Search PubMed⌕ Search

Biomedical subjects

L H Price

Publications and source records attributed to L H Price.

At least 55 records · Page 3Linked to original sources
PubMed1997

Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse.

BACKGROUND: Short-term depletion of plasma tryptophan has been shown to result in depressive relapse in patients with remission of major depression. Positron emission tomography and single photon emission computed tomography studies implicated the dorsolateral prefrontal cortex, orbitofrontal cortex, thalamus, and caudate nucleus in the pathogenesis of depression. The purpose of this study was to measure cerebral metabolic correlates of tryptophan depletion-induced depressive relapse. METHODS: Patients diagnosed as having major depression (N = 21) who clinically improved with serotonin reuptake inhibitors underwent 2 test days involving tryptophan depletion or placebo, followed 6 hours later by positron emission tomography scanning with fludeoxy-glucose F18. Brain metabolism was compared in patients with (n = 7) and without (n = 14) a tryptophan depletion-induced depressive relapse. RESULTS: Tryptophan depletion resulted in a decrease in brain metabolism in the middle frontal gyrus (dorsolateral prefrontal cortex), thalamus, and orbitofrontal cortex in patients with a depletion-induced depressive relapse (but not in patients without depletion-induced relapse). Decreased brain metabolism in these regions correlated with increased depressive symptoms. Baseline metabolism was increased in prefrontal and limbic regions in relapse-prone patients. CONCLUSION: Specific brain regions, including the middle frontal gyrus, thalamus, and orbitofrontal cortex, may mediate the symptoms of patients with major depression.

Antidepressive Agents↗
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

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↗
PubMed1996

Effects of tryptophan depletion in drug-free adults with autistic disorder.

BACKGROUND: The primary objective of this study was to investigate the behavioral and biochemical responses to acute tryptophan depletion in drug-free adult patients with autistic disorder. METHODS: Twenty drug-free adults with autistic disorder (16 men and 4 women) (mean [+/- SD] age, 30.5 +/- 8.5 years) underwent short-term tryptophan depletion in a double-blind, placebo-controlled, randomized crossover design. Patients received a 24-hour, low-tryptophan diet followed the next morning by an amino acid drink. Behavioral ratings were obtained on the morning of the amino acid drink (baseline) and 180, 300, and 420 minutes after the drink. Plasma free and total tryptophan levels were obtained at baseline and 5 hours after the drink. The active and sham testing sessions were separated by 7 days. RESULTS: Eleven (65%) of the 17 patients who completed both test days showed a significant global worsening of behavioral symptoms with short-term tryptophan depletion, but none of the 17 patients showed any significant change in clinical status from baseline after sham depletion (P = .001). Tryptophan depletion led to a significant increase in behaviors such as whirling, flapping, pacing, banging and hitting self, rocking, and toe walking (P < .05). In addition, patients were significantly less calm and happy and more anxious. No significant change was observed in social relatedness or repetitive thoughts and behavior. Plasma total and free tryptophan levels were reduced 86% and 69%, respectively, 5 hours after the tryptophan-deficient amino acid drink. Patients who had a significant global exacerbation of symptoms had significantly higher baseline plasma total tryptophan levels (P < .001) and Autism Behavior Checklist scores (P = .005) than did patients who showed no significant change in symptoms after tryptophan depletion. CONCLUSIONS: The results of this study are consistent with previous research that has implicated a dysregulation in serotonin function in some patients with autism. These data suggest that the short-term reduction of serotonin precursor availability may exacerbate some symptoms characteristic of autism in some patients. Continued investigation into the role of serotonin in the pathogenesis and treatment of autistic disorder is warranted.

Adult↗
PubMed1996

A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder.

BACKGROUND: Autistic disorder is characterized by a fundamental disturbance in social interaction, impairments in communication, and a markedly restricted repertoire of activities and interests. Abnormalities in the serotonin neurotransmitter system have been identified in some persons with autism. No consistently effective and safe drugs have been developed for treating the symptoms of autism. METHODS: Thirty adults with autistic disorder completed a 12-week double-blind, placebo-controlled trial of the potent and selective serotonin uptake inhibitor fluvoxamine maleate. Behavioral ratings were obtained at baseline and after 4, 8, and 12 weeks of treatment. RESULTS: Eight (53%) of 15 patients in the fluvoxamine-treated group were categorized as responders compared with none of 15 in the placebo group (P = .001). Fluvoxamine was superior to placebo in reducing repetitive thoughts and behavior (P < .001), maladaptive behavior (P < .001), and aggression (P < .03), and in improving some aspects of social relatedness (P < .04), especially language usage (P < .008). Treatment response was not correlated with age level of autistic behavior, or full-scale IQ. Other than mild sedation and nausea in a few patients, fluvoxamine was well tolerated. No dyskinesias, adverse cardiovascular events, or seizures occurred. CONCLUSIONS: Fluvoxamine is more effective than placebo in the short-term treatment of the symptoms of autistic disorder in adults. Controlled studies of fluvoxamine and other potent and selective serotonin uptake inhibitors seem warranted in children and adolescents with autism.

Adolescent↗
PubMed1996

Seasonal variation in neuroendocrine and mood responses to i.v. L-tryptophan in depressed patients and healthy subjects.

Seasonality of mood disorders might involve alterations in the rhythmicity of serotonin [5-HT] function. We examined seasonal effects on the neuroendocrine and mood responses to L-tryptophan (L-TRP) in depressed patients and healthy subjects. In this study, 126 drug-free patients with DSM-III-R major depression and 58 healthy subjects received in i.v. infusion of L-TRP. Serum prolactin (PRL) and plasma tryptophan levels were measured. Mood was assessed with visual analogue scales. Cosinor analysis revealed seasonal variation in peak change (delta) PRL and baseline tryptophan levels in the combined depressed and in unipolar, nonmelancholic, and nonpsychotic patients. Peak delta PRL and tryptophan levels were inversely correlated in combined depressed and unipolar patients. Seasonality was more evident in female than in male patients. These data support previous evidence that 5-HT function is abnormal in depression and further suggest a seasonal variability of such abnormalities that is absent in healthy subjects.

Adult↗
PubMed1996

A risk-benefit assessment of drugs used in the management of obsessive-compulsive disorder.

Established efficacy and tolerability in large multicentre controlled studies have made serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SRIs) the mainstay of monotherapy for adult obsessive-compulsive disorder (OCD). When compared with the selective serotonin reuptake inhibitors (SSRIs), the tricyclic compound clomipramine has a higher incidence of adverse effects but is well tolerated by most OCD patients and may confer the best overall antiobsessional effects. Consideration of specific adverse effect profiles, special patient population characteristics, drug interactions and relative cost of the various agents may direct clinicians in choosing the most appropriate first-line drug. Alternative agents as monotherapies have been explored, but none has consistently proven effective to date. Investigations of SRI augmentation with serotonin-enhancing agents have also failed to demonstrate substantial benefits for treatment-refractory OCD. Combination treatment with SRIs and dopamine receptor antagonist drugs appears to provide an improved response for the subpopulation of OCD patients who have comorbid 'tic-spectrum' disorders, though large-scale studies of the efficacy and tolerability of these regimens are not yet available.

1-Naphthylamine↗