A grounded theory on acceptance of diagnosis as a pathway to recovery in bipolar disorder.

The recovery process in bipolar disorder is a subjective and multidimensional experience that seeks to develop new meanings and purposes for living a satisfying life despite the limitations imposed by the disorder. Thus, this qualitative study aimed to explore the perceptions of recovery and the meanings attributed by individuals undergoing treatment for bipolar disorder to the elements considered relevant in this process. Semi-structured interviews with open-ended questions were conducted to explore the experiences and perspectives of recovery in individuals undergoing treatment for bipolar disorder. Grounded Theory was used as the method for qualitative analysis. The study included 26 participants aged between 18 and 65 years. Based on the analysis of participant reports, we identified two main themes: living with the illness and what it means to be in recovery. The perception of recovery is an individual process and can differ from the medical model. Participants suggest that accepting the diagnosis of bipolar disorder and finding meaning in life are essential to their recovery. They also describe how mental health professionals can facilitate or hinder this process. Understanding patients' perceptions can facilitate access to healthcare services and treatment adherence.

An overview of metabolomic and proteomic profiling in bipolar disorder and its clinical value.

INTRODUCTION: Bipolar disorder (BD) is a complex psychiatric disease characterized by alternating mood episodes. As for any other psychiatric illness, currently there is no biochemical test that is able to support diagnosis or therapeutic decisions for BD. In this context, the discovery and validation of biomarkers are interesting strategies that can be achieved through proteomics and metabolomics. AREAS COVERED: In this descriptive review, a literature search including original articles and systematic reviews published in the last decade was performed with the objective to discuss the results of BD proteomic and metabolomic profiling analyses and indicate proteins and metabolites (or metabolic pathways) with potential clinical value. EXPERT OPINION: A large number of proteins and metabolites have been reported as potential BD biomarkers; however, most studies do not reach biomarker validation stages. An effort from the scientific community should be directed toward the validation of biomarkers and the development of simplified bioanalytical techniques or protocols to determine them in biological samples, in order to translate proteomic and metabolomic findings into clinical routine assays.

Social cognition across bipolar disorder and behavioral variant frontotemporal dementia: an exploratory study.

OBJECTIVES: Bipolar disorder type 1 (BD1) and behavioral-variant frontotemporal dementia (bvFTD) share similar behavioral and cognitive symptoms, rendering the differential diagnosis between them a clinical challenge. We investigated the accuracy of social cognition (SC) measures to differentiate bvFTD from BD. METHODS: We included three groups of participants: early-onset BD1 (in remission, n=20), bvFTD (n=18), and cognitively healthy controls (HC) (n=40), matched for age, schooling, and sex. All participants underwent cognitive assessment, including the Facial Emotion Recognition (FER) and Modified Faux-Pas (mFP) tests, which assess mentalizing. RESULTS: Compared to HC, BD1 and bvFTD patients underperformed on both SC measures. BD1 and bvFTD did not differ regarding FER or mFP total scores, although patients with bvFTD had significantly higher difficulties than those in the BD1 group to detect social faux-pas (p < 0.001, d = 1.35). CONCLUSION: BD1 and bvFTD share deficits in the core SC functions. These findings should be considered in the development of tasks aiming to improve clinical differentiation between the two disorders.

Correlates of neurological soft signs in bipolar disorder.

Recent research has focused on neurological soft signs (NSS) in bipolar disorder (BD), but there is still scarce evidence on their correlates with other relevant variables. The aim of this study was to explore the association between NSS and clinical demographic, neurocognitive, and functional variables. Eighty-eight euthymic BD patients were included in whom NSS were assessed using the Neurological Evaluation Scale. All subjects performed an extensive neurocognitive battery selected to assess premorbid IQ, attention, language, verbal memory, and executive functions. Psychosocial outcomes were assessed by means of the Functioning Assessment Short Test. Among the demographical variables, NSS tended to be negatively associated with years of education and increased with age. Likewise, NSS were higher in BD type I than in BD type II, but independent of age at illness onset and number of previous affective episodes. There was a negative correlation between NSS and premorbid IQ, as well as with performance in attention, language, and executive functions. Results tended to be unchanged when controlled for potential confounders. Although NSS were associated with poor psychosocial functioning in the bivariate analysis, when added to a multiple regression model including neurocognition, these neurological features did not significantly contribute to the variance of the functional outcome. Our findings contribute to a better characterization of NSS in BD; their potential clinical and theoretical implications are discussed in the manuscript.

"Addressing the core trait of bipolar disorder": A concept analysis of mood-stabilizing drugs.

OBJECTIVE: The term "mood stabilizer" is controversial in the literature and criticized for being imprecise and overly inclusive, having its retirement suggested to avoid misuse. Nevertheless, it continues to be employed as it may still carry important meaning. METHODS: We employed document analysis for reviewing relevant definitions of mood stabilizer employed in the literature. Then, we clarify the meanings associated with the term by employing evolutionary concept analysis. Based on its results, we present a theoretical model for a mood stabilizer and further match it with evidence gathered from published meta-analyses and other sources for drugs used in the treatment of bipolar disorder. RESULTS: Concept analysis unearthed four attributes of a mood stabilizer that were nested into the following ascending hierarchy: "not worsening," "acute effects," "prophylactic effects," and "advanced effects." "Prophylactic effects" were often considered the core aspect of a legitimate mood stabilizer. CONCLUSION: The proposed model uses a hierarchy of attributes that take into account the complexity of the term and help to determine whether a drug is a mood stabilizer. Prophylaxis is pivotal to the concept, whose utility lies in implying a drug able to truly treat bipolar disorder, as opposed to merely targeting symptoms. Consistent use of the term could encourage investigation of drugs that modify long-term outcomes and illness trajectory, instead of simply approaching symptom clusters.

Managing drug-induced psychosis.

Substance-induced psychosis is a secondary psychotic disorder resulting from drug abuse, characterized by one or more psychotic episodes. Drug-induced psychosis is expected to resolve after a 30-day period of sobriety, however, individuals with this condition are more likely to develop severe drug addiction. Compared to primary psychosis, participants with drug-induced psychosis exhibit poorer family history of psychotic diseases, higher insight, fewer positive and negative symptoms, more depressive symptoms, and greater anxiety. Substance-induced psychosis is strongly associated with the emergence of bipolar illness or schizophrenia spectrum disorder, with an increased chance of developing schizophrenia at a younger age. Episodes of self-harm after substance-induced psychosis are strongly linked to an elevated likelihood of developing schizophrenia or bipolar disorder. Effective treatment involves ruling out emergencies, investigating underlying causes, and addressing acute intoxication and withdrawal. Management includes dynamic assessment, intervention, and vigilant monitoring in cases of suicidal behaviour. Antipsychotics may be used for short term, with gradual discontinuation when a person is in a stable condition. Relapse prevention strategies, both medication and non-medication-based, are crucial in long-term management. Conversion rates to schizophrenia or bipolar disorder can be as high as one in three individuals, with cannabis users and those with early-onset substance abuse at the highest risk.

Distractibility, anxiety, irritability, and agitation symptoms are associated with the severity of depressive and manic symptoms in mixed depression.

OBJECTIVE: To explore whether there is an association between distractibility, anxiety, irritability, and agitation (DAIA) symptoms and the severity of depressive and manic symptoms. METHODS: Patients with unipolar and bipolar disorder (I and II) and mixed depression were evaluated. DAIA symptoms were assessed using previously described definitions. RESULTS: The full analysis set comprised 100 patients. The severity of depressive symptoms in mixed depression, assessed by Montgomery-Åsberg Depression Rating Scale (MADRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample, influenced mainly by anxiety. The severity of manic symptoms in mixed depression, assessed by Young Mania Rating Scale (YMRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample and three or four DAIA symptoms in the unipolar sample. CONCLUSION: DAIA symptoms were associated with greater severity of manic symptoms in mixed depression. DAIA symptoms must be evaluated in all patients with mixed features and are associated with the severity of depressive and manic symptoms in mixed depression.

Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression.

BACKGROUND AND OBJECTIVE: Affective disorders account for most cases of suicide. The pharmacological arsenal to treat suicidality is limited and available agents take too long to take effect. A large body of evidence shows optimal results of ketamine for treating depression, but the evidence concerning suicidality has not been fully described. We report the first real-world study of severely depressed patients presenting with suicide ideation who were treated with repeated administration of subcutaneous esketamine. METHODS: We analyzed data from 70 acutely depressed subjects diagnosed with resistant major depressive disorder or bipolar depression. Subjects were administered subcutaneous esketamine once a week for 6 weeks. The primary efficacy endpoint, the change from baseline to 24-h post-administration 6 in the item 10 Montgomery-Åsberg Depression Rating Scale score, was analyzed using a mixed-effects repeated-measures model. RESULTS: There were significant effects for time on item 10 Montgomery-Åsberg Depression Rating Scale scores (p < 0.0001) but not for a time × diagnosis interaction (p = 0.164) from baseline to the end of the study. Efficacy of esketamine did not differ between groups (major depressive disorder vs bipolar depression) at any timepoint. Statistical significance on suicidality scores was observed from 24 h after the first administration (p < 0.001), and a further reduction was observed with repeated administrations. Esketamine was safe and well tolerated. Mean heart rate remained stable during the administrations and the blood pressure increase was self-limited. CONCLUSIONS: Repeated subcutaneous esketamine administration had significant anti-suicidality effects in both major depressive disorder and bipolar groups, with a rapid onset of action and a good tolerability profile. Large randomized controlled trials are warranted to confirm these preliminary findings.

Demographic and clinical characteristics of lithium-treated older adults with bipolar disorder.

OBJECTIVES: There is limited information on the characteristics of older adults with bipolar disorder (OABD) treated with lithium, along with safety concerns about its use by older adults. The aim of the present study is to describe the demographic and clinical characteristics of OABD receiving lithium therapy, using data from the Global Ageing & Geriatric Experiments in Bipolar Disorder (GAGE-BD). EXPERIMENTAL PROCEDURES: Cross-sectional analysis of the GAGE-BD dataset to determine differences and similarities between lithium users and non-users. We analysed data from 986 participants aged 50 years or older (mean age 63.5 years; 57.5% females) from 12 study sites. Two subgroups ('Lithium'; 'Non-lithium') were defined according to the current prescription of lithium. We compared several outcomes between these groups, controlling for age, gender, and study site. RESULTS: OABD treated with lithium had lower scores on depression rating scales and were less likely to be categorised as with moderate or severe depression. There was a lower proportion of lithium users than non-users among those with evidence of rapid cycling and non-bipolar psychiatric diagnoses. Assessment of global cognitive state and functionality indicated better performance among lithium users. The current use of antipsychotics was less frequent among lithium users, who also reported fewer cardiovascular comorbidities than non-users. CONCLUSION: We found several potentially relevant differences in the clinical profile of OABD treated with lithium compared with those treated with other mood stabilisers. However, the interpretation of the present results must take into account the methodological limitations inherent to the cross-sectional approach and data harmonisation.

[Evaluation of the functionality and subjective well-being of bipolar patients with the Functioning Assessment Short Test (FAST) and the World Health Organization - Five Well- Being Index (WHO-5)]. / Evaluación de la funcionalidad y el bienestar subjetivo de pacientes bipolares con el Functioning Assessment Short Test (FAST) y el World Health Organization - Five Well-Being Index (WHO-5).

INTRODUCTION: Bipolar Disorders (BD) are a mood disorders group charactered by recurrent manic or hypomanic episodes, alternating with depressive episodes. Its prevalence is 4%, and several studies have shown that they generate disability. There are effective therapeutic options for acute episodes. However, the ultimate goal is to achieve functional recovery and adequate well-being. MATERIAL AND METHODS: There was done in Buenos Aires, Argentina a cross-sectional study comparing psychosocial functioning, with the Functioning Assessment Short Test (FAST) and subjective well-being with the Five Well-Being Index (WHO-5), among a sample of stabilized BD patients undergoing treatment at the Center of Medical Education and Clinical Research (Centro de Educación Médica e Investigaciones Clínicas) and the Bipolar Foundation (Fundación Bipolares de Argentina), with a control group. RESULTS: A total of 102 BD patients and 52 controls where included. The FAST mean for patients and controls was 20.71 and 9.73 respectively (P=0.0000). The WHO-5 mean for patients was 59.11 and 69.76 for controls (P=0.0011). More than 70% of the patients presented functional alteration (FAST ≥12), and almost 35% presented inadequate subjective well-being (WHO-5 ≤52). Depressive symptoms conditioned worse scores on both scales. FAST scores were better among those who participated in mutual aid groups (P=0.026). While patients who underwent psychoeducation and those who received anticonvulsant drugs, presented better WHO-5 scores (P = 0.028 and P=0.048 respectively). CONCLUSIONS: Patients with BD showed poor Functionality and poor Well-being despite being stabilized. There is direct relationship between both conditions. Depressive symptoms generated worst scores on the scales.

Biomarker potential of hsa-miR-145-5p in peripheral whole blood of manic bipolar I patients.

OBJECTIVE: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. METHODS: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. RESULTS: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987. CONCLUSION: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene.

Assessment of the diagnostic performance of two new tools versus routine screening instruments for bipolar disorder: a meta-analysis.

OBJECTIVE: The present meta-analysis was conducted to determine the diagnostic accuracy of the bipolarity index (BI) and Rapid Mode Screener (RMS) as compared with the Bipolar Spectrum Diagnostic Scale (BSDS), the Hypomania Checklist (HCL-32), and the Mood Disorder Questionnaire (MDQ) in people with bipolar disorder (BD). METHODS: We systematically searched five databases using standard search terms, and relevant articles published between May 1990 and November 30, 2021 were collected and reviewed. RESULTS: Ninety-three original studies were included (n=62,291). At the recommended cutoffs for the BI, HCL-32, BSDS, MDQ, and RMS, the pooled sensitivities were 0.82, 0.75, 0.71, 0.71, and 0.78, respectively, while the corresponding pooled specificities were 0.73, 0.63, 0.73, 0.77, and 0.72, respectively. However, there was evidence that the accuracy of the BI was superior to that of the other tests, with a relative diagnostic odds ratio (RDOR) of 1.22 (0.98-1.52, p < 0.0001). The RMS was significantly more accurate than the other tests, with an RDOR (95%CI) of 0.79 (0.67-0.92, p < 0.0001) for the detection of BD type I (BD-I). However, there was evidence that the accuracy of the MDQ was superior to that of the other tests, with an RDOR of 1.93 (0.89-2.79, p = 0.0019), for the detection of BD type II (BD-II). CONCLUSION: The psychometric properties of two new instruments, the BI and RMS, in people with BD were consistent with considerably higher diagnostic accuracy than the HCL-32, BSDS, and MDQ. However, a positive screening should be confirmed by a clinical diagnostic evaluation for BD.

Pediatric bipolar disorder: Executive, linguistic, mnemonic, and cognitive efficiency mapping.

Neuropsychological assessment can enrich our understanding of Pediatric Bipolar Disorder (PB). This study aimed to: (1) analyze the occurrence of neuropsychological frequency of deficits and difficulties in children with PB; (2) verify whether there is a performance difference between PB type I (PB-I) and PB type II (PB-II)/unspecified, and between PB with and without ADHD; and (3) verify the cognitive efficiency differences within the PB group and control groups, and among clinical subgroups. Participants in the study were 16 children diagnosed with PB and 40 children with typical development (6-12 years old). The results indicated a high frequency of deficits/difficulties in verbal fluency, cognitive efficiency in performing basic abilities, inhibitory control, cognitive flexibility, and working memory, with emphasis on verbal and executive losses. There were indications that type PB-I and comorbidity with ADHD negatively impact a child's neuropsychological development. The clinical group showed more cognitive efficiency losses compared with the control group, and greater losses were observed in PB-I and in PB with ADHD. The role of neuropsychological evaluation in multidomain and nonlinear statistical analysis is critical to gaining an understanding of the clinical and cognitive heterogeneity of PB.

Antenatal screening of depressive and manic symptoms in south Brazilian childbearing women: A transversal study in advance of the pandemic scenario.

BACKGROUND: The diagnosis of mood disorders (MD) during pregnancy is challenging and may bring negative consequences to the maternal-fetal binomial. The long waitlist for specialized psychiatric evaluation in Brazil contributes to the treatment omission. Almost 20.0% of women treated with antidepressants have a positive screening for bipolar disorder. Therefore, it has been recommended the investigation of depressive and bipolar disorder during prenatal care. Unfortunately, the screening for mood disorders is not a reality in Brazil and many childbearing women remain undiagnosed. The objective of this study is to observe the frequency of MD and the effectiveness of screening scales for routine use by health professionals during prenatal care in high-risk pregnancies. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study included 61 childbearing women in their second trimester who were interviewed using the Edinburgh Postnatal Depression Scale (EPDS) and the Mood Disorder Questionnaire (MDQ). The cut-off point was EPDS ≥ 13 and MDQ ≥ 7 and the SCID-5 was the gold standard diagnosis. MD were diagnosed in 24.6% of the high-risk pregnancies. EDPS was positive in 19.7% and the frequency of major depression was 8.2%. 16.4% of the childbearing women were diagnosed with bipolar disorder, while MDQ was positive in 36.1%. 11.5% of the women had EPDS and MDQ positive. EPDS sensitivity was 80.0% and specificity 92.1%, whereas MDQ presented a sensitivity of 70.0% and specificity of 70.6%. CONCLUSION/SIGNIFICANCE: There is a high prevalence of MD in high-risk pregnancies. The routine use of EPDS simultaneously to MDQ during antenatal care is effective and plays an important role in early diagnosis, counselling, and promotion of perinatal mental health.

Manía unipolar: un ineludible diagnóstico: revisión de la literatura a propósito de un caso / Unipolar mania: an unavoidable diagnosis: case report and literature review

Resumen Introducción: La manía unipolar (MU) es un trastorno que se comporta de manera distinta al trastorno bipolar-I (TB-I), sin embargo, no es considerado como una entidad independiente por los manuales diagnósticos vigentes, sino que es incluido dentro del diagnóstico de TB-I. Caso clínico: Hombre de 21 años presenta cuadro clínico de 3 meses de evolución caracterizado por ánimo exaltado y síntomas psicóticos congruentes al estado de ánimo. El paciente niega episodios depresivos previos. Se instaura tratamiento con litio y aripiprazol que resulta satisfactorio, sin presentar recurrencias tras 5 años de seguimiento. Revisión de la literatura y discusión: Los manuales diagnósticos describen que para diagnosticar TB-I no se requiere la presencia de un episodio depresivo mayor, lo que implica que pacientes con MU quedan dentro de la misma categoría diagnóstica que pacientes con TB-I. Diferencias entre MU y TB-I han sido demostradas en estudios epidemiológicos, clínicos y genéticos, por lo tanto, incluir pacientes heterogéneos dentro de la misma categoría podría dificultar la interpretación de estudios y limitar los avances en el conocimiento de ambos trastornos. Conclusión: De la revisión de la literatura se sugiere que la MU debe ser reconocida como un diagnóstico independiente. A pesar de su baja prevalencia, al validarlo como tal, en un futuro podríamos contar con mayor cantidad y mejor calidad de datos sobre este. De esta forma se podrá definir de manera más concreta sus características distintivas, y por consiguiente mejorar el abordaje clínico de estos pacientes.

Introduction: Unipolar mania (UM) is a disorder that behaves differently from bipolar-I disorder (BP-I), however, it is not considered an independent entity by current diagnostic manuals, but rather included within the diagnosis of BP-I. Case report: A 21-year-old man presented a 3-month-long episode characterized by exalted mood and mood-congruent psychotic symptoms. The patient denies previous depressive episodes. Treatment with lithium and aripiprazole was established, which was satisfactory, not showing recurrence after 5 years of follow-up. Literature review and discussion: Diagnostic manuals describe that to diagnose BP-I the presence of a major depressive episode is not required, which implies that patients with UM fall into the same diagnostic category as patients with BP-I. Differences between UM and BP-I have been demonstrated in epidemiological, clinical, and genetic studies, therefore, including heterogeneous patients within the same category could hinder the interpretation of studies and limit advances in the knowledge of both disorders. Conclusion: Based on the literature review, it is suggested that UM should be recognized as an independent diagnosis. Despite its low prevalence, by validating it as such, in the future we could have more and better-quality data about this diagnosis. In this way, its distinctive characteristics can be defined more concretely, and therefore improve the clinical approach of these patients.

Bipolar Disorder and Cardiovascular Risk in Rural versus Urban Populations in Colombia: A Comparative Clinical and Epidemiological Evaluation.

Background: Various multifactorial elements may contribute toward the urban and rural disparities in cardiovascular disease (CVD) risk, particularly among patients with psychiatric diseases. Objective: To investigate whether rural patients diagnosed and treated for Bipolar Disorder (BD) have different risk profiles and outcomes of CVD compared to urban (BD) patients. Methods: We conducted a case-control study that included 125 BD patients (cases) from rural Filadelfia, Colombia and 250 BD patients (controls) treated in Bogotá, Colombia. Cases and controls were 2:1, matched by age and sex. We applied the Framingham Heart Study (FHS) risk calculator to assess risk. Differences by rural/urban status (i.e., case-control status) were assessed by chi-square, paired t-tests, and logistic regression. Findings: Rural BD patients were found to have lower education (p = 1.0 × 10-4), alcohol consumption (p = 3.0 × 10-4), smoking (p = 0.015), psychiatric (p = 1.0 × 10-4) and CV family history (p = 0.0042) compared to urban BD patients. Rural BD patients were 81% more likely to have a more favorable CVD risk profile (OR: 0.19, 95% CI [0.06-0.62]) than urban BD patients, despite rural BD patients having increased CVD morbidity (p = 1.0 × 10-2). Conclusion: Based on increase in morbidity but lower predictive risk in the rural population, our study suggests that the FHS-CVD calculator may not be optimal to assess CVD risk in this population.

Exploring machine learning to predict depressive relapses of bipolar disorder patients.

BACKGROUND: Bipolar disorder (BD) is a chronic mood disorder characterized by recurrent episodes of mania or hypomania and depression, expressed by changes in energy levels and behavior. However, most of relapse studies use evidence-based approaches with statistical methods. With the advance of the precision medicine this study aims to use machine learning (ML) approaches as a possible predictor in depressive relapses in BD. METHOD: Four accepted and well used ML algorithms (Support Vector Machines, Random Forests, Naïve Bayes, and Multilayer Perceptron) were applied to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) dataset in a cohort of 800 patients (507 patients presented depressive relapse and 293 did not), who became euthymic during the study and were followed for one year. RESULTS: The ML algorithms presented reasonable performance in the prediction task, ranging from 61 to 80% in the F-measure. The Random Forest algorithm obtained a higher average of performance (Relapse Group 68%; No Relapse Group 74%). The three most important mood symptoms observed in the relapse visit (Random Forest) were: interest; depression mood and energy. LIMITATIONS: Social and psychological parameters such as marital status, social support system, personality traits, might be an important predictor in depressive relapses, although we did not compute this data in our study. CONCLUSIONS: Our findings indicate that applying precision medicine models by means of machine learning in BD studies could be feasible as a sensible approach to better support medical decision-making in the BD treatment and prevention of future relapses.