catechol-O-methyltransferase Research Articles

Establishing a Collaborative Genomic Repository for Adult Burn Survivors: A Burn Model System Feasibility Study

In this study, we aimed to integrate a genetic repository with an existing longitudinal national burn database. We set out two primary objectives, namely (1) to develop standard operating procedures for genetic sample collection and storage, DNA isolation, and data integration into an existing multicenter database; and (2) to demonstrate the feasibility of correlating genetic variation to functional outcomes in a pilot study, using the catechol-O-methyltransferase (COMT) gene. Dubbed the worrier/warrior gene, COMT variants have been associated with varying phenotypes of post-traumatic stress, wellbeing, and resilience. Between August 2018 and July 2020, COMT variants were identified for 111 participants from three sites and correlated with their outcome data. We found no association between COMT variants and functional outcomes, likely due to the inadequate sample size. We also asked all potential participants why they consented to or refused genetic analysis. A thematic analysis of responses revealed altruism and personal interest/enthusiasm in the study as top reasons for consenting. Privacy concerns were the most common reason for refusal. In conclusion, we successfully developed standard operating procedures for genetic sample collection and storage, DNA isolation, and data integration into an existing database, and we demonstrated the feasibility of conducting a multicenter collaborative study using a centralized lab location.

Chemical profiling, in-silico investigation and in vivo toxicity assessment of lacatomtom (a psychoactive mixture) on selected indices in albino wistar rats

aims: To evaluate the safety and identify the psychoactive constituent of a new psychoactive cocktail that is abused among African youths. background: The use of lacatomtom (LTT), a psychoactive mixture of tomtom (TT) candies with lacasera (LC) beverage, has recently increased among young Nigerians and Africans. There isn't much scientific study on the constituent and effects of this psychoactive substance. objective: To chemically-profile the mixture using GCMS analysis, and evaluate the effect of the constituent of neural targets. To evaluate the toxicological effects in albino rats. To identify neur method: Herein, LTT was chemically-profiled using GCMS analysis, and the toxicological effects were examined in albino rats. In vivo experiment consists of five groups of six rats each (group 2 - LTT ad libitum; groups 1, 3, & 4 - TTT, TT, LC (1 mL) mg/mL kg/body weight once/day respectively, group 5 - distilled water ad libitum). Identified constituents were examined against human monoamine oxidase (hMOA) and human catechol O-methyltransferase (hCOMT) using in silico methods. result: Forty-seven chemical compounds were identified. Ad libitum intake of LTT elevated plasma alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatinine, total cholesterol, and LDL-cholesterol levels. The docked poses, binding scores, and interactions with amino acids informed the selection of (4-Methoxymethoxy-hex-5-ynylidene)-cyclohexane (MM) (-9.4 kcal/mol) and 3-(hydroxyphenylmethyl)-3,4-dimethyl-1-phenylpentan-2-one (HP) for hCOMT (-9.4 kcal/mol), while propionylcodeine (-10.1 kcal/mol) and HP (-8.9 kcal/mol) for hMOA. Top-docked compounds (TDC) demonstrated the potential to permeate the blood-brain barrier. TDC was predicted to be a positive substrate of the P-glycoprotein and presents inhibitory potential for cytochrome P450 descriptors. HP was mutagenic and could induce human hepatotoxicity and drug-induced liver injury, while propionylcodeine had human hepatotoxic prediction. conclusion: The present study, for the first time, confirmed the potential toxicity of lacatomtom to the liver, kidney, heart, and central nervous system supported by the identified top-docked compounds regarded as potential psychoactive constituents of hMOA and hCOMT. other: Nono

Cognitive Impairments Related to COMT and Neuregulin 1 Phenotypes as Transdiagnostic Markers in Schizophrenia Spectrum Patients.

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.

Pain Candidate Genes 5-HTTLPR and COMT Affect Anxiety and Mood in Japanese Ballet Dancers: A Cross-Sectional and Longitudinal Study

The balance of mental, physical, and technical aspects is essential in improving ballet performance. Ballet dancers’ emotional and behavioral characteristics vary, even under identical stress conditions. This study aimed to investigate the association between the pain candidate genes 5-HTTLPR and COMT and anxiety in Japanese ballet dancers. Participants were 18 youth elite ballet students with professional aspirations (Y-Elite) and 16 dancers in a professional ballet company (Pro). We administered psychological questionnaires, the State-Trait Anxiety Inventory (STAI) and Brunel Mood Scale (BRUMS), to participants under the following four different stress conditions: standard practice day, cast decision day, rehearsal day, and one week before competition day. In addition, the genotypes of 5-HTTLPR and COMT Val158Met were examined. The distribution of 5-HTTLPR was not different between Y-Elite and Pro dancers, although one of the COMT genotypes was different. Y-Elite dancers had higher trait anxiety scores than Pro dancers for these genotypes before competition (ps &lt; 0.03), although no significant association was observed between both genotypes and scores on the STAI across conditions. Their moods were significantly different through the four conditions (p &lt; 0.004). Pro dancers’ moods were also more stable than those of the Y-Elite dancers in the presence of pain. The results indicate that 5-HTTLPR and COMT play a crucial role in dancers’ anxiety and mood during pain (ps &lt; 0.05). Pro dancers are probably predicted by their lower neuroticism and mood scores and their better adaptation to stress than Y-Elite dancers. The 5-HTTLPR and COMT genes may be influencing the sensitivity to the environment. Youth elite ballet dancers need to understand the relationship between pain and physical activity from an early stage.

Insilico Identification of Association between Nicotine Dependence and Pathogenic Missense Mutations of Catechol-O-Methyltransferase Gene

Introduction: Oral cancers are known to be strongly associated with the usage of tobacco, which is majorly composed of nicotine. Genetic studies evidenced the nicotine addiction as hereditary. AIM: The aim of the present study is to analyse any genetically functional missense mutations in Catechol-O-methyl-transferase (COMT) gene and derive an association with nicotine dependence that might influence tobacco habit initiation, addiction, and cessation. Methodology: The study involved an insilico analysis about the association between COMT gene and nicotine dependence. This was done with the help of different databases available in website. Initially, database called Ensembl (https://asia.ensembl.org) was used to pool the genetic data on missense mutations of the human COMT gene. The collected data was then fed into computational tools such as SIFT, PolyPhen, PROVEAN, I-Mutant, MutPred to discover the pathogenic mutations if exists. Results: Among 78 missense mutations collected, 74 were identified as damaging variants in which 8 variants were found to cause increased protein stability and 66 were found to cause decreased protein stability. Among those 66 missense variants causing decreased protein stability, 25 variants were identified as highly pathogenic while 19 variants were identified as pathogenic. Conclusion: The in-silico analysis discovered the existence of highly pathogenic mutations in COMT gene which might have a strong association with nicotine dependence that can influence the tobacco habit initiation, addiction, and cessation.

Recent Progress in Synthetic and Natural Catechol-O-methyltransferase Inhibitors for Neurological Disorders.

Catechol-O-methyltransferase (COMT) inhibitors have played a crucial role in the development of potent and selective drugs for the treatment of Parkinson's disease, depression, and anxiety disorders. This review provides a comprehensive analysis of the structure-activity relationship (SAR) of COMT inhibitors, highlighting key structural features and pharmacophoric elements that govern their potency, selectivity, and pharmacokinetic properties. This review also discusses the application of SAR principles in the design and optimization of COMT inhibitors. Our analysis reveals the emergence of novel chemical scaffolds and the potential for COMT inhibitors to address unmet medical needs in neurology and psychiatry. This Perspective serves as a valuable resource for clinicians and researchers, providing insights into the rational design of COMT inhibitors and the development of next-generation therapeutics.

Investigation of the effect of catechol-o-methyltransferase gene rs4680 polymorphism on trigeminal neuralgia susceptibility

Research has been conducted to explore the genetic basis of trigeminal neuralgia, a persistent pain condition that impacts the trigeminal nerve. COMT is an enzyme responsible for inactivating substances and hormones containing catechol and catecholamines. Previous research has linked COMT gene polymorphism with various pain conditions, including migraine. Our research aimed to investigate the correlation between trigeminal neuralgia and the rs4680 polymorphism of the COMT gene. We conducted a research project which included 10 individuals diagnosed with trigeminal neuralgia and 30 healthy individuals as controls. Following collection of blood samples, we isolated DNA from the samples and then genotyping of COMT rs4680 polymorphism was performed with Real-Time PCR, using TaqMan SNP Genotyping Assay. Among the trigeminal neuralgia patients, 2 of them exhibited the AA genotype, 6 had the AG genotype, and 2 had the GG genotype for COMT rs4680. The AG genotype was notably prevalent. No statistically significant differences in the distributions of COMT genotypes and allele frequencies were found between the experimental (patients) and the control group. However, the AG genotype appeared to be more frequent in the patient group. Moving forward, we plan to expand our study by increasing the number of patients and control subjects. This will enable us to further elucidate the potential relationship between COMT gene polymorphism and trigeminal neuralgia.

Investigating the Association between Catechol-O-Methyltransferase Gene Activity and Pain Perception in South African Patients with Different Temporomandibular Disorders Diagnoses.

Background: Temporomandibular disorders (TMD) affect a significant portion of the population, with profound psychological, behavioral, and social repercussions. Recent investigations have explored the genetic basis underlying pain perception in individuals with TMD, aiming to elucidate the role of specific genetic factors in modulating the condition. Notably, genetic variations have been implicated in the pathogenesis of TMD, particularly genes involved in pain perception pathways. One of the primary candidates is the Catechol-O-Methyltransferase (COMT) gene, which plays a crucial role in the catecholaminergic system and has been associated with the regulation of nociceptive processes. This study seeks to investigate the correlation between COMT gene activity and pain perception among South African patients diagnosed with varying forms of TMD. Methodology: In this study, a total of 196 participants were enrolled, comprising 97 patients diagnosed with TMD and 99 control participants. The control group was meticulously matched with the TMD group for age, gender, and ethnicity. Data collection involved clinical and radiological investigations, and saliva sampling. The English version of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I was utilized to evaluate all TMD participants, focusing on standard diagnostic measures based on clinical signs and symptoms of TMD, which primarily describe common physical manifestations of the disorder. Genomic DNA was extracted from saliva samples, enabling the analysis of single-nucleotide polymorphisms (SNPs) in the COMT gene, specifically targeting polymorphisms rs165774, rs9332377, rs6269, rs4646310, rs165656, and rs4680. Results: The current study demonstrated a pronounced gender disparity, with 80.41% of the participants being female and 19.59% male, suggesting that women in South Africa either exhibit a higher susceptibility to TMD or are more likely to seek treatment for the condition compared to men. The highest prevalence of TMD was observed in the white population (58.76%). Additionally, over 65% of TMD patients were diagnosed with at least two Axis I diagnoses, a figure that increased to 89% for those diagnosed with three Axis I diagnoses. The findings further indicated significant associations between several single-nucleotide polymorphisms (SNPs) in the Catechol-O-Methyltransferase (COMT) gene-specifically rs165656, rs9332377, rs4646310, rs6269, and rs165774-and both TMD and TMD-related pain. Myofascial pain with referral and myalgia showed a strong association with the COMT SNPs rs9332377 and rs4646310. Furthermore, COMT SNP rs4646310 was also associated with disability related to TMD. Conclusions: This study substantiates the hypothesis that pain is prevalent in a considerable proportion of patients affected by TMD. Furthermore, the findings reveal a significant association between COMT gene activity and pain perception in South African patients diagnosed with TMD.

Association between the Val66Met (rs6265) polymorphism of the brain-derived neurotrophic factor (BDNF) gene, BDNF protein level in the blood and the risk of developing early‑onset Parkinson's disease.

Brain-derived neurotrophic factor (BDNF) is involved in the maintenance of dopamine level and the survival of dopaminergic neurons, which may affect the functionality of brain structures responsible for motor and cognitive function. The aim of the study was to assess the association of individual and combined single nucleotide polymorphism (SNP) in the rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) genes with early‑onset of Parkinson's disease (PD) patients. Moreover, we assessed the association between the BDNF Val66Met polymorphism and the level of BDNF protein in the serum of patients with PD and controls. The study involved 163 patients with idiopathic PD divided into early onset (<55 years) and late‑onset (>55 years) groups and 91 healthy age‑matched people (Control). The SNP were determined using the TaqMan Real‑Time PCR method. Serum BDNF levels were determined by ELISA assay. The risk of developing early PD in people with the BDNF genotype AG increases threefold in comparison with the carriers of the BDNF genotype GG. In PD patients and healthy people with the BDNF genotypes AG and AA, a lower serum BDNF level was found compared to those with the BDNF genotype GG in both groups. The results of our study indicate that the presence of the Val66Met BDNF gene polymorphism is associated with reduced blood BDNF levels and an elevated risk of developing early‑onset PD. This effect appears to be more pronounced in men.

Adaptive copy number variations of ancient prokaryotic genes in marine fish colonization

During extensive evolution, higher eukaryotes have acquired numerous prokaryotic genes, some of which have experienced adaptive copy number variations (CNVs) in response to changing environments. The specific contribution of ancient prokaryotic genes to the evolutionary dynamics of marine fish remains unclear. In this study, we investigated ancient prokaryotic genes in 33 freshwater and 14 non-freshwater fish species. Non-freshwater fish exhibited a higher proportion of these genes (25.84 %) compared to freshwater fish (17.66 %), though functional categories showed similarity, suggesting genetic conservation. Comprehensive CNV analysis identified 24 genes with significantly higher copy numbers in non-freshwater fish, enriched in glycerolipid metabolism, immune regulation, and catechol O-methyltransferase activity. Eight of these genes displayed increased copy numbers in marine populations compared to Asian freshwater populations. These findings indicate that CNVs in genes related to glycerolipid metabolism, immune regulation, and methyltransferase activity may play crucial roles in marine adaptation at global and regional evolutionary scales.

The relationship between COMT, proline, and negative symptoms in clinical high risk and recent psychosis onset

Individuals at clinical high-risk (CHR) of developing psychosis, as well as patients with recent psychosis onset (RO), experience significant negative symptoms that detrimentally impact daily-life functioning and are associated with poor outcomes, even in those who do not convert to psychosis. Targeting negative symptoms may thus hold promise for the treatment of CHR and RO patients. Building from previous findings we examined whether the catechol-O-methyltransferase (COMT) Val158Met functional polymorphism and fasting peripheral proline concentration predicts the severity of negative symptoms experienced by adolescents and young adults at CHR or those with RO. As hypothesized, the interaction between fasting plasma proline and COMT predicted negative symptoms, as measured via the Scale for the Assessment of Negative Symptoms (SANS) total (n = 50, β = 0.066, adjusted p = 0.007) and global severity scores (n = 50, coefficient = 0.026, adjusted p = 0.003): Higher proline was beneficial for Val/Val subjects, but detrimental to those with the Met allele. In a secondary analysis, the COMT x proline interaction also predicted symptoms measured via the Clinical Assessment Interview for Negative Symptoms (CAINS) total scores (n = 50, β-coefficient = 0.035, adjusted p = 0.044), although this result did not reach the Benjamini-Hochberg’s threshold for significance. Further, there was a trend towards significance for an association with social and interpersonal function (Global Functioning-Social, coefficient = −0.005, adjusted p = 0.055). Negative symptoms are intractable and largely unaddressed by current medications. This study further supports a relationship between peripheral proline and COMT influencing negative symptoms such as anhedonia, in young CHR individuals and those with RO. That higher proline has converse effects on symptoms by COMT may have implications for the development of therapeutics to intervene early and specifically target the interaction pathway.

Levodopa / opicapone as a complement to STN-DBS in clinical practice. A retrospective single-centre analysis.

ObjectiveDeep brain stimulation of the subthalamic nucleus (STN-DBS) is a well-established treatment option in Parkinson's disease with motor and non-motor fluctuations allowing for postoperative reduction of dopaminergic medication. However, evidence is scarce on optimal medication adjustments following STN-DBS implantation. Opicapone allows for long-lasting inhibition of the catechol-O-methyltransferase (COMT) thereby enabling more constant dopaminergic stimulation compared to levodopa alone. However, especially COMT inhibitors are regularly discontinued after STN-DBS surgery. In this single-centre retrospective analysis, we aimed to analyse the clinical phenotype of patients selected for opicapone treatment following STN-DBS implantation and to define clinical determinants of patients requiring more intense dopamine-stabilising strategies after STN-DBS implantation. MethodsA patient cohort treated with STN-DBS + levodopa + opicapone (n = 16) was compared to an age-matched control cohort without opicapone treatment at baseline before and ≥ 5 months post-surgery. As main outcomes we assessed the MDS-UPDRS III and IV scores and reduction of the cumulative dopaminergic medication quantified by the levodopa equivalent dosages (LED). ResultsWhilst the MDS-UPDRS III (median [min – max]) in patients with STN-DBS as well as anatomical electrode positions did not differ significantly between the opicapone 20 [4–40] and control cohort 14 [1–44], the patients selected for opicapone treatment showed a significantly higher degree of dyskinesias already preoperatively as reflected by a UPDRS-IV A subscore of 2 [0–4] compared to controls 0 [0–4]. Postoperatively, the opicapone cohort showed stronger motor fluctuations MDS-UPDRS IV 6 [0–14] compared to the controls 0 [0−10], albeit without statistical significance. Moreover, the opicapone cohort showed significantly less reduction of dopaminergic medication (−36.4 % vs. -46.2 % in the control cohort) following STN-DBS implantation independent from the intake of dopamine agonists. ConclusionThese results indicate a clinical phenotype characterised by more motor fluctuations requiring a more stable dopamine replacement therapy to address the patients' disease biology. In these cases, levodopa + COMT inhibition by opicapone represents a therapeutic approach but determination of the potential clinical benefit requires further prospective studies.

Personality and COMT gene: molecular-genetic and epigenetic associations with NEO-PI-R personality domains and facets in monozygotic twins.

This study investigates the relationship between MB-COMT DNA methylation (DNAm) and the personality traits outlined in the NEO-PI-R model through an epigenetic study of monozygotic twins. DNAm, a critical epigenetic mechanism, regulates gene expression and has been linked to various biological processes and disorders. By leveraging the genetic similarities of monozygotic twins, this research explores how epigenetic variations influenced by environmental factors correlate with personality differences. The study utilized the Five-Factor Model (FFM) to categorize personality traits into five domains: Neuroticism, Extraversion, Conscientiousness, Agreeableness, and Openness to Experience. Each domain comprises six facets, providing a granular view of personality. The research centered on the catechol-O-methyltransferase (COMT) gene, focusing on its role in dopamine metabolism, which is hypothesized to influence personality traits through the dopaminergic system. DNAm status in the MB-COMT promoter region was examined to determine its association with personality facets. Preliminary findings suggest a complex interaction between MB-COMT DNAm patterns and personality traits. Specific methylation patterns at different CpG sites were linked to varying expressions of traits such as impulsivity and aggression, highlighting the nuanced impact of epigenetics on personality. This study underscores the potential of integrating genetic, epigenetic, and environmental data to enhance our understanding of personality formation. The results contribute to a broader understanding of how genetic predispositions shaped by environmental factors manifest in complex trait differences, paving the way for future research in genetic psychiatry and personalized medicine.

Molecular Mechanics Demonstrate S-COMT as promising therapeutic receptor when analyzed with secondary plant metabolites

Major depressive disorder (MDD) and other psychiatric conditions are debilitating illnesses affecting millions globally. Catechol-O-methyltransferase (COMT), an enzyme that regulates dopamine and norepinephrine breakdown in the brain, has emerged as a potential therapeutic target for these disorders. This study explores the inhibitory potential of plant secondary metabolites against S-COMT using computational techniques. COMT exists in two isoforms: membrane-bound COMT (MB-COMT), primarily found in brain neurons, and soluble COMT (S-COMT), present in peripheral tissues. S-COMT, particularly in the prefrontal cortex, is crucial for regulating neurotransmitters and maintaining cognitive function. Studies suggest S-COMT variants might be linked to the development of depression, schizophrenia, and other psychiatric disorders. Current COMT inhibitors often suffer from limitations, necessitating the exploration of novel therapeutic strategies. This study employed in-silico methods to investigate plant secondary metabolites as potential S-COMT inhibitors. Here, we describe the S-COMT protein structure retrieval and validation, followed by molecular docking simulations to identify plant compounds with the strongest binding affinity to the receptor's active site. Key amino acid residues involved in these interactions were also analyzed. Furthermore, molecular dynamics simulations were conducted to assess the stability of the top-scoring protein-ligand complexes over a 100-ns timeframe. The results explored the stability of ligand binding within the active site and its impact on the overall conformation of the S-COMT receptor. Our findings highlight promising therapeutic potential for these plant-derived compounds. Further in vitro and in vivo studies are warranted to validate their efficacy and safety for potential clinical applications in treating S-COMT-related disorders. SubjectsBioinformatics and Computational Biology, Proteomics, Neurogenerative Diseases.

Exploring Lignin Biosynthesis Genes in Rice: Evolution, Function, and Expression.

Lignin is nature's second most abundant vascular plant biopolymer, playing significant roles in mechanical support, water transport, and stress responses. This study identified 90 lignin biosynthesis genes in rice based on phylogeny and motif constitution, and they belong to PAL, C4H, 4CL, HCT, C3H, CCoAOMT, CCR, F5H, COMT, and CAD families. Duplication events contributed largely to the expansion of these gene families, such as PAL, CCoAOMT, CCR, and CAD families, mainly attributed to tandem and segmental duplication. Microarray data of 33 tissue samples covering the entire life cycle of rice suggested fairly high PAL, HCT, C3H, CCoAOMT, CCR, COMT, and CAD gene expressions and rather variable C4H, 4CL, and F5H expressions. Some members of lignin-related genes (OsCCRL11, OsHCT1/2/5, OsCCoAOMT1/3/5, OsCOMT, OsC3H, OsCAD2, and OsPAL1/6) were expressed in all tissues examined. The expression patterns of lignin-related genes can be divided into two major groups with eight subgroups, each showing a distinct co-expression in tissues representing typically primary and secondary cell wall constitutions. Some lignin-related genes were strongly co-expressed in tissues typical of secondary cell walls. Combined HPLC analysis showed increased lignin monomer (H, G, and S) contents from young to old growth stages in five genotypes. Based on 90 genes' microarray data, 27 genes were selected for qRT-PCR gene expression analysis. Four genes (OsPAL9, OsCAD8C, OsCCR8, and OsCOMTL4) were significantly negatively correlated with lignin monomers. Furthermore, eleven genes were co-expressed in certain genotypes during secondary growth stages. Among them, six genes (OsC3H, OsCAD2, OsCCR2, OsCOMT, OsPAL2, and OsPAL8) were overlapped with microarray gene expressions, highlighting their importance in lignin biosynthesis.

UNRAVELING THE GENETIC AND BIOLOGICAL INTRICACIES OF ANESTHESIA FOR CHRONIC PAIN: A COMPREHENSIVE REVIEW OF COMT GENE VARIATIONS AND THEIR IMPACT ON TREATMENT EFFICACY ACROSS ETHNICITIES

Chronic pain management remains a significant challenge, with individual responses to anesthesia and analgesics varying widely due to genetic and biological factors. This review explores the influence of the catechol-O-methyltransferase (COMT) gene, particularly the Val158Met polymorphism, on pain sensitivity and opioid efficacy across different ethnicities. COMT variations play a crucial role in modulating pain perception and analgesic response, with Met allele carriers generally exhibiting higher pain sensitivity and lower opioid requirements. Ethnic differences in COMT gene frequencies further impact anesthesia efficacy, underscoring the importance of personalized pain management strategies. The review also discusses the potential of pharmacogenetic approaches, a beacon of hope for improving treatment outcomes. It highlights emerging technologies in genetic-based pain management, such as epigenetic modulation and gene editing.

Prediction of molecular targets for antidepressant potential of hydroalcoholic extract of Tamarindus indica using network pharmacology approach and evaluating its efficacy in Chronic Unpredictable Mild Stress model in mice.

The prevalence of psychological disorders has surged since the 1990s, posing a significant global health burden with depressed individuals averaging six lost hours per week and contributing to over 20% of all missed workdays. Current antidepressants, while effective for some, have limited efficacy, dietary restrictions, and adverse effects, including liver damage and hypertension. Natural remedies offer promising therapeutic potential with minimal side effects. Tamarindus indica (TI) is a plant that grows in the shape of a tree. Network pharmacology of TI revealed the key targets MAPK, D1-6, 5HT, DAT, MAO, COMT, PKA, PKC, AKT, and VMAT, which are linked to prominent key pathways such as dopaminergic and serotonergic. The cell viability assays on SH-Sy5y cells indicated a favourable safety profile with an IC50 of 573.99µg/ml and further, the in vivo efficacy was observed through Chronic Unpredictable Mild Stress (CUMS) model in mice. The hydroalcoholic extract of TI demonstrated antidepressant effects, significantly reducing immobility time in the Tail Suspension Test (TST) and Forced Swim Test (FST). Additionally, locomotor activity, assessed via the Open Field Test (OFT), was significantly increased in the treatment group compared to CUMS mice. Biochemical analyses revealed elevated Brain Derived Neurotropic Factor (BDNF), decreased cortisol levels, and reduced catechol-O-methyltransferase (COMT) concentration in TI-treated (50mg/kg) groups. These findings underscore the potential of TI as a natural antidepressant, offering a promising avenue for further therapeutic development in depression management. The current study did not evaluate the level of neurotransmitters in the brain, which will be evaluated in future studies.

Reward system neurodynamics during menstrual pain modulated by COMT Val158Met polymorphisms.

Primary dysmenorrhea (PDM), characterized by cyclic pain, may involve pain modulation within the reward system (RS). The Catechol-O-methyltransferase (COMT) Val158Met polymorphism, which significantly influences dopamine activity, is linked to the regulation of both acute and chronic pain. This study examines the differential neurodynamic modulation in the RS associated with COMT Val158Met polymorphisms during menstrual pain among PDM subjects. Ninety-one PDM subjects underwent resting-state fMRI during menstruation and were genotyped for COMT Val158Met polymorphisms. The amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) analyses were used to assess the RS response. Psychological evaluations included the McGill Pain Questionnaire, Pain Catastrophizing Scale, Beck Anxiety Inventory, and Beck Depression Inventory. Val/Val homozygotes (n = 50) and Met carriers (n = 41) showed no significant differences in McGill Pain Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory. However, Met carriers exhibited lower scores on the Pain Catastrophizing Scale. Distinct FC patterns was observed between Val/Val homozygotes and Met carriers, specifically between the nucleus accumbens (NAc) and prefrontal cortex, NAc and inferior parietal lobe, ventral tegmental area (VTA) and prefrontal cortex, VTA and precentral gyrus, and VTA and superior parietal lobe. Only Met carriers showed significant correlations between ALFF and FC values of the NAc and VTA with pain-related metrics (McGill Pain Questionnaire and Pain Catastrophizing Scale scores). NAc ALFF and NAc-prefrontal cortex FC values positively correlated with pain-related metrics, while VTA ALFF and VTA-prefrontal cortex and VTA-superior parietal lobe FC values negatively correlated with pain-related metrics. This study reveals that the COMT Val158Met polymorphism results in genotype-specific functional changes in the brain's RS during menstrual pain. In Met carriers, engagement of these regions is potentially linked to motivational reward-seeking and top-down modulation. This polymorphism likely influences the RS's responses, significantly contributing to individual differences in pain regulation.

Addressing the Ethnicity Gap in Catechol O-Methyl Transferase Inhibitor Trials in Parkinson's Disease: A Review of Available Global Data.

Catechol-O-methyltransferase inhibitors (COMT-Is) have significantly improved the quality of life and symptom management for those at advanced stages of Parkinson's Disease (PD). Given that PD is one of the fastest-growing neurodegenerative diseases worldwide, there is a need to establish a clear framework for the systematic distribution of COMT-Is, considering inter-individual and intra-individual variations in patient response. One major barrier to this is the underrepresentation of ethnic minority participants in clinical trials investigating COMT-Is. To investigate this, we performed a narrative review. We searched PubMed for clinical trials investigating COMT-Is in patients with PD and examined the ethnic diversity of cohorts. A total of 63 articles were identified, with 34 trials found to match our inclusion criteria. Among the 34 trials meeting our inclusion criteria, only 8 reported participants' ethnic backgrounds. Our findings reveal a consistent underrepresentation of ethnic minority groups in trials investigating COMT-Is in PD cohorts-a trend that reflects broader concerns across clinical research. In this review, we explore potential reasons for the underrepresentation of ethnic minorities in clinical trials and propose strategies to address this issue.

Living with Parkinson's disease in Portugal: Findings from PRISM study

BackgroundParkinson's disease (PD) ranks second in global neurodegenerative disorders. The “Parkinson's Real-world Impact assesSMent (PRISM)” study addressed the disease burden and treatment of European PD patients. Yet, the burden on Portuguese PD patients remains unexplored. Here, we outline the demographics, clinical features, and impact of PD in the Portuguese PRISM cohort. MethodsDescriptive analysis of the PRISM Portuguese cohort (80 patients) was performed, emphasizing socio-demographic data, anti-PD medication usage, PD impact on patients' lives and healthcare resources utilization. ResultsThe predominant comorbidities in the Portuguese PD cohort (55 % male; mean age 66.2 years; mean disease duration 8.8 years) included depression (26.3 %) and anxiety (26.3 %). Levodopa was the initial prescribed anti-PD medication for 88 % of patients. Among Portuguese PDP, dopamine agonists (DA), monoamine oxidase-B (MAO-B) inhibitors, and catechol-O-methyltransferase (COMT) inhibitors were used by 50 %, 44.4 %, and 18.3 %, respectively. Portuguese PDP experienced impaired quality of life (PDQ-39 score: 31.3 ± 16.8), various non-motor symptoms, namely sadness/blues (65.4 %), urinary urgency (63.5 %), high/low sex interest (57.7 %), while 56 % reported at least one impulse control behavior. Additionally, 30.8 % retired early due to PD and 31.8 % reduced hours in daily activities. Mental health appointments were attended by 31 %, primarily in psychiatry (19 %) and psychology (6 %), and psychotherapy. ConclusionThis study uncovers the burden of PD among Portuguese patients, revealing current treatment methods, impact on daily life and healthcare resources employed in Portugal. It emphasizes the need for personalized clinical strategies at national and international levels to improve long-term health outcomes and quality of life of PD patients.