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Biomedical subjects

J Zohar

Publications and source records attributed to J Zohar.

At least 73 records · Page 4Linked to original sources
PubMed1988

Return of symptoms after discontinuation of clomipramine in patients with obsessive-compulsive disorder.

To evaluate the need for maintenance drug therapy in patients with obsessive-compulsive disorder, the authors assessed 21 patients with obsessive-compulsive disorder who manifested sustained improvement during 5 to 27 months of clomipramine treatment and who agreed to participate in a double-blind discontinuation study. Of 18 patients who completed the study, 16 had substantial recurrence of obsessive-compulsive symptoms by the end of the 7-week placebo period. In addition, 11 had a significant increase in depressive symptoms. Treatment duration before discontinuation of clomipramine was not related to the frequency or severity of obsessive-compulsive or depressive symptom appearance. These findings suggest that prolonged drug treatment may be warranted for obsessive-compulsive disorder.

Adult↗
PubMed1987

Chronic lithium treatment increases the phosphorylation of a 64-kDa protein in rat brains.

Despite the wide clinical use of lithium in the treatment of manic depressive illness there is no adequate explanation for its mechanism of action. In the light of lithium's suggestive effects on the second messenger system in the brain, we studied the effects of chronic dietary lithium treatment (achieving blood levels in the therapeutic range) on protein phosphorylation in different areas of rat brain. An increase in the phosphorylation of a 64-kDa membrane-associated protein was evident in the lithium-treated rats compared to controls. This increase was observed only under basal phosphorylating conditions and was abolished when the phosphorylation was performed in the presence of Ca2+ or Ca2+ and calmodulin. The possibility that this 64-kDa protein affected by lithium is the beta-subunit of the calmodulin-dependent protein kinase or a different protein which co-migrates with it is discussed.

Animals↗
PubMed1987

Serotonergic responsivity in obsessive-compulsive disorder. Comparison of patients and healthy controls.

To examine the "serotonin hypothesis" of obsessive-compulsive disorder (OCD), we studied the behavioral and neuroendocrine effects of metachlorophenylpiperazine (mCPP), a serotonergic agonist, in patients with OCD and healthy controls. Twelve patients and 20 controls were given a single dose of 0.5 mg/kg of mCPP, administered orally under double-blind, placebo-controlled, random-assignment conditions. Following mCPP, but not following placebo, patients with OCD experienced a transient but marked exacerbation of obsessive-compulsive symptoms. Moreover, compared with healthy controls, patients exhibited greater other behavioral (but not endocrinologic or thermal) changes after mCPP. These findings are consistent with a special role for the neurotransmitter serotonin in OCD psychopathology.

Adult↗
PubMed1987

Obsessive-compulsive disorder: psychobiological approaches to diagnosis, treatment, and pathophysiology.

The diagnosis, treatment, and pathophysiology of obsessive-compulsive disorder (OCD) were examined in a series of studies utilizing psychobiological approaches. Putative biological markers previously reported in depression were studied in this disorder and revealed that on some measures [Dexamethasone Suppression Test and rapid eye movement (REM) latency on sleep electroencephalogram (EEG)], OCD patients resemble those with major depressive disorder (MDD), whereas on others [REM density, platelet serotonin uptake, probably platelet 3H-imipramine binding, and 5-hydroxy-indoleacetic acid (5-HIAA) in cerebral spinal fluid (CSF)] they do not. The relationship between OCD and MDD was further explored in a double-blind, randomized crossover study designed to compare the antiobsessional effects of two tricyclic antidepressants, clomipramine (CMI) and desipramine (DMI), in a nondepressed cohort of OCD patients. CMI was found to have significant antiobsessional effects in this group, whereas in the same patients, DMI lacked therapeutic effects. These results suggest that not all antidepressants are antiobsessive and that some property of CMI, such as its potent serotonergic effects, may be of pathophysiological relevance for OCD. The role of serotonin in this disorder was then tested using the pharmacological challenge strategy. A novel serotonin postsynaptic receptor (5HT-1) agonist, m-chlorophenylpiperazine (m-CPP), was administered orally (0.5 mg/kg) under double-blind, placebo-controlled conditions to OCD patients and controls. In addition, a serotonergic receptor antagonist, metergoline (4 mg), was given to a subset of OCD patients. Relative to healthy volunteers, the OCD patients became significantly more anxious, depressed, and dysphoric after m-CPP administration. Moreover, in the OCD patients, obsessive-compulsive symptoms increased markedly after m-CPP and decreased significantly following metergoline administration. These results demonstrate that agents that bind to the 5HT-1 receptor can acutely affect the symptoms of OCD patients. The striking behavioral effects of these direct postsynaptic receptor ligands and the relative specificity of clomipramine as an antiobsessional agent suggest that serotonergic neurons may play a role in the pathophysiology, as well as mediating the pharmacological reduction, of obsessional symptoms.

Adult↗
PubMed1987

Long-term imipramine treatment enhances locomotor and food intake suppressant effects of m-chlorophenylpiperazine in rats.

1 Administration of the 5-HT1B receptor agonist m-chlorophenylpiperazine (m-CPP) to rats produces dose-dependent decreases in locomotor activity and food intake. 2 The locomotor suppressant effect of m-CPP was inhibited by the 5-hydroxytryptaminergic antagonist, metergoline, but not by phentolamine, propranolol, clonidine, or haloperidol. 3 The locomotor suppressant effects of m-CPP were enhanced following long-term (but not short-term) treatment with imipramine, possibly reflecting the postulated development of a functional supersensitivity of 5-HT1B receptors mediating locomotion during longer-term antidepressant drug treatment. 4 The food intake suppressant effects of m-CPP were enhanced following both short (3-5 days) and longer-term (21 days) treatment with imipramine. Rapidly developing 5-hydroxytryptamine uptake inhibition may be responsible for this change, or it may represent an earlier adaptive change in the 5-HT1B receptors mediating food intake compared to more complexly modulated motor responses.

Animals↗
PubMed1986

Utility of neuroleptic blood levels in the treatment of acute psychosis.

Twenty-two acutely psychotic patients were treated with a flexible dose of haloperidol in a 5-week study. The neuroleptic blood levels of all patients were measured; however, for 10 of the patients, the treating physician remained blind to the drug blood level. The Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions (CGI) scale were administered at study entry and once a week by a blind rater. No clinical differences were seen between the two groups at any time point. However, blood levels within an operative therapeutic range of 10-20 ng/ml were seen at the same rate in both groups of patients. These data do not contradict other findings which suggest a correlation between clinical outcome and blood level but rather suggest that responsible clinicians using clinical signs can maintain the "average patient" within the range of therapeutic blood levels, even without the laboratory monitoring of such levels.

Acute Disease↗
PubMed1985

Effect of lysine vasopressin in depressed patients on mood and 24-hour rhythm of growth hormone, cortisol, melatonin and prolactin.

Lysine-8-vasopressin (LVP) for 10 days and in doses up to 13.5 LVP units did not significantly alter the Hamilton Depression Rating Scale scores of 12 severely depressed, treatment-resistant patients who were evaluated in a double-blind crossover study. The 24-h rhythms of melatonin, cortisol, growth hormone and prolactin appeared remarkably stable over the course of repeated measurement. LVP administration did not affect these 24-h rhythms.

Adult↗
PubMed1984

The effects of chronic lithium and ECT on A1 and A2 adenosine receptor systems in rat brain.

The influence of chronic dietary lithium administration and electroconvulsive therapy on adenosine A1 and A2 receptors in rat brain were determined. A2 receptor activity was measured by accumulation of cyclic AMP in a cerebral cortical slice preparation after in vitro addition of 2-chloro-adenosine, and was unchanged in animals which received chronic Li but reduced following chronic ECT. A similar reduction was found in the response to noradrenaline and a combination of the two agents. A1 receptors were measured by binding of [3H]cyclohexyladenosine. Both Kd and Bmax values were unchanged after chronic Li or a single ECS, but chronic ECT led to a 70% increase in Bmax. It is proposed that this effect may mediate the reduced locomotor activity seen after chronic ECT in rats, and that it may also be related to the increase in seizure thresholds seen during a course of ECS treatment in humans.

Adenosine↗
PubMed1983

The response of lymphocyte beta-adrenergic receptors to chronic propranolol treatment in depressed patients, schizophrenic patients, and normal controls.

The ability of beta-adrenergic receptors to adapt to reductions in stimulation might be impaired in depressed or schizophrenic patients. To test this hypothesis 12 normal controls, 12 depressed patients resistant to tricyclic antidepressants, and 8 chronic schizophrenic patients were treated with propranolol 160 mg/day for 10 days. A previous study had reported that this dose regimen led to a rise in lymphocyte beta-adrenergic receptors in normal volunteers. Blood was sampled before propranolol treatment and 60 hr after the last propranolol dose. There were no significant differences between any of the groups in lymphocyte beta-adrenergic receptors after 10 days of propranolol treatment.

Adult↗
PubMed1982

The effect of chronic lithium pretreatment on rat brain muscarinic receptor regulation.

The effect of two weeks of lithium (Li) pretreatment on up and down regulation of muscarinic receptors in rat brain was measured in two groups of rats. After two weeks of feeding 0.2% LiCL in ground pellets, one group of rats was injected with atropine (3 mg/kg daily for 5 days) and another group with diisopropyl fluorophosphate, a cholinesterase inhibitor (1.2 mg/kg). Li pretreatment completely abolishes the significant 23% rise in QNB binding induced by atropine but does not prevent the significant 16% decline in QNB binding induced by DFP. These results suggest that chronic Li pretreatment prevents supersensitivity but does not prevent subsensitivity of rat brain muscarinic receptors.

Animals↗
PubMed1982

Lithium does not prevent agonist-induced subsensitivity of human adenylate cyclase.

In a previous study 11 depressed patients were treated with salbutamol, a beta-2 adrenergic agonist, and beta-2 adrenergic receptor sensitivity was evaluated by measuring the plasma cyclic AMP rise after an iv dose of salbutamol. Salbutamol treatment induced subsensitivity of the beta-adrenergic adenylate cyclase with a time course paralleling the antidepressant effects. In the present study nine patients who were depressed despite treatment with lithium were treated with salbutamol plus lithium. Subsensitivity of the beta-adrenergic adenylate cyclase developed in the presence of lithium to the same degree as in patients treated with salbutamol alone. These results represent the first human study of the theory that lithium stabilizes receptor sensitivity changes. Lithium's failure to prevent subsensitivity agrees with reports that lithium fails to prevent impramine-induced subsensitivity of beta-adrenergic receptors in rat cortex. Lithium stabilization of receptor sensitivity of beta-adrenergic receptors in rat cortex. Lithium stabilization of receptor sensitivity would therefore appear to be unidirectional, preventing supersensitivity but not subsensitivity.

Adenylyl Cyclases↗