Red-cell lithium transport and affective disorders in a multigeneration pedigree: evidence for genetic transmission of affective disorders.
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Adolescent↗
Biomedical subjects
G N Pandey
Publications and source records attributed to G N Pandey.
Beta adrenergic receptor function in depression and the effect of antidepressant drugs.
It has been suggested that alterations of monoamine receptor sensitivity in the central nervous system may be associated with some forms of affective illness. It has been observed by several investigators that chronic treatment with antidepressant drugs causes down regulation of NE receptor coupled adenylate cyclase and beta adrenergic receptor binding in rat brain. This observation has led to the suggestion that the therapeutic effects of antidepressant drugs may be related to the changes in the responsivity of beta adrenergic receptors. In order to examine if depressive illness may be associated with altered beta adrenergic function, we studied adenylate cyclase and its responsiveness to norepinephrine and isoproterenol in the leukocytes obtained from patients with psychiatric illness and normal controls as an index of beta adrenergic receptor function. We also studied the effects of antidepressant drugs, in vitro, on isoproterenol sensitive leukocyte adenylate cyclase. We observed that norepinephrine and isoproterenol sensitive leukocyte adenylate cyclase in depressed patients are significantly decreased as compared to normal controls. Our results appear to have been replicated by another group of investigators. We also observed that certain antidepressant drugs potentiate isoproterenol stimulated accumulation of cyclic AMP in human leukocytes. This potentiation was most pronounced in the case of iprindole. These results thus indicated a decreased beta adrenergic receptor function in patients with depressive illness. Whether or not such decreased receptor function is associated with depressive illness or is a manifestation of some other changes unrelated to the illness is not clear. Our results also indicate that some antidepressant drugs may enhance adrenergic transmission by potentiating the effects of neurotransmitters on beta adrenergic receptors.
Adenylyl Cyclases↗
Studies of beta-adrenergic receptors in leukocytes of patients with affective illness and effects of antidepressant drugs.
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Adenylyl Cyclases↗
Effect of heavy metals on fish--a review.
Heavy metals are being utilized in a variety of ways in industries, agriculture, food processing and household in many forms. Metals are unique environmental and industrial pollutants in the sense that they are neither created nor destroyed by human beings but are only transported and transformed into various products. The present communication deals with the findings of various investigators on the effect of heavy metals on fresh water fish.
Animals↗
Effects of antidepressants on the uptake and release of norepinephrine from rat cerebral cortex.
The effects of several antidepressants on the release of (3H)-norepinephrine (NE) from homogenates of rat cerebral cortex were studied. A continuous superfusion collection system was used in order to differentiate these effects from effects on reuptake. Amitriptyline, maprotiline, mianserin, and trazodone produced a statistically significant decrease in spontaneous tritium efflux when present in the superfusion medium at a concentration of 1.0 microM. The other antidepressants studied had no effect. We used a buffer with the K+ concentration raised to 56 mM as a model of depolarization-induced release. Desipramine, fluoxetine, and iprindole (again at 1.0 microM) caused a significant decrease in this measure. These results indicate that some of both the tricyclic and atypical antidepressants may alter spontaneous or depolarization-induced release of NE.
Animals↗
Lithium transport in red cells of patients with affective disorders.
Variation in red cell Li+ transport as mediated by the Li+-Na+ exchange pathway (Li+-Na+ counterflow) appears to cause wide variation between psychiatric patients in the Li+ ratio (erythrocyte/plasma) in vivo during Li+ treatment. We obtained significant correlations between Li+ ratios determined in vivo and several measures of Li+ transport as mediated by Li+-Na+ exchange. Patients with bipolar illness had significantly lower rates of Li+ transport as mediated by this pathway than did normal subjects.
Bipolar Disorder↗
Mixture distributions in psychiatric research.
This paper describes the application of Gaussian mixture distributions to biological marker research in psychiatry. Mixtures of univariate and multivariate normal distributions can be used to determine if diagnostically similar psychiatric patients belong to biologically distinct subpopulations. The resulting biological subtypes may be important in understanding the etiology of psychiatric disorders. The general model and estimation procedure are described (EM algorithm; Dempster, Laird and Rubin 1977). The method is illustrated using two examples of biological data: (1) red cell membranes and monoamine oxidase activity data in normal individuals having no family history of psychiatric illness, the first-degree relatives of bipolar depressed patients and a heterogeneous patient population; and (2) smooth pursuit eye movements that classify relatives of schizophrenics, nonschizophrenics and normal controls into biologically distinct populations.
Bipolar Disorder↗
Lithium ion transport and affective disorders within families of bipolar patients. Identification of a major gene locus.
We have identified a genetic polymorphism in which one allele results in elevated RBC lithium ion ratios and also contributes to vulnerability to some forms of affective disorders. Interindividual variability in the lithium ion ratio (the ratio of the RBC to the plasma lithium ion concentration) is determined by variability in a lithium ion ratio (the ratio of the RBC to the plasma lithium ion concentration) is determined by variability in a lithium-sodium ion counterflow mechanism. Segregation analyses were conducted on lithium ion ratios in vitro in members of 120 normal families and on both the lithium ion ratio and the history of affective disorder in first-degree relatives of 31 bipolar patients. These analyses provided evidence for an autosomal major gene locus that influences the lithium ion ratio both in members of normal families and in relatives of bipolar patients. The allele at the major locus resulting in elevated lithium ion ratios was associated with an increased likelihood of psychiatric hospitalization among relatives of bipolar patients.
Alleles↗
Treatment with antidepressants and histamine receptor mediated 3H-cyclic AMP formation in guinea pig cortex.
It has been recently reported that most of the antidepressant drugs block histamine H1 and H2 receptors in the brain under in vitro conditions and it has been suggested that this may be related in part to their therapeutic effect. Since the in vitro and in vivo effects of these drugs may differ, we studied the effect of treatment with antidepressant drugs on histamine receptor sensitivity in the guinea pig brain and observed that chronic treatment with tricyclic antidepressants or phenelzine (an MAO inhibitor) causes a reduction in histamine receptor sensitivity. This reduction is probably mediated through two different mechanisms, since only tricyclic antidepressants cause a reduction after acute treatment. Although some of the side effects of antidepressant treatment may be related to the blockade of histamine receptors, these results do not support the assumption that this effect of antidepressant treatment contributes to their clinical effects.
Animals↗
Platelet monoamine oxidase activity and behavioral response to pharmacotherapy in psychiatric patients.
Platelet monoamine oxidase (MAO) levels were determined for drug-free psychiatric inpatients who were subsequently treated with neuroleptics, tricyclics, or lithium. Weekly, time-sampled recordings of specific behaviors were also made during both drug-free and medication periods. Significant correlations were obtained between MAO levels and changes in behavior scores subsequent to drug administration. For six of the seven recorded behaviors, correlations for patients treated with lithium vs. tricyclics were in the opposite direction. The results suggest that MAO levels, measured during a drug-free period, can predict some of the behavioral responses to antidepressant medications.
Adult↗
Evaluation of fluorometric assay methods for serotonin in platelets. Plasma and whole blood samples by comparison with GC-MS-SIM Technique.
Different methods have been used for the determination of serotonin (5HT) in human blood platelets, whole blood and plasma samples, but there have been very few reports on inter-method correlations. We now report the evaluation of fluorometric method using o-phthalaldehyde (OPT), with 3H-5HT as internal standard and GC-MS method using deuterated (d4-) 5-HT as internal standard. Basic extracts (pH 9.5) of sonicated platelet samples, hemolyzed blood or plasma samples are converted to trifluoroacetyl (TFA) or pentafluoropropionyl (PFP) derivatives. An aliquot of this derivatized sample (10%) was used for 3H count for determining the percent recovery, a second aliquot for GC-MS, and the rest for quantitation of OPT fluorescence (Emax360 millimicrons and Fmax 470 millimicrons). In another series, duplicate samples are extracted, one for fluorometry and the second for GS-MS with d4-5-HT as internal standard. Ions m/e 351 and 354 are monitored for the TFA and m/e 451 and 454 for PFP derivatives. The correlation between OPT fluorescence and GS-MS methods was good (0.95) for the platelets, but was poor (0.63) for whole blood and plasma samples. Thin layer chromatography of whole blood and plasma extracts showed multiple spots which yield characteristic fluorescence with OPT spray having same Emax or high background fluorescence. Serotonin levels in platelet samples of normal controls, and patients with different diagnoses of psychiatric disorders are presented.
Blood Platelets↗
Li-Na counterflow in families of schizo-affective patients.
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Adolescent↗
Characterization of alpha-adrenergic receptors in guinea pig cerebral cortex: effect of chronic antidepressant treatments.
Alpha-adrenergic receptor sites in cerebral cortex membranes of the guinea pig have been characterized by the specific binding of 3H-WB4101, an alpha-adrenergic antagonist. The binding was rapid, reversible, saturable, and stereoselective. The maximal binding site (Bmax) and dissociation constant (kd) for 3H-WB4101 were calculated to be 251 fmol/mg protein and 1.23 nM, respectively. Ligand displacement experiments suggest that 3H-WB4101 binds to alpha 1-adrenergic receptors. Chronic treatment of guinea pigs with desipramine, amitriptyline, phenelzine, or electroconvulsive shock failed to show any statistically significant change in alpha-adrenergic receptor sensitivity as measured by the binding of 3H-WB4101.
Adrenergic alpha-Agonists↗
Effect of chronic treatment with antidepressants on beta-adrenergic receptor binding in guinea pig brain.
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Animals↗
Lithium transport across the RBC membrane. A study of genetic factors.
The measurement of the ratio of RBC to plasma lithium ion levels in vitro in 291 members of 120 families indicated that genetic factors contribute substantially to interindividual variability in the lithium ion distribution across the RBC membrane. These factors affect the lithium-sodium ion exchange system that determines the lithium ion distribution.
Adolescent↗
Personality correlates of platelet monoamine oxidase activity anbd red cell lithium transport.
Platelet monoamine oxidase (MAO) activity and the ratio of red cell to plasma lithium concentrations (Li ratio) may be important in the pathophysiology of, and genetic vulnerability to, some psychiatric disorders. By using the Clinical Analysis Questionnaire, we assessed personality correlates of MAO activity and the Li ratio in vitro in a sample of psychiatrically normal adult women. We found that there were correlates of each variable, and a unique constellation of personality traits when the two variables were considered simultaneously.
Adolescent↗
Reduced platelet MAO activity and vulnerability to psychiatric disorders.
Platelet monoamine oxidase (MAO) is a genetically controlled mitochondrial enzyme that metabolizes amines in the brain by deamination. We investigated the relationship between MAO activity and the presence or absence of psychopathology by determining MAO activity and the psychiatric diagnosis in 61 first-degree relatives of 31 patients with bipolar (manic-depressive) illness. Relatives who themselves were diagnosed as having bipolar I illness or alcoholism had a significantly lower mean MAO activity level than did other relatives or 255 normal individuals. These findings indicate that a relationship exists within pedigrees between MAO activity and psychiatric disorders. Reduced MAO activity may play a role in vulnerability to some types of psychopathology.
Alcoholism↗