Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.

A single nucleotide polymorphism rs12807809 located upstream of the neurogranin (NRGN) gene has been identified as a risk variant for schizophrenia in recent genome-wide association studies. To date, there has been little investigation of the endophenotypic consequences of this variant, and our own investigations have suggested that the effects of this gene are not apparent at the level of cognitive function in patients or controls. Because the impact of risk variants may be more apparent at the level of brain, the aim of this investigation was to delineate whether NRGN genotype predicted variability in brain structure and/or function. Healthy individuals participated in structural (N = 140) and/or functional (N = 36) magnetic resonance imaging (s/fMRI). Voxel-based morphometry was used to compare gray and white matter volumes between carriers of the non-risk C allele (i.e., CC/CT) and those who were homozygous for the risk T allele. Functional imaging data were acquired during the performance of a spatial working memory task, and were also analyzed with respect to the difference between C carriers and T homozygotes. There was no effect of the NRGN variant rs12807809 on behavioral performance or brain structure. However, there was a main effect of genotype on brain activity during performance of the working memory task, such that while C carriers exhibited a load-independent decrease in left superior frontal gyrus/BA10, TT individuals failed to show a similar decrease in activity. The failure to disengage this ventromedial prefrontal region, despite preserved performance, may be indicative of a reduction in processing efficiency in healthy TT carriers. Although it remains to be established whether this holds true in larger samples and in patient cohorts, if valid, this suggests a potential mechanism by which NRGN variability might contribute to schizophrenia risk.

Poor insight is associated with impaired cognitive function in psychosis. Whether poor clinical insight overlaps with other aspects of self-awareness in schizophrenia, such as cognitive self-awareness, is unclear. We investigated whether awareness of clinical state (“clinical insight”) and awareness of cognitive deficits (“cognitive insight”) overlap in schizophrenia in a sample of 51 stabilized patients with chronic schizophrenia. Cognitive insight was assessed in terms of the agreement between subjective self-report and neuropsychological assessment. Patients who show good cognitive insight did not necessarily show good clinical insight. By contrast, self-report and objective neuropsychological assessment only correlated for patients in the intact clinical insight group and not for those in the impairment clinical insight group. We conclude that while good cognitive insight may not be necessary for good clinical insight, good cognitive awareness is at least partly reliant on the processes involved in clinical insight. (JINS, 2009, 15, 471–475.)

Objective: The aim of this study was to investigate the attitudes to medication in relation to insight, purpose in life, symptoms and sociodemographic factors among a cohort of stable patients with a diagnosis of schizophrenia and schizoaffective disorder.

Method: We included 70 patients with a diagnosis of schizophrenia and schizoaffective disorder attending a Dublin suburban mental health service. All participants were 18 years or older and were excluded if they had a learning disability, acquired brain injury resulting in unconsciousness, and psychosis secondary to a general medical condition or illicit substance misuse. All participants were given self report questionnaires which included Drug Attitude Inventory (DAI-30), Birchwood Insight Scale, and Purpose in Life test. Symptoms were assessed using the Scale for Assessment of Positive and Negative symptoms. All data was analysed using the Statistical Package for the Social Sciences.

Results: We found that 86% (n = 60) of the participants had positive attitudes to medication, and 82% (n = 58) had good insight into their illness. Only 27% (n = 19) were found to have a definite purpose in life. There was a significant negative relationship between attitudes to medication and delusions (r = -0.25, n = 70, p < 0.05) and a significant positive relationship between insight and attitudes to medication (r = 0.0.28, n = 70, p < 0.05).

Conclusion: Many factors are involved in the multifaceted issue of attitudes to medication. Researchers must realise that these factors do not remain constant and may change with time and over the course of illness and treatment.

Theory of mind deficits in schizophrenia have been parsed into mental state reasoning and mental state decoding components. We report that mental state decoding as measured by the ‘Eyes task’ better predicted social function than mental state reasoning as measured by the ‘Hinting task’ in 73 out-patients with chronic schizophrenia. Mental state decoding task performance also partly mediated the influence of basic neuropsychological performance on social function. We discuss these findings in terms of the accumulating evidence that mental state decoding has particular relevance for understanding deficits in social function in schizophrenia

Objectives: People with schizophrenia are at increased risk of cardiovascular and endocrine disease. National guidelines recommend the physical health of people with schizophrenia be monitored by primary care, but little is known about whether such people attend primary care. We sought to examine the prevalence of cardiovascular and endocrine disease in a stable population with schizophrenia, and factors associated with attending primary care.

Method: A cross sectional survey of people with a diagnosis of schizophrenia/schizoaffective disorder was taken from a larger cohort participating in the Resource for Psychoses and Genomics in Ireland (RPGI) study. Participants were interviewed using standardised clinical assessments, and underwent anthropometric measurements, and further information was collected by medical record review and contacting the general practitioner (GP).

Results: Thirteen percent (n = 14) had established cardiovascular disease and 4.3% (n = 4) had type 2 diabetes. Risk factors for cardiovascular disease and type 2 diabetes were higher than the general population. Sixty-eight point five percent (n = 63) had attended their GP at least once in the previous year. Only 35% self reported a physical illness. Females (p = 0.03), those with both self-reported presence of physical illness (p = 0.007), and diagnosed physical illness (p = 0.001) were more likely to attend their GP. Other psychosocial, psychological and illness related variables did not predict attendance at primary care.

Conclusion: While established patients attend their GP, they had significant unidentified risk factors for cardiovascular disease and type 2 diabetes. It is likely that non-attendees at secondary care would fare worse yet.

Background: Despite its inhibitory control requirements, antisaccade deficits have been consistently associated with working memory impairments in schizophrenia. We investigated whether variance in antisaccade performance could be better accounted for in terms of a specific inhibitory function. Method: We assessed 48 clinically stable out-patients with schizophrenia on an antisaccade task, as well as on measures of spatial and verbal working memory, sustained selective attention, and a simple motoric go/no-go measure of response inhibition. Results: In a stepwise multiple regression analysis, go/no-go task performance accounted for a considerably greater percentage of variance in antisaccade performance (25.3%) than either working memory (8.4%) or sustained selective attention task (9.1%). Discussion: We conclude that antisaccade deficits in schizophrenia appear to be better understood in terms of a specific deficit of inhibitory control than in terms of more general difficulties with context maintenance or goal neglect. (JINS, 2006, 12, 901–906.)

Objectives: To assess the current attitudes of Irish psychiatric trainees to their training and to determine whether problems identified five years ago have improved.

Method: A postal questionnaire was circulated to all identified psychiatric trainees in the eastern region of Ireland over a six-month period in 2000.

Results: 153 (62%) trainees responded to the study, and 81% described their training as ‘adequate’ or better. Significant demographic changes over the last five years are recorded. Satisfactory induction, regular supervision and access to tutors are all associated with higher overall satisfaction with training. Sixty-seven per cent report receiving an induction course, but just 40% describe this as satisfactory, and only 49% of trainees receive regular supervision. Specific difficulties in training are reported less frequently than in 1995, but 35% of non-EU doctors report racial discrimination in training and only 59% of trainees received a practical demonstration prior to administering electroconvulsive therapy (ECT).

Conclusions: Trainees continue to express high levels of satisfaction with their training. Improvements have been made in a number of key areas, although difficulties remain. For example, regular supervision, which was associated with a positive outlook on training, are unavailable to a majority of trainees.

Asperger syndrome is an uncommon condition, but probably more common than classic autism (the only published population study estimated prevalence at 36 per 10 000 children for Asperger syndrome and 5 per 10 000 for autism (Ehlers & Gillberg, 1993)). Misdiagnosis or delayed diagnosis of this disorder is a serious problem, and the average age at diagnosis is several years later than for autism (Gillberg, 1989). Obviously, this can be traumatic for individuals and families; furthermore, the most effective intervention programmes begin early, and establishing management strategies at an early age can minimise later behavioural problems (Howlin, 1998).