Risk Factor For Psychosis Research Articles

An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis.

Identifying rare, highly penetrant risk mutations may be an important step in dissecting the molecular etiology of schizophrenia. We conducted a gene-based analysis of large (>100 kb), rare copy-number variants (CNVs) in the Wellcome Trust Case Control Consortium 2 (WTCCC2) schizophrenia sample of 1564 cases and 1748 controls all from Ireland, and further extended the analysis to include an additional 5196 UK controls. We found association with duplications at chr20p12.2 (P = 0.007) and evidence of replication in large independent European schizophrenia (P = 0.052) and UK bipolar disorder case-control cohorts (P = 0.047). A combined analysis of Irish/UK subjects including additional psychosis cases (schizophrenia and bipolar disorder) identified 22 carriers in 11 707 cases and 10 carriers in 21 204 controls [meta-analysis Cochran–Mantel–Haenszel P-value = 2 × 10−4; odds ratio (OR) = 11.3, 95% CI = 3.7, ∞]. Nineteen of the 22 cases and 8 of the 10 controls carried duplications starting at 9.68 Mb with similar breakpoints across samples. By haplotype analysis and sequencing, we identified a tandem ∼149 kb duplication overlapping the gene p21 Protein-Activated Kinase 7 (PAK7, also called PAK5) which was in linkage disequilibrium with local haplotypes (P = 2.5 × 10−21), indicative of a single ancestral duplication event. We confirmed the breakpoints in 8/8 carriers tested and found co-segregation of the duplication with illness in two additional family members of one of the affected probands. We demonstrate that PAK7 is developmentally co-expressed with another known psychosis risk gene (DISC1) suggesting a potential molecular mechanism involving aberrant synapse development and plasticity.

EPA-1417 – Migration history and first episode psychosis: Results from EUGEI project- Italy

The excess of psychosis among migrants and ethnic minorities is a well defined phenomenon in North Europe, while it should be still demonstrated in south Europe. Because of the variation in prevalence and distribution of risk factors in different national contexts, similar studies in different countries are needed to test the hypotheses and to ensure the generalizability of the findings. Moreover, available studies have been mostly focused on risk factors of psychosis during the post migration phase (such as ethnic fragmentation, unemployment, etc) and among well established ethnic minorities (second and further generations of migrants). In Italy, first generation migrants are still the larger component of the ethnic minorities’ populations and we can evaluate risk factors of psychosis related to the migration history as whole considered (pre-migration, migration and post migration phases). I will present results on risk factors of psychosis among first generations migrants in the three sites involved in the EU-GEI Project in Italy (Bologna, Palermo and Verona) (European Network of National Schizophrenia Networks Studying Gene Environment Interactions Project EU-GEI European Community's Seventh Framework Program, grant agreement No. HEALTH-F2-2009-241909). Particularly, I will discuss our efforts to understand the role of the migration process characteristics in the development of psychosis.

Prevalence of cannabis residues in psychiatric patients: a case study of two mental health referral hospitals in Uganda.

Various studies have reported that abuse of cannabis is a risk factor for psychosis. The aims of this study were to determine the prevalence of delta 9-tetrahydrocanabinol (Δ9-THC), a major metabolite of cannabis, in psychiatric patients in Uganda, and to assess the diagnostic capacity of two referral mental health hospitals to screen patients for exposure to cannabis in Uganda. Socio-demographic characteristics of the patients were collected through questionnaires and review of medical records. Urine samples were collected from 100 patients and analyzed using Δ9-THC immunochromatographic kit (Standard Diagnostics®, South Korea). Seventeen percent of the patients tested positive for Δ9-THC residues in their urine. There was strong association (P < 0.05) between history of previous abuse of cannabis and presence of Δ9-THC residues in the urine. Alcohol, cocaine, heroin, pethidine, tobacco, khat and kuber were the other substances abused in various combinations. Both referral hospitals lacked laboratory diagnostic kits for detection of cannabis in psychiatric patients. In conclusion, previous abuse of cannabis is associated with occurrence of the residues in psychiatric patients, yet referral mental health facilities in Uganda do not have the appropriate diagnostic kits for detection of cannabis residues as a basis for evidence-based psychotherapy.

EPA-0765 – Coping, self-efficacy, and control beliefs between patients at-risk for psychosis and patients with firstepisode psychosis

Background Dysfunctional coping patterns, low self-efficacy, and an excessive use of external control beliefs are assumed to be risk factors for psychosis. They are already present in patients with first-epsiode psychosis (FEP). However, it remains unclear if help-seeking patients symptomatically at-risk for psychosis (AR) show similar patterns of coping and competence/control beliefs as FEP patients. Methods We compared the frequency of deficits in coping, self-efficacy, and competence beliefs between AR according to the ultra-high risk and/or basic symptom criteria (n=21; mean age: 19.4±4.6) and FEP patients (n=22; mean age: 20.0±4.6). Coping strategies were assessed through the Stress-Coping-Questionnaires (SVF-120/SVF-KJ); self-efficacy and competence beliefs through the Competence and Control Beliefs Questionnaire (FKK). Results Most AR and FEP patients demonstrated dysfunctional coping patterns, low self-efficicacy, and biases in control beliefs. Compared to FEP, AR patients reported even more deficits in positive coping strategies and self-efficacy than FEP. Moreover, they showed an excessive use of external fatalistic beliefs. In contrast, FEP patients demonstrated to be overly self-confident. Conclusions Dysfunctional coping and competence/control belief patterns are present before the onset of psychosis and are promising predictors of conversion to psychosis. Therefore, they appear to be important treatment targets for early intervention in psychosis. As deficit patterns of AR differ from those of FEP patients, interventions need to be tailored to the special treatment needs of both groups to prevent transition or relapse to psychosis.

Risk Factors for Psychosis Secondary to Temporal Lobe Epilepsy: A Systematic Review

The authors critically reviewed all relevant peer-reviewed quantitative research pertaining to the risk factors for psychosis secondary to temporal lobe epilepsy, carrying out an extensive literature search to identify all relevant research studies, and applying specific exclusion criteria; the search yielded 27 original research articles for critical review. These studies were individually assessed for methodological quality. Authors reached consensus on a number of important risk factors for psychosis, including early age at epilepsy onset, history of status epilepticus, hippocampal sclerosis, and left-hemisphere abnormalities. Inconsistencies in defining and diagnosing epileptic psychoses were apparent, as well as the sole use of case-control, cross-sectional, and/or retrospective study designs. There remains a need for research using consistent classification criteria and longitudinal study designs.

An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis

An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis

EPA-1403 – Testing alternative hypotheses for the increased rate of psychotic disorder in immigrants

Increased incidence rates of psychotic disorder have been consistently observed in immigrants with significant variability across ethnic groups. These findings have been attributed to cross-cultural biases, i.e. misinterpretation of culturally appropriate ideas leading to an overestimation of these disorders among ethnic minorities. Another alternative explanation constitutes the selection hypothesis positing that the increased rate is due to selective migration of predisposed people. We will present two studies that aimed at testing these hypotheses by examining (a) whether risk factors for psychosis are more prevalent among future emigrants, and (b) whether psychotic symptoms differ in severity and nature according to ethnic group. The first study was conducted among a cohort of 50 087 conscripts who were assessed at age 18 on cannabis use, IQ, psychiatric diagnosis, social adjustment, history of trauma and urbanicity of place of upbringing. Through data linkage we examined whether these exposures predicted emigration out of Sweden. The second study included 301 first episode psychosis (FEP) patients within a defined catchment area in Montreal, Canada. Patients were administered scales for the assessment of positive and negative symptoms, as well as general psychopathology. Symptom scores of the reference group were compared to those of patients with different ethnic backgrounds. The results of these studies will be discussed in light of candidate explanations for the increased risk of psychotic disorder among immigrants. Future avenues using data from the EUropean Gene-Environment Interaction (EU-GEI) project will be proposed.

A pilot study: Investigating the neural correlates of social cognition in neuropsychiatric disorders using fMRI

Event Abstract Back to Event A pilot study: Investigating the neural correlates of social cognition in neuropsychiatric disorders using fMRI Charlotte Knee-Zaska1*, Omar Mothersill1 and Gary Donohoe1 1 NUI Galway, Psychology, Ireland Social cognition can be defined as mental processes allowing people to perceive and process information about themselves and others, enabling successful navigation of the social world (Van Overwalle, 2009). Social cognitive defects (such as emotion recognition and mental state reasoning, or ‘theory of mind’) are a core feature of several psychiatric disorders, including schizophrenia (Couture et al., 2006) and strongly predict functional outcome (Fett et al., 2011). For this reason social cognition is a potential target for new pharmacological and/or cognitive treatments. A better understanding of the neurobiological mechanisms involved are a critcal step towards this. The present study aims to elucidate these mechanisms using functional MRI across a sample of psychosis patients (N = 30) and demographically-matched healthy controls (N = 30). Three robust social cognitive tasks will be used during fMRI, including (1) emotion recognition, where participants observe video clips of angry or neutral facial expressions (Grosbras and Paus, 2006), (2) theory of mind, where participants view cartoons and contemplate the mental states of the characters (Brüne et al., 2008) and (3) social exclusion, where participants experience social exclusion from a computer ball game (Sebastian et al., 2011).This study will also examine effects of putative risk factors for psychosis, including effects of genome-wide associated genetic risk variants (Ripke et al., 2011) and environmental factors. Using a single healthy volunteer, this pilot fMRI study highlighted several brain regions that were activated during each of these social cognitive tasks at a p<0.05 level, including corticolimbic and default mode networks, consistent with previous social neuroimaging studies. References Van Overwalle, F. (2009). Social cognition and the brain: a meta‐analysis.Human brain mapping, 30(3), 829-858. Couture, S. M., Penn, D. L., & Roberts, D. L. (2006). The functional significance of social cognition in schizophrenia: a review. Schizophrenia bulletin, 32(suppl 1), S44-S63. Fett, A. K. J., Viechtbauer, W., Dominguez, M. D. G., Penn, D. L., van Os, J., & Krabbendam, L. (2011). The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neuroscience & Biobehavioral Reviews, 35(3), 573-588. Grosbras, M. H., & Paus, T. (2006). Brain networks involved in viewing angry hands or faces. Cerebral Cortex, 16(8), 1087-1096. Brüne, M., Lissek, S., Fuchs, N., Witthaus, H., Peters, S., Nicolas, V., ... & Tegenthoff, M. (2008). An fMRI study of theory of mind in schizophrenic patients with “passivity” symptoms. Neuropsychologia, 46(7), 1992-2001. Sebastian, C. L., Tan, G. C., Roiser, J. P., Viding, E., Dumontheil, I., & Blakemore, S. J. (2011). Developmental influences on the neural bases of responses to social rejection: implications of social neuroscience for education. Neuroimage, 57(3), 686-694. Keywords: social cognition, functional magnetic resonance imaging (fMRI), Schizophrenia, theory of mind (ToM), Emotion recogntion, social exclusion Conference: Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014. Presentation Type: Poster Presentation Topic: Early Career Neuroscience Citation: Knee-Zaska C, Mothersill O and Donohoe G (2014). A pilot study: Investigating the neural correlates of social cognition in neuropsychiatric disorders using fMRI . Front. Neurosci. Conference Abstract: Neuroscience Ireland Young Neuroscientists Symposium 2014 . doi: 10.3389/conf.fnins.2014.87.00020 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Sep 2014; Published Online: 12 Sep 2014. * Correspondence: Mrs. Charlotte Knee-Zaska, NUI Galway, Psychology, Galway, Ireland, kneec@tcd.ie Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Charlotte Knee-Zaska Omar Mothersill Gary Donohoe Google Charlotte Knee-Zaska Omar Mothersill Gary Donohoe Google Scholar Charlotte Knee-Zaska Omar Mothersill Gary Donohoe PubMed Charlotte Knee-Zaska Omar Mothersill Gary Donohoe Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Vitamin D deficiency in first episode psychosis: A case–control study

BackgroundVitamin D deficiency is seen in a high proportion of people with established psychotic disorders, but it is not known if this is present at onset of the illness. We set out to examine vitamin D levels in people with their first episode of psychosis (FEP). MethodWe conducted a matched case–control study to examine vitamin D levels and rates of vitamin D deficiency in sixty nine patients presenting with their FEP and sixty nine controls matched for age, sex and ethnicity. Differences between groups were tested using student's-t tests, paired t-tests and odds ratios for further analysis. ResultsVitamin D levels were significantly lower in cases than in controls (p<0.001). The odds ratio of being vitamin D deficient was 2.99 in the FEP group relative to the control group. There was no correlation between vitamin D levels and length of hospitalisation in the patient group (r=−0.027, p=0.827). ConclusionsWe found higher rates of vitamin D deficiency in people with FEP compared to matched controls. Given that vitamin D is neuroprotective; that developmental vitamin D deficiency may be a risk factor for psychosis, and that incipient psychosis may affect lifestyle factors and diet, future studies are required to examine this association further. In the meantime, there is a need for more widespread testing of vitamin D levels in FEP and for the development of appropriate management strategies.

Cannabis use and brain structural alterations of the cingulate cortex in early psychosis

As cannabis use is more frequent in patients with psychosis than in the general population and is known to be a risk factor for psychosis, the question arises whether cannabis contributes to recently detected brain volume reductions in schizophrenic psychoses. This study is the first to investigate how cannabis use is related to the cingulum volume, a brain region involved in the pathogenesis of schizophrenia, in a sample of both at-risk mental state (ARMS) and first episode psychosis (FEP) subjects. A cross-sectional magnetic resonance imaging (MRI) study of manually traced cingulum in 23 FEP and 37 ARMS subjects was performed. Cannabis use was assessed with the Basel Interview for Psychosis. By using repeated measures analyses of covariance, we investigated whether current cannabis use is associated with the cingulum volume, correcting for age, gender, alcohol consumption, whole brain volume and antipsychotic medication. There was a significant three-way interaction between region (anterior/posterior cingulum), hemisphere (left/right cingulum) and cannabis use (yes/no). Post-hoc analyses revealed that this was due to a significant negative effect of cannabis use on the volume of the posterior cingulum which was independent of the hemisphere and diagnostic group and all other covariates we controlled for. In the anterior cingulum, we found a significant negative effect only for the left hemisphere, which was again independent of the diagnostic group. Overall, we found negative associations of current cannabis use with grey matter volume of the cingulate cortex, a region rich in cannabinoid CB1 receptors. As this finding has not been consistently found in healthy controls, it might suggest that both ARMS and FEP subjects are particularly sensitive to exogenous activation of these receptors.

From sexual abuse to psychosis: A pilot study exploring the social deafferentation hypothesis and the mediating role of avoidance

The social deafferentation hypothesis posits that social withdrawal in vulnerable individuals may result in anomalous perceptual and cognitive experiences that are consistent with psychotic hallucinations and delusions. Both psychosis vulnerability and social withdrawal are characteristic of many individuals who have experienced sexual abuse and a growing literature continues to document associations between experiences of sexual abuse and psychosis. The current study investigated if avoidant personality traits (characterised by social withdrawal) mediated the relationship between sexual abuse and psychosis symptom experience. Using data from the British Psychiatric Morbidity Survey (N = 8580), a mediation model was specified and estimated. The estimates showed that the regression coefficients of avoidant personality traits on sexual abuse (B =.70), psychosis scores on avoidant personality traits (B = .09), and psychosis scores on sexual abuse (B =.45) were statistically significant. The mediated effect of sexual abuse on psychosis scores via avoidant personality traits was also significant (B = .06). The parameters of this mediated model were statistically significant after controlling for a range of demographic variables and potential risk factors for psychosis. Avoidance and social deafferentation may constitute a plausible hypothesis for exploring experiences of psychosis among victims of sexual abuse in some cases.

2701 – Negative association between neurological soft signs and cannabis use in tunisian patients with first-episode psychosis

Neurological soft signs (NSS) are minor or subtle neurological signs indicating non-specific cerebral dysfunction. They have been conceptualized as neurodevelopmental markers that mediate the biological propensity for the development of psychosis. Their interaction with the environmental factors such as cannabis use remains little studied. To study the relationship between the NSS and the use of cannabis which is considered an environmental risk factor of psychotic disorder. Sixty one in-patients (fifty three men and eight women; mean age: 28.9 ± 9.4 years) with a first-episode non affective psychosis according with DSM-IV were recruited. Neurological evaluations were carried-out by using the NSS scale of Krebs et al. (2000). We ascertained the use of cannabis with the cannabis subsection, included within the section of substance use, in the Composite International Diagnostic Interview (CIDI). The prevalence of cannabis use was 16.4%. The mean NSS total score was 15.3 ± 6.7. Significant lower NSS total score was found in cannabis users: 11.2 ± 5.6 versus 16.0 ± 6.7 (p=0.04). There was also an inverse but not significant relation between the use of cannabis and the motor coordination and the involuntary movements sub-scores. Similar results have been reported in patients with schizophrenia and first-episode psychosis suggesting the existence of fewer NSS in the cannabis user patients. The cannabis could enhance the effects of genetic risk factors for psychosis. More work in the area of genetic-environment interactions in predicting psychosis is necessary.

Structural abnormalities in cortical volume, thickness, and surface area in 22q11.2 microdeletion syndrome: Relationship with psychotic symptoms.

Introduction22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins.MethodsHigh-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10–25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed.ResultsRelative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS.ConclusionDifferential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population.

The Ultra-High Risk Concept—A Review

Attempts to identify people at imminent risk of psychotic disorder have been made during the past 20 years. High-risk criteria have been developed, and despite findings of a recent decline in the rate of onset of psychosis associated with these criteria, people identified still have a significantly greater risk, compared with the general population. Intervention studies in this group indicate that psychological treatments and fish oil appear to be just as effective as antipsychotics. Future research should refine risk factors for psychosis and examine outcomes other than psychosis. Research is also needed into what harms and benefits are associated with making the high-risk criteria into a formal diagnosis.

The Social Determinants of Schizophrenia: An African Journey in Social Epidemiology

The epidemiology of schizophrenia in developing countries, and especially in Africa, is controversial. One of the major findings of the World Health Organization multisite studies of schizophrenia conducted during the 1970s–1990s was that outcome of schizophrenia was better in developing countries. More recent research suggests this may not be the case in contemporary Africa. Rapid urbanization, industrialization, migration, conflict and ongoing poverty and deprivation characterize most of sub-Saharan Africa in recent decades; and it is likely that these potent risk factors for psychosis have contributed to shifts in the social epidemiology of psychosis and schizophrenia in that continent. In studying the epidemiology of schizophrenia, it is also necessary to examine evidence on first-episode psychosis (FEP) since it is often difficult to confirm a diagnosis of schizophrenia at onset. The author reviews nearly 50 years of epidemiological research on psychosis and schizophrenia in Africa; and argues that novel and flexible methods are required in contemporary efforts to study schizophrenia in the region. Specific contexts require specific approaches that are relevant and sensitive to local political, socio-economic and cultural conditions and dynamics. The future role of social epidemiology in helping clarify the burden, risk factors and natural history of schizophrenia within Africa depends largely on its success in integrating classic approaches with novel methods that are relevant to the specific socio-economic, political and cultural transformations taking place on that continent.

Psychosis is Emerging as a Learning and Memory Disorder

The difficulty in developing mechanistic models for psychiatric diseases may be that we are using the incorrect disease targets. Recently, clinical scientists have been attempting to examine alterations in dimensions of cognition and affect, rather than diagnoses of neuropsychiatric disease for clues to neural mechanisms of psychopathology. The RDoCs (Research Domain Criteria) (http://www.nimh.nih.gov/research-funding/rdoc/nimh-research-domain-criteria-rdoc.shtml) system is a leading example of this reorientation. In RDoCs, dimensions of cognition and affect (alterations of which combine to compose the psychiatric diseases that we know) are the unifying, homogenous units generating psychopathology. ‘Psychosis' is a ready example and can be conceptualized as a learning and memory disorder. We have been studying this dimension across psychotic diagnoses, with the goal of identifying the normal cognition system(s) whose pathology could generate psychosis (Ivleva et al, 2012). The hippocampus is altered in schizophrenic psychosis, with structural, functional, and molecular pathology; specifically, psychosis is associated with increases in basal hippocampal activity and reductions in associational memory processing (Tamminga et al, 2010). The hippocampus is one of the most actively studied regions in brain; initial studies were focused on human memory, stimulated by HM, and more recent research has greatly extended early studies to explicate systems of signaling molecules involved in memory computations, as well as changes in synaptic plasticity underlying learning and memory. Hippocampal structures, including subfields, fiber pathways, and the one-way trisynaptic circuit, are critical in generating normal memory behaviors; subfields contribute uniquely to memory. Memory behaviors emerge from the smooth functioning and proper connectivity of dentate gyrus and the cornu ammonis fields of CA3 and CA1 (Liu et al, 2012). Neural activity in the mossy fiber pathway from DG to CA3 can cause categorical changes in CA3 activity, dependent on the level of afferent stimulation from DG (Pelkey and, McBain, 2008). And within CA3, the recurrent collateral system is dependent on a controlled positive feed-forward system for productive ‘pattern completion' function (Kremin and Hasselmo, 2007). Molecular and anatomic synaptic markers of memory-associated plasticity are well described (Abraham and Bear, 1996). These protein markers of normal memory behavior can be examined in human tissue to test for psychosis risk factors that could underlie psychosis. It is plausible that psychosis is dependent on a pathologically increased level of neuronal function in CA3, which exceeds the associational capacity of this subfield and results in mistaken and false associations, some with psychotic content, which then get consolidated, as normal memory, albeit with psychotic content. These memories utilize normal declarative memory neural pathways, including limbic and prefrontal cortical regions, even though they have psychotic content. To demonstrate these ideas will require convergent sources of evidence from humans with psychosis using multimodal brain imaging, behavioral testing, and human tissue chemistry to create confidence in this kind of a novel approach. Our recent findings, including increased molecular plasticity-related proteins in CA3 accompanied by increased perfusion in CA3 and CA1 measured by MR, show the power of convergent methodologies. Finding the common elements in hippocampal pathology across the psychotic disorders would support new dimensional disease concepts.

Ethnic density as a buffer for psychotic experiences: findings from a national survey (EMPIRIC).

Aetiological mechanisms underlying ethnic density associations with psychosis remain unclear. To assess potential mechanisms underlying the observation that minority ethnic groups experience an increased risk of psychosis when living in neighbourhoods of lower own-group density. Multilevel analysis of nationally representative community-level data (from the Ethnic Minorities Psychiatric Illness Rates in the Community survey), which included the main minority ethnic groups living in England, and a White British group. Structured instruments assessed discrimination, chronic strains and social support. The Psychosis Screening Questionnaire ascertained psychotic experiences. For every ten percentage point reduction in own-group density, the relative odds of reporting psychotic experiences increased 1.07 times (95% CI 1.01-1.14, P = 0.03 (trend)) for the total minority ethnic sample. In general, people living in areas of lower own-group density experienced greater social adversity that was in turn associated with reporting psychotic experiences. People resident in neighbourhoods of higher own-group density experience 'buffering' effects from the social risk factors for psychosis.

Decreased Birth Weight in Psychosis: Influence of Prenatal Exposure to Serologically Determined Influenza and Hypoxia

Decreased birth weight (BW) is associated with later psychosis, but the sources of decreased BW for those at risk for psychosis remain unclear. To determine whether fetal exposure to influenza and/or hypoxia accounts for BW decreases among psychotic cases and controls. Subjects were 111 cases diagnosed with schizophrenia or affective psychosis and 333 matched controls from the Collaborative Perinatal Project. Psychiatric diagnoses were ascertained from medical records. Influenza and hypoxia were determined from maternal and cord sera collected at birth. Cases exposed to severe fetal hypoxia or influenza had significantly lower BW compared with unexposed cases and controls, regardless of exposure status. No significant differences in BW were observed among controls based on exposure status. Decreased BW appears to be a risk factor for psychosis only in the presence of other teratogens. Liability to psychosis likely renders fetuses vulnerable to decreased fetal growth in response to hypoxia and influenza.

Obstetric complications in early psychosis: Relation with family history of psychosis

The people classified as being at ultra-high risk (UHR) of developing psychosis are expected to share many risk factors for psychosis with the patients diagnosed with schizophrenia, including an enhanced incidence of obstetric complications (OCs). This study set out to investigate the incidence and correlates of OCs in a sample of patients accessing an early intervention center. Patients' mothers were asked whether they had suffered from any somatic complication during pregnancy from a list of OCs with potential direct relevance to the physical wellbeing of the offspring. Out of 86 patients diagnosed with first-episode psychosis, 20 (23%) cases were positive for the occurrence of severe OCs, as reported by their mothers during an interview; out of 83 UHR patients, 21 (25%) cases were positive for OCs. OCs were more common in individuals with a family history of psychosis than in those without such a history. OCs might interact with genetic vulnerability to increase the risk of psychosis. Lack of comparison to healthy controls is a limitation that decreases the value of these findings.

‘At-risk’ for psychosis research: where are we heading?

The 'at-risk' criteria are a useful paradigm for investigating the psychological, neurocognitive, neurobiological and genetic risk factors for psychosis, specifically schizophrenia. To date, the primary outcome of interest in at-risk research has been the development of psychotic disorder, whereby patients are categorized as either having 'transitioned' or 'not transitioned'. Despite the acceptance of this dichotomy, it is important to consider that the threshold at which psychotic symptoms progress from attenuated to frank 'psychotic disorder' is arbitrary and may be incorrect or meaningless in terms of neurobiological and functional changes associated with psychosis. This has implications for clinical care and the search for markers of schizophrenia. We present recent research suggesting that the term 'outcome' needs to be broadened to incorporate non-psychotic diagnoses, functioning and negative symptoms. Shifting the traditional notion of outcome is the future challenge for at-risk research, but the inclusion of outcomes other than psychosis is likely to result in better aetiological models of psychotic illness.