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Rob Nicolson

Publications and source records attributed to Rob Nicolson.

18 recordsLinked to original sources
PubMed2006

Detection and mapping of hippocampal abnormalities in autism.

Brain imaging studies of the hippocampus in autism have yielded inconsistent results. In this study, a computational mapping strategy was used to examine the three-dimensional profile of hippocampal abnormalities in autism. Twenty-one males with autism (age: 9.5+/-3.3 years) and 24 male controls (age: 10.3+/-2.4 years) underwent a volumetric magnetic resonance imaging scan at 3 Tesla. The hippocampus was delineated, using an anatomical protocol, and hippocampal volumes were compared between the two groups. Hippocampal traces were also converted into three-dimensional parametric surface meshes, and statistical brain maps were created to visualize morphological differences in the shape and thickness of the hippocampus between groups. Parametric surface meshes and shape analysis revealed subtle differences between patients and controls, particularly in the right posterior hippocampus. These deficits were significant even though the groups did not differ significantly with traditional measures of hippocampal volume. These results suggest that autism may be associated with subtle regional reductions in the size of the hippocampus. The increased statistical and spatial power of computational mapping methods provided the ability to detect these differences, which were not found with traditional volumetric methods.

Adolescent↗
PubMed2006

Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity.

BACKGROUND: Volumetric studies have reported reductions in the size of the corpus callosum (CC) in autism, but the callosal regions contributing to this deficit have differed among studies. In this study, a computational method was used to detect and map the spatial pattern of CC abnormalities in male patients with autism. METHODS: Twenty-four boys with autism (aged 10.0 +/- 3.3 years) and 26 control boys (aged 11.0 +/- 2.5 years) underwent a magnetic resonance imaging (MRI) scan at 3 Tesla. Total and regional areas of the CC were determined using traditional morphometric methods. Three-dimensional (3D) surface models of the CC were also created from the MRI scans. Statistical maps were created to visualize morphologic variability of the CC and to localize regions of callosal thinning in autism. RESULTS: Traditional morphometric methods detected a significant reduction in the total callosal area and in the anterior third of the CC in patients with autism; however, 3D maps revealed significant reductions in both the splenium and genu of the CC in patients. CONCLUSIONS: Statistical maps of the CC revealed callosal deficits in autism with greater precision than traditional morphometric methods. These abnormalities suggest aberrant connections between cortical regions, which is consistent with the hypothesis of abnormal cortical connectivity in autism.

Adolescent↗
PubMed2006

Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia.

CONTEXT: We previously detected a dynamic wave of gray matter loss in childhood-onset schizophrenia that started in parietal association cortices and proceeded frontally to envelop dorsolateral prefrontal and temporal cortices, including superior temporal gyri. OBJECTIVE: To map gray matter loss rates across the medial hemispheric surface, including the cingulate and medial frontal cortex, in the same cohort studied previously. DESIGN: Five-year longitudinal study. SETTING: National Institute of Mental Health, Bethesda, Md. Subjects Twelve subjects with childhood-onset schizophrenia, 12 healthy controls, and 9 medication- and IQ-matched subjects with psychosis not otherwise specified. INTERVENTIONS: Three-dimensional magnetic resonance imaging at baseline and follow-up. MAIN OUTCOME MEASURES: Gyral pattern and shape variations encoded by means of high-dimensional elastic deformation mappings driving each subject's cortical anatomy onto a group average; changes in cortical gray matter mapped by computing warping fields that matched sulcal patterns across hemispheres, subjects, and time. RESULTS: Selective, severe frontal gray matter loss occurred bilaterally in a dorsal-to-ventral pattern across the medial hemispheric surfaces in the schizophrenic subjects. A sharp boundary in the pattern of gray matter loss separated frontal regions and cingulate-limbic areas. CONCLUSION: Frontal and limbic regions may not be equally vulnerable to gray matter attrition, which is consistent with the cognitive, metabolic, and functional vulnerability of the frontal cortices in schizophrenia.

Adolescent↗
PubMed2006

A prospective, open-label trial of galantamine in autistic disorder.

OBJECTIVE: Post-mortem studies have reported abnormalities of the cholinergic system in autism. The purpose of this study was to assess the use of galantamine, an acetylcholinesterase inhibitor and nicotinic receptor modulator, in the treatment of interfering behaviors in children with autism. METHODS: Thirteen medication-free children with autism (mean age, 8.8 +/- 3.5 years) participated in a 12-week, open-label trial of galantamine. Patients were rated monthly by parents on the Aberrant Behavior Checklist (ABC) and the Conners' Parent Rating Scale-Revised, and by a physician using the Children's Psychiatric Rating Scale and the Clinical Global Impressions scale. RESULTS: Patients showed a significant reduction in parent-rated irritability and social withdrawal on the ABC as well as significant improvements in emotional lability and inattention on the Conners' Parent Rating Scale--Revised. Similarly, clinician ratings showed reductions in the anger subscale of the Children's Psychiatric Rating Scale. Eight of 13 participants were rated as responders on the basis of their improvement scores on the Clinical Global Impressions scale. Overall, galantamine was well-tolerated, with no significant adverse effects apart from headaches in one patient. CONCLUSION: In this open trial, galantamine was well-tolerated and appeared to be beneficial for the treatment of interfering behaviors in children with autism, particularly aggression, behavioral dyscontrol, and inattention. Further controlled trials are warranted.

Adolescent↗
PubMed2005

White matter abnormalities in autism detected through transverse relaxation time imaging.

While neuroimaging studies have reported neurobiological abnormalities in autism, the underlying tissue abnormalities remain unclear. Quantitative transverse relaxation time (T2) imaging permits the examination of tissue abnormalities in vivo, with increased T2 largely reflecting increased tissue water. Blood flow and the presence of tissue iron may also affect T2. In this study, we used voxel-based relaxometry of the cerebrum and global averages to examine T2 abnormalities in autism. Nineteen males with autism (age: 9.2 +/- 3.0 years) and 20 male controls (age: 10.7 +/- 2.9 years) underwent magnetic resonance imaging at 3.0 T. Quantitative T2 maps, generated through gradient echo sampling of the free induction decay and echo, were segmented into gray matter, white matter, and cerebrospinal fluid. Average cerebral gray and white matter T2 were determined and compared between groups. To assess localized T2 differences, the quantitative T2 maps were warped to a template created for this study, smoothed, and compared using statistical parametric mapping. Patients with autism had an increase in average cerebral white matter T2, although no group differences were seen in average cerebral gray matter T2. Patients with autism also had bilateral regional T2 increases in the gray matter and associated white matter of the parietal lobes (primary sensory association areas) and occipital lobes (visual association areas) and in the white matter within the supplementary motor areas in the frontal lobes. The regional and global elevations in white matter T2 suggest abnormalities of white matter tissue water content in autism, which may represent a neurobiological basis for the aberrant cortical connectivity hypothesized to underlie the disorder.

Adolescent↗
PubMed2005

Childhood-onset schizophrenia: smooth pursuit eye-tracking dysfunction in family members.

BACKGROUND: Childhood-onset schizophrenia (COS), a severe form of the disorder, is of interest for etiologic studies. Smooth pursuit eye-tracking dysfunction (ETD) is a biological marker for schizophrenia. AIMS: To compare familial eye-tracking abnormalities for COS and adult-onset schizophrenia (AOS). METHOD: Eye-tracking performance for 70 COS parents, 64 AOS parents and 20 COS siblings was compared to their respective age-matched control groups. RESULTS: COS and AOS parents had higher rate of dichotomously rated eye-tracking dysfunction than their respective controls (16% vs. 1% and 22% vs. 4%, respectively). COS parents and siblings also differed from controls on several continuous measures. However, scores for COS, AOS and control groups overlapped extensively. CONCLUSIONS: Genetic factors underlying eye-tracking dysfunction appear more salient for COS. However, eye-tracking measures have to be used with caution for endophenotypic definition due to low predictive power. DECLARATION OF INTEREST: The study was done at the National Institutes of Health.

Adult↗
PubMed2005

A randomized, double-blind, placebo-controlled trial of metoclopramide for the treatment of Tourette's disorder.

OBJECTIVE: The pattern of dopamine antagonism by metoclopramide suggests benefits in the treatment of tic disorders. The purpose of this study was to examine the efficacy and safety of metoclopramide in the treatment of children and adolescents with tic disorders. METHOD: Twenty-seven medication-free patients (age 11.9 +/- 2.7 years) with Tourette's disorder or a chronic tic disorder participated in an 8-week double-blind, randomized, placebo-controlled trial of metoclopramide. Metoclopramide was started at 5 mg daily and titrated as needed to a maximum dose of 40 mg daily. Tics were rated every 2 weeks, and adverse effects, including weight, cardiac, and laboratory measures, were monitored. RESULTS: After 8 weeks of treatment, subjects receiving metoclopramide showed a 39% reduction in their total tic score on the Yale Global Tic Severity Scale, while subjects receiving placebo showed only a 13% reduction in tic severity (p = .001). Metoclopramide was well tolerated with no significant laboratory or cardiac changes noted other than an increase in serum prolactin. CONCLUSIONS: The results of this small controlled study suggest that metoclopramide is an effective and well-tolerated treatment for children and adolescents with tic disorders. Further trials are needed to confirm its efficacy and safety in pediatric patients and adults.

Adolescent↗
PubMed2005

Parental perception of sleep problems in children of normal intelligence with pervasive developmental disorders: prevalence, severity, and pattern.

OBJECTIVE: This study compares parents' perceptions of the prevalence, severity, and pattern of sleep problems in children of normal intelligence with pervasive developmental disorders (PDDs) with a normative comparison group of children. METHOD: A survey including the Children's Sleep Habits Questionnaire was mailed to a sample of parents of children (age range 5-12 years) with PDDs (diagnosed by the Autism Diagnostic Interview-Revised) obtained by chart review of the past 7 years and to parents of comparison children matched on age, gender, and postal code. RESULTS: The response rate in the PDD group was 82.2% (37/45) and 55.8% (43/77) in the comparison group. By individually matching, 23 pairs were obtained. The prevalence of sleep problems in the PDD group was reported by parents as being significantly higher than in the comparison group (78% and 26%, respectively; p < .002), as was the severity (mean score 48.2 and 39.0, respectively; p < .001). Values for four of eight sleep subscales including sleep onset delay, sleep duration, sleep anxiety, and parasomnias were significantly higher in the PDD group. CONCLUSIONS: Parents report that sleep problems are significantly more prevalent and severe in children of normal intelligence with PDDs compared with normally developing children, and the pattern appears diverse. Sleep problems in children with PDDs require further research and clinical attention.

Canada↗
PubMed2005

Brain magnetic resonance spectroscopy in Tourette's disorder.

OBJECTIVE: Although abnormalities of neural circuits involving the cortex, striatum, and thalamus are hypothesized to underlie Tourette's disorder, the neuronal abnormalities within components of these circuits are unknown. The purpose of this study was to examine the cellular neurochemistry within these circuits in Tourette's disorder using proton magnetic resonance spectroscopy, a method that has not previously been used in neurobiological investigations of the disorder. METHOD: Proton magnetic resonance spectroscopic imaging examinations were conducted in 25 males with Tourette's disorder (age 10.9 +/- 2.0 years) and 32 male comparison subjects (age 11.5 +/- 2.7 years). Spectra from frontal cortex, caudate nucleus, putamen, and thalamus were analyzed, and N-acetylaspartate, creatine, choline, myoinositol, and glutamate + glutamine were quantified and compared between the groups. RESULTS: Patients with Tourette's disorder demonstrated a reduction in N-acetylaspartate and choline in the left putamen, along with reduced levels of creatine bilaterally in the putamen. In the frontal cortex, patients had significantly lower concentrations of N-acetylaspartate bilaterally, lower levels of creatine on the right side, and reduced myoinositol on the left side. CONCLUSIONS: The results of this study suggest compromised neuronal integrity and deficits in density of neuronal and nonneuronal cells in components of the neural circuits implicated in Tourette's disorder.

Adolescent↗
PubMed2004

Childhood onset schizophrenia: familial neurocognitive measures.

OBJECTIVE: Early onset disorders may have more salient familial/genetic etiology. Neurocognitive deficits which are seen in families of adult onset schizophrenic patients were examined in healthy family members of patients with childhood-onset schizophrenia (COS). METHODS: Trail Making Tests (TMT) A and B, Wechsler Intelligence Scale-Revised Digit Span and Vocabulary subtests were administered to 67 parents and 24 siblings of patients with childhood-onset schizophrenia and 114 healthy community controls (CC) comparable in sex, age, and educational level. RESULTS: COS siblings performed significantly more poorly than did controls on Trails Making Test B with a trend for poorer performance evident on Trails Making Test A. COS parents performed more poorly than controls only on Trails Making Test A. CONCLUSIONS: Healthy first-degree relatives of COS probands have subtle deficits in tests involving oculomotor/psychomotor speed, working memory and executive function. This provides further support for continuity between COS and later onset schizophrenia and for a familial/genetic factor associated with the illness.

Adult↗
PubMed2004

Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses.

BACKGROUND: Recent anatomical brain magnetic resonance imaging (MRI) studies show a striking postpsychotic progressive loss of cortical gray matter (GM) in patients with childhood-onset schizophrenia (COS), which appears greater than that seen for adult patients. However, the diagnostic specificity and the relationship of these changes to drug treatment and cognitive functioning remain unclear. We performed a comparative prospective brain MRI study in patients with COS and pediatric patients with transient psychosis with behavior problems (psychosis not otherwise specified) provisionally considered multidimensionally impaired (MDI). We hypothesized that cortical GM loss would occur in patients with COS but not in adolescents with atypical psychoses. METHODS: Anatomical brain MRI was performed at baseline and follow-up in 19 patients in the MDI group (mean [SD] age of 13.3 [3.1] years); in 23 patients with COS matched for age, sex, IQ score, and drug treatment (mean [SD] age of 13.9 [2.5] years); and 38 healthy control subjects matched for age and sex (mean [SD] age of 13.3 [3.1] years). The mean (SD) follow-up was 2.5 (0.8) years. Volumes of the cerebrum and total and regional GM were obtained by using automated analysis, and percent change in volume across time was calculated. One-way analyses of variance with post hoc Tukey Honestly Significantly Different comparisons were performed to examine group differences in the percent change in GM across follow-up. RESULTS: The COS group had significantly greater total, frontal, temporal, and parietal GM loss than did the MDI or healthy control groups; analysis of variance post hoc P values ranged from.03 to.001. The MDI and control groups did not differ significantly from each other. CONCLUSIONS: The cortical GM volume loss in COS appears diagnostically specific; it was not seen in children and adolescents with atypical psychosis. Because both patient groups had similar early developmental patterns, cognitive functioning, medications, and hospitalizations, this progressive loss appears to be intrinsic to COS. An ongoing neurodevelopmental process and/or brain response specific to the illness could account for these changes.

Adolescent↗
PubMed2003

Parental schizophrenia spectrum disorders in childhood-onset and adult-onset schizophrenia.

OBJECTIVE: Childhood onset of "adult" psychiatric disorders may be caused, in part, by more salient genetic risk. In this study, the rates of schizophrenia spectrum disorders among parents of patients with childhood-onset and adult-onset schizophrenia and parents of community comparison subjects were compared. METHOD: To assess the presence of axis I and axis II disorders associated with schizophrenia, parents of patients with childhood-onset schizophrenia (95 parents), patients with adult-onset schizophrenia (86 parents), and community comparison subjects (123 parents) were interviewed directly by using semistructured instruments. Information on 19 additional parents (parents of childhood-onset patients, N=2; parents of adult-onset patients, N=11; parents of community comparison subjects, N=6) was obtained by using a family history interview with the same instruments. Transcribed interviews were scored by a rater blind to group membership, and the morbid risks for schizophrenia spectrum disorders in the three groups were compared. RESULTS: Parents of patients with childhood-onset schizophrenia had a significantly higher morbid risk of schizophrenia spectrum disorders (24.74%) than parents of patients with adult-onset schizophrenia (11.35%), and parents of both patient groups had a greater risk of schizophrenia spectrum disorders than did parents of comparison subjects (1.55%). CONCLUSIONS: Parents of patients with childhood-onset schizophrenia have a higher rate of schizophrenia spectrum disorders than parents of patients with adult-onset illness. This is consistent with the hypothesis that a childhood onset of schizophrenia is due, at least in part, to a greater familial diathesis for the disorder.

Adult↗
PubMed2003

Genetic and neurodevelopmental influences in autistic disorder.

OBJECTIVE: In the past, autism was considered to be largely psychogenic. However, research in the last 2 decades indicates that autism is largely caused by genetic factors that lead to abnormal brain development. This article reviews research into the genetic and neurodevelopmental factors underlying autism. METHODS: We review the findings from genetic and brain-imaging studies of autism over the past 15 years and synthesize these findings as a guide for future research. RESULTS: Genome scans and association studies have suggested potential genomic regions and genes, respectively, that may be involved in the etiology of autism, and there have been some replications of these results. Similarly, the findings that brain volume is exaggerated in autism and corpus callosum size is reduced have also been independently replicated. Unfortunately, studies of other subcortical structures remain inconclusive or contradictory. CONCLUSIONS: Overwhelming evidence now supports a neurobiological basis for autism. However, further refinements will be needed to guide future studies, particularly to identify the most informative phenotypes to investigate. Additionally, studies examining the role of genetic factors in the brain abnormalities underlying autism will likely lead to further findings that will enhance our understanding of autism's causes.

Agenesis of Corpus Callosum↗
PubMed2002

Defining guilt in depression: a comparison of subjects with major depression, chronic medical illness and healthy controls.

BACKGROUND: Although guilt is a widely accepted feature of depression, there is limited and inconsistent data defining the nature of this symptom. The purpose of the current study was to examine the specificity and nature of guilt in subjects with major depression as compared to patients with another chronic medical illness and healthy controls. METHODS: Outpatients with current major depressive episode (MDE; n=34), past-MDE (n=22), chronic cardiac illness (n=20) and healthy controls (n=59) were administered the following measures: The Guilt Inventory (GI), State Shame and Guilt Scale (SSGS), 17-item Hamilton Rating Scale for Depression (Ham-D) and the Structured Clinical Interview for DSM-IV. RESULTS: Overall multivariate analysis of covariance comparing mean scores for the six guilt subscales [state-guilt, trait-guilt, moral standards (from the GI); state-guilt, -pride, and -shame (from the SSGS)] across the four groups was significant (F=9.1, df=6:121, p<0.0001). Post-hoc analysis revealed the following differences (each at least p<0.01): for state-guilt (GI), current-MDE>past-MDE>cardiac=healthy controls; for trait-guilt (GI), current-MDE=past-MDE>cardiac=healthy controls; for state-shame, -guilt and -pride (SSGS), current-MDE>past-MDE, past-MDE=cardiac, past-MDE>healthy, cardiac=healthy controls. Among depressed patients, there was significant correlation between Ham-D score and all guilt sub-scales (p<0.01), except moral standards. LIMITATIONS: The cardiac group may have less illness burden than currently depressed. CONCLUSIONS: State expression of guilt, shame and low pride distinguish acutely depressed from all other groups, and are highly influenced by severity of depression. Trait-guilt does not differentiate acute from past depressed. Data suggests guilt may represent both an enduring and fluctuating feature of depressive illness over its longitudinal course.

Adult↗
PubMed2002

Correlation of antipsychotic and prolactin concentrations in children and adolescents acutely treated with haloperidol, clozapine, or olanzapine.

Patients with a Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) diagnosis of schizophrenia or psychotic disorder not otherwise specified with onset of psychosis before the age of 13 participated in 6- to 8-week open or double-blind trials of haloperidol (n = 15, mean dose 15.4 +/- 8.1 mg/day [0.27 +/- 0.15 mg/kg/day]), clozapine (n = 30, mean dose 269.9 +/- 173.3 mg/day [4.4 +/- 2.6 mg/kg/day]), or olanzapine (n = 12, mean dose 17.5 +/- 2.8 mg/day [0.30 +/- 0.13 mg/kg/day]). Blood samples were obtained at 6 weeks for evaluation of haloperidol, reduced haloperidol, clozapine, desmethylclozapine, and olanzapine plasma concentrations and serum prolactin concentrations. No gender differences were noted for antipsychotic dose or concentration within each treatment group. Correlations between antipsychotic plasma concentration and serum prolactin concentration were significant only for the olanzapine treatment group (r = 0.80, p = 0.002). Separate correlations for gender were significant only for females receiving olanzapine (r = 0.91, p = 0.03); the patient with the highest serum prolactin experienced galactorrhea. Further studies evaluating the prolactin-elevating properties of antipsychotics are warranted in this population.

Adolescent↗
PubMed2002

A retrospective assessment of citalopram in children and adolescents with pervasive developmental disorders.

Although selective serotonin reuptake inhibitors have been used to treat symptoms of aggression and anxiety in children and adolescents with pervasive developmental disorders (PDDs), there are no published reports of the use of citalopram in this population. The purpose of this study was to examine the benefits and adverse effects of citalopram in a group of children and adolescents with PDDs. Target behaviors included aggression, anxiety, stereotypies, and preoccupations. Seventeen patients with PDDs (14 with autistic disorder, three with Asperger's disorder) (mean age = 9.4 +/- 2.9 years; range 4-15 years) were treated with citalopram for at least 2 months (mean duration of treatment = 7.4 +/- 5.3 months; range 1-15 months). Treatment was initiated at a low dose (5 mg daily) and was increased by 5 mg weekly as tolerated and as necessary. The mean final dose was 19.7 +/- 7.8 mg (range 5-40 mg). Outcome was based on a consensus between clinician and parents, using the Improvement item of the Clinical Global Impressions Scale as a guide. Ten (59%) children were judged to be much improved or very much improved regarding target behaviors. Core symptoms of PDDs (social interactions, communication) did not show clinically significant improvement. Citalopram was generally well tolerated, although four patients developed treatment-limiting adverse effects: two with increased agitation, one with insomnia, and one with possible tics. The results of this case series suggest that citalopram has beneficial effects on some interfering behaviors associated with PDDs with few adverse effects. Controlled trials are warranted.

Adolescent↗