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Wozniak J, O'Connor H, Iorini M, Ambrose AJH. Pediatric Bipolar Disorder: Challenges in Diagnosis and Treatment. Paediatr Drugs 2025; 27:125-142. [PMID: 39592559 PMCID: PMC11829910 DOI: 10.1007/s40272-024-00669-z] [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] [Accepted: 11/06/2024] [Indexed: 11/28/2024]
Abstract
Despite an opportunity to prevent adult psychopathology associated with bipolar disorder through early diagnosis in children, there is insufficient information and awareness among healthcare providers about the unique features and treatment of mania and its comorbid conditions in children. Converging evidence from disparate sites describe a developmentally distinct presentation of bipolar disorder in youth that is highly morbid, persistent and responds to treatment with the mood stabilizer medications used in the treatment of adult bipolar disorder, such as divalproex sodium and carbamazepine. Some are additionally approved for use in pediatric populations including, for manic or mixed states, risperidone, aripiprazole, and asenapine for those aged 10-17 years and also including lithium and olanzapine for ages 13-17 years. Quetiapine is approved as monotherapy or as adjunct to lithium or divalproex sodium for manic states in those aged 10-17 years. Delayed or missed diagnosis, inappropriate treatment, worsening course, and treatment resistance unfortunately still occur. While an array of mood-stabilizing medications is available for treatment, such as second-generation antipsychotics, lithium, and anticonvulsants, these can be only partially effective and fraught with annoying and serious side effects. This article will review current practice in the diagnosis and treatment of pediatric bipolar disorder and its comorbid conditions, highlighting areas of need for future research.
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Affiliation(s)
- Janet Wozniak
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, 02114, USA.
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
| | - Hannah O'Connor
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, 02114, USA
| | - Maria Iorini
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, 02114, USA
| | - Adrian Jacques H Ambrose
- Department of Psychiatry, Columbia University Irving Medical Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Wang B, Sheu YH, Lee H, Mealer RG, Castro VM, Smoller JW. Prediction of early-onset bipolar using electronic health records. J Child Psychol Psychiatry 2025. [PMID: 39967306 DOI: 10.1111/jcpp.14131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/11/2024] [Indexed: 02/20/2025]
Abstract
BACKGROUND Early identification of bipolar disorder (BD) provides an important opportunity for timely intervention. In this study, we aimed to develop machine learning models using large-scale electronic health record (EHR) data including clinical notes for predicting early-onset BD. METHODS Structured and unstructured data were extracted from the longitudinal EHR of the Mass General Brigham health system. We defined three cohorts aged 10-25 years: (1) the full youth cohort (N = 300,398); (2) a subcohort defined by having a mental health visit (N = 105,461); and (3) a subcohort defined by having a diagnosis of mood disorder or ADHD (N = 35,213). By adopting a prospective landmark modeling approach that aligns with clinical practice, we developed and validated a range of machine learning models, across different cohorts and prediction windows. RESULTS We found the two tree-based models, random forests (RF) and light gradient-boosting machine (LGBM), achieving good discriminative performance across different clinical settings (area under the receiver operating characteristic curve 0.76-0.88 for RF and 0.74-0.89 for LGBM). In addition, we showed comparable performance can be achieved with a greatly reduced set of features, demonstrating computational efficiency can be attained without significant compromise of model accuracy. CONCLUSIONS Good discriminative performance for models predicting early-onset BD can be achieved utilizing large-scale EHR data. Our study offers a scalable and accurate method for identifying youth at risk for BD that could help inform clinical decision-making and facilitate early intervention. Future work includes evaluating the portability of our approach to other healthcare systems and exploring considerations regarding possible implementation.
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Affiliation(s)
- Bo Wang
- Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Yi-Han Sheu
- Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Hyunjoon Lee
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Robert G Mealer
- Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA
| | - Victor M Castro
- Research Information Science and Computing, Mass General Brigham, Somerville, MA, USA
| | - Jordan W Smoller
- Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Hooshyari Z, Mohammadi MR, Salmanian M, Ahmadi N, Khaleghi A, Garakani A. Lifetime prevalence, comorbidities, and Sociodemographic predictors of post-traumatic stress disorder (PTSD): the National Epidemiology of Iranian Children and adolescents Psychiatric disorders (IRCAP). Eur Child Adolesc Psychiatry 2024; 33:3965-3978. [PMID: 38656607 DOI: 10.1007/s00787-024-02441-7] [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: 01/07/2023] [Accepted: 04/07/2024] [Indexed: 04/26/2024]
Abstract
OBJECTIVE The aims of this study were to (a) evaluate the lifetime prevalence of post-traumatic stress disorder (PTSD) according to sociodemographic characteristics, (b) determine sociodemographic factors associated with PTSD, (c) estimate the lifetime prevalence rates of comorbidities by age and gender, and (d) assess the proportion of traumatic events in the non-PTSD sample and the PTSD sample, according to gender. METHODS The data used for the present study were obtained from the IRCAP study which was a cross-sectional, community-based study on 29,250 children and adolescents aged 6-18 years from all provinces of Iran, which was done using multistage cluster sampling. Trained psychologists conducted diagnostic interviews with parents, children, and adolescents using the Persian version of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). RESULTS In this study, the prevalence of PTSD across the sample population was 0.6% (95% CI, 0.5-0.7%). Higher rates of PTSD were observed among girls (0.7%, CI 0.5-0.8%), adolescents aged 15-18 years (0.8%, CI 0.6-1.0%), and participants who had unemployed (1.5%, CI 0.8-2.8%), or farmer fathers (1.1%, CI 0.5-2.5%). Of the participants with PTSD, 65.1% met the criteria for at least one other psychiatric disorder. PTSD had a high rate of comorbidity with oppositional defiant disorder (22.9%, CI 17.5-29.4%), generalized anxiety disorder (20.8%, CI 15.7-27.1%), separation anxiety disorder (20.3%, CI 15.2-26.6%), and major depressive disorder (19.8%, CI 14.8-26.0%). We found 9.5% of non-PTSD sample experienced at least one traumatic event. Witness to domestic violence was the most common traumatic event experienced by 32.8% of PTSD sample. CONCLUSION Our results in the prevalence, comorbidities, and sociodemographic factors associated with PTSD supported findings of previous studies that used a structured diagnostic interview. It is recommended to use purposive sampling and to investigate comorbidities of PTSD and type of traumatic events in a large clinical population.
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Affiliation(s)
- Zahra Hooshyari
- School of Psychology and Educational Sciences, University of Tehran, Tehran, Iran
| | - Mohammad Reza Mohammadi
- Psychiatry and Psychology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Salmanian
- Psychiatry and Psychology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Nastaran Ahmadi
- Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Ali Khaleghi
- Psychiatry and Psychology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Garakani
- Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, United States of America
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Kaçar A, Karakuş OB, Aydın ZE, Adak İ. Effectiveness of Agomelatine in Generalized Anxiety Disorder Comorbid to Bipolar 1 Disorder in a Male Adolescent Patient. Clin Neuropharmacol 2024; 47:143-145. [PMID: 39140640 DOI: 10.1097/wnf.0000000000000604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2024]
Abstract
ABSTRACT Anxiety comorbidity in bipolar disorder (BD) is important and thus significantly affects the course of BD and its outcomes. The treatment of generalized anxiety disorder comorbid with BD involves certain challenges, as antidepressant medications, which are standard in the treatment of anxiety disorder, have the risk of shifting to manic episodes and rapid cycling. In this case report, the response to agomelatine treatment in generalized anxiety disorder comorbid with bipolar 1 disorder was evaluated.
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Affiliation(s)
- Aysu Kaçar
- Department of Child and Adolescent Psychiatry, Istanbul Erenköy Mental Health and Neurological Diseases Training and Research Hospital, Istanbul
| | - Oğuz Bilal Karakuş
- Department of Child and Adolescent Psychiatry, Trabzon Kanuni Training and Research Hospital, Trabzon, Turkey
| | - Zeynep Ece Aydın
- Department of Child and Adolescent Psychiatry, Istanbul Erenköy Mental Health and Neurological Diseases Training and Research Hospital, Istanbul
| | - İbrahim Adak
- Department of Child and Adolescent Psychiatry, Istanbul Erenköy Mental Health and Neurological Diseases Training and Research Hospital, Istanbul
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Anona K, Olaomi O, Udegbe E, Uwumiro F, Tuaka EB, Okafor N, Adeyinka A, Obijuru C, Okpujie V, Bojerenu M, Opeyemi M. Co-occurrence of bipolar disorder and personality disorders in the United States: Prevalence, suicidality, and the impact of substance abuse. J Affect Disord 2024; 345:1-7. [PMID: 37848089 DOI: 10.1016/j.jad.2023.10.087] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 10/07/2023] [Accepted: 10/13/2023] [Indexed: 10/19/2023]
Abstract
BACKGROUND This study investigates prevalence rates of specific personality disorders (PDs) in individuals with bipolar disorder (BD) and their impact on substance abuse and suicidality, addressing existing gaps in the literature. METHODS Using Nationwide Inpatient Sample data (2016-2020), adult hospitalizations for BD with coexisting PDs were analyzed. Study variables were defined using ICD-10-CM codes. Prevalence of PD were reported as cases per 100,000 BD admissions. Regression models assessed the association between substance abuse and suicidality. RESULTS About 993,000 admissions for BD were analyzed. The cohort was predominantly Caucasian (70.5 %) with higher female representation (54.5 %). The mean age was 41 years. 89.4 % of individuals had a Charlson Comorbidity Index score ≤ 1. The most common diagnostic subtype was manic episode of BD with or without psychotic features (32.3 %). Coexisting PDs were observed in 12.2 % of the population, with borderline PD (8.2 %) and antisocial PD (2.6 %) being most prevalent. Substance abuse was common (44.8 %), with cannabis (23.8 %), alcohol (19.4 %), cocaine (10.5 %), and opioids (9.6 %) being most reported. Substance abuse was higher in individuals with BD and PD (50 %) compared to BD alone (44.1 %). 596 suicide attempts were recorded (60 per 100,000 BD admissions). Substance abuse and coexisting PD in bipolar individuals elevated the likelihood of attempts (P < 0.001). LIMITATIONS Use of administrative data (retrospective, inpatient); treatment not studied. CONCLUSION The study reveals a notable prevalence of PDs in individuals with BD, with increased likelihood of substance abuse and suicide attempts in those with coexisting BD and PD compared to BD alone.
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Affiliation(s)
- Kenechukwu Anona
- Greater Manchester Mental Health National Health Service Foundation Trust, UK
| | | | | | - Fidelis Uwumiro
- Jos University Teaching Hospital, Jos, Plateau State, Nigeria.
| | - Ebere-Bank Tuaka
- Rivers State University Teaching Hospital, Port Harcourt, Nigeria
| | - Nnenna Okafor
- All Saints University College of Medicine, Belair Kingstown, Saint Vincent and the Grenadines
| | | | - Chinwendu Obijuru
- College of Medicine, University of Nigeria, Ituku-Ozalla, Enugu State, Nigeria
| | - Victory Okpujie
- College of Medicine, University of Benin, Benin City, Edo State, Nigeria
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Woodward D, Wilens TE, Yule AM, DiSalvo M, Taubin D, Berger A, Stone M, Wozniak J, Burke C, Biederman J. Examining the clinical correlates of conduct disorder in youth with bipolar disorder. J Affect Disord 2023; 329:300-306. [PMID: 36863464 PMCID: PMC10041394 DOI: 10.1016/j.jad.2023.02.119] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 02/16/2023] [Accepted: 02/22/2023] [Indexed: 03/04/2023]
Abstract
BACKGROUND Conduct Disorder (CD) is highly comorbid with Bipolar Disorder (BP) and this comorbidity is associated with high morbidity and dysfunction. We sought to better understand the clinical characteristics and familiality of comorbid BP + CD by examining children with BP with and without co-morbid CD. METHODS 357 subjects with BP were derived from two independent datasets of youth with and without BP. All subjects were evaluated with structured diagnostic interviews, the Child Behavior Checklist (CBCL), and neuropsychological testing. We stratified the sample of subjects with BP by the presence or absence of CD and compared the two groups on measures of psychopathology, school functioning, and neurocognitive functioning. First-degree relatives of subjects with BP +/- CD were compared on rates of psychopathology in relatives. RESULTS Subjects with BP + CD compared to BP without CD had significantly more impaired scores on the CBCL Aggressive Behavior (p < 0.001), Attention Problems (p = 0.002), Rule-Breaking Behavior (p < 0.001), Social Problems (p < 0.001), Withdrawn/Depressed clinical scales (p = 0.005), the Externalizing Problems (p < 0.001), and Total Problems composite scales(p < 0.001). Subjects with BP + CD had significantly higher rates of oppositional defiant disorder (ODD) (p = 0.002), any SUD (p < 0.001), and cigarette smoking (p = 0.001). First-degree relatives of subjects with BP + CD had significantly higher rates of CD/ODD/ASPD and cigarette smoking compared to first-degree relatives of subjects without CD. LIMITATIONS The generalization of our findings was limited due to a largely homogeneous sample and no CD only comparison group. CONCLUSIONS Given the deleterious outcomes associated with comorbid BP + CD, further efforts in identification and treatment are necessary.
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Affiliation(s)
- Diana Woodward
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States
| | - Timothy E Wilens
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States.
| | - Amy M Yule
- Department of Psychiatry, Boston University School of Medicine, Boston Medical Center, 720 Harrison Avenue, Suite 915, Boston, MA 02118, United States
| | - Maura DiSalvo
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States
| | - Daria Taubin
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States
| | - Amy Berger
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States
| | - Mira Stone
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States
| | - Janet Wozniak
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States
| | - Colin Burke
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States
| | - Joseph Biederman
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States
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Hours C. Pediatric Bipolar Disorder: A Practical Guide for Clinicians. Child Psychiatry Hum Dev 2023:10.1007/s10578-023-01534-9. [PMID: 37097506 DOI: 10.1007/s10578-023-01534-9] [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] [Accepted: 04/04/2023] [Indexed: 04/26/2023]
Abstract
Pediatric bipolar disorder (PBD) is a controversial clinical entity and it still needs to be satisfactorily defined. Having a polymorphous presentation and associated with numerous symptoms of comorbid psychiatric illnesses often diagnosed during childhood and adolescence, including attention deficit hyperactivity disorder, its symptoms do not completely parallel those of bipolar disorder in adults. The clinician must be able to reach a diagnosis of PBD in the presence of fluctuating and atypical symptoms, especially in children, who tend to experience mixed episodes and very rapid cycles. Historically a key symptom for diagnosing PBD is episodic irritability. Proper diagnosis is critical due to the gravity of its prognosis. Clinicians may find supporting evidence for a diagnosis through careful study of the medical and developmental history of the young patient in addition to psychometric data. Treatment prioritizes psychotherapeutic intervention and assigns important roles to family involvement and a healthy lifestyle.
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Saxena K, Chang K, Sani G. Pediatric Bipolar Disorder: Evolution in Clinical and Biological Markers and Future Perspectives. Curr Neuropharmacol 2023; 21:1300-1301. [PMID: 37190778 PMCID: PMC10324340 DOI: 10.2174/1570159x2106230410111947] [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] [Indexed: 05/17/2023] Open
Affiliation(s)
- Kirti Saxena
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Tx, USA
| | | | - Gabriele Sani
- Department of Neuroscience, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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Wozniak J, Farrell A, DiSalvo M, Ceranoglu A, Uchida M, Vaudreuil C, Joshi G, Faraone SV, Cook E, Biederman J. A Randomized, Double-Blind, Controlled Clinical Trial of Omega-3 Fatty Acids and Inositol as Monotherapies and in Combination for the Treatment of Pediatric Bipolar Spectrum Disorder in Children Age 5-12. PSYCHOPHARMACOLOGY BULLETIN 2022; 52:31-51. [PMID: 36339275 PMCID: PMC9611796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Objectives The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (FAs) and inositol alone and in combination for the treatment of pediatric bipolar (BP) spectrum disorder in young children. Methods Participants were male and female children ages 5-12 meeting DSM-IV diagnostic criteria for a BP spectrum disorder and displaying mixed, manic, or hypomanic symptoms without psychotic features at the time of evaluation. Results Participants concomitantly taking psychotropic medication were excluded from efficacy analyses. There were significant reductions in YMRS and HDRS mean scores in the inositol and combination treatment groups (all p < 0.05) and in CDRS mean scores in the combination treatment group (p < 0.001), with the largest changes seen in the combination group. Those receiving the combination treatment had the highest rates of antimanic and antidepressant response. The odds ratios for the combination group compared to the omega-3 FAs and inositol groups were clinically meaningful (ORs ≥2) for 50% improvement on the YMRS, normalization of the YMRS (score <12) (vs. inositol group only), 50% improvement on the HDRS, 50% improvement on CDRS (vs. omega-3 FAs group only), and CGI-I Mania, CGI-I MDD, and CGI-I Anxiety scores <2. Conclusion The antimanic and antidepressant effects of the combination treatment of omega-3 FAs and inositol were consistently superior to either treatment used alone. This combination may offer a safe and effective alternative or augmenting treatment for youth with BP spectrum disorder, but more work is needed to confirm the statistical significance of this finding.
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Affiliation(s)
- Janet Wozniak
- Janet Wozniak, MD, Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA, Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Abigail Farrell
- Abigail Farrell, BS, Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA
| | - Maura DiSalvo
- Maura DiSalvo, MPH, Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA
| | - Atilla Ceranoglu
- Atilla Ceranoglu, MD, Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA, Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Mai Uchida
- Mai Uchida, MD, Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA, Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Carrie Vaudreuil
- Carrie Vaudreuil, MD, Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA, Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Gagan Joshi
- Gagan Joshi, MD, Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA, Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Stephen V Faraone
- Stephen V. Faraone, PhD, Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Emmaline Cook
- Emmaline Cook, BA, Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA
| | - Joseph Biederman
- Joseph Biederman, MD, Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA, Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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Wozniak J, DiSalvo M, Farrell A, Vaudreuil C, Uchida M, Ceranoglu TA, Joshi G, Cook E, Faraone SV, Biederman J. Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania. BMC Psychiatry 2022; 22:314. [PMID: 35505312 PMCID: PMC9066881 DOI: 10.1186/s12888-022-03943-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 04/07/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder. METHODS We conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5-17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children's Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression. RESULTS This study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint. CONCLUSIONS These pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02357290 . First Registration 06/02/2015.
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Affiliation(s)
- Janet Wozniak
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, USA.
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
| | - Maura DiSalvo
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, USA
| | - Abigail Farrell
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, USA
| | - Carrie Vaudreuil
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Mai Uchida
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - T Atilla Ceranoglu
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Gagan Joshi
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Emmaline Cook
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, USA
| | - Stephen V Faraone
- Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Joseph Biederman
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, 55 Fruit St., Warren 705, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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Wozniak J, DiSalvo M, Farrell A, Yule A, Joshi G, Cook E, Faraone SV, Biederman J. Can pediatric bipolar disorder be successfully treated when comorbid with conduct disorder? A secondary analysis of clinical trials of risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole. J Psychopharmacol 2022; 36:637-644. [PMID: 35510655 DOI: 10.1177/02698811221087673] [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] [Indexed: 11/17/2022]
Abstract
BACKGROUND Pediatric bipolar disorder (BP) is frequently comorbid with conduct disorder (CD) and its presence adds to the morbidity of BP. While there are no known pharmacological treatments for CD, pediatric BP is responsive to treatment with medications initially indicated for the treatment of psychosis, several of which have Food and Drug Administration (FDA) approval for the treatment of pediatric mania. AIMS The main aim of this secondary analysis was to examine whether pediatric BP comorbid with CD responds similarly to treatment with such selected medications. Considering the well-documented morbidity of CD, this finding could have important clinical and public health significance. METHODS We conducted a secondary analysis of six prospective 8-week open-label trials of selected medications (risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) using identical methodology in youth with BP with and without comorbid CD. Results: Of 165 youths with BP, 54% (N = 89) met criteria for comorbid CD. The antimanic effects observed did not significantly differ between BP youths with and without comorbid CD, as measured either by a reduction in Young Mania Rating Scale (YMRS) ⩾ 30% or Clinical Global Impression (CGI)-Improvement ⩽ 2 (p = 0.23), or by the more stringent definition of a reduction in YMRS ⩾ 50% (p = 0.61). CONCLUSION Pediatric BP can be effectively treated with the abovementioned medications in the context of comorbid CD. Based on previous research showing that remission of BP is associated with remission of CD, if confirmed, these findings raise the possibility that antimanic treatment of youth with BP comorbid with CD could have secondary benefits in mitigating the morbidity associated with CD. This is a pilot scale finding, the results of which are promising and should be confirmed by larger and long-term follow-up studies.
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Affiliation(s)
- Janet Wozniak
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA.,Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Maura DiSalvo
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA
| | - Abigail Farrell
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA
| | - Amy Yule
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA.,Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Gagan Joshi
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA.,Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Emmaline Cook
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA
| | - Stephen V Faraone
- Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Joseph Biederman
- Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA, USA.,Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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12
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Schiweck C, Arteaga-Henriquez G, Aichholzer M, Edwin Thanarajah S, Vargas-Cáceres S, Matura S, Grimm O, Haavik J, Kittel-Schneider S, Ramos-Quiroga JA, Faraone SV, Reif A. Comorbidity of ADHD and adult bipolar disorder: A systematic review and meta-analysis. Neurosci Biobehav Rev 2021; 124:100-123. [PMID: 33515607 DOI: 10.1016/j.neubiorev.2021.01.017] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 01/12/2021] [Accepted: 01/19/2021] [Indexed: 12/17/2022]
Abstract
Attention-deficit / hyperactivity disorder (ADHD) and Bipolar Disorder (BD) are common mental disorders with a high degree of comorbidity. However, no systematic review with meta-analysis has aimed to quantify the degree of comorbidity between both disorders. To this end we performed a systematic search of the literature in October 2020. In a meta-analysis of 71 studies with 646,766 participants from 18 countries, it was found that about one in thirteen adults with ADHD was also diagnosed with BD (7.95 %; 95 % CI: 5.31-11.06), and nearly one in six adults with BD had ADHD (17.11 %; 95 % CI: 13.05-21.59 %). Substantial heterogeneity of comorbidity rates was present, highlighting the importance of contextual factors: Heterogeneity could partially be explained by diagnostic system, sample size and geographical location. Age of BD onset occurred earlier in patients with comorbid ADHD (3.96 years; 95 % CI: 2.65-5.26, p < 0.001). Cultural and methodological differences deserve attention for evaluating diagnostic criteria and clinicians should be aware of the high comorbidity rates to prevent misdiagnosis and provide optimal care for both disorders.
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Affiliation(s)
- Carmen Schiweck
- Department for Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt- Goethe University, Germany.
| | - Gara Arteaga-Henriquez
- Department for Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain; Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain; Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain
| | - Mareike Aichholzer
- Department for Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt- Goethe University, Germany
| | - Sharmili Edwin Thanarajah
- Department for Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt- Goethe University, Germany; Max-Planck-Institute for Metabolism Research, Cologne, Germany
| | - Sebastian Vargas-Cáceres
- Department for Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
| | - Silke Matura
- Department for Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt- Goethe University, Germany
| | - Oliver Grimm
- Department for Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt- Goethe University, Germany
| | - Jan Haavik
- Department of Biomedicine, University of Bergen, Bergen, Norway; Bergen Center of Brain Plasticity, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
| | - Sarah Kittel-Schneider
- Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital, University of Würzburg, Würzburg, Germany
| | - Josep Antoni Ramos-Quiroga
- Department for Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain; Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain; Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain
| | - Stephen V Faraone
- Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Andreas Reif
- Department for Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt- Goethe University, Germany
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13
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Grunze H, Schaefer M, Scherk H, Born C, Preuss UW. Comorbid Bipolar and Alcohol Use Disorder-A Therapeutic Challenge. Front Psychiatry 2021; 12:660432. [PMID: 33833701 PMCID: PMC8021702 DOI: 10.3389/fpsyt.2021.660432] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 03/01/2021] [Indexed: 02/05/2023] Open
Abstract
Comorbidity rates in Bipolar disorder rank highest among major mental disorders, especially comorbid substance use. Besides cannabis, alcohol is the most frequent substance of abuse as it is societally accepted and can be purchased and consumed legally. Estimates for lifetime comorbidity of bipolar disorder and alcohol use disorder are substantial and in the range of 40-70%, both for Bipolar I and II disorder, and with male preponderance. Alcohol use disorder and bipolarity significantly influence each other's severity and prognosis with a more complicated course of both disorders. Modern treatment concepts acknowledge the interplay between these disorders using an integrated therapy approach where both disorders are tackled in the same setting by a multi-professional team. Motivational interviewing, cognitive behavioral and socio- therapies incorporating the family and social environment are cornerstones in psychotherapy whereas the accompanying pharmacological treatment aims to reduce craving and to optimize mood stability. Adding valproate to lithium may reduce alcohol consumption whereas studies with antipsychotics or naltrexone and acamprosate did not affect mood fluctuations or drinking patterns. In summary, there is a continuous need for more research in order to develop evidence-based approaches for integrated treatment of this frequent comorbidity.
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Affiliation(s)
- Heinz Grunze
- Psychiatrie Schwäbisch Hall, Schwäbisch Hall, Germany
- Paracelsus Medical University Nuremberg, Nuremberg, Germany
- *Correspondence: Heinz Grunze
| | - Martin Schaefer
- Klinik für Psychiatrie, Psychotherapie, Psychosomatik, und Suchtmedizin, Evang. Kliniken Essen-Mitte, Essen, Germany
- Klinik für Psychiatrie und Psychotherapie, Campus Charité Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany
| | | | - Christoph Born
- Psychiatrie Schwäbisch Hall, Schwäbisch Hall, Germany
- Paracelsus Medical University Nuremberg, Nuremberg, Germany
| | - Ulrich W. Preuss
- Vitos Klinik Psychiatrie und Psychotherapie, Herborn, Germany
- Klinik für Psychiatrie, Psychotherapie, und Psychosomatik, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany
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14
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Zsamboky M, Haskell B, Vick R, Schroer M. Treating Child and Adolescent Depression and Anxiety in Primary Care. J Nurse Pract 2021. [DOI: 10.1016/j.nurpra.2020.08.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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15
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Suicidal ideation and attempts in unipolar versus bipolar depression: analysis of 131,740 adolescent inpatients nationwide. Psychiatry Res 2020; 291:113231. [PMID: 32574899 DOI: 10.1016/j.psychres.2020.113231] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 06/12/2020] [Accepted: 06/13/2020] [Indexed: 12/16/2022]
Abstract
Objective To evaluate the risk of suicidal ideation and suicidal attempt in adolescents with unipolar depression (UD) versus bipolar depression (BD). Method We included 131,740 adolescents (12-17y), with primary diagnoses of UD (92.6%) and BD (7.4%) from the nationwide inpatient sample. We calculated odds ratio (OR) for suicidal behaviors using logistic regression adjusted for demographic confounders and comorbidities. Results Suicidal ideation and suicidal attempt were seen in 14.5% and 38.6% respectively of total inpatients and both were seen in higher proportion of UD. Females have higher odds for suicidal attempt (OR 1.13, 95%CI 1.09-1.16) compared to males. After adjusting for confounders, UD had a marginally higher odds (OR 1.06, 95%CI 1.02-1.11) of suicidal attempt and 1.2 times higher odds (95%CI 1.11-1.26) of suicidal ideation compared to BD. Among adolescents with suicidal attempt, 93.2% had bipolar depression and 6.8% had unipolar depression.The majority of suicidal attempt in the inpatient setting was seen in females, with bipolar depression (74.6% vs. 67.3% in unipolar). Conclusion Our finding is clinically relevant and accentuates the need for early identification of BD, accurate differentiation of UD versus BD for targeted and adequate treatment to minimize suicidal behaviors, treat and manage them per treatment guidelines, and evolving research.
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16
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Wang YS, Lee SY, Chen SL, Chang YH, Wang TY, Lin SH, Wang CL, Huang SY, Lee I, Chen P, Yang Y, Lu RB. Role of DRD2 and ALDH2 genes in bipolar II disorder with and without comorbid anxiety disorder. Eur Psychiatry 2020; 29:142-8. [DOI: 10.1016/j.eurpsy.2013.05.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2013] [Revised: 05/05/2013] [Accepted: 05/06/2013] [Indexed: 10/26/2022] Open
Abstract
AbstractThe presence of comorbid anxiety disorders (AD) and bipolar II disorders (BP-II) compounds disability complicates treatment, worsens prognosis, and has been understudied. The genes involved in metabolizing dopamine and encoding dopamine receptors, such as aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor (DRD2) genes, may be important to the pathogenesis of BP-II comorbid with AD. We aimed to clarify ALDH2 and DRD2 genes for predisposition to BP-II comorbid with and without AD. The sample consisted of 335 subjects BP-II without AD, 127 subjects BP-II with AD and 348 healthy subjects as normal control. The genotypes of the ALDH2 and DRD2 Taq-IA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a statistically significant association between DRD2 Taq-I A1/A2 genotype and BP-II with AD (OR = 2.231, P = 0.021). Moreover, a significant interaction of the DRD2 Taq-I A1/A1 and the ALDH2*1*1 genotypes in BP-II without AD was revealed (OR = 5.623, P = 0.001) compared with normal control. Our findings support the hypothesis that a unique genetic distinction between BP-II with and without AD, and suggest a novel association between DRD2 Taq-I A1/A2 genotype and BP-II with AD. Our study also provides further evidence that the ALDH2 and DRD2 genes interact in BP-II, particularly BP-II without AD.
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17
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Fili J, Nojomi M, Razjouyan K, Kahdemi M, Davari-Ashtiani R. Association between Attention Deficit Hyperactivity Disorder and Suicide Attempts in Patients with Bipolar Disorder. IRANIAN JOURNAL OF PSYCHIATRY 2019; 14:242-247. [PMID: 31598128 PMCID: PMC6778605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 07/06/2019] [Accepted: 07/20/2019] [Indexed: 10/27/2022]
Abstract
Objective: The present study aimed to examine the association between ADHD and suicide attempts among adolescents with bipolar disorder. Method : Participants were 168 adolescents who fulfilled DSM-IV-TR criteria for bipolar disorder. They were divided into 2 groups: The first group of patients with bipolar disorder with a history of suicide attempts (n = 84) and the second group without a history of suicide attempts (n = 84). ADHD and other variables were analyzed using a chi-squared test and logistic regression model. Results: No significant difference was observed between the 2 groups in comorbidity of ADHD and other psychiatric disorders (P > 0/05). In the logistic regression model, and after controlling for other factors, gender (OR = 3.9, CI 95%: 1.5-9.6) and history of sexual abuse (OR = 3.4; CI 95%: 1.06-11.3) were the only 2 factors associated with a history of suicide attempts. Conclusion: No significant association was found between ADHD and suicide attempts in adolescents with bipolar disorder.
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Affiliation(s)
- Jafar Fili
- Department of Psychiatry, Shafa Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Marzieh Nojomi
- Preventive Medicine & Public Health Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Katayoon Razjouyan
- Department of Psychiatry, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Behavioral Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mojgan Kahdemi
- Department of Psychiatry, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Behavioral Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rozita Davari-Ashtiani
- Department of Psychiatry, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Behavioral Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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18
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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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19
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Gautam S, Jain A, Gautam M, Gautam A, Jagawat T. Clinical Practice Guidelines for Bipolar Affective Disorder (BPAD) in Children and Adolescents. Indian J Psychiatry 2019; 61:294-305. [PMID: 30745704 PMCID: PMC6345130 DOI: 10.4103/psychiatry.indianjpsychiatry_570_18] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- Shiv Gautam
- Director Professor, Gautam Hospital and Institute of Behavioural Sciences, Jaipur, Rajasthan, India
| | - Akhilesh Jain
- HOD, Department of Psychiatry, ESI Model Hospital, Jaipur, Rajasthan, India
| | - Manaswi Gautam
- Director & Consultant Psychiatrist, Gautam Hospital & Research Center, Jaipur, Rajasthan, India
| | - Anita Gautam
- Director Clinical Operation & Consultant Psychiatrist, Gautam Hospital & Research Center, Jaipur, Rajasthan, India
| | - Tushar Jagawat
- Prof., Department of Psychiatry, NIMS Medical College, Jaipur, Rajasthan, India
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20
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Wang YC, Yu YH, Tsai ML, Huang ACW. Motor function in an animal model with ouabain-induced bipolar disorder and comorbid anxiety behavior. Psychiatry Res 2018; 268:508-513. [PMID: 30165326 DOI: 10.1016/j.psychres.2018.07.031] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Revised: 04/10/2018] [Accepted: 07/18/2018] [Indexed: 12/26/2022]
Abstract
In a clinical setting, anxiety disorder is highly correlated with bipolar I disorder in humans. However, the comorbidity of anxiety behavior and bipolar disorder still remains unclear in an animal model. This study utilized an ouabain-induced animal mode to examine anxiety and mania in an open field test. In the present study, 5 µl of artificial cerebrospinal fluid (aCSF) or ouabain (10-5, 10-4, and 10-3 M) were administered into the left ventricle. The animals' motor functions and anxiety behaviors were measured for 15 min. The results showed that 10-3 M ouabain significantly increased the animal's total distance traveled, average speed, and maximum speed compared to the control group. The time spent inside (i.e., how much time rats spent in the center of the square) and the inside-outside times of the central square (i.e., how many times rats ran across the center square) of the higher-concentration groups (10-4 M and 10-3 M) were significantly decreased. Therefore, a high concentration of ouabain may induce hyperactivity. The 10-4 M and 10-3 M ouabain groups exhibited more anxiety behaviors. The study is the first model to examine comorbid anxiety behaviors and bipolar disorder in an animal model. The study provides some insights for comorbid anxiety and bipolar disorder in clinics.
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Affiliation(s)
- Ying-Chou Wang
- Department of Clinical Psychology, Fu Jen Catholic University, New Taipei City 24205, Taiwan
| | - Ying Hao Yu
- Department of Psychology, Fo Guang University, Yilan County 26247, Taiwan
| | - Meng-Li Tsai
- Department of Biomechatronic Engineering, National Ilan University, Ilan, Taiwan
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21
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King JB, Anderson JS, Yurgelun-Todd DA, Subramaniam P, Ehrler MR, Lopez-Larson MP. Decreased anterior cingulate activation in a motor task in youths with bipolar disorder. J Child Psychol Psychiatry 2018; 59:900-907. [PMID: 29451300 PMCID: PMC6041159 DOI: 10.1111/jcpp.12875] [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] [Accepted: 01/03/2018] [Indexed: 11/30/2022]
Abstract
BACKGROUND Bipolar disorder (BP) is characterized by abnormal shifts in mood between episodes of mania and severe depression, both of which have been linked with psychomotor disturbances. This study compares brain activation patterns in motor networks between euthymic youths with BP and healthy controls (HC) during the completion of a simple motor task. METHODS Thirty-five youths with BP and 35 HC (aged 10-19) completed a self-paced sequential bilateral finger-tapping task, consisting of a 4-minute scan block with alternating 20-second periods of either the tapping task (six blocks) or rest (six blocks), while undergoing functional magnetic resonance imaging. Clinical and behavioral symptoms were assessed using the Child Behavior Checklist (CBCL). A between-group whole-brain analysis compared activation pattern differences while controlling for effects of age and sex. Clusters meeting whole-brain false discovery rate (FDR) correction (qFDR < .05) were considered statistically significant. Post hoc analyses evaluating comorbid attention-deficit/hyperactivity disorder (ADHD) in the BP group were also conducted. RESULTS Significantly decreased activation was found in the anterior cingulate cortex (ACC) in youths with BP compared to HC. Furthermore, ACC activation was negatively correlated with CBCL mood dysregulation profile scores in the BP group. No significant differences in functional activation patterns were found between youths with BP and comorbid ADHD and those with only BP. CONCLUSIONS These findings suggest a potential common mechanism of impaired ACC modulation between emotion dysregulation and motor processing in youths with BP.
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Affiliation(s)
- Jace B. King
- Department of Radiology, University of Utah, Salt Lake City, UT, USA,Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT, USA,Diagnostic Neuroimaging, University of Utah, Salt Lake City, UT USA,Correspondence: Jace B. King, University of Utah, Imaging and Neurosciences Center, 729 Arapeen Drive, Salt Lake City, UT, 84108, USA; Phone: 801-585-9667;
| | - Jeffrey S. Anderson
- Department of Radiology, University of Utah, Salt Lake City, UT, USA,Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT, USA,School of Medicine, University of Utah, Salt Lake City, UT, USA
| | - Deborah A. Yurgelun-Todd
- Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT, USA,Diagnostic Neuroimaging, University of Utah, Salt Lake City, UT USA,School of Medicine, University of Utah, Salt Lake City, UT, USA
| | - Punitha Subramaniam
- Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT, USA,Diagnostic Neuroimaging, University of Utah, Salt Lake City, UT USA
| | | | - Melissa P. Lopez-Larson
- Diagnostic Neuroimaging, University of Utah, Salt Lake City, UT USA,School of Medicine, University of Utah, Salt Lake City, UT, USA
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Akbaş S, Nahir M, Pirzirenli ME, Dündar C, Ceyhan M, Sarısoy G, Şahin B. Quantitative analysis of the amygdala, thalamus and hippocampus on magnetic resonance images in paediatric bipolar disorders and compared with the children of bipolar parents and healthy control. Psychiatry Res Neuroimaging 2017; 270:61-67. [PMID: 29065344 DOI: 10.1016/j.pscychresns.2017.08.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Revised: 06/29/2017] [Accepted: 08/29/2017] [Indexed: 12/28/2022]
Abstract
MR imaging studies in paediatric bipolar disorder have particularly focused on the amygdala and hippocampus, subcortical structures, and to a lesser extent on the thalamus. The purpose of this study was to perform structural analysis of the regions of interest (ROI) associated with mood regulation. In this study 18 children (between the ages of 12-18) were matched according to their age and sex and were divided into three groups. These were: a paediatric bipolar disorder group, risk group and a healthy control group. The structured diagnostic interviews were performed with children and their parents. T1 weighted MR images in the sagittal plane with a thickness of 1mm were taken from the subjects. Automatic structural brain analysis was performed, and the volume and volume fraction (VF) of the ROIs were obtained. Brain size in the patients with paediatric bipolar disorder (742.4 ± 110.1cm3) was significantly smaller than the healthy control group (880.7 ± 73.8cm3) (p≤0.05). MRI analysis between the paediatric bipolar disorder, risk group and healthy control group revealed no difference between them in terms of amygdala, thalamus or hippocampal volumes. In this study, there was no difference between the volumes of amygdala, thalamus or hippocampus.
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Affiliation(s)
- Seher Akbaş
- Department of Child and Adolescent Psychiatry, Erenkoy Mental Health and Neurology Training and Research Hospital, Istanbul, Turkey.
| | - Mert Nahir
- Ondokuz Mayıs University Faculty of Medicine Department of Anatomy, Turkey
| | | | - Cihat Dündar
- Ondokuz Mayıs University Faculty of Medicine Department of Public Health, Turkey
| | - Meltem Ceyhan
- Ondokuz Mayıs University Faculty of Medicine Department of Radiology, Turkey
| | - Gökhan Sarısoy
- Ondokuz Mayıs University Faculty of Medicine Department of Psychiatry, Turkey
| | - Bünyamin Şahin
- Ondokuz Mayıs University Faculty of Medicine Department of Anatomy, Turkey
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23
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Fontanella CA, Hiance-Steelesmith DL, Gilchrist R, Bridge JA, Weston D, Campo JV. Quality of care for Medicaid-enrolled youth with bipolar disorders. ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH 2016; 42:126-38. [PMID: 24729042 DOI: 10.1007/s10488-014-0553-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This study examined conformance to clinical practice guidelines for children and adolescents with bipolar disorders and identified patient and provider factors associated with guideline concordant care. Administrative records were examined for 4,047 Medicaid covered youth aged 5-18 years with new episodes of bipolar disorder during 2006-2010. Main outcome measures included 5 claims-based quality of care measures reflecting national treatment guidelines. Measures addressed appropriate pharmacotherapy, therapeutic drug monitoring, and psychosocial treatment. The results indicated that current treatment practices for youth diagnosed with bipolar disorder typically fall short of recommended practice guidelines. Although the majority of affected youth are treated with recommended first-line pharmacotherapy, only a minority receive therapeutic drug monitoring and/or psychotherapy of recommended duration, underscoring the need for quality improvement initiatives.
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Affiliation(s)
- Cynthia A Fontanella
- Department of Psychiatry, College of Medicine, The Ohio State University, 1670 Upham Road, Columbus, OH, 43210, USA,
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Pan PY, Yeh CB. Mood disturbance in adolescents screened by the Mood Disorder Questionnaire predicts poorer social adjustment. J Adolesc Health 2015; 56:652-7. [PMID: 26003581 DOI: 10.1016/j.jadohealth.2015.02.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 02/06/2015] [Accepted: 02/07/2015] [Indexed: 10/23/2022]
Abstract
PURPOSE Early-onset bipolar disorder is associated with a more severe illness course and poorer outcome. Its identification in adolescents may provide the opportunity for adequate intervention to improve global functioning and long-term prognosis. Thus, this study aimed to screen mood disturbance in a sample of high school students using Mood Disorder Questionnaire (MDQ) and follow up their adaptive functioning 1 year later. METHODS In the first year, adolescents aged 15-17 years old from a Taiwanese senior high school (N = 1,151) completed the Chinese version of MDQ, the Impulsiveness Scale, and a set of questions about risky behaviors. A subgroup of respondents (N = 184) picked randomly were interviewed to validate the diagnosis of bipolar disorder. In the second year, the Social Adjustment Inventory for Children and Adolescents was applied for the same sample of subjects for the measurement of their adaptive functions. RESULTS The intraclass correlation coefficient and the Cronbach α coefficient of the MDQ were .68 and .61, respectively. MDQ score of at least 7 showed modest sensitivity (.57) and specificity (.64) for bipolar disorder. Higher MDQ score predicted risky behaviors in adolescents at baseline measurement. MDQ score was found significantly correlated with Impulsiveness Scale total score. In follow-up evaluation, participants with an MDQ score of ≥7 had poorer social adjustment. CONCLUSIONS Our findings suggest that untreated mood disturbance among adolescents leads to impaired social adaptive functioning in the next year. The application of MDQ in adolescents may help clinicians in early intervention for their emotional disturbance.
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Affiliation(s)
- Pei-Yin Pan
- Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Chin-Bin Yeh
- Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
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Frías Á, Palma C, Farriols N. Comorbidity in pediatric bipolar disorder: prevalence, clinical impact, etiology and treatment. J Affect Disord 2015; 174:378-89. [PMID: 25545605 DOI: 10.1016/j.jad.2014.12.008] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Revised: 12/03/2014] [Accepted: 12/04/2014] [Indexed: 01/02/2023]
Abstract
BACKGROUND Research on pediatric bipolar disorder (PBD) is providing a plethora of empirical findings regarding its comorbidity. We addressed this question through a systematic review concerning the prevalence, clinical impact, etiology and treatment of main comorbid disorders involved. METHOD A comprehensive database search was performed from 1990 to August 2014. Overall, 167 studies fulfilled the inclusion criteria. RESULTS Bipolar youth tend to suffer from comorbid disorders, with highest weighted mean prevalence rate arising from anxiety disorders (54%), followed by attention deficit hyperactivity disorder (ADHD) (48%), disruptive behavior disorders (31%), and substance use disorders (SUD) (31%). Furthermore, evidence indicates that ADHD and anxiety disorders negatively affect the symptomatology, neurocognitive profile, clinical course and the global functioning of PBD. Likewise, several theories have been posited to explain comorbidity rates in PBD, specifically common risk factors, one disorder being a risk factor for the other and nosological artefacts. Lastly, randomized controlled trials highlight a stronger therapeutic response to stimulants and atomoxetine (vs. placebo) as adjunctive interventions for comorbid ADHD symptoms. In addition, research focused on the treatment of other comorbid disorders postulates some benefits from mood stabilizers and/or SGA. LIMITATIONS Epidemiologic follow-up studies are needed to avoid the risk of nosological artefacts. Likewise, more research is needed on pervasive developmental disorders and anxiety disorders, especially regarding their etiology and treatment. CONCLUSIONS Psychiatric comorbidity is highly prevalent and is associated with a deleterious clinical effect on pediatric bipolarity. Different etiological pathways may explain the presence of these comorbid disorders among bipolar youth. Standardized treatments are providing ongoing data regarding their effectiveness for these comorbidities among bipolar youth.
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Affiliation(s)
- Álvaro Frías
- FPCEE Blanquerna, University of Ramon-Llull, Císterst 34, 08022 Barcelona, Spain; Adult Outpatient Mental Health Center, Hospital of Mataró, Mataró, Spain.
| | - Cárol Palma
- FPCEE Blanquerna, University of Ramon-Llull, Císterst 34, 08022 Barcelona, Spain; Adult Outpatient Mental Health Center, Hospital of Mataró, Mataró, Spain
| | - Núria Farriols
- FPCEE Blanquerna, University of Ramon-Llull, Císterst 34, 08022 Barcelona, Spain; Adult Outpatient Mental Health Center, Hospital of Mataró, Mataró, Spain
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Díaz-Caneja CM, Moreno C, Llorente C, Espliego A, Arango C, Moreno D. Practitioner review: Long-term pharmacological treatment of pediatric bipolar disorder. J Child Psychol Psychiatry 2014; 55:959-80. [PMID: 24905547 DOI: 10.1111/jcpp.12271] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/27/2014] [Indexed: 11/26/2022]
Abstract
BACKGROUND Although long-term treatment is a core aspect of the management of children and adolescents with bipolar disorder (BD), most clinical recommendations are based on results from short-term studies or adult data. In order to guide clinical practice, we review the efficacy and safety profile of mood stabilizers, antipsychotics, and other pharmacological strategies for the long-term treatment of BD in pediatric patients. METHODS A MEDLINE, EMBASE, Cochrane and PsycInfo search (inception through November 2013) was performed to identify prospective studies longer than 12 weeks assessing the use of pharmacological strategies for the long-term treatment of BD in pediatric patients (0-18 years of age). RESULTS Four randomized controlled trials (RCT) [three placebo-controlled (assessing aripiprazole (2) and flax oil), and one head-to-head comparison of lithium vs. divalproex], and thirteen noncontrolled studies (six open-label studies assessing lithium or anticonvulsants, five assessing second-generation antipsychotics (SGAs) and four assessing combination strategies) were included in the review. Aripiprazole has shown efficacy for relapse prevention in children with pediatric bipolar disorder (PBD) 4-9 years of age in one placebo-controlled RCT. Positive results have been reported in noncontrolled studies with quetiapine and lithium for relapse prevention, as well as with lithium, quetiapine, ziprasidone, and the combination of risperidone and divalproex or lithium for long-term symptom reduction in PBD. The most frequently reported adverse events in children and adolescents treated with lithium and anticonvulsants are gastrointestinal and neurological, whereas use of SGAs is mainly related to weight gain and sedation. CONCLUSION According to the limited empirical evidence, aripiprazole can be useful for relapse prevention in children with PBD. Given the lack of consistent efficacy data, clinical decision making should be based on individual clinical aspects and safety concerns.
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Affiliation(s)
- Covadonga M Díaz-Caneja
- Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, CIBERSAM, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain
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Muneer A. Aripiprazole in the treatment of refractory mood disorders: a case series. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE 2014; 12:157-9. [PMID: 25191507 PMCID: PMC4153863 DOI: 10.9758/cpn.2014.12.2.157] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Revised: 01/03/2014] [Accepted: 01/06/2014] [Indexed: 12/26/2022]
Abstract
Major depressive disorder and bipolar disorders are among the commonest neuropsychiatric conditions, affecting persons of both sexes which belong to all age groups. Comorbidity is the rule rather than the exception; anxiety spectrum disorders, somatoform disorders, eating disorders and substance use disorders frequently co-exist with mood disorders. Catatonia is a serious complication of the latter and every patient with a severe affective exacerbation should be assessed for the presence of catatonic signs and symptoms. In a significant minority of patients, symptoms show treatment resistance; many patients experience severe hopelessness and suicidal ideation, causing high rates of morbidity and mortality in afflicted individuals. Pharmacological management is challenging and currently available psychotropic agents often fall short of inducing remission. Second generation antipsychotics have been shown in a number of studies as having an antidepressant and mood stabilizing effect. Aripiprazole is a novel antipsychotic which is being increasingly used in difficult to treat mood disorders patients. Several controlled and uncontrolled studies have shown the efficacy and safety of this medication in subjects of all ages. Here a case series of three patients is presented who suffered from refractory mood disorders but responded to aripiprazole with complete remission of affective symptoms.
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Affiliation(s)
- Ather Muneer
- Department of Psychiatry, Islamic International Medical College, Pakistan Railway Teaching Hospital, Rawalpindi, Pakistan
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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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Seymour KE, Pescosolido MF, Reidy BL, Galvan T, Kim KL, Young M, Dickstein DP. Emotional face identification in youths with primary bipolar disorder or primary attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2013; 52:537-546.e3. [PMID: 23622855 PMCID: PMC4418014 DOI: 10.1016/j.jaac.2013.03.011] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Revised: 02/28/2013] [Accepted: 03/15/2013] [Indexed: 11/17/2022]
Abstract
OBJECTIVE Bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) are often comorbid or confounded; therefore, we evaluated emotional face identification to better understand brain/behavior interactions in children and adolescents with either primary BD, primary ADHD, or typically developing controls (TDC). METHOD Participants included individuals 7 to 17 years of age (overall sample mean age 12.40 ± 3.01 years), with "narrow-phenotype" pediatric BD (n = 30) or ADHD (n = 38), or typically developing controls (TDC) with no psychiatric disorders themselves or in their first-degree relatives (n = 41). In the BD group, comorbid diagnoses were allowed; however, youth in the ADHD group were excluded for comorbid mood or anxiety disorders. Patient groups were not excluded for psychotropic medication use. Emotional face identification was assessed using the computerized Diagnostic Analysis of Non-Verbal Accuracy (DANVA). RESULTS Participants with BD made significantly more identification errors on child happy faces than either TDCs (p = .03) or participants with ADHD (p = .01). Furthermore, youth with BD (0.33 ± 0.55) were more likely than youth with ADHD (0.11 ± 0.31) to make errors on low-intensity child happy faces (p = .05) but not high-intensity happy faces (p = NS). Participants with BD and ADHD made significantly more total errors in child face labeling than did TDCs, although participants with BD and ADHD did not differ from one another. CONCLUSION Our data suggest that youths with BD have specific alterations in emotional face identification of happy faces, an important finding that supports theories that response to positively valenced emotional stimuli may be especially salient in BD. Clinical trial registration information-Brain Imaging and Computer Games in Children With Either Bipolar Disorder, ADHD, Anxiety or Healthy Controls (BBPP); http://clinicaltrials.gov/; NCT01570426.
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Affiliation(s)
- Karen E Seymour
- Bradley Hospital's Pediatric Mood, Imaging, and NeuroDevelopmental (PediMIND) Program and the Alpert Medical School of Brown University, RI 02915, USA.
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Stevens JR, Wilens TE, Stern TA. Using stimulants for attention-deficit/hyperactivity disorder: clinical approaches and challenges. Prim Care Companion CNS Disord 2013; 15:12f01472. [PMID: 23930227 DOI: 10.4088/pcc.12f01472] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2012] [Accepted: 10/22/2012] [Indexed: 01/20/2023] Open
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Cummings CM, Fristad MA. Anxiety in children with mood disorders: a treatment help or hindrance? JOURNAL OF ABNORMAL CHILD PSYCHOLOGY 2012; 40:339-51. [PMID: 21912843 PMCID: PMC4340699 DOI: 10.1007/s10802-011-9568-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
This study examined the role of comorbid anxiety in treatment outcome for children with mood disorders (N = 165; age 8-11) participating in Multi-Family Psychoeducational Psychotherapy (MF-PEP). Assessments occurred at baseline, 6, 12, and 18 months for two randomly assigned groups: immediate treatment and 1-year wait-list. Most children (69%) had comorbid anxiety disorders. Baseline comorbid anxiety, as reported on the Children's Interview for Psychiatric Syndromes (ChIPS), was associated with higher Children's Depression Rating Scale- Revised (CDRS-R) scores but not Young Mania Rating Scale (YMRS) scores. Higher levels of anxiety symptoms were associated with lower Children's Global Assessment Scale (C-GAS) scores. Participation in MF-PEP did not significantly reduce anxiety symptoms (p = 0.62). However, presence of comorbid anxiety did not impede reduction in depressive (CDRS-R, p = 0.74) or manic (YMRS scores, p = 0.94) symptoms following MF-PEP. More baseline anxiety symptoms were associated with greater improvement in C-GAS scores post-treatment (p = 0.02). Implications are discussed.
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Affiliation(s)
- Colleen M Cummings
- Department of Psychology, Temple University, Weiss Hall, 1701 N. 13th St., Philadelphia, PA 19122, USA.
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Sala R, Axelson DA, Castro-Fornieles J, Goldstein TR, Goldstein BI, Ha W, Liao F, Gill MK, Iyengar S, Strober MA, Yen S, Hower H, Hunt JI, Dickstein DP, Ryan ND, Keller MB, Birmaher B. Factors associated with the persistence and onset of new anxiety disorders in youth with bipolar spectrum disorders. J Clin Psychiatry 2012; 73:87-94. [PMID: 22226375 PMCID: PMC3600866 DOI: 10.4088/jcp.10m06720] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2010] [Accepted: 04/13/2011] [Indexed: 01/29/2023]
Abstract
OBJECTIVE Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder, but, to our knowledge, no studies examined the course of anxiety disorders in youth and adults with bipolar disorder. METHOD As part of the Course and Outcome of Bipolar Youth study, 413 youth, ages 7 to 17 years who met criteria for Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) bipolar I disorder (n = 244), bipolar II disorder (n = 28), and operationally defined bipolar disorder not otherwise specified (n = 141) were recruited primarily from outpatient clinics. Subjects were followed on average for 5 years using the Longitudinal Interval Follow-Up Evaluation. We examined factors associated with the persistence (> 50% of the follow-up time) and onset of new anxiety disorders in youth with bipolar disorder. RESULTS Of the 170 youth who had anxiety at intake, 80.6% had an anxiety disorder at any time during the follow-up. Most of the anxiety disorders during the follow-up were of the same type as those present at intake. About 50% of the youth had persistent anxiety, particularly generalized anxiety disorder (GAD). Persistence was associated with multiple anxiety disorders, less follow-up time in euthymia, less conduct disorder, and less treatment with antimanic and antidepressant medications (all P values ≤ .05). Twenty-five percent of the sample who did not have an anxiety disorder at intake developed new anxiety disorders during follow-up, most commonly GAD. The onset of new anxiety disorders was significantly associated with being female, lower socioeconomic status, presence of attention-deficit/hyperactivity disorder and substance use disorder, and more follow-up time with manic or hypomanic symptoms (all P values ≤ .05) CONCLUSIONS Anxiety disorders in youth with bipolar disorder tend to persist, and new-onset anxiety disorders developed in a substantial proportion of the sample. Early identification of factors associated with the persistence and onset of new anxiety disorders may enable the development of strategies for treatment and prevention.
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Affiliation(s)
- Regina Sala
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Abstract
The psychosocial impact of human immunodeficiency virus (HIV) disease has been recognized since the beginning of the epidemic for affected adults, but there has been less focus on the impact of HIV on young people. Among HIV-positive (HIV+) adults, high levels of distress, psychiatric symptoms, and their associations with worse health outcomes were recognized early in the epidemic. Subsequently, many studies have focused on understanding the prevalence of psychiatric symptoms among HIV+ adults and on identifying effective treatments for these symptoms. Fewer studies have examined these symptoms and their treatments among HIV+ children and adolescents. This article reviews what is known about psychiatric syndromes among HIV+ youths, their treatments, and other psychosocial factors of concern to the psychiatrist when treating children and adolescents with HIV disease.
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Affiliation(s)
- Tami D Benton
- Department of Child and Adolescent Psychiatry, The Children's Hospital of Philadelphia, 3440 Market Street, Suite 410, Philadelphia, PA 19104, USA.
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Thomas T, Stansifer L, Findling RL. Psychopharmacology of pediatric bipolar disorders in children and adolescents. Pediatr Clin North Am 2011; 58:173-87, xii. [PMID: 21281855 DOI: 10.1016/j.pcl.2010.10.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Pediatric bipolar disorder (PBD) is a chronic and disabling illness often leading to serious disruption in the lives of children and adolescents with this condition. Until recently, methodologically stringent data to guide pharmacologic interventions in the youth were scarce. However, clinical trials conducted recently have expanded the existing evidence base, and new data are emerging rapidly. Recent studies have examined the use of lithium, anticonvulsants, and atypical antipsychotics for acute and long-term treatment of PBD. Despite these new advances, further placebo-controlled trials investigating the efficacy and safety of pharmacologic treatment strategies for young people with bipolar disorder are still needed.
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Affiliation(s)
- Tiffany Thomas
- Division of Child and Adolescent Psychiatry, University Hospitals Case Medical Center, Cleveland, OH 44106-5080, USA.
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Zappitelli MC, Bordin IA, Hatch JP, Caetano SC, Zunta-Soares G, Olvera RL, Soares JC. Lifetime psychopathology among the offspring of Bipolar I parents. Clinics (Sao Paulo) 2011; 66:725-30. [PMID: 21789371 PMCID: PMC3109366 DOI: 10.1590/s1807-59322011000500003] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2011] [Accepted: 01/20/2011] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Recent studies have demonstrated high rates of psychopathology in the offspring of parents with bipolar disorder. The aim of this study was to identify psychiatric diagnoses in a sample of children of bipolar parents. METHOD This case series comprised 35 children and adolescents aged 6 to 17 years, with a mean age of 12.5 ± 2.9 years (20 males and 15 females), who had at least one parent with bipolar disorder type I. The subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime version (K-SADS-PL). Family psychiatric history and demographics were also evaluated. RESULTS Of the offspring studied, 71.4% had a lifetime diagnosis of at least one psychiatric disorder (28.6% with a mood disorder, 40% with a disruptive behavior disorder and 20% with an anxiety disorder). Pure mood disorders (11.4%) occurred less frequently than mood disorders comorbid with attention deficit hyperactivity disorder (17.1%). Psychopathology was commonly reported in second-degree relatives of the offspring of parents with bipolar disorder (71.4%). CONCLUSIONS Our results support previous findings of an increased risk for developing psychopathology, predominantly mood and disruptive disorders, in the offspring of bipolar individuals. Prospective studies with larger samples are needed to confirm and expand these results.
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Sala R, Axelson DA, Castro-Fornieles J, Goldstein TR, Ha W, Liao F, Gill MK, Iyengar S, Strober MA, Goldstein BI, Yen S, Hower H, Hunt J, Ryan ND, Dickstein D, Keller MB, Birmaher B. Comorbid anxiety in children and adolescents with bipolar spectrum disorders: prevalence and clinical correlates. J Clin Psychiatry 2010; 71:1344-50. [PMID: 20868643 PMCID: PMC2978760 DOI: 10.4088/jcp.09m05845gre] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2009] [Accepted: 04/13/2010] [Indexed: 12/23/2022]
Abstract
OBJECTIVE Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder. We aimed to examine the prevalence and correlates of comorbid anxiety disorders among youth with bipolar disorder. METHOD As part of the Course and Outcome of Bipolar Youth study, 446 youth, ages 7 to 17 years, who met DSM-IV criteria for bipolar I disorder (n = 260) or bipolar II disorder (n = 32) or met operationalized criteria for bipolar disorder not otherwise specified (n = 154) were included. Subjects were evaluated for current and lifetime Axis I psychiatric disorders at intake using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime version, and standardized instruments were used to assess functioning and family history. RESULTS Forty-four percent (n = 194) of the sample met DSM-IV criteria for at least 1 lifetime anxiety disorder, most commonly separation anxiety (24%) and generalized anxiety disorders (16%). Nearly 20% met criteria for 2 or more anxiety disorders. Overall, anxiety disorders predated the onset of bipolar disorder. Subjects with bipolar II disorder were more likely than subjects with bipolar I disorder or bipolar disorder not otherwise specified to have a comorbid anxiety disorder. After adjusting for confounding factors, youth with bipolar disorder with anxiety were more likely to have bipolar II disorder; longer duration of mood symptoms; more severe ratings of depression; and family history of depression, hopelessness, and somatic complaints during their worst lifetime depressive episode than those without anxiety. CONCLUSIONS Comorbid anxiety disorders are common in youth with bipolar disorder, and they most often predate bipolar disorder onset. Bipolar II disorder, a family history of depression, and more severe lifetime depressive episodes distinguish youth with bipolar disorder with comorbid anxiety disorders from those without. Careful consideration should be given to the assessment of comorbid anxiety in youth with bipolar disorder.
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Affiliation(s)
- Regina Sala
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
| | - David A. Axelson
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Josefina Castro-Fornieles
- Department of Child and Adolescent Psychiatry and Psychology, IDIBAPS, CIBERSAM, Neurosciences Institute, Hospital Clinic de Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - Tina R. Goldstein
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Wonho Ha
- 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
| | - Mary Kay Gill
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Satish Iyengar
- Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Michael A Strober
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Benjamin I. Goldstein
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
| | - Shirley Yen
- Department of Psychiatry and Butler Hospital, Brown University School of Medicine, Providence, RI, USA
| | - Heather Hower
- Department of Psychiatry and Butler Hospital, Brown University School of Medicine, Providence, RI, USA
| | - Jeffrey Hunt
- Department of Psychiatry and Butler Hospital, Brown University School of Medicine, Providence, RI, USA
| | - Neal D. Ryan
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Daniel Dickstein
- Department of Psychiatry and Butler Hospital, Brown University School of Medicine, Providence, RI, USA
| | - Martin B. Keller
- Department of Psychiatry and Butler Hospital, Brown University School of Medicine, Providence, RI, USA
| | - Boris Birmaher
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Murphy DL, Timpano KR, Wheaton MG, Greenberg BD, Miguel EC. Obsessive-compulsive disorder and its related disorders: a reappraisal of obsessive-compulsive spectrum concepts. DIALOGUES IN CLINICAL NEUROSCIENCE 2010. [PMID: 20623919 PMCID: PMC3181955 DOI: 10.31887/dcns.2010.12.2/dmurphy] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Obsessive-compulsive disorder (OCD) is a clinical syndrome whose hallmarks are
excessive, anxiety-evoking thoughts and compulsive behaviors that are generally
recognized as unreasonable, but which cause significant distress and impairment.
When these are the exclusive symptoms, they constitute uncomplicated OCD. OCD
may also occur in the context of other neuropsychiatric disorders, most commonly
other anxiety and mood disorders. The question remains as to whether these
combinations of disorders should be regarded as independent, cooccurring
disorders or as different manifestations of an incompletely understood
constellation of OCD spectrum disorders with a common etiology. Additional
considerations are given here to two potential etiology-based subgroups: (i) an
environmentally based group in which OCD occurs following apparent causal events
such as streptococcal infections, brain injury, or atypical neuroleptic
treatment; and (ii) a genomically based group in which OCD is related to
chromosomal anomalies or specific genes. Considering the status of current
research, the concept of OCD and OCD-related spectrum conditions seems fluid in
2010, and in need of ongoing reappraisal.
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Affiliation(s)
- Dennis L Murphy
- Laboratory of Clinical Science, NIMH Intramural Research Program, Bethesda, Maryland 20892, USA.
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Ryan-Krause P. Attention deficit hyperactivity disorder: part I. J Pediatr Health Care 2010; 24:194-8. [PMID: 20417892 DOI: 10.1016/j.pedhc.2010.02.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Accepted: 02/10/2010] [Indexed: 02/02/2023]
Affiliation(s)
- Patricia Ryan-Krause
- Yale University School of Nursing, 100 Church St South, PO Box 9740, New Haven, CT 06536-0740, USA
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Benton TD. Psychiatric considerations in children and adolescents with HIV/AIDS. Child Adolesc Psychiatr Clin N Am 2010; 19:387-400, x. [PMID: 20478506 DOI: 10.1016/j.chc.2010.02.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The psychosocial impact of human immunodeficiency virus (HIV) disease has been recognized since the beginning of the epidemic for affected adults, but there has been less focus on the impact of HIV on young people. Among HIV-positive (HIV+) adults, high levels of distress, psychiatric symptoms, and their associations with worse health outcomes were recognized early in the epidemic. Subsequently, many studies have focused on understanding the prevalence of psychiatric symptoms among HIV+ adults and on identifying effective treatments for these symptoms. Fewer studies have examined these symptoms and their treatments among HIV+ children and adolescents. This article reviews what is known about psychiatric syndromes among HIV+ youths, their treatments, and other psychosocial factors of concern to the psychiatrist when treating children and adolescents with HIV disease.
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Affiliation(s)
- Tami D Benton
- Department of Child and Adolescent Psychiatry, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
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Nandagopal JJ, DelBello MP. Pharmacotherapy for Pediatric Bipolar Disorder. Psychiatr Ann 2010. [DOI: 10.3928/00485713-20100330-07] [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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