Cross-sectional and longitudinal network analysis of bipolar depression and mania during early pharmacological treatment.

Isolating the Genetic Component of Mania in Bipolar Disorder.

Introduction Bipolar affective disorder (BD) is a chronic psychiatric illness characterized by alternating manic and depressive episodes. Despite extensive research, its underlying mechanisms remain unclear. Recent studies suggest that purinergic signaling and inflammation may play key roles in BD pathophysiology. This study aimed to explore biomarkers related to these systems to improve understanding of BD and identify potential diagnostic and prognostic indicators. Methods The study included 76 BD patients and 20 healthy controls from the Department of Adult Psychiatry, Poznan University of Medical Sciences. Blood samples were collected during acute episodes and after symptom remission. Biomarkers analyzed included uric acid (UA), interleukin-6 (IL-6), NACHT, P2X7 receptor, adenosine deaminase (ADA), xanthine dehydrogenase (XDH), and adenosine (ADO), measured by ELISA. Results NACHT (p = 0.004) and P2X7 (p = 0.001) were significantly higher post-treatment. Age positively correlated with NACHT, and BMI with UA. P2X7 levels negatively correlated with depressive symptom improvement. Gender differences revealed higher pre-treatment ADA levels in women and greater post-treatment increases in NACHT, ADA, and XDH in men. IL-6 was elevated during depressive episodes, while NACHT and XDH were higher in manic states. ROC analysis indicated strong diagnostic potential for XDH (AUC=0.917) and ADA (AUC=0.903). Logistic regression identified post-treatment NACHT and P2X7 as significant BD predictors. Conclusions The study highlights the involvement of purinergic and inflammatory pathways in BD pathophysiology. Biomarkers such as NACHT, P2X7, ADA, and XDH may aid in diagnosing BD and monitoring treatment responses, offering potential for biologically informed therapies.

ABSTRACT There is limited research offering experiential knowledge of severe mental illness in elite athletes. Adopting a narrative approach, this study explored how an Olympic athlete constructed his illness identity and how this construction shaped his experience of living with bipolar disorder. We conducted five semi-structured interviews with Darrel, a male Olympic athlete diagnosed with bipolar disorder, over a ten-month period in the lead-up to the Paris 2024 Olympic Games. 10 hours of data were collected, with interviews an average of 90 minutes in duration. Interviews were transcribed verbatim and analysed using dialogical narrative analysis, attending to both the content of Darrel’s stories and the ways in which he told them. Through various storytelling strategies, Darrel constructed a de-stigmatised illness identity that reinforced his sense of self as an athlete. His narratives emphasised athletic accomplishment despite – and sometimes because of – his bipolar disorder. He distanced himself from the stigmatised stereotypes of severe mental illness by telling stories of his high functioning. Emotionally difficult moments were laced with humour, while manic episodes were portrayed in a glamourised way. These narrative strategies appeared to manage self-stigma and resist the potentially marginalising meanings associated with mental illness in elite sport. However, such storytelling also has implications for how others perceive and respond to athlete distress. For example, the glamourisation of mania may lead staff to underestimate the severity of the athlete’s mental illness. This study demonstrates the value of narrative methods for exploring how athletes make sense of severe mental illness and construct identities within the cultural context of elite sport.

Bipolar disorder (BD) is a severe mental illness associated with marked functional impairment and reduced life expectancy. Early indicators such as mood instability, circadian rhythm disturbance, and anxiety symptoms often precede the first manic or depressive episode, providing a potential window for preventive intervention. Currently, no structured early intervention program exists for individuals at risk for BD who do not yet meet diagnostic criteria. This study aims to evaluate the feasibility and acceptability of a novel, personalized early intervention program combining light therapy, lifestyle psychoeducation, and imagery-focused cognitive therapy (ImCT) for individuals at risk for BD. The study employs a single-case experimental A-B-A design with staggered baseline and multiple daily assessments. Fifty participants aged 16-35 years identified as being at risk for BD by a specialized early detection team will be included. The intervention consists of three core components: (1) a chronotherapeutic intervention (bright light therapy or blue-light blocking glasses) tailored to individual symptom profiles; (2) one session of lifestyle-focused psychoeducation targeting sleep, nutrition, and physical activity; and (3) six sessions of ImCT to address mood instability and maladaptive mental imagery. Feasibility and acceptability will be assessed through drop-out rates, adherence, and participant feedback. Secondary outcomes include changes in depressive, hyperactive, anxiety, and imagery-related symptoms, as well as sleep quality and activity levels, measured through validated questionnaires and actigraphy. By combining chronotherapeutic, psychological, and lifestyle components, this intervention targets multiple mechanisms implicated in BD risk. Findings will inform the development of preventive strategies for individuals in an at-risk mental state for BD. The study will also provide data on the feasibility of integrating early interventions within routine mental health services and guide the design of future randomized controlled trials. Medical Ethical Committee Brabant (METC Brabant; identifier P2314); ClinicalTrials.gov Identifier: NCT06282250. Registered 20 February 2024.

The correlational study of the 24 solar terms and meteorological factors with the acute exacerbation of bipolar disorder

BackgroundBipolar disorder requires immediate and frequent daily symptom monitoring due to its extreme mood fluctuations. Ecological momentary assessment (EMA) technology uses high-frequency data collection to achieve ecologically valid capture of patient symptoms. Investigating EMA compliance among Chinese patients with bipolar disorder and its influencing factors is essential for developing more feasible daily symptom monitoring protocols.ObjectiveThis study aimed to investigate the 14-day compliance rate of EMA among Chinese individuals with bipolar disorder and to examine the demographic and clinical characteristics associated with that compliance.MethodsA total of 100 adults (63 female individuals) with bipolar disorder across mood states (depressive episode, n=29, 29%; hypomanic or manic episode, n=17, 17%; euthymic state, n=54, 54%) completed self-monitoring via the WeChat Mini Program “Xunkang Assessment System” 3 times daily for 14 days. The compliance rate was calculated as the percentage of completed questionnaires out of the total required over 2 weeks. Multivariate ordinal logistic regression was used to explore the factors associated with the compliance rate.ResultsThe median compliance rate was 75% (IQR 35.7%-90.4%). Compliance did not differ significantly across mood states (P=.15). In multivariable models, higher Bech-Rafaelsen Mania Scale scores and lower Functioning Assessment Short Test scores were independently associated with better compliance (Bech-Rafaelsen Mania Scale: B=0.11; P=.03 and Functioning Assessment Short Test: B=−0.06; P=.01).ConclusionsTwo-week EMA monitoring via the WeChat Mini Program is feasible among Chinese individuals with bipolar disorder across mood states. Manic symptom severity and functional impairment were associated with EMA adherence and should be considered in study design and interpretation.

Exploring temperamental and clinical predictors of lithium treatment outcomes in bipolar disorder using diverse machine learning approaches.

ABSTRACTBackgroundBD is a chronic, cyclical condition marked by severe mood instability and significant impairment. Although pharmacological and psychotherapeutic interventions have demonstrated efficacy, challenges remain in preventing relapse and sustaining long‐term euthymia. This study evaluates a CBT‐based intervention designed to reduce symptom severity and recurrence by targeting three core maintenance factors: intolerance of anergic states, addiction to mania, and meta‐emotional problems.MethodFour individuals diagnosed with BD participated in a one‐year CBT intervention tailored to address these key vulnerabilities. Assessments were conducted at baseline, post‐treatment, and at 18‐ and 24‐month follow‐ups, measuring depression, mania, quality of life, and personality functioning. Changes were evaluated with RCI and repeated measures ANOVA.ResultsAll four patients showed a marked reduction in depressive symptoms at the end of treatment and at the 24‐month follow‐up, with a large effect size (η2 = 0.83). Improvements were also observed in the quality of life and maladaptive personality traits over time. Notably, euthymia was maintained throughout the follow‐up period, with no recurrence of manic episodes or new affective cycles.ConclusionDespite limitations, these preliminary findings suggest that this three‐goal CBT intervention targeting core maintenance factors in bipolar disorder may promote sustained clinical improvements, increase long‐term stability, and reduce reliance on medication.

Navigating the paradoxes and potential of digital phenotyping for bipolar relapse prediction.

BackgroundBipolar disorders (BD) are severe mental illnesses with recurrent depressive and (hypo-)manic episodes and a chronic course. While anecdotal and cross-sectional studies suggest a link between BD and creativity, longitudinal evidence is limited. This study investigates the role of creativity in individuals with varying risk for developing BD, using data from the multicenter, prospective Early-BipoLife study. N = 1,255 individuals aged 15–35 years were assessed and followed for over two years. Of these, N = 1,105 were included in the analyses; 150 were excluded due to missing creativity questionnaires. Creativity was measured with the Barron-Welsh Art Scale (BWAS) and the Creative Achievement Questionnaire (CAQ); BD risk was assessed with the EPIbipolar. Analyses included comparisons of mean creativity scores across BD risk groups and logistic regressions testing prospective associations between continuous creativity scores and transition to manifest BD. To enhance clinical applicability, group comparisons and odds ratios (ORs) were also calculated, providing estimates of relative risk across subgroups defined by BD risk status and creativity level.ResultsAt baseline (BL), participants at high BD risk scored significantly higher on the CAQ than those at low risk, while no differences were observed for BWAS scores. During FU, 25 of 1,105 individuals transitioned to manifest BD. Logistic regression analyses did not reveal significant associations between creativity and transitions. However, group comparisons indicated elevated transition likelihood in individuals with high BD risk, with the highest ORs in those combining high BD risk and high creativity (BWAS: OR = 7.05, 95% CI: 1.94–25.56; CAQ: OR = 5.57, 95% CI: 1.88–16.54) compared to low-risk individuals with low creativity.ConclusionsHigh BD risk was associated with higher CAQ scores at BL, suggesting heightened creativity may precede transition. Prospective analyses over two years did not confirm this association, likely due to the small number of transitions. Nonetheless, cross-sectional differences and group comparisons suggest that individuals with both high BD risk and high creativity, particularly real-world accomplishments captured by the CAQ, may show an increased likelihood of transition. These preliminary findings warrant replication in larger, longer-term studies. Importantly, creativity should not be pathologized but considered both as a resource and as a potential modifier of risk trajectories.

Sleep is critical for emotional regulation, memory, and cognitive performance. Sleep disturbances, including insomnia, hypersomnia, and circadian misalignment, are highly prevalent and clinically significant across various psychiatric disorders. Once considered secondary, sleep problems are now recognized as active contributors to the onset, course, and relapse of mental illness. This narrative review synthesizes current evidence on the bidirectional interactions between sleep and major psychiatric conditions such as major depressive disorder, bipolar disorder, anxiety disorders, posttraumatic stress disorder, schizophrenia, attention deficit and hyperactivity disorder, and substance use disorders. We highlight convergent neurobiological mechanisms, including dysregulation of circadian systems, neurotransmitter networks (GABA, serotonin, dopamine, orexin), affective circuitry (prefrontal-amygdala interactions), and stress-immune pathways. Findings consistently show that sleep problems are transdiagnostic features, impacting diagnostic presentation, prognostic trajectories, and underlying pathology. For instance, chronic insomnia increases depression risk, sleep loss can precipitate manic episodes, and distinct sleep architecture anomalies are linked to schizophrenia. Sleep disturbances also predict worse outcomes in substance use disorders, including increased craving and relapse risk. Sleep is a tractable factor in mental health, offering a potent intervention leverage point. Routine, structured sleep assessment should be integrated into psychiatric care, emphasizing first-line behavioral and chronobiological strategies like Cognitive Behavioral Therapy for Insomnia (CBT-I) and light/rhythm therapies. Directly addressing sleep significantly improves psychiatric outcomes, reducing symptoms of depression and anxiety, decreasing suicidal ideation, and lowering relapse risk in bipolar disorder and psychoses. Future research should prioritize causal designs, mechanistic neuroimaging, biomarker identification, and responsible integration of objective measurement technologies and artificial intelligence for early warning systems and personalized treatment protocols.

Bipolar disorder (BD) is a significant mental health condition characterized by alternating episodes of mania and depression, impacting millions worldwide. Genetic factors are known to play a major role in BD, but the influence of circulating micronutrient levels remains unclear. Two-sample Mendelian randomization (MR) and multiple MR were used to assess the impact of 15 circulating micronutrients, including copper, selenium, zinc, calcium, iron, magnesium, potassium, carotene, folate, and vitamins A, B6, B12, C, D, and E on BD risk. Genetic data were sourced from Genome-Wide Association Studies, and BD case–control data were obtained from the FinnGen consortium. Inverse variance weighted was the main analysis method. The heterogeneity of the instrumental variables was assessed using inverse variance weighted and MR-Egger, simple mode, weighted median, and weighted mode, and the horizontal pleiotropy of the instrumental variables was assessed using MR-Egger and MR-PRESSO. Higher genetically predicted levels of vitamin B12 (odds ratio = 1.81, 95% confidence interval: 1.19–2.74, P = .005) and carotene (odds ratio = 1.49, 95% confidence interval: 1.07–2.08, P = .017) are associated with an increased risk of BD. No significant causal associations were found between BD and the levels of other circulating micronutrients. Sensitivity analyses confirmed the robustness of these findings, with no evidence of heterogeneity or horizontal pleiotropy detected. This study suggests that elevated levels of vitamin B12 and carotene may increase the risk of BD, pointing to potential nutritional targets for intervention. Further research is needed to elucidate these findings and understand their underlying mechanisms.

Aims/Background:Patients with bipolar disorder experience lipid metabolism disorders and endocrine dysregulation, which may affect emotional regulation, behavioural habits and cognitive function. This study aimed to investigate the correlations amongst lipid metabolism indicators, thyroid hormone levels, and manic episodes, aggressive behaviours, cognitive function and disease severity in patients with bipolar disorder.Methods:This retrospective analysis included 656 patients with bipolar disorder admitted to Wuhan Mental Health Center. Baseline data, including manic symptoms (Young Mania Rating Scale), aggressive behaviours (Modified Overt Aggression Scale), cognitive function (Montreal Cognitive Assessment), disease severity (Clinical Global Impressions-Severity), lipid metabolism indicators {total cholesterol (TC), triglycerides (TGs), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and thyroid hormone levels [thyroid-stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), free triiodothyronine (FT3) and free thyroxine (FT4)]}, were collected through electronic medical records.Results:No statistically significant differences were observed in serum TC, LDL, TSH, T4 or FT3 levels between the manic episode group and the non-manic group (p > 0.05). However, the manic episode group exhibited significantly higher serum TG, T3 and FT4 levels (p < 0.05) and significantly lower HDL levels (p < 0.05) than the non-manic group. No significant differences were observed in serum TC, TG, HDL or LDL levels between the aggressive behaviour group and the non-aggressive group (p > 0.05). However, the aggressive behaviour group showed significantly higher TSH, T4, T3, FT3 and FT4 levels (p < 0.05) than the non-aggressive group. No significant differences were observed in serum TC, TG, LDL, TSH, T4, T3 or FT3 levels between the cognitive impairment and normal cognition groups (p > 0.05). However, the cognitive impairment group had significantly lower HDL and FT4 levels (p < 0.05) than the normal cognition group. No statistically significant differences were observed in the serum levels of TC, TG, HDL, LDL, TSH, T4, T3, FT3 or FT4 between the moderate and severe bipolar disorder groups (p > 0.05).Conclusion:Changes in lipid metabolism indicators and thyroid hormone levels in patients with bipolar disorder are closely related to manic episodes, aggressive behaviours and cognitive dysfunction, but no correlation was found with disease severity. This evidence supports precision management of bipolar disorder by utilizing specific lipid and thyroid hormone profiles to guide cardiovascular screening, aggression risk assessment, and early detection of cognitive decline.

Objectives: The main aim was to evaluate the origin and empirical support of the current diagnostic criteria for (hypo)manic and depressive episodes in BD focusing on their nosological (i.e., is it a real entity?) and diagnostic validity (i.e., how well do the criteria for the category portray the entity?). Methods: A narrative review of relevant textbooks/reports and articles published in peer-reviewed English-language journals (from the online databases PubMed and PsycInfo), covering the period 1900-2024 and using the terms "validity" OR "diagnosis" AND "manic-depressive"; "mania"; "hypomania"; "depression"; and "melancholia" was performed. Results: Mania appears to be a valid construct in nosological terms, although its validity in the diagnostic domain requires further research. There are scant and controversial empirical data on the nosological validity of separating hypomania from mania as different episodes. The current concept of bipolar depression combines different forms of episodes (melancholic and non-melancholic, with or without psychosis, recurrent or not) without conclusive evidence that all of them are necessarily part of the illness (i.e., limited nosological validity). Conclusions: The validity of the current definition of BD is limited and should be the focus of future research. A valid definition of BD would improve our ability to understand the pathophysiological basis of the illness and contribute to more tailored therapeutic approaches.

Patients experiencing manic episodes often suffer from significant emotional instability, impairing treatment adherence and prolonging hospitalization. Nonpharmacological interventions such as music therapy may offer additional benefits. This study aimed to evaluate the impact of group music therapy combined with routine nursing on emotional stability, symptom severity, and patient satisfaction in inpatients with manic episodes. In this retrospective study, 102 inpatients diagnosed with manic episodes between January 2022 and December 2023 were enrolled and divided into a control group (n = 50) receiving routine nursing care and an observation group (n = 52) receiving additional group music therapy. Group music sessions were held 3 times weekly for 4 weeks. The Young Mania Rating Scale (YMRS), the Emotional Stability subscale of the Eysenck Personality Questionnaire (EPQ-ES), and patient satisfaction were assessed before and after intervention. Statistical comparisons were performed within and between groups. At baseline, there were no significant differences between groups in age, gender, illness duration, YMRS, or EPQ-ES scores. After intervention, the observation group showed significantly lower YMRS scores (15.2 ± 3.7 vs 21.6 ± 4.1, P < .001), higher EPQ-ES scores (28.5 ± 5.2 vs 22.3 ± 5.0, P < .001), and greater satisfaction (86.5% vs 64.0%, P = .012) compared to the control group. Group music therapy significantly enhances emotional stability and satisfaction among hospitalized manic patients. This intervention is a feasible and effective supplement to routine psychiatric nursing care.

Bipolar Affective Disorder is a chronic and recurrent psychiatric condition characterized by mood swings that alternate between depressive and manic episodes. The manic phase, in turn, represents one of the most disruptive aspects of the disease, as it significantly interferes with self-perception and perception of others, interpersonal relationships, and the individual's functionality.The objective of this study was to analyze the manifestation of mania in Bipolar Affective Disorder, considering its clinical characteristics and its impacts on different contexts of the individual's life.The methodology adopted was a literature review, based on scientific articles, diagnostic manuals, and clinical studies published in the main databases in the field of mental health. It was concluded that the effective management of mania requires a combination of strategies, involving the use of mood-stabilizing psychotropic drugs, psychotherapeutic interventions, family support, and social reintegration actions.

BackgroundHallucinogen use for both recreational and medical purposes is rapidly increasing globally, raising concerns about potential adverse effects. This study examined the risk of incident mania or bipolar disorder (BD) diagnosis associated with having an emergency department (ED) visit or hospitalization involving hallucinogens.Methods and findingsWe used a population-based cohort study of all individuals aged 14–65 years with no baseline history of BD and registered in the Ontario Health Insurance Plan in Ontario, Canada, between 2008–2022. Incident mania (primary outcome) and incident BD (secondary outcome) were compared between individuals with acute care (an ED visit or hospitalization) involving hallucinogens and the general population using overlap propensity score weighted Cox proportional hazard models. Models were adjusted for age, sex, rural residence, income quintile, recent documentation of homelessness, and healthcare encounters for mental health or other substance use in the past five years. The study included 9,311,844 individuals of which 7,285 (0.08%) had acute care involving hallucinogens. Within 3-years of acute care involving hallucinogens, 1.43% (n = 104) of individuals had an incident episode of mania requiring acute care compared to 0.06% (n = 41) of individuals in the age-sex matched general population, a 25-fold increase in risk. After weighting, acute care for hallucinogens was associated with a 6-fold (weighted Hazard Ratio [HR] 5.97, 95% CI 3.29, 10.82) increase in risk of incident mania relative to individuals without hallucinogen acute care who had otherwise similar demographic and mental health histories. Associated increases were also observed for risk of an incident diagnosis of BD (HR 3.75 95%CI 2.49, 5.65, absolute proportion 2.50% versus 0.11%). The main limitation of the study is the risk associated with the exposure examined in this study may not generalize to the majority of people who use hallucinogens who do not require acute care.ConclusionsThese findings suggest the need for ongoing caution regarding hallucinogen use in individuals at risk of bipolar disorder. They also have potential implications for clinical practice, research, and public health policy, including substance regulation and targeted education for high-risk groups in the context of rising hallucinogen use.

Early warning signals of bipolar relapse: Investigating critical slowing down in smartphone data.

Loss and bereavement may precede mood episodes in bipolar disorders (BD). When a loved one dies, this is a stressful life event with a negative connotation that can trigger the onset of symptoms of both polarities (depressive or manic) of BD or lead to the emergence of the first mood episodes. Even though the relationships between death and depression are better known in the literature and clinical practice, the associations between bereavement and (hypo-)mania are less clear. To date, information on "funeral mania", also called "grief mania" or "bereavement mania", is rather limited, remaining in fact an underestimated topic. Aiming to draw more attention to this overlooked issue, the purpose of this mini-review is to update the knowledge currently available on this topic. We reviewed the existing literature exploring the possible associations between bereavement and the onset of a (hypo-)manic episode, both a first or recurrent episode, supporting the role of loss events as a potential risk factor for BD progression. Our findings emphasize the positive association between the loss of a loved one and (hypo-)manic symptoms in bipolar disorders, although no prospective studies have assessed the impact of these life events on the course of (hypo-)mania in a large sample. We recommend the clinical assessment of this association, in order to provide patients with BD with the most adequate and prompt treatments.