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Bipolar Disorder – New Opportunities and Challenges

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A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Psychiatry".

Deadline for manuscript submissions: closed (30 March 2021) | Viewed by 65720

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Prof. Alfonso Tortorella

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Guest Editor

Università degli Studi di Perugia, Perugia, Italy
Interests: bipolar spectrum; psychotic spectrum; eating disorders; psychiatric genetics; cross-disorder genetics; neurodevelopment; psychopharmacology; neuropsychoendocrinology

Dr. Luca Steardo Jr.

E-Mail Website
Co-Guest Editor

Department of Physiology and Pharmacology, University of Catanzaro “Magna Graecia”, 88100 Catanzaro, Italy
Interests: bipolar disorder; lithium; psychopharmacology; sleep disturbance; high risk
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Special Issue Information

Dear Colleagues,

Bipolar disorder (BD) is a chronic and severe psychiatric illness. It is reported as responsible for the loss of more disability-adjusted life-years than all forms of cancer and major neurological conditions. Despite the serious burden on patients and the health system, many aspects of its pathobiology remain unclear. In recent years, research has provided impressive progresses in many areas of BD.

The aim of this Special Issue is to invite researchers to contribute in broadening the current knowledge in genetics, proteomics, neuroimaging, biochemical physiopathology, neuropathology, biopsychosocial interactions, precise psychiatry, and innovative treatments in the field of BD. Particular attention is devoted to high-risk subjects and mixed states.

Prof. Alfonso Tortorella
Dr. Luca Steardo Jr.
Guest Editors

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Keywords

bipolar disorder
lithium
psychopharmacology
sleep disturbance
high risk
neuroimaging
genetic
circadian rhythm

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Published Papers (10 papers)

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Research

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12 pages, 350 KiB

Open AccessArticle

Predominant Polarity and Polarity Index of Maintenance Treatments for Bipolar Disorder: A Validation Study in a Large Naturalistic Sample in Italy

by Umberto Albert, Mirko Manchia, Sofia Burato, Bernardo Carpiniello, Gabriele Di Salvo, Federica Pinna, Gianluca Rosso and Giuseppe Maina

Medicina 2021, 57(6), 598; https://doi.org/10.3390/medicina57060598 - 10 Jun 2021

Cited by 5 | Viewed by 2401

Abstract

Background and Objectives: Predominant polarity (PP) may be a useful course specifier in at least a significant proportion of patients with Bipolar Disorder (BD), being associated with several clinically relevant correlates. Emerging evidence suggests that the concept of PP might influence the selection of maintenance treatments, based on a drug polarity index (PI) which measures the greater antidepressive vs. antimanic preventive efficacy of mood stabilizers over long-term maintenance treatment. In this study, we aimed to validate the PI in a large sample of Italian BD patients with accurate longitudinal characterization of the clinical course, which ensured a robust definition of the PP. Materials and Methods: Our sample is comprised of 653 patients with BD, divided into groups based on the predominant polarity (manic/hypomanic predominant polarity—MPP, depressive predominant polarity—DPP and no predominant polarity). Subsequently we calculated the mean total polarity index for each group, and we compared the groups. Results: When we examined the mean PI of treatments prescribed to individuals with DPP, MPP and no predominant polarity, calculated using two different methods, we failed to find significant differences, with the exception of the PI calculated with the Popovic method and using the less stringent criterion for predominant polarity (PP_50%). Conclusions: Future prospective studies are needed in order to determine whether the predominant polarity is indeed one clinical factor that might guide the clinician in choosing the right mood stabilizer for BD maintenance treatment. Full article

(This article belongs to the Special Issue Bipolar Disorder – New Opportunities and Challenges)

13 pages, 545 KiB

Open AccessArticle

Comparison of Emotional Dysregulation Features in Cyclothymia and Adult ADHD

by Giulio Emilio Brancati, Margherita Barbuti, Elisa Schiavi, Paola Colombini, Martina Moriconi, Alessandro Pallucchini, Marco Maiello, Giulia Menculini and Giulio Perugi

Medicina 2021, 57(5), 489; https://doi.org/10.3390/medicina57050489 - 12 May 2021

Cited by 11 | Viewed by 5120

Abstract

Background and Objectives: Emotional dysregulation is central to the problem of the overlap between attention-deficit/hyperactivity disorder (ADHD) and cyclothymia. The aim of the study was to evaluate comorbidity rates between ADHD and cyclothymic disorder and to explore demographic and clinical differences among the groups, focusing on affective temperament and emotional dysregulation. Materials and Methods: One hundred sixty-five outpatients attending the Second Psychiatry Unit at the Santa Chiara University Hospital (Pisa) were consecutively recruited: 80 were diagnosed with ADHD, 60 with cyclothymic disorder, and 25 with both conditions. Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-M) and the 40-item version of Reactivity, Intensity, Polarity, and Stability questionnaire (RI-PoSt-40) were administered. Results: Cyclothymic patients were more frequently female and older with respect to the ADHD groups. Both comorbid and non-comorbid ADHD patients showed significantly lower educational attainment and more frequently had substance use disorders. Panic disorder was common in non-comorbid cyclothymic patients, who showed significantly higher rates of familial panic disorder, major depressive disorder and suicide attempts in comparison with patients only diagnosed with ADHD. Cyclothymic patients without ADHD were also characterized by fewer hyperthymic temperamental traits, higher depressive and anxious dispositions, and a greater negative emotionality. No significant differences among groups were observed for cyclothymic temperament and overall negative emotional dysregulation, but comorbid patients with both conditions scored the highest in these subscales. This group also showed significantly higher affective instability with respect to ADHD patients without cyclothymia and was less frequently diagnosed with bipolar disorder type II than patients from both the other groups. Conclusions: ADHD and cyclothymia often co-occur and show similar levels of emotional dysregulation. However, cyclothymic patients may be more prone to negative emotionality in clinical settings. Subjects with “sunny” cyclothymic features might escape the attention of clinicians unless ADHD is present. Full article

(This article belongs to the Special Issue Bipolar Disorder – New Opportunities and Challenges)

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11 pages, 356 KiB

Open AccessArticle

Comorbidities, Depression Severity, and Circadian Rhythms Disturbances as Clinical Correlates of Duration of Untreated Illness in Affective Disorders

by Giulia Menculini, Norma Verdolini, Francesca Brufani, Valentina Pierotti, Federica Cirimbilli, Agata Di Buò, Giulio Spollon, Filippo De Giorgi, Tiziana Sciarma, Alfonso Tortorella and Patrizia Moretti

Medicina 2021, 57(5), 459; https://doi.org/10.3390/medicina57050459 - 8 May 2021

Cited by 8 | Viewed by 2318

Abstract

Background and Objectives: Affective disorders, namely bipolar (BDs) and depressive disorders (DDs) are characterized by high prevalence and functional impairment. From a dimensional point of view, BDs and DDs can be considered as psychopathological entities lying on a continuum. A delay in treatment initiation might increase the burden associated with affective disorders. The aim of this study is to analyze the correlates of a long duration of untreated illness (DUI) in these conditions. Materials and Methods: Subjects with BDs and DDs, both in- and outpatients, were recruited. Long DUI was defined according to previous research criteria as >2 years for BDs or >1 year for DDs. Socio-demographic, clinical and psychopathological characteristics of the recruited subjects were collected. Bivariate analyses were performed to compare subjects with a long and short DUI (p < 0.05). Results: In our sample (n = 61), 34.4% of subjects presented a long DUI. A long DUI was significantly associated with longer overall illness duration (p = 0.022) and a higher rate of psychiatric (p = 0.048) and physical comorbidities (p = 0.023). As for psychopathological features, depressive symptoms were more severe in the long DUI subgroup, as demonstrated by a higher score at the Clinical Global Impression-severity of depression (p = 0.012) item and at the anxiety/depression factor of the Positive and Negative Syndrome Scale (p = 0.041). Furthermore, subjects with a long DUI displayed more severe disruption of circadian rhythms, as evaluated by the Biological Rhythms Interview for Assessment in Neuropsychiatry total (p = 0.044) and social domain (p = 0.005) scores and by the Hamilton Depression Rating Scale diurnal variation items (18a: p = 0.029, 18b: p = 0.047). Conclusions: A long DUI may underpin higher clinical severity, as well as worse illness course and unfavorable prognosis in affective disorders. Intervention strategies targeting comorbidities, depressive symptoms and circadian rhythms may decrease disease burden in subjects with a long DUI. Full article

(This article belongs to the Special Issue Bipolar Disorder – New Opportunities and Challenges)

8 pages, 327 KiB

Open AccessArticle

Clinical Impact of Psychopathy on Bipolar Disorder

by Giuseppina Calabrò, Antonio Francesco Musolino, Andrea Adolfo Filippo, Renato de Filippis, Elvira Anna Carbone, Marianna Rania, Matteo Aloi, Valentina Pugliese and Cristina Segura-Garcia

Medicina 2021, 57(2), 165; https://doi.org/10.3390/medicina57020165 - 12 Feb 2021

Cited by 1 | Viewed by 2989

Abstract

Background and Objectives. Bipolar disorder (BD) is associated with a significant burden due to affective symptoms and behavioral manifestations, but also cognitive and functional impairment. Comorbidity with other psychiatric conditions, including personality disorders, is frequent. The comorbidity with psychopathy deserves special consideration given that both disorders share some clinical characteristics, such as grandiosity, risky behavior or poor insight, among others, that can worsen the outcome of BD. Therefore, this study aimed to evaluate the prevalence of psychopathy in a sample of clinically stabilized patients with BD and its impact on the severity of BD. Materials and Methods. A sample of 111 patients with BD (38 type I and 73 type II) was studied. The Hamilton Depression Rating Scale (HAM-D) and the Young Mania Rating Scale (YMRS) served to assess the severity of BD. Psychopathy was measured by means of the Psychopathic Personality Inventory-Revised (PPI-R). Patients were divided into three groups according to the severity of psychopathy (Group 1: no psychopathy; Group 2: “psychopathic” trait; Group 3: clinical psychopathy). Other measures regarded impulsiveness (Barratt Impulsiveness Scale-11, BIS-11) and empathy (Empathy Quotient, EQ). Comparisons of mania, depression, impulsivity and empathy scores were run with MANOVA considering psychopathy and diagnosis as independent variables. Results. The prevalence of psychopathy was 5.4%. A significant association between the level of psychopathy and YMRS, attentional/cognitive impulsivity and motor impulsivity scores emerged. No interaction between psychopathy and BD diagnosis was found. Post hoc analysis demonstrated significantly higher YMRS scores in Group 3 than in Group 1; that is, patients with psychopathy have more manic symptoms. Conclusion. Psychopathy seems quite frequent among patients with BD. The association of psychopathy with BD results in higher impulsivity and manic symptoms. In light of this, psychopathy should be investigated when assessing patients with BD, regardless of the comorbidity of BD with other personality disorders. Full article

(This article belongs to the Special Issue Bipolar Disorder – New Opportunities and Challenges)

11 pages, 499 KiB

Open AccessArticle

Affective Temperaments and Illness Severity in Patients with Bipolar Disorder

by Mario Luciano, Luca Steardo, Jr., Gaia Sampogna, Vito Caivano, Carmen Ciampi, Valeria Del Vecchio, Arcangelo Di Cerbo, Vincenzo Giallonardo, Francesca Zinno, Pasquale De Fazio and Andrea Fiorillo

Medicina 2021, 57(1), 54; https://doi.org/10.3390/medicina57010054 - 9 Jan 2021

Cited by 20 | Viewed by 3538

Abstract

Background and objectives: Bipolar disorder (BD) is one of the most burdensome psychiatric illnesses, being associated with a negative long-term outcome and the highest suicide rate. Although affective temperaments can impact on BD long-term outcome, their role remains poorly investigated. The aims of the present study are to describe the clinical characteristics of patients with BD more frequently associated with the different affective temperaments and to assess the relation between affective temperaments and severity of clinical picture in a sample of patients with BD. Materials and Methods: A total of 199 patients have been recruited in the outpatients units of two university sites. Patients’ psychiatric symptoms, affective temperaments, and quality of life were investigated through validated assessment instruments. Results: Predominant cyclothymic and irritable temperaments are associated to higher number of relapses, poorer quality of life, higher rates of aggressive behaviors, and suicide attempts. Conversely, the predominant hyperthymic disposition was a protective factor for several outcome measures, including relapse rate, severity of anxiety, depressive and manic symptoms, suicidality, and earlier age at onset. One limitation of the present study is that the recruitment took place in two university sites; therefore, our findings cannot be fully generalized to the whole community of BD patients. Other limitations are the lack of a control group and the cross-sectional design of the study. Conclusions: The early identification of affective temperaments can help clinicians to identify those BD patients who are more likely to show a poor long-term outcome. An early screening of affective temperaments can be useful to develop targeted integrated pharmacological and psychosocial interventions. Full article

(This article belongs to the Special Issue Bipolar Disorder – New Opportunities and Challenges)

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10 pages, 324 KiB

Open AccessArticle

Lipid and Glycemic Profiles in Patients with Bipolar Disorder: Cholesterol Levels Are Reduced in Mania

by Laura Fusar-Poli, Andrea Amerio, Patriciu Cimpoesu, Antimo Natale, Virginio Salvi, Guendalina Zappa, Gianluca Serafini, Mario Amore, Eugenio Aguglia and Andrea Aguglia

Medicina 2021, 57(1), 28; https://doi.org/10.3390/medicina57010028 - 30 Dec 2020

Cited by 21 | Viewed by 3212

Abstract

Background and Objectives: Bipolar disorder (BD) is a severe mental condition with a lifetime prevalence estimated around 2% among the general population. Due to risk factors, etiological mechanisms, and the chronic use of psychotropic medications, people with BD are frequently affected by medical comorbidities, such as metabolic syndrome (MetS), associated with altered blood levels of glucose, cholesterol, and triglycerides. Moreover, the lipid concentration may be associated with the severity of psychiatric symptoms. Materials and Methods: Five hundred and forty-two in- and outpatients (418 affected by BD and 124 affected by schizophrenia) were recruited in two Italian university hospitals. A blood examination assessing the fasting glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides was performed. Results: No significant differences were found in the lipid and glycemic profiles between patients with BD and schizophrenia. When considering only the BD sample, we found that patients experiencing a manic episode had significantly lower total cholesterol, HDL, and LDL than euthymic patients. Moreover, the total and LDL cholesterol levels were significantly lower in (hypo)manic than depressed patients. Mood episodes did not influence the triglyceride and glucose levels in our sample. Conclusions: Clinicians should pay attention to blood cholesterol levels in patients with BD, as differences in concentrations may predispose them to severe medical conditions and can be associated with the onset of mood episodes. Full article

(This article belongs to the Special Issue Bipolar Disorder – New Opportunities and Challenges)

8 pages, 708 KiB

Open AccessArticle

Aripiprazole Augmentation to Mood Stabilizers for Obsessive-Compulsive Symptoms in Bipolar Disorder

by Gabriele Di Salvo, Giuseppe Maina, Enrico Pessina, Elena Teobaldi, Francesca Barbaro, Azzurra Martini, Umberto Albert and Gianluca Rosso

Medicina 2021, 57(1), 9; https://doi.org/10.3390/medicina57010009 - 24 Dec 2020

Cited by 5 | Viewed by 4341

Abstract

Background and Objectives: Aripiprazole is a first-line agent in the treatment of bipolar disorder (BD) and available data demonstrates its efficacy on clinical symptoms in serotonin reuptake inhibitors-resistant obsessive-compulsive disorder (OCD) patients. Therefore, aripiprazole augmentation to mood stabilizers could represent a promising treatment in BD patients with comorbid OCD. The study examined the efficacy and safety of aripiprazole added to lithium or valproate for the treatment of obsessive-compulsive (OC) symptoms in euthymic BD patients with comorbid OCD. Materials and Methods: This is a 12-week prospective observational study. The efficacy of aripiprazole on OC symptoms was assessed through the mean change of Yale–Brown Obsessive-Compulsive (YBOCS) total score. Tolerability was assessed with the Utvalg for Kliniske Undersogelser (UKU) side effect scale and by reporting adverse events. Results: A total of 70 patients were included in the analyses. The withdrawal rate was 21.4%, mainly due to adverse events. Mean ± SD final aripiprazole dose was 15.2 ± 5.3 in the completer sample (N = 55). The Y-BOCS mean score decreased from 24.0 ± 4.1 at baseline to 17.1 ± 4.3 at 12 weeks. Treatment response rate (Y-BOCS reduction ≥ 35%) was 41.8%, while partial response rate (Y-BOCS reduction greater than 25% but less than 35% from baseline) accounted for the other 18.2% of patients. Overall, 91.4% of completers had at least 1 adverse effect (tremor, tension/inner unrest, reduced duration of sleep, akathisia). No significant differences emerged comparing aripiprazole efficacy and tolerability between patients treated with lithium or valproate. Conclusion: Our findings show that aripiprazole addition to lithium or valproate can reduce OC symptoms in real-world BD euthymic patients. Full article

(This article belongs to the Special Issue Bipolar Disorder – New Opportunities and Challenges)

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23 pages, 701 KiB

Open AccessFeature PaperReview

The Management of Prodromal Symptoms of Bipolar Disorder: Available Options and Future Perspectives

by Elisa Del Favero, Cristiana Montemagni, Paola Bozzatello, Claudio Brasso, Cecilia Riccardi and Paola Rocca

Medicina 2021, 57(6), 545; https://doi.org/10.3390/medicina57060545 - 28 May 2021

Cited by 4 | Viewed by 4386

Abstract

The onset of prodromal symptoms in subjects who are at familial or clinical risk for bipolar disorder could be considered as an important alarm bell for the development of the disease and should be carefully detected. The management of prodromes in bipolar high-risk patients appears to be an important means of prevention; nevertheless, at the moment, there aren’t clear and widely shared treatment indications. The aim of this review is to summarize the available treatment options (pharmacological, psychosocial and nutraceutical) for the management of prodromal symptoms in subjects who are at familial or clinical risk for bipolar disorder. Full article

(This article belongs to the Special Issue Bipolar Disorder – New Opportunities and Challenges)

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11 pages, 323 KiB

Open AccessReview

ADHD and Bipolar Disorder in Adulthood: Clinical and Treatment Implications

by Virginio Salvi, Enrico Ribuoli, Michele Servasi, Laura Orsolini and Umberto Volpe

Medicina 2021, 57(5), 466; https://doi.org/10.3390/medicina57050466 - 10 May 2021

Cited by 31 | Viewed by 19201

Abstract

Attention deficit hyperactivity disorder (ADHD) is a condition that usually has its onset in childhood. Although the disorder persists into adulthood in half of cases, adult ADHD is often not recognized due to different psychopathological characteristics, quite often overlapping with other diagnoses such as mood, anxiety and personality disorders. This is especially true for bipolar disorder (BD), which shares several symptoms with adult ADHD. Moreover, besides an overlapping clinical presentation, BD is often co-occurring in adults with ADHD, with comorbidity figures as high as 20%. This review will focus on the comorbidity between ADHD and BD by exploring the magnitude of the phenomenon and evaluating the clinical and functional characteristics associated with ADHD–BD comorbidity in adults. Finally, the review will address the implications of pharmacologically treating the ADHD–BD comorbidity, providing suggestions in how to treat these complex patients and addressing the issue of treatment-induced manic switch with the use of stimulants and other medications for ADHD. Full article

(This article belongs to the Special Issue Bipolar Disorder – New Opportunities and Challenges)

15 pages, 1496 KiB

Open AccessReview

Antisocial Personality Disorder in Bipolar Disorder: A Systematic Review

by Elvira Anna Carbone, Renato de Filippis, Mariarita Caroleo, Giuseppina Calabrò, Filippo Antonio Staltari, Laura Destefano, Raffaele Gaetano, Luca Steardo, Jr. and Pasquale De Fazio

Medicina 2021, 57(2), 183; https://doi.org/10.3390/medicina57020183 - 20 Feb 2021

Cited by 7 | Viewed by 16795

Abstract

Background and Objectives: Bipolar Disorder (BD) is a severe psychiatric disorder that worsens quality of life and functional impairment. Personality disorders (PDs), in particular Cluster B personality, have a high incidence among BD patients and is considered a poor prognostic factor. The study of this co-morbidity represents an important clinical and diagnostic challenge in psychiatry. Particularly, clinical overlap has been shown between antisocial personality disorder (ASPD) and BD that could worsen the course of both disorders. We aimed to detect the frequency of ASPD in bipolar patients with greater accuracy and the impact of ASPD on the clinical course of BD. Materials and Methods: A systematic literature search was conducted in PubMed, Embase, MEDLINE and the Cochrane Library through December 2020 without language or time restriction, according to PRISMA statement guidelines. Results: Initially, 3203 items were identified. After duplicates or irrelevant paper deletion, 17 studies met the inclusion criteria and were included in this review. ASPD was more frequent among BD patients, especially in BD type I. BD patients with ASPD as a comorbidity seemed to have early onset, higher number and more severe affective episodes, higher levels of aggressive and impulsive behaviors, suicidality and poor clinical outcome. ASPD symptoms in BD seem to be associated with a frequent comorbidity with addictive disorders (cocaine and alcohol) and criminal behaviors, probably due to a shared impulsivity core feature. Conclusions: Considering the shared symptoms such as impulsive and dangerous behaviors, in patients with only one disease, misdiagnosis is a common phenomenon due to the overlapping symptoms of ASPD and BD. It may be useful to recognize the co-occurrence of the disorders and better characterize the patient with ASPD and BD evaluating all dysfunctional aspects and their influence on core symptoms. Full article

(This article belongs to the Special Issue Bipolar Disorder – New Opportunities and Challenges)

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