Clinical and functional outcomes at 7-year follow-up of children presenting putative antecedents of schizophrenia at age 9-12 years

Identification of youth presenting early risk factors for psychosis may facilitate preventive intervention. Through school-based screening, we recruited 112 children aged 9-12 years who presented multiple putative antecedents of schizophrenia (ASz), a family history of schizophrenia (FHx), or neither of these risk factors (typically-developing; TD). Clinical and functional outcomes were assessed at age 17-21 years (N=93). Compared to the TD group, the ASz group had higher total Prodromal Questionnaire (PQ) scores (β=10.59, 95% CI=3.76, 17.42) and total psychopathology scores (β= 6.13, 95% CI: 1.03, 11.23), were more likely to score above-threshold on the PQ positive symptoms scale (OR=4.00, 95% CI=1.08, 14.83), and had lower scores on the Social and Occupational Functioning Scale (β=-9.43, 95% CI=-15.08, -3.77) at follow-up. The FHx and TD groups did not differ on any outcome. Findings suggest that population screening for putative antecedents of schizophrenia may identify children who would benefit from preventative intervention

Conditional disclosure on pathways to care: coping preferences of young people at risk of psychosis

The interrelationship between stigma and help-seeking is under-researched among children and adolescents. This study explored stigma in relation to pathways to care among young people putatively in an early stage of increased risk of developing psychotic disorders. “Pathways to care” was defined as help-seeking and support from informal and formal resources, and increased risk was determined through the presence of persistent psychotic-like experiences and internalizing/externalizing psychopathology. Twenty-nine qualitative interviews were analyzed using thematic analysis. We defined the superordinate theme in these data as “conditional disclosure,” a concept reflecting the rules and prerequisites that influenced how/whether participants sought help. Through parallels between these findings and established stigma theory, we examined how these conditions could be interpreted as influenced by stigma. Our findings demonstrate the influence of stigma on young people’s perceptions of a range of pre-clinical symptoms, and on how they seek support for these symptoms

Multivariate neuroanatomical classification of cognitive subtypes in schizophrenia: A support vector machine learning approach

AbstractHeterogeneity in the structural brain abnormalities associated with schizophrenia has made identification of reliable neuroanatomical markers of the disease difficult. The use of more homogenous clinical phenotypes may improve the accuracy of predicting psychotic disorder/s on the basis of observable brain disturbances. Here we investigate the utility of cognitive subtypes of schizophrenia – ‘cognitive deficit’ and ‘cognitively spared’ – in determining whether multivariate patterns of volumetric brain differences can accurately discriminate these clinical subtypes from healthy controls, and from each other. We applied support vector machine classification to grey- and white-matter volume data from 126 schizophrenia patients previously allocated to the cognitive spared subtype, 74 cognitive deficit schizophrenia patients, and 134 healthy controls. Using this method, cognitive subtypes were distinguished from healthy controls with up to 72% accuracy. Cross-validation analyses between subtypes achieved an accuracy of 71%, suggesting that some common neuroanatomical patterns distinguish both subtypes from healthy controls. Notably, cognitive subtypes were best distinguished from one another when the sample was stratified by sex prior to classification analysis: cognitive subtype classification accuracy was relatively low (<60%) without stratification, and increased to 83% for females with sex stratification. Distinct neuroanatomical patterns predicted cognitive subtype status in each sex: sex-specific multivariate patterns did not predict cognitive subtype status in the other sex above chance, and weight map analyses demonstrated negative correlations between the spatial patterns of weights underlying classification for each sex. These results suggest that in typical mixed-sex samples of schizophrenia patients, the volumetric brain differences between cognitive subtypes are relatively minor in contrast to the large common disease-associated changes. Volumetric differences that distinguish between cognitive subtypes on a case-by-case basis appear to occur in a sex-specific manner that is consistent with previous evidence of disrupted relationships between brain structure and cognition in male, but not female, schizophrenia patients. Consideration of sex-specific differences in brain organization is thus likely to assist future attempts to distinguish subgroups of schizophrenia patients on the basis of neuroanatomical features

Amygdala Hypoactivity to Fearful Faces in Boys With Conduct Problems and Callous-Unemotional Traits

OBJECTIVE: Although early-onset conduct problems predict both psychiatric and health problems in adult life, little research has been done to index neural correlates of conduct problems. Emerging research suggests that a subgroup of children with conduct problems and elevated levels of callous-unemotional traits may be genetically vulnerable to manifesting disturbances in neural reactivity to emotional stimuli indexing distress. Using functional MRI, the authors evaluated differences in neural response to emotional stimuli between boys with conduct problems and elevated levels of callous-unemotional traits and comparison boys. METHOD: Seventeen boys with conduct problems and elevated levels of callous-unemotional traits and 13 comparison boys of equivalent age (mean=11 years) and IQ (mean=100) viewed blocked presentations of fearful and neutral faces. For each face, participants distinguished the sex of the face via manual response. RESULTS: Relative to the comparison group, boys with conduct problems and elevated levels of callous-unemotional traits manifested lesser right amygdala activity to fearful faces. CONCLUSIONS: This finding is in line with data from studies of adults with antisocial behavior and callous-unemotional traits (i.e., psychopaths), as well as from a recent study of adolescents with callous-unemotional traits, and suggests that the neural substrates of emotional impairment associated with callous-unemotional antisocial behavior are already present in childhood

Self-harm and suicidal ideation among young people is more often recorded by child protection than health services in an Australian population cohort

OBJECTIVE: We investigated patterns of service contact for self-harm and suicidal ideation recorded by a range of human service agencies - including health, police and child protection - with specific focus on overlap and sequences of contacts, age of first contact and demographic and intergenerational characteristics associated with different service responses to self-harm.METHODS: Participants were 91,597 adolescents for whom multi-agency linked data were available in a longitudinal study of a population cohort in New South Wales, Australia. Self-harm and suicide-related incidents from birth to 18 years of age were derived from emergency department, inpatient hospital admission, mental health ambulatory, child protection and police administrative records. Descriptive statistics and binomial logistic regression were used to examine patterns of service contacts.RESULTS: Child protection services recorded the largest proportion of youth with reported self-harm and suicidal ideation, in which the age of first contact for self-harm was younger relative to other incidents of self-harm recorded by other agencies. Nearly 40% of youth with a health service contact for self-harm also had contact with child protection and/or police services for self-harm. Girls were more likely to access health services for self-harm than boys, but not child protection or police services.CONCLUSION: Suicide prevention is not solely the responsibility of health services; police and child protection services also respond to a significant proportion of self-harm and suicide-related incidents. High rates of overlap among different services responding to self-harm suggest the need for cross-agency strategies to prevent suicide in young people.</p

Influence of stigma, sociodemographic and clinical characteristics on mental health-related service use and associated costs among young people in the United Kingdom

This study examined the influence of stigma, psychopathology, and sociodemographic characteristics on mental health-related service use and costs related to service use in a cohort of young people in the UK. Using data from a community sample of young people aged 9–17 years and their caregivers, we assessed 407 young people’s use of services due to mental health problems, young people’s psychopathology, demographic characteristics, maternal education and caregivers’ stigma-related beliefs. Unit costs related to services were gathered from national annual compendia and other widely used sources. We assessed predictors of service use through logistic regression analysis and developed generalised linear models to identify factors associated with costs of mental health-related service utilisation. Persistent psychopathology, socioeconomic disadvantage, and low caregiver intended stigma-related behaviour were associated with increased likelihood of service use among young people. Older age and socioeconomic disadvantage were associated with increased costs. Different factors influenced contact with services and the cost associated with their use — persistent psychopathology and socioeconomic disadvantage increased, and caregivers’ intended stigma-related behaviour decreased the likelihood of using services, whereas socioeconomic disadvantage and older age were associated with increased costs. Social determinants of mental health problems play an important role in the use and costs of different types of mental health-related services for young people. Discordance between drivers of service use and costs implies that young people who are more likely to access services due to mental health problems do not necessarily receive care at the intensity they need

The relationship between salivary C-reactive protein and cognitive function in children aged 11-14 years: Does psychopathology have a moderating effect?

Elevated C-reactive protein (CRP), a non-specific biomarker of systemic bodily inflammation, has been associated with more pronounced cognitive impairments in adults with psychiatric disorders, particularly in the domains of memory and executive function. Whether this association is present in early life (i.e., the time at which the cognitive impairments that characterise these disorders become evident), and is specific to those with emerging psychiatric disorders, has yet to be investigated. To this end, we examined the association between salivary CRP and cognitive function in children aged 11- 14 years and explored the moderating effect of psychopathology. The study utilised data from an established longitudinal investigation of children recruited from the community (N=107) that had purposively over-sampled individuals experiencing psychopathology (determined using questionnaires). CRP was measured in saliva samples and participants completed assessments of cognition (memory and executive function) and psychopathology (internalising and externalising symptoms and psychotic-like experiences). Linear regression models indicated that higher salivary CRP was associated with poorer letter fluency (β=-0.24, p=0.006) and scores on the inhibition (β=-0.28, p=0.004) and inhibition/switching (β=-0.36, p<0.001) subtests of the colour-word interference test, but not with performance on any of the memory tasks (working, visual, and verbal memory tasks). Results were largely unchanged after adjustment for psychopathology and no significant interactions between CRP and psychopathology were observed on any cognitive measure. Our findings provide preliminary evidence that elevated salivary CRP is associated with poorer cognitive function in early life, but that this association is not moderated by concurrent psychopathology. These findings have implications for early intervention strategies that attempt to ameliorate cognitive deficits associated with emerging psychiatric disorders. Further research is needed to determine whether salivary CRP levels can be used as a valid marker of peripheral inflammation among healthy adolescents

Childhood bullying victimization, self-labelling and help-seeking for mental health problems

Purpose: Previous research found sustained high levels of mental health service use among adults who experienced bullying victimization during childhood. This could be due to increased psychopathology among this group, but other factors, such as self-perception as having a mental health problem, might contribute to increased service use. Additionally, the relationship between informal help-seeking for mental health problems and bullying victimization is incompletely understood. Methods: The present study examined associations between the frequency of bullying victimization and both formal service use and informal help-seeking for mental health problems independent from psychopathology. Data on bullying victimization, service use, informal help-seeking for mental health problems, psychopathology, and self-labelling as a person with mental illness were collected among 422 young people aged 13-22 years. Results: In logistic regression models, controlling for past and current psychopathology and using no bullying victimization as the reference category, we identified a greater likelihood of mental health service use among persons who experienced frequent bullying victimization, as well as a greater likelihood of seeking informal help among persons who experienced occasional victimization. Increased self-identification as a person with mental illness completely mediated the positive association between frequent bullying victimization and mental health service use. Conclusions: Our findings suggest that services to support persons who experienced frequent bullying victimization should focus on improving empowerment and self-perception. Additionally, there might be unserved need for formal support among those who experienced occasional bullying victimization

Author index for volume 103

Coping with unusual experiences for 12–18 year olds (CUES+): SPIRIT Checklist. (DOC 122 kb

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead