Krzysztof Chmielowiec

Ageing is associated with increasing metabolic heterogeneity driven by interactions between adipose tissue dysfunction and altered glucose-lipid metabolism. The vitamin D receptor (VDR) rs7975232 polymorphism has been investigated in relation to metabolic traits; however, its relationship with glucose–lipid metabolic characteristics remains unclear. This study aimed to investigate the association of the VDR rs7975232 polymorphism with metabolic markers and whether their relationships with the TyG index differ according to genotype in older adults. The study included 95 older adults living in a long-term care facility (mean age 62.71 ± 14.13 years). Anthropometric and fasting biochemical parameters were assessed, and the triglyceride–glucose (TyG) index, homeostatic model assessment of insulin resistance (HOMA-IR), and atherogenic index of plasma (AIP) were calculated. VDR rs7975232 genotyping was performed using real-time PCR. Multivariable linear regression models assessed genotype × TyG interactions after adjustment for age, sex, and waist-to-hip ratio. The rs7975232 genotype was not independently associated with TyG, NEFA, AIP, or other metabolic characteristics. In multivariable models using continuous TyG, genotype × TyG interactions were not statistically significant for NEFA or AIP. A nominal interaction was observed for fasting glucose, whereas no significant interactions were observed for log-transformed fasting insulin or log-transformed HOMA-IR. None of the genotype × TyG interactions remained statistically significant after Benjamini–Hochberg false-discovery-rate correction. In the exploratory categorical sensitivity analysis, AA genotype × higher TyG category interactions had nominal p-values < 0.05 for NEFA and AIP. In this exploratory cross-sectional cohort, VDR rs7975232 was not independently associated with the assessed metabolic traits. The primary analyses did not provide robust evidence of genotype-dependent differences in TyG–metabolic associations. Nevertheless, exploratory analysis using categorized TyG suggested potential genotype-dependent differences in associations with NEFA and AIP. These findings are hypothesis-generating and require confirmation in larger independent cohorts.

Cel pracy: W prezentowanym badaniu przeanalizowano polimorfizm genu receptora dopaminy DRD2, który jest szeroko opisywany w literaturze jako związany z poszukiwaniem doznań. Zaburzenia hazardowe (GD) mają podobne mechanizmy biologiczne i objawy do zaburzeń związanych z używaniem substancji (SUD). Metoda: Grupa badana składała się z 307 uczestników. W grupie przebadano 107 mężczyzn z rozpoznaniem uzależnienia od hazardu i od amfetaminy oraz 200 mężczyzn nieuzależnionych, bez zaburzeń psychicznych - stanowiło grupę kontrolną (obie grupy poddano ocenie psychometrycznej przy użyciu kwestionariusza State-Trait Anxiety Inventory oraz NEO Five-Factor Personality Inventory oraz przebadani przez specjalistę psychiatrę). Genomowe DNA wyekstrahowano z krwi żylnej zgodnie ze standardowymi protokołami. Oznaczenie genu polimorfizmu DRD4 Ex3 przeprowadzono przy użyciu techniki PCR. Wyniki: U osób uzależnionych od hazardu i amfetaminy z wyższym poziomem skali cechy STAI i wyższym poziomem skali Neurotyczności, polimorfizm genu DRD4 Ex3 s/s występował istotnie częściej w porównaniu z grupą kontrolną z polimorfizmem s/s oraz polimorfizmem l/l i s/l. Podobnie u osób uzależnionych od hazardu i amfetaminy z wyższym poziomem skali cechy STAI i wyższym poziomem Neurotyczności, polimorfizm genu DRD4 Ex3 s/l występował istotnie częściej w porównaniu do grupy kontrolnej z polimorfizmem s/s. Wyniki wykazały, że genotypy s/s oraz s/l występowały istotnie częściej u mężczyzn uzależnionych od hazardu i amfetaminy niż w grupie kontrolnej, co może sugerować związek tych wariantów DRD4 Ex3 z podatnością na uzależnienie. Wnioski: W przedstawionym badaniu widzimy, że uzależnienia należy analizować wieloczynnikowo. Zaobserwowano korelację między polimorfizmem DRD4 a cechami osobowości związanymi z uzależnieniem.

Addiction neuroscience has advanced the identification of vulnerability and mechanisms involving reward learning, salience, cognitive control, interoception, cue reactivity, and stress regulation. Yet a key translational question remains unresolved: when does an evolving post-perturbation brain–behavior trajectory become relevant to treatment benefit? Prediction models can estimate future craving, lapse, or deterioration, and adaptive-intervention systems can deliver support using prespecified tailoring variables, but neither dynamic treatment regimes, just-in-time adaptive interventions, nor causal machine learning specifies what evidence a temporal quantity must satisfy before it may serve as the tailoring variable itself. This Perspective asks whether prospective recovery position modifies the benefit of the same intervention, and introduces BRAIN-TIME as a falsifiable episode-level architecture for answering that question. It begins with a defined cue, stress, affective, or sleep-related perturbation, follows one prespecified recovery domain relative to an individualized reference, and separates retrospectively adjudicated sustained re-entry from a prospective estimate of incomplete recovery computed only from information available at the decision point, with no use of later observations. Its decisive Stage 1 test is treatment-effect moderation: at a common locked landmark, the benefit of the same intervention and dose must vary across prospectively estimated recovery positions by a prespecified, practically meaningful amount. A minimal proof of concept combines a standardized low-intensity challenge, repeated craving or autonomic sampling, an independent outward-function criterion, negative controls, and randomized fixed-content intervention. No original data are reported, and every quantity specified here is a proposed construct, estimand, or falsification criterion rather than an observed result. BRAIN-TIME is therefore neither a relapse classifier nor an autonomous treatment rule. Its central claim is deliberately narrow: temporal recovery information becomes relevant to treatment timing only when prospective episode position is shown to modify the benefit of the same intervention.

Background: Ageing is associated with increasing metabolic heterogeneity driven by interactions between adipose tissue dysfunction and altered glucose–lipid metabolism. The vitamin D receptor (VDR) may contribute to individual differences in metabolic regula-tion; however, its role in modifying metabolic responses remains unclear. This study aimed to investigate the association of the VDR rs7975232 polymorphism with metabolic markers and whether genotype modifies the relationship between glucose–lipid disturbances and metabolic phenotype in older adults. Methods: The study included 95 older adults living in a long-term care facility (mean age 62.5 ± 14.1 years). Anthropometric and fasting biochemical parameters were assessed, and the triglyceride-glucose (TyG) index, homeostatic model assessment of insulin resistance (HOMA-IR), and atherogenic index of plasma (AIP) were calculated. VDR rs7975232 genotyping was performed using real-time PCR. Multivariable linear regression models assessed genotype × TyG interactions after adjustment for age, sex, and waist-to-hip ratio. Results: The rs7975232 genotype was not independently associated with TyG, NEFA, AIP, or other metabolic characteristics. However, significant genotype × TyG interactions were observed for NEFA and AIP in AA genotype carriers compared with the AC reference genotype. A similar interaction was observed for fasting insulin, whereas no significant interactions were found for glucose and only a borderline interaction was observed for log-transformed HOMA-IR. Conclusions: The VDR rs7975232 polymorphism may modify metabolic responses rather than independently determine metabolic phenotype, potentially influencing susceptibility to adverse metabolic alterations in older adults with greater glucose–lipid disturbances.

The ANKK1 TaqIA polymorphism (rs1800497) has been linked to substance dependence, possibly through reduced striatal D2 receptor density and altered dopamine signaling. Beyond addiction, dopaminergic pathways are also implicated in motivation, reward, and athletic behavior. Personality further contributes to performance, as traits influence athletes’ engagement and preparation. The aim of this study was to examine: (1) the association between ANKK1 TaqIA rs1800497 and elite athletic status; (2) differences in personality traits measured by the NEO Five-Factor Inventory (NEO-FFI) between athletes and controls; and (3) interactions between the genotype, athletic status, and personality. The study included 141 competitive athletes competing nationally or internationally and 182 controls (total N = 323). Genotype analysis revealed significant differences between groups (p = 0.0439), with the C allele more frequent in athletes and the T allele in controls (p = 0.0158). Athletes scored higher on conscientiousness (p = 0.0001). Interaction analyses showed significant effects of genotype × athletic status for neuroticism (p = 0.0065), extraversion (p = 0.0403), and agreeableness (p = 0.0191). These findings not only provide a compelling rationale for further investigation into the role of ANKK1 in modulating personality traits relevant to athletic performance, but also suggest potential practical applications in the field of sports science—for example, in talent identification, a personalized training program design, and psychological support strategies aimed at optimizing athletes’ performance and well-being.

The rs1544410 (BsmI) polymorphism of the vitamin D receptor (VDR) gene has been implicated in metabolic regulation, although its role in metabolic syndrome (MetS) and related phenotypes remains unclear. This study aimed to evaluate associations between rs1544410, MetS status, and anthropometric and biochemical parameters in institutionalized older adults. A total of 95 participants were included, of whom 40% met the criteria for MetS. Anthropometric and biochemical profiles were assessed, and rs1544410 genotyping was performed. Differences between MetS and non-MetS groups were analyzed, and two-way ANOVA was used to evaluate genotype, MetS status, and their interaction effects. Participants with MetS showed an adverse cardiometabolic profile, characterized by higher triglycerides (TGs), waist-to-hip ratio (WHR), and atherogenic index of plasma (AIP), as well as lower HDL-C levels compared with non-MetS individuals. No differences were observed for total cholesterol (TC), LDL-C, or non-esterified fatty acids (NEFAs) between groups. Genotype distributions did not differ between MetS and non-MetS participants. However, significant genotype × MetS interactions were observed for TG and NEFA, with a borderline interaction for WHR that was not confirmed in post hoc analyses. Carriers of the rs1544410 AA genotype within the MetS group exhibited higher TG and NEFA levels compared with other genotypes, whereas no genotype-dependent differences were observed in the non-MetS group. Importantly, AIP was higher in participants with MetS, with the highest values observed in AA genotype carriers. In conclusion, the rs1544410 polymorphism was not associated with MetS status but was linked to MetS-related differences in TG, NEFA, and AIP, suggesting selective effects on lipid metabolism.

Behavioral addiction in digital environments is an increasingly relevant neurobehavioral phenomenon characterized by persistent engagement with high-frequency, algorithmically optimized reward stimuli. Although neural correlates of addictive behaviors have been widely studied, current models only partly explain how modern reinforcement environments reorganize behavior at the systems level. This review introduces Reward Instability Theory, a conceptual dynamical systems framework proposing that behavioral addiction may emerge as an attractor-like state within distorted reward landscapes shaped by high-density and high-variance reinforcement signals. The model shifts focus from static behavioral descriptions toward a systems account of motivation involving reinforcement learning, salience attribution, executive control, and environmental reward structure. We propose that digital environments may increase reinforcement density and reward variance, promoting dominant reward peaks and reducing behavioral diversity. To formalize these dynamics, we outline the Behavioral Reward Instability Index (BRII) as a heuristic systems construct integrating individual reward sensitivity, environmental reinforcement structure, and behavioral variability. The framework also situates established addiction models—including incentive sensitization, habit formation, and allostatic regulation—within a shared dynamical architecture. In addition, digital phenotyping is discussed as a potential empirical strategy for testing reward instability, while acknowledging limitations related to signal noise, ecological validity, bias, and privacy. This model is intended to explain problematic patterns characterized by reduced behavioral flexibility, persistence despite negative consequences, and functional impairment, rather than all forms of frequent digital use. Attractor-like terminology is used throughout as a conceptual heuristic to describe behavioral persistence and reduced flexibility, rather than as evidence of formally verified mathematical attractors.

The rs1544410 (BsmI) polymorphism of the vitamin D receptor (VDR) gene has been implicated in metabolic regulation, although its role in metabolic syndrome (MetS) and related phenotypes remains unclear. This study aimed to evaluate associations between rs1544410, MetS status, and anthropometric and biochemical parameters in institutionalized older adults. A total of 95 participants were included, of whom 40% met the criteria for MetS. Anthropometric and biochemical profiles were assessed, and rs1544410 genotyping was performed. Differences between MetS and non-MetS groups were analyzed, and two-way ANOVA was used to evaluate genotype, MetS status, and their interaction effects. Participants with MetS showed an adverse cardiometabolic profile, characterized by higher triglycerides (TG), waist-to-hip ratio (WHR), and atherogenic index of plasma (AIP), as well as lower HDL-C levels compared with non-MetS individuals. No differences were observed for total cholesterol (TC), LDL-C, or non-esterified fatty acids (NEFA) between groups. Genotype distributions did not differ between MetS and non-MetS participants. However, significant genotype × MetS interactions were observed for TG and NEFA, with a borderline interaction for WHR that was not confirmed in post hoc analyses. Carriers of the rs1544410 AA genotype within the MetS group exhibited higher TG and NEFA levels compared with other genotypes, whereas no genotype-dependent differences were observed in the non-MetS group. Importantly, AIP was higher in participants with MetS, with the highest values observed in AA genotype carriers. In conclusion, the rs1544410 polymorphism was not associated with MetS status but was linked to MetS-related differences in TG, NEFA, and AIP, suggesting selective effects on lipid metabolism.

Behavioral addiction in digital environments is an increasingly relevant neurobehavioral phenomenon characterized by persistent engagement with high-frequency, algorithmically optimized reward stimuli. Although neural correlates of addictive behaviors have been widely studied, current models only partly explain how modern reinforcement environments reorganize behavior at the systems level. This review introduces Reward Instability Theory, a conceptual dynamical systems framework proposing that behavioral addiction may emerge as an attractor-like state within distorted reward landscapes shaped by high-density and high-variance reinforcement signals. The model shifts focus from static behavioral descriptions toward a systems account of motivation involving reinforcement learning, salience attribution, executive control, and environmental reward structure. We propose that digital environments may increase reinforcement density and reward variance, promoting dominant reward peaks and reducing behavioral diversity. To formalize these dynamics, we outline the Behavioral Reward Instability Index (BRII) as a heuristic systems construct integrating individual reward sensitivity, environmental reinforcement structure, and behavioral variability. The framework also situates established addiction models—including incentive sensitization, habit formation, and allostatic regulation—within a shared dynamical architecture. In addition, digital phenotyping is discussed as a potential empirical strategy for testing reward instability, while acknowledging limitations related to signal noise, ecological validity, bias, and privacy.

Background: Vitamin D deficiency remains a widespread public health issue in Europe, despite the availability of sunlight, dietary sources, supplements, and food fortification. National fortification strategies differ substantially in their regulatory approaches, food vehicles, and fortification levels, influencing the population’s vitamin D intake and status. Objective: The primary objective of this study was to map vitamin D food fortification policies across European Union (EU) Member States, European Free Trade Association (EFTA) countries, and the United Kingdom (UK), focusing on regulatory frameworks, eligible food categories, and implementation models. Methods: A structured review of national legislation and official guidance on vitamin D food fortification was conducted between December 2025 and March 2026 across EU Member States (n = 27), EFTA countries (n = 4), and the UK. For EU Member States, the framework established by Regulation (EC) No 1925/2006 was examined alongside national implementation measures. For EFTA countries and the UK, corresponding national legislation and official regulatory guidance were reviewed. Data were extracted on fortification policy status, eligible food categories, legal basis, and fortification levels. Targeted searches of PubMed and Scopus were performed to identify modeling studies and policy analyses supporting the interpretation of the findings. Results: Fortification policies show marked heterogeneity. Mandatory fortification is limited to a few countries and specific foods: Finland (homogenized skim milk), Sweden (low-fat milk, fermented dairy, plant-based alternatives, and fat spreads), Belgium (margarine and selected fats), and Poland (margarine and fat spreads). In most other European countries, vitamin D fortification is voluntary under EU legislation or equivalent national legislation, depending on market uptake. Food vehicles vary regionally, with Northern Europe extending fortification beyond fats to include fluid milk and plant-based drinks, whereas other regions mainly fortify margarines, cereals, dairy products, and plant-based beverages. Fortification levels also differ, with some countries specifying maximal or exact levels, while others lack national standards. Data on fortified foods are limited in several Central and Southern European countries. Modeling indicates that multi-vehicle fortification is more effective than single-vehicle approaches, safely increasing population intakes while reducing deficiency prevalence. Conclusions: Vitamin D fortification policies across Europe are highly heterogeneous. Most countries rely on voluntary approaches, which provide limited coverage. Strengthening policy through mandatory and well-coordinated multi-vehicle strategies, informed by modeling and population-based studies, can improve vitamin D intake, reduce deficiency prevalence, and enhance health equity.