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Jiang J, He W, Huang H. Lithium in cardiovascular health and disease: Pharmacological and clinical implications. Eur J Pharmacol 2025; 999:177657. [PMID: 40324573 DOI: 10.1016/j.ejphar.2025.177657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 04/12/2025] [Accepted: 04/22/2025] [Indexed: 05/07/2025]
Abstract
Lithium, a cornerstone therapy for bipolar disorder (BD), produces complex and dual effects on cardiovascular health. This review synthesizes current evidence on the direct and indirect cardiovascular effects of lithium. Direct effects include dose-dependent influences on cardiac development, hypertrophy, fibrosis, mitochondrial function, and arrhythmia. While therapeutic doses may confer cardioprotective benefits by inhibiting GSK-3β, which activates the Wnt/β-catenin signaling pathway and modulates anti-inflammatory pathways, supratherapeutic levels exacerbate oxidative stress, mitochondrial dysfunction, and arrhythmogenicity. Indirectly, lithium modulates cardiovascular outcomes caused by renal dysfunction, metabolic syndrome, and neuroendocrine-immune interactions. Clinical studies suggested that there is reduced cardiovascular mortality in lithium-treated BD patients, potentially offsetting its adverse metabolic effects. However, conflicting evidence persists, particularly regarding dose specificity and long-term outcomes. Future research should focus on high-quality clinical trials to clarify the balance between therapeutic benefits and adverse effects of lithium to ensure its safe and effective use in clinical practice.
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Affiliation(s)
- Jingya Jiang
- Department of Cardiology, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518033, China
| | - Wanbing He
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Hui Huang
- Department of Cardiology, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518033, China.
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Yoshida S, Aizawa E, Ishihara N, Hattori K, Segawa K, Kunugi H. High Rates of Abnormal Glucose Metabolism Detected by 75 g Oral Glucose Tolerance Test in Major Psychiatric Patients with Normal HbA1c and Fasting Glucose Levels. Nutrients 2025; 17:613. [PMID: 40004942 PMCID: PMC11858036 DOI: 10.3390/nu17040613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 02/06/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Objectives: Comorbid diabetes is an important factor in the treatment of major psychiatric disorders. However, a substantial proportion of diabetic patients remain undetected by routine diabetic indices such as blood glucose and HbA1c. This study tried to estimate rates of such unidentified diabetic or prediabetic patients by using a 75 g oral glucose tolerance test (OGTT). Methods: Participants in the test were 25 patients with major depressive disorder (MDD), 28 patients with bipolar disorder (BP), 26 patients with schizophrenia, and 28 psychiatrically normal controls. They were all Japanese, and showed non-diabetic levels of blood glucose (<126 mg/dL) and HbA1c (<6.0%). Results: Relatively high rates of psychiatric patients showed diabetes mellites (DM)-type abnormality (32% of MDD, 21.4% of BP and 42.3% of schizophrenia v. 10.7% of controls). The difference in the rates between schizophrenia and control groups was statistically significant (p = 0.008). When abnormal glucose metabolism was defined as a prediabetic state (either normal high glycemia, impaired fast glycemia or impaired glucose tolerance) or DM type in OGTT, it was more frequently seen in the psychiatric patients than in controls (64% of MDD, 46.4% of BP and 46.2% of schizophrenia v. 35.7% of controls). Individuals with DM type showed higher HbA1c values compared with those with normal (p < 0.001) and prediabetic (p = 0.021) states. Conclusions: The results suggest that relatively high proportions of patients with a major psychiatric disorder remain undetected by routine indices for abnormal glucose metabolism, indicating the importance of OGTT even if the patients showed non-diabetic levels in blood glucose or HbA1c.
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Affiliation(s)
- Sumiko Yoshida
- Department of Psychiatric Rehabilitation, National Center of Neurology and Psychiatry Hospital, Tokyo 187-8551, Japan
- Mood Disorder Center for Advanced Therapy, National Center of Neurology and Psychiatry Hospital, Tokyo 187-8551, Japan;
- Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan;
| | - Emiko Aizawa
- Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan;
- Faculty of Human Sciences, Sendai Shirayuri Women’s University, Sendai 981-3107, Japan
| | - Naoko Ishihara
- Mood Disorder Center for Advanced Therapy, National Center of Neurology and Psychiatry Hospital, Tokyo 187-8551, Japan;
- Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan;
| | - Kotaro Hattori
- Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan;
- Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan;
| | - Kazuhiko Segawa
- Department of General Medicine, National Center of Neurology and Psychiatry Hospital, Tokyo 187-8551, Japan;
| | - Hiroshi Kunugi
- Mood Disorder Center for Advanced Therapy, National Center of Neurology and Psychiatry Hospital, Tokyo 187-8551, Japan;
- Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan;
- Department of Psychiatry, Teikyo University School of Medicine, Tokyo 173-8605, Japan
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Xiao Z, Xu J, Li Z, Chen Z, Xu Z, Li Y, Du P, Wang C. Causality of multiple serum metabolites on emotional lability: A two-sample Mendelian randomization study. J Affect Disord 2025; 368:704-710. [PMID: 39307429 DOI: 10.1016/j.jad.2024.09.130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 09/17/2024] [Accepted: 09/19/2024] [Indexed: 09/27/2024]
Abstract
BACKGROUND Emotional lability (EL)-a transdiagnostic feature characterized by rapid emotional shifts-contributes significantly to functional impairment across psychiatric disorders, such as depression, bipolar disorder, and schizophrenia. Despite its clinical significance, its etiology remains poorly understood, hindering effective screening and interventions. Growing evidence suggests that metabolic alterations may play a crucial role in the pathophysiology of psychiatric disorders. METHODS A comprehensive Mendelian randomization (MR) design incorporated summary-level data from extensive genome-wide association studies (GWAS) on serum metabolites (8299 European participants) and EL (3268 European samples) to investigate causal associations between genetically determined metabolite levels and EL. Assumptions of instrumental variables, heterogeneity, horizontal pleiotropy, and directionality were assessed alongside sensitivity analyses. RESULTS Out of 1400 metabolites and ratios analyzed, 30 metabolites demonstrated causal associations with an increased risk of EL based on the inverse-variance weighted method. Sensitivity analyses identified three potential causal metabolites: hydrocinnamate (OR: 1.277, CI: 1.071-1.522, P = 0.0063), which is associated with an increased risk, while glycolithocholate (OR: 0.779, CI: 0.667-0.911, P = 0.0017) and 3β-hydroxy-5-cholenoic acid (OR: 0.857, CI: 0.756-0.971, P = 0.015) are associated with a decreased risk. CONCLUSION This MR study supports a causal link between hydrocinnamate, glycolithocholate, and 3β-hydroxy-5-cholenoic acid levels and the incidence of EL, offering potential metabolic biomarkers and therapeutic targets for EL in psychiatric disorders.
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Affiliation(s)
- Zhen Xiao
- Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China; Taizhou Fifth People's Hospital, Taizhou, China
| | - Jieyi Xu
- Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Zhengyi Li
- Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Zixin Chen
- Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Zifeng Xu
- Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Yisheng Li
- Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Pengyu Du
- Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Chun Wang
- Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China; Cognitive Behavioral Therapy Institute of Nanjing Medical University, Nanjing, China.
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Zhou J, Zeng Z, He L, Guo C, Ding N, Su Y, Qin J. The association of depressive symptoms with adverse clinical outcomes in hypertension: Data from SPRINT randomized trail. J Affect Disord 2024; 359:59-69. [PMID: 38768819 DOI: 10.1016/j.jad.2024.05.079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 05/11/2024] [Accepted: 05/17/2024] [Indexed: 05/22/2024]
Abstract
OBJECTIVE This study intends to explore the effect of depressive symptoms on adverse clinical outcomes in middle-aged and elderly hypertensive patients. METHODS This post hoc analysis was conducted using data from the Systolic Blood Pressure Intervention Trial (SPRINT), and we used cox proportional risk regression to examine the relationship between depressive symptoms and adverse clinical outcomes (primary outcome, all-cause mortality, cardiovascular disease(CVD) mortality, heart failure(HF), myocardial infarction(MI), non-myocardial infarction acute coronary syndrome(non-MI ACS)). RESULTS In a follow-up study of 9259 participants, we found that depression symptoms was significantly and positively associated with the primary outcome (HR 1.03, 95%CI 1.01-1.05; p for trend = 0.0038), all-cause mortality (HR 1.03, 95%CI 1.01-1.05; p for trend = 0.0308), HF(HR 1.05, 95%CI 1.01-1.08; p for trend = 0.0107), and non-MI ACS(HR 1.06, 95%CI 1.01-1.10; p for trend = 0.0120). Kaplan-Meier survival curves for depression symptoms severity (none, mild, moderate, and above) and adverse clinical outcomes suggested that for all but primary clinical outcomes, the cumulative risk of adverse clinical outcomes increased with increasing depression symptoms severity. CONCLUSION For middle-aged and elderly hypertensive patients, depression symptoms exacerbates the risk of adverse clinical outcomes (primary outcome, all-cause mortality, CVD death, MI, HF, and non-MI ACS), and the risk increases with the severity of depression symptoms.
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Affiliation(s)
- Junfeng Zhou
- Endoscopic Medical Center, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan 410000, China.
| | - Zhao Zeng
- Department of Emergency Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, NO.161 Shaoshan South Road, Changsha, Hunan 410004, China
| | - Liudang He
- Department of Emergency Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, NO.161 Shaoshan South Road, Changsha, Hunan 410004, China
| | - Cuirong Guo
- Department of Emergency Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, NO.161 Shaoshan South Road, Changsha, Hunan 410004, China
| | - Ning Ding
- Department of Emergency Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, NO.161 Shaoshan South Road, Changsha, Hunan 410004, China.
| | - Yingjie Su
- Department of Emergency Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, NO.161 Shaoshan South Road, Changsha, Hunan 410004, China.
| | - Jiao Qin
- Department of Nephrology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, NO.161 Shaoshan South Road, Changsha, Hunan 410004, China.
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Zhou LN, Ma XC, Wang W. Incidence and risk factors of depression in patients with metabolic syndrome. World J Psychiatry 2024; 14:245-254. [PMID: 38464768 PMCID: PMC10921290 DOI: 10.5498/wjp.v14.i2.245] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/14/2023] [Accepted: 01/08/2024] [Indexed: 02/06/2024] Open
Abstract
BACKGROUND Many studies have explored the relationship between depression and metabolic syndrome (MetS), especially in older people. China has entered an aging society. However, there are still few studies on the elderly in Chinese communities. AIM To investigate the incidence and risk factors of depression in MetS patients in mainland China and to construct a predictive model. METHODS Data from four waves of the China Health and Retirement Longitudinal Study were selected, and middle-aged and elderly patients with MetS (n = 2533) were included based on the first wave. According to the center for epidemiological survey-depression scale (CESD), participants with MetS were divided into depression (n = 938) and non-depression groups (n = 1595), and factors related to depression were screened out. Subsequently, the 2-, 4-, and 7-year follow-up data were analyzed, and a prediction model for depression in MetS patients was constructed. RESULTS The prevalence of depression in middle-aged and elderly patients with MetS was 37.02%. The prevalence of depression at the 2-, 4-, and 7-year follow-up was 29.55%, 34.53%, and 38.15%, respectively. The prediction model, constructed using baseline CESD and Physical Self-Maintenance Scale scores, average sleep duration, number of chronic diseases, age, and weight had a good predictive effect on the risk of depression in MetS patients at the 2-year follow-up (area under the curve = 0.775, 95% confidence interval: 0.750-0.800, P < 0.001), with a sensitivity of 68% and a specificity of 74%. CONCLUSION The prevalence of depression in middle-aged and elderly patients with MetS has increased over time. The early identification of and intervention for depressive symptoms requires greater attention in MetS patients.
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Affiliation(s)
- Li-Na Zhou
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Xian-Cang Ma
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Wei Wang
- Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
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Baek JH, Han K, Kim H, Yang K, Jeon HJ. Increased metabolic variability in Korean patients with new onset bipolar disorder: a nationwide cohort study. Front Psychiatry 2024; 14:1256458. [PMID: 38260805 PMCID: PMC10800849 DOI: 10.3389/fpsyt.2023.1256458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 12/15/2023] [Indexed: 01/24/2024] Open
Abstract
Introduction The aim of this study was to determine associations between changes of metabolic parameters and the development of BD using nationally representative data. Methods We used health examination data provided by the South Korean National Health Insurance System (NHIS) (n = 8,326,953). The variability of each metabolic parameter including weight circumference, blood pressure, fasting blood glucose, high-density lipoprotein cholesterol, and triglyceride levels was caculated using variability independent of mean (VIM) indices. The presence of metabolic syndrome was associated with new onset BD. Each metabolic parameter with high variability was associated with a higher risk of new onset BD compared to those with low variability after adjusting for age, sex, smoking, alcohol drinking, regular exercise, income status, baseline diabetes, hypertension, and dyslipidemia. Results As the number of highly variable metabolic parameters increased, the risk for new onset depression also increased even after covariates adjustment. The associations between new onset BD and metabolic variability were greater in populations with age > 50 years. In addition, these associations remained significant after adjusting for the presence of depression prior to diagnoses of BD. Discussion Our results suggest possibility of metabolic variability as an independent environmental risk factor for BD even after adjusting for the presence of metabolic syndrome.
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Affiliation(s)
- Ji Hyun Baek
- Department of Psychiatry, Depression Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital, Boston, MA, United States
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Hyewon Kim
- Department of Psychiatry, Depression Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyojin Yang
- Department of Psychiatry, Depression Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hong Jin Jeon
- Department of Psychiatry, Depression Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Health Sciences & Technology, Department of Medical Device Management & Research, and Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea
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Patel RS, Majumder P, Correll CU. Characteristics and Correlates of Metabolic Syndrome in Adolescents with Unipolar and Bipolar Depression: Results from a Cross-National Inpatient Case-Control Study. J Child Adolesc Psychopharmacol 2022; 32:426-433. [PMID: 36282769 DOI: 10.1089/cap.2022.0017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Abstract Objectives: To assess characteristics and correlates of metabolic syndrome (MetS) in adolescents with major depressive disorder (MDD) or bipolar disorder-depressive episode (BP-d). Methods: Case-control study, using national inpatient sample data, including adolescents (age, 12-18 years) with a primary diagnosis of MDD or BP-d. Using propensity score matching (based on age, sex, and race/ethnicity), we extracted cases with MetS (≥3 of the following conditions: obesity, diabetes, hypercholesterolemia, and hypertension) and controls without MetS. We used a multivariable logistic regression model calculating adjusted odds ratios (aORs) for potential correlates of MetS, focusing on primary mood disorders and psychiatric comorbidities. Results: In 607 age-/sex-/race/ethnicity-matched adolescents (MDD = 83.5%, BP-d = 16.5%), comparing those with (N = 332) versus without MetS (N = 275), MetS was most prevalent in later-age adolescents (mean age 16.3 years), females (58.1%), Whites (40.3%), and Blacks (31.5%). MetS was characterized by obesity (84.9% vs. 3.6%), hypertension (81% vs. 1.8%), diabetes (72.8% vs. 9.1%), and hypercholesterolemia (67.2% vs. 3.6%) (all p < 0.001). MetS was associated with a primary diagnosis of BP-d versus MDD (aOR 2.42, 95% confidence interval [CI] 1.47-3.97) and comorbid disruptive behavior disorders (DBD) (aOR 4.45, 95% CI 1.55-12.78), while comorbid substance use disorder reduced MetS risk (aOR 0.31, 95% CI 0.19-0.50). Conclusion: In adolescents with MDD or BP-d, MetS was associated with a primary BP-d diagnosis, and comorbid DBD. MetS-related parameters should be screened for early in adolescents with depression-spectrum disorders aiming to prevent the development or effects of MetS.
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Affiliation(s)
- Rikinkumar S Patel
- Department of Child and Adolescent Psychiatry, Duke University Medical Center, Durham, North Carolina, USA
| | - Pradipta Majumder
- Department of Psychiatry, WellSpan Health, York, Pennsylvania, USA.,Department of Behavioral Health, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
| | - Christoph U Correll
- Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, USA.,Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.,Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany
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Tao H, Shen D, Zhou Y, Sun F, Li G, Jin W. A Systematic Review and Meta-Analysis of Metabolic Syndrome Prevalence in Chinese Inpatients with Bipolar Disorder. Horm Metab Res 2022; 54:587-592. [PMID: 35738391 DOI: 10.1055/a-1882-8423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
The aim of the work was to study the prevalence of metabolic syndrome in Chinese patients with bipolar disorder. We searched Chinese literature related to the study in prevalence of metabolic syndrome in bipolar disorder in Chinese language, among which results such as comments, letters, reviews and case reports were excluded. The prevalence of metabolic syndrome in bipolar disorder was researched and discussed. A total of 1562 subjects were included in 11 studies. The prevalence of MetS in bipolar disorder was 33% (95% CI=0.29-0.37), which was higher significantly than normal control (10.82%), but similar to schizophrenia (31.59%). The 41.41% prevalence of MetS in male patients was higher significantly than that in females (26.83%).The prevalence of MetS in BD treated by AAP was 47.54%, by MS was 19.19%, by MS+AAP was 40%.The prevalence of MetS in BD treated by carbamazepine was 28.21%, by lithium was 30%, by valproate was 21.71%, by clozepine was 51.43%, by olanzapine was 39.84%, by quetiapine was 39.44%, and by risperidone was 35%. The prevalence of MetS in bipolar disorder was 33% (95% CI=0.29-0.37), which was higher significantly than normal control (10.82%), but similar to schizophrenia (31.59%). AAP and MS were the main one risks of MetS in BD.
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Affiliation(s)
- Hejian Tao
- Psychiatry Department, Zhejiang Chinese Medical University, Hangzhou, China
| | - Dong Shen
- Psychiatry Department, Jiaxing Kangci Hospital, Jiaxing, China
| | - Yong Zhou
- Psychiatry Department, Jiaxing Kangci Hospital, Jiaxing, China
| | - Fengli Sun
- Psychiatry Department, Zhejiang Province Mental Health Center, Hangzhou, China
| | - Guorong Li
- Psychiatry Department, Jiaxing Kangci Hospital, Jiaxing, China
| | - Weidong Jin
- Psychiatry Department, Zhejiang Chinese Medical University, Hangzhou, China
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Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Levels in Adolescent with Bipolar Disorder and Their Relationship with Metabolic Parameters. J Mol Neurosci 2022; 72:1313-1321. [PMID: 35318563 DOI: 10.1007/s12031-022-02000-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/13/2022] [Indexed: 10/18/2022]
Abstract
Peroxisome proliferator-activated receptor gamma (PPARγ) is one of the immune and metabolic regulatory agents. This study examined the serum PPARγ levels and metabolic syndrome (MetS) parameters in pediatric bipolar disorder (PBD) adolescents and compared them with healthy subjects. Serum PPARγ levels, fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and fasting insulin levels of 39 PBD-type I (age range: 14-18) and 36 age- and sex-matched healthy control subjects were compared. The anthropometric measurements were also analyzed, including body weight, height, body mass index (BMI), waist circumference (WC), and blood pressure measurements. The PPARγ levels were significantly lower, and the MetS prevalence was significantly higher in the PBD group than in the control group. The mean BMI, WC, serum TG, and FBG values of the PBD group were statistically higher than the healthy control group. There was no significant relationship between the PPARγ levels and metabolic parameters except fasting glucose. Lower PPARγ activity and higher MetS prevalence in PBD indicate dysregulation of immune and metabolic regulatory parameters. These results may shed light on developing new PBD medications.
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Association between abnormal glycolipid level and cognitive dysfunction in drug-naïve patients with bipolar disorder. J Affect Disord 2022; 297:477-485. [PMID: 34715186 DOI: 10.1016/j.jad.2021.10.100] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 09/13/2021] [Accepted: 10/23/2021] [Indexed: 01/10/2023]
Abstract
OBJECTIVES Cognitive impairment and abnormal glycolipid metabolism are common clinical features of bipolar disorder (BD). The purpose of this study was to investigate the relationship between conventional glycolipid metabolism indicators and cognitive impairment in patients with BD. METHODS A total of 132 drug-naïve patients with BD and 129 healthy controls (HC) were recruited in the study. Five serum glycolipid metabolism indicators were measured and cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test) for each participant. RESULTS The scores of immediate memory, attention, language and delayed memory in BD group were significantly lower than those in HC group (P < 0.05). The triglyceride (TG) level in BD group was higher than that in HC group (P = 0.011), and the total cholesterol and high-density lipoprotein cholesterol (HDL) levels were lower than those in HC group (P = 0.026; P = 0.001). Regression analysis showed that TG level was significantly correlated with RBANS total score (β = 0.245, P = 0.008), attention (β = 0.289, P = 0.03) and delayed memory (β = 0.221, P = 0.023). Fasting blood glucose (FBG) level was significantly correlated with language subscale score (β = -0.187, P = 0.046) in BD. LIMITATIONS Cross-sectional design and limited control variables. CONCLUSIONS Elevated FBG and TG levels may be associated with cognitive dysfunction in BD patients. Improving glycolipid metabolism in patients with BD may help to improve certain domain-specific cognitive functions.
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Yi W, Wu H, Li R, Li H, Song Z, She S, Zheng Y. Prevalence and associated factors of obesity and overweight in Chinese patients with bipolar disorder. Front Psychiatry 2022; 13:984829. [PMID: 36147966 PMCID: PMC9485538 DOI: 10.3389/fpsyt.2022.984829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 08/01/2022] [Indexed: 11/21/2022] Open
Abstract
OBJECT Despite abundant literature demonstrating a high prevalence of obesity and overweight in people with bipolar disorder (BD), little is known about this topic in China. Therefore, we assessed the prevalence and associated factors of obesity and overweight among inpatients with BD in our hospital, one of the largest public psychiatric hospitals in China. METHODS In this retrospective, cross-sectional study, 1,169 inpatients ≥18 years with BD during 2019 were included. Obesity was defined as having a BMI ≥25 kg/m2, and overweight was defined as having a BMI from 23 kg/m2 to <25 kg/m2. Binary logistic regression analysis was performed to identify factors associated with obesity and overweight. RESULTS The prevalence of obesity and overweight was 21.0% and 32.2% in patients with BD, respectively. Compared to patients with overweight and normal weight, patients with obesity were older, had a longer duration of BD and a longer length of hospital stay, had a higher prevalence of diabetes and hypertension, and had a higher level of all metabolic indices, except for HDL cholesterol. Binary logistic regression analysis showed that duration of BD, uric acid, alanine aminotransferase (ALT), triglyceride, and LDL cholesterol were significantly associated with obesity, and male sex and uric acid level were significantly associated with overweight (p < 0.05). CONCLUSIONS Obesity and overweight were fairly prevalent in Chinese BD patients, and several factors were related to obesity and overweight. The results of the present study call for the need to implement early screening, prevention and interventions for obesity and overweight in patients with BD in China.
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Affiliation(s)
- Wenying Yi
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Haibo Wu
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Ruikeng Li
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Haijing Li
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zhen Song
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Shenglin She
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yingjun Zheng
- The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
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Impact of bipolar disorder on health-related quality of life and work productivity: Estimates from the national health and wellness survey in Japan. J Affect Disord 2021; 295:203-214. [PMID: 34479128 DOI: 10.1016/j.jad.2021.07.104] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 07/25/2021] [Accepted: 07/27/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Previous studies have shown that bipolar disorder (BD) patients frequently present with difficulties in interpersonal relationships, education or employment and suffer poorer quality of life. This study aimed to estimate the impact of BD on health-related quality of life (HRQOL), work productivity loss and indirect costs. METHODS Data was from the online, self-administered 2019 National Health and Wellness Survey. Outcomes were compared for those who self-reported a physician diagnosis of BD (N=179), major depressive disorder (MDD, N=1,549) and controls who have never experienced BD, MDD and schizophrenia (N=27,485). RESULTS The lifetime prevalence was estimated to be 0.60% for BD and 5.16% for MDD. Significantly lower Mental Component Summary (MCS), Role Component Summary (RCS) scores and EuroQol 5-dimension scale (EQ-5D-5L) summary index and significantly higher presenteeism, total work productivity impairment and activity impairment assessed by Work Productivity and Activity Impairment questionnaire and indirect costs for BD versus controls and BD PHQ-9≥10 versus PHQ-9<10 were observed. Compared to MDD patients, BD patients had significantly lower RCS score and greater work productivity loss and activity impairment. The national morbidity cost of BD in Japan was estimated to be Japanese yen 1,236 billion using a human-capital approach. LIMITATIONS The data used were self-reported and is cross-sectional in nature, thus causal relationship cannot be assumed. CONCLUSION BD patients and those with severe depressive symptoms experience significantly poorer HRQOL and greater work productivity loss and indirect costs. These findings highlight the importance of proper screening, diagnosis and treatment of BD and bipolar depression.
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Schuster MP, Borkent J, Chrispijn M, Ioannou M, Doornbos B, Burger H, Haarman BCM. Increased prevalence of metabolic syndrome in patients with bipolar disorder compared to a selected control group-a Northern Netherlands LifeLines population cohort study. J Affect Disord 2021; 295:1161-1168. [PMID: 34706429 DOI: 10.1016/j.jad.2021.08.139] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 07/31/2021] [Accepted: 08/27/2021] [Indexed: 11/28/2022]
Abstract
OBJECTIVES Metabolic syndrome (MetS) is highly prevalent among patients with bipolar disorder (BD). The aims of this cross-sectional study were to determine the prevalence of MetS in Dutch BD subjects and compare it with a control group, to examine the association of demographic and clinical characteristics with MetS in BD, and to determine the extent to which metabolic dysregulation is treated in those patients. METHODS 493 Dutch adult patients (≥ 18 years) with BD receiving psychotropic drugs and 493 matched control subjects were compared using data from the biobank Lifelines. We determined MetS according to the National Cholesterol Education Program Adult Treatment Panel III-Adapted (NCEP ATP III-A) criteria. The difference in the prevalence of MetS and the associations with characteristics were analyzed with logistic regression. RESULTS BD subjects (30.6%) showed a significantly higher prevalence of MetS compared to the control group (14.2%) (p < .001, OR:2.67, 95% CI:1.94-3.66). Univariate analysis showed that smoking, body mass index (BMI) and antidepressant drug use were associated with MetS. Multivariate analysis showed that smoking (OR:2.01) was independently associated with MetS in BD. For hypertension, hyperglycemia and lipid disorder pharmacological treatment was provided to respectively 69.5%, 24% and 18.4% of the BD subjects in our sample. LIMITATIONS Duration of illness of BD subjects was unknown. CONCLUSIONS This study demonstrated a higher prevalence of MetS in Dutch BD subjects compared to persons without BD. In addition, a remarkable undertreatment of some of the components of MetS was found.
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Affiliation(s)
- M P Schuster
- Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Rob Giel Onderzoekscentrum, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - J Borkent
- Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Rob Giel Onderzoekscentrum, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
| | - M Chrispijn
- Dimence Mental Health, Zwolle, the Netherlands
| | - M Ioannou
- Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Rob Giel Onderzoekscentrum, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - B Doornbos
- Rob Giel Onderzoekscentrum, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; GGZ Drenthe, Assen, the Netherlands
| | - H Burger
- Department of General Practice and Elderly Care Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - B C M Haarman
- Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Rob Giel Onderzoekscentrum, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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Depressive Symptoms among Individuals Hospitalized with COVID-19: Three-Month Follow-Up. Brain Sci 2021; 11:brainsci11091175. [PMID: 34573196 PMCID: PMC8471767 DOI: 10.3390/brainsci11091175] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 01/08/2023] Open
Abstract
Individuals affected by Coronavirus Disease 2019 (COVID-19) may experience psychiatric symptoms, including depression and suicidal ideation, that could lead to chronic impairment and a reduction in quality of life. Specifically, depressive disorder shows high incidence and may lead to chronic impairment and a reduction in the quality of life. To date, no studies on the presence of suicidality and quantitative analysis of depressive symptoms and their risk factors have yet been published. In this study, we aim to assess the prevalence of depressive symptoms and related risk factors at 3 months after discharge to home care following hospitalization for COVID-19 infection. METHODS Participants were contacted three months after hospital discharge from one of the five COVID-19 hospitals in Rome, as part of a larger project on health outcomes in COVID-19 inpatients (Long Term Neuropsychiatric Disorder in COVID-19 Project), and the Patient Health Questionnaire-9 (PHQ-9) was administered by telephone interview. RESULTS Of 115 participants, 14.8% (N = 17) received a PHQ-9-based diagnosis of depression, and n = 7 of them scored 1 or more on the item on suicidality. A linear regression model showed the predictive role of female sex, pulmonary chronic condition and previous mental disorder in the development of depressive disorder; the latter was confirmed also by binary logistic regression. Severity indexes of disease (length of hospitalization and intensive care treatment) were found not to be associated with the development of depressive symptoms. CONCLUSIONS A small but clinically meaningful number of participants in the current study reported that they experienced symptoms of depression and suicidal ideation 3 months post-discharge from their COVID-19 hospitalization. In particular, given the findings that a history of prior psychiatric disorders was predictive of the development of depression symptoms, clinicians should carefully monitor for the presence of all psychiatric symptoms at follow-up visits.
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Fusar-Poli L, Amerio A, Cimpoesu P, Natale A, Salvi V, Zappa G, Serafini G, Amore M, Aguglia E, Aguglia A. Lipid and Glycemic Profiles in Patients with Bipolar Disorder: Cholesterol Levels Are Reduced in Mania. ACTA ACUST UNITED AC 2020; 57:medicina57010028. [PMID: 33396922 PMCID: PMC7824186 DOI: 10.3390/medicina57010028] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 12/24/2020] [Accepted: 12/27/2020] [Indexed: 12/20/2022]
Abstract
Background and Objectives: Bipolar disorder (BD) is a severe mental condition with a lifetime prevalence estimated around 2% among the general population. Due to risk factors, etiological mechanisms, and the chronic use of psychotropic medications, people with BD are frequently affected by medical comorbidities, such as metabolic syndrome (MetS), associated with altered blood levels of glucose, cholesterol, and triglycerides. Moreover, the lipid concentration may be associated with the severity of psychiatric symptoms. Materials and Methods: Five hundred and forty-two in- and outpatients (418 affected by BD and 124 affected by schizophrenia) were recruited in two Italian university hospitals. A blood examination assessing the fasting glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides was performed. Results: No significant differences were found in the lipid and glycemic profiles between patients with BD and schizophrenia. When considering only the BD sample, we found that patients experiencing a manic episode had significantly lower total cholesterol, HDL, and LDL than euthymic patients. Moreover, the total and LDL cholesterol levels were significantly lower in (hypo)manic than depressed patients. Mood episodes did not influence the triglyceride and glucose levels in our sample. Conclusions: Clinicians should pay attention to blood cholesterol levels in patients with BD, as differences in concentrations may predispose them to severe medical conditions and can be associated with the onset of mood episodes.
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Affiliation(s)
- Laura Fusar-Poli
- Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, 95123 Catania, Italy; (A.N.); (E.A.)
- Correspondence: ; Tel.: +39-095-378-2470
| | - Andrea Amerio
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, 16123 Genoa, Italy; (A.A.); (P.C.); (G.Z.); (G.S.); (M.A.); (A.A.)
- IRCCS Ospedale Policlinico San Martino, 16123 Genoa, Italy
- Department of Psychiatry, Tufts University, Boston, MA 02111, USA
| | - Patriciu Cimpoesu
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, 16123 Genoa, Italy; (A.A.); (P.C.); (G.Z.); (G.S.); (M.A.); (A.A.)
- IRCCS Ospedale Policlinico San Martino, 16123 Genoa, Italy
| | - Antimo Natale
- Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, 95123 Catania, Italy; (A.N.); (E.A.)
| | - Virginio Salvi
- Department of Clinical Neurosciences, Polytechnic University of Marche, 60121 Ancona, Italy;
| | - Guendalina Zappa
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, 16123 Genoa, Italy; (A.A.); (P.C.); (G.Z.); (G.S.); (M.A.); (A.A.)
- IRCCS Ospedale Policlinico San Martino, 16123 Genoa, Italy
| | - Gianluca Serafini
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, 16123 Genoa, Italy; (A.A.); (P.C.); (G.Z.); (G.S.); (M.A.); (A.A.)
- IRCCS Ospedale Policlinico San Martino, 16123 Genoa, Italy
| | - Mario Amore
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, 16123 Genoa, Italy; (A.A.); (P.C.); (G.Z.); (G.S.); (M.A.); (A.A.)
- IRCCS Ospedale Policlinico San Martino, 16123 Genoa, Italy
| | - Eugenio Aguglia
- Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, 95123 Catania, Italy; (A.N.); (E.A.)
| | - Andrea Aguglia
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, 16123 Genoa, Italy; (A.A.); (P.C.); (G.Z.); (G.S.); (M.A.); (A.A.)
- IRCCS Ospedale Policlinico San Martino, 16123 Genoa, Italy
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Colomer L, Anmella G, Vieta E, Grande I. Physical health in affective disorders: a narrative review of the literature. BRAZILIAN JOURNAL OF PSYCHIATRY 2020; 43:621-630. [PMID: 33146344 PMCID: PMC8639004 DOI: 10.1590/1516-4446-2020-1246] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 09/03/2020] [Indexed: 12/11/2022]
Abstract
This article reviews the most common non-psychiatric comorbidities associated with affective disorders, examining the implications of their possible bidirectional link. A narrative review was conducted on the association among the three most common non-psychiatric diseases in major depressive disorder and bipolar disorder (obesity, metabolic syndrome, and cardiovascular diseases) in articles published from January 1994 to April 2020. The evidence suggests that obesity, metabolic syndrome, and cardiovascular diseases are highly prevalent in patients diagnosed with affective disorders. The presence of non-psychiatric comorbidities significantly worsens the therapeutic management and prognosis of affective disorders and vice versa. In many cases, these comorbidities may precede the onset of affective disorders, although in most cases they appear after it. The presence of these concurrent non-psychiatric diseases in an individual diagnosed with an affective disorder is associated with a more complex disease presentation and management. For professionals, the evidence unequivocally supports routine surveillance of comorbidities from a multidisciplinary approach.
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Affiliation(s)
- Lluc Colomer
- Institute of Neuroscience, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Gerard Anmella
- Institute of Neuroscience, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Eduard Vieta
- Institute of Neuroscience, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Iria Grande
- Institute of Neuroscience, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
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Lis M, Stańczykiewicz B, Liśkiewicz P, Misiak B. Impaired hormonal regulation of appetite in schizophrenia: A narrative review dissecting intrinsic mechanisms and the effects of antipsychotics. Psychoneuroendocrinology 2020; 119:104744. [PMID: 32534330 DOI: 10.1016/j.psyneuen.2020.104744] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 05/25/2020] [Accepted: 05/30/2020] [Indexed: 12/14/2022]
Abstract
Cardiometabolic diseases are the main contributor of reduced life expectancy in patients with schizophrenia. It is now widely accepted that antipsychotic treatment plays an important role in the development of obesity and its consequences. However, some intrinsic mechanisms need to be taken into consideration. One of these mechanisms might be related to impaired hormonal regulation of appetite in this group of patients. In this narrative review, we aimed to dissect impairments of appetite-regulating hormones attributable to intrinsic mechanisms and those related to medication effects. Early hormonal alterations that might be associated with intrinsic mechanisms include low levels of leptin and glucagon-like peptide-1 (GLP-1) together with elevated insulin levels in first-episode psychosis (FEP) patients. However, evidence regarding low GLP-1 levels in FEP patients is based on one large study. In turn, multiple-episode schizophrenia patients show elevated levels of insulin, leptin and orexin A together with decreased levels of adiponectin. In addition, patients receiving olanzapine may present with low ghrelin levels. Post mortem studies have also demonstrated reduced number of neuropeptide Y neurons in the prefrontal cortex of patients with schizophrenia. Treatment with certain second-generation antipsychotics may also point to these alterations. Although our understanding of hormonal regulation of appetite in schizophrenia has largely been improved, several limitations and directions for future studies need to be addressed. This is of particular importance since several novel pharmacological interventions for obesity and diabetes have already been developed and translation of these developments to the treatment of cardiometabolic comorbidities in schizophrenia patients is needed.
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Affiliation(s)
- Michał Lis
- Clinical Department of Internal Diseases, Endocrinology and Diabetology, The Central Clinical Hospital of the Ministry of the Interior in Warsaw, Wołoska 137 Street, 02-507 Warsaw, Poland
| | - Bartłomiej Stańczykiewicz
- Department of Nervous System Diseases, Wroclaw Medical University, Bartla 5 Street, 51-618, Wroclaw, Poland
| | - Paweł Liśkiewicz
- Department of Psychiatry, Pomeranian Medical University, Broniewskiego 26 Street, 71-460, Szczecin, Poland
| | - Błażej Misiak
- Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1 Street, 50-368 Wroclaw, Poland.
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Regan AS, Valcourt SC. Metabolic Syndrome in Bipolar Disorder: Review and Management. Psychiatr Ann 2020. [DOI: 10.3928/00485713-20200713-01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Dolab N, Kamkar MZ, Amiriani T, Yuzugulen J, Marjani M, Marjani A. The association between leptin and adiponectin, and metabolic syndrome components and serum levels of lipid peroxidation in bipolar disorder patients treated with lithium and valproic acid. Heliyon 2020; 6:e04553. [PMID: 32760840 PMCID: PMC7393417 DOI: 10.1016/j.heliyon.2020.e04553] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 07/04/2020] [Accepted: 07/22/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND The aim of study is to assess a relation between the adiponectin and leptin levels, and metabolic syndrome components and lipid peroxidation treated with Li and VPA in bipolar disorder patients and compared with controls. MATERIALS AND METHODS 56 patients and 31 healthy controls were enrolled. The ATP III criteria were used to determine metabolic syndrome components. Leptin, adiponectin, lipid peroxidation and lipid profiles were measured. RESULTS Malondialdehyde in Li patients was higher than VPA patients. BMI, waist circumference (WC), triglyceride, malondialdehyde and adiponectin levels were increased, whereas HDL-cholesterol (VPA treated patients) and leptin were decreased in patients compared with controls. Leptin and adiponectin were correlated with WC, triglyceride and malondialdehyde in both groups. Adiponectin was correlated with HDL-cholesterol in VPA patients. CONCLUSION Patients should be checked metabolic syndrome components, serum leptin and adiponectin level occasionally to prevent possible deficiency or pathologic increase of these parameters.
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Affiliation(s)
- Neda Dolab
- Student Research Committee, Metabolic Disorders Research Center, Department of Biochemistry and Biophysics, Gorgan Faculty of Medicine, Golestan University Medical Sciences, Gorgan, Iran
| | - Mohammad Zaman Kamkar
- Department of Psychiatry, Golestan Research Center of Psychiatry, Golestan University of Medical Sciences, Gorgan, Golestan Province, Iran
| | - Taghi Amiriani
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Jale Yuzugulen
- Faculty of Pharmacy, Eastern Mediterranean University, Mersin 10, Famagusta, North Cyprus, Turkey
| | - Majid Marjani
- Faculty of Pharmacy, Eastern Mediterranean University, Mersin 10, Famagusta, North Cyprus, Turkey
| | - Abdoljalal Marjani
- Metabolic Disorders Research Center, Department of Biochemistry and Biophysics, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Golestan province, Iran
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Fernandes B, Dash S, Jacka F, Dodd S, Carvalho A, Köhler C, Steiner J, da Graça Cantarelli M, Nardin P, Gonçalves CA, Berk M. Leptin in bipolar disorder: A systematic review and meta-analysis. Eur Psychiatry 2020; 35:1-7. [DOI: 10.1016/j.eurpsy.2016.02.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2015] [Revised: 02/20/2016] [Accepted: 02/21/2016] [Indexed: 12/30/2022] Open
Abstract
AbstractBackgroundBipolar disorder (BD) is a psychiatric disorder associated with increased rates of obesity and inflammation. Leptin is an adipokine that is mainly produced by the white adipose tissue in response to insulin. It stimulates the immune system, increasing the production of pro-inflammatory cytokines. There is currently uncertainty regarding possible alterations in peripheral leptin levels across the mood states in BD.MethodsThis study comprises a between-group meta-analysis comparing serum and plasma leptin levels in people with BD in mania, depression or euthymia and healthy controls. We conducted a systematic search for all possibly eligible-English and non-English peer-reviewed articles. We calculated the effect size (ES) utilizing Hedges’ adjusted g using random effects.ResultsEleven studies were included in the meta-analyses, providing data on 1118 participants. Serum and plasma leptin levels were not altered in subjects with BD when compared to healthy controls in mania (g = −0.99, 95% CI −2.43 to 0.43, P = 0.171), in depression (g = 0.17, 95% CI −0.45 to 0.79, P = 0.584), or in euthymia (g = 0.03, 95% CI −0.39 to 0.46, P = 0.882). However, we did observe a stronger association between leptin levels and both age and BMI in patients with BD in euthymia compared to healthy controls, such that the greater the age of the individuals, the greater the difference in leptin levels between BD and controls; and the higher the BMI, the greater the difference in leptin levels between BD and controls.ConclusionsOur meta-analysis provides evidence that leptin levels are not altered in BD across the mood spectrum compared to healthy controls. The disproportionate increase of leptin levels with increase in BMI in BD speaks in favour of a potential inflammatory role of white adipose tissue in BD and a disproportionate increase of leptin levels with increase in age.
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Figueroa JF, Phelan J, Orav EJ, Patel V, Jha AK. Association of Mental Health Disorders With Health Care Spending in the Medicare Population. JAMA Netw Open 2020; 3:e201210. [PMID: 32191329 PMCID: PMC7082719 DOI: 10.1001/jamanetworkopen.2020.1210] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
IMPORTANCE The degree to which the presence of mental health disorders is associated with additional medical spending on non-mental health conditions is largely unknown. OBJECTIVE To determine the proportion and degree of total spending directly associated with mental health conditions vs spending on other non-mental health conditions. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study of 4 358 975 fee-for-service Medicare beneficiaries in the US in 2015 compared spending and health care utilization among Medicare patients with serious mental illness (SMI; defined as bipolar disease, schizophrenia or related psychotic disorders, and major depressive disorder), patients with other common mental health disorders (defined as anxiety disorders, personality disorders, and posttraumatic stress disorder), and patients with no known mental health disorders. Data analysis was conducted from February to October 2019. EXPOSURE Diagnosis of an SMI or other common mental health disorder. MAIN OUTCOMES AND MEASURES Risk-adjusted, standardized spending and health care utilization. Multivariable linear regression models were used to adjust for patient characteristics, including demographic characteristics and other medical comorbidities, using hospital referral region fixed effects. RESULTS Of 4 358 975 Medicare beneficiaries, 987 379 (22.7%) had an SMI, 326 991 (7.5%) had another common mental health disorder, and 3 044 587 (69.8%) had no known mental illness. Compared with patients with no known mental illness, patients with an SMI were younger (mean [SD] age, 72.3 [11.6] years vs 67.4 [15.7] years; P < .001) and more likely to have dual eligibility (633 274 [20.8%] vs 434 447 [44.0%]; P < .001). Patients with an SMI incurred more mean (SE) spending on mental health services than those with other common mental health disorders or no known mental illness ($2024 [3.9] vs $343 [6.2] vs $189 [2.1], respectively; P < .001). Patients with an SMI also had substantially higher mean (SE) spending on medical services for physical conditions than those with other common mental health disorders or no known mental illness ($17 651 [23.6] vs $15 253 [38.2] vs $12 883 [12.8], respectively; P < .001), reflecting $4768 (95% CI, $4713-$4823; 37% increase) more in costs for patients with an SMI and $2370 (95% CI, $2290-$2449; 18.4% increase) more in costs for patients with other common mental health disorders. Among Medicare beneficiaries, $2 686 016 110 of $64 326 262 104 total Medicare spending (4.2%) went to mental health services and an additional $5 482 791 747 (8.5%) went to additional medical spending associated with mental illness, representing a total of 12.7% of spending associated with mental health disorders. CONCLUSIONS AND RELEVANCE In this study, having a mental health disorder was associated with spending substantially more on other medical conditions. These findings quantify the extent of additional spending in the Medicare fee-for-service population associated with a diagnosis of a mental health disorder.
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Affiliation(s)
- Jose F. Figueroa
- Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Medicine, Harvard Medical School, Boston, Massachusetts
- Division of General Internal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
| | - Jessica Phelan
- Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - E. John Orav
- Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Division of General Internal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
| | - Vikram Patel
- Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts
| | - Ashish K. Jha
- Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Medicine, Harvard Medical School, Boston, Massachusetts
- Harvard Global Health Institute, Harvard University, Cambridge, Massachusetts
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Trastornos afectivos y salud física, implicaciones de la comorbilidad con enfermedades médicas: una revisión de la literatura. REVISTA MÉDICA CLÍNICA LAS CONDES 2020. [DOI: 10.1016/j.rmclc.2020.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Nestsiarovich A, Kerner B, Mazurie AJ, Cannon DC, Hurwitz NG, Zhu Y, Nelson SJ, Oprea TI, Crisanti AS, Tohen M, Perkins DJ, Lambert CG. Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder. Psychoneuroendocrinology 2020; 112:104511. [PMID: 31744781 DOI: 10.1016/j.psyneuen.2019.104511] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 08/28/2019] [Accepted: 11/07/2019] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To compare the largest set of bipolar disorder pharmacotherapies to date (102 drugs and drug combinations) for risk of diabetes mellitus (DM). METHODS The IBM MarketScan® database was used to retrospectively analyze data on 565,253 adults with bipolar disorder without prior glucose metabolism-related diagnoses. The pharmacotherapies compared were lithium, mood-stabilizing anticonvulsants, antipsychotics, and antidepressants (monotherapy and multi-class polypharmacy). Cox regression modeling included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus "No drug". RESULTS The annual incidence of new-onset diabetes during the exposure period was 3.09 % (22,951 patients). The HR of drug-dependent DM ranged from 0.79 to 2.37. One-third of the studied pharmacotherapies, including most of the antipsychotic-containing regimens, had a significantly higher risk of DM compared to "No drug". A significantly lower DM risk was associated with lithium, lamotrigine, oxcarbazepine and bupropion monotherapies, selective serotonin reuptake inhibitors (SSRI) mono-class therapy and several drug combinations containing bupropion and an SSRI. As additional drugs were combined in more complex polypharmacy, higher HRs were consistently observed. CONCLUSIONS There is an increased risk of diabetes mellitus associated with antipsychotic and psychotropic polypharmacy use in bipolar disorder. The evidence of a lower-than-baseline risk of DM with lamotrigine, oxcarbazepine, lithium, and bupropion monotherapy should be further investigated.
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Affiliation(s)
- Anastasiya Nestsiarovich
- Center for Global Health, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Berit Kerner
- Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | | | | | | | - Yiliang Zhu
- Division of Epidemiology, Biostatistics, and Preventive Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Stuart J Nelson
- University of New Mexico Health Sciences Library and Informatics Center, Albuquerque, NM, USA; Translational Informatics Division, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Tudor I Oprea
- Translational Informatics Division, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Annette S Crisanti
- Department of Psychiatry & Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Mauricio Tohen
- Department of Psychiatry & Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Douglas J Perkins
- Center for Global Health, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Christophe G Lambert
- Center for Global Health, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Translational Informatics Division, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
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Hepatic gene expression explains primary drug toxicity in bipolar disorder. Transl Psychiatry 2019; 9:331. [PMID: 31819046 PMCID: PMC6901567 DOI: 10.1038/s41398-019-0666-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 10/23/2019] [Accepted: 11/06/2019] [Indexed: 11/16/2022] Open
Abstract
In bipolar disorder (BPD), long-term psychotropic drug treatment is often necessary to prevent relapse or recurrence. Nevertheless, adverse drug effects including disturbances in hepatic metabolism are observed and still poorly understood. Here, the association between hepatic gene expression and histopathological changes of the liver was investigated. By the use of microarrays (Affymetrix U133 plus2.0), a genome-wide expression study was performed on BPD patients with psychotropic drug treatment (n = 29) compared to unaffected controls (n = 20) and validated by quantitative real-time PCR. WebGestalt was used to identify over-represented functional pathways of the Reactome database. Association analyses between histopathological changes and differentially expressed genes comprised in the over-represented functional pathways were performed using regression analyses, from which feature-expression heatmaps were drawn. The majority of identified genes were underexpressed and involved in energy supply, metabolism of lipids and proteins, and the innate immune system. Positive associations were found for genes involved in all pathways and degenerative changes. The strongest negative association was observed between genes involved in energy supply and hepatic activity, as well as inflammation. In summary, we found a possible association between gene expression involved in various biological pathways and histopathological changes of the liver in BPD. Further, we found support for the probable primary toxic effect of psychotropic drugs on hepatic injury in BPD. Even if the safety of psychotropic drugs improves, adverse effects especially on hepatic function should not be underestimated.
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Abstract
Objective: We reviewed important clinical aspects of bipolar depression, a progressive psychiatric condition that is commonly treated in primary care. Bipolar depression is associated with considerable burden of illness, high suicide risk, and greater morbidity and mortality than bipolar mania. Methods: We identified articles relevant to our narrative review using a multistep search of the literature and applying terms that were relevant to bipolar depression or bipolar disorder. Results: Bipolar depression accounts for the majority of time spent unwell for patients with bipolar disorder; high rates of morbidity and mortality arise from full symptomatic episodes and interepisode subsyndromal symptoms. Bipolar depression is an important contributor to long-term dysfunction for patients with bipolar disorder due to psychosocial impairment, loss of work productivity and high rates of substance abuse. Missed and delayed diagnosis is prevalent due to overlapping symptoms with unipolar depression and other diagnoses. Medical comorbidities (i.e. cardiovascular disease, hypertension, obesity, metabolic syndrome) and psychiatric comorbidities (i.e. anxiety disorder, personality disorder, eating disorder, attention-deficit/hyperactivity disorder) are common. Currently, only three treatments are FDA-approved for bipolar depression; monotherapy antidepressants are not a recommended treatment option. Conclusions: Bipolar disorder is common among primary care patients presenting with depression; it is often treated exclusively in primary care. Clinicians should be alert for symptoms of bipolar disorder in undiagnosed patients, know what symptoms probabilistically suggest bipolar versus unipolar depression, have expertise in providing ongoing treatment to diagnosed patients, and be knowledgeable about managing common medication-related side effects and comorbidities. Prompt and accurate diagnosis is critical.
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Affiliation(s)
- Roger S McIntyre
- Mood Disorders Psychopharmacology Unit, University Health Network , Toronto , Canada
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26
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Rosenblat JD. Targeting the immune system in the treatment of bipolar disorder. Psychopharmacology (Berl) 2019; 236:2909-2921. [PMID: 30756134 DOI: 10.1007/s00213-019-5175-x] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 01/16/2019] [Indexed: 12/14/2022]
Abstract
RATIONALE Immune dysfunction has been strongly implicated in the pathophysiology of bipolar disorder (BD). As such, numerous clinical trials have investigated the effects of anti-inflammatory agents in the treatment of BD. OBJECTIVES Review clinical studies evaluating the effects of anti-inflammatory agents in the treatment of BD during all illness phases (e.g., depression, mania, and euthymia). METHODS Relevant databases were searched from inception to August 27, 2018 for clinical studies evaluating the effects of anti-inflammatory agents in BD. RESULTS The majority of identified clinical trials evaluated adjunctive anti-inflammatory agents in the acute treatment of bipolar depression, demonstrating antidepressant effects with N-acetylcysteine (NAC), pioglitazone, minocycline, and coenzyme Q10, along with mixed evidence for omega-3s, and non-steroidal anti-inflammatory drugs (NSAIDs). The anti-manic effects of adjunctive anti-inflammatory agents have been minimally studied, with some promising preliminary results supporting potential anti-manic effects of adjunctive celecoxib and NAC. Maintenance studies are also limited, with inadequate evidence to support mood stabilizing effects of anti-inflammatories while euthymic. Regardless of illness phase, early results suggest that anti-inflammatory agents are likely most beneficial in the subgroup of BD with immune dysregulation. CONCLUSIONS Several proof-of-concept clinical trials have shown promising results for anti-inflammatory agents in the treatment of bipolar depression with moderate effect sizes and good tolerability. The effects of anti-inflammatory agents during manic and euthymic periods remains uncertain. Future larger studies, using stratified samples, enriched for participants with immune dysfunction, are required to determine the role of immune modulating agents in the treatment of BD.
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Affiliation(s)
- Joshua D Rosenblat
- Mood Disorder Psychopharmacology Unit, Department of Psychiatry and Pharmacology, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
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Elamragy AA, Abdelhalim AA, Arafa ME, Baghdady YM. Anxiety and depression relationship with coronary slow flow. PLoS One 2019; 14:e0221918. [PMID: 31487310 PMCID: PMC6728014 DOI: 10.1371/journal.pone.0221918] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 08/19/2019] [Indexed: 11/18/2022] Open
Abstract
Background Psychiatric disorders (depression / anxiety) are linked to coronary artery disease (CAD). Coronary slow flow (CSF) is a relatively common form of CAD with the same underlying mechanisms that are attributed to many anatomic and pathophysiologic factors. However, the relationship between psychiatric disorders and CSF is less well-established; and this is the aim of this study. Methods This cross-sectional observational study was conducted on the first 50 consecutive patients diagnosed with CSF by elective coronary angiography (CAG). They were compared with another 50 consecutive patients showing normal coronaries by CAG. Beck Anxiety Inventory and Beck Depression Inventory were used for assessment. CSF was diagnosed by coronary angiography “Thrombolysis In Myocardial Infarction” frame count. Lipid profile was obtained for all patients. Results Traditional risk factors (male gender, smoking, total cholesterol, low-density lipoproteins and triglycerides) were higher in the CSF group. Depression and anxiety scores were also higher in the CSF group. On multivariate analysis, male gender, depression and high triglycerides were the only significant independent predictors of CSF. A significant correlation existed between CSF and both anxiety and depression scores. Both scores were also significantly higher in multivessel vs single vessel affection. Conclusion Psychiatric depression, male gender and high triglycerides are highly associated with CSF in patients undergoing elective CAG. There is a significant correlation between CSF severity and the severity of both anxiety and depression. Further studies are warranted to explore the impact of psychological intervention on CSF and its long-term outcome.
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Fiedorowicz JG, Cyranowski JM, Liu Z, Swartz HA. Changes in inflammation with treatment for bipolar II depression: Pilot trial data on differential effects of psychotherapy and medication. NEUROLOGY, PSYCHIATRY, AND BRAIN RESEARCH 2019; 33:112-118. [PMID: 31920220 PMCID: PMC6952070 DOI: 10.1016/j.npbr.2019.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
OBJECTIVES Limited prospective data, mostly focused on bipolar I disorder, suggests that pro-inflammatory cytokines are elevated in abnormal mood states. We evaluated whether treatment normalizes peripheral markers of inflammation in bipolar II disorder. METHODS Using data from a randomized clinical trial of Interpersonal and Social Rhythm Therapy (IPSRT) + quetiapine vs. IPSRT + placebo for bipolar II depression, we examined whether these treatments for bipolar II depression impact inflammatory cytokines and whether observed changes in cytokines are associated with changes in depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD-17). RESULTS Cytokine values were available for 33 participants who completed baseline and 20-week followup visits. After excluding those with CRP values >=10 mg/L, there were 27 patients available for analysis (IPSRT+quetiapine N=10, IPSRT+placebo N=17). Baseline measure of inflammation did not appear to moderate treatment response, nor was change in HRSD-17 score correlated with changes in cytokines. Those who received IPSRT+quetiapine had significantly greater increases in IL-6 (p=0.02) and TNF-α (p=0.04), even after adjusting for changes in body mass index, than the IPSRT alone group. Descriptively, the quetiapine group showed increases in pro-inflammatory and decreases in anti-inflammatory cytokines and the psychotherapy group showed reduced pro-inflammatory cytokines. CONCLUSIONS Despite both groups showing depression improvement, this small study suggests a more pro-inflammatory cytokine profile over time with quetiapine plus psychotherapy compared to psychotherapy alone. Elevated risk of cardiovascular morbidity and mortality among those with bipolar II disorder underscores the importance of delivering treatments that do not exacerbate these risk factors.
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Li C, Birmaher B, Rooks B, Gill MK, Hower H, Axelson DA, Dickstein DP, Goldstein TR, Liao F, Yen S, Hunt J, Iyengar S, Ryan ND, Strober MA, Keller MB, Goldstein BI. High Prevalence of Metabolic Syndrome Among Adolescents and Young Adults With Bipolar Disorder. J Clin Psychiatry 2019; 80:18m12422. [PMID: 31365195 PMCID: PMC6802953 DOI: 10.4088/jcp.18m12422] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Accepted: 04/17/2019] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Despite abundant literature demonstrating increased metabolic syndrome (MetS) prevalence and important clinical correlates of MetS among middle-age adults with bipolar disorder, little is known about this topic among adolescents and young adults early in their course of bipolar disorder. We therefore examined this topic in the Course and Outcome of Bipolar Youth (COBY) study. METHODS A cross-sectional, retrospective study was conducted of 162 adolescents and young adults (mean ± SD age = 20.8 ± 3.7 years; range, 13.6-28.3 years) with bipolar disorder (I, II, or not otherwise specified, based on DSM-IV) enrolled in COBY between 2000 and 2006. MetS measures (blood pressure, glucose, high-density lipoprotein cholesterol [HDL-C], triglycerides, and waist circumference), defined using the International Diabetes Federation criteria, were obtained at a single timepoint. Mood, comorbidity, and treatment over the 6 months preceding the MetS assessment were evaluated using the Longitudinal Interval Follow-Up Evaluation. RESULTS The prevalence of MetS in the sample was 19.8% (32/162). Low HDL-C (56.5%) and abdominal obesity (46.9%) were the most common MetS criteria. MetS was nominally associated with lower lifetime global functioning at COBY intake (odds ratio [OR] = 0.97, P = .06). MetS was significantly associated with percentage of weeks in full-threshold pure depression (OR = 1.07, P = .02) and percentage of weeks receiving antidepressant medications (OR = 1.06, P = .001) in the preceding 6 months. MetS was not associated with manic symptoms or medications other than antidepressants. CONCLUSIONS The prevalence of MetS in this sample was at least double compared to the general population. Moreover, MetS is associated with increased burden of depression symptoms in this group. Management of early-onset bipolar disorder should integrate strategies focused on modifying MetS risk factors.
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Affiliation(s)
- Christine Li
- Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada,University of Toronto Faculty of Medicine, Toronto, Ontario, Canada
| | - Boris Birmaher
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Brian Rooks
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Mary Kay Gill
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Heather Hower
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Box G-BH, Providence, RI, USA
| | - David A. Axelson
- Department of Psychiatry, Nationwide Children’s Hospital and The Ohio State College of Medicine, Columbus, OH, USA
| | - Daniel P. Dickstein
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Box G-BH, Providence, RI, USA.,Bradley Hospital, Riverside, RI, USA
| | - Tina R. Goldstein
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Fangzi Liao
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Shirley Yen
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Box G-BH, Providence, RI, USA.,Butler Hospital, Riverside, RI, USA
| | - Jeffrey Hunt
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Box G-BH, Providence, RI, USA.,Bradley Hospital, Riverside, RI, USA
| | - Satish Iyengar
- Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Neal D. Ryan
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Michael A. Strober
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | | | - Benjamin I. Goldstein
- Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada,University of Toronto Faculty of Medicine, Toronto, Ontario, Canada
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Cuellar-Barboza AB, Winham SJ, Biernacka JM, Frye MA, McElroy SL. Clinical phenotype and genetic risk factors for bipolar disorder with binge eating: an update. Expert Rev Neurother 2019; 19:867-879. [PMID: 31269819 DOI: 10.1080/14737175.2019.1638764] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Introduction: Clinical and genetic study of psychiatric conditions has underscored the co-occurrence of complex phenotypes and the need to refine them. Bipolar Disorder (BD) and Binge Eating (BE) behavior are common psychiatric conditions that have high heritability and high co-occurrence, such that at least one quarter of BD patients have BE (BD + BE). Genetic studies of BD alone and of BE alone suggest complex polygenic risk models, with many genetic risk loci yet to be identified. Areas covered: We review studies of the epidemiology of BD+BE, its clinical features (cognitive traits, psychiatric comorbidity, and role of obesity), genomic studies (of BD, eating disorders (ED) defined by BE, and BD + BE), and therapeutic implications of BD + BE. Expert opinion: Subphenotyping of complex psychiatric disorders reduces heterogeneity and increases statistical power and effect size; thus, it enhances our capacity to find missing genetic (and other) risk factors. BD + BE has a severe clinical picture and genetic studies suggests a distinct genetic architecture. Differential therapeutic interventions may be needed for patients with BD + BE compared with BD patients without BE. Recognizing the BD + BE subphenotype is an example of moving towards more precise clinical and genetic entities.
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Affiliation(s)
- Alfredo B Cuellar-Barboza
- Universidad Autonoma de Nuevo Leon, Department of Psychiatry, School of Medicine , Monterrey , NL , Mexico.,Department of Psychiatry and Psychology, Mayo Clinic , Rochester , MN , USA
| | - Stacey J Winham
- Department of Psychiatry and Psychology, Mayo Clinic , Rochester , MN , USA.,Department of Health Sciences Research, Mayo Clinic , Rochester , MN , USA
| | - Joanna M Biernacka
- Department of Psychiatry and Psychology, Mayo Clinic , Rochester , MN , USA.,Department of Health Sciences Research, Mayo Clinic , Rochester , MN , USA
| | - Mark A Frye
- Department of Psychiatry and Psychology, Mayo Clinic , Rochester , MN , USA.,Department of Health Sciences Research, Mayo Clinic , Rochester , MN , USA
| | - Susan L McElroy
- Lindner Center of HOPE , Mason , OH , USA.,Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati , Cincinnati , OH , USA
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Murru A, Guiso G, Barbuti M, Anmella G, Verdolini N, Samalin L, Azorin JM, Angst JJ, Bowden CL, Mosolov S, Young AH, Popovic D, Valdes M, Perugi G, Vieta E, Pacchiarotti I. The implications of hypersomnia in the context of major depression: Results from a large, international, observational study. Eur Neuropsychopharmacol 2019; 29:471-481. [PMID: 30846287 DOI: 10.1016/j.euroneuro.2019.02.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/31/2019] [Accepted: 02/14/2019] [Indexed: 02/07/2023]
Abstract
According to the DSM-5, "reduction in the need for sleep" is the only sleep-related criteria for mixed features in depressive episodes. We aimed at studying the prevalence, clinical correlates and the role of hypersomnia in a sample of acutely depressed patients. Secondarily, we factors significantly increasing the odds of hypersomnia were studied. We conducted a post-hoc analysis of the BRIDGE-II-Mix study. Variables were compared between patients with hypersomnia (SLEEP+) and with insomnia (SLEEP-) with standard bivariate tests. A stepwise backward logistic regression model was performed with SLEEP+ as dependent variable. A total of 2514 subjects were dichotomized into SLEEP+ (n = 423, 16.8%) and SLEEP- (n = 2091, 83.2%). SLEEP+ had significant higher rates of obese BMI (p < 0.001), BD diagnosis (p = 0.027), severe BD (p < 0.001), lifetime suicide attempts (p < 0.001), lower age at first depression (p = 0.004) than SLEEP-. Also, SLEEP+ had significantly poorer response to antidepressants (AD) such as (hypo)manic switches, AD resistance, affective lability, or irritability (all 0<0.005). Moreover, SLEEP+ had significantly higher rates of mixed-state specifiers than SLEEP- (all 0 < 0.006). A significant contribution to hypersomnia in our regression model was driven by metabolic-related features, such as "current bulimia" (OR = 4.21) and "overweight/obese BMI (OR = 1.42)". Globally, hypersomnia is associated with poor outcome in acute depression. Hypersomnia is strongly associated with mixed features and bipolarity. Metabolic aspects could influence the expression of hypersomnia, worsening the overall clinical outcome. Along with commonly used screening tools, detection of hypersomnia has potential, costless discriminative validity in the differential diagnosis unipolar and bipolar depression.
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Affiliation(s)
- A Murru
- Barcelona Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
| | - G Guiso
- Barcelona Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Clinica Psichiatrica, Dipartimento di Igiene e Sanità, Università di Cagliari, Italy
| | - M Barbuti
- Division of Psychiatry, Clinical Psychology and Rehabilitation, Department of Medicine, University of Perugia, Santa Maria della Misericordia Hospital, Edificio Ellisse, 8 Piano, Sant'Andrea delle Fratte, 06132, Perugia, Italy
| | - G Anmella
- Barcelona Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
| | - N Verdolini
- Barcelona Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Sant Boi de Llobregat, Barcelona, Catalonia, Spain; Division of Psychiatry, Clinical Psychology and Rehabilitation, Department of Medicine, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
| | - L Samalin
- Barcelona Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; CHU Clermont-Ferrand, Department of Psychiatry, University of Auvergne, Clermont-Ferrand, France; Fondation FondaMental, Hôpital Albert Chenevier, Pôle de Psychiatrie, Créteil, France
| | - J M Azorin
- Fondation FondaMental, Hôpital Albert Chenevier, Pôle de Psychiatrie, Créteil, France
| | - J Jules Angst
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
| | - C L Bowden
- University of Texas Health Science Center, San Antonio, USA
| | - S Mosolov
- Moscow Research Institute of Psychiatry, Russia
| | - A H Young
- Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - D Popovic
- Barcelona Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Psychiatry B, Sheba Medical Center, Israel
| | - M Valdes
- Department of Medicine, Sleep Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM; Barcelona, Catalonia, Spain
| | - G Perugi
- Division of Psychiatry, Clinical Psychology and Rehabilitation, Department of Medicine, University of Perugia, Santa Maria della Misericordia Hospital, Edificio Ellisse, 8 Piano, Sant'Andrea delle Fratte, 06132, Perugia, Italy
| | - E Vieta
- Barcelona Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
| | - I Pacchiarotti
- Barcelona Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
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Huang TT, Lai JB, Du YL, Xu Y, Ruan LM, Hu SH. Current Understanding of Gut Microbiota in Mood Disorders: An Update of Human Studies. Front Genet 2019; 10:98. [PMID: 30838027 PMCID: PMC6389720 DOI: 10.3389/fgene.2019.00098] [Citation(s) in RCA: 168] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 01/29/2019] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota plays an important role in the bidirectional communication between the gut and the central nervous system. Mounting evidence suggests that gut microbiota can influence the brain function via neuroimmune and neuroendocrine pathways as well as the nervous system. Advances in gene sequencing techniques further facilitate investigating the underlying relationship between gut microbiota and psychiatric disorders. In recent years, researchers have preliminarily explored the gut microbiota in patients with mood disorders. The current review aims to summarize the published human studies of gut microbiota in mood disorders. The findings showed that microbial diversity and taxonomic compositions were significantly changed compared with healthy individuals. Most of these findings revealed that short-chain fatty acids-producing bacterial genera were decreased, while pro-inflammatory genera and those involved in lipid metabolism were increased in patients with depressive episodes. Interestingly, the abundance of Actinobacteria, Enterobacteriaceae was increased and Faecalibacterium was decreased consistently in patients with either bipolar disorder or major depressive disorder. Some studies further indicated that specific bacteria were associated with clinical characteristics, inflammatory profiles, metabolic markers, and pharmacological treatment. These studies present preliminary evidence of the important role of gut microbiota in mood disorders, through the brain-gut-microbiota axis, which emerges as a promising target for disease diagnosis and therapeutic interventions in the future.
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Affiliation(s)
- Ting-Ting Huang
- Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian-Bo Lai
- Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,The Key Laboratory of Mental Disorder's Management of Zhejiang Province, Hangzhou, China.,Brain Research Institute of Zhejiang University, Hangzhou, China
| | - Yan-Li Du
- Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yi Xu
- Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,The Key Laboratory of Mental Disorder's Management of Zhejiang Province, Hangzhou, China.,Brain Research Institute of Zhejiang University, Hangzhou, China
| | - Lie-Min Ruan
- Department of Mental Health, Ningbo First Hospital, Ningbo, China
| | - Shao-Hua Hu
- Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,The Key Laboratory of Mental Disorder's Management of Zhejiang Province, Hangzhou, China.,Brain Research Institute of Zhejiang University, Hangzhou, China
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Wulsin LR, Blom TJ, Durling M, Welge JA, DelBello MP, Adler CM, McNamara RK, Strakowski SM. Cardiometabolic risks and omega-3 index in recent-onset bipolar I disorder. Bipolar Disord 2018; 20:658-665. [PMID: 29479787 DOI: 10.1111/bdi.12633] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVES The aims of the present study were to characterize cardiometabolic risk factors in a cohort of bipolar disorder patients with limited exposure to psychotropic medications, and to evaluate their associations with mood symptoms and omega-3 polyunsaturated fatty acid (PUFA) blood levels. METHODS Cardiometabolic risk assessments were compared in individuals with bipolar I disorder experiencing a first manic or mixed episode or an early depressive episode (n=117) and healthy subjects (n=56). Patients were medication free at assessment and had no or limited exposure to mood-stabilizer or antipsychotic medications prior to the current admission. Associations among cardiometabolic parameters and Clinical Global Impression-Severity scale (CGI-S), manic (Young Mania Rating Scale [YMRS]), and depressive (Hamilton Depression Rating Scale [HDRS]) symptom ratings were evaluated within the bipolar group. RESULTS Following adjustment for demographic variables (i.e., age, gender, and parental education), significantly higher fasting triglyceride levels were observed in the bipolar group compared to the healthy group (121.7 mg/dL vs 87.0 mg/dL; P<.01). There were no clear trends for other metabolic indicators, including blood pressure, body mass index, and fasting glucose. Nineteen percent of the bipolar group and 6% of the healthy group met the criteria for metabolic syndrome (P=.23). The omega-3 index was lower in the bipolar group (3.4% vs 3.9%; P<.01). Within the bipolar group, no associations were found between the cardiometabolic parameters and CGI-S, YMRS, and HDRS symptom ratings. CONCLUSIONS Recent-onset medication-free bipolar disorder is associated with higher triglyceride levels. These findings are suggestive of early metabolic dysregulation prior to long-term psychotropic medication exposure. Lower omega-3 PUFA levels in individuals with bipolar I disorder represent a potential therapeutic target for additional investigation.
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Affiliation(s)
- Lawson R Wulsin
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Thomas J Blom
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Michelle Durling
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Jeffrey A Welge
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Melissa P DelBello
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Caleb M Adler
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Robert K McNamara
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Stephen M Strakowski
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment. Sci Rep 2018; 8:12743. [PMID: 30143692 PMCID: PMC6109159 DOI: 10.1038/s41598-018-31122-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 08/08/2018] [Indexed: 02/06/2023] Open
Abstract
Mitochondrial pathology has been implicated in the pathogenesis of psychotic disorders. A few studies have proposed reduced leukocyte mitochondrial DNA (mtDNA) copy number in schizophrenia and bipolar disorder type I, compared to healthy controls. However, it is unknown if mtDNA copy number alteration is driven by psychosis, comorbidity or treatment. Whole blood mtDNA copy number was determined in 594 psychosis patients and corrected for platelet to leukocyte count ratio (mtDNAcnres). The dependence of mtDNAcnres on clinical profile, metabolic comorbidity and antipsychotic drug exposure was assessed. mtDNAcnres was reduced with age (β = −0.210, p < 0.001), use of clozapine (β = −0.110,p = 0.012) and risperidone (β = −0.109,p = 0.014), dependent on prescribed dosage (p = 0.006 and p = 0.026, respectively), and the proportion of life on treatment (p = 0.006). Clozapine (p = 0.0005) and risperidone (p = 0.0126) had a reducing effect on the mtDNA copy number also in stem cell-derived human neurons in vitro at therapeutic plasma levels. For patients not on these drugs, psychosis severity had an effect (β = −0.129, p = 0.017), similar to age (β = −0.159, p = 0.003) and LDL (β = −0.119, p = 0.029) on whole blood mtDNAcnres. Further research is required to determine if mtDNAcnres reflects any psychosis-intrinsic mitochondrial changes.
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Socioeconomic Disparities and Metabolic Risk in Veterans with Serious Mental Illness. Community Ment Health J 2018; 54:725-734. [PMID: 29285684 DOI: 10.1007/s10597-017-0215-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Accepted: 12/23/2017] [Indexed: 01/26/2023]
Abstract
Socioeconomic disparities were assessed in predicting metabolic risk among veterans with serious mental illness. Veterans with schizophrenia, schizoaffective, or bipolar disorders were identified in VISN 4 facilities from 10/1/2010 to 9/30/2012. Differences between patients with and without metabolic syndrome were compared using t-tests, Chi square tests and multivariate logistic regressions. Among 10,132 veterans with mental illness, 48.8% had metabolic syndrome. Multivariate logistic regression analysis confirmed that patients with metabolic syndrome were significantly more likely to be older, male, African-American, married, and receiving disability pensions but less likely to be homeless. They were more likely to receive antipsychotics, antidepressants, or anticonvulsants. Bivariate cross-sectional analysis revealed that patients with metabolic syndrome had higher rates of coronary artery disease, cerebrovascular disease, and mortality, and that metabolic syndrome was more often associated with emergency visits and psychiatric or medical hospitalizations. Demographics, socioeconomic status and medications are independent predictors of metabolic syndrome and should be considered in broader screening of risk factors in order to provide preventive interventions for metabolic syndrome.
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Brand S, Colledge F, Ludyga S, Emmenegger R, Kalak N, Sadeghi Bahmani D, Holsboer-Trachsler E, Pühse U, Gerber M. Acute Bouts of Exercising Improved Mood, Rumination and Social Interaction in Inpatients With Mental Disorders. Front Psychol 2018; 9:249. [PMID: 29593592 PMCID: PMC5859016 DOI: 10.3389/fpsyg.2018.00249] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 02/15/2018] [Indexed: 11/13/2022] Open
Abstract
Background: Studies at the macro level (such as longer-term interventions) showed that physical activity impacts positively on cognitive-emotional processes of patients with mental disorders. However, research focusing on the immediate impact of acute bouts of exercise (micro level) are missing. The aim of the present study was therefore to investigate whether and to what extent single bouts of moderately intense exercise can influence dimensions of psychological functioning in inpatients with mental disorders. Method: 129 inpatients (mean age: 38.16 years; 50.4% females) took part and completed a questionnaire both immediately before and immediately after exercising. Thirty inpatients completed the questionnaires a second time in the same week. The questionnaire covered socio-demographic and illness-related information. Further, the questionnaire asked about current psychological states such as mood, rumination, social interactions, and attention, tiredness, and physical strengths as a proxy of physiological states. Results: Psychological states improved from pre- to post-session. Improvements were observed for mood, social interactions, attention, and physical strengths. Likewise, rumination and tiredness decreased. Mood, rumination, and tiredness further improved, when patients completed the questionnaires the second time in the same week. Conclusion: At micro level, single bouts of exercise impacted positively on cognitive-emotional processes such as mood, rumination, attention and social interactions, and physiological states of tiredness and physical strengths among inpatients with mental disorders. In addition, further improvements were observed, if patients participated in physical activities a second time.
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Affiliation(s)
- Serge Brand
- Division of Sport Science and Psychosocial Health, Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
- Center for Affective, Stress and Sleep Disorders, Psychiatric Clinics, University of Basel, Basel, Switzerland
- Substance Abuse Prevention Research Center and Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Flora Colledge
- Division of Sport Science and Psychosocial Health, Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
| | - Sebastian Ludyga
- Division of Sport Science and Psychosocial Health, Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
| | - Raphael Emmenegger
- Division of Sport Science and Psychosocial Health, Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
| | - Nadeem Kalak
- Center for Affective, Stress and Sleep Disorders, Psychiatric Clinics, University of Basel, Basel, Switzerland
| | - Dena Sadeghi Bahmani
- Center for Affective, Stress and Sleep Disorders, Psychiatric Clinics, University of Basel, Basel, Switzerland
- Substance Abuse Prevention Research Center and Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Edith Holsboer-Trachsler
- Center for Affective, Stress and Sleep Disorders, Psychiatric Clinics, University of Basel, Basel, Switzerland
| | - Uwe Pühse
- Division of Sport Science and Psychosocial Health, Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
| | - Markus Gerber
- Division of Sport Science and Psychosocial Health, Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
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Kristensen M, Nierenberg AA, Østergaard SD. Face and predictive validity of the ClockΔ19 mouse as an animal model for bipolar disorder: a systematic review. Mol Psychiatry 2018; 23:70-80. [PMID: 29112195 DOI: 10.1038/mp.2017.192] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 07/13/2017] [Accepted: 07/17/2017] [Indexed: 02/07/2023]
Abstract
Mice carrying the circadian locomotor output cycles Kaput delta 19 N-ethyl-N-nitrosoure (ENU) mutation (ClockΔ19) are used as an animal model for bipolar disorder (BD). We aimed to systematically review the face validity (phenotypical and pathophysiological resemblance with BD) and predictive validity (responsiveness to treatments used in BD) of this model in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We carried out a systematic search of the databases PubMed and Embase, combining search terms covering BD and ClockΔ19. The 22 studies included in the review (from a total of 1281 identified records) show that the behavioral phenotype of the ClockΔ19 mouse is characterized by hyperactivity, decreased anxiety-like behavior, decreased depression-like behavior and increased preference for rewarding stimuli. This is highly consistent with mania in humans. Moreover, the ClockΔ19 mouse exhibits rapid mood cycling (a manic-like phenotype during the day followed by euthymia at night), which is consistent with BD. Chronic administration of lithium, a drug with well established mood-stabilizing effect in humans with BD, reverses the majority of the bipolar-like traits and most of the neurobiological abnormalities observed in the ClockΔ19 mouse. In conclusion, the ClockΔ19 mouse has substantial face validity as an animal model for BD. The predictive validity of the ClockΔ19 mouse has primarily been investigated via studies using lithium challenge. Therefore, further studies are needed to determine how the ClockΔ19 mouse responds to other mood-stabilizing treatments of BD such as valproate, lamotrigine, carbamazepine, oxcarbazepine, antipsychotics, electroconvulsive therapy and various light interventions.
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Affiliation(s)
- M Kristensen
- Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - A A Nierenberg
- Bipolar Clinic and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - S D Østergaard
- Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark
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Depression and cardiovascular disease in elderly: Current understanding. J Clin Neurosci 2018; 47:1-5. [DOI: 10.1016/j.jocn.2017.09.022] [Citation(s) in RCA: 164] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Revised: 09/25/2017] [Accepted: 09/29/2017] [Indexed: 12/18/2022]
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Duarte-Guerra LS, Coêlho BM, Santo MA, Lotufo-Neto F, Wang YP. Morbidity persistence and comorbidity of mood, anxiety, and eating disorders among preoperative bariatric patients. Psychiatry Res 2017; 257:1-6. [PMID: 28709116 DOI: 10.1016/j.psychres.2017.07.020] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Revised: 07/01/2017] [Accepted: 07/10/2017] [Indexed: 11/26/2022]
Abstract
The current study investigates the patterns of disease persistence and comorbidity of psychiatric disorders among patients with class III obesity in pre-operative period. For 393 treatment-seeking patients with severe obesity recruited from a bariatric center, we ascertained their psychiatric diagnosis through Structured Clinical Interview for DSM-IV (SCID-I). Following, the frequency, persistence and comorbidity pattern of psychiatric disorders in this sample were determined. Current psychiatric disorders were observed in over half of patients during preoperative period, being anxiety disorders the most frequent diagnosis. For lifetime disorders, mood disorders were the most frequent diagnosis. Most of the sample presented 2 or more concurrent lifetime psychiatric disorders. While mood and eating disorders were frequent conditions, anxiety disorders were the most persistent conditions (the highest one month-to-lifetime prevalence ratio) and were significantly correlated with bipolar, depressive and eating disorders. Psychiatric disorders are frequent and enduring conditions among patients looking for bariatric surgery. Comorbid anxiety, mood, and eating disorders are remarkable features in treatment-seeking patients with obesity. Prognostic implications of preoperative psychiatric disorders on surgery outcome should be demonstrated prospectively in intervention studies.
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Affiliation(s)
| | - Bruno Mendonça Coêlho
- Department and Institute of Psychiatry (LIM-23), University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Marco Aurélio Santo
- Department of Surgery, University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Francisco Lotufo-Neto
- Department and Institute of Psychiatry (LIM-23), University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Yuan-Pang Wang
- Department and Institute of Psychiatry (LIM-23), University of São Paulo Medical School, São Paulo, SP, Brazil.
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Bipolar Disorder and Immune Dysfunction: Epidemiological Findings, Proposed Pathophysiology and Clinical Implications. Brain Sci 2017; 7:brainsci7110144. [PMID: 29084144 PMCID: PMC5704151 DOI: 10.3390/brainsci7110144] [Citation(s) in RCA: 163] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 10/25/2017] [Accepted: 10/27/2017] [Indexed: 12/22/2022] Open
Abstract
Bipolar disorder (BD) is strongly associated with immune dysfunction. Replicated epidemiological studies have demonstrated that BD has high rates of inflammatory medical comorbidities, including autoimmune disorders, chronic infections, cardiovascular disease and metabolic disorders. Cytokine studies have demonstrated that BD is associated with chronic low-grade inflammation with further increases in pro-inflammatory cytokine levels during mood episodes. Several mechanisms have been identified to explain the bidirectional relationship between BD and immune dysfunction. Key mechanisms include cytokine-induced monoamine changes, increased oxidative stress, pathological microglial over-activation, hypothalamic-pituitary-adrenal (HPA) axis over-activation, alterations of the microbiome-gut-brain axis and sleep-related immune changes. The inflammatory-mood pathway presents several potential novel targets in the treatment of BD. Several proof-of-concept clinical trials have shown a positive effect of anti-inflammatory agents in the treatment of BD; however, further research is needed to determine the clinical utility of these treatments. Immune dysfunction is likely to only play a role in a subset of BD patients and as such, future clinical trials should also strive to identify which specific group(s) of BD patients may benefit from anti-inflammatory treatments.
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Subramaniapillai M, Carmona NE, Rong C, McIntyre RS. Inflammation: opportunities for treatment stratification among individuals diagnosed with mood disorders. DIALOGUES IN CLINICAL NEUROSCIENCE 2017. [PMID: 28566945 PMCID: PMC5442361 DOI: 10.31887/dcns.2017.19.1/rmcintyre] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Mood disorders continue to be a significant burden to those affected, resulting in significant illness-associated disability and premature mortality. In addition to mood disturbance, individuals also suffer from other transdiagnostic impairments (eg, anhedonia and cognitive impairment). Although there have been significant advancements in psychiatric treatment over the last few decades, treatment efficacy (eg, symptom remission, lack of functional recovery, and disease modification) continues to be an important limitation. Consequently, there is an urgent need to identify novel approaches capable of addressing the foregoing needs, providing the basis for the exploration of conceptual models and treatment opportunities that consider inflammation to be a key factor in mood disorder development. In part driven by metabolic comorbidities, a large proportion of individuals with mood disorders also have an imbalance in the inflammatory milieu. The aim of this review is to highlight evidence implicating inflammation in various effector systems in mood disorders, with a particular focus on the intercommunication with glutamatergic signaling, immune system signaling, as well as metabolic parameters (eg, L-methyl folate bioavailability). This article also briefly reviews novel and repurposed agents that are capable of targeting the innate immune inflammatory system and possibly correcting an abnormal immune/inflammatory milieu (eg, infliximab).
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Affiliation(s)
| | | | | | - Roger S McIntyre
- Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada ; Department of Pharmacology, University of Toronto, Toronto, Canada
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de Melo LGP, Nunes SOV, Anderson G, Vargas HO, Barbosa DS, Galecki P, Carvalho AF, Maes M. Shared metabolic and immune-inflammatory, oxidative and nitrosative stress pathways in the metabolic syndrome and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry 2017; 78:34-50. [PMID: 28438472 DOI: 10.1016/j.pnpbp.2017.04.027] [Citation(s) in RCA: 119] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 03/27/2017] [Accepted: 04/08/2017] [Indexed: 02/08/2023]
Abstract
This review examines the shared immune-inflammatory, oxidative and nitrosative stress (IO&NS) and metabolic pathways underpinning metabolic syndrome (MetS), bipolar disorder (BD) and major depressive disorder (MDD). Shared pathways in both MetS and mood disorders are low grade inflammation, including increased levels of pro-inflammatory cytokines and acute phase proteins, increased lipid peroxidation with formation of malondialdehyde and oxidized low density lipoprotein cholesterol (LDL-c), hypernitrosylation, lowered levels of antioxidants, most importantly zinc and paraoxonase (PON1), increased bacterial translocation (leaky gut), increased atherogenic index of plasma and Castelli risk indices; and reduced levels of high-density lipoprotein (HDL-c) cholesterol. Insulin resistance is probably not a major factor associated with mood disorders. Given the high levels of IO&NS and metabolic dysregulation in BD and MDD and the high comorbidity with the atherogenic components of the MetS, mood disorders should be viewed as systemic neuro-IO&NS-metabolic disorders. The IO&NS-metabolic biomarkers may have prognostic value and may contribute to the development of novel treatments targeting neuro-immune, neuro-oxidative and neuro-nitrosative pathways.
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Affiliation(s)
- Luiz Gustavo Piccoli de Melo
- Department of Clinical Medicine, Londrina State University (UEL), Health Sciences Centre, Londrina, Paraná, Brazil; Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, University Campus, Londrina, Paraná, Brazil; Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil
| | - Sandra Odebrecht Vargas Nunes
- Department of Clinical Medicine, Londrina State University (UEL), Health Sciences Centre, Londrina, Paraná, Brazil; Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, University Campus, Londrina, Paraná, Brazil; Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil
| | | | - Heber Odebrecht Vargas
- Department of Clinical Medicine, Londrina State University (UEL), Health Sciences Centre, Londrina, Paraná, Brazil; Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, University Campus, Londrina, Paraná, Brazil; Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil
| | - Décio Sabbattini Barbosa
- Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil; Department of Clinical and Toxicological Analysis, State University of Londrina, Londrina, Paraná, Brazil
| | - Piotr Galecki
- Department of Adult Psychiatry, University of Lodz, Lodz, Poland
| | - André F Carvalho
- Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Michael Maes
- Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil; Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand; Department of Psychiatry, Plovdiv University, Plovdiv, Bulgaria; Revitalis, Waalre, The Netherlands; Impact Strategic Research Center, Deakin University, Geelong, Australia.
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Abstract
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) mixed features specifier provides a less restrictive definition of mixed mood states, compared to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), including mood episodes that manifest with subthreshold symptoms of the opposite mood state. A limited number of studies have assessed the efficacy of treatments specifically for DSM-5-defined mixed features in mood disorders. As such, there is currently an inadequate amount of data to appropriately inform evidence-based treatment guidelines of DSM-5 defined mixed features. However, given the high prevalence and morbidity of mixed features, treatment recommendations based on the currently available evidence along with expert opinion may be of benefit. This article serves to provide these interim treatment recommendations while humbly acknowledging the limited amount of evidence currently available. Second-generation antipsychotics (SGAs) appear to have the greatest promise in the treatment of bipolar disorder (BD) with mixed features. Conventional mood stabilizing agents (ie, lithium and divalproex) may also be of benefit; however, they have been inadequately studied. In the treatment of major depressive disorder (MDD) with mixed features, the comparable efficacy of antidepressants versus other treatments, such as SGAs, remains unknown. As such, antidepressants remain first-line treatment of MDD with or without mixed features; however, there are significant safety concerns associated with antidepressant monotherapy when mixed features are present, which merits increased monitoring. Lurasidone is the only SGA monotherapy that has been shown to be efficacious specifically in the treatment of MDD with mixed features. Further research is needed to accurately determine the efficacy, safety, and tolerability of treatments specifically for mood episodes with mixed features to adequately inform future treatment guidelines.
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SayuriYamagata A, Brietzke E, Rosenblat JD, Kakar R, McIntyre RS. Medical comorbidity in bipolar disorder: The link with metabolic-inflammatory systems. J Affect Disord 2017; 211:99-106. [PMID: 28107669 DOI: 10.1016/j.jad.2016.12.059] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 12/23/2016] [Accepted: 12/31/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Bipolar disorder (BD) is associated with chronic low-grade inflammation, several medical comorbidities and a decreased life expectancy. Metabolic-inflammatory changes have been postulated as one of the main links between BD and medical comorbidity, although there are few studies exploring possible mechanisms underlying this relationship. Therefore, the aims of the current narrative review were 1) synthesize the evidence for metabolic-inflammatory changes that may facilitate the link between medical comorbidity and BD and 2) discuss therapeutic and preventive implications of these pathways. METHODS The PubMed and Google Scholar databases were searched for relevant studies. RESULTS Identified studies suggested that there is an increased risk of medical comorbidities, such as autoimmune disorders, obesity, diabetes and cardiovascular disease in patients with BD. The association between BD and general medical comorbidities seems to be bidirectional and potentially mediated by immune dysfunction. Targeting the metabolic-inflammatory-mood pathway may potential yield improved outcomes in BD; however, further study is needed to determine which specific interventions may be beneficial. LIMITATIONS The majority of identified studies had cross-sectional designs, small sample sizes and limited measurements of inflammation. CONCLUSIONS Treatment and prevention of general medical comorbidities in mood disorders should include preferential prescribing of metabolically neutral agents and adjunctive lifestyle modifications including increased physical activity, improved diet and decreased substance abuse. In addition, the use of anti-inflammatory agents could be a relevant therapeutic target in future research.
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Affiliation(s)
- Ana SayuriYamagata
- University of São Paulo (USP), São Paulo, Brazil; Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Federal University of São Paulo (Unifesp), São Paulo, Brazil
| | - Elisa Brietzke
- Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Federal University of São Paulo (Unifesp), São Paulo, Brazil
| | - Joshua D Rosenblat
- Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto, Toronto, Canada
| | - Ron Kakar
- Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto, Toronto, Canada
| | - Roger S McIntyre
- Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto, Toronto, Canada.
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Pikalov A, Tsai J, Mao Y, Silva R, Cucchiaro J, Loebel A. Long-term use of lurasidone in patients with bipolar disorder: safety and effectiveness over 2 years of treatment. Int J Bipolar Disord 2017; 5:9. [PMID: 28168632 PMCID: PMC5332323 DOI: 10.1186/s40345-017-0075-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 01/13/2017] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Bipolar disorder is a chronic illness with a 2-year recurrence rate of approximately 50% among individuals receiving treatment in the community. The aim of this 18-month, open-label, continuation study was to evaluate the long-term safety and effectiveness of lurasidone in patients who initially presented with a major depressive episode associated with bipolar disorder, and who had completed at least 6 months of initial treatment with lurasidone. METHODS Patients with bipolar I depression were enrolled in one of three 6-week, double-blind, placebo-controlled trials (monotherapy with lurasidone, 1 study; adjunctive therapy with lurasidone; and lithium or valproate, 2 studies). Study completers were eligible for a 6-month, open-label extension study of lurasidone utilizing flexible daily doses of 20-120 mg; extension completers were then eligible for an additional 18 months of continuation treatment with flexible, once-daily doses of lurasidone in the range of 20-80 mg. Concomitant therapy with mood stabilizers was permitted throughout the open-label extension and continuation studies. RESULTS A total of 1199 patients entered, and 941 (78.5%) completed initial, double-blind, acute treatment, of whom 817/941 (86.8%) entered, and 559 (68.4%) completed the 6-month extension study; 122/559 patients (21.8%) entered the 18-month continuation study, of whom 19.7% of discontinued, including 6.6% due to adverse events and 1.6% due to insufficient efficacy. The mean dose of lurasidone during the 18-month continuation study was 61.8 mg/day, and the modal dose was 60 mg/day. Mean change in weight, from acute baseline to 18-month continuation endpoint was +0.8 kg (completers, n = 55); median changes in cholesterol and triglycerides were -3.0 mg/dL and +26.0 mg/dL, respectively. Based on a Kaplan-Meier analysis, the probability of relapse during 18 months of continuation treatment with lurasidone was estimated to be 18.3% in the monotherapy group and 29.1% in the adjunctive therapy group. Improvement in global illness severity was also maintained during 18 months of continuation therapy (CGI-S at continuation baseline, 2.1; 18-month completers, 1.7; LOCF-endpoint, 1.9). CONCLUSIONS Up to 2 years of treatment with lurasidone was safe and well tolerated in this bipolar disorder population presenting with an index episode of depression. Improvement in depressive symptoms was maintained in the majority of patients treated with lurasidone, with relatively low rates of relapse, and with minimal effects on weight and metabolic parameters.
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Affiliation(s)
- Andrei Pikalov
- Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ, 07024, USA.
| | - Joyce Tsai
- Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ, 07024, USA
| | - Yongcai Mao
- Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ, 07024, USA
| | - Robert Silva
- Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ, 07024, USA
| | - Josephine Cucchiaro
- Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ, 07024, USA
| | - Antony Loebel
- Sunovion Pharmaceuticals Inc., One Bridge Plaza North, Suite 510, Fort Lee, NJ, 07024, USA
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47
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Chen PH, Chang CK, Chiang SJ, Lin YK, Tsai SY, Huang SH. Diabetes mellitus and first episode mania associated with cardiovascular diseases in patients with older-age bipolar disorder. Psychiatry Res 2017; 249:65-69. [PMID: 28073032 DOI: 10.1016/j.psychres.2017.01.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 01/01/2017] [Accepted: 01/01/2017] [Indexed: 01/06/2023]
Abstract
Patients with bipolar disorder (BD) are at high risk for developing cardiovascular diseases (CVDs) during aging process. However, investigations are lacking regarding the risk factors for CVDs specific to BD patients. The aim of this study was to examine the relationship between CVDs and traditional risk factors in association with the characteristics of BD in older age. Totally, we recruited 124 patients with BD-I (DSM-IV) who had at least one psychiatric admission and cardiologist-confirmed CVD diagnosis (ICD-9 code 401-414) at mean age of 61.7+4.9 years. Each case subject was matched with one BD-I patient without CVDs based on age, sex, and date of the most recent psychiatric admission (+2 years). Clinical data were obtained by retrospectively reviewing the medical record. A multiple logistic regression model showed that not only traditional risk factor (e.g., diabetes mellitus) but also non-traditional one associated with BD (e.g., first episode mania) significantly increased the risk of CVDs. Given the limitation of this cross-sectional study, longitudinal investigations are needed to elucidate the contributions of both traditional risk factors and the BD characteristics for CVD risk in patients with BD.
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Affiliation(s)
- Pao-Huan Chen
- Department of Psychiatry, Taipei Medical University Hospital, Taipei, Taiwan; Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
| | - Chi-Kang Chang
- Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan
| | - Shuo-Ju Chiang
- Division of Cardiology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yen-Kuang Lin
- Biostatistics Center, Taipei Medical University, Taipei, Taiwan
| | - Shang-Ying Tsai
- Department of Psychiatry, Taipei Medical University Hospital, Taipei, Taiwan; Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Shou-Hung Huang
- Department of Psychiatry, Taipei Medical University Hospital, Taipei, Taiwan; Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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48
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Duque-Guimarães D, Ong TP, de Almeida-Faria J, Guest PC, Ozanne SE. SILAC Mass Spectrometry Profiling: A Psychiatric Disorder Perspective. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 974:289-298. [PMID: 28353248 DOI: 10.1007/978-3-319-52479-5_27] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/15/2024]
Abstract
Stable isotope labelling by amino acids in cell culture (SILAC) is a technique that allows proteomic profiling of cells. In this chapter we describe a protocol for the identification and quantification of newly synthesised proteins. The methodology can be applied to any cultured cell system with relevance to schizophrenia, affective disorders and autism spectrum conditions including those addressing responses to pharmacological stimuli.
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Affiliation(s)
- Daniella Duque-Guimarães
- University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Thomas Prates Ong
- University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
- Food Research Center (FoRC) and Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Juliana de Almeida-Faria
- University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
- Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
| | - Paul C Guest
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Rua Monteiro Lobato 255 F/01, Cidade Universitária ZeferinoVaz, 13083-862, Campinas, Brazil
| | - Susan E Ozanne
- University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
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49
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Bai YM, Li CT, Tsai SJ, Tu PC, Chen MH, Su TP. Metabolic syndrome and adverse clinical outcomes in patients with bipolar disorder. BMC Psychiatry 2016; 16:448. [PMID: 27978821 PMCID: PMC5159954 DOI: 10.1186/s12888-016-1143-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Accepted: 11/25/2016] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Metabolic syndrome (MetS) is highly prevalent among patients with bipolar disorder. MetS may cause complications in the brain, but studies investigating MetS-associated clinical psychiatric outcomes remain scant. METHODS We enrolled clinically stable outpatients with bipolar disorder aged 18-65 years and performed anthropometric and fasting biochemical assessments to investigate MetS prevalence. We then performed clinical assessments by using the Young Mania Rating Scale for manic symptoms, the Montgomery-Åsberg Depression Rating Scale for depressive symptoms, the Positive and Negative Symptom Scale for psychotic symptoms, the Involuntary Movement Scale for tardive dyskinesia, the Barnes Akathisia Rating Scale for akathisia, the Udvalg for Kliniske Undersogelser for general side effects, the Schedule for Assessment of Insight for insight, the Global Assessment of Functioning scale for global functioning, and the Wisconsin Card Sorting Test (WCST) for cognitive executive function. RESULTS In total, 143 patients were enrolled and had a MetS prevalence of 29.4%. The patients treated with atypical antipsychotics plus mood stabilizers (36.3%) and atypical antipsychotics alone (36.0%) had a significantly higher prevalence of MetS than did those treated with mood stabilizers alone (10.5%; p = 0.012). According to multivariate regression analyses adjusted for age, sex, smoking status, bipolar disorder subtype (I or II), pharmacological treatment duration, and psychiatric medication, compared with patients without MetS, those with MetS had significantly more previous hospitalizations (p = 0.036), severer tardive dyskinesia (p = 0.030), poorer insight (p = 0.036), poorer global function (p = 0.046), and more impaired executive function (conceptual level response on the WCST; p = 0.042). CONCLUSIONS Our results indicated that patients with comorbid bipolar disorder and MetS have more adverse clinical outcomes than those without, with more hospitalizations, severer tardive dyskinesia, poorer insight, poorer global function, and more impaired executive function. Monitoring MetS is crucial for assessing not only physical burden, but also psychiatric outcomes.
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Affiliation(s)
- Ya-Mei Bai
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. .,Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Cheng-Ta Li
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan ,Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Shih-Jen Tsai
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan ,Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Pei-Chi Tu
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan ,Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Mu-Hong Chen
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan ,Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Tung-Ping Su
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan ,Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan
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50
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Fjukstad KK, Engum A, Lydersen S, Dieset I, Steen NE, Andreassen OA, Spigset O. Metabolic Abnormalities Related to Treatment With Selective Serotonin Reuptake Inhibitors in Patients With Schizophrenia or Bipolar Disorder. J Clin Psychopharmacol 2016; 36:615-620. [PMID: 27749681 PMCID: PMC5098465 DOI: 10.1097/jcp.0000000000000582] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE The aim of the present study was to examine the effect of selective serotonin reuptake inhibitors (SSRIs) on cardiovascular risk factors in patients with schizophrenia or bipolar disorder. METHOD We used data from a cross-sectional study on 1301 patients with schizophrenia or bipolar disorder, of whom 280 were treated with SSRIs. The primary outcome variable was the serum concentration of total cholesterol. Secondary outcome variables were low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglyceride and glucose levels, body mass index, waist circumference, and systolic and diastolic blood pressure. RESULTS After adjusting for potential confounders, an SSRI serum concentration in the middle of the reference interval was associated with an increase of the total cholesterol level by 14.56 mg/dL (95% confidence interval (CI) 5.27-23.85 mg/dL, P = 0.002), the LDL cholesterol level by 8.50 mg/dL (CI 0.22-16.77 mg/dL, P = 0.044), the triglyceride level by 46.49 mg/dL (CI 26.53-66.46 mg/dL, P < 0.001) and the occurrence of the metabolic syndrome by a factor of 2.10 (CI 1.21-3.62, P = 0.008). There were also significant associations between the SSRI dose and total cholesterol and LDL cholesterol levels. CONCLUSIONS This study is the first to reveal significant associations between SSRI use and metabolic abnormalities in patients with schizophrenia or bipolar disorder. Although the effects were statistically significant, alterations were small. Thus, the clinical impact of the findings is most likely limited.
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Affiliation(s)
- Katrine Kveli Fjukstad
- From the *Department of Psychiatry, Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger; †Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology; ‡Department of Psychiatry, St. Olavs University Hospital; §Regional Centre for Child and Youth Mental Health and Child Welfare-Central Norway, Trondheim; ‖NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo; ¶Drammen District Psychiatric Center, Clinic of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen; and #Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway
| | - Anne Engum
- From the *Department of Psychiatry, Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger; †Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology; ‡Department of Psychiatry, St. Olavs University Hospital; §Regional Centre for Child and Youth Mental Health and Child Welfare-Central Norway, Trondheim; ‖NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo; ¶Drammen District Psychiatric Center, Clinic of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen; and #Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway
| | - Stian Lydersen
- From the *Department of Psychiatry, Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger; †Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology; ‡Department of Psychiatry, St. Olavs University Hospital; §Regional Centre for Child and Youth Mental Health and Child Welfare-Central Norway, Trondheim; ‖NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo; ¶Drammen District Psychiatric Center, Clinic of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen; and #Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway
| | - Ingrid Dieset
- From the *Department of Psychiatry, Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger; †Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology; ‡Department of Psychiatry, St. Olavs University Hospital; §Regional Centre for Child and Youth Mental Health and Child Welfare-Central Norway, Trondheim; ‖NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo; ¶Drammen District Psychiatric Center, Clinic of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen; and #Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway
| | - Nils Eiel Steen
- From the *Department of Psychiatry, Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger; †Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology; ‡Department of Psychiatry, St. Olavs University Hospital; §Regional Centre for Child and Youth Mental Health and Child Welfare-Central Norway, Trondheim; ‖NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo; ¶Drammen District Psychiatric Center, Clinic of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen; and #Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway
| | - Ole A. Andreassen
- From the *Department of Psychiatry, Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger; †Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology; ‡Department of Psychiatry, St. Olavs University Hospital; §Regional Centre for Child and Youth Mental Health and Child Welfare-Central Norway, Trondheim; ‖NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo; ¶Drammen District Psychiatric Center, Clinic of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen; and #Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway
| | - Olav Spigset
- From the *Department of Psychiatry, Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger; †Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology; ‡Department of Psychiatry, St. Olavs University Hospital; §Regional Centre for Child and Youth Mental Health and Child Welfare-Central Norway, Trondheim; ‖NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo; ¶Drammen District Psychiatric Center, Clinic of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen; and #Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway
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