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JAMA Psychiatry Jul 2023General and specific factors of psychopathology are associated with future adverse outcomes, indicating that they might be useful for identifying individuals at greatest...
IMPORTANCE
General and specific factors of psychopathology are associated with future adverse outcomes, indicating that they might be useful for identifying individuals at greatest risk. However, it remains unknown if these associations are attributable to confounders that may influence both the psychopathology factors and later outcomes.
OBJECTIVE
To analyze associations between psychopathology factors and clinically relevant outcomes within family pairs, adjusting for unmeasured confounds by applying co-twin control and sibling comparison designs.
DESIGN, SETTING, AND PARTICIPANTS
This longitudinal cohort study with a follow-up range of 9 to 13 years included all Swedish twins born from 1959 to 1985 who participated in the Study of Twin Adults: Genes and Environment (60% response rate) and the oldest pair of all Swedish siblings born from 1959 to 1985 per the Multi-Generation Register. Twins were evaluated based on responses to a hierarchical factor model derived using multivariate statistics. Sibling pairs were evaluated based on psychiatric diagnoses per the Swedish National Patient Register. Information on outcome events and prescriptions were derived from the National Patient Register, Prescribed Drug Register, and Crime Register. Baseline assessment was in August 2005, and data were analyzed from January 2022 to February 2023.
EXPOSURES
Hierarchical factor model consisting of 1 general and 4 specific factors fit to 48 psychiatric symptoms on which twin participants self-reported in 2005 and 1 general and 3 specific factors fit to 9 register-based psychiatric diagnoses assigned to sibling participants prior to 2005.
MAIN OUTCOMES AND MEASURES
Outcomes consisted of 7 register-based events occurring after 2005, including suicidal behavior, substance overdoses, and criminal suspicion or convictions (data available until the end of 2013), and prescription of antidepressants, antialcohol or antiopioid medication, antipsychotics, and stimulants (data available until the end of 2017).
RESULTS
The study included 32 328 twins (mean [SD] age, 34 [8] years; 16 076 [49.73%] male) and 1 942 106 siblings (mean [SD] age, 34 [7] years; 991 500 [51.05%] male). General psychopathology was significantly associated with all 7 outcomes within sibling pairs (mean within-pair odds ratio [OR], 2.28; 95% CI, 2.19-2.37) and dizygotic twin pairs (within-pairs OR, 1.65; 95% CI, 1.38-1.98) and with 3 outcomes within monozygotic twin pairs (mean within-pairs OR, 1.77; 95% CI, 1.35-2.36). Within sibling pairs, the specific internalizing factor was associated with antidepressant prescriptions (within-pairs OR, 1.65; 95% CI, 1.59-1.71), the specific substance misuse factor was associated prescription of antialcohol and antiopioid medication (within-pairs OR, 2.36; 95% CI, 2.20-2.54), and the specific psychotic factor was associated with antipsychotic medications (within-pairs OR, 1.61; 95% CI, 1.51-1.72). Similar results emerged within twin pairs.
CONCLUSION AND RELEVANCE
In this cohort study, general psychopathology was significantly associated with all 7 outcomes within sibling and dizygotic twin pairs and 3 outcomes within monozygotic twin pairs at 10 years. Within twin and sibling pairs, the specific factors were primarily associated with related outcomes. Several of the associations in this cohort study could not be attributed to unmeasured confounds shared by family members, suggesting that interventions toward broad psychopathology dimensions might help reduce the risk of future clinically relevant events.
Topics: Humans; Adult; Male; Female; Siblings; Longitudinal Studies; Sweden; Twins, Monozygotic; Mental Disorders; Twins, Dizygotic; Registries
PubMed: 37163290
DOI: 10.1001/jamapsychiatry.2023.1162 -
JAMA Psychiatry Jul 2023Subjective memory concern has long been considered a state-related indicator of impending cognitive decline or dementia. The possibility that subjective memory concern...
IMPORTANCE
Subjective memory concern has long been considered a state-related indicator of impending cognitive decline or dementia. The possibility that subjective memory concern may itself be a heritable trait is largely ignored, yet such an association would substantially confound its use in clinical or research settings.
OBJECTIVE
To assess the heritability and traitlike dimensions of subjective memory concern and its clinical correlates.
DESIGN, SETTING, AND PARTICIPANTS
This longitudinal twin cohort study was conducted from 1967 to 2019 among male adults with a mean (SD) age of 37.75 (2.52) years to follow-up at mean ages of 56.15 (2.72), 61.50 (2.43), and 67.35 (2.57) years (hereafter, 38, 56, 62, and 67 years, respectively) in the Vietnam Era Twin Study of Aging. The study included a national community-dwelling sample with health, education, and lifestyle characteristics comparable to a general sample of US men in this age cohort. Participants were monozygotic and dizygotic twins randomly recruited from the Vietnam Era Twin Registry. Data were analyzed from May 2021 to December 2022.
MAIN OUTCOMES AND MEASURES
Measures included subjective memory concern at 4 time points; objective memory, depressive symptoms, and anxiety at the last 3 time points; negative emotionality (trait neuroticism) at age 56 years; polygenic risk scores (PRSs) for neuroticism, depression, and Alzheimer disease; APOE genotype; and parental history of dementia. Primary outcomes were heritability and correlations between subjective memory concern and other measures.
RESULTS
The sample included 1555 male adults examined at age 38 years, 520 at age 56 years (due to late introduction of subjective memory concern questions), 1199 at age 62 years, and 1192 at age 67 years. Phenotypically, subjective memory concerns were relatively stable over time. At age 56 years, subjective memory concern had larger correlations with depressive symptoms (r, 0.32; 95% CI, 0.21 to 0.42), anxiety (r, 0.36; 95% CI, 0.18 to 0.51), and neuroticism (r, 0.34; 95% CI, 0.26 to 0.41) than with objective memory (r, -0.24; 95% CI, -0.33 to -0.13). Phenotypic results were similar at ages 62 and 67 years. A best-fitting autoregressive twin model indicated that genetic influences on subjective memory concern accumulated and persisted over time (h2 = 0.26-0.34 from age 38-67 years). At age 56 years, genetic influences for subjective memory concern were moderately correlated with genetic influences for anxiety (r, 0.36; 95% CI, 0.18 to 0.51), negative emotionality (r, 0.51; 95% CI, 0.44-0.57), and depressive symptoms (r, 0.20; 95% CI, 0.10 to 0.29) as well as objective memory (r, -0.22; 95% CI, -0.30 to -0.14). Similar genetic correlations were seen at ages 62 and 67 years. The neuroticism PRS was associated with subjective memory concern at age 38 years (r, 0.10; 95% CI, 0.03. to 0.18) and age 67 years (r, 0.09; 95% CI, 0.01 to 0.16). Subjective memory concern was not associated with any Alzheimer disease risk measures.
CONCLUSIONS AND RELEVANCE
This cohort study found stable genetic influences underlying subjective memory concern dating back to age 38 years. Subjective memory concern had larger correlations with affect-related measures than with memory-related measures. Improving the utility of subjective memory concern as an indicator of impending cognitive decline and dementia may depend on isolating its statelike component from its traitlike component.
Topics: Humans; Male; Adult; Middle Aged; Aged; Cohort Studies; Alzheimer Disease; Twins, Dizygotic; Longitudinal Studies; Risk Factors; Twins, Monozygotic
PubMed: 37163244
DOI: 10.1001/jamapsychiatry.2023.1004 -
Psychological Medicine Nov 2023Are genetic risk factors for current depressive symptoms good proxies for genetic risk factors for syndromal major depression (MD)?
BACKGROUND
Are genetic risk factors for current depressive symptoms good proxies for genetic risk factors for syndromal major depression (MD)?
METHODS
In over 9000 twins from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, the occurrence of all nine DSM symptomatic criteria for MD in the last year was assessed at personal interview and then grouped by their temporal co-occurrence. The DSM criteria which occurred outside (OUT) inside of (IN) MD episodes were then separated. We calculated tetrachoric correlations for OUT and IN depressive criteria in monozygotic (MZ) and dizygotic (DZ) pairs and fitted univariate and bivariate ACE twin models using OpenMx.
RESULTS
The mean twin correlations (±95% CIs) for IN depressive criteria were substantially higher than for OUT depressive criteria in both MZ [+0.35 (0.32-0.38) 0.20 (0.17-0.24)] and DZ pairs [0.20 (0.17-0.24) 0.10 (0.04-0.16]. The mean IN-OUT cross-correlation in MZ and DZ pairs was modest [+0.15 (0.07-0.24) and +0.07 (0.03-0.12)]. The mean heritability estimates for the nine In Out depressive criteria was 0.31 (0.22-0.41) and 0.15 (0.08-0.21), in MZ and DZ pairs, respectively. The mean genetic correlation between the nine IN and OUT depressive criteria was +0.07 (-0.07 to 0.21).
CONCLUSIONS
Depressive criteria occurring outside depressive episodes are less heritable than those occurring within. These two ways criteria can manifest are not closely genetically related. Current depressive symptoms - most of which are occurring outside of depressive episodes - are not, for genetic studies, good proxies for MD.
Topics: Adult; Humans; Depressive Disorder, Major; Depression; Twins, Monozygotic; Twins, Dizygotic; Diseases in Twins
PubMed: 37154209
DOI: 10.1017/S0033291723001241 -
Behavior Genetics May 2023Using baseline (ages 9-10) and two-year follow-up (ages 11-12) data from monozygotic and dizygotic twins enrolled in the longitudinal Adolescent Brain Cognitive...
Using baseline (ages 9-10) and two-year follow-up (ages 11-12) data from monozygotic and dizygotic twins enrolled in the longitudinal Adolescent Brain Cognitive Development Study, we investigated the genetic and environmental contributions to microstructure and volume of nine subcortical gray matter regions. Microstructure was assessed using diffusion MRI data analyzed using restriction spectrum imaging (RSI) and diffusion tensor imaging (DTI) models. The highest heritability estimates (estimate [95% confidence interval]) for microstructure were found using the RSI model in the pallidum (baseline: 0.859 [0.818, 0.889], follow-up: 0.835 [0.787, 0.871]), putamen (baseline: 0.859 [0.819, 0.889], follow-up: 0.874 [0.838, 0.902]), and thalamus (baseline: 0.855 [0.814, 0.887], follow-up: 0.819 [0.769, 0.857]). For volumes the corresponding regions were the caudate (baseline: 0.831 [0.688, 0.992], follow-up: 0.848 [0.701, 1.011]) and putamen (baseline: 0.906 [0.875, 0.914], follow-up: 0.906 [0.885, 0.923]). The subcortical regions displayed high genetic stability (rA = 0.743-1.000) across time and exhibited unique environmental correlations (rE = 0.194-0.610). Individual differences in both gray matter microstructure and volumes can be largely explained by additive genetic effects in this sample.
Topics: Adolescent; Humans; Child; Gray Matter; Diffusion Tensor Imaging; Brain; Twins, Dizygotic; Cognition; Magnetic Resonance Imaging
PubMed: 37129746
DOI: 10.1007/s10519-023-10142-1 -
The Journal of Maternal-fetal &... Dec 2023Strong evidence imply that delayed cord clamping (DCC) provides significant benefits for singleton neonates. However, there is little information about the safety or...
OBJECTIVES
Strong evidence imply that delayed cord clamping (DCC) provides significant benefits for singleton neonates. However, there is little information about the safety or efficacy of DCC in twins to recommend for or against DCC in twins in guidelines. We aimed to determine the effect of DCC on dichorionic twins born at <32 weeks of gestation.
STUDY DESIGN
This is a retrospective cohort study comparing the neonatal and maternal outcomes of immediate cord clamping (ICC) [<15 second (s)] versus DCC (at 60 s). Generalized estimating equations models were performed accounting for twin correlation
RESULTS
A total of 82 pairs of twins (DCC: 41; ICC: 41) were included in analysis. The primary outcome of death before discharge occurred in 3.66% of twins in the DCC group and 7.32% in the ICC group, without a significant difference between the groups. Compared to ICC group, DCC was associated with increased hemoglobin levels [β1 coefficient 6.51; 95% confidence interval (CI) 0.69-12.32. β2 coefficient 5.80; 95% CI 0.07-11.54] at 12-24 h of life. There were no significant differences between the groups in neonatal death, neonatal major morbidities and maternal bleeding complications, although DCC was associated with higher estimated maternal blood loss in the cesarean section group ( = .005).
CONCLUSIONS
DCC for 60 s in dichorionic twins born at <32 weeks of gestation was associated with increased neonatal hemoglobin levels, when compared with ICC. The finding of a higher estimated maternal blood loss by cesarean section in the DCC group calls for further trials to assess maternal safety of this procedure in this patient population.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Cesarean Section; Retrospective Studies; Umbilical Cord Clamping; Umbilical Cord; Twins, Dizygotic; Constriction; Hemoglobins
PubMed: 37120713
DOI: 10.1080/14767058.2023.2203300 -
The Journal of International Medical... Apr 2023The current case report describes the clinical, biochemical and genetic characteristics of carnitine-acylcarnitine translocase deficiency (CACTD) in infant male and...
The current case report describes the clinical, biochemical and genetic characteristics of carnitine-acylcarnitine translocase deficiency (CACTD) in infant male and female twins that presented with symptoms shortly after elective caesarean delivery. The clinical manifestations were neonatal hypoglycaemia, arrhythmia and sudden death. The age of onset was 1.5 days and the age of the death was 1.5-3.5 days. Dried blood filter paper analysis was used for the detection of acylcarnitine. Peripheral venous blood and skin samples were used for next-generation sequencing. The twins and their parents underwent gene analysis and whole exome sequencing analyses of the solute carrier family 25 member 20 (; also known as carnitine-acylcarnitine translocase) gene. Both infants carried compound heterozygous variants of the gene: variant M1:c.706_707insT:p.R236L fs*12 and variant M2:c.689C>G:p.P230R. The M1 variant was paternal and had not been previously reported regarding CACTD. The M2 variant was maternal. CACTD has severe clinical manifestations and a poor prognosis, which is manifested as hypoketotic hypoglycaemia, hyperammonaemia, liver function damage and elevated creatine kinase.
Topics: Female; Humans; Infant, Newborn; Male; Carnitine Acyltransferases; Hypoglycemia; Lipid Metabolism, Inborn Errors; Membrane Transport Proteins; Mutation; Twins, Dizygotic
PubMed: 37115522
DOI: 10.1177/03000605231163811 -
BMC Oral Health Apr 2023The interplay between genetic and environmental impacts on dental and facial morphology has been widely analyzed, but little is known about their relative contributions...
BACKGROUND
The interplay between genetic and environmental impacts on dental and facial morphology has been widely analyzed, but little is known about their relative contributions to airway morphology. The aim of this study was to evaluate the genetic and environmental influences on the cephalometric variables of airway morphology in a group of postpubertal twins with completed craniofacial growth.
MATERIALS AND METHODS
The materials comprised lateral head cephalograms of 94 pairs of twins (50 monozygotic, 44 dizygotic) with completed craniofacial growth. Zygosity was determined using 15 specific DNA markers. The computerized cephalometric analysis included 22 craniofacial, hyoideal, pharyngeal structural linear and angular variables. Genetic analysis and heritability estimation were performed using maximum likelihood genetic structural equation modeling (GSEM). Principal component analysis (PCA) was used to assess the correlations between cephalometric measurement variables.
RESULTS
Upper airway dimensions showed moderate to high genetic determination (SPPW-SPP and U-MPW: a = 0.64 and 0.5, respectively). Lower airway parameters showed only common and specific environmental determination (PPW-TPP a = 0.24, e = 0.38; LPW-V c = 0.2, e = 0.63; PCV-AH c = 0.47, e = 0.28). The relationship between the maxilla and the hyoid bone (for variables PNS-AH, ANS-AH d = 0.9, 0.92, respectively) showed very strong additive genetic determination. The size of the soft palate was affected by additive and dominant genes. Its length (SPL) was strongly influenced by dominant genes, while its width (SPW) showed a moderate additive genetic influence. Owing to correlations in the behavior of variables, the data could be expressed in 5 principal components that jointly explained 36.8% of the total variance.
CONCLUSIONS
The dimensions of the upper airway are strongly determined by genes, while the parameters of the lower airway depend mainly on environmental factors.
TRIAL REGISTRATION
The protocol has been approved by the Kaunas Regional Ethical Committee (No. BE - 2-41., May 13, 2020).
Topics: Humans; Cephalometry; Maxilla; Face; Pharynx
PubMed: 37106360
DOI: 10.1186/s12903-023-02919-x -
CASE (Philadelphia, Pa.) Mar 2023• Cardiac rhabdomyomas are commonly associated with TSC. • They are often the first presentation of TSC, diagnosed prenatally or in neonates. • Fetal or neonatal...
• Cardiac rhabdomyomas are commonly associated with TSC. • They are often the first presentation of TSC, diagnosed prenatally or in neonates. • Fetal or neonatal echocardiography is useful for their early detection. • Familial TSC may be seen even in cases with phenotypically normal parents. • Rhabdomyomas in both dizygotic twins, suggesting familial TSC, is very rare.
PubMed: 37065831
DOI: 10.1016/j.case.2022.11.008 -
Neuropsychologia Jun 2023Reared-apart twin studies are a powerful means for identifying the relative contributions of heredity and environment to variation in human physical and behavioural... (Review)
Review
Reared-apart twin studies are a powerful means for identifying the relative contributions of heredity and environment to variation in human physical and behavioural traits. One such characteristic is handedness, for which it has long been noted that approximately 20% of twin pairs are comprised of one right-handed cotwin and one left-handed cotwin. Reared-together twin studies suggest a slightly greater concordance in monozygotic (MZT) than dizygotic (DZT) twins, implying that genetics influences hand preference. We report here two studies of handedness in reared-apart twins. Study 1 synthesizes the available data and estimates that at least N = 560 same-sex reared-apart twin pairs (for which zygosity is known with reasonable confidence) have been identified. Of these, handedness data are available for both members of n = 415 pairs. We observed similar levels of concordance/discordance for reared-apart monozygotic (MZA) and dizygotic (DZA) twins. However, although direction of handedness (right or left) has frequently been examined, strength of handedness (strong or weak) has not. Study 2 examined strength of hand preference and relative hand skill, as well as right- and left-hand speed, information available for participants in the Minnesota Study of Twins Reared Apart (MISTRA). We provide evidence of heritability for right-hand and left-hand speed. We also found hand preference strength was more alike than chance in DZA, but not MZA, twins. Findings are discussed in relation to genetic and environmental influences on human handedness.
Topics: Humans; Twins, Monozygotic; Functional Laterality; Twins, Dizygotic; Mental Processes
PubMed: 37059260
DOI: 10.1016/j.neuropsychologia.2023.108523 -
Cureus Mar 2023Neonatal alloimmune thrombocytopenia (NAIT) and neonatal alloimmune neutropenia (NAIN) may have severe consequences in the neonatal period. We report two dizygotic twins...
Neonatal alloimmune thrombocytopenia (NAIT) and neonatal alloimmune neutropenia (NAIN) may have severe consequences in the neonatal period. We report two dizygotic twins conceived after donated oocytes, suffering NAIT and NAIN in the context of alloantibodies to human platelet antigens (anti-HPA-5b) and human leukocyte antigens (anti-HLA class I). Genotyping demonstrated paternal homozygosity for HPA-5a, while the neonates were heterozygous for HPA-5b.
PubMed: 37050990
DOI: 10.7759/cureus.35950