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Children suffering from chronic physical illness are considered to be at increased risk for behavioural problems. There is also evidence that their siblings are at risk for behavioural problems. This study investigated parent-reported behavioural problems in chronically ill children and their siblings. There were significant positive correlations between the behaviour problem scores of the ill children and the scores of their siblings. Siblings older than the ill child had significantly higher behaviour problem scores of an internalizing nature than did the younger siblings. Sibling behaviour problem scores were similar to those of a comparison group of normal children and significantly different from those of a comparison group of psychiatrically referred children. Siblings of chronically ill children showed no greater likelihood of receiving scores in the clinical range of behaviour problems than children in the general population. Implications of the findings and suggestions for future research are discussed. [ABSTRACT FROM AUTHOR]

Increased intrasubject variability of reaction time (RT) refers to inconsistency in an individual's speed of responding to a task. This increased variability has been suggested as a fundamental feature of attention deficit hyperactivity disorder (ADHD), however, its neural sources are still unclear. In this study, we aimed to examine whether such inconsistency at the behavioral level would be accompanied by inconsistency at the neural level; and whether different types of neural and behavioral variability would be related to ADHD symptomatology. We recorded electroencephalogram (EEG) data from 62 adolescents, who were part of a prospective longitudinal study on the development of ADHD. We examined trial-by-trial neural variability in response to visual stimuli in two cognitive tasks. Adolescents with high ADHD symptomatology exhibited an increased neural variability before the presentation of the stimulus, but when presented with a visual stimulus, this variability decreased to a level that was similar to that exhibited by participants with low ADHD symptomatology. In contrast with our prediction, neural variability was unrelated to the magnitude of behavioral variability. Our findings suggest that adolescents with higher symptoms are characterized by increased neural variability before the stimulation, which might reflect a difficulty in alertness to the forthcoming stimulus; but this increased neural variability does not seem to account for their RT variability., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Neurocognitive deficits have been proposed as endophenotypes for schizophrenia. Although neurocognitive functioning has been studied extensively in first-degree relatives of schizophrenia patients at single time points, little is known about the change or continuity in deficits across development., Method: The longitudinal sample was composed of 86 nonpsychotic participants who had a parent with schizophrenia (n = 28), a parent with a nonschizophrenia mental disorder (n = 31) or parents without mental illness (n = 27). Executive functioning (EF) was assessed during adolescence (M = 18 years) and adulthood (M = 32 years); attention and memory were assessed at adulthood., Results: The schizophrenia group, as adults, showed deficits in attention and memory relative to the no mental illness group. Only on one memory task did the schizophrenia group perform more poorly than the other mental illness group. Executive functioning improved with age for all three groups on Wisconsin Card Sorting Test perseverative errors; the rate of improvement was significantly slower for the schizophrenia and the other mental illness groups, compared to the no mental illness group. Stability in EF functioning over the 16-year period, measured by intraclass correlations, was low., Conclusions: Adults at familial risk for schizophrenia showed deficits in neurocognitive functioning. The similarity of performance between those whose parents had schizophrenia and those whose parents had other mental illness, in all but the measures of memory, raises the question as to whether the neurocognitive functions examined are endophenotypes of vulnerability to schizophrenia specifically. Modest stability of EF and improved performance with age may reflect cortical maturation during early adulthood., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We examined the longitudinal predictors of electrophysiological and behavioral markers of inhibitory control in adolescence. Participants were 63 adolescent boys who have been followed since birth as part of a prospective longitudinal study on the developmental pathways to attention-deficit hyperactivity disorder (ADHD). At 17 years of age, they completed the stop-signal task (SST) while electroencephalography (EEG) was continuously recorded. Inhibitory control was evaluated by the stop-signal reaction time (SSRT) as well as by the amplitude of the event-related potential (ERP) component of N2 during successful inhibition. We found that higher inattention symptoms throughout childhood predicted reduced amplitude (i.e., less negative) of the N2 in adolescence. Furthermore, the N2 amplitude was longitudinally predicted by the early precursors of child familial risk for ADHD and early childhood temperament. Specifically, father's inattention symptoms (measured in the child's early infancy) and child's effortful control at 36 months of age directly predicted the N2 amplitude in adolescence, even beyond the consistency of inattention symptoms throughout development. The SSRT was predicted by ADHD symptoms throughout childhood but not by the early precursors. Our findings emphasize the relevance of early familial and temperamental risk for ADHD to the prediction of a later dysfunction in inhibitory control.

Extreme levels of certain temperament traits can be early markers of different developmental pathways of attention-deficit/hyperactivity disorder (ADHD). However, the long-term utility of using these traits as predictors of ADHD is not fully known. This study includes 64 male adolescents (M age = 13.5), who have been followed since birth as part of a longitudinal study. The primary aim was to test effortful control (EC), activity level, and anger, measured in early childhood - both with mother's reports and laboratory assessments -as predictors of ADHD symptoms in adolescence. Further, we investigated the specificity of this prediction to the different ADHD symptom domains. The results demonstrated that early temperament dimensions of EC and activity level were predictive of ADHD symptoms about 10 years later, when the participants reached adolescence. Moreover, activity level showed specificity only to hyperactivity-impulsivity symptoms whereas EC was a predictor of the two symptom domains. Anger had a predictive correlation with ADHD symptoms; however, it did not have a unique predictive contribution. These results emphasize the relevance of EC and activity level in the developmental course of ADHD. Identification of early risk factors can lead to more efficient design and implementation of intervention programs.

Children of mothers with attention-deficit/hyperactivity disorder (ADHD) have an increased genetic and environmental risk for ADHD. The unique and interactive contributions of a maternal dopamine receptor gene (DAT1), maternal ADHD symptoms (hyperactive- impulsive, inattentive), and home atmosphere to the prediction of ADHD symptoms (hyperactive- impulsive, inattentive) in 7- year-old boys (N = 96) were examined using data from a longitudinal study of familial risk for ADHD. During the first 6 months of the study, mothers and their spouses completed a questionnaire about the mother's ADHD symptoms. Home atmosphere questionnaire data were collected 4 years later. At the 7-year assessment, mothers reported on their child's ADHD symptoms. Negative home atmosphere was significantly associated with child hyperactive-impulsive and inattentive symptoms. Maternal inattentive symptoms were significantly correlated with both child symptom dimensions. Regression models, with child genotype and maternal education controlled, showed main effects for maternal inattentive symptoms, maternal DAT1 10/10 genotype, and home atmosphere in the prediction of child inattentive symptoms. Only home atmosphere predicted child hyperactive-impulsive symptoms. There was a significant home atmosphere x maternal hyperactive-impulsive symptoms interaction in the prediction of child hyperactive-impulsive symptoms. Boys with higher levels of symptoms came from homes characterized by higher levels of negative atmosphere and had mothers with higher levels of hyperactive-impulsive symptoms. There was also a trend (p = 0.075) for a maternal DAT1 x home atmosphere interaction. Boys with higher levels of inattentive symptoms came from homes with higher levels of negative atmosphere and had mothers with the homozygous 10/10 genotype. The maternal heterozygous 9/10 genotype did not predict child symptoms.

Background: The prevalence of ADHD is controversial, with many feeling that this disorder is over- or under-diagnosed., Objectives: To study the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its association with sociodemographic characteristics, comorbid mental disorders, medical services, and methylphenidate use in the Israeli adolescent population., Methods: The Israel Survey of Mental Health among Adolescents was conducted in a representative national sample of 14-17 year olds and their mothers. The Development and Well-Being Assessment was administered to identify DSM-IV diagnoses of ADHD and comorbid mental and learning disorders, and the results were verified by senior child psychiatrists. Respondents were also asked about their use of medical services and psychotropic drug intake in the past 12 months., Results: Three percent of the adolescents met the DSM-IV criteria for ADHD. ADHD was significantly associated with gender (higher prevalence in boys than girls), ethnicity (higher prevalence in Jews than Arabs/Druze), referral to a medical professional, and maternal help-seeking for the emotional or behavioral problems of the adolescent. Medication was prescribed to 2.9% of adolescents: 34.6% with a diagnosis of ADHD had not been prescribed methylphenidate in the past year, and 34.6% of the medicated subjects did not have a diagnosis of ADHD. None of the Arab/Druze adolescents was receiving stimulants compared to 3.7% of the Jewish adolescents., Conclusions: Despite advances in public awareness of mental disorders in youth, a substantial proportion of older Israeli adolescents, especially from minority groups, are under-diagnosed or untreated. At the same time, many, especially from the Jewish majority, are over-diagnosed and potentially over-treated. Ethnic disparities in rates of mental health care highlight the urgent need to identify and overcome barriers to the recognition and treatment of these conditions.

This study investigated the influence of a child's DRD4 risk, parental levels of ADHD symptoms, and the interactive influence of these factors on the development of preschool aggression. Additionally, the study investigated the role of home chaos as a mediator between parental ADHD symptoms and child aggression. The sample consisted of 84 4.5-year-old children and their parents. Children were genotyped for the DRD4 polymorphism. ADHD symptoms were self-reported by parents when the child was 2 to 6 months old. Parental reports of home chaos and the child's aggression were collected 4 years later. Child's DRD4 risk and parental ADHD symptoms significantly contributed to the prediction of preschool aggression. However, contrary to our hypotheses, no interactions were found between the child's DRD4 risk and the levels of parental ADHD symptoms. Home chaos played a mediating role in the relation between paternal ADHD symptoms and the child's aggression. The relation between maternal ADHD symptoms and the child's aggression was not significantly mediated through the level of home chaos. The current study emphasizes the importance of longitudinally investigating the contribution of parental ADHD symptoms to child aggression, while also exploring the differential contribution of maternal/paternal inattention and hyperactivity-impulsivity symptoms. Moreover, home chaos was found to be a significant environmental mechanism through which paternal ADHD symptoms affect children's aggression in the preschool years.

Children participating in the Ben-Gurion Infant Development Study were assessed with a dynamic-tracking version of the stop-signal task at the age of 5 years. The sample consisted of 60 males. Stop-signal reaction time (SSRT) was correlated with concurrent ratings of the child's attention deficit hyperactivity disorder (ADHD) symptoms. Paternal symptoms measured in the child's early infancy predicted the child's performance in the stop-signal task: Paternal inattentiveness predicted SSRT, whereas hyperactivity predicted error proportion. Maternal symptoms were not correlated with the performance of the child in the task. A subsample of children, who were tested while electrophysiological brain activity was measured, showed that having higher ADHD symptomatology, especially hyperactivity, correlated with less activity in the brain areas that are usually recruited by children for successful inhibition., (© 2013 The Authors. Child Development © 2013 Society for Research in Child Development, Inc.)

Sleep patterns of 26 seven-week-old boys at familial risk for attention deficit hyperactivity disorder (ADHD) and 18 control infants were compared by objective (actigraph) and subjective (maternal sleep diary) measures, over five consecutive 24-hr periods. Actigraph findings indicated that the groups differed on stability (SD) of quiet sleep only during the day. Reports in maternal sleep diaries indicated that they also differed on stability of waking and stability of sleep duration, again only during the day. No group differences were found in terms of average scores, whether calculated for the entire 24-hr periods, for nights, or for days. Mothers in the risk group reported that fathers were less involved in infant care than did those in the control group. These findings suggest that as early as 7 weeks of age, infants at risk for ADHD differ from controls only on stability of their sleep patterns during the day, when environmental regulatory factors are more intensive., (Copyright © 2010 Michigan Association for Infant Mental Health.)

Objective: This study examined the influence of allelic variation in two dopamine genes, the dopamine receptor D4 (DRD4) gene and the dopamine transporter D1 (DAT1) gene, and paternal attention-deficit hyperactivity disorder (ADHD) symptomatology on the level of ADHD symptoms in 96 four and a half-year-old boys., Method: DNA was collected by means of a buccal swab and genotyped for DRD4 and DAT1. Mothers completed the Dupaul ADHD checklist on their sons. ADHD symptomatology ratings for fathers were based on a summed father self-reported and spouse-reported symptoms (Conners Adult ADHD Rating Scale)., Results: There were main effects for DAT1 and father symptomatology for the child Total ADHD and Hyperactivity-Impulsivity scores. The main effects for DRD4 were limited to the child Hyperactivity-Impulsivity scores. Child Inattentive scores were influenced only by father symptomatology. Interaction effects between DAT1 and DRD4 and between DAT1 and the father ADHD risk group were found for child Hyperactivity-Impulsivity scores. Boys with the highest level of symptomatology were those with the 10/10 DAT1 genotype and the DRD4-7 genotype or fathers with high symptomatology., Conclusion: The findings of this study indicate that the risk for ADHD, particularly hyperactivity-impulsivity, is exacerbated in the presence of dopamine risk genes and paternal ADHD symptomatology. This study adds to the growing literature on the efficacy of including multiple genetic and environmental risk factors in studies related to the development of psychopathology.

Patterns of interaction between parents and 7-month-old boys at familial risk for attention deficit/hyperactivity disorder (ADHD) and a comparison group were studied during a warm-up and two play episodes. The sample included 78 (47 at-risk, 31 comparison) mother-child and 45 (27 at-risk, 18 comparison) father-child dyads. A coding system developed by G. Kochanska (1997, 1998) was used. Infants in the risk group did not differ from the comparison group in the rate of emission of infant-related events. However, they received less adequate responsivity from both their fathers and their mothers to these events, and specifically to negative emotions or distress, than did the comparison group. Maternal psychopathology did not account for these findings. Mothers were more adequately responsive than were fathers, especially for physiological needs. The association between nonoptimal interaction in infancy and the development of ADHD is discussed., (Copyright © 2010 Michigan Association for Infant Mental Health.)

Schizophrenia has come to be viewed as a neurodevelopmental disorder that is characterized by genetic vulnerability, stressors during the prenatal period that may be marked by minor physical anomalies and neurobehavioral deficits that emerge in early development. Less is known about the neurodevelopmental origins of schizotypal personality symptoms. The present study examines schizotypal symptoms in Israeli adolescents (mean age = 16.79 years) who have not yet reached the developmental period during which first schizophrenic episode is most likely to emerge: 39 adolescent offspring of parents with schizophrenia, 39 offspring of parents with other psychiatric disorders, and 36 offspring of parents with no history of mental illness. The Semi-Structured Kiddie Interview for Personality Syndromes was used to assess cognitive-perceptual, interpersonal, and disorganized schizotypal symptoms. Interpersonal schizotypal symptoms were more prevalent in the schizophrenia offspring group than in the no-mental-illness offspring group. Among the schizophrenia offspring group, interpersonal, but not cognitive-perceptual, schizotypal symptoms were associated with minor physical anomalies, fine motor dyscoordination, and deficits in executive functioning during adolescence. Among young people whose parents did not have schizophrenia, cognitive-perceptual schizotypal symptoms were correlated with deficits in executive functioning. Adolescent schizotypal symptoms were associated with neurobehavioral symptoms measured during middle childhood in a subgroup of the sample that had been assessed prospectively. Finally, young people who had genetic risk for schizophrenia, minor physical anomalies, and neurobehavioral signs together were at markedly increased risk for symptoms of interpersonal schizotypal symptoms, compared to young people with one or none of these risk factors.

Patterns of interaction of 34 mothers and fathers with their 7-month-old boys at familial risk for ADHD and 25 comparison families were studied during infant play with blocks. The parents were instructed to refrain from intervening as much as possible. Infants in the risk group did not differ from those in the comparison group in frequency of needing help or involving parents in play. Nonetheless, they received adequate responsivity from their mothers less often than infants in the comparison group. Mothers in the risk group were also more likely not to respond to these needs at all. Mothers in the comparison group were more physically intrusive. No group difference was found for maternal rebuilding of the infant's play. No group differences were found for any of father's behaviors. However, fathers in both groups rebuilt their infant's play more frequently than mothers, infants looked at them more often, and a larger number of infants involved the father in their play.

The authors examined behavior problems in a matched sample of 58 youths with persistent dyscalculia (PD) and nonpersistent dyscalculia (NPD). Participants were classified as having dyscalculia at age 10-11 years. Parents completed the Child Behavior Checklist for their children at ages 10-11, 13-14, and 16-17 years, while the youths did so at the last two age periods. Only at age 16-17 years were there significantly more problems, particularly attention problems and externalizing problems, reported by parents for PD youths compared to NPD youths. A higher percentage in the PD group than in the NPD group received scores in the clinical range for externalizing problems. However, the mean levels of behavior problems at this age and the earlier ages were within the normal range for both groups. For youth-reported problems, the only significant difference was for attention problems at 16-17 years. Therapeutic interventions should focus on the academic domain and improving and altering behavioral patterns.

Background: Current concepts of Attention-Deficit/Hyperactivity Disorder (ADHD) emphasize the role of higher-order cognitive functions and reinforcement processes attributed to structural and biochemical anomalies in cortical and limbic neural networks innervated by the monoamines, dopamine, noradrenaline and serotonin. However, these explanations do not account for the ubiquitous findings in ADHD of intra-individual performance variability, particularly on tasks that require continual responses to rapid, externally-paced stimuli. Nor do they consider attention as a temporal process dependent upon a continuous energy supply for efficient and consistent function. A consideration of this feature of intra-individual response variability, which is not unique to ADHD but is also found in other disorders, leads to a new perspective on the causes and potential remedies of specific aspects of ADHD., The Hypothesis: We propose that in ADHD, astrocyte function is insufficient, particularly in terms of its formation and supply of lactate. This insufficiency has implications both for performance and development: H1) In rapidly firing neurons there is deficient ATP production, slow restoration of ionic gradients across neuronal membranes and delayed neuronal firing; H2) In oligodendrocytes insufficient lactate supply impairs fatty acid synthesis and myelination of axons during development. These effects occur over vastly different time scales: those due to deficient ATP (H1) occur over milliseconds, whereas those due to deficient myelination (H2) occur over months and years. Collectively the neural outcomes of impaired astrocytic release of lactate manifest behaviourally as inefficient and inconsistent performance (variable response times across the lifespan, especially during activities that require sustained speeded responses and complex information processing)., Testing the Hypothesis: Multi-level and multi-method approaches are required. These include: 1) Use of dynamic strategies to evaluate cognitive performance under conditions that vary in duration, complexity, speed, and reinforcement; 2) Use of sensitive neuroimaging techniques such as diffusion tensor imaging, magnetic resonance spectroscopy, electroencephalography or magnetoencephalopathy to quantify developmental changes in myelination in ADHD as a potential basis for the delayed maturation of brain function and coordination, and 3) Investigation of the prevalence of genetic markers for factors that regulate energy metabolism (lactate, glutamate, glucose transporters, glycogen synthase, glycogen phosphorylase, glycolytic enzymes), release of glutamate from synaptic terminals and glutamate-stimulated lactate production (SNAP25, glutamate receptors, adenosine receptors, neurexins, intracellular Ca2+), as well as astrocyte function (alpha1, alpha2 and beta-adrenoceptors, dopamine D1 receptors) and myelin synthesis (lactate transporter, Lingo-1, Quaking homolog, leukemia inhibitory factor, and Transferrin)., Implications of the Hypothesis: The hypothesis extends existing theories of ADHD by proposing a physiological basis for specific aspects of the ADHD phenotype - namely frequent, transient and impairing fluctuations in functioning, particularly during performance of speeded, effortful tasks. The immediate effects of deficient ATP production and slow restoration of ionic gradients across membranes of rapidly firing neurons have implications for daily functioning: For individuals with ADHD, performance efficacy would be enhanced if repetitive and lengthy effortful tasks were segmented to reduce concurrent demands for speed and accuracy of response (introduction of breaks into lengthy/effortful activities such as examinations, motorway driving, assembly-line production). Also, variations in task or modality and the use of self- rather than system-paced schedules would be helpful. This would enable energetic demands to be distributed to alternate neural resources, and energy reserves to be re-established. Longer-term effects may manifest as reduction in regional brain volumes since brain areas with the highest energy demand will be most affected by a restricted energy supply and may be reduced in size. Novel forms of therapeutic agent and delivery system could be based on factors that regulate energy production and myelin synthesis. Since the phenomena and our proposed basis for it are not unique to ADHD but also manifests in other disorders, the implications of our hypotheses may be relevant to understanding and remediating these other conditions as well.

Objective: Offspring of patients with schizophrenia are at-risk for developing schizophrenia in adult life. The aim of this paper is to describe the development from infancy through adolescence of a sample of Israeli young people at-risk for schizophrenia., Methods: The Jerusalem Infant Development Study (JIDS) has followed prospectively from birth through adolescence 15 young people who have a parent with schizophrenia. Neurobehavioral data were gathered at infancy, middle childhood, and adolescence. Mental disorder was assessed at adolescence., Results: Data suggest that some children whose parents have schizophrenia are at increased risk for a variety of neuromotor, cognitive, and attentional problems during infancy and childhood, compared to children whose parents had no mental disorder or nonschizophrenia mental disorder. Those high-risk children with neurobehavioral signs are also more likely to have poorer social adjustment, greater social withdrawal, and more symptoms within the schizophrenia spectrum. Case studies are presented of two children with early neurobehavioral impairment who, as adolescents, developed disorders within the schizophrenia spectrum., Conclusion: Because neurobehavioral impairment may be marking genetic vulnerability to schizophrenia spectrum disorders, clinicians treating children whose parents have schizophrenia need to thoroughly evaluate symptoms of mental disorder--but also neuromotor and neuropsychological functioning.

Sixty-six male infants participating in the Ben-Gurion Infant Development Study of familial risk for attention deficit hyperactivity disorder (ADHD) were assessed at 7 months of age using observational and mother report measures. Risk for ADHD was based on ADHD symptoms in the father. Infants whose fathers had seven or more symptoms formed the ADHD risk group; infants whose fathers had three or less symptoms formed the comparison group. The ADHD risk group significantly differed from the comparison group on measures of interest, anger, and activity level and showed less interest in block play and more anger reactivity but less directed anger in a barrier task. According to mother report, the ADHD risk group had higher levels of activity than the comparison group. Measures of neonatal immaturity and activity were related to behavior at 7 months. The findings suggest that possible developmental pathways to ADHD may be emerging in early infancy.

Although offspring of parents with schizophrenia are at risk for schizophrenic illness as adults, little is known about their pattern of symptoms as children and adolescents. Lifetime Axis I and II DSM-III-R diagnoses were made for 116 young people (ages 12-22). Forty-one subjects had a parent with schizophrenia, 39 had a parent with a nonschizophrenic mental disorder, and 36 had parents with no mental illness. Schizophrenia spectrum disorders occurred at higher rates among young people with a parent with schizophrenia (17.1%) than in other young people (5.3%), even after controlling for mental disorder in the nonproband parent. Schizophrenia and schizotypal personality disorder occurred exclusively in offspring of parents with schizophrenia. Offspring of parents with schizophrenia were also at increased risk for avoidant personality disorder but not paranoid personality disorder. Although lifetime anxiety disorders were common in all young people regardless of parent diagnosis, current anxiety disorders were more prevalent for the adolescent offspring of parents with schizophrenia. These data strongly suggest familial vulnerability to schizophrenia spectrum disorder that is observable before adulthood, particularly for males.

Slowness is a common complaint in children with attention-deficit hyperactivity disorder (ADHD) and with developmental right hemisphere syndrome. However, it was our clinical impression that slowness in developmental right hemisphere syndrome was more prominent than in ADHD. Our objective was to assess slowness as operationalized by speed of performance in children with developmental right hemisphere syndrome, children with ADHD, and controls. The research sample comprised 19 children in each group, matched for age, gender, socioeconomic status, IQ, and handedness. The subjects were administered a reaction time battery assessing speed of performance. Overall, the average performance differed among the three study groups (F(2,53) = 2.40, P < .01). Children with developmental right hemisphere syndrome were slower than their peers with ADHD (t(35) = 1.99, P < .05) and slower than controls (t(35) = 4.55, P < .001). Children with ADHD performed more slowly than controls, although for the majority of tasks, this was nonsignificant. We conclude that slowness is an integral and consistent component of developmental right hemisphere syndrome and cannot be attributed only to the ADHD symptomatology.

This study examined the association between two common polymorphisms, the dopamine D4 receptor (DRD4) gene and the serotonin transporter promoter (5-HTTLPR) gene and temperament in 61 infants aged 12 months. Twenty-two infants had a least one copy of the 6-8 repeat DRD4 alleles (L-DRD4) and 39 had two copies of the 2-5 repeat allele (S-DRD4). Twenty infants were homozygous for the short form (s/s) of 5-HTTLPR while 41 were either heterozygous for the short and the long form (l/s) or were homozygous for the long form (l/l). The infants were observed in a series of standard temperament episodes that elicited fear, anger, pleasure, interest, and activity. L-DRD4 infants showed less interest in a structured block play situation and more activity in a free play situation. They also displayed less anger in an episode of mild physical restraint. Infants with s/s 5-HTTLPR showed less fearful distress to stranger approach and less pleasure in a structured play situation than infants with l/l or l/s 5-HTTLPR. Duration of looking during block play was affected by a significant interaction between DRD4 and 5-HTTLPR. Shortest duration of looking was associated with the L-DRD4 and s/s 5-HTTLPR genotypes. The implications and limitations of these findings are discussed.

The dopamine D4 receptor (DRD4) exon III polymorphism has generated interest because of its association with attention deficit hyperactivity disorder (ADHD), with an increased frequency of the seven-repeat allele being reported in children with ADHD. Deficits in sustained attention and information processing characterize ADHD, and individual differences in these functions are apparent from infancy. We found that in a structured play situation and on an information-processing task, 1-year-old infants with the 7-DRD4 allele showed less sustained attention and novelty preference than do infants without the 7-DRD4 allele. There was also a significant interaction between DRD4 and the serotonin transporter promoter (5-HTTLPR) gene on a measure of sustained attention. Our results provide evidence for a possible developmental link between DRD4 and ADHD via early sustained attention and information processing. It also points to the importance of considering the influence of more than one gene in studies of behavior.

Objective: To better understand whether poor social adjustment, a core characteristic of schizophrenic illness, may also be an indicator of vulnerability in young people who are at genetic risk for schizophrenia, but who do not have schizophrenia., Method: Between 1992 and 1996, 27 Israeli adolescents with a schizophrenic parent, 29 adolescents with no mentally ill parent, and 30 adolescents with a parent having a nonschizophrenic mental disorder were assessed on multiple domains of social adjustment measured using the Social Adjustment Inventory for Children and Adolescents and the Youth Self-Report., Results: Young people with a schizophrenic parent showed poor peer engagement, particularly heterosexual engagement, and social problems characterized by immaturity and unpopularity with peers. These social adjustment difficulties in youths at risk for schizophrenia could not be attributed solely to the presence of early-onset mental disorders, although problems were greater in those with disorders in the schizophrenia spectrum. Young people whose parents had other disorders showed different patterns of social maladjustment characterized by difficult, conflictual relationships with peers and family., Conclusion: Adolescents at risk for schizophrenia have social deficits that extend beyond early-onset psychopathology and that may reflect vulnerability to schizophrenic disorder.

Background: The Jerusalem Infant Development Study is a prospective investigation comparing offspring of schizophrenic parents with offspring of parents who have no mental disorder or have nonschizophrenic mental disorders. During infancy and school age, a subgroup of offspring of schizophrenic parents showed global neurobehavioral deficits that were hypothesized to be indicators of vulnerability to schizophrenia. The purposes of the present investigation were to determine if neurobehavioral deficits were present in the offspring of schizophrenics at adolescence, to examine their stability over time, and to explore their relation to concurrent mental adjustment., Methods: Sixty-five Israeli adolescents were assessed on a battery of neurologic and neuropsychological assessments. They were also administered psychiatric interviews from which best-estimate DSM-III-R diagnoses and scores of global adjustment were derived., Results: Adolescents with poor neurobehavioral functioning were identified from composites of motor and cognitive-attentional variables. A disproportionate number of offspring of schizophrenic parents (42%; 10/24), and especially male offspring of schizophrenic parents (73%; 8/11), showed poor neurobehavioral functioning relative to offspring of nonschizophrenic parents (22%; 9/41). Adolescent offspring of schizophrenics with poor neurobehavioral functioning had been poorly functioning at earlier ages and had poor psychiatric adjustment at adolescence. All 4 offspring of schizophrenics receiving schizophrenia spectrum diagnoses by adolescence showed a pattern of poor neurobehavioral functioning across developmental periods., Conclusions: Results are consistent with the hypothesis that individuals at genetic risk for schizophrenia may display lifelong neurobehavioral signs that are indicators of vulnerability to schizophrenia and that are associated with psychiatric adjustment generally and schizophrenic spectrum disorder specifically.

We studied clinical aspects of attention in three groups: children with developmental right-hemisphere syndrome and attention-deficit hyperactivity disorder (ADHD), children with ADHD only, and normal controls. The three groups (N = 54) were case-matched for age, sex, IQ, hand dominance, and socioeconomic status. ADHD was diagnosed clinically using the Diagnostic and Statistical Manual of Mental Disorders-III-Revised criteria and the Conners' Abbreviated Teacher Questionnaire. Additional aspects of attention and behavior were measured by the Child Behavior Checklist, a low-cognitive-load continuous performance task, and the visual target cancellation test (paper and pencil). Although the Child Behavior Checklist profile of attentional deficits in the two clinical groups was similar, we found that the developmental right-hemisphere syndrome group was more severely impaired on parameters of attention measured by the continuous performance task and visual target cancellation test than the children with ADHD. We conclude that the profile of attentional deficits in developmental right-hemisphere syndrome is different than that seen in children with ADHD only, possibly reflecting disparate neurologic underpinnings for the two syndromes.

Objective: We examined potential early markers of schizophrenia using measures of formal thought disorder in offspring of parents with schizophrenia, other mental illness and no mental illness., Methods: Two blind raters coded formal thought disorder in adolescent/early adult offspring of 42 schizophrenic, 39 other mental illness, and 36 no mental illness parents. In addition to parental diagnosis, we compared the individual offspring diagnosis with severity of formal thought disorder. Within the schizophrenia, other mental illness and no mental illness offspring groups, we examined the relationship between severity of formal thought disorder and performance on cognitive and motor tasks., Results: There were no statistically significant differences in formal thought disorder by parent or offspring diagnoses. Within the offspring group of parents with schizophrenia, the subjects with higher formal thought disorder scores performed significantly worse on the cognitive battery than those with lower formal thought disorder scores. Offspring of the other mental illness group with higher formal thought disorder scores, however, showed more deficits on motor tasks than those with lower formal thought disorder scores., Conclusion: Formal thought disorder may reflect underlying cognitive dysfunction in the offspring of parents with schizophrenia. Motor dysfunction in the offspring of parents with other psychiatric illness might be associated with formal thought disorder.

The development of school-age children born to parents with serious mental disorders was assessed on a variety of perceptual-cognitive and motoric tasks. These same children have been followed up from birth as part of the Jerusalem Infant Development Study. Children with schizophrenic parents, when compared with children with healthy parents or parents having other psychiatric disorders, were more likely to show neurobehavioral dysfunctioning in perceptual-cognitive and motoric areas. Forty-four percent of the offspring of schizophrenics (11 of 25 subjects) showed such dysfunctioning. Male subjects were overrepresented in this poorly functioning group. A stable subgroup (40%) of the offspring of schizophrenics (six of 15 subjects) showed dysfunctioning during infancy and school age. None of the offspring of nonschizophrenic parents showed dysfunctioning during both age periods. While most of the poorly functioning children with schizophrenic parents showed perceptual-cognitive and motoric signs, only perceptual-cognitive signs were strongly linked to parental diagnosis and infant dysfunctioning. Motoric signs, but not cognitive signs, were related to pregnancy and birth complications. These findings provide further support to the schizotaxia hypothesis that some neurointegrative deficits may reflect vulnerability to schizophrenia and that these deficits are clearly apparent at school age, long before the onset of illness. However, these signs are not exclusive to schizophrenic illness, although they occur with a greater prevalence in this group. Definitive statements about the validity of early neurobehavioral signs as indicators of genetic vulnerability await further longitudinal follow-up into the age of risk for actual schizophrenic breakdown or when a diagnosis of schizotypal personality disorder may be made.

The neurobehavioral functioning and social behavior of children with mentally ill and mentally healthy parents were examined. The children, 8 to 13 years of age, were assessed with a battery of neurobehavioral tests. The children's teachers rated their interpersonal behavior. Each of the families was rated on quality of childbearing environment. Children of schizophrenic parents performed more poorly on the neurobehavioral tests, in particular those assessing perceptual-cognitive functioning, than children of parents with other psychiatric disorders or with no history of mental illness. There were no group differences in aggressive behavior. Sons of schizophrenic parents were rated as more withdrawn than the other children in the study. The relationship between childrearing environment, neurobehavioral functioning, and social behavior was in the expected direction for the children of mentally healthy parents. An atypical pattern emerged for the offspring of mentally ill parents.

Investigations of the childhood antecedents of adult schizophrenia may clarify our understanding of the etiology of the disease, provide guidelines for meaningful classification of subtypes of schizophrenic illness, point to strategies for identifying those individuals in need for early intervention, and suggest appropriate techniques for early intervention. Among the more salient characteristics of schizophrenic illness are disturbances in interpersonal relations, especially withdrawal from normal social interaction.

A sample of 29 psychiatrically ill women and a non-ill comparison group were recruited during pregnancy. Twelve of the ill mothers were receiving antipsychotic and anti-anxiety medication during the final trimester of pregnancy. The behavior of their infants was assessed at 3 and 14 days of age using the Brazelton Neonatal Behavioral Assessment Scale. Compared to infants of non-ill mothers and infants of ill nonmedicated mothers, infants whose mothers received antipsychotic drugs--particularly those in the phenothiazine family--showed a stable pattern of poor neonatal motor functioning that included tremulousness, hypertonicity, and poor motor maturity. It was speculated that this behavior was symptomatic of a neonatal abstinence or withdrawal syndrome.

A 1975 report stated that a schizophrenic genotype may be manifested in infants by a neurointegrative defect called pandysmaturation. Recent evidence supports this: (1) 12 studies found delayed development in schizophrenics' infants and in preschizophrenics; (2) "blind" psychometric evaluations favored an adult schizotypal disorder in four to six of seven high-risk subjects with pandysmaturation in the New York study; and (3) finally, in a partial replication of this method using the Jerusalem data, blind diagnoses of "probable" and "possible" pandysmaturation were significantly related to a parental diagnosis of schizophrenia and to cognitive and motor neurointegrative deficits at 10 years. Obstetrical complications were unrelated to diagnosis, pandysmaturation, or outcome in the overall sample. However, we found a small subgroup of schizophrenic offspring in whom the most severe motor deficits at follow-up were related to obstetrical complications, pandysmaturation, and low birth weight.

Child Behavior Checklists (CBCL) were completed by parents of 450 clinically referred Israeli boys aged 6-11. Principal components analyses with varimax rotation yielded 10 syndromes: aggressive, uncommunicative/social withdrawal, depressed, delinquent, hyperactive, somatic complaints, anxious, immature, unpopular, and odd. The first seven syndromes were highly correlated with American and Dutch syndromes derived from the CBCL providing further evidence of their cross-cultural robustness.

As part of a longitudinal follow-up study of the development of adopted and biological children in Israel, 87 couples were administered the Bates Infant Characteristics Questionnaire when their first infants were 21 to 30 days old. Middleclass adoptive parents and a middle-class biological-parent control sample constituted one group. A second group comprised a lower-class sample. Mothers in all groups saw the child as more difficult in terms of strength of cry and reactions to being dressed as compared to fathers. Mothers perceived the child as more predictable for diaper changes and sleep. Adoptive parents saw their child as easier, that is, having more stable and positive mood states. Adoptive mothers saw their neonates as more active than the biological mothers. Middle-class parents saw their children as more soothable and as less disturbing in their emotional behavior than lower-class parents. The results indicate that neonatal temperament can be studied and that parental perception is influenced by sex of parent, biological relationship to the child and environmental factors, such as social class and early intervention.

The National Institute of Mental Health (NIMH) Israeli Kibbutz-City Study has followed the development of offspring of schizophrenic parents from middle childhood through early adulthood. During childhood, a subgroup of offspring of schizophrenic patients showed clear neurobehavioral deficits often accompanied by poor social competence. Early followup data suggest that this subgroup of high-risk children is at greatest risk for adult schizophrenia spectrum illness. The Jerusalem Infant Development Study has followed a similar population of children at risk for schizophrenia from before birth through middle childhood. A subgroup of dysfunctioning in the high-risk children showed sensorimotor dysfunctioning in the first year of life, which was followed by perceptual, motor, and attentional dysfunctioning in childhood--identical to that found in the NIMH cohort. Results from both studies support the hypothesis that schizophrenic illness involves constitutional factors whose expression can be observed as early as infancy. Results also illustrate the importance of using data-analytic approaches that (1) look for subgroups within high-risk groups rather than only group differences between high- and low-risk groups, and (2) examine profiles of behavior rather than only single variables.