Biomedical subjects

Peter H Silverstone

Publications and source records attributed to Peter H Silverstone.

At least 19 recordsLinked to original sources

PubMed2006

Lithium alters regional rat brain myo-inositol at 2 and 4 weeks: an ex-vivo magnetic resonance spectroscopy study at 18.8 T.

Lithium has been the mainstay of treatment for bipolar disorder. Early studies suggest that lithium acts via inositol depletion. This study assesses the effect of 1, 2 and 4 weeks of lithium treatment on myo-inositol concentrations across several brain regions. Thirty-six Sprague-Dawley rats were treated for 2 weeks with an intraperitoneal injection of either 1 mmol/kg/day, twice daily lithium chloride (n=18) or placebo (2 ml/kg of saline) (n=18). The rats were separated into three groups: 1 week, 2 weeks and 4 weeks. Brains were dissected into prefrontal, temporal and occipital cortical areas, as well as hippocampus, and analyzed at 18.8 T. Myo-inositol was quantified using the Chenomx Profiler software. Lithium did not alter myo-inositol concentrations at 1 week. A significant reduction exists in myo-inositol concentrations in lithium-treated rats at 2 and 4 weeks, across all four brain regions. Studies suggest brain region-specific alterations in myo-inositol concentrations among bipolar patients. Our findings suggest that lithium-induced reduction of myo-inositol is more global.

Animals↗

PubMed2005

Males and females differ in brain activation during cognitive tasks.

To examine the effect of gender on regional brain activity, we utilized functional magnetic resonance imaging (fMRI) during a motor task and three cognitive tasks; a word generation task, a spatial attention task, and a working memory task in healthy male (n = 23) and female (n = 10) volunteers. Functional data were examined for group differences both in the number of pixels activated, and the blood-oxygen-level-dependent (BOLD) magnitude during each task. Males had a significantly greater mean activation than females in the working memory task with a greater number of pixels being activated in the right superior parietal gyrus and right inferior occipital gyrus, and a greater BOLD magnitude occurring in the left inferior parietal lobe. However, despite these fMRI changes, there were no significant differences between males and females on cognitive performance of the task. In contrast, in the spatial attention task, men performed better at this task than women, but there were no significant functional differences between the two groups. In the word generation task, there were no external measures of performance, but in the functional measurements, males had a significantly greater mean activation than females, where males had a significantly greater BOLD signal magnitude in the left and right dorsolateral prefrontal cortex, the right inferior parietal lobe, and the cingulate. In neither of the motor tasks (right or left hand) did males and females perform differently. Our fMRI findings during the motor tasks were a greater mean BOLD signal magnitude in males in the right hand motor task, compared to females where males had an increased BOLD signal magnitude in the right inferior parietal gyrus and in the left inferior frontal gyrus. In conclusion, these results demonstrate differential patterns of activation in males and females during a variety of cognitive tasks, even though performance in these tasks may not vary, and also that variability in performance may not be reflected in differences in brain activation. These results suggest that in functional imaging studies in clinical populations it may be sensible to examine each sex independently until this effect is more fully understood.

Adult↗

PubMed2005

Lithium alters brain activation in bipolar disorder in a task- and state-dependent manner: an fMRI study.

BACKGROUND: It is unknown if medications used to treat bipolar disorder have effects on brain activation, and whether or not any such changes are mood-independent. METHODS: Patients with bipolar disorder who were depressed (n = 5) or euthymic (n = 5) were examined using fMRI before, and 14 days after, being started on lithium (as monotherapy in 6 of these patients). Patients were examined using a word generation task and verbal memory task, both of which have been shown to be sensitive to change in previous fMRI studies. Differences in blood oxygenated level dependent (BOLD) magnitude between the pre- and post-lithium results were determined in previously defined regions of interest. Severity of mood was determined by the Hamilton Depression Scale for Depression (HAM-D) and the Young mania rating scale (YMRS). RESULTS: The mean HAM-D score at baseline in the depressed group was 15.4 +/- 0.7, and after 2 weeks of lithium it was 11.0 +/- 2.6. In the euthymic group it was 7.6 +/- 1.4 and 3.2 +/- 1.3 respectively. At baseline mean BOLD signal magnitude in the regions of interest for the euthymic and depressed patients were similar in both the word generation task (1.56 +/- 0.10 and 1.49 +/- 0.10 respectively) and working memory task (1.02 +/- 0.04 and 1.12 +/- 0.06 respectively). However, after lithium the mean BOLD signal decreased significantly in the euthymic group in the word generation task only (1.56 +/- 0.10 to 1.00 +/- 0.07, p < 0.001). Post-hoc analysis showed that these differences were statistically significant in Broca's area, the left pre-central gyrus, and the supplemental motor area. CONCLUSION: This is the first study to examine the effects of lithium on brain activation in bipolar patients. The results suggest that lithium has an effect on euthymic patients very similar to that seen in healthy volunteers. The same effects are not seen in depressed bipolar patients, although it is uncertain if this lack of change is linked to the lack of major improvements in mood in this group of patients. In conclusion, this study suggests that lithium may have effects on brain activation that are task- and state-dependent. Given the small study size and the mildness of the patient's depression these results require replication.

Journal Article↗

PubMed2005

Valproate attenuates dextroamphetamine-induced subjective changes more than lithium.

Dextroamphetamine administration in healthy controls produces a range of subjective and physiological effects, which have been likened to those occurring during mania. However, it is uncertain if these can be attenuated by lithium since conflicting results have been reported. To date there have been no previous studies examining the effects of valproate on dextroamphetamine-induced mood and physiological changes. The current study was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n=12), 900 mg lithium (n=9), or placebo (n=12) pre-treatment for 14 days. Subjective and physiological measures were then obtained prior to administration of a 25 mg dose of dextroamphetamine, and at two time points after administration. Differences in the response to dextroamphetamine were assessed between the three treatment groups. The results of this study show that pre-treatment with lithium only significantly attenuated dextroamphetamine-induced change in happiness, while valproate pre-treatment significantly attenuated the effects of dextroamphetamine on happiness, energy, alertness and on the diastolic blood pressure. These results suggest that lithium and valproate do not have the same mechanism of action on dextroamphetamine-induced changes, and this finding may relate to differences in their mechanism of action in mood disorders.

Adolescent↗

PubMed2005

Lithium and valproate attenuate dextroamphetamine-induced changes in brain activation.

BACKGROUND: Previous studies have suggested that both lithium and valproate may decrease phosphoinositol second messenger system (PI-cycle) activity. There is also evidence that dextroamphetamine may increase PI cycle activity. It was previously demonstrated that dextroamphetamine administration in volunteers causes a region and task dependent decrease in brain activation in healthy volunteers. The current study assessed the effect of 14 days pretreatment with lithium and valproate on these dextroamphetamine-induced changes in regional brain activity in healthy volunteers. METHODS: This was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n = 12), 900 mg lithium (n = 9) or placebo (n = 12). Functional images were acquired using functional magnetic resonance imaging (fMRI) while subjects performed three cognitive tasks, a word generation paradigm, a spatial attention task and a working memory task. fMRI was carried out both before and after administration of dextroamphetamine (25 mg). Changes in the number of activated pixels and changes in the magnitude of the blood-oxygen-level-dependent (BOLD) signal after dextroamphetamine administration were then determined. RESULTS: In keeping with previous findings dextroamphetamine administration decreased regional brain activation in all three tasks. Pretreatment with lithium attenuated changes in the word generation paradigm and the spatial attention task, while pretreatment with valproate attenuated the changes in the working memory task. CONCLUSIONS: These results suggest that both lithium and valproate can significantly attenuate dextroamphetamine-induced changes in brain activity in a task dependent and region specific manner. This is the first human evidence to suggest that both lithium and valproate may have a similar effect on regional brain activation, conceivably via similar effects on PI-cycle activity.

Adult↗

PubMed2005

A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI-cycle) to psychiatric disorders--focus on magnetic resonance spectroscopy (MRS) studies.

Myo-inositol is an important part of the phosphatidylinositol second messenger system (PI-cycle). Abnormalities in nerve cell myo-inositol levels and/or PI-cycle regulation has been suggested as being involved in the pathophysiology and/or treatment of many psychiatric disorders including bipolar disorder, major depressive disorder, panic disorder, obsessive-compulsive disorder, eating disorders and schizophrenia. This review examines the metabolism and biochemical importance of myo-inositol and the PI-cycle. It relates this to the current in vivo evidence for myo-inositol and PI-cycle involvement in these psychiatric disorders, particularly focusing upon the magnetic resonance spectroscopy (MRS) findings in patient studies to date. From this review it is concluded that while the evidence suggests probable relevance to the pathophysiology and/or treatment of bipolar disorder, there is much less support for a significant role for the PI-cycle or myo-inositol in any other psychiatric disorder. More definitive investigation is required before PI-cycle dysfunction can be considered specific to bipolar disorder.

Bipolar Disorder↗

PubMed2005

Differential effects of chronic lithium and valproate on brain activation in healthy volunteers.

RATIONALE: Previous functional imaging studies have shown altered brain activity during cognitive task performance in bipolar patients. However, the fact that these patients are often on medication makes it unclear to what extent these changes reflect treatment effects. OBJECTIVES: This study aims to identify regional brain activity changes occurring following lithium and valproate treatment in healthy volunteers. METHODS: This was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n = 12), 900 mg lithium (n = 9), or placebo (n = 12). Functional images were acquired using functional magnetic resonance imaging (fMRI) while subjects performed three cognitive tasks, a word generation paradigm, a spatial attention task and a working memory task. fMRI was carried out both before and after 14 days of treatment with valproate, lithium or placebo. The changes in the magnitude of the blood-oxygen-level-dependent (BOLD) signal after treatment were compared between the groups using a one-way ANOVA for each task followed by a post-hoc multiple comparisons correction. RESULTS: A significant group effect was noted in the change in BOLD signal magnitude from baseline to post-treatment, in all three tasks (working memory p< 0.000; spatial attention task p = 0.003; word generation paradigm p = 0.030). In the working memory task, the lithium group had a significant decrease in BOLD signal change, compared with the control group (p< 0.000). A decrease in BOLD signal change was also noted in the valproate group, in the spatial attention task (p = 0.004). Both lithium and valproate groups had a decreased BOLD signal in the verbal task, following treatment, compared with the placebo group (p = 0.061 (lithium approached significance); p = 0.050 (valproate)). CONCLUSIONS: These findings suggest that lithium and valproate have independent effects on brain activation that vary in a task and region-dependent manner.

Adult↗

PubMed2005

Bipolar disorder and myo-inositol: a review of the magnetic resonance spectroscopy findings.

OBJECTIVES: Myo-inositol is an important component of the phosphatidylinositol second messenger system (PI-cycle). Alterations in PI-cycle activity have been suggested to be involved in the pathophysiology and/or treatment of bipolar disorder. More specifically, lithium has been suggested to act primarily by lowering myo-inositol concentrations, the so-called inositol-depletion hypothesis. myo-Inositol concentrations can be measured in vivo with magnetic resonance spectroscopy (MRS). METHODS: The current review primarily examines animal and human MRS studies that evaluated the role of myo-inositol in bipolar illness and treatment. RESULTS: Studies have been carried out in patients who are manic, depressed, and euthymic, both on and off treatment. However, there are several limitations of these studies. CONCLUSIONS: The preclinical and clinical MRS findings were generally supportive of the involvement of myo-inositol in bipolar disorder and its treatment. Overall, in bipolar patients who are manic or depressed there are abnormalities in brain myo-inositol concentrations, with changes in frontal and temporal lobes, as well as the cingulate gyrus and basal ganglia. These abnormalities are not seen in either euthymic patients or healthy controls, possibly due to a normalizing effect of treatment with either lithium or sodium valproate. There is also increasing evidence that sodium valproate may also act upon the PI-cycle. Nonetheless, it remains uncertain if these changes in myo-inositol concentration are primary or secondary. Findings regarding the specific inositol-depletion hypothesis are also generally supportive in acutely ill patients, although it is not yet possible to definitively confirm or refute this hypothesis based on the current MRS evidence.

Animals↗

PubMed2004

Dextroamphetamine causes a change in regional brain activity in vivo during cognitive tasks: a functional magnetic resonance imaging study of blood oxygen level-dependent response.

BACKGROUND: Dextroamphetamine is known to have profound effects on both subjective and physiologic measurements, but it is unclear to what extent these behavioral changes are a direct result of altered regional brain activation. One method to measure this is to use functional magnetic resonance imaging (fMRI). METHODS: In the present study, fMRI was used to measure both the spatial extent of changes (the number of pixels activated) and the magnitude of the blood oxygen level-dependent (BOLD) response. We examined the effects of motor, verbal, memory, and spatial attention task during fMRI in 18 healthy volunteers. Functional MRI measurements were obtained at baseline and again 75 min after an oral dose of 25 mg dextroamphetamine. RESULTS: Dextroamphetamine caused a decrease in the number of activated pixels and the magnitude of the BOLD response during the three cognitive tasks tested but not during the motor task. These changes were region and task specific. CONCLUSIONS: This is the first study to examine the effect of dextroamphetamine on the number of activated pixels and the BOLD response during the performance of a range of cognitive and motor tasks. Our results suggest that dextroamphetamine causes measurable decreases in brain activity in a variety of regions during cognitive tasks. These changes might be linked to behavioral changes observed after dextroamphetamine administration and could possibly be mediated by alterations in dopaminergic activation.

Adult↗

PubMed2004

Brain choline concentrations may not be altered in euthymic bipolar disorder patients chronically treated with either lithium or sodium valproate.

BACKGROUND: It has been suggested that lithium increases choline concentrations, although previous human studies examining this possibility using 1H magnetic resonance spectroscopy (1H MRS) have had mixed results: some found increases while most found no differences. METHODS: The present study utilized 1H MRS, in a 3 T scanner to examine the effects of both lithium and sodium valproate upon choline concentrations in treated euthymic bipolar patients utilizing two different methodologies. In the first part of the study healthy controls (n = 18) were compared with euthymic Bipolar Disorder patients (Type I and Type II) who were taking either lithium (n = 14) or sodium valproate (n = 11), and temporal lobe choline/creatine (Cho/Cr) ratios were determined. In the second part we examined a separate group of euthymic Bipolar Disorder Type I patients taking sodium valproate (n = 9) and compared these to controls (n = 11). Here we measured the absolute concentrations of choline in both temporal and frontal lobes. RESULTS: The results from the first part of the study showed that bipolar patients chronically treated with both lithium and sodium valproate had significantly reduced temporal lobe Cho/Cr ratios. In contrast, in the second part of the study, there were no effects of sodium valproate on either absolute choline concentrations or on Cho/Cr ratios in either temporal or frontal lobes. CONCLUSIONS: These findings suggest that measuring Cho/Cr ratios may not accurately reflect brain choline concentrations. In addition, the results do not support previous suggestions that either lithium or valproate increases choline concentrations in bipolar patients.

Journal Article↗

PubMed2004

Lithium and valproate protect against dextro-amphetamine induced brain choline concentration changes in bipolar disorder patients.

BACKGROUND: Lithium may affect brain choline concentrations, and this effect has been proposed to potentially explain its clinical efficacy. Since dextro-amphetamine is a useful human model of mania, we were interested in determining firstly whether dextro-amphetamine would alter brain choline concentrations, and secondly to determine if lithium would protect against any such changes in bipolar patients. In addition, we wanted to determine if valproate would also have any effects upon choline levels. METHODS: Healthy controls (n=18) were compared with euthymic Bipolar Disorder patients (Type I and Type II) who were taking lithium (n=14) or valproate (n=11). We utilized (1)H-magnetic resonance spectroscopy ((1)H-MRS) in a 3.0T scanner to examine brain choline/phosphocholine+creatine (Cho/Cr) ratios. Changes in this ratio were measured to determine any changes in choline concentrations in the temporal lobe. RESULTS: The results showed that administration of dextro-amphetamine decreased the Cho/Cr ratios. In contrast, in both the lithium-treated and valproate-treated patients this decrease was not seen; this attenuation in the change in Cho/Cr ratio changes was statistically significant. It should be noted that Cho/Cr ratios were significantly higher at baseline in the controls compared to both groups of patients, which may have influenced the results. CONCLUSIONS: These findings are the first to examine the effects of dextro-amphetamine on brain choline concentrations. They show that while in controls dextro-amphetamine decreases choline concentrations, lithium and valproate both appear to protect against this effect in bipolar patients. However, as brain ratios were measured rather than the absolute concentration of choline, and these ratios were lowered in patients at baseline, these results must be regarded as preliminary and require replication in future studies.

Antipsychotic Agents↗

PubMed2004

A review of acute treatments for bipolar depression.

Bipolar patients generally spend much more time in the depressed phase of their illness than the manic phase, and there are many more bipolar type II and bipolar spectrum disorder patients than there are bipolar type I. Additionally, there is a significant risk of suicide in bipolar patients when depressed. The treatment of the depressed phase of bipolar disorder is therefore a matter of some priority. Here, we review current evidence supporting the use of five groups of treatments: anti-depressants; lithium; anti-convulsants (valproate, and carbamazepine, lamotrigine, gabapentin); anti-psychotics; and other treatments (electroconvulsive therapy, benzodiazepines, sleep-deprivation, and dopamine agonists). From this review, it is apparent that the literature regarding the treatment of bipolar depression is significantly limited in several key areas. Nonetheless, from the evidence currently available, the treatments with the best evidence for efficacy are selective serotonin reuptake inhibitors (SSRIs) and lamotrigine. There is also some evidence in favour of bupropion and moclobemide. Although lithium and olanzapine monotherapies can also be beneficial, they appear less efficacious than antidepressants. One of the major concerns about treatment with antidepressants has been the risk of precipitating a switch into mania. However, recent studies suggest that, if a mood stabilizer and antidepressant are given concurrently, then the risk of switching is minimized. There is also recent evidence for an independent antidepressant action for at least one atypical antipsychotic. Therefore, the conclusion from this review, in contrast to previous suggestions, is that a combination of an atypical antipsychotic and either an SSRI or lamotrigine may provide a useful first-line treatment for depressed bipolar disorder patients. Further research is clearly required to examine this approach and compare it with other possible treatment options.

Anticonvulsants↗

PubMed2004

Neurobiological findings in bipolar II disorder compared with findings in bipolar I disorder.

OBJECTIVE: To determine whether there are consistent neurobiological differences between patients with bipolar I disorder (BD I) and those with bipolar II disorder (BD II). METHOD: We reviewed the literature in areas where the most consistent neurobiological findings have been reported for bipolar disorder, specifically, neuroimaging and brain metabolism. The imaging studies reviewed examined structure, using magnetic resonance imaging (MRI), and function, using functional MRI, positron emission tomography, and single photon emission computed tomography. We used magnetic resonance spectroscopy to examine brain chemistry. We reviewed those metabolic studies that examined cell calcium, 3-methoxy-4-hydroxyphenylglycol, and protein kinase C. RESULTS: Some genetic studies suggest that there may be differences between BD II and BD I patients. However, our review of the imaging and metabolic studies identified few studies directly comparing these 2 groups. In those studies, there were few differences, if any, and these were not consistent. CONCLUSIONS: While genetic data suggest there may be differences between BD II patients and BD I patients, the neurobiological findings to date do not provide support. However, this may be owing to the small number of studies directly comparing the 2 groups and also to the fact that those carried out have not been adequately powered to detect possible small true differences. This is an important issue because, if there are no neurobiological differences, it would be anticipated that similar treatments would be similarly effective in both groups. Given the importance of understanding whether there are neurochemical differences between these groups, further research in this area is clearly needed.

Bipolar Disorder↗

PubMed2004

Qualitative review of SNRIs in anxiety.

Anxiety disorders pose a problem for a significant number of individuals, with a 1-year prevalence rate estimated at 13.1% to 17.1%. Many pharmacologic agents have been used to treat anxiety disorders, and among those in current use are newer benzodiazepines (alprazolam), azapirones (buspirone), selective serotonin reuptake inhibitors (paroxetine and sertraline), and venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI). The likely role of abnormal serotonergic neurotransmission in anxiety is widely supported, while the role of norepinephrine is less clear. Still, many lines of evidence support the hypothesis that a perturbation in norepinephrine neurotransmission contributes to the symptoms of anxiety. Therefore, it is conceivable that modulation of both serotonin and norepinephrine systems by dual-reuptake inhibitors may be an advantage in the treatment of anxiety disorders. Given this, the current review examines evidence on the possible role of venlafaxine in the treatment of anxiety disorders. From this review it is clear that venlafaxine is as efficacious as selective serotonin reuptake inhibitors in treating anxiety, with comparable tolerability. Future research will be valuable in determining if antidepressants that combine pharmacologic actions on serotonergic and noradrenergic systems have advantages over more selective agents in treating anxiety disorders.

Adrenergic Uptake Inhibitors↗

PubMed2003

Low self-esteem and psychiatric patients: Part I - The relationship between low self-esteem and psychiatric diagnosis.

BACKGROUND: The objective of the current study was to determine the prevalence and the degree of lowered self-esteem across the spectrum of psychiatric disorders. METHOD: The present study was carried out on a consecutive sample of 1,190 individuals attending an open-access psychiatric outpatient clinic. There were 957 psychiatric patients, 182 cases with conditions not attributable to a mental disorder, and 51 control subjects. Patients were diagnosed according to DSM III-R diagnostic criteria following detailed assessments. At screening, individuals completed two questionnaires to measure self-esteem, the Rosenberg self-esteem scale and the Janis and Field Social Adequacy scale. Statistical analyses were performed on the scores of the two self-esteem scales. RESULTS: The results of the present study demonstrate that all psychiatric patients suffer some degree of lowered self-esteem. Furthermore, the degree to which self-esteem was lowered differed among various diagnostic groups. Self-esteem was lowest in patients with major depressive disorder, eating disorders, and substance abuse. Also, there is evidence of cumulative effects of psychiatric disorders on self-esteem. Patients who had comorbid diagnoses, particularly when one of the diagnoses was depressive disorders, tended to show lower self-esteem. CONCLUSIONS: Based on both the previous literature, and the results from the current study, we propose that there is a vicious cycle between low self-esteem and onset of psychiatric disorders. Thus, low self-esteem increases the susceptibility for development of psychiatric disorders, and the presence of a psychiatric disorder, in turn, lowers self-esteem. Our findings suggest that this effect is more pronounced with certain psychiatric disorders, such as major depression and eating disorders.

Journal Article↗

PubMed2003

Low self-esteem and psychiatric patients: Part II - The relationship between self-esteem and demographic factors and psychosocial stressors in psychiatric patients.

BACKGROUND: The objective of the present study was to identify the effects and relative importance of demographic factors and psychosocial stressors on self-esteem of psychiatric patients. METHOD: The present study was carried out on a consecutive sample of 1,190 individuals attending an open-access psychiatric outpatient clinic. Patients were diagnosed according to DSM III-R diagnostic criteria following detailed assessments. At screening, patients and controls completed two self-esteem questionnaires, the Rosenberg self-esteem scale and the Janis and Field Social Adequacy scale. In addition, a large amount of demographic and psychosocial data was collected on all patients. RESULTS: Significantly increased self-esteem was observed with an increase in age, educational achievement and income. Employed patients showed significantly higher self-esteem compared to unemployed patients. Female patients had a significantly lower self-esteem compared to male patients. The self-esteem of psychiatric patients did not vary significantly with their marital status. No relationship was detected between acute stressors and the self-esteem of psychiatric patients, although severe enduring stressors were associated with lower self-esteem in psychiatric patients. CONCLUSION: The results of this large study demonstrate that the self-esteem of adult psychiatric patients is affected by a number of demographic and psychosocial factors including age, sex, educational status, income, employment status, and enduring psychosocial stressors.

Journal Article↗

PubMed2003

Relationship of plasma amphetamine levels to physiological, subjective, cognitive and biochemical measures in healthy volunteers.

Acute administration of the stimulant dextro-amphetamine produces multiple physiological, subjective cognitive and biochemical changes. These effects are similar to those seen in mania, and may be a useful model for mania. The aim of the present study was more fully to determine the multiple effects of dextro-amphetamine and to relate these to changes in plasma levels of the drug. In a double-blind, placebo-controlled crossover study in 25 healthy volunteers (ages 18-45), the effects of 25 mg of oral dextro-amphetamine were examined. Physiological, subjective, cognitive changes, concentrations of amino acids and metabolites of biogenic amines period were related to changes in plasma amphetamine concentrations over 500 min. Peak concentrations of dextro-amphetamine occurred at 2.5-3.5 h post-administration and levels decreased to 75% of peak value after 500 min. The results from the present study indicate that the subjective psychological, cognitive and blood pressure changes frequently did not mirror the time course of plasma levels of the drug. Thus, there was no clear-cut relationship between plasma levels and effects. In addition, dextro-amphetamine caused no significant changes in amino acids or amino metabolite concentrations. In conclusion, while dextro-amphetamine administration definitely causes several changes which are seen in mania, there remain some physiological and metabolic differences between these two conditions.

Adolescent↗

PubMed2003

Chronic treatment with lithium, but not sodium valproate, increases cortical N-acetyl-aspartate concentrations in euthymic bipolar patients.

Previous studies have found that treatment with lithium over a 4-week period may increase the concentration of N-acetyl-aspartate (NAA) in both bipolar patients and controls. In view of other findings indicating that NAA concentrations may be a good marker for neuronal viability and/or functioning, it has been further suggested that some of the long term benefits of lithium may therefore be due to actions to improve these neuronal properties. The aim of the present study was to utilize H magnetic resonance spectroscopy ( H MRS) to further examine the effects of both lithium and sodium valproate upon NAA concentrations in treated euthymic bipolar patients. In the first part of the study, healthy controls (n =18) were compared with euthymic bipolar patients (type I and type II) who were taking either lithium (n =14) or sodium valproate (n =11), and NAA : creatine ratios were determined. In the second part, we examined a separate group of euthymic bipolar disorder patients taking sodium valproate (n =9) and compared these to age- and sex-matched healthy controls (n =11), and we quantified the exact concentrations of NAA using an external solution. The results from the first part of the study showed that bipolar patients chronically treated with lithium had a significant increase in NAA concentrations but, in contrast, there were no significant increases in the sodium valproate-treated patients compared to controls. The second part of the study also found no effects of sodium valproate on NAA concentrations. These findings are the first to compare NAA concentrations in euthymic bipolar patients being treated with lithium or sodium valproate. The results support suggestions that longer-term administration of lithium to bipolar patients may increase NAA concentrations. However, the study suggests that chronic administration of sodium valproate to patients does not lead to similar changes in NAA concentrations. These findings suggest that sodium valproate and lithium may not share a common mechanism of action in bipolar disorder involving neurotrophic or neuroprotective effects.

Adult↗