Nikolai Czajkowski

Individual differences in pain sensitivity: Genetic and environmental contributions

&NA; Large individual differences in pain sensitivity present a challenge for medical diagnosis and may be of importance for the development of chronic pain. Variance in pain sensitivity is partially mediated by genetic factors, but the extent of this contribution is uncertain. We examined cold‐pressor pain and contact heat pain in 53 identical (MZ) and 39 fraternal (DZ) twin pairs, and 4 single twins to determine the heritability of the two phenotypes, and the extent to which the same genetic and environmental factors affect both pain modalities. An estimated 60% of the variance in cold‐pressor pain and 26% of the variance in heat pain was genetically mediated. Genetic and environmental factors were only moderately correlated across pain modalities. Genetic factors common to both modalities explained 7% of the variance in cold‐pressor and 3% of the variance in heat pain. Environmental factors common to both modalities explained 5% of variance in cold‐pressor and 8% of the variance in heat pain. The remaining variance was due to factors that were specific to each pain modality. These findings demonstrate that cold‐pressor pain and contact heat pain are mainly distinct phenomena from both a genetic and an environmental standpoint. This may partly explain disparate results in genetic association studies and argues for caution in generalizing genetic findings from one pain modality to another. It also indicates that differences in pain scale usage account for a minor portion of the variance, providing strong support for the validity of subjective pain ratings as measures of experienced pain.

The Structure of Genetic and Environmental Risk Factors for DSM-IV Personality Disorders: A Multivariate Twin Study

CONTEXT Although both genetic and environmental factors affect risk of individual personality disorders (PDs), we know little of how they contribute to the pattern of comorbidity between the PDs in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV). OBJECTIVE To clarify the structure of the genetic and environmental risk factors for the 10 DSM-IV PDs. DESIGN Assessment of PDs at personal interview and multivariate twin modeling with the Mx program. SETTING General community. PARTICIPANTS A total of 2794 young adult members of the Norwegian Institute of Public Health Twin Panel. Main Outcome Measure Number of endorsed criteria for the 10 DSM-IV PDs. RESULTS The best-fit multivariate twin model required 3 genetic and 3 individual-specific environmental factors and genetic and individual-specific factors unique to each PD. The first genetic factor had high loadings on PDs from all 3 clusters including paranoid, histrionic, borderline, narcissistic, dependent, and obsessive-compulsive. The second genetic factor had substantial loadings only on borderline and antisocial PD. The third genetic factor had high loadings only on schizoid and avoidant PD. Several PDs had substantial disorder-specific genetic risk factors. The first, second, and third individual-specific environmental factors had high loadings on the cluster B, A, and C PDs, respectively, with 1 exception: obsessive-compulsive PD loaded with cluster B and not cluster C PDs. CONCLUSIONS Genetic risk factors for DSM-IV PDs do not reflect the cluster A, B, and C typology. Rather, 1 genetic factor reflects a broad vulnerability to PD pathology and/or negative emotionality. The 2 other genetic factors are more specific and reflect high impulsivity/low agreeableness and introversion. Unexpectedly, the cluster A, B, and C typology is well reflected in the structure of environmental risk factors, suggesting that environmental experiences may be responsible for the tendency of cluster A, B, and C PDs to co-occur.

Genetic and environmental influences on dimensional representations of DSM-IV cluster C personality disorders : a population-based multivariate twin study

BACKGROUND The DSM-IV cluster C Axis II disorders include avoidant (AVPD), dependent (DEPD) and obsessive-compulsive (OCPD) personality disorders. We aimed to estimate the genetic and environmental influences on dimensional representations of these disorders and examine the validity of the cluster C construct by determining to what extent common familial factors influence the individual PDs. METHOD PDs were assessed using the Structured Interview for DSM-IV Personality (SIDP-IV) in a sample of 1386 young adult twin pairs from the Norwegian Institute of Public Health Twin Panel (NIPHTP). A single-factor independent pathway multivariate model was applied to the number of endorsed criteria for the three cluster C disorders, using the statistical modeling program Mx. RESULTS The best-fitting model included genetic and unique environmental factors only, and equated parameters for males and females. Heritability ranged from 27% to 35%. The proportion of genetic variance explained by a common factor was 83, 48 and 15% respectively for AVPD, DEPD and OCPD. Common genetic and environmental factors accounted for 54% and 64% respectively of the variance in AVPD and DEPD but only 11% of the variance in OCPD. CONCLUSION Cluster C PDs are moderately heritable. No evidence was found for shared environmental or sex effects. Common genetic and individual environmental factors account for a substantial proportion of the variance in AVPD and DEPD. However, OCPD appears to be largely etiologically distinct from the other two PDs. The results do not support the validity of the DSM-IV cluster C construct in its present form.

Major depression and life satisfaction: A population-based twin study

BACKGROUND The extent to which positive and negative indicators of mental health share etiological influences has been studied to a limited degree only. This study examines the genetic and environmental influences on association between liability to lifetime DSM-IV Major Depressive Disorder (MDD) and dispositional life satisfaction (LS). METHODS Two-wave questionnaire data on LS (assessed 6 years apart) and lifetime MDD obtained by structured clinical interviews in a population-based sample of adult twins were analysed using structural equation modelling in Mx. RESULTS The prevalence of lifetime MDD was estimated to be 11.1% and 15.8% in males and females, respectively. Individuals fulfilling the criteria for MDD reported significantly lower levels of LS. The co-variation in MDD and dispositional LS was found to be accounted for by genetic and unique environmental influences only. The phenotypic correlation was estimated to be 0.36, of which genetic influences accounted for 74% and environmental factors the remaining 26%. The correlation between genetic factors for MDD and LS was estimated to be -0.55 and the correlation between unique environmental factors to be -0.22. Heritability was estimated to 0.34 and 0.72 for MDD and LS, respectively. LIMITATIONS The sample consists of twins only and there are limitations associated with the twin design. CONCLUSIONS Whereas genetic influences on vulnerability to lifetime MDD are considerably shared with liability to (low) LS, environmental influences are more distinct. Thus, environmental factors associated with risk of MDD do not strongly impact on dispositional LS, and conversely, environmental factors influencing dispositional LS do not strongly buffer against MDD.

Major depression and dimensional representations of DSM-IV personality disorders: a population-based twin study

BACKGROUND Major depressive disorder (MDD) co-occurs frequently with personality disorders (PDs). The extent to which this results from shared genetic or environmental risk factors remains uncertain. METHOD Young adult twins (n=2801) from the population-based Norwegian Institute of Public Health Twin Panel were assessed at personal interview for DSM-IV lifetime MDD and the 10 Axis II PDs. The relationship between MDD and dimensional representations of all PDs was explored by stepwise logistic regression. Multivariate Cholesky twin models were fitted using the Mx program, and genetic and environmental correlations were estimated. RESULTS Dimensional representations of borderline (BPD), avoidant (AVPD) and paranoid personality disorder (PPD) were independently and significantly associated with increased risk for MDD. Multivariate twin modeling indicated that one latent factor accounted for the genetic covariance between MDD and the three PDs. The genetic correlations between MDD and dimensional representations of BPD, AVPD and PPD were +0.56, +0.22 and +0.40 respectively. No sex differences or shared environmental effects were found. The structure of the individual-specific environmental factors influencing MDD and the three PDs were similar to the genetic factors but the environmental correlations were lower: +0.39, +0.23 and +0.27 respectively. CONCLUSIONS There is substantial overlap between liability factors for MDD and BPD from cluster B, PPD from cluster A and AVPD from cluster C. The vulnerability to general PD pathology and MDD seem to be closely related. The patterns of co-morbidity observed between diverse psychiatric disorders might result from just a few liability factors.

Structure of Genetic and Environmental Risk Factors for Symptoms of DSM-IV Borderline Personality Disorder

IMPORTANCE Previous studies have indicated that the psychopathological dimensions of borderline personality disorder (BPD) are influenced by a unitary liability factor. However, to our knowledge, the underlying etiological nature of the individual criteria for BPD as defined by the DSM-IV has not been explored. OBJECTIVE To determine the structure of genetic and environmental risk factors for the symptoms of BPD. DESIGN, SETTING, AND PARTICIPANTS Multivariate twin study with BPD criteria assessed by personal interview within a general community setting. Participants included 2794 young adults from the Norwegian Institute of Public Health Twin Panel. MAIN OUTCOMES AND MEASURES The 9 criteria for BPD assessed by the Structured Interview for DSM-IV Personality. RESULTS A common pathway model dominated by 1 highly heritable (55%) general BPD factor that strongly influenced all 9 BPD criteria (standardized path coefficients, 0.53-0.79) fit the data best. The model also included 2 additional common liability factors, mainly influencing criteria reflecting the affective and interpersonal dimensions. Both of these were mostly influenced by environmental liability factors (heritability, 29.3% and 2.2%). With 1 exception (criterion 2, unstable and intense relationships), the specific criteria were strongly influenced by environmental factors. Five of the 9 criterion-specific genetic effects were either 0 or negligible. CONCLUSIONS AND RELEVANCE These results indicate that most of the genetic effects on the individual BPD criteria derive from 1 highly heritable general BPD factor, whereas the environmental influences were mostly criterion specific.

Genetic and Environmental Contributions to Long-Term Sick Leave and Disability Pension: A Population-Based Study of Young Adult Norwegian Twins

Although exclusion from the workforce due to long-term sick leave (LTSL) and disability pension (DP) is a major problem in many Western countries, the etiology of LTSL and DP is not well understood. These phenomena have a strong association as most patients receiving DP have first been on LTSL. However, only a few of those on LTSL end up with DP. The present study aimed to investigate the common and specific genetic and environmental risk factors for LTSL and DP. The present study utilizes a population-based sample of 7,710 young adult twins from the Norwegian Institute of Public Health Twin Panel, which has been linked to the Historical-Event Database (FD-Trygd; 1998-2008). Univariate and bivariate twin models were fitted to determine to what degree genetic and environmental factors contribute to variation in LTSL and DP. The estimated heritabilities of LTSL and DP were 0.49 and 0.66, respectively. There was no evidence for shared environmental or sex-specific factors. The phenotypic-, genetic-, and non-familial environmental correlations between the variables were 0.86, 0.82, and 0.94, respectively. Our results indicate that familial transmission of LTSL and DP is due to genetic and not environmental factors. The risk factors contributing to LTSL and DP were mainly shared, suggesting that what increases risk for LTSL also increases risk for DP. However, a non-negligible part of the genetic variance was not shared between the variables, which may contribute to explaining why some progress from LTSL to DP, whereas others return to work.

Well-being and ill-being: shared environments, shared genes?

The nature of the associations between life satisfaction, anxiety, and depression remains elusive. Using questionnaire data from a large population-based sample (N = 6326) of young adult Norwegian twins (aged 18–31 years) we explored the extent to which latent genetic and environmental factors are (1) common or distinct, and (2) sex-specific. Phenotypic correlations ranged between 0.44 and 0.70 in females, and between 0.41 and 0.69 in males. Environmental influences accounted for 75% of these correlations in females, and less than 50% in males. Genetic and environmental sources of life satisfaction, symptoms of anxiety, and symptoms of depression were shared mostly, but the magnitude of the effects was different in males and females. In both sexes, however, aetiological factors enhancing life satisfaction were simultaneously protecting against feelings of sadness and displeasure, but contributed less to countervailing anxiety and tension.

The structure of genetic and environmental risk factors for phobias in women

BACKGROUND To explore the genetic and environmental factors underlying the co-occurrence of lifetime diagnoses of DSM-IV phobia. METHOD Female twins (n=1430) from the population-based Norwegian Institute of Public Health Twin Panel were assessed at personal interview for DSM-IV lifetime specific phobia, social phobia and agoraphobia. Comorbidity between the phobias were assessed by odds ratios (ORs) and polychoric correlations and multivariate twin models were fitted in Mx. RESULTS Phenotypic correlations of lifetime phobia diagnoses ranged from 0.55 (agoraphobia and social phobia, OR 10.95) to 0.06 (animal phobia and social phobia, OR 1.21). In the best fitting twin model, which did not include shared environmental factors, heritability estimates for the phobias ranged from 0.43 to 0.63. Comorbidity between the phobias was accounted for by two common liability factors. The first loaded principally on animal phobia and did not influence the complex phobias (agoraphobia and social phobia). The second liability factor strongly influenced the complex phobias, but also loaded weak to moderate on all the other phobias. Blood phobia was mainly influenced by a specific genetic factor, which accounted for 51% of the total and 81% of the genetic variance. CONCLUSIONS Phobias are highly co-morbid and heritable. Our results suggest that the co-morbidity between phobias is best explained by two distinct liability factors rather than a single factor, as has been assumed in most previous multivariate twin analyses. One of these factors was specific to the simple phobias, while the other was more general. Blood phobia was mainly influenced by disorder specific genetic factors.

Heritability of hearing loss.

Background: Hearing impairment is one of the most common permanent disabilities in the western world. Although hearing ability normally declines with age, there is great individual variation in age of onset, progression, and severity, indicating that individual susceptibility plays a role. The aim of the present study was to explore the relative importance of genetic and environmental effects in the etiology of impaired hearing. Methods: From August 1995 to June 1997, the total adult population of Nord-Trøndelag County, Norway, was invited to take part in the Nord-Trøndelag Health Study. The survey included as an integrated project the Nord-Trøndelag Hearing Loss Study with pure-tone audiometry assessment of the standard frequencies 0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz on 51,574 participants aged 20 to 101 years. We obtained information from Statistics Norway identifying 11,263 sibling pairs. After age stratification, we assessed similarity in hearing thresholds between siblings using polychoric correlations. The contribution of genetic effects in hearing ability was calculated. Results: The upper limit of the heritability of hearing loss was 0.36. We found little evidence for sex differences in the relative importance of genetic effects. Conclusions: There is a substantial genetic contribution to individual variation in hearing thresholds.