Serge Beaulieu | McGill University (original) (raw)

Papers by Serge Beaulieu

Journal of Affective Disorders, 2019

Statins have recently been linked to having effects on cognition and mood in mood disorders, thou... more Statins have recently been linked to having effects on cognition and mood in mood disorders, though results are mixed. In this paper, we use data from a recent randomized controlled trial (RCT) to examine the effect of statins on cognition and mood in patients with Bipolar Disorder (BD) and Major Depressive Disorder (MDD). Methods: This is a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial (n = 60) originally designed to examine the effect of atorvastatin (n = 27) versus placebo (n = 33) for lithium-induced diabetes insipidus in BD and MDD patients who were using lithium. For this analysis, the primary outcome was global cognition Z-score at 12-weeks adjusted for baseline. The secondary cognition outcomes were (1) Screen for Cognitive Impairment in Psychiatry (SCIP), and (2) executive function Z-score. The primary mood outcome (secondary outcome of this analysis) was depression relapse during 12-week follow-up (Mongomery Asberg Depression Rating Scale (MADRS) ≥10). The secondary mood outcomes were (1) relapse rate into a manic episode, and (2) relapse rate into any mood episode. Results: After 12 weeks follow-up, atorvastatin and placebo groups did not differ in terms of global cognition Zscore (β = −0.009287 (−0.1698,0.1512), p-value = 0.91). Similarly, composite Z-scores for SCIP and executive functions did not differ significantly. Depression relapse during 12-week follow-up was not significantly different between the groups (χ 2 (1) = 0.148, p-value = 0.70). Similarly, there was no difference between groups regarding relapse into mania. Conclusion: In BD and MDD patients with lithium-induced nephrogenic diabetes insipidus randomized to atorvastatin or placebo, we found no significant differences in cognition and mood outcomes at 12-week follow-up.

Journal of Clinical Psychopharmacology, 2001

Bipolar Disorders, Oct 7, 2021

OBJECTIVES While clinical guidelines exist for the management of bipolar disorder (BD), there are... more OBJECTIVES While clinical guidelines exist for the management of bipolar disorder (BD), there are significant challenges to their widespread dissemination and implementation in clinical practice. The Canadian Network of Mood and Anxiety Treatment Improving Patient Care and Outcomes in the Treatment of Bipolar Disorder (C-IMPACT BD) web-based application was developed for use at the point-of-care to improve adherence to guidelines for evidence-based pharmacological management of BD. METHODS C-IMPACT BD uses a point-of-care practice assessment which, via adaptive questioning of patient-specific information, text/ video descriptions of the guidelines, and pop-up prompts delivers personalized, evidence-based treatment recommendations for patients with BD. In order to inform quality improvement of the newly developed tool, a sample of Canadian physicians were invited to use the application and record its influence on their prescribing behavior. RESULTS Of 375 patients with bipolar I (BD-I) or bipolar II (BD-II) disorder for whom a point- of- care practice assessment was completed, a change in therapy was considered for 225 (60.0%). Prior to completing the assessment, 59.6% of these patients were receiving first-line therapy recommended for their phase of illness. Following the assessment, the overall number of patients for whom a first-line recommended therapy was being considered increased significantly to 76.9% (p=0.0001). CONCLUSIONS Outcomes suggest that the C-IMPACT BD web-based application has the potential to improve physician adherence to clinical treatment guidelines. Formal research investigations are warranted to explore the impact of this tool on physician prescribing behavior and patient outcomes.

Molecular Endocrinology, Aug 1, 1988

We have verified the possibility that the POMC gene of the rat hypothalamus might be subject to r... more We have verified the possibility that the POMC gene of the rat hypothalamus might be subject to regulation by glucocorticoids. Adrenalectomy increased the concentration of POMC mRNA in anterior pituitary and in hypothalamus, but not in the neurointermediate lobe of the pituitary gland. Dexamethasone and, to a slightly lesser extent, corticosterone treatments reversed the adrenalectomy-induced increase in POMC mRNA concentrations in both anterior pituitary and hypothalamus. Dexamethasone caused a slight decrease of POMC mRNA levels in the neurointermediate lobe of the pituitary gland, while corticosterone had no effect. These results indicate that the POMC gene of the rat brain hypothalamus is also under negative control by glucocorticoids. (Molecular Endocrinology 2: 727-731, 1988) of the hypothalamus by ACTH and /3-end-containing terminals (14) and of the stimulatory role of opioid peptides in the control of the secretion of CRF (15). Recent immunohistochemical studies have also demonstrated the presence of glucocorticoid receptor immunoreactivity in numerous monoaminergic neurons including those of the arcuate nucleus (16). Finally, it is of primordial importance to gain a better understanding of the limbic-hypothalamic mechanisms regulating ACTH secretion, particularly in view of the ACTH and CRF hypersecretion observed in patients suffering from endogenous depressive illness (17-19) and of the abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa (20). Our results demonstrate a negative regulation of hypothalamic POMC gene expression by glucocorticoids.

Neuropsychopharmacology, Feb 4, 2022

Exogenous melatonergic agents are widely used to treat insomnia and sleep disturbance. Several st... more Exogenous melatonergic agents are widely used to treat insomnia and sleep disturbance. Several studies have shown that they might also modulate circadian rhythms. The purpose of this systematic review and meta-analysis was to summarize current knowledge about the effects of melatonin supplements and melatonin agonists on the sleep-wake cycle as well as on the circadian rhythm of melatonin in healthy participants and in patients with psychiatric disorders. The following electronic databases were searched: EMBASE, PubMed, Web of Science, CINAHL, and Cochrane Library. Of the 12,719 articles, we finally selected 30 studies including 1294 healthy participants and 8 studies including 687 patients with psychiatric disorders. Cochrane risk of bias tool was used to assess the risk of bias. Using meta-ANOVA, studies on healthy participants showed advancing effects of melatonergic supplements and agonists on sleep-wake cycle according to dosing time and dosage, despite the fact that the original individual melatonin rhythm was within a normal range (fixed effect model standardized mean difference [95% Confidence Interval] = −0.639 [−0.968 to −0.310]). In a limited number of randomized controlled trials with psychiatric patients, the findings seemed similar to those with healthy participants, despite the psychiatric disorders and treatment related factors affecting circadian rhythms. Given the unmet clinical need for evidence-based treatments to correct circadian rhythms in psychiatric disorders, efficacy of melatonergic agents seen in healthy participants, and similarity of findings among psychiatric patients, large scale, well-designed randomized controlled trials are needed to test efficacy on circadian parameters in psychiatric disorders.

Nutritional Neuroscience, Mar 15, 2019

Objective: We present novel dimensional methods to describe the timing of eating in psychopatholo... more Objective: We present novel dimensional methods to describe the timing of eating in psychopathology. We focused on the relationship between current mood in bipolar disorder (BD) and the stability of the temporal pattern of daily eating events. Methods: Consenting BD patients (n = 69) from an outpatient, tertiary care clinic completed hourly charts of mood and eating for two weeks. Mood was also evaluated with Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). Results: Illustrative displays, or eatograms, enabling visualization of all recorded eating events were used to guide assessment of the temporal structure of eating across the two week assessment period. We computed indices to quantify irregularities in timing of eating, namely I FRQ , I TIM and I INT for the variability of frequency, timing, and interval of eating events, respectively. In this cohort, irregular temporal pattern of eating correlated with hypomanic symptoms (YMRS with I FRQ , Spearman rank order rh = 0.28, p = .019, with I TIM , rh = 0.44, p < .001, and with I INT rh = 0.38, p = .001), but not depressive symptoms or anthropometric measures. Conclusions: Our data suggest a link between the instability of the temporal order of daily eating and mood. The dimensional measures for eating pattern introduced here enable future investigations of correlations with psychopathology.

Psychological Medicine, May 22, 2015

Background. Bipolar disorder type I (BD-I) is associated with emotion dysregulation. However, exp... more Background. Bipolar disorder type I (BD-I) is associated with emotion dysregulation. However, experimentally controlled studies of emotion regulation (ER), particularly those examining the brain correlates of the putative deficits, are scarce and their results inconsistent. Method. Nineteen euthymic BD-I patients and 17 healthy controls (HC) underwent functional magnetic resonance imaging while performing a visual ER 2 × 2 factorial task, with instruction (Look or Decrease) and valence (Negative or Neutral) as within-subject factors. Emotional ratings were collected after each picture presentation to assess regulation success. Results. BD-I patients were successful at downregulating their emotions, although to a lesser degree than HC. Both groups engaged brain regions previously implicated in ER; however, unlike HC, patients engaged some of those regions, particularly the ventrolateral prefrontal cortex (VLPFC) in the Negative Look and Neutral Decrease conditions. Moreover, patients failed to show the reduced amygdala activation in the Negative Decrease condition observed in HC. Conclusion. Our findings suggest that BD-I patients are able to downregulate their emotions when instructed to do so. However, they also appear to engage their ER network, particularly the VLPFC, even when not required to do so. These findings may help explain their often-reported difficulty in regulating emotions in everyday life despite their attempts to do so.

Acta Neuropsychiatrica, 2009

The Society for Neuroscience Abstracts, Mar 24, 1985

International Journal of Bipolar Disorders, Mar 25, 2023

Background Bipolar disorder type-I (BD-I) patients are known to show emotion regulation abnormali... more Background Bipolar disorder type-I (BD-I) patients are known to show emotion regulation abnormalities. In a previous fMRI study using an explicit emotion regulation paradigm, we compared responses from 19 BD-I patients and 17 matched healthy controls (HC). A standard general linear model-based univariate analysis revealed that BD patients showed increased activations in inferior frontal gyrus when instructed to decrease their emotional response as elicited by neutral images. We implemented multivariate pattern recognition analyses on the same data to examine if we could classify conditions within-group as well as HC versus BD. Methods We reanalyzed explicit emotion regulation data using a multivariate pattern recognition approach, as implemented in PRONTO software. The original experimental paradigm consisted of a full 2 × 2 factorial design, with valence (Negative/Neutral) and instruction (Look/Decrease) as within subject factors. Results The multivariate models were able to accurately classify different task conditions when HC and BD were analyzed separately (63.24%-75.00%, p = 0.001-0.012). In addition, the models were able to correctly classify HC versus BD with significant accuracy in conditions where subjects were instructed to downregulate their felt emotion (59.60%-60.84%, p = 0.014-0.018). The results for HC versus BD classification demonstrated contributions from the salience network, several occipital and frontal regions, inferior parietal lobes, as well as other cortical regions, to achieve above-chance classifications. Conclusions Our multivariate analysis successfully reproduced some of the main results obtained in the previous univariate analysis, confirming that these findings are not dependent on the analysis approach. In particular, both types of analyses suggest that there is a significant difference of neural patterns between conditions within each subject group. The multivariate approach also revealed that reappraisal conditions provide the most informative activity for differentiating HC versus BD, irrespective of emotional valence (negative or neutral). The current results illustrate the importance of investigating the cognitive control of emotion in BD. We also propose a set of candidate regions for further study of emotional control in BD.

http://isrctn.com/, Jul 22, 2020

Very little is known about treatment-resistant depression and studies researching this increasing... more Very little is known about treatment-resistant depression and studies researching this increasing clinical reality are quite new to the field (Rush, Thase, & Dube, 2003a). The World Health Organization (Greden, 2001) has predicted that unipolar depression alone will be the second most important contributor to disability by the year 2020 worldwide. The epidemiology of treatment-resistant depression however is not well known and varies according to the population studied (primary care, general population or secondary care), and most of all, according to the definition used. Numerous patients (up to 15%) remain very depressed, even after multiple interventions with aggressive pharmacological and psychotherapeutic treatments (Berlim & Turecki, 2007a). Only about 20% to 40% of patients receiving their first treatment for a major depressive episode are expected to achieve a relatively asymptomatic state (Sackeim, 2001). Even then, there is often a lag until a full recovery of social and occupational functioning is achieved (Sackeim, 2001). Other authors report a 50% response (i.e. have a > or equal 50% reduction in baseline symptom severity) rate for outpatients with nonpsychotic major depressive disorder (MDD) initially treated with either a time-limited depressiontargeted psychotherapy or a single antidepressant medication (Rush et al., 2004). Another 20% to 40% of patients in a major depressive episode (unipolar or bipolar) do not show substantial clinical improvement to the first treatment with antidepressant medication, with improvement defined as at least a 50% reduction in symptom scores (Sackeim, 2001), or they respond but have residual symptoms, therefore do not remit (Rush et al., 2004). About half of the patients who show symptom reduction have significant residual symptoms that are associated with continued functional disability and a worse prognosis (Fava, Ruini, & Belaise, 2007; Rush et al., 2004). It is common to find that patients who respond with or without remission can continue to experience residual attenuated depressive symptoms and even symptoms not usually considered among the core symptoms of depression. These may include irritability, problems with depressive thinking, and problems with functioning socially at work (Fava et al., 2007). Some residual attenuated depressive symptoms may include insomnia, fatigue, anxiety, excessive reactivity to social stress and mild dysphoria. Patients may take time before

Bipolar Disorders, Sep 1, 2009

Objectives: Safety monitoring is an important aspect of bipolar disorder treatment, as mood‐stab... more Objectives: Safety monitoring is an important aspect of bipolar disorder treatment, as mood‐stabilising medications have potentially serious side effects, some of which may also aggravate existing medical comorbidities. This paper sets out the International Society for Bipolar Disorders (ISBD) guidelines for the safety monitoring of widely used agents in the treatment of bipolar disorder. These guidelines aim to provide recommendations that take into consideration the balance between safety and cost‐effectiveness, to highlight iatrogenic and preventive clinical issues, and to facilitate the broad implementation of therapeutic safety monitoring as a standard component of treatment for bipolar disorder.Methods: These guidelines were developed by an ISBD workgroup, headed by the senior author (MB), through an iterative process of serial consensus‐based revisions. After this, feedback from a multidisciplinary group of health professionals on the applicability of these guidelines was sought to develop the final recommendations.Results: General safety monitoring recommendations for all bipolar disorder patients receiving treatment and specific monitoring recommendations for individual agents are outlined.Conclusions: These guidelines are derived from evolving and often indirect data, with minimal empirical cost‐effectiveness data available to provide guidance. These guidelines will therefore need to be modified to adapt to different clinical settings and health resources. Clinical acumen and vigilance remain critical ingredients for safe treatment practice.

BMC Psychiatry, Nov 10, 2021

Background: Bipolar disorders (BD) are associated with increased prevalence of obesity and metabo... more Background: Bipolar disorders (BD) are associated with increased prevalence of obesity and metabolic syndrome (MetS). Nevertheless, there is a wide range in prevalence estimates, with little known about the contributions of pharmacotherapy. It has been suggested that lithium might have a more favorable metabolic profile. We hypothesized that lithium use is associated with less increased body mass index (BMI), MetS, and type II diabetes, when compared with non-lithium users (those on anticonvulsants, second-generation antipsychotics). Methods: Cross-sectional study of 129 patients aged 18-85 with bipolar disorder, followed at tertiary care clinics in Montreal. Patients using lithium were compared with those not on lithium, for body mass index and metabolic syndrome. Results: The prevalence of obesity and metabolic syndrome in the sample of lithium-using patients with BD was 42.4 and 35.7% respectively, with an average BMI of 29.10 (+/− 6.70). Lithium and non-lithium groups did not differ in BMI or prevalence of MetS. However, compared to the non-lithium group, lithium users had lower hemoglobin A1C (5.24 +/− 0.53 versus 6.01 +/− 1.83, U = 753.5, p = 0.006) and lower triglycerides (1.46 +/− 0.88 versus 2.01 +/− 1.25, U = 947, p = 0.020). Conclusions: There is a high prevalence of obesity and metabolic syndrome among patients with bipolar disorder. However, this did not appear to be associated with lithium use, when compared to those not on lithium. The lithium subgroup was also associated with lower prevalence of type II diabetes. Future prospective and intervention studies with larger sample sizes are necessary to further explore the association between lithium and insulin resistance, as well as its underlying mechanisms.

Neuroendocrinology, 1987

Bilateral lesions of the amygdaloid central nucleus (ACE) significantly diminished the secretion ... more Bilateral lesions of the amygdaloid central nucleus (ACE) significantly diminished the secretion of ACTH in response to immobilization stress. Stress is associated with increased noradrenergic activity in the ACE and in the anterior and lateral hypothalamic areas. In comparison with intact stressed animals, lesion of the ACE reduced the noradrenergic activity in response to stress within the anterior and lateral hypothalamic areas, the arcuate and paraventricular nuclei of the hypothalamus and the bed nucleus of the stria terminalis. These results support the hypothesis of a stimulatory role for the noradrenergic system in the ACE on ACTH secretion. Stress decreased dopaminergic activity in the ACE, the cortical nucleus of the amygdala, the dorsomedial and ventromedial nuclei of the hypothalamus and the ventral tegmental area. In comparison with intact stressed rats, lesion of the ACE reduced dopaminergic activity in the anterior and lateral hypothalamic areas. Our results support the hypothesis of an inhibitory role of the dopaminergic system, particularly in the ACE, on ACTH secretion. This study also indicates that, in the control of ACTH secretion in response to immobilization stress, the noradrenergic and dopaminergic systems act in opposition to one another in certain brain structures such as the anterior and lateral hypothalamic areas and the ACE.

Bipolar Disorders, Mar 1, 2018

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Pharmacopsychiatry, 2009

Excessive body weight gain (BWG), hyperglycemia and dyslipidemia are important side effects of ol... more Excessive body weight gain (BWG), hyperglycemia and dyslipidemia are important side effects of olanzapine. We assessed the effects of rosiglitazone on BWG, the insulin resistance index (HOMA-IR), lipids, glycated hemoglobin and fibrinogen in olanzapine-treated schizophrenia patients. Thirty patients taking olanzapine (10-20 mg daily for 8 months) were randomly allocated to rosiglitazone (n=15; 4 to 8 mg daily) or placebo (n=15) in a 12-week double-blind protocol. Anthropometric and biochemical variables were evaluated at baseline, weeks 6 and 12. The rosiglitazone and placebo groups gained 3.2+/-4.5 and 2.2+/-2.3 kg, respectively (p=0.65). Insulin and the HOMA-IR significantly decreased after rosiglitazone (p<0.05). Rosiglitazone did not improve the lipid profile, fibrinogen and Hb1c levels. The positive impact of rosiglitazone was limited to improved glycemic control. It cannot be recommended for metabolic control during olanzapine treatment.

The British Journal of Psychiatry, 2001

Yuste,R. & Bonhoeffer,T. (2001) Morphologicalchanges Morphologicalchanges in dendritic spines ass... more Yuste,R. & Bonhoeffer,T. (2001) Morphologicalchanges Morphologicalchanges in dendritic spines associated withlong-term synaptic in dendritic spines associated withlong-term synaptic plasticity. plasticity. Annual Review of Neuroscience Annual Review of Neuroscience, , 24 24,1071^1089. ,1071^1089.