High-risk Twins Research Articles

Emotional Mental Imagery Abnormalities in Monozygotic Twins With, at High-Risk of, and Without Affective Disorders: Present in Affected Twins in Remission but Absent in High-Risk Twins.

Background: Mental imagery abnormalities feature across affective disorders including bipolar disorder (BD) and unipolar depression (UD). Maladaptive emotional imagery has been proposed as a maintenance factor for affective symptomatology and a target for mechanism-driven psychological treatment developments. Where imagery abnormalities feature beyond acute affective episodes, further opportunities for innovation arise beyond treatments, such as for tertiary/relapse prevention (e.g., in remitted individuals) or primary prevention (e.g., in non-affected but at-risk individuals). The aim of our study was to investigate for the first time the presence of possible mental imagery abnormalities in affected individuals in remission and at-risk individuals for affective disorders using a familial risk design. Methods: A population-based cohort of monozygotic twins was recruited through linkage between the Danish national registries (N=204). Participants were grouped as: affected (remitted BD/UD; n = 115); high-risk (co-twin with history of BD/UD; n = 49), or low-risk (no co-twin history of BD/UD; n = 40). Twins completed mental imagery measures spanning key subjective domains (spontaneous imagery use and emotional imagery) and cognitive domains (imagery inspection and imagery manipulation). Results: Affected twins in remission reported enhanced emotional mental imagery compared to both low- and high-risk twins. This was characterized by greater impact of i) intrusive prospective imagery (Impact of Future Events Scale) and ii) deliberately-generated prospective imagery of negative scenarios (Prospective Imagery Task). There were no significant differences in these key measures between affected BD and UD twins in remission. Additionally, low- and high-risk twins did not significantly differ on these emotional imagery measures. There were also no significant differences between the three groups on non-emotional measures including spontaneous imagery use and cognitive stages of imagery. Conclusions: Abnormalities in emotional prospective imagery are present in monozygotic twins with affective disorders in remission—despite preserved cognitive stages of imagery—but absent in unaffected high-risk twins, and thus do not appear to index familial risk (i.e., unlikely to qualify as “endophenotypes”). Elevated emotional prospective imagery represents a promising treatment/prevention target in affective disorders.

Neural response to emotional faces in monozygotic twins: association with familial risk of affective disorders

Aberrant neural and cognitive response to emotional faces has been observed in people at familial risk of an affective disorder. In this functional MRI study of monozygotic twins, we explored neural correlates of the attentional avoidance of emotional faces that we had previously observed in high-risk versus affected twins, and whether an abnormal neural response to emotional faces represents a risk endophenotype. We recruited unaffected monozygotic twins with a co-twin history of mood episodes (high-risk), monozygotic twins with previous mood episodes (affected) and monozygotic twins with no personal or first-degree history of mood episodes (low-risk) between December 2014 and January 2017 based on a nationwide register linkage. Participants viewed fearful and happy faces while performing a gender discrimination task during functional MRI (fMRI) and performed emotional faces dot-probe and facial expression recognition tasks outside the scanner. A total of 129 monozygotic twins underwent whole-brain fMRI. Highrisk twins (n = 38) displayed greater medial and superior prefrontal response to emotional faces than affected twins (n = 62). This greater activity correlated with stronger attentional avoidance of emotional faces in high-risk twins. In contrast, high-risk and affected twins showed no aberrant neural activity to emotional faces compared with low-risk twins (n = 29). A limitation of this study was its cross-sectional design. Greater recruitment of the medial and superior prefrontal cortex during implicit emotion processing in high-risk versus affected twins may represent a compensatory or resilience mechanism. In contrast, aberrant neural response to emotional faces does not seem to be a risk endophenotype for affective disorders.

Clinical Characteristics, Life Adversities and Personality Traits in Monozygotic Twins With, at Risk of and Without Affective Disorders.

Background: Affective disorders have a long-term impact on psychiatric health and are caused by multiple interacting factors including familial risk, childhood adversity, life events and personality traits.Methods: In this study, monozygotic twins (MZ) at familial risk (indexed by affective disorder in their co-twin; high-risk group), affected MZ twins (indexed by a diagnosis with affective disorder) and MZ twins with no family history of affective disorder (low-risk group) were identified through cross-linking of nation-wide Danish registers. In total, 204 MZ twins were included and psychopathology, personality traits and life adversity were evaluated by semi-structured interviews and questionnaires.Results: Affected MZ twins presented with more subclinical affective symptoms and were functionally impaired as evidenced by higher unemployment rates and reduced functional status. The affected and the high-risk groups reported more childhood adversity and had experienced more stressful life events than the low-risk group. A direct comparison within the discordant twin pairs showed that the high-risk twins presented fewer affective symptoms, better functional status, more extraversion and lower neuroticism scores than their affected co-twins although they had equal levels of life adversity as their affected co-twins.Conclusion: These findings add to the evidence indicating that patients experience higher neuroticism, persistent subclinical symptoms and reduced socio-occupational function after affective episodes. Additionally, neuroticism and extraversion seem capable of moderating the sensitivity to exposure from the environment.

Is aberrant affective cognition an endophenotype for affective disorders? - A monozygotic twin study.

Identification of endophenotypes can improve prevention, detection and development of new treatments. We therefore investigated whether aberrant affective cognition constitutes an endophenotype for affective disorders by being present in monozygotic (MZ) twins with unipolar or bipolar disorder in partial remission (i.e. affected) and their unaffected co-twins (i.e. high-risk) relative to twins with no family history of affective disorder (i.e. low-risk). We conducted an assessor blind cross-sectional study from 2014 to 2017 of MZ twins using Danish population-based registers in recruitment. Twins attended one test session involving neurocognitive testing, clinical ratings and questionnaires. Main outcomes were attention to and recognition of emotional facial expressions, the memory of emotional self-referential words, emotion regulation and coping strategies. Participants were 103 affected, 44 high-risk and 36 low-risk MZ twins. Groups were demographically well-balanced and showed comparable non-affective cognitive performance. We observed no aberrant affective cognition in affected and high-risk relative to low-risk twins. However, high-risk twins displayed attentional avoidance of emotional faces (ps ⩽ 0.009) and more use of task-oriented coping strategies (p = 0.01) compared with affected twins. In contrast did affected twins show more emotion-oriented coping than high- and low-risk twins (ps ⩽ 0.004). Our findings provide no support of aberrant affective cognition as an endophenotype for affective disorders. High-risk twins' attentional avoidance of emotional faces and greater use of task-oriented coping strategies may reflect compensatory mechanisms.

Increased sensitivity to positive social stimuli in monozygotic twins at risk of bipolar vs. unipolar disorder

BackgroundAbnormalities in affective cognition are putative endophenotypes for bipolar and unipolar disorders but it is unclear whether some abnormalities are disorder-specific. We therefore investigated affective cognition in monozygotic twins at familial risk of bipolar disorder relative to those at risk of unipolar disorder and to low-risk twins. MethodsSeventy monozygotic twins with a co-twin history of bipolar disorder (n = 11), of unipolar disorder (n = 38) or without co-twin history of affective disorder (n = 21) were included. Variables of interest were recognition of and vigilance to emotional faces, emotional reactivity and -regulation in social scenarios and non-affective cognition. ResultsTwins at familial risk of bipolar disorder showed increased recognition of low to moderate intensity of happy facial expressions relative to both unipolar disorder high-risk twins and low-risk twins. Bipolar disorder high-risk twins also displayed supraliminal attentional avoidance of happy faces compared with unipolar disorder high-risk twins and greater emotional reactivity in positive and neutral social scenarios and less reactivity in negative social scenarios than low-risk twins. In contrast with our hypothesis, there was no negative bias in unipolar disorder high-risk twins. There were no differences between the groups in demographic characteristics or non-affective cognition. LimitationsThe modest sample size limited the statistical power of the study. ConclusionsIncreased sensitivity and reactivity to positive social stimuli may be a neurocognitive endophenotype that is specific for bipolar disorder. If replicated in larger samples, this ‘positive endophenotype’ could potentially aid future diagnostic differentiation between unipolar and bipolar disorder.

Risk for affective disorders is associated with greater prefrontal gray matter volumes: A prospective longitudinal study.

BackgroundMajor depression and bipolar disorders aggregates in families and are linked with a wide range of neurobiological abnormalities including cortical gray matter (GM) alterations. Prospective studies of individuals at familial risk may expose the neural mechanisms underlying risk transmission.MethodsWe used voxel based morphometry to investigate changes in regional GM brain volume, over a seven-year period, in 37 initially healthy individuals having a mono- or di-zygotic twin diagnosed with major depression or bipolar disorder (high-risk group; mean age 41.6 yrs.) as compared to 36 individuals with no history of affective disorders in the index twin and first-degree relatives (low-risk group; mean age 38.5 yrs.).ResultsGroups did not differ in regional GM volume changes over time. However, independent of time, high-risk twins had significantly greater GM volumes in bilateral dorsal anterior cingulate, inferior frontal gyrus and temporoparietal regions as compared to low-risk twins. Further, individuals who developed an affective disorder at follow-up (n = 12), had relatively the largest GM volumes, both at baseline and follow-up, in the right dorsal anterior cingulate cortex and right inferior frontal cortex compared to high- and low-risk twins who remained well at follow-up.ConclusionThis pattern of apparently stable grater regional GM volume may constitute a neural marker of an increased risk for developing an affective disorder in individuals at familial risk.

Is negative self-referent bias an endophenotype for depression? An fMRI study of emotional self-referent words in twins at high vs. low risk of depression

BackgroundNegative cognitive bias and aberrant neural processing of self-referent emotional words seem to be trait-marks of depression. However, it is unclear whether these neurocognitive changes are present in unaffected first-degree relatives and constitute an illness endophenotype. MethodsFifty-three healthy, never-depressed monozygotic or dizygotic twins with a co-twin history of depression (high-risk group: n = 26) or no first-degree family history of depression (low-risk group: n = 27) underwent neurocognitive testing and functional magnetic imaging (fMRI) as part of a follow-up cohort study. Participants performed a self-referent emotional word categorisation task and free word recall task followed by a recognition task during fMRI. Participants also completed questionnaires assessing mood, personality traits and coping strategies. ResultsHigh-risk and low-risk twins (age, mean ± SD: 40 ± 11) were well-balanced for demographic variables, mood, coping and neuroticism. High-risk twins showed lower accuracy during self-referent categorisation of emotional words independent of valence and more false recollections of negative words than low-risk twins during free recall. Functional MRI yielded no differences between high-risk and low-risk twins in retrieval-specific neural activity for positive or negative words or during the recognition of negative versus positive words within the hippocampus or prefrontal cortex. ConclusionsThe subtle display of negative recall bias is consistent with the hypothesis that self-referent negative memory bias is an endophenotype for depression. High-risk twins’ lower categorisation accuracy adds to the evidence for valence-independent cognitive deficits in individuals at familial risk for depression.

Differences in neural and cognitive response to emotional faces in middle-aged dizygotic twins at familial risk of depression.

Negative bias and aberrant neural processing of emotional faces are trait-marks of depression but findings in healthy high-risk groups are conflicting. Healthy middle-aged dizygotic twins (N = 42) underwent functional magnetic resonance imaging (fMRI): 22 twins had a co-twin history of depression (high-risk) and 20 were without co-twin history of depression (low-risk). During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping. Unexpectedly, high-risk twins showed reduced fear vigilance and lower recognition of fear and happiness relative to low-risk twins. During face processing in the scanner, high-risk twins displayed distinct negative functional coupling between the amygdala and ventral prefrontal cortex and pregenual anterior cingulate. This was accompanied by greater fear-specific fronto-temporal response and reduced fronto-occipital response to all emotional faces relative to baseline. The risk groups showed no differences in mood, subjective state or coping. Less susceptibility to fearful faces and negative cortico-limbic coupling during emotional face processing may reflect neurocognitive compensatory mechanisms in middle-aged dizygotic twins who remain healthy despite their familial risk of depression.

Healthy co-twins of patients with affective disorders show reduced risk-related activation of the insula during a monetary gambling task.

Healthy first-degree relatives of patients with affective disorders are at increased risk for affective disorders and express discrete structural and functional abnormalities in the brain reward system. However, value-based decision making is not well understood in these at-risk individuals. We investigated healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorders (high-risk and low-risk groups, respectively) using functional MRI during a gambling task. We assessed group differences in activity related to gambling risk over the entire brain. We included 30 monozygotic and 37 dizygotic twins in our analysis. Neural activity in the anterior insula and ventral striatum increased linearly with the amount of gambling risk in the entire cohort. Individual neuroticism scores were positively correlated with the neural response in the ventral striatum to increasing gambling risk and negatively correlated with individual risk-taking behaviour. Compared with low-risk twins, the high-risk twins showed a bilateral reduction of risk-related activity in the middle insula extending into the temporal cortex with increasing gambling risk. Post hoc analyses revealed that this effect was strongest in dizygotic twins. The relatively old average age of the mono- and dizygotic twin cohort (49.2 yr) may indicate an increased resilience to affective disorders. The size of the monozygotic high-risk group was relatively small (n = 13). The reduced processing of risk magnitude in the middle insula may indicate a deficient integration of exteroceptive information related to risk-related cues with interoceptive states in individuals at familial risk for affective disorders. Impaired risk processing might contribute to increased vulnerability to affective disorders.

Different neural and cognitive response to emotional faces in healthy monozygotic twins at risk of depression.

Negative cognitive bias and aberrant neural processing of emotional faces are trait-marks of depression. Yet it is unclear whether these changes constitute an endophenotype for depression and are also present in healthy individuals with hereditary risk for depression. Thirty healthy, never-depressed monozygotic (MZ) twins with a co-twin history of depression (high risk group: n=13) or without co-twin history of depression (low-risk group: n=17) were enrolled in a functional magnetic resonance imaging (fMRI) study. During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping strategies. High-risk twins showed increased neural response to happy and fearful faces in dorsal anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), pre-supplementary motor area and occipito-parietal regions compared to low-risk twins. They also displayed stronger negative coupling between amygdala and pregenual ACC, dmPFC and temporo-parietal regions during emotional face processing. These task-related changes in neural responses in high-risk twins were accompanied by impaired gender discrimination performance during face processing. They also displayed increased attention vigilance for fearful faces and were slower at recognizing facial expressions relative to low-risk controls. These effects occurred in the absence of differences between groups in mood, subjective state or coping. Different neural response and functional connectivity within fronto-limbic and occipito-parietal regions during emotional face processing and enhanced fear vigilance may be key endophenotypes for depression.

EPA-0403 - Healthy individuals at familial risk for depression show stronger activation of left insular cortex with riskiness of choices

Healthy first-degree relatives to patients with depression have increased risk for developing depression and show brain structure and response anomalies in regions responsible for processing rewards. However, inherent behavioral and neural abnormalities related to valuebased decision making have not been explored in these individuals. To address this, in a functional MRI study we investigated healthy mono- or dizygotic twins with or without a co-twin history of depression (high risk: n=36 and low-risk: n=31, respectively). Using SPSS10 and SPM8 statistical packages we compared behavioral and neural responses to gambling choices of twins at increased familial risk with twins without familial risk for depression. We found no differences in risk choice behavior between high- and low-risk twins. Across groups, increased behavioral risk correlated with response in anterior and posterior cingulate cortex, ventral striatum, insula and raphe nucleus, as expected. Compared with twins at low risk, high-risk twins showed increased activation of left insula with increasingly risky choices (Fig1). Healthy individuals at high hereditary risk for depression show elevated activity in left insula when making high-risk choices, region previously found to be causally involved in value-based decision-making by promoting risk taking. This might indicate a higher neural effort in these individuals during risk taking.

Serotonin transporter genotype, salivary cortisol, neuroticism and life events: Impact on subsequent psychopathology in healthy twins at high and low risk for affective disorder

To investigate if cortisol alone or in interaction with other risk factors (familial risk, the serotonin transporter genotype, neuroticism and life events (LEs)) predicts onset of psychiatric disorder in healthy individuals at heritable risk. In a high-risk study, 234 healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorder (high and low risk twins) were baseline assessed. Participants were followed up for seven years and then reassessed with a personal interview revealing whether they had developed psychiatric illness. 36 participants (15.4%) developed psychiatric disorder. Using Cox proportional hazards ratio (HR) estimates neither morning nor evening salivary cortisol at baseline did predict illness onset. In multivariate Cox models, the two-way interaction between morning cortisol and LEs lifetime before baseline was significantly associated with onset. Further, the HR of onset was higher concerning individuals carrying the short allele of the 5-HTTPLR and having experienced more LEs lifetime. Familial risk for affective disorder predicted illness and the risk of onset was further increased in individuals at familial risk carrying the short allele of the 5-HTTPLR. Cortisol levels alone do not increase the risk of onset of psychiatric illness but the interaction of a lower cortisol level and the experience of more LEs do. The 5-HTTLPR genotype seems to interact and contribute to increased stress vulnerability in combination with other stress indicators of illness thereby adding to the risk of subsequent psychopathology.

Brain Derived Neurotrophic Factor (BDNF) levels as a possible predictor of psychopathology in healthy twins at high and low risk for affective disorder

Brain Derived Neurotrophic Factor (BDNF) is a potential biomarker of affective disorder. However, longitudinal studies evaluating a potential predictive role of BDNF on subsequent psychopathology are lacking. The aim of this study was to investigate whether BDNF alone or in interaction with the BDNF Val66Met polymorphism predict onset of affective disorder in healthy individuals at heritable risk for affective disorder. In a high-risk study, we assessed whole blood levels of BDNF in 234 healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorder (high and low risk twins, respectively). Participants were followed up longitudinally with questionnaires at 6-month intervals for mean seven years and then reassessed with a personal interview to obtain information about whether they had developed psychiatric illness. At follow-up 36 participants (15.4%) had developed psychiatric disorder. Cox regression analysis revealed that BDNF levels at baseline were not associated with onset of illness in this explorative study. Further, two-way interactions between BDNF levels and the Val66Met polymorphism or between familial risk and the Val66Met polymorphism did not predict illness onset.

Impairment of Executive Function and Attention Predicts Onset of Affective Disorder in Healthy High-Risk Twins

To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk. In a high-risk study, 234 healthy monozygotic and dizygotic twins with and without a co-twin history of affective disorder (high- and low-risk twins, respectively) were identified through nationwide registers and assessed at baseline using the Schedules for Clinical Assessment in Neuropsychiatry, the 17-item Hamilton Depression Rating Scale (HDRS), and the cognitive tests Trail Making Test Parts A and B, the Stroop test, and the Cambridge Cognitive Examination-Revised (CAMCOR). Participants were followed longitudinally at 6-month intervals for up to 9 years and finally reassessed with a personal interview to obtain information on whether they had developed psychiatric illness. The study was conducted between 2003 and 2012. 36 participants (15.4%) developed psychiatric disorder, mainly affective and anxiety disorders (31 diagnoses) (ICD-10). Onset was predicted by decreased executive function as reflected by performance on the Trail Making Test A - B (hazard ratio [HR] = 1.02; 95% CI, 1.00-1.03) when adjusted for sex, age, years of education and HDRS score at baseline. Reduced global cognitive function as indicated by a lower CAMCOR score at baseline showed a trend toward an association with subsequent illness onset (P = .08). With regard to the 5 CAMCOR subscales, lower scores on attention (HR = 0.71; 95%, CI, 0.54-0.94) and language (HR = 0.76; 95% CI, 0.58-0.99) were significantly associated with subsequent illness onset. Among healthy individuals at heritable risk for affective disorder, discrete cognitive deficits, especially within executive function and attention, seem to predict subsequent onset of affective illness.

Risk markers for affective disorder, a seven-years follow up study of a twin cohort at low and high risk for affective disorder

This study aims to investigate whether: familial history of affective disorder, subclinical depressive symptoms and life events (LEs) are predictive of a later development of mood disorder (onset). In a high-risk study, 234 healthy monozygotic and dizygotic twins with and without a co-twin history of affective disorder (high and low risk twins, respectively) were identified through nationwide registers and assessed from 2002 to 2005. Participants were followed longitudinally at 6-months intervals for up to nine years and finally reassessed with a personal interview to obtain information on whether they had an onset. During the follow-up period (mean time 7.0 years), 36 participants (15.4%) developed onset. Onset was significantly associated with risk status (Hazard ratio (HR) = 1.38, 95% CI 1.08–1.76), female sex, HR = 2.70, 95% CI 1.19–6.97, age HR = 0.97, 95% CI 0.93-0.99), and also with baseline Hamilton 17 score (HR = 1.30, 95% CI 1.13–1.48), Becks Depression Inventory 21 (HR = 1.14, 95% CI, 1.05–1.24) and neuroticism (HR = 1.08, 95% 1.02–1.12). Finally, the experience of LEs lifetime before baseline predicted onset (HR = 1.20, 95% CI 1.01–1.46) and the experience of LEs during follow-up also predicted onset (HR = 1.06, 95% CI 1.01–1.11). These findings suggest that young individuals at familial risk of affective disorders are at enhanced risk of onset and at further risk when having female sex and more subclinical depressive symptoms at baseline. Further, they seem to experience more LEs and to be more vulnerable to these.

Vaginal micronized progesterone and risk of preterm delivery in high‐risk twin pregnancies: secondary analysis of a placebo‐controlled randomized trial and meta‐analysis

Progesterone treatment reduces the risk of preterm delivery in high-risk singleton pregnancies. Our aim was to evaluate the preventive effect of vaginal progesterone in high-risk twins. This was a subanalysis of a Danish-Austrian, double-blind, placebo-controlled, randomized trial (PREDICT study), in which women with twin pregnancies were randomized to daily treatment with progesterone or placebo pessaries from 20-24 weeks until 34 weeks' gestation. This subpopulation consisted of high-risk pregnancies, defined by the finding of cervical length ≤ 10th centile at 20-24 weeks' gestation or history of either spontaneous delivery before 34 weeks or miscarriage after 12 weeks. Primary outcome was delivery before 34 weeks. Secondary outcomes were complications for infants including long-term follow-up by Ages and Stages Questionnaire (ASQ) at 6 and 18 months of age. In 72 (10.6%) of the 677 women participating in the PREDICT study, the pregnancy was considered to be high-risk, including 47 with cervical length ≤ 10th centile, 28 with a history of preterm delivery or late miscarriage and three fulfilling both criteria. Baseline characteristics for progesterone and placebo groups were similar. Mean gestational age at delivery did not differ significantly between the two groups either in patients with a short cervix (34.3 ± 4.1 vs. 34.5 ± 3.0 weeks, P = 0.87) or in those with a history of preterm delivery or late miscarriage (34.6 ± 4.2 vs. 35.2 ± 2.7 weeks, P = 0.62). Similarly, there were no significant differences between the treatment groups in maternal or neonatal complications and mean ASQ score at 6 and 18 months of age. In high-risk twin pregnancies, progesterone treatment does not significantly improve outcome.

Brain activation during cognitive planning in twins discordant or concordant for obsessive-compulsive symptoms

Neuroimaging studies have indicated abnormalities in cortico-striatal-thalamo-cortical circuits in patients with obsessive–compulsive disorder compared with controls. However, there are inconsistencies between studies regarding the exact set of brain structures involved and the direction of anatomical and functional changes. These inconsistencies may reflect the differential impact of environmental and genetic risk factors for obsessive–compulsive disorder on different parts of the brain. To distinguish between functional brain changes underlying environmentally and genetically mediated obsessive–compulsive disorder, we compared task performance and brain activation during a Tower of London planning paradigm in monozygotic twins discordant (n = 38) or concordant (n = 100) for obsessive–compulsive symptoms. Twins who score high on obsessive–compulsive symptoms can be considered at high risk for obsessive–compulsive disorder. We found that subjects at high risk for obsessive–compulsive disorder did not differ from the low-risk subjects behaviourally, but we obtained evidence that the high-risk subjects differed from the low-risk subjects in the patterns of brain activation accompanying task execution. These regions can be separated into those that were affected by mainly environmental risk (dorsolateral prefrontal cortex and lingual cortex), genetic risk (frontopolar cortex, inferior frontal cortex, globus pallidus and caudate nucleus) and regions affected by both environmental and genetic risk factors (cingulate cortex, premotor cortex and parts of the parietal cortex). Our results suggest that neurobiological changes related to obsessive–compulsive symptoms induced by environmental factors involve primarily the dorsolateral prefrontal cortex, whereas neurobiological changes induced by genetic factors involve orbitofrontal–basal ganglia structures. Regions showing similar changes in high-risk twins from discordant and concordant pairs may be part of compensatory networks that keep planning performance intact, in spite of cortico-striatal-thalamo-cortical deficits.

Hippocampal volume changes in healthy subjects at risk of unipolar depression

Unipolar depression is moderately heritable. It is unclear whether structural brain changes associated with unipolar depression are present in healthy persons at risk of the disorder. Here we investigated whether a genetic predisposition to unipolar depression is associated with structural brain changes. A priori, hippocampal volume reductions were hypothesized. Using a high-risk study design, magnetic resonance imaging brain scans were obtained from 59 healthy high-risk subjects having a co-twin with unipolar depression, and 53 healthy low-risk subjects without a first-degree family history of major psychiatric disorder. High-risk twins had smaller hippocampal volumes than low-risk twins ( p < 0.04). The finding was most pronounced in DZ twins. Groups did not differ on global brain tissue volumes or regional tissue volumes assessed in exploratory voxel-wise whole cerebrum analyses. In conclusion, hippocampal volume reduction may index a predisposition to develop depression and thus may be predictive of future onset of the disorder. Further studies are needed to elucidate the role of (shared) environmental and genetic factors.

Efficacy of Independent Component Analysis on Twin Fetal Signal Extraction from fMCG data

Event Abstract Back to Event Efficacy of Independent Component Analysis on Twin Fetal Signal Extraction from fMCG data Nana Aba Mensah-Brown1*, Silvia Comani2 and Ronald Wakai1 1 University of Wisconsin , United States 2 University of Chieti, Italy We assess the overall performance of the FastICA algorithm on 13 sessions of normal and high-risk twins ranging from 20 weeks to 37 weeks’ gestation. The quality of the separated components was rated on: 1) percentage peak detection of QRS peaks 2) comparison of signal-to-noise ratio (SNR) of twin ICA datasets against SNR of raw match-filtered datasets 3) Magnitude of twin residue in each twin ICA dataset 4) Visual correlation of twin ICA datasets and raw datasets as a measure of distortion. 5) visibility of important cardiac cycle components such as QRS, p-wave and t-wave. The average peak detection for the twin datasets was 97.5±3.6%. The average SNR using ICA was 3.95±0.28 compared with the average SNR from the raw match-filtered data of 3.27±0.26. Twin residue averaged 67±4% before ICA and 45±3% after ICA, with an average noise:signal ratio of 29±2%. The average waveforms of the ICA and raw data, were aligned in time implying that the distortion in time was insignificant. However, the QRS phase distortion was largely noticeable in 8 of 26 subjects. Although the SNR of the ICA datasets was greater than that of the raw datasets, the amplitude of p-wave was significantly diminished in 8 of 26 studies. The fast ICA algorithm effectively separates twin datasets while enhancing the relative amplitude of the QRS complex, at times distorting its phase, and reducing the relative amplitude of the p and T waves. Conference: Biomag 2010 - 17th International Conference on Biomagnetism , Dubrovnik, Croatia, 28 Mar - 1 Apr, 2010. Presentation Type: Poster Presentation Topic: Fetal and neonatal biomagnetism Citation: Mensah-Brown N, Comani S and Wakai R (2010). Efficacy of Independent Component Analysis on Twin Fetal Signal Extraction from fMCG data. Front. Neurosci. Conference Abstract: Biomag 2010 - 17th International Conference on Biomagnetism . doi: 10.3389/conf.fnins.2010.06.00142 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Mar 2010; Published Online: 25 Mar 2010. * Correspondence: Nana Aba Mensah-Brown, University of Wisconsin, Madison, United States, mensahbrown@wisc.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Nana Aba Mensah-Brown Silvia Comani Ronald Wakai Google Nana Aba Mensah-Brown Silvia Comani Ronald Wakai Google Scholar Nana Aba Mensah-Brown Silvia Comani Ronald Wakai PubMed Nana Aba Mensah-Brown Silvia Comani Ronald Wakai Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Variations in 5-HTTLPR: Relation to familiar risk of affective disorder, life events, neuroticism and cortisol

Background Variations in the serotonin transporter gene (5-HTTLPR) and stressful life events are associated with affective disorders. Aim To investigate whether the distribution of the alleles of the 5-HTTLPR is associated with a genetic predisposition to affective disorder and whether these variations interact with life events in relation to depressive symptoms, neuroticism and salivary cortisol. Method In a high-risk population 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 nationwide registers. Results When comparing the 81 individuals homozygote for the long allele with the 125 individuals hetero- and homozygote for the short allele no associations between the allele distribution and a genetic predisposition were found. The presence of the short allele of the 5-HTTLPR and the experience of SLE was associated with a higher neuroticism score, but not with depressive symptoms nor awakening or evening salivary cortisol. Conclusion A combination of variants in 5-HTTLPR and environmental stress seems to increase neuroticism in healthy individuals.