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Background There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood. In the current study, we investigated the relationship of erythrocyte omega-3 FAs with plasma immune markers in a clinical high risk for psychosis (CHR) sample. In addition, a mediation analysis was performed to examine whether previously reported associations between omega-3 FAs and clinical outcomes were mediated via plasma immune markers. Clinical outcomes for CHR participants in the NEURAPRO clinical trial were measured using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Scale of Assessment of Negative Symptoms (SANS) and Social and Occupational Functioning Assessment Scale (SOFAS) scales. The erythrocyte omega-3 index [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] and plasma concentrations of inflammatory markers were quantified at baseline (n = 268) and 6 month follow-up (n = 146) by gas chromatography and multiplex immunoassay, respectively. In linear regression models, the baseline plasma concentrations of Interleukin (IL)-15, Intercellular adhesion molecule (ICAM)-1 and Vascular cell adhesion molecule (VCAM)-1 were negatively associated with baseline omega-3 index. In addition, 6-month change in IL-12p40 and TNF-α showed a negative association with change in omega-3 index. In longitudinal analyses, the baseline and 6 month change in omega-3 index was negatively associated with VCAM-1 and TNF-α respectively at follow-up. Mediation analyses provided little evidence for mediating effects of plasma immune markers on the relationship between omega-3 FAs and clinical outcomes (psychotic symptoms and functioning) in CHR participants. Our results indicate a predominantly anti-inflammatory relationship of omega-3 FAs on plasma inflammatory status in CHR individuals, but this did not appear to convey clinical benefits at 6 month and 12 month follow-up. Both immune and non-immune biological effects of omega-3 FAs would be resourceful in understanding the clinical benefits of omega-3 FAs in CHR papulation.

Background No biological treatment has been firmly established for the at-risk stage of psychotic disorder. In this study we aim to test if subthreshold psychotic symptoms can be effectively treated with cannabidiol (CBD), a non-psychoactive compound of the plant Cannabis sativa. The question has taken on increased importance in the wake of evidence questioning both the need and efficacy of specific pharmacological interventions in the ultra-high risk (UHR) for psychosis group. Methods Three-arm randomized controlled trial of 405 patients (135 per arm) aged 12-25 years who meet UHR for psychosis criteria. The study includes a 6-week lead-in phase during which 10% of UHR individuals are expected to experience symptom remission. Participants will receive CBD (per oral) at doses 600 or 1000 mg per day (fixed schedule) for 12 weeks. Participants in the third arm of the trial will receive matching placebo capsules. Primary outcome is severity of positive psychotic symptoms as measured by the Comprehensive Assessment of At-Risk Mental States at 12 weeks. We hypothesize that CBD will be significantly more effective than placebo in improving positive psychotic symptoms in UHR patients. All participants will also be followed up 6 months post baseline to evaluate if treatment effects are sustained. Conclusion This paper reports on the rationale and protocol of the Cannabidiol for At Risk for psychosis Youth (CanARY) study. This study will test CBD for the first time in the UHR phase of psychotic disorder.

OBJECTIVE There is conflicting evidence in recent literature about whether the incidence of schizophrenia is increasing or decreasing. A role for prenatal and early childhood viral infections in the aetiology of schizophrenia has also been debated. We examined the incidence of schizophrenia and the catatonic subtype of schizophrenia over a 30-year period in Finland. We also investigated whether the incidence rate of the catatonic subtype of schizophrenia was linked to changes in exposure to viral infection (polio and measles) during the prenatal or infant period. METHODS Persons with schizophrenia were identified from the Hospital Discharge Register. Cumulative incidence of schizophrenia from 1956 to 1989 in 4 age groups was calculated with follow-up from 1972 to 2014. Annual rates of polio and measles were derived from nationwide registers. The association between log-transformed polio and measles incidence and incidence of schizophrenia, and specifically catatonic schizophrenia, were analysed using linear models. RESULTS Cumulative incidence of schizophrenia among individuals born 1956-1989 decreased by 23% (from 13 to 10 cases per 1000 live births). The decline was the most prominent in those with onset of schizophrenia diagnosed 16-25 years of age (-41%). The incidence of catatonic schizophrenia declined by 90% over three decades, and there was a significant association between annual polio incidence during the birth year and incidence of catatonic schizophrenia. CONCLUSIONS The results indicate that the incidence of schizophrenia in Finland has declined for individuals born between 1956 and 1989, and that the decline of catatonic schizophrenia may be partially attributable to eradication of polio.

Aim: Among different types of poly unsaturated fatty acids, omega-3 fatty acids (FA) play a substantial role in brain development and functioning. This review was designed to evaluate and synthesize available evidence regarding omega-3 FAs and functional outcome in the ultra-high-risk (UHR) population.Methods: An electronic search in PubMed, EMBASE, PSYCINFO and COCHRANE search engines has been performed for all articles published until January 2019. The studies that have data regarding omega-3 FAs and functional outcome in UHR population were included.Results: Out of 397 nonduplicate citations, 19 articles met selection criteria. These articles were from four different primary studies, namely the Program of Rehabilitation and Therapy (PORT), the North American Prodromal Longitudinal Studies (NAPLS), Vienna High Risk study (VHR) and the NEURAPRO. The data from the NAPLS study found a positive correlation between functional improvement and frequency of dietary intake omega-3 FA. Moreover, among the erythrocyte omega-3 FA only eicosapentaenoic acid (EPA) showed a positive correlation with functional score. The VHR study found long-term improvement in functional outcome in omega-3 group compared to control, whereas such difference was noticed in the NEURAPRO. In the VHR study both omega-3 and omega-6 together predicted the functional improvement at 12 weeks.Conclusions: The number of studies available remains insufficient and more studies with standardized outcome measures in a clinically comparable UHR population would be of more value to understand the clinical benefits of omega-3 FA in the UHR population.

Objectives:On-call and crisis psychiatry is a very challenging aspect of psychiatric training. This study aimed to describe the experiences of psychiatric trainees on-call in hospitals, emergency departments and psychiatric units in Ireland.Methods:In total, 193 psychiatric trainees in Ireland were emailed a survey in 2017. The survey included questions regarding the duties expected of the trainee, frequency of on-call obligations, un-rostered hours worked, level of senior support, assessment facilities available and doctors’ satisfaction with the on-call experience.Results:Overall, 68 trainees responded to the survey. In total, 35% of respondents reported dissatisfaction with their experience of on-call and crisis psychiatry, 46% reported that they were not provided with training in risk assessment and 21% of respondents stated that there was not a suitable room available to perform their assessments.Conclusions:This survey has raised important issues facing those on the frontline of psychiatric services in Ireland. Of particular concern are resource issues faced by trainees and the need for further training and support related to risk assessment when on-call. Remedying these issues may lead to a decreased rate of dropout as well as a safer and better environment for patients and doctors alike.

Objectives:To determine if the initial COVID-19 societal restrictions, introduced in Ireland in March 2020, impacted on the number and nature of psychiatry presentations to the emergency department (ED) of a large academic teaching hospital.Methods:We examined anonymised clinical data of psychiatry presentations to the ED during the initial 8-week period of COVID-19 restrictions. Data from corresponding 8-week periods in 2018 and 2019 were also extracted for comparison.Results:Psychiatry presentations to ED reduced by 21% during the COVID-19 restrictions, from 24/week to 19/week when compared with corresponding periods in 2018/2019 (Poisson’s Rate Test estimate of difference −5.2/week, 95% CI 1.3–9.1, p = 0.012). Numbers attending for out-of-hours assessment remained unchanged (81 v. 80), but numbers seeking assessment during normal hours decreased (71 v. 114). We observed increased presentations from the p = 0.002). We recorded an increase in anxiety disorders during the initial COVID-19 restrictions (31 v. 23), and a reduction in alcohol disorders (28 v. 52). The proportion of presentations with suicidal ideation (SI) or self-harm as factors remained unchanged.Conclusions:Rates of emergency presentation with mental illness reduced during the initial COVID-19 restrictions. This may represent an unmet burden of mental health needs. Younger people may be experiencing greater distress and mental illness during the current crisis. More people sought help for anxiety disorders during the COVID-19 restrictions compared with corresponding data from 2018 and 2019.

Background There is renewed focus on the complement system in the pathogenesis of schizophrenia. In addition to providing aetiological insights, consistently dysregulated complement proteins in serum or plasma may have clinical utility as biomarkers. Methods We performed a systematic literature review searching PubMed, Embase and PsycINFO for studies measuring complement system activity or complement protein concentrations in serum or plasma from patients with schizophrenia compared to controls. Random-effects meta-analyses were performed to calculate pooled effect estimates (Hedges' g standardised mean difference [SMD]) for complement proteins whose concentrations were measured in three or more studies. The review was pre-registered on the PROSPERO database (CRD42018109012). Results Database searching identified 1146 records. Fifty-eight full-text articles were assessed for eligibility and 24 studies included. Seven studies measured complement system activity. Activity of the classical pathway did not differ between cases and controls in four of six studies, and conflicting results were noted in two studies of alternative pathway activity. Twenty studies quantified complement protein concentrations of which complement components 3 (C3) and 4 (C4) were measured in more than three studies. Meta-analyses showed no evidence of significant differences between cases and controls for 11 studies of C3 (SMD 0.04, 95% confidence interval [CI] -0.29–0.36) and 10 studies of C4 (SMD 0.10, 95% CI -0.21–0.41). Conclusions Serological studies provide mixed evidence regarding dysregulation of the complement system in schizophrenia. Larger studies of a longitudinal nature, focusing on early phenotypes, could provide further insights regarding the potential role of the complement system in psychotic disorders.

Polyunsaturated fatty acids (PUFAs) may be pertinent to the development of mental disorders, for example via modulation of inflammation and synaptogenesis. We wished to examine cross-sectional and longitudinal associations between PUFAs and mental disorders in a large cohort of young people. Participants in the Avon Longitudinal Study of Parents and Children were interviewed and provided blood samples at two sampling periods when approximately 17 and 24 years old. Plasma PUFA measures (total omega-6 [n-6], total omega-3 [n-3], n-6:n-3 ratio and docosahexaenoic acid [DHA] percentage of total fatty acids) were assessed using nuclear magnetic resonance spectroscopy. Cross-sectional and longitudinal associations between standardised PUFA measures and three mental disorders (psychotic disorder, moderate/severe depressive disorder and generalised anxiety disorder [GAD]) were measured by logistic regression, adjusting for age, sex, body mass index and cigarette smoking. There was little evidence of cross-sectional associations between PUFA measures and mental disorders at age 17. At age 24, the n-6:n-3 ratio was positively associated with psychotic disorder, depressive disorder and GAD, while DHA was inversely associated with psychotic disorder. In longitudinal analyses, there was evidence of an inverse association between DHA at age 17 and incident psychotic disorder at age 24 (adjusted odds ratio 0.44, 95% confidence interval 0.22–0.87) with little such evidence for depressive disorder or GAD. There was little evidence for associations between change in PUFA measures from 17 to 24 years and incident mental disorders at 24 years. These findings provide support for associations between PUFAs and mental disorders in early adulthood, and in particular, for DHA in adolescence in relation to prevention of psychosis.

Objectives: There is a high rate of psychiatric comorbidity in patients with epilepsy. However, the impact of surgical treatment of refractory epilepsy on psychopathology remains under investigation. We aimed to examine the impact of epilepsy surgery on psychopathology and quality of life at 1-year post-surgery in a population of patients with epilepsy refractory to medication. Methods: This study initially assessed 48 patients with refractory epilepsy using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life in Epilepsy Inventory 89 (QOLIE-89) on admission to an Epilepsy Monitoring Unit (EMU) as part of their pre-surgical assessment. These patients were again assessed using the SCID-I, QOLIE-89 and HADS at 1-year follow-up post-surgery. Results: There was a significant reduction in psychopathology, particularly psychosis, following surgery at 1-year follow-up (p < 0.021). There were no new cases of de novo psychosis and surgery was also associated with a significant improvement in the quality of life scores (p < 0.001). Conclusions: This study demonstrates the impact of epilepsy surgery on psychopathology and quality of life in a patient population with refractory surgery. The presence of a psychiatric illness should not be a barrier to access surgical treatment.

Objectives: Over 50% of inpatients with neurological disorders may present with a co-morbid psychiatric illness. Delirium has a reported point prevalence of 20% in hospital inpatients and is frequently undetected. We aimed to (1) examine inpatient referrals to a Liaison Neuropsychiatry service and (2) review the diagnosis and management of delirium before and after an educational intervention. Methods: An initial 6-month audit of referrals to the inpatient Liaison Neuropsychiatry service was conducted in 2018. We then undertook a psychoeducational intervention to raise awareness of the diagnosis and management of delirium. We conducted a re-audit of referrals to the service in 2019. Results: On initial audit, of 84 referrals, the most common referral was for mood (38%; n = 32). Just 4% (n = 3) had a specific delirium query. Following assessment by Neuropsychiatry, organic disorders (43%; n = 32), including delirium (33%; n = 25), were the most common diagnoses. On re-audit, of 86 referrals, mood assessment remained the most common reason for referral (38%; n = 33) and 2% (n = 2) were referred for possible delirium. Organic disorders remained the most common diagnoses (53%; n = 45) including delirium (38%; n = 32). We found a significant increase in the use of the delirium protocol from 12% (n = 3) on initial audit to 47% (n = 15); p < 0.01 on re-audit despite no increase in the number of specific delirium queries. Conclusions: A psychoeducational intervention improves the management of delirium by Neurologists and Neurosurgeons in patients with brain disorders.

ObjectivesTo examine the delivery and assessment of psychiatry at undergraduate level in the six medical schools in the Republic of Ireland offering a medical degree programme.MethodsA narrative description of the delivery and assessment of psychiatry at undergraduate level by collaborative senior faculty members from all six universities in Ireland.ResultsPsychiatry is integrated to varying degrees across all medical schools. Clinical experience in general adult psychiatry and sub-specialities is provided by each medical school; however, the duration of clinical attachment varies, and the provision of some sub-specialities (i.e. forensic psychiatry) is dependent on locally available resources. Five medical schools provide ‘live’ large group teaching sessions (lectures), and all medical schools provide an array of small group teaching sessions. Continuous assessment encompasses 10–35% of the total assessment marks, depending on the medical school. Only one medical school does not provide a clinical examination in the form of an Objective Structured Clinical Examination with viva examinations occurring at three medical schools.ConclusionsMany similarities exist in relation to the delivery of psychiatry at undergraduate level in Ireland. Significant variability exists in relation to assessment with differences in continuous assessment, written and clinical exams and the use of vivas noted. The use of e-learning platforms has increased significantly in recent years, with their role envisaged to include cross-disciplinary teaching sessions and analysis of examinations and individual components within examinations which will help refine future examinations and enable greater sharing of resources between medical schools.

It has been recently shown that COVID-19 is associated with a clinically significant coagulopathy. Several studies have indicated that elevated markers of fibrin degradation (D-dimers) in hospitalised patients are associated with poorer prognosis (death or ICU admission) (Fogarty et al., 2020, Connors and Levy, 2020). Coagulation test screening is suggested and routine thromboprophylaxis measures (including use of low molecular weight heparin) are recommended, although full anticoagulation is not yet advised in the management of such patients unless otherwise clinically indicated (Connors and Levy, 2020). We wish to draw attention to a potentially enhanced risk of thromboembolic complications in patients with psychotic disorders.

Psychotic disorders are central to mental health service provision and a common theme of academic research programmes in Ireland, which explore the neurobiological and psychosocial risk factors underpinning the development and progression of these illnesses. While we await the discovery of novel pharmacological treatment targets for psychotic disorders, it is important to employ our existing management strategies to optimal effect. In this special issue on psychosis, a selection of clinical research studies and reviews from Irish researchers, and often of Irish populations, are brought together which span the trajectory of psychotic illness from early intervention to treatment resistance. The topics include the characteristics and course of first episode psychosis cohorts, real-world evaluation of early intervention services, management strategies for treatment resistant schizophrenia and neurobiological research into social stress. The current editorial provides an overview of these papers and highlights the initial steps of the Irish Psychosis Research Network towards developing an integrated clinical research network focusing on the treatment and research into psychotic disorders.

The identification of early biological changes associated with the psychotic disorder (PD) is important as it may provide clues to the underlying pathophysiological mechanisms. We undertook the first proteomic profiling of blood plasma samples of children who later develop a PD. Participants were recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who also participated in psychiatric assessment interviews at age 18. Protein expression levels at age 11 were compared between individuals who developed PD at age 18 (n = 37) with population-based age-matched controls (n = 38). Sixty out of 181 plasma proteins profiled were found to be differentially expressed (P < .05) in children with an outcome of the PD. Thirty-four of these proteins were found to be differentially expressed following correction for multiple comparisons. Pathway analysis implicated the complement and coagulation cascade. A second, targeted proteomic approach was used to verify these findings in age 11 plasma from subjects who reported psychotic experiences at age 18 (n = 40) in comparison to age-matched controls (n = 66). Our findings indicate that the complement and coagulation system is dysregulated in the blood during childhood before the development of the PD.

Background Individuals at clinical high risk (CHR) of psychosis have an approximately 20% probability of developing psychosis within 2 years, as well as an associated risk of non-psychotic disorders and functional impairment. People with subclinical psychotic experiences (PEs) are also at risk of future psychotic and non-psychotic disorders and decreased functioning. It is difficult to accurately predict outcomes in individuals at risk of psychosis on the basis of symptoms alone. Biomarkers for accurate prediction of outcomes could inform the clinical management of this group. Methods We conducted two nested case-control studies. We employed discovery-based proteomic methods to analyse protein expression in baseline plasma samples in EU-GEI and age 12 plasma samples in ALSPAC using liquid chromatography mass spectrometry. Differential expression of quantified proteomic markers was determined by analyses of covariance (with false discovery rate of 5%) comparing expression levels for each marker between those who did not and did not develop psychosis in Study 1 (adjusting for age, gender, body mass index and years in education), and between those who did and did not develop PEs in Study 2 (adjusting for gender, body mass index and maternal social class). Support vector machine algorithms were used to develop models for prediction of transition vs. non-transition (as determined by the Comprehensive Assessment of At Risk Mental States) and poor vs. good functional outcome at 2 years in Study 1 (General Assessment of Functioning: Disability subscale score 60). Similar algorithms were used to develop a model for prediction of PEs vs. no PEs at age 18 in Study 2 (as determined by the Psychosis Like Symptoms Interview). Results In Study 1, 35 of 166 quantified proteins were significantly differentially expressed between CHR participants who did and did not develop psychosis. Functional enrichment analysis provided evidence for particular implication of the complement and coagulation cascade (false discovery rate-adjusted Fisher’s exact test p=2.23E-21). Using 65 clinical and 166 proteomic features a model demonstrated excellent performance for prediction of transition status (area under the receiver-operating curve [AUC] 0.96, positive predictive value [PPV] 83.0%, negative predictive value [NPV] 93.8%). A model based on the ten most predictive proteins accurately predicted transition status in training (AUC 0.96, PPV 87.5%, NPV 95.8%) and withheld data (AUC 0.92, PPV 88.9%, NPV 91.4%). A model using the same 65 clinical and 166 proteomic features predicted 2-year functional outcome with AUC 0.72 (PPV 67.6%, NPV 47.6%). In Study 2, 5 of 265 quantified proteins were significantly differentially expressed between participants who did and did not report PEs at age 18. A model using 265 proteomic features predicted PEs at age 18 with AUC 0.76 (PPV 69.1%, NPV 74.2%). Discussion With external validation, models incorporating proteomic data may contribute to improved prediction of clinical outcomes in individuals at risk of psychosis.

Background: Previous systematic reviews and meta-analyses of cross-sectional data assessing the effect of cannabis on cognition show inconsistent results. We hypothesized that frequent and dependent cannabis use in the neurodevelopmental period would be associated with Intelligence Quotient (IQ) decline. Methods: This is a systematic review and meta-analysis. We searched Embase, PubMed and PsychInfo from inception to 24/01/2020. We included studies with non-treatment seeking samples of subjects as cases if they reported frequent or dependent cannabis use. We excluded studies if they did not have a pre-exposure measure of IQ and if the period of cannabis use did not start before age 26. We requested data from authors if summary data was not available from published work. We used the Newcastle Ottawa scale to assess study quality. We used random effects meta-analysis to calculate a Cohen’s D statistic. We preregistered our review with PROSPERO (ID no. CRD42019125624). Findings: We found seven cohort studies including 956 cases 5946 controls. There was a modest effect for the association between frequent or dependent cannabis use in adolescence and IQ decline, Cohen’s D = -0.122, (95% CI -0.207- -0.037) P=0.005. Study quality was moderate to high. Statistical heterogeneity between studies was also low at I2 = 15.2%. Interpretation: There are modest decreases in IQ over time in frequent and dependent adolescent cannabis users equating to loss of 1.83 IQ points (95% CI 0.56- 3.11). Funding Statement: EP was supported by Health Research Board of Ireland ‘YouLead’ Collaborative Doctoral Award (grant code 18210). MC, CH & AON were supported by European Research Council Consolidator Award to MC (Grant code 724809 iHEAR). SS was supported by Health Research Board PHR 2015-1293 awarded to DC. Declaration of Interests: The authors declare no competing interests.

Background The identification of early biomarkers of psychotic experiences (PEs) is of interest because early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures of later PEs in subjects from the Avon Longitudinal Study of Parents and Children cohort. Methods Plasma of 115 children (12 years of age) who were first identified as experiencing PEs at 18 years of age (48 cases and 67 controls) were assessed through integrated and targeted lipidomics and semitargeted proteomics approaches. We assessed the lipids, lysophosphatidylcholines (n = 11) and phosphatidylcholines (n = 61), and the protein members of the coagulation pathway (n = 22) and integrated these data with complement pathway protein data already available on these subjects. Results Twelve phosphatidylcholines, four lysophosphatidylcholines, and the coagulation protein plasminogen were altered between the control and PEs groups after correction for multiple comparisons. Lipidomic and proteomic datasets were integrated into a multivariate network displaying a strong relationship between most lipids that were significantly associated with PEs and plasminogen. Finally, an unsupervised clustering approach identified four different clusters, with one of the clusters presenting the highest case-control ratio (p < .01) and associated with a higher concentration of smaller low-density lipoprotein cholesterol particles. Conclusions Our findings indicate that the lipidome and proteome of subjects who report PEs at 18 years of age are already altered at 12 years of age, indicating that metabolic dysregulation may contribute to an early vulnerability to PEs and suggesting crosstalk between these lysophosphatidylcholines, phosphatidylcholines, and coagulation and complement proteins.

The complement cascade is a major component of the immune defence against infection, and there is increasing evidence for a role of dysregulated complement in major psychiatric disorders. We undertook a hypothesis-driven proteomic analysis of the complement signalling pathway (n=29 proteins) using Data Independent Acquisition. Participants were recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who participated in psychiatric assessment interviews at ages 12 and 18. Protein expression levels at age 12, among individuals who first reported psychotic experiences (PEs) at age 18 (n=64), were compared with age-matched controls (n=67). Six out of the 29 targeted complement proteins or protein subcomponents were significantly upregulated following correction for multiple comparisons (VTN↑, C1RL↑, C8B↑, C8A↑, CFH↑, C5↑).Using the same methods, we examined participants with Persistent Psychotic Experiences (PPE) at both age 12 and age 18 (n=38) compared to age-matched controls who only experienced PEs at age 12 (n=38). Here, we observed that five of 29 targeted complement proteins were differentially expressed (C1RL↑, C2↑, C4BPB↑, C9↑, CFD↑). Finally, we undertook an unbiased plasma proteomic analysis of mice exposed to chronic social stress and observed dysregulation of 10 complement proteins including five that were altered in the same direction in individuals with either PE or PPE (C1R↑, CFH↑, C4BP↑, C5↑, C9↑). Our findings indicate that dysregulation of the complement protein pathway in blood is associated with incidence and persistence of psychotic experiences and that these changes may reflect exposure to stress.

Objectives: The commonest psychiatric presentation in most emergency departments (EDs) is deliberate self-harm. However, there are other significant categories of psychiatric presentation which include alcohol and substance misuse, acute psychosis and mood disorder. In addition to the NICE Guidelines for deliberate self-harm, there are good practice guidelines available for the management of other psychiatric attendances to the ED. The aim of this study was to identify the psychiatric attendances other than deliberate self-harm to Beaumont Hospital ED over a 12-month period with the objective of studying the rates and characteristics of attendances and to investigate whether good practice guidelines were met.Method: From a total of 657 psychiatric attendances other than deliberate self-harm which were recorded, data was collected on demographics, provision of a psychosocial assessment and adherence to good practice guidelines.Results: Alcohol (38%) was the most common reason for presentation. Of the total number of attendees, only 44% received a psychosocial assessment compared to 59% of attendees who had presented following deliberate self-harm during the same 12-month period.Conclusions: The attendees who did not receive a psychosocial assessment represent a vulnerable group in which the levels of psychosocial assessment need to be improved in order to meet good practice guidelines standards of care.

Aim1) to assess compliance with the Data Protection Acts (DPA) by a Department of Psychiatry in a general hospital, 2) to implement measures that are likely to maximize compliance with the hospital data protection policy, 3) to close the audit cycle by assessing the impact of such measures on departmental compliance with the DPA over five months period.MethodAn individual, anonymised staff questionnaire on data collection practices, procedure of disclosure of data to third parties and previous training on DPA was used to collect information from the department staff. The premises were inspected at different times over a week period using structured checklist. Default points were recorded during each inspection. Post-audit interventions included a mixture of educational interventions and practical solutions. A re-audited took place five months later using the same method.ResultsThe baseline audit demonstrated significant lack of compliance with the DPA among staff members and lack of staff training on the DPA. Following the interventions, staff awareness of the requirements of the act rose which in turn lead to better adherence to recommend practices in data handling and to mean default points dropped significantly. Management of manual files appears to constitute the biggest problem in this audit. Daytime breaks were found to pose higher risk to stored data compared with before and after working hours.ConclusionsA combination of educational and practical interventions including training of staff on the DPA results in overall improvement in compliance and reduction in default points. However, management of manual (physical) data proves to be more difficult and hence will need more input.

Neuropathological changes of the hippocampus have been associated with psychotic disorders such as schizophrenia and bipolar disorder. Recent work has particularly implicated hippocampal GABAergic interneurons in the pathophysiology of these diseases. However, the molecular mechanisms underlying structural and cellular hippocampal pathology remain poorly understood. We used data from comprehensive difference-in-gel electrophoresis (2-D DIGE) investigations of postmortem human hippocampus of people with schizophrenia and bipolar disorder, covering the acidic (isoelectric point (pI) between pH4 and 7) and, separately, the basic (pI between pH6 and 11) sub-proteome, for Ingenuity Pathway Analysis (IPA) of implicated protein networks and pathways. Comparing disease and control cases, we identified 58 unique differentially expressed proteins in schizophrenia, and 70 differentially expressed proteins in bipolar disorder, using mass spectrometry. IPA implicated, most prominently, 14-3-3 and aryl hydrocarbon receptor signaling in schizophrenia, and gluconeogenesis/glycolysis in bipolar disorder. Both disorders were characterized by alterations of proteins involved in the oxidative stress response, mitochondrial function, and protein-endocytosis, -trafficking, -degradation, and -ubiquitination. These findings are interpreted with a focus on GABAergic interneuron pathology in the hippocampus.

Background: Maternal infection is a risk factor for schizophrenia but the molecular and cellular mechanisms are not fully known. Myelin abnormalities are amongst the most robust neuropathological changes observed in schizophrenia, and preliminary evidence suggests that prenatal inflammation may play a role. Methods: Label-free liquid chromatography-mass spectrometry was performed on the prefrontal cortex (PFC) of adult rat offspring born to dams that were exposed on gestational day 15 to the viral mimic polyinosinic:polycytidylic acid [poly(I:C), 4 mg/kg] or saline and treated with the atypical antipsychotic drug risperidone (0.045 mg/kg) or saline in adolescence. Western blotting was employed to validate protein changes. Results: Over 1,000 proteins were quantified in the PFC with pathway analyses implicating changes in core metabolic pathways, following prenatal poly(I:C) exposure. Some of these protein changes were absent in the PFC of poly(I:C)-treated offspring that subsequently received risperidone treatment in adolescence. Particularly interesting reductions in the expression of the myelin-related proteins myelin basic protein isoform 3 (MBP1) and rhombex 29 were observed, which were reversed by risperidone treatment. Validation by Western blotting confirmed changes in MBP1 and mitogen-activated kinase 1 (MAPK1). Western blotting was extended to assess the MAPK signalling proteins due to their roles in inflammation, namely phosphorylated MAPK1 and phosphorylated MAPK-activated protein kinase 2. Both were upregulated by poly(I:C) treatment and reversed by risperidone treatment. Conclusions: Overall, our data suggest that maternal inflammation may contribute to an increased risk for schizophrenia through mechanisms involving metabolic function and myelin formation and that risperidone in adolescence may prevent or reverse such changes.

The identification of an early biomarker of psychotic disorder is important as early treatment is associated with improved patient outcome. Metabolomic and lipidomic approaches in combination with multivariate statistical analysis were applied to identify plasma alterations in children (age 11) (38 cases vs 67 controls) and adolescents (age 18) (36 cases vs 117 controls) preceeding or coincident with the development of psychotic disorder (PD) at age 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC). Overall, 179 lipids were identified at age 11, with 32 found to be significantly altered between the control and PD groups. Following correction for multiple comparisons, 8 of these lipids remained significant (lysophosphatidlycholines (LPCs) LPC(18:1), LPC(18:2), LPC(20:3); phosphatidlycholines (PCs) PC(32:2; PC(34:2), PC(36:4), PC(0-34-3) and sphingomyelin (SM) SM(d18:1/24:0)), all of which were elevated in the PD group. At age 18, 23 lipids were significantly different between the control and PD groups, although none remained significant following correction for multiple comparisons. In conclusion, the findings indicate that the lipidome is altered in the blood during childhood, long before the development of psychotic disorder. LPCs in particular are elevated in those who develop PD, indicating inflammatory abnormalities and altered phospholipid metabolism. These findings were not found at age 18, suggesting there may be ongoing alterations in the pathophysiological processes from prodrome to onset of PD. European Research Council Health Research Board Wellcome Trust UK Medical Council

Background: Alcohol is widely consumed in Ireland; more so in major urban centers. Alcohol‑related problems account for a significant number of Accident and Emergency (A and E) department presentations in Ireland. As a result, the national alcohol policy calls on doctors to be proactive in screening for and addressing alcohol misuse. Aim: The aim of the following study is to determine if patients presenting to a tertiary North Dublin A and E were asked about their alcohol use habit and if it was recorded. Materials and Methods: This was a descriptive observational study involving the retrospective review of case‑notes for all patients who were assessed at the A and E Department of a North Dublin general hospital over a 1 week period for screening about their alcohol use habit. Data was entered into and analyzed using Microsoft Excel. Results: Only 17% (106/613) of the A and E attendees over the study period were asked about their alcohol use habit or had it recorded. No case‑note examined documented use of alcohol screening instruments. Conclusion: This study has revealed an inadequacy of enquiry about alcohol use habit. In light of high rates of alcohol misuse in Ireland we suggest the need for improved enquiry/screening and recording of alcohol use among all patients attending A and E’s. Keywords: Alcohol, Screening, Recording, Accident

Prenatal stress influences the development of the fetal brain and so contributes to the risk of the development of psychiatric disorders in later life. The hippocampus is particularly sensitive to prenatal stress, and robust abnormalities have been described in the hippocampus in schizophrenia and depression. The aim of this study was to determine whether prenatal stress is associated with distinct patterns of differential protein expression in the hippocampus using a validated mouse model. We therefore performed a comparative proteomic study assessing female hippocampal samples from 8 prenatally stressed mice and 8 control mice. Differential protein expression was assessed using 2-dimensional difference in gel electrophoresis and subsequent mass spectrometry. The observed changes in a selected group of differentially expressed proteins were confirmed by Western blotting. In comparison to controls, 47 protein spots (38 individual proteins) were found to be differentially expressed in the hippocampus of prenatally stressed mice. Functional grouping of these proteins revealed that prenatal stress influenced the expression of proteins involved in brain development, cytoskeletal composition, stress response, and energy metabolism. Western blotting was utilized to validate the changes in calretinin, hippocalcin, profilin-1 and the signal-transducing adaptor molecule STAM1. Septin-5 could not be validated via Western blotting due to methodological issues. Closer investigation of the validated proteins also pointed to an interesting role for membrane trafficking deficits mediated by prenatal stress. Our findings demonstrate that prenatal stress leads to altered hippocampal protein expression, implicating numerous molecular pathways that may provide new targets for psychotropic drug development.

Current diagnosis of schizophrenia relies exclusively on the potentially subjective interpretation of clinical symptoms and social functioning as more objective biological measurement and medical diagnostic tests are not presently available. The use of metabolomics in the discovery of disease biomarkers has grown in recent years. Metabolomic methods could aid in the discovery of diagnostic biomarkers of schizophrenia. This systematic review focuses on biofluid metabolites associated with schizophrenia. A systematic search of Web of Science and Ovid Medline databases was conducted and 63 studies investigating metabolite biomarkers of schizophrenia were included. A review of these studies revealed several potential metabolite signatures of schizophrenia including reduced levels of essential polyunsaturated fatty acids (EPUFAs), vitamin E and creatinine; and elevated levels of lipid peroxidation metabolites and glutamate. Further research is needed to validate these biomarkers and would benefit from large cohort studies and more homogeneous and well-defined subject groups. European Research Council Health Research Board

Background: The identification of biomarkers of transition from the at-risk mental state (ARMS) to psychotic disorder is important because early treatment of psychosis is associated with improved outcome. Increasing evidence points to an inflammatory contribution to psychosis. We questioned whether raised levels of plasma inflammatory markers predict transition from ARMS to psychotic disorder and whether any such predictors could be reduced by omega-3 (ω-3) polyunsaturated fatty acids (PUFAs). Methods: We measured the levels of 40 neuroinflammation biomarkers using a commercially available immunoassay kit. Firstly, we compared inflammatory markers in subjects in the ARMS who transitioned to psychotic disorder (n = 11) compared to subjects who did not (n = 28). Then we compared inflammatory markers in all subjects before and after ω-3 PUFA treatment (n = 40). Results: Our data provides preliminary evidence that elevations in the baseline plasma levels of the inflammatory marker IL12/IL23p40 are associated with transition from ARMS to psychotic disorder. IL12/IL23p40 levels did not change following 12 weeks administration of ω-3 PUFAs. These findings provide evidence that elevated plasma IL12/IL23p40 is a potential biomarker of increased risk for transition to psychotic disorder. Conclusion: Further studies are required to confirm and extend this finding. Our results do not provide support for the possibility that administration of ω-3 PUFAs act to reduced transition to psychotic disorder by reducing blood levels of IL12/IL23p40. Trial registration: ClinicalTrials.gov, a service of the U.S. National Institutes of Health, Identifier: NCT00396643, last updated December 20, 2007. Retrospectively registered.

A cortico-subcortico-cerebellar neural circuit has been postulated to be important in the pathophysiology of schizophrenia. This study investigated whether there are synaptic changes in the cerebellum to accompany its putative involvement in the disorder. We measured the expression of three synaptic proteins (synaptophysin, complexin I and complexin II) in the cerebellar cortex of 16 subjects with schizophrenia and 16 controls using in situ hybridisation histochemistry and immunoautoradiography. Complexin I and II are expressed predominantly by inhibitory and excitatory neurones respectively. In schizophrenia, synaptophysin mRNA was decreased, as was complexin II and its mRNA. Complexin I mRNA and protein levels were unaltered. Expression of the mRNAs in the rat cerebellum was unaffected by 2 weeks administration of antipsychotic drugs (haloperidol, chlorpromazine, risperidone, olanzapine or clozapine). We conclude that there is synaptic pathology in the cerebellum in schizophrenia. By disrupting neural circuits, the alterations may contribute to the cerebellar dysfunction thought to occur in the disorder.

Abnormalities of the anterior cingulate cortex have previously been described in schizophrenia, major depressive disorder and bipolar disorder. In this study 2-DE was performed followed by mass spectrometric sequencing to identify disease-specific protein changes within the anterior cingulate cortex in these psychiatric disorders. The 2-DE system comprised IPGs 4-7 and 6-9 in the first, IEF dimension and SDS-PAGE in the second dimension. Resultant protein spots were compared between control and disease groups. Statistical analysis indicated that 35 spots were differentially expressed in one or more groups. Proteins comprising 26 of these spots were identified by mass spectroscopy. These represented 19 distinct proteins; aconitate hydratase, malate dehydrogenase, fructose bisphosphate aldolase A, ATP synthase, succinyl CoA ketoacid transferase, carbonic anhydrase, alpha- and beta-tubulin, dihydropyrimidinase-related protein-1 and -2, neuronal protein 25, trypsin precursor, glutamate dehydrogenase, glutamine synthetase, sorcin, vacuolar ATPase, creatine kinase, albumin and guanine nucleotide binding protein beta subunit. All but three of these proteins have previously been associated with the major psychiatric disorders. These findings provide support for the view that cytoskeletal and mitochondrial dysfunction are important components of the neuropathology of the major psychiatric disorders.

O1: Assessing the protective effect of dexrazoxane against doxorubicin-induced toxicity in HL-1 cardiomyocytes

Background There is emerging evidence of an etiological overlap between a range of neurodevelopmental disorders, including schizophrenia and epilepsy. Here we investigate shared familial vulnerability to psychotic illness and epilepsy in a family-based study. Methods The study population consisted of parents and their children born in Helsinki between 1947 and 1990. The Finnish Hospital Discharge Register was used to determine psychiatric and neurological outcomes in adulthood for all offspring. Parental history of psychosis and epilepsy was determined by linking the Hospital Discharge Register and the Finnish Population Register. Results Our total sample comprised 9653 families and 23,404 offspring. Individuals with epilepsy had a 5.5-fold increase in the risk of having a broadly defined psychotic disorder, an almost 8.5-fold increase in the risk of having schizophrenia, and a 6.3-fold increase in the risk of having bipolar disorder. There was strong evidence of clustering of the association between epilepsy and psychosis within families. Individuals with a parental history of epilepsy had a 2-fold increase in the risk of developing psychosis, compared with individuals without a parental history of epilepsy. Individuals with a parental history of psychosis had, reciprocally, a 2.7-fold increase in the risk of having a diagnosis of generalized epilepsy, compared with individuals without a parental history of psychosis. Post hoc analyses showed that these associations were not driven by the comorbidity of epilepsy and psychosis in the parents. Conclusions These findings support recent evidence of overlapping etiological factors between epilepsy and schizophrenia, especially recent evidence of a genetic overlap between these disorders.

Introduction FGF-2 is important for stem cell proliferation, neocortical development and adult neuronal survival and growth. Reduced frontal cortical FGF-2 expression is described in major depression and is attenuated by antidepressants. We determined the distribution of hippocampal FGF-2 and its receptor (FGFR1) mRNA in post-mortem brains of people who suffered from major depression, bipolar disorder and schizophrenia and those of controls. Methods FGF-2 and FGFR1 mRNA were measured within hippocampal CA1, CA4 regions and the dentate gyrus (DG), using in situ hybridization. Within hippocampal regions, cellular staining was compared between diagnostic groups, using repeated measures analysis of variance. Results The density of FGF-2 mRNA+ cells in CA4 was reduced in depression compared to controls. The percentage of FGFR1 mRNA+ cells was higher in depression (CA1 and CA4) and schizophrenia (CA4) than in controls. FGFR1 mRNA expression was higher in depression than in the other groups in CA1, CA4 and DG. Overall FGF-2 mRNA expression was higher in DG than in CA1 and CA4. Conclusions We found raised measures of FGFR1 mRNA+ in major depression and, less so, in schizophrenia, along with reduced FGF-2 mRNA density in depression. Perturbations of FGF regulation could be relevant to the pathogenesis of both disorders as FGF-2 and FGFR1 are implicated in normal hippocampal synaptology, stem cell recruitment, and connectivity, and are modulated by corticosteroids.

Reductions in neuronal size and glial cell density have been described in the frontal cortex in major psychiatric disorders. In this investigation, we performed a cytoarchitectural assessment within the planum temporale (PT), an auditory association region located within the superior temporal gyrus, using two-dimensional (2D) measures of cell size and density and spatial point pattern analysis. In sections of the PT from subjects with schizophrenia, bipolar disorder, major depressive disorder and controls (15 subjects per group), the laminar distribution and size of all neurons and glial cell nuclei was recorded. Spatial point pattern investigation demonstrated reduced neuronal clustering in bipolar disorder (p=0.033) and schizophrenia (p=0.027) compared with controls. Statistical analyses comparing each of the patient groups with the control group failed to identify differences in neuronal density between groups. Neuronal size was reduced in cortical layer 3 (p=0.02) and glial cell density reduced in cortical layer 6 (p=0.05) in bipolar disorder relative to controls but these findings did not remain significant after adjusting for six layer-wise comparisons. We propose that alterations in cortical cytoarchitecture within this region are subtle and involve reduced clustering of neurons, which may be due to altered neuronal organisation within cortical mini-columns or within cortical layers.

Schizophrenia is associated with altered neural development. We assessed neurological soft signs (NSS) and dermatoglyphic anomalies (total a–b ridge count (TABRC) and total finger ridge count) in 15 pairs of twins concordant and discordant for schizophrenia. Within-pair differences in both NSS and TABRC scores were significantly greater in discordant compared to concordant monozygotic pairs. There was no significant difference in NSS and TABRC scores between subjects with schizophrenia and their co-twins without the illness. However, monozygotic discordant twins with schizophrenia had higher ABRCs on their right hands compared to their co-twins without the illness. These findings suggest that an unidentified environmental event acting between weeks 6 and 15 of gestation affects the development of monozygotic twins who go on to develop schizophrenia but does not have a corresponding effect on their co-twins who do not develop the illness. The effect of such an event on dermatoglyphic profiles appears lateralised to the right hand in affected twins.

Prenatal iron deficiency (pID) has been described to increase the risk for neurodevelopmental disorders such as autism and schizophrenia; however, the precise molecular mechanisms are still unknown. Here, we utilized high throughput mass spectrometry to examine the proteomic effects of pID in adulthood on the rat frontal cortex area (FCA). In addition, the FCA proteome was examined in adulthood following risperidone treatment in adolescence to see if these effects could be prevented. We identified 1501 proteins of which 100 were significantly differentially expressed in the FCA at post-natal day 90. Pathway Analysis of proteins affected by pID revealed changes in metabolic processes, including the tricyclic acid cycle, mitochondrial dysfunction, and P13K/Akt signaling. Interestingly, most of these protein changes were not present in the adult pID offspring who received risperidone in adolescence. Considering the link between prenatal iron deficiency and several neurodevelopmental disorders such as autism and schizophrenia these presented results bring new perspectives to understand the role of iron in metabolic pathways and provide novel biomarkers for future studies of prenatal iron deficiency. Fil: Farrelly, Lorna. Beaumont Hospital; Irlanda Fil: Rosato Siri, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Föcking, Melanie. Beaumont Hospital; Irlanda Fil: Codagnone, Martín Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Reines, Analia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Dicker, Patrick. College of Surgeons in Ireland; Irlanda Fil: Wynne, Kieran. University College Dublin; Irlanda Fil: Farrell, Michael. Beaumont Hospital; Irlanda Fil: Cannon, Mary. Beaumont Hospital; Irlanda Fil: Cagney, Gerard. University College Dublin; Irlanda Fil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Cotter, David R.. Beaumont Hospital; Irlanda

Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately one billion individuals worldwide. The mechanisms driving progressive steatohepatitis remain incompletely defined. Here we use a murine model of mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2)-deficiency (using anti-sense oligonucleotides) to demonstrate a critical role for ketogenesis in prevention of diet-induced steatohepatitis. Adult-onset loss of HMGCS2 caused mild hyperglycemia and increased hepatic gluconeogenesis from pyruvate in chow-fed mice. High-fat diet (HFD) feeding of ketogenesis insufficient mice caused extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic tricarboxylic acid (TCA) cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to fatty acid-induced sequestration of coenzyme A (CoASH). CoASH precursor supplementation (pantothenic acid and cysteine) normalized TCA intermediates and gluconeogenesis in ketogenesis insufficient livers. These find...

Omega-3 fatty acid (n-3 FA) deficiency is an environmental risk factor for schizophrenia, yet characterization of the consequences of deficiency at the protein level in the brain is limited. We aimed to identify the protein pathways disrupted as a consequence of chronic n-3 deficiency in the hippocampus of mice. Fatty acid analysis of the hippocampus following chronic dietary deficiency revealed a 3-fold decrease (p < 0.001) in n-3 FA levels. Label free LC-MS/MS analysis identified and profiled 1008 proteins, of which 114 were observed to be differentially expressed between n-3 deficient and control groups (n = 8 per group). The cellular processes that were most implicated were neuritogenesis, endocytosis, and exocytosis, while specific protein pathways that were most significantly dysregulated were mitochondrial dysfunction and clathrin mediated endocytosis (CME). In order to characterize whether these processes and pathways are ones influenced by antipsychotic medication, we used LC-MS/MS to test the differential expression of these 114 proteins in the hippocampus of mice chronically treated with the antipsychotic agent haloperidol. We observed 23 of the 114 proteins to be differentially expressed, 17 of which were altered in the opposite direction to that observed following n-3 deficiency. Overall, our findings point to disturbed synaptic function, neuritogenesis, and mitochondrial function as a consequence of dietary deficiency in n-3 FA. This study greatly aids our understanding of the molecular mechanism by which n-3 deficiency impairs normal brain function, and provides clues as to how n-3 FA exert their therapeutic effect in early psychosis.

Background Temporal lobe epilepsy is associated with a significant risk of psychosis but there are only limited studies investigating the underlying neurobiology. Aims To characterise neuroanatomical changes in temporal lobe epilepsy and comorbid psychosis. Method The study population comprised all individuals with temporal lobe epilepsy on the epilepsy database at the National Centre for Epilepsy and Epilepsy Neurosurgery in Ireland (Beaumont Hospital) between 2002 and 2006. Ten people with temporal lobe epilepsy with psychosis were matched for age, gender, handedness, epilepsy duration, seizure laterality, severity of epilepsy and anti-epileptic medication with ten comparison participants with temporal lobe epilepsy only. Participants received a magnetic resonance imaging scan and voxel-based morphometry analyses were applied to grey and white matter anatomy. Results Significant grey matter reduction was found bilaterally in those with temporal lobe epilepsy with psychosis in the temporal lobes in the inferior, middle and superior temporal gyri and fusiform gyri, and unilaterally in the left parahippocampal gyrus and hippocampus. Significant extra-temporal grey matter reduction was found bilaterally in the insula, cerebellum, caudate nuclei and in the right cingulum and left inferior parietal lobule. Significant white matter reduction in those with temporal lobe epilepsy with psychosis was found bilaterally in the hippocampus, parahippocampal/fusiform gyri, middle/inferior temporal gyri, cingulum, corpus callosum, posterior thalamic radiation, anterior limb of internal capsule and white matter fibres from the caudate nuclei, and unilaterally in the left lingual gyrus and right midbrain and superior temporal gyrus. Conclusions Significant grey and white matter deficits occur in temporal lobe epilepsy with psychosis. These encompass the medial temporal lobe structures but also extend to lateral temporal and extra-temporal regions. Some of these deficits overlap with those found in schizophrenia.

Cannabis use confers a two-fold increase in the risk for psychosis, with adolescent use conferring even greater risk. A high–low activity catechol-O-methyltransferase (COMT) polymorphism may modulate the effects of adolescent Δ-9-tetrahydrocannabinol (THC) exposure on the risk for adult psychosis. Mice with knockout of the COMT gene were treated chronically with THC (4.0 and 8.0 mg/kg over 20 days) during either adolescence (postnatal days (PDs) 32–52) or adulthood (PDs 70–90). The effects of THC exposure were then assessed in adulthood across behavioral phenotypes relevant for psychosis: exploratory activity, spatial working memory (spontaneous and delayed alternation), object recognition memory, social interaction (sociability and social novelty preference), and anxiety (elevated plus maze). Adolescent THC administration induced a larger increase in exploratory activity, greater impairment in spatial working memory, and a stronger anti-anxiety effect in COMT knockouts than in wild types, primarily among males. No such effects of selective adolescent THC administration were evident for other behaviors. Both object recognition memory and social novelty preference were disrupted by either adolescent or adult THC administration, independent of genotype. The COMT genotype exerts specific modulation of responsivity to chronic THC administration during adolescence in terms of exploratory activity, spatial working memory, and anxiety. These findings illuminate the interaction between genes and adverse environmental exposures over a particular stage of development in the expression of the psychosis phenotype.

The mechanisms underlying white matter changes in psychiatric disease are not known. We aimed to characterise the differential protein expression in deep white matter from the dorsolateral prefrontal cortex from 35 schizophrenia, 35 bipolar disorder, and 35 control subjects, from the Stanley Array Collection. We used 2-D DIGE to profile for protein expression changes in the brain. We found 70 protein spots to be significantly differentially expressed between disease and control subjects (ANCOVA, p

The dorsolateral prefrontal cortex (dlpfc) is strongly implicated in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BPD) and, within this region, abnormalities in glutamatergic neurotransmission and synaptic function have been described. Proteins associated with these functions are enriched in membrane microdomains (MM). In the current study, we used two complementary proteomic methods, two-dimensional difference gel electrophoresis and one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis followed by reverse phase-liquid chromatography-tandem mass spectrometry (RP-LC-MS/MS) (gel separation liquid chromatography-tandem mass spectrometry (GeLC-MS/MS)) to assess protein expression in MM in pooled samples of dlpfc from SCZ, BPD and control cases (n=10 per group) from the Stanley Foundation Brain series. We identified 16 proteins altered in one/both disorders using proteomic methods. We selected three proteins with roles in synaptic function (syntaxin-binding protein 1 (STXBP1), brain abundant membrane-attached signal protein 1 (BASP1) and limbic system-associated membrane protein (LAMP)) for validation by western blotting. This revealed significantly increased expression of these proteins in SCZ (STXBP1 (24% difference; P

There are high rates of psychiatric morbidity associated with refractory epilepsy. It is unclear whether seizure frequency or comorbid psychiatric illness impacts more upon patients’ quality of life in epilepsy. The objective of this study was to establish which of these two factors impacted more upon patients. Patients with medically refractory epilepsy who were admitted to the National Neurological Centre in Beaumont Hospital were recruited to the study. Structural Clinical Interview for DSM IV (Axis I) (SCID I) and SCID II (Axis II) were the objective measures and HADS, and QOLIE-89 were the subjective measures utilized. A total of 138 patients had SCIDs conducted over the four year study. 75 patients (54.4%) had an Axis I disorder. Of these 30 patients (21.7%) had a mood disorder, 18 patients (13%) had an anxiety disorder and 49 patients (35.5%) were diagnosed with a psychotic disorder. There was no relationship between patient seizure frequency and HADS (p=0.94) or QOLIE-89 (p=0.93) scores. Patients having a high number of seizures were not more likely to have a SCID Axis I diagnosis than patients with a low number of seizures (p=0.246). Patients with a mood disorder were more likely to have a lower QOLIE-89 score than patients without a mood disorder (p=0.0001). Patients with medically refractory epilepsy have high rates of psychopathology. Seizure frequency is not correlated with the presence, severity of psychiatric symptoms or quality of life. The presence of a psychiatric disorder and its severity is strongly correlated with quality of life.

The orbitofrontal cortex is involved in the monitoring of reward and in judgement. Lesion studies and functional neuroimaging investigations implicate this region in affective disorders, and altered neuronal and glial cell composition have been observed in this region in subjects with major depressive disorder (MDD).Stereologically based investigation of caudal orbitofrontal cortex (cOFC), in 60 postmortem brains from four groups of 14 subjects each with bipolar disorder (BPD), schizophrenia and MDD.Glial cell and neuronal size and density were examined in all subjects using stereological probes such as the nucleator and the optical disector.We found statistical evidence for a neuronal size reduction in BPD in layer 1 (21%, p=0.007) and a trend for a reduction in layer 5 (20%, p=0.05). There was a significant interaction effect of brain hemisphere and group on neuronal size in layer 3 (p=0.001), with evidence for reduced layer 3 neuronal sizes in MDD (30%, p0.001). We found no evidence for group differences in glial cell size nor for differences in glial or neuronal density.These findings provide preliminary evidence that neuronal size reduction in cOFC is a component of the pathology of BPD. Overall, the data implicate this cortical region in affective disorders, but provide no evidence for neuronal or glial pathology in this region in schizophrenia.