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Differential susceptibility theory (DST) posits that individuals differ in their developmental plasticity: some children are highly responsive to both environmental adversity and support, while others are less affected. According to this theory, “plasticity” genes that confer risk for psychopathology in adverse environments may promote superior functioning in supportive environments. We tested DST using a broad measure of child genetic liability (based on birth parent psychopathology), adoptive home environmental variables (e.g., marital warmth, parenting stress, and internalizing symptoms), and measures of child externalizing problems (n = 337) and social competence (n = 330) in 54-month-old adopted children from the Early Growth and Development Study. This adoption design is useful for examining DST because children are placed at birth or shortly thereafter with nongenetically related adoptive parents, naturally disentangling heritable and postnatal environmental effects. We conducted a series of multivariable regression analyses that included Gene × Environment interaction terms and found little evidence of DST; rather, interactions varied depending on the environmental factor of interest, in both significance and shape. Our mixed findings suggest further investigation of DST is warranted before tailoring screening and intervention recommendations to children based on their genetic liability or “sensitivity.”
La dépression maternelle en période périnatale est fréquente et peut avoir des répercussions négatives sur le développement des enfants. La prévention de la dépression chez les femmes qui ont des enfants en bas âge est donc un objectif de santé publique prioritaire. Ceci exige une bonne connaissance des facteurs associés à la dépression maternelle, des conséquences sur le développement des enfants, et des mesures préventives pouvant être efficaces. Cette session thématique abordera chacun de ces trois axes à partir de résultats récents d’études épidémiologiques et d’intervention menées en France (ELFE, EDEN, CAPEDP). Les facteurs associés à la dépression maternelle au cours de la grossesse et en post-partum, ainsi que l’accès à des interventions de prévention qui visent à prévenir les difficultés psychologiques des mères, telles que l’entretien prénatal précoce et les cours de préparation à la parentalité, ont pu être étudiés à partir des données de la cohorte ELFE, une étude représentative au niveau national. Les résultats montrent notamment que les femmes qui ont une situation sociale défavorisée ont des niveaux élevés de difficultés psychologiques, alors que ce sont celles qui bénéficient le moins des interventions de prévention. L’impact en termes de difficultés comportementales ou développementales chez les enfants a pu être étudié à partir des données de la cohorte EDEN montrant l’importance de différentes trajectoires longitudinales de dépression maternelle vis-à-vis du développement émotionnel, comportemental et cognitif des enfants jusqu’à 6 ans. Enfin, la faisabilité et l’efficacité d’interventions de prévention de la dépression maternelle seront discutées à partir des résultats de l’étude CAPEDP, un programme de visites à domicile chez des familles en situation difficile.
The resection of a subaortic membrane remains far from a curative operation. We sought to examine factors associated with reoperation and the degree of aortic valve regurgitation as a potential long-term source for reoperation.
All patients who underwent resection of an isolated subaortic membrane between 1995 and 2018 were included. Patients who underwent other procedures were excluded. Paired categorical data were compared using McNemar’s test. Univariate time-to-event analyses were performed using Kaplan–Meier methods with log-rank tests for categorical variables and univariate Cox models for continuous variables.
A total of 84 patients (median age 6.6, 31% females) underwent resection of isolated subaortic membrane. At a median follow-up of 9.3 years (interquartile range 0.6–22.5), 12 (14%) patients required one reoperation and 1 patient required two reoperations. Median time to first reoperation was 4.6 years. The degree of aortic valve regurgitation improved post-operatively from pre-operatively (p = 0.0007); however, the degree of aortic valve regurgitation worsened over the course of follow-up (p = 0.010) to equivalence with pre-operative aortic valve regurgitation (p = 0.18). Performance of a septal myectomy was associated with longer freedom from reoperation (p = 0.004).
In patients with isolated subaortic membranes, performance of a septal myectomy can minimise risk for reoperation. Patients should be serially monitored for degradation of the aortic valve, even if aortic regurgitation is not present post-operatively.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Distinguishing a disorder of persistent and impairing grief from normative grief allows clinicians to identify this often undetected and disabling condition. As four diagnostic criteria sets for a grief disorder have been proposed, their similarities and differences need to be elucidated.
Participants were family members bereaved by US military service death (N = 1732). We conducted analyses to assess the accuracy of each criteria set in identifying threshold cases (participants who endorsed baseline Inventory of Complicated Grief ⩾30 and Work and Social Adjustment Scale ⩾20) and excluding those below this threshold. We also calculated agreement among criteria sets by varying numbers of required associated symptoms.
All four criteria sets accurately excluded participants below our identified clinical threshold (i.e. correctly excluding 86–96% of those subthreshold), but they varied in identification of threshold cases (i.e. correctly identifying 47–82%). When the number of associated symptoms was held constant, criteria sets performed similarly. Accurate case identification was optimized when one or two associated symptoms were required. When employing optimized symptom numbers, pairwise agreements among criteria became correspondingly ‘very good’ (κ = 0.86–0.96).
The four proposed criteria sets describe a similar condition of persistent and impairing grief, but differ primarily in criteria restrictiveness. Diagnostic guidance for prolonged grief disorder in International Classification of Diseases, 11th Edition (ICD-11) functions well, whereas the criteria put forth in Section III of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are unnecessarily restrictive.
Vulnerability to depression can be measured in different ways. We here examine how genetic risk factors are inter-related for lifetime major depression (MD), self-report current depressive symptoms and the personality trait Neuroticism.
We obtained data from three population-based adult twin samples (Virginia n = 4672, Australia #1 n = 3598 and Australia #2 n = 1878) to which we fitted a common factor model where risk for ‘broadly defined depression’ was indexed by (i) lifetime MD assessed at personal interview, (ii) depressive symptoms, and (iii) neuroticism. We examined the proportion of genetic risk for MD deriving from the common factor v. specific to MD in each sample and then analyzed them jointly. Structural equation modeling was conducted in Mx.
The best fit models in all samples included additive genetic and unique environmental effects. The proportion of genetic effects unique to lifetime MD and not shared with the broad depression common factor in the three samples were estimated as 77, 61, and 65%, respectively. A cross-sample mega-analysis model fit well and estimated that 65% of the genetic risk for MD was unique.
A large proportion of genetic risk factors for lifetime MD was not, in the samples studied, captured by a common factor for broadly defined depression utilizing MD and self-report measures of current depressive symptoms and Neuroticism. The genetic substrate for MD may reflect neurobiological processes underlying the episodic nature of its cognitive, motor and neurovegetative manifestations, which are not well indexed by current depressive symptom and neuroticism.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
Anomalous aortic origin of a coronary artery is the second leading cause of sudden cardiac arrest/death in young athletes in the United States of America. Limited data are available regarding family history in this patient population.
Patients were evaluated prospectively from 12/2012 to 02/2017 in the Coronary Anomalies Program at Texas Children’s Hospital. Relevant family history included the presence of CHD, sudden cardiac arrest/death, arrhythmia/pacemaker use, cardiomyopathy, and atherosclerotic coronary artery disease before the age of 50 years. The presence of one or more of these in 1st- or 2nd-degree relatives was considered significant.
Of 168 unrelated probands (171 patients total) included, 36 (21%) had significant family history involving 19 (53%) 1st-degree and 17 (47%) 2nd-degree relatives. Positive family history led to cardiology referral in nine (5%) patients and the presence of abnormal tests/symptoms in the remaining patients. Coronary anomalies in probands with positive family history were anomalous right (27), anomalous left (five), single right coronary artery (two), myocardial bridge (one), and anomalous circumflex coronary artery (one). Conditions present in their family members included sudden cardiac arrest/death (15, 42%), atherosclerotic coronary artery disease (14, 39%), cardiomyopathy (12, 33%), CHD (11, 31%), coronary anomalies (3, 8%), myocardial bridge (1, 3%), long-QT syndrome (2, 6%), and Wolff–Parkinson–White (1, 3%).
In patients with anomalous aortic origin of a coronary artery and/or myocardial bridges, there appears to be familial clustering of cardiac diseases in approximately 20% of patients, half of these with early occurrence of sudden cardiac arrest/death in the family.
The goal of this study was to assess the utility of serial electrocardiograms in routine follow-up of paediatric Marfan patients.
Children ⩽18 years who met the revised Ghent criteria for Marfan syndrome and received a 12-lead electrocardiogram and echocardiogram within a 3-month period were included. Controls were matched by age, body surface area, gender, race, and ethnicity, and consisted of patients assessed in clinic with a normal cardiac evaluation. Demographic, clinical, echocardiographic, and electrocardiographic data were collected.
A total of 45 Marfan patients (10.8 [2.4–17.1] years) and 37 controls (12.8 [1.3–17.1] years) were included. Left atrial enlargement and left ventricular hypertrophy were more frequently present on 12-lead electrocardiogram of Marfan patients compared with controls (12 (27%) versus 0 (0%), p<0.001; and 8 (18%) versus 0 (0%), p=0.008, respectively); however, only two patients with left atrial enlargement on 12-lead electrocardiogram were confirmed to have left atrial enlargement by echocardiogram, and one patient had mild left ventricular hypertrophy by echocardiogram, not appreciated on 12-lead electrocardiogram. QTc interval was longer in Marfan patients compared with controls (427±16 versus 417±22 ms, p=0.03), with four Marfan patients demonstrating borderline prolonged QTc intervals for gender.
While Marfan patients exhibited a higher frequency of left atrial enlargement and left ventricular hypertrophy on 12-lead electrocardiograms compared with controls, these findings were not supported by echocardiography. Serial 12-lead electrocardiograms in routine follow-up of asymptomatic paediatric Marfan patients may be more appropriate for a subgroup of Marfan patients only, specifically those with prolonged QTc interval at their baseline visit.
The deep subsurface of other planetary bodies is of special interest for robotic and human exploration. The subsurface provides access to planetary interior processes, thus yielding insights into planetary formation and evolution. On Mars, the subsurface might harbour the most habitable conditions. In the context of human exploration, the subsurface can provide refugia for habitation from extreme surface conditions. We describe the fifth Mine Analogue Research (MINAR 5) programme at 1 km depth in the Boulby Mine, UK in collaboration with Spaceward Bound NASA and the Kalam Centre, India, to test instruments and methods for the robotic and human exploration of deep environments on the Moon and Mars. The geological context in Permian evaporites provides an analogue to evaporitic materials on other planetary bodies such as Mars. A wide range of sample acquisition instruments (NASA drills, Small Planetary Impulse Tool (SPLIT) robotic hammer, universal sampling bags), analytical instruments (Raman spectroscopy, Close-Up Imager, Minion DNA sequencing technology, methane stable isotope analysis, biomolecule and metabolic life detection instruments) and environmental monitoring equipment (passive air particle sampler, particle detectors and environmental monitoring equipment) was deployed in an integrated campaign. Investigations included studying the geochemical signatures of chloride and sulphate evaporitic minerals, testing methods for life detection and planetary protection around human-tended operations, and investigations on the radiation environment of the deep subsurface. The MINAR analogue activity occurs in an active mine, showing how the development of space exploration technology can be used to contribute to addressing immediate Earth-based challenges. During the campaign, in collaboration with European Space Agency (ESA), MINAR was used for astronaut familiarization with future exploration tools and techniques. The campaign was used to develop primary and secondary school and primary to secondary transition curriculum materials on-site during the campaign which was focused on a classroom extra vehicular activity simulation.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Family-based strategies to reduce the risk of overweight in childhood are needed in the Caribbean.
To investigate the associations between parental characteristics and risk of overweight and explore possible mechanisms.
Data from a parenting intervention were analysed. Parental characteristics were obtained by questionnaire at enrolment. At 18 months, 501 infants (82.9% of cohort) had weight and length measured using standardized methods. The association of parents’ characteristics with risk of infant overweight was assessed using random-effects logistic regression. Four focus groups among mothers in Jamaica were conducted to explore mechanisms.
Overall, 20.6% of infants were ‘at risk of overweight’. Fathers were present in 52% of households. Fathers’ presence [OR (95% CI) 0.60 (0.37–0.96)] was associated with reduced risk of overweight independent of socioeconomic status. Mothers reported that fathers encouraged healthier practices.
Fathers may be important agents of change in intervention strategies to prevent childhood overweight.
Major depression (MD) occurs about twice as often in women as in men, but it is unclear whether sex differences subsist after disease onset. This study aims to elucidate potential sex differences in rates and risk factors for MD recurrence, in order to improve prediction of course of illness and understanding of its underlying mechanisms.
We used prospective data from a general population sample (n = 653) that experienced a recent episode of MD. A diverse set of potential risk factors for recurrence of MD was analyzed using Cox models subject to elastic net regularization for males and females separately. Accuracy of the prediction models was tested in same-sex and opposite-sex test data. Additionally, interactions between sex and each of the risk factors were investigated to identify potential sex differences.
Recurrence rates and the impact of most risk factors were similar for men and women. For both sexes, prediction models were highly multifactorial including risk factors such as comorbid anxiety, early traumas, and family history. Some subtle sex differences were detected: for men, prediction models included more risk factors concerning characteristics of the depressive episode and family history of MD and generalized anxiety, whereas for women, models included more risk factors concerning early and recent adverse life events and socioeconomic problems.
No prominent sex differences in risk factors for recurrence of MD were found, potentially indicating similar disease maintaining mechanisms for both sexes. Course of MD is a multifactorial phenomenon for both males and females.
Cerebrovascular reactivity monitoring has been used to identify the lower limit of pressure autoregulation in adult patients with brain injury. We hypothesise that impaired cerebrovascular reactivity and time spent below the lower limit of autoregulation during cardiopulmonary bypass will result in hypoperfusion injuries to the brain detectable by elevation in serum glial fibrillary acidic protein level.
We designed a multicentre observational pilot study combining concurrent cerebrovascular reactivity and biomarker monitoring during cardiopulmonary bypass. All children undergoing bypass for CHD were eligible. Autoregulation was monitored with the haemoglobin volume index, a moving correlation coefficient between the mean arterial blood pressure and the near-infrared spectroscopy-based trend of cerebral blood volume. Both haemoglobin volume index and glial fibrillary acidic protein data were analysed by phases of bypass. Each patient’s autoregulation curve was analysed to identify the lower limit of autoregulation and optimal arterial blood pressure.
A total of 57 children had autoregulation and biomarker data for all phases of bypass. The mean baseline haemoglobin volume index was 0.084. Haemoglobin volume index increased with lowering of pressure with 82% demonstrating a lower limit of autoregulation (41±9 mmHg), whereas 100% demonstrated optimal blood pressure (48±11 mmHg). There was a significant association between an individual’s peak autoregulation and biomarker values (p=0.01).
Individual, dynamic non-invasive cerebrovascular reactivity monitoring demonstrated transient periods of impairment related to possible silent brain injury. The association between an impaired autoregulation burden and elevation in the serum brain biomarker may identify brain perfusion risk that could result in injury.