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Various psychological and biological pathways have been proposed as mediators between childhood adversity (CA) and psychosis. A systematic review of the evidence in this domain is needed. Our aim is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This review followed PRISMA guidelines. Articles published between 1979 and July 2019 were identified through a literature search in OVID (PsychINFO, Medline and Embase) and Cochrane Libraries. The evidence by each analysis and each study is presented by group of mediator categories found. The percentage of total effect mediated was calculated. Forty-eight studies were included, 21 in clinical samples and 27 in the general population (GP) with a total of 82 352 subjects from GP and 3189 from clinical studies. The quality of studies was judged as ‘fair’. Our results showed (i) solid evidence of mediation between CA and psychosis by negative cognitive schemas about the self, the world and others (NS); by dissociation and other post-traumatic stress disorder symptoms; and through an affective pathway in GP but not in subjects with disorder; (iii) lack of studies exploring biological mediators. We found evidence suggesting that various overlapping and not competing pathways involving post-traumatic and mood symptoms, as well as negative cognitions contribute partially to the link between CA and psychosis. Experiences of CA, along with relevant mediators should be routinely assessed in patients with psychosis. Evidence testing efficacy of interventions targeting such mediators through cognitive behavioural approaches and/or pharmacological means is needed in future.
The association between childhood adversity (CA) and psychosis has been extensively investigated in recent years. An increasing body of research has also focused on the mediating or moderating role of biological and psychological mechanisms, as well as other risk factors that might account for the link between CA and psychosis. We conducted a systematic search of the PsychINFO, Embase, Ovid, and Web of Science databases for original articles investigating the role of genetic vulnerabilities, environmental factors, psychological and psychopathological mechanisms in the association between CA and psychosis up to August 2019. We included studies with individuals at different stages of the psychosis continuum, from subclinical psychotic experiences to diagnosed disorders. From the 28 944 records identified, a total of 121 studies were included in this review. Only 26% of the studies identified met the criteria for methodological robustness. Overall, the current evidence suggests that CA may be associated with psychosis largely independently of genetic vulnerabilities. More consistent and robust evidence supports interaction between early and recent adversities, as well as the mediating role of attachment and mood symptoms, which is suggestive of an affective pathway between CA and psychosis across the continuum from subclinical experiences to diagnosable disorder. This review highlighted numerous methodological issues with the existing literature, including selection bias, heterogeneity of measurement instruments utilised, and lack of control for potential confounders. Future research should address these limitations to more accurately estimate mediation and moderation effects on the CA-psychosis association to inform the development of preventive interventions.
The Reaction Centers (RCs) proteins are membrane proteins representing the key component so flight energy transduction in photosynthetic organisms. Upon photon absorption, these photoenzymes produce a long lasting intra protein hole electron couples whose charges are separated by 3 nanometers. The dipoles formed within the RCs can be effectively employed as transducing cores of several biological-organic hybrid devices whose design can accomplish photocurrents generation or act as phototransistor. To widen the application of the RCs to as many substrate as possible one valuable strategy is the bioconjugation of the protein with specific molecules ad-hoc selected to improve enzymatic performance and/or integration in proper scaffolding. In the present manuscript, we investigate the changes of the isoelectric point of the RC from the carotenoidless strain of the photosynthetic bacterium Rhodobacter sphaeroides R26 by inducing “in silico” mutations to predict on the role of the aminoacids involved in the bioconjugation.
Dilute aqueous solutions of dopamine buffered to an alkaline pH and in the presence of dissolved oxygen undergo to a series of autoxidation and rearrangement reactions that lead to the formation of a dark insoluble material called polydopamine (PDA) with melanin reminiscent properties. In this work we carried out this reaction in the presence of the photosynthetic reaction center (RC), a transmembrane pigment-protein complex responsible for the first light-induced reactions in the photosynthetic process. We have found that PDA grows in colloidal form around the RC and in the appropriate conditions the protein is entrapped in the PDA matrix without loss of functionality. The protein is still capable to perform its natural photocycle leading to the generation of photocurrents and the ubiquinone acceptor complex function is modulated by the PDA/RC ratio.
Most of the photochemical activity of bacterial photosynthetic apparatuses occurs in the reaction center, a transmembrane protein complex which converts photons into charge-separated states across the membrane with a quantum yield close to unity, fuelling the metabolism of the organism. Integrating the reaction center from the bacterium Rhodobacter sphaeroides onto electroactive surfaces, it is possible to technologically exploit the efficiency of this natural machinery to generate a photovoltage upon Near Infra-Red illumination, which can be used in electronic architectures working in the electrolytic environment such as electrolyte-gated organic transistors and bio-photonic power cells. Here, photovoltage generation in reaction center-based bio-hybrid architectures is investigated by means of chronopotentiometry, isolating the contribution of the functionalisation layers and defining novel surface functionalization strategies for photovoltage tuning.
Bioelectronics requires versatile, efficient, and low-cost interfaces between the biological entities and the conductive unit. Conductive polymers represent a valid choice to assemble such interfaces able to extract or impinge charges between the biological units and the conductive electronic systems. A drawback in the use of such systems is that the polymerization reaction often takes place in environments whose chemical and physical characteristics clash with the mild conditions required for living biological systems. In the present work, we successfully prove that the conductive polymer poly(gallic acid) can be synthesized in medium designed for bacterial growth, characterised by the presence of several adverse conditions including numerous chemicals, high ionic strength, and almost neutral pH. The gallic acid successfully polymerizes within few hours and with a 40% yield, by exploiting the catalytic activity of the enzyme laccase from the polypore mushroom Trametes versicolor. The resulting polymer is characterised by absorption and Nuclear Magnetic Resonance spectroscopies. The viability of Rhodobacter sphaeroides culture, assessed via the coffee-ring technique, shows an important, but not complete detrimental effect of the gallic acid on the bacterial growth.
Risk prediction algorithms have long been used in health research and practice (e.g. prediction of cardiovascular disease and diabetes). However, similar tools have not been developed for mental health. For example, for psychotic disorders, attempts to sum environmental risk are rare, unsystematic and dictated by available data. In light of this, we sought to develop a valid, easy to use measure of the aggregate environmental risk score (ERS) for psychotic disorders.
We reviewed the literature to identify well-replicated and validated environmental risk factors for psychosis that combine a significant effect and large-enough prevalence. Pooled estimates of relative risks were taken from the largest available meta-analyses. We devised a method of scoring the level of exposure to each risk factor to estimate ERS. Relative risks were rounded as, due to the heterogeneity of the original studies, risk effects are imprecisely measured.
Six risk factors (ethnic minority status, urbanicity, high paternal age, obstetric complications, cannabis use and childhood adversity) were used to generate the ERS. A distribution for different levels of risk based on simulated data showed that most of the population would be at low/moderate risk with a small minority at increased environmental risk for psychosis.
This is the first systematic approach to develop an aggregate measure of environmental risk for psychoses in asymptomatic individuals. This can be used as a continuous measure of liability to disease; mostly relevant to areas where the original studies took place. Its predictive ability will improve with the collection of additional, population-specific data.
This article discusses the role of music performance in football matches, highlighting the importance of the belief in its sonic powers as a trigger for causal relations between events. Music functions as a communicational axis linking the physical realm to mystical or intangible dimensions. By performing music and sounds on terraces, fans believe that they can change the course of the match, interfering in the mood, the bodies and, eventually, the result. Magic is a shared belief among fans, players and journalists, one that is activated through sounds and rituals. In football, the idea of magic is often perceived and referred to as a causal explanation for achievements and defeats that could hardly be understood or explained through rational and scientific knowledge. Music is a key feature in this process.
Particular attention has been recently devoted to the development of biohybrid photoconverters based on the bacterial Reaction Center (RC) of Rhodobacter sphaeroides. This highly efficient photoenzyme has a conversion yield close to unit that makes it extremely appealing in the field of artificial photosynthesis. Isolated RCs suffer of a limited absorption cross-section in the visible spectral region that limits their applicative employment. Here we report the synthesis of two heptamethine cyanine molecules, whose photophysical properties make them potentially suitable as light harvesting antennas for the RC.
Optimizing interfaces between photosynthetic natural photoconverters, like photosynthetic bacterial Reaction Centers (RCs) and electrode surfaces represents a challenge in the progress of bio-optoelectronic devices. The features of the surfaces may result detrimental for the tertiary and quaternary structures of the RC, even resulting in the denaturation of the enzyme. Functional surfaces possessing both confinement capability and conductive features able to preserve the conformation of the biomolecule and its bioelectronic behaviours are highly needed. In this work, the RC is adsorbed on diatomaceous silica and plasma treated hydrophobic silicon based materials. Both the materials are demonstrated to be able to preserve and enhance the RC photoconverting activity. In particular, we evaluate the functioning of isolated bacterial RC interacting with flat pSi electrode through two nanotextured interfaces designed to address the RC: a thin conductive silicon film nanotextured in pillars via plasma treatment, and a cast film of nanostructured dielectric biosilica obtained from diatomaceous earth. The characterization of these interfaces, together with the RC photocurrent production measurements, pave the way to new generation RC based bio-devices for photocurrent investigation.
The photosynthetic Reaction Center from the carotenoidless mutant strain of the purple non sulphur bacterium Rhodobacter (R.) sphaeroides was reconstituted in artificial phospholipid vesicles (liposomes) to mimic the physiological membrane environment. The pH dependence in the interval 5 – 10 of the rate of the charge-recombination reactions from the final electron acceptors QA and QB to the primary electron donor (namely kAD and kBD) have been investigated. The liposomes were constituted of either the zwitterionic phosphatidylcholine (PC) or the negatively charged phosphatidylglycerol (PG), two of the main phospholipids found in the photosynthetic membrane of the bacterium. In both cases, the kAD has no pH dependence similarly to the detergent case. The kBD also has a pH dependence similar to the detergent case, having two distinct regions below pH 7 and above pH 9. Fitting of the titration curve to a function involving two protonation sites results in a marked shift of the pKAs between the different solubilizing environments. These differences are discussed in the frame of possible physiological implications.
Sunlight is the most environmental friendly energy source available on Earth; many efforts devoted to design artificial photoconversion systems are ongoing, nevertheless they are still expensive and poorly efficient. Photoconversion devices made with organic-biological hybrids, or biohybrids, based on the photosynthetic reaction center (RC) have been introduced. In these systems, the photoenzyme is garnished with artificial antennas to enhance the photoactivity of the RC. Here we present a newly synthesized heptamethine cyanine dye that fulfills requisites to act as efficient RC light harvesting antenna.
Jumping to conclusions (JTC), which is the proneness to require less information before forming beliefs or making a decision, has been related to formation and maintenance of delusions. Using data from the National Institute of Health Research Biomedical Research Centre Genetics and Psychosis (GAP) case–control study of first-episode psychosis (FEP), we set out to test whether the presence of JTC would predict poor clinical outcome at 4 years.
One-hundred and twenty-three FEP patients were assessed with the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and the probabilistic reasoning ‘Beads’ Task at the time of recruitment. The sample was split into two groups based on the presence of JTC bias. Follow-up data over an average of 4 years were obtained concerning clinical course and outcomes (remission, intervention of police, use of involuntary treatment – the Mental Health Act (MHA) – and inpatient days).
FEP who presented JTC at baseline were more likely during the follow-up period to be detained under the MHA [adjusted OR 15.62, 95% confidence interval (CI) 2.92–83.54, p = 0.001], require intervention by the police (adjusted OR 14.95, 95% CI 2.68–83.34, p = 0.002) and have longer admissions (adjusted IRR = 5.03, 95% CI 1.91–13.24, p = 0.001). These associations were not accounted for by socio-demographic variables, IQ and symptom dimensions.
JTC in FEP is associated with poorer outcome as indicated and defined by more compulsion police intervention and longer periods of admission. Our findings raise the question of whether the implementation of specific interventions to reduce JTC, such as Metacognition Training, may be a useful addition in early psychosis intervention programmes.
We present a continuously tunable 52-to-67 GHz push–push dual-core voltage-controlled oscillator (VCO) in a 40 nm bulk complementary metal–oxide–semiconductor (CMOS) technology. The circuit is suitable for 60 GHz frequency-modulated-continuous-wave radar applications requiring a continuously tunable ultra-wide modulation bandwidth. The LC-tank inductor is used to couple the two VCO cores. The fundamental frequency of the VCO can be tuned from 26 to 33.5 GHz, which corresponds to a frequency tuning range of 25%. The second harmonic is extracted in a non-invasive way using a transformer. The primary side acts simultaneously as a second harmonic filter. The VCO achieves in measurement a low phase noise of −91.8 dBc/Hz at 1 MHz offset at 62 GHz and an output power of −20 dBm. The VCO including buffers dissipates in the dual-core operation mode 60 mA from a single 1.1 V supply and consumes a chip area of 0.58 mm2.
The association between childhood adversity and psychosis in adulthood is well established. However, genetic factors might confound or moderate this association.
Using a catchment-based case-control sample, we explored the main effects of, and interplay between, childhood adversity and family psychiatric history on the onset of psychosis.
Childhood adversity (parental separation and death, physical and sexual abuse) was assessed retrospectively in 224 individuals with a first presentation of psychosis and 256 community controls from South London, UK. Occurrence of psychotic and affective disorders in first-degree relatives was ascertained with the Family Interview for Genetic Studies (FIGS).
Parental history of psychosis did not confound the association between childhood adversity and psychotic disorder. There was no evidence that childhood adversity and familial liability combined synergistically to increase odds of psychosis beyond the effect of each individually.
Our results do not support the hypothesis that family psychiatric history amplifies the effect of childhood adversity on odds of psychosis.
MoO2-Fe2O3 nanoparticle system was successfully synthesized by mechanochemical activation of MoO2 and α-Fe2O3 equimolar mixtures for 0-12 hours of ball milling time. The study aims at exploring the formation of magnetic oxide semiconductors at the nanoscale. X-ray powder diffraction (XRD), Mössbauer spectroscopy and magnetic measurements were used to study the phase evolution of MoO2-Fe2O3 nanoparticle system under the mechanochemical activation process. The Mössbauer studies showed that the spectrum of the mechanochemically activated composites evolved from a sextet for hematite to sextet and a doublet upon duration of the milling process with molybdenum dioxide. Recoilless fraction was determined using our dual absorber method and was found to decrease with increasing ball milling time. Magnetic measurements recorded at 5 and 300 K in an applied magnetic field of 50,000 Oe showed the magnetic properties in the antiferromagnetic and canted ferromagnetic states. The Morin transformation was evidenced by zero-field cooling-field cooling (ZFC-FC) measurements in 200 Oe and the transformation characteristic temperatures were shifted to lower values.
The photosynthetic reaction center (RC) is an integral membrane protein that, upon absorption of photons, generates a hole-electron couple with a yield close to one. This energetic state has numerous possible applications in several biotechnological fields given that its lifetime is long enough to allow non-metabolic ancillary redox chemistry to take place. Here we focus on RCs reconstituted in liposomes, formed with sole phospholipids or in blends with other lipids, and show that the electrical charge sitting on the polar head of such hydrophobic molecules does play an important role on the stability of the hole-electron couple. More specifically this study shows that the presence of negative charges in the surrounding of the protein stabilizes the charge-separated state while positive charges have a strong opposite effect.
Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.
This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.
Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25–4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44–9.56); and patients of male gender (OR 3.13 95% CI 1.35–7.23).
For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.
A high-throughput crystallographic investigation on several crystals of photosynthetic reaction center covalently bound to an ad-hoc synthesized artificial antenna (AE600) is presented. The investigation did not show a preferential binding site of the antenna molecule AE600 to the reaction center in the solid phase. An accurate crystallographic study allowed identifying a lysine residue sitting on periplasmic side of the protein as one of the bioconjugation sites. The residue sits on subunit M of the protein, in close proximity to the bacteriochlorophylls of the reaction center involved in the light absorption and conversion processes. Distances obtained from the crystallographic structure confirm that energy transfer between the antenna and the protein proceed with the Förster resonance mechanism.