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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.

Objective To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic mental disorders in adulthood. Methods Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, longitudinal cohort studies in the English language examining child or adolescent exposure to trauma, and adult-diagnosed depression, anxiety, psychotic disorder or bipolar disorder. A total of 23 manuscripts were retained. Results Results revealed a significant association between the following childhood exposures and adult mental disorder: bullying (victimhood, perpetration and frequency); emotional abuse; physical neglect; parental loss; and general maltreatment (unspecified and/or multiple trauma exposure). There was some evidence of a dose-response relationship with those exposed to multiple forms of maltreatment having more than three times the odds of developing a mental disorder (Odds ratio = 3.11, 95% CI = 1.36-7.14). There was no significant association found between physical or sexual abuse and adult mental disorder; however, this is likely an artefact of how these adversities were assessed. Conclusion There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for later mental illness, and an important period in which to focus intervention strategies.

Previous systematic reviews and meta-analyses of cross-sectional data assessing the effect of cannabis on cognitive functioning and intelligence show inconsistent results. We hypothesized that frequent and dependent cannabis use in youth would be associated with Intelligence Quotient (IQ) decline. This study is a systematic review and meta-analysis. We searched Embase, PubMed and PsychInfo from inception to 24 January 2020. We included studies with non-treatment seeking samples and pre- and post-exposure measures of IQ. We requested data from authors if summary data was not available from published work. We preregistered our review with PROSPERO (ID no. CRD42019125624). We found seven cohort studies including 808 cases and 5308 controls. We found a significant effect for the association between frequent or dependent cannabis use in youth and IQ change, Cohen's d = −0.132 (95% CI −0.198 to −0.066) p < 0.001. Statistical heterogeneity between studies was also low at I2 = 0.2%. Study quality was moderate to high. This translates to an average decline of approximately 2 IQ points following exposure to cannabis in youth. Future studies should have longer periods of follow up to assess the magnitude of developmental impact.

Objective This study aims to examine the associations between prenatal exposure to maternal smoking, birth weight and persistent offspring psychiatric symptoms. Additionally, we aim to examine whether the relationship between prenatal maternal smoking and persistent offspring psychiatric symptoms is mediated by offspring birth weight. Methods This study used the Growing Up in Ireland (GUI) longitudinal cohort. The GUI is a nationally representative longitudinal study of children which consisted of three data collection waves, at ages 9, 13, and 17 years. Logistic regression analysis was used to examine associations between prenatal tobacco exposure, and offspring psychiatric symptoms. Linear regression was used to examine associations between prenatal tobacco exposure and offspring birth weight. We conducted a mediation analysis examining potential etiological pathways linking maternal smoking during pregnancy, offspring birth weight, and later offspring psychiatric symptoms. All analyses were adjusted for confounders including household income, maternal level of education, and family psychiatric history. Additionally, examination of birth weight and subsequent psychiatric symptoms also was controlled for prematurity. Results We found that the association between prenatal tobacco exposure and later psychiatric symptoms is mediated by birth weight. Conclusions This work provides further evidence that maternal smoking during pregnancy is an important modifiable lifestyle factor that has an impact not just on the physical health of offspring but also their mental wellbeing. Supporting women with structured smoking cessation programs at the earliest stages of pregnancy should be a public health priority.

Background. Abnormal body mass index (BMI) has been associated with development of psychopathology. This association in children is well documented, for both overweight and underweight children. However, the association between change in BMI and the development of psychopathology has been less investigated. Aim. To investigate the association between change in BMI between childhood and adolescence and psychopathology in adolescence. Methods. Data from the Growing Up in Ireland cohort were used. We investigated the ’98 cohort (also known as the child cohort) at age 9/13. BMI, defined using internationally recognised definitions as underweight, healthy or overweight, was used as the exposure, and abnormal Strength and Difficulties Questionnaire scores were used as the outcome. Logistic regression was undertaken for the analysis. All analyses were adjusted for confounders. Results. A change to overweight from healthy BMI was significantly associated with increased risk of psychopathology (adjusted OR 1.66; 95% CI 1.19–2.32). Both change from underweight to healthy (adjusted OR 0.12; 95% CI 0.03–0.43) or from overweight to healthy (adjusted OR 0.47; 95% CI 0.79–0.8) was associated with a significantly reduced risk of developing psychopathology. Discussion. As a child’s BMI returns to within the healthy range, their risk of adolescent psychopathology is reduced. Interventions to restore healthy BMI, in both underweight and overweight, children may reduce their risk of adolescent psychopathology.

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.

Objective To systematically review evidence for an association between parental death in childhood, and the subsequent development of an anxiety, affective or psychotic disorder. Methods Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, cohort studies in the English language. Meta-analyses were performed for studies reporting hazard ratios, incidence rate ratios and odds ratios. Two studies reported risk ratios, and these were included in an overall pool of odds, risk and incidence rate ratios. Sensitivity analyses were performed (removal of one study at a time) for all meta-analyses, and study quality assessed using the Newcastle-Ottawa Scale. Results Fifteen studies were retained, and where required, data were averaged in advance of pooling. Significant results were observed in studies reporting hazard ratios (k = 4, 1.48 [95% CI = 1.32-1.66]), incidence rate ratios (k = 3, 1.37 [95% CI = 1.01-1.85]), but not odds ratios (k = 4, 0.87 [95% CI = 0.72, 1.05]). However, the overall pooled effect (using odds, incidence rate and risk ratios) was statistically significant (k = 9, 1.22 [95% CI = 1.03-1.44]). Conclusion Overall, the evidence suggests that there is a positive association between the death of a parent before age 18, and the subsequent development of an anxiety, affective or psychotic disorder. The lack of a significant pooled effect in studies reporting results as odds ratios is likely an artefact of study design. Limitations Data were clustered in four countries making generalizability uncertain. Studies adjusted for a variety of possible confounders, and follow-up after death varied considerably.

Background Exposure to childhood adversity has been linked to long-term negative mental health consequences in adulthood. Purpose This review examined the association between exposure to the death of a family member (i.e., parent or sibling) during childhood or adolescence and the subsequent diagnosis of a substance use disorder. Methods Electronic databases (Scopus, Medline (for Ovid), EMBASE, and PsychINFO) were searched for cohort and case-control studies in the English language. Studies were retained if it was demonstrable that exposure to death occurred before age 18, and that disorder was diagnosed subsequently. Sensitivity analyses were performed for the meta-analysis, and study quality assessed using the Newcastle-Ottawa Scale. Results Nine studies, seven cohort and two case-control, were retained. Due to differential metrics (hazard ratios [HRs] versus odds/risk ratios [ORs/RRs]), only one meta-analysis was possible. Individuals experiencing familial death had 1.42 (95% CI = 0.96, 2.09) times the odds of developing a substance use disorder compared to those non-exposed. Where there was a statistically significant effect in other studies, these were mostly studies using National Registers (1.4 ≤ HR ≤ 2.51). Limitations Meta-analysis options were limited by the variety of study designs. Conclusions Evidence for a significant association between familial death and subsequent disorder appears to be an artefact of the study design. Implications of key findings. Further studies are required to better understand and estimate the association between familial death and substance use disorders. Registration and funding. The review was pre-registered (PROSPERO Reg No: CRD42020192892) and funded by the Irish Research Council (COALESCE/2019/61).

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 There is growing concern around youth mental health. A population health approach to improve mental health must address, among other issues, economic insecurity, access to housing and education, harm reduction from substance use. As a universal public health intervention, increasing physical activity at a population level may have an important role in our approach. The aim of this study was to examine the longitudinal association between physical activity patterns between childhood and early adolescence and emotional-behavioural difficulties in later adolescence. METHODS This study was based on data from the '98 Child cohort of the Growing Up in Ireland Study. Participants were categorized according to physical activity levels at ages 9 and 13. Emotional-behavioural difficulties at age 17 were measured using the parent-reported Strengths and Difficulties Questionnaire. Logistic regression was used to examine the association between physical activity and emotional-behavioural outcomes. RESULTS Among 4618 participants included in the regression model, those categorized as Inactive (n=1607) or Reducer (n=1662) were more than twice as likely to have emotional-behavioural difficulties at age 17 compared with those who were Active [adjusted odds ratio (AOR) 2.1, 95% CI 1.46-3.01, P

Over the past twodecades, a growing body of literature has assisted in reshaping the perception of psychotic phenomena and their meaning within psychiatry. This shift in view is particularly owing to epidemiological research, which has steered the focus away from phenomena suffered by those with debilitating psychiatric conditions, to what is now seen as an extension of “normal” experience evident within the general population, namely psychotic-like experiences (PLEs). For most, PLEs are transient and relate to difficulties coping with current life adversity. For a minority (20%), PLEs will persist, and persistence appears to accentuate the “risk” of comorbid/subsequent psychiatric disorders and psychosocial dysfunction. PLEs seem to emerge from the interaction between genetic predisposition and certain environmental factors particularly exposure to trauma, a poor social environment, and cannabis use. While the prevalence and relevance of PLEs are increasingly understood, several questions remain: Which PLEs are pathological and/or persist? Do persistant PLEs require intervention? Finally, given the prevalence of PLEs, it is important to disseminate existing findings regarding their meaning? Guiding this narrative will hopefully cause shifts in public opinion regarding psychosis.

BackgroundPsychotic experiences (PEs) are reported by a significant minority of adolescents and are associated with the development of psychiatric disorders. The aims of this study were to examine associations between PEs and a range of factors including psychopathology, adversity and lifestyle, and to investigate mediating effects of coping style and parental support on associations between adversity and PEs in a general population adolescent sample.MethodCross-sectional data were drawn from the Irish centre of the Saving and Empowering Young Lives in Europe study. Students completed a self-report questionnaire and 973 adolescents, of whom 522 (53.6%) were boys, participated. PEs were assessed using the 7-item Adolescent Psychotic Symptom Screener.ResultsOf the total sample, 81 (8.7%) of the sample were found to be at risk of PEs. In multivariate analysis, associations were found between PEs and number of adverse events reported (OR 4.48, CI 1.41–14.25; p < 0.011), maladaptive/pathological internet use (OR 2.70, CI 1.30–5.58; p = 0.007), alcohol intoxication (OR 2.12, CI 1.10–4.12; p = 0.025) and anxiety symptoms (OR 4.03, CI 1.57–10.33; p = 0.004). There were small mediating effects of parental supervision, parental support and maladaptive coping on associations between adversity and PEs.ConclusionWe have identified potential risk factors for PEs from multiple domains including adversity, mental health and lifestyle factors. The mediating effect of parental support on associations between adversity and PEs suggests that poor family relationships may account for some of this mechanism. These findings can inform the development of interventions for adolescents at risk.

Aims: Smaller hippocampal volumes are among the most consistently reported neuroimaging findings in schizophrenia. However, little is known about hippocampal volumes in people who report psychotic experiences. This study investigated differences in hippocampal volume between young people without formal diagnoses who report psychotic experiences (PEs) and those who do not report such experiences. This study also investigated if any differences persisted over two years. Methods: A nested case-control study of 25 adolescents (mean age 13.5 years) with reported PEs and 25 matched controls (mean age 13.36 years) without PEs were drawn from a sample of 100 local schoolchildren. High-resolution T1-weighted anatomical imaging and subsequent automated cortical segmentation (Freesurfer 6.0) was undertaken to determine total hippocampal volumes. Comprehensive semi-structured clinical interviews were also performed including information on PEs, mental diagnoses and early life stress (bullying). Participants were invited for a second scan at two years. Results: 19 adolescents with PEs and 19 controls completed both scans. Hippocampal volumes were bilaterally lower in the PE group compared to the controls with moderate effects sizes both at baseline [left hippocampus p = 0.024 d = 0.736, right hippocampus p = 0.018, d = 0.738] and at 2 year follow up [left hippocampus p = 0.027 d = 0.702, right = 0.048 d = 0.659] throughout. These differences survived adjustment for co-morbid mental disorders and early life stress. Conclusions: Psychotic experiences are associated with total hippocampal volume loss in young people and this volume loss appears to be independent of possible confounders such as co-morbid disorders and early life stress.

Photon upconversion is the generation of high energy output photons from low energy input photons and has potential biomedical and solar energy applications. Recently, self-assembled materials have emerged as a platform to achieve upconversion via the triplet–triplet annihilation (TTA) mechanism. A prerequisite for TTA upconversion in a condensed phase is efficient triplet exciton migration through the material. In this regard, self-assembled materials (which include metal–organic frameworks (MOFs), covalent organic frameworks (COFs) and gels) contain non-photoactive structural elements which organise the spatial relationship between chromophores within the material, to allow systematic control over the triplet energy migration and upconversion efficiency to be made. In this review, we summarise recent results in this field, including the influence of chromophore spacing on upconversion vs. excimer formation, and the influence of particle morphology on threshold values. This is a promising area of research, but we conclude that a wider range of sensitiser-annihilator pairs are needed to expand the applicability of these materials more greatly. We hope that this review serves as a useful introductory text for those wishing to combine photon upconversion with the principles of self-assembly.

Background Cannabis use in adolescence is a known risk factor for developing schizophrenia. Decline in intellectual functioning is a well-studied phenomenon of schizophrenia. Schizophrenia in its first classification was conceptualized as a dementia - ‘Dementia Praecox’ indicating a dominance of effect of cognitive symptoms on functioning at that time. First episode psychosis patients with histories of cannabis use compared to those without cannabis use have superior cognitive functioning suggesting different disease phenotypes. Our aim was to investigate whether cannabis had an effect on full scale IQ in general population samples to further inform understanding of this disease pathway. Methods We developed a search strategy through an iterative approach with a qualified information specialist. We searched three databases: Medline, Embase and PsychInfo. We included conference abstracts and full text publications in English. We contacted authors for additional information in cases where an effect size was not calculable. We included longitudinal studies of non-help-seeking young people in the community with a pre-drug exposure standardized measure of IQ prior to the age of 18 and a comparable measure at subsequent follow up. We defined the case group as individuals with a history of heavy cannabis use (more than 25 lifetime uses, at least weekly use for 6 months and/or meeting criteria for a cannabis use disorder) and the control group as similar young people who had no or very minimal experimental exposure to cannabis ( Results We identified 7 cohort studies detailed in 6 reports including over 650 subjects and 5600 controls. Study designs included twin cohorts, representative cluster sampled community cohorts and birth cohort studies. Range of follow up was between 2 and 23 years. All studies showed relative decline in IQ of which two were statistically significant. Our findings show that cannabis use in youth is associated with modest IQ differences that equate to approximately to a 2-point decrease in young cannabis users. Studies examining twin pairs showed that twins discordant for cannabis use did not have divergent cognitive trajectories, however these analyses were relatively underpowered to find an effect. Discussion Our findings demonstrate the harmful effects of cannabis use on brain development in young people. These findings are of public health importance and provide further evidence for the detrimental effects of early cannabis use on mental health and cognition.

BACKGROUND Psychotic experiences (PEs) are common in childhood and have been associated with concurrent mental disorder and poorer global functioning. Little is known about the effects of childhood PEs on future functioning. We investigated the effects of childhood PEs on global functioning from childhood into early adulthood. METHOD Fifty-six participants from a community sample completed all three waves of the Adolescent Brain Development study (T1x¯ Age: 11.69, T2x¯ Age: 15.80 T3x¯Age: 18.80). At each phase, participants completed a clinical interview assessing for PEs, mental disorder and global function. Repeated measures models, adjusted for mental disorder and gender, were used to compare current (C-GAF) and most severe past (MSP-GAF) functioning in participants who had reported PEs in childhood and controls. RESULTS Participants with a history of PEs had significantly poorer C-GAF (P

Around 1 in 5 children under 13 years old experience sub-clinical psychotic experiences (PEs) like hallucinations and delusions. While PEs in childhood are a significant risk factor for adult psychotic disorders, the majority of those experiencing childhood PEs do not develop a psychotic disorder. Individual differences in regional brain maturation rates may be responsible for this age-related and often transient emergence of PEs. Fronto-temporal association tracts undergo extensive maturation and myelination throughout childhood and adolescence, thus we focus on individual differences in one such tract, the arcuate fasciculus. A normative population-based sample of children (aged 11–13) attended a clinical interview and MRI (n = 100), 25 of whom were identified as reporting strong PEs. This group had reduced mean and radial diffusivity in the arcuate fasciculus compared with a group of matched controls (n = 25) who reported no PEs. The group difference was greater in the left hemisphere than the right. Mediation analyses showed that this group difference was driven predominantly by perceptual disturbances and an along-tract analysis showed that the group difference was greatest approximately halfway between the frontal and temporal termination points of the tract (adjacent to the left lateral ventricle). This study is the first to investigate links between arcuate fasciculus diffusivity and psychotic experiences in a population sample of children.

A recent and growing body of evidence on youngpeople’s mental health has pointed to the need foran international response to the increasing and con-cerning rates of mental ill-health among youngpeople.1,2The periods of adolescence and emergingadulthood3are considered the peak periods for theonset of mental ill-health4with 75% of all adult diag-noses of mental ill-health having had an onsetbefore the age of 25 years.5In an era when the physi-cal health of young people has never been better,6their psychological and mental health has neverbeen worse.7This leaves young people vulnerable todeveloping potentially intractable and enduringmental health difficulties with the inevitable per-sonal, familial, social and vocational consequencesthat accompany the experience of mentalill-health

Background: The behavioral effect of frontal lesions may be influenced by confounding factors such as aetiology, age and cogntive reserve. Yet no studies have investigated their effects on patients with focal lesions. Objective: Is the grouping of patients with frontal lesions caused by stroke or tumours methodologically appropriate; does age affect cognitive performance, can cognitive reserve protect against cognitive impairment? Patients and Methods/Material and Methods: Cognitive performance was compared across a large sample of frontal patients with stroke, high or low grade tumour, or meningioma. The effect of age, education and NART IQ on the cognitive performance of patients with focal lesions was investigated. Assessments of lesion location, volume, global brain atrophy and non-specific white matter changes were undertaken. Results: No significant difference in cognitive performance between the different aetiologies was found. Age of frontal patients significantly predicted the magnitude of their impairment on executive but not on nominal or perceptual tasks. In contrast, non frontal patients' age did not predict the magnitude of their impairments. After accounting for chronicity, age and severity of frontal lesion, NART IQ contributed to performance on the executive and naming tests whilst education contributed to fluid intelligence. The interactions between lesion severity and our CR proxies were not significant. Conclusion: The grouping of patients with frontal lesions caused by different aetiologies is a justified methodology that helps to further the understanding of frontal executive functions. The frontal cortex plays a critical role in aging to counteract cognitive and neuronal decline and when lesioned greater cognitive reserve does not better withstand neuropathology.

Background Superior Longitudinal Fasciculus (SLF) differences are consistently reported in psychotic disorders. The SLF is a complex large bundle of association white matter fibers that bidirectionally connect caudal, temporal cortex and inferior parietal cortex to locations in the frontal lobe. Advances in tractography methodologies detail four discrete subdivisions (SLF I, II, III and IV, more often referred to as the arcuate fasciculus (AF)). Greater specificity of the SLF subdivisions and associated cognitive networks may clarify the mechanisms of divergent tract developmental and functional aspects associated with psychotic experience symptomology in population based samples of adolescents within the extended psychosis continuum Methods A case-control sample of 25 adolescents reporting psychotic experiences versus 25 controls (mean age 13.7 years). We employed High Angular Resolution Diffusion Imaging (HARDI) based data with constrained spherical deconvolution (CSD) based fibre tractography to delineate the discrete subdivisions of the SLF including the arcuate fasciculous. Following tract identification, standard diffusion metrics, (fractional anisotrophy (FA), and Diffusivity measures MD, AD and RD), were assessed. A secondary supportive “along-tract” analysis to ascertain more subtle patterns of variation of tract integrity over the tract length was applied. White matter nodal analysis exploring the structural connectivity was applied to investigate additional functional networks recruited by and interconnected via the SFL. We investigate the ability of tractography of the SLF subdivisions and nodal analysis to identify possible differences between adolescents experiencing subclinical psychotic like experiences and those who don’t. Results Our results agree with recent studies of the SLF I and AF (Fernandes-Miranda et al 2015) revealing a pattern of asymmetry of these tracts with more extensive tract bundles being consistently identified in the left hemisphere compared to the right. Along-tract analysis revealed subtle patterns of change in discrete subdivisions of the SLF while nodal analysis shows promise in its ability to define precise organisational networks Discussion Delineating the SLF subdivisions may clarify potential developmental trajectories between frontal and parieto-temporal speech-related areas contributing to the pathogenesis of psychotic like experiences. These results reveal the presence of aberrant structural connectivity in young adolescents with psychotic experiences.

Background Psychotic experiences (PEs) are relatively common in childhood and early adolescence, being present in 17% of children aged 9 to 12 (Kelleher et al., 2012). Research suggests that young people who experience PEs are more vulnerable to psychopathology later in life, despite PEs being transient in 78.7% of cases (Zammit et al., 2013). While childhood PEs are associated with poorer functioning (Kelleher et al., 2015), it has not yet been established whether the impact of PEs on functioning persists into later life. Methods 52 participants from a prospective cohort study (retention rate: 60.4%) of Irish young people were included on the basis that they had completed a clinical interview at all three data-collection time points (T1 mean age: 11.69; T2: 15.80; T3 18.80). Following each interview, participants were scored on the Global Assessment of Functioning (GAF) scale, and given a Current (C-GAF) score and a Most Severe Past (MSP-GAF) score. Fixed-effects repeated-measures models were used to compare the scores of those with a history of PEs at T1 (n=18) to those without (n=34), accounting for age, gender, and childhood functioning. Secondary analyses investigated whether differences in functioning were evident in those who reported transient PEs (only at T1; n=12). Results Overall, participants who had reported childhood PEs (T1) received significantly lower C-GAF scores (F = 31.553, p < .001) and MSP-GAF scores (F = 79.377, p < .001) than those without PEs. Simple effects analysis indicated that deficits in the PE group were evident at each time point for both C-GAF scores (T1: p = .001; T2: p

Background Neurocognitive impairments are a prevalent aspect of psychosis which, on average, begin in early adolescents, with particular impairment apparent in speed of processing and nonverbal working memory in early stages (Kelleher et al., 2012). It is important to understand the impact of cognitive impairment on functional ability, particularly in early stages of illness which may assist in the development of targeted therapeutic strategies. Methods A population sample of 212 school going adolescents aged 11–13 years partook in the study, which included community-based adolescents who report experiencing psychotic symptoms but who were not clinically diagnosed. Psychotic symptoms were assessed using the psychosis section of the Schedule for Affective Disorders and Schizophrenia. Six cognitive domains were assessed using the MATRICS consensus cognitive battery. Functioning was assessed using the Children’s Global Assessment Scale. Six separate linear regression analyses were performed to test if each cognitive domain of the MATRICS battery predicted functioning. Results In the entire sample (including those who experienced psychotic experiences and those who did not) (n=211), speed of processing significantly explained 8% of the variance in functioning (F(1, 76) = 6.61, p = .0012, R-squared = 0.08.), (Beta = 0.39, p = 0.012). When the sample was subdivided into those who ever experienced auditory hallucinations (AH) (n=62) versus those that did not (n=149), speed of processing significantly predicted 18% of the variance in functioning in the group experiencing AHs (F(2, 33) = 3.82, p =0.032, R-squared = 0.18), (Beta = 0.43, p = 0.06). However, no effect was found in the group without AVs (F(1,40) = 1.19, p =0.28). No other cognitive domain predicted functioning. Discussion Speed of processing appears to be a core cognitive deficit in psychosis which impacts on functioning in young adolescents particularly in those experiencing psychotic symptoms such as auditory hallucinations, however the variance predicted by processing speed is relatively low. This research highlights the potential of speed of processing as a possible viable target for early intervention in psychotic disorders.

BackgroundCognitive and motor dysfunction are hallmark features of the psychosis continuum, and have been detected during late childhood and adolescence in youth who report psychotic experiences (PE). However, previous investigations have not explored infancy and early childhood development. It remains unclear whether such deficits emerge much earlier in life, and whether they are associated with psychotic, specifically hallucinatory, experiences (HE).MethodsThis study included data from Gen2 participants of The Raine Study (n = 1101), a population-based longitudinal cohort study in Western Australia. Five areas of childhood development comprising: communication; fine motor; gross motor; adaptive (problem-solving); and personal-social skills, were assessed serially at ages 1, 2 and 3 years. Information on HE, depression and anxiety at ages 10, 14 and 17 years was obtained. HE were further subdivided into those with transient or recurrent experiences. Mixed effects logistic regression models and cumulative risk analyses based on multiple domain delays were performed.ResultsEarly poorer development in multiple areas was noted from ages 1, 2 and 3 years among youth who reported HE. Early developmental delays significantly increased the risk for later HE. This association was particularly marked in the recurrent HE group, with over 40% having early developmental delays in multiple domains. There was no significant association between early childhood development and later anxiety/depression apart from lower gross motor scores at age 3.ConclusionsThe findings suggest that early pan-developmental deficits are associated with later HE, with the effect strongest for young people who report recurrent HE throughout childhood and adolescence.

BackgroundPsychotic experiences (PE) are highly prevalent in childhood and are known to be associated with co-morbid mental health disorders and functional difficulties in adolescence. However, little is known about the long-term outcomes of young people who report PE.MethodsAs part of the Adolescent Brain Development Study, 211 young people were recruited in childhood (mean age 11.7 years) and underwent detailed clinical interviews, with 25% reporting PE. A 10 year follow-up study was completed and 103 participants returned (mean age 20.9 years). Structured clinical interviews for DSM-5 (SCID-5) and interviewer-rated assessments of functioning were conducted. A detailed neuropsychological battery was also administered. Analyses investigated group differences between those who had ever reported PE and controls in early adulthood.ResultsThe PE group was at a significantly higher risk of meeting DSM-5 criteria for a current (OR 4.08, CI 1.16–14.29, p = 0.03) and lifetime psychiatric disorder (OR 3.27, CI 1.43–7.47, p = 0.005). They were also at a significantly higher risk of multi-morbid lifetime psychiatric disorders. Significantly lower scores on current social and global functioning measures were observed for the PE group. Overall, there were no differences in neuropsychological performance between groups apart from significantly lower scores on the Stroop Word task and the Purdue Pegboard task for the PE group.ConclusionsOur findings suggest that reports of PE are associated with poorer mental health and functional outcomes in early adulthood, with some persisting cognitive and motor deficits. Young people who report such symptoms could be considered a target group for interventions to aid functional outcomes.

AIMS (a) To investigate the utility of childhood PE as a predictor of adolescent psychopathology while accounting for three known risk factors: childhood mental disorder; traumatic experiences and poor childhood functioning, and (b) to investigate the additive effects of including childhood PE in predictive clinical model of adolescent psychopathology. METHOD The study sample comprised of 86 Irish youths who completed two waves of the "Adolescent Brain Development" study (baseline age: 11.7 and follow-up age: 15.7). At baseline, participants completed a clinical interview assessing for PE, mental disorders, traumatic experiences and global functioning in childhood. The internalizing and externalizing problems sub-scales from the Youth Self Report questionnaire were used as follow-up outcomes variables in adolescence. RESULTS Logistic regression analyses revealed that childhood PE was the only predictor significantly associated with both internalizing (univariate OR: 7.58, CI: 2.59-22.15; multivariate OR: 5.43, CI: 1.53-19.29) and externalizing (univariate OR: 11.76, CI: 3.70-37.41; multivariate OR: 30.39, CI: 5.28-174.80) problems in adolescence. All predictive models with PE significantly predicted adolescent outcomes (area under the curve range: 0.70-0.81; all P