Mindfulness trait and the potential mediating role of emotional regulation strategies in bipolar disorder / Mindfulness rasgo y el potencial papel mediador de las estrategias de regulación emocional en el trastorno bipolar

En este estudio transversal se investiga la asociación entre los principales síntomas del Trastorno bipolar (TB) y las dificultades asociadas a las estrategias de regulación emocional (ERE) adaptativas y desadaptativas. Además, este estudio examina los efectos mediadores de las ERE con el mindfulness rasgo y el TB. Método. Veinticuatro adultos con TB completaron la Escala de Conciencia de Atención Plena (MAAS), el Inventario de Depresión de Beck (BDI-II), la Escala de Autoevaluación de Manía de Altman (ARSM), el Inventario de Ansiedad Rasgo (STAI-R), y el Cuestionario de Regulación Emocional Cognitiva (CERQ). Resultados. El análisis de regresión múltiple mostró cómo la depresión se relacionaba significativa y positivamente con la autoculpabilización, mientras que la ansiedad rasgo estaba positivamente asociada con la autoculpabilización y el catastrofismo. En segundo lugar, el análisis de mediación mostró un efecto de mediación significativo para la autoculpabilidad en la relación entre mindfulness y depresión (a*b = -.15; ICB 95% [-.36, -.03]) y entre mindfulness y ansiedad rasgo (a*b = -.09; ICB 95% [-.27, -.01]). Conclusiones. Nuestros resultados informan del papel de la auto-culpabilidad y el catastrofismo en el TB y de cómo éstas podrían mediar significativamente entre el mindfulness rasgo y el TB. Estos resultados sugieren que una práctica de meditación enfocada en el catastrofismo y la autoculpabilidad puede ser especialmente útil para reducir los síntomas en los pacientes bipolares.(AU)

This cross-sectional study investigates the association between the main symptoms of Bipolar disorder (BD) and emotional regulation dif-ficulties in adaptive and maladaptive emotional regulation strategies (ERS). In addition, this study examines the possible mediating effects of ERS with dispositional mindfulnessand bipolar symptoms. Method.Twenty-four adults diagnosed with BD completed the Mindful Attention Awareness Scale (MAAS), the Beck Depression Inventory (BDI-II), the Altman Mania Self-Assessment Scale (ARSM), the Trait Anxiety Inventory (STAI-R), and the Cognitive Emotional Regulation Questionnaire (CERQ). Results. First, mul-tiple regression analysis showed how depression was significantly positively related to self-blame, whereas trait anxietywas positively associated with self-blame and catastrophizing. Second, the results of the mediation analy-sis have shown a significant mediation effect for the self-blamein the rela-tionship between mindfulnessand depression (a*b = -.15; BCI 95% [-.36, -.03]) and between mindfulnessand trait anxiety (a*b = -.09; BCI 95% [-.27, -.01]). Conclusions. Our results report the role of self-blame and catastrophiz-ing in BD and how these might significantly mediate between dispositional mindfulness and symptoms of depression and anxiety. These results suggest that a meditation practice focused on reducing catastrophizing and self-blame may be especially helpful for symptoms of depression and anxiety in bipolar patients.(AU)

Cerebrospinal fluid synaptic biomarker changes in bipolar disorder - A longitudinal case-control study.

BACKGROUND: This exploratory study investigated cerebrospinal fluid (CSF) synaptic protein biomarkers in bipolar disorder (BD), aiming to highlight the neurobiological basis of the disorder. With shared cognitive impairment features between BD and Alzheimer's disease, and considering increased dementia risk in BD patients, the study explores potential connections. METHODS: Fifty-nine well-characterized patients with BD and thirty-seven healthy control individuals were examined and followed for one year. Synaptic proteins encompassing neuronal pentraxins (NPTX)1, NPTX2, and NPTX-receptor, 14-3-3 protein family epsilon, and zeta/delta, activating protein-2 complex subunit beta, synucleins beta-synuclein and gamma-synuclein, complexin-2, phosphatidylethanolamine-binding protein 1, rab GDP dissociation inhibitor alpha, and syntaxins 1B and 7 were measured in CSF using a microflow liquid chromatography-mass spectrometric multiple reaction monitoring set-up. Biomarker levels were compared between BD and HC and in BD before, during, and after mood episodes. RESULTS: The synaptic proteins revealed no statistically significant differences between BD and HC, neither at baseline, one-year follow-up, or in terms of changes from baseline to follow-up. Moreover, the CSF synaptic protein levels in patients with BD were unaltered compared to baseline when they stabilized in euthymia following an affective episode and at one-year follow-up. LIMITATION: It is uncertain what the CSF biomarker concentrations reflect since we yet do not know the mechanisms of release of these proteins, and we are uncertain of what increased or decreased levels reflect. CONCLUSION: This first-ever investigation of a panel of CSF protein biomarkers of synaptic dysfunction in patients with BD and HC individuals found no statistically significant differences cross-sectionally or longitudinally.

Behavioral evidence of impaired self-referential processing in patients with affective disorders and first-episode schizophrenia.

Despite the critical role of self-disturbance in psychiatric diagnosis and treatment, its diverse behavioral manifestations remain poorly understood. This investigation aimed to elucidate unique patterns of self-referential processing in affective disorders and first-episode schizophrenia. A total of 156 participants (41 first-episode schizophrenia [SZ], 33 bipolar disorder [BD], 44 major depressive disorder [MDD], and 38 healthy controls [HC]) engaged in a self-referential effect (SRE) task, assessing trait adjectives for self-descriptiveness, applicability to mother, or others, followed by an unexpected recognition test. All groups displayed preferential self- and mother-referential processing with no significant differences in recognition scores. However, MDD patients showed significantly enhanced self-referential recognition scores and increased bias compared to HC, first-episode SZ, and BD. The present study provides empirical evidence for increased self-focus in MDD and demonstrates that first-episode SZ and BD patients maintain intact self-referential processing abilities. These findings refine our understanding of self-referential processing impairments across psychiatric conditions, suggesting that it could serve as a supplementary measure for assessing treatment response in first-episode SZ and potentially function as a discriminative diagnostic criterion between MDD and BD.

The role of bipolar disorder and family wealth in choosing creative occupations.

Research in psychology and medicine has linked mental health disorders, and particularly bipolar disorder (BD), to employment in creative professions. Little is known, however, about the mechanisms for this link, which could be due to biology (primarily through a person's genes) or environmental (through socioeconomic status). Using administrative data on mental health diagnoses and occupations for the population of Denmark, we find that people with BD are more likely to be musicians than the population, but less likely to hold other creative jobs. Yet, we also show that healthy siblings of people with BD are significantly more likely to work in creative professions. Notably, people from wealthy families are consistently more likely to work in creative professions, and access to family wealth amplifies the likelihood that siblings of people with BD pursue creative occupations. Nevertheless, family wealth explains only a small share of the correlation between BD and creative employment.

Mental illness and pulmonary tuberculosis: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies have confirmed that mental illness and pulmonary tuberculosis are closely related and increase each other's incidence; however, whether there is a causal genetic association between the two diseases remains unknown. We attempted to answer this question using bidirectional two-sample Mendelian randomization (MR) in a large cohort study. Method: We performed a bidirectional MR analysis between mental illness (major depressive, anxiety disorder, bipolar disorder, and schizophrenia) and pulmonary tuberculosis using summary statistics from genome-wide association studies in European individuals. The inverse-variance weighted method was used as the primary analytical method to assess causality. In addition, other additional MR methods (weighted median, MR-Egger, and weighted mode) were used to supplement the inverse-variance weighted results. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Result: We identified no causal genetic association between mental illness and pulmonary tuberculosis after applying the inverse variance weighted method (major depressive: odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.59-1.71, P = 0.98; anxiety disorder: OR = 1.72, 95% CI = 0.05-67.67, P = 0.76; bipolar disorder OR = 0.89, 95% CI = 0.66-1.22, P = 0.48; and schizophrenia: OR = 1.05, 95% CI = 0.91-1.20, P = 0.51). Similarly, pulmonary tuberculosis was not caustically associated with mental illness (major depressive: OR = 1.01, 95% CI = 1.00-1.02, P = 0.17; anxiety disorder: OR = 1.00, 95% CI = 0.99-1.01, P = 0.06; bipolar disorder: OR = 1.02, 95% CI = 0.98-1.07, P = 0.38; and schizophrenia: OR = 1.01, 95% CI = 0.97-1.05, P = 0.66). Conclusion: Our research does not support a bidirectional causal association between the aforementioned mental illnesses and pulmonary tuberculosis.

Homocysteine, hopelessness, rumination, affective temperaments, and clinical course in patients with bipolar disorder-1.

PURPOSE: This study aimed to explore the associations between homocysteine, rumination, affective temperaments, clinical features, and hopelessness in bipolar disorder-1 (BD-1). MATERIALS AND METHODS: In total, 57 euthymic patients with BD-1 and 57 healthy controls were included. The Beck Hopelessness Scale (BHS), Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A), and Ruminative Responses Scale Short Form (RRS-SF) were administered. Homocysteine, folate, and vitamin B12 levels were measured. RESULTS: The BHS total (p = 0.047), TEMPS-A irritable (p = 0.007), and TEMPS-A cyclothymic (p= 0.001) scores were significantly higher than the control group in the BD-1 group. Hyperhomocysteinemia (HHcy) was found in 33.3% of the patients (n = 19). In the HHcy group, age of onset of disease (p = 0.020) was significantly lower than the non-HHcy group in patients. Previous suicide attempt number was significantly correlated with scores of reflective pondering, brooding, and global rumination in BD-1 (p Ë‚ 0.05). Except for hyperthymic temperament, all types of affective temperaments were correlated with the scores of RRS-SF brooding (p Ë‚ 0.05) in the BD-1 group. The RRS-SF brooding scores significantly correlated with the BHS total scores (r = 0.263, p < 0.05); the TEMPS-A hyperthymic (ß = -0.351, p = 0.001) and TEMPS-A irritable (ß = 0.536, p < 0.001) scores significantly predicted the BHS total scores in the BD-1 group. CONCLUSIONS: The findings may lead clinical efforts and future clinical trials to explore and intervene in related sources and presentations of BD-1's adverse consequences.

Use of a virtual environment to promote self-management and lifestyle changes in persons with bipolar disorder.

PURPOSE: Self-management and lifestyle interventions are a key factor in treatment outcomes for persons with bipolar disorder (BD). A virtual environment (VE), due to it's ability to provide flexibility of involvement in its platform, may be an alternative to face-to-face treatment to provide support for self-management. The purpose of this study is to explore how a VE, developed for chronic illness self-management, may be modified to promote self-management and lifestyle changes in those with BD. METHOD: This study used a qualitative description design with focus groups. Data were collected via minimally structured interviews and analyzed using thematic content analysis. A total of seven focus groups were conducted, and the sample consisted of 30 adults with BD. Age range was 21-77 years with 21 females, seven males, and two non-binary individuals. RESULTS: Five themes emerged from the findings: Self-management and lifestyle interventions with regards to (1) mental health; (2) holistic health; (3) role of peers; (4) involvement of the family; (5) technological aspects of the VE. CONCLUSIONS: Focus group participants suggested that the VE may be an efficacious way to enhance self-management and promote lifestyle interventions in those with BD. Research is needed to adapt such platforms to the need of the patients and examine its' effect on health outcomes.

Circulating metabolite abundances associated with risks of bipolar disorder, schizophrenia, and depression: a Mendelian randomization study.

BACKGROUND: Preventive measures and treatments for psychiatric disorders are limited. Circulating metabolites are potential candidates for biomarker and therapeutic target identification, given their measurability and essential roles in biological processes. METHODS: Leveraging large-scale genome-wide association studies, we conducted Mendelian randomization (MR) analyses to assess the associations between circulating metabolite abundances and the risks of bipolar disorder, schizophrenia, and depression. Genetic instruments were selected for 94 metabolites measured in the Canadian Longitudinal Study of Aging (N=8,299) cohort. We repeated MR analyses based on the UK Biobank, INTERVAL, and EPIC-Norfolk studies. RESULTS: After validating MR assumptions and colocalization evidence, we found that a one standard deviation (SD) increase in genetically predicted circulating abundances of eicosapentaenoate (EPA) and docosapentaenoate (n3 DPA) was associated with odds ratios (ORs) of 0.72 (95% CI: 0.65-0.79) and 0.63 (95% CI: 0.55-0.72) for bipolar disorder, respectively. Genetically increased Ω-3 unsaturated fatty acids abundance and Ω-3-to-total fatty acids ratio, as well as genetically decreased Ω-6-to-Ω-3 ratio were negatively associated with the risk of bipolar disorder in the UK Biobank. Genetically increased circulating abundances of three N-acetyl-amino acids were associated with an increased risk of schizophrenia with a maximum OR of 1.31 (95% CI: 1.18-1.44) per one SD increase. Furthermore, a one SD increase in genetically predicted circulating abundance of hypotaurine was associated with an OR of 0.85 (95% CI: 0.78-0.93) for depression. CONCLUSIONS: The biological mechanisms underlying Ω-3 unsaturated fatty acids, NAT8-catalyzed N-acetyl-amino acids, and hypotaurine warrant exploration to identify new biomarkers and potential therapeutic targets.

Neuroprogression in bipolar disorder: why right is wrong.

The controversy on whether bipolar disorder is a neurodevelopmental versus a neuroprogressive illness is still around, despite some reductionistic claims that only one model is right. The current diagnostic classifications are not helpful to address this issue, and there is conflicting evidence in favor and against either model. In practice, though, understanding that many patients may show a progressive cognitive and functional decline which may be correlated with the number and severity of episodes may lead to better outcomes through early intervention strategies.

Psychometric Properties of the Spanish Version of the Cognitive Problems and Strategies Assessment in Patients with Bipolar Disorder.

Cognitive deficits play an important role in Bipolar Disorder (BPD). The Cognitive Problems and Strategies Assessment (CPSA) is a measure that evaluates the patient's perception of cognitive difficulties, and the spontaneous use of compensatory strategies and could thus have potential utility for clinical practice in patients with BPD. Our aim was to determine the validity and reliability of the Cognitive Problems and Strategies Assessment (CPSA) in Bipolar Disorder (BPD). Ninety-three BPD outpatients and 90 controls completed the Assessment of Problems with Thinking and Memory (APTM) questionnaire and the Assessment of Memory and Thinking Strategies (AMTS) questionnaire which constitute the CPSA, the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA), as a measure of convergent validity, and general sociodemographic data. Cronbach's alpha coefficient, Spearman's correlation coefficient and independent sample t tests were used for Internal consistency, Convergent validity and Discriminant validity. The APTM had a Cronbach's alpha coefficient of 0.93 and the AMTS 0.90. The COBRA score and the APTM were significantly correlated. BPD patients exhibited higher scores on the APTM and lower scores on the AMTS than controls. The present instrument enriches the clinician's repertoire for rapid and inexpensive cognitive evaluation in BPD.

Comparison of early risk factors between healthy siblings and subjects with schizophrenia and bipolar disorder.

Introduction: The following work aims to compare the types and magnitude of risk events in patients with Schizophrenia and Bipolar Disorder and each of those groups with of a group of healthy siblings, exploring differences and similarities of the two psychotic disorders. Methods: Retrospective interviews were conducted with 20 families to investigate maternal and obstetric health, social support and the presence of early trauma for the affected family members and healthy siblings. Mothers were interviewed with the Prenatal Psychosocial Profile and each family participant was assessed with the Early Trauma Inventory, Screening Questionnaire of the Genomic Psychiatry Cohort and the Diagnostic Interview for Psychosis and Affective Disorders. Results: Obstetric and gestational history, pregnancy weight changes and early trauma were associated with offspring's mental illness, including statistically significant findings for complications of pregnancy, pregnancy weight changes, general trauma, physical punishment and emotional abuse. Conclusion: These findings highlight the different risk factor exposures that occur within a family, which may increase the risk for severe mental illness.

Bipolar disorders and schizophrenia: discrete disorders?

Background: With similarities in heritability, neurobiology and symptomatology, the question has been raised whether schizophrenia and bipolar disorder are truly distinctive disorders or belong to a continuum. This narrative review summarizes common and distinctive findings from genetics, neuroimaging, cognition and clinical course that may help to solve this ethiopathogenetic puzzle. Methods: The authors conducted a literature search for papers listed in PubMed and Google Scholar, using the search terms "schizophrenia" and "bipolar disorder" combined with different terms such as "genes", "neuroimaging studies", "phenomenology differences", "cognition", "epidemiology". Articles were considered for inclusion if they were written in English or Spanish, published as full articles, if they compared subjects with schizophrenia and bipolar disorder, or subjects with either disorder with healthy controls, addressing differences between groups. Results: Several findings support the hypothesis that schizophrenia and bipolar disorder are discrete disorders, yet some overlapping of findings exists. The evidence for heritability of both SZ and BD is obvious, as well as the environmental impact on individual manifestations of both disorders. Neuroimaging studies support subtle differences between disorders, it appears to be rather a pattern of irregularities than an unequivocally unique finding distinguishing schizophrenia from bipolar disorder. The cognitive profile displays differences between disorders in certain domains, such as premorbid intellectual functioning and executive functions. Finally, the timing and trajectory of cognitive impairment in both disorders also differs. Conclusion: The question whether SZ and BD belong to a continuum or are separate disorders remains a challenge for further research. Currently, our research tools may be not precise enough to carve out distinctive, unique and undisputable differences between SZ and BD, but current evidence favors separate disorders. Given that differences are subtle, a way to overcome diagnostic uncertainties in the future could be the application of artificial intelligence based on BigData. Limitations: Despite the detailed search, this article is not a full and complete review of all available studies on the topic. The search and selection of papers was also limited to articles in English and Spanish. Selection of papers and conclusions may be biased by the personal view and clinical experience of the authors.

Effect of γ-tACS on prefrontal hemodynamics in bipolar disorder: A functional near-infrared study.

OBJECTIVES: Transcranial alternating current stimulation (tACS) is a potential therapeutic psychiatric tool that has been shown to modulate clinical symptoms and brain function by inducing brain oscillations. However, direct evidence on the effects of gamma-tACS (γ-tACS) on Bipolar I Disorder (BD-I) is limited. In the present study we used functional near-infrared spectroscopy to explore prefrontal hemodynamic changes in BD-I patients receiving combined γ-tACS intervention in addition to pharmacological treatment. METHODS: Only 39 male patients with BD-I in the acute manic phase were included, and they were randomly divided into an intervention group (n = 18) and a control group (n = 21). The intervention group received γ-tACS treatment on a weekday for a total of 10 sessions in the right prefrontal cortex and left prefrontal cortex. All participants were pretested (baseline) and posttested (2 weeks after) with questionnaires to assess clinical symptoms and cognitive abilities, and with functional near infrared spectroscopy (fNIRS) to assess spontaneous cortical hemodynamic activities. RESULTS: Compared to the control group, the intervention group had greater increases in Montreal Cognitive Assessment (MoCA) scores, and greater decreases in Bech-Rafaelsen Mania Rating Scale (BRMS) scores. In the intervention group, functional connectivity (FC) was significantly greater in the left hemisphere. γ-tACS treatment resulted in a left hemispheric lateralization effect of resting state FC in BD-I patients, increasing the hemodynamic activity of the patient's left prefrontal cortex. CONCLUSIONS: γ-tACS can improve cognitive impairment and mood symptoms with BD-I patients in an acute manic episode by enhancing FC in the patients' left prefrontal cortex.

Investigating light sensitivity in bipolar disorder (HELIOS-BD).

Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour cycle. Circadian rhythms are strongly influenced by light levels and previous research suggests that people with bipolar disorder might have a heightened sensitivity to light, causing more circadian rhythm disruption, increasing the potential for triggering a mood switch into mania or depression. Lithium has been in clinical use for over 70 years and is acknowledged to be the most effective long-term treatment for bipolar disorder. Lithium has many reported actions in the body but the precise mechanism of action in bipolar disorder remains an active area of research. Central to this project is recent evidence that lithium may work by stabilising circadian rhythms of mood, cognition and rest/activity. Our primary hypothesis is that people with bipolar disorder have some pathophysiological change at the level of the retina which makes them hypersensitive to the visual and non-visual effects of light, and therefore more susceptible to circadian rhythm dysfunction. We additionally hypothesise that the mood-stabilising medication lithium is effective in bipolar disorder because it reduces this hypersensitivity, making individuals less vulnerable to light-induced circadian disruption. We will recruit 180 participants into the HELIOS-BD study. Over an 18-month period, we will assess visual and non-visual responses to light, as well as retinal microstructure, in people with bipolar disorder compared to healthy controls. Further, we will assess whether individuals with bipolar disorder who are being treated with lithium have less pronounced light responses and attenuated retinal changes compared to individuals with bipolar disorder not being treated with lithium. This study represents a comprehensive investigation of visual and non-visual light responses in a large bipolar disorder population, with great translational potential for patient stratification and treatment innovation.

Genomic landscape and functional characterization of structural variations in schizophrenia and bipolar disorder.

Multiple types of variations have been postulated to confer risk of schizophrenia and bipolar disorder, but majority of present GWAS solely focused on SNPs or small indels, and the impacts of structural variations (SVs) remain less understood. Nevertheless, accumulating evidence suggest that SVs may explain the association signals in certain GWAS hits. Here, we conducted pairwise linkage disequilibrium (LD) analyses of SNPs and SVs in populations from 1000 Genomes Project. Among the 299 psychiatric GWAS loci, 1213 SVs showed an LD of r2 > 0.1 with GWAS risk SNPs, and 66 of them were in moderate to strong LD (r2 > 0.6) with at least one GWAS risk SNP. Nine SVs were subject to further explorative analyses, including eQTL analysis in DLPFC, luciferase reporter gene assays, CRISPR/Cas9-mediated genome deletion and RT-qPCR. These assays highlighted several functional SVs showing regulatory effects on transcriptional activities, and some risk genes (e.g., BORCS7, GNL3) affected by the SVs were also annotated. Finally, mice overexpressing Borcs7 in the mPFC exhibited schizophrenia-like behaviors, such as abnormal prepulse inhibition and social dysfunction. These data suggest that SNPs association signals at GWAS loci might be driven by SVs, highlighting the necessities of considering such variants in future.

Uncovering novel drug targets for bipolar disorder: a Mendelian randomization analysis of brain, cerebrospinal fluid, and plasma proteomes.

BACKGROUND: There is a clear demand for innovative therapeutics for bipolar disorder (BD). METHODS: We integrated the largest BD genome-wide association study (GWAS) dataset (NCase = 41 917, NControl = 371 549) with protein quantitative trait loci from brain, cerebrospinal fluid, and plasma. Using a range of integrative analyses, including Mendelian randomization (MR), Steiger filter analysis, Bayesian colocalization, and phenome-wide MR analysis, we prioritized novel drug targets for BD. Additionally, we incorporated data from the UK Biobank (NCase = 1064, NControl = 365 476) and the FinnGen study (NCase = 7006, NControl = 329 192) for robust biological validation. RESULTS: Through MR analysis, we found that in the brain, downregulation of DNM3, MCTP1, ABCB8 and elevation of DFNA5 and PDF were risk factors for BD. In cerebrospinal fluid, increased BD risk was associated with increased levels of FRZB, AGRP, and IL36A and decreased CTSF and LRP8. Plasma analysis revealed that decreased LMAN2L, CX3CL1, PI3, NCAM1, and TIMP4 correlated with increased BD risk, but ITIH1 did not. All these proteins passed Steiger filtering, and Bayesian colocalization confirmed that 12 proteins were colocalized with BD. Phenome-wide MR analysis revealed no significant side effects for potential drug targets, except for LRP8. External validation further underscored the concordance between the primary and validation cohorts, confirming MCTP1, DNM3, PDF, CTSF, AGRP, FRZB, LMAN2L, NCAM1, and TIMP4 are intriguing targets for BD. CONCLUSIONS: Our study identified druggable proteins for BD, including MCTP1, DNM3, and PDF in the brain; CTSF, AGRP, and FRZB in cerebrospinal fluid; and LMAN2L, NCAM1, and TIMP4 in plasma, delineating promising avenues to development of novel therapies.

Care trajectories around a first dementia diagnosis in patients with serious mental illness.

AIM: To develop a typology of care trajectories (CTs) 1 year before and after a first dementia diagnosis in individuals aged ≥65 years, with prevalent schizophrenia or bipolar disorder. METHODS: This was a longitudinal, retrospective cohort study using health administrative data (1996-2016) from Quebec (Canada). We selected patients aged ≥65 years with an incident diagnosis of dementia between 1 January 2014 and 31 December 2016, and a diagnosis of schizophrenia and/or or bipolar disorder. A CT typology was generated by a multidimensional state sequence analysis based on the "6 W" model of CTs. Three dimensions were considered: the care setting ("where"), the reason for consultation ("why") and the specialty of care providers ("which"). RESULTS: In total, 3868 patients were categorized into seven distinct types of CTs, with varying patterns of healthcare use and comorbidities. Healthcare use differed in terms of intensity, but also in its distribution around the diagnosis. For instance, whereas one group showed low healthcare use, healthcare use abruptly increased or decreased after the diagnosis in other groups, or was equally distributed. Other significant differences between CTs included mortality rates and use of long-term care after the diagnosis. Most patients (67%) received their first dementia diagnosis during hospitalization. CONCLUSIONS: Our innovative approach provides a unique insight into the complex healthcare patterns of people living with serious mental illness and dementia, and provides an avenue to support data-driven decision-making by highlighting fragility areas in allocating care resources. Geriatr Gerontol Int 2024; ••: ••-••.

Putative Risk Biomarkers of Bipolar Disorder in At-risk Youth.

Bipolar disorder is a highly heritable and functionally impairing disease. The recognition and intervention of BD especially that characterized by early onset remains challenging. Risk biomarkers for predicting BD transition among at-risk youth may improve disease prognosis. We reviewed the more recent clinical studies to find possible pre-diagnostic biomarkers in youth at familial or (and) clinical risk of BD. Here we found that putative biomarkers for predicting conversion to BD include findings from multiple sample sources based on different hypotheses. Putative risk biomarkers shown by perspective studies are higher bipolar polygenetic risk scores, epigenetic alterations, elevated immune parameters, front-limbic system deficits, and brain circuit dysfunction associated with emotion and reward processing. Future studies need to enhance machine learning integration, make clinical detection methods more objective, and improve the quality of cohort studies.

Plasma IGFBP-3 and IGFBP-5 levels are decreased during acute manic episodes in bipolar disorder patients.

Introduction: Bipolar disorder (BD) is a recurrent and disabling psychiatric disorder related to low-grade peripheral inflammation and altered levels of the members of the insulin-like growth factor (IGF) family. The aim of this study was to evaluate the plasma levels of IGF-2, insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-3, IGFBP-5, IGFBP-7, and inflammatory markers such as tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1ß (MIP-1ß). Methods: We used the Young Mania Rating Scale (YMRS) to determine the severity of the symptomatology, while proteins were measured by enzyme-linked immunosorbent assay (ELISA). We included 20 patients with BD who suffered a manic episode and 20 controls. Some BD patients (n = 10) were evaluated after a period (17 ± 8 days) of pharmacological treatment. Results: No statistical difference was found in IGF-2, IGFBP-1, IGFBP-7, TNF-α, and MIP-1ß levels. However, IGFBP-3 and IGFBP-5 levels were found to be statistically decreased in BD patients. Conversely, the MCP-1 level was significantly increased in BD patients, but their levels were normalized after treatment. Intriguingly, only IGFBP-1 levels were significantly decreased after treatment. No significant correlation was found between the YMRS and any of the proteins studied either before or after treatment or between IGF proteins and inflammatory markers. Discussion: To some extent, IGFBP-3 and IGFBP-5 might be further explored as potential indicators of treatment responsiveness or diagnosis biomarkers in BD.

Assessment of symptom severity in psychotic disorder patients based on heart rate variability and accelerometer mobility data.

BACKGROUND: Advancement in mental health care requires easily accessible, efficient diagnostic and treatment assessment tools. Viable biomarkers could enable objectification and automation of the diagnostic and treatment process, currently dependent on a psychiatric interview. Available wearable technology and computational methods make it possible to incorporate heart rate variability (HRV), an indicator of autonomic nervous system (ANS) activity, into potential diagnostic and treatment assessment frameworks as a biomarker of disease severity in mental disorders, including schizophrenia and bipolar disorder (BD). METHOD: We used a commercially available electrocardiography (ECG) chest strap with a built-in accelerometer, i.e. Polar H10, to record R-R intervals and physical activity of 30 hospitalized schizophrenia or BD patients and 30 control participants through ca. 1.5-2 h time periods. We validated a novel approach to data acquisition based on a flexible, patient-friendly and cost-effective setting. We analyzed the relationship between HRV and the Positive and Negative Syndrome Scale (PANSS) test scores, as well as the HRV and mobility coefficient. We also proposed a method of rest period selection based on R-R intervals and mobility data. The source code for reproducing all experiments is available on GitHub, while the dataset is published on Zenodo. RESULTS: Mean HRV values were lower in the patient compared to the control group and negatively correlated with the results of the PANSS general subcategory. For the control group, we also discovered the inversely proportional dependency between the mobility coefficient, based on accelerometer data, and HRV. This relationship was less pronounced for the treatment group. CONCLUSIONS: HRV value itself, as well as the relationship between HRV and mobility, may be promising biomarkers in disease diagnostics. These findings can be used to develop a flexible monitoring system for symptom severity assessment.