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Biomedical subjects

G N Pandey

Publications and source records attributed to G N Pandey.

At least 55 records · Page 3Linked to original sources
PubMed1991

Platelet 3H-imipramine binding sites in obsessive-compulsive behavior.

Several studies indicate a serotonergic dysfunction in patients with obsessive-compulsive disorder (OCD). We examined serotonergic function in OCD by determining platelet 3H-impiramine binding sites in patients with OCD during a drug-free baseline period as well as normal control volunteers. The maximum number of binding sites (Bmax) and apparent dissociation constant (Kd) was determined using 3H-imipramine (IMI) as the binding ligand. We observed that the mean 3H-IMI binding Bmax (fmol/mg protein) determined in 24 patients with OCD was not significantly different from that in 23 normal control subjects. There were no significant differences in the Kd between patients with OCD and normal control subjects. Our results are thus similar to those reported by Insel et al (1985) and Black et al (1990), who observed no significant differences in platelet 3H-IMI binding between OCD patients and controls; but different from those reported by Weizmann et al (1986), who observed decreased 3H-IMI Bmax in OCD patients. The discrepancy in the results is not clear, but may be related to several factors. Our results thus indicate that any abnormality in serotonergic function present in patients with OCD is not related to imipramine binding sites in the platelets. However, the possibility that there may be an abnormal platelet serotonin uptake or other serotonergic function in OCD cannot be ruled out.

Adult↗
PubMed1991

Effect of antidepressants and neuroleptics on phosphoinositide metabolism in human platelets.

The effect of tricyclic antidepressants (imipramine, desipramine, amitriptyline) and several other antidepressants like iprindole, a monoamine oxidase inhibitor phenelzine, trazodone and mianserin as well as cocaine (a potent inhibitor of norepinephrine uptake), and neuroleptics (haloperidol, thioridazine, chlorpromazine) on [3H]inositol phosphate formation was investigated in human platelets. Basal and thrombin-induced [3H]inositol monophosphate ([3H]IP1), [3H]inositol bisphosphate ([3H]IP2) and [3H]inositol trisphosphate ([3H]IP3) production were measured in [3H]myoinositol-labeled platelets in the presence of lithium chloride and in the presence or absence of test drugs. Desipramine, imipramine, amitriptyline and iprindole inhibited thrombin-stimulated formation of [3H]IP2 and [3H]IP3 in human platelets but had no significant effect on [3H]IP1 formation. In contrast, trazodone, mianserin, cocaine and phenelzine had no effect on inositol phosphate formation in thrombin-stimulated human platelets. The neuroleptics thioridazine and chlorpromazine also decreased thrombin-stimulated [3H]IP2 and [3H]IP3 production but not [3H]IP1 in human platelets, whereas haloperidol had no significant effect. The effect of antidepressants and neuroleptics on the level of [3H]phosphatidylinositol ([3H]PI), [3H]phosphatidylinositol 4-phosphate ([3H]PIP) and [3H]phosphatidylinositol 4,5-bisphosphate ([3H]PIP2) was also determined. All of the drugs tested except phenelzine and thioridazine increased the accumulation of [3H]PI, [3H]PIP and [3H]PIP2. Thioridazine increased levels of [3H]PI but decreased the level of [3H]PIP and [3H]PIP2, whereas phenelzine had no effect on [3H]PI, [3H]PIP and [3H]PIP2 interconversion in human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidepressive Agents, Tricyclic↗
PubMed1991

Effect of desipramine on inositol phosphate formation and inositol phospholipids in rat brain and human platelets.

To examine the mechanism of action of antidepressant drugs, we studied the effect of desipramine (DMI) in vitro on agonist-stimulated inositol phosphate formation and inositol phospholipids in rat brain and human platelets. We observed that DMI inhibited thrombin-stimulated 3H-inositol bisphosphate (IP2) and 3H-inositol trisphosphate (IP3) but not 3H-inositol monophosphate (IP1) formation in human platelets. DMI also inhibited norepinephrine (NE) and serotonin (5-HT) stimulated 3H-IP1 formation in rat cerebral cortex. DMI increased levels of all three 3H-inositol phospholipids, 3H-phosphatidyl inositol (PI), 3H-PI-4-phosphate (PIP), and 3H-PI 4,5-bisphosphate (PIP2), in both platelets and rat cortex. The decreased formation of inositol phosphates and increased levels of [3H]-PI, [3H]-PIP, and [3H]-PIP2 by DMI appears to be due to the inhibition of the enzyme phospholipase C rather than its effects on receptors. It is thus possible that interaction of tricyclic antidepressant drugs with the PI-signaling system may be related to their mechanism of action.

Animals↗
PubMed1990

Platelet serotonin-2 receptor binding sites in depression and suicide.

In order to examine the role of serotonin-2 (5HT2) receptors in depression and suicide, we determined 5HT2 receptors using 125I-lysergic acid diethylamide (LSD) as the binding ligand in platelets obtained from 20 normal control and 23 drug-free depressed patients. Our results indicate significantly increased 125I-LSD binding sites (Bmax) in the platelets of depressed patients compared with normal control subjects. We also observed that a subgroup of depressed patients with a recent history of suicide attempts or suicidal ideation had significantly higher 5HT2 binding sites as compared with nonsuicidal depressed patients and normal controls. There were no significant differences in the apparent dissociation constant (Kd) values in the platelets of depressed patients compared with normal control subjects. To examine if the baseline 5HT2 receptors are related to either the severity of illness or treatment response, we determined the relationships of the baseline Bmax and Kd with baseline Hamilton Depression Rating Scale (HDRS) and Brief Psychiatric Rating Scale (BPRS) scores and change in scores after treatment. We found no significant correlation between baseline Bmax and Kd with the baseline HDRS or BPRS scores or change in these scores after psychoactive drug treatment. These results thus indicate increased platelet 5HT2 receptors in depression, but much more so in depressed patients with suicidal ideation or attempts.

Adult↗
PubMed1990

Pharmacological effects of methylphenidate on plasma homovanillic acid and growth hormone.

The acute pharmacological actions of methylphenidate, a potent psychotogenic stimulant, were studied by measuring plasma homovanillic acid (HVA) and serum growth hormone (GH) as indices of presynaptic and postsynaptic functions, respectively. Twenty psychiatric inpatients participated in a double-blind, placebo-randomized study of methylphenidate infusion. Multiple samples of plasma HVA and GH were measured before and up to 24 hours after both methylphenidate and placebo infusions. There was a robust and significant GH response during the 2-hour postmethylphenidate period when compared to placebo. The peak response was significantly greater in male patients than in female patients. Although there were no changes in plasma HVA during the 2 hours following the infusion, there was a significant decrease in HVA 24 hours after methylphenidate as compared to preinfusion baseline values. Plasma HVA values also tended to be lower 24 hours after methylphenidate when compared to the corresponding postplacebo value. Schizophrenic patients did not differ significantly from nonschizophrenic patients in their physiological or biochemical responses.

Adult↗
PubMed1990

Lithium distribution in mania: single-dose pharmacokinetics and sympathoadrenal function.

We examined lithium distribution after a single dose of 25 mEq in 14 drug-free manic patients. Lithium concentrations were measured in plasma, red blood cells, and urine. Maximum concentrations of lithium, times at which they were attained, and influx and efflux rate constants for extracellular fluid, red blood cell, and muscle-like compartments were estimated using a three-compartment pharmacokinetic model. Tissue lithium concentrations may continue to increase for hours after plasma lithium concentrations have peaked. Rate constants for absorption, excretion, and influx and efflux for the tissue compartments were similar to those previously reported for normal subjects. Rate constants for transport into and out of the tissue compartments correlated negatively with norepinephrine or epinephrine excretion and positively with the plasma/red cell Na+ gradient. Rate constants for efflux from red blood cell and muscle compartments correlated with measures of adrenocortical function and were higher in dexamethasone nonsuppressors than in suppressors. These data show that distribution of lithium may be related to sympathodrenal activity and Na+ distribution in manic patients.

Adrenal Cortex↗
PubMed1990

Platelet MAO inhibition, urinary MHPG, and leukocyte beta-adrenergic receptors in depressed patients treated with phenelzine.

The authors investigated three biochemical indices of peripheral catecholamine activity in 36 depressed inpatients treated with the monoamine oxidase (MAO) inhibitor phenelzine. Platelet MAO activity, urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), and leukocyte beta-adrenergic receptor functions were measured before and during the 4th week of phenelzine treatment. There were significant reductions in platelet MAO activity, urinary MHPG excretion, and depressive symptoms in all of the patients. Responders had the same decrease in MHPG as nonresponders. There were no changes in leukocyte beta-receptor function in a small subgroup of the patients.

Blood Platelets↗
PubMed1990

MAO inhibition and clinical response in depressed patients treated with phenelzine.

The authors studied clinical response in 47 depressed inpatients treated with the monoamine oxidase (MAO) inhibitor phenelzine. Improvement on ratings for depression at Week 2 of treatment was correlated with percent MAO inhibition at Week 2 (r = .35, p less than .03), and the modest positive correlation that was found remained after the authors adjusted for the effects of baseline scores on the Hamilton Rating Scale for Depression, dose (mg/kg), and psychosis (partial correlation = .49, p less than .002). Further, the 23 patients ultimately classified as responders had a significantly greater percent MAO inhibition at Week 2 than did the 24 nonresponders (t = 3.02, p less than .005). Thus, the rate of MAO inhibition at Week 2 was significantly correlated with clinical improvement at Week 2 and final response status. These findings could not be explained by other potentially moderating variables such as sex, age, endogenicity, recurrence, and incapacitation.

Adult↗
PubMed1989

Increased 3H-clonidine binding in the platelets of patients with depressive and schizophrenic disorders.

To examine whether alpha 2-adrenergic receptor function is altered in affective and schizophrenic disorders, we determined 3H-clonidine binding in platelets obtained from 33 normal control subjects and from 24 patients with depressive, 22 patients with schizophrenic, 18 with bipolar, and 8 patients with schizoaffective disorders during a drug-free period. The maximum number of binding sites (Bmax) and apparent dissociation constant (Kd) for high affinity 3H-clonidine binding was computed by Scatchard analysis. Comparison of the diagnostic groups indicated that the Bmax in depressed, schizophrenic, and schizoaffective patients was significantly higher than in normal controls, but there were no significant Bmax differences between bipolar patients and controls. Comparison of the Kd among the diagnostic groups indicated no significant differences among the groups or between patient diagnostic groups and normal controls. Baseline Bmax in schizophrenic patients was significantly correlated with the decrease in Brief Psychiatric Rating Scale (BPRS) scores after treatment, suggesting a relationship between baseline Bmax and clinical response. Treatment with lithium caused a significant decrease in the baseline Bmax, whereas treatment with desipramine or trifluoperazine did not cause significant changes in the baseline Bmax. Our results thus indicate an increase in the number of alpha 2-adrenergic receptors in depressed and schizophrenic patients as compared to normal controls.

Bipolar Disorder↗
PubMed1988

Platelet monoamine oxidase in alcoholism.

We studied platelet monamine oxidase (MAO) activity using 14C-tyramine as substrate in hospitalized alcoholic patients in the early phases of abstinence and in nonhospitalized normal control volunteers. Platelet MAO was determined in 75 patients (67 men, 8 women) with alcoholism and 123 normal control volunteers (52 men, 71 women). The platelet MAO activity in alcoholic patients was significantly lower than in normal control volunteers. We also observed that the mean platelet MAO activity in male alcoholics was significantly lower than in normal males. The analysis of platelet MAO in alcoholics revealed a mixture of two normal distributions. Alcoholic patients falling into the low MAO component were younger in age, with a lower age of onset of alcoholism, and had higher frequencies of family history of alcoholism. They thus resembled type II alcoholics described by other investigators. Platelet MAO may thus serve as a useful biological marker for subtyping alcoholism and identifying high-risk groups at an early stage. The findings of this study are consistent with previous reports of low platelet MAO activity in alcoholic patients.

Adult↗
PubMed1988

The effect of diagnosis and age on the DST: a metaanalytic approach.

The authors present new data on the results of the pretreatment Dexamethasone Suppression Test (DST) in 164 drug-free inpatients, as well as on the effects of age on postdexamethasone cortisol values. Nonsuppression rates were 18% in schizophrenic patients (n = 44), versus 46% in patients with a major depression (n = 56). In addition, a significant correlation was found between age and the 4:00 PM postdexamethasone cortisol value among the depressed patients (r = 0.33). The authors then applied a metaanalysis to summarize 25 other studies that have addressed the schizophrenia/major depression dichotomy as it relates to the DST outcome. Nonsuppression rates were consistently different in schizophrenic patients (19%) when compared to patients with a major depression (51%) or normal controls (7%). These differences were highly significant as measured by the Mantel-Haenszel chi-square statistic. A metaanalysis applied to a series of correlations obtained from 14 other studies reporting an age/postdexamethasone cortisol relationship in affective patients indicated a modest, but significant correlation (r = 0.24) in a total of 1284 patients (p less than 1 x 10(-8)).

Adolescent↗
PubMed1988

EEG sleep, lithium transport, dexamethasone suppression, and monoamine oxidase activity in borderline personality disorder.

Twenty-one patients who met DSM-III criteria for borderline personality disorder (BPD) and also scored at least 7 on the Diagnostic Interview for Borderlines (DIB) were assessed on four biological markers: electroencephalographic (EEG) sleep, in vitro lithium ratio, platelet monoamine oxidase (MAO), and dexamethasone suppression test (DST). REM latency averaged 58.66 (SD 14.39); platelet MAO averaged 21.74 (SD 10.33); and lithium ratio was 0.357 (SD 0.139) in the BPD patients. All of those values were significantly abnormal. Many patients had abnormalities on three or four measures. These patients in general had multiple Axis I diagnoses from the Diagnostic Interview Schedule (DIS), and these Axis I diagnoses tended to produce patient clusters. Patients with a DIS diagnosis of schizophrenia, mania, hypomania, or schizoaffective mania had elevated lithium, low MAO, and normal EEG sleep, while those patients with coexisting major depression tended to have short rapid eye movement (REM) latency, high REM density, and normal MAO and lithium ratio. Only two patients were nonsuppressors on the DST, confirming recent reports of normal DST results in personality disorders.

Adult↗
PubMed1988

Response of psychotic and nonpsychotic depression to phenelzine.

The authors studied 52 depressed inpatients to examine treatment response to phenelzine, a monoamine oxidase (MAO) inhibitor. All patients were classified into one of three RDC categories (definitely psychotic, probably psychotic, and nonpsychotic). For the entire sample, the mean platelet MAO inhibition level achieved with phenelzine was greater than 80%. Response to treatment was determined by independent clinical assessment and by the change in rating scores from baseline; 68% of the nonpsychotic, 43% of the probably psychotic, and 21% of the definitely psychotic patients were classified as responders. This differential response rate is similar to that reported in the literature for tricyclic antidepressants.

Antidepressive Agents, Tricyclic↗
PubMed1987

Decreased beta-adrenergic receptors in the leukocytes of depressed patients.

We studied beta-adrenergic receptor binding, using 125I-cyanopindolol as the ligand, in the leukocyte membranes of depressed patients, schizophrenic patients, and normal control subjects during a drug-free period. We also determined plasma cortisol levels and dexamethasone suppression in these subjects. The maximum number of beta-adrenergic receptor sites (Bmax) was significantly lower in depressed patients than in normal control subjects. Nonsuppressors on the dexamethasone suppression test tended to have a decreased Bmax in comparison to suppressors. There was no significant difference in the Kd between any of the groups. These results indicate that decreased beta-adrenergic receptor responsiveness in the leukocytes of depressed patients is probably due to a decrease in the number of beta-adrenergic receptor sites.

Adult↗
PubMed1987

Pretreatment dexamethasone suppression test as a predictor of response to phenelzine.

Twenty inpatients who met Research Diagnostic Criteria and DSM-III criteria for depression underwent a 2-week washout period before the administration of a pretreatment dexamethasone suppression test (DST); the patients then received the monoamine oxidase inhibitor (MAOI) phenelzine. The mean MAO inhibition level achieved during treatment was greater than 80%. On the basis of clinical global evaluation and changes in Hamilton Rating Scale for Depression scores, 7 of the 9 baseline DST suppressors were classified as responders, 1 as a partial responder, and 1 as a nonresponder; of the 11 baseline DST nonsuppressors, 3 were responders, 1 a partial responder, and 7 nonresponders. The Mann-Whitney U test yielded p less than .02, indicating that an abnormally high pretreatment level of cortisol in response to the DST appeared to be predictive of nonresponse to phenelzine.

Adult↗
PubMed1985

Pharmacologic evidence for specificity of pursuit dysfunction to schizophrenia. Lithium carbonate associated with abnormal pursuit.

Conflicting findings regarding the prevalence of abnormal smooth-pursuit eye movements in patients with major affective disorders call into question the specificity of impaired smooth-pursuit eye movements to schizophrenia. We report that pursuit is impaired in 88% of lithium carbonate-treated affective disorder patients whose pursuit was normal prior to receiving this drug. Over half of lithium carbonate-treated affective disorder patients in remission also showed impairment of smooth-pursuit eye movements. In conjunction with recent prevalence data on family members of psychiatric patients, the findings support the specificity of abnormal pursuit as a biological trait associated with schizophrenia, but not with the major affective disorders. The mechanisms by which lithium carbonate impairs pursuit are discussed.

Adult↗