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S Gershon

Publications and source records attributed to S Gershon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Lifetime prevalence of substance or alcohol abuse and dependence among subjects with bipolar I and II disorders in a voluntary registry.

OBJECTIVE: To evaluate the prevalence of substance abuse dependence and/or alcohol abuse dependence among subjects with bipolar I versus bipolar II disorder in a voluntary registry. METHOD: One hundred randomly selected registrants in a voluntary case registry for bipolar disorder were interviewed, using the Structured Clinical Interview for DSM-IV Axis I Disorders, to validate the diagnosis of this registry. Corroborative information was obtained from medical records, family members and the treating psychiatrist. Eighty-nine adults (18-65 years) met criteria for bipolar disorder (bipolar I = 71, bipolar II = 18) and were included in this analysis. RESULTS: Forty-one (57.8%) subjects with bipolar I disorder abused, or were dependent on one or more substances or alcohol, 28.2% abused, or were dependent on, two substances or alcohol, and 11.3% abused or were dependent on three or more substances or alcohol. Nearly 39% of bipolar II subjects abused or were dependent on one or more substances, nearly 17% were dependent on two or more substances or alcohol, and 11% were dependent on three or more substances or alcohol. Alcohol was the most commonly abused drug among either bipolar I or II subjects. CONCLUSIONS: Consistent with other epidemiologic and hospital population studies, this voluntary bipolar disorder registry suggests a high prevalence of comorbidity with alcohol and/or substance abuse dependence. Bipolar I subjects appear to have higher rates of these comorbid conditions than bipolar II subjects; however, as the number of bipolar II subjects was rather small, this suggestion needs confirmation.

Adolescent↗
PubMed2000

Time-dependent sensitization: the odyssey of a scientific heresy from the laboratory to the door of the clinic.

This review provides both a biological and clinical perspective on Time-Dependent Sensitization (TDS), an ancient amplified memory response to threat manifest in the ability of both drugs and nondrug stressors to induce neuronal and behavioral effects which strengthen entirely as a function of the passage of time following even a single or acute exposure. Evidence is presented to show that TDS may be involved in the development of a spectrum of diseases and how drug regimens based on the principles of TDS could provide a novel and revolutionary means of treating psychiatric and other illnesses.

Antipsychotic Agents↗
PubMed2000

Apoptosis and apoptosis-related proteins (Fas, Fas ligand, Blc-2, p53) in lymphoid elements of human ovarian tumors.

Different types of lymphocytes have different roles in tumor suppression. Thus, their expression of apoptosis-related proteins (ARP - Fas and Fas ligand, bcl-2, p53) in lymphocytes and their apoptosis were analyzed immunohistochemically in ovarian tumors of different grades. Ovaries without oncologic disorders had few lymphocytes, mainly T cells, and no ARP. Benign cysts presented features of weak immune reaction: small lymphoid infiltration and few lymphocytes. The ARP were present in 13.7% to 23.5% of the lymphocytes, and apoptosis was rare. In borderline tumors, expansion of lymphoid infiltrates and increased density of lymphocytes resulted in a tenfold rise in total lymphocytes, reflecting intensification of the immune response. Most lymphocytes were T cells (92%) predominated by CD8+ cells that were in direct contact with tumor epithelial cells. ARP species were found in 47% to 65% of the lymphocytes, and apoptosis in 2.2%. In carcinomas with ligh lymphoid infiltration, lymphocytes were 2.5 times more abundant, and the apoptotic index as well as the number of CD20+ and CD25+ lymphocytes rose sharply, whereas bcl-2 positive lymphocytes decreased to 8% of their number in borderline tumors. In carcinomas with low lymphoid infiltration, the total lymphocyte count decreased eightfold compared to carcinomas with high lymphoid infiltration, reflecting the deep subcompensation of the lymphoid system. Few p53-positive lymphocytes were found in the carcinomas. In conclusion, we found a positive correlation between apoptosis and the numbers of CD4+ or CD8+ lymphocytes in epithelial ovarian tumors. This correlation could reflect the antitumor activity of T cells. However, the high expression of ARP studied by immune cells at the vicinity of the tumor ARP reveals the lymphoid vulnerability to apoptosis, resulting in devastation of the lymphoid tissue, and consequently in tumor progression.

Adenocarcinoma↗
PubMed2000

The psychopharmacologic specificity of the lithium ion: origins and trajectory.

This article examines the development of lithium therapy since its dramatic introduction into psychiatry in 1949. Since that time, lithium has been examined in the treatment of a variety of neuropsychiatric conditions, but it is in the treatment of bipolar disorder that it is most effective. This suggests that it has specificity in the treatment of this disorder. These findings are very relevant as they suggest that understanding the mechanism of action of lithium in bipolar disorder may hold keys to elucidating its pathophysiology and to developing newer and more effective treatments. We review the published data on the effectiveness of lithium in bipolar disorder and various neuropsychiatric conditions and also the available data on anticonvulsants and newer therapeutic agents in the treatment of this condition.

Anticonvulsants↗
PubMed2000

Apoptosis and apoptosis-related proteins (Fas, Fas ligand, bcl-2, p53) in macrophages of human ovarian epithelial tumors.

Apoptosis and the apoptosis-related proteins (ARP) (Fas, Fas ligand (FasL), bcl-2 and p53) were analyzed in macrophages of different human ovarian epithelial tumors. Few macrophages were found in ovaries of women without oncologic disorders. In ovarian benign cysts, macrophagic density reached 4.9+/-1.2 per 50,000 microm2, most were present in lymphoid-macrophagic infiltrates of the sub-epithelial stroma (3.7+/-0.5% of the area of a slide), and 23.4% were Fas and FasL positive. In borderline tumors, the expanse of lymphoid infiltrates increased to 15.6% of the area of a slide, and the number of macrophages increased 2.4-fold compared to benign cysts. Of the macrophages, 83-88% expressed Fas and FasL, few had bcl-2 and CD25 receptors, and isolated ones were apoptotic. In carcinomas with high lymphoid-macrophagic infiltration, the infiltrate occupied 17.5% of the slide and macrophages amounted to 12.1+/-1.5/50,000 microm2. Many macrophages were in regions of grouping apoptosis of tumor epithelial cells and significantly fewer expressed Fas, FasL and bcl-2. Macrophages destroyed by apoptosis accounted for 4.6%. In carcinomas with low lymphoid-macrophageal infiltration, the area of the last was 5.1% of the slide. There were 8.6+/-0.8 macrophages/50,000 microm2, mainly at the margins of zones of necrosis and of tumor cells' grouping apoptosis. Extensive macrophagic infiltration into tumor parenchyma is one way by which the host immune system destroys tumors. Fas and FasL appear in macrophages of benign cysts, but in borderline tumors and in carcinomas with low infiltration their concentration increases sharply, to 79.8% and 96.6%, respectively. In 4.5% of these cells, apoptosis of macrophages was seen. The findings suggest that macrophages participate in the transfer of ARP to tumor epithelial cells, thereby inducing their apoptosis, but undergoing the simultaneous apoptosis.

Aged↗
PubMed1999

Pills or placebos?

Explore the source record for details and available documents.

Antidepressive Agents↗
PubMed1999

Cocaine-induced oscillation is conditionable.

We have recently shown that under some circumstances, sensitization produced by a stimulant such as cocaine (COC) can give way, with successive drug administrations, to alternating attenuations and reinstatements of the effect, an outcome that we have termed oscillation. Because sensitization to COC can be conditioned, we inquired whether COC-induced oscillation also was conditionable. The end point used was shock-induced hypoalgesia (paw withdrawal from a hot plate), as we have previously shown that oscillation follows initial sensitization of this measure with one to five pretreatments of 12 mg/kg (IP) of COC spaced at 1-week intervals, with the last COC injection occurring 30 min prior to the footshock. Experiment 1 indicated that a conditioned stimulus (CS)--a distinctive environment--which repeatedly had been paired with COC, would substitute for the last COC injection in sustaining the oscillatory effect. Experiment 2 showed that a previously established CS successfully substituted for all COC injections in first inducing sensitization that was then followed by oscillation. These findings strongly suggest that COC-induced oscillation shares with COC-induced sensitization, the property that both can be conditioned.

Anesthetics, Local↗
PubMed1999

Early North American research on lithium.

Research and clinical interest in lithium in the USA lagged behind that in Europe, largely because of the experience of deaths due to lithium in cardiac patients. The first American report on lithium was published in 1960 by Sam Gershon, the Australian psychiatrist who had undertaken lithium studies in Melbourne in conjunction with the physiologist Trautner. Major USA clinical trials originated in the 1960s; and the clinical significance of lithium was recognised in a special section in the American Journal of Psychiatry in 1968. The US Food and Drug Administration (FDA) approval of lithium for control of manic episodes was finally given in 1970.

Antimanic Agents↗
PubMed1998

Oscillatory effects of repeated morphine on shock-induced hypoalgesia and beta-endorphin.

Recent research indicates that the sensitization that results from repeated drug or non-drug stress exposure may develop into a pattern of alternating increases and decreases (i.e., oscillation) in response to each subsequent stressor exposure. Oscillation, with or without prior sensitization, has been observed for a number of drug and non-drug stressors, and for various neurochemical and endocrine endpoints. The present studies investigated whether oscillation also occurs in the behavioral and endocrine effects of repeated morphine treatment and if a drug that normalizes the mood swings of bipolar disorder in humans will also attenuate drug oscillation in this animal model. In the first experiment, rats were given 1-5 pretreatments with morphine (15 mg/kg, i.p.), separated by 1-week intervals with the last injection occurring 1 hour prior to being tested for stressor-induced (i.e., 5 seconds, 2-mA electric footshock) hypoalgesia, as measured by latency to paw-lift or jump from a hot-plate. Plasma beta-endorphin also was measured. The second experiment replicated the behavioral findings of the first study and, in addition, assessed the effect of continuous lithium chloride, in the drinking water, on morphine-induced oscillation. Caffeine was used as a partial control for the lithium. The results were that one injection of morphine enhanced stress-induced hypoalgesia and subsequent morphine administrations resulted in oscillation. Beta-endorphin exhibited sensitization but not oscillation, suggesting that it did not mediate oscillation of the behavioral response. In addition, lithium, but not caffeine, eliminated oscillations of the behavioral response without affecting its initial enhancement.

Analysis of Variance↗
PubMed1998

Clinical application of time-dependent sensitization to antidepressant therapy.

1. A number of animal studies have shown that the actions of numerous drugs can grow or sensitize with the passage of time following even a single treatment, to achieve results equal to or greater than those seen after chronic administration. 2. Our laboratory earlier proposed that this principle might be applied to the treatment of human disorders. It was suggested that the same results might be achieved by giving drugs once every one or two weeks rather than daily, or, even more likely, several-times-daily. 3. Here the authors review the clinical literature relevant to that hypothesis, as it relates to antidepressant therapies. 4. The evidence uniformly supports our earlier thesis that the therapeutic influence of antidepressants would grow with the passage of time, even as their pharmacokinetic actions are declining.

Animals↗
PubMed1998

The effects of lithium on a potential cycling model of bipolar disorder.

1. Although bipolar disorder constitutes a major public health problem, with a high risk of suicide and an economic cost exceeding that of unipolar depression, it has received comparatively little attention, particularly at the basic science level. Perhaps as a result of this neglect, there is currently no animal model able to simulate the cyclicity which is its defining characteristic. 2. Consequently, drug development in this area is meager and has proceeded serendipitously rather than empirically. 3. The authors have recently reported that repeated exposure to cocaine and other stressors can induce an oscillation or cycling in a host of neurochemical and physiological systems. 4. In order to test whether such cycling might be of potential relevance to bipolar disorder, the authors examined whether cocaine-induced cyclicity of amphetamine-evoked efflux of dopamine from slices of rat nucleus accumbens and striatum and/or cocaine induced oscillation of a behavior, stress-induced hypoalgesia, could be prevented by lithium, the agent of choice in treating this disease. 5. The authors report that prophylactic treatment with lithium, completely and specifically prevented oscillations in each instance. This may represent an important initial step toward the development of the first cycling model of bipolar disorder.

Amphetamine↗
PubMed1998

Oscillatory-sensitization model of repeated drug exposure: cocaine's effects on shock-induced hypoalgesia.

1. The authors have recently proposed that the sensitization produced by repeated exposure to drugs or stress may give way to an alternating pattern of increases and decreases in the response to each subsequent exposure (i.e., oscillate), as the limits of the physiological system are approached. 2. Evidence for oscillation has been obtained for 6 drug/non-drug stressors and 9 neurochemical or endocrine endpoints. This paper extends the model to a behavioral outcome. 3. In the first experiment, rats were given 0, 1, 2 or 3 pretreatments with cocaine hydrochloride (COC; 12 mg/kg i.p.), separated by 1-week intervals, and then were tested for footshock-induced hypoalgesia (5-sec, 2-mA), as measured by withdrawal latencies from a hot-plate. 4. The second experiment replicated the first and extended the pretreatment sequence to 5 COC injections. 5. In both experiments, shock significantly increased latencies over the no-shock controls. COC enhanced shock-induced hypoalgesia and this sensitization reached its maximum after 2 COC pretreatments. Thereafter, oscillation developed such that the sensitization was attenuated by 3 as compared to 2 COC injections, enhanced by 4 injections, and reattenuated after 5 COC pretreatments. 6. These data complement other findings by demonstrating that the oscillation model extends to a stress-induced behavioral outcome.

Animals↗
PubMed1998

The lithium ion: a foundation for psychopharmacological specificity.

The idea of lithium's specificity for bipolar disorder was proposed in Cade's original work in 1949. Since then, many controlled studies have been performed, examining lithium for treatment of bipolar disorder and other psychiatric conditions. This review was undertaken to determine if the suggestion of lithium's specificity has support in the controlled studies conducted after Cade's initial proposal. Studies were selected in a Medline search, dating back to 1966 and also identified from the bibliography of some of these papers. The controlled trials with lithium for the treatment of mania and bipolar depression, unipolar depression, schizophrenia, and schizoaffective disorder were reviewed. The published studies with lithium in other neuropsychiatric conditions were also considered. Additionally, we reviewed literature on other therapeutic agents proposed for bipolar disorder, looking at their comparative effectiveness to lithium. The data analyzed give strong support for lithium's being most effective in bipolar disorder, with minimal or no therapeutic effects in other neuropsychiatric disorders. The neurochemical underpinnings of this specificity are being investigated, without conclusive findings to date. The study of this paradigm of specificity in neuropsychopharmacology research may lead to meaningful contributions to understanding the pathophysiology of bipolar disorder and may help to develop newer treatments for this condition.

Animals↗
PubMed1997

Therapeutic targets in late-life psychoses: review of concepts and critical issues.

Psychoses in late life are a diagnostic challenge because of disagreement over how these entities should be classified. The main diagnostic categories of late-life psychoses include dementia with psychotic symptoms, late-onset schizophrenia, delusional disorder, early-onset psychotic disorders extending through late life, late-onset mood disorders, psychotic disorders caused by medical conditions or medications, and delirium. First onset of psychotic symptoms in late life is commonly associated with identifiable structural brain abnormalities and reflects underlying brain pathology. We reviewed the available literature on late-life psychotic manifestations, focusing on diagnostic classification and treatment approaches. Antipsychotics are the mainstay of treatment for these conditions, but should be used cautiously in elderly patients because of their increased sensitivity to side effects. Overall, appropriate research data on the effectiveness of various antipsychotic agents for late-life psychotic conditions are lacking. Non-antipsychotic psychotropic medications may be of value in managing some of these conditions.

Affective Disorders, Psychotic↗
PubMed1997

The role of antipsychotic agents in the treatment of bipolar disorder patients.

Antipsychotic agents have been an important adjunct in the acute and at times prophylactic management of bipolar disorder patients. As a result of safety considerations, particularly the risk of tardive dyskinesia, there are concerns about their long-term use as adjunctive treatment. Although alternative agents have been proposed, some treatment-refractory cases may not respond as well to other regimens. This sub-group of patients has not been well characterized, but may result from overinclusive criteria in defining bipolar disorder. A comprehensive Medline search dating back to 1966 was conducted to identify published studies on antipsychotic utilization in bipolar disorder patients. We investigated the support for their use, and their effectiveness in this population, and attempted to define the group of patients requiring antipsychotic treatment. Additionally, we reviewed specific safety considerations, and suggested standards for their use in bipolar patients.

Antipsychotic Agents↗
PubMed1997

Time-dependent sensitization--possible implications for clinical psychopharmacology.

Time-dependent sensitization (TDS) has been described in animal models over the past 20 years. It is a phenomenon that occurs in a variety of biological systems, and corresponds to the cellular and systems response to a foreign or stressful stimulus. The exposure to the stimulus triggers the responses typical of that particular biological system, which are progressively amplified with time. This phenomenon has potential major implications for clinical pharmacology. Some human studies have investigated this phenomenon to date. Antidepressant action, with its typical lag in the onset of effects, may be a fruitful paradigm to understand the relevance of TDS for psychopharmacological treatment. In this paper we review these emerging findings, and suggest that clinical pharmacology research should investigate this process further in expanded human studies.

Animals↗