Biomedical subjects

Peter H Silverstone

Publications and source records attributed to Peter H Silverstone.

22 records · Page 2Linked to original sources

PubMed2003

Defining anxious depression: going beyond comorbidity.

OBJECTIVE: Since publication of the DSM-IV, there remains a group of patients with depression and anxiety symptoms who are not well classified. We therefore wanted to determine more accurately the type of patients best described by the term "anxious depression." We also wanted to review the literature to assess the most appropriate treatment(s) for these patients. METHOD: We surveyed the medical literature published after 1994 for all articles containing the relevant terms and assessed all possible articles in detail to determine those relevant to the diagnosis and those that involved relevant clinical studies. RESULTS: The term anxious depression can encompass 3 groups of patients: those with comorbid major depressive disorder (MDD) and an anxiety disorder, those with MDD but with subthreshold anxiety symptoms, and those with subthreshold depressive and subthreshold anxiety symptoms (also called mixed anxiety and depressive disorder). CONCLUSIONS: Based upon our literature review, we believe that the term anxious depression should only be used for the second group; that is, those patients with an MDD and subthreshold anxiety symptoms. From our literature review to determine the most appropriate treatment for this group of patients, it appears likely that drugs inhibiting the reuptake of both noradrenaline and serotonin may have greater clinical utility than single-action drugs such as the selective serotonin reuptake inhibitors (SSRIs). However, it is also clear that much more research needs to be undertaken in this important patient group so that we can better understand its prevalence, clinical features, and treatment.

Anxiety↗

PubMed2003

Effects of dextroamphetamine, lithium chloride, sodium valproate and carbamazepine on intraplatelet Ca2+ levels.

OBJECTIVE: To explore the possible involvement of second-messenger pathways in the pathophysiology of bipolar disorder and the mechanism of action of mood stabilizers, we investigated the effects of dextroamphetamine (a model for mania) and the most widely used mood stabilizers, lithium chloride, sodium valproate and carbamazepine, on intraplatelet levels of calcium ion ([Ca2+). DESIGN: In the first part of the study, dextroamphetamine was administered in vivo in a double-blind, placebo-controlled, crossover design. In the second part of the study, platelets from untreated subjects were incubated in vitro with dextroamphetamine, lithium chloride, sodium valproate or carbamazepine. PARTICIPANTS: Fifteen healthy men between 18 and 45 years of age. OUTCOME MEASURES: Basal, thrombin-induced and serotonin- (5-HT) induced intraplatelet [Ca2+] determined by means of fura-2 fluorescent intensity. RESULTS: In vivo administration of dextroamphetamine had no effect on basal or agonist-induced intraplatelet [Ca2+]. However, in vitro basal platelet [Ca2+] was significantly higher in samples incubated with dextroamphetamine (86.8 nmol/L [standard error of the mean, SEM, 3.9], p < 0.001), lithium chloride (76.4 nmol/L [SEM 3.1], p < 0.002), sodium valproate (82.7 nmol/L [SEM 3.7], p < 0.001) and carbamazepine (84.8 nmol/L [SEM 3.3], p < 0.001) than in the controls (58.2 nmol/L [SEM 2.3]). Thrombin-induced and 5-HT-induced peak cytosolic [Ca2+] were significantly greater than control levels in samples incubated with carbamazepine (277.1 nmol/L [SEM 19.9] v. 195.8 nmol/L [SEM 12.2], p < 0.002; and 153.0 nmol/L [SEM 8.2] v. 115.4 nmol/L [SEM 5.7], p < 0.003, respectively). CONCLUSIONS: This study does not support the involvement of intraplatelet [Ca2+] in the dextroamphetamine model of mania; however, the modulation of intraplatelet [Ca2+] by the mood stabilizers lithium chloride, sodium valproate and carbamazepine implicates intracellular [Ca2+] in the therapeutic mechanisms of these drugs and the pathophysiological basis of mania.

Adolescent↗

PubMed2002

Chronic treatment with both lithium and sodium valproate may normalize phosphoinositol cycle activity in bipolar patients.

BACKGROUND: It has been proposed that lithium may be clinically effective due to its actions on the phosphoinositol second messenger system (PI-cycle). Studies have also suggested that untreated manic patients may have raised myo-inositol and phosphomonoester (PME) concentrations and also that unmedicated euthymic bipolar patients may have lowered PME concentrations. The objective of the present study was to test the hypothesis that chronic treatment with either lithium or sodium valproate in patients with bipolar mood disorder leads to a normalization in the activity of the PI-cycle. METHODS: This study had two parts each with different MRS methodology. The first part compared healthy controls (n = 19) with euthymic bipolar patients who were taking either lithium (n = 16) or sodium valproate (n = 11) using both (1)H-MRS and (31)P-MRS. In the second part we examined a separate group of euthymic bipolar disorder patients taking sodium valproate (n = 9) and compared these with age and sex-matched healthy controls (n = 11) using (1)H-MRS. RESULTS: Both studies showed that there were no differences in either myo-inositol or phosphomonoester (PME) concentrations between controls and patients taking either medication. CONCLUSIONS: These findings examine two key components of the PI-cycle in treated euthymic bipolar (myo-inositol and PME concentrations). The results from this study are consistent with the suggestion that chronic treatment with either lithium or sodium valproate in bipolar patients may normalize PI-cycle functioning.

Adult↗

PubMed2002

Dextro-amphetamine increases phosphoinositol cycle activity in volunteers: an MRS study.

AIMS: To help determine the effects of dextro-amphetamine on the phosphoinositol cycle (PI-cycle) in humans, (1)H and (31)P magnetic resonance spectroscopy (MRS) was utilized in 17 healthy volunteers. This was an open-label study carried out before and after administration of 20 mg oral dextro-amphetamine. Subjects also rated the subjective effects of dextro-amphetamine administration using visual analog scales (VAS). MAJOR FINDINGS: Following dextro-amphetamine administration there was a significant increase in the concentrations of both myo-inositol and phosphomonoesters. CONCLUSIONS: These findings are in keeping with suggestions that dextro-amphetamine administration increases the activity of the phosphoinositol cycle, probably via an indirect release of dopamine and noradrenaline. These results are the first time that this has been confirmed in humans.

Adult↗