Alessandra Costanza

Introduction: Bipolar Disorders (BD) are severe, recurrent, and well-characterized psychiatric conditions with lithium as the first-line approved treatment for BD. This study aims to evaluate lithium response using the ALDA scale and to identify reliable predictors in a cohort of patients with BD. Methods: In this cross-sectional observational study, one hundred and fourteen consecutively recruited patients with a primary diagnosis of BD type I or II were included between June 2022 and June 2025. Sociodemographic and clinical characteristics were collected through a semi-structured interview. Lithium response was retrospectively assessed using the ALDA scale. Psychometric instruments (CTQ, MEQ, MWQ, DDFS, RRS, BIS-11) were administered. Logistic regression analyses were performed to identify independent predictors of lithium response. Results: Forty-one (36%) individuals were classified as lithium responders according to the ALDA Scale. Lithium responders were younger, engaged in physical activity more frequently, were more frequently diagnosed with BD type II, had a shorter illness duration, a Manic–Depressive–Interval (MDI) course, and showed fewer residual symptoms. Non-responders were associated with rapid cycling, psychotic symptoms, more hospitalizations, and illicit substance use. Childhood trauma, impulsivity, and rumination were more common among non-responders, while morning chronotype was more prevalent among responders. In the regression analysis, the MDI pattern, higher total scores for attentional impulsivity and rumination, and morning chronotype were all significantly associated with lithium responsiveness. On the other hand, the presence of psychotic symptoms, a history of ≥ 5 hospitalizations, comorbid substance use, and higher scores of emotional abuse were associated with a lower likelihood of response to lithium. Discussion: Integrating the evaluation of trauma history, impulsive profiles, ruminative tendencies, and circadian features into clinical assessment may enhance the prediction of lithium response. conclusion: Our findings support the development of personalized treatment strategies for BD. Conclusion: Our findings support the development of personalized treatment strategies for BD.

Background/Objectives: Bipolar disorder (BD) is increasingly recognized as a multisystem condition in which metabolic abnormalities, particularly insulin resistance (IR), may be linked to illness severity and neuroprogression. Despite growing evidence linking IR to adverse clinical outcomes, the data is heterogeneous and preliminary, and its specific association in hospitalized patients with BD remains underexplored. Methods: This cross-sectional study included 86 inpatients with a primary diagnosis with BD at the IRCCS Ospedale Policlinico San Martino, Genoa, Italy, between July 2023 and January 2024. Sociodemographic, clinical, and metabolic characteristics were systematically investigated. IR was defined as a HOMA-IR index ≥ 2.5. Results: Twenty-eight patients met criteria for IR. Insulin resistant patients showed a significantly longer illness duration, more frequent residual symptoms, and higher rates of ≥5 lifetime psychiatric hospitalizations. They also exhibited greater polypharmacy (≥4 psychotropics at discharge) and daily alcohol use. Furthermore, the IR subgroup was significantly associated with higher body mass index and triglycerides, lower HDL cholesterol and physical activity levels. Conclusions: Our findings indicate that IR is associated with markers of greater illness burden in BD. While these results are consistent with emerging hypotheses on metabolic dysfunction in BD, longitudinal studies are required to clarify temporal and causal relationships. These associations suggest that IR may represent a clinically relevant component of BD rather than a secondary metabolic consequence. Routine metabolic screening and the preferential use of metabolically neutral agents may improve long-term outcomes and align with the emerging paradigm of precision psychiatry.

Background: Understanding how suicide rates vary across age, sex, and geography is essential to designing effective prevention strategies. We examined long-term trends in suicide mortality across European countries over three decades, with a focus on age-specific trajectories. Methods: Using the WHO mortality database, we computed annual sex- and age-specific suicide rates (10–14 to 85+ age groups) from 1990 to 2022, for the most populous European countries, and aggregated rates for the EU-27 and four geographical areas (North, West, South, and Centre-East Europe). We also calculated percentage differences across four time periods (1990–1994, 2000–2004, 2010–2014, and 2020–2022), according to data availability. Results: Suicide rates increased with age, peaking in older individuals (85+) in most countries (e.g., 82.0/100,000 in France in 2020–2022, 77.1/100,000 in Germany among males, in 2020), except in the UK and Northern Europe, where rates peaked at middle age (∼22/100,000 at 45–49, in 2020). EU-27 suicide rates in 2020 ranged from 5.5/100,000 (age 15–19) to 58.2/100,000 (85+) among males, and from 2.6 (15–19) to 8.6/100,000 (85+) among females. Male suicide rates were 3 to 8 times higher than female rates across all ages. While overall rates declined since 1990 in most countries, youth suicide increased after 2010 in Western (e.g., +12%, girls 15–19), Southern (+24.5%, girls 15–19), and Northern (+44%, girls 15–19 and 20–24) Europe. Rates among young and middle-aged adults recently rose in Spain, the UK, and Northern Europe, while they declined in Eastern Europe after the 1990s. Conclusions: Despite overall declines, our findings highlight marked heterogeneity in sex- and age-specific trends in suicide mortality across Europe. These patterns call for age-tailored prevention strategies that address evolving psychosocial stressors and structural determinants across the lifespan.

Background: Suicidal behaviour (SB) is one of the most complex neuropsychiatric conditions, with an etiopathogenesis that remains elusive despite a myriad of studies revealing its multifaceted nature, influenced by various biological, psychological, socioeconomic and cultural factors, usually with complex reciprocal and synergistic interactions. Emerging evidence has recently suggested a potential involvement of pathogens and host-tissue derived microbial species in contributing to SB. This review aims to provide a concise synthesis of clinical evidence focusing on the presence of microbial alterations in subjects with SB and in those exhibiting risk factors for SB, thereby exploring a possible new perspective in suicidology. Summary: We conducted a surveillance of the literature in the PUBMED database, from its inception to 10 May 2025, to identify associations between infection/microbial alterations with SB and some of its risk factors (by focusing on two pathologic examples of psychiatric and somatic origins, respectively: depression and chronic pain, two often closely related conditions). Major clinical findings were selected and synthesised into a hypothetical framework to support the presence of a microbe-related origin of SB. We found that SB was associated with selected infections, such as Toxoplasma gondii and Cytomegalovirus. Dysbiosis, including changes in diversity and/or abundance of selected microbial species, in the oral cavity, gastrointestinal tract, and other mucosal tissues, was observed in subjects with SB and individuals with psychiatric (depression) and somatic (chronic pain) risk factors of SB. Key Message: Microbial dysbiosis might contribute to SB etiopathogenesis. Further studies in this emerging field of research are expected to provide additional mechanistic insights for an improved understanding, prevention, and therapeutic management of this neuropsychiatric condition.

Post-COVID-19 syndrome (PCS) is an escalating global health concern, marked by persistent cognitive, neurological, and psychiatric symptoms following acute SARS-CoV-2 infection. Although its underlying mechanisms remain incompletely understood, mounting evidence implicates chronic neuroinflammation as a key driver. Sustained microglial and astrocyte activation, blood-brain barrier disruption, and aberrant cytokine signaling contribute to prolonged immune dysregulation within the central nervous system, promoting long-term brain dysfunction. In this expert review, we synthesize emerging insights into how neuroimmune processes impair brain function in PCS. We explore novel mechanistic pathways - including local sleep intrusions, impaired memory reconsolidation, and astrocyte-mediated destabilization of functional networks - that may underlie the syndrome's fluctuating and heterogeneous presentation. We evaluate fluid biomarkers of neuroinflammation, including glial fibrillary acidic protein (GFAP), soluble TREM2, S100β, and pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-a. In parallel, we highlight converging neuroimaging biomarkers derived from PET and MRI studies. These include increased TSPO-PET binding in limbic and frontal regions, alterations in cerebral blood flow and oxygen metabolism, neurometabolic changes detected via MR spectroscopy (e.g., elevated myo-inositol and choline), and increased free water content on diffusion imaging - each suggestive of glial activation and network-level dysfunction. We propose a multiscale, longitudinal framework that integrates molecular, neuroimaging, and behavioral data to link immune dysregulation with brain network instability and symptom emergence. Such integrative approaches are critical for advancing precision diagnostics and informing the development of targeted, mechanism-based treatments for individuals affected by PCS.

Background/Objectives: The understanding of the mechanisms involved in the etiopathogenesis and maintenance of Bipolar Disorder (BD) should be a priority to identify potential early clinical markers that could help in improving treatment strategies and prevention. The aim of this study was to investigate the potential correlation between hopelessness, alexithymia, mind wandering, and rumination in patients with a primary diagnosis of BD, evaluating whether these psychopathological aspects could negatively affect bipolar illness. Methods: A semi-structured interview was used to collect sociodemographic and clinical characteristics. Several psychometric tools were administered: the Beck Hopelessness Scale; Toronto Alexithymia Scale; Rumination Response Scale; Mind Wandering Questionnaire; Mind Wandering: Deliberate; Mind Wandering: Spontaneous; and the Daydreaming Frequency Scale. Results: Patients with high levels of hopelessness have a greater number of psychiatric and medical comorbidities and are more frequently on polypharmacotherapy. Additionally, patients with high levels of hopelessness show a greater likelihood of having attempted suicide during their lifetime. The presence of alexithymia is associated with longer hospitalization and psychiatric comorbidities. Higher levels of rumination correlate with a greater number of psychiatric and medical comorbidities, and with the presence of residual symptoms. Mind wandering is associated with the presence of medical comorbidities and residual symptoms. Conclusions: Hopelessness, alexithymia, mind wandering, and rumination should be identified as important proxies of impaired subjective well-being that should be carefully monitored because they could further worsen the clinical course of BD and suicidal risk in this vulnerable population.

The association between inflammation with depression and suicide has prompted many investigations of the potential contributors to inflammatory pathology in these psychiatric illnesses. However, a distillation of diverse clinical findings into an integrated framework of the possible involvement of major physiological processes in the elicitation of pathological inflammation in depression and suicide has not yet been explored. Therefore, this review aims to provide a concise synthesis of notable clinical correlates of inflammatory pathology in subjects with various depressive and suicidal clinical subtypes into a mechanistic framework, which includes aberrant immune activation, deregulated neuroendocrine signaling, and impaired host-microbe interaction. These issues are of significant research interest as their possible interplays might be involved in the development of distinct subtypes of depression and suicide. We conclude the review with discussion of a pathway-focused therapeutic approach to address inflammatory pathology in these psychiatric illnesses within the realm of personalized care for affected patients.