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J N Giedd

Publications and source records attributed to J N Giedd.

At least 37 records · Page 2Linked to original sources

Structural maturation of neural pathways in children and adolescents: in vivo study.

Structural maturation of fiber tracts in the human brain, including an increase in the diameter and myelination of axons, may play a role in cognitive development during childhood and adolescence. A computational analysis of structural magnetic resonance images obtained in 111 children and adolescents revealed age-related increases in white matter density in fiber tracts constituting putative corticospinal and frontotemporal pathways. The maturation of the corticospinal tract was bilateral, whereas that of the frontotemporal pathway was found predominantly in the left (speech-dominant) hemisphere. These findings provide evidence for a gradual maturation, during late childhood and adolescence, of fiber pathways presumably supporting motor and speech functions.

Adolescent↗

Progressive cortical change during adolescence in childhood-onset schizophrenia. A longitudinal magnetic resonance imaging study.

BACKGROUND: Adolescence provides a window to examine regional and disease-specific late abnormal brain development in schizophrenia. Because previous data showed progressive brain ventricular enlargement for a group of adolescents with childhood-onset schizophrenia at 2-year follow-up, with no significant changes for healthy controls, we hypothesized that there would be a progressive decrease in volume in other brain tissue in these patients during adolescence. METHODS: To examine cortical change, we used anatomical brain magnetic resonance imaging scans for 15 patients with childhood-onset schizophrenia (defined as onset of psychosis by age 12 years) and 34 temporally yoked, healthy adolescents at a mean (SD) age of 13.17 (2.73) years at initial baseline scan and 17.46 (2.96) years at follow-up scan. Cortical gray and white matter volumes were obtained with an automated analysis system that classifies brain tissue into gray matter, white matter, and cerebrospinal fluid and separates the cortex into anatomically defined lobar regions. RESULTS: A significant decrease in cortical gray matter volume was seen for healthy controls in the frontal (2.6%) and parietal (4.1%) regions. For the childhood-onset schizophrenia group, there was a decrease in volume in these regions (10.9% and 8.5%, respectively) as well as a 7% decrease in volume in the temporal gray matter. Thus, the childhood-onset schizophrenia group showed a distinctive disease-specific pattern (multivariate analysis of variance for change X region X diagnosis: F, 3.68; P = .004), with the frontal and temporal regions showing the greatest between-group differences. Changes in white matter volume did not differ significantly between the 2 groups. CONCLUSIONS: Patients with very early-onset schizophrenia had both a 4-fold greater decrease in cortical gray matter volume during adolescence and a disease-specific pattern of change. Etiologic models for these patients' illness, which seem clinically and neurobiologically continuous with later-onset schizophrenia, must take into account both early and late disruptions of brain development.

Adolescent↗

Development of the human corpus callosum during childhood and adolescence: a longitudinal MRI study.

1. Interest in the morphologic development of the corpus callosum (CC) during childhood and adolescence stems from adolescent changes in cognitive functions subserved by the CC, reports of CC anomalies for a wide variety of childhood neuropsychiatric illnesses, and controversy regarding sexual dimorphism. 2. Characterization of the normal developmental pattern of the CC is hindered by enormous variability of its size. This is especially problematic for cross-sectional studies seeking to assess possible non-linear developmental curves. 3. To more accurately characterize developmental changes, a longitudinal brain magnetic resonance imaging study with subjects rescanned at approximately 2 year intervals was conducted resulting in 251 scans from 139 healthy children and adolescents. 4. Midsagittal area of the CC, especially the posterior regions, increased robustly from ages 5 to 18 years. 5. Although the genu of the CC was significantly larger in males there were no sex differences in mean area after adjustment for total cerebral volume and the growth patterns did not differ between sexes. 6. Analysis revealed a non-linear increase in the splenium, the most posterior region, with increases greatest in the younger years. 7. The results of this longitudinal study, in addition to confirming and extending previous cross-sectional reports, provide an increasingly accurate yardstick from which to assess pathological development.

Adolescent↗

Clinical and neurobiological correlates of cytogenetic abnormalities in childhood-onset schizophrenia.

OBJECTIVE: Cytogenetic abnormalities are increased in schizophrenia, suggesting a possible etiologic contribution. However, their clinical and pathophysiologic roles in the disorder are unknown. To investigate this, a group of children and adolescents participating in a comprehensive study of childhood-onset schizophrenia were screened for chromosomal abnormalities, and their clinical and neurobiological correlates were examined. METHOD: Cytogenetic screening with the use of high-resolution banding, fluorescent in situ hybridization for chromosome 22q11 deletions, and molecular fragile X testing was undertaken in a group of 47 children and adolescents with very early onset of schizophrenia. Clinical, neurobiological (including brain morphometry), and risk factor measures of the subjects with cytogenetic abnormalities were compared with those of the remaining patients without cytogenetic anomalies. RESULTS: Five patients had previously undiagnosed cytogenetic abnormalities. Lower performance IQ and more pronounced premorbid developmental impairments were seen in this subgroup. Rates of obstetric complications, familial schizophrenia spectrum disorders, and familial eye tracking dysfunction were similar for the patients with and without cytogenetic abnormalities. CONCLUSIONS: Cytogenetic abnormalities appear to be increased in childhood-onset schizophrenia, suggesting an association with a very early age at onset. The data from the subgroup of patients with cytogenetic anomalies are consistent with a model in which a childhood onset of schizophrenia is due to a greater impairment of neurodevelopment secondary to the interaction of a number of factors, particularly genetic ones.

Adolescent↗

Obstetrical complications and childhood-onset schizophrenia.

OBJECTIVE: Increased obstetrical complications have been reported in individuals with adult-onset schizophrenia, with several studies finding an association between such complications and an earlier age at onset. Consequently, obstetrical records were examined for individuals with childhood-onset schizophrenia to determine if birth complications were more prevalent. METHOD: The birth records of 36 patients with childhood-onset schizophrenia and 35 sibling comparison subjects were rated for birth complications by two psychiatrists who were unaware of group membership. RESULTS: There were no significant differences between the groups in rates of obstetrical complications. Patients with such complications did not have a relatively earlier age at onset of schizophrenia. CONCLUSIONS: A very early age at onset of schizophrenia is probably not due to birth complications.

Age of Onset↗

Lack of an association between a dopamine-4 receptor polymorphism and attention-deficit/hyperactivity disorder: genetic and brain morphometric analyses.

Although the etiology of attention-deficit/hyperactivity disorder (ADHD) is likely multifactorial, family, adoption, and twin studies suggest that genetic factors contribute significantly. Polymorphisms of the dopamine 4 receptor (DRD4) affect receptor binding, and one allele with seven tandem repeats in exon 3 (DRD4*7R) has been associated with ADHD. We examined this putative association in 41 children with severe ADHD and 56 healthy controls who were group matched for ethnicity and sex. The frequency of the DRD4*7R allele did not vary by diagnosis (0.220 vs 0.205 in patients and controls, respectively). Behavioral and brain anatomic MRI measures, previously found to discriminate patients from controls, did not differ significantly between subjects having and those lacking a DRD4*7R allele. These data do not support the reported association between DRD4*7R and the behavioral or brain morphometric phenotype associated with ADHD.

Alleles↗

Case series: pediatric seasonal affective disorder. A follow-up report.

Six subjects who as children had received a diagnosis of seasonal affective disorder consented to participate in a 7-year follow-up study. Structured and semistructured interviews were conducted to assess the course of illness, response to treatment, and current clinical state. Seasonal patterns of symptoms and response to light therapy remained relatively stable over a 7-year period. Two subjects were using adjunctive fluoxetine. Seasonal affective disorder can occur in children and adolescents, responds to light therapy, and should be considered in the differential diagnosis of pediatric affective symptoms or cyclic school performance.

Adolescent↗

Progressive reduction of temporal lobe structures in childhood-onset schizophrenia.

OBJECTIVE: A previous cross-sectional study of brain morphology in childhood-onset schizophrenia indicated sparing of the temporal lobes from processes reducing total cerebral volume in this population. In the present study, subjects with childhood-onset schizophrenia and healthy subjects were rescanned at 2-year follow-up to determine whether this pattern of temporal lobe sparing persists with ongoing illness. METHOD: Anatomic brain magnetic resonance imaging scans were acquired for 10 adolescent patients with average onset of schizophrenia at 10.4 years (SD = 1.7) and 17 healthy adolescents. Scans were obtained on initial admission and at 2-year follow-up by using identical equipment and measurement methodology. RESULTS: Schizophrenic subjects showed significantly greater decreases than healthy subjects in right temporal lobe, bilateral superior temporal gyrus and posterior superior temporal gyrus, right anterior superior temporal gyrus, and left hippocampal volumes during the follow-up interval. Decline in right posterior superior temporal gyrus was associated with high total scores on the Scale for the Assessment of Positive Symptoms at baseline and at follow-up. CONCLUSIONS: Progressive reduction of temporal lobe structures occurs with ongoing illness in childhood-onset schizophrenia.

Adolescent↗

Frequency and severity of enlarged cavum septi pellucidi in childhood-onset schizophrenia.

OBJECTIVE: Patients with schizophrenia have been reported to have a higher frequency of enlarged cavum septi pellucidi (CSP) in comparison with normal subjects. Neurodevelopmental models of schizophrenia suggest that the more severe the brain dysgenesis, the earlier the onset of psychotic symptoms. Study of patients with childhood-onset schizophrenia allows the opportunity to test this hypothesis. METHOD: Two groups of subjects were evaluated: healthy volunteers (N=95, mean age=11.7 years) and patients with childhood-onset schizophrenia (N=24, mean age=14.6 years). Magnetic resonance images of 1-mm resampled contiguous brain slices were rated blind to diagnosis. The size of the CSP was recorded as the number of consecutive slices in which the CSP was present. Abnormal enlargement was defined as a CSP greater than 6 mm in length. RESULTS: The frequency of an enlarged CSP was significantly higher in the patient group: 12.5% (three of 24 subjects) versus 1.1% (one of 95 subjects). Also, two of the three patients with an enlarged CSP had complete nonfusion of the septal leaflets, a more severe anomaly than was found in the one comparison subject with an enlarged CSP and typically more severe than anomalies seen in groups with adult-onset schizophrenia. CONCLUSIONS: These findings suggest that patients with extremely early-onset (childhood) forms of schizophrenia may have more severe developmental brain anomalies than those with adult onset.

Adolescent↗

Cerebellum in attention-deficit hyperactivity disorder: a morphometric MRI study.

Clinical, neuroanatomic, neurobehavioral, and functional brain-imaging studies suggest a role for the cerebellum in cognitive functions, including attention. However, the cerebellum has not been systematically studied in attention-deficit hyperactivity disorder (ADHD). We quantified the cerebellar and vermal volumes, and the midsagittal areas of three vermal regions, from MRIs of 46 right-handed boys with ADHD and 47 matched healthy controls. Vermal volume was significantly less in the boys with ADHD. This reduction involved mainly the posterior inferior lobe (lobules VIII to X) but not the posterior superior lobe (lobules VI to VII). These results remained significant even after adjustment for brain volume and IQ. A cerebello-thalamo-prefrontal circuit dysfunction may subserve the motor control, inhibition, and executive function deficits encountered in ADHD.

Adolescent↗

Variability of human brain structure size: ages 4-20 years.

Understanding variability of human brain structure sizes during development is important for the design and interpretation of pediatric neuroimaging studies. In this study we analyze the effects of hemisphere, sex and age on size variability of the total cerebrum, cerebellum, lateral ventricles, temporal lobe, amygdala, hippocampus, superior temporal gyrus, corpus callosum, caudate, putamen, and globus pallidus in 115 healthy children and adolescents, ages 4-20 years. Variability differed significantly across structures, with the lateral ventricles demonstrating the highest coefficient of variation and the putamen the lowest. Males varied significantly more than females in the left cerebrum and left superior temporal gyrus, whereas females varied more than males in the right caudate and right putamen. Age effects were seen in increased variability after puberty for the lateral ventricles, hippocampus and superior temporal gyrus. These variances are important determinants of minimum sample sizes required to detect group differences in both cross-sectional and longitudinal studies.

Adolescent↗

Quantitative magnetic resonance imaging of the corpus callosum in childhood onset schizophrenia.

Corpus callosum size has been found to be abnormal in adult schizophrenia, and other studies have implicated abnormal interhemispheric communication in this disorder. To assess continuity with brain abnormalities in the later onset disorder and to further localize brain maldevelopment, this structure was examined in a unique sample of childhood onset schizophrenics. Anatomic brain magnetic resonance imaging scans were acquired for 25 patients (mean age 13.9 +/- 2.1) who had onset of schizophrenia by age 12 (mean age at onset 9.9 +/- 1.9) and 55 normal children. The midsagittal area of the corpus callosum was divided into seven sections. With no adjustment for brain volume, no diagnostic differences were observed. After adjustment for the smaller cerebral volume of the schizophrenics, larger total, anterior and posterior corpus callosum areas emerged for the schizophrenics. These findings provide further evidence for continuity between childhood onset and later onset schizophrenia and support other studies showing white matter sparing in the context of decreased cortical volume.

Adolescent↗

A magnetic resonance imaging study of planum temporale asymmetry in men with developmental dyslexia.

BACKGROUND: Imaging studies have suggested anomalous anatomical asymmetries in language-related regions of the temporal and parietal lobes in individuals with developmental dyslexia. Autopsy studies have reported unusual symmetry of the planum temporale (PT) in patients with dyslexia. Methodological limitations characterize much of this literature, however. OBJECTIVE: To examine the size and asymmetry of the PT and its extension into the parietal lobe (planum parietale [PP]) in men with well-characterized, persistent dyslexia by using magnetic resonance imaging and 3-dimensional surface rendering techniques. METHODS: The brains of 16 right-handed dyslexic men aged 18 to 40 years and 14 matched control subjects were studied with magnetic resonance imaging. Most of these subjects were previously studied with positron emission tomography, which demonstrated functional abnormalities in temporal and parietal brain regions in the dyslexic group. The area of the PT was determined with the aid of 3-dimensional surface-rendering techniques. The size of the PP was estimated by measuring the length of the posterior ascending ramus on 3 parasagittal slices. RESULTS: Approximately 70% to 80% of both groups showed equivalent leftward (left > right) asymmetries of the PT; approximately 50% to 60% showed equivalent rightward (right > left) asymmetries of the PP. These asymmetries showed equivalent moderate inverse correlations with each other in both groups. CONCLUSIONS: These results challenge the notion that anomalous asymmetry of the PT is strongly associated with developmental dyslexia. Given the heterogeneity of the dyslexic population, some subgroup of dyslexic individuals (i.e., those with developmental language disorders) may show unusual symmetry or reversed asymmetry in this region. However, anomalous asymmetry of the planum did not contribute to functional abnormalities demonstrated in these patients by positron emission tomography.

Adolescent↗

Sexual dimorphism of the developing human brain.

1. Sexual dimorphism of human brain anatomy has not been well-studied between 4 and 18 years of age, a time of emerging sex differences in behavior and the sexually specific hormonal changes of adrenarche (the predominantly androgenic augmentation of adrenal cortex function occurring at approximately age 8) and puberty. 2. To assess sex differences in brain structures during this developmental period volumes of the cerebrum, lateral ventricles, caudate, putamen, globus pallidus temporal lobe, amygdala, and hippocampus, and midsagittal area measurements of the corpus callosum were quantified from brain magnetic resonance images of 121 healthy children and adolescent and examined in relation to age and sex. 3. Males had a 9% larger cerebral volume. When adjusted for cerebral volume by ANCOVA only the basal ganglia demonstrated sex differences in mean volume with the caudate being relatively larger in females and the globus pallidus being relatively larger in males. The lateral ventricles demonstrated a prominent sex difference in brain maturation with robust increases in size in males only. A piecewise-linear model revealed a significant change in the linear regression slope of lateral ventricular volume in males after age 11 that was not shared by females at that or other ages. 4. Amygdala and hippocampal volume increased for both sexes but with the amygdala increasing significantly more in males than females and hippocampal volume increasing more in females. 5. These sexually dimorphic patterns of brain development may be related to the observed sex differences in age of onset, prevalence, and symptomatology seen in nearly all neuropsychiatric disorders of childhood.

Adolescent↗

Online access to journal abstracts and articles.

Advances in information technology now offer several options for child and adolescent psychopharmacologists to navigate the increasingly complex terrain of scientific literature and keep abreast of the rapidly changing advances in our field. MEDLINE, the world's largest database of medical literature, can be accessed and searched by a variety of free or fee-based services. In addition to efficient retrieval of citations and abstracts based on subject, author, or title, many of these services now provide, for a fee, the entire text and graphics of articles (displayed on computer screen, faxed, or mailed). There are also current awareness services to alert the user when new requested literature become available as well as services to send via e-mail the tables of contents of requested journals (sometimes prior to paper publication). For online citation and abstract retrieval, we found that free services, such as PubMed, performed as good or better than fee-based services. Physicians' Online, sponsored by the pharmaceutical industry, offered the lowest price for full-text manuscript delivery. In this article, we review literature search, delivery, and update services and offer some tips on how to most effectively use these resources.

Child↗

Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine the relation between specific frontostriatal structures (prefrontal cortex and basal ganglia) and response inhibition deficits observed in attention-deficit/hyperactivity disorder (ADHD). METHOD: Children with ADHD and age-matched normal controls were scanned using magnetic resonance imaging (MRI) and tested on three response inhibition tasks. Behavioral performance was correlated with MRI-based anatomical measures of frontostriatal circuitry (prefrontal cortex and basal ganglia) implicated in ADHD. RESULTS: First, significant differences in performance by children with ADHD and normal volunteers were observed on all three response inhibition tasks. Second, performance on these tasks correlated only with those anatomical measures of frontostriatal circuitry observed to be abnormal in children with ADHD (e.g., the region of the prefrontal cortex, caudate, and globus pallidus, but not the putamen) in the authors' previous study. Third, significant correlations between task performance and anatomical measures of the prefrontal cortex and caudate nuclei were predominantly in the right hemisphere, supporting a role of right frontostriatal circuitry in response inhibition and ADHD. CONCLUSION: The data suggest a role of the right prefrontal cortex in suppressing responses to salient, but otherwise irrelevant events while the basal ganglia appear to be involved in executing these behavioral responses.

Adolescent↗

Controlled stimulant treatment of ADHD and comorbid Tourette's syndrome: effects of stimulant and dose.

OBJECTIVE: To determine the effects of methylphenidate (MPH) and dextroamphetamine (DEX) on tic severity in boys with attention-deficit/hyperactivity disorder (ADHD) comorbid with Tourette's syndrome. METHOD: A 9-week, placebo-controlled, double-blind crossover using a wide range of doses was completed by 20 subjects in three cohorts. RESULTS: Relatively high doses of MPH and DEX in the first cohort produced significant increases in tic severity which were sustained on higher doses of DEX but which attenuated on MPH. Overall, 14 of 20 subjects continued stimulant treatment for 1 to 3 years, generally in combination with other psychotropics. Stimulant-associated adverse effects, including tic exacerbations, were reversible in all cases. CONCLUSION: A substantial minority of comorbid subjects had consistent worsening of tics on stimulants, although the majority experienced improvement in ADHD symptoms with acceptable effects on tics. MPH was better tolerated than DEX.

Analysis of Variance↗