Major Research Focus
The Twin Interdisciplinary Neuroticism Study (TWINS) is a three-wave study including >800 twin pairs from the northern part of the Netherlands (see Appendix A Table A1 for an overview of the study). The aim of the study is to unravel why neuroticism is a marker of vulnerability to affective disorders (e.g., depression and anxiety). The unique aspect of this twin study is the a priori selection of studied underlying mechanisms that may (partly) explain neuroticism's association with affective disorders. We hypothesize that biased cognitions for negative (emotional) stimuli and the major physiological stress mechanisms (cardiac autonomic nervous system and the hypothalamus-pituitary adrenal axis function) represent mechanisms that underlie the relationship between neuroticism and onset, maintenance, or recurrence of affective disorders. More specifically, we hypothesize that cognitive deviations in capacities for decoding and encoding negative (emotional) stimuli (Rijsdijk et al., Reference Rijsdijk, Riese, Tops, Snieder, Brouwer, Smid and Ormel2009), and deregulated physiological stress mechanisms account for part of the association (Riese et al., Reference Riese, Rosmalen, Ormel, van Roon, Oldehinkel and Rijsdijk2007, Reference Riese, Rijsdijk, Rosmalen, Snieder and Ormel2009). Classic behavioral genetic analyses were used to test if a single common genetic factor can account for the phenotypic correlation between neuroticism, and each of the cognitive and physiological stress measures.
Recruitment and Zygosity Determination
The sample for TWINS was selected from the Groningen Twin Register (GTR). To establish the GTR, in 2001 nine municipalities with more than 31,000 inhabitants in the north of The Netherlands were requested to provide addresses of inhabitants born between 1972 and 1992, from the same mother with an identical date of birth. All the twins identified in this way received an invitation to participate in the GTR. In 2002 (T1), 1,047 participants filled out a survey, which included, among others, a zygosity questionnaire (Nichols & Bilbro, Reference Nichols and Bilbro1966) and the NEO Five Factor Inventory (NEO-FFI) neuroticism scale (Hoekstra et al., Reference Hoekstra, Ormel and De Fruyt1996). In 2003 (T2), 125 female twin pairs aged between 18 and 30 years old were invited to visit our psychophysiological laboratory to perform various tasks (Riese et al., Reference Riese, Rijsdijk, Ormel, van Roon, Neeleman and Rosmalen2006; Rijsdijk et al., Reference Rijsdijk, Riese, Tops, Snieder, Brouwer, Smid and Ormel2009). At T2, neuroticism was evaluated again with the NEO-FFI inventory, and additionally with the Eysenck Personality Questionnaire (Sanderman et al., Reference Sanderman, Eysenck and Arrindell1991), along with a co-twin report on the earlier mentioned NEO-FFI scale. Zygosity of this target group was determined using 10 micro-satellite markers. Due to technical failures, zygosity of three twin pairs could not be determined by DNA genotyping; for these pairs, survey data on zygosity were used instead. In 2006, all registered and additionally recruited twins aged 15–35 (N = 1,128) were asked to fill out a survey, which 815 (72%) twins returned. This survey included a zygosity questionnaire (Nichols & Bilbro, Reference Nichols and Bilbro1966), and four facets (hostility, self-consciousness, impulsiveness, and vulnerability) of the neuroticism scales of the NEO-PI-R inventory (Hoekstra et al., Reference Hoekstra, Ormel and De Fruyt1996). A more detailed overview of the measures assessed is given in Table 1.
TABLE 1 Overview of Measures Assessed in the Groningen Twin Register (GTR) and Twin Interdisciplinary Neuroticism Study (TWINS)
Major Achievements
The genetic relationship between neuroticism and the psychophysiological variables and cognitive deviations were tested. The psychophysiological variables measured were the cortisol awakening response (CAR) and cardiovascular measures (inter-beat interval, heart rate variability [HRV] and baroreflexsensitivity [BRS]). Neuroticism and the CAR were both found to be heritable, but did not share any genetic influences (Riese et al., Reference Riese, Rijsdijk, Rosmalen, Snieder and Ormel2009). The three cardiovascular measures were found to be heritable (Riese et al., Reference Riese, Rijsdijk, Ormel, van Roon, Neeleman and Rosmalen2006, Reference Riese, Rosmalen, Ormel, van Roon, Oldehinkel and Rijsdijk2007). Neuroticism was moderately negatively correlated with BRS and HRV. For BRS, this correlation with neuroticism was entirely determined by shared genetic influences; for HRV largely by genetic influences. We concluded that high neuroticism is associated with a deregulated cardiac autonomic nervous system, which may be partly due to pleiotropic genetic effects. Cognitive deviations were measured by means of cognitive tasks tapping into memory recall bias and an attention bias for emotional stimuli (Rijsdijk et al., Reference Rijsdijk, Riese, Tops, Snieder, Brouwer, Smid and Ormel2009). At the higher end of the distribution of the neuroticism scale, neuroticism was correlated with the proportion of recalled unpleasant words. This effect was due to shared environmental influences, rather than genetic influences. There was no evidence that the cognitive predisposition to focus on negative (emotional) stimuli is a possible underlying genetic mechanism of neuroticism.
Future Plans
From the target group (e.g., the 125 female twin pairs) DNA was isolated and both candidate gene and genome-wide genotyping were conducted. Future works include candidate gene studies and the study participates in several meta-genome-wide association study consortia.
Appendix A
TABLE A1 Overview of the Twin Interdisciplinary Neuroticism Study (TWINS)
