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The pathogenesis of Alzheimer's disease is complex. The amyloid hypothesis
has directed research efforts for many years, but it has recently been
questioned after failed drug trials. Here, we review the evidence for and
against and suggest that it might be premature to abandon the amyloid
There is a growing research interest in childhood hallucinations as
predictors of psychotic states. This work appears to have limited direct
relevance for clinical child psychiatric practice, but it highlights the
continuing relevance of research into precursors of psychotic states and
into the determinants of clinically relevant hallucinations in children.
Language dictates how individuals process and understand concepts. This
phenomenon is examined for the terms ‘antipsychotic’ and ‘antidepressant’.
When the use of medications is extended in new directions (for example when
an antipsychotic is used as an antidepressant), the name not only loses its
utility, but may become an obstacle to treatment. Clinicians need to be
aware of these issues.
Cardiac vagal tone, indexed by heart rate variability (HRV), is a proxy
for the functional integrity of feedback mechanisms integrating central
and peripheral physiology.
To quantify differences in HRV in individuals with schizophrenia compared
with healthy controls.
Databases were systematically searched for studies eligible for
inclusion. Random effect meta-analyses of standardised mean differences
were calculated for vagal activity indicated by high-frequency HRV and
the root mean square of successive R–R interval differences (RMSSD).
Thirty-four studies were included. Significant main effects were found
for high-frequency HRV (P = 0.0008; Hedges'
g =–0.98, 95% CI −1.56 to −0.41, k =
29) and RMSSD (P<0.0001; g =–0.91,
95% CI −1.19 to −0.62, k = 24), indicating lower vagal
activity in individuals with schizophrenia than in healthy controls.
Considerable heterogeneity was evident but effects were robust in
subsequent sensitivity analyses.
Given the association between low HRV, threat processing, emotion
regulation and executive functioning, reduced vagal tone may be an
endophenotype for the development of psychotic symptoms.
Secure hospitals are a high-cost, low-volume service consuming around a
fifth of the overall mental health budget in England and Wales.
A systematic review and meta-analysis of adverse outcomes after discharge
along with a comparison with rates in other clinical and forensic groups
in order to inform public health and policy.
We searched for primary studies that followed patients discharged from a
secure hospital, and reported mortality, readmissions or reconvictions.
We determined crude rates for all adverse outcomes.
In total, 35 studies from 10 countries were included, involving 12 056
patients out of which 53% were violent offenders. The crude death rate
for all-cause mortality was 1538 per 100 000 person-years (95% CI
1175–1901). For suicide, the crude death rate was 325 per 100 000
person-years (95% CI 235– 415). The readmission rate was 7208 per 100 000
person-years (95% CI 5916–8500). Crude reoffending rates were 4484 per
100 000 person-years (95% CI 3679–5287), with lower rates in more recent
There is some evidence that patients discharged from forensic psychiatric
services have lower offending outcomes than many comparative groups.
Services could consider improving interventions aimed at reducing
premature mortality, particularly suicide, in discharged patients.
The aetiological boundary between obsessive–compulsive related disorders
(OCRDs) including obsessive–compulsive disorder (OCD) and anxiety
disorders is unclear and continues to generate debate.
To determine the genetic overlap and the pattern of causal relationships
among OCRDs and anxiety disorders.
Multivariate twin modelling methods and a new regression analysis to
infer causation were used, involving 2495 male and female twins.
The amount of common genetic liability observed for OCD symptoms was
higher when considering anxiety disorders and OCRDs in the model
v. modelling OCRD symptoms alone. OCD symptoms
emerged as risk factors for the presence of generalised anxiety, panic
and hoarding symptoms, whereas social phobia appeared as a risk factor
for OCD symptoms.
OCD represents a complex phenotype that includes important shared
features with anxiety disorders and OCRDs. The novel patterns of risk
identified between OCD and anxiety disorder may help to explain their
Early-life adversity is a risk for obsessive–compulsive disorder (OCD),
but the impact at the neural level is less clear.
To investigate the association between brain volumes and early-life
adversity in individuals with a diagnosis of OCD only.
The Childhood Trauma Questionnaire (CTQ-28) was used to assess early-life
adversity in 21 participants with OCD and 25 matched healthy controls.
The relationship between global and regional brain volume and early-life
adversity was measured using voxel-based morphometry (VBM). All data were
corrected for multiple comparisons using family-wise error (FWE) at
In the OCD group, correlations with total CTQ scores were positively
associated with a larger right orbitofrontal cortex volume. Physical
neglect was higher in the OCD group than in controls and was positively
associated with larger right cerebellum volume in the OCD group only.
Larger brain volumes may reflect underlying developmental neuropathology
in adults with OCD who also have experience of childhood trauma.
The monoamine oxidase A (MAOA) gene has been shown to
moderate the impact of maltreatment on antisocial behaviour. Replication
efforts have, however, yielded inconsistent results.
To investigate whether the interaction between the MAOA
gene and violence is present across the full distribution of violence or
emerges at higher levels of exposure.
Participants were 327 male members of the Québec Longitudinal Study of
Kindergarten Children. Exposure to violence comprised retrospective
reports of mother's and father's maltreatment, sexual and physical abuse.
Conduct disorder and antisocial personality symptoms were assessed in
semi-structured interviews and partner violence, property-violent crimes
and arrest were self-reported.
Non-linear interactions between the MAOA gene and
violence were detected, suggesting that the genetic moderation may come
about once a certain level of violence is experienced.
Future studies should investigate the mechanisms translating substantial
violence exposure, which could, subsequently, trigger the expression of
genetically based differences in antisocial behaviour.
The relationship between ethnic density and psychiatric disorder in
postnatal women in the UK is unclear.
To examine the effect of own and overall ethnic density on postnatal
depression (PND) and personality dysfunction.
Multilevel analysis of ethnically mixed community-level data gathered
from a sample of 2262 mothers screened at 6 weeks postpartum for PND and
Living in areas of higher own ethnic density was protective against
screening positive for PND in White women (z =–3.18,
P = 0.001), even after adjusting for area level
deprivation, maternal age, relationship status, screening positive for
personality dysfunction, parity and geographical clustering (odds ratio
(OR) 0.98 (95% CI 0.96–0.99); P = 0.002), whereas the
effect on personality dysfunction (z =–2.42,
P = 0.016) was no longer present once the effect of
PND was taken into account (OR = 0.99 (95% CI 0.90–1.0);
P = 0.13). No overall ethnic density effect was found
for women screening positive for PND or personality dysfunction.
In White women, living in areas of higher own ethnic density was
protective against developing PND.
Light severely affects the occurrence of seasonal affective disorder
To compare the prevalence of SAD in persons with severe visual impairment
and persons with full sight, and in persons with severe visual impairment
with or without light perception.
This cross-sectional study assessed the Global Seasonality Score (GSS)
and the prevalence of SAD among 2781 persons with visual impairment and
4099 persons with full sight using the Seasonal Pattern Assessment
Respondents with visual impairment had significantly higher GSS and
prevalence of SAD compared with full sight controls,
P<0.001. Light perception respondents were more
vulnerable to seasonal change than both full sight and no light
The study showed a highly significant association between visual
impairment and SPAQ-defined SAD parameters, supporting the hypothesis
that decreased retinal light input plays a role in the pathogenesis of
Clinical and aetiological heterogeneity have impeded our understanding of
To evaluate differences in psychiatric and somatic course between people
with depression subtypes that differed clinically (severity) and
aetiologically (melancholic v. atypical).
Data from baseline, 2-, 4- and 6-year follow-up of The Netherlands Study
of Depression and Anxiety were used, and included 600 controls and 648
people with major depressive disorder (subtypes: severe melancholic
n = 308; severe atypical n = 167;
moderate n = 173, established using latent class
Those with the moderate subtype had a significantly better psychiatric
clinical course than the severe melancholic and atypical subtype groups.
Suicidal thoughts and anxiety persisted longer in those with the
melancholic subtype. The atypical subtype group continued to have the
highest body mass index and highest prevalence of metabolic syndrome
during follow-up, although differences between groups became less
pronounced over time.
Course trajectories of depressive subtypes mostly ran parallel to each
other, with baseline severity being the most important differentiator in
course between groups.
Depression is a highly prevalent disorder, causing a large burden of
disease and substantial economic costs. Web-based self-help interventions
seem promising in promoting mental health.
To compare the efficacy of a guided web-based intervention based on
acceptance and commitment therapy (ACT) with an active control
(expressive writing) and a waiting-list control condition (Netherlands
Trial Register NTR1296).
Adults with depressive symptoms from the general population were
randomised to ACT (n = 82), expressive writing
(n = 67) or waiting-list control (n
= 87). The main outcome was reduction in depressive symptoms assessed
with the Center for Epidemiological Studies – Depression scale.
Significant reductions in depressive symptoms were found following the
ACT intervention, compared with the control group (Cohen's
d = 0.56) and the expressive writing intervention
(d = 0.36). The effects were sustained at 6-month and
Acceptance and commitment therapy as a web-based public mental health
intervention for adults with depressive symptoms can be effective and
Adjunctive antidepressant therapy is commonly used to treat acute bipolar
depression but few studies have examined this strategy.
To examine the efficacy of agomelatine v. placebo as
adjuncts to lithium or valproate in bipolar depression.
Patients who were currently depressed despite taking lithium or valproate
for at least 6 weeks were randomised to treatment with agomelatine
(n = 172) or placebo (n = 172) for 8
weeks of acute therapy and 44 weeks of continuation therapy (trial
No significant differences in improvement of depressive symptoms were
observed between the two groups either at 8 weeks or 52 weeks on the
primary efficacy measure of change in Montgomery–Åsberg Depression Rating
Scale scores from baseline to end-point. Adverse events including
switches into mania/hypomania were low and similar in both groups.
Agomelatine adjunctive therapy was not superior to placebo adjunctive
therapy for acute bipolar depression.
Few randomised clinical trials have examined the efficacy of an
intervention aimed at improving psychosocial functioning in bipolar
To examine changes in psychosocial functioning in a group that has been
enrolled in a functional remediation programme 1 year after baseline.
This was a multicentre, randomised, rater-masked clinical trial comparing
three patient groups: functional remediation, psychoeducation and
treatment as usual over 1-year follow-up. The primary outcome was change
in psychosocial functioning measured by means of the Functioning
Assessment Short Test (FAST). Group×time effects for overall psychosocial
functioning were examined using repeated-measures ANOVA (trial
There was a significant group×time interaction for overall psychosocial
functioning, favouring patients in the functional remediation group
(F = 3.071, d.f. = 2, P =
Improvement in psychosocial functioning is maintained after 1-year
follow-up in patients with bipolar disorder receiving functional