Publications (57)273.09 Total impact
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Article: The impact of childhood trauma on cognitive functioning in patients recently recovered from a first manic episode: Data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).
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ABSTRACT: Background: Both bipolar disorder (BD) and childhood trauma are associated with cognitive impairment. People with BD have high rates of childhood trauma, which confer greater overall disease severity, but, it is unknown if childhood trauma is associated with greater neurocognitive impairment in BD patients early in the course of their illnesses. In this study, we investigated the impact of childhood trauma on specific cognitive dysfunction in patients who recently recovered from their first episode of mania. Methods: Data were available for 64 patients and 28 healthy subjects matched by age, gender and pre-morbid IQ, recruited from a large university medical center. History of childhood trauma was measured using the Childhood Trauma Questionnaire. Cognitive function was assessed through a comprehensive neuropsychological test battery. Results: Trauma was associated with poorer cognitive performance in patients on cognitive measures of IQ, auditory attention and verbal and working memory, and a different pattern was observed in healthy subjects. Limitations: We had a modest sample size, particularly in the group of healthy subjects with trauma. Conclusions: Childhood trauma was associated with poorer cognition in BD patients who recently recovered from a first episode of mania compared to healthy subjects. The results require replication, but suggest that the co-occurrence of trauma and bipolar disorder can affect those cognitive areas that are already more susceptible in patients with BD.Journal of affective disorders 12/2012; · 3.76 Impact Factor -
Article: Decreased mRNA expression of uncoupling protein 2, a mitochondrial proton transporter, in post-mortem prefrontal cortex from patients with bipolar disorder and schizophrenia.
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ABSTRACT: Although the neurobiological basis of bipolar disorder (BD) remains unknown, mitochondrial dysfunction, oxidative stress and oxidative cell damage have been identified in this disease. Uncoupling proteins (UCP) are proton carriers located in the inner membrane of the mitochondria involved in controlling the production of mitochondrial reactive oxygen species (ROS). Therefore, in this study we wished to investigate the involvement of UCP in BD. We analyzed the RNA and protein levels of UCP2 in the dorsolateral prefrontal cortex (DLPFC) of subjects with BD and schizophrenia (SCZ) and assessed the potential relationship between the antioxidant superoxide dismutase (SOD1 and SOD2) and UCP2 in the same region. Our results showed a downregulation of UCP2 mRNA levels in the DLPFC of subjects with BD and SCZ. There were no differences in UCP2 protein, SOD1 and SOD2 levels between patients and controls. Although more studies are necessary, our results suggest that UCP2 is not been used as a compensatory mechanism to oppose the higher levels of oxidative stress found in BD and SCZ.Neuroscience Letters 11/2011; 505(1):47-51. · 2.11 Impact Factor -
Article: Relationship between cognitive functioning and 6-month clinical and functional outcome in patients with first manic episode bipolar I disorder.
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ABSTRACT: Although cognitive deficits in bipolar disorder have been associated with diminished functional outcome, this relationship has been studied primarily through cross-sectional designs, and has not been studied in patients early in the course of illness. The purpose of this study was to evaluate the impact of cognitive functioning on longitudinal 6-month functional and clinical outcome in recently diagnosed clinically stable patients with bipolar disorder. A total of 53 recently diagnosed patients with DSM-IV bipolar disorder type I were assessed within 3 months of their first manic episode using a neuropsychological battery measuring verbal/pre-morbid intellectual functioning, learning/memory, spatial/non-verbal reasoning, attention/processing speed and executive function. Functional outcome was assessed at baseline and 6 months using the Multidimensional Scale of Independent Functioning (MSIF) and DSM-IV Global Assessment of Functioning Scale (GAF). Clinical outcome was assessed with symptom ratings and by monitoring onset of new mood episodes. Memory, particularly verbal learning/memory, was robustly associated with 6-month functional outcome on the MSIF, even after partialling out the influence of mood symptoms and substance abuse co-morbidity. Depression ratings at 6 months, but not cognitive variables, were associated with 6-month GAF scores. Cognitive functioning was not associated with 6-month clinical outcome. Memory was associated with 6-month longitudinal functional but not clinical outcome in recently diagnosed patients with bipolar disorder. These data further support the distinction between clinical and functional outcome, and emphasize the need for identification of, and development of treatments for, cognitive impairments early in the course of bipolar disorder.Psychological Medicine 05/2011; 41(5):971-82. · 6.16 Impact Factor -
Article: Neuropsychological functioning in euthymic bipolar disorder: a meta-analysis.
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ABSTRACT: Although cognitive deficits are prominent in symptomatic patients with bipolar disorder, the extent and pattern of cognitive impairment in euthymic patients remain uncertain. Neuropsychological studies comparing euthymic bipolar patients and healthy controls were evaluated. Across studies, effect sizes reflecting patient-control differences in task performance were computed for the 15 most frequently studied cognitive measures in the literature. Across the broad cognitive domains of attention/processing speed, episodic memory, and executive functioning, medium-to-large performance effect size differences were consistently observed between patients and controls, favoring the latter. Deficits were not observed on measures of vocabulary and premorbid IQ. Meta-analytic findings provide evidence of a trait-related neuropsychological deficit in bipolar disorder involving attention/processing speed, memory, and executive function. Findings are discussed with regard to potential moderators, etiologic considerations, limitations, and future directions in neuropsychological research on bipolar disorder.Acta psychiatrica Scandinavica. Supplementum 02/2007; -
Article: Depot antipsychotic medications in bipolar disorder: a review of the literature.
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ABSTRACT: To review the literature on the efficacy and safety of depot formulations of first- and second-generation antipsychotic medications (FGAs and SGAs) in patients with bipolar disorder. We conducted a computer-aided MEDLINE search using the search terms 'depot antipsychotic', 'bipolar disorder' and 'compliance.' We identified eight published reports in bipolar patients regarding the use of depot FGAs, and six preliminary reports on the use of depot SGAs. These studies suggest that depots FGAs are efficacious in preventing manic episodes during the maintenance treatment of bipolar disorder. Several studies, however, indicate that depot FGAs may be associated with increased time with depressive symptoms, particularly in patients with a predominantly depressive course of illness. Preliminary data on the role of depot formulations of SGAs suggest that they reduce the frequency of both manic and depressive episodes during maintenance treatment, and are well tolerated by patients. After a careful risk-benefit analysis, depot antipsychotics may be considered for the long-term control of mood episodes in bipolar patients who have relapsed due to medication non-adherence or who have failed to respond to standard therapies. Depot FGAs should be avoided in patients with a high burden of illness from depressive symptoms and particularly in those judged to be at high risk of suicide. The available data on depot formulations of SGAs indicate that they are efficacious in the maintenance treatment of bipolar illness without increasing the burden of the depressive pole of the illness, but further systematic studies are required to definitively assess this.Acta psychiatrica Scandinavica. Supplementum 02/2007; -
Article: A 6-month randomized open-label comparison of continuation of oral atypical antipsychotic therapy or switch to long acting injectable risperidone in patients with bipolar disorder.
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ABSTRACT: To determine the safety and effectiveness of long-acting injectable risperidone (LAI-ris) add-on in bipolar patients. A 6-month, open-label, randomized, pilot trial enrolled 49 bipolar out-patients who were taking a mood stabilizer and an atypical antipsychotic (AAP). Patients were maintained on a mood stabilizer and were randomized to continuation of their current AAP or switched to LAI-ris treatment. Safety outcomes included adverse events and changes in vital signs, laboratory tests and extrapyramidal symptoms (EPS). Effectiveness measures included Clinical Global Impression-Severity, scales assessing mania, depression, anxiety, resource utilization, quality of life, subject satisfaction with treatment, and time to intervention. Twenty-three subjects were randomized to LAI-ris and 26 to oral AAP. There were no significant differences between the groups in adverse events, EPS change scores, weight or other safety measures. LAI-ris group had significant reductions in symptoms as measured by changes in Clinical Global Impression-Severity scores and Young Mania Rating Scale at endpoint relative to baseline and oral AAP group had reductions in Hamilton Anxiety Rating Scale scores relative to baseline but no significant differences were noted between the groups on any of the efficacy measures. LAI-ris demonstrated similar effectiveness, safety and tolerability compared to oral AAP in this 6 month pilot trial.Acta psychiatrica Scandinavica. Supplementum 02/2007; -
Article: Bipolaroids: functional imaging in bipolar disorder.
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ABSTRACT: To evaluate the literature pertaining to the use of functional magnetic resonance imaging (fMRI) in bipolar disorder research. A search for papers published in English in journals from 1984 onwards was conducted using MedLine and EMBASE with the following terms: functional neuroimaging or fMRI and depression or bipolar disorder. In addition, retrieved papers and literature known to the authors was also scrutinized for further relevant reports. The research findings from 26 articles are tabulated and the results from 10 articles dealing specifically with bipolar disorder are discussed in detail. fMRI is a useful tool for investigating bipolar disorder. Preliminary studies point to trait and state abnormalities involving structures known to be associated with the generation and modulation of emotion. The patterns of fMRI activation are different to those found in healthy subjects and patients with major depression. FMRI studies are likely to provide valuable insights into the pathophysiology of bipolar disorder.Acta psychiatrica Scandinavica. Supplementum 02/2004; -
Article: Effects of alpha-methyl-para-tyrosine-induced catecholamine depletion in patients with seasonal affective disorder in summer remission.
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ABSTRACT: Noradrenergic and dopaminergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder (SAD). We investigated the effects of catecholamine depletion using alpha-methyl-para-tyrosine (AMPT), an inhibitor of tyrosine hydroxylase, in patients with SAD in natural summer remission. Nine drug-free patients with SAD by DSM-IV criteria, in summer remission for at least eight weeks, completed a double-blind, crossover study. Behavioral ratings and serum HVA and MHPG levels were obtained for 3-day sessions during which patients took AMPT or an active control drug, diphenhydramine. The active AMPT session significantly reduced serum levels of HVA and MHPG compared with the control diphenhydramine session. The AMPT session resulted in higher depression ratings with all nine patients having significant clinical relapse, compared with two patients during the diphenhydramine session. All patients returned to baseline scores after drug discontinuation. Catecholamine depletion results in significant clinical relapse in patients with SAD in the untreated, summer-remitted state. AMPT-induced depressive relapse may be a trait marker for SAD, and/or brain catecholamines may play a direct role in the pathogenesis of SAD.Neuropsychopharmacology 12/2001; 25(5 Suppl):S97-101. · 7.99 Impact Factor -
Article: Comparative efficacy of typical and atypical antipsychotics as add-on therapy to mood stabilizers in the treatment of acute mania.
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ABSTRACT: Typical antipsychotics are commonly used in combination with mood stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add-on therapy to mood stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to mood stabilizers in a clinically relevant, naturalistic setting. This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) mood stabilizer and typical antipsychotic, (2) mood stabilizer and atypical antipsychotic, and (3) combination: mood stabilizer plus a typical antipsychotic, then switched to mood stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart. Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001). Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to mood stabilizers for the treatment of patients with mania.The Journal of Clinical Psychiatry 12/2001; 62(12):975-80. · 5.80 Impact Factor -
Article: Effects of rapid tryptophan depletion on brain 5-HT(2) receptors: a PET study.
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ABSTRACT: The mechanism by which rapid tryptophan depletion (RTD) paradigm induces depressive relapse in recently remitted patients with depression is unknown. To determine the effects of RTD on brain 5-HT(2) receptors using positron emission tomography (PET) and (18)F-labelled setoperone. Ten healthy women under went two PET scans. Each scan was done 5 h after the ingestion of either a balanced or a tryptophan-deficient amino acid mixture, and the two test sessions were separated by at least 5 days. The RTD decreased plasma free tryptophan levels significantly but it had no significant effects on mood. Subjects showed a significant decrease in brain 5-HT(2) receptor binding in various cortical regions following the RTD session. When taken with the evidence that antidepressant treatment is associated with a decrease in brain 5-HT(2) receptors, these findings suggest that a decrease in 5-HT(2) binding following RTD might be an adaptive response that provides protection against depressive symptoms.The British Journal of Psychiatry 06/2001; 178:448-53. · 6.62 Impact Factor -
Article: Seasonal depression: the dual vulnerability hypothesis revisited.
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ABSTRACT: In DSM-IV, winter seasonal affective disorder (SAD) is classified as a seasonal pattern of recurrent major depressive episodes in winter with full remission of symptoms in summer. However, other groups with "winter depression" have been identified, including patients with incomplete summer remission (ISR) and subsyndromal SAD (sub-SAD, winter depressive symptoms that do not meet criteria for major depression). In this study, we compare the clinical characteristics of these three seasonal groups and their response to light therapy. 558 patients assessed at a specialized SAD Clinic were diagnosed using DSM-III-R or DSM-IV criteria. Clinical information was recorded using a checklist at index assessment. A subset of patients (N=192) were treated with an open, 2 week trial of light therapy using a 10000 lux fluorescent light box for 30 min per day in the early morning. Patients were assessed before and after treatment with the 29 item modified Hamilton Depression Rating Scale and clinical response was defined as greater than 50% improvement in scores. The rates of some melancholic symptoms, anxiety, panic, suicidal ideation, and family history of mood disorder were lowest in the sub-SAD group. The clinical response rates to light therapy were highest in the sub-SAD group (N=32, 78%), intermediate in the SAD group (N=113, 66%), and lowest in the ISR group (N=47, 51%). This was a retrospective study of patients seen in a specialty clinic, although information was obtained in a standardized format. The light therapy trial had an open design so that placebo response could not be determined. There are differences in both the patterns of clinical symptoms and the response to light therapy in these three groups with winter depression. These results are consistent with a dual vulnerability hypothesis that considers these groups to result from interaction of separate factors for seasonality and depression.Journal of Affective Disorders 04/2001; 63(1-3):123-32. · 3.52 Impact Factor -
Article: Immune-inflammatory markers in patients with seasonal affective disorder: effects of light therapy.
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ABSTRACT: There is increasing evidence that an activation of the immune-inflammatory system is involved in the pathophysiology of depressive disorders. The purposes of this study were to (1) compare immune-inflammatory markers in patients with seasonal affective disorder (SAD) with those in matched normal controls; and (2) examine the effects of light therapy on the immune-inflammatory markers in patients with SAD. Plasma concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble IL-2 receptor (sIL-2R) were measured in 15 patients with SAD and 15 age- and sex-matched normal controls. Of the 15 patients, 14 had repeated blood sampling for these variables following 2 weeks of light therapy. We found that patients with SAD had significantly increased IL-6 levels compared to normal controls (P<0.0005). There was a trend toward increased sIL-2R in patients with SAD (P=0.09). There was no significant difference in sIL-6R level between the two diagnostic groups (P=0.18), but the product term (IL-6xsIL-6R) was significantly higher in patients with SAD than that in normal control controls (P<0.0003). Furthermore, all 14 patients who completed the study improved with 2 weeks of light therapy and nine of them (64%) had 50% reduction in score of the Hamilton Depression Rating Scale-SAD version post-treatment compared to baseline. However, the initially increased immune markers in SAD patients were not significantly altered by the therapeutic light therapy. This study was limited to a small sample size and other immune inflammatory markers should be measured for further evidence of immune activation in seasonal depression. Our results of increased IL-6, IL-6xsIL-6R, and sIL-2R in patients with SAD suggest an activation of the immune-inflammatory system in winter depression, which is not altered by 2 weeks of successful light therapy.Journal of Affective Disorders 04/2001; 63(1-3):27-34. · 3.52 Impact Factor -
Article: An open trial of light therapy for women with seasonal affective disorder and comorbid bulimia nervosa.
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ABSTRACT: Many patients with seasonal affective disorder (SAD) have dysfunctional eating behaviors. Conversely, many women with bulimia nervosa have marked winter worsening of mood and bulimic symptoms. Controlled studies of light therapy in SAD and in bulimia nervosa have shown beneficial effects on mood and binge/purge symptoms. We explored the clinical use of light therapy in women with SAD who also had comorbid bulimia nervosa. Twenty-two female patients diagnosed using DSM-IV criteria with both bulimia nervosa and major depressive disorder with a seasonal (winter) pattern were treated with an open design, 4-week trial of light therapy (10,000 lux fluorescent light box with an ultraviolet filter, 30 to 60 minutes per day in the early morning). Patients were assessed before and after treatment with depression scales and with binge/purge diaries. Light therapy resulted in significant improvement in mood, with a mean 56% reduction in 29-item Hamilton Rating Scale for Depression scores following treatment (p < .001). The frequency of binges and purges per week also significantly decreased (p < .001) from baseline by a mean of 46% and 36%, respectively. Two (9%) of 22 patients became abstinent of binge/ purge episodes, compared with 10 (45%) of 22 patients who met criteria for remission of depressive symptoms. The light therapy was well tolerated by patients. These results suggest that therapeutic effects of light therapy on mood and bulimic symptoms in patients with SAD and comorbid bulimia nervosa are sustained over at least 4 weeks. However, the low abstinence rate in bulimic symptoms indicates that light therapy may be most effectively used as an adjunctive treatment to medications and/or psychotherapy for bulimia nervosa.The Journal of Clinical Psychiatry 03/2001; 62(3):164-8. · 5.80 Impact Factor -
Article: A PET study of brain 5-HT2 receptors and their correlation with platelet 5-HT2 receptors in healthy humans.
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ABSTRACT: Platelets share many properties with brain serotonergic neurons such as active 5-hydroxytryptamine (5-HT) transport, 5-HT2 receptors, and mitochondrial monoamine oxidase. We measured brain 5-HT2 receptors and platelet 5-HT2 receptors in healthy volunteers to determine if there was any correlation between the two measures. Ten healthy volunteers with no lifetime history of psychiatric illness or family history in first-degree relatives were recruited. 5-HT2 receptor binding was determined for each subject with positron emission tomography and [18F]setoperone scan in the brain and with 3H-LSD binding in platelets. We found no significant correlation between 5-HT2 binding potential (BP) in platelets (Bmax/Kd) and a semiquantitative estimate of 5-HT2 BP in frontal, parietal, and temporal cortical regions. SPM voxel based analysis also showed no significant correlation between the 5-HT2 BP in platelets and in the brains of the study subjects. Brain 5-HT2 receptor binding was not significantly correlated to platelet 3H-LSD binding in healthy subjects. This raises questions about the validity of generalizing findings from platelet studies to 5-HT neurons in the brain.Psychopharmacologia 10/2000; 151(4):424-7. · 4.08 Impact Factor -
Article: Brain serotonin2 receptors in major depression: a positron emission tomography study.
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ABSTRACT: Postmortem and brain imaging studies that measured brain serotinin(2) (5-HT(2)) receptors in major depression reported an increase, decrease, and no change compared with controls. In this study, we assessed brain 5-HT(2) receptors in 20 depressed patients (mean +/- SD age, 40.1 +/- 9.5 years; range, 22-60 years) and 20 healthy controls similar in age (37.2 +/- 12.6 years; range, 19-59 years) using positron emission tomography and setoperone labeled with fluorine 18 ([(18)F]setoperone). Patients with DSM-IV major depression and healthy controls underwent scanning with [(18)F]setoperone. All study subjects were drug free for at least 2 weeks. The 5-HT(2) binding images were created using region-to-cerebellum ratios. The differences in 5-HT(2) receptor binding potential between the two groups were determined with statistical parametric mapping software and region of interest analysis. There was a significant negative correlation between 5-HT(2) receptor binding potential and age in both patients and controls, and the magnitude of this correlation was similar in both groups. Both statistical parametric mapping and region of interest analyses showed that, compared with healthy controls, depressed patients had significantly lower 5-HT(2) receptor binding potential in frontal, temporal, parietal, and occipital cortical regions. Statistical parametric mapping analysis showed that the mean decrease in 5-HT(2) receptor binding potential for the entire cluster in these regions was 22%, and it ranged from 22% to 27% for local maxima within the clusters of significant voxels. This study suggests that brain 5-HT(2) receptors are decreased in patients with major depression.Archives of General Psychiatry 10/2000; 57(9):850-8. · 12.02 Impact Factor -
Article: Divalproex sodium increases plasma GABA levels in healthy volunteers.
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ABSTRACT: The purpose of this study was to ascertain the effects of divalproex sodium (DVP), an anticonvulsant and mood stabilizer, on plasma gamma-aminobutyric acid (GABA) levels in healthy humans. Twenty healthy volunteers with no lifetime history of psychiatric illness or family history in first-degree relatives were recruited. Each subject received DVP 1000 mg per day for 1 week. Blood samples for assay of plasma levels of GABA were taken from each subject before and after the administration of DVP. GABA concentrations were analysed using high pressure liquid chromatography with fluorescence detection after derivatization with o-phthaldialdehyde. It was found that DVP administration for 1 week resulted in a small, but significant, increase in plasma levels of GABA. Our results suggest that DVP enhances GABA activity in humans. Further treatment studies of DVP on GABA function in patients with psychiatric disorders are needed to explore the significance of the enhancing effect of DVP on GABA activity.International Clinical Psychopharmacology 08/2000; 15(4):221-5. · 2.92 Impact Factor -
Article: Decreased serotonin 2A receptor densities in neuroleptic-naive patients with schizophrenia: A PET study using [(18)F]setoperone.
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ABSTRACT: The authors compared serotonin receptor binding in patients with schizophrenia and healthy comparison subjects. They used positron emission tomography with [(18)F]setoperone to examine six patients with schizophrenia who had never been given neuroleptics and seven age-matched subjects who did not have schizophrenia. A nondirected voxel-based analysis of the subjects' entire search volume found that serotonin 2A binding potential in the frontal cortex index was significantly smaller (by 16.3%) in patients with schizophrenia than in healthy subjects. The authors conclude that the decrease in serotonin receptor densities previously reported in postmortem studies of subjects with schizophrenia are present at the onset of the illness, before exposure to neuroleptics.American Journal of Psychiatry 07/2000; 157(6):1016-8. · 12.54 Impact Factor -
Article: A preliminary study of the effects of electroconvulsive therapy on regional brain glucose metabolism in patients with major depression.
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ABSTRACT: Animal studies have shown that a course of electroconvulsive shock (ECS) leads to a significant reduction in glucose metabolism in rat brains 1 day after the last ECS. In humans, of the two positron emission tomography (PET) studies that assessed the effects of a course of electroconvulsive therapy (ECT) on brain glucose metabolism in depressed patients, one reported no change while the other found a trend for reduction in glucose metabolism in frontal cortical region 24 hours after last ECT. The changes in glucose metabolism detected 24 hours after the last ECS/ECT treatment might simply be due to subacute effects of a seizure. We hypothesized that the changes in brain metabolism that persist 1 week after a course of ECT are more likely to underlie the therapeutic effects of ECT. We, therefore, investigated the effects of a course of ECT on brain glucose metabolism 1 week after last ECT by using PET and [18F]fluorodeoxyglucose (FDG). Six patients who met DSM-IV criteria for a diagnosis of major depressive disorder (unipolar), and were referred for ECT as the clinically indicated treatment were recruited. They underwent two PET scans, one prior to first ECT and the second a week after last ECT. The number of ECT treatments subjects received ranged from 8 to 12 with a mean of 11. Five out of six patients responded to the ECT treatment. Cerebral metabolic rates for glucose were slightly lower in most regions post treatment compared with pretreatment but the differences were not statistically significant. Similarly, there was no significant correlation between changes in regional cerebral metabolic rates for glucose (rCMRglc) and changes in Hamilton Depression Rating Scale (HAM-D 21-item) scores. Our results might suggest that rCMRglc rates are not altered 1 week after a therapeutic course of ECT in depressed patients. Further studies using new generation PET scanners, which have a higher resolution, in larger numbers of depressed patients, are clearly needed before firm conclusions can be drawn.Journal of Ect 07/2000; 16(2):171-6. · 1.54 Impact Factor -
Article: Serotonin in mania and in the mechanism of action of mood stabilizers: a review of clinical studies.
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ABSTRACT: Serotonin (5-hydroxytryptamine, 5-HT) was implicated in the pathophysiology of manic-depressive illness as early as 1958. Although extensive evidence has accumulated since then to support 5-HT's role in depression, relatively fewer studies examined its role in mania. The purpose of this paper was to review and summarize the current state of knowledge on the role of 5-HT in mania and its treatment. We systemically reviewed clinical studies of 1) 5-HT function in mania and 2) 5-HT in the mechanism of action of mood stabilizers, including lithium and anticonvulsants. Review showed that cerebrospinal fluid, postmortem, platelet, neuroendocrine challenge, and tryptophan depletion studies provided some evidence to support the hypothesis that a 5-HT deficit is involved in mania and that enhancement of 5-HT neurotransmission exerts a mood-stabilizing effect. There is some evidence from clinical studies for the contribution of 5-HT in mania and in the mechanism of action of mood stabilizers. However, it is very likely that other neurotransmitters also play important roles. Future directions for research include 1) in vivo study of 5-HT receptor subtypes using positron emission tomography, 2) investigation of the interaction between 5-HT and other neurotransmitter systems, and 3) determination of the relationships between diagnostic subtypes of mania and 5-HT function and other neurotransmitter systems.Bipolar Disorders 07/2000; 2(2):77-92. · 5.29 Impact Factor -
Article: Does the addition of pindolol accelerate the response to electroconvulsive therapy in patients with major depression? A double-blind, placebo-controlled pilot study.
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ABSTRACT: There is evidence that addition of pindolol, a beta-adrenergic/5-hydroxytryptamine-1A antagonist, can accelerate the onset of action of antidepressant medications. The purpose of this study was to determine whether pindolol administration can induce a rapid improvement in depressive symptoms in patients receiving electroconvulsive therapy (ECT) within six ECT treatments. A total of 20 patients with DSM-IV-diagnosed major depression who were undergoing a course of ECT as the clinically indicated treatment were recruited. They were neuroleptic, lithium, and antidepressant free for at least 1 week before the study. Of the 20 patients, 9 patients had been randomly assigned to receive pindolol 2.5 mg three times daily, and 11 patients received identical placebo three times daily for the duration of the first 6 ECT treatments. One of 9 patients in the pindolol group and 4 of 11 patients in the placebo group dropped out of the study. Using an outcome measure of a score < or =12 on the 29-item Hamilton Rating Scale for Depression (HAM-D), the authors found that four (50%) of eight patients responded to the combination treatment of ECT and pindolol within six ECT treatments. In contrast, none (0%) of seven patients who received placebo responded to ECT treatment. Furthermore, both mean 29-item HAM-D and Clinical Global Impression Scale scores after the sixth ECT treatment were significantly lower in patients treated with pindolol compared with those treated with placebo. However, the number of total ECT treatments within a course or the overall efficacy of ECT treatment was not altered by the addition of pindolol. The results of this study suggest that within six ECT treatments, pindolol administration hastens antidepressant effects of ECT in some depressed patients.Journal of Clinical Psychopharmacology 06/2000; 20(3):373-8. · 4.10 Impact Factor
Top co-authors
Top Journals
Institutions
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2012
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Universidade Federal do Rio Grande do Sul
Porto Alegre, Estado do Rio Grande do Sul, Brazil
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1995–2011
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University of British Columbia - Vancouver
- Department of Psychiatry
Vancouver, British Columbia, Canada
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2007
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Simon Fraser University
- Department of Psychology
Burnaby, British Columbia, Canada
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2004
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University of New South Wales
- School of Psychiatry
Kensington, New South Wales, Australia
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1997
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The University of Western Ontario
- Department of Psychiatry
London, Ontario, Canada -
University of Toronto
- Department of Psychiatry
Toronto, Ontario, Canada
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1995–1997
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Dalhousie University
- Department of Psychiatry
Halifax, Nova Scotia, Canada
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