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Biomedical subjects

J Rovet

Publications and source records attributed to J Rovet.

At least 19 recordsLinked to original sources

Identifying the behavioural phenotype in Fetal Alcohol Spectrum Disorder: sensitivity, specificity and screening potential.

BACKGROUND: In most cases of Fetal Alcohol Spectrum Disorder (FASD), the pathognomonic facial features are absent making diagnosis challenging, if not impossible, particularly when no history of maternal drinking is available. Also because FASD is often comorbid with Attention Deficit Hyperactivity Disorder (ADHD), children with FASD are frequently improperly diagnosed and receive the wrong treatment. Since access to psychological testing is typically limited or non-existent in remote areas, other diagnostic methods are needed to provide necessary interventions. OBJECTIVES: To determine if a characteristic behavioural phenotype distinguishes children with FASD from typically developing children and children with ADHD and use this information to create a screening tool for FASD diagnosis. METHODS: Parents and caregivers completed the Child Behavior Checklist (CBCL), a well-established standardized tool for evaluating children's behavioural problems. Results from 30 children with Fetal Alcohol Syndrome or Alcohol-Related Neurodevelopmental Disability, 30 children with ADHD, and 30 typically developing healthy children matched for age and socioeconomic status with FASD were analyzed. Based on our previous work, 12 CBCL items that significantly differentiated FASD and control groups were selected for further analyses. Stepwise discriminant function analysis identified behavioural characteristics most strongly differentiating groups and Receiver Operating Characteristics (ROC) curve analyses determined sensitivity and specificity of different item combinations. RESULTS: Seven items reflecting hyperactivity, inattention, lying and cheating, lack of guilt, and disobedience significantly differentiated children with FASD from controls. ROC analyses showed scores of 6 or higher on these items differentiated groups with a sensitivity of 86%, specificity of 82%. For FASD and ADHD, two combinations of items significantly differentiated groups with high sensitivity and specificity (i) no guilt, cruelty, and acts young (sensitivity = 70%; specificity = 80% (ii) acts young, cruelty, no guilt, lying or cheating, steals from home, and steals outside (sensitivity = 81%; specificity = 72%). These items were used to construct a potential FASD screening tool. CONCLUSIONS: Our findings identifying the behavioural characteristics differentiating children with FASD from typically developing children or children with ADHD have the potential for development of an empirically derived tool for FASD tool to be used in remote areas where psychological services are not readily available. This technique may speed up diagnosis and intervention for children without ready access to formal assessments.

Attention Deficit Disorder with Hyperactivity↗

Binge alcohol consumption by non-alcohol-dependent women during pregnancy affects child behaviour, but not general intellectual functioning; a prospective controlled study.

Effects of binge ethanol consumption during early gestation on child neurodevelopment have not been elucidated. To study whether binge drinking affects cognitive abilities and behavior of exposed children, a prospective observational study comparing 51 children exposed to binge drinking during the first trimester of pregnancy to 51 children not exposed to any teratogens was conducted. The children's physical development, intelligence, language abilities and behavior were assessed. Temperament test results showed that children exposed in utero to maternal binge drinking displayed a greater degree of disinhibited behavior and that this behavior was associated with early drinking variables. Although binge alcohol drinking by non-alcohol-dependent women during the first trimester of pregnancy does not appear to affect intelligence or cognitive and language development of young children, binge drinking in pregnancy does increase the likelihood of certain behavioral characteristics that might predispose these children to later behavioral dysfunction.

Adult↗

Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings.

Abstract The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congenital hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions.

Animals↗

The Toronto experience in diagnosing alcohol-related neurodevelopmental disorder: a unique profile of deficits and assets.

BACKGROUND: Fetal alcohol syndrome (FAS), which involves the triad of features reflecting facial dysmorphology, growth retardation and intellectual impairments, encompasses a relatively small proportion of the children affected prenatally by alcohol. Unfortunately, in the absence of facial dysmorphology, the diagnosis is difficult in the majority of children, who are considered to have alcohol-related neurodevelopmental disorder (ARND). Because accepted clinical methods are not pathognomonic, a novel profile approach was used to examine neuropsychological abilities and disabilities to identify children with ARND who do not meet the diagnostic criteria of FAS. OBJECTIVE: To establish a set of criteria, to be validated in future studies, for characterizing the neuropsychological profile of children with ARND. By describing the procedures at this preliminary stage of our work, the goal is to draw attention to this neglected topic and to suggest a model that can be replicated and validated by others, and to provide the first systematic clinical report on diagnosing ARND in Canada. PROCEDURES: On the basis of the literature, parents' descriptions and the authors' own experience with ARND, a profile of neuropsychological characteristics, including both deficits and assets, that are associated with prenatal alcohol exposure was hypothesized. A group of children was then evaluated, mostly adoptees or children in foster care, who were referred for learning and behavioural problems potentially associated with gestational exposure. Their results were submitted to a profile analysis by comparing their deficits and assets according to a list describing a hypothetical ARND profile to determine whether each child fit or did not fit the ARND profile. Groups were compared for background characteristics, FAS symptomatology, and results on specific neuropsychological and behavioural tests. Finally, the characteristics most strongly differentiating the two groups were identified. SETTING: Hospital-based outpatient program. PARTICIPANTS: Fifty-two children aged four to 18 years who were referred for a diagnostic assessment related to suspected or known prenatal alcohol exposure. OUTCOME MEASURES: Each child's assessment results were compared against a list of 21 deficits and six assets by two independent raters. Children with an average of more than 60% deficits and 50% assets were considered to have ARND, while the remainder were not. RESULTS: Twenty-eight children (54%) were assigned to the ARND group and 24 to the non-ARND group. The groups did not differ in physical features or home background characteristics, with the exception of higher parental intelligence quotient in the non-ARND group. The ARND group was more likely to have repeated a grade or received special education and scored lower on standardized measures of intelligence, language and memory abilities. Frequency of behaviour or social problems were equivalent in both groups. CONCLUSIONS: A profile approach used to identify children with ARND discriminates problems in neuropsychological but not behavioural domains. Because elevated scores on behavioural tasks in both ARND and non-ARND groups were clinically significant, more research is needed to identify what behavioural problems are unique to children with ARND compared with other clinic-referred children.

Adolescent↗

Piracetam therapy does not enhance cognitive functioning in children with down syndrome.

BACKGROUND: Piracetam is widely used as a purported means of improving cognitive function in children with Down syndrome. Its efficacy, however, has not been rigorously assessed. OBJECTIVE: To determine whether 4 months of piracetam therapy (80-100 mg/kg per day) enhances cognitive function in children with Down syndrome. DESIGN: A randomized, double-blind, placebo-controlled crossover study. PARTICIPANTS AND METHODS: Twenty-five children with Down syndrome (aged 6.5-13 years) and their caregivers participated. After undergoing a baseline cognitive assessment, children were randomly assigned to 1 of 2 treatment groups: piracetam-placebo or placebo-piracetam. MAIN OUTCOME MEASURE: The difference in performance while taking piracetam vs while taking placebo on tests assessing a wide range of cognitive functions, including attention, learning, and memory. RESULTS: Eighteen children completed the study, 4 withdrew, and 3 were excluded at baseline. Piracetam therapy did not significantly improve cognitive performance over placebo use but was associated with central nervous system stimulatory effects in 7 children: aggressiveness (n = 4), agitation or irritability (n = 2), sexual arousal (n = 2), poor sleep (n = 1), and decreased appetite (n = 1). CONCLUSION: Piracetam therapy did not enhance cognition or behavior but was associated with adverse effects.

Adolescent↗

Where and what visuospatial processing in adolescents with congenital hypothyroidism.

Visuospatial processing is accomplished in distinct neuroanatomic pathways. One such pathway, known as the where pathway, involves a dorsal route through magnocellular thalamic cells to occipital and parietal cortices and conveys location and motion information. A second pathway, known as the what pathway, involves a ventral route through parvocellular thalamic cells to occipital and temporal cortices and conveys color and form information. The where pathway is thought to be responsible for processing spatial relationships while the what pathway is responsible for object identification. Children with early-treated congenital hypothyroidism (CH) who exhibit selective visuospatial deficits may provide a good model to study the differential development of these pathways. Because children with CH lacked thyroid hormone at a time when needed by developing brain regions such as the parietal cortex, these children may be affected to a greater degree on tasks tapping where but not what pathway processing. We tested this hypothesis via retrospective analysis of their performance on 6 spatial tasks. Compared were 49 adolescents with CH and 49 matched control participants. On the basis of confirmatory factor analysis, tasks were assigned to either where or that pathway groupings. A repeated measures ANOVA showed the CH group was impaired relative to a normal comparison group only on where pathway tasks. Regression analyses indicated that severity of early hypothyroidism was the strongest predictor of where pathway processing but had no effect on what pathway tasks. It is concluded that thyroid hormone is required during late gestation and early life for the normal development of the where aspects of visuospatial processing.

Adolescent↗

The influence of etiology and treatment factors on intellectual outcome in congenital hypothyroidism.

To determine the effects of hypothyroidism and hormonal patterns on outcome, we tested 65 7- to 12-year-old children with congenital hypothyroidism using standardized tests of intelligence, neuropsychological functioning, memory, and achievement. Results were analyzed by etiology, time to thyrotropin normalization, and hormone levels at testing. Children with athyreosis scored below other etiologies on visuospatial, attention, and arithmetic indices. Children whose thyroid-stimulating hormone levels normalized by 1 to 2 months of age scored higher than later normalizers on indices of visual memory, attention, and arithmetic. Normalization of thyroid-stimulating hormone by 3 months of age was associated with better memory and learning abilities than later normalization. Thyroid hormone levels at testing were correlated with indices of sensorimotor, spatial, and language abilities. Two children with persistently elevated thyrotropin levels were not adversely affected. Present findings signify the need to establish etiology, normalize thyrotropin early, and maintain hormone levels in the normal range throughout childhood in children with congenital hypothyroidism.

Age Factors↗

Relationship of etiology to treatment in congenital hypothyroidism.

We examined the patterns of TSH, T(4), and treatment schedules from diagnosis to 4 yr of age in 125 children (50 males anf 75 females) with congenital hypothyroidism (CH). Subjects were divided into 3 groups based on their thyroid scans: 1) athyreosis (n = 31), 2) dysgenesis (n = 54; 49 lingual and 5 hypoplastic), and 3) dyshormonogenesis (n = 40). Follow-up evaluation was carried out at 2-4 wk and 3, 6, 9, 12, 24, 36, and 48 months of age. Median gestational age, age at onset of therapy, and starting L-T(4) dose were similar in the three groups. In infants with athyreosis median screening TSH levels were higher (P < 0.02) and confirmatory T(4) levels were lower than in the other two groups (P < 0.01 vs. dysgenetic; P < 0.05 vs. dyshormonogenetic CH). During the first 6 months of therapy, mean TSH levels were highest in the athyrotic group, intermediate in the dysgenetic group, and lowest in the dyshormonogenetic group. In children with athyreosis, TSH levels normalized by 12 months of age. At 12 months dysgenetic patients had the highest TSH levels (P < 0.05). During the entire study period, TSH levels were lowest in patients with dyshormonogenesis (except at 48 months) and normalized earlier. Mean T(4) levels normalized by 2-4 weeks in all groups. At 3 and 6 months, the percentage of patients who required dose changes was highest in the athyrotic group, and at 12 months it was highest in the dysgenetic group. The athyrotic group received the highest dose of L-T(4), and dyshormonogenetic group received the lowest dose. We conclude that treatment and follow-up schedules for CH may differ in the three etiological categories based on the different hormonal patterns and responses to therapy. Children with athyreosis need close monitoring particularly early in life, whereas those with dysgenesis and dyshormonogenesis require more attention later in life.

Child, Preschool↗

Neurodevelopment of adopted children exposed in utero to cocaine: the Toronto Adoption Study.

BACKGROUND: Published studies of children's neurodevelopment after in utero exposure to cocaine have not separated intrauterine from postnatal environmental effects as cocaine-using mothers cluster in low socioeconomic classes and have other risk factors. METHODS: To overcome this limitation, a study was done to assess physical and neurodevelopmental characteristics of 52 children: 26 were adopted by parents who sought counselling in the Motherisk Program at the University of Toronto for prenatal cocaine exposure, and 26 were controls matched for maternal intelligence quotient (IQ), socioeconomic status and gestational age. MAIN OUTCOME MEASURES: Head circumference, McCarthy General Cognitive Index (GCI) score, language performance and temperament tests. RESULTS: The children in the study group had smaller head circumferences (34th versus 54th percentiles p = 0.009), lower McCarthy GCI scores (102.8 versus 114.2, p = 0.02), poorer receptive and expressive language performance on the Reynell test, and higher activity levels, less persistence and increased distractibility on temperament tests. On multivariate analysis, cocaine exposure was significantly (p = 0.001) associated with lower IQ and poorer language development independent of intrauterine growth retardation and other potential confounders. INTERPRETATION: By controlling for postnatal environmental factors, this adoption study documents intrauterine developmental risks associated with cocaine exposure. Follow-up into school years is warranted to evaluate the extent of these effects.

Adoption↗

Hypothyroxinemia of prematurity and infant neurodevelopment: a pilot study.

To assess whether hypothyroxinemia has specific effects on neurodevelopment in premature infants, thyroid hormone levels were determined at 2 weeks of life and 40 weeks postconceptional age (PCA), and infants were evaluated at 3 months corrected age using the Bayley Scales of Infant Development and Early Infancy Temperament Questionnaire. Additional attention scales were derived from the factor analysis of relevant Bayley items. Fifteen infants born between 30 and 35 weeks and 21 full-term infants were studied. Results indicated no group differences on the Bayley or derived attention scales, whereas the temperament questionnaire revealed lower sensory thresholds and greater reactivity in the preterm group. The preterm group had normal thyroxine (T4) levels at 2 weeks of age, which declined by 40 weeks PCA for both free T4 (p < .01 for reference value and p < .0001 for gestational age-adjusted value) and total T4 (p < .05 for age-adjusted value). Correlations revealed that higher 40-week PCA free T4 levels were associated with better attentiveness ratings (p < .01 for reference and p < .0001 for gestational-age values) and sustained attention (p < .05) and higher 40-week total T4 with better motor skills (p < .05 for gestational-age value). These findings signify that a mild degree of hypothyroxinemia is evident in preterm infants without neurological risk and predicts subsequently poorer cognitive and motor abilities.

Brain↗

Effect of methylphenidate on attention in children with attention deficit hyperactivity disorder (ADHD): ERP evidence.

Methylphenidate is the most common treatment for attention deficit hyperactivity disorder (ADHD) and has been shown to improve attention and behaviour. However, the precise nature of methylphenidate on specific aspects of attention at different dose levels remains unclear. We studied methylphenidate effects in ADHD from a neurophysiological perspective, recording event-related potentials (ERPs) during attention task performance in normal controls and children with ADHD under different dose conditions. Twenty children with ADHD and 20 age matched controls were assessed with a continuous performance task requiring subjects to identify repeating alphabetic characters. ERPs and behavioural measures were recorded and analyzed for trials where a correct response was made. The ADHD group was assessed off drug (baseline) and on placebo, low (0.28 mg/kg) and high (0.56 mg/kg) dose levels of methylphenidate. The results showed that the ADHD group at baseline was more impulsive and inattentive than controls and had shorter P2 and N2 latencies and longer P3 latencies. Low dose methylphenidate was associated with reduced impulsivity (fewer false alarms) and decreased P3 latencies, whereas the higher dose level was associated with reduced impulsivity and less inattention (more hits), as well as increased P2 and N2 latencies and decreased P3 latencies. Amplitudes were unaffected and there were no adverse effects of the higher dose for any of the children. These results suggest differential dosage effects and a dissociation between dose levels and aspects of processing.

Attention↗

Long-term neurodevelopmental risks in children exposed in utero to cocaine. The Toronto Adoption Study.

Children exposed in utero to cocaine are at risk for long-term neurobehavioral damage not just because of the drug itself; but also because of clustering of other health determinants, including low socioeconomic status, low maternal education, and maternal addiction, to mention a few. One methodologic approach to separate the direct neurotoxic effects of cocaine from these synergistic insults is to follow up a cohort of children exposed in utero to cocaine and given up for adoption to middle-upper class families. The Toronto Adoption Study, supported by Health Canada, has proven the direct neurotoxic effects of cocaine on IQ and language. These effects are mild to moderate as compared to those measured in children exposed in utero to cocaine and reared by their natural mothers.

Adoption↗

Neurodevelopment of children exposed in utero to antidepressant drugs.

BACKGROUND: Many women of reproductive age have depression, necessitating therapy with either a tricyclic antidepressant drug or a drug, such as fluoxetine, that inhibits the reuptake of serotonin. Whether these drugs affect fetal neurodevelopment is not known. METHODS: We studied the children of 80 mothers who had received a tricyclic antidepressant drug during pregnancy, 55 children whose mothers had received fluoxetine during pregnancy, and 84 children whose mothers had not been exposed during pregnancy to any agent known to affect the fetus adversely. The children's global IQ and language development were assessed between 16 and 86 months of postnatal age by age-appropriate Bayley Scales of Infant Development or the McCarthy Scales of Children's Abilities (for IQ) and the Reynell Developmental Language Scales. RESULTS: The mean (+/-SD) global IQ scores were 118+/-17 in the children of mothers who received a tricyclic antidepressant drug, 117+/-17 in those whose mothers received fluoxetine, and 115+/-14 in those in the control group. The language scores were similar in all three groups. The results were similar in children exposed to a tricyclic antidepressant drug or fluoxetine during the first trimester and those exposed throughout pregnancy. There were also no significant differences in temperament, mood, arousability, activity level, distractibility, or behavior problems in the three groups of children. CONCLUSIONS: In utero exposure to either tricyclic antidepressant drugs or fluoxetine does not affect global IQ, language development, or behavioral development in preschool children.

Adult↗

Attentional functioning in children and adolescents with IDDM.

OBJECTIVE: To determine whether specific attentional cognitive processes are disrupted in children and adolescents with IDDM. RESEARCH DESIGN AND METHODS: We tested 103 children and adolescents with IDDM and 100 healthy control subjects (age range 9.3-18.3 years) for intelligence and attention. Subjects were given multiple clinical tests of attention and a computerized vigilance test, all of which served to provide information about multiple components of attentional processing. Specific components studied were the abilities to focus, select, shift, suppress, inhibit, and sustain attention. A diabetic history was obtained for the IDDM group, and blood glucose levels were determined before and after computerized attention testing. RESULTS: Across tests, IDDM subjects differed from control subjects only in the select component of attention, which was accounted for mainly by the poorer performance of children with early-onset diabetes (< 6 years). When subgrouped by history of seizures from hypoglycemia, those having had seizures demonstrated a lower verbal IQ and greater difficulty with select, focus, and inhibit attentional components, whereas sustain, suppress, and shift attentional components were unaffected. Correlation analyses showed that higher concurrent blood glucose levels were associated with less adequate ability to inhibit impulsive responses, whereas multiple regression analyses indicated that inhibit and focus were best predicted by onset age and concurrent blood glucose. CONCLUSIONS: In children and adolescents with IDDM, attention is poorer in several but not all aspects of attention; these aspects are affected by a history of seizures from hypoglycemia and higher ambient blood glucose levels at time of testing. These results suggest both organizational and activational effects of diabetes on specific subcomponents of attention in diabetes.

Adolescent↗

Long-term sequelae of hearing impairment in congenital hypothyroidism.

Hearing loss and its functional consequences were evaluated retrospectively in children with congenital hypothyroidism. From a cohort of 101 children followed longitudinally to evaluate newborn screening, 75 with previous hearing tests were studied. Fifteen (20%) were found to have hearing problems. Of these, nine had unilateral or sensorineural loss mostly at high frequencies, five had a conductive loss, and one had both problems. Hearing impaired children differed from children with normal hearing in age of treatment onset (22 vs 14 days) but not disease severity or duration. A comparison of language and auditory processing skills at ages 3, 5, and 7 years revealed that early speech was delayed in hearing impaired children, whereas deficits persisted in later receptive language and auditory discrimination skills. Comparing hearing impaired children and children with normal hearing with matched control subjects at grade 3 showed that hearing impaired children were poorer readers because of less adequate phonologic processing skills.

Child↗

Thyroid hormone and attention in school-age children with congenital hypothyroidism.

The relationship between attention and thyroid hormone was examined using a retrospective database of 85 7-year-old children with congenital hypothyroidism who received psychological evaluations and thyroid function tests on the same day. Four unique subgroups with different levels of thyroxine and thyrotropin were compared on psychological tasks and measures of attention. Children with high levels of both hormones were found to be significantly more distractable on an index of cognitive attention but were reportedly less hyperactive. Level of thyroxine accounted for over 10% of the variance in attention.

Attention↗

The psychoeducational profile of boys with Klinefelter syndrome.

Klinefelter syndrome (KS) affects about 1 in 900 males due to an extra X chromosome. Although there are no obvious physical features associated with childhood KS, many boys demonstrate a cognitive deficit in verbal processing. The first section of this article integrates the extant literature on intelligence and achievement outcomes in boys with KS. The second section presents our findings from a 20-year study involving one of the largest unselected cohorts of boys with KS. We followed 36 boys with KS and 33 sibling controls from 6 until 20 years of age. Boys with KS are shown to demonstrate a verbal cognitive deficit and significant underachievement in reading and spelling, as well as in arithmetic. These problems, which are evident from early school years, increase with age such that by late adolescence, boys with KS are four to five grade levels behind. In addition, we also found that they were most likely to have a generalized type of learning disability, with very few boys indicating a pure reading or pure arithmetic problem. They also showed deficits in written language skills and acquisition of knowledge-based subject material were also problematic. Despite significant underachievement and frequent grade failure, many boys with KS had completed high school, and a few were also pursuing postsecondary educations. The discussion section examines how their language-based disability affects comprehension and learning, leading to underachievement.

Achievement↗