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PubMed2025

SARS-CoV-2 genomic diversity and within-host evolution in individuals with persistent infection in the UK: an observational, longitudinal, population-based surveillance study.

BACKGROUND: Persistent SARS-CoV-2 infections in hospitalised immunocompromised individuals are known to facilitate accelerated within-host viral evolution, potentially contributing to the emergence of highly divergent variants. However, little is known about the evolutionary dynamics and transmission risks of persistent infections in the general population. We aimed to characterise the within-host evolution of SARS-CoV-2 during persistent infections identified through a large community surveillance study. METHODS: We used data from the Office for National Statistics COVID-19 Infection Survey (ONS-CIS), a large-scale, longitudinal, population-based surveillance study conducted in the UK from April, 2020, to March, 2023. For this analysis, we focused on infections with high viral load (cycle threshold ≤30) and available genome sequences, from seven major SARS-CoV-2 lineages (alpha, delta, BA.1, BA.2, BA.4, BA.5, and XBB). ONS-CIS participants were randomly selected from the general population and tested regularly by RT-PCR, regardless of symptoms. We defined persistent infections as those with sustained or rebounding high viral RNA titres for 26 days or longer. We examined associated host characteristics and used raw sequence data to identify de novo mutations and estimate within-host synonymous and non-synonymous evolutionary rates across the SARS-CoV-2 genome. FINDINGS: Between Nov 2, 2020, and March 21, 2023, we identified 576 persistent infections with at least two sequences, including 11 alpha, 106 delta, 102 BA.1, 204 BA.2, 16 BA.4, 133 BA.5, and 4 XBB. Persistent infections were more common in males than females (p<0·0001) and individuals older than 60 years (p=0·0027). The median within-host genome-wide evolutionary rate was 7·9 × 10-4 substitutions per site per year (IQR 7·0-9·0 × 10-4), with high inter-individual variability driven largely by non-synonymous mutations, particularly in the N-terminal and receptor-binding domains of the spike protein. Longer infection duration was associated with higher evolutionary rates, while no associations were found with age, sex, vaccination status, previous infection, or virus lineage. We found no clear evidence of transmission beyond the first month of infection in any of the 84 persistent infections lasting 56 days or longer. In total, we identified 379 recurrent mutations, including many with known or predicted negative fitness effects and low prevalence at the population level, as well as de novo reversions to the Wuhan-Hu-1 reference sequence, which were likely under positive selection within those individuals. INTERPRETATION: This study highlights the heterogeneous nature of within-host SARS-CoV-2 evolution in individuals with persistent infection in the community. Notably, a small subset of persistent infections with high viral loads underwent accelerated viral evolution or recurrently acquired hallmark mutations found in novel variants. In addition, onward transmission from a persistent infection during the later stages of infection is likely to be rare. These insights have important implications for prioritising genomic surveillance and managing patients with persistent infections. FUNDING: Department of Health and Social Care.

Humans↗

PubMed2003

Intrinsic susceptibility to radiation-induced apoptosis of human lymphocyte subpopulations.

PURPOSE: With the aim to evaluate intrinsic radiosensitivity, the susceptibility of lymphocyte subpopulations to radiation-induced apoptosis was determined. The investigated parameters included measurement reliability, phenotypic variance, intra- and inter-individual variability, and correlations between radiation-induced and spontaneous apoptosis. METHODS AND MATERIALS: Quiescent lymphocytes of 63 healthy volunteers, sampled up to four times over a 1-year period were gamma-irradiated in vitro. Subsequent apoptosis (annexin V) was measured for T4-, T8-, and B-lymphocyte subpopulations using 6-color flow cytometry. Spontaneous apoptosis was measured and radiosensitivity was quantified from the dose-effect curves. RESULTS: After thawing and short-term culture, both spontaneous apoptosis as well as radiation-induced apoptosis (radiosensitivity) differed among the three lymphocyte subpopulations, with T4 being most resistant, and B most sensitive. Spontaneous and radiation-induced apoptosis were correlated in all cell types, and variance between individuals was considerably higher than variance within individuals for both. A small but highly significant increase of both spontaneous and radiation-induced apoptosis was observed with age for T8, but not for T4 and B. Radiosensitivity of T8 and B proved to be sex-independent, whereas female T4 lymphocytes were less radiosensitive than those from males. T4 and T8 radiosensitivities were loosely correlated, and neither of them was related to B radiosensitivity. CONCLUSION: Tendency to spontaneous and radiation-induced apoptosis of lymphocyte subpopulations differs among individuals. In addition, depending on the cell types, age and sex are factors influencing these parameters.

Apoptosis↗

PubMed1999

Nicodermal patch adherence and its correlates.

The patch adherence behavior of 101 smokers receiving 8 weeks of the nicodermal patch was examined while undergoing one of three levels of adjunctive psychosocial treatment. Additionally, regression analyses were undertaken to: (1) identify subject variables predictive of patch adherence and (2) to determine the predictive validity of patch treatment dropout, smoking and patch adherence during patch treatment to smoking 9 and 26 weeks post-treatment entry. Fifty-five percent of the patients wore the patch as prescribed for at least 50 of 56 treatment days. A multiple regression model including the Fagerström severity of dependence score, psychosocial treatment group, and the URICA commitment score predicted 18% of the variance in days of patch use. All treatment dropouts were found to be smoking at followup. Although both smoking and low patch compliance during treatment were significant predictors subjects of week 9 and 26 smoking for the remaining subjects, at the individual variable level of analysis, only smoking during treatment predicted week 9 and 26 outcomes in a two-variable predictor model.

Administration, Cutaneous↗

PubMed2006

Smoking and education: Do psychosocial variables explain the relationship between education and smoking behavior?

The effect of education, depressive symptoms, trait anxiety, and coping traits (approach-belief, monitoring-creating-executing, and self-regulating) were tested on smoking behavior among 574 young adult males. We hypothesized that depression, anxiety, and coping traits were mediators in the relationship between education and smoking. Univariate analyses showed a significant association between smoking behavior and depressive symptoms, higher trait anxiety score, and lower scores on approach-belief and self-regulating traits. Education was significantly associated with depressive symptoms and coping traits. Although we found significant associations between smoking and education, smoking and depression, and education and depression, the hypothesis was not supported. A similar pattern was found in the case of coping traits. A multivariate logistic regression showed that low education (OR = 4.29), severe depression (OR = 1.84), and low self-regulating coping traits (OR = 2.19) were independent risk factors for smoking. The relationship between education and smoking cannot be explained by these individual variables.

Adaptation, Psychological↗

PubMed2005

Differential exploitation of the inertia tensor in multi-joint arm reaching.

The identification of the kinaesthetic information used for directing 3D multi-joint arm movements toward a target remains an open question. Several psychophysical studies have suggested that the ability to perceive and control the spatial orientation of our limbs depends on the exploitation of the eigenvectors (e (3)) of the inertia tensor (I ( ij )), which correspond to the arm rotational inertial axes. The present experiment aimed at investigating whether e (3) was used as a collective variable to direct the masses toward the target and hence to control the spatial accuracy of the final hand position. Natural, unconstrained, three-dimensional multi-joint reaching movements were submitted to alterations of forearm mass distribution. Given the existence of several "sensorimotor strategies" for the control of arm movements, the participants were a priori contrasted and ranged in groups according to their reliance on either visual or kinaesthetic information. The results indicated (1) the dependency of the arm's directional control on I ( ij ) parameters, (2) a non-linear relationship between the performance predicted by the inertia tensor and the observed performance, depending on the deviation amplitude and (3) the presence of a large inter-individual variability suggesting the existence of different strategies, including proprioceptive compensation mechanisms. This study validates in unconstrained multi-joint arm movements the exploitation of the inertia tensor by the central nervous system, thus simplifying the coordination of the segments' masses during reaching. The results also provide evidence for the existence of motor alternatives in exploiting proprioceptive information that may depend on spatial referencing modes.

Adult↗

PubMed2004

Colour perception in twins: individual variation beyond common genetic inheritance.

BACKGROUND: The twin method was used to examine the genotype/phenotype relationship in colour vision, by determining concordance in colour perception within pairs of monozygotic (MZ) twins and dizygotic (DZ) twins. For MZ twins, whose photopigments are genetically identical, higher concordance in colour perception was expected; conversely, differences within each MZ pair would indicate a non-genetic contribution. METHOD: Ratings of dissimilarity between successively presented colours were elicited from four MZ and three DZ twin pairs. A non-twin sibling pair and three unrelated normal trichromats were enrolled, for comparison. Concordance for each twin (sibling) pair was estimated by Spearman correlations (rs) between data matrices and by Procrustes distances (gl) between colour spaces, reconstructed from individual data using multidimensional scaling (MDS). RESULTS: For MZ twins, rs) values (0.94-0.97) were comparable to intra-individual variability and significantly higher than those for DZ twins and siblings (0.72-0.82). Further, colour spaces for MZ co-twins were less discordant, with gl values (0.008-0.029) lower than for DZ co-twins (0.073-0.079) and siblings (0.052). Finally, concordances among all pairs of subjects were summarised by a geometrical 'subject space': the mean distance between MZ co-twins was 29 per cent of that between DZ and sibling pairs. DISCUSSION: Lower concordance rates in DZ twins and siblings can be attributed to differences in the inherited arrays of photopigment genes. The high concordance for MZ twins is in line with their shared photopigment genotype, placing an upper limit on contributions to discordance from possible individual variations in non-genetic factors. Potential photoreceptor, ocular and cognitive sources of inter-twin variation are discussed.

Adolescent↗

PubMed2026

To longevity and beyond: A systems view of aging and stress resilience.

Aging is a dynamic and time-dependent process characterized by progressive functional decline across biological systems. Key hallmarks, including genomic instability, telomere attrition, loss of proteostasis, mitochondrial dysfunction, and immunosenescence, have been widely described, each reflecting distinct yet interconnected mechanistic frameworks. Rather than acting in isolation, these processes arise from complex interactions among cellular stressors, impaired repair mechanisms, and the cumulative burden of maladaptive responses. This system-level perspective explains the inter-individual variability in aging trajectories. Centenarians represent an extreme and informative model of successful aging, in which the balance between damage accumulation and repair is shifted toward the maintenance of physiological function. Their exceptional longevity is supported by coordinated genetic, epigenetic, metabolic, and immunological adaptations that enhance resilience to age-related stressors. Here, we summarize the biological drivers and theoretical frameworks of aging within an integrative context, focusing on mechanisms associated with extended healthspan in centenarians. We also examine the contribution of major animal models, highlighting their complementary roles in elucidating conserved and species-specific aging pathways. Overall, aging outcomes reflect a dynamic equilibrium between damage and repair processes. Understanding how this balance is modulated in long-lived individuals may inform strategies to promote healthy aging and delay the onset of age-related diseases.

Humans↗

PubMed2006

Can near infrared spectroscopy measure the effect of pressure on oxygenation of sacral soft tissue?

OBJECTIVE: To test whether near infrared spectroscopy (NIRS) is applicable for the examination of the influence of external pressure on oxygenation of the soft tissues in the sacral area. METHOD: Tissue oxygenation was measured in 33 healthy volunteers in the prone position. A NIRS probe was positioned over the sacrum and external pressure was applied in 10 mmHg increments, from 20 mmHg to 200 mmHg and then decreased. At each level, tissue oxygen saturation (StO2) was measured. To test reproducibility, the protocol was repeated in six volunteers, in whom the thickness of the soft-tissue envelope at different levels of external pressure was assessed using ultrasound. RESULTS: There was wide variability in StO2 courses between the 33 subjects, with a non-linear relationship between pressure and StO2. The only consistent finding was that the StO2 was significantly higher after decreasing pressure than at the initial pressure of 20 mmHg, which is indicative of reactive hyperaemia. Despite the application of high external pressures, reasonable tissue oxygenation was maintained in 19 of 33 subjects. Reproducibility of the measurements was poor. Comparison of soft-tissue thickness with corresponding StO2 values showed that, with increasing pressure, the percentage decrease in tissue thickness was higher than the decrease in tissue oxygenation. CONCLUSION: This study confirms that NIRS is not useful for assessing tissue oxygenation in pressure ulcer research due to unacceptable inter-individual variability and poor reproducibility of measurements.

Adult↗

PubMed1996

Effect of educational level, gender and age on the performance in a multi-user computerized psychometric test system for use in clinical pharmacological studies.

197 native, drug-free healthy young volunteers performed psychometric tests on a single occasion, using a new multi-user computerized test system which consists of tests of simple reaction time, complex reaction time, vigilance, concentration, motor coordination, short-term memory (word pairs or figures) and abstract language-free reasoning (2 versions). Normality of distribution of all psychometric variables was checked. For the reasoning tests and the memory tests, internal consistency and parallel test reliability were determined. Cross-correlations between the variables and factor analysis were done to evaluate whether different tests measure different brain functions. Multivariate variance analysis was carried out to test the effect of the independent factors school education, gender and age on the performance in the psychometric tests. Subjects with a lower school education level performed worse in the reasoning tests, the concentration test and the memory tests. Females were slower in the coordination test and made fewer correct solutions in the concentration test. Older subjects performed worse in the reasoning tests and had a longer working time in the memory tests than younger ones. The results show the necessity of psychometric screening of volunteers before recruitment for clinical pharmacological psychometric studies in order to reduce-individual variability.

Adolescent↗

PubMed2005

Lung fibre burden in lung cancer cases employed in the rock and slag wool industry.

OBJECTIVES: To evaluate the relationship between estimated exposure to man-made vitreous fibres (MMVF) and to asbestos fibres and their concentration in the lung tissue of lung cancer cases amongst MMVF production workers. METHODS: Retrospective retrieval of available lung tissue specimens was conducted following a case-control study that assessed estimated occupational exposures of MMVF workers. Fibre recovery and analysis by transmission electron microscopy (TEM) were conducted to determine fibre type, fibre dimension and numbers per gram of dry lung tissue. For cases with detailed exposure data, geometric mean (GM) concentrations were compared across the exposure categories, and regression models were used to investigate the relationship between the lung fibres and the variables of estimated exposure, with and without additional variables that may affect fibre retention. RESULTS: A total of 24 samples from 17 cases of lung cancer were available for analysis: MMVF were detected in all cases. Asbestos fibres were detected in 16. No difference or trend in GM MMVF concentration was observed across the estimated exposure categories. Odds ratio (OR) for MMVF g(-1) dry lung was 0.5 (95% confidence interval: 0.1-2.4) for the second, and 3.5 (0.6-18.9) for the third quartile of index of average exposure to MMVF in industry, compared with the first (lowest exposed) quartile (no cases in the highest quartile). CONCLUSIONS: No observable relationship existed between estimated exposure and directly-measured lung fibres among this sample of cases. Retrospective specimen collection, intra-individual variability in fibre concentration, effect of unknown factors on fibre retention and small sample size militated against this study providing evidence for or against a relationship between estimated exposure and lung fibre concentrations.

Adult↗

PubMed2002

Non-linear hierarchical models for monitoring compliance.

As biomarkers transformable by specific drug agents increasingly become available, so their usefulness also increases for monitoring compliance in clinical and prevention trials, and for subsequent monitoring in the general population if a treatment is found successful. Marker levels measured over the course of a treatment yield a longitudinal trajectory that is typically non-linear, with varying velocities during the phase-in and steady-state periods of treatment, followed by decays back to normal in the presence of non-compliance. There is often considerable between-individual variability both in the mean parameters of the trajectory and the variability over time. An example is the biomarker mean corpuscular volume (MCV), which increases by 20 per cent from the drug zidovudine (AZT), and has been used to monitor compliance to AZT. Using MCV data from a previous AIDS clinical trial as an example, we describe a non-linear hierarchical growth model suitable for biomarkers that exhibit sigmoidal and/or asymptotic growth behaviour and show how such models can be supplemented with a change-point to identify potential times of non-compliance. We perform a fully Bayesian analysis to obtain a variety of posterior summaries for the behaviour of the longitudinal trajectory and the times of non-compliance, and describe how to obtain predictions of non-compliance for new individuals.

Acquired Immunodeficiency Syndrome↗

PubMed1989

[Pharmacokinetics of azlocillin in critical conditions: an individualized schedule of drug administration in relation to anatomo-physiologic and pathologic factors].

Azlocillin pharmacokinetics was studied after a single intravenous injection of the antibiotic in a dose of 4 g in 20 patients in critical state. To elucidate the causes of significant individual variability of the antibiotic pharmacokinetics observed in the patients, multiple correlation analysis of the main pharmacokinetic parameters i. e. the area under the concentration/time curve, total clearance, steady-state volume of distribution and mean residence time was performed in regard to the "patient factors" such as sex, age, the volumes of transfused liquid, blood, plasma and blood substitutes, hemoglobin levels, erythrocyte count and ESR. Adequate correspondence of the predicted by the "patient factor" values of the areas under the concentration/time curve and the total clearance to the actually determined values was observed. Correspondence of the predicted values to the steady-state volume of distribution and the mean residence time to the actually determined values was satisfactory. A procedure for design of azlocillin individual dosage regimens based on calculating individual clearance by the "patient factors" is described.

Azlocillin↗

PubMed1996

Comparison of in vivo and in vitro haemodynamic function in experimental heart failure: use of echocardiography.

OBJECTIVE: To compare in vivo and in vitro haemodynamic performance in two models of experimental cardiac failure. To validate echocardiography as a means of non-invasive assessment of left ventricular dysfunction in rabbits. METHODS: Cardiac failure was induced by doxorubicin injection (1-1.25 mg.kg-1 twice weekly for 8 weeks (n = 16)) or coronary ligation (n = 12), with 12 controls. Left ventricular diastolic dimension and ejection fraction were assessed in vivo by echocardiography. The doxorubicin-treated and ligation hearts were subdivided by ejection fraction > 0.40 or < or = 0.40 into non-failing and failing groups. Thermodilution cardiac output was measured in vivo at baseline and after a fluid load. Basal cardiac output and peak cardiac output achieved by increased preload were measured in vitro in the working heart mode. RESULTS: The mean ejection fractions in the doxorubicin-treated and ligation groups were significantly (P < 0.001) lower than in controls, but there was wide inter-individual variability ranging from normal to severely impaired function [mean +/- s.d. (range) controls 0.65 +/- 0.03 (0.59-0.72), doxorubicin 0.45 +/- 0.11 (0.30-0.67), ligation 0.42 +/- 0.12 (0.25-0.65)]. Basal and peak cardiac outputs in vivo and in vitro were significantly lower in the doxorubicin and coronary ligation groups than in controls, although there was a wider scatter of values in the pathological groups. Among the doxorubicin and coronary ligation groups, hearts with ejection fractions < or = 0.40 demonstrated significantly impaired haemodynamic function compared with those with ejection fractions > 0.40. There were significant correlations between ejection fraction and all indices of haemodynamic function in vivo and in vitro. CONCLUSIONS: Simple non-invasive measurement of ejection fraction allowed improved characterization of haemodynamic responses in vivo and in vitro. Individual assessment of animals by echocardiography will improve interpretation of cellular or molecular studies in experimental heart failure by relating observed abnormalities to the degree of global cardiac dysfunction.

Animals↗

PubMedDate not supplied

[Role of genetic factors in the formation of trace reactions in man].

Trace processes due to presentation of visual nonverbal information, and the dynamics of the bioelectrical parameter (mean level of asymmetry of EEG-waves) were studies in 32 pairs of monozygote and 38 pairs of dizygote twins with twins method. Statistical processing of the data revealed a significant effect of genetic factors on the formation of individual variability of the characteristics of trace processes in humans. The results obtained showed that with increased functional load the intrapair similarity of trace reactions increased in monozygote twins and did not change or decrease in dizygote twins and in unrelated pairs. This fact is interpreted at a dependence of appearance of geneticly determined neurophysiological characteristics on the level of functional activity of the nervous system.

Adolescent↗

PubMed2000

Interpretation of computed tomography does not correlate with laboratory or pathologic findings in surgically confirmed acute appendicitis.

BACKGROUND: Computed tomography (CT) is used increasingly to diagnose acute appendicitis, despite variable technique and interpretation. We hypothesized that CT interpretation would not reflect actual clinical-pathologic findings in all demographic patient groups. METHODS: A prospective university hospital database of 625 consecutive patients (1995-1999), all of whom were operated on for appendicitis (261, or 41.8%, within 24 hours of discretionary CT), was reviewed. CT and pathology data were obtained from final, written reports. CT criteria included free fluid or air, appendiceal visualization, mesenteric fat stranding, and blurred pericecal fat. Appendix pathology included acute, gangrenous, and perforated organs. Statistics were performed with the Fisher exact test (coordinate data) and univariate analysis of variance (continuous data); multivariate analysis of variance for independent effects on dependent variable (positive CT or pathology; P <.05). RESULTS: The mean age was 35 +/- 1 years with 46.6% being female patients. CT was done more often in women and after 1997 (both P <.05). The sensitivity and specificity of CT were 96.1% and 16.1%, respectively. The positive predictive value (PPV) and accuracy rate (A) were 90%, and 88%, respectively. After CT, the incidence of finding a normal appendix was lower (19.3% vs 12.3%, P <.05), especially if the white blood cell count (WBC) was normal (< or = 11K/microL, 6.1% vs 23.2%, P <.001). If the WBC was < or = 11K/microL with positive CT, PPV/A was 73. 7%/71.3%, whereas with WBC > 11K/microL and positive CT, PPV/A was 99.4%/93.3%. Multivariate analysis of variance showed that none of the individual variables used by the radiologist to determine a positive CT scan correlated with outcome determined by surgical pathology. A healthy appendix was predicted by a CT interpreted as negative and younger age (both P <.05), and especially by lower WBC (P <.0001), but not by gender or surgeon. CONCLUSIONS: Although the negative appendectomy rate was decreased by CT, there was no correlation between CT findings and pathologically proved disease. Other factors such as more precise patient selection by clinical criteria may also be improving outcome. A positive CT scan in a patient with a normal WBC should be interpreted with caution.

Acute Disease↗

PubMed1995

Differential transcription efficiency of two Ig VH promoters in vitro.

Each Ig variable region gene segment is transcribed from its own unique promoter. While all of these promoters share common consensus elements that contribute to the B cell-specific expression of these genes, the DNA sequence of each promoter is distinct. In this study, we have directly compared the transcription efficiencies of two murine heavy chain (VH) promoters in a murine B cell in vitro transcription system. We found that the promoters differed in both transcription efficiency and the ability to bind specific protein complexes. While some of the transcription differences may be attributed to differences in basal promoter elements, the spacing between the octamer and the heptamer consensus elements was found to be important. Others have reported a direct correlation between transcription efficiency and the probability that individual variable region gene segments will rearrange. Our studies may be of direct importance to those interested in identifying B cell-specific transcription factors and may ultimately help to explain differences in the expression of some VH gene segments.

Animals↗

PubMed2000

Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable?

Studies on structural-functional associations in the visual system require precise information on the location and variability of Brodmann's areas 17 and 18. Usually, these studies are based on the Talairach atlas, which does not rely on cytoarchitectonic observations, but on comparisons of macroscopic features in the Talairach brain and Brodmann's drawing. In addition, in this atlas are found only the approximate positions of cytoarchitectonic areas and not the exact borders. We have cytoarchitectonically mapped both areas in 10 human brains and marked their borders in corresponding computerized images. Borders were defined on the basis of quantitative cytoarchitecture and multivariate statistics. In addition to borders of areas 17 and 18, subparcellations within both areas were found. The cytoarchitectonically defined areas were 3-D reconstructed and transferred into the stereotaxic space of the standard reference brain. Surface rendering of the brains revealed high individual variability in size and shape of the areas and in the relationship to the free surface and sulci. Ranges and centers of gravity of both areas were calculated in Talairach coordinates. The positions of areas 17 and 18 in the stereotaxic space differed between the hemispheres. Both areas reached significantly more caudal and medial positions on the left than on the right. Probability maps were created in which the degree of overlap in each stereotaxic position was quantified. These maps of areas 17 and 18 are the first of their kind and contain precise stereotaxic information on both interhemispheric and interindividual differences.

Adult↗

PubMed2006

A clinical genetic method to identify mechanisms by which pain causes depression and anxiety.

BACKGROUND: Pain patients are often depressed and anxious, and benefit less from psychotropic drugs than pain-free patients. We hypothesize that this partial resistance is due to the unique neurochemical contribution to mood by afferent pain projections through the spino-parabrachial-hypothalamic-amygdalar systems and their projections to other mood-mediating systems. New psychotropic drugs for pain patients might target molecules in such brain systems. We propose a method to prioritize molecular targets by studying polymorphic genes in cohorts of patients undergoing surgical procedures associated with a variable pain relief response. We seek molecules that show a significant statistical interaction between (1) the amount of surgical pain relief, and (2) the alleles of the gene, on depression and anxiety during the first postoperative year. RESULTS: We collected DNA from 280 patients with sciatica due to a lumbar disc herniation, 162 treated surgically and 118 non-surgically, who had been followed for 10 years in the Maine Lumbar Spine Study, a large, prospective, observational study. In patients whose pain was reduced >25% by surgery, symptoms of depression and anxiety, assessed with the SF-36 Mental Health Scale, improved briskly at the first postoperative measurement. In patients with little or no surgical pain reduction, mood scores stayed about the same on average. There was large inter-individual variability at each level of residual pain. Polymorphisms in three pre-specified pain-mood candidate genes, catechol-O-methyl transferase (COMT), serotonin transporter, and brain-derived neurotrophic factor (BDNF) were not associated with late postoperative mood or with a pain-gene interaction on mood. Although the sample size did not provide enough power to persuasively search through a larger number of genes, an exploratory survey of 25 other genes provides illustrations of pain-gene interactions on postoperative mood--the mu opioid receptor for short-term effects of acute sciatica on mood, and the galanin-2 receptor for effects of unrelieved post-discectomy pain on mood one year after surgery. CONCLUSION: Genomic analysis of longitudinal studies of pain, depression, and anxiety in patients undergoing pain-relieving surgery may help to identify molecules through which pain alters mood. Detection of alleles with modest-sized effects will require larger cohorts.

Anxiety Disorders↗