Genetic risk for schizophrenia is associated with increased proportion of indirect connections in brain networks revealed by a semi-metric analysis: evidence from population sample stratified for polygenic risk.

Research studies based on tractography have revealed a prominent reduction of asymmetry in some key white-matter tracts in schizophrenia (SCZ). However, we know little about the influence of common genetic risk factors for SCZ on the efficiency of routing on structural brain networks (SBNs). Here, we use a novel recall-by-genotype approach, where we sample young adults from a population-based cohort (ALSPAC:N genotyped = 8,365) based on their burden of common SCZ risk alleles as defined by polygenic risk score (PRS). We compared 181 individuals at extremes of low (N = 91) or high (N = 90) SCZ-PRS under a robust diffusion MRI-based graph theoretical SBN framework. We applied a semi-metric analysis revealing higher SMR values for the high SCZ-PRS group compared with the low SCZ-PRS group in the left hemisphere. Furthermore, a hemispheric asymmetry index showed a higher leftward preponderance of indirect connections for the high SCZ-PRS group compared with the low SCZ-PRS group (PFDR < 0.05). These findings might indicate less efficient structural connectivity in the higher genetic risk group. This is the first study in a population-based sample that reveals differences in the efficiency of SBNs associated with common genetic risk variants for SCZ.

Insulin resistance and obesity, and their association with depression in relatively young people: findings from a large UK birth cohort.

BACKGROUND: Depression frequently co-occurs with disorders of glucose and insulin homeostasis (DGIH) and obesity. Low-grade systemic inflammation and lifestyle factors in childhood may predispose to DGIH, obesity and depression. We aim to investigate the cross-sectional and longitudinal associations among DGIH, obesity and depression, and to examine the effect of demographics, lifestyle factors and antecedent low-grade inflammation on such associations in young people. METHODS: Using the Avon Longitudinal Study of Parents and Children birth cohort, we used regression analyses to examine: (1) cross-sectional and (2) longitudinal associations between measures of DGIH [insulin resistance (IR); impaired glucose tolerance] and body mass index (BMI) at ages 9 and 18 years, and depression (depressive symptoms and depressive episode) at age 18 years and (3) whether sociodemographics, lifestyle factors or inflammation [interleukin-6 (IL-6) at age 9 years] confounded any such associations. RESULTS: We included 3208 participants. At age 18 years, IR and BMI were positively associated with depression. These associations may be explained by sociodemographic and lifestyle factors. There were no longitudinal associations between DGIH/BMI and depression, and adjustment for IL-6 and C-reactive protein did not attenuate associations between IR/BMI and depression; however, the longitudinal analyses may have been underpowered. CONCLUSIONS: Young people with depression show evidence of DGIH and raised BMI, which may be related to sociodemographic and lifestyle effects such as deprivation, smoking, ethnicity and gender. In future, studies with larger samples are required to confirm this. Preventative strategies for the poorer physical health outcomes associated with depression should focus on malleable lifestyle factors.

ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties.

Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.

Childhood inflammatory markers and intelligence as predictors of subsequent persistent depressive symptoms: a longitudinal cohort study.

BACKGROUND: To identify developmental sub-groups of depressive symptoms during the second decade of life, a critical period of brain development, using data from a prospective birth cohort. To test whether childhood intelligence and inflammatory markers are associated with subsequent persistent depressive symptoms. METHODS: IQ, a proxy for neurodevelopment, was measured at age 8 years. Interleukin 6 (IL-6) and C-reactive protein, typical inflammatory markers, were measured at age 9 years. Depressive symptoms were measured six times between 10 and 19 years using the short mood and feelings questionnaire (SMFQ), which were coded as binary variable and then used in latent class analysis to identify developmental sub-groups of depressive symptoms. RESULTS: Longitudinal SMFQ data from 9156 participants yielded three distinct population sub-groups of depressive symptoms: no symptoms (81.2%); adolescent-onset symptoms (13.2%); persistent symptoms (5.6%). Lower IQ and higher IL-6 levels in childhood were independently associated with subsequent persistent depressive symptoms in a linear, dose-response fashion, but not with adolescent-onset symptoms. Compared with the group with no symptoms the adjusted odds ratio for persistent depressive symptoms per s.d. increase in IQ was 0.80 (95% CI, 0.68-0.95); that for IL-6 was 1.20 (95% CI, 1.03-1.39). Evidence for an association with IL-6 remained after controlling for initial severity of depressive symptoms at 10 years. There was no evidence that IL-6 moderated or mediated the IQ-persistent depressive symptom relationship. CONCLUSIONS: The results indicate potentially important roles for two distinct biological processes, neurodevelopment and inflammation, in the aetiology of persistent depressive symptoms in young people.

Association between childhood infection, serum inflammatory markers and intelligence: findings from a population-based prospective birth cohort study.

A link between infection, inflammation, neurodevelopment and adult illnesses has been proposed. The objective of this study was to examine the association between infection burden during childhood - a critical period of development for the immune and nervous systems - and subsequent systemic inflammatory markers and general intelligence. In the Avon Longitudinal Study of Parents and Children, a prospective birth cohort in England, we examined the association of exposure to infections during childhood, assessed at seven follow-ups between age 1·5 and 7·5 years, with subsequent: (1) serum interleukin 6 and C-reactive protein (CRP) levels at age 9; (2) intelligence quotient (IQ) at age 8. We also examined the relationship between inflammatory markers and IQ. Very high infection burden (90+ percentile) was associated with higher CRP levels, but this relationship was explained by body mass index (adjusted odds ratio (OR) 1·19; 95% confidence interval (CI) 0·95-1·50), maternal occupation (adjusted OR 1·23; 95% CI 0·98-1·55) and atopic disorders (adjusted OR 1·24; 95% CI 0·98-1·55). Higher CRP levels were associated with lower IQ; adjusted ß = -0·79 (95% CI -1·31 to -0·27); P = 0·003. There was no strong evidence for an association between infection and IQ. The findings indicate that childhood infections do not have an independent, lasting effect on circulating inflammatory marker levels subsequently in childhood; however, elevated inflammatory markers may be harmful for intellectual development/function.

Assessing causality in associations between cannabis use and schizophrenia risk: a two-sample Mendelian randomization study.

BACKGROUND: Observational associations between cannabis and schizophrenia are well documented, but ascertaining causation is more challenging. We used Mendelian randomization (MR), utilizing publicly available data as a method for ascertaining causation from observational data. METHOD: We performed bi-directional two-sample MR using summary-level genome-wide data from the International Cannabis Consortium (ICC) and the Psychiatric Genomics Consortium (PGC2). Single nucleotide polymorphisms (SNPs) associated with cannabis initiation (p < 10-5) and schizophrenia (p < 5 × 10-8) were combined using an inverse-variance-weighted fixed-effects approach. We also used height and education genome-wide association study data, representing negative and positive control analyses. RESULTS: There was some evidence consistent with a causal effect of cannabis initiation on risk of schizophrenia [odds ratio (OR) 1.04 per doubling odds of cannabis initiation, 95% confidence interval (CI) 1.01-1.07, p = 0.019]. There was strong evidence consistent with a causal effect of schizophrenia risk on likelihood of cannabis initiation (OR 1.10 per doubling of the odds of schizophrenia, 95% CI 1.05-1.14, p = 2.64 × 10-5). Findings were as predicted for the negative control (height: OR 1.00, 95% CI 0.99-1.01, p = 0.90) but weaker than predicted for the positive control (years in education: OR 0.99, 95% CI 0.97-1.00, p = 0.066) analyses. CONCLUSIONS: Our results provide some that cannabis initiation increases the risk of schizophrenia, although the size of the causal estimate is small. We find stronger evidence that schizophrenia risk predicts cannabis initiation, possibly as genetic instruments for schizophrenia are stronger than for cannabis initiation.

Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study.

BACKGROUND: There are no existing longitudinal studies of inflammatory markers and atopic disorders in childhood and risk of hypomanic symptoms in adulthood. This study examined if childhood: (1) serum interleukin-6 (IL-6) and C-reactive protein (CRP); and (2) asthma and/or eczema are associated with features of hypomania in young adulthood. METHOD: Participants in the Avon Longitudinal Study of Parents and Children, a prospective general population UK birth cohort, had non-fasting blood samples for IL-6 and CRP measurement at the age of 9 years (n = 4645), and parents answered a question about doctor-diagnosed atopic illness before the age of 10 years (n = 7809). These participants completed the Hypomania Checklist at age 22 years (n = 3361). RESULTS: After adjusting for age, sex, ethnicity, socio-economic status, past psychological and behavioural problems, body mass index and maternal postnatal depression, participants in the top third of IL-6 values at 9 years, compared with the bottom third, had an increased risk of hypomanic symptoms by age 22 years [adjusted odds ratio 1.77, 95% confidence interval (CI) 1.10-2.85, p < 0.001]. Higher IL-6 levels in childhood were associated with adult hypomania features in a dose-response fashion. After further adjustment for depression at the age of 18 years this association remained (adjusted odds ratio 1.70, 95% CI 1.03-2.81, p = 0.038). There was no evidence of an association of hypomanic symptoms with CRP levels, asthma or eczema in childhood. CONCLUSIONS: Higher levels of systemic inflammatory marker IL-6 in childhood were associated with hypomanic symptoms in young adulthood, suggesting that inflammation may play a role in the pathophysiology of mania. Inflammatory pathways may be suitable targets for the prevention and intervention for bipolar disorder.

Lanreotide in the management of small bowel angioectasias: seven-year data from a tertiary centre.

BACKGROUND AND AIMS: Haemorrhage from small bowel angioectasias (SBAs) can be debilitating to patients who are very often elderly and have multiple comorbidities. Our aim was to assess the use of lanreotide in addition to endotherapy in patients with SBAs. METHOD: Patients with SBAs on capsule endoscopy (CE) who received lanreotide injections from January 2010 to till the present day at the Royal Hallamshire Hospital in Sheffield were included. Baseline demographics were recorded. Efficacy was evaluated in terms of improvement in mean haemoglobin, transfusion requirements and bleeding episodes. RESULTS: Twelve patients (67% males, mean age 74 SD ± 15.5 years) were included. All patients had multiple comorbidities. Lanreotide was given at a dosage of 60 mg (42%), 90 mg (33%) or 120 mg (25%). It was given at a four-week interval in 75% of patients and at a six-week interval in 17% of patients. One patient (8%) received a single dose. The mean duration of treatment was 19 months SD ± 14.5. Only 17% of patients had their lanreotide stopped due to cholelithiasis. There was a significant improvement in mean haemoglobin: 86.8 versus 98.0 (131-166 g/L, p = .012). The mean number of bleeding episodes (4.18 versus 1.09, p = .010) and packed red cells (323 versus 152, p = .006) received improved. Patients required less DBEs ± APCs after starting lanreotide (19 versus 11 p = .048). CONCLUSION: Lanreotide is a useful adjuvant treatment to therapeutic enteroscopy in patients with refractory obscure gastrointestinal bleeding due to SBAs. It improves haemoglobin levels, reduces transfusion requirements, bleeding episodes and number of DBEs. Overall, it has a good safety profile.

Explaining risk for suicidal ideation in adolescent offspring of mothers with depression.

BACKGROUND: It is well-established that offspring of depressed mothers are at increased risk for suicidal ideation. However, pathways involved in the transmission of risk for suicidal ideation from depressed mothers to offspring are poorly understood. The aim of this study was to examine the contribution of potential mediators of this association, including maternal suicide attempt, offspring psychiatric disorder and the parent-child relationship. METHOD: Data were utilized from a population-based birth cohort (ALSPAC). Three distinct classes of maternal depression symptoms across the first 11 years of the child's life had already been identified (minimal, moderate, chronic-severe). Offspring suicidal ideation was assessed at age 16 years. Data were analysed using structural equation modelling. RESULTS: There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms compared to offspring of mothers with minimal symptoms (odds ratio 3.04, 95% confidence interval 2.19-4.21). The majority of this association was explained through maternal suicide attempt and offspring psychiatric disorder. There was also evidence for an independent indirect effect via the parent-child relationship in middle childhood. There was no longer evidence of a direct effect of maternal depression on offspring suicidal ideation after accounting for all three mediators. The pattern of results was similar when examining mechanisms for maternal moderate depression symptoms. CONCLUSIONS: Findings highlight that suicide prevention efforts in offspring of depressed mothers should be particularly targeted at both offspring with a psychiatric disorder and offspring whose mothers have made a suicide attempt. Interventions aimed at improving the parent-child relationship may also be beneficial.

Childhood sleep disturbance and risk of psychotic experiences at 18: UK birth cohort.

BACKGROUND: Sleep disturbances are commonly reported in the psychosis prodrome, but rarely explored in relation to psychotic experiences. AIMS: To investigate the relationship between specific parasomnias (nightmares, night terrors and sleepwalking) in childhood and later adolescent psychotic experiences. METHOD: The sample comprised 4720 individuals from a UK birth cohort. Mothers reported on children's experience of regular nightmares at several time points between 2 and 9 years. Experience of nightmares, night terrors and sleepwalking was assessed using a semi-structured interview at age 12. Psychotic experiences were assessed at ages 12 and 18 using a semi-structured clinical interview. RESULTS: There was a significant association between the presence of nightmares at 12 and psychotic experiences at 18 when adjusted for possible confounders and psychotic experiences at 12 (OR = 1.62, 95% CI 1.19-2.20). The odds ratios were larger for those who reported persistent psychotic experiences. CONCLUSIONS: The presence of nightmares might be an early risk indicator for psychosis.

Mood, anxiety and psychotic phenomena measure a common psychopathological factor.

BACKGROUND: Psychotic phenomena are common in the general population but are excluded from diagnostic criteria for mild to moderate depression and anxiety despite their co-occurrence and shared risk factors. We used item response theory modelling to examine whether the co-occurrence of depressive, anxiety and psychotic phenomena is best explained by: (1) a single underlying factor; (2) two separate, uncorrelated factors; (3) two separate yet linked factors; or (4) two separate domains along with an underlying 'common mental distress' (CMD) factor. We defined where, along any latent continuum, the psychopathological items contributed most information. METHOD: We performed a secondary analysis of cross-sectional, item-level information from measures of depression, anxiety and psychotic experiences in 6617 participants aged 13 years from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and 977 participants aged 18 years from the ROOTS schools-based sample. We replicated results from one sample in the other and validated the latent factors against an earlier parental measure of mental state. RESULTS: In both cohorts depression, anxiety and psychotic items were best represented as a bi-factor model with a single, unitary CMD factor on which psychotic items conveyed information about the more severe end (model 4); residual variation remained for psychotic items. The CMD factor was significantly associated with the prior parental measure. CONCLUSIONS: Psychotic phenomena co-occur with depression and anxiety in teenagers and may be a marker of severity in a single, unitary dimension of CMD. Psychotic phenomena should be routinely included in epidemiological assessments of psychiatric morbidity, otherwise the most severe symptomatology remains unmeasured.

A population-based longitudinal study of childhood neurodevelopmental disorders, IQ and subsequent risk of psychotic experiences in adolescence.

BACKGROUND: Schizophrenia has a neurodevelopmental component to its origin, and may share overlapping pathogenic mechanisms with childhood neurodevelopmental disorders (NDs). Nevertheless, longitudinal studies of psychotic outcomes among individuals with NDs are limited. We report a population-based prospective study of six common childhood NDs, subsequent neurocognitive performance and the risk of psychotic experiences (PEs) in early adolescence. METHOD: PEs were assessed by semi-structured interviews at age 13 years. IQ and working memory were measured between ages 9 and 11 years. The presence of six NDs (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent-completed questionnaires at age 9 years. Linear regression calculated the mean difference in cognitive scores between children with and without NDs. Associations between NDs and PEs were expressed as odds ratios (ORs) with 95% confidence intervals (CIs); effects of cognitive deficits were examined. Potential confounders included age, gender, father's social class, ethnicity and maternal education. RESULTS: Out of 8220 children, 487 (5.9%) were reported to have NDs at age 9 years. Children with, compared with those without, NDs performed worse on all cognitive measures; the adjusted mean difference in total IQ was 6.84 (95% CI 5.00-8.69). The association between total IQ and NDs was linear (p < 0.0001). The risk of PEs was higher in those with, compared with those without, NDs; the adjusted OR for definite PEs was 1.76 (95% CI 1.11-2.79). IQ (but not working memory) deficit partly explained this association. CONCLUSIONS: Higher risk of PEs in early adolescence among individuals with childhood ND is consistent with the neurodevelopmental hypothesis of schizophrenia.

Individual- and area-level influence on suicide risk: a multilevel longitudinal study of Swedish schoolchildren.

BACKGROUND: Characteristics related to the areas where people live have been associated with suicide risk, although these might reflect aggregation into these communities of individuals with mental health or social problems. No studies have examined whether area characteristics during childhood are associated with subsequent suicide, or whether risk associated with individual characteristics varies according to childhood neighbourhood context. METHOD: We conducted a longitudinal study of 204,323 individuals born in Sweden in 1972 and 1977 with childhood data linked to suicide (n = 314; 0.15%) up to age 26-31 years. Multilevel modelling was used to examine: (i) whether school-, municipality- or county-level characteristics during childhood are associated with later suicide, independently of individual effects, and (ii) whether associations between individual characteristics and suicide vary according to school context (reflecting both peer group and neighbourhood effects). RESULTS: Associations between suicide and most contextual measures, except for school-level gender composition, were explained by individual characteristics. There was some evidence of cross-level effects of individual- and school-level markers of ethnicity and deprivation on suicide risk, with qualitative interaction patterns. For example, having foreign-born parents increased the risk for individuals raised in areas where they were in a relative minority, but protected against suicide in areas where larger proportions of the population had foreign-born parents. CONCLUSIONS: Characteristics that define individuals as being different from most people in their local environment as they grow up may increase suicide risk. If robustly replicated, these findings have potentially important implications for understanding the aetiology of suicide and informing social policy.

Bullying in elementary school and psychotic experiences at 18 years: a longitudinal, population-based cohort study.

BACKGROUND: Victims of bullying are at risk for psychotic experiences in early adolescence. It is unclear if this elevated risk extends into late adolescence. The aim of this study was to test whether bullying perpetration and victimization in elementary school predict psychotic experiences in late adolescence. METHOD: The current study is based on the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective community-based study. A total of 4720 subjects with bullying perpetration and victimization were repeatedly assessed between the ages of 8 and 11 years by child and mother reports. Suspected or definite psychotic experiences were assessed with the Psychosis-Like Symptoms semi-structured interview at age 18 years. RESULTS: Controlling for child's gender, intelligence quotient at age 8 years, childhood behavioural and emotional problems, and also depression symptoms and psychotic experiences in early adolescence, victims [child report at 10 years: odds ratio (OR) 2.4, 95% confidence interval (CI) 1.6-3.4; mother report: OR 1.6, 95% CI 1.1-2.3], bully/victims (child report at 10 years: OR 3.1, 95% CI 1.7-5.8; mother: OR 2.9, 95% CI 1.7-5.0) and bullies (child report at 10 years: OR 4.9, 95% CI 1.3-17.7; mother: OR 1.2, 95% CI 0.46-3.1, n.s.) had a higher prevalence of psychotic experiences at age 18 years. Path analysis revealed that the association between peer victimization in childhood and psychotic experiences at age 18 years was only partially mediated by psychotic or depression symptoms in early adolescence. CONCLUSIONS: Involvement in bullying, whether as victim, bully/victim or bully, may increase the risk of developing psychotic experiences in adolescence. Health professionals should ask routinely during consultations with children about their bullying of and by peers.

Associations of cannabis and cigarette use with psychotic experiences at age 18: findings from the Avon Longitudinal Study of Parents and Children.

BACKGROUND: A clearer understanding of the basis for the association between cannabis use and psychotic experiences (PEs) is required. Our aim was to examine the extent to which associations between cannabis and cigarette use and PEs are due to confounding. METHOD: A cohort study of 1756 adolescents with data on cannabis use, cigarette use and PEs. RESULTS: Cannabis use and cigarette use at age 16 were both associated, to a similar degree, with PEs at age 18 [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.18-1.86 for cannabis and OR 1.61, 95% CI 1.31-1.98 for cigarettes]. Adjustment for cigarette smoking frequency (OR 1.27, 95% CI 0.91-1.76) or other illicit drug use (OR 1.25, 95% CI 0.91-1.73) substantially attenuated the relationship between cannabis and PEs. The attenuation was to a lesser degree when cannabis use was adjusted for in the cigarette PE association (OR 1.42, 95% CI 1.05-1.92). However, almost all of the participants used cannabis with tobacco, including those who classed themselves as non-cigarette smokers. CONCLUSIONS: Teasing out the effects of cannabis from tobacco is highly complex and may not have been dealt with adequately in studies to date, including this one. Complementary methods are required to robustly examine the independent effects of cannabis, tobacco and other illicit drugs on PEs.

Prognosis of schizophrenia in persons with and without a history of cannabis use.

BACKGROUND: The aim of the study was to determinate whether schizophrenia patients with a history of cannabis use have a different prognosis, with regards to readmission and hospital duration, compared with those without a history of cannabis use. METHOD: The present investigation was a cohort study of 50,087 Swedish men with data on cannabis use at the ages of 18-20 years. A total of 357 cases of schizophrenia were identified from in-patient care and followed up from 1973 to 2007. RESULTS: Schizophrenia patients with a history of cannabis use had a higher median duration of first hospital episode (59 days v. 30 days). Patients with a history of cannabis use had a higher median rate of readmission (10 times v. four times). Also, total number of hospital days was higher in patients with a history of cannabis use compared with those without (547 days v. 184 days). Patients with a history of cannabis use had an increased odds of having more than 20 hospital readmissions compared with non-users [3.1, 95% confidence interval (CI) 1.3-7.3] as well as an increased odds of hospital admission lasting more than 2 years (2.4, 95% CI 1.1-7.4) after controlling for diagnosis of personality disorders, family socio-economic position, IQ score, civil status, place of residence, risky use of alcohol and use of other drugs. Patients with a history of cannabis use were less likely to have paranoid schizophrenia compared with never users (8% v. 17%) in the first admission. CONCLUSIONS: Schizophrenia patients with a history of cannabis use had a significantly higher burden of lifetime in-patient care than non-cannabis users. Not only does cannabis increase the risk of schizophrenia, but also our findings indicate that the course and prognosis of schizophrenia may be more severe than schizophrenia cases in general.

Common versus psychopathology-specific risk factors for psychotic experiences and depression during adolescence.

BACKGROUND: An argument often used to support the view that psychotic experiences (PEs) in general population samples are a valid phenotype for studying the aetiology of schizophrenia is that risk factors for schizophrenia show similar patterns of association with PEs. However, PEs often co-occur with depression, and no study has explicitly tested whether risk factors for schizophrenia are shared between PEs and depression, or are psychopathology specific, while jointly modelling both outcomes. METHOD: We used data from 7030 subjects from a birth cohort study. Depression and PEs at age 18 years were assessed using self-report questionnaires and semi-structured interviews. We compared the extent to which risk factors for schizophrenia across sociodemographic, familial, neurodevelopmental, stress-adversity, emotional-behavioural and substance use domains showed different associations with PEs and depression within bivariate models that allowed for their correlation. RESULTS: Most of the exposures examined were associated, to a similar degree, with an increased risk of both outcomes. However, whereas female sex and family history of depression showed some discrimination as potential risk factors for depression and PEs, with stronger associations in the former, markers of abnormal neurodevelopment showed stronger associations with PEs. CONCLUSIONS: The argument that PEs are valid markers for studying the aetiology of schizophrenia, made simply on the basis that they share risk factors in common, is not well supported. PEs seem to be a weak index of genetic and environmental risk for schizophrenia; however, studies disentangling aetiological pathways to PEs from those impacting upon co-morbid psychopathology might provide important insights into the aetiology of psychotic disorders.

Wound swab use and misuse at a regional general hospital.

OBJECTIVE: Guidelines for swab use at our centre cover lower-limb wounds, ulcers and postoperative wound infections but not all types of wound. The objective of this study was to assess current practices in wound management at Mater Dei Hospital and to identify areas for improvement. METHOD: Wound swabs received at the microbiology department between February and April 2013 from adult inpatients departments were included. Wound swabs from the ophthalmology and paediatric departments were excluded. Patient comorbidities, detailed wound descriptions, acknowledgement of and documentation of culture and sensitivity results, and antibiotic changes during treatment were collected. Indictors of infection including white cell counts (WCCs) and C-reactive protein (CRP) were recorded. RESULTS: The study included 134 patients. Diabetes mellitus (61.9%, n=83) was the most common underlying comorbidity. Postoperative wounds were the most common type of wounds swabbed (34.3%). The wound swab characteristics were not fully documented in 27 patients (20.1%). The CRP results were not recorded in 39.6% and WCCs were not taken in 10.4% of patients. Wound swab results were not acknowledged in the medical notes of 76% of cases. CONCLUSION: Wound swabs that were not indicated, lack of documentation and untimely acknowledgement of results were evident. This suggests that a significant proportion of wound swabs may not have been justified and had no impact on wound management. Our study clearly underlines the need for a more comprehensive guideline. DECLARATION OF INTEREST: There was no sponsorship of this study. The authors have no conflict of interest to declare.

Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls.

A genetic association between NOTCH4 and schizophrenia has previously been proposed. Unsing all markers previously shown to be associated, we found no evidence for such in three independent family-based samples (n=519 parent-offspring trios), and a case-control sample derived from the same ethnic background as the original observation. These data strongly suggest that NOTCH4 is not a significant susceptibility allele for schizophrenia.