linkage and association with schizophrenia in not only the European-American sample but also in a combined sample (European-American and Chinese samples). Notably, D22S683 is located nearby and between D22S278 and D22S283, which have shown linkage and association to schizophrenia in prior reports. However, we found no significant association for the African-American sample. In conclusion, our data provide further support for the idea that the region around D22S683 contains a susceptibility gene for schizophrenia. © 2003 Wiley-Liss, Inc.
    • Further evidence of an association between maternal smoking during pregnancy and attention deficit hyperactivity disorder: Findings from a high-risk sample of siblings

      Milberger, Sharon; Biederman, Joseph; Faraone, Stephen V.; Jones, Janice (Informa UK Limited, 1998-09)
      The authors investigated the relationship between attentiondeficit/byperactivity disorder (ADHD) and cigarette smoking in siblings of ADHD and non-ADHD probands. They conducted a 4-year follow-up of siblings from ADHD and control-group families. In the siblings of ADHD probands, ADHD was associated with higher rates and earlier onset of cigarette smoking. There was also a significant positive association between cigarette smoking and conduct disorder, major depression, and drug abuse in the siblings, even after adjusting for confounding variables. Moreover, smoking was found to be familial among ADHD families but not control-group families. Our findings indicate that ADHD is a risk factor for early initiation of cigarette smoking in the high-risk siblings of ADHD probands
    • Further Evidence of Association Between Behavioral Inhibition and Social Anxiety in Children

      Biederman, Joseph; Hirshfeld-Becker, Dina R.; Rosenbaum, Jerrold F.; Hérot, Christine; Friedman, Deborah; Snidman, Nancy; Kagan, Jerome; Faraone, Stephen V. (American Psychiatric Association Publishing, 2001-10)
      Objective: The authors sought to examine psychopathological correlates of behavioral inhibition in young offspring of parents with panic disorder and/or major depression. Method: Behavioral inhibition, determined by using standard laboratory observations, was assessed in four groups of children (age 2–6 years): 129 children of parents with both panic disorder and major depression, 22 children of parents with panic disorder alone, 49 children of parents with major depression alone, and 84 comparison children of parents with neither panic disorder nor major depression. Psychopathology in children ≥5 years was compared between children with behavioral inhibition (N=64) and without (N=152). Results: Social anxiety disorder (social phobia or avoidant disorder) was significantly more likely to be found in the children with behavioral inhibition (17%) than in those without (5%). Noninhibited children were significantly more likely than inhibited children to have disruptive behavior disorders (20% versus 6%, respectively) and had higher scores on the attention problems scale of the Child Behavior Checklist (mean=52.1 versus 50.8). Conclusions: This study adds to the growing literature suggesting an association between behavioral inhibition and social anxiety disorder and an inverse relationship between inhibition and disruptive behavior disorders.