High-risk Twins Research Articles

The Enrichment Study of the Minnesota Twin Family Study: Increasing the Yield of Twin Families at High Risk for Externalizing Psychopathology

The Enrichment Study (ES) was designed to extend the Minnesota Twin Family Study (MTFS) by oversampling 11-year-old twins at especially high risk for substance use disorders by virtue of having a childhood disruptive disorder. The sample was ascertained from Minnesota birth records. To identify high-risk twins, we conducted telephone screening interviews for parent-reported symptoms of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) as well as indications of academic disengagement. Twins who exceeded a predetermined threshold were invited to participate. To facilitate comparison with the previously ascertained MTFS participants, a random sample of 11-year-old twins was also recruited. As part of the ES study, 499 twin pairs, and their parents, visited the University of Minnesota, where each participant completed a clinical interview, psychophysiological evaluation, and thorough assessment of environmental risk. We were highly successful in recruiting at-risk twins; 52% of the screened male twins and 41% of the screened females met criteria for a diagnosis of ADHD, CD, or oppositional defiant disorder (ODD). At the pair level, 63% of the screened pairs had at least one member with a childhood disruptive disorder. This article provides an overview of the study design and includes a review of recent findings using this sample of twins.

Salivary cortisol in unaffected twins discordant for affective disorder

Dysfunction in the hypothalamic–pituitary–adrenal (HPA) axis has been proposed as a biological endophenotype for affective disorders. In the present study the hypothesis that a high genetic liability to affective disorder is associated with higher cortisol levels was tested in a cross-sectional high-risk study. Healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. Awakening and evening salivary cortisol levels were compared between the 190 High- and Low-Risk twins. The 109 High-Risk twins had significantly higher evening cortisol levels than the 81 Low-Risk MZ twins, also after adjustment for age, sex, and the level of subclinical depressive symptoms. No significant difference was found in awakening cortisol levels between High-Risk and Low-Risk twins. In conclusion, a high genetic liability to affective disorder was associated with a higher evening cortisol level, but not with awakening cortisol level. Future prospective family, high-risk and twin studies are needed to decide whether abnormalities in the HPA axis can be identified as an endophenotype of affective disorder.

Amygdala responses to emotional faces in twins discordant or concordant for the risk for anxiety and depression

BackgroundFunctional brain imaging studies have shown deviant amygdala responses to emotional stimuli in subjects suffering from anxiety and depressive disorder, but both hyperactivity and hypoactivity compared to healthy controls have been reported. To account for these discrepant findings, we hypothesize that genetic and environmental risk factors differently impact on amygdala functioning. MethodsTo test this hypothesis, we assessed amygdala responses to an emotional faces paradigm during functional magnetic resonance imaging in monozygotic twin pairs discordant for the risk of anxiety and depression (n=10 pairs) and in monozygotic twin pairs concordant for high (n=7 pairs) or low (n=15 pairs) risk for anxiety and depression. ResultsMain effects (all faces vs. baseline) revealed robust bilateral amygdala activity across groups. In discordant twins, increased amygdala responses were found for negatively valenced stimuli (angry/anxious faces) in high-risk twins compared to their low-risk co-twins. In contrast, concordant high-risk pairs revealed blunted amygdala reactivity to both positive and negative faces compared with concordant low-risk pairs. Post-hoc analyses showed that these findings were independent of 5-HTTLPR genotype. ConclusionsOur findings indicate amygdala hyperactivity in subjects who are at high risk for anxiety and depression through environmental factors and amygdala hypoactivity in those at risk mainly through genetic factors. We suggest that this result reflects a difference in baseline amygdala activation in these groups. Future imaging studies on anxiety and depression should aim to avoid admixture of subjects who are at genetic risk with those at risk due to environmental factors.

Personality traits in unaffected twins discordant for affective disorder

To examine whether a high genetic liability to develop affective disorder is associated with specific personality traits. A cross-sectional, high-risk, case-control study. Through nation-wide registers, healthy monozygotic (MZ) and dizygotic (DZ) twins with (high-risk twins) and without (the control group/low-risk twins) a co-twin history of affective disorder were identified. Personality traits were compared for a total of 211 high-risk and low-risk twins. In univariate analyses, the high-risk twins had a higher level of neuroticism than the control twins (P = 0.03). In multivariate analyses, a high genetic liability to affective disorder was not significantly associated with neuroticism but correlated to sex, minor psychopathology and recent life events. A high genetic liability to affective disorder showed an association with neuroticism, but the association interacts with other predictors of affective disorder such as female gender, minor psychopathology and recent adversity.

A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: Evidence for genetic and environmental heterogeneity in the developing brain

Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the etiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes, we performed Voxel-Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high-risk for ADHD. Brain differences between concordant high-risk twin pairs and concordant low-risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low-risk and high-risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low-risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high-risk pairs showed volume loss in orbitofrontal subdivisions. High-risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high-risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed action-attentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) vs. environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD.

Quality of life in unaffected twins discordant for affective disorder

Background The disability and hardship associated with affective disorder is shared by the family members of affective patients and might affect the family member's quality of life. Method In a cross-sectional, high-risk, case–control study, monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. The aim of the present study was to investigate the hypothesis that a genetic liability to affective disorder is associated with a lower perception of quality of life. Results Univariate analyses showed that quality of life in all domains was impaired for the 121 High-Risk twins compared to the 84 Low-Risk twins. In multiple regression analyses, the differences remained significant after adjustment for sex, age, marital status and years of education. Adjusted for the effect of subclinical anxiety and depressive symptoms, the differences were significant on the domain environment and total WHOQoL-BREF and marginally significant on the domain physical health and overall quality of life. Limitations It is not possible from the cross-sectional analyses to distinguish between subsyndromal state and trait scores. Conclusions Perceived health related quality of life might share common familial vulnerability with affective disorders. Having a co-twin with affective disorder seem to have a negative influence on quality of life of the healthy co-twin and this influence might be due to the genetic liability to affective disorder. These findings need to be replicated in future family studies.

Cognitive function in unaffected twins discordant for affective disorder

Patients may present with cognitive impairment in the euthymic phase of affective disorder, but it is unclear whether the impairment is prevalent before onset of the illness. The aim of the present study was to examine the hypothesis that genetic liability to affective disorder is associated with cognitive impairment. In a cross-sectional high-risk case-control study, healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. Cognitive performance of 203 High-Risk and Low-Risk twins was compared. Healthy twins discordant for unipolar disorder showed lower performance on almost all measures of cognitive function: selective and sustained attention, executive function, language processing and working and declarative memory, and also after adjustment for demographic variables, subclinical symptoms and minor psychopathology. Healthy twins discordant for bipolar disorder showed lower performance on tests measuring episodic and working memory, also after adjustment for the above-mentioned covariables. The discrete cognitive impairment found seemed to be related to genetic liability, as the MZ High-Risk twins showed significant impairment on selective and sustained attention, executive function, language processing and working and declarative memory, whereas the DZ High-Risk twins presented with significantly lower scores only on language processing and episodic memory. The hypothesis that discrete cognitive impairment is present before the onset of the affective disorder and is genetically transmitted was supported. Thus, cognitive function may be a candidate endophenotype for affective disorders.

Subclinical psychopathology and socio-economic status in unaffected twins discordant for affective disorder

Background The most potent risk factor for affective disorders is a family history of affective disorder but the specific factors that are transmitted in families are unknown. It is possible to investigate the relation between risk factors and affective disorder by using a high-risk design e.g.: a study of the healthy relatives of patients with affective disorders. Aim To compare psychopathology and socio-economic status between twins with a co-twin history of affective disorder and twins without. Methods In a cross-sectional high-risk case-control study, healthy monozygotic and dizygotic twins with (High-Risk twins) and without (Low-Risk twins) a co-twin history of affective disorder were identified through nation-wide registers. Participants were assessed using semi-structured psychiatric interviews and self-rating of psychopathology. Results High-Risk twins had a lower education level, a lower work position and tendency towards being more often unemployed and early retired than the Low-Risk twins. Furthermore, they presented higher rates of subclinical affective symptoms and were more likely to experience a minor psychiatric diagnosis. Conclusion Healthy twins with a high genetic liability to affective disorder seem to present lower socio-economic status, higher rates of subclinical affective symptoms and more often experience a minor psychiatric diagnosis than twins with no familial history of affective disorder. It is not possible from the present cross-sectional data to determine the causality of these findings, thus genetic liability to affective disorder, socio-economic status and minor psychopathology seem to have a complex interrelation.

Early developmental progress of preterm twins discordant for birthweight and risk.

Studies of developmental progress in high-risk twins have disparate findings. In this study, we report the outcome of 45 twin pairs born between 26 and 37 weeks gestation, and whose birthweights ranged from 840 to 2000 g. No significant differences were found for weight, risk and birth order. However, earlier preterm infants were found to have significantly lower mental scores on the Bayley Scales of Infant Development at 24 months, and lower IQ scores on the Stanford Binet Intelligence Scale at 36 months. These findings imply that gestational age is a powerful variable in determining developmental outcome.