catechol-O-methyltransferase Polymorphism Research Articles

Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls.

Objective:Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role.Methods:We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs.Results:We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients.Conclusion:These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.

Interaction Between Val158Met Catechol-O-Methyltransferase Polymorphism and Social Cognitive Functioning in Schizophrenia: Pilot Study.

The Val158Met catechol-O-methyltransferase (COMT) functional polymorphism may influence social cognitive functioning in patients with schizophrenia. Aspects of social cognition were evaluated with the Facial Expression Recognition Test, the Voice Emotion Recognition Test, and the Reading the Mind in the Eyes Test. The Short Recognition Memory Test for Faces was used as a control measure. The Schedule for the Assessment of Negative Symptoms, Schedule for the Assessment of Positive Symptoms, and Beck Depression Inventory were used to rate of patient symptoms. There were 100 patients with the following genotypes: Val/Val (21), Met/Met (30), and Val/Met (49). The genotype distribution of polymorphism of Val158Met COMT did not differ between the patient and control groups. Schizophrenia carriers of the Val/Val genotype performed worse in social cognitive measures, in comparison with the other groups. No statistically significant correlations were recorded between age at schizophrenia onset and polymorphism of Val158Met COMT. There was an influence of genotype in the control group: the Met homozygotes performing better. Schizophrenia patients homozygous for the Val allele showed significant disadvantages over patients homozygous or heterozygous for the Met allele in social cognitive processes. The COMT genotype may not, however, contribute to the age of onset of schizophrenia.

Catechol-O-methyltransferase polymorphism is associated with the cortico-cerebellar functional connectivity of executive function in children with attention-deficit/hyperactivity disorder

The cerebellum, although traditionally considered a motor structure, has been increasingly recognized to play a role in regulating executive function, the dysfunction of which is a factor in attention-deficit/hyperactivity disorder (ADHD). Additionally, catechol-O-methyltransferase (COMT) polymorphism has been reported to be associated with executive function. We examined whether the cortico-cerebellar executive function network is altered in children with ADHD and whether COMT polymorphism is associated with the altered network. Thirty-one children with ADHD and thirty age- and IQ-matched typically developing (TD) controls underwent resting-state functional MRI, and functional connectivity of executive function-related Crus I/II in the cerebellum was analysed. COMT Val158Met genotype data were also obtained from children with ADHD. Relative to TD controls, children with ADHD showed significantly lower functional connectivity of the right Crus I/II with the left dorsolateral prefrontal cortex. Additionally, the functional connectivity of children with ADHD was modulated by COMT polymorphism, with Met-carriers exhibiting significantly lower functional connectivity than the Val/Val genotype. These results suggest the existence of variations, such as ethnic differences, in COMT genetic effects on the cortico-cerebellar executive function network. These variations contribute to heterogeneity in ADHD. Further neuroimaging genetics study might lead to the development of fundamental therapies that target ADHD pathophysiology.

Are dopaminergic genotypes risk factors for eating behavior and obesity in adults?

Dopamine (DA) is the main modulator of the brain reward system and significantly regulates food intake. The idea that obesity is a neurobiological disease rather than a metabolic disorder, is the basis of the study. Changes in dopamine neurotransmission affect the brain reward system in a direct way. Furthermore, changes in the reward system influence the eating behavior in human. The enzymes monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) terminate the DA function by metabolizing it. In our study, the control group which included 214 individuals and 234 subjects with obesity were investigated for MAOA-u VNTR and COMT (rs4680) polymorphisms. In our study, statistical analysis has showed that in control group Val/Met COMT genotype was significantly higher compared with the patient group (p=0.04). When the groups were compared in terms of eating behavior, the number of the subjects who ate for reward was significantly higher in patient group (p=0.03). Our findings demonstrated that eating behavior might have an effect on obesity and dopaminergic polymorphisms could be risk factors for the development of obesity in Turkish population.

Effects of β-Adrenoceptor and Catechol-O-Methyl-Transferase (COMT) Polymorphism on Postoperative Outcome in Cardiac Surgery Patients.

BackgroundThere is a long-standing debate about the role of beta-adrenoceptor polymorphisms in the cardiovascular system. We wanted to elucidate whether β1-adrenoceptor-polymorphisms affects the postoperative catecholamine consumption and the length of intermediate care unit stay in patients undergoing cardiac surgery, and whether this might be enhanced or attenuated by catechol-O-methyl-transferase (COMT) polymorphism.Material/MethodsWe included 116 patients (63±1.2 years; 34% females; 81±1 kg) undergoing cardiac surgery. We assessed Arg389Gly and Ser49Gly-β1-adrenoceptor (B1AR) polymorphism together with Val158Met-COMT polymorphism by real-time PCR using fluorescence resonance energy transfer (PCR-FRET). The preoperative risk was assessed by EuroSCORE. In addition, we measured the endogenous preoperative epinephrine and norepinephrine plasma concentrations using an electrochemical HPLC method.Results84.6% were homozygous for Ser49Ser, 52.1% homozygous for Arg389Arg B1AR, and 32.5% for Val158Val-COMT, while 15.4% showed Ser49Gly B1AR, 38.5% Arg389Gly-B1AR, and 35.6% Val158Met-COMT. We found that the Gly49-variant, the Gly389-variant, and the Val158-COMT-variant were associated with higher postoperative norepinephrine consumption. All patients carrying the Val158-COMT allele exhibited higher preoperative norepinephrine concentrations. Moreover, we found that both β1-adrenoceptor polymorphisms were associated with a longer stay in hospital, which was modulated by the COMT polymorphism.ConclusionsThese data show that the β1-adrenoceptor polymorphisms, together with the COMT polymorphism, affect norepinephrine consumption and stay in hospital in a situation of enhanced cardiovascular stress, reflected here by the postoperative period after cardiac surgery. Moreover, we conclude that patients with the Val158-COMT genotype exhibit higher endogenous resting plasma norepinephrine levels.

Efficacy of insulin detemir treatment in type 2 diabetes mellitus is associated with a allele od the catechol o-methyltransferase polymorphism

Efficacy of insulin detemir treatment in type 2 diabetes mellitus is associated with a allele od the catechol o-methyltransferase polymorphism

Implications of COMT and subclinical psychiatric symptoms on the phenotypic variability of 22q11.2 deletion syndrome: A transversal and longitudinal approach

Introduction22q11.2 deletion syndrome (22q11.2DS) results from a hemizygous microdeletion on chromosome 22 and is characterized by phenotypic variability. Several studies have been conducted on the impact of COMT functional polymorphism in 22q11DS, suggesting that attenuated psychotic manifestations are frequent in children and adolescents and represent one of the strongest predictors for the onset of psychotic disorder.ObjectivesWe explored possible interaction between COMT polymorphism and subclinical psychiatric symptoms in a 22q11.2DS cohort of 42 participants aged 6 to 26 years: 17 hemizygosity for COMT-Met and 25 hemizygosity for COMT-Val.AimsTo analyse impact of COMT gene in 22q11DS and its related psychiatric correlates.MethodEach participant, genotyped for the catechol O-methyltransferase (COMT) Met/Val polymorphism, underwent structured psychiatric and cognitive assessment. Analysis of positive and negative symptoms was performed by the structured interview for prodromal syndromes (SIPS). Finally, longitudinal data available in a subsample of 24 individuals were used to explore the developmental trajectories of psychotic symptoms one year later.ResultsThere was a significant positive correlation between COMT Val polymorphism and positive symptoms; at follow-up, no significant correlation were found between COMT polymorphism and psychiatric symptoms. No other significant differences were found between groups (Comt/Met-Comt/Val) on any other CBCL or QI score.ConclusionsCOMT and additional genes microdeleted might interact in the susceptibility to schizophrenia in 22q11.2DS: psychotic symptoms might result from an epistatic interaction with other genes. Moreover, gene-environment, in presence of genetic vulnerability could increase the risk of schizophrenia in 22q11DS.Disclosure of interestThe authors have not supplied their declaration of competing interest.

COMT Val158Met Polymorphism and Symptom Improvement Following a Cognitively Focused Intervention for Irritable Bowel Syndrome.

Our nurse-delivered comprehensive self-management (CSM) program, a cognitive behavioral therapy intervention, is effective in reducing gastrointestinal and psychological distress symptoms in patients with irritable bowel syndrome (IBS). Findings from non-IBS studies indicate that the catechol-O-methyltransferase (COMT) Val158Met polymorphism may moderate the efficacy of cognitive behavioral therapy. It is unknown whether this COMT polymorphism is associated with symptom improvements in patients with IBS. We tested whether this COMT Val158Met polymorphism influences the efficacy of our 2-month CSM intervention. We analyzed data from two published randomized controlled trials of CSM. The combined European American sample included 149 women and 23 men with IBS (CSM, n = 111; usual care [UC], n = 61). The primary outcomes were daily reports of abdominal pain, depression, anxiety, and feeling stressed measured 3 and 6 months after randomization. Secondary outcomes were additional daily symptoms, retrospective psychological distress, IBS quality of life, and cognitive beliefs about IBS. The interaction between COMT Val158Met polymorphism and treatment group (CSM vs. UC) in a generalized estimating equation model tested the main objective. At 3 months, participants with at least one Val allele benefited more from CSM than did those with the Met/Met genotype (p = .01 for anxiety and feeling stressed, and p < .16 for abdominal pain and depression). The moderating effect of genotype was weaker at 6 months. Persons with at least one Val allele may benefit more from CSM than those homozygous for the Met allele. Future studies with larger and more racially diverse samples are needed to confirm these findings. Parent studies were registered at ClinicalTrials.gov (NCT00167635 and NCT00907790).

COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume.

Memory-based alterations are among the hallmark symptoms of posttraumatic stress disorder (PTSD) and may be associated with the integrity of the hippocampus. However, neuroimaging studies of hippocampal volume in individuals with PTSD have yielded inconsistent results, raising the possibility that various moderators, such as genetic factors, may influence this association. We examined whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism, which has previously been shown to be associated with hippocampal volume in healthy individuals, moderates the association between PTSD and hippocampal volume. Recent war veterans underwent structural MRI on a 3 T scanner. We extracted volumes of the right and left hippocampus using FreeSurfer and adjusted them for individual differences in intracranial volume. We assessed PTSD severity using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to model the genotype (Val158Met polymorphism) × PTSD severity interaction and its association with hippocampal volume. We included 146 white, non-Hispanic recent war veterans (90% male, 53% with diagnosed PTSD) in our analyses. A significant genotype × PTSD symptom severity interaction emerged such that individuals with greater current PTSD symptom severity who were homozygous for the Val allele showed significant reductions in left hippocampal volume. The direction of proposed effects is unknown, thus precluding definitive assessment of whether differences in hippocampal volume reflect a consequence of PTSD, a pre-existing characteristic, or both. Our findings suggest that the COMT polymorphism moderates the association between PTSD and hippocampal volume. These results highlight the role that the dopaminergic system has in brain structure and suggest a possible mechanism for memory disturbance in individuals with PTSD.

Risk assessment of aggressive behavior in Chinese patients with schizophrenia by fMRI and COMT gene.

BackgroundBlood–oxygen-level dependent functional magnetic resonance imaging (BOLD-fMRI) maps cerebral activity by the hemodynamic response. Catechol-O-methyltransferase (COMT) gene is involved in the metabolism of dopamine. It is reported that both of these can be used to assess the aggression risk in patients with schizophrenia. However, these methods to assess the aggression risk patients with schizophrenia have not been established in China. Therefore, we deliver here a systematic review and meta-analysis based on the studies dealing with Chinese patients.MethodNine fMRI studies and 12 gene studies were included. The data of each study were extracted and summarized. Odds ratios with 95% confidence intervals were estimated on allele, dominant, and recessive models. Publication bias was evaluated by Begg’s funnel plot.ResultsPositive BOLD-fMRI values in the lower central neural system (CNS) and negative values in the high-level CNS were observed in the patients with aggression risk. A strong association was derived from the recessive gene model of COMT polymorphism rs4680 and risk in aggression behavior (odds ratio =2.10). No significant publication bias was identified.ConclusionAggression behavior in patients with schizophrenia can be indicated by positive BOLD-fMRI values in the lower CNS and negative values in the high-level CNS and by a recessive gene model in COMT polymorphism rs4680. A combined test of fMRI and COMT gene could increase the predictive value.

Investigation of polymorphisms in genes involved in estrogen metabolism in menstrual migraine

Migraine is a common, disabling headache disorder, which is influenced by multiple genes and environmental triggers. After puberty, the prevalence of migraine in women is three times higher than in men and >50% of females suffering from migraine report a menstrual association, suggesting hormonal fluctuations can influence the risk of migraine attacks. It has been hypothesized that the drop in estrogen during menses is an important trigger for menstrual migraine. Catechol-O-methyltransferase (COMT) and Cytochrome P450 (CYP) enzymes are involved in estrogen synthesis and metabolism. Functional polymorphisms in these genes can influence estrogen levels and therefore may be associated with risk of menstrual migraine. In this study we investigated four single nucleotide polymorphisms in three genes involved in estrogen metabolism that have been reported to impact enzyme levels or function, in a specific menstrual migraine cohort. 268 menstrual migraine cases and 142 controls were genotyped for rs4680 in COMT (Val158Met), rs4646903 and rs1048943 in CYP1A1 (T3801C and Ile462Val) and rs700519 in CYP19A1 (Cys264Arg). Neither genotype nor allele frequencies for the COMT and CYP SNPs genotyped were found to be significantly different between menstrual migraineurs and controls by chi-square analysis (P>0.05). Therefore we did not find association of functional polymorphisms in the estrogen metabolism genes COMT, CYP1A1 or CYP19A1 with menstrual migraine. Further studies are required to assess whether menstrual migraine is genetically distinct from the common migraine subtypes and identify genes that influence risk.

Catechol-O-methyltransferase Val(108/158)Met polymorphism affects fronto-limbic connectivity during emotional processing in bipolar disorder

Catechol-O-methyltransferase (COMT) inactivates catecholamines, Val/Val genotype was associated to an increased amygdala (Amy) response to negative stimuli and can influence the symptoms severity and the outcome of bipolar disorder, probably mediated by the COMT polymorphism (rs4680) interaction between cortical and subcortical dopaminergic neurotransmission. The aim of this study is to explore how rs4680 and implicit emotional processing of negative emotional stimuli could interact in affecting the Amy connectivity in bipolar depression. Forty-five BD patients (34 Met carriers vs. 11 Val/Val) underwent fMRI scanning during implicit processing of fearful and angry faces. We explore the effect of rs4680 on the strength of functional connectivity from the amygdalae to whole brain. Val/Val and Met carriers significantly differed for the connectivity between Amy and dorsolateral prefrontal cortex (DLPFC) and supramarginal gyrus. Val/Val patients showed a significant positive connectivity for all of these areas, where Met carriers presented a significant negative one for the connection between DLPFC and Amy. Our findings reveal a COMT genotype-dependent difference in corticolimbic connectivity during affective regulation, possibly identifying a neurobiological underpinning of clinical and prognostic outcome of BD. Specifically, a worse antidepressant recovery and clinical outcome previously detected in Val/Val patients could be associated to a specific increased sensitivity to negative emotional stimuli.

Association between cerebrospinal fluid dopamine concentrations and catechol-O-methyltransferase gene polymorphisms in forensic autopsy cases of methamphetamine abusers

Methamphetamine (MA) is an illicit psychostimulant that stimulates the release of catecholamines from sympathetic nerve terminals and is widely abused worldwide. Since catechol-O-methyltransferase (COMT) metabolizes catecholamines and mediates adrenergic, noradrenergic, and dopaminergic signaling responses, we investigated the effects of the COMT polymorphisms rs4633 and rs4680 on cerebrospinal fluid (CSF) catecholamine concentrations in autopsies of subjects who died of drug intoxication. 28 MA abusers and 22 fatal psychotropic drug intoxication cases were evaluated. No correlations were identified between rs4633 or rs4680 polymorphisms and CSF concentrations of adrenaline (Adr), noradrenaline (Nad), or dopamine (DA) in fatal psychotropic cases. However, among MA abusers, DA concentrations in the CSF were significantly higher in those with the T allele (CT and TT) of rs4633 than in CC genotype carriers (p=0.004). Moreover, among MA abusers, DA concentrations were significantly higher in those with the A allele (GA and AA) of rs4680 than in GG genotype carriers (p=0.017). In subsequent haplotype analyses of MA abusers, a strong correlation was identified between two COMT haplotypes and CSF DA concentrations (p=0.002). However, the CSF concentrations of Adr and Nad were not associated with COMT genotypes or haplotypes. The present results indicate that rs4633 and rs4680 polymorphisms influence CSF DA concentrations and MA toxicity in MA abusers.

Association of DISC1, BDNF, and COMT polymorphisms with exploratory eye movement of schizophrenia in a Chinese Han population.

Previous studies suggested that exploratory eye movement (EEM) dysfunction appears to be a biological marker specific to schizophrenia, with an unknown molecular mechanism. Genetic studies indicate that disrupted-in-schizophrenia-1 (DISC1), brain-derived neurotrophic factor (BDNF), and catechol-O-methyl transferase (COMT) genes might be implicated in the etiology of schizophrenia, but not in all populations. The present study aimed to explore associations between these candidate genes and EEM endophenotypes for schizophrenia in a Chinese Han population. EEM recordings were examined in 139 patients with schizophrenia and 143 healthy control participants. All five EEM parameters, responsive search score, cognitive search score, number of eye fixations, total eye scanning length, and mean eye scanning length, of schizophrenic patients differed significantly from those of healthy controls (P<0.001). The DISC1 SerCys, BDNF ValMet, and COMT ValMet were genotyped in a total sample of 818 schizophrenic patients and 827 healthy control participants, including the above EEM samples. We found that DISC1 Cys and BDNF Met were associated with an increased risk of developing schizophrenia (P<0.001). Furthermore, responsive search score scores of BDNF Met/Met carriers were significantly lower than those of Val allele carriers (P=0.022), which remained modest after Bonferroni correction. The BDNF MetMet polymorphism might be associated with the EEM dysfunction of schizophrenia.

OPRM1 and COMT Gene-Gene Interaction Is Associated With Postoperative Pain and Opioid Consumption After Orthopedic Trauma.

mu-opioid receptor ( OPRM1) and catechol-O-methyltransferase ( COMT) contribute to the neurotransmission pathway of pain. COMT affects mu receptor expression and density in the brain. The aim of this study was to explore the OPRM1 and COMT interaction effects on postoperative pain and opioid consumption. This cross-sectional exploratory study used genotype and clinical data from 153 postoperative patients. Using multiple regression analyses, four single-nucleotide polymorphisms of COMT (rs6269, rs4633, rs4818, and rs4680), their haplotypes, and diplotypes were considered for their interactions with A118G of OPRM1 regarding postoperative pain and opioid consumption. For opioid consumption, significant interactions were found between OPRM1 A118G and COMT rs4680 ( p = .037) and between OPRM1 and COMT rs4633 ( p = .037). Patients having Met158Met of COMT rs4680 and AG/GG of OPRM1 or TT of COMT rs4633 and AG/GG of OPRM1 consumed the largest amount of opioid compared to those having other combinations. For postoperative pain, a significant interaction was found between OPRM1 and the low pain sensitivity (LPS; GCGG) haplotype of COMT ( p = .017). For patients with no copies of the LPS haplotype, AA of OPRM1 A118G was significantly associated with higher pain scores compared to the variant AG/GG. However, the opposite direction was observed for patients with at least one copy of the LPS haplotype. The interaction of OPRM1 with COMT may contribute to variability in postoperative pain and opioid consumption. Additional larger studies are needed to confirm findings.

Association between genetic variation in the dopamine system and motor recovery after stroke.

The dopamine system plays a key role in motor learning and neuroplasticity. Several studies have studied the efficacy of dopaminergic drugs in enhancing motor recovery after stroke, but the effects are controversial. Although genetic variations in plasticity-related genes influence each individual's capacity for recovery after stroke, limited studies have investigated the effects of polymorphism of dopamine-related genes. We aimed to investigate the association between motor recovery in stroke patients and polymorphisms in the dopamine-related genes catechol-O-methyltransferase (COMT), dopamine receptor D1 (DRD1), DRD2, and DRD3. We enrolled 74 patients with first-ever stroke (42 males, 32 females, mean age: 61.4±14.1 y). During admission, blood samples were collected, and the genotypes of COMT, DRD1, DRD2, and DRD3 were analyzed. The primary outcome was assessed with Fugl-Meyer Assessment (FMA) at 1 week, 3 months, and 6 months after stroke; secondary outcomes were assessed with Functional Independence Measure (FIM) and mini-mental state examination at 3 and 6 months after stroke. The association between polymorphisms and functional outcome was analyzed. There were no significant associations between COMT polymorphisms and FMA or FIM scores at 1 week after stroke or between DRD1, DRD2, or DRD3 genotypes and FMA or FIM scores at any point. COMT genotypes were significantly associated with FMA and FIM at 3 months (p < 0.01 and p < 0.05, respectively) and at 6 months (p < 0.01 and p < 0.05, respectively). These data suggest that genetic variation of dopamine-related genes may affect motor recovery after stroke and that COMT polymorphism could be useful for predicting motor recovery.

Interaction Effects of BDNF and COMT Genes on Resting-State Brain Activity and Working Memory.

Catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) genes have been found to interactively influence working memory (WM) as well as brain activation during WM tasks. However, whether the two genes have interactive effects on resting-state activities of the brain and whether these spontaneous activations correlate with WM are still unknown. This study included behavioral data from WM tasks and genetic data (COMT rs4680 and BDNF Val66Met) from 417 healthy Chinese adults and resting-state fMRI data from 298 of them. Significant interactive effects of BDNF and COMT were found for WM performance as well as for resting-state regional homogeneity (ReHo) in WM-related brain areas, including the left medial frontal gyrus (lMeFG), left superior frontal gyrus (lSFG), right superior and medial frontal gyrus (rSMFG), right medial orbitofrontal gyrus (rMOFG), right middle frontal gyrus (rMFG), precuneus, bilateral superior temporal gyrus, left superior occipital gyrus, right middle occipital gyrus, and right inferior parietal lobule. Simple effects analyses showed that compared to other genotypes, subjects with COMT-VV/BDNF-VV had higher WM and lower ReHo in all five frontal brain areas. The results supported the hypothesis that COMT and BDNF polymorphisms influence WM performance and spontaneous brain activity (i.e., ReHo).

Associations between genetic risk, functional brain network organization and neuroticism

Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on neuroticism. The aim of the current study was to investigate how genetic risk factors impact functional network organization and whether genetic risk factors moderate the association between neuroticism and functional network organization. We applied graph theory analysis on resting-state fMRI data in a sample of 120 women selected based on their neuroticism score, and genotyped two polymorphisms: 5-HTTLPR (S-carriers and L-homozygotes) and COMT (rs4680-rs165599; COMT risk group and COMT non-risk group). For the 5-HTTLPR polymorphism, we found that subnetworks related to cognitive control show less connections with other subnetworks in S-carriers compared to L-homozygotes. The COMT polymorphism moderated the association between neuroticism and functional network organization. We found that neuroticism was associated with lower efficiency coefficients in visual and somatosensory-motor subnetworks in the COMT risk group compared to the COMT non-risk group. The findings of altered topology of specific subnetworks point to different cognitive-emotional processes that may be affected in relation to the genetic risk factors, concerning emotion regulation in S-carriers (5-HTTLPR) and emotional salience processing in COMT risk carriers.

Genetic Polymorphisms of Catechol-O-Methyltransferase: Association with Temporomandibular Disorders and Postoperative Pain.

To evaluate the association between catechol-O-methyltransferase (COMT) gene polymorphisms and temporomandibular disorders (TMD), TMD pain, psychosocial impairment related to TMD, and postoperative pain. A total of 90 patients with a diagnosis of painful TMD and 92 matched controls were investigated for the presence of TMD, TMD pain, and psychosocial variables by the Research Diagnostic Criteria for TMD. In a prospective cohort study of 40 subjects who underwent extraction of at least one fully impacted mandibular third molar, subjects had 6 months post-surgery follow-up of postoperative pain. DNA extracted from peripheral blood was genotyped for three COMT polymorphisms (rs4680, rs6269, and rs165774) by real-time TaqMan method. The association between COMT polymorphisms and clinical variables was determined by calculating odds ratios (OR) and their 95% confidence intervals (CI). Homozygous AA genotype and heterozygous variant A allele carriers (genotype AG/AA) for rs165774 polymorphism were associated with increased risk of TMD compared to wild type (wt) GG genotype (OR = 9.448, P = .006; OR = 2.088, P = .017, respectively). In addition, AA genotype was associated with increased risk of arthralgia (OR = 4.448, P = .011), myofascial pain (OR = 3.543, P = .035), and chronic TMD pain (OR = 6.173, P = .006), compared to wt genotype. AA genotype for rs6269 polymorphism was related to less postoperative chronic TMD pain (P = .025) and lower postoperative acute pain at the extraction site (P = .030). No associations with depression and somatization were observed. AA genotype of rs165774 could be a significant risk factor for the development of TMD and TMD pain, while AA genotype of rs6269 presents less postoperative chronic TMD pain and acute pain at a dental extraction site.

Common functional pain syndromes

### Key points When a patient presents with pain of no obvious organic origin, they are often labelled as having ‘functional’ pain. The exact diagnosis is derived from the organ system displaying the predominant symptoms e.g. musculoskeletal pain in fibromyalgia (FM) or visceral pain in irritable bowel syndrome (IBS). The worldwide prevalence of all functional pain syndromes (FPS) is 15–20%. World Health Organization (WHO) surveys reveal that ∼10% of primary care patients develop a chronic pain condition within 12 months of initial registration. Of these, at least 50% continue to have symptoms beyond 1 yr. FPS cause enormous economic burden on society with concurrent ramifications for the individual's family in particular and society in general. FM alone has been estimated to cost around £4000 per patient per year. There has been a paradigm shift in the understanding of FPS. The old model of multiple discrete chronic pain conditions is being replaced by a more overarching, although no less complex, state of central sensitivity syndrome (CSS). Evidence is being accrued that FPS represent the phenotypic output of a complex interplay between genetic susceptibility, gene–environment interactions, and environmental triggers. Four common FPS will be reviewed in this article: FM, IBS, temporomandibular dysfunction (TMD), and chronic cardiac chest pain (CCCP). The pathophysiology and management of each will be examined and the case presented for a shared underlying mechanism called CSS. Once this new mechanism is adopted more widely, it will allow for future novel management options to be …