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Etiology, Pharmacological, and Brain Stimulation Interventions for Bipolar Disorders

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A special issue of Brain Sciences (ISSN 2076-3425).

Deadline for manuscript submissions: closed (29 February 2020) | Viewed by 28787

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Special Issue Editor

Dr. Nagy Youssef

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Guest Editor

Department of Psychiatry & Health Behavior & Office of Academic Affairs, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA
Interests: mood disorders including bipolar disorders and suicide prevention; brain stimulation interventions; psychopharmacology; PTSD

Special Issue Information

Editorial: Improving the lives of our patients suffering from bipolar disorder

Dear Colleagues,

Bipolar disorder (BD) is one of the most common brain diseases that affects multiple areas of functioning and if not properly treated can cause significant impairment of function disability, suffering, and high rates of mortality from suicide or physical illnesses associated with bipolar disorder. Although studies examining either the mechanistic undertaking or therapeutics of BD have been pursued for decades, our understanding of the etiology and mechanism for bipolar disorder is still limited.

Moreover, the pharmacological treatments that were initially studied for bipolar disorder are so limited to lithium only (that was initially and specifically studied for BD). All the other available pharmacological treatments for BD (whether for manic, mixed or depressive symptoms) were originally studied and marketed for other indications, such as schizophrenia or epilepsy and then tried in BD later. This reflects the more limited research for BD. Despite BD being a major and prevalent psychiatric disorder, there is disproportionally more limited research for BD therapeutics compared to other major psychiatric disorders such as schizophrenia or major depressive disorder.

Psychopharmacological agents, the main and most common treatment for BD, are still very limited for treating bipolar depressive symptoms, which constitute the heaviest and most prevalent symptom burden for BD. Though there are more treatment options for manic episodes, decreasing side effect burden for the available treatments continues to be an important priority. With regards to brain stimulation and apart from ECT (which has more research support), most available brain stimulation and neuromodulation interventions, whether primary electric or magnetic, are still in their infancy (except for ECT).

Thus, we dedicate this special issue as a step to further our understanding of the etiology and mechanism of BD and/or to help refine or develop better therapeutics for BD. I believe that any step in the right direction can have significant impact on improving the lives of our patients suffering from BD.

As the Guest Editor of this Special Issue: “Etiology, Pharmacological, and Brain Stimulation Interventions for Bipolar Disorders,” I welcome your contribution for this special issue in this exciting and rapidly evolving field. And I thank you in advance for your interest and contributions to furthering the science in this important field!

Prof. Nagy Youssef
Guest Editor

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Keywords

Bipolar disorders
Mechanism
Therapeutics
Psychopharmacology
Brain stimulation

Published Papers (5 papers)

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Research

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9 pages, 1329 KiB

Open AccessArticle

Clinical Role of Aspirin in Mood Disorders: A Systematic Review

by Qin Xiang Ng, Krishnapriya Ramamoorthy, Wayren Loke, Matthew Wei Liang Lee, Wee Song Yeo, Donovan Yutong Lim and Vivekanandan Sivalingam

Brain Sci. 2019, 9(11), 296; https://doi.org/10.3390/brainsci9110296 - 29 Oct 2019

Cited by 19 | Viewed by 4996

Abstract

Worldwide, depression and bipolar disorder affect a large and growing number of people. However, current pharmacotherapy options remain limited. Despite adequate treatment, many patients continue to have subsyndromal symptoms, which predict relapse in bipolar illness and often result in functional impairments. Aspirin, a common nonsteroidal anti-inflammatory drug (NSAID), has purported beneficial effects on mood symptoms, showing protective effects against depression in early cohort studies. This systematic review thus aimed to investigate the role of aspirin in mood disorders. Using the keywords (aspirin or acetylsalicy* or asa) and (mood or depress* or bipolar or mania or suicid*), a comprehensive search of PubMed, EMBASE, Medline, PsycINFO, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), Clinicaltrials.gov and Google Scholar databases found 13,952 papers published in English between 1 January 1988 and 1 May 2019. A total of six clinical studies were reviewed. There were two randomized, placebo-controlled, double-blind trials and populations drawn from two main cohort studies (i.e., the Geelong Osteoporosis Study and the Osteoarthritis Initiative study). Using a random-effects model, the pooled hazard ratio of the three cohort studies was 0.624 (95% confidence interval: 0.0503 to 1.198, p = 0.033), supporting a reduced risk of depression with aspirin exposure. Overall, the dropout rates were low, and aspirin appears to be well-tolerated with minimal risk of affective switch. In terms of methodological quality, most studies had a generally low risk of bias. Low-dose aspirin (80 to 100 mg/day) is safe, well-tolerated and potentially efficacious for improving depressive symptoms in both unipolar and bipolar depression. Due to its ability to modulate neuroinflammation and central nervous system processes, aspirin may also have valuable neuroprotective and pro-cognitive effects that deserve further exploration. Further randomized, controlled trials involving the adjunctive use of aspirin should be encouraged to confirm its therapeutic benefits. Full article

(This article belongs to the Special Issue Etiology, Pharmacological, and Brain Stimulation Interventions for Bipolar Disorders)

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15 pages, 1618 KiB

Open AccessArticle

Genetic Predisposition and Disease Expression of Bipolar Disorder Reflected in Shape Changes of the Anterior Limbic Network

by Chia-Feng Lu, Yu-Te Wu, Shin Teng, Po-Shan Wang, Pei-Chi Tu, Tung-Ping Su, Chi-Wen Jao and Cheng-Ta Li

Brain Sci. 2019, 9(9), 240; https://doi.org/10.3390/brainsci9090240 - 19 Sep 2019

Cited by 2 | Viewed by 3101

Abstract

Bipolar disorder (BD) is a genetically and phenotypically complex psychiatric disease. Although previous studies have suggested that the relatives of BD patients have an increased risk of experiencing affective disturbances, most relatives who have similar genotypes may not manifest the disorder. We aim to identify the neuroimaging alterations—specifically, the cortical folding structures of the anterior limbic network (ALN)—in BD patients and their siblings, compared to healthy controls. The shared alterations in patients and their siblings may indicate the hereditary predisposition of BD, and the altered cortical structures unique to BD patients may be a probe of BD expression. High-resolution, T1-weighted magnetic resonance images for 17 euthymic patients with BD, 17 unaffected siblings of BD patients, and 22 healthy controls were acquired. We categorized the cortical regions within the ALN into sulcal and gyral areas, based on the shape index, followed by the measurement of the folding degree, using the curvedness. Our results revealed that the changes in cortical folding in the orbitofrontal and temporal regions were associated with a hereditary predisposition to BD. Cortical folding structures in multiple regions of the ALN, particularly in the striatal–thalamic circuit and anterior cingulate cortex, could be used to differentiate BD patients from healthy controls and unaffected siblings. We concluded that the cortical folding structures of ALN can provide potential biomarkers for clinical diagnosis of BD and differentiation from the unaffected siblings. Full article

(This article belongs to the Special Issue Etiology, Pharmacological, and Brain Stimulation Interventions for Bipolar Disorders)

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10 pages, 779 KiB

Open AccessArticle

Magnitude of Reduction and Speed of Remission of Suicidality for Low Amplitude Seizure Therapy (LAP-ST) Compared to Standard Right Unilateral Electroconvulsive Therapy: A Pilot Double-Blinded Randomized Clinical Trial

by Nagy A. Youssef, Dheeraj Ravilla, Cherishma Patel, Mark Yassa, Ramses Sadek, Li Fang Zhang, Laryssa McCloud, William V. McCall and Peter B. Rosenquist

Brain Sci. 2019, 9(5), 99; https://doi.org/10.3390/brainsci9050099 - 29 Apr 2019

Cited by 9 | Viewed by 7043

Abstract

Background: Although treatment guidelines support use of electroconvulsive therapy (ECT) for acute suicidality, it is associated with cognitive side effects. The effect of Low Amplitude Seizure Therapy (LAP-ST) on suicidality is unknown. Our prior precision LAP-ST (pLAP-ST) performing titrating in the current domain has provided initial proof of concept data in humans of its advantage in terms of reduction of cognitive side effects. The aims of this report are to: 1) compare LAP-ST (at 500mA) versus standard Right Unilateral (RUL) ECT (at 900 mA) in terms of magnitude of remission of suicidality in a randomized allocation and 2) compare the speed of remission of suicidality between LAP-ST versus RUL ECT. Methods: Patients were randomized to either LAP-ST or RUL ECT. The scores pertaining to the suicidal ideation (SI) item on the Montgomery-Åsberg Depression Rating Scale (MADRS) were analyzed using descriptive analysis and no confirmatory statistical analysis was performed due to a priori sample size limitations for this pilot study. SI item remission was defined as 2 or below on this item. Results: Eleven patients with major depressive episode (MDE) of mainly unipolar or bipolar disorders signed consent. Of these, 7 were eligible and were randomized and included in the analysis; all were actively suicidal at baseline (suicide item above 2), except 1 patient who had suicide item at 2 in the RUL ECT group. Suicidality remitted on average by session 3 and remission occurred for all patients by session 4. The SI mean score improvement from baseline to endpoint for LAP-ST was 5.1 and for RUL ECT was 3.0. Conclusions: LAP-ST has larger effect size and speed of remission of suicidality compared to standard RUL ECT. Future studies are warranted for replicating these findings. (ClinicalTrials.gov ID: NCT02583490). Full article

(This article belongs to the Special Issue Etiology, Pharmacological, and Brain Stimulation Interventions for Bipolar Disorders)

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11 pages, 663 KiB

Open AccessArticle

Gender Differences and Comorbidities in U.S. Adults with Bipolar Disorder

by Rikinkumar S. Patel, Sanya Virani, Hina Saeed, Sai Nimmagadda, Jupi Talukdar and Nagy A. Youssef

Brain Sci. 2018, 8(9), 168; https://doi.org/10.3390/brainsci8090168 - 01 Sep 2018

Cited by 30 | Viewed by 8304

Abstract

Background: Past studies have evaluated the association of various comorbidities with bipolar disorder. This study analyzes differences in the prevalence and association of medical and psychiatric comorbidities in bipolar patients by gender. Methods: A retrospective analysis was conducted using the Nationwide Inpatient Sample (2010–2014). Using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes, we narrowed the study population to comprise those with a primary diagnosis of bipolar disorder and then obtained information about comorbidities. The differences in comorbidities by gender were quantified using chi-square tests and the logistic regression model (odds ratio (OR)). Results: Hypertension (20.5%), asthma (12.5%) and hypothyroidism (8.1%) were the top medical comorbidities found in bipolar patients. Migraine and hypothyroidism were seen three times higher in females (OR = 3.074 and OR = 3.001; respectively). Females with bipolar disorder had higher odds of comorbid inflammatory disorders like asthma (OR = 1.755), Crohn’s disease (OR = 1.197) and multiple sclerosis (OR = 2.440) compared to males. Females had a two-fold higher likelihood of comorbid post-traumatic stress disorder (PTSD) (OR = 2.253) followed by personality disorders (OR = 1.692) and anxiety disorders (OR = 1.663) compared to males. Conclusion: Women with bipolar disorder have a much higher medical comorbidity burden than men and may highly benefit from an integrated team of physicians to manage their condition and improve their health-related quality of life. Full article

(This article belongs to the Special Issue Etiology, Pharmacological, and Brain Stimulation Interventions for Bipolar Disorders)

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6 pages, 529 KiB

Open AccessCase Report

Valproic Acid-Induced Hyperammonemic Encephalopathy in a Patient with Bipolar Disorder: A Case Report

by Meng-Yu Wu, Fang-Yu Chang, Jian-Yu Ke, Chien-Sheng Chen, Po-Chen Lin and Tzong-Shi Wang

Brain Sci. 2020, 10(3), 187; https://doi.org/10.3390/brainsci10030187 - 24 Mar 2020

Cited by 7 | Viewed by 4557

Abstract

Valproic acid (VPA) is widely used to control various seizure disorders and psychiatric disorders. Valproic acid-induced hyperammonemic encephalopathy (VHE) is a rare but dangerous complication of VPA-induced toxicity. For this case report, several risk factors were identified, including young age, polytherapy regimens, VPA overdose, poor liver function, and carnitine deficiency. The detailed mechanisms of VHE remained unclear. Hyperammonemia may be caused by hypocarnitinemia, leading to imbalanced VPA metabolism. VHE may initially cause gastrointestinal symptoms, followed by a decreased level of consciousness and seizure. Early diagnosis of VHE is important for physicians for the timely reversal of VHE by discontinuing administration of VPA and administering lactulose or levocarnitine. Here, we describe a patient with a bipolar disorder who presented with VHE after receiving a strict vegetarian diet in our hospital. We recommend that VHE be included in the differential diagnosis of patients with high serum VPA levels and strictly vegetarian diets, especially those presenting with acute gastrointestinal symptoms. Full article

(This article belongs to the Special Issue Etiology, Pharmacological, and Brain Stimulation Interventions for Bipolar Disorders)

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