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Hostility often co-occurs in parents and associates with increased aggression and inattention problems in children. In this population-based cohort of 484 mother-father-child neuroimaging trios, we investigated the degree to which associations of prenatal and childhood parental hostility would be associated with maternal, paternal, and child brain structural differences. Also, we examined whether hippocampal volumes of the parents or child mediate the association of prenatal parental hostility with child externalizing behaviors. Maternal and paternal hostility was assessed with the hostility subscale of the Brief Symptom Inventory at three time points: prenatally at 30 weeks' gestation and when the child was 3 and 10 years old. During adolescence assessment wave (age 14), maternal, paternal, and offspring assessment included a magnetic resonance imaging. Child externalizing problems were assessed with Youth Self-Report Child Behavior Checklist. Our findings suggest that maternal and paternal hostility were each associated with smaller gray matter, white matter, and hippocampal volumes of their own and their partner's brain. Prenatal maternal but not paternal hostility was associated with smaller total gray matter, white matter, and hippocampal volumes in the offspring. The child's hippocampal volumes partially mediated the associations of prenatal parental hostility (latent construct) with adolescent externalizing behavior, even after adjusting for prior child externalizing problems. Moreover, parental psychopathology may have long-lasting neurodevelopmental correlates in children that underlie the intergenerational transmission of behavioral problems. The behavior of family members results from a system of interdependent dyadic relationships over time that associate with specific brain structural differences., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Data from the Czech part of the European Longitudinal Study of Pregnancy and Childhood offer a unique opportunity to examine a period of changing socioeconomic structure of the country. Our aim was to analyse the association between socioeconomic status, family structure and children's psychosocial problems at the age of 7, 11, 15 and 18 years in 3,261 subjects and compare our results with findings from western settings. The Strengths and Difficulties Questionnaire (SDQ) and its five subscales were used to assess individual problem areas (emotional symptoms, peer problems, hyperactivity, conduct problems) and prosocial behaviour. Socioeconomic status was represented by maternal education and three forms of family structure were identified: nuclear family, new partner family and single parent family. The SDQ subscale score over time was modelled as a quadratic growth curve using a linear mixed-effects model. Maternal university education was associated with a faster decline in problems over time for all five SDQ subscales. Problems in children from nuclear families were found to be significantly lower than in children from single parent families for all SDQ subscales with the exception of peer problems. Compared to nuclear families, children from new partner families scored significantly higher in hyperactivity and conduct problems subscales. The nuclear family structure and higher maternal education have been identified as protective factors for children's psychosocial problems, in agreement with findings from western settings. Adopting a longitudinal perspective was shown as essential for providing a more complex view of children's psychosocial problems over time., Competing Interests: The authors have declared that no competing interests exist.

Selective mutism (SM) is classified under the category of anxiety disorders in DSM-5 [1], although concrete fears that underlie the condition are not specified contrary to all other anxiety disorders. Given the lack of studies systematically investigating fears in SM, content and frequency of concrete fears as well as related cognitions have remained unclear so far. One hundred and twenty-four participants [M = 13.25 years (SD = 3.24), range 8-18 years] with SM (n = 65), social phobia (SP n = 18) or with typical development (TD n = 51) took part in an online survey. Participants with SM (n = 65) answered an open-ended question concerning fears that might cause the consistent failure to speak in select situations. Additionally, participants with SM, SP and TD completed a survey containing 34 fear-related cognitions that might occur in speech-demanding situations. Open text answers were systematically evaluated by extracting higher-order categories using a Qualitative Content Analysis. Single item scores of the survey were compared between the three groups. 59% of all spontaneously reported fears were assigned to the cluster of social fears. Other reported fears represented the categories fear of mistakes (28%), language-related fears (8%) and voice-related fears (5%). The SM- and SP group only differed regarding the cognition that one's own voice might sound funny (SM > SP). Social fears and the fear of mistakes account for the majority of fears in SM. Therefore, future interventions should consider specifically targeting these types of fears.

Aim: The aim of this study was to evaluate long-term behavioural and neurodevelopmental complications of neonatal necrotizing enterocolitis at school age., Method: This was a historic cohort study comparing all surviving children born in Denmark between 1st of January 2002 and 31st of December 2011 with a diagnosis of necrotizing enterocolitis to a group of children without necrotizing enterocolitis, but same gestational age, birth weight and year of birth. Outcomes were investigated through a parental questionnaire. The primary outcome was the Strength and Difficulties Questionnaire score and secondary outcomes were cerebral palsy and impaired head growth., Results: Response rates were 50% (163 of 328) and 36% (237 of 652) among children with and without necrotizing enterocolitis, respectively. There was a higher rate of abnormal Strength and Difficulties score (23.9 versus 17.8%), moderate/severe cerebral palsy (3.1 versus 0.9%) and small head circumference for age (11.7 versus 7.2%) among children with necrotizing enterocolitis. However, these differences were all statistically insignificant and did not change significantly by adjustment for potential confounders., Conclusion: To our knowledge, this study includes the largest cohort of necrotizing enterocolitis children evaluated for possible long-term complications at school age. The increased risks of behavioural- and neurodevelopmental impairments were statistically insignificant, moderate in magnitude and may be of little clinical importance for management in the neonatal period or when planning follow-up., Competing Interests: The authors have declared that no competing interests exist.

Objective: Previous studies evaluating the association between early childhood adversities and eating disorders have yielded conflicting results. The aim of this study is to examine the association between a range of adversities and risk of anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS) in 495,244 women., Method: In this nationwide, register-based cohort study, nine types of early childhood adversity (family disruption, residential instability, placement in out-of-home care, familial death, parental somatic illness, parental psychiatric illness, parental disability, severe parental criminality, and parental substance use disorder) were defined and exposure during the first 6 years of life was determined. Hazard ratios for eating disorders were calculated using Cox regression., Results: Few adversities were significantly associated with AN, and for each, the presence of the adversity was associated with lower risk for AN. BN, and EDNOS were positively associated with several types of adversities. AN rates were unchanged or reduced by up to 54% by adversities, whereas rates of BN and EDNOS were unchanged or increased by adversities by up to 49 and 89%, respectively., Discussion: Our findings indicate that childhood adversities appear to be associated with an increased risk of BN and in particular EDNOS, whereas they seem to be either unassociated or associated with a decreased risk of AN., (© 2017 Wiley Periodicals, Inc.)

Mood disorders and behavioral are broad psychiatric diagnostic categories that have different symptoms and neurobiological mechanisms, but share some neurocognitive similarities, one of which is an elevated risk for reading deficit. Our aim was to determine the influence of mood versus behavioral dysregulation on reading ability and neural correlates supporting these skills in youth, using diffusion tensor imaging in 11- to 17-year-old children and youths with mood disorders or behavioral disorders and age-matched healthy controls. The three groups differed only in phonological processing and passage comprehension. Youth with mood disorders scored higher on the phonological test but had lower comprehension scores than children with behavioral disorders and controls; control participants scored the highest. Correlations between fractional anisotropy and phonological processing in the left Arcuate Fasciculus showed a significant difference between groups and were strongest in behavioral disorders, intermediate in mood disorders, and lowest in controls. Correlations between these measures in the left Inferior Longitudinal Fasciculus were significantly greater than in controls for mood but not for behavioral disorders. Youth with mood disorders share a deficit in the executive-limbic pathway (Arcuate Fasciculus) with behavioral-disordered youth, suggesting reduced capacity for engaging frontal regions for phonological processing or passage comprehension tasks and increased reliance on the ventral tract (e.g., the Inferior Longitudinal Fasciculus). The low passage comprehension scores in mood disorder may result from engaging the left hemisphere. Neural pathways for reading differ mainly in executive-limbic circuitry. This new insight may aid clinicians in providing appropriate intervention for each disorder.

Background: Preterm infants are at risk for white matter (WM) injury and adverse neurodevelopmental outcomes., Methods: Serial diffusion tensor magnetic resonance imaging data were obtained from very preterm infants (N = 78) born <30 wk gestation imaged up to four times from 26-42 wk postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ≥2 scans (N = 50). Sixty-five children underwent neurodevelopmental testing at 2 y of age., Results: FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum, and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with patent ductus arteriosus had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At 2 y of age, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent age. Better social-emotional competence was related to lower FA in the left cingulum bundle., Conclusion: This study demonstrates regional variability in the susceptibility/sensitivity of WM maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates.

Research into Pathological Demand Avoidance (PDA), which has been suggested to be a subgroup within the Autism Spectrum Disorder (ASD), is almost nonexistent in spite of the frequent reference to the condition in clinical practice. The total population of 15 to 24-year-olds in the Faroe Islands was screened for ASD, and 67 individuals were identified who met diagnostic criteria for ASD (corresponding to a general population prevalence of ASD of almost 1 %). Of these 67, 50 had parents who were interviewed using the Diagnostic Interview for Social and Communication Disorders (DISCO-11) which contains 15 "PDA-specific" items. Nine individuals met criteria for "possible clinical diagnosis of PDA", meaning that almost one in five of all with ASD also had indications of having had PDA in childhood, and that 0.18 % of the total population had had the combination of ASD and PDA. However, at the time of assessment, only one of the 9 individuals with possible PDA still met "full criteria". PDA possibly constitutes a considerable minority of all cases with ASD diagnosed in childhood, but criteria for the condition are unlikely to be still met in later adolescence and early adult life.

Objective: Our objective was to report and describe a case of psychosocial short stature in an adolescent girl with psychotic features. Psychosocial short stature is a rare condition in which emotional stress or deprivation in childhood profoundly reduces growth, leading to persistent short stature. This disorder is variably known as psychosocial dwarfism, hyperphagic short stature or maternal deprivation dwarfism. In the literature, psychosocial short stature has not been associated previously with psychosis., Conclusions: We formulate that our patient's short stature, developmental regression and psychotic features were culminations of insecure mother-child attachment, personal traumatic experiences, immigrant status, high family expressed emotions and social isolation. Neuropsychiatric influences were critically regarded due to our patient's fluctuations in behaviour and affect, in the setting of cortical volume loss on brain MRI. Diagnostic hypotheses included childhood disintegrative disorder or childhood-onset schizophrenia. The management plan involved inpatient family psychoeducation, a pharmacological trial with an atypical antipsychotic and community mental health service follow-up for family therapy and psychotherapy., (© The Royal Australian and New Zealand College of Psychiatrists 2014.)

Background: On March 11, 2011, a massive undersea earthquake and tsunami struck East Japan. Few studies have investigated the impact of exposure to a natural disaster on preschool children. We investigated the association of trauma experiences during the Great East Japan Earthquake on clinically significant behavior problems among preschool children 2 years after the earthquake., Method: Participants were children who were exposed to the 2011 disaster at preschool age (affected area, n = 178; unaffected area, n = 82). Data were collected from September 2012 to June 2013 (around 2 years after the earthquake), thus participants were aged 5 to 8 years when assessed. Severe trauma exposures related to the earthquake (e.g., loss of family members) were assessed by interview, and trauma events in the physical environment related to the earthquake (e.g. housing damage), and other trauma exposure before the earthquake, were assessed by questionnaire. Behavior problems were assessed by caregivers using the Child Behavior Checklist (CBCL), which encompasses internalizing, externalizing, and total problems. Children who exceeded clinical cut-off of the CBCL were defined as having clinically significant behavior problems., Results: Rates of internalizing, externalizing, and total problems in the affected area were 27.7%, 21.2%, and 25.9%, respectively. The rate ratio suggests that children who lost distant relatives or friends were 2.36 times more likely to have internalizing behavior problems (47.6% vs. 20.2%, 95% CI: 1.10-5.07). Other trauma experiences before the earthquake also showed significant positive association with internalizing, externalizing, and total behavior problems, which were not observed in the unaffected area., Conclusions: One in four children still had behavior problems even 2 years after the Great East Japan Earthquake. Children who had other trauma experiences before the earthquake were more likely to have behavior problems. These data will be useful for developing future interventions in child mental health after a natural disaster.

Parental harsh disciplining, like corporal punishment, has consistently been associated with adverse mental health outcomes in children. It remains a challenge to accurately assess the consequences of harsh discipline, as researchers and clinicians generally rely on parent report of young children's problem behaviors. If parents rate their parenting styles and their child's behavior this may bias results. The use of child self-report on problem behaviors is not common but may provide extra information about the relation of harsh parental discipline and problem behavior. We examined the independent contribution of young children's self-report above parental report of emotional and behavioral problems in a study of maternal and paternal harsh discipline in a birth cohort. Maternal and paternal harsh discipline predicted both parent reported behavioral and parent reported emotional problems, but only child reported behavioral problems. Associations were not explained by pre-existing behavioral problems at age 3. Importantly, the association with child reported outcomes was independent from parent reported problem behavior. These results suggest that young children's self-reports of behavioral problems provide unique information on the effects of harsh parental discipline. Inclusion of child self-reports can therefore help estimate the effects of harsh parental discipline more accurately.

Purpose: Neurobehavioral comorbidities are common in pediatric epilepsy with enduring adverse effects on functioning, but their neuroanatomic underpinning is unclear. Striatal and thalamic abnormalities have been associated with childhood-onset epilepsies, suggesting that epilepsy-related changes in the subcortical circuit might be associated with the comorbidities of children with epilepsy. We aimed to compare subcortical volumes and their relationship with age in children with complex partial seizures (CPS), childhood absence epilepsy (CAE), and healthy controls (HC). We examined the shared versus unique structural-functional relationships of these volumes with behavior problems, intelligence, language, peer interaction, and epilepsy variables in these two epilepsy syndromes., Methods: We investigated volumetric differences of caudate, putamen, pallidum, and thalamus in children with CPS (N = 21), CAE (N = 20), and HC (N = 27). Study subjects underwent structural magnetic resonance imaging (MRI), intelligence, and language testing. Parent-completed Child Behavior Checklists provided behavior problem and peer interaction scores. We examined the association of age, intelligence quotient (IQ), language, behavioral problems, and epilepsy variables with subcortical volumes that were significantly different between the children with epilepsy and HC., Key Findings: Both children with CPS and CAE exhibited significantly smaller left thalamic volume compared to HC. In terms of developmental trajectory, greater thalamic volume was significantly correlated with increasing age in children with CPS and CAE but not in HC. With regard to the comorbidities, reduced left thalamic volumes were related to more social problems in children with CPS and CAE. Smaller left thalamic volumes in children with CPS were also associated with poor attention, lower IQ and language scores, and impaired peer interaction., Significance: Our study is the first to directly compare and detect shared thalamic structural abnormalities in children with CPS and CAE. These findings highlight the vulnerability of the thalamus and provide important new insights on its possible role in the neurobehavioral comorbidities of childhood-onset epilepsy., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34 additional patients from 21 families to further delineate the clinical, neurological, behavioral, and brain imaging findings. We found a highly diverse phenotype with inter- and intrafamilial variability, especially in cognitive development. The most specific phenotype occurred in individuals with large duplications that include both the YWHAE and LIS1 genes. These patients had a relatively distinct facial phenotype and frequent structural brain abnormalities involving the corpus callosum, cerebellar vermis, and cranial base. Autism spectrum disorders were seen in a third of duplication probands, most commonly in those with duplications of YWHAE and flanking genes such as CRK. The typical neurobehavioral phenotype was usually seen in those with the larger duplications. We did not confirm the association of early overgrowth with involvement of YWHAE and CRK, or growth failure with duplications of LIS1. Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome., (Copyright © 2013 Wiley Periodicals, Inc.)

Adolescence is characterized by dynamic changes in structural brain maturation. At the same time, adolescence is a critical time for the development of affective and anxiety-related disorders. Individual differences in typically developing children and adolescents may prove more valuable for identifying which brain regions correspond with internalizing behavior problems (i.e., anxious/depressive, withdrawal and somatic symptoms) on a continuous scale compared to clinical studies. Participants were 179 (92 males, 87 females) typically developing children and adolescents between ages 8 and 17. Hippocampal and amygdala volumes were measured automatically with FreeSurfer. Internalizing behavior was assessed with the Child Behavior Checklist (CBCL) completed by the parent, and associated with hippocampal and amygdala volumes. Hippocampal volume was inversely related with the total internalizing problems scale of the CBCL, irrespective of gender, age, or informant (mother or father). The effects were most prominent for the withdrawal and anxiety/depression subscales and the left hippocampus: more withdrawal and anxiety/depression was related to smaller left hippocampal volume. No associations were found between internalizing behavior and amygdala volume. This study shows that typically developing children and adolescents with high internalizing behavior share some of the neuroanatomical features of adult depression and anxiety-related disorders., (Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.)

We assessed trajectories of children's internalizing symptoms, indexed through anxiety and depression, with a focus on the role of interactions between interparental marital conflict, children's sympathetic nervous system activity indexed by skin conductance level (SCL), and parasympathetic nervous system activity indexed by respiratory sinus arrhythmia (RSA) as predictors of growth. Children participated in 3 waves of data collection with a 1-year lag between each wave. At T1, 128 girls and 123 boys participated (M age = 8.23 years; SD = 0.73). The most important findings reveal that girls with either low RSA in conjunction with low SCL (i.e., coinhibition) at baseline or with increasing RSA and decreasing SCL in response to a challenging task (i.e., reciprocal parasympathetic activation) are susceptible to high or escalating anxiety and depression symptoms, particularly in the context of marital conflict. Findings support the importance of concurrent examinations of environmental risk factors and physiological activity for better prediction of the development of anxiety and depression symptoms.

There exists an extensive terminology for defining the situation of children who, in varying circumstances, suffer from affective deprivation (AD), within an unsatisfactory family situation or in institutions. Nevertheless, the neuroendocrine mechanisms (if they exist) determining it have yet to be identified. Our objective was to determine if specific neuroendocrine markers, all of them previously implicated in affective disorders, could be modified, and in which sense, in affective deprivation syndrome of the child. For this purpose, we studied three separate groups of children: (1) control group (CG); (2) children suffering from AD; and (3) children with non-organic failure to thrive (NOFT). In every case, we studied the serum levels of melatonin, serotonin, β-endorphins and adrenocorticotropic hormone (ACTH); and kynurenine pathway tryptophan metabolites (both during the day and at night). Significantly, there was a conspicuous reduction in the levels of each of the neuroendocrine markers (melatonin, serotonin, β-endorphins and ACTH) in the group suffering from affective deficiency, a diminution which was even more noticeable in the group of patients presenting delayed growth. Furthermore, as also occurs in other affective disorders, there were corresponding modifications in the metabolisation of tryptophan. We report the existence of neuroendocrine mechanisms that are associated with the above-mentioned clinical manifestations in these patients, mechanisms that may underlie the close connection existing between AD syndrome and the cause of NOFT. These data suggest that the AD syndrome and NOFT comprise a single process, but one with a different evolutionary continuum of psychosocial dwarfism., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

We investigated regional grey matter (GM) density in adolescents with Down syndrome (DS) compared to age-matched controls and correlated MRI data with neuropsychological measures in the DS group. Inter-group comparisons documented several GM concentration abnormalities in the participants with DS compared to controls. In the adolescents with DS, intra-group results also showed associations between regional GM density and the neuropsychological measures considered. In particular, GM density of the cerebellum and middle and inferior temporal gyrus was associated with linguistic measures. Short-term memory performances were correlated with the inferior parietal lobule, insula, superior temporal gyrus, medial occipital lobe, and cerebellum. Long-term memory abilities were correlated with GM density in the orbitofrontal cortex, lateral and medial temporal lobe regions, and anterior cingulum and visuo-perceptual abilities with GM density the left middle frontal gyrus. Results of this preliminary study are consistent with a not always efficient brain organization in DS.

Individuals who experience early adversity, such as child maltreatment, are at heightened risk for a broad array of social and health difficulties. However, little is known about how this behavioral risk is instantiated in the brain. Here we examine a neurobiological contribution to individual differences in human behavior using methodology appropriate for use with pediatric populations paired with an in-depth measure of social behavior. We show that alterations in the orbitofrontal cortex among individuals who experienced physical abuse are related to social difficulties. These data suggest a biological mechanism linking early social learning to later behavioral outcomes.

The aim of the present study was to review and update historical controversies in relation to the limbic system in light of advances in the neuroanatmy and neurobiology of cortico-striatal-thalamic-cortical (CSTC) neural circuits. It is hypothesized that observed comorbidities between internalizing and externalizing childhood syndromes may be better understood in terms of excess communication between subcortical brain circuits. A neuroanatomical understanding of reciprocal and non-reciprocal connections between modular circuits provides a basis for understanding previously puzzling aspects of internalizing, externalizing comorbidity. Function depends on the degree of cooperative integration of goal orientation, Pavlovian stimulus response, and operant processing in cortical-subcortical circuits, and interventions may be targeted at any of these functions.

Objective: To find out the rate of comorbidities of depression, anxiety disorder and attention deficit hyperactivity disorder (ADHD) symptoms in children with epilepsy and to analyze the relevant affecting factors and impacts on quality of life., Method: Totally 142 children with various types of epilepsy underwent neuropsychological assessment with the Depression Self-rating Scale for Children, the Screen for Child Anxiety Related Emotional Disorders and the ADHD Rating Scale-IV, an 18-item parent-rated questionnaire based on the diagnostic criteria for ADHD, the quality of life was measured in 100 cases on antiepileptic medications by the Quality of Life in Epilepsy Inventory (QOLIE-31). The comorbidity rates were calculated using t-test, chi(2) test and multiple logistic analysis, the variables associated with psychiatric comorbidities were determined, and the impact on quality of life was analyzed., Result: (1) The total rate of emotional and behavioral comorbidities was 57.7% (82/142), the frequency of depressive disorder, anxiety disorder and ADHD was 14.8%, 44.4% and 17.6%, respectively. The suicidal ideation occasionally occurred in 5.6% of the cases and 0.7% of cases often had the ideation, but no suicidal action was found in any case. (2) Risk factors for the emotional and behavioral disorders: multiple logistic analysis indicated that age, gender and epilepsy illness-related variables were not relative to the comorbidities, P > 0.05, there were interactions among the disorders. (3) The impact on the quality of life: The emotional and behavioral conditions were associated with the low quality of life, which was significantly lower in epileptic children with co-morbid disorder compared to non-comorbidities epilepsy group. Especially negative impact on the total score of quality of life and four sub-items such as overall quality, emotional well-being, cognitive and social function, P < 0.001. There were also significant differences between the two groups in the other three sub-items including fear for seizure attack, energy/fatigue and medication effects (P < 0.05)., Conclusions: The frequency of emotional and behavioral disorders including depress disorder, anxiety disorder and ADHD was considerably high in children with epilepsy. Age, gender and epilepsy illness-related variables are not associated with the emotional and behavioral comorbidities, which interfere with each other. Emotional and behavioral disorder is one of the negative factors to the quality of life in epileptic patients. Neuropsychological assessment and treatment are important for improvement of the quality of life in children with epilepsy.

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted.

Brain imaging studies of adults with psychopathy have identified structural and functional abnormalities in limbic and prefrontal regions that are involved in emotion recognition, decision-making, morality and empathy. Among children with conduct problems, a small subgroup presents callous-unemotional traits thought to be antecedents of psychopathy. No structural brain imaging study has examined this subgroup of children. The present study used voxel-based morphometry to compare whole brain grey matter volumes and concentrations of boys with elevated levels of callous-unemotional conduct problems and typically developing boys and explored four a priori regions of interest. sMRI scans were collected from 23 boys with elevated levels of callous-unemotional conduct problems (mean age = 11 years 8 months) and 25 typically developing boys (mean age = 11 years 6 months) selected from a community sample of children. Data were analysed using optimized voxel-based morphometry. Study-specific probability maps were created and four a priori regions of interest identified (orbitofrontal, anterior cingulate and anterior insular cortices and amygdala). Both grey matter volume and concentration were examined controlling for cognitive ability and hyperactivity-inattention symptoms. Boys with callous-unemotional conduct problems, as compared with typically developing boys, presented increased grey matter concentration in the medial orbitofrontal and anterior cingulate cortices, as well as increased grey matter volume and concentration in the temporal lobes bilaterally. These findings may indicate a delay in cortical maturation in several brain areas implicated in decision making, morality and empathy in boys with callous-unemotional conduct problems.

Objective: To investigate the influence of tonsillar and adenoidal hypertrophy on mental behavior of children., Method: Mentality and behavior of total sixty-one children suffering from tonsillar and adenoidal hypertrophy were tested with Achenbach Child Behavior Checklist (CBCL) edited by Gong Yaoxian in 1986., Result: The mentality and behavior of the children suffering from tonsillar and adenoidal hypertrophy were distinctly abnormal compared to control children (P<0.01). The behavioral abnormalities of boys appeared as divisiveness, social difficulties, compel, hyperkinetic syndrome and attack, and the girls appeared as hyperkinetic syndrome and attack, which was significantly different from the control children (P<0.01). The second test was performed three months after tonsillectomy and adenoidectomy, and compared with the first one. Boys were found that the divisiveness, hypochondria, compel and unwell of body cursory mark were evidently lower than the first test (P<0.05). Girls were found that divisiveness, hypochondria, disobeyed discipline and attack mark were evidently lower than the first test (P<0.05). The abnormal rates of mentality and behavior positively correlated with the age of children., Conclusion: Tonsillar and adenoidal hypertrophy evidently affected the mentality and behavior of children. The psychological and behavioral intervention were necessary for children suffering from tonsillar and adenoidal hypertrophy.

This review critically examines the research findings which characterize the cognitive, behavioral, and neuroanatomical features of Williams syndrome (WS). This article analyzes 178 published studies in the WS literature covering the following areas: 1) General intelligence, 2) Language skills, 3) Visuospatial and face processing skills, 4) Behavior patterns and hypersociability, 5) Musical abilities, and 6) Brain structure and function. We identify methodological issues relating to small sample size, use and type of control groups, and multiple measures of task performance. Previously described 'peaks' within the cognitive profile are closely examined to assess their veracity. This review highlights the need for methodologically sound studies that utilize multiple comparison groups, developmental trajectories, and longitudinal analyses to examine the WS phenotype, as well as those that link brain structure and function to the cognitive and behavioral phenotype of WS individuals.

Objective: To determine how neuroanatomic variation in children and adolescents with fragile X syndrome is linked to reduced levels of the fragile X mental retardation-1 protein and to aberrant cognition and behavior., Methods: This study included 84 children and adolescents with the fragile X full mutation and 72 typically developing control subjects matched for age and sex. Brain morphology was assessed with volumetric, voxel-based, and surface-based modeling approaches. Intelligence quotient was evaluated with standard cognitive testing, whereas abnormal behaviors were measured with the Autism Behavior Checklist and the Aberrant Behavior Checklist., Results: Significantly increased size of the caudate nucleus and decreased size of the posterior cerebellar vermis, amygdala, and superior temporal gyrus were present in the fragile X group. Subjects with fragile X also demonstrated an abnormal profile of cortical lobe volumes. A receiver operating characteristic analysis identified the combination of a large caudate with small posterior cerebellar vermis, amygdala, and superior temporal gyrus as distinguishing children with fragile X from control subjects with a high level of sensitivity and specificity. Large caudate and small posterior cerebellar vermis were associated with lower fragile X mental retardation protein levels and more pronounced cognitive deficits and aberrant behaviors., Interpretation: Abnormal development of specific brain regions characterizes a neuroanatomic phenotype associated with fragile X syndrome and may mediate the effects of FMR1 gene mutations on the cognitive and behavioral features of the disorder. Fragile X syndrome provides a model for elucidating critical linkages among gene, brain, and cognition in children with serious neurodevelopmental disorders.

Epilepsia partialis continua (EPC) is characterized by focal seizures that cannot be stopped. The most common cause of EPC in children is Rasmussen's encephalitis. In this video case report, we describe an 11-year old female with continuous lingual EPC for two years. She has shown no signs of Rasmussen's Encephalitis or other neurodegenerative process and structural MRI is normal. [Published with video sequences].

Damage to the prefrontal cortex in childhood can produce long-term impairments of emotion, behavior regulation, and executive functions, but little is known regarding the earliest expression of these impairments. We describe here detailed behavioral studies of a boy at 14 months of age ('PF1') who sustained focal damage in the right inferior dorsolateral prefrontal cortex due to resection of a vascular malformation on day 3 of life. The surgery was followed by a good medical recovery, and he reached developmental milestones at a normal rate. His neurological examination was normal, as were his mother's ratings of communication abilities, daily living skills, socialization, and motor skills. Multiple standardized laboratory paradigms were used to evaluate his behavior in structured and relatively unstructured situations designed to elicit positive and negative emotions and to place demands on attention. Relative to a comparison group of 50 age-matched boys with no neurological history, PF1 demonstrated significant impairments in the regulation of emotion and engagement of attention, particularly in unstructured conditions. These findings indicate that damage to prefrontal cortex in infancy begins to impact on emotional and cognitive development already during the first months of life.

Morphometric cerebral characteristics were studied in children with prenatal poly-substance exposure (n=14) compared to controls (n=14) without such exposure. Ten of the substance-exposed children were born to mothers who used opiates (heroin) throughout the pregnancy. Groups were compared across 16 brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, lateral ventricles, inferior lateral ventricles, and the 3rd and 4th ventricles. In addition, continuous measurement of thickness across the entire cortical mantle was performed. Volumetric characteristics were correlated with ability and questionnaire assessments 2 years prior to scan. Compared to controls, the substance-exposed children had smaller intracranial and brain volumes, including smaller cerebral cortex, amygdala, accumbens area, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, and inferior lateral ventricles, and thinner cortex of the right anterior cingulate and lateral orbitofrontal cortex. Pallidum and putamen appeared especially reduced in the subgroup exposed to opiates. Only volumes of the right anterior cingulate, the right lateral orbitofrontal cortex and the accumbens area, showed some association with ability and questionnaire measures. The sample studied is rare and hence small, so conclusions cannot be drawn with certainty. Morphometric group differences were observed, but associations with previous behavioral assessment were generally weak. Some of the volumetric differences, particularly thinner cortex in part of the right lateral orbitofrontal cortex, may be moderately involved in cognitive and behavioral difficulties more frequently experienced by opiate and poly-substance-exposed children.

This study examined the sensitivity of diffusion tensor imaging (DTI) to microstructural white matter (WM) damage in mild and moderate pediatric traumatic brain injury (TBI). Fourteen children with TBI and 14 controls ages 10-18 had DTI scans and neurocognitive evaluations at 6-12 months post-injury. Groups did not differ in intelligence, but children with TBI showed slower processing speed, working memory and executive deficits, and greater behavioral dysregulation. The TBI group had lower fractional anisotropy (FA) in three WM regions: inferior frontal, superior frontal, and supracallosal. There were no group differences in corpus callosum. FA in the frontal and supracallosal regions was correlated with executive functioning. Supracallosal FA was also correlated with motor speed. Behavior ratings showed correlations with supracallosal FA. Parent-reported executive deficits were inversely correlated with FA. Results suggest that DTI measures are sensitive to long-term WM changes and associated with cognitive functioning following pediatric TBI.

Although manganese (Mn) is an essential mineral, high concentrations of the metal can result in a neurotoxic syndrome affecting dopamine balance and behavior control. We report an exploratory study showing an association between Mn deposits in tooth enamel, dating to the 20th and 62-64th gestational weeks, and childhood behavioral outcomes. In a sample of 27 children, 20th week Mn level was significantly and positively correlated with measures of behavioral disinhibition, specifically, play with a forbidden toy (36 months), impulsive errors on a continuous performance and a children's Stroop test (54 months), parents' and teachers' ratings of externalizing and attention problems on the Child Behavior Checklist (1st and 3rd grades), and teacher ratings on the Disruptive Behavior Disorders Scale (3rd grade). By way of contrast, Mn level in tooth enamel formed at the 62-64th gestational week was correlated only with teachers' reports of externalizing behavior in 1st and 3rd grades. Although the source(s) of Mn exposure in this sample are unknown, one hypothesis, overabsorption of Mn secondary to gestational iron-deficiency anemia, is discussed.

Neuronal ceroid lipofuscinoses (NCLs) are relatively common storage diseases of childhood and early adolescence. Ultrastructural shape of storage cytosomes, type of disease gene, and age of onset serve to classify the different NCLs, some of which appear to cluster in Scandinavian countries. The CLN5 form usually presents as a classical epileptiform encephalopathy of late infancy but a more aggressive cognitive impairment has been described in a single family. We report two sibs harbouring a novel mutation (p.Tyr258Asp) in the CLN5 gene and displaying behaviour disturbances and mental deterioration, rather than epilepsy, as the dominant disease manifestation at onset.

In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of developing attention-deficit/hyperactivity disorder and autism spectrum disorders in childhood, and schizophrenia in adolescence or adult life. However, the neurobiology of 22qDS, and the relationship between abnormalities in brain anatomy and behaviour, is poorly understood. Thus, we studied the neuroanatomy of 22qDS children using fully automated voxel-based morphometry (VBM) and manually traced single region-of-interest (ROI) analysis. Also, we investigated whether those brain regions that differed significantly between groups were related to behavioural differences within children with 22qDS. We compared the brain morphometry of 39 children and adolescents with 22qDS (mean age: 11 years, SD +/-3, IQ = 67, SD +/-10) and 26 sibling controls (mean age: 11 years, SD +/-3, IQ = 102, SD +/-12). Using VBM, we found, after correction for IQ, that individuals with 22qDS compared with controls had a significant reduction in cerebellar grey matter, and white matter reductions in the frontal lobe, cerebellum and internal capsule. Using single ROI analysis, we found that people with 22qDS had a significant (P < 0.05) reduction in bulk volume bilaterally in the occipital-parietal lobes, but a larger right caudate nucleus and lateral ventricles. Further, within people with 22qDS, there was a significant positive correlation between severity of (i) schizotypy score and grey matter volume of the temporo-occipital regions and the corpus striatum; (ii) emotional problems and grey matter volume of frontostriatal regions; and (iii) social behavioural difficulties and grey matter in frontostriatal regions. Thus, subjects with 22qDS have widespread changes in brain anatomy, particularly affecting white matter, basal ganglia and cerebellum. Also, within 22qDS, regionally specific differences in brain development may partially underpin behavioural differences. We suggest that there is preliminary evidence for specific vulnerability of the frontostriatal and cerebellar-cortical networks in 22qDS.

We report on a girl with mental retardation, dysmorphic features, and behavioral problems. A small terminal deletion of the long arm of chromosome 10 was detected by subtelomeric fluorescence in situ hybridization (FISH) studies in all analyzed metaphases. The deletion was shown to be a de novo terminal deletion of approximately 6.1 Mb, with the deletion breakpoint localized at band 10q26.2, between BAC probes RP11-498K22 and RP11-42K2. A subterminal 10q deletion as found in the present patient has, to our knowledge, only been reported in 15 patients (including 8 familial cases). We review the clinical and behavioral phenotype of these patients with "pure" subterminal 10q deletion., (Copyright (c) 2006 Wiley-Liss, Inc.)

The rate of autism spectrum disorders (ASDs) and brain abnormalities was analyzed in 31 individuals (15 males, 16 females; age range 1mo to 31y, mean age 8y 11mo) with CHARGE association, as part of a multidisciplinary study. A meticulous neuropsychiatric examination was performed, including standardized autism diagnostic interviews. Judgement regarding ASDs was impossible in three infants and three patients who were deaf and blind. Five individuals met diagnostic criteria for autism, five for an autistic-like condition, and seven for autistic traits. Brain abnormalities were indicated in almost three-quarters of examined individuals, and midline abnormalities of the forebrain in one-third. Awareness of the coexistence of CHARGE and ASDs is important in habilitation care in CHARGE. Moreover, the results indicate that a subgroup of ASDs may be associated with errors in early embryonic brain development.

Smith-Magenis Syndrome (SMS) is a complex, pediatric, neurobehavioral, contiguous gene syndrome ascribed to interstitial microdeletion of chromosome 17, band 11.2. The syndrome is characterized by distinctive behavioral, neurocognitive, and neuropsychiatric abnormalities. This genetically mediated disorder of mental retardation prompts behavioral researchers to examine the links between genes, brain, and behavior in order to solve the gene-behavior puzzle and the genotype/phenotype correlation. In this article, the authors review literature on behavioral profile and its associated psychopathologies, cognitive profiles, multisystem abnormalities, and genetic correlates that highlight the complexities of the disorder.

Smith-Magenis syndrome (SMS) is a mental retardation syndrome with distinctive behavioral characteristics, dysmorphic features, and congenital anomalies usually associated with an interstitial deletion of chromosome 17p11.2. While high quality G-banding will identify most SMS patients, fluorescent in situ hybridization (FISH) is the recommended test for confirmation of an SMS diagnosis. Recently, haploinsufficiency of the RAI1 gene due to deletion or mutation was determined to be the likely cause of SMS. All diagnostic FISH probes available commercially contain the FLII gene and are approximately 580 kb centromeric to RAI1. We present two patients with SMS who have interstitial deletions at 17p11.2 but are not deleted for currently available commercial FISH probes that include FLII; both patients have deletions that are demonstrated with probes containing the RAI1 gene. We recommend that for diagnostic accuracy, all future FISH tests for SMS be performed with probes containing the RAI1 gene, as some atypical deletions in the region critical to the SMS phenotype will otherwise be missed., ((c) 2004 Wiley-Liss, Inc.)

Smith Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion of chromosome 17p11.2. The neurobehavioral phenotype of SMS includes mental retardation, speech delay, hyperactivity, attention deficit, decreased sensitivity to pain, self-injury, aggressive behavior and sleep disturbance. Therefore, we performed anatomical and functional brain imaging studies in five SMS boys. Anatomical magnetic resonance imaging (MRI) was analyzed using optimized voxel-based morphometry (VBM). This method can detect structural anomalies not apparent on visual inspection of the scans. Two comparison groups with similar mean age were studied: Group A with 12 healthy control children and Group B with 5 children with idiopathic mental retardation. In addition, positron emission tomography (PET) and water-labeled method were used to investigate a putative localized brain dysfunction in SMS. The control group was composed of mentally retarded children (Group B). A significant bilateral decrease of grey matter concentration was detected in the insula and lenticular nucleus in SMS children. In addition, a significant hypoperfusion was found in the same regions in SMS. These anatomo-functional evidences of bilateral insulo-lenticular anomalies in SMS are consistent with neurobehavioral symptoms of the disease. The identification of localized brain anomalies in SMS may help in understanding how this well-defined genetic entity can lead to a relatively specific severe neurobehavioral syndrome.

Clinical diagnosis of attention-deficit hyperactivity disorder (ADHD) is based on evaluation of behavioral functioning in three domains: inattentiveness, hyperactivity, and impulsivity. Caudate and frontal lobe function figures prominently in several neuroanatomic models of attentional functioning. Studies comparing children with and without ADHD have found differences in the size and symmetry of the caudate nuclei. Using multiple regression, we tested the hypothesis that caudate volume symmetry (log left minus log right caudate volume) measured from serial sagittal magnetic resonance images in a sample of nonreferred children (12 girls/15 boys, 7.0 to 16.6 years, 81 to 129 IQ) would predict the cumulative severity of parent-reported ADHD diagnostic behaviors beyond variance predicted by age, sex, and level of internalizing problems as measured by the Child Behavior Checklist. No child had been previously diagnosed with ADHD, although one child was found to meet diagnostic criteria based on the rating scale used for the study. The degree of caudate asymmetry significantly predicted cumulative severity ratings of inattentive behaviors (P = .015), uniquely accounting for 17.1% of the variance in inattention symptomatology over demographic variables and internalizing problems, which collectively predicted 28.9% of the variance. Caudate asymmetry uniquely accounted for only 4.3% of the variance in cumulative severity ratings of hyperactive/impulsive symptomatology over demographic variables and internalizing problems that collectively predicted 21.2% of the variance. A greater degree of right to left caudate volume asymmetry predicted subclinical inattentive behaviors in a sample of nonreferred children. This finding is congruent with neuroanatomic models of attention emphasizing lateralized alteration in prefrontal/striatal systems. The results support the view that clinical ADHD is the extreme of a behavioral continuum that extends into the normal population.

There is evidence from animal experiments that the mu- and delta-opioid receptors may play a role in anxiety and depression. It might therefore be expected that functional polymorphisms of these genes in humans are associated with anxiety and depression. We investigated a single-nucleotide polymorphism (Asn40Asp) of the mu-opioid receptor gene (OPRM1). This association was investigated in two samples: 1) a cross-sectional survey of 867 community-living adults aged 18-79 years who were assessed for anxiety and depression symptoms and related personality traits; and 2) a longitudinal study of childhood temperament in which 660 children were followed from infancy to the mid-teens and assessed for anxiety-related temperament and behavior problems. The data did not support a role for the Asn40Asp polymorphism in anxiety and depression, despite adequate statistical power to detect small effects., (Copyright 2002 Wiley-Liss, Inc.)

A rec(4) dup 4p inherited from a maternal inv(4)(p15q35) was detected in a four-year-old girl with malformations, developmental delay, and behavioral problems that resemble those for trisomy 4p. A review of eight other liveborns with rec(4) dup 4p shows that about 40% of them also have manifestations in common with trisomy 4p, but the rest have a variable spectrum of malformations. Overall, the rec(4) dup 4p phenotype is not specific, and a diagnosis would not have been feasible without cytogenetic studies. This lack of a clinically recognizable phenotype could reflect the effects of the variable sizes of deletions of 4q, molecular differences in the break points, or the known variable expression of trisomy 4p. The fact that 79% of the recombinants in the offspring of inv(4)(p13-p15q35) carriers are rec(4) dup 4p suggests that meiotic recombination favors its generation or that rec(4) dup 4q are more lethal in utero., (Copyright 2002 Wiley-Liss, Inc.)

Psychopathological profiles were investigated in children with focal unilateral radiologically documented cortical lesions (15 right lesions and 22 left lesions). The 8 clinical subscales of the Child Behavior Checklist Parent Form (CBCL-P) and the Internalizing and Externalizing subscales were the dependent measures. The Internalizing and Externalizing scores did not dissociate as a function of lesion side. There were more Internalizing than Externalizing symptoms. Only the Attention Problems subscale yielded a significant difference as a function of lesion side; children with left lesions unexpectedly presented more problems. No significant differences were observed as a function offrontal versus nonfrontal lesion site, gender, or neurological variables on the Child Behavior Checklist (CBCL) subscales. Although sensitive to the presence of a focal lesion, the CBCL-P scarcely or misleadingly reflects any of the characteristics offocal unilateral cortical lesions in children. As suggested by the literature, most of the CBCL elevations in children with brain lesions could derive from the parent's and child's emotional response to any threatening medical condition.

Objectives: Opsoclonus-myoclonus-ataxia (OMA) syndrome affects 2% to 3% of patients with neuroblastoma. This study examined relationships between long-term neurobehavioral outcomes and potential biologic markers of OMA, including chronic changes on magnetic resonance imaging (MRI) brain scanning and prevalence of late antineuronal antibodies., Study Design: Children with neuroblastoma and OMA were identified through medical record review of patients treated at the University of California at San Francisco Medical Center from 1979 to 1999. Eleven patients with a mean follow-up time of 7.6 years underwent standard neurologic, neurocognitive, developmental/behavioral, and academic assessments. Consenting patients underwent MRI brain scanning and a blood draw. Sera were analyzed for the presence of antineuronal immunoreactivity., Results: Two (18%) patients had no observed neurologic abnormalities, 7 (64%) demonstrated mild deficits, and 2 (18%) had severe neurologic deficits. However, on neurocognitive, behavioral, and academic assessments, 6 (55%) children performed within the average range, 1 (9%) was moderately below average and 4 (36%) had severe cognitive and behavioral deficiencies. Brain MRI in 5 of 5 patients was notable for cerebellar atrophy without supratentorial involvement. Antineuronal activity was detected in sera of 0 of 10 children at follow-up., Conclusions: Certain patients with neuroblastoma associated OMA may achieve average-range neurobehavioral function in spite of residual neurologic abnormalities, with suggestion of continued improvement over time. Late cerebellar atrophy appears to be a common finding regardless of neurologic outcome, whereas antineuronal immune reactivity does not appear to be a long-term feature of OMA.

There have been reports that a variable number of tandem repeats (VNTR) polymorphism situated in the 3' untranslated region of the dopamine transporter gene is associated with attention-deficit hyperactivity disorder. On the basis of these findings, we predicted an association of this polymorphism with hyperactivity, other externalizing behavior problems, and related temperament traits in a general population sample. The association was investigated using children participating in a longitudinal study of childhood temperament and development. DNA was taken from 660 children who had been assessed for temperament from 4-8 months to 15-16 years, and for behavior problems from 3-4 to 15-16 years. No significant associations were found at any age. There are a number of methodological differences from earlier studies that might explain the lack of associations with hyperactivity. It is also possible that the earlier findings are not replicable., (Copyright 2001 Wiley-Liss, Inc.)

Objective: To describe the association between a unilateral mid-temporal rhythmic theta discharge ("psychomotor variant of Gibbs") with neuroimaging-demonstrated underlying mass lesion., Methods: Standard routine awake and scalp electroencephalography, continuous video-EEG monitoring and magnetic resonance brain imaging were employed in the diagnostic work-up of a 9-year-old boy with a severe behavioural disturbance and episodic outbursts of aggression., Results: EEG showed a unilateral mid-temporal rhythmic discharge which was continuous in drowsiness and which remained confined to the right hemisphere. MRI showed a lesion in the temporal horn of the right lateral ventricle displacing superiorly the white matter stem of the right temporal lobe., Conclusion: A rhythmic mid-temporal theta discharge, commonly regarded as a benign EEG variant, may, in some patients, reflect underlying structural pathology. Neuroimaging should be considered particularly when this EEG pattern remains confined to one hemisphere.

Epilepsy and mental retardation, two relatively common childhood conditions, are both associated with a wide range of behavioral disorders. This article reviews the behavioral disturbances found in children with epilepsy, mental retardation, and both conditions. The behavioral disturbances found in children with epilepsy are associated with seizure-related, cognitive, developmental, and psychosocial factors. Although children with mental retardation also demonstrate a broad spectrum of behavioral disturbances, children with specific mental retardation syndromes have better-defined patterns of psychopathology. The presence of epilepsy and mental retardation seems to increase the severity of psychopathology. Further studies are needed, however, to define better the interaction of these two conditions and how they impact the behavior of children.

We report on two boys, monozygotic twins born to normal and nonconsanguineous parents, presenting with an unusual facial appearance, cortical atrophy, dolichocephaly, short stature, cleft palate, micrognathia, prominent upper central incisors, bilateral Sidney line, minor foot deformities, unstableness in walking, early hypotonia, hyperreflexia, hyperactivity, psychomotor retardation, and severe delay in language development. These manifestations resemble those previously described in the Smith-Fineman-Myers syndrome.