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Brain Sciences
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Bipolar Disorders: Progressing from Bench to Bedside
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Bipolar Disorders: Progressing from Bench to Bedside

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Psychiatric Diseases".

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 24656

Special Issue Editor

Dr. Rebecca Strawbridge

E-Mail Website
Guest Editor
1. Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, PO74, King’s College London, De Crespigny Park, London SE5 8AZ, UK
2. National Institute for Health Research Maudsley Biomedical Research Centre, South London & Maudsley NHS Foundation Trust, London SE5 8AZ, UK
Interests: affective disorders; treatment-resistant depression; bipolar disorder; meta-analysis; clinical trials; personalised medicine; inflammation; cognitive remediation

Special Issue Information

Dear Colleagues,

I would like to ask you to consider submitting a piece to this Special Issue on bipolar disorders in Brain Sciences. This could be, for example, novel findings from primary or secondary research studies, a mini-review or a perspective commentary.

The key aim of this Special Issue is to bring together cutting-edge topics focused on how we can help people affected by bipolar disorders.

The main reason for this is that, in spite of notable advances in academic examinations surrounding bipolar disorders, we do not yet have evidence that this progress is reaching the ‘bedside’.

  • Bipolar illness is still under-recognised, with average delays to correct diagnosis remaining around a decade. Delayed intervention is detrimental to short- and long-term outcomes.
  • In routine care, there appears to persist an underuse of evidenced effective treatments (such as lithium) and overuse of treatment strategies that have been evidenced to destabilise affect.
  • Treating bipolar depression, mixed features and rapid cycling remain unsolved clinical challenges.

Recent developments in the field show real potential for interdisciplinary collaborative research to better integrate domains including neurobiological, neuropsychological, social and clinical facets towards a better comprehension of pathogenesis and mechanisms of illness, and, critically, to prioritise translational approaches to help improve the lives of people affected by bipolar disorders.

Dr. Rebecca Strawbridge
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bipolar
  • mania
  • depression
  • psychopharmacology
  • early intervention
  • multidisciplinary
  • neurobiology
  • neuropsychology
  • personalised medicine

Published Papers (11 papers)

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Editorial

Jump to: Research, Review, Other

4 pages, 202 KiB  
Editorial
Collecting Contributions for a Critical Issue: Progressing from Bench to Bedside in Bipolar Disorders
by Rebecca Strawbridge
Brain Sci. 2023, 13(9), 1254; https://doi.org/10.3390/brainsci13091254 - 28 Aug 2023
Viewed by 560
Abstract
It was a joy reading the submissions for the Brain Sciences Special Issue that I edited, entitled “Bipolar Disorders: Progressing from Bench to Bedside” [...] Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)

Research

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10 pages, 1149 KiB  
Article
Long-Term Lithium Therapy and Thyroid Disorders in Bipolar Disorder: A Historical Cohort Study
by Boney Joseph, Nicolas A. Nunez, Vanessa Pazdernik, Rakesh Kumar, Mehak Pahwa, Mete Ercis, Aysegul Ozerdem, Alfredo B. Cuellar-Barboza, Francisco Romo-Nava, Susan L. McElroy, Brandon J. Coombes, Joanna M. Biernacka, Marius N. Stan, Mark A. Frye and Balwinder Singh
Brain Sci. 2023, 13(1), 133; https://doi.org/10.3390/brainsci13010133 - 12 Jan 2023
Cited by 8 | Viewed by 3025
Abstract
Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of [...] Read more.
Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact on clinical outcomes in the course of illness have not been fully characterized. In this study we aimed to compare clinical characteristics of adult BD patients with and without thyroid disorders who were on LTLT. We aimed to identify the incidence of thyroid disorders in patients with BD on LTLT and response to lithium between patients with and without thyroid disorders in BD. The Cox proportional model was used to find the median time to the development of a thyroid disorder. Our results showed that up to 32% of patients with BD on LTLT developed a thyroid disorder, of which 79% developed hypothyroidism, which was corrected with thyroid hormone replacement. We did not find significant differences in lithium response between patients with or without thyroid disorders in BD. Findings from this study suggest that patients with BD and comorbid thyroid disorders when adequately treated have a response to lithium similar to patients with BD and no thyroid disorders. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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11 pages, 648 KiB  
Article
Validation of the Longitudinal Interval Follow-Up Evaluation for the Long-Term Measurement of Mood Symptoms in Bipolar Disorder
by Richard J. Porter, Will Moot, Maree L. Inder, Marie T. Crowe, Katie M. Douglas, Janet D. Carter and Christopher Frampton
Brain Sci. 2022, 12(12), 1717; https://doi.org/10.3390/brainsci12121717 - 15 Dec 2022
Cited by 2 | Viewed by 1341
Abstract
The long-term burden of symptoms is an important outcome in bipolar disorder (BD). A method which has minimal burden of assessment uses a retrospective interview, the Longitudinal Interval Follow-up Examination (LIFE), although this may be subject to problems with recall. This study examines [...] Read more.
The long-term burden of symptoms is an important outcome in bipolar disorder (BD). A method which has minimal burden of assessment uses a retrospective interview, the Longitudinal Interval Follow-up Examination (LIFE), although this may be subject to problems with recall. This study examines the relationship between the retrospective LIFE scale and concurrently-rated mood rating scales in two clinical trials of 18 months of psychotherapy for patients with BD. The Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were administered every eight to nine weeks and the LIFE was carried out every 6 months. Correlations between scores on mood rating scales and at equivalent times on the LIFE were examined, as well as of potential clinical moderators. There were significant correlations between LIFE depression ratings and concurrent MADRS score (r = 0.57) and between LIFE mania ratings and YMRS score (r = 0.40). In determining “mild depression” on the MADRS, a receiver operating characteristics (ROC) analysis showed an AUC of 0.78 for LIFE scores. Correlations, particularly for depression scores, were high even when the LIFE rating was several months before the interview, suggesting that the LIFE has validity in examining the burden of mood symptoms over time, with relatively little burden of assessment. Future research should examine the relationship between symptom burden and quality of life measured in this way. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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21 pages, 684 KiB  
Article
Differential Diagnosis of Major Depressive Disorder and Bipolar Disorder: Genetic and Hormonal Assessment and the Influence of Early-Life Stress
by Itiana Castro Menezes, Cristiane von Werne Baes, Fernanda Viana Fígaro-Drumond, Brisa Burgos Dias Macedo, Ana Carolina Bueno, Riccardo Lacchini, Marcelo Feijó de Mello, Margaret de Castro and Mario Francisco Juruena
Brain Sci. 2022, 12(11), 1476; https://doi.org/10.3390/brainsci12111476 - 31 Oct 2022
Cited by 4 | Viewed by 2438
Abstract
Few studies have assessed biomarkers for the differentiation of major depressive disorder (MDD) and bipolar disorder (BD). However, some elements of depression such as hormones and receptors of the renin–angiotensin–adrenal system (RAAS), the hypothalamus–pituitary–adrenal (HPA) axis, and history of early-life stress (ELS) could [...] Read more.
Few studies have assessed biomarkers for the differentiation of major depressive disorder (MDD) and bipolar disorder (BD). However, some elements of depression such as hormones and receptors of the renin–angiotensin–adrenal system (RAAS), the hypothalamus–pituitary–adrenal (HPA) axis, and history of early-life stress (ELS) could be considered for differential diagnosis. Therefore, this study aimed to assess aldosterone and cortisol levels, MR and GR gene polymorphisms, and ELS as potential biomarkers for differentiating MDD and BD. This study presents a case–control design. Groups comprised samples for genetic, cortisol, and aldosterone analysis: healthy control (HC; n = 113/97/103), MDD (n = 78/69/67) and BD (n = 82/68/65) subjects. Furthermore, all subjects were assessed for diagnostic screening, the severity of depression, and history of ELS by applying MINI-PLUS, GRID-HDRS, and CTQ, respectively. In addition, genotype and allelic frequencies of GR (N363S, R22/23K and BclI) and MR (MI180V and -2G/C) polymorphisms were evaluated via PCR. Our findings demonstrate that basal aldosterone levels may be a biomarker for differentiating BD and MDD. Furthermore, ELS affects the HPA axis in BD, cortisol may be considered a biomarker for distinguishing BD and MDD, but only in the absence of ELS, and, finally, history of ELS and MR-2G/C variant alleles are factors that contribute to the severity of depressive symptoms in MDD and BD. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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16 pages, 865 KiB  
Article
Adapted Behavioural Activation for Bipolar Depression: A Randomised Multiple Baseline Case Series
by Kim Wright, Mohammod Mostazir, Ella Bailey, Barnaby D. Dunn, Heather O’Mahen, Michaela Sibsey and Zoe Thomas
Brain Sci. 2022, 12(10), 1407; https://doi.org/10.3390/brainsci12101407 - 19 Oct 2022
Cited by 2 | Viewed by 1698
Abstract
Behavioural Activation (BA) is associated with a substantial evidence base for treatment of acute unipolar depression, and has promise as an easily disseminable psychological intervention for bipolar depression. Using a randomised multiple baseline case series design we examined the feasibility and acceptability of [...] Read more.
Behavioural Activation (BA) is associated with a substantial evidence base for treatment of acute unipolar depression, and has promise as an easily disseminable psychological intervention for bipolar depression. Using a randomised multiple baseline case series design we examined the feasibility and acceptability of an adapted version of BA in a U.K. outpatient sample of 12 adults with acute bipolar depression. Participants were allocated at random to a 3–8 week wait period before being offered up to 20 sessions of BA. They completed outcome measures at intake, pre- and post-treatment and weekly symptom measures across the study period. Retention in therapy was high (11/12 participants completed the target minimum number of sessions), and all participants returning acceptability measures reported high levels of satisfaction with the intervention. No therapy-related serious adverse events were reported, nor were there exacerbations in manic symptoms that were judged to be a result of the intervention. The pattern of change on outcome measures is consistent with the potential for clinical benefit; six of the nine participants with a stable baseline showed clinically significant improvement on the primary outcome measure. The findings suggest adapted BA for bipolar depression is a feasible and acceptable approach that merits further investigation. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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Review

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14 pages, 442 KiB  
Review
Acetazolamide for Bipolar Disorders: A Scoping Review
by Rebecca Strawbridge, Nefize Yalin, Stelios Orfanos and Allan H. Young
Brain Sci. 2023, 13(1), 140; https://doi.org/10.3390/brainsci13010140 - 13 Jan 2023
Cited by 2 | Viewed by 2527
Abstract
Acetazolamide, a carbonic anhydrase inhibitor, is used to treat a variety of ailments. It has been highlighted for its potential to benefit people with bipolar disorders, for whom there are clear current unmet treatment needs. This scoping review sought to synthesise all available [...] Read more.
Acetazolamide, a carbonic anhydrase inhibitor, is used to treat a variety of ailments. It has been highlighted for its potential to benefit people with bipolar disorders, for whom there are clear current unmet treatment needs. This scoping review sought to synthesise all available evidence related to the potential effects of acetazolamide on symptoms related to bipolar disorder, acceptability and tolerability, and intervention characteristics (e.g., dose and duration). Following publication of the review protocol, the Pubmed, Embase, and PsycInfo databases were searched (all dated to 31 August 2022). A systematic approach was undertaken to identify eligible articles and extract relevant data from these. Five studies were included, assessing a total of 50 patients treated with acetazolamide. Most patients were from two open-label trials, while the others were case reports. Approximately one third of patients were experiencing psychosis or mania before treatment initiation, and one third had refractory depression. Forty-four percent of patients were estimated to achieve a response (not seemingly affected by the baseline episode type, acetazolamide dose, or duration), while a further 22% appeared to experience minimal benefits from the intervention. Acetazolamide was generally reported to be tolerated well and acceptable for up to 2 years, although reporting for acceptability and tolerability was suboptimal. The reviewed evidence is extremely limited in size and methodology (e.g., no randomised studies, blinding, or standardised outcome assessment). We posit that the current findings are sufficiently encouraging to recommend substantive clinical trials, but we emphasise that at present, the evidence is exceedingly preliminary, and there remains evident uncertainty as to whether acetazolamide could be a viable treatment for bipolar disorders. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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13 pages, 954 KiB  
Review
Astrocytes in the Neuropathology of Bipolar Disorder: Review of Current Evidence
by Nasia Dai, Brett D. M. Jones and Muhammad Ishrat Husain
Brain Sci. 2022, 12(11), 1513; https://doi.org/10.3390/brainsci12111513 - 08 Nov 2022
Cited by 2 | Viewed by 1770
Abstract
(1) Background: Approximately one-third of patients with bipolar disorder (BD) do not experience sustained remission with current treatments. Presently, astrocytes, i.e., glial cells that act as key regulators of neuroinflammation, have been a target for therapeutic development. Research regarding their role in the [...] Read more.
(1) Background: Approximately one-third of patients with bipolar disorder (BD) do not experience sustained remission with current treatments. Presently, astrocytes, i.e., glial cells that act as key regulators of neuroinflammation, have been a target for therapeutic development. Research regarding their role in the neuropathology of BD is limited. We conducted a scoping review on evidence linking astrocytes to the pathology of BD. (2) Methods: The search was conducted in MEDLINE for studies published from inception to August 2022. Studies of interest were data-extracted and reported based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols. (3) Results: Overall, 650 publications were identified, of which 122 full texts were evaluated and 12 included. Four were in vitro, seven were ex vivo, and one study was both in vitro and in vivo. In vitro investigations focused on plasma levels of neuroinflammatory biomarkers S100B and glial fibrillary acidic protein (GFAP). Ex vivo investigations were post-mortem brain studies assessing astrocytes in regions of interest (i.e., anterior cingulate cortex, dorsolateral prefrontal cortex) using phosphorylated GFAP and ASCT-1. The in vivo and in vitro study evaluated morphological and chemical variations of YKL-40 between cohorts. (4) Conclusions: Reports indicate an association between astrocyte dysfunction and BD although larger studies are required to validate this association. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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16 pages, 1218 KiB  
Review
Impulsivity in Bipolar Disorder: State or Trait?
by Rachel Primo Santana, Jess Kerr-Gaffney, Anda Ancane and Allan H. Young
Brain Sci. 2022, 12(10), 1351; https://doi.org/10.3390/brainsci12101351 - 05 Oct 2022
Cited by 11 | Viewed by 2086
Abstract
Impulsive behaviour is a key characteristic of mania in bipolar disorder (BD). However, there is mixed evidence as to whether impulsivity is a trait feature of the disorder, present in the euthymic state in the absence of mania. The aim of this systematic [...] Read more.
Impulsive behaviour is a key characteristic of mania in bipolar disorder (BD). However, there is mixed evidence as to whether impulsivity is a trait feature of the disorder, present in the euthymic state in the absence of mania. The aim of this systematic review and meta-analysis was to examine whether impulsivity is elevated in euthymic BD in comparison to controls. Electronic databases were searched for papers published until April 2022 reporting data on a self-report or behavioural measure of impulsivity in a euthymic BD group and a healthy control group. In total, 46 studies were identified. Euthymic BD showed significantly higher levels of self-reported impulsivity compared to controls (large effect size). Euthymic BD also showed significantly higher levels of impulsivity on response inhibition and inattention tasks, with moderate and large effect sizes, respectively. Only two studies measured delay of gratification, finding no significant differences between groups. Our results suggest impulsivity may be a trait feature of BD, however longitudinal cohort studies are required to confirm whether elevated impulsivity is present before illness onset. Future research should establish whether cognitive interventions are beneficial in improving impulsivity in BD. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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Other

21 pages, 796 KiB  
Systematic Review
The Role of Ketamine in the Treatment of Bipolar Depression: A Scoping Review
by Muhammad Youshay Jawad, Saleha Qasim, Menglu Ni, Ziji Guo, Joshua D. Di Vincenzo, Giacomo d’Andrea, Aniqa Tabassum, Andrea Mckenzie, Sebastian Badulescu, Iria Grande and Roger S. McIntyre
Brain Sci. 2023, 13(6), 909; https://doi.org/10.3390/brainsci13060909 - 04 Jun 2023
Cited by 5 | Viewed by 3965
Abstract
Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively [...] Read more.
Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively synthesize the current clinical literature around ketamine use in bipolar depression. A total of 10 clinical studies (5 randomized controlled trials and 5 open label studies) were selected. The preliminary evidence, albeit weak, suggests that ketamine is a promising treatment and calls for further interest from the research community. Overall, ketamine treatment appeared to be tolerable with minimal risk for manic/hypomanic switching and showed some effectiveness across parameters of depression and suicidality. Moreover, ketamine is a potential treatment agent in patients with treatment-resistant bipolar depression with promising data extracted from extant controlled trials and real-world effectiveness studies. Future studies are needed to identify ketamine’s role in acute and maintenance treatment phases of bipolar depression. Moreover, future researchers should study the recurrence prevention and anti-suicidal effects of ketamine in the treatment of bipolar depression. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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15 pages, 1124 KiB  
Systematic Review
The Relationship between Mood Symptom Severity and Perfectionism Subtypes in Mood Disorders: A Systematic Review and Meta-Analysis
by Katy Lea, Thomas Richardson and Nina Rauze
Brain Sci. 2023, 13(3), 377; https://doi.org/10.3390/brainsci13030377 - 21 Feb 2023
Cited by 2 | Viewed by 1655
Abstract
Background: Previous research suggests that there is a link between perfectionism and symptoms of depression. This study aimed to see if different types of perfectionism are linked differently to symptoms of depression in mood disorders and if there is a relationship between perfectionism [...] Read more.
Background: Previous research suggests that there is a link between perfectionism and symptoms of depression. This study aimed to see if different types of perfectionism are linked differently to symptoms of depression in mood disorders and if there is a relationship between perfectionism and symptoms of mania in bipolar disorder. Methods: A systematic search was conducted in the databases PsycINFO, EMBASE, Web of Science, and PubMed to find papers which examined the relationship in clinical depression and bipolar disorder. A meta-analysis pooled the correlation effect sizes for mood symptoms severity and the severity of the perfectionism subtype. Results: Twelve papers were included in the review, with five of these being included in the meta-analysis. The meta-analysis found statistically significant positive correlations between greater severity of depression symptoms and more severe perfectionism for the following subtypes: concern over mistakes, doubts about actions, other-oriented perfectionism, parental criticism, self-oriented perfectionism, and socially prescribed perfectionism. There was no significant relationship between depression symptoms and perfectionism subtypes of organisation and personal standards. There were not enough studies reporting data for manic symptoms for the meta-analysis or for any firm conclusions to be drawn. Conclusions: The relationship between depression and perfectionism differs depending on the particular type of perfectionism examined. Most studies were cross-sectional and correlational, so causation cannot be inferred, and future longitudinal studies are needed. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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13 pages, 861 KiB  
Systematic Review
Thyroid Hormone Augmentation for Bipolar Disorder: A Systematic Review
by Ashok Seshadri, Vishnu Sundaresh, Larry J. Prokop and Balwinder Singh
Brain Sci. 2022, 12(11), 1540; https://doi.org/10.3390/brainsci12111540 - 14 Nov 2022
Cited by 6 | Viewed by 2550
Abstract
Thyroid hormone (TH) augmentation, although commonly used for major depression, is sparingly used for bipolar disorder (BD) after the failure of mood-stabilizing agents. While the exact mechanisms of thyroid hormone action in BD remains unclear, central thyroid hormone deficit has been postulated as [...] Read more.
Thyroid hormone (TH) augmentation, although commonly used for major depression, is sparingly used for bipolar disorder (BD) after the failure of mood-stabilizing agents. While the exact mechanisms of thyroid hormone action in BD remains unclear, central thyroid hormone deficit has been postulated as a mechanism for rapid cycling. This systematic review—conducted in accordance with the PRISMA guidelines—of eight studies synthesizes the evidence for TH augmentation in BD. A systematic search of the Ovid MEDLINE, Embase, PsycINFO, and Cochrane databases was conducted for randomized controlled trials (RCT), open-label trials, and observational studies of levothyroxine (LT4) and triiodothyronine (T3) for BD. Open-label studies of high dose LT4 augmentation for bipolar depression and rapid cycling showed improvement in depression outcomes and reduction in recurrence, respectively. However, an RCT of high-dose LT4 did not show benefit in contrast to placebo. An RCT comparing LT4, T3, and placebo showed benefit only in rapid-cycling bipolar women. A meta-analysis could not be completed due to significant differences in study designs, interventions, and outcomes. Our systematic review shows mixed evidence and a lack of high-quality studies. The initial promise of supratherapeutic LT4 augmentation from open-label trials has not been consistently replicated in RCTs. Limited data are available for T3. The studies did not report significant thyrotoxicosis, and TH augmentation were well tolerated. Therefore, TH augmentation, especially with supratherapeutic doses, should be reserved for highly treatment-resistant bipolar depression and rapid-cycling BD. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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