Annemarie Succop

Infant eye movement asymmetries : stationary counterphase gratings elicit temporal-to-nasal optokinetic nystagmus in two-month-old infants under monocular test conditions

Tested monocularly, young infants classically show directional eye movement asymmetries, with optokinetic nystagmus (OKN) being more readily elicited by stimuli moving in the temporal-to-nasal (T-N) than in the nasal-to-temporal (N-T) direction. Since a counterphase grating is physically identical to two superimposed sinusoidal components moving in opposite directions, we wondered whether or not a counterphase grating would elicit T-N OKN in monocularly tested infants. Two-month-old infants were tested in a motion nulling paradigm. Under monocular test conditions, all infants showed T-N OKN in response to the counterphase grating. The results suggest that the young infants visual system represents the counterphase grating in terms of its T-N and N-T components, and reduces the effective contrast of the N-T component prior to the generation of OKN. The results are discussed in relation to models of OKN asymmetries and the responses of direction-selective neurons to counterphase gratings.

C-Reactive Protein and Pain Sensitivity: Findings from Female Twins

BackgroundSystemic inflammation and pain sensitivity may contribute to the development and maintenance of chronic pain conditions.PurposeWe examined the relationship between systemic inflammation as measured by C-reactive protein (CRP) and cold pain sensitivity in 198 female twins from the University of Washington Twin Registry. We also explored the potential role of familial factors in this relationship.MethodsLinear regression modeling with generalized estimating equations examined the overall and within-pair associations.ResultsHigher levels of CRP were associated with higher pain sensitivity ratings at pain threshold (p = 0.02) and tolerance (p = 0.03) after adjusting for age, body mass index, time to reach pain threshold or tolerance, and clinical pain status. The magnitude of the associations remained the same in within-pair analyses controlling for familial factors.ConclusionsThe link between CRP and pain sensitivity may be due to non-shared environmental factors. CRP and pain sensitivity can be examined as potential biomarkers for chronic pain and other inflammatory conditions.

Salivary Cortisol and Cold Pain Sensitivity in Female Twins

BackgroundThere is a dearth of knowledge about the link between cortisol and pain sensitivity.PurposeWe examined the association of salivary cortisol with indices of cold pain sensitivity in 198 female twins and explored the role of familial confounding.MethodsThree-day saliva samples were collected for cortisol levels and a cold pressor test was used to collect pain ratings and time to threshold and tolerance. Linear regression modeling with generalized estimating equations examined the overall and within-pair associations.ResultsLower diurnal variation of cortisol was associated with higher pain ratings at threshold (p = 0.02) and tolerance (p < 0.01). The relationship of diurnal variation with pain ratings at threshold and tolerance was minimally influenced by familial factors (i.e., genetics and common environment).ConclusionsUnderstanding the genetic and non-genetic mechanisms underlying the link between HPA axis dysregulation and pain sensitivity may help to prevent chronic pain development and maintenance.

Clinical and evoked pain, personality traits, and emotional states: Can familial confounding explain the associations?

OBJECTIVES Pain is a complex phenomenon influenced by context and person-specific factors. Affective dimensions of pain involve both enduring personality traits and fleeting emotional states. We examined how personality traits and emotional states are linked with clinical and evoked pain in a twin sample. METHODS 99 female twin pairs were evaluated for clinical and evoked pain using the McGill Pain Questionnaire (MPQ) and dolorimetry, and completed the 120-item International Personality Item Pool (IPIP), the Positive and Negative Affect Scale (PANAS), and ratings of stress and mood. Using a co-twin control design we examined a) the relationship of personality traits and emotional states with clinical and evoked pain and b) whether genetics and common environment (i.e. familial factors) may account for the associations. RESULTS Neuroticism was associated with the sensory component of the MPQ; this relationship was not confounded by familial factors. None of the emotional state measures was associated with the MPQ. PANAS negative affect was associated with lower evoked pressure pain threshold and tolerance; these associations were confounded by familial factors. There were no associations between IPIP traits and evoked pain. CONCLUSIONS A relationship exists between neuroticism and clinical pain that is not confounded by familial factors. There is no similar relationship between negative emotional states and clinical pain. In contrast, the relationship between negative emotional states and evoked pain is strong while the relationship with enduring personality traits is weak. The relationship between negative emotional states and evoked pain appears to be non-causal and due to familial factors.

Adverse childhood experiences, health perception, and the role of shared familial factors in adult twins

To examine the relationship between adverse childhood experiences (ACE) and health perception in adulthood, and to explore the contribution of shared familial factors to these associations. Data were collected from 180 female twins (90 pairs) from the community-based University of Washington Twin Registry. Participants completed questionnaires including the modified ACE Questionnaire, Traumatic Life Events Questionnaire, McGill Pain Questionnaire-Short Form, and the SF-36. Mixed effects linear regression modeling investigated the effects of ACE on indices of health perception controlling for correlated twin data. Additional models examined the associations while controlling for the experience of physical and/or sexual abuse in childhood; within-twin pair models that inherently adjust for familial factors explored shared familial influences. After controlling for relevant demographic variables, more ACE was associated with worse perceptions of general health (p=.01) and vitality (p=.05) on the SF-36. After controlling for childhood physical and/or sexual abuse, the relationship between ACE and general health remained significant (p=.01) while vitality was no longer significant. None of the associations remained significant after accounting for the influence of familial factors. These results support previous findings on the negative link between ACE and perceived health in adulthood. The detrimental effects of ACE on vitality may be accounted for by the experience of childhood physical and/or sexual abuse. Shared familial factors might play a partial role in the relationship between ACE and health perception. Future research should further investigate the genetic and environmental mechanisms that may explain this relationship.

DNA methylation associated with healthy aging of elderly twins

Variation in healthy aging and lifespan is ascribed more to various non-genetic factors than to inherited genetic determinants, and a major goal in aging research is to reveal the epigenetic basis of aging. One approach to this goal is to find genomic sites or regions where DNA methylation correlates with biological age. Using health data from 134 elderly twins, we calculated a frailty index as a quantitative indicator of biological age, and by applying the Infinium HumanMethylation450K BeadChip technology to their leukocyte DNA samples, we obtained quantitative DNA methylation data on genome-wide CpG sites. We analyzed the health and epigenome data by taking two independent associative approaches: the parametric regression-based approach and a non-parametric machine learning approach followed by GO ontology analysis. Our results indicate that DNA methylation at CpG sites in the promoter region of PCDHGA3 is associated with biological age. PCDHGA3 belongs to clustered protocadherin genes, which are all located in a single locus on chromosome 5 in human. Previous studies of the clustered protocadherin genes showed that (1) DNA methylation is associated with age or age-related phenotypes; (2) DNA methylation can modulate gene expression; (3) dysregulated gene expression is associated with various pathologies; and (4) DNA methylation patterns at this locus are associated with adverse lifetime experiences. All these observations suggest that DNA methylation at the clustered protocadherin genes, including PCDHGA3, is a key mediator of healthy aging.

Dexamethasone-suppressed Salivary Cortisol and Pain Sensitivity in Female Twins

Objectives: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with chronic pain. Studying pain sensitivity and the HPA axis could elucidate the role of stress in chronic pain development, which might be influenced by familial factors, including genes. Methods: Associations between pain sensitivity and salivary cortisol and familial confounding in these associations were examined in 88 female, community-based twin pairs (75% monozygotic, mean age 29 y). Cortisol was assessed after 0.25 mg dexamethasone (DEX), recovery from 0.25 mg DEX, and after 0.5 mg DEX. Cold pressor task (CPT) pain ratings were obtained at threshold and at tolerance. Conditioned pain modulation (CPM) was examined using thermal heat as the testing stimulus and hot water as the conditioning stimulus. Generalized estimating equation models were used and adjusted for baseline pain rating, age, and other relevant covariates. Results: After controlling for baseline cortisol, greater cortisol suppression following DEX administration and lower recovery cortisol levels were associated with higher pain ratings at tolerance during the CPT (Bs=−2.42 to −17.82; Ps=0.031 to<0.001) as well as with reduced CPM (Bs=−0.92 to −1.68; Ps=0.003 to 0.046). Interestingly, familial confounding was evident in the CPT and CPM during recovery from DEX administration, but not immediately following DEX administration. Discussion: These findings contribute to understanding possible mechanisms underlying chronic pain by demonstrating that HPA axis response to negative feedback is related to pain sensitivity.