Meta-analytical prognostic accuracy of the Comprehensive Assessment of at Risk Mental States (CAARMS): The need for refined prediction.

Primary indicated prevention is reliant on accurate tools to predict the onset of psychosis. The gold standard assessment for detecting individuals at clinical high risk (CHR-P) for psychosis in the UK and many other countries is the Comprehensive Assessment for At Risk Mental States (CAARMS). While the prognostic accuracy of CHR-P instruments has been assessed in general, this is the first study to specifically analyse that of the CAARMS. As such, the CAARMS was used as the index test, with the reference index being psychosis onset within 2 years. Six independent studies were analysed using MIDAS (STATA 14), with a total of 1876 help-seeking subjects referred to high risk services (CHR-P+: n=892; CHR-P-: n=984). Area under the curve (AUC), summary receiver operating characteristic curves (SROC), quality assessment, likelihood ratios, and probability modified plots were computed, along with sensitivity analyses and meta-regressions. The current meta-analysis confirmed that the 2-year prognostic accuracy of the CAARMS is only acceptable (AUC=0.79 95% CI: 0.75-0.83) and not outstanding as previously reported. In particular, specificity was poor. Sensitivity of the CAARMS is inferior compared to the SIPS, while specificity is comparably low. However, due to the difficulties in performing these types of studies, power in this meta-analysis was low. These results indicate that refining and improving the prognostic accuracy of the CAARMS should be the mainstream area of research for the next era. Avenues of prediction improvement are critically discussed and presented to better benefit patients and improve outcomes of first episode psychosis.

From neurological soft signs to functional outcome in young individuals in treatment with secondary services for non-psychotic disorders: a path analysis.

BACKGROUND: Functional decline among patients with mental illness is not unique to individuals with psychotic disorders. Despite this, research on early predictors of functional outcome mainly focused on individuals thought to have an 'at risk mental state' (ARMS) for psychosis. There is evidence suggesting that certain early vulnerability markers, such as neurological soft signs (NSS), may explain variability in functional outcomes independent of the level of psychosis risk and the traditional diagnostic classification. METHOD: Structural equation modeling was applied to baseline data from a prospective longitudinal study of 138 young individuals in treatment with secondary services for non-psychotic disorders. We evaluated theoretically based models of pathways to functional outcome starting from NSS. The intervening variables were established according to previous evidence and drawn from two general categories: cognition (neuro- and social-) and negative symptoms (expressive and experiential). RESULTS: A final trimmed model was a single path running from NSS to neurocognition to experiential negative symptoms to outcome. It could not be improved by adding or dropping connections that would change the single path to multiple paths. The indirect effect from NSS to outcome was significant. The validity of the model was independent of the ARMS status and the psychiatric diagnosis. CONCLUSIONS: Our results provide evidence for a single pathway model in which the starting and intervening variables represent modifiable trans-diagnostic therapeutic targets to improve functional trajectories in young individuals with a recent-onset psychiatric diagnosis and different levels of psychosis risk.

Psychosis prediction in secondary mental health services. A broad, comprehensive approach to the "at risk mental state" syndrome.

BACKGROUND: Accuracy of risk algorithms for psychosis prediction in "at risk mental state" (ARMS) samples may differ according to the recruitment setting. Standardized criteria used to detect ARMS individuals may lack specificity if the recruitment setting is a secondary mental health service. The authors tested a modified strategy to predict psychosis conversion in this setting by using a systematic selection of trait-markers of the psychosis prodrome in a sample with a heterogeneous ARMS status. METHODS: 138 non-psychotic outpatients (aged 17-31) were consecutively recruited in secondary mental health services and followed-up for up to 3 years (mean follow-up time, 2.2 years; SD=0.9). Baseline ARMS status, clinical, demographic, cognitive, and neurological soft signs measures were collected. Cox regression was used to derive a risk index. RESULTS: 48% individuals met ARMS criteria (ARMS-Positive, ARMS+). Conversion rate to psychosis was 21% for the overall sample, 34% for ARMS+, and 9% for ARMS-Negative (ARMS-). The final predictor model with a positive predictive validity of 80% consisted of four variables: Disorder of Thought Content, visuospatial/constructional deficits, sensory-integration, and theory-of-mind abnormalities. Removing Disorder of Thought Content from the model only slightly modified the predictive accuracy (-6.2%), but increased the sensitivity (+9.5%). CONCLUSIONS: These results suggest that in a secondary mental health setting the use of trait-markers of the psychosis prodrome may predict psychosis conversion with great accuracy despite the heterogeneity of the ARMS status. The use of the proposed predictive algorithm may enable a selective recruitment, potentially reducing duration of untreated psychosis and improving prognostic outcomes.

Negative symptoms as key features of depression among cannabis users: a preliminary report.

OBJECTIVE: Cannabis use is frequent among depressed patients and may lead to the so-called "amotivational syndrome", which combines symptoms of affective flattening and loss of emotional reactivity (i.e. the so-called "negative" symptomatology). The aim of this study was to investigate the negative symptomatology in depressed patients with concomitant cannabis use disorders (CUDs) in comparison with depressed patients without CUDs. PATIENTS AND METHODS: Fifty-one patients with a diagnosis of Major Depressive Disorder (MDD) and concomitant CUD and fifty-one MDD patients were enrolled in the study. The 21-Item Hamilton Depression Rating Scale (HDRS) and the negative symptoms subscales of the Positive and Negative Syndrome Scale (PANSS) were used to assess depressive and negative symptomatology. RESULTS: Patients with cannabis use disorders presented significantly more severe negative symptoms in comparison with patients without cannabis use (15.18 ± 2.25 vs 13.75 ± 2.44; t100 = 3.25 p = 0.002). DISCUSSION: A deeper knowledge of the "negative" psychopathological profile of MDD patients who use cannabis may lead to novel etiopathogenetic models of MDD and to more appropriate treatment approaches.

The "Eyeballing" technique: an emerging and alerting trend of alcohol misuse.

OBJECTIVE: Alternative methods of alcohol consumption have recently emerged among adolescents and young adults, including the alcohol "eyeballing", which consist in the direct pouring of alcoholic substances on the ocular surface epithelium. In a context of drug and behavioural addictions change, "eyeballing" can be seen as one of the latest and potentially highly risky new trends. We aimed to analyze the existing medical literature as well as online material on this emerging trend of alcohol misuse. MATERIALS AND METHODS: Literature on alcohol eyeballing was searched in PsychInfo and Pubmed databases. Results were integrated with a multilingual qualitative assessment of the database provided by The Global Public Health Intelligence Network (GPHIN) and of a range of websites, drug fora and other online resources between March 2013 and July 2013. RESULTS: Alcohol eyeballing is common among adolescents and young adults; substances with high alcohol content, typically vodka, are used for this practice across the EU and internationally. The need for a rapid/intense effect of alcohol, competitiveness, novelty seeking and avoidance of "alcoholic fetor" are the most frequently reported motivations of "eyeballers". Local effects of alcohol eyeballing include pain, burning, blurred vision, conjunctive injection, corneal ulcers or scarring, permanent vision damage and eventually blindness. CONCLUSIONS: Alcohol eyeballing represents a phenomenon with potential permanent adverse consequences, deserving the attention of families and healthcare providers. Health and other professionals should be informed about this alerting trend of misuse. Larger observational studies are warranted to estimate the prevalence, characterize the effects, and identify adequate forms of interventions for this emerging phenomenon.

Cingulate Cortex in Schizophrenia: its relation with negative symptoms and psychotic onset. A review study.

OBJECTIVE: The cingulate cortex is a functionally heterogeneous region involved in diverse cognitive and emotional processes. It is a region of special interest to investigate the neurological substrate of schizophrenia. The aim of this paper is to review all the studies that investigated the relation between the cingulate cortex and two of the most important and little known areas of this disease: the psychotic onset and the negative symptoms. MATERIAL AND METHODS: Relevant literature was identified through a search in PubMed, Web of Science, and Cochrane database. Search terms included negative symptoms, cingulate cortex, cingulate gyrus, schizophrenia, PET, SPECT, MRI, fMRI, BOLD, deficit schizophrenia, early-onset schizophrenia, psychotic onset, psychosis. RESULTS: 9 studies evidenced a link between negative symptoms and hypoactivity of cingulate cortex, whereas 7 studies did not. A positive relationship between anterior cingulate cortex gray matter thinning and high risk for schizophrenia is well characterized in literature. CONCLUSIONS: In a large portion of patients hypoactivity of cingulate cortex underlie the presence of negative symptoms. In particular, ACC (anterior cingulated cortex) thinning seems to be related to the increasing social withdrawal that is characteristic of the psychosis prodrome. New therapies focused on the brain stimulation of the cingulate cortex could represent an important aid for patients with this kind of symptoms.

Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: a comprehensive review.

Deep transcranial magnetic stimulation (TMS) is a technique of neuromodulation and neurostimulation based on the principle of electromagnetic induction of an electric field in the brain. The coil (H-coil) used in deep TMS is able to modulate cortical excitability up to a maximum depth of 6 cm and is therefore able not only to modulate the activity of the cerebral cortex but also the activity of deeper neural circuits. Deep TMS is largely used for the treatment of drug-resistant major depressive disorder (MDD) and is being tested to treat a very wide range of neurological, psychiatric and medical conditions. The aim of this review is to illustrate the biophysical principles of deep TMS, to explain the pathophysiological basis for its utilization in each psychiatric disorder (major depression, autism, bipolar depression, auditory hallucinations, negative symptoms of schizophrenia), to summarize the results presented thus far in the international scientific literature regarding the use of deep TMS in psychiatry, its side effects and its effects on cognitive functions.

The properties of (2Fo - Fc) and (Fo - Fc) electron-density maps at medium-to-high resolutions.

This paper reports on the efficacy of (F(o) - F(c)) versus (2F(o) - F(c)) electron-density maps at 3.2 A resolution. Firstly, a study is reported of a simple truncation at 2.3 and 3.2 A of the 1.6 A resolution crystal structure of concanavalin A at room temperature [Emmerich et al. (1994), Acta Cryst. D50, 749-756] with 149 known bound water molecules. Secondly, the concanavalin A 1.6 A resolution model was re-refined but with the data truncated to 3.2 A. In a similar evaluation, these procedures were repeated for the apocrustacyanin A1 cryotemperature 1.4 A resolution model [Cianci et al. (2001), Acta Cryst. D57, 1219-1229]. Maps at 1.4, 2.3 and 3.2 A resolutions were first generated and the structure was then re-refined at 3.2 A and additionally at 2.3 A resolution. The results on concanavalin A show that the number of bound water molecules that are resolved decreases by two thirds from 1.6 to 3.2 A, but that key structural waters, for example at the transition metal and the calcium ion, are still resolved in the (F(o) - F(c)) map but not in the (2F(o) - F(c)) map. For apocrustacyanin A1, the results with these two difference maps were less clear-cut. Two key structural bound waters (w93 and w105) were selected that had been previously identified in beta-crustacyanin [Cianci et al. (2002), Proc. Natl Acad. Sci. USA, 99, 9795-9800] in protein-carotenoid interactions. The behaviour of w93 is similar to that of concanavalin A key waters, but that of w105 is not. These behaviours were therefore explored in finer resolution increments, namely 2.9, 2.7 and 2.5 A. Finally, further tests on "real" data sets for peanut lectin and concanavalin A at medium resolution confirm these map properties, namely that an (F(o) - F(c)) difference electron-density map is more effective than a (2F(o) - F(c)) map in showing bound water structure at lower resolutions ( approximately 3.2 A). This result is important since a growing number of protein crystal structure studies are concerned with multi-macromolecular complexes and are at such resolutions. Details of the bound solvent can still be revealed at 3.2 A via the (F(o) - F(c)) map calculation. The physical basis of the limitation of the (2F(o) - F(c)) map presumably lies in the series-termination error effect on such a map involving the first negative ripple from the protein atom to which a bound water oxygen is hydrogen bonded, sufficiently cancelling its peak. In addition, re-refinements at 3.2 A show distances that can agree with known values but B values that do not agree with known values.