Female Twins Research Articles

Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health

BackgroundTobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic health, remains unclear.MethodsWe investigated smoking-associated DNA methylation and gene expression variation in adipose tissue biopsies from 542 healthy female twins. Replication, tissue specificity, and longitudinal stability of the smoking-associated effects were explored in additional adipose, blood, skin, and lung samples. We characterized the impact of adipose tissue smoking methylation and expression signals on metabolic disease risk phenotypes, including visceral fat.ResultsWe identified 42 smoking-methylation and 42 smoking-expression signals, where five genes (AHRR, CYP1A1, CYP1B1, CYTL1, F2RL3) were both hypo-methylated and upregulated in current smokers. CYP1A1 gene expression achieved 95% prediction performance of current smoking status. We validated and replicated a proportion of the signals in additional primary tissue samples, identifying tissue-shared effects. Smoking leaves systemic imprints on DNA methylation after smoking cessation, with stronger but shorter-lived effects on gene expression. Metabolic disease risk traits such as visceral fat and android-to-gynoid ratio showed association with methylation at smoking markers with functional impacts on expression, such as CYP1A1, and at tissue-shared smoking signals, such as NOTCH1. At smoking-signals, BHLHE40 and AHRR DNA methylation and gene expression levels in current smokers were predictive of future gain in visceral fat upon smoking cessation.ConclusionsOur results provide the first comprehensive characterization of coordinated DNA methylation and gene expression markers of smoking in adipose tissue. The findings relate to human metabolic health and give insights into understanding the widespread health consequence of smoking outside of the lung.

Genetic and environmental effects on the development of depressive symptoms from adolescence to adulthood in a nationally representative sample

BackgroundPrevious research has shown substantial heritability for depressive symptoms, yet, there are few genetically-informed studies which focused on developmental changes. The current study sought to model prototypical developmental trajectories of depressive symptoms from adolescence to adulthood and to elucidate genetic and environmental contributions to these changes. MethodsThe Add Health data set, a nationally representative sample of adolescents, was used. For the genetically-informed analyses, a subsample of N = 531 same-sex monozygotic and dizygotic male and female twin pairs was selected. Longitudinal development was modeled separately for two waves in early adolescence and for four waves from middle adolescence to young adulthood using a latent growth model (LGM). Both models were extended to twin models to estimate the effects of heritability and the environment. ResultsThe rates of depressive symptoms peaked in mid-adolescence and then sharply declined as individuals moved from adolescence to young adulthood, leveling off in the twenties. The effects of the shared environment were substantial among early adolescents, but negligible for middle-to-late adolescents. An opposite pattern was found for heritability. The largest proportion of developmental changes was driven by nonshared environmental effects. LimitationsThe study only used same-sex twins as there exist mixed findings regarding the possibility of qualitative or quantitative genetic effects. ConclusionsThe salience of unique experiences and, to a lesser extent, heritable factors in affecting developmental changes in depressive symptoms underscore the need for targeting environments that place individuals with genetic predisposition at double the risk for the development of depression.

Sexual Arousal Patterns of Identical Twins with Discordant Sexual Orientations

Genetically identical twins can differ in their self-reported sexual orientations. However, whether the twins’ subjective reports reflect valid differences in their sexual orientations is unknown. Measures of sexual orientation, which are free of the limitations of self-report, include genital arousal and pupil dilation while viewing sexual stimuli depicting men or women. We examined these responses in 6 male twin pairs and 9 female twin pairs who reported discordant sexual orientations. Across measures, heterosexual male twins responded more strongly to women than to men. Their homosexual co-twins showed an opposite pattern. Heterosexual female twins responded equally to both sexes, whereas their homosexual co-twins responded somewhat more to women than men. These differences within pairs were similar to differences between unrelated heterosexual and homosexual males and females. Our study provides physiological evidence confirming twins’ discordant sexual orientations, thereby supporting the importance of the non-shared environment for the development of sexual orientation and sexual arousal.

The narrow-sense and common single nucleotide polymorphism heritability of early repolarization

BackgroundEarly repolarization (ER) is a risk marker for sudden cardiac death. Higher risk is associated with horizontal/descending ST-segment ER in the inferior or inferolateral ECG leads. Studies in family cohorts have demonstrated substantial heritability for the ER pattern, but genome-wide association studies (GWAS) have failed to identify statistically significant and replicable genetic signals. Methods and resultsWe assessed the narrow-sense and common single nucleotide polymorphism (SNP) heritability of ER and ER subtypes using ECG data from 5829 individuals (TwinsUK, BRIGHT and GRAPHIC cohorts). ER prevalence was 8.3%. In 455 monozygous vs 808 dizygous twin pairs, concordances and twin correlations for ER subtypes (except horizontal/descending ST-segment ER) were higher and familial resemblance (except notched ER) was significant. Narrow-sense heritability estimates derived from 1263 female twin pairs using the structural equation program Mx ranged from 0.00–0.47 and common SNP heritability estimates derived from 4009 unrelated individuals of both sexes using Genome-wide Restricted Maximum Likelihood (GREML) ranged from 0.00–0.36, but none were statistically significant. ConclusionFrom our data, ER shows limited genetic predisposition. There appears to be significant environmental influence and these modest narrow-sense and common SNP heritability estimates may explain why previous GWAS have been unsuccessful.

Prenatal testosterone does not explain sex differences in spatial ability

The most consistent sex differences in cognition are found for spatial ability, in which males, on average, outperform females. Utilizing a twin design, two studies have shown that females with male co-twins perform better than females with female co-twins on a mental rotation task. According to the Twin Testosterone Transfer hypothesis (TTT) this advantage is due to in-uterine transmission of testosterone from males to females. The present study tested the TTT across 14 different spatial ability measures, including mental rotation tasks, in a large sample of 19–21-year-old twins. Males performed significantly better than females on all spatial tasks, with effect sizes ranging from η2 = 0.02 to η2 = 0.16. Females with a male co-twin outperformed females with a female co-twin in two of the tasks. The effect sizes for both differences were negligible (η2 < 0.02). Contrary to the previous studies, our results gave no indication that prenatally transferred testosterone, from a male to a female twin, influences sex differences in spatial ability.

Varicella-zoster virus CNS vasculitis and RNA polymerase III gene mutation in identical twins.

ObjectiveDeficiency in the cytosolic DNA sensor RNA Polymerase III (POL III) was recently described in children with severe varicella-zoster virus (VZV) infection in the CNS or lungs. Here, we describe a pair of monozygotic female twins, who both experienced severe recurrent CNS vasculitis caused by VZV reactivation. The clinical presentation and findings included recurrent episodes of headache, dizziness, and neurologic deficits, CSF with pleocytosis and intrathecal VZV antibody production, and MRI of the brain showing ischemic lesions.MethodsWe performed whole-exome sequencing and identified a rare mutation in the POL III subunit POLR3F. Subsequently, antiviral responses in patient peripheral blood mononuclear cells (PBMCs) were examined and compared with healthy controls.ResultsThe identified R50W POLR3F mutation is predicted by bioinformatics to be damaging, and when tested in functional assays, patient PBMCs exhibited impaired antiviral and inflammatory responses to the POL III agonist poly(dA:dT) and increased viral replication compared with controls.ConclusionsAltogether, these cases add genetic and immunologic evidence to the novel association between defects in sensing of AT-rich DNA present in the VZV genome and increased susceptibility to severe manifestations of VZV infection in the CNS in humans.

Does education attenuate the genetic risk of obesity? Evidence from U.K. Twins

More education is associated with a lower body mass index (BMI) and likelihood of being obese. Obesity and BMI also have a strong genetic basis. Given these observations, we investigate whether more education can reduce obesity by attenuating the underlying genetic risk of being obese, through gene-environment (GxE) interactions. We estimate associations between (i) education, (ii) a genetic risk score (GRS) and (iii) GxE interactions between education and the GRS through Ordinary least Squares (OLS) and twins fixed-effect regressions using data on female twins from the TwinsUK database. OLS estimates show that there are significant associations of education and genetics. Female twins with a university education are 14.3 percentage points less likely to be obese compared to twins with less than compulsory education, and a 1 standard deviation increase in the GRS increases the likelihood of being obese by 5.2 percentage points. The GxE interactions are statistically insignificant, suggesting that the marginal association of the GRS with obesity does not differ by educational attainment. When controlling for confounding through twins fixed-effects, we find a smaller role of genetics. The association of the GRS with obesity decreases to 0.040. Associations of educational attainment are substantially reduced and insignificant. GxE interactions also remain insignificant. Overall, we find little evidence of any GxE interactions.

Illicit Drug Use, Cigarette Smoking, and Eating Disorder Symptoms: Associations in an Adolescent Twin Sample

Twin studies have shown that genetic factors in part explain the established relation between alcohol use (i.e., problematic use or abuse/dependence) and eating disorder symptoms in adolescent and adult females. However, studies have yet to elucidate if there are similar shared genetic factors between other aspects of substance involvement, such as illicit drug use and repeated cigarette smoking. For those sex-specific phenotypic correlations above our threshold of .20, we used a behavioral genetic design to examine potential shared genetic overlap between self-reported lifetime illicit drug use and repeated cigarette smoking and the eating disorder symptoms of drive for thinness (DT), bulimia (BU), and body dissatisfaction (BD), as assessed with the Eating Disorder Inventory-II, in 16- to 17-year-old female and male twin pairs. Only phenotypic correlations with illicit drug use met our threshold for twin modeling. Small to moderate genetic correlations were observed between illicit drug use and BU in both girls and boys and between illicit drug use and DT in girls. Similar etiological factors are at play in the overlap between illicit drug use and certain eating disorder symptoms in girls and boys during adolescence, such that genetic factors are important for covariance. Specifically, illicit drug use was associated with bulimia nervosa symptoms in girls and boys, which parallels previous substance use research finding a genetic overlap between alcohol use and bulimia nervosa symptoms. Future research should prospectively examine developmental trajectories to further understand the etiological overlap between substance involvement and eating disorder symptoms.

Identical twins with borderline lepromatous leprosy mimicking extensive alopecia areata: A rare presentation

Nineteen-year old identical female twins presented with complaints of progressive hair loss all over the body, sparing the scalp, axillae and pubic region along with a few atrophic scars on the knees, thighs and elbows. A possible diagnosis of atypical presentation of alopecia areata was made. However, in view of history of borderline tuberculoid leprosy in their younger sibling, a complete examination for leprosy was done. There was asymmetrical enlargement of multiple peripheral nerves without any sensory or motor loss. Histopathology confirms the diagnosis of BL Hansens. Such a presentation of leprosy in identical twins is not reported in literature.

Genetic and environmental influences on gambling disorder liability: a replication and combined analysis of two twin studies.

Gambling disorder (GD), recognized in Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM-5) as a behavioral addiction, is associated with a range of adverse outcomes. However, there has been little research on the genetic and environmental influences on the development of this disorder. This study reports results from the largest twin study of GD conducted to date. Replication and combined analyses were based on samples of 3292 (mean age 31.8, born 1972-79) and 4764 (mean age 37.7, born 1964-71) male, female, and unlike-sex twin pairs from the Australian Twin Registry. Univariate biometric twin models estimated the proportion of variation in the latent GD liability that could be attributed to genetic, shared environmental, and unique environmental factors, and whether these differed quantitatively or qualitatively for men and women. In the replication study, when using a lower GD threshold, there was evidence for significant genetic (60%; 95% confidence interval (CI) 45-76%) and unique environmental (40%; 95% CI 24-56%), but not shared environmental contributions (0%; 95% CI 0-0%) to GD liability; this did not significantly differ from the original study. In the combined analysis, higher GD thresholds (such as one consistent with DSM-5 GD) and a multiple threshold definitions of GD yielded similar results. There was no evidence for quantitative or qualitative sex differences in the liability for GD. Twin studies of GD are few in number but they tell a remarkably similar story: substantial genetic and unique environmental influences, with no evidence for shared environmental contributions or sex differences in GD liability.

Increased body fat mass and androgen metabolism – A twin study in healthy young women

ObjectiveObesity may alter serum steroid concentrations and metabolism. We investigated this in healthy young women with increased body fat and their leaner co-twin sisters. DesignAge and genetic background both strongly influence serum steroid levels and body composition. This is a cross-sectional study of 13 female monozygotic twin pairs (age, 23–36 years), ten of which were discordant for body mass index (median difference in body weight between the co-twins, 19 kg). MethodsWe determined body composition by dual energy X-ray absorptiometry and magnetic resonance imaging, serum androgens by liquid chromatography-tandem mass spectrometry, and mRNA expression of genes in subcutaneous adipose tissue and adipocytes. ResultsThe heavier women had lower serum dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) (P < 0.05 for all) compared to their leaner co-twins with no differences in serum testosterone or androstenedione levels. Serum DHEA correlated inversely with %body fat (r = −0.905, P = 0.002), and DHT positively with SHBG (r = 0.842, P = 0.002). In adipose tissue or adipocytes, expressions of STS (steroid sulfatase) and androgen-related genes were significantly higher in the heavier compared to the leaner co-twin, and within pairs, correlated positively with adiposity but were not related to serum androgen levels. None of the serum androgen or SHBG levels correlated with indices of insulin resistance. ConclusionsSerum DHEA levels were best predicted by %body fat, and serum DHT by SHBG. These or other serum androgen concentrations did not reflect differences in androgen-related genes in adipose tissue. General or intra-abdominal adiposity were not associated with increased androgenicity in young women.

Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways.

Chronic widespread musculoskeletal pain (CWP) and frailty are prevalent conditions in older people. We have shown previously that interindividual variation in frailty and CWP is genetically determined. We also reported an association of frailty and CWP caused by shared genetic and common environmental factors. The aim of this study was to use omic approaches to identify molecular genetic factors underlying the heritability of frailty and its genetic correlation with CWP. Frailty was quantified through the Rockwood Frailty Index (FI) as a proportion of deficits from 33 binary health deficit questions in 3626 female twins. Common widespread pain was assessed using a screening questionnaire. OMICS analysis included 305 metabolites and whole-genome (>2.5 × 10 SNPs) and epigenome (∼1 × 10 MeDIP-seq regions) assessments performed on fasting blood samples. Using family-based statistical analyses, including path analysis, we examined how FI scores were related to molecular genetic factors and to CWP, taking into account known risk factors such as fat mass and smoking. Frailty Index was significantly correlated with 51 metabolites after correction for multiple testing, with 20 metabolites having P-values between 2.1 × 10 and 4.0 × 10. Three metabolites (uridine, C-glycosyl tryptophan, and N-acetyl glycine) were statistically independent and thought to exert a direct effect on FI. Epiandrosterone sulphate, previously shown to be highly inversely associated with CWP, was found to exert an indirect influence on FI. Bioinformatics analysis of genome-wide association study and EWAS showed that FI and its covariation with CWP was through genomic regions involved in neurological pathways. Neurological pathway involvement accounts for the associated conditions of aging CWP and FI.

Four-Generation Pedigree of Monozygotic Female Twins Reveals Genetic Factors in Twinning Process by Whole-Genome Sequencing.

Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5'UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism.

5328Generation of disease specific iPSC-derived cardiomyocyte and investigation of their characteristics: study with clinically divergent female monozygotic twins with Danon disease

5328Generation of disease specific iPSC-derived cardiomyocyte and investigation of their characteristics: study with clinically divergent female monozygotic twins with Danon disease

Tracing the structural origins of atypical language representation: consequences of prenatal mirror-imaged brain asymmetries in a dizygotic twin couple

We investigated the predictive value of prenatal superior temporal sulcus (STS) depth asymmetry in a special case of a female dizygotic twin that showed inverted prenatal asymmetry of this structure. For this purpose, we performed a follow-up investigation in this former fetus at the age of seven, where we assessed the functional language lateralization using task-based and resting-state functional magnetic resonance imaging (fMRI). As control group we employed her twin brother, who showed a typical folding pattern prenatally, as well as a complementary set of four age-matched children that had fetal MRI of their brains and typical STS depth asymmetry. We could show that the twin with the atypical fetal asymmetry of the STS also showed significantly differing rightward language lateralization in the frontal and temporal lobes. Additionally, resting-state data suggest a stronger connectivity between inferior frontal gyri in this case. The twin showed normal cognitive development. This result gives a first glimpse into the STS’ atypical asymmetry being a very early morphological marker for later language lateralization.

Handedness and the Corpus Callosum: A Review and Further Analyses of Discordant Twins

Handedness effects with respect to regional corpus callosum (CC) anatomy remain open to question. Midsagittal CC tracings were obtained from structural MRIs in 21 female monozygotic twin pairs with discordant handedness (MZHd). The CC was divided into 99 percentile widths which were grouped into seven regions based on Denenberg’s (1989, 1991b) factor analysis. Results showed that left handed (LH) twins had significantly larger regional widths in CC region W22–39 compared to right handed (RH) twins, an effect present in 19/21 MZHd pairs. Cross-study analyses revealed CC W22–39 to have the highest variation across female singletons (Cowell et al., 1992, 1993). In the adjacent genu region (W3–18), CC size did not differ between RH and LH twins. However, when twins were reclassified according to handedness direction and consistency to form consistent RH, non-consistent RH, consistent LH and non-consistent LH groups, patterns of CC size in W3–18 closely matched those of singleton women (Cowell et al., 1993). Namely, CC W3–18 was larger in consistent compared to non-consistent RHs. Results support a claim that CC region W22–39, interconnecting premotor cortex in females, provides for environmentally influenced components of handedness, given the difference within MZHd twin pairs. By contrast, CC W3–18, connecting prefrontal cortex, was sensitive to direction and consistency of handedness, both in twins and singletons, a result consistent with combined genetic and environmental effects. Findings highlight the significance of MZHd twin studies in elucidating the developmental mechanisms underpinning structure–function asymmetry, cortical interconnectivity and neurodevelopmental bases of left hand preference.

Finger Length Ratios of Identical Twins with Discordant Sexual Orientations.

A proposed marker of prenatal androgen exposure is the ratio of the index finger to ring finger (2D:4D). Within each sex, this ratio may be lower for those who were exposed to higher levels of androgens and become attracted to women, as compared to those who were exposed to lower levels of androgens and become attracted to men. We examined these patterns in identical twins with discordant sexual orientations. Because these twins are genetically identical, differences in prenatal androgen exposure, as reflected in their different finger length ratios, might contribute to their discordance. For 18 female twin pairs, non-straight (bisexual or lesbian) twins had significantly lower, or more masculinized, 2D:4D ratios than their straight co-twins, but only in the left hand. For 14 male pairs, non-straight twins had, contrary to our prediction, more masculinized finger length ratios than straight co-twins, but this difference was not significant. A reanalysis of present and previous data (Hall & Love, 2003; Hiraishi, Sasaki, Shikishima, & Ando, 2012) suggested that these patterns were robust. Furthermore, males had more masculinized 2D:4D ratios than females. This sex difference did not vary by sexual orientation.

Abstract 3228: Tobacco smoking and circulating immune-related biomarkers in monozygotic twins

Abstract Background: Tobacco smoking is a cause of a variety of cancers by various mechanisms. Paradoxically, smoking also increases the risk of atopy and asthma, which are inversely associated with some cancers such as glioma, colorectal cancer and non-Hodgkin lymphoma, but positively associated with others such as lung cancer. Tobacco smoking may affect the immune system, which may explain some of these associations. We assessed the association between smoking and levels of 27 serum immune/inflammatory markers and DNA methylation in healthy monozygotic (MZ) twins. Methods: 67 MZ twin pairs were identified from the Finnish Twin Cohort Study. Cotinine and immune related biomarkers were measured from fasting serum samples using LC-MS/MS and Luminex multiples assays. Current smoking status was defined by cotinine &amp;gt;3.08 ng/mL. Current smokers were further categorized into low vs high smoking level by the median cotinine (78.17 ng/mL) among smokers. Questionnaire reports of current and former smoking included duration, amount (cigarettes per day [CPD]) and years since quitting. Linear mixed models were used to assess the association between smoking variables and each individual biomarker. For each smoking variable P values were adjusted for multiple comparisons using Pact, taking into account correlations among biomarkers. For biomarkers significantly associated with smoking, we assessed whether blood DNA methylation of biomarker-related genes mediated the smoking-biomarker association. Results: The median age of the study population was 24.8 years (range 21.0-68.9 years) and 56.7% were female twins. 32.1% of the twins were current smokers according to cotinine levels. Current smoking, defined by either cotinine or self-reports, was significantly associated with CCL17, B-cell activating factor (BAFF) and haptoglobin (Hp) levels respectively, after adjusting for multiple comparisons. For instance, serum cotinine was associated with increasing CCL17 levels (Pact for trend test = 0.002): the geometric mean CCL17, adjusted for age and sex among current high-level smokers was approximately 8.2% higher than noncurrent smokers. Similar positive dose-response relationships were observed for self-reported smoking variables with the 3 biomarkers. However, we found no associations between former smoking and any of the 27 biomarkers. We also found that smoking-associated DNA methylation alterations in 3 CpG sites of BAFF affected circulating CCL17 (CpG site: cg11726530) and Hp (cg09158314 and cg21784254) levels, respectively. Conclusion: Current but not former smoking may be associated with alterations in circulating levels of CCL17, BAFF and Hp, suggesting that smoking may promote B-cell activation and affect Th2 immune response, which may play a role in carcinogenesis. Further, preliminary mediation analysis suggests that smoking-induced alterations in these biomarkers may partially mediate through DNA methylation. Citation Format: Jun Wang, David Conti, Marta Epeldegui, Miina Ollikainen, Amie E. Hwang, Ann S. Hamilton, Larry Magpantay, Rachel Tyndale, Thomas M. Mack, Otoniel Martinez-Maza, Jaakko Kaprio, Wendy Cozen. Tobacco smoking and circulating immune-related biomarkers in monozygotic twins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3228.

Case 1: Late-Onset Hypoglycemia in an Extremely Low-Birthweight Infant

An 800-g extremely low-birthweight female (25 5/7 weeks) twin A of a dichorionic-diamniotic gestation is born via primary low transverse cesarean delivery to a 37-year-old gravida 5, para 0-4-0-0 woman. The mother of the child is group B Streptococcus positive, and received 1 dose of penicillin less than 4 hours before delivery. Results of other antenatal testing had been reassuring. Preterm delivery is indicated for prolonged rupture of membranes of twin B, and the mother had received 2 doses of betamethasone 24 hours apart at the estimated 24th week of gestation. The neonate has Apgar scores of 3 and 8 at 1 and 5 minutes, respectively. She is stabilized on continuous positive airway pressure and transferred to the NICU by 5 minutes after birth. In the NICU, she requires intubation and fraction of inspired oxygen greater than 60% to maintain oxygenation. An umbilical artery catheter and umbilical venous catheter are established and she is treated with ampicillin and gentamicin. She initially has hypotension requiring a 10-mL/kg bolus of normal saline without improvement, necessitating institution of a dopamine drip titrated from 2 to 5 μg/kg per minute to maintain mean arterial pressures above 25 mm Hg. She is started on intravenous fluids of 100 mL/kg per day with a glucose infusion rate (GIR) of 5 mg/kg per minute, which is reduced to 3.1 mg/kg per minute by 1 day after birth because of worsening hyperglycemia. Despite serial reduction of GIR, she persistently demonstrates capillary blood …

Using person-specific neural networks to characterize heterogeneity in eating disorders: Illustrative links between emotional eating and ovarian hormones.

Emotional eating has been linked to ovarian hormone functioning, but no studies to-date have considered the role of brain function. This knowledge gap may stem from methodological challenges: Data are heterogeneous, violating assumptions of homogeneity made by between-subjects analyses. The primary aim of this paper is to describe an innovative within-subjects analysis that models heterogeneity and has potential for filling knowledge gaps in eating disorder research. We illustrate its utility in an application to pilot neuroimaging, hormone, and emotional eating data across the menstrual cycle. Group iterative multiple model estimation (GIMME) is a person-specific network approach for estimating sample-, subgroup-, and individual-level connections between brain regions. To illustrate its potential for eating disorder research, we apply it to pilot data from 10 female twins (N = 5 pairs) discordant for emotional eating and/or anxiety, who provided two resting state fMRI scans and hormone assays. We then demonstrate how the multimodal data can be linked in multilevel models. GIMME generated person-specific neural networks that contained connections common across the sample, shared between co-twins, and unique to individuals. Illustrative analyses revealed positive relations between hormones and default mode connectivity strength for control twins, but no relations for their co-twins who engage in emotional eating or who had anxiety. This paper showcases the value of person-specific neuroimaging network analysis and its multimodal associations in the study of heterogeneous biopsychosocial phenomena, such as eating behavior.