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Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.
Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.
Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.
Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
Genetic predispositions play an important role in the development of internalizing and externalizing behaviors. Understanding the mechanisms through which genetic risk unfolds to influence these developmental outcomes is critical for developing prevention and intervention efforts, capturing key elements of Irv's research agenda and scientific legacy. In this study, we examined the role of parenting and personality in mediating the effect of genetic risk on adolescents’ major depressive disorder and conduct disorder symptoms. Longitudinal data were drawn from a sample of 709 European American adolescents and their mothers from the Collaborative Studies on Genetics of Alcoholism. Results from multivariate path analysis indicated that adolescents’ depressive symptoms genome-wide polygenic scores (DS_GPS) predicted lower parental knowledge, which in turn was associated with more subsequent major depressive disorder and conduct disorder symptoms. Adolescents’ DS_GPS also had indirect effects on these outcomes via personality, with a mediating effect via agreeableness but not via other dimensions of personality. Findings revealed that the pattern of associations was similar across adolescent gender. Our findings emphasize the important role of evocative gene–environment correlation processes and intermediate phenotypes in the pathways of risk from genetic predispositions to complex adolescent outcomes.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
Women with bipolar disorder are at increased risk of having a severe episode of illness associated with childbirth.
To explore the factors that influence the decision-making of women with bipolar disorder regarding pregnancy and childbirth.
Qualitative study with a purposive sample of women with bipolar disorder considering pregnancy, or currently or previously pregnant, supplemented by data from an online forum. Data were analysed using thematic analysis.
Twenty-one women with bipolar disorder from an NHS organisation were interviewed, and data were used from 50 women's comments via the online forum of the UK's national bipolar charity. The centrality of motherhood, social and economic contextual factors, stigma and fear were major themes. Within these themes, new findings included women considering an elective Caesarian section in an attempt to avoid the deleterious effects of a long labour and loss of sleep, or trying to avoid the risks of pregnancy altogether by means of adoption or surrogacy.
This study highlights the information needs of women with bipolar disorder, both pre-conception and when childbearing, and the need for improved training for all health professionals working with women with bipolar disorder of childbearing age to reduce stigmatising attitudes and increase knowledge of the evidence base on treatment in the perinatal period.
To determine the patterns and predictors of treatment response trajectories for veterans with post-traumatic stress disorder (PTSD).
Conditional latent growth mixture modelling was used to identify classes and predictors of class membership. In total, 2686 veterans treated for PTSD between 2002 and 2015 across 14 hospitals in Australia completed the PTSD Checklist at intake, discharge, and 3 and 9 months follow-up. Predictor variables included co-morbid mental health problems, relationship functioning, employment and compensation status.
Five distinct classes were found: those with the most severe PTSD at intake separated into a relatively large class (32.5%) with small change, and a small class (3%) with a large change. Those with slightly less severe PTSD separated into one class comprising 49.9% of the total sample with large change effects, and a second class comprising 7.9% with extremely large treatment effects. The final class (6.7%) with least severe PTSD at intake also showed a large treatment effect. Of the multiple predictor variables, depression and guilt were the only two found to predict differences in response trajectories.
These findings highlight the importance of assessing guilt and depression prior to treatment for PTSD, and for severe cases with co-morbid guilt and depression, considering an approach to trauma-focused therapy that specifically targets guilt and depression-related cognitions.
Elemental, chemical, and structural analysis of polycrystalline materials at the micron scale is frequently carried out using microfocused synchrotron X-ray beams, sometimes on multiple instruments. The Maia pixelated energy-dispersive X-ray area detector enables the simultaneous collection of X-ray fluorescence (XRF) and diffraction because of the relatively large solid angle and number of pixels when compared with other systems. The large solid angle also permits extraction of surface topography because of changes in self-absorption. This work demonstrates the capability of the Maia detector for simultaneous measurement of XRF and diffraction for mapping the short- and long-range order across the grain structure in a Ni polycrystalline foil.
The impact of underlying parental psychological vulnerability on the future mental health of offspring is not fully understood. Using a prospective cohort design, we investigated the association between dysfunctional parental personality traits and risks of offspring self-harm, depression and anxiety.
The association between dysfunctional parental personality traits (monotony avoidance, impulsivity, anger, suspicion, and detachment), measured in both mothers and fathers when offspring were age 9 years, and risk of offspring depression, anxiety and self-harm at age 18 years, was investigated in a population-based cohort (ALSPAC) from over 8000 parents and children.
Higher levels of dysfunctional maternal, but not paternal, personality traits were associated with an increased risk of self-harm, depression, and anxiety in offspring. Maternal associations were best explained by the accumulation of dysfunctional traits. Associations were strongest for offspring depression: Offspring of mothers with three or more dysfunctional personality traits were 2.27 (1.45–3.54, p < 0.001) times as likely to be depressed, compared with offspring of mothers with no dysfunctional personality traits, independently of maternal depression and other variables.
The accumulation of dysfunctional maternal personality traits is associated with the risk of self-harm, depression, anxiety in offspring independently of maternal depression and other confounding variables. The absence of associations for equivalent paternal traits makes a genetic explanation for the findings unlikely. Further research is required to elucidate the underlying mechanism. Mothers with high levels of dysfunctional personality traits may benefit from additional support to reduce the risk of adverse psychological outcomes occurring in their offspring.
The objective of the present study was to examine the relationship of dietary fried fish consumption and risk of cardiovascular events and all-cause mortality.
Prospective cohort study among participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who resided in the USA.
The primary outcome measures included the hazard ratios (HR) of incident CVD including first incident fatal or non-fatal ischaemic stroke or myocardial infarction and all-cause mortality, based on cumulative average fish consumption ascertained at baseline.
Participants (n 16 479) were enrolled between 2003 and 2007, completed the self-administered Block98 FFQ and were free of CVD at baseline.
There were 700 cardiovascular events over a mean follow-up of 5·1 years. After adjustment for sociodemographic variables, health behaviours and other CVD risk factors, participants eating ≥2 servings fried fish/week (v. <1 serving/month) were at a significantly increased risk of cardiovascular events (HR=1·63; 95 % CI 1·11, 2·40). Intake of non-fried fish was not associated with risk of incident CVD. There was no association found with dietary fried or non-fried fish intake and cardiovascular or all-cause mortality.
Fried fish intake of two or more servings per week is associated with an increased risk of cardiovascular events. Given the increased intake of fried fish in the stroke belt and among African Americans, these data suggest that dietary fried fish intake may contribute to geographic and racial disparities in CVD.
The white light corona (K + F) between 3 and 10 Rs was observed from October, 1971 through June, 1974 by the NRL coronagraph orbiting on 0S0-7. Daily images from October, 1971 through December, 1972 have been calibrated to yield the daily variation of the coronal brightness as measured through a segmented polarizing plate. This plate had segments of tangential and radial polarization which enabled the separation of the observed brightness into its polarized and unpolarized components at about 5 and 7 Rs. Each image was scanned at 35 heights above the solar limb between 3 and 10 Rs and at every 1° in heliographic position angle. The brightness of selected points in the corona was plotted to obtain the time history of the variations. Curvilinear regression of the radial brightness distributions for each month shows fluctuations in the gradient, magnitude and standard deviation from regression associated with solar activity. Taking means over the entire set of observations yields curves representing the average, the minimum and the maximum coronal brightnesses. The minimum curve derived for each position angle is interpreted as an upper limit of the F coronal brightness. The equatorial minimum curve agrees extremely well with the F model of Saito (1970) in both shape and absolute value after a corrector for stray light has been subtracted. However the minimum curve for the polar regions lies approximately 3 standard deviations (30%) below that for the equator. This implies that the F-corona is not independent of azimuth or alternatively, the minimum equatorial curve may contain a contribution from the K-corona.
Since March 28, 1979, the Solwind coronagraph has been observing the Sun's white light corona (2.6 − 10.0 R⊙) routinely with a spatial resolution of approximately 1.25 arc min and a repetition rate of 10 minutes during the one-hour sunlit portion of each 97-minute satellite orbital period. These are the first satellite observations of the outer corona near the peak of a sunspot cycle when coronal transients and high-latitude streamers are common.
This paper shows the first satellite observations of the Sun's white light corona (2.6 R⊙ −10.0 R⊙) during the active phase of a sunspot cycle. Since March 28, 1979, these observations have been obtained routinely with a spatial resolution of 1.25 arc min and a repetition rate of 10 minutes during the one-hour sunlit portion of each 97-minute satellite orbital period. As an illustration of these new observations, we show the coronal changes associated with the great mass ejection of May 8, 1979.
This paper describes the main features of the 8 May 1979 solar mass ejection, including the eruption of a polar crown filament to 1.5 R ⊙ during 0810-1036 UT and the passage of material through the outer corona, from 2.6 to 10.0 R⊙, during 1028-1246 UT.
Stress and vulnerability likely interact to play a major role in psychosis. While much has been written about the neural diathesis-stress model in psychosis and its clinical risk states, little is known about HPA axis biomarkers in non-help-seeking individuals at familial high risk (FHR). We sought to prospectively measure pituitary volume (PV) in adolescents and young adults at FHR for schizophrenia and to follow their emerging sub-clinical psychotic symptoms and clinical trajectories.
Forty healthy controls and 38 relatives of patients with schizophrenia or schizoaffective disorder were identified in Pittsburgh, USA. PV was derived from baseline 1.5 T magnetic resonance imaging. Chapman's schizotypy scales were acquired at baseline, and structured clinical interviews for DSM-IV-TR Axis I diagnoses were attempted annually for up to 3 years.
Seven individuals converted to psychosis. PV did not differ between FHR and control groups overall. Within the FHR group, PV was positively correlated with Chapman's positive schizotypy (Magical Ideation and Perceptual Aberration) scores, and there was a significant group × PV interaction with schizotypy. PV was significantly higher in FHR subjects carrying any baseline Axis I diagnosis (p = 0.004), and higher still in individuals who went on to convert to psychosis (p = 0.0007).
Increased PV is a correlate of early positive schizotypy, and may predict trait vulnerability to subsequent psychosis in FHR relatives. These preliminary findings support a model of stress-vulnerability and HPA axis activation in the early phases of psychosis.
Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG < 40), and 148 FM and 90 SCA individuals. MS-QMA identified: (i) most SCAs if combined with a Y chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility.