Mauro García-Toro

Background: Accumulating evidence suggests that bipolar disorder (BD) and epilepsy share important clinical, neurobiological, and therapeutic features. Both disorders are characterized by recurrent episodes and fluctuating clinical courses, raising the possibility that partially overlapping or analogous regulatory processes may contribute to some aspects of their clinical expression and progression. This review examines current evidence regarding the overlap between BD and epilepsy and explores integrative perspectives that may help explain their similarities. Methods: A narrative review of the literature was conducted. Evidence related to genetics, neuroimaging, cognition, neuroplasticity, neuroinflammation, stress biology, network neuroscience, and treatment response was examined. Results: Findings across BD and epilepsy reveal partially overlapping biological and clinical features, including alterations in excitation–inhibition balance, neuromodulatory disturbances, neuroinflammatory processes, and neuroplastic changes. Neuroimaging studies in both conditions reveal abnormalities in large-scale brain networks involved in emotional regulation, cognitive control, and behavioral adaptation. Clinically, both disorders show sensitivity to environmental and physiological stressors and sleep disruption, cognitive impairment, and partial responsiveness to overlapping pharmacological and neuromodulatory interventions. These observations are compatible with the hypothesis that recurrent episodes and prolonged network dysregulation may reinforce maladaptive patterns of instability through interacting feedback processes, although this interpretation remains to be tested directly. Conclusions: Current evidence identifies several clinical and biological similarities between BD and epilepsy but does not yet establish that these similarities reflect identical or directly shared causal mechanisms. An integrative perspective combining network dysfunction, neuroplasticity, and systemic regulatory processes may provide a useful heuristic framework for investigating disease heterogeneity, progression, and treatment response. Further longitudinal and comparative studies are required before this perspective can support personalized monitoring strategies or mechanism-informed interventions.

BACKGROUND Suicide is a major public health concern, and primary care has an important role in detecting and intervening in at-risk cases. However, many primary healthcare workers claim to feel inadequately prepared when it comes to properly identifying, preventing, and handling suicidal behaviour in clinical practice. OBJECTIVE The objective of this study is to develop and evaluate an intervention for improving primary healthcare workers ability to identify, prevent, and handle suicidal behaviour. METHODS This protocol describes the PROMESA study, which uses a multimethod design in four sequential phases, in line with some of the phases laid out in the Medical Research Council framework for developing and evaluating complex interventions. In phase 1, a qualitative study will be performed using four focus groups and at least 20 semi-structured interviews with primary healthcare professionals, people with lived experience, and bereaved family members, via a thematic analysis. Phase 2 will involve a retrospective case-control study covering the period 2019-2023. The analysis will focus on sociodemographic and clinical factors as well as patterns of use of healthcare services utilization among individuals who showed suicidal behaviour. Data will be obtained from Electronic Health Records to identify cases and matched controls, enabling the assessment of associations between these factors and suicidal behaviour. Two interventions will be designed for phase 3: (1) the specific training and delivery of a report with the results of the study from phase 2 to PC HCWs, and (2) the same intervention plus the inclusion of a tool in which patients self-evaluate their risk of suicide. Phase 4 will consist of a controlled, phase II, single-blind, randomized clinical trial with three parallel arms (intervention 1, intervention 2, and a control group), which will assess the feasibility and effectiveness of these interventions including 126 primary healthcare workers. RESULTS The study was funded in 2024, March. Recruitment of health care professionals is currently ongoing. The study findings will be reported in future publications. CONCLUSIONS The epidemiological trends and documented gaps in primary care preparedness highlight the need for strengthened strategies in the early detection and management of suicidal behaviour. This study is expected to provide essential insights into the feasibility and acceptability of implementing tailored training and decision‑support tools for primary healthcare workers. By combining qualitative perspectives, epidemiological evidence, and a controlled feasibility trial, the project will help determine whether the interventions can be integrated into routine practice and whether they show promise for improving clinical response to suicidal behaviour. The findings will inform the refinement of the intervention and guide the development of a future full‑scale evaluation aimed at advancing suicide prevention efforts in primary care. CLINICALTRIAL Registration number ISRCTN8134762 on 25/04/2025.

Objectives: Depressive and anxiety disorders are highly prevalent conditions characterized by recurrent episodes and substantial heritability. From an evolutionary perspective, their persistence poses a longstanding question, given their association with functional impairment. Several explanatory models have been proposed in evolutionary psychiatry, yet no single account fully explains their clinical and epidemiological complexity. This non-systematic review aims to summarize the main evolutionary hypotheses proposed to explain the persistence of depressive and anxiety disorders and to explore the potential contribution of systems-oriented perspectives. Methods: A narrative review of the literature published mainly between 2010 and 2026 was conducted, prioritizing integrative reviews, theoretical models, and representative empirical studies in evolutionary psychiatry, psychiatric genetics, and systems approaches to psychopathology. Results: Proposed explanations include adaptive defense models, evolutionary mismatch, trade-offs and pleiotropy, mutation–selection balance in highly polygenic traits, and pathogen-defense hypotheses. In parallel, recent genetic and network approaches increasingly conceptualize depression and anxiety as emergent properties of complex regulatory systems. Within this context, the schismogenesis hypothesis is discussed as a possible integrative framework describing how reciprocal amplification processes triggered by stress may contribute to reversible biopsychosocial disconnection states. Conclusions: The persistence of depressive and anxiety disorders is most plausibly explained by multicausal models involving evolutionary trade-offs, context dependence, and dynamic regulatory processes. Systems-level perspectives may help integrate existing theories and generate new hypotheses for research and clinical practice.

Anxiety spectrum disorders (ASDs) often have an unsatisfactory prognosis, suggesting the opportunity for complementary explanatory frameworks to advance their therapeutics. This text advocates for a framework rooted in cybernetics and complex systems theory, which views the mind, brain, and social networks as deeply interdependent systems. A characteristic feature of such systems is the operation of similar organizational principles and laws across different levels of analysis, a phenomenon termed isomorphism. Thus, the mind, brain, and social systems operate under isomorphic principles, requiring a critical balance between stability (homeostasis) and the capacity for change (homeodynamics) to successfully adapt to environmental perturbations. From this perspective, the central challenge under stress is to prevent excessive fragmentation and functional dissociation, a process termed schismogenesis in cybernetics. ASDs are, therefore, reconceptualized as biopsychosocial dissociations stemming from a schismogenic mechanism. This framework posits that mental health is contingent upon maintaining a dynamic equilibrium between connectedness and independence across social, mental, and neural levels. It also suggests that any intervention promoting reintegration can be therapeutic when dissociation occurs. While single-component psychosocial approaches may suffice for mild cases of ASDs, the ideal therapeutic plan for severe or refractory cases should be rapidly implemented, personalized, multicomponent and synchronous.

The need to reach an agreement between two fixed positions arises in many practical problems. A typical example of this type of situation is given when two independent and reputed physicians provide two different patient descriptions. Here, healthcare professionals need to identify the most relevant description to support the diagnostic outcome. In 2003, Nieto and Torres provided an appropriated mathematical framework for decision-making when the aforementioned situation is under consideration through the application of the midpoint notion between fuzzy sets. They stated that the decision-maker can adopt the consensus position within a typically unbounded (in general) collection of midpoints. Inspired by the preceding fact, in this paper we focus our efforts on developing an assisted decision-making technique based on the use of midpoints between fuzzy sets and a scoring function. This approach reduces the consensus position between the two fixed ones to a finite number of distinguished midpoints, i.e., those midpoints at which the scoring is minimized and maximized, respectively. Concretely, we provide two possible alternatives. The first one consists of letting the decision-maker choose between the minimizer or maximizer midpoints of the scoring function values. The second alternative consists in providing a working midpoint which is obtained as a weighted average of the minimizer and maximizer criterions. An example of the applicability of the exposed theory is presented in the framework of medical diagnosis when two physicians want to determine whether a patient has a potential risk of suicide.

BACKGROUND Depression is a prevalent and disabling mental health disorder that significantly affects quality of life and remains a leading global contributor to disability. Although pharmacological and psychological interventions are effective, many patients fail to achieve complete remission of depressive symptoms. Current evidence suggests that lifestyle-related interventions may offer a promising strategy as an adjuvant treatment for depression. OBJECTIVE To evaluate the effectiveness of lifestyle-based interventions in reducing depressive symptoms in adults. METHODS An umbrella review of systematic reviews and meta-analyses of randomized controlled trials (RCTs) evaluating lifestyle-based interventions for adults with depression was conducted. The literature search was conducted in Medline/PubMed, PsycINFO, Web of Science, Cochrane Library, and Scopus from inception to March 2025. The review followed the PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD42024420246). Two reviewers independently screened titles and abstracts, reviewed full texts for eligibility, extracted data and evaluate the methodological quality of included reviews using AMSTAR-2. Discrepancies were resolved through discussion with a third author. A narrative synthesis of findings was conducted. RESULTS A total of 46 systematic reviews were included, of which 32 incorporated meta-analysis. Aerobic and resistance exercise showed moderate-to-large effects, particularly when delivered in supervised settings. Mind-body therapies achieved similar benefits and were associated with high adherence rates. Multicomponent interventions showed small-to-moderate effect, although their effectiveness was limited by heterogeneity and follow-up decline. CONCLUSIONS Lifestyle-based interventions are safe, scalable, and effective adjuvant treatments for depression. However, further high-quality, standardized trials are needed to optimize intervention protocols and confirm their long-term benefits. CLINICALTRIAL The protocol for this umbrella review was prospectively registered in the PROSPERO database (International Prospective Register of Systematic Reviews, under registration number CRD42024420246.

Introduction About 30% of depressed patients suffer from a protracted course in which the disorder continues to cause significant burden despite treatment efforts. While originally developed for relapse prevention, Mindfulness-Based Cognitive Therapy (MBCT) has increasingly been investigated in depressed patients with such ‘difficult-to-treat’ courses. This is a protocol for an individual participant data (IPD) meta-analysis aiming to determine efficacy and potential moderators of MBCT treatment effects in this group based on evidence from randomised controlled trials. Methods and analysis Systematic searches in PubMed, Web of Science, Scopus, PsycINFO, EMBASE, and the Cochrane Controlled Trials Register for randomised controlled trials were completed on 17 June 2024. Authors of identified studies have contributed IPD and data extractions have been completed. An update search will be conducted immediately before the start of data analyses. We will investigate the following outcomes: (a) self-reported and observer-reported severity of depression symptomatology, (b) remission, (c) clinically meaningful improvement and deterioration. One-stage and two-stage IPD meta-analyses will be conducted with one-stage models using the observed IPD from all studies simultaneously as the primary approach. One-stage IPD models will include stratified study intercepts and error terms as well as random effects to capture between-study heterogeneity. Moderator analyses will test treatment-covariate interactions for both individual patient level and study level characteristics. Ethics and dissemination The results will inform understanding of the use of MBCT in patients with current ‘difficult-to-treat’ depression and will contribute to arguments in favour of or against implementing MBCT as a treatment for this group. They will be published in a peer reviewed journal and made available to stakeholders in accessible formats. No local ethical review was necessary following consultation with the Ethics and Governance Board of the University of Surrey. Guidance on patient data storage and management will be adhered to throughout. PROSPERO registration number CRD42022332039 STRENGTHS AND LIMITATIONS OF THIS STUDY The chosen approach using IPD has several advantages over conventional meta-analyses including the possibility to assess whether individual participant level characteristics influence treatment effects with more specificity and power Limitations of the approach include the fact that inconsistencies across studies regarding the format and type of variables reported may restrict our ability to investigate moderators of treatment effects Transformation of outcome measures to a common metric across all studies may come with a small loss of information.