The association of the dopamine D4 receptor gene (DRD4) and the serotonin transporter promoter gene (5-HTTLPR) with temperament in 12-month-old infants.

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.

DRD4 related to infant attention and information processing: a developmental link to ADHD?

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.

Social adjustment of adolescents at risk for schizophrenia: the Jerusalem Infant Development Study.

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.

Neurobehavioral deficits at adolescence in children at risk for schizophrenia: The Jerusalem Infant Development Study.

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.

Attention-deficit hyperactivity disorder and developmental right-hemisphere syndrome: congruence and incongruence of cognitive and behavioral aspects of attention.

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.

Behavioural problems of children with chronic physical illness and their siblings.

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 problems 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.

Formal thought disorder in offspring of schizophrenic parents.

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.

Behavioral problems of adolescents with chronic physical illness: a comparison of parent-report and self-report measures.

This study reports on the extent of behavior problems in Israeli adolescents suffering from chronic illness. A comparison was made between parent-reported and self-reported behavioral symptomatology using the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). 103 outpatients, aged 11-16 years, suffering from cystic fibrosis (CF), asthma, or hematological/oncological conditions were assessed. Healthy adolescents and adolescents referred for psychiatric assessment comprised the comparison groups. Parent- and self-reports were significantly positively correlated in each group (all chronically ill children r = .22; Healthy group r = .27; psychiatric group r = .50), but the correlations were particularly low (and non-significant) in younger adolescents with hematological/oncological conditions or HCF., pointing to the need for physicians to include parents' and adolescents' viewpoints in their assessments of these adolescents' psychosocial state. The mean number of parent-reported and self-reported behavior problems in the illness groups was no different from that of the Healthy group but significantly lower than that of the psychiatric group.

Children at risk for schizophrenia: the Jerusalem Infant Development Study. II. Neurobehavioral deficits at school age.

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.

Neurobehavioral functioning and social behavior of children at risk for schizophrenia.

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.

Interpersonal behavior of children at risk for schizophrenia.

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.

Maternal psychotropic medication and neonatal behavior.

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.

Infants at risk for schizophrenia: sequelae of a genetic neurointegrative defect. A review and replication analysis of pandysmaturation in the Jerusalem Infant Development Study.

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.

Syndromes derived from the Child Behavior Checklist for clinically referred Israeli boys aged 6-11: a research note.

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.

Fathers' and mothers' perceptions of temperament in Israeli neonates: effects of adoption and social class.

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.

Review of the NIMH Israeli Kibbutz-City Study and the Jerusalem Infant Development Study.

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.