Although now believed to be two distinct disorders, autism spectrum disorders (ASD) and schizophrenia spectrum disorders (SSD) share multiple phenotypic similarities and risk factors, and have been ...reported to co-occur at elevated rates. In this narrative review, we give a brief overview of the phenomenological, genetic, environmental, and imaging evidence for the overlap between ASD and SSD, highlighting similarities and areas of distinction. We examine eight possible alternate models of explanation for the association and comorbidity between the disorders, and set out a research agenda to test these models. Understanding how and why these disorders co-occur has important implications for diagnosis, treatment, and prognosis, as well as for developing fundamental aetiological models of the disorders.
ATP citrate lyase is an enzyme in the cholesterol-biosynthesis pathway upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the target of statins. Whether the genetic inhibition of ...ATP citrate lyase is associated with deleterious outcomes and whether it has the same effect, per unit decrease in the low-density lipoprotein (LDL) cholesterol level, as the genetic inhibition of HMGCR is unclear.
We constructed genetic scores composed of independently inherited variants in the genes encoding ATP citrate lyase (
) and HMGCR to create instruments that mimic the effect of ATP citrate lyase inhibitors and HMGCR inhibitors (statins), respectively. We then compared the associations of these genetic scores with plasma lipid levels, lipoprotein levels, and the risk of cardiovascular events and cancer.
A total of 654,783 participants, including 105,429 participants who had major cardiovascular events, were included in the study. The
and
scores were associated with similar patterns of changes in plasma lipid and lipoprotein levels and with similar effects on the risk of cardiovascular events per decrease of 10 mg per deciliter in the LDL cholesterol level: odds ratio for cardiovascular events, 0.823 (95% confidence interval CI, 0.78 to 0.87; P = 4.0×10
) for the
score and 0.836 (95% CI, 0.81 to 0.87; P = 3.9×10
) for the
score. Neither lifelong genetic inhibition of ATP citrate lyase nor lifelong genetic inhibition of HMGCR was associated with an increased risk of cancer.
Genetic variants that mimic the effect of ATP citrate lyase inhibitors and statins appeared to lower plasma LDL cholesterol levels by the same mechanism of action and were associated with similar effects on the risk of cardiovascular disease per unit decrease in the LDL cholesterol level. (Funded by Esperion Therapeutics and others.).
Two-thirds of individuals identified as at ultra-high risk for psychosis do not develop psychotic disorder over the medium term. The authors examined outcomes in a group of such patients.
...Participants were help-seeking individuals identified as being at ultra-high risk for psychosis 2-14 years previously. The 226 participants (125 female, 101 male) completed a follow-up assessment and had not developed psychosis. Their mean age at follow-up was 25.5 years (SD=4.8).
At follow-up, 28% of the participants reported attenuated psychotic symptoms. Over the follow-up period, 68% experienced nonpsychotic disorders: mood disorder in 49%, anxiety disorder in 35%, and substance use disorder in 29%. For the majority (90%), nonpsychotic disorder was present at baseline, and it persisted for 52% of them. During follow-up, 26% of the cohort had remission of a disorder, but 38% developed a new disorder. Only 7% did not experience any disorder at baseline or during follow up. The incidence of nonpsychotic disorder was associated with more negative symptoms at baseline. Female participants experienced higher rates of persistent or recurrent disorder. Meeting criteria for brief limited intermittent psychotic symptoms at intake was associated with lower risk for persistent or recurrent disorder.
Individuals at ultra-high risk for psychosis who do not transition to psychosis are at significant risk for continued attenuated psychotic symptoms, persistent or recurrent disorders, and incident disorders. Findings have implications for ongoing clinical care.
Objective
To provide a comprehensive analysis of cytokine perturbations in antipsychotic‐naïve first‐episode psychosis (FEP) populations and assess the relationship between inflammatory biomarkers ...and negative symptom severity.
Methods
A systematic review and meta‐analysis following PRISMA guidelines were conducted. A total of 1042 records were identified via systematic search of EMBASE, MEDLINE and APA PsycInfo databases. Sixteen studies met the inclusion criteria and were eligible for inclusion in the review. Ten of these studies had sufficient data for inclusion in a random effects, pooled‐effect meta‐analysis.
Results
A significant and large effect size was reported for IFN‐γ, IL‐6 and IL‐12, and a moderate effect size reported for IL‐17 (p = <0.05) in people with antipsychotic naive first episode psychosis, compared to healthy controls, suggesting a significant elevation in proinflammatory cytokine concentration. Non‐significant effect sizes were reported for TNF‐α, IL‐1β, IL‐2, IL‐4, IL‐8 and IL‐10 (p = >0.05). Regarding proinflammatory cytokines and relationships to negative symptomology, moderate positive relationships were reported for negative symptoms and IL‐1β, IL‐2, IL‐6 and TNF‐α, across four studies. For anti‐inflammatory cytokines, one strong and one weak‐to‐moderate negative relationship was described for IL‐10 and negative symptoms. Contrastingly, a strong positive relationship was reported for IL‐4 and negative symptoms.
Conclusion
There is evidence of significantly elevated proinflammatory cytokines in antipsychotic‐naïve FEP populations, alongside promising findings from cohort data suggesting an interaction between inflammation and primary negative symptomology. Future studies should seek to come to a consensus on a panel of cytokines that relate most specifically to negative symptoms, and consider longitudinal studies to investigate how cytokine fluctuations may relate to exacerbation of symptoms.
This study investigated the influence of personality characteristics and gender on adolescents' perception of risk and their risk-taking behaviour. Male and female participants (157 females: 116 ...males, aged 13-20) completed self-report measures on risk perception, risk-taking and personality. Male participants perceived behaviours as less risky, reportedly took more risks, were less sensitive to negative outcomes and less socially anxious than female participants. Path analysis identified a model in which age, behavioural inhibition and impulsiveness directly influenced risk perception, while age, social anxiety, impulsiveness, sensitivity to reward, behavioural inhibition and risk perception itself were directly or indirectly associated with risk-taking behaviour. Age and behavioural inhibition had direct relationships with social anxiety, and reward sensitivity was associated with impulsiveness. The model was representative for the whole sample and male and female groups separately. The observed relationship between age and social anxiety and the influence this may have on risk-taking behaviour could be key for reducing adolescent risk-taking behaviour. Even though adolescents may understand the riskiness of their behaviour and estimate their vulnerability to risk at a similar level to adults, factors such as anxiety regarding social situations, sensitivity to reward and impulsiveness may exert their influence and make these individuals prone to taking risks. If these associations are proven causal, these factors are, and will continue to be, important targets in prevention and intervention efforts.
Satellite Estimation of Falling Snow Skofronick-Jackson, Gail; Kulie, Mark; Milani, Lisa ...
Journal of applied meteorology and climatology,
07/2019, Letnik:
58, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Retrievals of falling snow from space-based observations represent key inputs for understanding and linking Earth’s atmospheric, hydrological, and energy cycles. This work quantifies and investigates ...causes of differences among the first stable falling snow retrieval products from the Global Precipitation Measurement (GPM) Core Observatory satellite and CloudSat’s Cloud Profiling Radar (CPR) falling snow product. An important part of this analysis details the challenges associated with comparing the various GPM and CloudSat snow estimates arising from different snow–rain classification methods, orbits, resolutions, sampling, instrument specifications, and algorithm assumptions. After equalizing snow–rain classification methodologies and limiting latitudinal extent, CPR observes nearly 10 (3) times the occurrence (accumulation) of falling snow as GPM’s Dual-Frequency Precipitation Radar (DPR). The occurrence disparity is substantially reduced if CloudSat pixels are averaged to simulate DPR radar pixels and CPR observations are truncated below the 8-dBZ reflectivity threshold. However, even though the truncated CPR- and DPR-based data have similar falling snow occurrences, average snowfall rate from the truncated CPR record remains significantly higher (43%) than the DPR, indicating that retrieval assumptions (microphysics and snow scattering properties) are quite different. Diagnostic reflectivity (Z)–snow rate (S) relationships were therefore developed at Ku and W band using the same snow scattering properties and particle size distributions in a final effort to minimize algorithm differences. CPR–DPR snowfall amount differences were reduced to ~16% after adopting this diagnostic Z–S approach.
Neurobiological heterogeneity in schizophrenia is poorly understood and confounds current analyses. We investigated neuroanatomical subtypes in a multi-institutional multi-ethnic cohort, using novel ...semi-supervised machine learning methods designed to discover patterns associated with disease rather than normal anatomical variation. Structural MRI and clinical measures in established schizophrenia (n = 307) and healthy controls (n = 364) were analysed across three sites of PHENOM (Psychosis Heterogeneity Evaluated via Dimensional Neuroimaging) consortium. Regional volumetric measures of grey matter, white matter, and CSF were used to identify distinct and reproducible neuroanatomical subtypes of schizophrenia. Two distinct neuroanatomical subtypes were found. Subtype 1 showed widespread lower grey matter volumes, most prominent in thalamus, nucleus accumbens, medial temporal, medial prefrontal/frontal and insular cortices. Subtype 2 showed increased volume in the basal ganglia and internal capsule, and otherwise normal brain volumes. Grey matter volume correlated negatively with illness duration in Subtype 1 (r = -0.201, P = 0.016) but not in Subtype 2 (r = -0.045, P = 0.652), potentially indicating different underlying neuropathological processes. The subtypes did not differ in age (t = -1.603, df = 305, P = 0.109), sex (chi-square = 0.013, df = 1, P = 0.910), illness duration (t = -0.167, df = 277, P = 0.868), antipsychotic dose (t = -0.439, df = 210, P = 0.521), age of illness onset (t = -1.355, df = 277, P = 0.177), positive symptoms (t = 0.249, df = 289, P = 0.803), negative symptoms (t = 0.151, df = 289, P = 0.879), or antipsychotic type (chi-square = 6.670, df = 3, P = 0.083). Subtype 1 had lower educational attainment than Subtype 2 (chi-square = 6.389, df = 2, P = 0.041). In conclusion, we discovered two distinct and highly reproducible neuroanatomical subtypes. Subtype 1 displayed widespread volume reduction correlating with illness duration, and worse premorbid functioning. Subtype 2 had normal and stable anatomy, except for larger basal ganglia and internal capsule, not explained by antipsychotic dose. These subtypes challenge the notion that brain volume loss is a general feature of schizophrenia and suggest differential aetiologies. They can facilitate strategies for clinical trial enrichment and stratification, and precision diagnostics.
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