Search Results (68)

Background/Objectives: The variation in the treatment outcomes of extended-release naltrexone (XR-NTX) including the potential role of genetic factors are poorly understood. This study aimed to explore the potential association between the catechol-O-methyltransferase (COMT) rs4680 and mu-opioid receptor (OPRM₁) rs1799971 genotypes and XR-NTX treatment outcomes in patients with opioid use disorder (OUD) specifically focusing on treatment retention, relapse to opioids, number of days of opioid use, and opioid cravings. Methods: This was a 24-week, open-label clinical prospective, exploratory study involving patients with OUD who chose treatment with monthly injections of intramuscular XR-NTX. Men and women aged 18–65 years with OUD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included. The participants were interviewed using the European Addiction Severity Index. Survival analyses and linear mixed models were used to analyze the data. Results: Of the 162 participants included in this study, 138 (21% female) initiated treatment with XR-NTX, with 88 genotyped for COMT rs4680 and 86 for OPRM₁ rs1799971. Heterozygous Met/Val carriers of COMT rs4680 were less likely to relapse to opioids compared with those with the COMT rs4680 Met/Met genotype. No significant association was observed for the OPRM₁ polymorphism. Conclusions: Patients with the COMT rs4680 Met/Val genotype exhibit a reduced risk of relapse to opioids and may therefore derive greater benefit from XR-NTX treatment compared with those with the COMT rs4680 Met/Met genotype. Future studies should be conducted with a larger number of participants and possibly include other genetic variants and treatment outcomes. The trial is registered at ClinicalTrials.gov (#NCT03647774) and the EU Clinical Trial Register (#2017-004706-18). Full article

Objective: Genetic and environmental factors influence the expression of personality pathology and subsequent treatment efforts. This study associates genetics with a contemporary nosology of personality pathology represented in the Alternative Model for Personality Disorders (AMPD). We hypothesized traits from Criterion B of the AMPD would differ between genotypes of the catechol-O-methyltransferase (COMT) polymorphism (rs4680/Val158Met variation), given this genetic marker’s role in the metabolism of dopamine and norepinephrine, especially in the prefrontal cortex. Methods: The Personality Inventory for DSM-V (PID-5) was used to quantify personality traits, and the Genomind platform was used to identify the genotypes of the Val158Met COMT polymorphism in 84 psychiatric outpatients. Results: One of the five Criterion B personality domains and three of the twenty-five traits were significantly different among genotypes. Met/Met carriers had significantly higher pathological scores on the broad domain of negative affect and specific traits of perceptual dysregulation and separation insecurity, while the Val/Val carriers had significantly higher scores on the restricted affectivity trait. The COMT Val158Met polymorphism’s association with personality pathology was sexually dimorphic, with the two domains and nine traits significantly different across genotypes in males, but no differences were found in females. A substantial improvement in the regression of domains/traits score when gene–sex interactions were included further confirmed the dimorphism, e.g., the R-squared (adjusted) for the psychoticism improved from 0.03 (p = 0.15) to 0.19 (p < 0.001). Conclusions: Findings offer preliminary support for a link, potentially dimorphic across sexes, between the COMT Val158Met polymorphism and personality pathology as represented by the AMPD. Full article

Post-Traumatic Stress Disorder (PTSD) is consistently linked to multidimensional working memory (WM) impairments, encompassing deficits in sustained attention, verbal and visuospatial processing, and executive control, with inhibitory dysfunction emerging as a key feature. This scoping review synthesizes evidence from 39 studies examining neurobiological mechanisms, trauma-related factors, genetic and hormonal influences, gender differences, and task-specific variability. Findings indicated that PTSD is associated with altered activation and connectivity in the prefrontal cortex, hippocampus, and related neural networks, often resulting in compensatory but inefficient recruitment patterns. Emotional distraction and comorbidities such as depression, alcohol use, and traumatic brain injury can exacerbate cognitive deficits. Performance impairments are evident across both emotional and neutral WM tasks, with visuospatial and updating processes being particularly vulnerable. Risk factors include chronic trauma exposure, older age, APOE ε4 allele, and the BDNF Val66Met (rs6265) polymorphism, while modulators such as oxytocin, cortisol, and physical activity show potential cognitive benefits under specific conditions. Methodological heterogeneity and limited longitudinal data restrict generalizability. These findings underscore the importance of early screening, targeted cognitive interventions, and inclusion of underrepresented populations to refine prevention and treatment strategies for PTSD-related WM deficits. Full article

Background: Impulsivity is a multidimensional trait associated with the development and maintenance of behavioral and substance addictions. Genetic polymorphisms, particularly within the dopaminergic system, are thought to modulate individual differences in impulsivity. The COMT rs4680 (Val158Met) polymorphism influences enzymatic activity of catechol-O-methyltransferase and may alter dopaminergic tone in the prefrontal cortex. This study investigated whether COMT rs4680 genotype interacts with addiction status (behavioral and substance addictions) to influence trait impulsivity. Methods: The study included 309 Polish men: 128 with mixed behavioral and substance addictions and 181 healthy controls. All participants completed the Barratt Impulsiveness Scale (BIS-11) and were genotyped for COMT rs4680. A two-way ANOVA was used to assess main and interaction effects of genotype and group on total and subscale BIS-11 scores. Results: Individuals with mixed addictions scored significantly higher on all BIS-11 subscales (p < 0.01). A significant interaction effect was observed for the Non-Planning (F_2,303 = 4.40, p = 0.0131, η² = 0.028) and Total BIS-11 scale (F_2,303 = 5.77, p = 0.0035, η² = 0.037), with the A/A genotype associated with increased impulsivity, especially among the clinical group. Conclusions: These findings support a gene-by-environment interaction in impulsivity, where COMT rs4680 Met/Met homozygotes may be more susceptible to heightened impulsivity in addiction contexts. The results highlight the potential utility of COMT genotyping in personalizing therapeutic strategies for impulse-related disorders such as addictive disorders. This study extends evidence on dopaminergic modulation of impulsivity to behavioral and substance addictions. Full article

Cognitive aging trajectories differ widely across individuals, and genetic factors such as APOE and BDNF polymorphisms may contribute to this variability. While APOE ε4 has been widely studied, the influence of APOE ε2, particularly in interaction with sex, remains underexplored. This study aims to examine the longitudinal trajectory of APOE ε2 individuals on cognitive performance, and their interactions with sex, age, and BDNF Val66Met polymorphism, in a population-based cohort of older adults with vascular risk. We analyzed data from 386 participants (mean age: 71.8) from the Barcelona-AsIA Neuropsychology Study, followed over a 7-year period. Verbal memory, verbal fluency, and visuospatial domains were assessed. Linear regression models tested associations between cognitive change and genotypes, controlling for age, sex, education, depression, and vascular risk. Interaction terms and permutation testing were applied. Regression to the mean (RTM) effects were assessed. BDNF showed no significant associations with cognitive performance. RTM effects were evident across subgroups, particularly among ε2 carriers, suggesting this phenomenon partly explains the divergent results over time. APOE ε2 does not confer a consistent protective effect on cognition over time. Our results highlight that APOE ε2 may be detrimental to verbal memory in aging males. Full article

Background/Objectives: Cardiac surgery, particularly procedures performed with cardiopulmonary bypass (CPB), carries a high risk of neurological complications, including postoperative delirium (POD), which affects 16–73% of patients and increases the likelihood of long-term cognitive impairment. Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in neuronal function, synaptic plasticity, and inflammatory regulation processes, including its Val66Met polymorphism, has been implicated as a potential predictor of POD. This study aimed to evaluate the relationship between perioperative plasma BDNF levels, the BDNF Val66Met polymorphism, and the incidence of POD in patients undergoing elective cardiac surgery with CPB. Methods: This prospective observational single-center study enrolled 287 adults scheduled for elective isolated coronary artery bypass grafting (CABG) with CPB, of whom 107 met all inclusion criteria for final analysis. Exclusion criteria included urgent surgery and pre-existing cognitive or psychiatric disorders. Preoperative evaluation included cognitive testing (MoCA), laboratory and biochemical analysis, and genotyping for BDNF Val66Met. Postoperatively, patients were assessed for POD using the CAM-ICU scale for the first three consecutive days. Cognitive function (using MoCA) and other neurological complications were evaluated during hospitalization, at 30-day and 12-month follow-up. Associations between biomarkers, genetic factors, and clinical outcomes were analyzed. Results: POD occurred in 19.6% of patients who were older, had higher EuroSCORE II, greater coronary disease burden, more frequent prior stroke and chronic kidney disease, and lower neutrophil counts. POD was significantly associated with prolonged hospital stay, need for continuous renal replacement therapy, and reoperation. The BDNF Val66Met polymorphism was present in 31.8% of patients but was not associated with POD, although carriers exhibited higher plasma BDNF concentrations across all time points. Conclusions: Perioperative plasma BDNF concentrations and the BDNF Val66Met polymorphism were not independently associated with the occurrence of POD in elective CABG patients. However, POD was significantly linked to prolonged hospitalization and reoperations. Neurological complications remain an important challenge in cardiac surgery, emphasizing the need for further research and early identification strategies to improve postoperative outcomes. Full article

Brain-derived neurotrophic factor (BDNF) plays a crucial role in cognitive functions and dementia. In individuals with mild cognitive impairment (MCI) and dementia, we have investigated BDNF Val66Met genotype distribution, peripheral BDNF DNA methylation, mRNA and protein levels, and cognitive performance using the Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT). Lower BDNF_IV1 methylation had predictive value for dementia. Patients with mild-to-moderate dementia had lower levels of BDNF_IV2 methylation, whereas patients with severe dementia had higher levels than the MCI group, while BDNF_IV2 methylation positively correlated with CDT scores. An insignificant decline in BDNF mRNA levels in dementia patients positively correlated with significantly lower BDNF plasma levels, especially pronounced in severe dementia patients. BDNF mRNA and protein levels were positively correlated with CDT and MMSE scores, respectively. BDNF Val66Met polymorphism was associated with methylation of the BDNF_IX amplicon, but not with methylation in BDNF promoters I and IV, peripheral BDNF gene and protein expression, MMSE and CDT scores, or dementia. Methylation at the BDNF Val66Met site was positively correlated with overall BDNF_IX methylation and methylation at 5 BDNF_IX CpG loci but negatively correlated with methylation of BDNF_IV1, BDNF_IV3, and BDNF_I1 amplicons. Further studies should evaluate the translational potential of these peripheral BDNF-based biomarkers for dementia. Full article

Fatty acid binding proteins FABP3 and FABP4 act as intracellular lipid chaperones that influence fatty acid transport and metabolism in mammary tissue, and genetic variation in these genes may affect milk composition. We examined the associations between FABP3 and FABP4 polymorphisms and milk composition and fatty acid profiles in 200 lactating Native Southern Yellow (NSY) cows. DNA from each cow was PCR-amplified and Sanger-sequenced for FABP3 and FABP4; genotypes were tested for their association with milk fatty acid concentrations and standard composition traits using linear models adjusted for relevant covariates. We detected a missense variant in FABP3 (c.3656G > A; p.Val45Met) and an intronic SNP in FABP4 (g.3509T > C). The FABP3 p.Val45Met AA genotype was associated with higher concentrations of butyric, palmitic, oleic, and α-linolenic acids. Cows with the FABP4 TC genotype exhibited elevated levels of myristoleic, γ-linolenic, conjugated linoleic, and arachidic acids, along with increased fat-free dry matter, protein, and lactose. In silico analyses provided mixed evidence for the structural effects of p.Val45Met, molecular docking suggested altered ligand affinity for several fatty acids, and splice site prediction implicated g.3509T > C in possible transcript processing changes. These variants constitute candidate markers for milk fatty acid composition in NSY cattle; replication in independent cohorts and functional validation are recommended to confirm their utility for milk quality improvement. Full article

Dysregulated inflammatory processes contribute to depression, and gene–environment interactions may influence an individual’s risk and resilience. Reduced brain-derived neurotrophic factor (BDNF) expression increases susceptibility for developing depressive symptoms, and the Val66Met (rs6265) single-nucleotide polymorphism (SNP) on the BDNF gene is linked to mood disorders. However, whether Val66Met confers increased vulnerability to inflammation-induced depressive tendencies is unknown. Here, we tested the hypothesis that the Val66Met SNP increases vulnerability to inflammation-induced depressive symptoms in a mouse model of lipopolysaccharide (LPS)-induced depression-like behavior. Behavior and neuroinflammation, following a 24 h LPS challenge, were measured in mice expressing the human BDNF Val66Met gene variant or Val66Val littermates (control). The Val66Met genotype did not affect the peripheral inflammatory response, acute neuroinflammation, or the acute sickness behavior response. Val66Met mice exhibited anhedonia-like behavioral responses following LPS challenge, and we found increased mRNA expression of IL-1β and TNFα in the cerebrum compared to controls. The mRNA expression of IL-1β and TNFα in the hippocampus and the nucleus accumbens of Val66Met mice was increased following LPS, and a significant genotype × LPS interaction was detected for CD68 expression in the nucleus accumbens. In summary, these data suggest that immune activation in Val66Met mice increased susceptibility to anhedonic behavior and dysregulated negative regulation of inflammation. Full article

Background/Objectives: Genetic variants, such as the µ-opioid receptor 1 (OPRM1) rs1799971 and the catechol-O-methyltransferase (COMT) rs4680, have been considered among the potential causes in the development of some chronic pain conditions. In this regard, there are controversial results regarding their roles in fibromyalgia (FM). We aimed to investigate whether the OPRM1 rs1799971 and COMT rs4680 polymorphisms are associated with the development of or susceptibility to FM, as well as their potential association with syndrome characteristic variables, in a sample of the Spanish population with and without FM. Methods: The present study analysed COMT Val158Met and OPRM1 Asn40Asp genetic variants in 311 FM patients (301 women and 10 men) and 135 non-FM participants (120 women and 15 men). In addition to clinical variables, widespread pain index (WPI), symptom severity scale (SSS) (fatigue, rest quality, and cognitive symptoms), pain, stress episodes, and Borg scale were collected. Results: The main results indicate that women carrying the Val/Val genotype (i.e., high COMT activity) exhibited significantly lower levels of fatigue, cognitive impairment, and total SSS than heterozygote carriers. In addition, Met allele carriers (i.e., lower COMT activity) showed higher probabilities of suffering a stress episode and higher levels of exertion during daily activities. Conclusions: The present research suggests a link between dopaminergic dysfunction and exacerbated, frequently described symptoms in female FM patients. Although further research with wider genetic variants and recruited patients is needed, these results point out the necessity of considering gender as a separate category in chronic pain studies. Full article

Multiple sclerosis (MS) is a chronic, autoimmune pathology that affects the nervous system. It is characterized by inflammatory lesions that cause axonal damage with neurodegeneration. The signs and symptoms present in this pathology include among others, psychiatric disorders. In MS, depression is the most frequent psychiatric disorder, with prevalence levels of 40 to 60%; to date, the cause is unknown. The brain-derived neurotrophic factor (BDNF) is a neurotrophin related to neuroplasticity. The single-nucleotide polymorphism Val66Met, encoded by the BDNF gene, has been associated with various effects, including the presence of neuropsychiatric disorders. The purpose of our study was to evaluate the association between the BDNF Val66Met polymorphism and depression in MS patients. Methods: Study design, cases, and controls: Mexican mestizo MS patients. Cases: Patients diagnosed with depression. Controls: Patients without depression diagnosis. Measurements: For depression, the Beck Depression Inventory; for polymorphism, real-time PCR. Results: No statistically significant differences were found in sociodemographic and disease variables between the case and control groups. qPCR analysis showed that 68% of the participants were Val/Val wild-type homozygotes, 29% were Val/Met polymorphism heterozygotes, and 3% were Met/Met polymorphism homozygotes. The presence of the BDNF gene rs6265 polymorphism was associated with a 5.6-fold increase in the probability of depression in the cases compared to the controls. Conclusions: The BDNF Val66Met Polymorphism is associated with depression in Mexican mestizo patients diagnosed with MS. Full article

Obesity represents a complex interplay between genetics, nutrition, and lifestyle. This study aimed to elucidate the intricate relationship between genetic variants, energy intake, and bioactive compounds in influencing obesity risk, particularly in low energy intake, to reveal how dietary intake modulates molecular-level interactions. We analyzed 53,117 participants stratified by obesity status and energy intake levels. Genome-wide association studies explored the genetic variants associated with obesity risk in low-energy- and high-energy-intake subgroups. Advanced computational approaches, including molecular docking, k-means clustering, and uniform manifold approximation and projection (UMAP), were employed to analyze interactions between missense variants and natural compounds. Ten genetic variants were significantly associated with obesity, particularly in participants with low energy intake. The most prominent variants included brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265). Molecular docking identified 152 bioactive compounds with strong binding affinity to BDNF Val66Met, including 107 compounds binding to both wild and mutant types. Citrus fruits and green vegetables showed selective binding to the mutant type. Antioxidant nutrient intake (anthocyanins, isoflavonoids, vitamins C and E, selenium) was higher in lean versus obese individuals in the high-energy-intake group. Alcohol consumption and selenium intake modulated polygenic risk scores’ influence on obesity risk in high-energy-intake individuals. Notably, citrus fruit intake correlated with lower BMI across all BDNF rs6265 genotypes. In conclusion, energy intake-specific genetic associations with obesity and identifies potential bioactive compounds for targeted interventions. The findings suggest that antioxidant nutrient intake, particularly from citrus fruits, may help manage obesity risk, especially in individuals with specific genetic variants. Full article

This narrative review examines the relationship between dopamine-related genetic polymorphisms, personality traits, and athletic success. Advances in sports genetics have identified specific single nucleotide polymorphisms (SNPs) in dopamine-related genes linked to personality traits crucial for athletic performance, such as motivation, cognitive function, and emotional resilience. This review clarifies how genetic variations can influence athletic predisposition through dopaminergic pathways and environmental interactions. Key findings reveal associations between specific SNPs and enhanced performance in various sports. For example, polymorphisms such as COMT Val158Met rs4680 and BDNF Val66Met rs6265 are associated with traits that could benefit performance, such as increased focus, stress resilience and conscientiousness, especially in martial arts. DRD3 rs167771 is associated with higher agreeableness, benefiting teamwork in sports like football. This synthesis underscores the multidimensional role of genetics in shaping athletic ability and advocates for integrating genetic profiling into personalized training to optimize performance and well-being. However, research gaps remain, including the need for standardized training protocols and exploring gene–environment interactions in diverse populations. Future studies should focus on how genetic and epigenetic factors can inform tailored interventions to enhance both physical and psychological aspects of athletic performance. By bridging genetics, personality psychology, and exercise science, this review paves the way for innovative training and performance optimization strategies. Full article

Background: Research on the interaction between antipsychotic treatment and cognitive dysfunction in schizophrenia spectrum disorders (SSDs) is extensive, yet the role of genetic polymorphisms in catechol-O-methyltransferase (COMT) and neuregulin 1 (NRG1) remains underexplored. Methods: This study evaluates the impact of COMT (rs4680) and NRG1 (rs3924999 and rs35753505) polymorphisms on cognitive functions in SSD patients. A cross-sectional study was conducted with fifty-four patients, assessed using the Positive and Negative Syndrome Scale (PANSS) and the CNS Vital Signs battery. Results: Significant cognitive function differences were observed across SSD diagnostic categories (p < 0.001). The NRG1 rs35753505 TT genotype was significantly associated with better verbal memory performance compared to the CC genotype (p = 0.03), while no significant differences were observed for other genotypes. The NRG1 rs3924999 AA genotype showed superior reasoning performance compared to AG and GG genotypes (p = 0.01), with AG and GG associated with lower scores (p = 0.01 and p = 0.02, respectively). Additionally, the COMT Val158Met genotype significantly influenced processing speed, with patients at the first episode of psychosis showing higher scores than chronic patients (p = 0.01). Conclusions: These findings suggest that NRG1 and COMT polymorphisms may influence cognitive domains in schizophrenia spectrum disorders, potentially informing personalized treatment and cognitive rehabilitation strategies. Full article

Background/Objectives: Post-traumatic stress disorder (PTSD) is a complex condition influenced by both genetic and environmental factors. This longitudinal study aimed to explore the connection between two specific genetic polymorphisms, Val66Met and 5-HTTLPR, and the lifetime prevalence of PTSD in patients from primary care settings. We also examined the role of sociodemographic and psychosocial factors to provide a more comprehensive view of PTSD risk. Methods: We recruited a cohort of primary care patients and diagnosed PTSD using a standardized diagnostic interview. Genetic analyses focused on Val66Met and 5-HTTLPR polymorphisms. We applied logistic regression to assess the association between these genetic markers and PTSD, considering factors such as gender, family history of depression, and experiences of childhood maltreatment. Results: Our findings show that women, individuals with a family history of depression, and those exposed to childhood maltreatment have a higher risk of developing PTSD. While the Val66Met polymorphism was not significantly associated with PTSD, the 5-HTTLPR polymorphism showed a marginal relationship. No significant interaction was found between the two polymorphisms in relation to PTSD. Conclusions: This study underscores the multifactorial nature of PTSD, influenced by both genetic and environmental factors. The findings point to the importance of further research on genetic predispositions and highlight the value of early interventions for high-risk populations in primary care settings. Full article