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Attention-deficit/hyperactivity disorder (ADHD) is among the most prevalent, inheritable, and heterogeneous childhood-onset neurodevelopmental disorders. Children with a hereditary background of ADHD have heightened risk of having ADHD and persistent impairment symptoms into adulthood. These facts suggest distinct familial-specific neuropathological substrates in ADHD that may exist in anatomical components subserving attention and cognitive control processing pathways during development. The objective of this study is to investigate the topological properties of the gray matter (GM) structural brain networks in children with familial ADHD (ADHD-F), non-familial ADHD (ADHD-NF), as well as matched controls. A total of 452 participants were involved, including 132, 165 and 155 in groups of ADHD-F, ADHD-NF and typically developed children, respectively. The GM structural brain network was constructed for each group using graph theoretical techniques with cortical and subcortical structures as nodes and correlations between volume of each pair of the nodes within each group as edges, while controlled for confounding factors using regression analysis. Relative to controls, children in both ADHD-F and ADHD-NF groups showed significantly higher nodal global and nodal local efficiencies in the left caudal middle frontal gyrus. Compared to controls and ADHD-NF, children with ADHD-F showed distinct structural network topological patterns associated with right precuneus (significantly higher nodal global efficiency and significantly higher nodal strength), left paracentral gyrus (significantly higher nodal strength and trend toward significantly higher nodal local efficiency) and left putamen (significantly higher nodal global efficiency and trend toward significantly higher nodal local efficiency). Our results for the first time in the field provide evidence of familial-specific structural brain network alterations in ADHD, that may contribute to distinct clinical/behavioral symptomology and developmental trajectories in children with ADHD-F.

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Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high prevalence, heritability, and heterogeneity. Children with a positive family history of ADHD have a heightened risk of ADHD emergence, persistence, and executive function deficits, with the neural mechanisms having been under investigated. The objective of this study was to investigate working memory-related functional brain activation patterns in children with ADHD (with vs. without positive family histories (ADHD-F vs. ADHD-NF)) and matched typically developing children (TDC). Voxel-based and region of interest analyses were conducted on two-back task-based fMRI data of 362 subjects, including 186, 96, and 80 children in groups of TDC, ADHD-NF, and ADHD-F, respectively. Relative to TDC, both ADHD groups had significantly reduced activation in the left inferior frontal gyrus (IFG). And the ADHD-F group demonstrated a significant positive association of left IFG activation with task reaction time, a negative association of the right IFG with ADHD symptomatology, and a negative association of the IFG activation laterality index with the inattention symptom score. These results suggest that working memory-related functional alterations in bilateral IFGs may play distinct roles in ADHD-F, with the functional underdevelopment of the left IFG significantly informing the onset of ADHD symptoms. Our findings have the potential to assist in tailored diagnoses and targeted interventions in children with ADHD-F.

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Background: Traumatic brain injury (TBI)-induced attention deficits are among the most common long-term cognitive consequences in children. Most of the existing studies attempting to understand the neuropathological underpinnings of cognitive and behavioral impairments in TBI have utilized heterogeneous samples and resulted in inconsistent findings. The current research proposed to investigate topological properties of the structural brain network in children with TBI and their relationship with post-TBI attention problems in a more homogeneous subgroup of children who had severe post-TBI attention deficits (TBI-A). Materials and Methods: A total of 31 children with TBI-A and 35 group-matched controls were involved in the study. Diffusion tensor imaging-based probabilistic tractography and graph theoretical techniques were used to construct the structural brain network in each subject. Network topological properties were calculated in both global level and regional (nodal) level. Between-group comparisons among the topological network measures and analyses for searching brain-behavioral were all corrected for multiple comparisons using Bonferroni method. Results: Compared with controls, the TBI-A group showed significantly higher nodal local efficiency and nodal clustering coefficient in left inferior frontal gyrus and right transverse temporal gyrus, whereas significantly lower nodal clustering coefficient in left supramarginal gyrus and lower nodal local efficiency in left parahippocampal gyrus. The temporal lobe topological alterations were significantly associated with the post-TBI inattentive and hyperactive symptoms in the TBI-A group. Conclusion: The results suggest that TBI-related structural re-modularity in the white matter subnetworks associated with temporal lobe may play a critical role in the onset of severe post-TBI attention deficits in children. These findings provide valuable input for understanding the neurobiological substrates of post-TBI attention deficits, and have the potential to serve as quantitatively measurable criteria guiding the development of more timely and tailored strategies for diagnoses and treatments to the affected individuals. Impact statement This study provides a new insight into the neurobiological substrates associated with post-traumatic brain injury attention deficits (TBI-A) in children, by evaluating topological alterations of the structural brain network. The results demonstrated that relative to group-matched controls, the children with TBI-A had significantly altered nodal local efficiency and nodal clustering coefficient in temporal lobe, which strongly linked to elevated inattentive and hyperactive symptoms in the TBI-A group. These findings suggested that white matter structural re-modularity in subnetworks associated with temporal lobe may serve as quantitatively measurable biomarkers for early prediction and diagnosis of post-TBI attention deficits in children.

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OBJECTIVE: This longitudinal study examined whether preschool attention deficit hyperactivity disorder (ADHD) symptoms and neuropsychological functioning predicted trajectories of children's social functioning from age 3 to 4 through 12 years. METHODS: Three- and four-year-old children (N = 208; 72.6% boys) were evaluated annually through age 12. Parent and teacher Attention Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition responses during the initial evaluation were used to categorize preschoolers as "High" or "Low" risk for ADHD. Children's neuropsychological functioning was assessed using the NEPSY. Teachers' reports of children's social functioning were obtained annually from preschool through age 12 years using the Adaptability, Functional Communication, and Social Skills subscales of the Behavioral Assessment System for Children, Second Edition. Hierarchical linear modeling was used to assess the trajectories of social functioning and determine whether preschoolers' neuropsychological functioning and ADHD risk status predicted social functioning at age 12 years, and/or change in social functioning throughout childhood. All models controlled for baseline socioeconomic status. RESULTS: High Risk children had significantly lower teacher-rated Adaptability and Social Skills at age 12 years. High Risk children and those with lower Verbal neuropsychological functioning in preschool had lower teacher-rated Functional Communication at 12 years old. Lower preschool Verbal neuropsychological functioning predicted greater positive change in teacher-rated Functional Communication across childhood. CONCLUSIONS: Early identification of and intervention for children exhibiting ADHD behaviors is critical given the enduring negative impact of these behaviors on social functioning. Screening preschoolers for verbal difficulties is encouraged given their long-term impact on children's ability to clearly express thoughts and feelings and obtain and provide information.

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Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and heterogeneous neurodevelopmental disorder, which is diagnosed using subjective symptom reports. Machine learning classifiers have been utilized to assist in the development of neuroimaging-based biomarkers for objective diagnosis of ADHD. However, existing basic model-based studies in ADHD report suboptimal classification performances and inconclusive results, mainly due to the limited flexibility for each type of basic classifier to appropriately handle multi-dimensional source features with varying properties. This study applied ensemble learning techniques (ELTs), a meta-algorithm that combine several basic machine learning models into one predictive model in order to decrease variance, bias, or improve predictions, in multimodal neuroimaging data collected from 72 young adults, including 36 probands (18 remitters and 18 persisters of childhood ADHD) and 36 group-matched controls. All currently available optimization strategies for ELTs (i.e., voting, bagging, boosting and stacking techniques) were tested in a pool of semifinal classification results generated by seven basic classifiers. The high-dimensional neuroimaging features for classification included regional cortical gray matter (GM) thickness and surface area, GM volume of subcortical structures, volume and fractional anisotropy of major white matter fiber tracts, pair-wise regional connectivity and global/nodal topological properties of the functional brain network for cue-evoked attention process. As a result, the bagging-based ELT with the base model of support vector machine achieved the best results, with significant improvement of the area under the receiver of operating characteristic curve (0.89 for ADHD vs. controls and 0.9 for ADHD persisters vs. remitters). Features of nodal efficiency in right inferior frontal gyrus, right middle frontal (MFG)-inferior parietal (IPL) functional connectivity, and right amygdala volume significantly contributed to accurate discrimination between ADHD probands and controls; higher nodal efficiency of right MFG greatly contributed to inattentive and hyperactive/impulsive symptom remission, while higher right MFG-IPL functional connectivity strongly linked to symptom persistence in adults with childhood ADHD. Considering their improved robustness than the commonly implemented basic classifiers, findings suggest that ELTs may have the potential to identify more reliable neurobiological markers for neurodevelopmental disorders.

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Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder that emerges in childhood and persists into adulthood in a sizeable portion of afflicted individuals. The persistence of ADHD symptoms elevates the risk of adverse outcomes that result in substantial individual and societal burden. The objective of this study was to delineate neuroanatomical substrates associated with the diversity of adult outcomes of childhood ADHD, which may have considerable value for development of novel interventions that target mechanisms associated with recovery. Structural MRI and diffusion tensor imaging data from 32 young adults who were diagnosed with ADHD combined-type during childhood and 35 group-matched controls were analyzed. Adults with childhood ADHD were divided into 16 remitters and 16 persisters based on DSM-IV criteria. Compared to the controls, ADHD probands showed significantly reduced gray matter (GM) volume in right putamen and white matter (WM) volume in left parieto-insular fiber tracts. Within the ADHD probands, the remitters, as compared to persisters, showed significantly greater volume of right hippocampo-frontal and right parieto-insular WM fiber tracts, and those connecting caudate with the frontal, parietal, occipital, temporal, and insular cortices. Among ADHD probands, increased fractional anisotropy value of left caudate-parietal tract was significantly correlated with reduced hyperactive/impulsive symptoms. These findings suggest that optimal structural development in the WM tracts that connect caudate with cortical areas, especially in the caudate-parietal path, may play an important role in symptom remission in young adults with childhood ADHD.

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This preliminary randomized controlled trial compared Training Executive, Attention and Motor Skills (TEAMS), a played-based intervention for preschool children with attention-deficit/hyperactivity disorder (ADHD), to an active comparison intervention consisting of parent education and support (ClinicalTrials.gov Identifier: NCT01462032). The primary aims were to gauge preliminary efficacy and assist in further development of TEAMS. Four- and 5-year-old children with ADHD were randomly assigned to receive TEAMS (N = 26) or the comparison intervention (N = 26) with blinded assessments by parents, teachers and clinicians ascertained pretreatment, post-treatment, and 1- and 3-months post-treatment. Changes in ADHD severity, impairment, parenting factors, and neuropsychological functioning over time as a function of treatment condition were assessed using the PROC MIXED procedure in SAS. Across most measures, significant main effects for Time emerged; both treatments were associated with reduced ADHD symptoms that persisted for three months post-treatment. There were no significant Treatment effects or Time x Treatment interactions on symptom and impairment measures, suggesting that the magnitude of improvement did not differ between the two interventions. However, significant correlations emerged between the magnitude of behavioral change, as assessed by parents and clinicians, and the amount of time families engaged in TEAMS-related activities during treatment. Across a wide array of parenting and neuropsychological measures, there were few significant group differences over time. TEAMS and other psychosocial interventions appear to provide similar levels of benefit. Play-based interventions like TEAMS represent a potentially viable alternative/addition to current ADHD treatments, particularly for young children, but more research and further development of techniques are necessary.

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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects approximately 8%-12% of children worldwide. Throughout an individual's lifetime, ADHD can significantly increase risk for other psychiatric disorders, educational and occupational failure, accidents, criminality, social disability and addictions. No single risk factor is necessary or sufficient to cause ADHD. The multifactorial causation of ADHD is reflected in the heterogeneity of this disorder, as indicated by its diversity of psychiatric comorbidities, varied clinical profiles, patterns of neurocognitive impairment and developmental trajectories, and the wide range of structural and functional brain anomalies. Although evidence-based treatments can reduce ADHD symptoms in a substantial portion of affected individuals, there is yet no curative treatment for ADHD. A number of theoretical models of the emergence and developmental trajectories of ADHD have been proposed, aimed at providing systematic guides for clinical research and practice. We conducted a comprehensive review of the current status of research in understanding the heterogeneity of ADHD in terms of etiology, clinical profiles and trajectories, and neurobiological mechanisms. We suggest that further research focus on investigating the impact of the etiological risk factors and their interactions with developmental neural mechanisms and clinical profiles in ADHD. Such research would have heuristic value for identifying biologically homogeneous subgroups and could facilitate the development of novel and more tailored interventions that target underlying neural anomalies characteristic of more homogeneous subgroups.

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BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) often emerges during the preschool years and remains impairing throughout the life span. Early identification and intervention may yield lasting benefits that alter the often-adverse trajectory of the disorder. METHODS: This Practitioner Review provides up-to-date information regarding the evaluation and treatment of ADHD in preschool children. The clinical presentation of ADHD in preschool children, its persistence into later childhood, the applicability of DSM-5 criteria for preschoolers with ADHD, and early predictors of long-term trajectories are addressed, as well as current findings from randomized controlled trials of both nonpharmacological and pharmacological interventions. RESULTS: Symptoms of hyperactivity/impulsivity extend down to age 3, but several inattention symptoms, as defined by DSM-V, less accurately differentiate preschoolers with and without ADHD. Most preschool youth with ADHD symptoms continue to manifest symptoms and impairment into school-age and adolescence. However, few predictors of persistence beyond early severity have been identified. Behavioral interventions constitute a first-line treatment for preschool ADHD symptoms, with telepsychiatry increasing in prominence to help to mitigate financial, geographic, and/or logistical barriers to care. Pharmacological interventions, particularly psychostimulants, also confer demonstrable benefits, yet efficacy and safety profiles are less desirable relative to findings in school-age youth. CONCLUSIONS: Acute treatments have demonstrable efficacy, but do not appear to fundamentally alter underlying mechanisms or long-term trajectories.

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This goal of this study was to assess the initial feasibility and efficacy of a play-based intervention targeting executive functions (EF) and parent-child relationships in preschoolers compared with an active control group. Preschoolers with EF deficits (M age = 3.7 ± 0.47, predominantly White boys) and their parents were randomized to intervention (n = 36) or active control (n = 32) conditions. Child performance on EF tasks, parent and masked teacher ratings of EF and behavior, and masked clinician ratings of severity were collected at baseline and at 3 and 6 months postbaseline. Partial eta-squared effect sizes at .02 or higher comparing performance across the two groups was considered evidence of meaningful, albeit small, intervention effects. Intervention effects were observed for parent ratings of inattention, hyperactivity/impulsivity, and number/severity of problems experienced in various home situations, teacher ratings of severity of problems in various school situations, parent and teacher ratings of overall impairment, and clinician ratings of impairment. Intervention effects for functional improvements were maintained at the 6-month follow-up. No effect of the intervention was observed on the objective EF measures, although parent ratings of emotional control were improved for children in the intervention group. An intervention utilizing play-based activities targeting EF, when administered in a structured way by parents, is a promising approach for improving behavior in preschoolers with self-regulation deficits. More work is needed to investigate potential impact on EF and to disentangle mechanisms of action. It may be that the intervention's focus on the structure and quality of parent-child interactions is a mediator of outcomes, rather than improved EFs.

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Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing neurodevelopmental disorder that persists into adulthood in a sizeable portion of afflicted children. The persistence of ADHD elevates the risk for adverse outcomes that result in substantial individual and societal burden. The objective of this study is to assess neurobiological substrates associated with variability of clinical outcomes in childhood ADHD, which has considerable value for the development of novel interventions that target mechanisms associated with recovery. A total of 36 young adults who were diagnosed with ADHD combined-type during childhood and 33 group-matched controls were involved in the study. Adults with childhood ADHD were further divided into 17 persisters and 19 remitters based on DSM-5 criteria. Functional magnetic resonance imaging data during a cue-evoked attention task were collected from each subject. The cue-evoked attention processing network was constructed using graph theoretic techniques. Network properties, including global-, local-, and nodal-efficiency, and network hubs were computed. Group comparisons of the network properties were conducted. Significantly lower nodal efficiency in right inferior frontal gyrus and reduced left side frontal-parietal functional interactions were observed in both remitters and persisters relative to the controls. The ADHD persisters showed a unique pattern of significantly lower nodal efficiency in right middle frontal gyrus (MFG) and hyper-interactions between bilateral MFG. This study suggests that right MFG functional impairments may relate to inactive fronto-parietal functional interactions for sensory and cognitive information processing and symptom persistence in young adults with childhood ADHD.

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Longitudinal studies have shown that clinical precursors of antisocial personality disorder (ASPD) include attention-deficit/hyperactivity disorder (ADHD) and more notably comorbid ADHD and conduct disorder (CD). Despite existing evidence for the purported role of abnormal serotonergic function in aggressive youth and adults, little evidence exists on the role of serotonin in the progression from childhood disruptive behavior disorders to adult psychopathology, including ASPD. This study examined the relation between serotonergic function in children diagnosed with ADHD and the development of ASPD in early adulthood. We hypothesized that low serotonin response to a pharmacological probe in childhood would predict the development of adult ASPD. Towards this goal we divided 40 adults (M = 37, F = 3), ages 23-26 (m-24.57, sd-2.33) diagnosed with childhood ADHD into 2 groups: participants with (n = 21) and without (n = 19) ASPD. We used logistic regression to assess whether serotonergic measures in childhood assessed via prolactin and cortisol responses to a fenfluramine challenge, would selectively predict the development of ASPD in early adulthood. Logistic regression models showed that low central serotonergic response in childhood indexed by cortisol response significantly predicted adult ASPD (Wald = 4.427, p = .035) but not ADHD diagnosis in adulthood. Adults without ASPD had the highest serotonergic response whereas adults with adolescent ASPD (i.e. early onset ASPD) had the lowest response. Thus we provide new evidence of the link between low serotonergic function in childhood and the development of ASPD in adulthood, particularly for boys with adolescent onset of ASPD. These findings are relevant for understanding the contribution of childhood neurobiology to risk for later ASPD.

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We are pleased to present this special issue of JCPP, which brings together a collection of cutting-edge empirical studies that focuses on developmental trajectories and pathways associated with ADHD, conduct problems and other externalizing behaviors. JCPP has had a long-standing focus on theoretically strong prospective longitudinal studies that elucidate behavioral change and outcomes over time, including in the areas of ADHD and externalizing disorders (Kuja-Halkola, Lichtenstein, D'Onofrio & Larsson, 2015; Sonuga-Barke & Halperin, 2010). Keeping with that tradition, all of the papers in this special issue employ a prospective longitudinal design and a focus on changes that unfold over development.

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This study examined whether working memory (WM), inattentive symptoms, and/or hyperactive/impulsive symptoms significantly contributed to academic, behavioral, and global functioning in 8-year-old children. One-hundred-sixty 8-year-old children (75.6% male), who were originally recruited as preschoolers, completed subtests from the Wechsler Intelligence Scale for Children-Fourth Edition, Integrated and Wechsler Individual Achievement Test-Second Edition to assess WM and academic achievement, respectively. Teachers rated children's academic and behavioral functioning using the Vanderbilt Rating Scale. Global functioning, as rated by clinicians, was assessed by the Children's Global Assessment Scale. Multiple linear regressions were completed to determine the extent to which WM (auditory-verbal and visual-spatial) and/or inattentive and hyperactive/impulsive symptom severity significantly contributed to academic, behavioral, and/or global functioning. Both auditory-verbal and visual-spatial WM but not ADHD symptom severity, significantly and independently contributed to measures of academic achievement (all p < 0.01). In contrast, both WM and inattention symptoms (p < 0.01), but not hyperactivity-impulsivity (p > 0.05) significantly contributed to teacher-ratings of academic functioning. Further, inattention and hyperactivity/impulsivity (p < 0.04), but not WM (p > 0.10) were significantly associated with teacher-ratings of behavioral functioning and clinician-ratings of global functioning. Taken together, it appears that WM in children may be uniquely related to academic skills, but not necessarily to overall behavioral functioning.

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PURPOSE OF REVIEW: This paper summarizes key, recently published research examining longitudinal outcomes for preschoolers with high levels of inattention and/or hyperactivity/impulsivity. RECENT FINDINGS: Symptom trajectories show that hyperactivity/impulsivity declines across childhood. At the group level, the course of inattention appears more variable. However, identification of subgroups of children showing stable, rising, and falling inattention over time is promising. Early ADHD-like symptoms portend risk for academic and social difficulties, as well as comorbid emotional and behavioral problems in childhood and adolescence. Several early risk factors appear to moderate these relations, including comorbid symptoms, parental psychopathology, socioeconomic disadvantage, and perhaps neuropsychological dysfunction. Furthermore, high levels of inattention and/or hyperactivity/impulsivity during the preschool period appear to compromise development of regulatory and neuropsychological functions, which in turn increases risk for negative outcomes later in childhood. Identified risk factors are targets for novel interventions, which ideally would be delivered early to at-risk children.

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OBJECTIVE: Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). METHOD: A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. RESULTS: Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F1,30 = 17.00; p < .001). Elevated caudate activation was associated with robust improvement for methylphenidate and little improvement for atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F1,30 = 14.99; p < .001). CONCLUSION: Enhanced caudate activation for response inhibition may be a candidate biomarker of superior response to methylphenidate over atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. CLINICAL TRIAL REGISTRATION INFORMATION: Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391.

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The protracted and highly variable development of prefrontal cortex regions that support cognitive control has been purported to shape the adult outcome of attention-deficit/hyperactivity disorder (ADHD). This neurodevelopmental model was tested in a prospectively followed sample of 27 adult probands who were diagnosed with ADHD in childhood and 28 carefully matched comparison subjects aged 21-28 years. Probands were classified with persistent ADHD or remitted ADHD. Behavioral and neural responses to the Stimulus and Response Conflict Task (SRCT) performed during functional magnetic resonance imaging (fMRI) were compared in probands and comparison subjects and in probands with persistent and remitted ADHD. Response speed and accuracy for stimulus, response, and combined conflicts did not differ across groups. Orbitofrontal, inferior frontal and parietal activation was lower in probands than comparison subjects, but only for combined conflicts, when demand for cognitive control was highest. Reduced activation for combined conflicts in probands was almost wholly attributable to the persistence of ADHD; orbitofrontal, inferior frontal, anterior cingulate and parietal activation was lower in probands with persistent ADHD than both probands with remitted ADHD and comparison subjects, but did not differ between probands with remitted ADHD and comparison subjects. These data provide the first evidence that prefrontal and parietal activation during cognitive control parallels the adult outcome of ADHD diagnosed in childhood, with persistence of symptoms linked to reduced activation and symptom recovery associated with activation indistinguishable from adults with no history of ADHD.

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One only has to quickly look through the Table of Contents for this issue of JCPP to gain an appreciation of the ever-increasing influence of genetic research in the field of developmental psychopathology. Among the 13 articles in this issue that follow this editorial: two employ large family and/or twin studies to provide compelling behavioral genetic findings bolstering the importance of genes in the emergence of ADHD (Chen, Brikell, Lichtenstein, Serlachius, Kuja-Halkola, Sandin, and Larsson) and level of educational achievement in adolescents (Lewis, Asbury, and Plomin); one paper focuses on cortical development in patients with 22q11.2 deletion syndrome and its association with positive symptoms of psychosis (Radoeva, Bansal, Antshel, Fremont, Peterson, and Kates); a Commentary (Border and Keller) and Response to Commentary (Moore) debate the relative advantages and disadvantages of candidate gene versus genome-wide approaches to detecting certain genetic markers, particularly in relation to interactions with the environment; and two more focus on the identification of endophenotypes for autism spectrum disorders which will presumably facilitate the identification of genes for this complex disorder (Jones, Venema, Earl, Lowy, and Webb; Van Eylen, Boets, Cosemans, Peeters, Steyaert, Wagemans, and Noens).

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BACKGROUND: We recently developed the Child Behavior Checklist-Mania Scale (CBCL-MS), a novel and short instrument for the assessment of mania-like symptoms in children and adolescents derived from the CBCL item pool and have demonstrated its construct validity and temporal stability in a longitudinal general population sample. OBJECTIVE: The aim of this study was to evaluate the construct validity of the 19-item CBCL-MS in a clinical sample and to compare its discriminatory ability to that of the 40-item CBCL-dysregulation profile (CBCL-DP) and the 34-item CBCL-Externalizing Scale. METHODS: The study sample comprised 202 children, aged 7-12 years, diagnosed with DSM-defined attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), oppositional defiant disorder (ODD), and mood and anxiety disorders based on the Diagnostic Interview Schedule for Children. The construct validity of the CBCL-MS was tested by means of a confirmatory factor analysis. Receiver operating characteristics (ROC) curves and logistic regression analyses adjusted for sex and age were used to assess the discriminatory ability relative to that of the CBCL-DP and the CBCL-Externalizing Scale. RESULTS: The CBCL-MS had excellent construct validity (comparative fit index = 0.97; Tucker-Lewis index = 0.96; root mean square error of approximation = 0.04). Despite similar overall performance across scales, the clinical range scores of the CBCL-DP and the CBCL-Externalizing Scale were associated with higher odds for ODD and CD, while the clinical range scores of the CBCL-MS were associated with higher odds for mood disorders. The concordance rate among the children who scored within the clinical range of each scale was over 90%. CONCLUSION: CBCL-MS has good construct validity in general population and clinical samples and is therefore suitable for both clinical practice and research.