The TWIN-E Project in Emotional Wellbeing: Study Protocol and Preliminary Heritability Results Across Four MRI and DTI Measures

Abstract

Despite the significant advancements being made in the neurogenetics for mental health, the identification and validation of potential endophenotype markers of risk and resilience remain to be confirmed. The TWIN-E study (The Twin study in Wellbeing using Integrative Neuroscience of Emotion) aims to validate endophenotype markers of mental health across cognitive, brain, and autonomic measures by testing the heritability, clinical plausibility, and reliability of each of these measures in a large adult twin cohort. The specific gene and environmental mechanisms that moderate prospective links between endophenotypephenotype markers and the final outcome of wellbeing will also be identified. TWIN-E is a national prospective study with three phases: I) baseline testing on a battery of online questionnaires and cognitive tasks, and EEG, MRI, and autonomic testing; II) 12-month follow-up testing on the online assessments; and III) randomized controlled trial of brain training. Minimum target numbers include 1,500 male/female twins (18-65 years) for the online assessments (Phase I and II), 300 twins for the EEG testing component, and 244 twins for the MRI testing component. For Phase III, each twin out of the pair will be randomized to either the treatment or waitlist control group to test the effects of brain training on mental health over a 30-day period, and to confirm the gene-environment and endophenotype contributions to treatment response. Preliminary heritability results are provided for the first 50% of the MRI subgroup (n = 142) for the grey matter volume, thickness, and surface area measures, and white matter diffuse tensor imaging fractional anisotropy.

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA–DTI working group

“…A mean measure from these specific regions or tracts may serve as a good endophenotype, by independently showing high heritability for at least one of the measures (Brouwer et al, 2010; Gatt et al, 2012) (although these studies also found high heritability elsewhere as well), by showing genetic associations with white matter alterations in one or more of these regions (Barnes et al, 2012; Sprooten et al, 2011b) or by associating the mean measure to a genetically-mediated disease such as Rett Syndrome (Mahmood et al, 2010), psychosis (Karlsgodt et al, 2009) or schizophrenia (Clark et al, 2011). …”

Genetics of brain structure: Contributions from the vietnam era twin study of aging

“…Of the remaining 12 with both MZ and DZ twin pairs, the median sample size was 64 (range: 28–284). Including our sample [Panizzon et al, 2009, 2012a] and five other more recent samples [Gilmore et al, 2010; Chiang et al, 2011; Gatt et al, 2012; Yoon et al, 2012; van Soelen et al, 2012], there are 18 samples with both MZ and DZ twins; these 18 have a median sample size of 137 twins (range: 28–603). Out of the total of 25 samples, only three have more than 300 twins, and six now have more than 200.…”

Australian Twin Registry: 30 Years of Progress

“…White-matter of the brain has higher heritability than gray-matter. This has led to a randomized controlled trial to study the effect of targeted brain training to boost resilience (Gatt et al, 2012). Bone density Calcium supplementation increases bone density over 12-18 months but these gains were not maintained to 2 years (Cameron et al, 2004).…”