Biomedical subjects

K N Botteron

Publications and source records attributed to K N Botteron.

10 recordsLinked to original sources

PubMed2001

Is attention-deficit/hyperactivity disorder an energy deficiency syndrome?

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable yet clinically heterogeneous syndrome associated with hypocatecholamine function in subcortical and prefrontal cortical regions and clinical response to medications that enhance catecholamine function. The goal of this article is to present a hypothesis about the etiology of ADHD by synthesizing these findings with recent experiments indicating that activity-dependent neuronal energy consumption is regulated by cortical astrocytes. The scientific literature was searched from 1966 to the present using MEDLINE and relevant key words. Inattention and impulsivity may be related to hypofunctionality of catecholamine projection pathways to prefrontal cortical areas, resulting in decreased neuronal energy availability. This may be mediated by astrocyte catecholamine receptors that normally regulate energy availability during neuronal activation. At least some forms of ADHD may be viewed as cortical, energy-deficit syndromes secondary to catecholamine-mediated hypofunctionality of astrocyte glucose and glycogen metabolism, which provides activity-dependent energy to cortical neurons. Several tests of this hypothesis are proposed.

Astrocytes↗

PubMed2001

Validating cortical surface analysis of medial prefrontal cortex.

This paper describes cortical analysis of 19 high resolution MRI subvolumes of medial prefrontal cortex (MPFC), a region that has been implicated in major depressive disorder. An automated Bayesian segmentation is used to delineate the MRI subvolumes into cerebrospinal fluid (CSF), gray matter (GM), white matter (WM), and partial volumes of either CSF/GM or GM/WM. The intensity value at which there is equal probability of GM and GM/WM partial volume is used to reconstruct MPFC cortical surfaces based on a 3-D isocontouring algorithm. The segmented data and the generated surfaces are validated by comparison with hand segmented data and semiautomated contours, respectively. The L(1) distances between Bayesian and hand segmented data are 0.05-0.10 (n = 5). Fifty percent of the voxels of the reconstructed surface lie within 0.12-0.28 mm (n = 14) from the semiautomated contours. Cortical thickness metrics are generated in the form of frequency of occurrence histograms for GM and WM labelled voxels as a function of their position from the cortical surface. An algorithm to compute the surface area of the GM/WM interface of the MPFC subvolume is described. These methods represent a novel approach to morphometric chacterization of regional cortex features which may be important in the study of psychiatric disorders such as major depression.

Adult↗

PubMed2001

Obsessive-compulsive scale of the child behavior checklist: specificity, sensitivity, and predictive power.

OBJECTIVE: To create an obsessive-compulsive disorder subscale (OCS) of the Child Behavior Checklist (CBCL) and to determine its internal consistency, sensitivity, specificity, and positive and negative predictive power to identify obsessive-compulsive disorder (OCD) in children and adolescents. METHODS: Three samples of equal size (n = 73) of children and adolescents, matched for age, gender, and race, were selected for these analyses: 1) a clinically ascertained OCD group, 2) a psychiatrically treated group whose records revealed no evidence of OCD, and 3) a general population control group. An OCS was created by applying factor analysis to 11 CBCL items. Examinations of internal consistency, sensitivity, specificity, and positive and negative predictive value were undertaken. RESULTS: Of 11 items hypothesized to predict OCD, 8 items were retained after factor analyses (smallest factor loading: 0.49) and used to calculate OCS scores. The retained items displayed excellent internal consistency (Cronbach's alpha coefficient = 0.84). OCD participants had significantly higher OCS scores than either psychiatrically treated or general population control groups. With the use of the 2 cutoff scores closest to the true rate of OCD in the overall sample, sensitivity was 75.3% to 84.9%, specificity was 82.2% to 92.5%, positive predictive value was 70.5% to 83.3%, and negative predictive value was 88.2% to 91.6%. CONCLUSION: The performance of the proposed CBCL OCS compares favorably with that of the only previously studied screening instrument for OCD, the Leyton Obsessional Inventory-Child Version. Unlike the Leyton Obsessional Inventory-Child Version, the CBCL is already in widespread use as a screen for most other forms of psychopathology. As the performance of the CBCL OCS will need to be replicated in other sample populations, data with various cutoff levels are provided to enable investigators and clinicians to tailor its use to specific study populations.

Adolescent↗

PubMed2001

Genetic analysis of brain imaging abnormalities.

A number of child psychiatric disorders have recently been associated with specific structural brain abnormalities. This article discusses the advantages of neuroimaging for genetic studies, such as clarifying etiologic heterogeneity and establishing pathophysiology. The advantages of twin or family designs for neuroimaging investigations are also discussed.

Adolescent↗

PubMed2001

Family, genetic, and imaging studies of early-onset depression.

As with other psychiatric disorders, most studies dealing with the familiality and genetics of depression have been limited to adults; however, several studies suggest that there is continuity between childhood- and adolescent-onset depression and adult depression. More direct estimates of the heritability of depressive symptoms or episodes in children and adolescents are compatible with the genetic contributions being greater than 50%. A number of functional and structural imaging studies have implicated particular circuitry as being involved in the generation of emotion and depression. Imaging studies of twins have suggested that regional brain volume and characteristics of brain shape are heritable. This suggests that a potentially important new avenue of research will be the correlation of the genetics of brain structure and/or function with the genetics of depression. Preliminary studies of adolescent and young adult twins suggest a significant correspondence between the genetic contributions to some regional brain volumes and early-onset depression.

Adolescent↗

PubMed2000

Bayesian construction of geometrically based cortical thickness metrics.

This paper describes the construction of cortical metrics quantifying the probabilistic occurrence of gray matter, white matter, and cerebrospinal fluid compartments in their correlation to the geometry of the neocortex as measured in 0.5-1.0 mm magnetic resonance imagery. These cortical profiles represent the density of the tissue types as a function of distance to the cortical surface. These metrics are consistent when generated across multiple brains indicating a fundamental property of the neocortex. Methods are proposed for incorporating such metrics into automated Bayes segmentation.

Anthropometry↗

PubMed1997

Refractory depression in children and adolescents.

Refractory or treatments resistant depression in child and adolescent populations is a difficult construct to operationalize currently. To date, only one of the small number of completed double-blind placebo-controlled treatment investigations have not demonstrated a significant effect of antidepressants in comparison to placebo. However, it has been established that child and adolescent MDD is a serious disorder that appears to have clinical continuity with adult affective disorders and is generally of long duration with high rates of recurrence and eventual progression to mania, substance abuse, or other serious psychopathology. In addition, families of children with affective disorders evidence substantial genetic loading with high rates of affective disorders contributing both genetic vulnerability and potential environmental risk as well. There have been no empirically identified treatments that alter the long-term course of the illness. Thus treatment resistance is a significant issue for this population. This review will focus on controlled treatment trials and will examine the potential relevance of psychosocial impairment, genetic-familial risk, and neuromorphometric brain differences to treatment resistance in children and adolescents with major depression.

Adolescent↗

PubMed1996

Treatment-resistant depression in children and adolescents.

Treatment resistance in depressed children and adolescents cannot yet be defined fully because of the paucity of controlled studies that demonstrate efficacy. Therefore, this article addresses several of the age-specific, developmental considerations that may impinge upon treatment response. Areas covered include familial-genetic, psychosocial, and neuroimaging studies in addition to a review of controlled studies to date.

Adolescent↗

PubMed1995

Preliminary study of magnetic resonance imaging characteristics in 8- to 16-year-olds with mania.

OBJECTIVE: To examine magnetic resonance imaging (MRI) characteristics in children and adolescents with mania according to DSM-III-R criteria. METHOD: A convenience sample of consecutively referred 8- to 16-year-old manic (n = 10) and normal (n = 5) subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode Version, the Children's Global Assessment Scale, and the Family History-Research Diagnostic Criteria. MRI scans were obtained from unsedated subjects using a 1.5 T MR scanner to acquire T1-weighted coronal and sagittal images and T2-weighted axial images. Images were assessed by blind clinical interpretation, ratings of T2-weighted deep white matter hyperintensities and petalia, and computer-assisted volumetric analysis of ventricular and cerebral volumes. RESULTS: Eight of 10 manic subjects and all 5 controls completed the scans. Scans of 4 manic subjects and 1 control subject showed ventricular or white matter abnormalities by clinical interpretation. Significant findings were positive correlations between increasing age and both right and left ventricular volumes. Two of the 8 manic subjects and no controls had confluent subcortical hyperintensities. CONCLUSIONS: MRI brain scanning was feasible in 8- to 16-year-olds. Preliminary findings from clinical interpretations and structured ratings suggest structural differences between young manic and normal subjects. Investigations of larger samples are needed to better characterize the differences.

Adolescent↗

PubMed1992

MRI abnormalities in adolescent bipolar affective disorder.

There is increasing evidence for structural differences in the brains of patients with affective disorders. Recent magnetic resonance imaging (MRI) studies have reported focal signal hyperintensities in the deep white matter of bipolar patients. These previous reports had focused on adult patients with prior episodes of illness. In this case report, the authors discuss a young adolescent patient during her first episode of mania and the finding of subcortical focal signal hyperintensities on brain MRI. The etiology, pathophysiology, and clinical correlates of these lesions will be reviewed.

Adolescent↗