There is a great deal of debate on the usefulness and accuracy of prodromal criteria in predicting schizophrenia. The risk of treating people who screen false positive with medication is considerable. Yet intervening during the prodromal stage of illness may reduce the burden caused by schizophrenia.

To draw together the evidence base for the predictive validity of prodromal criteria in identifying individuals at high risk of developing schizophrenia.

We conducted a systematic review of prospective studies investigating the predictive validity of prodromal criteria in schizophrenia.

Our study found two main criteria, ultra-high-risk criteria and basic-symptoms criteria, used in studies investigating the predictive validity of prodromal symptoms. The sensitivity and specificity of ultra-high-risk criteria was 0.81 (95% CI 0.76–0.85) and 0.67 (95% CI 0.64–0.70) respectively and for basic-symptoms criteria sensitivity and specificity was 0.97 (95% CI 0.91–1.00) and 0.59 (95% CI 0.48–0.70) respectively.

Both ultra-high-risk criteria and basic-symptoms criteria are useful in predicting the development of schizophrenia among high-risk populations.

Biological or genetic models of mental illness are commonly expected to increase tolerance towards people with mental illness, by reducing notions of responsibility and blame.

To investigate whether biogenetic causal attributions of mental illness among the general public are associated with more tolerant attitudes, whether such attributions are related to lower perceptions of guilt and responsibility, to what extent notions of responsibility are associated with rejection of people who are mentally ill, and how prevalent notions of responsibility are among the general public with regard to different mental disorders.

A systematic review was conducted of representative population studies examining attitudes towards people with mental illness and beliefs about such disorders.

We identified 33 studies relevant to this review. Generally, biogenetic causal attributions were not associated with more tolerant attitudes; they were related to stronger rejection in most studies examining schizophrenia. No published study reported on associations of biogenetic causal attributions and perceived responsibility. The stereotype of self-responsibility was unrelated to rejection in most studies. Public images of mental disorder are generally dominated by the stereotypes of unpredictability and dangerousness, whereas responsibility is less relevant.

Biogenetic causal models are an inappropriate means of reducing rejection of people with mental illness.

There is a long-standing belief that creativity is coupled with psychopathology.

To test this alleged association and to investigate whether any such association is the result of environmental or genetic factors.

We performed a nested case–control study based on Swedish registries. The likelihood of holding a creative occupation in individuals who had received in-patient treatment for schizophrenia, bipolar disorder or unipolar depression between 1973 and 2003 and their relatives without such a diagnosis was compared with that of controls.

Individuals with bipolar disorder and healthy siblings of people with schizophrenia or bipolar disorder were overrepresented in creative professions. People with schizophrenia had no increased rate of overall creative professions compared with controls, but an increased rate in the subgroup of artistic occupations. Neither individuals with unipolar depression nor their siblings differed from controls regarding creative professions.

A familial cosegregation of both schizophrenia and bipolar disorder with creativity is suggested.

A putative interaction between cannabis and variation at rs4680 within the catechol-methyl-transferase (COMT) gene on psychosis has been reported, but not adequately replicated.

To examine whether the relative risk of developing psychosis following use of cannabis is dependent upon variation within COMT.

A longitudinal study of 2630 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort who completed questionnaire-based assessments for cannabis use at age 14 and incident psychotic experiences at age 16. Six SNPs within COMT were genotyped.

There was no evidence of an interaction under multiplicative models between cannabis use and COMT on the risk of developing psychotic experiences in our primary analyses. In sensitivity analyses we observed highly variable evidence of interaction, whereby psychotomimetic effects of cannabis were greater in methionine homozygotes under some scenarios, but in valine homozygotes under others.

Cannabis increases risk of psychosis irrespective of underlying COMT genotypes. These findings argue against the widely held belief that the relative risk of developing psychosis following use of cannabis is dependent upon variation within COMT. The public health message about the potential increase in risk of psychotic disorders following cannabis use should not be tempered by reports that this harm is subgroup specific in the absence of robust evidence of replication.

No longitudinal study has yet examined the association between substance use and brain volume changes in a population at high risk of schizophrenia.

To examine the effects of cannabis on longitudinal thalamus and amygdala-hippocampal complex volumes within a population at high risk of schizophrenia.

Magnetic resonance imaging scans were obtained from individuals at high genetic risk of schizophrenia at the point of entry to the Edinburgh High-Risk Study (EHRS) and approximately 2 years later. Differential thalamic and amygdala-hippocampal complex volume change in high-risk individuals exposed (n = 25) and not exposed (n = 32) to cannabis in the intervening period was investigated using repeated-measures analysis of variance.

Cannabis exposure was associated with bilateral thalamic volume loss. This effect was significant on the left (F = 4.47, P = 0.04) and highly significant on the right (F=7.66, P=0.008). These results remained significant when individuals using other illicit drugs were removed from the analysis.

These are the first longitudinal data to demonstrate an association between thalamic volume loss and exposure to cannabis in currently unaffected people at familial high risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

Low serotonin transmission is thought to increase susceptibility to a wide range of substance use disorders and impulsive traits.

To investigate the effects of lowered serotonin on cocaine-induced (1.0 mg/kg cocaine, self-administered intranasally) dopamine responses and drug craving.

In non-dependent cocaine users, serotonin transmission was reduced using the acute tryptophan depletion method. Striatal dopamine responses were measured using positron emission tomography with [11C]raclopride.

Acute tryptophan depletion increased drug craving and striatal dopamine responses to cocaine. These acute tryptophan depletion-induced increases did not occur in the absence of cocaine.

The results suggest that low serotonin transmission can increase dopaminergic and appetitive responses to cocaine. These findings might identify a mechanism by which individuals with low serotonin are at elevated risk for both substance use disorders and comorbid conditions.

Submicroscopic, rare chromosomal copy number variants (CNVs) contribute to neurodevelopmental disorders but it is not known whether they define atypical clinical cases.

To identify whether large, rare CNVs in attention-deficit hyperactivity disorder (ADHD) are confined to a distinct clinical subgroup.

A total of 567 children with ADHD aged 5–17 years were recruited from community clinics. Psychopathology was assessed using the Child and Adolescent Psychiatric Assessment. Large, rare CNVs (>500 kb, <1% frequency) were defined from single nucleotide polymorphism data.

Copy number variant carriers (13.6%) showed no differences from non-carriers in ADHD symptom severity, symptom type, comorbidity, developmental features, family history or pre-/ perinatal markers. The only significant difference was a higher rate of intellectual disability (24% v. 9%, χ2 = 15.5, P = 0.001). Most CNV carriers did not have intellectual disability.

Large, rare CNVs are not restricted to an atypical form of ADHD but may be more highly enriched in children with cognitive problems.

Structural brain abnormalities are associated with late-life major depression, with numerous studies reporting increased white matter hyperintensities (WMH) and reduced cortical/subcortical grey matter volumes. There is strong evidence linking vascular disease to WMH, but limited evidence on its association with subcortical volumes.

To investigate the relationship of orthostatic blood pressure changes to WMH and subcortical grey matter volumes in late-life depression.

Thirty-eight people with depression and a similarly aged comparison group (n = 30) underwent fluid attenuated inversion recovery (FLAIR) and T1-weighted magnetic resonance imaging as well as systematic orthostatic blood pressure assessments. Volumetric estimates of WMH and subcortical grey matter were obtained for each participant and the relationship to blood pressure drop on active stand was examined.

An association between orthostatic systolic blood pressure drop and WMH volumes in temporal and parietal regions was found in the depression group (age-corrected partial correlation r’ = 0.31–0.35, P<0.05). Subcortical volumes were not related to blood pressure changes or WMH volumes in either group.

We found evidence for an association between the degree of orthostatic systolic blood pressure drop and WMH volume in the depression group. Since blood pressure drops lead to WMH in animals our findings suggest systolic blood pressure drops may be a factor contributing to these lesions in late-life depression.

Although there is speculation that individuals living in the vicinity of nuclear disasters have persistent mental health deterioration due to psychological stress, few attempts have been made to examine this issue.

To determine whether having been in the vicinity of the Nagasaki atomic bomb explosion in the absence of substantial exposure to radiation affected the mental health of local inhabitants more than half a century later.

Participants were randomly recruited from individuals who lived in the vicinity of the atomic bomb explosion in uncontaminated suburbs of Nagasaki. This sample (n = 347) was stratified by gender, age, perception of the explosion and current district of residence. Controls (n = 288) were recruited from among individuals who had moved into the area from outside Nagasaki 5–15 years after the bombing, matched for gender, age and district of residence. The primary outcome measure was the proportion of those at high risk of mental disorder based on the 28-item version of the General Health Questionnaire, with a cut-off point of 5/6. Other parameters related to individual perception of the explosion, health status, life events and habits were also assessed.

Having been in the vicinity of the explosion was the most significant factor (OR = 5.26, 95% CI 2.56–11.11) contributing to poorer mental health; erroneous knowledge of radiological hazard showed a mild association. In the sample group, anxiety after learning of the potential radiological hazard was significantly correlated with poor mental health (P<0.05), whereas anxiety about the explosion, or the degree of perception of it, was not; 74.5% of the sample group believed erroneously that the flash of the explosion was synonymous with radiation.

Having been in the vicinity of the atomic bomb explosion without radiological exposure continued to be associated with poorer mental health more than half a century after the event. Fear on learning about the potential radiological hazard and lack of knowledge about radiological risk are responsible for this association.

People with dementia often die badly, receiving end-of-life care of poorer quality than that given to those who are cognitively intact.

To define good end-of-life care for people with dementia and identify how it can be delivered across care settings in the UK.

In-depth interviews were conducted with 27 bereaved family carers and 23 care professionals recruited from the community, care homes, general hospitals and continuing care units. Data were analysed using the constant comparison method.

The data highlighted the challenge and imperative of ‘dementia-proofing’ end-of-life care for people with dementia. This requires using dementia expertise to meet physical care needs, going beyond task-focused care and prioritising planning and communication with families.

The quality of end-of-life care exists on a continuum across care settings. Together, the data reveal key elements of good end-of-life care and that staff education, supervision and specialist input can enable its provision.