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Dost Ongur - One of the best experts on this subject based on the ideXlab platform.
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diverse pathophysiological processes converge on network disruption in mania
Journal of Affective Disorders, 2019Co-Authors: Ivy Lee, Kathryn Nielsen, Uzma Nawaz, Meihua Hall, Dost OngurAbstract:Abstract Background Neuroimaging of psychiatric disease is challenged by the difficulty of establishing the causal role of neuroimaging abnormalities. Lesions that cause mania present a unique opportunity to understand how brain network disruption may cause mania in both lesions and in bipolar disorder. Methods A literature search revealed 23 case reports with imaged lesions that caused mania in patients without history of bipolar disorder. We traced these lesions and examined resting-state functional Magnetic Resonance Imaging (rsfMRI) connectivity to these lesions and control lesions to find networks that would be disrupted specifically by mania-causing lesions. The results were then used as regions-of-interest to examine rsfMRI connectivity in patients with bipolar disorder (n = 16) who underwent imaging longitudinally across states of both mania and euthymia alongside a cohort of healthy participants scanned longitudinally. We then sought to replicate these results in independent cohorts of manic (n = 26) and euthymic (n = 21) participants with bipolar disorder. Results Mania-inducing lesions overlap significantly in network connectivity. Mania-causing lesions selectively disrupt networks that include orbitofrontal cortex, dorsolateral prefrontal cortex, and temporal lobes. In bipolar disorder, the manic state was reflected in strong, significant, and specific disruption in network communication between these regions and regions implicated in bipolar pathophysiology: the amygdala and ventro-lateral prefrontal cortex. Limitations There was heterogeneity in the clinical characterization of mania causing lesions. Conclusions Lesions causing mania demonstrate shared and specific network disruptions. These disruptions are also observed in bipolar mania and suggest a convergence of multiple disorders on shared circuit dysfunction to cause mania.
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diverse pathophysiological processes converge on network disruption in mania
bioRxiv, 2018Co-Authors: Ivy Lee, Kathryn Nielsen, Meihua Hall, Dost Ongur, Matcheri S KeshavanAbstract:Background: Neuroimaging of psychiatric disease is challenged by the difficulty of establishing the causal role of neuroimaging abnormalities. Lesions that cause mania present a unique opportunity to understand how brain network disruption may cause mania in both lesions and in bipolar disorder. Methods: A literature search revealed 23 case reports with imaged lesions that caused mania in patients without history of bipolar disorder. We traced these lesions and examined resting-state functional Magnetic Resonance Imaging (rsfMRI) connectivity to these lesions and control lesions to find networks that would be disrupted specifically by mania-causing lesions. The results were then used as regions-of-interest to examine rsfMRI connectivity in patients with bipolar disorder (n=16) who underwent imaging longitudinally across states of both mania and euthymia alongside a cohort of healthy participants scanned longitudinally. We then sought to replicate these results in independent cohorts of manic (n=26) and euthymic (n=21) participants with bipolar disorder. Results: Mania-inducing lesions overlap significantly in network connectivity. Mania-causing lesions selectively disrupt networks that include orbitofrontal cortex, dorsolateral prefrontal cortex, and temporal lobes. In bipolar disorder, the manic state was reflected in strong, significant, and specific disruption in network communication between these regions and regions implicated in bipolar pathophysiology: the amygdala and ventro-lateral prefrontal cortex. Limitations: The was heterogeneity in the clinical characterization of mania causing lesions. Conclusions: Lesions causing mania demonstrate shared and specific network disruptions. These disruptions are also observed in bipolar mania and suggest a convergence of multiple disorders on shared circuit dysfunction to cause mania.
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bipolar mood state reflected in cortico amygdala resting state connectivity a cohort and longitudinal study
Journal of Affective Disorders, 2017Co-Authors: Roscoe O Brady, Matcheri S Keshavan, Allison Margolis, Grace A Masters, Dost OngurAbstract:Abstract Background Using resting-state functional magnetic resonance imaging (rsfMRI), we previously compared cohorts of bipolar I subjects in a manic state to those in a euthymic state to identify mood state-specific patterns of cortico-amygdala connectivity. Our results suggested that mania is reflected in the disruption of emotion regulation circuits. We sought to replicate this finding in a group of subjects with bipolar disorder imaged longitudinally across states of mania and euthymia Methods We divided our subjects into three groups: 26 subjects imaged in a manic state, 21 subjects imaged in a euthymic state, and 10 subjects imaged longitudinally across both mood states. We measured differences in amygdala connectivity between the mania and euthymia cohorts. We then used these regions of altered connectivity to examine connectivity in the longitudinal bipolar group using a within-subjects design. Results Our findings in the mania vs euthymia cohort comparison were replicated in the longitudinal analysis. Bipolar mania was differentiated from euthymia by decreased connectivity between the amygdala and pre-genual anterior cingulate cortex. Mania was also characterized by increased connectivity between amygdala and the supplemental motor area, a region normally anti-correlated to the amygdala in emotion regulation tasks. Limitations Stringent controls for movement effects limited the number of subjects in the longitudinal sample. Conclusions In this first report of rsfMRI conducted longitudinally across mood states, we find that previously observed between-group differences in amygdala connectivity are also found longitudinally within subjects. These results suggest resting state cortico-amygdala connectivity is a biomarker of mood state in bipolar disorder.
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antimanic treatment with tamoxifen affects brain chemistry a double blind placebo controlled proton magnetic resonance spectroscopy study
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2016Co-Authors: Bruce M. Cohen, Dost Ongur, Aysegul Yildiz, Burc Aydin, Necati Gokmen, Aysegul Yurt, Pembe Keskinoglu, Perry F RenshawAbstract:Abstract Background The antimanic efficacy of a protein kinase C inhibitor, tamoxifen, has been tested in several clinical trials, all reporting positive results. However, mechanisms underlying the observed clinical effects require further confirmation through studies of biological markers. Methods We investigated the effect of tamoxifen versus placebo on brain metabolites via a proton magnetic resonance spectroscopy study. Scanning was performed in 48 adult manic patients with bipolar disorder type I (mean Young Mania Rating Scale score of 37.8 ± 5.8) at baseline and after 3 weeks of double-blind treatment. We hypothesized that alleviation of manic symptoms would improve the levels of markers associated with brain energy metabolism (creatine plus phosphocreatine [total creatine (tCr)]) and neuronal viability ( N -acetylaspartate). Results The Young Mania Rating Scale scores decreased from 38.6 ± 4.5 to 20.0 ± 11.1 in the tamoxifen group and increased from 37.0 ± 6.8 to 43.1 ± 7.8 in the placebo group ( p p = .027). A significant correlation between the Young Mania Rating Scale score change and tCr percent change was observed in the whole group (Spearman rho = .341, p = .029). Levels of both tCr and N -acetylaspartate in the responder group were increased by 9.4% ± 15.2% and 6.1% ± 11.7%, respectively, whereas levels in the nonresponder group were decreased by 2.1% ± 13.2% and 6.5%± 10.5%, respectively ( p Conclusions Tamoxifen effectively treated mania while increasing brain tCr levels, consistent with involvement of both excessive protein kinase C activation and impaired brain energy metabolism in the development of bipolar manic states.
Tiaolai Huang - One of the best experts on this subject based on the ideXlab platform.
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thiobarbituric acid reactive substances tbars is a state biomarker of oxidative stress in bipolar patients in a manic phase
Journal of Affective Disorders, 2015Co-Authors: Mengchang Tsai, Tiaolai HuangAbstract:Abstract Objectives Oxidative stress may contribute to the pathophysiology of bipolar disorder. The aim of this study was to investigate the serum levels or activities of oxidative stress markers in bipolar patients in a manic phase, and evaluate the changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC) and 8-hydroxy 2′-deoxyguanosine after treatment (8-OHdG). Methods We consecutively enrolled 23 bipolar inpatients in a manic phase and 40 healthy subjects. Serum oxidative stress markers were measured with assay kits. All patients were evaluated by examining the correlation between oxidative stress markers and Young Mania Rating Scale (YMRS) scores. Results The serum TBARS levels in bipolar patients in a manic phase were significantly higher than those of healthy subjects (p=0.006), and serum GPx activity was significant lower than that of healthy subjects (p Limitation Our sample size was limited. Conclusion Our results suggest that serum TBARS levels might be a state biomarker of oxidative stress in bipolar patients in a manic phase and after treatment. In addition, GPx deficit might be a trait biomarker of severity of mania.
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thiobarbituric acid reactive substances tbars is a state biomarker of oxidative stress in bipolar patients in a manic phase
Journal of Affective Disorders, 2015Co-Authors: Mengchang Tsai, Tiaolai HuangAbstract:OBJECTIVES: Oxidative stress may contribute to the pathophysiology of bipolar disorder. The aim of this study was to investigate the serum levels or activities of oxidative stress markers in bipolar patients in a manic phase, and evaluate the changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC) and 8-hydroxy 2'-deoxyguanosine after treatment (8-OHdG). METHODS: We consecutively enrolled 23 bipolar inpatients in a manic phase and 40 healthy subjects. Serum oxidative stress markers were measured with assay kits. All patients were evaluated by examining the correlation between oxidative stress markers and Young Mania Rating Scale (YMRS) scores. RESULTS: The serum TBARS levels in bipolar patients in a manic phase were significantly higher than those of healthy subjects (p=0.006), and serum GPx activity was significant lower than that of healthy subjects (p<0.05). The YMRS scores had a significantly positive association with CAT activity and PCC levels (p<0.05) and a negative association with GPx activity (p<0.05). Twenty bipolar patients were followed up, and their oxidative stress markers were measured at the end of treatment. We found significantly decreased changes in TBARS levels only in bipolar manic patients after treatment (p=0.019). LIMITATION: Our sample size was limited. CONCLUSION: Our results suggest that serum TBARS levels might be a state biomarker of oxidative stress in bipolar patients in a manic phase and after treatment. In addition, GPx deficit might be a trait biomarker of severity of mania.
Lori L Altshuler - One of the best experts on this subject based on the ideXlab platform.
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blunted activation in orbitofrontal cortex during mania a functional magnetic resonance imaging study
Biological Psychiatry, 2005Co-Authors: Jim Mintz, Lori L Altshuler, Susan Y Bookheimer, Jennifer Townsend, Manuel A Proenza, Naomi I Eisenberger, Fred W Sabb, Mark S CohenAbstract:Background Patients with bipolar disorder have been reported to have abnormal cortical function during mania. In this study, we sought to investigate neural activity in the frontal lobe during mania, using functional magnetic resonance imaging (fMRI). Specifically, we sought to evaluate activation in the lateral orbitofrontal cortex, a brain region that is normally activated during activities that require response inhibition. Methods Eleven manic subjects and 13 control subjects underwent fMRI while performing the Go-NoGo task, a neuropsychological paradigm known to activate the orbitofrontal cortex in normal subjects. Patterns of whole-brain activation during fMRI scanning were determined with statistical parametric mapping. Contrasts were made for each subject for the NoGo minus Go conditions. Contrasts were used in a second-level analysis with subject as a random factor. Results Functional MRI data revealed robust activation of the right orbitofrontal cortex (Brodmann’s area [BA] 47) in control subjects but not in manic subjects. Random-effects analyses demonstrated significantly less magnitude in signal intensity in the right lateral orbitofrontal cortex (BA 47), right hippocampus, and left cingulate (BA 24) in manic compared with control subjects. Conclusions Mania is associated with a significant attenuation of task-related activation of right lateral orbitofrontal function. This lack of activation of a brain region that is usually involved in suppression of responses might account for some of the disinhibition seen in mania. In addition, hippocampal and cingulate activation seem to be decreased. The relationship between this reduced function and the symptoms of mania remain to be further explored.
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olanzapine versus divalproex in the treatment of acute mania
American Journal of Psychiatry, 2002Co-Authors: Robert W Baker, Lori L Altshuler, Carlos A Zarate, Trisha Suppes, Terrence A Ketter, Denai R Milton, R C Risser, J A Gilmore, Alan BreierAbstract:OBJECTIVE: The effects of olanzapine and divalproex for the treatment of mania were compared in a large randomized clinical trial. METHOD: A 3-week, randomized, double-blind trial compared flexibly dosed olanzapine (5–20 mg/day) to divalproex (500–2500 mg/day in divided doses) for the treatment of patients hospitalized for acute bipolar manic or mixed episodes. The Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to quantify manic and depressive symptoms, respectively. Safety was assessed with several measures. RESULTS: The protocol defined baseline-to-endpoint improvement in the mean total score on the Young Mania Rating Scale as the primary outcome variable. The mean Young Mania Rating Scale score decreased by 13.4 for patients treated with olanzapine (N=125) and 10.4 for those treated with divalproex (N=123). A priori categorizations defined response and remission rates: 54.4% of olanzapine-treated patients responded (≥50% reduction in Young Mania Rating Scale score), compare...
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antidepressant induced mania and cycle acceleration a controversy revisited
American Journal of Psychiatry, 1995Co-Authors: Lori L Altshuler, Robert M Post, Gabriele S Leverich, Kirstin Mikalauskas, Ann Rosoff, Laura AckermanAbstract:Objective: The longitudinal course ofSl patients with treatment-refractory bipolar disorder was examined to assess possible effects ofheterocyclic antidepressants on occurrence of manic episodes and cycle acceleration. Method: Using criteria established from life charts, investigators rated the patients’ episodes of mania or cycle acceleration as likely or unlikely to have been induced by antidepressant therapy. Discriminant function analyses were performed to assess predictors of vulnerability to antidepressant-induced mania or cycle acceleration. Further, the likelihood of future antidepressant-induced episodes in persons who had had one such episode was assessed. Results: Thirty-five percent of the patients had a manic episode rated as likely to have been antidepressant-induced. No variable was a predictor of vulnerability to antidepressant-induced mania. Cycle acceleration was likely to be associated with antidepressant treatment in 2 6 % of the patients assessed. Younger age at first treatment was a predictor of vulnerability to antidepressant-induced cycle acceleration. Forty-six percent of patients with antidepressant-induced mania, but only 14% of those without, also showed antidepressant-induced cycle acceleration at some point in their illness. Conclusions: Mania is likely to be antidepressant-induced and not attributable to the expected course of illness in one-third of treatment-refractory bipolar patients, and rapid cycling is induced in one-fourth. Antidepressant-induced mania may be a marker for increased vulnerability to antidepressantinduced cycle acceleration. A ntidepressant-induced cycle acceleration (but not antidepressantinduced mania) is associated with younger age at first treatment and may be more likely to occur in women and in bipolar II patients. (Am J Psychiatry 1995; 152:1130-1138)
Mengchang Tsai - One of the best experts on this subject based on the ideXlab platform.
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thiobarbituric acid reactive substances tbars is a state biomarker of oxidative stress in bipolar patients in a manic phase
Journal of Affective Disorders, 2015Co-Authors: Mengchang Tsai, Tiaolai HuangAbstract:Abstract Objectives Oxidative stress may contribute to the pathophysiology of bipolar disorder. The aim of this study was to investigate the serum levels or activities of oxidative stress markers in bipolar patients in a manic phase, and evaluate the changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC) and 8-hydroxy 2′-deoxyguanosine after treatment (8-OHdG). Methods We consecutively enrolled 23 bipolar inpatients in a manic phase and 40 healthy subjects. Serum oxidative stress markers were measured with assay kits. All patients were evaluated by examining the correlation between oxidative stress markers and Young Mania Rating Scale (YMRS) scores. Results The serum TBARS levels in bipolar patients in a manic phase were significantly higher than those of healthy subjects (p=0.006), and serum GPx activity was significant lower than that of healthy subjects (p Limitation Our sample size was limited. Conclusion Our results suggest that serum TBARS levels might be a state biomarker of oxidative stress in bipolar patients in a manic phase and after treatment. In addition, GPx deficit might be a trait biomarker of severity of mania.
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thiobarbituric acid reactive substances tbars is a state biomarker of oxidative stress in bipolar patients in a manic phase
Journal of Affective Disorders, 2015Co-Authors: Mengchang Tsai, Tiaolai HuangAbstract:OBJECTIVES: Oxidative stress may contribute to the pathophysiology of bipolar disorder. The aim of this study was to investigate the serum levels or activities of oxidative stress markers in bipolar patients in a manic phase, and evaluate the changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC) and 8-hydroxy 2'-deoxyguanosine after treatment (8-OHdG). METHODS: We consecutively enrolled 23 bipolar inpatients in a manic phase and 40 healthy subjects. Serum oxidative stress markers were measured with assay kits. All patients were evaluated by examining the correlation between oxidative stress markers and Young Mania Rating Scale (YMRS) scores. RESULTS: The serum TBARS levels in bipolar patients in a manic phase were significantly higher than those of healthy subjects (p=0.006), and serum GPx activity was significant lower than that of healthy subjects (p<0.05). The YMRS scores had a significantly positive association with CAT activity and PCC levels (p<0.05) and a negative association with GPx activity (p<0.05). Twenty bipolar patients were followed up, and their oxidative stress markers were measured at the end of treatment. We found significantly decreased changes in TBARS levels only in bipolar manic patients after treatment (p=0.019). LIMITATION: Our sample size was limited. CONCLUSION: Our results suggest that serum TBARS levels might be a state biomarker of oxidative stress in bipolar patients in a manic phase and after treatment. In addition, GPx deficit might be a trait biomarker of severity of mania.
Swaran P Singh - One of the best experts on this subject based on the ideXlab platform.
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cannabis use and mania symptoms a systematic review and meta analysis
European Psychiatry, 2015Co-Authors: Melanie Gibbs, Catherine Winsper, Steven Marwaha, Eleanor Gilbert, Matthew R Broome, Swaran P SinghAbstract:Introduction Whilst cannabis use appears to be a causal risk factor for the development of schizophrenia-related psychosis, associations with mania remain relatively unknown. Objectives This review aimed to examine the impact of cannabis use on the incidence of manic symptoms and on their occurrence in those with pre-existing bipolar disorder Methods A systematic review of the scientific literature using the PRISMA guidelines. PsychINFO, Cochrane, Scopus, Embase and MEDLINE databases were searched for prospective studies. Results Six articles met inclusion criteria. These sampled 2,391 individuals who had experienced mania symptoms. The mean length of follow up was 3.9 years. Studies support an association between cannabis use and the exacerbation of manic symptoms in those with previously diagnosed bipolar disorder. Furthermore, a meta-analysis of two studies suggests that cannabis use is associated with an approximately 3-fold (Odds Ratio: 2.97; 95% CI: 1.80 to 4.90) increased risk for the new onset of manic symptoms. Conclusions Our findings whilst tentative, suggest that cannabis use may worsen the occurrence of manic symptoms in those diagnosed with bipolar disorder and may also act as a causal risk factor in the incidence of manic symptoms. This underscores the importance of discouraging cannabis use among youth and those with bipolar disorder to help prevent chronic psychiatric morbidity. More high quality prospective studies are required to fully elucidate how cannabis use may contribute to the development of mania over time.
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cannabis use and mania symptoms a systematic review and meta analysis
Journal of Affective Disorders, 2015Co-Authors: Melanie Gibbs, Catherine Winsper, Steven Marwaha, Eleanor Gilbert, Matthew R Broome, Swaran P SinghAbstract:Background: Whilst cannabis use appears to be a causal risk factor for the development of schizophrenia-related psychosis, associations with mania remain relatively unknown. This review aimed to examine the impact of cannabis use on the incidence of manic symptoms and on their occurrence in those with pre-existing bipolar disorder. Methods: A systematic review of the scientific literature using the PRISMA guidelines. PsychINFO, Cochrane, Scopus, Embase and MEDLINE databases were searched for prospective studies. Results: Six articles met inclusion criteria. These sampled 2391 individuals who had experienced mania symptoms. The mean length of follow up was 3.9 years. Studies support an association between cannabis use and the exacerbation of manic symptoms in those with previously diagnosed bipolar disorder. Furthermore, a meta-analysis of two studies suggests that cannabis use is associated with an approximately 3-fold (Odds Ratio: 2.97; 95% CI: 1.80–4.90) increased risk for the new onset of manic symptoms. Limitations: We were only able to identify a small number of studies of variable quality, thus our conclusions remain preliminary. Conclusions: Our findings whilst tentative, suggest that cannabis use may worsen the occurrence of manic symptoms in those diagnosed with bipolar disorder, and may also act as a causal risk factor in the incidence of manic symptoms. This underscores the importance of discouraging cannabis use among youth and those with bipolar disorder to help prevent chronic psychiatric morbidity. More high quality prospective studies are required to fully elucidate how cannabis use may contribute to the development of mania over time.