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Biomedical subjects

R Hitzemann

Publications and source records attributed to R Hitzemann.

At least 109 records · Page 6Linked to original sources
PubMed1986

Lithium ratio in vitro: familial patterns of illness.

Psychiatric illness in first-degree relatives of psychotic patients with low, intermediate, and high red blood cell (RBC) in vitro lithium ratio (LR) was investigated using the Schedule for Affective Disorders and Schizophrenia and DSM-III. Fewer schizophrenic spectrum disorders were found in the first-degree relatives of high and low LR probands as compared to intermediate LR probands; high LR psychotic probands had families with an increased frequency of depressive spectrum disorder. Alcohol dependence and abuse was particularly prominent in the first-degree relatives of the higher LR probands. High LR may identify a disease that does not belong to the familial-genetic disorders of the schizophrenic spectrum; this illness may bear a closer relationship to disorders of the depressive spectrum.

Adult↗
PubMed1985

Opiate receptor thermodynamics: agonist and antagonist binding.

The equilibrium thermodynamics of [3H]etorphine and [3H]diprenorphine binding to rat brain membranes were studied. In the absence of NaCl, the binding of [3H]etorphine was endothermic (delta Ho = +2.31 kcal/mol) and driven by a large increase in entropy (delta So = +51.8 e.u.). Under similar conditions, the binding of [3H]diprenorphine was exothermic (delta Ho = -2.78 kcal/mol). In the presence of 100 mM NaCl, [3H]etorphine binding was relatively isothermic (delta Ho = +0.61 kcal/mol) and driven by a large increase in entropy (delta So = +45.6 e.u.). NaCl significantly decreased both delta Ho (-2.78 to -7.48 kcal/mol) and delta So (33.0 to 18.5 e.u.) for [3H]diprenorphine binding. The data suggest that the agonist configuration of the opiate receptor exists in a more open and mobile (higher entropy) conformation than does the antagonist form of the receptor.

Animals↗
PubMed1985

Characteristics of phospholipid methylation in human erythrocyte ghosts: relationship(s) to the psychoses and affective disorders.

Recent studies have shown that patients with a schizophrenic-like illness have a significant deficit in erythrocyte ghost membrane (EGM) phosphatidylcholine (PC); patients with the most severe deficiency showed a marked decrease in Na+-Li+ counterflow activity (Hitzemann et al. 1984a and b). The present study was undertaken to see if the decrement in PC is associated with a decrease in phospholipid methylation activity. Phospholipid methylation in human EGMs is distinctly different from that in rat EGMs (Hirata and Axelrod 1980) in that the human activity is not Mg++-dependent, and apparent methyltransferase I activity is located in the external membrane surface. The patient population consisted of 20 DSM-III schizophrenics (SCZ), 13 DSM-III schizophreniform (SF) disorder patients, and 11 DSM-III manics (M). Twelve age- and sex-matched controls were used for the comparison group. Methylation activity was significantly decreased in all three patient groups, although the M group had significantly higher activity than the SF group. Twenty-four of the SCZ and SF patients entered a Li+ trial. The Li+ responder group (n = 8) showed significantly lower activity than the nonresponder group (n = 16). Overall, we conclude that the decrement in phospholipid methylation activity partially contributes to the decrement in PC levels.

Adult↗
PubMed1984

Lithium ratio in vitro. Diagnosis and lithium carbonate response in psychotic patients.

The distribution of RBC lithium ratios in vitro in a recently hospitalized psychiatric population was found to be multimodal. Psychotic patients who had an antipsychotic response during open trials of lithium carbonate alone were identified with high sensitivity (89%), but low specificity (51%) before drug treatment, by lithium ratios that were in the extreme modes of the distribution (less than 0.30 or greater than 0.38). Diagnostic efficiency of the test was 61%. The DSM-III diagnosis of schizophreniform disorder demonstrated 90% diagnostic efficiency in predicting response/nonresponse during treatment with lithium carbonate alone. A subgroup of the psychotic disorders was similar to affective disorders with respect to course of illness, biological characteristics, and response to lithium carbonate.

Clinical Trials as Topic↗
PubMed1984

Dopamine and non-dopamine psychoses.

The time course of antipsychotic response following the initiation of an antipsychotic drug and functional dopamine receptor sensitivity were explored in a cohort of recently admitted psychotic (mood-incongruent) patients. The distribution of the latencies of antipsychotic response suggested at least two populations. Rapid responders (RRs) had 60% reduction of baseline psychotic symptoms by a mean of 5.5 days of drug treatment. Delayed/nonresponders required 2-7 weeks for a similar reduction of psychotic symptoms. The sensitivity of postsynaptic dopamine receptors was explored using a neuroendocrine probe: growth hormone response to the dopamine agonist, apomorphine (AP). RRs had an exaggerated growth hormone response to AP in comparison to delayed/nonresponders (P less than 0.05). Exaggerated sensitivity of postsynaptic dopamine receptors and rapid antipsychotic response following dopamine receptor blockade in RRs suggest a true functional dopamine hypersensitivity disorder in the RR group. In contrast, lower postsynaptic receptor sensitivity (as reflected by lower growth hormone response to AP) and failure of early response following dopamine receptor blockade focus attention away from dopamine hyperactivity as a relevant etiologic mechanism in delayed/nonresponders. Response rates to neuroleptic drugs and neuroendocrine probes of receptor sensitivity may separate two or more etiologically distinct diseases with schizophrenic-like symptoms.

Antipsychotic Agents↗
PubMed1984

Membrane abnormalities in the psychoses and affective disorders.

Erythrocyte ghost phospholipid data were collected on 67 psychotic and/or manic patients and compared to a group of 35 age and sex matched controls. Patients meeting DSM-III criteria for schizophreniform disorder or schizophrenia but not mania showed a small but significant decrease in membrane phosphatidylcholine (PC). In 53 of the patients data were available on lithium transport across red cell membranes. Patients in the upper quartile of the PC distribution showed a significant (-47%) decrease in the 24 h in vitro lithium ratio as compared to patients in the lower PC quartile. This difference was due to an increase in Na-Li+ counterflow activity in the upper PC quartile and not to a change in passive lithium leak. These data illustrate one example of a possible relationship between membrane composition and a membrane function, counterflow activity, which has been associated with the underlying mechanism(s) of lithium action.

Adult↗
PubMed1984

Membranes, methylation and lithium responsive psychoses.

Data are presented showing that the erythrocyte ghost membranes of lithium-responsive and non-responsive schizophrenic-like patients are different from control membranes. In both groups of patients there was a significant decrement of phosphatidylcholine (PC) which was largely compensated for by an increase in sphingomyelin. The decrement in PC may in part be associated with a decrease in phospholipid methylation which converts phosphatidylethanolmine (PE) to PC. Interestingly, in the lithium-responsive but not the non-responsive patients, lithium stimulates methylation activity. This stimulation may affect a variety of membrane functions, e.g. adenyl cyclase activity, which would be involved in lithium's therapeutic actions.

Blood Platelets↗
PubMed1982

Effects of free fatty acids, ethanol and development on gamma-aminobutyric acid and glutamate fluxes in rat nerve endings.

The effects of type A (cis-unsaturated) and type B (trans-unsaturated and saturated) fatty acids, 1% and 3% ethanol (v/v), and development (7 days) on the thermodynamics of glutamate and gamma-aminobutyric acid (GABA) transport into cortical rat brain nerve endings were examined. The effects of the various manipulations, which are known to affect membrane fluidity, may be summarized. Three percent ethanol and oleic acid increased delta S degrees and delta S+ for glutamate transport and decreased delta H degrees and delta H+. Type B fatty acids had the opposite effects. In comparison to glutamate transport, GABA transport was less affected by the various manipulations and showed less specificity in terms of the fatty acid effects. Similarly, the effects of development on the thermodynamic parameters for glutamate and GABA transport were not consistent. Glutamate transport into 7-day nerve endings showed thermodynamic behavior similar to that seen when type A fatty acids were incorporated into adult nerve endings. In contrast, GABA transport into 7-day nerve endings had the character of adult nerve endings into which type B fatty acids were incorporated.

Aging↗
PubMed1982

Developmental regulation of phospholipid methylation in rat brain synaptosomes.

Phospholipid methylation was studied in cortical synaptosomes prepared from 7 and 14 day and adult rat brain. Using varying concentrations of [3H] S-adenosylmethionine, Km and Vmax values were determined for the formation of [3H] phosphatidylmonomethylethanolamine (PME), [3H] phosphatidyl-dimethylethanolamine and [3H] phosphatidylcholine (PC). At 25 degree C, the Km values for the formation of all three products, significantly decreased with development. Increasing the temperature to 37 degree C increased the Km values in the 14 day and adult but not the 7 day preparation. The Vmax values at 25 degree C were highest at 7 and 14 days, depending on the product and then decreased in the adult. At 37 degree C, the Vmax values were highest in the 14 day preparation. The overall results are discussed in terms of the developmentally regulated decrease in both synaptic membrane PC and membrane fluidity.

Animals↗
PubMed1982

Effects of naloxone on d-amphetamine- and apomorphine-induced behavior.

The effects of acute naloxone administration on d-amphetamine- and apomorphine-induced behavior were studied. Naloxone, in doses of 0.3-10 mg/kg (s.c.), antagonized the increase in ambulation and rearing induced by 1 mg/kg of d-amphetamine. When the dose of d-amphetamine was increased to 3 mg/kg, naloxone (3 mg/kg) antagonized only the increase in rearing activity. No dose (0.3-10 mg/kg, s.c.) of naloxone significantly affected d-amphetamine- or apomorphine-induced stereotyped activity. Naloxone (3 mg/kg) significantly augmented the apomorphine (1 mg/kg, s.c.)-induced increase in ambulation but attenuated the apomorphine (0.3 mg/kg)-induced increase in rearing activity. Naloxone (3 mg/kg) or apomorphine (0.03 mg/kg) significantly decreased the ambulation and rearing induced by a novel environment. In combination and in these doses, naloxone and apomorphine produced an additive effect on these behaviors. The neurochemical mechanisms by which naloxone affects d-amphetamine- and apomorphine-induced behavior were investigated. Naloxone (10(-6) M) had no significant effect on [3H]spiroperidol binding in either the caudate nucleus or nucleus accumbens except for a modest inhibition (24%) of both the Km and Bmax in the accumbens microsomal fraction. Similarly, naloxone (10(-6) M) had no significant effect on [3H]dopamine(DA) uptake into either brain region nor did naloxone alter the d-amphetamine-inhibition of uptake. Using perfused tissue slices, naloxone (10(-6)-10(-5) M) significantly attenuated the increase in [3H]DA release induced by d-amphetamine (10(-5) M) in both brain regions. Naloxone (1 mg/kg) had no significant effect on DA or dihydroxyphenyl-acetic acid (DOPAC) levels or on the DA/DOPAC ratio in the caudate nucleus or nucleus accumbens. However, naloxone did reverse the marked increases in the DA-DOPAC ratio induced by d-amphetamine (1 mg/kg) in both brain regions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

The transport and turnover of phospholipids in the rat nigrostriatal system: effects of d-amphetamine and haloperidol.

the nigrostriatal transport of phospholipids was studied using [3H] glycerol, 32Pi and [3H] choline. [3H] glycerol was rapidly incorporated into phospholipid and significant amounts of labelled phospholipid were found in the striatum one hour after injection into the substantia nigra. In contrast, both 32Pi and [3H] choline were more slowly incorporated into phospholipid and significant amounts of labelled phospholipid were not found in the striatum until 24 hours after injection. Once incorporated into the striatum, the [3H-glycerol] phospholipids showed both a rapid (t 1/2 = 1-4 days) and a slow (t 1/2 = 14 + days) turnover component while the [32p] and [3H-Ch] phospholipids showed only a slow turnover component. The subcellular distribution of the rapidly transported [3H-glycerol] phospholipids was studied. Only [3H] phosphatidylcholine (PC) was specifically enriched in the synaptic membrane fraction. The hypothesis was tested that an increase in vesicular lysophosphatidylcholine (LPC) content is associated with dopamine (DA) release. The DA containing vesicles in the striatum were labelled by the intranigral injection of [3H]choline; seven days later, the animals were administered haloperidol to stimulate firing of the nigral-striatal DA neurons. Haloperidol significantly decreased rather than increased the [3H]LPC/[3H]PC ratio. The hypothesis was tested that chronic amphetamine treatment would inhibit phospholipid transport as a result of the decrease in neuronal activity. Chronic d-amphetamine treatment was found to have no effect on the fast component of [3H-glycerol] phospholipid turnover.

Animals↗
PubMed1981

Developmental changes in the fatty acids of synaptic membrane phospholipids: effect of protein malnutrition.

The acyl-linked fatty acid composition of the major phospholipid species in rat cortical synaptic membranes was determined at various stages of development. For most species there was a decrease during development in the short chain saturated fatty acids, 14:0 and 16:0, an increase in 18:0 and 22:6 (n-3) and an increase in ratio of 22:6 (n-3)/22:5 (n-6). Pups were protein deprived by feeding the dams a 12% casein diet as compared to the 24% casein control diet. Protein malnutrition markedly affected the composition of acyl-linked fatty acids in the synaptic membranes. The increases in the ratio of 22:6 (n-3)/22:5 (n-6) fatty acids were especially compromised.

Aging↗
PubMed1980

Brain locations controlling the behavioral effects of chronic amphetamine intoxication.

Rats were administered D-amphetamine repeatedly for 4 days. After day 1 of treatment, the amphetamine-induced increases in ambulation, rearing, and stereotyped activity were augmented. However, after 4 days treatment, the rearing and ambulatory responses became attenuated while the stereotyped activities remained augmented. Micro-injection studies revealed that both the augmentation and attenuation of nonstereotyped ambulation were generated from the nucleus accumbens. The augmentation of stereotyped behaviors was generated from the caudate nucleus. Chronically treated animals who were administered 0.7 but not 1.0 mg/kg apomorphine showed augmented behavioral response. Chronic amphetamine treatment significantly decreased (3H) spiroperidol binding in both the nucleus accumbens and caudate nucleus. However, no effect on the DA-stimulated adenyl cyclase activity was observed in either brain region. It is concluded that repeated D-amphetamine administration selectively augments and attenuates D-amphetamine-induced behaviors and that these selective effects are mediated by different dopamine systems.

Adenylyl Cyclases↗