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Biomedical subjects

J F Leckman

Publications and source records attributed to J F Leckman.

At least 19 recordsLinked to original sources
PubMed1995

Behavioral laterality in individuals with Gilles de la Tourette's syndrome and basal ganglia alterations: a preliminary report.

This study aims to investigate whether abnormalities in structural basal ganglia asymmetries in Tourette's syndrome (GTS) have functional significance. Eleven adult GTS patients and 11 normal controls who had participated in the previous MRI study where GTS patients lacked the normal left-greater-than-right (L > R) lenticular asymmetry were re-recruited. They were administered a battery of lateralizing neuropsychological tasks believed to require intact basal ganglia function. GTS subjects lacked normal functional asymmetries on these measures, as predicted. The neuropsychological measures also accounted for a significant portion of the variance in the severity of tic symptoms. These findings suggest that GTS subjects who lack normal basal ganglia structural asymmetries also lack normal functional asymmetries on related neuropsychological measures.

Adult↗
PubMed1995

Functional significance of individual variations in callosal area.

We considered the hypothesis that the richness of callosal interhemispheric connections has a role in determining the degree of behavioural laterality and time-sharing ability in dual-task performance. Behavioural laterality as measured by dichotic word listening, line bisection and turning bias tests correlated inversely with the midsagittal cross-sectional area of the corpus callosum, as seen on MRI. The amount of dual task interference was strongly inversely correlated with the callosal area in both within-hemisphere and between-hemispheres conditions. These relationships between normal variations in callosal area, and outcomes on tests both of laterally and time-sharing capacity in normal adults suggest that the corpus callosum assumes a cross-excitatory role when subjects perform these tasks.

Adult↗
PubMed1995

Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette's syndrome, and healthy controls.

To examine the role of noradrenergic, dopaminergic, and serotonergic mechanisms in the pathobiology of obsessive compulsive disorder (OCD) and Tourette's syndrome (TS), concentrations of tyrosine (TYR), norepinephrine (NE), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), homovanillic acid (HVA), tryptophan (TRP), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the lumbar cerebrospinal fluid (CSF) of 39 medication-free OCD patients, 33 medication-free TS patients, and 44 healthy volunteers. CSF TYR concentrations were reduced (p < .05) in the OCD patients compared to the healthy subjects. CSF NE in TS patients was 55% higher than in healthy controls (p < .001) and 35% higher than in OCD patients (p < .001). After covarying for height, CSF HVA levels were reduced (p < .05) in the OCD group compared to TS patients but not compared to the normal volunteers. No mean differences in CSF MHPG, TRP, and 5-HIAA were observed in this study across the three groups. The CSF NE data support the hypothesis that noradrenergic mechanisms are involved in the pathobiology of TS. Alterations in the balance of noradrenergic, dopaminergic, and serotonergic systems are likely involved in the pathobiology of OCD.

Adolescent↗
PubMed1995

Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: preliminary clinical experience.

OBJECTIVE: Many children with Tourette's syndrome (TS) are handicapped more by difficulties with inattention, impulsivity, and hyperactivity than by their tics. However, stimulant medications used to treat attention-deficit hyperactivity disorder (ADHD) can exacerbate tics. Guanfacine is an alpha 2-adrenergic agonist that may have beneficial effects on attention, without the hypotensive or sedative effects of clonidine, which is often used as an alternative to stimulants. METHOD: An open-label study of guanfacine was performed in 10 children with TS+ADHD, aged 8 to 16 years. The duration of follow-up was 4 to 20 weeks, and the majority of subjects were treated with 1.5 mg/day. Ratings of tic severity and ADHD symptoms were obtained using the Yale Global Tic Severity Scale (YGTSS), the Tic Symptom Self Report (TSSR), and the Conners Parent Rating Scale. In addition, blind Continuous Performance Tests (CPTs) were performed at baseline and at two follow-up intervals in eight subjects. RESULTS: Guanfacine was associated with significant decreases in both commission errors (p < .02) and omission errors (p < .01) on the CPT. In addition, guanfacine caused a significant decrease in severity of motor (p < .02) and phonic (p < .02) tics as measured by the TSSR and the YGTSS, respectively. The most common side effects were transient sedation and headaches. CONCLUSION: Guanfacine may provide a safe alternative therapy for children with ADHD in the presence of tics. Future double-blind, controlled trials should be undertaken.

Adolescent↗
PubMed1995

Risperidone treatment of children and adolescents with chronic tic disorders: a preliminary report.

OBJECTIVE: The purpose of this trial was to investigate the short-term safety and efficacy of risperidone in the treatment of chronic tic disorders in children and adolescents. METHOD: This was an 11-week open-label trial and included seven subjects (five boys and two girls) with a mean age of 12.9 +/- 1.9 years. The sample included five patients with Tourette's syndrome and two with chronic motor tic disorder. The children were seen at baseline and for two follow-up visits. Three children had a comorbid diagnosis of obsessive-compulsive disorder (OCD). RESULTS: Clinical response, as measured by the Yale Global Tic Severity Scale and the Children's version of the Yale-Brown Obsessive Compulsive Scale, revealed a statistically significant reduction in tic scores ranging from 26% [corrected] to 66%. One of three children with comorbid OCD showed substantial improvement; the other two subjects showed no change. The most frequent side effect was weight gain, which ranged from 8 to 14 lb. CONCLUSIONS: Risperidone, a neuroleptic with both serotonin- and dopamine-blocking properties, appears to be effective in reducing tic frequency and intensity in children and adolescents with chronic tic disorders.

Adolescent↗
PubMed1995

A family study of obsessive-compulsive disorder.

OBJECTIVE: The goal of this study was to determine 1) whether obsessive-compulsive disorder is familial, 2) whether there is a familial relationship between obsessive-compulsive disorder and Gilles de la Tourette's syndrome and chronic tics, and 3) whether different familial types of obsessive-compulsive disorder exist. METHOD: In this family study, all available first-degree relatives of 100 probands with obsessive-compulsive disorder were interviewed directly with structured interviews, and best-estimate diagnoses were assigned. In addition to the 466 first-degree relatives of the probands, 113 comparison subjects who were first-degree relatives of 33 psychiatrically unaffected subjects were studied with the same interviews. RESULTS: The rates of obsessive-compulsive disorder and subthreshold obsessive-compulsive disorder were significantly greater among the relatives of the probands with obsessive-compulsive disorder (10.3% and 7.9%, respectively) than among the comparison subjects (1.9% and 2.0%, respectively). Furthermore, the rate of tics (Tourette's disorder and chronic tics) was also significantly greater among the relatives of the probands (4.6%) than among the comparison subjects (1.0%). The relatives of female probands with obsessive-compulsive disorder were more likely to have tics, and the relatives of probands with early onset were at higher risk for both obsessive-compulsive disorder and tics. CONCLUSIONS: Obsessive-compulsive disorder is a heterogeneous condition. Some cases are familial and related to tic disorders, some cases are familial and unrelated to tics, and in other cases there appears to be no family history of either obsessive-compulsive disorder or tics.

Adolescent↗
PubMed1995

[123I]beta-CIT SPECT imaging of striatal dopamine transporter binding in Tourette's disorder.

OBJECTIVE: The authors examined whether subjects with Tourette's disorder have greater than normal striatal dopamine transporter densities, as suggested by previous post-mortem findings. METHOD: Single photon emission computed tomography (SPECT) and [123I]2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I]beta-CIT) were used to assess dopamine transporter levels in five adult patients with Tourette's disorder and five age- and gender-matched healthy comparison subjects. RESULTS: Striatal [123I]beta-CIT binding was a mean of 37% (range = 6%-79%) higher in the subjects with Tourette's disorder than in the comparison subjects, and each Tourette's disorder patient had a higher level than his or her paired comparison subject. CONCLUSIONS: These findings corroborate post-mortem results and support the hypothesis of a dysregulation in presynaptic dopamine function in Tourette's disorder.

Adult↗
PubMed1995

Risperidone addition in fluvoxamine-refractory obsessive-compulsive disorder: three cases.

BACKGROUND: Forty percent to 60% of patients with obsessive-compulsive disorder (OCD) remain unimproved after adequate treatment with serotonin uptake inhibitors (SUIs). The addition of low-dose haloperidol and pimozide to ongoing SUI treatment has been shown to be effective in up to 65% of SUI-refractory OCD patients, particularly in those with comorbid chronic tic disorder. Because OCD patients typically require prolonged pharmacotherapy, they are subject to the development of tardive dyskinesia during neuroleptic treatment. Risperidone is a highly potent and selective serotonin2 and dopamine2 receptor antagonist with a side effect profile that appears to be much more tolerable and safer than that of typical neuroleptics. METHOD: We report our experience with three OCD patients who were unimproved after a minimum of 12 weeks of treatment with the potent and selective SUI fluvoxamine, in whom we added risperidone in an open-label manner. RESULTS: All three patients showed significant improvement in their obsessive-compulsive symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after risperidone 1 mg/day was added to ongoing fluvoxamine (250-300 mg/day). Within 4 weeks of adding risperidone, the three patients' Y-BOCS scores had decreased by 65%, 56%, and 43%, respectively. Other than mild or moderate sedation, no side effects were observed. CONCLUSION: These results suggest that risperidone addition to ongoing SUIs may be an effective treatment strategy for refractory OCD.

Adult↗
PubMed1995

Sensory phenomena in Tourette's syndrome.

Sensory phenomena in the form of premonitory urges and "just right" perceptions appear to be common features of tic disorders including TS. Shapiro et al. (5) proposed that these sensory phenomena are an idiosyncratic feature of TS that is present in a minority of TS patients. However, data from recent studies suggest that premonitory urges are common in TS and may even be a defining feature of the disorder. These findings further indicate that clinicians should inquire about the presence of premonitory urges during the assessment of individuals with movement disorders. Of particular interest for future research is the relationship of the anatomical location of the premonitory urge and the site of the tic. Further study of sensory phenomena in other movement disorders is also warranted.

Dyskinesia, Drug-Induced↗
PubMed1994

Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics.

BACKGROUND: To determine the efficacy of adding haloperidol to the treatment of patients with obsessive-compulsive disorder (OCD), with or without a comorbid chronic tic disorder, who were refractory to adequate treatment with the serotonin-uptake inhibitor fluvoxamine alone. It was hypothesized that OCD patients with a concurrent chronic tic disorder would preferentially respond to this treatment. METHODS: Sixty-two patients with a primary DSM-III-R diagnosis of OCD received placebo fluvoxamine for 1 week, followed by 8 weeks of active fluvoxamine. Thirty-four of these patients were refractory to fluvoxamine and were randomized in a double-blind fashion to 4 weeks of treatment with either haloperidol (n = 17) or placebo (n = 17) added to ongoing fluvoxamine treatment. The placebo-treated group included five women and 12 men, six inpatients and 11 outpatients, and eight patients with a comorbid chronic tic disorder. The haloperidol-treated group consisted of two women and 15 men, three inpatients and 14 outpatients, and seven patients with a comorbid chronic tic disorder. All 34 patients completed the entire study. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression scale were the principal measures of treatment outcome. RESULTS: Haloperidol addition was significantly better than placebo in reducing the severity of obsessive-compulsive symptoms as measured by the Y-BOCS. Eleven of 17 patients responded to the haloperidol, compared with none of 17 patients given placebo. Eight of eight patients with comorbid chronic tic disorders, such as Tourette's disorder, responded to double-blind haloperidol addition to ongoing fluvoxamine treatment. Haloperidol addition was of little benefit in treating OCD patients without tics. Fluvoxamine blood levels were not related to treatment response. CONCLUSIONS: The results of this study suggest that OCD patients with a comorbid chronic tic disorder constitute a clinically meaningful subtype of OCD that might require conjoint serotonin-uptake inhibitor/neuroleptic therapy for effective symptom reduction.

Adolescent↗
PubMed1994

Elevated cerebrospinal fluid levels of oxytocin in obsessive-compulsive disorder. Comparison with Tourette's syndrome and healthy controls.

BACKGROUND: Limited neurobiological data have implicated central arginine vasopressin in the pathobiology of obsessive-compulsive disorder (OCD). Based on twin, family genetic, and pharmacological studies, some forms of OCD are etiologically related to Tourette's syndrome. The role of arginine vasopressin and related compounds such as oxytocin in Tourette's syndrome has not been previously explored. METHODS: To compare cerebrospinal fluid (CSF) levels of arginine vasopressin and oxytocin, we collected CSF at midday in a standardized fashion from a total of 83 individuals (29 patients with OCD, 23 patients with Tourette's syndrome, and 31 normal controls). We also collected family study data on each subject to determine which subjects had a family history positive for Tourette's syndrome, OCD, or related syndromes. RESULTS: In contrast to previous reports, we report similar concentrations of arginine vasopressin for all three groups but increased oxytocin levels in patients with OCD. Remarkably, this increase was observed only in a subset of patients with OCD (n = 22) independently identified as being without a personal or family history of tic disorders (P = .0003). In this subgroup of patients, the CSF oxytocin level was correlated with current severity of OCD (n = 19, r = .47, P < .05). CONCLUSIONS: A possible role for oxytocin in the neurobiology of a subtype of OCD is suggested by the elevated CSF levels of oxytocin and by the correlation between CSF oxytocin levels and OCD severity. These findings reinforce the value of family genetic data in identifying biologically homogeneous (and perhaps more etiologically homogeneous) groups of patients with OCD. Together with emerging pharmacological data showing differential responsiveness to treatment of tic-related OCD vs non-tic-related OCD, these data also argue strongly for the incorporation of tic-relatedness as a variable in biological and behavioral studies of patients with OCD.

Adolescent↗
PubMed1994

Abnormal magnetic resonance imaging T2 relaxation time asymmetries in Tourette's syndrome.

Recent imaging studies in Tourette's syndrome (TS) have reported a loss of normal asymmetry in basal ganglia volumes. Our recent report of reduced midline sagittal cross-sectional area in TS suggests that altered lateralization may be widespread throughout the TS cerebrum. We report here our analyses of cerebral asymmetries of T2 (transverse or spin-spin) relaxation times derived from multi-echo/multi-planar/spin-echo magnetic resonance images in 14 adult TS subjects and 14 matched normal control subjects. T2 relaxation times were found to be asymmetric throughout the cerebrum of normal control subjects, with differences seen between T2 times of corresponding regions of both cerebral hemispheres that were small in magnitude (2-5%) but of a high degree of statistical significance in all regions examined. Our hypothesis of altered T2 relaxation time asymmetries in TS was confirmed in a multivariate analysis of variance, with post hoc analyses suggesting that group differences were attributable to specific asymmetry differences in the TS insular cortex and frontal white matter. Exploratory analyses revealed group differences in T2 times of the amygdala and red nucleus, as well as significantly lower ferritin levels in the TS group. These findings are discussed in relation to the previous TS volumetric studies, and the tissue characteristics that might produce normal and abnormal relaxation time asymmetries are considered.

Adolescent↗
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

Developmental psychopathology and neurobiology of Tourette's syndrome.

OBJECTIVE: The authors present a model of the developmental psychopathology and neurobiology of Tourette's syndrome that provides a framework for ongoing research and treatment. METHOD: The model is based on clinical experience and a selective review of relevant scientific literature. RESULTS: During the past decade, Tourette's syndrome and related conditions have emerged as model disorders to study the interplay of genetic, neurobiological, psychological, and environmental factors during development. Although prevention and treatment are paramount, the effectiveness of these interventions depends on the quality and extent of our knowledge. Programmatic research combined with sustained clinical care has led to advances in our knowledge of the natural history of these disorders over the course of development and glimpses of the pathophysiologic and psychopathological mechanisms that mediate their expression in vulnerable persons. CONCLUSIONS: In the future, we expect that our understanding will extend from the molecular level of how specific genes and epigenetic factors confer and mediate vulnerability to an understanding of why certain symptoms emerge when they do in the course of central nervous system development.

Adolescent↗
PubMed1994

Genetic mechanisms in childhood psychiatric disorders.

OBJECTIVE: This review summarizes research findings on the genetics of several childhood psychiatric disorders. METHOD: One hundred fifty papers were reviewed from the past several decades and were selected because they have suggested that genetic factors may play a role in the etiology of certain childhood disorders. This review is not meant to be exhaustive but rather has emphasized those disorders for which a genetic etiology has been proposed by different research groups. RESULTS: The more classical approaches to genetic research are reviewed and critiqued. The status of research for a number of childhood disorders is summarized. The molecular basis for several developmental disorders is presented and the prospects for arriving at a similar molecular understanding for other childhood psychiatric illnesses are discussed. CONCLUSIONS: Genetic factors play a determining role for certain developmental disorders. However, the molecular basis for other psychiatric disorders has yet to be elucidated and there are complicating factors that bear on genetic research of complex behavioral disorders.

Adoption↗
PubMed1994

"Just right" perceptions associated with compulsive behavior in Tourette's syndrome.

OBJECTIVE: Tourette's syndrome is a chronic disorder of childhood onset that is characterized by motor and phonic tics and a broad range of associated behavior including obsessive-compulsive symptoms. Less well appreciated are the sensory and other perceptually tinged mental phenomena associated with both tic and compulsive behavior. This cross-sectional study evaluated the "just-right" phenomena commonly associated with compulsive behavior in subjects with tic disorders. METHOD: A total of 134 subjects with tic disorders, aged 9 to 71 years, completed a questionnaire concerning their current and past tic symptoms. Subjects were also asked to describe their "just right" perceptions. The Yale-Brown Obsessive Compulsive Scale was used to assess severity of current obsessive-compulsive symptoms. RESULTS: Eight-one percent of the subjects with both Tourette's syndrome and obsessive-compulsive disorder (N = 31) and 56% of the subjects with Tourette's syndrome and obsessive-compulsive symptoms (N = 61) reported being aware of a need to perform compulsions until they were "just right." This awareness most commonly referred to visual or tactile (as opposed to auditory) features of the compulsive act or its consequences. Three-quarters of the subjects with these perceptions reported that they usually were aware of them immediately before or concurrently with the initiation of compulsions. CONCLUSIONS: While epidemiological studies of tic disorders and obsessive-compulsive disorder have yet to incorporate questions concerning "just right" perceptions, these results suggest that such perceptions may be commonplace in adolescent and adult subjects with both obsessive-compulsive disorder and tic disorders. They also implicate brain regions involved in the processing of sensorimotor information in the pathobiology of tic disorders.

Adolescent↗
PubMed1994

Evidence against a genetic relationship between Tourette's syndrome and anxiety, depression, panic and phobic disorders.

Analyses were undertaken to examine whether a wide range of psychiatric disorders, including anxiety, affective, substance abuse and psychotic disorders, represent variant manifestations of Tourette's syndrome (TS). Previous studies have suggested that chronic tics (CT) and obsessive-compulsive disorder (OCD) are variant expressions of TS since both CT and OCD are elevated among relatives of TS probands. In the current study, no other psychiatric disorder was significantly elevated among the relatives who did not have TS, CT or OCD when compared with a control sample. These findings are not consistent with the hypothesis that a wide range of psychiatric and behavioural disorders are variant expressions of TS.

Adolescent↗