No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF)

The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p. Analysis of linkage disequilibrium (LD) across the 252 kb interval encompassing the 7 marker core Icelandic/Scottish NRG1 haplotype revealed two separate regions of modest LD, comprising markers SNP8NRG255133, SNP8NRG249130 and SNP8NRG243177 (telomeric) and microsatellites 478B14-428, 420M9-1395, D8S1810 and 420M9-116I12 (centromeric). From single marker analysis by TRANSMIT and FBAT we found no evidence for association with schizophrenia for any marker. Haplotype analysis for the three SNPs in LD region 1 and, separately, the four microsatellites in LD region 2 (analyzed in overlapping 2-marker windows), showed no evidence for overtransmission of specific haplotypes to affected individuals. We therefore conclude that if NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the ISHDSF.

Relationship between a high-risk haplotype in the DTNBP1 (dysbindin) gene and clinical features of schizophrenia

The purpose of this study was to determine whether a haplotype in the dystrobrevin binding protein 1 (DTNBP1) gene previously associated with schizophrenia not only increases the susceptibility to psychotic illness but also to a more or less clinically specific form of psychotic illness.

Interleukin 3 and schizophrenia:the impact of sex and family history

Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia. In this paper, we report evidence that multiple single nucleotide polymorphisms in and around interleukin 3 (IL3) are associated with the disease in the Irish Study of High-Density Schizophrenia Families (ISHDSF), the Irish Case-Control Study of Schizophrenia (ICCSS) and the Irish Trio Study of Schizophrenia (ITRIO). The associations are sex-specific and depend on the family history (FH) of schizophrenia. In all three samples, rs31400 shows female-specific and FH-dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and ITRIO, respectively). Several markers have similar associations in one or two of the three samples. In haplotype analyses, identical risk and protective haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker combinations. For ICCSS, the same haplotypes are implicated; however, the risk haplotypes observed in the family samples become protective. Several significant markers, rs440970, rs31400 and rs2069803, are located in and around known estrogen response elements, promoter and enhancer of the IL3 gene. They may explain the sex-specific associations and be functional for the expression of IL3 gene.

Religion and the risk of suicide: longitudinal study of over 1 million people

Background: Durkheim’s seminal historical study demonstrated that religious affiliation reduces suicide risk, but it is unclear whether this protective effect persists in modern, more secular societies.

Aims: To examine suicide risk according to Christian religious affiliation and by inference to examine underlying mechanisms for suicide risk. If church attendance is important, risk should be lowest for Roman Catholics and highest for those with no religion; if religiosity is important, then ‘conservative’ Christians should fare best.

Method: A 9-year study followed 1 106 104 people aged 16–74 years at the 2001 UK census, using Cox proportional hazards models adjusted for census-based cohort attributes.

Results: In fully adjusted models analysing 1119 cases of suicide, Roman Catholics, Protestants and those professing no religion recorded similar risks. The risk associated with conservative Christians was lower than that for Catholics (HR = 0.71, 95% CI 0.52–0.97).

Conclusions: The relationship between religious affiliation and suicide established by Durkheim may not pertain in societies where suicide rates are highest at younger ages. Risks are similar for those with and without a religious affiliation, and Catholics (who traditionally are characterised by higher levels of church attendance) do not demonstrate lower risk of suicide. However, religious affiliation is a poor measure of religiosity, except for a small group of conservative Christians, although their lower risk of suicide may be attributable to factors such as lower risk behaviour and alcohol consumption.

A systematic review and meta-analysis of the ethnic density effect in psychotic disorders

A number of studies have found an ethnic density effect in psychotic disorders, where the incidence for ethnic minorities increases as the neighbourhood proportional ethnic composition decreases [Morgan and Hutchinson, Psychol Med 40:705-709, (2010); Singh, Psychol Med 39:1402-1403, (2009); Schofield et al., Psychol Med 41:1263-1269, (2010)]. However, there is a mixed picture with some studies reporting no effect [Schofield et al., Psychol Med 41:1263-1269, (2010)]. This review aimed to establish the existence of the effect by answering the review question: is there an ethnic density dose effect in the prevalence of psychotic disorders?

Evidence that duplications of 22q11.2 protect against schizophrenia

A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47?005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5-3.0?Mb) at 22q11.2-the reciprocal of the well-known, risk-inducing deletion of this locus-are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia.

Paranoia and self-concepts in psychosis: A systematic review of the literature.

The purpose of the present study was to review systematically, research exploring the relationship between self-concepts and paranoia in psychosis. A literature search was performed by two independent raters in relevant databases (MedLine, PsychInfo and Web of Science) and articles meeting the inclusion criteria were cross-referenced. Following scrutiny according to inclusion criteria, 18 studies were selected for review. A narrative synthesis of findings, in which methodological variability is discussed, is presented relative to three key areas: the nature of the relationship between paranoia and self-concepts; the association between paranoia and discrepancies in self-concepts; the nature of the relationship between paranoia and self-concepts when other, dimensional aspects of these constructs are taken into account. The systematic literature review indicated relatively consistent findings, that paranoia is associated with more negative self-concepts when measured cross-sectionally. Results are somewhat more mixed in regards to research on paranoia and self-concept discrepancies. Studies investigating dimensional aspects of self-concepts and paranoia yield findings of particular interest, especially in regards to the association indicated between instability of self-concepts and paranoia. Limitations in research and of the present systematic review are discussed. Clinical and theoretical implications of findings are outlined and possible directions for future research are suggested.

Awareness and knowledge of autism and autism interventions: A general population survey.

Recent figures show that Autism Spectrum Disorder (ASD) affects at least 1 in 88 of the population, yet for years, international public awareness of ASD was limited. Over the past 5-10 years intense efforts have been made to raise autism awareness in the general population in countries such as UK and US. In this paper we report data from a large-scale general population survey (n=1204) in which we assessed autism awareness, knowledge about autism, and perceptions about autism interventions in Northern Ireland. We found high levels of autism awareness, in fact over 80% of the sample were aware of ASD and over 60% of these respondents knew someone with ASD in their own family, circle of friends or work colleagues. Generally, knowledge of strengths and challenges faced by individuals with ASD was relatively accurate. However, perceptions of interventions and service provider responsibilities were vague and uncertain. Results show that local and international autism awareness campaigns have largely been successful and that the focus should shift towards disseminating accurate information regarding intervention and service provider responsibilities.

Temper outbursts in Prader-Willi syndrome: causes, behavioural and emotional sequence and responses by carers

Background: Temper outbursts are common in Prader-Willi syndrome but rarely described in detail. This study investigated the phenomenology of temper outbursts in terms of antecedents, sequence of behaviours and emotions and intervention strategies used.

Method: A semi-structured interview about temper outbursts was conducted with the main carers of seven children (9.5 to 16.7 years) and seven adults (24.7 to 47.10 years) with Prader-Willi syndrome (10 male, 4 female). Reliability and validity of the interview results was established.

Results: Various setting events increased and reduced the likelihood of temper outbursts. The most common antecedent was a change to routine or expectation. There were marked similarities in the sequence of behaviours and emotions during temper outbursts, with anger rising quickly followed by expressions of remorse and distress at the end of an outburst.

Discussion: The sequence of behaviours and emotions within outbursts was similar to that described in temper tantrums in typical development. Cognitive and emotional processes are likely to be important in the understanding of temper outbursts with implications for early intervention.

No evidence that runs of homozygosity are associated with schizophrenia in an Irish genome-wide association dataset

Runs of homozygosity (ROH), regions of the genome containing many consecutive homozygous SNPs, may represent two copies of a haplotype inherited from a common ancestor. A rare variant on this haplotype could thus be present in a homozygous and potentially recessive state. To detect rare risk variants for schizophrenia, we performed an ROH analysis in a homogeneous Irish genome wide association study (GWAS) dataset consisting of 1606 cases and 1794 controls. There was no genome-wide excess of ROH in cases compared to controls (p=0.7986). No consensus ROH at individual loci showed association with schizophrenia after genome-wide correction.

Age related differences in mental health scale scores and depression diagnosis: Adult responses to the CIDI-SF and MHI-5.

Inconsistencies surrounding the prevalence levels of depression in later life suggest that the measurement of depression in older people may be problematic. The current study aimed to map responses to a depressive symptom scale, the Mental Health Index-5 (MHI-5) which is part of the Short form 36 (SF-36, Ware et al., 1993) against the diagnostic screening items of the Composite International Diagnostic Instrument-Short Form (CIDI-SF, Kessler et al., 1998) to examine disagreement rates across age groups. The study examined data from a national random sample of 10,641 participants living in Ireland, 58.8% were female and 19% were over 65 (SLÁN, 2007). CIDI-SF depression screening endorsement was lower in older groups, whereas mean MHI-5 depressive symptoms showed less change across age groups. Results showed that the odds of MHI-5 endorsers aged 18–44 endorsing CIDI-SF screening questions were 5 times and 4.5 times (dysphoria and anhedonia, respectively) greater than the odds of people aged 75 or more endorsing these items. Findings suggest that although the risk of depressive disorder may decrease with age, complex diagnostic screening questions may exaggerate lower rates of depression among older people.