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C J McDougle

Publications and source records attributed to C J McDougle.

At least 19 recordsLinked to original sources
PubMed1998

The neurobiology of tryptophan depletion in depression: effects of intravenous tryptophan infusion.

BACKGROUND: Previous work has suggested that acute depletion of the serotonin (5-HT) precursor tryptophan (TRP) causes transient compensatory changes in the 5-HT system that might be exploited for their antidepressant effects. In this study, neuroendocrine and mood responses to intravenous (i.v.) infusion of TRP were examined in order to evaluate central 5-HT function in depressed patients undergoing acute TRP depletion. METHODS: Thirty-eight drug-free patients with DSM-III-R major depression participated. Each patient underwent two randomized, double-blind TRP depletion tests, one sham and one active. At the estimated time of maximum TRP depletion, each patient received an i.v. infusion of TRP 100 mg/kg. Blood was obtained for serum cortisol, prolactin, and growth hormone. Mood was assessed using standardized rating scales. RESULTS: The cortisol response to i.v. TRP was significantly greater during TRP depletion than during sham depletion. Depressive symptoms showed a tendency to decrease after i.v. TRP following active, but not sham, TRP depletion. CONCLUSIONS: These findings are consistent with the present hypothesis and previous evidence that acute TRP depletion in drug-free depressed patients induces compensatory upregulation of postsynaptic 5-HT receptors. These changes are insufficient to serve as a means of effecting clinical improvement, but suggest that the antidepressant properties of rapid, marked manipulations of 5-HT function warrant further study.

Adult↗
PubMed1998

Tryptophan depletion during continuous CSF sampling in healthy human subjects.

The tryptophan (TRP) depletion paradigm has been employed to investigate mood and behavioral effects of acutely lowering plasma TRP, and presumably brain serotonin (5-hydroxytryptamine [5-HT]) levels through administration of a special diet and/or amino acid drink. Our goal was to test the assumption that a corresponding fall in central levels of TRP and 5-HT (measured by its major metabolite, 5-hydroxyindoleacetic acid [5-HIAA]) occurs during the standard execution of this method in healthy adult subjects. Three males and two females completed the protocol, which included a one-day low-TRP diet and a TRP-free amino acid drink. Lumbar puncture was performed, with placement of an indwelling catheter connected to a peristaltic pump and fraction collector. Cerebrospinal fluid (CSF) was sampled continuously for a 13.5-hour period (before, during, and after the drink), with fractions removed every 15 minutes. Plasma samples were simultaneously obtained. CSF TRP levels and plasma TRP levels were highly correlated, falling a mean of 92% and 85% from baseline, respectively. CSF nadirs were reached several hours after plasma nadirs. CSF 5-HIAA decreased modestly (24% to 40%, mean 31% change from baseline), with lowest concentrations observed 8-12 hours after the amino acid drink. These data suggest that TRP depletion results in substantial declines in central 5-HT turnover.

Adult↗
PubMed1998

Sertraline in adults with pervasive developmental disorders: a prospective open-label investigation.

The short-term efficacy and tolerability of sertraline for adults with pervasive developmental disorders (PDDs) were assessed in this investigation. Forty-two adults with PDDs (autistic disorder, N = 22; Asperger's disorder, N = 6; and PDD not otherwise specified [NOS], N = 14) participated in a 12-week, open-label, systematic trial of sertraline. Behavioral ratings of repetitive symptoms, aggression, and social relatedness were obtained at baseline and after 4, 8, and 12 weeks of sertraline administration. Twenty-four (57%) of 42 patients showed significant improvement, primarily in repetitive and aggressive symptoms. Statistically significant changes in measures of social relatedness did not occur. Patients with autistic disorder and PDD NOS did significantly better than those with Asperger's disorder. Based on global improvement item criteria from the Clinical Global Impression Scale, 15 of 22 (68%) patients with autistic disorder, none of six (0%) patients with Asperger's disorder, and 9 of 14 (64%) patients with PDD NOS were categorized as treatment responders. Sertraline was well tolerated; no adverse cardiovascular effects, extrapyramidal symptoms, or seizures were identified. These findings suggested that sertraline may be an effective treatment for interfering repetitive and aggressive symptoms in adults with PDDs. Definitive statements about the efficacy and tolerability of sertraline for treating adults with PDDs must await results from double-blind, placebo-controlled trials. These preliminary results should not be generalized to include children and adolescents with PDDs.

1-Naphthylamine↗
PubMed1998

Global functioning of inpatients with obsessive-compulsive disorder, schizophrenia, and major depression.

A chart review was conducted to compare the social, occupational, and daily functioning of 17 inpatients with obsessive-compulsive disorder, 17 with major depression, and 17 with schizophrenia. Current Global Assessment of Functioning (GAF) scores of patients with schizophrenia were significantly lower than those of patients with depression and with obsessive-compulsive disorder. However, on work performance, daily living skills, and past-year GAF scores, patients with obsessive-compulsive disorder and those with schizophrenia did not differ significantly, and both groups were significantly more impaired than patients with depression. Results show that inpatients with obsessive-compulsive disorder may exhibit severe and chronic functional impairments requiring extensive supportive and rehabilitative services.

Activities of Daily Living↗
PubMed1997

Autism.

Explore the source record for details and available documents.

Autistic Disorder↗
PubMed1997

Assessment of diurnal variation of cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in healthy human females.

The role of serotonin (5-HT) in the pathogenesis and treatment of major neuropsychiatric disorders, including mood and anxiety disorders, continues to be the subject of extensive research. Previous studies examining central 5-HT functioning measured cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA) by using single or multiple lumbar punctures. A number of investigators have demonstrated the feasibility of continuous CSF sampling via an indwelling lumbar catheter to study CSF neurochemistry in healthy subjects and patients with neuropsychiatric illness. Four healthy female volunteers, aged 21-34 years, underwent continuous CSF sampling. CSF was collected at a constant rate of 1 ml every 10 minutes over a 30-hour period, with levels of tryptophan (TRP) and 5-HIAA measured every hour. Plasma was also obtained hourly for TRP determination. The results of this study indicate that CSF 5-HIAA, CSF TRP, and plasma TRP levels showed variation over time, but failed to show diurnal fluctuation. Intra-individual coefficients of variation determined for CSF 5-HIAA, CSF TRP, and plasma TRP ranged from 9.2 to 14.9%, 8.8 to 14.6%, and 14.7 to 19.0%, respectively. Continuous CSF sampling is safe and feasible in humans, and may prove useful for studies of central 5-HT neurotransmission in neuropsychiatric illness.

Adult↗
PubMed1997

Effects of antiglucocorticoid treatment on 5-HT1A function in depressed patients and healthy subjects.

Clinical studies suggest that 5-HT1A receptor function may be blunted in depression, while 5-HT1A agonists may possess antidepressant activity. Preclinical findings implicate changes in 5-HT1A receptor sensitivity in the mechanism of antidepressant action. The hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in depression could be related to those observations, since 5-HT1A receptors are inhibited by glucocorticoids. To evaluate the interaction of the HPA and 5-HT1A systems, we pretreated 15 unipolar depressed patients and 12 healthy control subjects with the antiglucocorticoid ketoconazole (KTCZ) prior to administration of a test dose of the 5-HT1A agonist ipsapirone (IPS). Neuroendocrine (ACTH, cortisol, growth hormone), physiological (hypothermia), and behavioral responses to IPS were assessed. As expected, KTCZ inhibited cortisol biosynthesis, but non-HPA responses to IPS were not enhanced. This study failed to show that glucocorticoid modulation of 5-HT1A receptor function is altered in depression.

Adrenocorticotropic Hormone↗
PubMed1997

Neurobiology of tryptophan depletion in depression: effects of m-chlorophenylpiperazine (mCPP).

This study utilized neuroendocrine and mood responses to intravenous (i.v.) infusion of the serotonin (5-HT) agonist m-chlorophenylpiperazine (mCPP) to evaluate central 5-HT function in depressed patients undergoing acute tryptophan (TRP) depletion. Twenty-two drug-free patients with DSM-III-R major depression participated. Each patient underwent two randomized, double-blind TRP depletion tests, one sham and one active. At the estimated time of maximum TRP depletion, each patient received an i.v. infusion of mCPP 0.1 mg/kg. Blood was obtained for serum cortisol, prolactin, and growth hormone. Multiple rating scales were used to assess mood. The cortisol response to i.v. mCPP was significantly greater during TRP depletion than during sham depletion, and free plasma TRP was negatively correlated with the cortisol response during TRP depletion. These findings are consistent with the hypothesis that acute TRP depletion in drug-free depressed patients induces a compensatory up-regulation of postsynaptic 5-HT receptors, most likely of the 5-HT2A/2C subtype. Such changes suggest a mechanism by which acute and potent manipulations of 5-HT function in depressed patients could be used to effect rapid clinical improvement.

Adult↗
PubMed1997

Clomipramine in adults with pervasive developmental disorders: a prospective open-label investigation.

The purpose of this investigation was to determine the short-term efficacy and tolerability of clomipramine in a consecutive series of adults with pervasive developmental disorders (PDDs). Thirty-five adults with PDDs (DSM-IV), 16 of whom were nonverbal, entered a 12-week prospective open-label trial of clomipramine. The initial sample included 18 patients with autistic disorder, 6 patients with Asperger's disorder, and 11 patients with pervasive developmental disorder not otherwise specified (PDDNOS). Behavioral ratings were obtained at baseline and after 4, 8, and 12 weeks of clomipramine. Eighteen (55%) of the 33 patients who completed the trial were categorized as treatment responders based on scores of "much improved" or "very much improved" on the Clinical Global Impression (CGI) global improvement item (p < 0.001). Ten (63%) of 16 patients with autistic disorder, 2 (33%) of 6 patients with Asperger's disorder, and 6 (55%) of 11 patients with PDDNOS were considered responders to clomipramine treatment. In those 18 patients, clomipramine significantly reduced total repetitive thoughts and behavior (p < 0.001) and also aggression (p < 0.001), and improved some aspects of social relatedness, such as eye contact and verbal responsiveness (p < 0.001). Change in these specific symptom clusters over time was not related to DSM-IV subtype of PDD. The level of autistic behavior, as measured by the Autism Behavior Checklist (ABC) score, and full-scale intelligence quotient (IQ) were not significantly associated with global treatment response. Whereas clomipramine was well tolerated by most patients, 13 had clinically significant adverse effects. Three patients had seizures during clomipramine treatment, including 2 who had prior seizure disorders and were taking anticonvulsants. Of the 32 patients who had no history of prior seizures, only 1 had a seizure during clomipramine treatment. There were no adverse cardiovascular or extrapyramidal effects. All responders continued on clomipramine after completion of the study. The results of this open-label trial suggest that clomipramine may be an effective drug for reducing repetitive thoughts and actions and aggressive behavior and for improving some elements of social behavior, such as eye contact and verbal responsivity in adults with PDDs. Careful monitoring of adverse effects, particularly seizures, is warranted. Although an electroencephalogram (EEG) is not mandatory in patients with PDD prior to clomipramine treatment, we recommend that patients with PDD and a history of seizures be treated initially with a selective serotonin uptake inhibitor rather than with clomipramine. The findings of this study require replication in a double-blind placebo-controlled investigation before definitive statements of efficacy and tolerability can be made.

Adolescent↗
PubMed1997

Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective open-label study.

OBJECTIVE: To investigate the short-term safety and efficacy of risperidone in the treatment of children and adolescents with pervasive developmental disorders. METHOD: This was a 12-week, prospective, systematic, open-label trial that included 18 subjects (15 boys and 3 girls) with a mean age of 10.2 +/- 3.7 years. The sample included 11 subjects with autistic disorder, 3 with Asperger's disorder, 1 with childhood disintegrative disorder, and 3 with pervasive developmental disorder not otherwise specified. Fourteen subjects had comorbid mental retardation. Behavioral ratings were obtained during two baseline visits and again after 12 weeks of risperidone treatment. RESULTS: The optimal dose of risperidone for the 18 subjects was 1.8 +/- 1.0 mg/day. On the basis of the global improvement item of the Clinical Global Impression Scale, 12 of 18 subjects were considered responders. Significant improvement was seen in measures of interfering repetitive behavior, aggression and impulsivity, and some elements of impaired social relatedness. The most common side effect was weight gain (range 10 to 35 lb). CONCLUSIONS: These preliminary results suggest that risperidone may be effective for improving interfering behavioral symptoms in some children and adolescents with pervasive developmental disorders. Double-blind, placebo-controlled studies are needed before definitive statements of safety and efficacy can be made.

Adolescent↗
PubMed1997

Symptoms of obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder encompasses a broad range of symptoms that represent multiple psychological domains, including perception, cognition, emotion, social relatedness, and diverse motor behaviors. The purpose of these analyses was to evaluate the correlational relationships of the symptoms of obsessive-compulsive disorder. METHOD: This study examined the 13 a priori categories used to group types of obsessions and compulsions in the Yale-Brown Obsessive Compulsive Scale symptom checklist in two independent groups of patients with obsessive-compulsive disorder (N = 208 and N = 98). A principal-components factor analysis with varimax rotation was performed, followed by a series of other exploratory analyses. RESULTS: The two data sets yielded nearly identical results. Four factors--obsessions and checking, symmetry and ordering, cleanliness and washing, and boarding--emerged in each data set, in total accounting for more than 60% of the variance. CONCLUSIONS: Obsessive-compulsive disorder is a multidimensional and etiologically heterogeneous condition. The four symptom dimensions identified in this study are largely congruent with those identified in earlier reports. These factors may be of value in future genetic, neurobiological, and treatment response studies.

Adult↗
PubMed1997

Addition of desipramine to serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to determine whether combined treatment with a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor, desipramine, effectively reduces obsessive-compulsive symptoms in patients who do not respond to SSRIs. METHOD: In a double-blind study, desipramine or placebo was added for 6 or 10 weeks to the treatment of 30 patients with obsessive-compulsive disorder whose symptoms were refractory to SSRI treatment (fluvoxamine, fluoxetine, or sertraline) alone. RESULTS: There were no significant differences between the adjunctive desipramine and placebo groups in obsessive-compulsive or depressive symptoms. CONCLUSIONS: These data suggest that clomipramine's possibly superior efficacy in the treatment of obsessive-compulsive symptoms may not stem from its capacity to inhibit reuptake of norepinephrine.

1-Naphthylamine↗
PubMed1997

Update on pharmacologic management of OCD: agents and augmentation.

A preponderance of patients with obsessive-compulsive disorder (OCD) experience little or no improvement in their symptoms when treated with serotonin reuptake inhibitors (SRIs). It is hypothesized that SRI-refractory patients may have altered serotonin neurotransmission different from patients responsive to SRIs, or that they may have abnormalities in their dopamine function. When drugs affecting serotonin function (e.g., tryptophan, fenfluramine, lithium, buspirone) are added to SRI therapy in SRI-refractory patients, results are mixed and not consistently encouraging. However, when drugs affecting dopamine function (e.g., pimozide, haloperidol, risperidone) are added to SRI therapy in SRI-refractory OCD patients, individuals with either a personal history or family history of tics experience a reduction in their symptoms.

Clinical Trials as Topic↗