搜索结果：Biological psychology

Chronic psychological stress responses to discrimination may be associated with more accelerated paces of biological aging at a particular window of time through epigenetic changes in DNA methylation, including in third-generation epigenetic clocks (i.e., the DunedinPACE and GrimAge2). Although discrimination is often measured by frequency, fewer studies examine how its cumulative psychological toll is associated with biological age acceleration, which is a theoretical proposition aligned with the weathering hypothesis. The present study analyzed data from two national longitudinal studies: 397 adults completing eight daily diaries in the Midlife in the United States study and 2,059 adults completing five biennial surveys in the Health and Retirement Study. We modeled the within-person associations (i.e., slopes) between discrimination and negative affect as correlates of biological aging captured by the DunedinPACE and GrimAge2 clocks. Across both studies, adults who experienced more discrimination, on average, reported more negative affect. Stronger positive slopes between discrimination and negative affect were associated with faster paces of biological aging at the time of assessment in only the DunedinPACE clock in the Midlife in the United States study and in the DunedinPACE and GrimAge2 clocks in the Health and Retirement Study. These associations persisted after adjusting for the frequency of discrimination, highlighting the importance of modeling stress reactivity rather than exposure alone. Findings support the weathering hypothesis, suggesting cumulative negative emotions linked to discrimination relate to accelerated biological aging. Future research could leverage longitudinal approaches to identify vulnerable populations and inform interventions to reduce the biological embedding of discrimination. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Ageing is associated with reduced resilience to physiological stressors such as infection and surgery. This reduced resilience is believed to be underpinned by the hallmarks of ageing, the key biological mechanisms driving the aged phenotype. Geroprotectors are drugs that are proposed to slow down the ageing process and promote longevity and healthspan. Despite this, mechanistic studies in healthy older adults are lacking. This trial will test the hypothesis that geroprotectors targeted towards biological mechanisms associated with poor resilience can reverse these pathways within a three-week period. Three geroprotectors with a good safety profile in older adults and evidence of effect on the hallmarks of ageing will be administered to 60 (30 female; 30 male) adults 70 + . Participants will be randomised to one of three arms (Metformin MR 1500 mg, Fisetin 100 mg or Spermidine 15 mg). Participants will be extensively clinically characterised at baseline. Blood, abdominal adipose tissue and stool samples will be taken at baseline and following the three-week intervention. The primary research question will answer whether a three-week course of Metformin, Spermidine, or Fisetin reduce the number of senescent cells as measured by SA-β-GAL in adipose biopsies in healthy older volunteers. Additionally, there will be assessment of the effect of the geroprotectors on other hallmarks of ageing, including autophagy, immunosenescence, chronic inflammation, dysregulated mTOR signalling, epigenetic age, DNA damage, dysregulated metabolism, stem cell exhaustion and microbial composition. Ethical approval is in place (24/LO/0549). The main trial report and any sub-studies will be published in high impact peer-reviewed gerontology journals, presented at academic conferences and through a series of public engagement events. Participants enrolled in the study will be informed of the results by a written summary. REPROGRAM was registered with ISRCTN on 10/09/24. ISRCTN47919839. Available at https://www.isrctn.com/search?q=47919839.

Aging is associated with decline in spatial learning, cognitive flexibility, and working memory, yet the extent to which biological sex modulates changes in cognitive function remains unresolved. While sex differences are evident in pathological brain aging, sparse insights from healthy aging populations suggest that sex effects on cognition are modest and domain specific. To systematically test effects of biological sex across the lifespan on specific aspects of cognitive function, we examined age- and sex-related changes in spatial cognition in a large cohort of Fischer 344 rats (N = 373), including young (4-8 months), middle-aged (12-16 months), and older aged (22-26 months) males and females. Rats were assessed on spatial reference learning, reversal learning, and working memory versions of the Morris water maze, with performance quantified using proximity-based measures, providing sensitive, individualized indices of spatial learning. Across all tasks, age accounted for the largest proportion of variance, with older rats exhibiting impairments in spatial learning, flexibility, and working memory relative to young adults. In contrast, effects of sex or interactions with age were limited to certain aspects of performance and were substantially smaller relative to age and training effects. Specifically, a female-specific association between spatial reference memory and reversal learning was observed despite comparable overall performance. Performance on visible-platform control trials did not indicate gross sensorimotor impairments that would account for age-related spatial deficits. Together, findings demonstrate age is the primary determinant of spatial cognitive decline under normative conditions, while sex-related influences, if present, are subtle and task dependent. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

In many settings, postgraduate psychiatry training now emphasizes neuroscience, evidence-based treatment, diagnostic criteria, and structured psychological models. These advances have improved psychiatric care in important ways. They have strengthened diagnosis, expanded treatment options, and improved scientific understanding of mental illness. At the same time, this increasing focus on structure and measurable symptoms can unintentionally narrow clinicians' understanding of patients. Psychiatry deals with more than just the brain. It also deals with meaning, identity, relationships, suffering, and lived experience. Unlike many other medical specialties, psychiatry regularly requires clinicians to work with uncertainty, personal narratives, emotional complexity, and experiences that do not always fit neatly into diagnostic categories. In real clinical practice, patients rarely present as textbook cases. Clinicians must often decide whether a person's suffering reflects a meaningful human response to life circumstances, a psychiatric disorder requiring intervention, or sometimes both. In this editorial, I argue that postgraduate psychiatry training should integrate philosophy-informed and reflective approaches alongside scientific and evidence-based models. In this context, philosophy primarily encompasses phenomenology, ethics, philosophy of mind, reflective reasoning, and approaches that deepen clinicians' understanding of subjective experience. Earlier phenomenological perspectives emphasized the importance of understanding the patient's inner world. At the same time, more recent pluralistic and neuroscience-informed models support a broader understanding of psychiatric illness that integrates biological, psychological, and social dimensions. I also discuss how the rigid application of diagnostic frameworks can contribute to overmedicalization when clinicians fail to distinguish between distress and disorder carefully. Practical approaches such as reflective case discussions, formulation-focused supervision, phenomenological interviewing, ethics-based discussions, and narrative reflection can help integrate these perspectives into postgraduate training without requiring major curricular restructuring. This approach does not reject scientific psychiatry. Instead, it complements scientific practice by strengthening reflective thinking, patient-centered understanding, ethical reasoning, and tolerance of clinical complexity. Psychiatry needs both scientific rigor and humane understanding if it hopes to remain fully connected to patients' lived experiences.

The growing burden of aging-related disease and functional decline across Europe underscores the urgent need to optimize aging trajectories rather than simply extend lifespan. Achieving this goal requires identifying modifiable determinants that shape biological, psychological, and functional aging across the life course. Satisfaction with life (SWL) is emerging as one such integrative factor, linking adaptive capacity, resilience, and long-term healthspan outcomes. In this conceptual and translational paper, we integrate evidence from geroscience, psychology, and occupational health to position SWL as both a marker and a potentially modifiable determinant of healthspan. We review biological, psychological, and social mechanisms linking SWL to aging processes, including cardiovascular and inflammatory regulation, neural and affective processing, psychological resilience and reserve, and social integration and generativity. Collectively, these pathways suggest that SWL reflects the functional integrity of adaptive systems that shape vulnerability to age-related functional decline. We further argue that occupational settings represent a uniquely powerful and scalable context for targeting SWL, given their sustained influence on behavior, stress exposure, social roles, and meaning across adulthood. Building on this framework, we discuss the Semmelweis Study, a large prospective workplace-based cohort, together with the Semmelweis-EUniWell Workplace Health Promotion Program, as an integrated model for translating geroscience-informed insights into structured interventions. Such workplace health promotion programs can target core psychological capacities-including savoring, self-regulation, creative and executive efficiency, and resilience-that are closely linked to adaptive capacity and aging-related outcomes. Finally, we discuss implications for geroscience, public health, and policy, highlighting how embedding SWL as a strategic target within workplace systems may contribute to extending healthspan, strengthening workforce sustainability, and reducing the societal burden of population aging. Conceptualizing satisfaction with life not merely as a subjective outcome but as a dimension of biological aging and adaptive resilience opens new avenues for intervention at the interface of geroscience and real-world systems.

The ultimatum game (UG) is widely used to study mutually beneficial exchanges, fairness, and prosocial behavior across different societies. However, human behavior in UG experiments does not align with the game-theoretical prediction that proposers should offer the least positive amount and responders should accept such offers. Instead, proposers make generous offers that are greater than the minimum responders are willing to accept, resulting in generous offers with wide offer-acceptance gaps. Numerous evolutionary models of the UG have been created and studied to explain human behavior, particularly generous offers made in UG experiments. These models have recently faced criticism for lacking biological realism and not adequately explaining the data. Here, we present an agent-based model inspired by our hunter-gatherer ancestors and with a biologically more realistic selection process. We assume that (1) agents exist in group-structured and group-clustered populations, where reproduction (2) depends on resource accumulation, but (3) is limited by interbirth intervals. We ran simulations to assess whether this biologically more realistic model evolves patterns of behavior consistent with patterns in the data from meta-analyses of human behavior in the UG. For the proposed model, we show that generous offers robustly evolve, as well as the difficult-to-explain offer-acceptance gaps, only in group-structured populations with interbirth intervals. We demonstrate that these results are robust and may help explain variation in data across societies. We discuss how interbirth intervals interact with group structure to modulate offer and rejection costs, favoring the evolution of generous offers, offer-acceptance gaps, and other patterns in the data on human behavior in the UG. We also discuss why weak selection and/or high mutation rate models cannot explain all the patterns in UG experimental data. We discuss biological realism and conclude that group structure and interbirth intervals may be essential for explaining prosocial behavior across societies.

Bipolar disorder (BD) is associated with a substantial burden of somatic diseases, including cardiovascular, neurodegenerative, and inflammatory conditions. However, the biological continuity linking the core pathophysiology of BD to these somatic manifestations remains poorly understood. Oxidative stress is increasingly recognized as a shared biological process across many medical conditions that commonly co-occur with BD and has been extensively investigated using diverse biomarkers, consistently demonstrating redox imbalance across illness stages and mood states. This evidence supports oxidative stress as a core biological process contributing to multisystem vulnerability rather than merely a secondary consequence of affective episodes. This review employed a narrative synthesis approach. Somatic diseases most frequently observed in BD were identified through systematic reviews and meta-analyses, and oxidative stress-related biomarkers associated with BD were examined alongside their alterations in commonly comorbid somatic diseases. Evidence from epidemiological syntheses, biomarker studies, and mechanistic research was integrated to identify converging findings, inconsistencies, and key research gaps. Across systematic syntheses, thirteen major non-communicable somatic disease categories were consistently associated with BD, particularly cardiometabolic, cardiovascular, endocrine, inflammatory, and neurodegenerative conditions. In parallel, BD research demonstrates alterations across multiple oxidative stress domains, with the most consistent findings observed for lipid peroxidation markers (e.g., TBARS, MDA) and oxidative nucleic acid damage (e.g., 8-oxo-dG, 8-OHGuo), whereas evidence for protein oxidation and antioxidant enzyme activity is more heterogeneous and state dependent. Notably, no studies directly examine associations between oxidative stress markers and objectively measured somatic comorbidity or multimorbidity in BD, and current evidence therefore relies on indirect triangulation between robust redox alterations in BD and oxidative stress mechanisms established in general medical populations. Overall, oxidative stress appears to represent a systemic biological feature of BD that aligns mechanistically with the somatic diseases contributing to its mortality gap. However, biomarker heterogeneity, predominantly cross-sectional study designs, and the lack of integrated somatic phenotyping limit clinical interpretation. Longitudinal, state-sensitive studies linking redox dysregulation with somatic outcomes are needed to determine whether oxidative stress reflects cumulative systemic vulnerability rather than episodic illness activity.

In the 2026 landscape of global polycrisis, mass orphanhood in conflict zones has given rise to an underrecognized form of morbidity with profound societal implications. While medical literature has established parameters for prolonged grief disorder, current frameworks often fail to account for contexts in which the structural and relational conditions for mourning are entirely absent. Unlike prolonged grief, which focuses on temporal persistence; absent grief, which implies psychological denial; or disenfranchised grief, which stems from a lack of social validation, impossibilitated grief represents a structural category in which the biological and environmental scaffolds for any mourning process have been decimated. Among children exposed to armed conflict who have lost primary caregivers and lack surviving attachment figures, grief is not merely prolonged but structurally precluded. This phenomenon constitutes a silent morbidity driven by the large-scale interruption of mourning during critical neurodevelopmental periods. The physiological foundations of this crisis involve sustained neurohumoral stress dysregulation, characterized by persistent activation of the hypothalamic-pituitary-adrenal axis and catecholaminergic surges. In the absence of primary caregivers - who function as external regulators of a child's stress-response systems - this chronic hypervigilance may erode the biological substrates underlying emotional integration. Furthermore, the destruction of the domestic "holding environment" prevents the development of essential emotion regulation capacities, such as cognitive reappraisal, favoring instead chronic expressive suppression or dissociation. When experienced at scale, impossibilitated grief contributes to a progressive erosion of social health by undermining the developmental substrates of empathy, trust, and long-term social cooperation. This erosion represents a structural consequence of contemporary conflict, with implications for post-conflict recovery and global stability. Protecting the conditions for mourning must be recognized not only as a humanitarian necessity but also as a critical matter of public health and collective security. The medical community has a responsibility to address the neurobiological futures of children growing up amidst unresolved loss to ensure the long-term stability of future generations.

Early life adversity (ELA) is a heterogeneous construct that can include the consequences of poverty, maltreatment, or serious accidents. This study characterized associations between subtypes of ELA and the physiological responses of multiple systems to acute psychosocial stress. Studies to date have focused on HPA axis reactivity, often neglecting the stress-reactive SNS, HPG axis, metabolic, and innate immune systems. We hypothesized that emotional, physical, and non-intentional ELA would differentially affect stress reactivity in each of these systems. Nine salivary samples, collected serially across the administration of a Trier Social Stress Test for Children (TSST-C), were collected from 92 adolescents [mean age 13.9 (SD = 1.57)] and assayed for cortisol, testosterone, DHEA, uric acid, salivary ɑ-amylase, and interleukin-6 (IL-6). Emotional ELA was associated with a steeper cortisol response to the stressor [b(SE) = 0.007 (0.003), p = .013]. Physical ELA was associated with IL-6 having steeper activation [b(SE) = 0.002 (0.001), p = .047] and recovery slopes [b(SE) = 0.00002 (0.00001), p = .03]. After accounting for age, sex, and body mass index, associations between physical ELA and IL-6 were attenuated. Findings are aligned with the theory of biological salience, which states physiological systems are differentially sensitive to experiences of adversity throughout childhood. Indeed, that different types of ELA are differentially associated with stress reactivity suggests a need for specificity and nuance in studies exploring associations between childhood environment and later biological functioning. Different forms of ELA are likely differentially salient to physiological systems that have distinct and evolutionarily conserved functions which may shape how the individual responds to psychosocial stress later in life. If confirmed with further evidence, biological salience may help to explain previously equivocal associations between ELA and adverse lifespan health outcomes.

To identify multidimensional risk factors associated with poor sleep quality and to develop and temporally validate a machine learning-based model for predicting the 2-year risk of poor sleep quality among community-dwelling older adults in China. Data were drawn from the China Health and Retirement Longitudinal Study (2011-2018). Participants aged ≥ 60 years with good baseline sleep were included. Missing data were imputed using a random forest-based iterative method, and key predictors were selected using LASSO regression. Multiple machine learning algorithms were trained with cross-validation and evaluated using discrimination, calibration, and clinical utility metrics, with SHAP used for model interpretation. Among 3,471 participants, 23.2% developed poor sleep quality. Fifteen predictors across demographic, biological, psychological, and social-behavioral domains were identified. LightGBM performed slightly better overall (AUC = 0.641). The model demonstrated acceptable predictive performance and potential utility for early identification and targeted intervention. Poor sleep quality in older adults reflects the combined contributions of demographic, biological, psychological, and social factors, underscoring the need for multidimensional assessment framework in clinical and community settings. Identifying cumulative risk across emotional, physical, and social domains may facilitate earlier detection of high-risk individuals and more targeted prevention and intervention strategies.

Research into the functioning of the human brain is essential both for the biological assessment of the species and for our self-comprehension. However, following the "neuroscientific turn" in several areas of research, such as psychology, philosophy, and AI, interdisciplinary collaboration in this area gave birth to an important phenomenon that is still active today: "neuro-hype" or "brain-hype." In this paper, we will inquire about one particular aspect of this widespread phenomenon: for-profit neuro-related products. Due to the lack of a vast and robust literature on the topic, the first aspect of our inquiry will concern products that have two major similarities with our focus topic: they are direct-to-consumer (DTC) health-related products, and they have a certain effect on consumer health. The second aspect of our inquiry will delve deeper into DTC neurotechnology by investigating how such products are advertised on major online platforms. In our analysis, we will consider both supplements and biomedical devices, taking into account their ratings, their cost, how they are made, their patent (if present), and will compare this information with the available research data on such objects or similar ones. Finally, this paper argues that while DTC neurotechnologies democratize access to brain health tools, they frequently fail to align with core bioethical principles-autonomy, beneficence, non-maleficence, and justice. These shortcomings highlight an urgent need for robust regulatory frameworks and ethical guidelines to ensure responsible development, equitable access, and transparent commercialization.

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition frequently accompanied by cognitive difficulties. Although previous genetic studies have demonstrated substantial overlap between ADHD and intelligence, most have treated ADHD as a single phenotype. However, whether this shared genetic architecture differs across ADHD subtypes remains unclear. We conducted a genome-wide cross-trait analysis integrating large-scale genome-wide association study (GWAS) datasets of overall ADHD, its subtypes-childhood ADHD, persistent ADHD, and late-diagnosed ADHD-and intelligence (total N > 300,000). Genome-wide genetic correlations, polygenic overlap, local genetic correlations, and variant-level associations between ADHD phenotypes and intelligence were evaluated to characterize their shared genetic architecture. Shared variants were identified through cross-trait enrichment analyses and subsequently mapped to genes for functional annotation and gene-set enrichment. Bidirectional associations were evaluated using two-sample Mendelian randomization with sensitivity analyses. Additional GWAS datasets were used to validate the robustness of shared loci by assessing the consistency of effect directions. All ADHD phenotypes showed significant negative genetic correlations with intelligence (rg ranging from -0.3442 to -0.4205). Despite these modest genome-wide correlations, cross-trait analyses revealed substantial genetic overlap, including polygenic overlap, local genetic correlations, and variant-level associations. We identified 184 loci jointly associated with ADHD traits and intelligence, including 64 novel loci, whereas no shared loci were detected for persistent ADHD under the current analysis. Functional annotation revealed biologically distinct enrichment patterns across subtypes: childhood ADHD loci were linked to early neurodevelopmental processes, while late-diagnosed ADHD loci were enriched in synapse-related and neuronal signaling pathways. Mendelian randomization analyses suggested bidirectional associations, with stronger evidence supporting a directional association from intelligence to ADHD risk. Furthermore, these shared loci showed largely consistent effect directions across additional GWAS datasets, providing support for the robustness of the findings. The shared genetic architecture between ADHD and intelligence varies across ADHD subtypes, highlighting distinct biological pathways underlying cognitive heterogeneity in ADHD. These findings suggest that the relationship between ADHD liability and general cognitive ability is not uniform across ADHD subtypes and may inform future research on risk stratification and early identification in child and adolescent psychiatry.

Traumatic brain injury (TBI) is a leading cause of persistent cognitive, motor, and neuropsychiatric impairment, arising from both the initial mechanical insult and a prolonged cascade of secondary injury processes. While primary injury reflects structural damage, secondary mechanisms, including neuroinflammation, oxidative stress, apoptosis, and blood-brain barrier disruption, evolve over time and critically influence long-term outcomes. Despite extensive investigation, therapies targeting isolated components of secondary injury have demonstrated limited clinical success, highlighting the need for approaches that support coordinated neural repair. Stem cell-based therapies have emerged as a promising neurorestorative strategy. Rather than replacing lost neurons directly, transplanted cells primarily act through paracrine signaling, immunomodulation, neurotrophic support, and preservation of vulnerable neural networks. However, clinical translation has been constrained by heterogeneity in cell sources, delivery routes, treatment timing, and outcome measures, limiting mechanistic interpretability across trials. This review presents a mechanism-aligned translational framework linking injury stage, biological targets, route of administration, and clinically meaningful outcomes across stages of TBI. We integrate current knowledge of post-injury repair mechanisms with evidence from recent human clinical trials of stem cell therapies. Particular emphasis is placed on safety, feasibility, and emerging signals across structural and functional endpoints, as well as how injury stage, biological targets, delivery strategies, and meaningful endpoints interact to shape treatment responsiveness and inform biomarker-guided clinical trial design.

Normative modeling has become a cornerstone of computational neuroscience, offering a powerful framework for detecting individual deviations from typical brain function. This review traces its trajectory in electrophysiology of the brain, from early studies in the 1970s, through a period of relative neglect, to its recent revival driven by machine learning advances and the availability of large-scale datasets. We provide a structured overview of this evolution, showing the shift from small, site-specific age-based models to increasingly harmonized approaches that integrate diverse biological and methodological innovations. Key studies are compared with respect to cohort composition, modeling strategies, and validation procedures, situating each within the broader arc of methodological progress. Despite this momentum, significant challenges remain, such as a lack of standardized practices, limited comparability across studies, and the need for richer integration of complex neurophysiological signals. Looking ahead, we argue that the future of electrophysiological normative modeling lies in scaling and unifying efforts, through international collaborations, standardized pipelines, and the incorporation of novel features. By coupling machine learning with both cross-sectional and longitudinal designs, the field can progress from proof-of-concept demonstrations to precise, individualized brain mapping. Ultimately, such advances will provide the foundation for clinical applications, enabling cost-effective personalized treatment monitoring and a more refined understanding of individual differences in complex brain disorders.

Major depressive disorder (MDD) has been closely associated with gut microbiota dysbiosis; however, the role of the gut microbiota in the progression from depression to suicidal ideation (SI) remains unclear. We enrolled a well-characterized clinical cohort of first-episode, drug-naïve MDD patients, explicitly classified into those without SI (MDDNSI) and those with SI (MDDSI), and matched with healthy controls (HC) on demographic variables. A severity-ordered HC-MDDNSI-MDDSI framework was established to capture progressive microbial and functional shifts, and correlation analyses were used to evaluate their relationships with clinical symptoms and cognitive function. We identified a group of taxa showing clear severity-related trends, with the potential pathogenic species Bacteroides stercoris and Bacteroides eggerthii increasing across the clinical spectrum, while seven species, including Faecalibacillus intestinalis and Dialister massiliensis, showed a steady decrease. Functional annotation indicated that several major metabolic pathways, such as the bacterial secretion system, weakened progressively with disease severity and formed stable microbe-pathway modules together with pathways involved in energy metabolism and signal transduction. These differential taxa and pathways showed strong associations with clinical features, with Bacteroides stercoris positively correlated with SI, whereas Bifidobacterium pseudocatenulatum displayed a negative association. In addition, mediation analysis further showed that Bacteroides stercoris indirectly influenced SI through the bacterial secretion system pathway, suggesting a meaningful mediating role in SI. These results revealed progressive alterations in gut microbial composition and metabolic function associated with SI, indicating that gut dysbiosis serves as a potential biological marker for suicide risk in MDD.

Adolescent bipolar disorder is a severe psychiatric condition frequently complicated by school refusal behavior, a debilitating functional impairment that often persists even after the pharmacological stabilization of mood symptoms. While medication effectively targets biological dysregulation, it frequently fails to resolve the deep-seated separation-individuation conflicts and pathological family dynamics, such as triangulation, that actively maintain social withdrawal. Given the scarcity of manualized psychotherapeutic protocols for this specific clinical challenge, this article demonstrates a structured, stage-phased psychodynamic psychotherapy protocol for the treatment of adolescent bipolar disorder comorbid with severe school refusal behavior. We present a comprehensive 60-session intervention applied to a 17-year-old female patient. The protocol integrates standard pharmacotherapy with a three-phase psychodynamic model: (1) Alliance and stabilization; (2) Working through, utilizing dream analysis and transference interpretation; and (3) Termination and separation. Progress was monitored via serial electroencephalogram (EEG) topography and standardized psychological scales. Application of this protocol was associated with the resolution of school refusal and successful university entry in this patient. Longitudinal assessment demonstrated a significant reduction in depression scores to within normal ranges, although anxiety scores remained above the clinical threshold at follow-up. Furthermore, while EEG topography demonstrated overall stability, mild -band dysregulation persisted. This protocol provides a step-by-step roadmap for clinicians, highlighting that resolving underlying family triangulation may be a valuable component in supporting successful school reintegration in pediatric bipolar disorder.

Maladaptive affective responses to daily stress in adolescence are a robust risk factor for the development of psychopathology. Importantly, however, adolescents vary widely in the magnitude of their affective reactivity to stress. Although peripheral inflammation and fronto-amygdala circuitry during emotion regulation are both plausible biological contributors to this variability, no study has yet integrated inflammatory markers, neural metrics of emotion regulation, and real-world assessments of stress and affect to examine how these systems interact to shape affective reactivity to stress in adolescents' daily life. Adolescents (N = 124; 60% female) aged 13.07-20.10 years (M = 16.20) completed a 14-day ecological momentary assessment (EMA) protocol assessing stressor occurrence, stress severity, and momentary affect. A subset of participants provided peripheral blood samples assayed for C-reactive protein (CRP) to index systemic inflammation (N = 85), and a further subset completed an fMRI affect-labeling task to quantify task-related functional connectivity between the amygdala and lateral prefrontal cortex (LPFC; N = 68). Multilevel models tested whether higher CRP predicted stronger within-person coupling of stress and negative affect (NA), and whether LPFC-amygdala connectivity moderated this association. Higher stress severity predicted higher NA, and greater inflammation potentiated these stress-related increases in NA. A three-way interaction with DLPFC-amygdala connectivity may further moderate this association, but the effect did not survive correction for multiple comparisons, and the sample was underpowered to test it reliably. Inflammation was linked to stronger coupling of daily stress and negative affect in adolescents. Whether fronto-amygdala connectivity adds to this remains untested at adequate power.

Hemispheric specialization is a fundamental feature of human brain organization, with most individuals showing left hemisphere dominance for language and right hemisphere dominance for visuospatial attention. Although lateralized functions exist in other species, humans exhibit a pronounced, species-wide bias. Despite its evolutionary and functional significance, the molecular and cellular basis of this asymmetry remains unclear. Here, we identify neurochemical and cellular features associated with cortical lateralization. We show lateralized gradients in neurotransmitter receptor densities along the multimodal monoaminergic-cholinergic axis, alongside asymmetries in mitochondrial distribution and the prevalence of microglia and glutamatergic excitatory neurons. Integrating in vivo PET with post-mortem transcriptomic and cellular data, we delineate two cortical clusters: a left-lateralized language-related network and a right-lateralized visuospatial-related network. These findings reveal a biological substrate for lateralized cognition, with implications for evolution and neuropsychiatric disorders involving disrupted lateralization.

Family caregiving for individuals in a permanent vegetative state (PVS) represents an extreme form of ambiguous loss characterized by prolonged emotional strain, suspended grief, and profound identity disruption. Despite its complexity, few qualitative studies have examined how families navigate this uniquely challenging condition and construct meaning around it. Adopting a phenomenologically informed, interpretative approach, we conducted semistructured interviews with 13 family caregivers (in northeastern Italy). Data were analyzed via reflexive thematic analysis, following Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. Four interconnected themes emerged: (1) "the paradoxical coexistence of presence and absence"; (2) "identity disruption and emergent growth"; (3) "bodily relational practices that sustain emotional bonds and resist biomedical finality"; and (4) "the 'double face' of waiting and farewell, spanning ontological and biological loss." Caregivers described symbolic acts that maintain relational continuity and challenge dominant medical framings of the patient's body. Ambiguous loss in PVS should be understood as a dynamic relational and symbolic process rather than a static burden. Effective support must honor families as active meaning-makers. Clinical practice and policy should integrate narrative and relational ethics to mitigate prolonged grief and enhance caregiver resilience.