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Biomedical subjects

M A Riddle

Publications and source records attributed to M A Riddle.

At least 55 records · Page 3Linked to original sources
PubMed1994

The role of central oxytocin in obsessive compulsive disorder and related normal behavior.

Oxytocin (OT) is a neurosecretory nonapeptide synthesized in hypothalamic cells, which project to widely distributed sites in the CNS as well as the neurohypophysis. Central OT affects a variety of cognitive, grooming, affiliative, sexual, and reproductive behaviors in animals. Obsessive Compulsive Disorder (OCD) includes a range of cognitive and behavioral symptoms that bear some relationship to dimensions of behavior associated with OT. Anecdotal data and a recently completed cerebrospinal fluid (CSF) study provide evidence that some forms of OCD are related to OT dysfunction. Based on these findings, we hypothesize: 1) that some forms of OCD are at the extreme end of a range of normal behaviors that are mediated by OT and related systems; and that 2) some normal cognitive, affiliative, and sexual behaviors contain elements that are similar to features of OCD. Alternative hypotheses are considered, and a series of predictions are presented concerning the relationship between central OT and the onset, course, treatment response, and response to challenge procedures seen in this form of OCD.

Animals↗
PubMed1994

Corpus callosum morphology from magnetic resonance images in Tourette's syndrome.

We measured the midline cross-sectional area and other morphologic features of the corpus callosum (CC) from magnetic resonance (MR) images in 14 unmedicated patients with Tourette's syndrome (TS) and 14 normal control subjects matched for age, sex, handedness, and socioeconomic status. Each CC was manually circumscribed on midline images from a T1-weighted sagittal series, and the area of the entire CC and five anatomic subdivisions were measured. CC circumference, regional width, and mean callosal curvature were also measured. CC cross-sectional area correlated positively with brain size and basal ganglia volumes. The magnitude of reduction (17.7%) in total CC area in TS patients compared with control subjects was similar to the reductions seen in all CC subdivision areas. Analyses of covariance with total midsagittal cross-sectional head area as a covariate revealed the reductions to be statistically significant for the overall CC area and all subregion areas. CC width tended to be nonsignificantly thinner in all subdivisions (from 5% to 11%), and the overall length of the center line measured from rostrum to splenium was significantly reduced in the TS group (by 5.3%). Measures of mean callosal curvature suggested that CCs in TS patients are less rounded than those of normal control subjects. Worst-ever motor tic symptoms showed the strongest significant correlation with the length of the CC center line in TS patients (r = 0.88). These findings suggest that structural interhemispheric connectivity may be aberrant in the central nervous systems of TS patients, and they provide indirect supportive evidence for the presence of altered cerebral lateralization in the disorder.

Adolescent↗
PubMed1993

Human basal ganglia volume asymmetries on magnetic resonance images.

The brains of 19 healthy adults, ages 18-49, were imaged on a GE Signa 1.5 T MR scanner. Basal ganglia were circumscribed on sequential axial proton density-weighted images (TR 1700, TE 20) and submitted for 3-dimensional reconstruction and volumetric analysis at a computer graphics workstation. The 15 right-handed patients (12 men, 3 women) had significantly larger left total basal ganglia volumes, which included larger globus pallidus and lenticular nuclei on the left, but larger caudate nuclei on the right. In contrast, basal ganglia asymmetries were not seen in four left-handers. No sex differences were detected. The basal ganglia appear to belong to an increasing number of CNS structures that display anatomical hemispheric lateralization.

Adult↗
PubMed1993

Another sudden death in a child treated with desipramine.

The sudden death of three children receiving the tricyclic antidepressant medication desipramine for behavioral disorders was reported in 1990. We now provide new information about these children and describe a fourth case. Because desipramine is a useful medication for many children, these deaths pose clinical dilemmas for physicians and families. The cardiac long QT syndrome has been proposed as a mechanism for these sudden deaths. Considerable uncertainty remains about the basis of the apparent association between the use of desipramine and the sudden deaths.

Attention Deficit Disorder with Hyperactivity↗
PubMed1993

Reduced basal ganglia volumes in Tourette's syndrome using three-dimensional reconstruction techniques from magnetic resonance images.

Using a 1.5-tesla GE Signa MR scanner, we imaged the brains of 14 right-handed Tourette's syndrome (TS) patients (11 men, three women), aged 18 to 49 years, who had minimal lifetime neuroleptic exposure. We also studied an equal number of normal controls individually matched for age, sex, and handedness and group-matched for socioeconomic status. We circumscribed basal ganglia on sequential axial images from spin-echo proton density-weighted acquisitions (TR 1,700, TE 20; slice thickness, 3 mm with 1.5-mm skip) and submitted the images for three-dimensional processing at a computer graphics workstation. Our hypothesis of lenticular nucleus volume reduction in TS was confirmed for the left- but not the right-sided nucleus. Post hoc analyses revealed smaller mean volumes of the caudate, lenticular, and globus pallidus nuclei compared with controls on both the right and left. Further analyses of basal ganglia asymmetry indices suggest that TS basal ganglia do not have the volumetric asymmetry (left greater than right) seen in normal controls. These findings confirm and extend prior phenomenologic, neuropathologic, and neuroradiologic studies that implicate the basal ganglia in the pathogenesis of TS.

Adult↗
PubMed1992

Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder.

Rigorously designed clinical trials have demonstrated the efficacy and safety of fluoxetine in adults with major depressive disorder and obsessive-compulsive disorder (OCD) but not in patients below 18 years old. This report describes a randomized, double-blind, placebo-controlled, fixed-dose (20 mg qd) trial of fluoxetine in 14 children and adolescents with OCD, ages 8 to 15 years old; the study was 20 weeks long with crossover at 8 weeks. Obsessive-compulsive symptom severity was measured on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinician's Global Impression-Obsessive Compulsive Disorder scale (CGI-OCD). The CY-BOCS total score decreased 44% (N = 7, p = .003) after the initial 8 weeks of fluoxetine treatment, compared with a 27% decrease (N = 6, p = .13) after placebo. During the initial 8 weeks, the magnitude of improvement for the fluoxetine group significantly exceeded that for the placebo group as measured by the CGI-OCD (p = .01) but not by the CY-BOCS (p = .17). The most common drug side effects were generally well tolerated. The results suggest that fluoxetine is a generally safe and effective short-term treatment for children with OCD.

Adolescent↗
PubMed1992

Pharmacotherapy of Tourette's syndrome and associated disorders.

Tourette's syndrome (TS) is a chronic neuropsychiatric disorder characterized by multiform motor and phonic tics. Conditions that are commonly associated with TS include attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Medications used to treat tics include haloperidol, pimozide, and clonidine. Symptoms of ADHD may respond to clonidine or desipramine. Specific serotonin uptake inhibitors, such as fluoxetine or clomipramine, are used in the treatment of OCD symptoms. The decision to use medication and the monitoring of its impact require careful assessment of the child's overall development and not only the presence of tic symptoms.

Attention Deficit Disorder with Hyperactivity↗
PubMed1991

Clonidine treatment of Gilles de la Tourette's syndrome.

The safety and effectiveness of clonidine hydrochloride (3 to 5 micrograms/kg per day) were evaluated in 47 subjects with Gilles de la Tourette's syndrome, aged 7 to 48 years. Twenty-four subjects were randomly assigned to clonidine treatment and 23 to placebo. Forty subjects (21 given clonidine and 19 placebo) successfully completed the 12-week, double-blind clinical trial. Clinical ratings of tic severity improved for both groups. The magnitude of response was greater in the group receiving clonidine. Clinician-rated measures of motor tic severity, the degree to which the tics are "noticeable to others," motor tic counts from videotaped interviews, and parent-rated measures of impulsivity and hyperactivity were the most responsive to clonidine treatment. These results indicate that clonidine is more effective than placebo in reducing some of the tic and other behavioral symptoms associated with Gilles de la Tourette's syndrome.

Administration, Oral↗
PubMed1991

Sudden death in children receiving Norpramin: a review of three reported cases and commentary.

The 1990 "package insert" for Norpramin, the Merrell Dow Pharmaceuticals Inc., brand of desipramine, was changed to include the following statement in the Adverse Reactions section, "There has been a report of an 'acute collapse' and 'sudden death' in an eight-year-old (18 kg) male, treated for two years for hyperactivity. There have been additional reports of sudden death in children." The purpose of this commentary is to review what is known about the three reported cases of sudden death and to discuss the implications of these tragedies for children receiving treatment with tricyclic drugs.

Attention Deficit Disorder with Hyperactivity↗
PubMed1991

Emergence of self-destructive phenomena in children and adolescents during fluoxetine treatment.

Self-injurious ideation or behavior appeared de novo or intensified during fluoxetine treatment of obsessive-compulsive disorder in six patients, age 10 to 17 years old, who were among 42 young patients receiving fluoxetine for obsessive-compulsive disorder at a university clinical research center. These symptoms required the hospitalization of four patients. Before receiving fluoxetine, four patients had major risk factors for self-destructive behavior including depression or prior suicidal ideation or self-injury. Three hypotheses concerning the apparent association between fluoxetine and these self-injurious phenomena are discussed: (1) coincidence; (2) disorganization of vulnerable individuals secondary to drug-induced activation; and (3) a specific serotonergic-mediated effect on the regulation of aggression.

Adolescent↗
PubMed1990

Serotonin in human lumbar cerebrospinal fluid: a reassessment.

An inter-laboratory comparison study was carried out in order to ascertain mean levels of serotonin (5-HT) in human lumbar cerebrospinal fluid (CSF). Analyses were performed using high performance liquid chromatography (HPLC) coupled with either electrochemical (LC-EC) or fluorometric (LC-F) detection. With the detection limits obtained (7-8 pg/ml for LC-EC, 7-15 pg/ml for LC-F) 5-HT was not usually detected in human lumbar CSF. The findings indicate that the true mean concentration of CSF 5-HT is less than 10 pg/ml. This upper limit is substantially lower than all previous reports of 5-HT concentrations in normal human lumbar CSF. The extremely low concentrations of 5-HT present in CSF make it unlikely that CSF 5-HT will be of clinical utility in assessing central serotonergic function.

Chromatography, High Pressure Liquid↗