Bipolar Disorder: MacQueen G

Yatham LN, Kennedy SH, O'Donovan C, Parikh SV, MacQueen G, McIntyre RS, Sharma V, Beaulieu S, Anonymous00162. · Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada. · Bipolar Disord. · Pubmed #17156158 No free full text.

Abstract: In 2005, the Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder. This update reviews new evidence since the previous publication and incorporates recommendations based on the most current evidence for treatment of various phases of bipolar disorder. It is designed to be used in conjunction with the 2005 CANMAT Guidelines. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate and several atypical antipsychotics continue to be recommended as first-line treatments for acute mania. For the management of bipolar depression, new data support quetiapine monotherapy as a first-line option. Lithium and lamotrigine monotherapy, olanzapine plus selective serotonin reuptake inhibitors (SSRI), and lithium or divalproex plus SSRI/bupropion continue to remain the other first-line options. First-line options in the maintenance treatment of bipolar disorder continue to be lithium, lamotrigine, valproate and olanzapine. There is recent evidence to support the combination of olanzapine and fluoxetine as a second-line maintenance therapy for bipolar depression. New data also support quetiapine monotherapy as a second-line option for the management of acute bipolar II depression. The importance of comorbid psychiatric and medical conditions cannot be understated, and this update provides an expanded look at the prevalence, impact and management of comorbid conditions in patients with bipolar disorder.

Yatham LN, Kennedy SH, O'Donovan C, Parikh S, MacQueen G, McIntyre R, Sharma V, Silverstone P, Alda M, Baruch P, Beaulieu S, Daigneault A, Milev R, Young LT, Ravindran A, Schaffer A, Connolly M, Gorman CP, Anonymous00076. · Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. · Bipolar Disord. · Pubmed #15952957 No free full text.

Abstract: Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.

MacQueen G, Joffe RT. · No affiliation provided · Acta Psychiatr Scand. · Pubmed #14725586 No free full text.

This publication has no abstract.

Taylor V, MacQueen G. · Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada. · J Clin Psychiatry. · Pubmed #16889445 No free full text.

Abstract: OBJECTIVES: To examine the pathophysiologic mechanisms that may link bipolar disorder and metabolic syndrome and to discuss whether the consequences of metabolic syndrome underlie a substantive portion of the premature morbidity and mortality observed in persons with bipolar disorder. DATA SOURCES: A MEDLINE search, citing articles from 1966 onward, supplemented by a review of bibliographies, was conducted to identify relevant studies. Bipolar disorder, mood disorder, metabolic syndrome, diabetes, cardiovascular illness, and obesity were used as keywords. Criteria used to select studies included (1) English language, (2) published studies with original data in peer-reviewed journals, and (3) studies that confirmed the nature of the mood disorder examined. RESULTS: Ninety-seven studies met criteria and were reviewed for evidence of dysregulation in various physiologic systems. Bipolar disorder and metabolic syndrome share features of hormonal, immunologic, and autonomic nervous system dysregulation. CONCLUSION: Lifestyle features may account, in part, for the premature mortality observed in bipolar disorder, but the somatic correlates of the illness may also predispose patients to metabolic syndrome and the consequent increased risk of diseases such as diabetes and vascular disease.

Campbell S, MacQueen G. · McMaster University Medical Centre, Hamilton, Ontario, Canada. · Curr Opin Psychiatry. · Pubmed #16612175 No free full text.

Abstract: PURPOSE OF REVIEW: Structural brain changes are apparent in some magnetic resonance imaging studies of patients with mood disorders, but results are inconsistent. The focus of this review is to examine whether there are demographic or clinical characteristics of people with mood disorders that are associated with regional brain volume changes. A systematic search of the literature in English, from January 2004 to July 2005, was performed on MEDLINE. References cited in all reports were searched iteratively to identify missing studies. RECENT FINDINGS: Recent studies have focused on factors that might help to reconcile the divergent reports of regional brain volume changes in major depressive disorder and bipolar disorder. Small hippocampal volumes are apparent in patients with recurrent major depressive disorder, but not generally reported early in the course of adult onset depression. Small hippocampal volumes may be apparent in patients with childhood onset illness. Small hippocampal volumes are infrequently reported in bipolar disorder, but studies to date have not accounted for illness history or treatment status. Changes in amygdala volumes are inconsistently reported in patients with major depressive disorder or bipolar disorder. There are relatively fewer reports of other brain regions, including the areas of the frontal cortex and striatum. An extensive preclinical literature suggests that various psychotropic medications may have neurotrophic and neuroprotective effects, making documentation of treatment history essential. SUMMARY: Patients' age, sex, age at onset of disease, course of illness and treatment status may affect the detection of regional brain volume changes in people with mood disorders.

Yatham LN, Kennedy SH, Schaffer A, Parikh SV, Beaulieu S, O'Donovan C, MacQueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Young AH, Alda M, Milev R, Vieta E, Calabrese JR, Berk M, Ha K, Kapczinski F. · Department of Psychiatry, University of British Columbia,2255 Wesbrook Mall, Vancouver, BC V6T 2A1, , Canada. · Bipolar Disord. · Pubmed #19419382 No free full text.

Abstract: The Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder in 2005, with a 2007 update. This second update, in conjunction with the International Society for Bipolar Disorders (ISBD), reviews new evidence and is designed to be used in conjunction with the previous publications. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate, and several atypical antipsychotics continue to be first-line treatments for acute mania. Tamoxifen is now suggested as a third-line augmentation option. The combination of olanzapine and carbamazepine is not recommended. For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. New data support the use of adjunctive modafinil as a second-line option, but also indicate that aripiprazole should not be used as monotherapy for bipolar depression. Lithium, lamotrigine, valproate, and olanzapine continue to be first-line options for maintenance treatment of bipolar disorder. New data support the use of quetiapine monotherapy and adjunctive therapy for the prevention of manic and depressive events, aripiprazole monotherapy for the prevention of manic events, and risperidone long-acting injection monotherapy and adjunctive therapy, and adjunctive ziprasidone for the prevention of mood events. Bipolar II disorder is frequently overlooked in treatment guidelines, but has an important clinical impact on patients' lives. This update provides an expanded look at bipolar II disorder.

Duffy A, Hajek T, Alda M, Grof P, Milin R, MacQueen G. · Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #19390766 No free full text.

Abstract: INTRODUCTION: Cognitive deficits, including deficits in early information processing, are associated with remitted bipolar disorder. The temporal relationship between these deficits and the clinical course is not known. The current study investigated whether or not deficits in early information processing were present before the onset and/or during the early stages of bipolar disorder. METHODS: Unaffected and remitted high risk offspring of well-characterized bipolar parents completed a visual backward masking task. For comparison we included a cohort of unaffected offspring of well parents and a clinically referred group of remitted bipolar patients. RESULTS: There was no evidence of a deficit in early information processing in well high risk subjects. As expected, the referred patient group had the highest error rates. After excluding the patients, interaction effect showed that the affected remitted high risk subjects performed differently in terms of error rates than unaffected high risk and control subjects. There were no significant differences in response times across study groups. Exploratory analyses revealed an association between a lifetime history of psychosis and increased errors on the task. CONCLUSIONS: There was no evidence of a vulnerability in early information processing in offspring at risk for bipolar disorder. However, there were emergent changes in performance in the affected remitted high risk group. Psychosis appears to be an important clinical correlate associated with cognitive deficits. Mapping of the early course of bipolar disorder and associated changes in cognition has important implications for establishing critical periods for intervention.

Hajek T, Gunde E, Slaney C, Propper L, MacQueen G, Duffy A, Alda M. · Department of Psychiatry, Dalhousie University, 5909 Veteran's Memorial Lane, Halifax, Canada. · J Psychiatr Res. · Pubmed #19046588 No free full text.

Abstract: BACKGROUND: Striatal volume changes reported in bipolar disorders could represent artifacts of medication or comorbid conditions, or illness related changes, either biological predispositions or consequences of illness burden. We conducted volumetric high-risk study to investigate whether striatal volume changes represent primary biological risk factor for bipolar disorders. METHODS: High-risk (HR) participants (age range 15-30 years) were recruited from families multiply affected with bipolar disorders. They included 20 affected and 26 unaffected offspring of parents with primary mood disorders, matched by age and sex with 31 controls without a personal or family history of psychiatric disorders. Striatal volumes were measured on 1.5T 3D anatomical MRI images using standard methods. RESULTS: There was a significant difference between groups (affected, unaffected HR and control subjects) in caudate volumes (F=3.50, DF=2; 74 and p=0.04) in absence of putamen volume changes. The caudate volumes were largest in unaffected HR subjects without differences between affected and control or affected and unaffected HR subjects. The maximum changes were found in the head of the caudate. Controlling for non-independence of observations in multiple subjects per family yielded non-significant differences. CONCLUSIONS: Despite the biological plausibility, partial agreement with previous studies and nominal statistical significance, controlling for non-independence of observations within families changed the increased caudate volumes among unaffected subjects to non-significant. We thus present these findings as negative, pending further replication. Striatal volume abnormalities did not meet criteria for endophenotype in this study.

Hajek T, Bernier D, Slaney C, Propper L, Schmidt M, Carrey N, MacQueen G, Duffy A, Alda M. · Department of Psychiatry, Dalhousie University, Halifax, NS. · J Psychiatry Neurosci. · Pubmed #18982176 links to  free full text

Abstract: OBJECTIVE: Bipolar disorders have a strong genetic underpinning. Little is known about biological predispositions that convey vulnerability for the illness. We searched for biological vulnerability markers using proton magnetic resonance spectroscopy (MRS) in both affected and unaffected participants at high genetic risk for bipolar disorder. METHODS: We recruited high-risk participants aged 15-30 years from families in which multiple members were affected with bipolar disorder. Our primary sample included 14 affected and 15 unaffected relatives of probands with bipolar I disorder. Our extended sample comprised 19 affected and 21 unaffected participants with a family history of either bipolar I or bipolar II disorders. We matched both samples by age and sex with 31 control participants without a personal or family history of psychiatric disorders. We performed single voxel proton MRS at 1.5 T in bilateral dorsal and ventral medial prefrontal cortices with correction for grey matter proportion. RESULTS: We found comparable levels of choline, creatine, myo-inositol and N-acetylaspartate among the groups in both samples. There were no differences between regions of the medial prefrontal cortex or between hemispheres for any of the metabolites in any of the samples. The exclusion of 5 participants taking medication did not change our results. CONCLUSION: Neurochemical changes in the medial prefrontal cortex that are measurable using proton MRS do not appear to be antecedent to the onset of mood disorders in genetically susceptible individuals.

MacQueen G, Parkin C, Marriott M, Bégin H, Hasey G. · Mood Disorder Program, St. Joseph's Healthcare, McMaster University, Hamilton, Ont. · J Psychiatry Neurosci. · Pubmed #17653292 links to  free full text

Abstract: OBJECTIVE: Electroconvulsive therapy (ECT) has been controversially associated with long-lasting memory problems. Verbal learning and memory deficits are commonly reported in studies of people with bipolar disorder (BD). Whether memory deficits can be exacerbated in patients with BD who receive ECT has, to our knowledge, not been systematically examined. We aimed to examine whether long-term effects of ECT on discrete memory systems could be detected in patients with BD. METHODS: We studied several domains of memory in 3 groups of subjects who were matched for age and sex: a group of healthy comparison subjects, a group of people with BD who had received ECT at least 6 months before memory assessment and another group with BD that had an equal past illness burden but had never received ECT. Memory was assessed with the California Verbal Learning Test, the Continuous Visual Memory Test and a computerized process dissociation task that examines recollection and habit memory in a single paradigm. RESULTS: Compared with healthy subjects, patients had verbal learning and memory deficits. Subjects who had received remote ECT had further impairment on a variety of learning and memory tests when compared with patients with no past ECT. This degree of impairment could not be accounted for by illness state at the time of assessment or by differential past illness burden between patient groups. CONCLUSIONS: From a clinical perspective, it is unlikely that such findings, even if confirmed, would significantly change the risk-benefit ratio of this notably effective treatment. Nonetheless, they may highlight the importance of attending to cognitive factors in patients with BD who are about to receive ECT; further, they raise the question of whether certain strategies that minimize cognitive dysfunction with ECT should be routinely employed in this patient group.

Dowlatshahi D, MacQueen G, Wang JF, Chen B, Young LT. · Department of Psychiatry and Behavioural Neurosciences, MacMaster University, Hamilton, ON, Canada. · Neuroreport. · Pubmed #11117489 No free full text.

Abstract: Biochemical and structural abnormalities have been reported in hippocampus of subjects with mood disorders. This study examined the organization of mossy fibers in anterior hippocampus of subjects obtained from the Stanley Neuropathology Consortium. Frozen postmortem hippocampal sections from subjects with major depression, bipolar disorder, schizophrenia and non-psychiatric controls were stained using the Neo-Timm procedure, which selectively stains mossy fibers. Increased Timm staining in the supragranular layer was found in subjects with bipolar disorder relative to control subjects. These results are suggestive of neuronal sprouting in hippocampus of subjects with bipolar disorder. There were no significant associations between supragranular Timm staining and suicide, length illness or drug treatment at the time of death.

Bown C, Wang JF, MacQueen G, Young LT. · Mood Disorders Program, McMaster University, Hamilton, Ontario, Canada. · Neuropsychopharmacology. · Pubmed #10693161 links to  free full text

Abstract: Regulation of ER stress proteins, such as the 78-kilodalton glucose regulated protein (GRP78) by chronic treatment with mood stabilizing drugs suggests that this family of proteins may be involved in the pathophysiology of mood disorders. Indeed, increased levels of GRP78, GRP94, and calreticulin, a third member of the ER stress protein family, were found in temporal cortex of subjects with major depressive disorder who died by suicide compared with controls and subjects who died by other means. No such differences were found in subjects with other psychiatric disorders such as bipolar disorder or schizophrenia. These data suggest a potential role for ER stress proteins in severe depression that merits further study.