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Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to accurate role functioning prediction, calling for the investigation of additional risk dimensions. Role functioning may be more strongly associated with environmental adverse events than social functioning.
We aimed to predict role functioning in CHR, ROD and transdiagnostically, by adding environmental adverse events-related variables to clinical and sMRI data domains within the PRONIA sample.
Baseline clinical, environmental and sMRI data collected in 92 CHR and 95 ROD samples were trained to predict lower versus higher follow-up role functioning, using support vector classification and mixed k-fold/leave-site-out cross-validation. We built separate predictions for each domain, created multimodal predictions and validated them in independent cohorts (74 CHR, 66 ROD).
Models combining clinical and environmental data predicted role outcome in discovery and replication samples of CHR (balanced accuracies: 65.4% and 67.7%, respectively), ROD (balanced accuracies: 58.9% and 62.5%, respectively), and transdiagnostically (balanced accuracies: 62.4% and 68.2%, respectively). The most reliable environmental features for role outcome prediction were adult environmental adjustment, childhood trauma in CHR and childhood environmental adjustment in ROD.
Findings support the hypothesis that environmental variables inform role outcome prediction, highlight the existence of both transdiagnostic and syndrome-specific predictive environmental adverse events, and emphasise the importance of implementing real-world models by measuring multiple risk dimensions.
People presenting with first-episode psychosis (FEP) have heterogenous outcomes. More than 40% fail to achieve symptomatic remission. Accurate prediction of individual outcome in FEP could facilitate early intervention to change the clinical trajectory and improve prognosis.
We aim to systematically review evidence for prediction models developed for predicting poor outcome in FEP.
A protocol for this study was published on the International Prospective Register of Systematic Reviews, registration number CRD42019156897. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, we systematically searched six databases from inception to 28 January 2021. We used the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies and the Prediction Model Risk of Bias Assessment Tool to extract and appraise the outcome prediction models. We considered study characteristics, methodology and model performance.
Thirteen studies reporting 31 prediction models across a range of clinical outcomes met criteria for inclusion. Eleven studies used logistic regression with clinical and sociodemographic predictor variables. Just two studies were found to be at low risk of bias. Methodological limitations identified included a lack of appropriate validation, small sample sizes, poor handling of missing data and inadequate reporting of calibration and discrimination measures. To date, no model has been applied to clinical practice.
Future prediction studies in psychosis should prioritise methodological rigour and external validation in larger samples. The potential for prediction modelling in FEP is yet to be realised.
Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.
We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.
(i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains ‘emotional neglect’ and ‘emotional abuse’ were most predictive for CHR and ROP, while in ROD ‘physical abuse’ and ‘sexual abuse’ were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.
These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.
Cognitive screening is an efficient method of detecting cognitive impairment in adults and may signal need for comprehensive assessment. Cognitive screening is not, however, routinely used in youth aged 12–25, limiting clinical recommendations. The aims of this review were to describe performance-based cognitive screening tools used in people aged 12–25 and the contexts of use, review screening accuracy in detecting cognitive impairment relative to an objective reference standard, and evaluate the risk of bias of included studies.
Electronic databases (Scopus, Medline, PsychINFO, and ERIC) were searched for relevant studies according to pre-determined criteria. Risk of bias was rated using the Quality Assessment of Diagnostic Accuracy Studies-2. Dual screening, extraction, and quality ratings occurred at each review phase.
Twenty studies met the review inclusion criteria. A diverse range of screening tools (length, format) were used in youth aged 12–25 with or without health conditions. Six studies investigating cognitive screening were conducted as primary accuracy studies and reported some relevant psychometric parameters (e.g., sensitivity and specificity). Fourteen studies presented correlational data to investigate the cognitive measure utility. Studies generally presented limited data on classification accuracy, which impacted full screening tool appraisal. Risk of bias was high (or unclear) in most studies with poor adherence to the Standards for Reporting Diagnostic Accuracy Studies (STARD) criteria.
Few, high quality studies have investigated the utility of cognitive screening in youth aged 12–25, with no screening measure emerging as superior at detecting cognitive impairment in this age group.
There is increasing interest in the clinical and aetiological overlap between autism spectrum disorders and schizophrenia spectrum disorders, reported to co-occur at both diagnostic and trait levels. Individually, sub-clinical autistic and psychotic traits are associated with poor clinical outcomes, including increased depressive symptomatology, self-harming behaviour and suicidality. However, the implications when both traits co-occur remain poorly understood. The study aimed to (1) examine the relationship between autistic and psychotic traits and (2) determine if their co-occurrence increases depressive symptomatology, self-harm and suicidality.
Cross-sectional data from a self-selecting (online and poster advertising) sample of the adult UK population (n = 653) were collected using an online survey. Validated self-report measures were used to assess sub-clinical autistic and psychotic traits, depressive symptomatology, self-harming behaviour and suicidality. Correlation and regression analyses were performed.
A positive correlation between sub-clinical autistic and positive psychotic traits was confirmed (rs = 0.509, p < 0.001). Overall, autistic traits and psychotic traits were, independently, significant predictors of depression, self-harm and suicidality. Intriguingly, however, depression was associated with a negative interaction between the autistic domain attention to detail and psychotic traits.
This study supports previous findings that sub-clinical autistic and psychotic traits are largely independently associated with depression, self-harm and suicidality, and is novel in finding that their combined presence has no additional effect on depression, self-harm or suicidality. These findings highlight the importance of considering both autistic and psychotic traits and their symptom domains in research and when developing population-based depression prevention and intervention strategies.
In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate.
In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers.
Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring.
ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.
Despite knowing for many decades that depressive psychopathology is common in first-episode schizophrenia spectrum disorders (FES), there is limited knowledge regarding the extent and nature of such psychopathology (degree of comorbidity, caseness, severity) and its demographic, clinical, functional and treatment correlates. This study aimed to determine the pooled prevalence of depressive disorder and caseness, and the pooled mean severity of depressive symptoms, as well as the demographic, illness, functional and treatment correlates of depressive psychopathology in FES.
This systematic review, meta-analysis and meta-regression was prospectively registered (CRD42018084856) and conducted in accordance with PRISMA and MOOSE guidelines.
Forty studies comprising 4041 participants were included. The pooled prevalence of depressive disorder and caseness was 26.0% (seven samples, N = 855, 95% CI 22.1–30.3) and 43.9% (11 samples, N = 1312, 95% CI 30.3–58.4), respectively. The pooled mean percentage of maximum depressive symptom severity was 25.1 (38 samples, N = 3180, 95% CI 21.49–28.68). Correlates of depressive psychopathology were also found.
At least one-quarter of individuals with FES will experience, and therefore require treatment for, a full-threshold depressive disorder. Nearly half will experience levels of depressive symptoms that are severe enough to warrant diagnostic investigation and therefore clinical intervention – regardless of whether they actually fulfil diagnostic criteria for a depressive disorder. Depressive psychopathology is prominent in FES, manifesting not only as superimposed comorbidity, but also as an inextricable symptom domain.
Environmental and biological factors contribute to sleep development during infancy. Parenting plays a particularly important role in modulating infant sleep, potentially via the serotonin system, which is itself involved in regulating infant sleep. We hypothesized that maternal neglect and serotonin system dysregulation would be associated with daytime sleep in infant rhesus monkeys. Subjects were nursery-reared infant rhesus macaques (n = 287). During the first month of life, daytime sleep-wake states were rated bihourly (0800–2100). Infants were considered neglected (n = 16) if before nursery-rearing, their mother repeatedly failed to retrieve them. Serotonin transporter genotype and concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) were used as markers of central serotonin system functioning. t tests showed that neglected infants were observed sleeping less frequently, weighed less, and had higher 5-HIAA than non-neglected nursery-reared infants. Regression revealed that serotonin transporter genotype moderated the relationship between 5-HIAA and daytime sleep: in subjects possessing the Ls genotype, there was a positive correlation between 5-HIAA and daytime sleep, whereas in subjects possessing the LL genotype there was no association. These results highlight the pivotal roles that parents and the serotonin system play in sleep development. Daytime sleep alterations observed in neglected infants may partially derive from serotonin system dysregulation.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
In dimensional understanding of psychosis, auditory verbal hallucinations
(AVH) are unitary phenomena present on a continuum from non-clinical
voice hearing to severe mental illness. There is mixed evidence for this
approach and a relative absence of research into subjective experience of
AVH in early psychosis.
To conduct primary research into the nature of subjective experience of
AVH in first-episode psychosis.
A phenomenological study using diary and photo-elicitation qualitative
techniques investigating the subjective experience of AVH in 25 young
people with first-episode psychosis.
AVH are characterised by: (a) entity, as though from a living being with
complex social interchange; and (b) control, exerting authority with
ability to influence. AVH are also received with passivity, often
accompanied by sensation in other modalities.
A modern detailed phenomenological investigation, without presupposition,
gives results that echo known descriptive psychopathology. However, novel
findings also emerge that may be features of AVH in psychosis not
currently captured with standardised measures.
Autism and psychotic disorders such as schizophrenia co-occur more frequently than would be expected by chance alone. Exactly why this should be remains unclear, but a better understanding would have important implications for diagnosis, treatment and for biological explanations of both conditions.
Covalent functionalisation of collagen has been shown to be a promising strategy
to adjust the mechanical properties of highly swollen collagen hydrogels. At the
same time, secondary interactions between for example, amino acidic terminations
or introduced functional groups also play an important role and are often
challenging to predict and control. To explore this challenge, 4-vinylbenzyl
chloride (4VBC) and methacrylic anhydride (MA) were reacted with type I
collagen, and the swelling and rheological properties of resulting
photo-activated hydrogel systems investigated. 4VBC-based hydrogels showed
significantly increased swelling ratio, in light of the lower degree of collagen
functionalisation, with respect to methacrylated collagen networks, whilst
rheological storage moduli were found to be comparable between the two systems.
To explore the role of benzyl groups in the mechanical properties of the
4VBC-based collagen system, model chemical force microscopy (CFM) was carried
out in aqueous environment with an aromatised probe against an aromatised
gold-coated glass slide. A marked increase in adhesion force
(F: 0.11±0.01 nN) was measured between aromatised
samples, compared to the adhesion force observed between the non-modified probe
and a glass substrate (F: 2.64±1.82 nN). These results
suggest the formation of additional and reversible π-π
stacking interactions in aromatic 4VBC-based networks and explain the remarkable
rheological properties of this system in comparison to MA-based hydrogels.
The conservation of biodiversity is an increasingly challenging endeavour. Current pressures from a growing human population have led to concerns of a sixth mass extinction event, bringing mounting pressure to find effective ways of conserving biodiversity (Barnosky et al., 2011). However, our ability to meet this challenge is affected by the fact that not everyone supports conservation objectives. People naturally have different interests and priorities, some of which may be diametrically opposed to conservation objectives. In some cases, these differences lead to damaging and costly conflicts that we see emerging across the world and which present major challenges to modern conservation (MacDonald and Service, 2007).
At a cursory glance, the conflicts that surface around conservation often appear to be about impact: the impact of carnivores on livestock; the impact of wind farms on birds; or the impact of protected areas on livelihoods. Consequently, a common approach to these problems has been to build robust science and develop an evidence base to understand these impacts and find ways of reducing them, often through technical solutions. This approach, however, rarely works for the simple reason that many of these conflicts are about much more than impact. So even if we can develop the science to quantify impacts and show how they can be reduced, the conflicts can stubbornly persist. Indeed, beneath the surface of any of the conflicts discussed in this book is a complex layering of diverse issues related to different world views, issues of trust, power imbalances or latent historical issues – issues that lie well outside the sphere of the natural sciences. So, if we really want to understand and tackle these thorny problems, we need insights from other disciplines as well as from the practitioners specialising in resolving conflicts.
The growing recognition of the complexity within conflicts has led many authors to suggest more cross-disciplinary approaches, especially through better integration of ecological and social science (Manfredo and Dayer, 2004; Sillero-Zubiri et al., 2007; Treves, 2009; Dickman, 2010; White and Ward, 2010).