The authors have not supplied their declaration of competing interest.

Schizophrenia is a complex disorder involving both genetic and environmental factors. Epigenetic is a growing theory to explain these interactions at a molecular level. It is well-known that schizophrenia begins with prodromal symptoms and patients undergoing subthreshold symptoms are named ultra-high risk (UHR) subjects. Therapeutic and prognostic attitude remain challenging for this population. According to the model of the gene-environment interactions, the psychotic transition in adolescence could be related to epigenetic changes during the psychotic transition.

We designed and performed the first longitudinal study about whole-genome DNA methylation changes. Thirty-nine UHR patients were recruited in specialized center C’JAAD - Centre Hospitalier Ste Anne - Paris (France). During follow-up, 14 of them became psychotic (converters) according to the validated scale CAARMS. Initial and final methylation were investigated by Infinium Human Methylation450 BeadChip for 450,000 CpG after bisulfite conversion.

The psychotic transition was not associated with global methylation changes. Linear models failed to identify CpG and genes significantly associated with psychotic transition after Bonferroni correction. Analyses of the top results provided a cluster, which could classify perfectly converters and non-converters. These genes of interest are over-represented in biological pathways with relevance for psychotic physiopathology. Individual analyses highlighted the biological heterogeneity of the psychotic transition.

Improving physiopathological understanding of psychotic transition is a current challenge to identify biomarkers and to develop targeted preventive interventions available in clinical practice for UHR subjects. The epigenetic processes and in particular DNA methylation could be interesting factors.

The authors have not supplied their declaration of competing interest.

Anorexia nervosa (AN) is the most severe in terms of morbidity psychiatric illness with the highest mortality rate increased by 23 fold. Treatments are limited effectiveness. AN has a strong genetic component with heritability at 70% but despite ∼ 200 studies no major gene was identified. Epigenetics, such as DNA methylation, is another component of heritability that could explain the high heritability. Methylation is poorly studied in AN from small samples, and is focused on few candidate genes among publications. Under publication, a first genome-wide methylation study investigated 10 restrictive type AN patients, 19 binging/purging type of AN patients and 15 normal eaters using DNAs from whole blood (Booij, 2015). Of the 480K CpG sites that can be methylated of Infinium Human Methylation450 BeadChip Kit, authors focused on 24,000 sites located close to genes and they identified candidate genes with a different profile of methylation between AN and controls.

Our work is to replicate the results of Booji and also to investigate the AN remitters.

Our goal is to identify epigenetic signatures of the AN disorder and the prognostic of remission.

Twenty-four AN patients, 24 AN remitters will be compared to 48 healthy control women for methylation using the Infinium Human Methylation450.

As Booji et al., we will compare methylation for 24,000 sites located close to genes for 24 AN, 24 remitters and 48 controls.

We expected to replicate the published results of Booji and to identify genes with a methylation signature specific of the AN remission.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

The symptomatic distribution in schizophrenia spectrum disorder is heterogeneous. Patients may experience hallucinations, delusions and combinations thereof, in addition to disorganized and negative symptoms. We have previously found that patients with monosymptomatic hallucinations exhibited a different clinical profile than patients with monosymptomatic delusions or combinations of the two; with an earlier age at onset and more suicidal symptoms.

To replicate findings in a new group of patients with schizophrenia spectrum disorders.

A total of 421 consecutive patients with schizophrenia spectrum disorders were included into the study. They were comprehensively assessed by specifically trained psychiatrists or clinical psychologists; using the SCID for DSM-IV for diagnostic purposes, the PANSS to assess current clinical symptoms and CDSS to assess current depression. Lifetime presence of different symptom types was ascertained during the diagnostic interview.

A total of 346 (82%) had experienced both hallucinations and delusion, 63 (15%) had experienced delusions without hallucinations, 10 (2.5%) had experienced hallucinations without delusions and 2 patients (0.5%) had neither but experienced negative and severely disorganized symptoms. Contrary to hypothesis, we did not find any statistically significant differences in age at onset and in clinical symptoms (including suicidality) between these groups. We also did not find any differences in the type of hallucinatory experiences between hallucinating groups.

In a new sample of patients, we did not replicate previous findings of a different clinical profile in patients with monosymptomatic hallucinations. This type of psychotic disorder is relatively rare, which might pose a problem concerning statistical strength.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Mental disorders are a major cause of disability in Europe [1]. However, organizational structures and information systems are focused on delivery of care, rather than providing value [2]. In the digital era, we have the capacity to change priorities through the analysis of heterogeneous databases that could support patients’ and professionals’ decisions.

to analyse the contradictions between the design and the theoretical structure of mental health services and the possibilities to evaluate the actual value of the delivered care.

To reflect on changing the trend using a different conceptualization of objectives and evaluating methods.

We used a tool provided to clinicians by the Madrid's Regional Health Service SERMAS (‘ConsultaWeb’) combining primary care, pharmacy and hospital data (n = 395,073 patients for the catchment area), and a set of hospital-based data (patients attended by psychiatrists at the ER, n = 13,877, and patients admitted to the Psychiatric Inpatient unit n = 3318), to explore some of the present professional information resources.

Currently used healthcare databases only describe the diagnostic or therapeutic categories of patients and might be used to detect abnormal behaviours. However, they are neither able to show the functional status of patients nor designed to predict their clinical course.

A clearer definition of value in patient outcomes is needed. This might help to organize the healthcare delivery and to create a new information system that would allow to asses health outcomes.

The authors have not supplied their declaration of competing interest.

Mental disorder is a key public health challenge and a leading cause of disability-adjusted life years (DALYs) due to its high level of disability and mortality. Therefore, a slight improvement on mental care provision and management could generate solid benefits on relieving the social burden of mental diseases.

This paper presents a long-term vision of strategic collaboration between Fujitsu Laboratories, Fujitsu Spain, and Hospital Clinico San Carlos to generate value through predictive and preventive medicine improving healthcare outcomes for every clinical area, benefiting managers, clinicians, and patients.

The aim is to enable a data analytic approach towards a value-based healthcare system via health informatics. The project generates knowledge from heterogeneous data sources to obtain patterns assisting clinical decision-making.

This project leverages a data analytic platform named HIKARI (“light” in Japanese) to deliver the “right” information, to the “right” people, at the “right” time. HIKARI consists of a data-driven and evidence-based Decision Support and Recommendation System (DSRS), facilitating identification of patterns in large-scale hospital and open data sets and linking data from different sources and types.

Using multiple, heterogeneous data sets, HIKARI detects correlations from retrospective data and would facilitate early intervention when signs and symptoms prompt immediate actions. HIKARI also analyses resource consumption patterns and suggests better resource allocation, using real-world data.

With the advance of ICT, especially data-intensive computing paradigm, approaches mixing individual risk assessment and environmental conditions become increasingly available. As a key tool, HIKARI DSRS can assist clinicians in the daily management of mental disorders.

The author has not supplied his declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Several lines of evidence suggest that cognitive deficits represent a core feature of schizophrenia.

The concept of “cognitive dysmetria” has been introduced to characterize disintegration at the system level of frontal-thalamic-cerebellar circuitry which has been regarded as a key network for a wide range of neuropsychological symptoms in schizophrenia.

The present multimodal study aimed at investigating effective and structural connectivity of the frontal-thalamic circuitry in schizophrenia.

Univariate fMRI data analysis and effective connectivity analysis using dynamic causal modeling (DCM) were combined to examine cognitive control processes in 40 patients with schizophrenia and 40 matched healthy controls. BOLD signal and parameters of effective connectivity were related to parameters of corresponding white matter integrity assessed with diffusion tensor imaging (DTI).

In the DTI analysis, significantly decreased fractional anisotropy (FA) was detected in patients in the right anterior limb of the internal capsule (ALIC), the right thalamus and the right corpus callosum. During Stroop task performance patients demonstrated significantly lower activation relative to healthy controls in a predominantly right lateralized frontal-thalamic-cerebellar network. An abnormal effective connectivity was observed in the right lateralized connections between thalamus, anterior cingulate and dorsolateral prefrontal cortex. FA in the right ALIC was significantly correlated with the fronto-thalamic BOLD signal, effective connectivity and cognitive performance in patients.

Present data provide evidence for the notion of a structural and functional defect in the prefrontal-thalamic-cerebellar circuitry, which seems to be the basis of the cognitive control deficits in schizophrenia.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Antipsychotic medications play an important role in schizophrenia, and their efficacy in the relapse prevention and treatment of acute psychotic symptoms is clear-cut.

Data on the long-term use of antipsychotics and impact on prognostic issues is limited, although some previous studies noted a high risk of relapse during the first two years after the first acute psychosis.

Our aim was to study the characteristics and clinical course of medicated and unmedicated schizophrenia patients.

The study population consisted of schizophrenia patients from the Northern Finland 1966 Birth Cohort (n = 70). Use of antipsychotics was examined in the follow-up interview by asking about the subjects’ medication history during the previous three months. The sample was divided into a non-medicated group (n = 24) and a medicated group (n = 46).

Relapses during the follow-up were equally frequent between non-medicated and medicated subjects (47% vs. 53%). Not having been hospitalised during previous five years, but not previous two years, before the interview predicted long-term successful antipsychotic withdrawal without relapse. Fifteen of the subjects in the non-medicated group (63%) and 9 in the medicated group (20%) were in remission.

The present results imply that there are some individuals with schizophrenic psychoses not using antipsychotic medication whose psychotic illness and clinical course are so favourable that they do not necessarily need medication permanently. Changes in the antipsychotic dosing should not be made too fast and the patient and relatives should be able to contact without delay if exacerbation of psychotic symptoms is suspected.

The author has not supplied his declaration of competing interest.

Familial risk for psychosis may interact with environmental risk factors.

We are studying a large birth cohort of children of mothers with psychotic disorders, themselves at high risk of developing a psychotic illness, to understand the developmental aetiology of psychotic illness.

Our aim is to examine whether exposure to environmental stressors in childhood, including timing of exposure, is a risk factor for psychotic illness, independent of familial liability. Specificity to maternal schizophrenia is explored.

We used record-linkage across state-wide registers (midwives, psychiatric, child protection and mortality, among others) to identify 15,486 offspring born in Western Australia 1980–2001 to mothers with a lifetime history of psychotic illness (case children) and compared them with 452,459 offspring born in the same period to mothers with no known psychiatric history (comparison children).

A total of 4.1% of case children had developed a psychotic illness compared to 1.1% of comparison children. Exposure to environmental risk factors including obstetric complications, aboriginality, lower socioeconomic status, discontinuity in parenting and childhood abuse significantly increased risk of psychotic illness in offspring. Length and age at time of discontinuity in parenting impacted on risk. At the same time, case children were also significantly more likely than comparison children to be at risk of experiencing these adverse life events.

Exposure to environmental stressors is associated with psychotic illness, and timing of exposure is important. However, children already at increased familial risk for psychotic illness are also at increased risk of experiencing these environmental stressors.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

Studies mainly relied on hospital or case-control data have well documented that individuals with psychoses, and especially with schizophrenia have increased rates of physical illnesses. They have two to four-fold higher mortality risk, and about 10 to 25 years shorter life expectancy compared with the general population. The aim of this study is to evaluate the prevalence of physical illnesses in individuals with schizophrenia or with other psychoses and among people without psychoses until the age of 46 years using complete outpatient and inpatient data from birth cohort.

The study is based on The Northern Finland 1966 Birth Cohort (NFBC, 1966), which is a population-based prospective cohort concerning 12.058 live-born children in 1966 in the provinces of Lapland and Oulu.

The study population consisted of 10,933 individuals, who were alive at the age of 16-years, and followed serially until the age of 46-years The study population was divided into three groups: those having schizophrenia (n = 228) and those with other psychoses (n = 240) while individuals without psychosis (n = 10,465) formed the control group. The data was obtained from various national registers.

Diseases of the blood and blood forming organs (prevalence in SCZ was 17% versus 10% in controls, P < 0.001), endocrine, nutritional and metabolic diseases (45% vs. 27%, P < 0.001), diabetes mellitus (7% vs. 3%, P < 0.001) and nervous diseases (33% vs. 25%, P = 0.018) were more common among individuals with SCZ compared with controls. Diseases of musculoskeletal system and connective tissue were less common in SCZ than among controls (28% vs. 41%, P < 0.001).

People with other psychoses than SCZ had statistically significant association with all the diagnostic groups classified in ICD-10 except with neoplasms. Infections and parasitic diseases (prevalence in other psychoses was 44% versus 32% in controls, P < 0.001), diseases of the blood and blood forming organs (18% vs. 10%, P < 0.001), endocrine, nutritional and metabolic diseases (42% vs. 27%, P < 0.001) including diabetes mellitus (9% vs. 3%, P < 0.001), nervous diseases (40% vs. 25%, P < 0.001), diseases of the eye and adnexa (32% vs. 21%, P < 0.001), diseases of the ear and mastoid process (58% vs. 44%, P < 0.001), diseases of circulatory (50% vs. 37%, P < 0.001), respiratory (70% vs. 60%, P < 0.001) and digestive system (77% vs. 68%, P = 0.004), diseases of skin and subcutaneous tissue (23% vs. 16%, P = 0.006), diseases of musculoskeletal system and connective tissue (51% vs. 40%, P = 0.004) and diseases of genitourinary system (41% vs. 31%, P = 0.003) were more common among people with other psychoses than SCZ compared with controls.

A new finding is that not only people with schizophrenia but especially those with other psychoses show a greater occurrence of somatic diseases compared with those without psychosis. The increased occurrence of somatic comorbidity in other psychoses should be noted by medical professional, and further longitudinal studies are warranted to study its possible risk factors during lifespan.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.