An open-label pilot study of oral S-adenosylmethionine in major depression. An interim report.
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Administration, Oral↗
Biomedical subjects
G S Zubenko
Publications and source records attributed to G S Zubenko.
S-adenosyl-L-methionine in the treatment of Alzheimer's disease.
Patients with Alzheimer's disease (AD) have an apparent abnormality possibly representing an increase in the average fluidity of their cell membranes. Changes in membrane fluidity of similar magnitude to those observed in AD have been noted to lead to marked alterations in cell function. Therefore, the changes in fluidity observed in AD may be related to the symptoms of that disorder, representing either an underlying cause of dysfunction or cellular attempts to compensate for dysfunction in AD. To test these possibilities, we administered S-adenosyl-L-methionine (SAMe), an agent shown to increase membrane fluidity in animals, to patients with AD. Treatment with SAMe led to marked increases in membrane fluidity. However, it produced neither improvement nor worsening of symptoms. The results imply that while SAMe may be useful for other conditions associated with altered membrane fluidity (such as normal aging), changing membrane fluidity per se is not likely to lead to marked changes in symptoms in AD.
Aged↗
An open-label pilot study of oral S-adenosyl-L-methionine in major depression: interim results.
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Administration, Oral↗
Family study of platelet membrane fluidity in Alzheimer's disease.
The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in labeled platelet membranes, an index of membrane fluidity, identifies a prominent subgroup of patients with Alzheimer's disease who manifest distinct clinical features. In a family study, the prevalence of this platelet membrane abnormality was 3.2 to 11.5 times higher in asymptomatic, first-degree relatives of probands with Alzheimer's disease than in neurologically healthy control subjects chosen without regard to family history of dementia. The pattern of the platelet membrane abnormality within families was consistent with that of a fully penetrant autosomal dominant trait. Thus, this abnormality of platelet membranes may be an inherited factor that is related to the development of Alzheimer's disease.
Aged↗
Abnormal platelet membrane composition in Alzheimer's-type dementia.
An abnormality of membranes, possibly representing an increase in internal membranes, has been reported in fluorescence spectroscopic and electron microscopic studies of platelets of patients with Alzheimer's-type dementia (AD). To further define this abnormality, the cholesterol and phospholipid content of platelet and erythrocyte membranes was determined and compared for patients with AD and matched control subjects. No significant differences in either cholesterol or phospholipid, per se, were observed in comparing platelets from subjects in the two study groups. However, the ratio of cholesterol to phospholipid was significantly lower (p less than 0.01) in the platelets of patients with AD (9.37 +/- 1.11) than in the platelets of control subjects (10.20 +/- 1.04). Furthermore, the cholesterol to phospholipid ratio correlated significantly (rs = 0.53, p less than 0.01) with a separately determined measure of platelet membrane characteristics, the steady-state anisotropy of DPH (diphenylhexatriene). No differences were observed between the study groups for any of the same parameters measured in erythrocytes, which lack internal membranes. The findings suggest that there is no general abnormality of membrane lipids in Alzheimer's-type dementia. Rather, because normal internal membranes are reported to be low in their cholesterol to phospholipid ratio and in anisotropy of DPH, the results of these studies, together with the results of studies employing electron microscopy, suggest that platelets of patients with AD have an increase in internal membranes. Such membranes, while present in excess, may be normal in composition.
Aged↗
Adrenoceptors and the pharmacology of affective illness: a unifying theory.
Based on recent clinical and preclinical research, it is theorized that antimanic and antidepressant effects of clinically available drugs can be produced through their actions on alpha-1 adrenoreceptor-mediated neurotransmission in the central nervous system. The theory suggests that final effects on alpha-1 mediated neurotransmission may be produced not only by drugs which have direct effects on the alpha-1 receptor or its second messenger, but also by drugs having effects on neurotransmitter systems such as acetylcholine, GABA, and serotonin, among others, which modulate the activity of central norepinephrine neurons or, via feedback mechanisms, by drugs having effects on adrenergic receptors other than the alpha-1 receptor itself.
Adrenergic alpha-Agonists↗
Platelet membrane abnormality in Alzheimer's disease.
Fluorescence studies of membrane fluidity were conducted double-blind using platelet and red cell membranes prepared from 24 demented patients with probable Alzheimer's disease and 36 neurologically healthy subjects. The fluidity of the hydrocarbon and lipid-aqueous interface regions of cell membranes was determined at 37 degrees C by fluorescence spectroscopy using the lipid probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH), respectively. The rotation rate of TMA-DPH in labeled platelet membranes did not differ between the groups. In contrast, the rotation rate of DPH in labeled platelet membranes from the demented patients (2.15 +/- 0.24 X 10(8)/sec, SD) was greater than that for the normal controls (1.93 +/- 0.13 X 10(8)/sec, SD, p = 3.8 X 10(-5)). This difference was reflected by a reduction in the steady-state anisotropy of DPH in labeled platelets from the demented group (0.1887 +/- 0.0085, SD) when compared to the respective mean for the controls (0.2000 +/- 0.0060, SD; p = 1.3 X 10(-7)). Abnormal membrane fluidity was significantly correlated with severity of dementia, but not with duration of illness or apparent age of onset. The findings do not support the hypothesis that Alzheimer's disease results from a pathological acceleration of the normal aging process, since normal aging is associated with decreased fluidity of cell membranes from platelets, as well as from lymphocytes, hepatocytes, and neurons.
Aged↗
Temperature dependence of the molecular dynamics of platelet membranes in Alzheimer's disease.
The biophysical properties of platelet membranes from five patients with Alzheimer-type dementia and five neurologically healthy controls, matched for age and sex, were examined by fluorescence spectroscopy employing the fluorescent probes DPH and TMADPH. The anisotropy of DPH has previously been observed to be reduced in platelet membranes of patients with Alzheimer-type dementia. However, Alzheimer's disease was not associated with a significant change in the flow activation energy at either deep or superficial regions of platelet membranes. In addition, the temperature-dependent phase transition observed with TMADPH occurred at the same mean temperature in platelet membranes from the demented and control groups.
Aged↗
Water homeostasis in psychiatric patients.
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Drinking Behavior↗
Platelet membrane fluidity identifies a clinical subtype of Alzheimer's disease.
1. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) in labeled platelet membranes, an index of membrane fluidity, identifies a prominent subgroup (approx. 50%) of patients with Alzheimer's disease who manifest distinct clinical features. 2. We review an integrated series of studies that explore both the clinical significance of this finding and the biological basis for the platelet membrane alteration.
Aged↗
Proliferation of internal membranes in platelets from patients with Alzheimer's disease.
Platelets from six moderately demented patients with probable Alzheimer's disease (NINCDS-ADRDA criteria) and six neurologically healthy controls were examined by electron microscopy. While platelet preparations from the control group contained infrequent examples (4.6%) of platelets with an unusually abundant internal system of smooth membranes, the frequency of these atypical cells (15.5%) was over three times higher in the samples prepared from the demented patients (p = 2.2 X 10(-2)). Consistent with our previous reports, platelet membranes from the Alzheimer's disease group exhibited a significant increase in membrane fluidity, as reflected by the rotation rate and fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) at 37 degrees C. Moreover, membrane fluidity was correlated with the frequency of atypical platelets visualized by electron microscopy. Since internal platelet membranes have been reported to be more fluid than external platelet membranes, these and other results presented suggest that the increase in platelet membrane fluidity associated with Alzheimer's disease may be the result of a dysregulation of platelet membrane biosynthesis.
Aged↗
Sexual practices among patients with borderline personality disorder.
The authors found that 12 (57%) of 21 consecutive male patients with borderline personality disorder who presented for psychiatric treatment at two distant geographic sites were homosexual. They then obtained the sexual histories of 80 patients who met standardized criteria for borderline disorder and found that 17 (21%) of these patients were homosexual, four (5%) were bisexual, and nine (11%) had diagnoses of paraphilias. Ten (53%) of the 19 men with borderline disorder were homosexual, compared with seven (11%) of the 61 women. Homosexuality was 10 times more common among the men and six times more common among the women with borderline personality disorder than in the general population or in a depressed control group.
Adult↗
Platelet membrane fluidity in Alzheimer's disease and major depression.
Double-blind fluorescence studies of platelet membrane fluidity were conducted at 37 degrees C for 51 patients with Alzheimer-type dementia, 24 nondemented depressed patients, and 50 neurologically healthy subjects. The fluidity of the hydrocarbon region of platelet membranes from the demented group, as reflected by the steady-state anisotropy of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), was significantly greater than that for the depressed and normal control subjects. Within the demented group, platelet membrane fluidity was significantly correlated with severity of dementia but not with duration of illness or age at onset. Demented patients with "increased" platelet membrane fluidity had an earlier onset, were more severely demented, and deteriorated more rapidly.
Aged↗
Antidepressant-related akathisia.
Five neuroleptic-free patients exhibited syndromes that were indistinguishable from idiopathic or neuroleptic-induced akathisia in association with antidepressant administration. While antidepressant-related akathisia may be produced by any of a variety of antidepressants, the susceptibility of each individual patient to the development of this disorder may be limited to only one or a few of these agents. A considerably rarer syndrome than neuroleptic-induced akathisia, antidepressant-related akathisia appears to respond to established pharmacologic treatments for neuroleptic-induced akathisia.
Adult↗
Hippocampal membrane alteration in Alzheimer's disease.
The biophysical properties of hippocampal membrane preparations from patients with Alzheimer's disease were examined by fluorescence spectroscopy using the membrane lipid probe 1,6-diphenyl-1,3,5-hexatriene (DPH) and its cationic derivative 1-[4-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). Results of these experiments suggest that Alzheimer's disease is associated with a biophysical alteration in superficial regions of brain cell membranes, as reflected by the mobility of TMA-DPH. In contrast, no change in the mobility of DPH, which preferentially localizes to the hydrocarbon core, was observed. Although a trend was observed for TMA-DPH mobility to parallel histopathologic severity in hippocampal specimens, the biophysical changes did not appear to reflect a loss of neuronal membranes relative to glial membranes or the presence of senile plaques or neurofibrillary tangles.
Aged↗
A cell membrane correlate of tardive dyskinesia in patients treated with phenothiazines.
Phenothiazine administration to psychiatric patients is associated with an increase in the "structural order" of platelet membranes as determined by steady-state fluorescence polarization measurements with 1,6-diphenyl-1,3,5-hexatriene (DPH), a fluorescent probe that localizes preferentially in the hydrocarbon region of cell membranes (Zubenko and Cohen 1984, 1985a, b). In this study, platelet membranes prepared from a group of psychiatric patients who developed tardive dyskinesia following chronic treatment with phenothiazines exhibited a significant elevation in DPH fluorescence polarization when compared to similar preparations from an otherwise matched group of patients who had no symptoms or history of tardive dyskinesia. The distribution of polarization values obtained for the tardive dyskinesia group displayed minimal overlap with that of an unmedicated, psychiatrically-healthy control group matched for age and gender. The fluorescence polarization of DPH-labelled platelet membranes was not significantly correlated with phenothiazine daily dose or serum cholesterol concentration in the phenothiazine-treated patient groups, or with dyskinesia severity (AIMS rating) in the tardive dyskinesia group. Patient gender and the presence of an affective disorder did not significantly correlate with DPH fluorescence polarization. The potential physiological and clinical significance of these findings is discussed.
Adolescent↗
Cerebrospinal fluid levels of angiotensin-converting enzyme, acetylcholinesterase, and dopamine metabolites in dementia associated with Alzheimer's disease and Parkinson's disease: a correlative study.
Mean levels of the two hydrolases angiotensin-converting enzyme (ACE) and acetylcholinesterase (AChE), the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and total protein concentration were examined in cerebrospinal fluid (CSF) samples from a group of patients with dementia of the Alzheimer's type, a group of comparably demented patients with Parkinson's disease, and a neurologically healthy elderly control group. Both pathological groups exhibited a significant decrease in the mean levels of ACE activity and DOPAC per milliliter and were distinguishable from one another based on mean CSH HVA levels. Unlike the Parkinson's disease group, whose mean concentration of HVA was lower than, but not significantly different from that of the control group, the mean HVA concentration of the Alzheimer's disease group was significantly elevated. In contrast, comparisons of the mean CSF AChE activity (expressed per milliliter or per milligram of protein) and CSF total protein concentration did not reveal significant differences for any of the groups. Independent of CSF protein concentration, ACE activity per milliliter exhibited a positive correlation with AChE activity per milliliter within the control and Parkinson's disease groups, whereas a statistically significant correlation for these CSF hydrolases was not observed within the Alzheimer's disease group. Thus, the CSF profiles for patients with mild dementias associated with Alzheimer's or Parkinson's disease differed by at least two neurochemical criteria. Based on the levels of ACE activity, DOPAC, and HVA per milliliter of CSF, two discriminant functions were derived and resulted in the correct classification of 71% of all subjects (n = 38) into Alzheimer's disease, Parkinson's disease, and neurologically healthy control groups.
3,4-Dihydroxyphenylacetic Acid↗
Aging and the biophysical properties of cell membranes.
Fluorescence spectroscopy was used to examine the biophysical characteristics of human platelet membranes as a function of subject age. The structural order of membrane lipid domains was determined with the use of 1,6-diphenyl-1,3,5-hexatriene (DPH), a fluorescent probe that preferentially localizes in the hydrocarbon core of synthetic and biological membranes. Over the age range of subjects examined (17 to 86 years) the structural order of platelet membranes, as reflected by the steady-state fluorescence polarization of DPH, increased substantially. The magnitude of the observed increase in membrane structural order is sufficient to affect membrane-related cell functions including platelet aggregation. A major contributor to the increase in structural order of platelet membranes may have been an increase in the concentration of cholesterol in serum and tissue with age. The changes observed here in platelet membranes may be a general phenomenon of aging, as changes of similar type and magnitude have been observed in lymphocyte membranes and brain with age in other studies.
Adolescent↗