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Wang Y, Liu J, Zhang R, Luo G, Sun D. Untangling the complex relationship between bipolar disorder and anxiety: a comprehensive review of prevalence, prognosis, and therapy. J Neural Transm (Vienna) 2025; 132:567-578. [PMID: 39755917 DOI: 10.1007/s00702-024-02876-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 12/18/2024] [Indexed: 01/06/2025]
Abstract
Bipolar disorder (BD) frequently coexists with anxiety disorders, creating complex challenges in clinical therapy and management. This study investigates the prevalence, prognostic implications, and treatment strategies for comorbid BD and anxiety disorders. High comorbidity rates, particularly with generalized anxiety disorder, underscore the necessity of thorough clinical assessments to guide effective management. Our findings suggest that anxiety disorders may serve as precursors to BD, especially in high-risk populations, making early detection of anxiety symptoms crucial for timely intervention and prevention. We also found that comorbid anxiety can negatively affect the course of BD, increasing clinical severity, reducing treatment responsiveness, and worsening prognosis. These complexities highlight the need for caution in using antidepressants, which may destabilize mood. Alternatively, cognitive-behavioral therapy presents a promising, targeted approach for managing BD with comorbid anxiety. In summary, this study provides essential insights for clinicians and researchers, enhancing understanding of BD and anxiety comorbidity and guiding more precise diagnostics and tailored interventions to improve overall patient care.
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Affiliation(s)
- Yuting Wang
- The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders and Department of Psychiatry, Capital Medical University and Beijing Anding Hospital, Capital Medical University, 5 Ankang Lane, Dewai Avenue, Xicheng District, Beijing, 100088, China
| | - Jiao Liu
- Laboratory of Biological Psychiatry, Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, 13 Liulin Road, Tianjin, 300222, China
| | - Ran Zhang
- Laboratory of Biological Psychiatry, Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, 13 Liulin Road, Tianjin, 300222, China
| | - Guoshuai Luo
- Laboratory of Biological Psychiatry, Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, 13 Liulin Road, Tianjin, 300222, China.
| | - Daliang Sun
- Laboratory of Biological Psychiatry, Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, 13 Liulin Road, Tianjin, 300222, China.
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Tesfaye M, Jaholkowski P, Shadrin AA, van der Meer D, Hindley GF, Holen B, Parker N, Parekh P, Birkenæs V, Rahman Z, Bahrami S, Kutrolli G, Frei O, Djurovic S, Dale AM, Smeland OB, O'Connell KS, Andreassen OA. Identification of novel genomic loci for anxiety symptoms and extensive genetic overlap with psychiatric disorders. Psychiatry Clin Neurosci 2024; 78:783-791. [PMID: 39301620 PMCID: PMC11612548 DOI: 10.1111/pcn.13742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 08/16/2024] [Accepted: 08/29/2024] [Indexed: 09/22/2024]
Abstract
AIMS Anxiety disorders are prevalent and anxiety symptoms (ANX) co-occur with many psychiatric disorders. We aimed to identify genomic loci associated with ANX, characterize its genetic architecture, and genetic overlap with psychiatric disorders. METHODS We included a genome-wide association study of ANX (meta-analysis of UK Biobank and Million Veterans Program, n = 301,732), schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), and validated the findings in the Norwegian Mother, Father, and Child Cohort (n = 95,841). We employed the bivariate causal mixture model and local analysis of covariant association to characterize the genetic architecture including overlap between the phenotypes. Conditional and conjunctional false discovery rate analyses were performed to boost the identification of loci associated with anxiety and shared with psychiatric disorders. RESULTS Anxiety was polygenic with 12.9k genetic variants and overlapped extensively with psychiatric disorders (4.1k-11.4k variants) with predominantly positive genetic correlations between anxiety and psychiatric disorders. We identified 119 novel loci for anxiety by conditioning on the psychiatric disorders, and loci shared between anxiety and MDn = 47 , BIPn = 33 , SCZn = 71 , ADHDn = 20 , and ASDn = 5 . Genes annotated to anxiety loci exhibit enrichment for a broader range of biological pathways including cell adhesion and neurofibrillary tangle compared with genes annotated to the shared loci. CONCLUSIONS Anxiety is highly polygenic phenotype with extensive genetic overlap with psychiatric disorders, and we identified novel loci for anxiety implicating new molecular pathways. The shared genetic architecture may underlie the extensive cross-disorder comorbidity of anxiety, and the identified molecular underpinnings may lead to potential drug targets.
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Affiliation(s)
- Markos Tesfaye
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
- Department of Clinical ScienceUniversity of BergenBergenNorway
| | - Piotr Jaholkowski
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Alexey A. Shadrin
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
- KG Jebsen Centre for Neurodevelopmental DisordersUniversity of Oslo and Oslo University HospitalOsloNorway
| | - Dennis van der Meer
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Guy F.L. Hindley
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
- Institute of Psychiatry, Psychology and Neuroscience, King's College LondonLondonUK
| | - Børge Holen
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Nadine Parker
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Pravesh Parekh
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Viktoria Birkenæs
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Zillur Rahman
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Shahram Bahrami
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Gleda Kutrolli
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Oleksandr Frei
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
- Center for Bioinformatics, Department of InformaticsUniversity of OsloOsloNorway
| | - Srdjan Djurovic
- Department of Clinical ScienceUniversity of BergenBergenNorway
- KG Jebsen Centre for Neurodevelopmental DisordersUniversity of Oslo and Oslo University HospitalOsloNorway
- Department of Medical GeneticsOslo University HospitalOsloNorway
| | - Anders M. Dale
- Department of RadiologyUniversity of California, San DiegoLa JollaCaliforniaUSA
- Multimodal Imaging LaboratoryUniversity of California, San DiegoLa JollaCaliforniaUSA
- Department of NeurosciencesUniversity of California, San DiegoLa JollaCaliforniaUSA
| | - Olav B. Smeland
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Kevin S. O'Connell
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
| | - Ole A. Andreassen
- Centre for Precision Psychiatry, Division of Mental Health and AddictionOslo University Hospital, and Institute of Clinical Medicine, University of OsloOsloNorway
- KG Jebsen Centre for Neurodevelopmental DisordersUniversity of Oslo and Oslo University HospitalOsloNorway
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3
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Tesfaye M, Jaholkowski P, Shadrin AA, van der Meer D, Hindley GF, Holen B, Parker N, Parekh P, Birkenæs V, Rahman Z, Bahrami S, Kutrolli G, Frei O, Djurovic S, Dale AM, Smeland OB, O’Connell KS, Andreassen OA. Identification of Novel Genomic Loci for Anxiety and Extensive Genetic Overlap with Psychiatric Disorders. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2023.09.01.23294920. [PMID: 37693403 PMCID: PMC10491354 DOI: 10.1101/2023.09.01.23294920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
Abstract
Background Anxiety disorders are prevalent and anxiety symptoms co-occur with many psychiatric disorders. We aimed to identify genomic risk loci associated with anxiety, characterize its genetic architecture, and genetic overlap with psychiatric disorders. Methods We used the GWAS of anxiety symptoms, schizophrenia, bipolar disorder, major depression, and attention deficit hyperactivity disorder (ADHD). We employed MiXeR and LAVA to characterize the genetic architecture and genetic overlap between the phenotypes. Conditional and conjunctional false discovery rate analyses were performed to boost the identification of genomic loci associated with anxiety and those shared with psychiatric disorders. Gene annotation and gene set analyses were conducted using OpenTargets and FUMA, respectively. Results Anxiety was polygenic with 12.9k estimated genetic risk variants and overlapped extensively with psychiatric disorders (4.1-11.4k variants). MiXeR and LAVA revealed predominantly positive genetic correlations between anxiety and psychiatric disorders. We identified 114 novel loci for anxiety by conditioning on the psychiatric disorders. We also identified loci shared between anxiety and major depression (n = 47), bipolar disorder (n = 33), schizophrenia (n = 71), and ADHD (n = 20). Genes annotated to anxiety loci exhibit enrichment for a broader range of biological pathways and differential tissue expression in more diverse tissues than those annotated to the shared loci. Conclusions Anxiety is a highly polygenic phenotype with extensive genetic overlap with psychiatric disorders. These genetic overlaps enabled the identification of novel loci for anxiety. The shared genetic architecture may underlie the extensive cross-disorder comorbidity of anxiety, and the identified genetic loci implicate molecular pathways that may lead to potential drug targets.
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Affiliation(s)
- Markos Tesfaye
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Piotr Jaholkowski
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Alexey A. Shadrin
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo and Oslo University Hospital, Oslo, Norway
| | - Dennis van der Meer
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Guy F.L. Hindley
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
| | - Børge Holen
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Nadine Parker
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Pravesh Parekh
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Viktoria Birkenæs
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Zillur Rahman
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Shahram Bahrami
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Gleda Kutrolli
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Oleksandr Frei
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Center for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway
| | - Srdjan Djurovic
- Department of Clinical Science, University of Bergen, Bergen, Norway
- KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo and Oslo University Hospital, Oslo, Norway
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
| | - Anders M. Dale
- Department of Radiology, University of California, San Diego, La Jolla, CA, USA
- Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA, USA
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
- Department of Neurosciences, University of California San Diego, La Jolla, CA, USA
| | - Olav B. Smeland
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kevin S. O’Connell
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ole A. Andreassen
- Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo and Oslo University Hospital, Oslo, Norway
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Scala M, Biondi L, Fabbri C, Serretti A. Efficacy of Brexpiprazole Combination Therapy on Anhedonia in a Case of Treatment Resistant Bipolar II Depression. J Clin Psychopharmacol 2023; 43:453-455. [PMID: 37683234 DOI: 10.1097/jcp.0000000000001732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/10/2023]
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Liu J, Wang Y, Wilson A, Chen H, Liu P, Chen X, Tang H, Luo C, Tian Y, Wang X, Cao X, Zhou J. Anticipating Unipolar Depression and Bipolar Depression in young adult with first episode of depression using childhood trauma and personality. Front Public Health 2023; 10:1061894. [PMID: 36703813 PMCID: PMC9871579 DOI: 10.3389/fpubh.2022.1061894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 12/08/2022] [Indexed: 01/11/2023] Open
Abstract
Objective Relevant research focusing on young adults with Unipolar Depression (UD) and Bipolar Depression (BD) is limited. The current research aims to investigate childhood trauma and personality traits in young adults with UD and BD. Methods Two hundred and thirty-five patients in a first depressive episode (diagnosed UD and BD), 16-25 years old, were recruited from Second Xiangya Hospital. And 79 healthy controls (HC) were recruited from the community to form the comparison group. Patients' childhood trauma was measured by the Childhood Trauma Questionnaire (CTQ), and personality was measured by Eysenck Personality Inventory (EPI). The Kruskal-Wallis test was used to compare depression, anxiety, CTQ, and EPI scores between the HC (n = 79), UD (n = 131), and BD (n = 104) groups. Factors independently associated with mood disorders and BD were determined using binary logistic regression analyses. Results Compared with HC, mood disorders had more severe anxiety and depression symptoms, and higher CTQ. Emotional abuse (OR = 1.47; 95% CI = 1.08-2.01), emotional neglect (OR = 1.24; 95% CI = 1.05-1.46), and neuroticism (OR = 1.25; 95% CI = 1.16-1.35) were associated with significantly increased odds of mood disorders. Whereas, higher extraversion scores were a protective factor for mood disorders. Compared with UD, BD had more severe anxiety symptoms, and higher CTQ, than extraversion and neuroticism personality scores. Anxiety (OR = 1.06; 95% CI = 1.02-1.08) and extraversion (OR = 1.05; 95% CI = 1.03-1.09) were associated with significantly increased odds of BD. Conclusion Interventions to prevent childhood trauma may improve young adults' mental health. Using childhood trauma and personality to anticipate BD and UD creates more accurate treatment for young adults with first depression.
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Affiliation(s)
- Jiali Liu
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Yuanyuan Wang
- Division of Psychology, Faculty of Health and Life Sciences, De Montfort University, Leicester, United Kingdom
| | - Amanda Wilson
- Division of Psychology, Faculty of Health and Life Sciences, De Montfort University, Leicester, United Kingdom
| | - Hui Chen
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Peiqu Liu
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Xianliang Chen
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Huajia Tang
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Chenyuli Luo
- Dongguan Mental Health Center, Dongguan, Guangdong, China
| | - Yusheng Tian
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Xiaoping Wang
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Xia Cao
- Health Management Center, Health Management Research Center of Central South University, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China,Xia Cao ✉
| | - Jiansong Zhou
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China,*Correspondence: Jiansong Zhou ✉
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6
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Eseaton PO, Oladunjoye AF, Anugwom G, Onyeaka H, Edigin E, Osiezagha K. Emergency department utilization by patients with bipolar disorder: a national population-based study. J Affect Disord 2022; 313:232-234. [PMID: 35779671 DOI: 10.1016/j.jad.2022.06.086] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 06/25/2022] [Indexed: 10/17/2022]
Abstract
BACKGROUND There is a scarcity of national United States (US) data on emergency department (ED) utilization of patients with bipolar disorder (BD). This study aims to determine the most common reasons for ED visits of patients with BD, and baseline characteristics of patients who present due to BD. METHODS We obtained data from the Nationwide Emergency Department Sample (NEDS), the largest all-payer ED database in the US. Each ED visit in NEDS 2018, can have only 1 "principal" diagnosis, which is the main reason for hospitalization, and up to 34 "secondary" diagnoses. We extracted data for all ED visits with "any" diagnosis of BD, using the ICD-10 code. We highlighted the 5 most common "principal" diagnoses based on the organ system involved and the 10 most specific "principal" diagnoses for all ED visits by patients with "any" diagnosis of BD. We highlighted baseline characteristics of ED visits with a "principal" diagnosis of BD. RESULTS A total of 2,200,197 ED visits for patients with BD in 2018. Mental disorders such as BD, suicidal ideations, anxiety disorders and injuries and poisoning were common reasons for presentation to the ED. Among these, 291,319 had BD as the principal diagnosis. These patients were more likely to come from lower-income households. LIMITATIONS Possibility of coding errors due to ICD coding, and absence of data on race and medication compliance. CONCLUSIONS BD, suicidal ideation, and anxiety disorders were the most common specific psychiatric reasons for presentation to the ED among patients with BD.
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Affiliation(s)
- Precious Obehi Eseaton
- Department of Mental Health, University of Benin Teaching Hospital, Benin City, Edo, Nigeria.
| | - Adeolu Funso Oladunjoye
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
| | - Gibson Anugwom
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
| | - Henry Onyeaka
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Ehizogie Edigin
- Department of Medicine, Loma Linda University Health, Loma Linda, CA, USA
| | - Kenneth Osiezagha
- Department of Psychiatry, Meharry Medical College, Nashville, TN, USA
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Cañada Y, Sabater A, Sierra P, Balanzá-Martínez V, Berk M, Dodd S, Navalón P, Livianos L, García-Blanco A. The effect of concomitant benzodiazepine use on neurocognition in stable, long-term patients with bipolar disorder. Aust N Z J Psychiatry 2021; 55:1005-1016. [PMID: 33153268 DOI: 10.1177/0004867420969819] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Neurocognitive dysfunction is a common feature of bipolar disorder even in euthymia, and psychopharmacological treatment could have an effect on cognition. Long-term prescription of benzodiazepines in bipolar disorder is a common practice, and their effect on neurocognition has not been well studied in this population. The aim of this study was to evaluate the impact of concomitant benzodiazepine long-term use on neurocognitive function in stable euthymic bipolar disorder patients. METHODS Seventy-three euthymic bipolar disorder outpatients and 40 healthy individuals were assessed using a neurocognitive battery. Patients were classified in two groups according to the presence of benzodiazepines in their treatment: the benzodiazepine group (n = 34) and the non- benzodiazepine group (n = 39). Neurocognitive performance was compared between the groups using a multivariate analysis of covariance, considering age, number of depressive episodes, adjuvant antipsychotic drugs, Young Mania Rating Scale score and Hamilton Depression Rating Scale score as covariates. RESULTS Both bipolar disorder groups (benzodiazepine and non-benzodiazepine) showed an impairment in memory domains (Immediate Visual Memory [p = 0.013], Working Memory [p < 0.001], and Letter-Number Sequence [p < 0.001] from the Wechsler Memory Scale-Revised-III) and slower processing speed functions (Stroop Colour [p < 0.001]) relative to the control group. Nevertheless, the benzodiazepine group showed a greater impairment in executive functions (Conceptual Level Responses [p = 0.024] from the Wisconsin Card Sorting Test and Frontal Assessment Battery [p = 0.042]). CONCLUSION Although memory and processing speed impairments were found in bipolar disorder, regardless of their benzodiazepine treatment, benzodiazepine users presented additional neurocognitive impairments in terms of executive functioning. These findings support restricted prescription of benzodiazepines in individuals with bipolar disorder.
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Affiliation(s)
- Yolanda Cañada
- Department of Psychiatry and Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Ana Sabater
- Department of Psychiatry and Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Pilar Sierra
- Department of Psychiatry and Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain.,Department of Medicine, University of Valencia, Valencia, Spain
| | - Vicent Balanzá-Martínez
- Department of Psychiatry and Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain.,Department of Medicine, University of Valencia, Valencia, Spain.,Center of Biomedical Investigation Network in Mental Health (CIBERSAM), Madrid, Spain
| | - Michael Berk
- The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, VIC, Australia.,Orygen - The National Centre for Excellence in Youth Mental Health, Parkville, VIC, Australia.,Florey Institute for Neuroscience and Mental Health, Parkville, VIC, Australia.,Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia
| | - Seetal Dodd
- The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, VIC, Australia.,Orygen - The National Centre for Excellence in Youth Mental Health, Parkville, VIC, Australia.,Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia
| | - Pablo Navalón
- Department of Psychiatry and Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain.,Neonatal Research Unit, La Fe Health Research Institute, Valencia, Spain
| | - Lorenzo Livianos
- Department of Psychiatry and Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain.,Department of Medicine, University of Valencia, Valencia, Spain.,CIBERESP-17, Valencia, Spain
| | - Ana García-Blanco
- Department of Psychiatry and Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain.,Neonatal Research Unit, La Fe Health Research Institute, Valencia, Spain.,Department of Personality, Evaluation, and Psychological Treatments, University of Valencia, Valencia, Spain
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8
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Palego L, Giannaccini G, Betti L. Neuroendocrine Response to Psychosocial Stressors, Inflammation Mediators and Brain-periphery Pathways of Adaptation. Cent Nerv Syst Agents Med Chem 2020; 21:2-19. [PMID: 33319677 DOI: 10.2174/1871524920999201214231243] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 10/31/2020] [Accepted: 11/09/2020] [Indexed: 11/22/2022]
Abstract
Threats, challenging events, adverse experiences, predictable or unpredictable, namely stressors, characterize life, being unavoidable for humans. The hypothalamus-pituitary-adrenal axis (HPA) and the sympathetic nervous system (SNS) are well-known to underlie adaptation to psychosocial stress in the context of other interacting systems, signals and mediators. However, much more effort is necessary to elucidate these modulatory cues for a better understanding of how and why the "brain-body axis" acts for resilience or, on the contrary, cannot cope with stress from a biochemical and biological point of view. Indeed, failure to adapt increases the risk of developing and/or relapsing mental illnesses such as burnout, post-traumatic stress disorder (PTSD), and at least some types of depression, even favoring/worsening neurodegenerative and somatic comorbidities, especially in the elderly. We will review here the current knowledge on this area, focusing on works presenting the main brain centers responsible for stressor interpretation and processing, together with those underscoring the physiology/biochemistry of endogenous stress responses. Autonomic and HPA patterns, inflammatory cascades and energy/redox metabolic arrays will be presented as allostasis promoters, leading towards adaptation to psychosocial stress and homeostasis, but also as possible vulnerability factors for allostatic overload and non-adaptive reactions. Besides, the existence of allostasis buffering systems will be treated. Finally, we will suggest promising lines of future research, particularly the use of animal and cell culture models together with human studies by means of high-throughput multi-omics technologies, which could entangle the biochemical signature of resilience or stress-related illness, a considerably helpful facet for improving patients' treatment and monitoring.
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Affiliation(s)
- Lionella Palego
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Laura Betti
- Department of Pharmacy, University of Pisa, Pisa, Italy
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9
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The prevalence of anxiety and its association with the quality of life and illness severity among bipolar affective disorder patients in a developing country. Asian J Psychiatr 2020; 52:102044. [PMID: 32344280 DOI: 10.1016/j.ajp.2020.102044] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 03/24/2020] [Accepted: 03/25/2020] [Indexed: 01/04/2023]
Abstract
The objective of the study was to determine the prevalence of anxiety symptoms and describe the association with illness severity, quality of life (QOL) and current medications among patients with BPAD who are currently in remission. A descriptive cross-sectional study conducted among outpatient clinic patients at the University Professorial Unit of University of Ruhuna, Sri Lanka. The study population consisted of patients diagnosed with BPAD and who are currently in remission. Anxiety symptoms among BPAD patients were assessed using the DASS-21 anxiety subscale and QOL was assessed using WHOQoL-BREF. Medications and severity of illness related information were gathered from both the patent and from their medical records. The study population consisted of 145 patients. The prevalence of anxiety among patients with BPAD who are currently in remission was 48.3 % (95 %CI 40.0-56.6). Multiple logistic regression revealed that being anxious was independently associated with currently not being married (aOR 2.92) and currently not being employed (aOR 2.1). Presence of anxiety significantly reduced the QOL in all the domains. Having anxiety was significantly associated with having one or more relapses within the past three years (aOR 4.1), one or more hospital admissions within the past three years (aOR 6.1), needing more psychoactive medications to maintain a euthymic state (aOR 7.7), and one or more suicidal attempts in the past (aOR 6.5). Anxiety was highly prevalent among patients with BPAD. Those with anxiety experienced significantly lower QOL and were found to be having significantly high adverse outcomes from the disease.
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Spoorthy MS, Chakrabarti S, Grover S. Comorbidity of bipolar and anxiety disorders: An overview of trends in research. World J Psychiatry 2019; 9:7-29. [PMID: 30631749 PMCID: PMC6323556 DOI: 10.5498/wjp.v9.i1.7] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 11/04/2018] [Accepted: 12/05/2018] [Indexed: 02/05/2023] Open
Abstract
Over the last three decades burgeoning research has shown that anxiety disorder comorbidity is not only highly prevalent in bipolar disorder (BD), but it also adversely impacts the course, outcome, and treatment of BD. The present review provides an overview of the current trends in research on comorbid anxiety and BDs based on prior reviews and meta-analyses (n = 103), epidemiological surveys, and large-scale clinical studies. The results reiterated the fact that at least half of those with BD are likely to develop an anxiety disorder in their lifetimes and a third of them will manifest an anxiety disorder at any point of time. All types of anxiety disorders were equally common in BD. However, there was a wide variation in rates across different sources, with most of this discrepancy being accounted for by methodological differences between reports. Comorbid anxiety disorders negatively impacted the presentation and course of BD. This unfavourable clinical profile led to poorer outcome and functioning and impeded treatment of BD. Despite the extensive body of research there was paucity of data on aetiology and treatment of anxiety disorder comorbidity in BD. Nevertheless, the substantial burden and unique characteristics of this comorbidity has important clinical and research implications.
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Affiliation(s)
- Mamidipalli Sai Spoorthy
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Subho Chakrabarti
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Sandeep Grover
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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11
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Abstract
Anxiety disorders are the most prevalent comorbid diagnoses in patients with bipolar disorder (BD). A comorbid anxiety diagnosis can significantly impact the severity of bipolar symptoms, increase the risk of suicidality, and decrease psychosocial functioning and quality of life. The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force published recommendations for treatment in 2012 suggesting that specific anticonvulsant mood stabilizers and second-generation antipsychotics are the medications of choice to treat these comorbidities. Serotonergic antidepressant medications are first-line medications for the treatment of most anxiety disorders; however, this can be problematic for a patient with BD. Antidepressant use in BD has been associated with a risk of manic switch as well as potential destabilization of mood. Mood stabilizer therapy should be established for patients with comorbid BD and an anxiety disorder before other medications are added to address the anxiety disorder. While benzodiazepine medications are recommended as third-line therapy in the CANMAT task force recommendations, their use should be avoided in patients with comorbid BD, posttraumatic stress disorder, and substance use disorders. The use of benzodiazepines should in general be avoided for all patients if possible, based upon current clinical research. Interpersonal, cognitive behavioral, and relaxation therapy are effective for the treatment of anxiety symptoms, especially emotional experiences, in patients who are euthymic.
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Affiliation(s)
- Carol A Ott
- (Corresponding author) Clinical Professor of Pharmacy Practice, Department of Pharmacy Practice, Purdue University College of Pharmacy, Indianapolis, Indiana; Clinical Pharmacy Specialist, Outpatient Psychiatry, Prevention and Recovery Center for Early Psychosis, Mood Disorders Clinic, Midtown Community Mental Health, Eskenazi Health, Indianapolis, Indiana,
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12
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Pankowski S, Adler M, Andersson G, Lindefors N, Svanborg C. Group acceptance and commitment therapy (ACT) for bipolar disorder and co-existing anxiety - an open pilot study. Cogn Behav Ther 2016; 46:114-128. [PMID: 27647353 DOI: 10.1080/16506073.2016.1231218] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Previous studies have supported acceptance and commitment therapy (ACT) for reducing impairment related to various chronic conditions. ACT may possibly be beneficial for bipolar disorder (BD) with co-existing anxiety, which is associated with a poorer treatment outcome. Efforts are needed to identify suitable psychological interventions for BD and co-existing anxiety. In this open clinical trial, we included 26 patients with BD type 1 or 2 at an outpatient psychiatric unit specializing in affective disorders. The intervention consisted of a 12-session manualized group treatment that included psychoeducation, mindfulness, engaging in values-based behaviour, cognitive defusion, acceptance and relapse prevention modules. Participants completed four self-report questionnaires covering anxiety symptoms (Beck Anxiety Inventory - BAI), depressive symptoms (Beck Depression Inventory - BDI-II), quality of life (Quality of Life Inventory - QOLI) and psychological flexibility (Acceptance and Action Questionnaire - AAQ-2) before, during and after the treatment. At post-treatment, the participants reported significant improvements in all outcome measures, with large effects (Cohen's d between 0.73 and 1.98). The mean reduction in anxiety symptoms was 45%. At post-treatment, 96% of the patients were classified as responders on at least one of the outcome measures. A limitation is that the trial is uncontrolled. The results suggest that ACT has the potential to be an effective treatment for BD patients with co-existing anxiety. Further randomized studies are warranted.
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Affiliation(s)
- Sara Pankowski
- a Department of Clinical Neuroscience , Karolinska Institutet , Stockholm , Sweden
| | - Mats Adler
- a Department of Clinical Neuroscience , Karolinska Institutet , Stockholm , Sweden
| | - Gerhard Andersson
- a Department of Clinical Neuroscience , Karolinska Institutet , Stockholm , Sweden
.,b Department of Behavioural Sciences and Learning , Linköping University , Linköping , Sweden
| | - Nils Lindefors
- a Department of Clinical Neuroscience , Karolinska Institutet , Stockholm , Sweden
| | - Cecilia Svanborg
- a Department of Clinical Neuroscience , Karolinska Institutet , Stockholm , Sweden
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Yuen LD, Miller S, Wang PW, Hooshmand F, Holtzman JN, Goffin KC, Shah S, Ketter TA. Current irritability robustly related to current and prior anxiety in bipolar disorder. J Psychiatr Res 2016; 79:101-107. [PMID: 27218815 DOI: 10.1016/j.jpsychires.2016.05.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Revised: 05/05/2016] [Accepted: 05/09/2016] [Indexed: 01/24/2023]
Abstract
BACKGROUND Although current irritability and current/prior anxiety have been associated in unipolar depression, these relationships are less well understood in bipolar disorder (BD). We investigated relationships between current irritability and current/prior anxiety as well as other current emotions and BD illness characteristics. METHODS Outpatients referred to the Stanford Bipolar Disorders Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Prevalence and clinical correlates of current irritability and current/prior anxiety and other illness characteristics were examined. RESULTS Among 497 BD outpatients (239 Type I, 258 Type II; 58.1% female; mean ± SD age 35.6 ± 13.1 years), 301 (60.6%) had baseline current irritability. Patients with versus without current irritability had significantly higher rates of current anxiety (77.1% versus 42.9%, p < 0.0001) and history of anxiety disorder (73.1% versus 52.6%, p < 0.0001). Current irritability was more robustly related to current anxiety than to current anhedonia, sadness, or euphoria (all p < 0.001), and current irritability-current anxiety associations persisted across current predominant mood states. Current irritability was more robustly related to past anxiety than to all other assessed illness characteristics, including 1° family history of mood disorder, history of alcohol/substance use disorder, bipolar subtype, and current syndromal/subsyndromal depression (all p < 0.05). LIMITATIONS Limited generalizability beyond our predominately white, female, educated, insured American BD specialty clinic sample. CONCLUSIONS In BD, current irritability was robustly related to current/prior anxiety. Further studies are warranted to assess longitudinal clinical implications of relationships between irritability and anxiety in BD.
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Affiliation(s)
- Laura D Yuen
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Shefali Miller
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Po W Wang
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Farnaz Hooshmand
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Jessica N Holtzman
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Kathryn C Goffin
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Saloni Shah
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Terence A Ketter
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
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Piguet C, Cojan Y, Sterpenich V, Desseilles M, Bertschy G, Vuilleumier P. Alterations in neural systems mediating cognitive flexibility and inhibition in mood disorders. Hum Brain Mapp 2016; 37:1335-48. [PMID: 26787138 DOI: 10.1002/hbm.23104] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 08/22/2015] [Accepted: 12/18/2015] [Indexed: 01/25/2023] Open
Abstract
Impairment in mental flexibility may be a key component contributing to cardinal cognitive symptoms among mood disorders patients, particularly thought control disorders. Impaired ability to switch from one thought to another might reflect difficulties in either generating new mental states, inhibiting previous states, or both. However, the neural underpinnings of impaired cognitive flexibility in mood disorders remain largely unresolved. We compared a group of mood disorders patients (n = 29) and a group of matched healthy subjects (n = 32) on a novel task-switching paradigm involving happy and sad faces, that allowed us to separate generation of a new mental set (Switch Cost) and inhibition of the previous set during switching (Inhibition Cost), using fMRI. Behavioral data showed a larger Switch Cost in patients relative to controls, but the average Inhibition Cost did not differ between groups. At the neural level, a main effect of group was found with stronger activation of the subgenual cingulate cortex in patients. The larger Switch Cost in patients was reflected by a stronger recruitment of brain regions involved in attention and executive control, including the left intraparietal sulcus, precuneus, left inferior fontal gyrus, and right anterior cingulate. Critically, activity in the subgenual cingulate cortex was not downregulated by inhibition in patients relative to controls. In conclusion, mood disorder patients have exaggerated Switch Cost relative to controls, and this deficit in cognitive flexibility is associated with increased activation of the fronto-parietal attention networks, combined with impaired modulation of the subgenual cingulate cortex when inhibition of previous mental states is needed.
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Affiliation(s)
- Camille Piguet
- Neuroscience Department, Faculty of Medicine, University of Geneva, Switzerland
| | - Yann Cojan
- Neuroscience Department, Faculty of Medicine, University of Geneva, Switzerland
| | - Virginie Sterpenich
- Neuroscience Department, Faculty of Medicine, University of Geneva, Switzerland
| | - Martin Desseilles
- Neuroscience Department, Faculty of Medicine, University of Geneva, Switzerland.,Cyclotron Research Center, University of Liege, Belgium
| | - Gilles Bertschy
- Department of Psychiatry and Mental Health, Strasbourg University Hospital, University of Strasbourg, INSERMu666, France
| | - Patrik Vuilleumier
- Neuroscience Department, Faculty of Medicine, University of Geneva, Switzerland
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15
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Greco A, Valenza G, Lanata A, Rota G, Scilingo EP. Electrodermal activity in bipolar patients during affective elicitation. IEEE J Biomed Health Inform 2015; 18:1865-73. [PMID: 25375684 DOI: 10.1109/jbhi.2014.2300940] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Bipolar patients are characterized by a pathological unpredictable behavior, resulting in fluctuations between states of depression and episodes of mania or hypomania. In the current clinical practice, the psychiatric diagnosis is made through clinician-administered rating scales and questionnaires, disregarding the potential contribution provided by physiological signs. The aim of this paper is to investigate how changes in the autonomic nervous system activity can be correlated with clinical mood swings. More specifically, a group of ten bipolar patients underwent an emotional elicitation protocol to investigate the autonomic nervous system dynamics, through the electrodermal activity (EDA), among different mood states. In addition, a control group of ten healthy subjects were recruited and underwent the same protocol. Physiological signals were analyzed by applying the deconvolutive method to reconstruct EDA tonic and phasic components, from which several significant features were extracted to quantify the sympathetic activation. Experimental results performed on both the healthy subjects and the bipolar patients supported the hypothesis of a relationship between autonomic dysfunctions and pathological mood states.
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16
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Vázquez GH, Baldessarini RJ, Tondo L. Co-occurrence of anxiety and bipolar disorders: clinical and therapeutic overview. Depress Anxiety 2014; 31:196-206. [PMID: 24610817 DOI: 10.1002/da.22248] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Revised: 01/12/2014] [Accepted: 01/18/2014] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Anxiety commonly co-occurs with bipolar disorders (BDs), but the significance of such "co-morbidity" remains to be clarified and its optimal treatment adequately defined. METHODS We reviewed epidemiological, clinical, and treatment studies of the co-occurrence of BD and anxiety disorder through electronic searching of Pubmed/MEDLINE and EMBASE databases. RESULTS Nearly half of BD patients meet diagnostic criteria for an anxiety disorder at some time, and anxiety is associated with poor treatment responses, substance abuse, and disability. Reported rates of specific anxiety disorders with BD rank: panic ≥ phobias ≥ generalized anxiety ≥ posttraumatic stress ≥ obsessive-compulsive disorders. Their prevalence appears to be greater among women than men, but similar in types I and II BD. Anxiety may be more likely in depressive phases of BD, but relationships of anxiety phenomena to particular phases of BD, and their temporal distributions require clarification. Adequate treatment trials for anxiety syndromes in BD patients remain rare, and the impact on anxiety of treatments aimed at mood stabilization is not clear. Benzodiazepines are sometimes given empirically; antidepressants are employed cautiously to limit risks of mood switching and emotional destabilization; lamotrigine, valproate, and second-generation antipsychotics may be useful and relatively safe. CONCLUSIONS Anxiety symptoms and syndromes co-occur commonly in patients with BD, but "co-morbid" phenomena may be part of the BD phenotype rather than separate illnesses.
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Affiliation(s)
- Gustavo H Vázquez
- International Consortium for Bipolar and Psychotic Disorders Research, Mailman Research Center, McLean Hospital, Belmont, Massachusetts; Department of Neuroscience, Palermo University, Buenos Aires, Argentina
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17
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Bandelow B, Bauer M, Vieta E, El-Khalili N, Gustafsson U, Earley WR, Eriksson H. Extended release quetiapine fumarate as adjunct to antidepressant therapy in patients with major depressive disorder: pooled analyses of data in patients with anxious depression versus low levels of anxiety at baseline. World J Biol Psychiatry 2014; 15:155-66. [PMID: 24506289 DOI: 10.3109/15622975.2013.842654] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVES To evaluate quetiapine XR in patients with anxious depression, as defined by HAM-A total and HAM-D anxiety/somatisation factor scores. METHODS Post hoc analyses of pooled data from two 6-week, double-blind, randomised, placebo-controlled studies of adjunctive quetiapine XR (150 or 300 mg/day) in patients with MDD and inadequate response to antidepressants. Patients were stratified in a primary analysis using HAM-A (HAM-A total score at baseline ≥ 20 ["high"] or < 20 ["low"]) and a secondary analysis using HAM-D (anxious depression defined as HAM-D anxiety/somatisation factor score ≥ 7). Outcomes included change in MADRS total score. RESULTS In patients with high anxiety levels (HAM-A total score ≥ 20), reductions in MADRS total score were -15.20 (P = 0.122) and -15.92 (P < 0.05) for quetiapine XR 150 and 300 mg/day, respectively, vs. placebo (-13.49). In patients with low levels of anxiety (HAM-A total score < 20), both quetiapine XR doses (P < 0.001) improved MADRS total scores vs. placebo. In the secondary analysis, quetiapine XR 150 (P < 0.01) and 300 mg/day (P < 0.001) improved MADRS total score vs. placebo in patients with HAM-D anxiety/somatisation factor score ≥ 7. CONCLUSIONS Adjunct quetiapine XR demonstrates efficacy in patients with anxious and non-anxious depression, assessed using HAM-A total score, and anxious depression assessed using HAM-D anxiety/somatisation factor score.
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Affiliation(s)
- Borwin Bandelow
- Department of Psychiatry and Psychotherapy, University of Göttingen , Göttingen , Germany
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18
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Sala R, Strober MA, Axelson DA, Gill MK, Castro-Fornieles J, Goldstein TR, Goldstein BI, Ha W, Liao F, Iyengar S, Yen S, Hower H, Hunt J, Dickstein DP, Ryan ND, Keller MB, Birmaher B. Effects of comorbid anxiety disorders on the longitudinal course of pediatric bipolar disorders. J Am Acad Child Adolesc Psychiatry 2014; 53:72-81. [PMID: 24342387 PMCID: PMC3868011 DOI: 10.1016/j.jaac.2013.09.020] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Revised: 09/04/2013] [Accepted: 10/14/2013] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To examine the longitudinal effects of comorbid anxiety disorders in youth with bipolar spectrum disorder (BP). METHOD As part of the Course and Outcome of Bipolar Youth study, 413 youth, who were 7 through 17 years or age and who met criteria for DSM-IV BP-I (n = 244), BP-II (n = 28), and operationally defined bipolar disorder not otherwise specified (BP-NOS) (n = 141) were included. Subjects were followed on average 5 years using the Longitudinal Interval Follow-up Evaluation. Effects of anxiety on the time to mood recovery and recurrence and percentage of time with syndromal and subsyndromal mood symptomatology during the follow-up period were analyzed. RESULTS At intake and during the follow-up, 62% of youth with BP met criteria for at least 1 anxiety disorder. About 50% of the BP youth with anxiety had ≥2 anxiety disorders. Compared to BP youth without anxiety, those with anxiety had significantly more depressive recurrences and significantly longer median time to recovery. The effects of anxiety on recovery disappeared when the severity of depression at intake was taken into account. After adjusting for confounding factors, BP youth with anxiety, particularly those with ≥2 anxiety disorders, spent significantly less follow-up time asymptomatic and more time with syndromal mixed/cycling and subsyndromal depressive symptomatology compared to those without anxiety. CONCLUSIONS Anxiety disorders are common and adversely affect the course of BP in youth, as characterized by more mood recurrences, longer time to recovery, less time euthymic, and more time in mixed/cycling and depressive episodes. Prompt recognition and the development of treatments for BP youth with anxiety are warranted.
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Affiliation(s)
- Regina Sala
- Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine; Institute of Psychiatry, King's College London.
| | - Michael A Strober
- David Geffen School of Medicine, University of California at Los Angeles
| | - David A. Axelson
- Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine
| | - Mary Kay Gill
- Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine
| | | | - Tina R. Goldstein
- Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine
| | | | - Wonho Ha
- Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine
| | - Fangzi Liao
- Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine
| | | | - Shirley Yen
- Butler Hospital, Brown University School of Medicine
| | - Heather Hower
- Butler Hospital, Brown University School of Medicine
| | - Jeffrey Hunt
- Butler Hospital, Brown University School of Medicine
| | | | - Neal D. Ryan
- Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine
| | | | - Boris Birmaher
- Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine
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Hawke LD, Provencher MD, Parikh SV, Zagorski B. Comorbid anxiety disorders in Canadians with bipolar disorder: clinical characteristics and service use. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2013; 58:393-401. [PMID: 23870721 DOI: 10.1177/070674371305800704] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVE To examine the impact of anxiety disorders comorbid to bipolar disorder (BD) in a large, nationally representative sample, to describe the sociodemographic and clinical profiles of Canadians living with BD and with or without comorbid anxiety disorders, to identify the characteristics uniquely associated with comorbid anxiety, and to examine treatment patterns. METHOD We analyzed data from the Canadian Community Health Survey: Mental Health and Well-Being, conducted among 38 492 Canadians. People meeting the criteria for BD (n = 808) were compared based on the presence or absence of an assessed anxiety disorder (that is, social phobia, panic disorder, and agoraphobia). RESULTS People with BD and a comorbid anxiety disorder fare worse in terms of BD relapses, suicidality, and sleep disturbance, and are more likely to be taking psychiatric medication. They have more impairment in their work and social functioning and rate their health and life satisfaction lower. Despite the greater severity, they are not receiving additional psychological treatment, they feel they are not receiving the treatment they need, and they report more barriers to treatment. CONCLUSIONS This study confirms the critical impact of comorbid anxiety on the course of BD in a large, nationally representative sample and reveals that the psychological treatment needs of this population are not being met. Clinical and research implications are discussed.
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Affiliation(s)
- Lisa D Hawke
- University Health Network, Toronto, Ontario, Canada
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20
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González-Pinto A, Galán J, Martín-Carrasco M, Ballesteros J, Maurino J, Vieta E. Anxiety as a marker of severity in acute mania. Acta Psychiatr Scand 2012; 126:351-5. [PMID: 22620488 DOI: 10.1111/j.1600-0447.2012.01882.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Anxiety has scarcely been studied in acute mania. The aim of this study was to assess anxiety symptoms during manic episodes and their impact on clinical outcomes. METHOD Observational, cross-sectional multicentre study. Anxiety was measured using the Hamilton Anxiety Rating Scale (HARS). Bivariate and multiple linear regression analyses were performed using the HARS score as the dependent variable. RESULTS Two hundred and forty-two patients admitted with a diagnosis of acute manic episode according to DSM-IV TR criteria and a Young Mania Rating Scale>20 were analysed. Mean age was 43 years (SD=11.9) and 57% were women. Forty-six per cent of patients (n=104) presented moderate to severe anxiety symptoms (HARS score>14). Anxiety was significantly associated with severity of manic symptoms (P<0.0001). Patients with anxiety had 20% longer hospitalizations (mean 21 days, CI95% 19.7-23.7). CONCLUSION An association of anxiety symptoms with greater severity in acute mania was demonstrated. The close relationship between anxiety and manic symptoms highlights the need for greater clinical attention to anxiety in this population. Further studies are necessary to determine whether effective treatment of anxiety symptoms could improve clinical and care outcomes.
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Affiliation(s)
- A González-Pinto
- Hospital Santiago Apóstol, University of the Basque Country, CIBERSAM, ENBREC, Vitoria, Álava, Spain.
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21
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Sala R, Goldstein BI, Morcillo C, Liu SM, Castellanos M, Blanco C. Course of comorbid anxiety disorders among adults with bipolar disorder in the U.S. population. J Psychiatr Res 2012; 46:865-72. [PMID: 22534180 PMCID: PMC3372764 DOI: 10.1016/j.jpsychires.2012.03.024] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2012] [Revised: 03/23/2012] [Accepted: 03/29/2012] [Indexed: 01/12/2023]
Abstract
OBJECTIVE To examine the prevalence and correlates of comorbid anxiety disorders among individuals with bipolar disorders (BP) and their association with prospectively ascertained comorbidities, treatment, and psychosocial functioning. METHOD As part of the National Epidemiologic Survey on Alcohol and Related Conditions, 1600 adults who met lifetime DSM-IV criteria for BP-I (n = 1172) and BP-II (n = 428) were included. Individuals were evaluated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DMS-IV Version and data was analyzed from Waves 1 and 2, approximately 3 years apart. RESULTS Sixty percent of individuals with BP had at least one lifetime comorbid anxiety disorder. Individuals with BP and anxiety disorders shared lifetime risk factors for major depressive disorder and had prospectively more depressive and manic/hypomanic episodes, suicidal ideation, suicide attempts, and more treatment seeking than those without anxiety. During the follow-up, higher incidence of panic disorder, drug use disorders, and lower psychosocial functioning were found in individuals with BP with versus without anxiety disorders. CONCLUSIONS Anxiety disorders are prospectively associated with elevated BP severity and BP-related mental health service use. Early identification and treatment of anxiety disorders are warranted to improve the course and outcome of individuals with BP.
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Affiliation(s)
- Regina Sala
- Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 69, New York, NY 10032, USA.
| | - Benjamin I. Goldstein
- Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
| | - Carmen Morcillo
- Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA
| | - Shang-Min Liu
- Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA
| | - Mariela Castellanos
- Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA
| | - Carlos Blanco
- Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA
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22
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[Bipolar disorders and comorbid anxiety: prognostic impact and therapeutic challenges]. Encephale 2012; 39:66-74. [PMID: 23095585 DOI: 10.1016/j.encep.2012.04.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2011] [Accepted: 03/06/2012] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Anxiety disorders are among the main psychiatric conditions co-occuring with bipolar disorders. Many clinical and epidemiological studies have found much higher prevalence rates of generalized anxiety disorder, social phobia, obsessive-compulsive disorder, panic disorder and post-traumatic stress disorder in bipolar patients than in the general population, regardless of age. In the National Comorbidity Survey for instance, the diagnosis of at least one anxiety disorder was made for nearly 90% of bipolar subjects. Several issues arise from this high comorbidity, such as the way anxiety disorders alter the course and prognosis of the mood disorder, and challenge typical therapeutic strategies. This article reviews data on clinical and therapeutical significance of such comorbidity. LITERATURE FINDINGS Many studies point out the poorer outcome for bipolar patients with co-occurring anxiety symptoms: apart from the alarming increase of suicidal ideas and suicide attempts, authors have found a shorter duration of euthymia, more comorbid addictions, mixed states and rapid cycling, and lower response to treatments. This is the reason why monitoring the suicidal risk in those bipolar patients with co-occurring anxiety disorders is of critical importance. From a physiopathological standpoint, the precise links between both pathologies remains unclear. The frequency of this comorbidity and its significance on long term prognosis stands in sharp contrast with the very few therapeutic studies conducted in this indication so far. Pharmacological approaches are strongly limited by the risk of mood switching under antidepressants and drug dependence on anxiolytics such as benzodiazepines. Nevertheless, there is emerging evidence of the interest of atypical antipsychotics such as olanzapine and mood stabilisers such as lamotrigine to control anxiety symptoms in bipolar patients. There is weaker evidence for other molecules. Taking into account other therapeutic approaches than the pharmacological approach appears accurate. Psychosocial interventions such as cognitive-behavioral therapies or psychoeducation appear essential to improve in a correct way the global functioning and quality of life of these patients.
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Phelps J, Manipod V. Treating anxiety by discontinuing antidepressants: a case series. Med Hypotheses 2012; 79:338-41. [PMID: 22698959 DOI: 10.1016/j.mehy.2012.05.029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2012] [Revised: 04/25/2012] [Accepted: 05/21/2012] [Indexed: 11/16/2022]
Abstract
When a patient has symptoms of anxiety, while taking an antidepressant for depression, is it possible that the antidepressant is part of the problem? Can antidepressants cause anxiety? If this were so, even if relatively rare, it would have widespread implications because of the broad use of antidepressants. However, antidepressants are widely used as a treatment for anxiety. Therefore, unless suggestive evidence were to emerge to implicate them as a potential exacerbating factor, broad use of antidepressants would likely continue for patients whose depression has improved but whose anxiety has not responded, or worsened. In that context we present 12 patients whose anxiety diminished substantially when antidepressants were tapered off, as reflected in Clinical Global Improvement Scale scores assigned by their respective clinicians. Mean duration of antidepressant taper was 17 weeks (range 0-48), as suggested by limited prior evidence supporting very slow taper rates for this purpose. Alternative treatments for depression were often used for these patients as antidepressants were tapered, particularly lithium and lamotrigine, but none of the alternatives used are generally regarded as having anti-anxiety effects. Patients with bipolar disorder diagnoses, including schizoaffective disorder, were specifically excluded. In many of these cases, other medications that might have anti-anxiety effects (including buspirone, quetiapine, olanzapine, gabapentin, and diphenhydramine) were also tapered off. Results suggest that antidepressants may actually cause anxiety in some patients with unipolar depression. Alternatively, lamotrigine or lithium may have more anti-anxiety effects than generally recognized; or these patients may have had subtle bipolar disorder despite the absence of symptoms meeting formal criteria, supporting the "bipolar spectrum" perspective on mood disorder diagnosis. This study is limited by the outcome measure used, which assesses anxiety only indirectly in the context of global improvement. However, in view of the broad implications of the findings, these preliminary observations warrant further consideration. Some patients with anxiety may be treatable not by adding medications, but rather by tapering off existing ones.
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Comorbid anxiety in bipolar spectrum disorders: a neglected research and treatment issue? J Affect Disord 2012; 137:161-4. [PMID: 22209124 DOI: 10.1016/j.jad.2011.12.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2011] [Revised: 11/15/2011] [Accepted: 12/01/2011] [Indexed: 01/12/2023]
Abstract
BACKGROUND Anxiety disorders are highly prevalent among patients with bipolar disorder and have a substantial impact on the course of illness and response to treatment. Despite the substantial impact that comorbid anxiety disorders have on the prognosis of individuals with bipolar disorder, many aspects of this comorbidity have received little attention from researchers. This study aims to document the current state of the literature on the comorbidity between anxiety and bipolar disorders by analyzing publication trends on the subject. METHOD This study is a quantitative and qualitative review of articles on the comorbidity between anxiety disorders and bipolar disorder published between 1990 and 2010 in the ISI Web of Science, Medline and PsycINFO databases. The number of articles published each year on this comorbidity was calculated and compared to the literature published on bipolar disorder as a whole. Articles were classified into five categories and 13 subcategories to identify the main focuses of the literature and current gaps in the knowledge on the subject. RESULTS Interest in the comorbidity between anxiety disorders and bipolar disorder grew continually since 1990, but seems to have reached a plateau. The majority of articles addressing this comorbidity are descriptive in nature, with very few concrete studies examining the mechanisms and treatment approaches that might lead to positive advancements in the field. LIMITATIONS Articles written in languages other than English or French were not reviewed. CONCLUSIONS It is time to step up research efforts to better understand and manage this under-studied combination of disorders.
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Greco A, Lanatà A, Valenza G, Rota G, Vanello N, Scilingo EP. On the deconvolution analysis of electrodermal activity in bipolar patients. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2012; 2012:6691-6694. [PMID: 23367464 DOI: 10.1109/embc.2012.6347529] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
People affected by bipolar disorders experience alternating states of depression with episodes of mania or hypomania. This mental can lead to a poor handling of daily routines, can worsen personal relationships, and often can be life-threatening. This preliminary study aims at investigating how the autonomic nervous system, in terms of electrodermal activity, responds to specific controlled emotional stimuli in bipolar patients. More specifically, we present here a method to deploy the analysis of ElectroDermal Activity (EDA) to discriminate clinical mood states. EDA was analyzed by using a deconvolution method to separate tonic from phasic components. The three subjects recruited and the experimental protocol used here is part of the European project PSYCHE. Preliminary results show that the bipolar mood states can be related to electrodermal tonic activity.
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Affiliation(s)
- A Greco
- Department of Information Engineering and Interdepartmental Research Center E. Piaggio, Faculty of Engineering, University of Pisa, Pisa, Italy.
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Seo JS, Jamieson K, Cosgrove V, Gwizdowski IS, Yang H, Sheehan DV, McElroy SL, Suppes T. Characteristics of responders and non-responders to risperidone monotherapy or placebo in co-occurring bipolar disorder and anxiety disorder. Eur Psychiatry 2011; 28:190-6. [PMID: 22130178 DOI: 10.1016/j.eurpsy.2011.08.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Revised: 08/12/2011] [Accepted: 08/13/2011] [Indexed: 10/27/2022] Open
Abstract
Clinical characteristics predicting response and remission to psychopharmacological treatment of bipolar disorder (BD) and co-occurring anxiety disorders have been understudied. We hypothesized that non-response to risperidone or placebo in individuals with co-occurring BD and anxiety symptoms would be associated with a more severe clinical course of BD, and certain demographic variables. This study was a secondary analysis of a randomized, double-blind, parallel, 8-week study comparing risperidone monotherapy and placebo in individuals with BD plus current panic disorder, current generalized anxiety disorder (GAD), or lifetime panic disorder (n=111) [31]. We compared clinical characteristics of responders (50% improvement on the Hamilton Anxiety Scale [HAM-A]) and non-responders as well as remitters (HAM-A<7) and non-remitters in risperidone treatment (n=54) and placebo (n=57) groups. For non-responders in the risperidone group, co-occurring lifetime panic disorder was significantly more common than for non-responders in the placebo group. Apart from this, no significant differences in course of illness or demographics were found either between or across groups for patients with BD and co-occurring anxiety symptoms receiving risperidone or placebo in this acute phase study.
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Affiliation(s)
- J S Seo
- Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences, VA Palo Alto Health Care System, 3801, Miranda Avenue (151T), Palo Alto, CA 94304, USA
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Provencher MD, Hawke LD, Thienot E. Psychotherapies for comorbid anxiety in bipolar spectrum disorders. J Affect Disord 2011; 133:371-80. [PMID: 21093062 DOI: 10.1016/j.jad.2010.10.040] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2010] [Revised: 10/20/2010] [Accepted: 10/23/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND Comorbid anxiety disorders are highly prevalent in bipolar disorder and have been shown to have serious negative impacts on the course of illness. The pharmacological treatment of anxiety can interact with the bipolar disorder and has not been proven effective. As such, many have recommended the psychological treatment of anxiety. This paper reviews the literature on psychological treatments for anxiety comorbid to bipolar disorder. METHOD The Medline, PsychInfo and Web of Science databases were thoroughly examined for relevant treatment studies. RESULTS Despite frequent recommendations in the literature, surprisingly few have studied the psychological treatment of comorbid anxiety in bipolar disorders. Nevertheless, preliminary results suggest that comorbid anxiety disorders can be effectively treated in a bipolar clientele using cognitive-behavioral therapy, mindfulness-based cognitive-behavioral therapy or relaxation training. In contrast, interpersonal, family therapy and psychoeducation alone would not seem to be beneficial treatment alternatives for anxiety. Cognitive-behavioral therapy appears to reduce the symptoms of obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, post-traumatic stress disorder and general symptoms of anxiety among patients with bipolar disorder. However, the long-term maintenance of anxiety treatment effects may be somewhat reduced and adaptations may be called for to augment and sustain benefits. CONCLUSIONS There is an urgent need for randomized controlled trials of different forms of psychotherapy for anxiety disorders comorbid to bipolar disorder. Until such trials are available, the most promising approach would appear to be the sequential or modular CBT-based treatment of the anxiety disorder.
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Current world literature. Curr Opin Psychiatry 2011; 24:78-87. [PMID: 21116133 DOI: 10.1097/yco.0b013e3283423055] [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: 10/18/2022]
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Ferreira R, Bassi GS, Cabral A, Nobre MJ. Withdrawal from methylphenidate increases neural reactivity of dorsal midbrain. Neurosci Res 2010; 68:290-300. [PMID: 20832433 DOI: 10.1016/j.neures.2010.08.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2010] [Revised: 08/25/2010] [Accepted: 08/31/2010] [Indexed: 11/18/2022]
Abstract
Ritalin (methylphenidate hydrochloride, MP) is a non-amphetamine psychostimulant and is the drug of choice to treat children and adults diagnosed with the attention deficit hyperactivity disorder (ADHD). Several studies have demonstrated that rats treated with MP during early developmental stage exhibit alterations in anxiety-related processes such as an increased response to stressful stimuli and elevated plasma levels of corticosterone. Accordingly, the present study was designed to further characterize the neural and behavioral consequences of withdrawal from MP in adult rats and its influence on the neural reactivity of the dorsal midbrain. After initial exposure to an elevated plus-maze (EPM), brainstem neural activation, elicited by exposure to EPM aversive cues, was analyzed using a Fos-protein immunolabeling technique. Additional independent groups of animals were submitted to electrical stimulation of the dorsal column (DPAG) or the startle response procedure, in order to verify the influence of withdrawal from MP on the expression of unconditioned fear induced by DPAG activation and the effects of or withdrawal from MP on motor response, respectively. Our results provide new findings about the influence of MP treatment in adult rats, showing that, after a sudden MP treatment-break, increased anxiety, associated with the neural sensitization of anxiety-related regions, ensues.
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Affiliation(s)
- R Ferreira
- Instituto de Neurociências & Comportamento, University of São Paulo, Campus Ribeirão Preto, SP, Brazil
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