International treatment guidelines recommend that key elements to reduce the burden of psychosis are the early identification of people and the adoption of specific evidence based interventions.

To investigate the pathway to care and patterns of interventions provided by community based-mental health services (CMHS) to a cohort of first-episode psychosis (FEP) patients over 5-years period, exploring in which degree guidelines are met in routine clinical practice.

Study conducted in the context of the Psychosis Incident Cohort Outcome Study (PICOS), a multisite naturalistic research conducted in the Veneto Region (Italy) on FEP patients in a 4.6 million inhabitants catchment area. A comprehensive set of standardized measures was used, including ad hoc schedules to collect information on referrals to psychiatric services and on pharmacological and psycho-social treatments according to a multiwave follow-up design (1-, 2- and 5 years).

Three hundred and ninety-seven FEP patients were assessed at BL, 286 at 1 year, 233 at 2 years and 205 at 5 years. 47.4% of patients were helped to seek care by a relative and more than one half entered the treatment route through an emergency access. Regarding the interventions received, 96% of patients had been prescribed neuroleptics and atypical were the most prescribed class (66.9%). Only half received a psychosocial intervention during the first year and this percentage progressively decreased at each FU.

Findings highlight discrepancies between interventions provided by CMHS and the best treatment options recommended by guidelines, suggesting the need to implement specific initiatives aiming to close the gap between research and clinical practice.

The current literature indicates that people with intellectual disabilities (ID) present quantitative and qualitative peculiarities of various socio-environmental factors than the general population. Although the identification of such peculiarities would have very important implications for the development of preventive, rehabilitative and inclusive procedures, valuable data are still lacking. The aim of the present paper was to assess the significance of the relationship between socio-environmental variables in person with ID, with particular reference to individual history and life contexts.

A consecutively recruited sample of 112 participants with ID attending residential or clinic/rehabilitative services across Italy was evaluated by the administration of ISTORIA (Historiographical organized interview for adult intellectual retard), a semi-structured questionnaire designed to investigate clinical and personal history of the person. A considerable percentage of the samples have co-occurent psychiatric disorder. Scores obtained were statistically processed through frequency analysis and calculation of correlation indexes.

Significant correlations were found between the family, the educational/professional environments, and the inclusion in society. Further associations concerned social relationships within and outside the family, the changes of living accommodation, and the level of environmental stimulation received.

Both findings from previous research and the ones of this work confirm the importance of investigating the mechanisms involved in the acquisition of social skills by persons with ID, through family dynamics and participation in community life, as protective factor against the worsening of disabilities and potentially of psychopathological vulnerability that affects this population.

The last decades’ considerable advances of the psychiatric assessment in People with Intellectual Disability (PwID) do not include the ability to identify Behavioural Equivalents (BE) of psychiatric symptoms and their relationship with different psychiatric syndromes. Recent reports have found BE to be differentially associated with one or more specific Psychiatric Disorders (PD).

The present study was aimed at evaluating the correlations between BE and DSM-5 syndromic groups of symptoms, in a wide multicentric sample of PwID.

An observational cross-sectional analysis was performed for a sample of 843 adults with ID, randomly or consecutively recruited among those living in residential facilities of the National Healthcare System, or in private institutes of care, or those attending psychiatric outpatient clinics. The total sample was administered with the SPAID-G (Psychiatric Instrument for Intellectual Disabled Adult - General version), which is a checklist for the detection of significant behavioural changes from the baseline. The items of the checklist represents BE of the symptoms of the main psychiatric disorders included in the DSM-5.

Many significant correlations were found, some of the most relevant were for mood disorders. Psychomotor agitation, aggressivity, disorganised behaviour and distractibility were most pronounced in bipolar patients; for depressed patients, irritability and weight loss had higher correlations than in other diagnostic groups.

Although not diagnostically specific, some BE seem to be more strongly related with specific PD. This line of research could improve the definition of the specific expression and clustering of psychiatric symptoms in PwID.

Psychiatric assessment and care of people with Intellectual Disability (ID) is complex due to their cognitive and communication impairments. Demand for further training in this area by trainees in psychiatry has been well documented. The main of aims of this study were to explore the attitudes and perceptions of psychiatry residents and non-residents (non-trainees) with regards to care of patients with ID as well as their knowledge and training in this area.

The study was conducted as an anonymous survey at the Institute of Mental Health, Singapore. A survey questionnaire developed by the study team was sent to residents and non-residents in psychiatry.

Forty-eight out of the 76 questionnaires were returned with a response rate of 63.16%. Twenty-eight participants described themselves as non-residents and the rest were residents. All participants responded that postgraduate training was required in the area of ID and mental health and majority reported that available training was inadequate. Ninety percent of respondents believed that people with ID were vulnerable to exploitation by other patients in the inpatient unit and 94% of respondents believed that people with ID should be managed by a specialist team.

Currently residents and non-residents in psychiatry see that training in ID and mental health as well as services for people with ID as inadequate. Efforts should be made to include specialist training in psychiatry of ID in the Singapore psychiatry curriculum to enhance the confidence and expertise of psychiatrists in this field.

Epilepsy is the second most common cause of premorbid mortality in the ID population. Rates of SUDEP are considered up to 9 times higher in the ID population. Cornwall UK (population 600.000 i.e. 1% of UK) runs a specialist ID epilepsy community service for adults with ID. It delivers reasonable adjustments and person centered care to this population. We measured how service outcomes on SUDEP compared to regional and national averages.

Data of all Cornwall epilepsy deaths 2004–2015 using the Cornwall Coroner's database and the Public Health Cornwall was reviewed systemically. We identified patients with and without ID.

There were 113 epilepsy deaths of which 57 were SUDEPs of which 3 were identified to have a clinical diagnosis of ID. In another 2 cases it was not evident if they had an ID or not. None of the 5 was known to the ID Epilepsy service. Mean and 95% confidence intervals were calculated using a binomial calculation, making no prior assumptions about the population distribution.

Cornwall's specialist ID epilepsy service is a rarity in the UK. A recent study using the Leicestershire ID Register revealed 26 people with ID of the total deaths of 83 SUDEP. This contrasts greatly with Cornwall only 5.26% of SUDEP deaths had ID compared to 23.4% in Leicestershire and similarly when compared to neighboring Plymouth (population 300.000) which had 26% ID deaths in its SUDEPs between 2004–2012. It is possible that having an ID dedicated epilepsy service saves lives.

Schizophrenia is a devastating and complex disease, which occurs in approximately 1% of the general population. Symptoms include hallucinations, delusions and patients’ social withdrawal. Schizophrenia's etiology remains unclear, however, both patients’ genetic profile and environmental factors play a significant role.

Our study's primary objective was to identify genetic variants related with schizophrenia's development in non-Caucasians populations and to explore whether these polymorphisms can be also found in schizophrenia patients of Caucasian origin.

To achieve that, we screened Science Direct and PubMed medical literature databases to identify research articles correlating genes and variants with the development of schizophrenia. Next step was the categorization of studies according to samples’ origin and the identification of genomic variants that are correlated with schizophrenia (P < 0.001) but have never been studied in Caucasian populations.

In total, 108 and 47 studies, in non-Caucasian and Caucasian populations respectively, were identified, in which 157 (P < 0.05) and 18 (P < 0.001) variants were associated with the development of the disease in non-Caucasian populations.

From our qualitative meta-analysis 18 variants that were correlated with schizophrenia's etiology were identified (P < 0.001), which will be further investigated in a multi-cultural Caucasian cohort.

Neurocognitive disorders are the only psychiatric disorders which underlying pathogeny can potentially be determined. This has important implications, for it makes possible the use of biomarkers in order to gain better diagnosis, and opens a door to more accurate treatments. Nonetheless, as biomarkers are not exclusive of a single disorder, the lengths of its utility are still unknown.

To understand the values and limitations of biomarkers in differential diagnosis of dementias.

We present three cases followed in the Neurology ward of our hospital, in which they were admitted for diagnosis and treatment of a subacute form of dementia. Medical history, core symptoms, screening tests for cognitive impairment, MRI, EEG and biomarkers in cerebrospinal fluid were used for diagnosis.

Two cases had consistent clinical features and complementary explorations, and they were respectively diagnosed as Creutzfeldt-Jakob Disease and Lewy Body Dementia; however, the last case showed contradictory results between clinic and complementary explorations, particularly 14-3-3 protein, which was positive and led to the initial diagnosis as Creutzfeldt-Jakob Disease, which was proven wrong once necropsy was practiced.

Although complementary explorations, and biomarkers in particular, are of invaluable utility in the accurate diagnosis of multiple psychiatric diseases, they must always be considered within a context given by biography and clinical features, because, when failing to do so, they can lead to misdiagnosis and delay of correct treatment.

The peripersonal space is described as that area within the boundary between self and non-self. An accurate judgment of peripersonal space boundaries may depend on the capacity to create an organized and structured mental representation that integrates signals from different sensory modalities and brain regions. Empirical evidence suggests that these functions are altered in schizotypy, which is thought to reflect the subclinical expression of the symptoms of schizophrenia in the general population. A number of clinical studies reported that interpersonal interaction and social stimulation have an impact on the onset and progress of schizophrenia.

We conducted a study on personal space in a sample of student screened for schizotypal traits using a paradigm that was not affected by emotional and social interference.

The aim was to evaluate the relationship between personal space and schizotypy traits.

Thirty-four subject recruited for the study completed the Schizotypal Personality Questionnaire (SPQ). According to the SPQ results participants were splitted into two groups (High, Low). Each participant performed a PeriPersonal Space (PPS) task.

Our results show a more extended boundary of the peripersonal space in people with high schizotypy compared to people with low schizotypy even without emotional and social interference.

People with high traits of schizotypy suffer from a difficulty in social integration because of being unable to adapt the social behavior. A better understanding of the mechanisms for abnormal interactive behavior could provide significant valid guidelines for innovating insertion programs that aims to improve social functioning.

The authors have not supplied their declaration of competing interest.

Finding the right medication in psychiatry can be very demanding both for the doctor and for the patient. It becomes extremely grueling when the patient has a rare type of metabolizing enzymes, and many drugs may be ineffective or cause side effects.

To highlight the therapeutic difficulties in psychiatric treatment of the patient with complex genetic cytochrome P450 system alterations.

To provide an example on a complicated treatment course of the patient that is poor CYP2D6 and ultrarapid CYP2C19 metabolizer.

Literature review in scientific database–Pubmed–and case report presentation.

We report a case of a woman in her early twenties who was repeatedly referred for psychiatric treatment. A diagnosis of paranoid schizophrenia was established, but all treatment rounds were unsuccessful, the illness kept progressing, and major depressive disorder aggravated the clinical picture. The patient became suicidal and injured herself. During the sixth hospitalization in one year the CYP2D6, CYP2C19 and CYP2C9 genotyping was done. CYP2C19 ultrarapid (*1/*17) and CYP2D6 poor metabolizer (*4/*5) profile was discovered. Drugs, that should have been avoided due to the patient's genetic profile, had been prescribed throughout five hospitalizations in a row.

As ultrarapid CYP2C19 metabolizers compose around 3–4% and poor CYP2D6–6–10% of Caucasians, this case presents a rare genetic variant that only 0.18–0.4% of Caucasian population may have. These cases can be extremely clinically challenging and affect healthcare outcomes and costs. Further studies that would include clinical effectivity, drug concentration and genetic testing results are needed.

Weight gain is a side effect of pharmacological antidepressant treatments, causing a poorer compliance, increasing the risk of metabolic syndrome and periods of untreated disease.

The ability to precisely prescribe pharmacological treatments based on personal genetic makeups would increase the quality of the current antidepressant treatments.

The molecular pathways enriched during citalopram induced weight gain are identified.

643 depressed citalopram treated individuals with available clinical and genome-wide genetic information were investigated in the present contribution in order to identify the molecular pathways that holds the key to weight gain. Statistics were conducted in R environment (Bioconductor and Reactome packages), ANOVA and MANCOVA served when appropriate. Plink was used for genetic analysis in a linux environment.

One hundred and eleven individuals had their weight increased after treatment with citalopram. The axon guidance (P. adjust = 0.005) and the developmental biology pathway (P. adjust = 0.01) were found to be enriched in genetic variations associated with weight gain.

The development biology pathway includes molecular cascades involved in the regulation of beta-cell development, and the transcriptional regulation of white adipocyte differentiation. A number of variations were harboured by genes whose products are involved in the synthesis of collagen (COL4A3, COL5A1 and ITGA1), activity of the thyroid-hormones (NCOR1 and NCOR2), energy metabolism (ADIPOQ, PPARGC1A) and myogenic differentiation (CDON). A molecular pathway analysis conducted in a sample of depressed patients identifies new candidate genes whose future investigation may grant relevant insights in the molecular events that drive weight gain during antidepressant treatment.

Pharmacogenetics may inform an accurate prescribing of antidepressants by identifying the genetic background specifically responding to a certain drug. Despite decades of efforts though, pharmacogenetics appears to be still in its infancy.

A clearer understanding of the pharmacodynamics and pharmacokinetics events in combination with the genetic and epigenetic controls of cells and molecular cascade must inform the future of personalised medicine.

To systematically review the current cutting edge knowledge about pharmacognetics in the search for the next groundbreaking biological key events that may provide the keys to future treatments.

The major online databases are systematically searched with common keywords by two independent researchers and conflicting findings are solved during regular meetings dedicated to the topic in object. Manual searching of single bibliographies is also put in place.

Genes belonging to the serotoningeric, dopaminergic, glutamatergic and GABAergic systems are classic candidates for pharmacogenetics whose role was not confirmed by GWAS analyses, which, on the other hand, identified genes related to molecular pathways not associated with direct target of drugs used for the treatment of depression.

Both hypothesis driven candidate genetic investigations and GWAS analyses have been conducted so far, leading to the identification of a handful of potential good candidates, but the replication rate of the positive association findings lags behind expectations. The current knowledge about the pharmacodyncamic and pharmacokinetic genetic determinants of antidepressant response is critically analysed and new candidates are presented discussed.

Arrhythmia is a potentially fatal side effect of antipsychotics. A biologic predictive tool to prevent it is missing.

Identification of a genetic profile at risk for antipsychotic induced arrhythmia.

Identifying a molecular pathway enriched for antipsychotic induced QT-modifications.

Seven hundred and sixty-five SKZ individuals, M = 556, age = 40.93 ± 11.03 were included. QT-variation was a phase-specific created variable. A nested mixed regression served in R for clinical and molecular pathway analyses. Plink served for genetic analyses. Quality checking was standard, inflation factor was controlled by lambda values.

Quetiapine and Perphenazine were associated with QT variation (P = 0.002; Estimate = 5.79 and P = 5.67e-06; Estimate = 8.96 respectively). No other significant association was detected. No inflation was detected. Axon guidance and Collagen biosynthesis (Table 1) were associated with QT variation at a conservative (adjusted) P value < 0.01.

Two molecular pathways were identified as possibly involved in QT modifications during antispsychotic treatment in SKZ patients. Previous evidence supports a role of the same pathways in cardiac disorders [1,2]. Interaction of specific SNPs with the drugs will be focus of further research.

The authors have not supplied their declaration of competing interest.

Cognitive processes are impaired in Schizophrenia (SKZ). The nature of such impairment escapes definition.

Identification of a genetic profile at risk of cognitive impairment.

Identifying a molecular pathways enriched for mutations associated with cognitive impairment.

Seven hundred and sixty-five individuals from the CATIE, M = 556, mean age = 40.93 ± 11.03 were included. Verbal memory was outcome. R and Plink served for the analyses. Inflation factor was controlled by lambda values. Input for the pathway analysis were SNPs associated with outcome (P < 0.05) genomewide.

Gender (male, P = 2.34e–05;t = –4.26) and years of education (P = 1.57e–03;t = 6.502) were associated with verbal memory. Inflammation and oxidation were associated with outcome (Table 1, adj_P < 0.01).

Being male and poorly educated were associated with poorer verbal memory. Inflammation and the arachidonic acid pathway were enriched in mutations associated with poorer verbal memory. This finding is in line with previous reports [1,2,3].

The authors have not supplied their declaration of competing interest.

The glutamate system is implicated both in mood disorders and schizophrenia. Mice lacking metabotropic mGlu5 receptors (mGluR5 KO) display schizophrenia-like abnormalities. Additionally, mGluR5 antagonists represent promising alternative anxiolytics/antidepressants. However, the underlying age-specific molecular/cellular mechanisms are only partially understood.

We aimed at identifying molecular alterations associated with a genetically induced mGluR5 deletion, which results in a schizophrenia-like phenotype. Additionally, we investigated age-specific effects of mGluR5 antagonists on emotional behaviour and c-fos activation.

For analysis of mRNA and protein levels we performed Real-time RT-PCR and Western blot investigations of brains from mGluR5 KO and wild-type mice. Additionally we used classical behavioral tests for determining anxiety- and depression-like changes triggered by the mGluR5 antagonist 2-Methyl-6-(phenylethynyl)pyridine (MPEP). Finally, we used profiling of c-Fos expression, as marker of neuronal activity, induced by MPEP from postnatal day 16 (P16) to adulthood (P90).

We found reduced expression levels of reelin, GAD65, GAD67, parvalbumin, as well as NMDA and AMPA receptor subunits in mGluR5 KO mice, especially in the prefrontal cortex (PFC). We measured age-specific alterations in emotional behaviour of mGluR5 KO mice, with marked increase of anxiety during aging. There was a remarkably conserved activation of the paraventricular nucleus of the hypothalamus, implicated in stress regulation, by MPEP at all investigated ages, whereas the extended amygdala was specifically activated in adulthood only.

Our animal data provide new insights into the potential role of mGluR5 in neurochemical and behavioural changes associated with schizophrenia and mood disorders during the lifespan.

The authors have not supplied their declaration of competing interest.

Reactivity to acute psychosocial stress in the framework of a physiological multidimensional pattern affects several individual-level systems that include genetic factors and features related to personality development. The 5-HTTLPR genotype has been implicated in the modulation of susceptibility to environmental stimuli.

In the present study, 91 healthy young women were investigated (i) for their reactivity to a standardized psychosocial laboratory stressor (TSST), as measured by changes in salivary cortisol; (ii) in terms of 5-httlpr genotype and (iii) in terms of their personality profile according to the post-rationalist personal meaning organizations (PMOs), which are considered as adaptive modes of response to environmental stressors.

Participants were divided into three 5-HTTLPR genotype groups (s/s; s/l, and l/s). The quantitative and qualitative variables that may affect circulating cortisol were compared among the three groups. A multiple linear quantile regression analysis was then performed to evaluate the effect of the personality profile, as Outward/Inward PMO, and 5-HTTLPR genotype on the median level of cortisol, considered as dependent variable.

Comparison of the variables that may affect circulating cortisol no significant differences. Salivary cortisol changed significantly in the course of the TSST. Reactivity to stress was affected by personality profile and the 5-HTTLPR genotype and also by body mass index and age.

The present data suggest that the psychosocial stress response is a multidimensional physiological event that is affected by a variety of factors as diverse as 5-HTTLPR genotype, personality profile, BMI, and age.

The authors have not supplied their declaration of competing interest.

Right hemisphere damage (RHD) has been related to alterations in emotion processing. However, results regarding physiological responses are limited and inconsistent. More research regarding specific brain areas involved in emotional physiological responses is needed.

To examine the skin conductance response (SCR) to emotion eliciting images in patients with single RHD. To explore the relationship between SCR and brain injury location in patients with single RHD.

To examine the relationship between SCR and cortical and subcortical damage in RH regarding emotional processing.

Forty-one individuals with RHD due to stroke were assessed (mean age 68.5, SD 12.2, 51.1 males). The amplitude of event-related SCR was registered through a biofeedback system while observing 54 photographs from the international affective picture system (IAPS). Emotional images were classified using two different approaches: emotional valence (pleasant, unpleasant, neutral) and social vs. non-social content. Brain damage location, determined through medical records, included cortical (frontal, parietal, temporal and occipital lobes) as well as sub-cortical (caudate nucleus, thalamus, lenticular nucleus, insular cortex, basal ganglia and limbic system) structures.

Amplitude of SCR to emotional images was significantly lower in individuals with occipital cortex injury compared to those with damage in other brain locations (P < 0.05). These results were consistent through all stimuli categories but non-social pictures, which presented the same pattern though, did not reach statistical significance.

Results show a relationship between occipital areas in HD and SCR to emotional eliciting stimuli, suggesting occipital right lobe involvement in physiological emotional processing.

The authors have not supplied their declaration of competing interest.

Polygenic risk scores (PRS) incorporate many small genetic markers that are associated with conditions. This technique was first used to investigate mental illnesses in 2009. Since then, it has been widely used.

We wanted to explore how PRS have been used to the study the aetiology of psychosis, schizophrenia, bipolar disorder and depression.

We aimed to conduct a systematic review, identifying studies that have examined associations between PRS for bipolar disorder, schizophrenia/psychosis and depression and psychopathology-related outcome measures.

We searched EMBASE, Medline and PsychInfo from 06/08/2009 to 14/03/2016. We hand-searched the reference lists of related papers.

After removing duplicates, the search yielded 1043 publications. When irrelevant articles were excluded, 33 articles remained. We found 24 studies using schizophrenia PRS, three using bipolar PRS and nine using depression PRS. Many studies successfully used PRS to predict case/control status. Some studies showed associations between PRS and diagnostic sub-categories. A range of clinical phenotypes and symptoms has been explored. For example, specific PRS are associated with cognitive performance in schizophrenia, psychotic symptoms in bipolar disorder, and frequency of episodes of depression. PRS have also demonstrated genetic overlap between mental illnesses. It was difficult to assess the quality of some studies as not all reported sufficient methodological detail.

PRS have enabled us to explore the polygenic architecture of mental illness and demonstrate a genetic basis for some observed features. However, they have yet to give insights into the biology, which underpin mental illnesses.

The authors have not supplied their declaration of competing interest.

Single nucleotide polymorphisms (SNPs) contribute small increases in risk for late-onset Alzheimer's disease (LOAD). LOAD SNPs cluster around genes with similar biological functions (pathways). Polygenic risk scores (PRS) aggregate the effect of SNPs genome-wide. However, this approach has not been widely used for SNPs within specific pathways.

We investigated whether pathway-specific PRS were significant predictors of LOAD case/control status.

We mapped SNPs to genes within 8 pathways implicated in LOAD. For our polygenic analysis, the discovery sample comprised 13,831 LOAD cases and 29,877 controls. LOAD risk alleles for SNPs in our 8 pathways were identified at a P-value threshold of 0.5. Pathway-specific PRS were calculated in a target sample of 3332 cases and 9832 controls. The genetic data were pruned with R2 > 0.2 while retaining the SNPs most significantly associated with AD. We tested whether pathway-specific PRS were associated with LOAD using logistic regression, adjusting for age, sex, country, and principal components. We report the proportion of variance in liability explained by each pathway.

The most strongly associated pathways were the immune response (NSNPs = 9304, = 5.63 × 10−19, R2 = 0.04) and hemostasis (NSNPs = 7832, P = 5.47 × 10−7, R2 = 0.015). Regulation of endocytosis, hematopoietic cell lineage, cholesterol transport, clathrin and protein folding were also significantly associated but accounted for less than 1% of the variance. With APOE excluded, all pathways remained significant except proteasome-ubiquitin activity and protein folding.

Genetic risk for LOAD can be split into contributions from different biological pathways. These offer a means to explore disease mechanisms and to stratify patients.

The authors have not supplied their declaration of competing interest.