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Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
The Reinforcement Sensitivity Theory of Personality has as its main foundation a Behavioural Inhibition System (BIS), defined by anxiolytic drugs, in which high trait sensitivity should lead to internalising, anxiety, disorders. Conversely, it has been suggested that low BIS sensitivity would be a characteristic of externalising disorders. BIS output should lead to increased arousal and attention as well as behavioural inhibition. Here, therefore, we tested whether an externalising disorder, Attention Deficit Hyperactivity Disorder (ADHD), involves low BIS sensitivity. Goal-Conflict-Specific Rhythmicity (GCSR) in an auditory Stop Signal Task is a right frontal EEG biomarker of BIS function. We assessed children diagnosed with ADHD-I (inattentive) or ADHD-C (combined) and healthy control groups for GCSR in: a) an initial smaller study in Dunedin, New Zealand (population ~120,000: 15 control, 10 ADHD-I, 10 ADHD-C); and b) a main larger one in Tehran, Iran (population ~9 [city]-16 [metropolis] million: 27 control, 18 ADHD-I, 21 ADHD-C). GCSR was clear in controls (particularly at 6–7 Hz) and in ADHD-C (particularly at 8–9 Hz) but was reduced in ADHD-I. Reduced attention and arousal in ADHD-I could be due, in part, to BIS dysfunction. However, hyperactivity and impulsivity in ADHD-C are unlikely to reflect reduced BIS activity. Increased GCSR frequency in ADHD-C may be due to increased input to the BIS. BIS dysfunction may contribute to some aspects of ADHD (and potentially other externalising disorders) and to some differences between the ADHD subtypes but other prefrontal systems (and, e.g. dopamine) are also important.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Maternal mental health during pregnancy and postpartum predicts later emotional and behavioural problems in children. Even though most perinatal mental health problems begin before pregnancy, the consequences of preconception maternal mental health for children's early emotional development have not been prospectively studied.
We used data from two prospective Australian intergenerational cohorts, with 756 women assessed repeatedly for mental health problems before pregnancy between age 13 and 29 years, and during pregnancy and at 1 year postpartum for 1231 subsequent pregnancies. Offspring infant emotional reactivity, an early indicator of differential sensitivity denoting increased risk of emotional problems under adversity, was assessed at 1 year postpartum.
Thirty-seven percent of infants born to mothers with persistent preconception mental health problems were categorised as high in emotional reactivity, compared to 23% born to mothers without preconception history (adjusted OR 2.1, 95% CI 1.4–3.1). Ante- and postnatal maternal depressive symptoms were similarly associated with infant emotional reactivity, but these perinatal associations reduced somewhat after adjustment for prior exposure. Causal mediation analysis further showed that 88% of the preconception risk was a direct effect, not mediated by perinatal exposure.
Maternal preconception mental health problems predict infant emotional reactivity, independently of maternal perinatal mental health; while associations between perinatal depressive symptoms and infant reactivity are partially explained by prior exposure. Findings suggest that processes shaping early vulnerability for later mental disorders arise well before conception. There is an emerging case for expanding developmental theories and trialling preventive interventions in the years before pregnancy.
A robust biomedical informatics infrastructure is essential for academic health centers engaged in translational research. There are no templates for what such an infrastructure encompasses or how it is funded. An informatics workgroup within the Clinical and Translational Science Awards network conducted an analysis to identify the scope, governance, and funding of this infrastructure. After we identified the essential components of an informatics infrastructure, we surveyed informatics leaders at network institutions about the governance and sustainability of the different components. Results from 42 survey respondents showed significant variations in governance and sustainability; however, some trends also emerged. Core informatics components such as electronic data capture systems, electronic health records data repositories, and related tools had mixed models of funding including, fee-for-service, extramural grants, and institutional support. Several key components such as regulatory systems (e.g., electronic Institutional Review Board [IRB] systems, grants, and contracts), security systems, data warehouses, and clinical trials management systems were overwhelmingly supported as institutional infrastructure. The findings highlighted in this report are worth noting for academic health centers and funding agencies involved in planning current and future informatics infrastructure, which provides the foundation for a robust, data-driven clinical and translational research program.
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.
Low birth weight has been inconsistently associated with risk of
developing affective disorders, including major depressive disorder
(MDD). To date, studies investigating possible associations between birth
weight and bipolar disorder (BD), or personality traits known to
predispose to affective disorders such as neuroticism, have not been
conducted in large cohorts.
To assess whether very low birth weight (<1500 g) and low birth weight
(1500–2490 g) were associated with higher neuroticism scores assessed in
middle age, and lifetime history of either MDD or BD. We controlled for
possible confounding factors.
Retrospective cohort study using baseline data on the 83 545 UK Biobank
participants with detailed mental health and birth weight data. Main
outcomes were prevalent MDD and BD, and neuroticism assessed using the
Eysenck Personality Inventory Neuroticism scale - Revised (EPIN-R)
Referent to normal birth weight, very low/low birth weight were
associated with higher neuroticism scores, increased MDD and BD. The
associations between birth weight category and MDD were partially
mediated by higher neuroticism.
These findings suggest that intrauterine programming may play a role in
lifetime vulnerability to affective disorders.
Polygenic risk scores (PRS) for depression correlate with depression status and chronicity, and provide causal anchors to identify depressive mechanisms. Neuroticism is phenotypically and genetically positively associated with depression, whereas psychological resilience demonstrates negative phenotypic associations. Whether increased neuroticism and reduced resilience are downstream mediators of genetic risk for depression, and whether they contribute independently to risk remains unknown.
Moderating and mediating relationships between depression PRS, neuroticism, resilience and both clinical and self-reported depression were examined in a large, population-based cohort, Generation Scotland: Scottish Family Health Study (N = 4166), using linear regression and structural equation modelling. Neuroticism and resilience were measured by the Eysenck Personality Scale Short Form Revised and the Brief Resilience Scale, respectively.
PRS for depression was associated with increased likelihood of self-reported and clinical depression. No interaction was found between PRS and neuroticism, or between PRS and resilience. Neuroticism was associated with increased likelihood of self-reported and clinical depression, whereas resilience was associated with reduced risk. Structural equation modelling suggested the association between PRS and self-reported and clinical depression was mediated by neuroticism (43–57%), while resilience mediated the association in the opposite direction (37–40%). For both self-reported and clinical diagnoses, the genetic risk for depression was independently mediated by neuroticism and resilience.
Findings suggest polygenic risk for depression increases vulnerability for self-reported and clinical depression through independent effects on increased neuroticism and reduced psychological resilience. In addition, two partially independent mechanisms – neuroticism and resilience – may form part of the pathway of vulnerability to depression.
Feeding the dairy cow during the transition phase (dry to lactating) has been found to effect subsequent feed intake and milk yield (Moorby et al., 1996; Olsson et al., 1998). The aim of this study was to compare the effect of feeding a liquid feed during the prepartum period on; feed intake, milk yield, milk composition, live weight loss and blood metabolite levels.
California and Washington recently replaced traditional partisan elections with nonpartisan “top-two” election procedures. Some reform advocates hoped that voters would behave in a way to support moderate candidates in the primary stage; the limited evidence for this behaviour has led some scholars to conclude that the reform has little chance to change meaningful policy outcomes. Yet we find that the nonpartisan procedure has predictable and disparate political consequences: the general elections between two candidates of the same party, called copartisan general elections, tend to occur in districts without any meaningful crossparty competition. Furthermore, copartisan elections are more likely to occur with open seats, when a new legislator will begin building a network of relationships. The results, viewed through the lens of the Advocacy Coalition Framework, suggest that opportunities exist for coalitional rearrangement over time.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
The spatial distribution and polarization characteristics of the SiO (v=1, J=1-0) maser emission from several late type stars have been observed. The spatial distribution, derived from VLBI observations, generally shows a number of emitting regions but no clear velocity pattern or geometry. Some of these regions have well defined polarization characteristics. The results of high spatial resolution polarization measurements of RCas are similar to the lower spatial resolution polarimetry performed on this source.
Information on the structure of the molecular flow within 1″ of IRC-2, in Orion-KL, is sparse. Measurements of the continuum at 7.8μ and 12.5μ show a disk of size and suggest that the center of the disk may be dust free (Lester et al. 1985). Aperture synthesis mapping of water maser shell features (Sylber 1986) has provided information on the scale. Smaller scales can be studied by mapping SiO maser emission. We observed the 43 GHz, v=1, J = 1 → 0, transition of SiO using a 2 station interferometer with a 74 km baseline between Haystack Observatory, Westford, MA and Five College Radio Observatory, New Salem, MA. The fringe spacing was 20 milliarcseconds (mas) and the velocity resolution was 0.25 km-s−1. Our results provide the highest resolution view to date of what is likely to be the inner of IRC-2.
The Coronal Solar Magnetism Observatory (CoSMO) is a proposed new facility led by the High Altitude Observatory and a consortium of partners to measure magnetic field and plasma properties in a large (one degree) field of view extending down to the inner parts of the solar corona. CoSMO is intended as a research facility that will advance the understanding and prediction of space weather. The instrumentation elements of CoSMO are: a white-light coronagraph (KCor), already operational at the Mauna Loa Solar Observatory (MLSO); the Chromosphere and Prominence Magnetometer (ChroMag), due for deployment to MLSO next year; and the CoSMO Large Coronagraph (LC) which has completed Preliminary Design Review.
Introduction: This study evaluates the association of baseline e-cigarette use with smoking cessation in a sample of 2-year college student smokers.
Methods: Participants were 1,400 students from over 60 2-year colleges across 25 states who were current smokers enrolled in a web-assisted tobacco intervention (WATI) trial. Survey data at baseline, 1-, and 6-months, were evaluated.
Results: At 6-months, baseline e-cigarette users were more likely to report cessation of traditional cigarettes compared to non-users (OR 1.39, 95% CI 1.002–1.92). Cessation was also associated with higher baseline confidence in quitting and greater time to first cigarette after awakening. Baseline e-cigarette use was not associated with self-reported cessation of all nicotine/tobacco products (OR 1.09, 95% CI 0.75–1.58) nor biochemically verified cessation of all nicotine/tobacco products (OR 0.83, 95% CI 0.47–1.47). Higher confidence was again associated with both self-reported and biochemically verified cessation of all nicotines.
There is a lack of evidence pointing to the efficacy of any specific psychotherapy for adults with anorexia nervosa (AN). The aim of this study was to compare three psychological treatments for AN: Specialist Supportive Clinical Management, Maudsley Model Anorexia Nervosa Treatment for Adults and Enhanced Cognitive Behavioural Therapy.
A multi-centre randomised controlled trial was conducted with outcomes assessed at pre-, mid- and post-treatment, and 6- and 12-month follow-up by researchers blind to treatment allocation. All analyses were intention-to-treat. One hundred and twenty individuals meeting diagnostic criteria for AN were recruited from outpatient treatment settings in three Australian cities and offered 25–40 sessions over a 10-month period. Primary outcomes were body mass index (BMI) and eating disorder psychopathology. Secondary outcomes included depression, anxiety, stress and psychosocial impairment.
Treatment was completed by 60% of participants and 52.5% of the total sample completed 12-month follow-up. Completion rates did not differ between treatments. There were no significant differences between treatments on continuous outcomes; all resulted in clinically significant improvements in BMI, eating disorder psychopathology, general psychopathology and psychosocial impairment that were maintained over follow-up. There were no significant differences between treatments with regard to the achievement of a healthy weight (mean = 50%) or remission (mean = 28.3%) at 12-month follow-up.
The findings add to the evidence base for these three psychological treatments for adults with AN, but the results underscore the need for continued efforts to improve outpatient treatments for this disorder.