The aetiology of autism is unknown, although prenatal exposures have been the focus of epidemiological research for over 40 years.

Aims

To provide the first quantitative review and meta-analysis of the association between maternal pregnancy complications and pregnancy-related factors and risk of autism.

Method

PubMed, Embase and PsycINFO databases were searched for epidemiological studies that examined the association between pregnancy-related factors and autism. Forty studies were eligible for inclusion in the meta-analysis. Summary effect estimates were calculated for factors examined in multiple studies.

Results

Over 50 prenatal factors have been examined. The factors associated with autism risk in the meta-analysis were advanced parental age at birth, maternal prenatal medication use, bleeding, gestational diabetes, being first born v. third or later, and having a mother born abroad. The factors with the strongest evidence against a role in autism risk included previous fetal loss and maternal hypertension, proteinuria, pre-eclampsia and swelling.

Conclusions

There is insufficient evidence to implicate any one prenatal factor in autism aetiology, although there is some evidence to suggest that exposure to pregnancy complications may increase the risk.

Feedback of treatment outcome during the course of therapy (outcome management) is increasingly considered to be beneficial for improving the quality of mental healthcare.

Aims

To review the impact of feedback of outcome to practitioners and/or patients in specialist mental health services.

Method

A systematic search and meta-analysis of controlled trials using outcome management in mental health services published in English or German language.

Results

Twelve studies met inclusion criteria. Feeding back outcome showed a small, but significant (d = 0.10; 95% CI 0.01–0.19) positive short-term effect on the mental health of individuals that did not prevail in the long run. Subgroup analysis revealed no significant differences regarding feedback modalities. Outcome management did not contribute to a reduction of treatment duration.

Conclusions

Evidence on the effects of outcome management in mental healthcare is promising. More targeted research is needed in order to identify the effective ingredients of outcome feedback and to assess its cost-effectiveness.

Psychiatric phenotypes are currently defined according to sets of descriptive criteria. Although many of these phenotypes are heritable, it would be useful to know whether any of the various diagnostic categories in current use identify cases that are particularly helpful for biological–genetic research.

Aims

To use genome-wide genetic association data to explore the relative genetic utility of seven different descriptive operational diagnostic categories relevant to bipolar illness within a large UK case–control bipolar disorder sample.

Method

We analysed our previously published Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder genome-wide association data-set, comprising 1868 individuals with bipolar disorder and 2938 controls genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met stringent criteria for genotype quality. For each SNP we performed a test of association (bipolar disorder group v. control group) and used the number of associated independent SNPs statistically significant at P<0.00001 as a metric for the overall genetic signal in the sample. We next compared this metric with that obtained using each of seven diagnostic subsets of the group with bipolar disorder: Research Diagnostic Criteria (RDC): bipolar I disorder; manic disorder; bipolar II disorder; schizoaffective disorder, bipolar type; DSM–IV: bipolar I disorder; bipolar II disorder; schizoaffective disorder, bipolar type.

Results

The RDC schizoaffective disorder, bipolar type (v. controls) stood out from the other diagnostic subsets as having a significant excess of independent association signals (P<0.003) compared with that expected in samples of the same size selected randomly from the total bipolar disorder group data-set. The strongest association in this subset of participants with bipolar disorder was at rs4818065 (P = 2.42x10^–7). Biological systems implicated included gamma amniobutyric acid (GABA)_A receptors. Genes having at least one associated polymorphism at P<10^–4 included B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2 and CDH12.

Conclusions

Our findings show that individuals with broadly defined bipolar schizoaffective features have either a particularly strong genetic contribution or that, as a group, are genetically more homogeneous than the other phenotypes tested. The results point to the importance of using diagnostic approaches that recognise this group of individuals. Our approach can be applied to similar data-sets for other psychiatric and non-psychiatric phenotypes.

There have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR is modulated by gender, age and other variants in the serotonin transporter gene.

Aims

To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor).

Method

The 5-HTTLPR and 13 additional markers across the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project.

Results

The 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more than short-allele homozygotes. A significant three-way interaction between 5-HTTLPR, drug and gender indicated that the effect was concentrated in males treated with escitalopram. The single-nucleotide polymorphism rs2020933 also influenced outcome.

Conclusions

The effect of 5-HTTLPR on antidepressant response is SSRI specific conditional on gender and modulated by another polymorphism at the 5' end of the serotonin transporter gene.

The short (s) allele of the serotonin transporter gene promoter (5-HTTLPR) may be associated with exposure to social adversities and the subsequent onset of depressive illness in adulthood.

Aims

To test in adolescents at high risk for depression whether the short ‘s’ allele is associated with levels of morning cortisol and the subsequent onset of a depressive episode.

Method

High-risk adolescents (n = 403) were genotyped for 5-HTTLPR. Salivary samples were obtained on four consecutive school days within 1 h of waking from 393 (97.5%) individuals and 367 (91%) underwent a mental state reassessment at 12 months.

Results

Multilevel analysis revealed higher levels of salivary cortisol in short allele carriers (s/s>s/l>l/l). A subsequent episode of depression was increased in those with higher cortisol and the ‘s’ allele, and independently by depressive symptoms at entry, in both genders.

Conclusions

The short allele of 5-HTTLPR may moderate the association between morning cortisol and the subsequent onset of a depressive episode.

Little is known about the cross-national population prevalence or correlates of personality disorders.

Aims

To estimate prevalence and correlates of DSM–IV personality disorder clusters in the World Health Organization World Mental Health (WMH) Surveys.

Method

International Personality Disorder Examination (IPDE) screening questions in 13 countries (n = 21 162) were calibrated to masked IPDE clinical diagnoses. Prevalence and correlates were estimated using multiple imputation.

Results

Prevalence estimates are 6.1% (s.e. = 0.3) for any personality disorder and 3.6% (s.e. = 0.3), 1.5% (s.e. = 0.1) and 2.7% (s.e. = 0.2) for Clusters A, B and C respectively. Personality disorders are significantly elevated among males, the previously married (Cluster C), unemployed (Cluster C), the young (Clusters A and B) and the poorly educated. Personality disorders are highly comorbid with Axis I disorders. Impairments associated with personality disorders are only partially explained by comorbidity.

Conclusions

Personality disorders are relatively common disorders that often co-occur with Axis I disorders and are associated with significant role impairments beyond those due to comorbidity.

It has been suggested that rural–urban migration will have adverse consequences for older parents left behind.

Aims

To describe correlates of outmigration and to estimate any association between outmigration of children and depression in rural-dwelling older parents.

Method

Population-based survey of 1147 parents aged 60 and over in rural Thailand. We randomly oversampled parents living without children. We defined an outmigrant child as living outside their parent’s district, and measured depression as a continuous outcome with a Thai version of the EURO–D.

Results

Outmigration of all children, compared with outmigration of some or no children, was independently associated with less depression in parents. This association remained after taking account of social support, parent characteristics, health and wealth. Parents with all children outmigrated received more economic remittances and they perceived support to be as good as that of those with children close by.

Conclusions

Outmigration of children was not associated with greater depression in older parents and, after taking account of a range of possible covariables, was actually associated with less parental depression. This could be explained by pre-existing advantages in families sending more migrants and by the economic benefits of migration.

Increasing numbers of people will die with dementia, many in the acute hospital. It is often not perceived to be a life-limiting illness.

Aims

To investigate the prevalence of dementia in older people undergoing emergency medical admission and its effect on outcomes.

Method

Longitudinal cohort study of 617 people (aged over 70). The main outcome was mortality risk during admission.

Results

Of the cohort, 42.4% had dementia (only half diagnosed prior to admission). In men aged 70–79, dementia prevalence was 16.4%, rising to 48.8% of those over 90. In women, 29.6% aged 70–79 had dementia, rising to 75.0% aged over 90. Urinary tract infection or pneumonia was the principal cause of admission in 41.3% of the people with dementia. These individuals had markedly higher mortality; 24.0% of those with severe cognitive impairment died during admission (adjusted mortality risk 4.02, 95% CI 2.24–7.36).

Conclusions

The rising prevalence of dementia will have an impact on acute hospitals. Extra resources will be required for intermediate and palliative care and mental health liaison services.

Researching psychotic disorders in unison rather than as separate diagnostic groups is widely advocated, but the viability of such an approach requires careful consideration from a neurocognitive perspective.

Aims

To describe cognition in people with bipolar disorder and schizophrenia and to examine how known causes of variability in individual’s performance contribute to any observed diagnostic differences.

Method

Neurocognitive functioning in people with bipolar disorder (n = 32), schizophrenia (n = 46) and healthy controls (n = 67) was compared using analysis of covariance on data from the Northern Ireland First Episode Psychosis Study.

Results

The bipolar disorder and schizophrenia groups were most impaired on tests of memory, executive functioning and language. The bipolar group performed significantly better on tests of response inhibition, verbal fluency and callosal functioning. Between-group differences could be explained by the greater proclivity of individuals with schizophrenia to experience global cognitive impairment and negative symptoms.

Conclusions

Particular impairments are common to people with psychosis and may prove useful as endophenotypic markers. Considering the degree of individuals’ global cognitive impairment is critical when attempting to understand patterns of selective impairment both within and between these diagnostic groups.

Computerised cognitive–behavioural therapy (CCBT) might offer a solution to the current undertreatment of depression.

Aims

To determine the clinical effectiveness of online, unsupported CCBT for depression in primary care.

Method

Three hundred and three people with depression were randomly allocated to one of three groups: Colour Your Life; treatment as usual (TAU) by a general practitioner; or Colour Your Life and TAU combined. Colour Your Life is an online, multimedia, interactive CCBT programme. No assistance was offered. We had a 6-month follow-up period.

Results

No significant differences in outcome between the three interventions were found in the intention-to-treat and per protocol analyses.

Conclusions

Online, unsupported CCBT did not outperform usual care, and the combination of both did not have additional effects. Decrease in depressive symptoms in people with moderate to severe depression was moderate in all three interventions. Online CCBT without support is not beneficial for all individuals with depression.