The prevalence of developmental dyscalculia (DC) in the school population ranges from 3-6 %, a frequency similar to that of developmental dyslexia and ADHD. These studies fulfilled the criteria for an adequate prevalence study, i.e., were population based, using standardized measures to evaluate arithmetic function. Although the variation in prevalence is within a narrow range, the differences are probably due to which definition of dyscalculia was used, the age the diagnosis was made and the instrument chosen to test for DC. The relative predominance of girls with DC may reflect a greater vulnerability to environmental influences alone or in addition to a biological predisposition. DC is not only encountered as a specific learning disability but also in diverse neurological disorders, examples of which include ADHD, developmental language disorder, epilepsy, treated phenylketonuria and Fragile X syndrome. Although the long-term prognosis of DC is as yet unknown, current data indicate that DC is a stable learning disability persisting, at least for the short term, in about half of affected children. The long-term consequences of DC and its impact on education, employment and psychological well-being have yet to be determined.

We and others have previously shown that the dopamine D4 exon III repeat (D4DR) and the serotonin-transporter promoter region (5-HTTLPR) polymorphisms are not only associated with adult personality traits 1-7 but also with temperament in 2-week-old neonates. 8 We now report the results of a second study of these infants and their temperament at 2 months using Rothbart's Infant Behavior Questionnaire (IBQ).9 There were significant negative correlations between neonatal orientation and motor organization as measured by the Neonatal Behavioral Assessment Scale (NBAS) 10 at 2 weeks and negative emotionality, especially distress in daily situations, at 2 months of age. There were significant main effects for negative emotionality and distress when the infants were grouped by the D4DR and the 5-HTTLPR polymorphisms. Infants with long D4DR alleles had significantly lower scores on Negative Emotionality These infants showed most negative emotionality and most distress to daily situations, temperament traits that are perhaps the underpinning of adult neuroticism.The initial findings of associations between D4DR and adult Novelty Seeking 1,6 and 5-HTTLPR and Neuroticism or Harm Avoidance 5 fueled a number of similar investigations some of which did not corroborate these associations across cultural and ethnic groups. [11][12][13][14][15] We postulated that genetic effects on personality might be more clearly understood by studying the first expressions of personality, that is, infant temperament. In order to study the association between temperament and specific genetic polymorphisms, we initiated a longitudinal study of human temperament. We 8 examined a group of infants shortly after birth using the Brazelton Neonatal Assessment Scale (NBAS).10 Cord blood was collected at birth and DNA is available for these subjects. Significant multivariate and univariate main effects were observed for D4DR on four temperament clusters. Infants with long D4DR alleles received higher scores on these clusters than infants with short D4DR alleles. There was also a significant interaction between D4DR and 5-HTTLPR. The effect of s/s 5-HTTLPR was to lower the scores on the orientation cluster for the group of neonates lacking long D4DR alleles. Orientation is a behavioral cluster reflecting alertness and visual and auditory orienting behavior in neonates perhaps akin to adult Novelty Seeking.We are continuing to follow the development of these infants and have now assessed their temperament at 2 months of age using Rothbart's Infant Behavior Questionnaire (IBQ). 9 In the current report we examined the relationship between neonatal behavior and 2-month temperament and the association between two genetic polymorphisms, D4DR and 5-HTTLPR, and temperament at 2 months. All statistical tests were carried out using Statistica or SPSS for Windows. Analyses were based on the classification of the D4DR genotype into long (6-8) and short (2-5) repeats which we also used for the neonatal study. 8 We have discussed in some detail the rationale justific...

Genetic effects on behavior were evaluated at a time in early development when we hypothesized that environmental influences are minimal and least likely to confound associations between temperament and genes. The behavioral effects of two common polymorphisms linked respectively in some, but not all, studies to novelty seeking (dopamine D4 receptor -D4DR) and neuroticism and harm avoidance (serotonin transporter promoter region -STPR) were examined in a group of 81 two-week-old neonates. Neonate temperament was evaluated using the Brazelton neonatal assessment scale (NBAS). Multivariate tests of significance showed a significant association of D4DR across four behavioral clusters pertinent to temperament including orientation, motor organization, range of state and regulation of state. A significant multivariate interaction was also observed between D4DR and STPR. The effect of the homozygous short STPR genotype (s/s) was to lower the orientation score for the group of neonates lacking the long form (L) of D4DR. When adult subjects were grouped by the STPR polymorphism there is no significant effect of L-D4DR in those subjects homozygous for the STPR short form (s/s) whereas in the group without the homozygous genotype the effect of L-D4DR is significant and accounts for 13% of the variance in novelty seeking scores between groups.

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.

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.

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In this paper we examine the characteristics of preschool attention deficit hyperactivity disorder (ADHD) from both mental disorder and developmental psychopathology points of view. The equivalence of preschool and school-aged hyperactivity as a behavioral dimension is highlighted together with the potential value of extending the use of the ADHD diagnostic category to the preschool period where these behaviours take an extreme and impairing form (assuming age appropriate diagnostic items and thresholds can be developed). At the same time, the importance of identifying pathways between risk and later ADHD is emphasized. Developmental discontinuity and heterogeneity are identified as major characteristics of these pathways. We argue that models that distinguish among different developmental types of early-emerging problems are needed. An illustrative taxonomy of four developmental pathways implicating preschool hyperactivity is presented to provide a framework for future research.

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.