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Biomedical subjects

T R Insel

Publications and source records attributed to T R Insel.

At least 163 records · Page 9Linked to original sources
PubMed1985

Obsessive-compulsive disorder.

Obsessive-compulsive disorder is a heterogeneous cluster of syndromes that share aspects of both anxiety and affective disorders. Obsessive-compulsive disorder is epidemiologically and phenomenologically distinct from the compulsive character. Although both genetic and neuropsychological data suggest some biologic basis to obsessive-compulsive disorder, there is still insufficient information in both of these areas. Treatment with clomipramine, a tricyclic antidepressant, has proved useful for obsessional patients either as an adjunct to behavior therapy or as a primary treatment for patients who are not amenable to behavioral interventions.

Antidepressive Agents, Tricyclic↗
PubMed1984

Corticotropin-releasing factor receptors in rat forebrain: autoradiographic identification.

Corticotropin-releasing factor (CRF) receptors were identified in rat forebrain by autoradiography with an iodine-125-labeled analog of ovine CRF substituted with norleucine and tyrosine at amino acid residues 21 and 32, respectively. High-affinity receptors for CRF were found in discrete areas of rat forebrain, including laminae I and IV of the neocortex, the external layer of the medium eminence, the lateral nucleus of the amygdala, and the striatum. These results are consistent with earlier findings on the immunohistochemical distribution of CRF and suggest that endogenous CRF has a physiological role in regulating activity of the central nervous system.

Amygdala↗
PubMed1984

Plasma cortisol and catecholamine responses to intracerebroventricular administration of CRF to rhesus monkeys.

Synthetic ovine corticotropin releasing factor (CRF) was administered directly into the 4th ventricle of rhesus monkeys. A dose dependent increase in plasma cortisol was observed following 10 micrograms/kg, 20 micrograms/kg, and 60 micrograms/kg of CRF. Increases in plasma epinephrine were also evident following the highest dose of CRF. Plasma norepinephrine, mean arterial pressure, and heart rate did not increase significantly following CRF administration. These data suggest that in the rhesus monkey, central administration of ovine CRF leads to activation of the pituitary-adrenocortical axis at doses that do not raise plasma catecholamines.

Animals↗
PubMed1984

Neuroendocrine and behavioral effects of m-chlorophenylpiperazine administration in rhesus monkeys.

The effects of m-chlorophenylpiperazine (mCPP), a serotonin receptor agonist, on the release of plasma prolactin (PRL), growth hormone (GH), and cortisol in the rhesus monkey were studied. mCPP was administered intravenously at doses of 0.5, 1.5, and 3.0 mg/kg. GH and cortisol were increased significantly at all doses while PRL was significantly increased only following administration of 3.0 mg/kg mCPP. mCPP administration also produced behavioral alterations in each monkey, including sedation, penile erection, and defecation. PRL, GH and behavioral responses to mCPP were completely blocked by pretreatment with the serotonin antagonist metergoline (MTG). However, pretreatment treatment with MTG failed to entirely anagonize the cortisol response to mCPP. These data suggest that mCPP has prominent neuroendocrine and behavioral effects which are mediated, in part, by serotonergic mechanisms.

Animals↗
PubMed1984

A benzodiazepine receptor-mediated model of anxiety. Studies in nonhuman primates and clinical implications.

beta-Carboline-3-carboxylic acid ethyl ester (beta-CCE) binds with high affinity to brain benzodiazepine receptors and has potent behavioral and physiologic effects in primates. Dose-related increases in behavioral agitation, plasma cortisol level, BP, and heart rate were observed after administration of doses between 50 and 500 micrograms/kg of beta-CCE to rhesus monkeys. All of these effects were blocked by pretreatment with diazepam. Pretreatment with clonidine hydrochloride and propranolol hydrochloride, both of which have been reported to have anxiolytic actions in man, attenuated only selective aspects of the response to beta-CCE. The behavioral, endocrine, and physiologic effects of low doses of beta-CCE in monkeys are similar to those observed in anxious patients or normal subjects under anxiety-provoking or stressful situations. Administration of benzodiazepine receptor active antagonists such as beta-CCE to primates may, therefore, provide a valid and reproducible model of human anxiety that could be used to investigate specific biologic aspects of anxiety disorders.

Animals↗
PubMed1984

Biological markers in obsessive-compulsive and affective disorders.

To explore the relationship between obsessive-compulsive disorder (OCD) and affective disorder, patients with OCD were studied using a series of biological markers which have been previously reported to be abnormal in patients with affective illness. These "markers" included the dexamethasone suppression test, sleep electroencephalography, the plasma growth hormone response to clonidine, and platelet 3H-imipramine binding. Results from each of these studies suggested similarities between patients with obsessional disorder and those with affective illness. Many of these biological abnormalities were evident in obsessional patients who did not manifest depressive symptoms. As a tricyclic antidepressant, clomipramine, has been found to reduce obsessional symptoms, the relationship between these "affective-like" laboratory findings and the clinical response to clomipramine was studied in a subgroup of OCD patients. Preliminary results suggest that none of the markers studied predict clomipramine response.

Blood Platelets↗
PubMed1984

Families of origin in obsessive-compulsive disorder.

Family data were collected on 174 relatives of 10 severely obsessive-compulsive patients. No instances of obsessive-compulsive disorder were found, although 11.6 per cent of first degree relatives had been hospitalized for other psychiatric illness. These rather isolated families had cultures that emphasized cleanliness and perfection, but other family members did not develop rituals or obsessive rationales as the patient did. Typically, one or both parents in an unfulfilled marriage directed symbiotic needs toward the patient. Parents and offspring became trapped in an increasingly powerless struggle against symptoms that acted as a barrier to closeness, but that also prevented the patient from developing an autonomous existence. It was concluded that parental symbiotic needs combined with perfectionist family styles, possibly superimposed on a constitutional vulnerability to psychiatric disturbance, form a major contribution to obsessive-compulsive disorder.

Adolescent↗
PubMed1984

Psychophysiological changes during pharmacological treatment of patients with obsessive compulsive disorder.

Twelve patients with obsessive compulsive disorder were studied with psychophysiological measures during a randomised, double-blind placebo-controlled drug trial. Significant clinical improvement followed six weeks of treatment with the tricyclic antidepressant clomipramine, but was not evident after an equal period of treatment with the monoamine oxidase inhibitor (MAOI) clorgyline. Compared to placebo, both drugs reduced skin conductance indices of baseline arousal, but only clomipramine reduced skin conductance and heart rate responses to loud tones and tonic and phasic skin conductance responses in a two-flash discrimination task. This suggests that reductions in autonomic responses to important and/or aversive stimuli may be critical to clinical improvement in obsessive compulsive disorder.

Adolescent↗
PubMed1983

Increased plasma MHPG in dexamethasone-resistant depressed patients.

Severely depressed patients frequently show inadequate suppression of serum cortisol levels by dexamethasone. In a study of 15 depressed patients, we found a robust correlation between plasma levels of cortisol and 3-methoxy-4-hydroxy-phenylglycol after dexamethasone administration. These results suggest that dexamethasone resistance and adrenergic activation reflect parallel responses to illness-related stress in some depressed patients.

Adult↗
PubMed1983

Obsessive-compulsive disorder. A double-blind trial of clomipramine and clorgyline.

Patients with obsessive-compulsive disorder who met DSM-III criteria and who had been ill for at least one year were studied in a double-blind, randomized, crossover comparison of the tricyclic antidepressant clomipramine hydrochloride and the monoamine oxidase inhibitor clorgyline hydrochloride. No significant improvement was evident after four weeks of treatment with placebo prior to the crossover study. Treatment with clomipramine was associated with significant improvement after both four and six weeks in measures of obsessions, anxiety, and depression. Antiobsessional responses to clomipramine did not depend on presence of depression. Improvement was correlated with plasma concentrations of clomipramine, but not with the plasma concentrations of any of its metabolites. No significant improvement was evident for the entire group with clorgyline treatment, although the conditions of individual patients did respond to the drug.

Adult↗
PubMed1983

D-amphetamine in obsessive-compulsive disorder.

In a double-blind crossover study, single doses of d-amphetamine and placebo were administered to 12 patients with severe chronic obsessive-compulsive disorder (OCD). Improvement of obsessional symptoms was significant on clinical ratings and was correlated with improved performance on an attention task. Changes were also significant for self-rated measures of activation and altered reality. The behavior response to amphetamine was not statistically correlated with subsequent improvement during a 6-week clomipramine trial, although the direction of change was the same during both treatments for every patient studied.

Adolescent↗
PubMed1983

Effect of long-term clorgyline administration on human platelet alpha-adrenergic receptor binding and platelet cyclic AMP responses.

Platelet alpha 2-adrenergic receptor number and physiologic responsiveness, as well as plasma norepinephrine (NE), were evaluated in psychiatric patients with major depressive disorder before and during chronic clorgyline treatment. The alpha 2-adrenergic receptor number was determined by measuring the binding of tritiated dihydroergocriptine (3H-DHE) to platelet membranes. Physiologic responsiveness was determined by measuring the response of cyclic adenosine 3'-5'-monophosphate (cAMP) to prostaglandin E1 (PGE1), and the inhibition of the PGE1-stimulated cAMP response by NE in intact platelets. No significant differences from pretreatment values were observed in platelet alpha 2-adrenergic binding or responsiveness during clorgyline treatment. Baseline platelet cAMP production and plasma NE levels were significantly decreased after chronic clorgyline treatment. Previous studies on animals and humans have suggested that brain alpha 2-adrenergic receptor responsiveness decreases during chronic clorgyline treatment. The present findings therefore suggest that such changes may represent adaptations induced by long-term clorgyline administration which may differ between the brain and the platelet, thus illustrating potential limitations of the study of platelet alpha 2-adrenergic receptors as a model for central alpha 2-adrenergic receptor adaptation.

Adult↗
PubMed1983

Parents of patients with obsessive-compulsive disorder.

Family histories obtained from 27 patients with obsessive-compulsive disorder failed to find a single parent with the disorder. To augment the family history data the Leyton Obsessional Inventory was completed by a subset of 10 patients and by their 20 parents. Although as a group parents showed lower Leyton Obsessional Inventory symptom scores than their obsessional offspring, 3 parents who had not been identified by family history were distinguished by high symptom scores in the absence of significant resistance or interference.

Adolescent↗
PubMed1983

The dexamethasone suppression test: promises and problems of diagnostic laboratory tests in psychiatry.

Diagnostic tests in medicine must satisfy certain validity and accuracy criteria to be clinically useful. In psychiatry, the validity of a diagnostic procedure might be tested independently against clinical diagnosis, treatment response, and family history criteria; a strong relationship to any of the three would suggest clinical usefulness. Predictive value theory provides a model for such a test. The dexamethasone suppression test (DST) has a lower predictive value for major depressive disorder than most conventional laboratory tests used for diagnosis in medicine. In spite of promising early reports, the DST is not predictive of treatment response nor does it appear to identify genetic subtypes of depression. Although no diagnostic laboratory test is currently powerful enough for routine clinical use in psychiatry, laboratory tests may prove useful in predicting relapse and in continuing research on the psychobiology of mental disorders.

Circadian Rhythm↗
PubMed1983

Growth hormone response to clonidine in obsessive-compulsive patients.

We have observed a lesser growth hormone response to intravenous clonidine administration in nine obsessive-compulsive disorder patients meeting research diagnostic criteria than in nine matched controls. The obsessive-compulsive disorder patients had higher plasma free 3-methoxy-4-hydroxyphenylglycol and plasma norepinephrine levels before clonidine than the controls. As blunted growth hormone responses to clonidine are also characteristic of affective disorder patients, these results support other observations of a psychobiologic affinity between these two groups and are also compatible with an association between increased presynaptic noradrenergic activity and decreased post-synaptic receptor responsiveness.

Adolescent↗
PubMed1983

Neurological and neuropsychological studies of patients with obsessive-compulsive disorder.

We studied 18 DSM-III diagnosed obsessive-compulsive disorder patients with the Halstead-Reitan Battery (HRB), EEGs, and CT scans. Results for the group as a whole were within the normal range; however two patients had abnormal EEGs and four showed average impairment ratings on the HRB high enough to suggest organic deficits. More than half of the subjects were impaired on the tactual performance test from the HRB suggesting a possible deficit in spatial perception. These data, however, do not define a single neuropsychological deficit nor do they replicate an earlier report of left frontal lobe dysfunction in obsessive-compulsive disorder. Cerebral CT scans in ten patients, including all those with EEG and average impairment rating abnormalities, showed VBR, asymmetry, and sulcal prominence measures indistinguishable from a matched group of nonpsychiatric control subjects.

Adult↗