Carbamazepine and/or fluvoxamine drug interaction with risperidone in a patient on multiple psychotropic medications.
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Adult↗
Biomedical subjects
R Nicolson
Publications and source records attributed to R Nicolson.
Childhood-onset schizophrenia: rare but worth studying.
Childhood-onset schizophrenia (defined by an onset of psychosis by age 12) is a rare and severe form of the disorder that is clinically and neurobiologically continuous with the adult-onset disorder. There is growing evidence for more salient risk or etiologic factors, particularly familial, in this possibly more homogeneous patient population. For the 49 patients with very early onset schizophrenia studied to date at the National Institute of Mental Health, there were more severe premorbid neuro-developmental abnormalities, a higher rate of cytogenetic anomalies, and a seemingly higher rate of familial schizophrenia and spectrum disorders than later onset cases. There was no evidence for increased obstetric complications or environmental stress. These data, while preliminary, suggest that a very early age of onset of schizophrenia may be secondary to greater familial vulnerability. Consequently, genetic studies of these patients may be particularly informative and may provide important etiologic information.
Age Factors↗
Childhood-onset schizophrenia: progressive brain changes during adolescence.
BACKGROUND: Previous NIMH childhood onset schizophrenia (COS) anatomic brain MRI studies found progression of ventricular volume and other structural brain anomalies at 2-year follow up across mean ages 14 to 16 years. However, studies in adult patients generally do not show progression of ventricular volume or correlation of ventricular volume with duration of illness. To address issues of progression of brain anomalies in schizophrenia, this report extends previous studies to include a third longitudinal scan, uses a larger sample size, and includes measures of the amygdala and hippocampus. METHODS: Volumes of the total cerebrum, lateral ventricles, hippocampus, and amygdala were quantified on 208 brain magnetic resonance imaging scans from 42 adolescents with COS (23 with one or more repeat scan) and 74 age- and gender-matched controls (36 with one or more repeat scan). A statistical technique permitting combined use of cross-sectional and longitudinal data was used to assess age-related changes, linearity, and diagnostic group differences. RESULTS: Differential nonlinear progression of brain anomalies was seen during adolescence with the total cerebrum and hippocampus decreasing and lateral ventricles increasing in the COS group. The developmental curves for these structures reached an asymptote by early adulthood for the COS group and did not significantly change with age in the control group. CONCLUSIONS: These findings reconcile less striking progression of anatomic brain images usually seen for adult schizophrenia and complement other data consistent with time-limited, diagnostic-specific decreases in brain tissue. Adolescence appears to be a unique period of differential brain development in schizophrenia.
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↗
Elevated prolactin in pediatric patients on typical and atypical antipsychotics.
As part of systematic treatment trials of haloperidol, clozapine, and olanzapine with a total of 35 children and adolescents with early onset psychosis, prolactin was measured at baseline and week 6 of treatment. The National Institute of Mental Health patients--13 females, 22 males (mean age, 14.1+/-2.3 years; range, 9.1-19 years) with childhood onset schizophrenia (n = 32), or Psychotic Disorder not otherwise specified (NOS) (n = 3) with onset of psychosis before age 13--were recruited for open or double-blind trials of haloperidol, clozapine, or olanzapine. Baseline serum prolactin was measured after a 3-week washout period and after 6 weeks of treatment. Mean prolactin concentration after 6 weeks of treatment was significantly elevated on all three drugs; however, on clozapine, mean prolactin remained within the normal range. Prolactin was increased above the upper limit of normal for 100% of 10 patients on haloperidol, 70% of 10 patients on olanzapine, and 0% of 15 patients on clozapine (chi2 analyses: H > C, p = 0.004; O > C, p = 0.001). Given the potential endocrine and possible cardiac correlates of hyperprolactinemia, these more robust prolactin elevations in pediatric patients after short-term exposure to olanzapine than those reported for adults justify longer observation intervals with bigger samples to establish treatment safety of atypical antipsychotics in adolescents.
Adolescent↗
Velocardiofacial syndrome in childhood-onset schizophrenia.
OBJECTIVES: Deletion of chromosome 22q11 (velocardiofacial syndrome) is associated with early neurodevelopmental abnormalities and with schizophrenia in adults. The rate of 22q11 deletions was examined in a series of patients with childhood-onset schizophrenia (COS), in whom early premorbid developmental and cognitive impairments are more pronounced than in adult-onset cases. METHOD: Through extensive recruiting and screening, a cohort of 47 patients was enrolled in a comprehensive study of very-early-onset schizophrenia. All were tested with fluorescence in situ hybridization for deletions on chromosome 22q11. RESULTS: Three (6.4%) of 47 patients were found to have a 22q11 deletion. All 3 COS patients with 22q11 deletions had premorbid impairments of language, motor, and social development, although their physical characteristics varied. Brain magnetic resonance imaging revealed increased midbody corpus callosum area and ventricular volume in relation both to healthy controls and to other COS patients. CONCLUSIONS: The rate of 22q11 deletions in COS is higher than in the general population (0.025%, p < .001) and may be higher than reported for adult-onset schizophrenia (2.0%, p = .09). These results suggest that 22q11 deletions may be associated with an earlier age of onset of schizophrenia, possibly mediated by a more salient neurodevelopmental disruption.
Abnormalities, Multiple↗
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↗
An open trial of risperidone in young autistic children.
OBJECTIVE: To assess the benefits and side effects of risperidone in young autistic children. METHOD: In this open, prospective trial, subjects were treated with risperidone for 12 weeks. All subjects were started at 0.5 mg daily with individual titration to a maximum of 6 mg or 0.1 mg/kg daily. Behavioral ratings, completed by the investigators and the children's parents, included the Clinical Global Impressions (CGI), Children's Psychiatric Rating Scale, Conners Parent-Teacher Questionnaire, Childhood Autism Rating Scale, and Abnormal Involuntary Movement Scale. RESULTS: Ten boys, aged 4.5 to 10.8 years, were enrolled in the study and all completed the 12-week protocol. The mean final dose was 1.3 mg/day (range = 1 to 2.5 mg/day). On the basis of CGI-rated improvement, 8 of the 10 children were considered to be responders. Improvement was also demonstrated on the other scales. Transient sedation was common, and the children gained an average of 3.5 kg over the 12 weeks of the study. There was no evidence of either extrapyramidal symptoms or tardive dyskinesia. CONCLUSIONS: These results suggest that risperidone may be safe and leads to improvements in several behavioral symptoms in young children with autism. Controlled studies of risperidone in young autistic children are warranted.
Antipsychotic Agents↗
47,XYY karyotypes and pervasive developmental disorders.
OBJECTIVE: The presence of a 47, XYY karyotype in boys with pervasive developmental disorders (PDDs) has rarely been described in the past. Herein, 2 boys with PDDs and a supernumerary Y chromosome are presented. METHODS: The case histories of the 2 patients are described along with the results of associated testing. The literature on psychosocial development as well as brain morphology and physiology in males with 47, XYY karyotypes is reviewed. RESULTS: Both boys had presentations typical of PDDs, one with autistic disorder and the other with PDD not otherwise specified. CONCLUSION: The finding that, in a clinic for children with developmental disorders, 2 of 40 male referrals had 47, XYY karyotypes suggests that the rate of this sex chromosome anomaly may be increased in PDDs. An extra Y chromosome may be related to abnormal brain development, which may, in turn, predispose vulnerable males to PDDs.
Adolescent↗
Bridging the gap between theory and practice: a multimedia tutorial for students of voice therapy.
A computer-based tutorial for speech and language therapy students is described in which a digitized video-recording of a diagnostic interview with a voice-disordered client was dynamically linked to an on-screen transcript window. A student-centered tutorial package, which provided guidance through questions, assessment tasks, and commentary from an experienced speech and language pathologist as well as the lecturer in voice disorder, was constructed. Evaluation of the tutorial as an aid to active learning, including feedback from students and supervising clinicians, is reported and the role of this type of program as a preparation for clinical practice is discussed.
Adult↗
Predictors of early psychiatric readmission.
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Follow-Up Studies↗
Conversion, dissociation, and multiple sclerosis.
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Adult↗
The effect of oleic acid on the secretion of thyrotrophin and growth hormone by cultured rat anterior pituitary cells.
Elevation of non-esterified fatty acids (NEFA) in vivo is associated with abnormal control of TSH. To determine whether TSH secretion is directly inhibited by NEFA, as has been reported for GH, cultured rat anterior pituitary cells were exposed for 20 h to oleic acid in medium containing 7.7 x 10(-5) mol/l bovine serum albumin (BSA). In a molar ratio with albumin of 1.2 (total oleic acid 9 x 10(-5) mol/l), or greater, oleic acid inhibited basal GH secretion (maximum inhibition to 40% of control) while basal TSH was less affected, a ratio of 3 (2.3 x 10(-4) mol/l oleic acid) or greater causing a smaller degree of inhibition (maximum inhibition to 80% of control). In the presence of 10(-9) mol/l growth hormone-releasing hormone or 10(-8) mol/l TRH, inhibition was achieved at a ratio of 12 (9 x 10(-4) mol/l oleic acid) or greater. Basal TSH was less sensitive to inhibition by thyroxine (T4) in the presence of oleic acid/albumin at a ratio of 6 or greater, and inhibition by oleic acid was less than additive with T4 at a ratio of 6 or greater. Responses to tri-iodothyronine (T3) were unaffected at a ratio of 6 (4.6 x 10(-4) mol/l oleic acid), but a ratio of 12 inhibited the effects of both T3 and T4 on TSH.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Nucleotide sequence, organisation and structural analysis of the products of genes in the nirB-cysG region of the Escherichia coli K-12 chromosome.
The DNA sequence and derived amino-acid sequence of a 5618-base region in the 74-min area of the Escherichia coli chromosome has been determined in order to locate the structural gene, nirB, for the NADH-dependent nitrite reductase and a gene, cysG, required for the synthesis of the sirohaem prosthetic group. Three additional open reading frames, nirD, nirE and nirC, were found between nirB and cysG. Potential binding sites on the NirB protein for NADH and FAD, as well as conserved central core and interface domains, were deduced by comparing the derived amino-acid sequence with those of database proteins. A directly repeated sequence, which includes the motif -Cys-Xaa-Xaa-Cys-, is suggested as the binding site for either one [4Fe-4S] or two [2Fe-2S] clusters. The nirD gene potentially encodes a soluble, cytoplasmic protein of unknown function. No significant similarities were found between the derived amino-acid sequence of NirD and either NirB or any other protein in the database. If the nirE open reading frame is translated, it would encode a 33-amino-acid peptide of unknown function which includes 8 phenylalanyl residues. The product of the nirC gene is a highly hydrophobic protein with regions of amino-acid sequence similar to cytochrome oxidase polypeptide 1.
Amino Acid Sequence↗
Serum relaxin in pregnancy.
Serum relaxin immunoactivity was measured by means of a porcine radioimmunoassay in a cross-sectional study of 302 normal singleton pregnancies. Concentrations in the third trimester were lower than in early and mid pregnancy. At term, relaxin levels in patients who went into spontaneous labour within a week of sampling were significantly lower than in those who did not. However, relaxin levels were highest during labour and fell almost to non-pregnant levels by the third postnatal day. Levels in twin pregnancies in the third trimester were higher than those in singleton pregnancies. Serial samples from 4 patients with a history of premature labour showed declining, very low levels in the only patient who subsequently had a preterm delivery. These results are compatible with the proposed roles of relaxin during pregnancy: namely, to maintain myometrial quiescence, facilitate uterine stromal remodelling during uterine growth, and promote cervical ripening at the onset of parturition.
Female↗
Serum relaxin and pelvic pain of pregnancy.
Serum relaxin immunoreactivity was measured by means of a porcine relaxin radioimmunoassay in 35 patients with severe pelvic pain and pelvic joint instability during late pregnancy. Results were compared with a control group of 368 samples obtained throughout pregnancy from normal singleton pregnancies. Most of the relaxin concentrations in the study group were above the 95% confidence limits of the median for the corresponding gestational age in the control group. The difference in relaxin levels between the study and control groups in the third trimester was highly significant. Relaxin levels in patients with pelvic pain were close to normal non-pregnant levels by the third postnatal day. The highest relaxin levels during pregnancy were found in the patients who were the most incapacitated clinically. The results suggest that there may be an association between high serum relaxin levels and pelvic pain and joint laxity during late pregnancy.
Female↗
Ripening of the human cervix and induction of labor with intracervical purified porcine relaxin.
In a randomized double-blind placebo-controlled trial involving 71 patients, a viscous gel containing distilled water or 1 or 2 mg pure porcine relaxin was instilled in the cervical canal on the evening before the surgical induction of labor. Eleven of 48 patients receiving relaxin labored overnight, whereas only one of 23 patients went into labor. Only the 2-mg dose significantly improved the mean cervical score compared with the placebo treatment; the effect was greatest in primigravid patients with unripe cervixes. Intracervical application appeared to confer no benefit over vaginal application in effecting cervical ripening or inducing labor. Systemic absorption of the porcine relaxin after its intracervical application was confirmed by the measurement of immunoreactive relaxin in a homologous porcine relaxin radioimmunoassay. Thus, the cervical ripening effect of exogenous relaxin may be mediated either systemically or by direct action at the site of local application. This trial confirms the responsiveness of the human term cervix to exogenous relaxin and supports the suggestion that endogenous relaxin may play a similar role at term in facilitating cervical ripening and parturition.
Administration, Intravaginal↗