Since bipolar disorder seems to be associated with purinergic system dysfunction, allopurinol might be effective in treating symptoms of mania.

To estimate the efficacy and tolerability of allopurinol as adjunctive treatment for mania symptoms in people with bipolar affective disorder.

We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effects of adjunctive allopurinol and placebo on mania symptom changes.

Five RCTs were included in the meta-analysis. Participants with allopurinol augmentation had a significantly greater decrease in mania symptoms than those with placebo (SMD= −0.34, P = 0.007), especially in people with the most severe forms of mania. Remission rates, although based on only two studies (n = 177), were significantly higher among individuals receiving allopurinol, whereas for discontinuation and side-effects no difference was found.

Our finding of a small to moderate effect size and overall low evidence for add-on allopurinol in reducing mania symptoms indicate that its use in routine practice needs further elucidation.

Sponsorship bias has never been investigated for non-pharmacological treatments like psychotherapy.

We examined industry funding and author financial conflict of interest (COI) in randomised controlled trials directly comparing psychotherapy and pharmacotherapy in depression.

We conducted a meta-analysis with subgroup comparisons for industry v. non-industry-funded trials, and respectively for trial reports with author financial COI v. those without.

In total, 45 studies were included. In most analyses, pharmacotherapy consistently showed significant effectiveness over psychotherapy, g = −0.11 (95% CI −0.21 to −0.02) in industry-funded trials. Differences between industry and non-industry-funded trials were significant, a result only partly confirmed in sensitivity analyses. We identified five instances where authors of the original article had not reported financial COI.

Industry-funded trials for depression appear to subtly favour pharmacotherapy over psychotherapy. Disclosure of all financial ties with the pharmaceutical industry should be encouraged.

Clinical practice guidelines are not easily implemented, leading to a gap between research synthesis and their use in routine care.

To summarise the evidence relating to the impact of guideline implementation on provider performance and patient outcomes in mental healthcare settings, and to explore the performance of different strategies for guideline implementation.

A systematic review of randomised controlled trials, controlled clinical trials and before-and-after studies comparing guideline implementation strategies v. usual care, and different guideline implementation strategies, in patients with severe mental illness.

In total, 19 studies met our inclusion criteria. The studies did not show a consistent positive effect of guideline implementation on provider performance, but a more consistent small to modest positive effect on patient outcomes.

Guideline implementation does not seem to have an impact on provider performance, nonetheless it may influence patient outcomes positively.

Depression has been cross-sectionally associated with short telomeres as a measure of biological age. However, the direction and nature of the association is currently unclear.

We examined whether short telomere length is associated with depression cross-sectionally as well as prospectively and genetically.

Telomere length and three polymorphisms, TERT, TERC and OBFC1, were measured in 67306 individuals aged 20–100 years from the Danish general population and associated with register-based attendance at hospital for depression and purchase of antidepressant medication.

Attendance at hospital for depression was associated with short telomere length cross-sectionally, but not prospectively. Further, purchase of antidepressant medication was not associated with short telomere length cross-sectionally or prospectively. Mean follow-up was 7.6 years (range 0.0–21.5). The genetic analyses suggested that telomere length was not causally associated with attendance at hospital for depression or with purchase of antidepressant medication.

Short telomeres were not associated with depression in prospective or in causal, genetic analyses.

Observational studies report associations between early menarche and higher levels of depressive symptoms and depression. However, no studies have investigated whether this association is causal.

To determine whether earlier menarche is a causal risk factor for depressive symptoms and depression in adolescence.

The associations between a genetic score for age at menarche and depressive symptoms at 14, 17 and 19 years, and depression at 18 years, were examined using Mendelian randomisation analysis techniques.

Using a genetic risk score to indicate earlier timing of menarche, we found that early menarche is associated with higher levels of depressive symptoms at 14 years (odds ratio per risk allele 1.02, 95% CI 1.005–1.04, n=2404). We did not find an association between the early menarche risk score and depressive symptoms or depression after age 14.

Our results provide evidence for a causal effect of age at menarche on depressive symptoms at age 14.

Long-term conditions often coexist with depression and anxiety.

To assess the effectiveness of stepped-care psychological therapies for patients with long-term conditions.

Data from 28 498 patients were analysed using regression to model depression (Patient Health Questionnaire (PHQ-9)) and anxiety (Generalised Anxiety Disorder scale (GAD-7)) outcomes. Post-treatment symptoms and effect sizes (d) were estimated for individuals with and without long-term conditions, controlling for covariates. The likelihood of access and response to intensive psychological interventions was also examined.

Higher post-treatment symptoms were predicted for patients with musculoskeletal problems (d = 0.22–0.27), chronic obstructive pulmonary disease (d = 0.26–0.33), diabetes (d = 0.05–0.13) and psychotic disorders (d = 0.50–0.58). Most long-term conditions were associated with greater odds of accessing high-intensity therapies, yet individuals who accessed these continued to have higher average post-treatment symptoms.

Some long-term conditions are associated with greater intensity of care and poorer outcomes after therapy.

Residual symptoms and cognitive impairment are among important sources of disability in patients with bipolar disorder. Methylene blue could improve such symptoms because of its potential neuroprotective effects.

We conducted a double-blind crossover study of a low dose (15 mg, ‘placebo’) and an active dose (195 mg) of methylene blue in patients with bipolar disorder treated with lamotrigine.

Thirty-seven participants were enrolled in a 6-month trial (trial registration: NCT00214877). The outcome measures included severity of depression, mania and anxiety, and cognitive functioning.

The active dose of methylene blue significantly improved symptoms of depression both on the Montgomery–Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression (P = 0.02 and 0.05 in last-observation-carried-forward analysis). It also reduced the symptoms of anxiety measured by the Hamilton Rating Scale for Anxiety (P = 0.02). The symptoms of mania remained low and stable throughout the study. The effects of methylene blue on cognitive symptoms were not significant. The medication was well tolerated with transient and mild side-effects.

Methylene blue used as an adjunctive medication improved residual symptoms of depression and anxiety in patients with bipolar disorder.

Interventions that improve cognitive function in Alzheimer's disease are urgently required.

To assess whether a novel cognitive training paradigm based on ‘chunking’ improves working memory and general cognitive function, and is associated with reorganisation of functional activity in prefrontal and parietal cortices (trial registration: ISRCTN43007027).

Thirty patients with mild Alzheimer's disease were randomly allocated to receive 18 sessions of 30 min of either adaptive chunking training or an active control intervention over approximately 8 weeks. Pre- and post-intervention functional magnetic resonance imaging (fMRI) scans were also conducted.

Adaptive chunking training led to significant improvements in verbal working memory and untrained clinical measures of general cognitive function. Further, fMRI revealed a bilateral reduction in task-related lateral prefrontal and parietal cortex activation in the training group compared with controls.

Chunking-based cognitive training is a simple and potentially scalable intervention to improve cognitive function in early Alzheimer's disease.

There is accumulating evidence for the role of fronto-striatal and associated circuits in obsessive–compulsive disorder (OCD) but limited and conflicting data on alterations in cortical thickness.

To investigate alterations in cortical thickness and subcortical volume in OCD.

In total, 412 patients with OCD and 368 healthy adults underwent magnetic resonance imaging scans. Between-group analysis of covariance of cortical thickness and subcortical volumes was performed and regression analyses undertaken.

Significantly decreased cortical thickness was found in the OCD group compared with controls in the superior and inferior frontal, precentral, posterior cingulate, middle temporal, inferior parietal and precuneus gyri. There was also a group x age interaction in the parietal cortex, with increased thinning with age in the OCD group relative to controls.

Our findings are partially consistent with earlier work, suggesting that group differences in grey matter volume and cortical thickness could relate to the same underlying pathology of OCD. They partially support a frontostriatal model of OCD, but also suggest that limbic, temporal and parietal regions play a role in the pathophysiology of the disorder. The group x age interaction effects may be the result of altered neuroplasticity.

In patients with schizophrenia in a psychotic episode, intra-striatal intrinsic connectivity is increased in the putamen but not ventral striatum. Furthermore, multimodal changes have been observed in the anterior insula that interact extensively with the putamen.

We hypothesised that during psychosis, putamen extra-striatal functional connectivity is altered with both the anterior insula and areas normally connected with the ventral striatum (i.e. altered functional connectivity distinctiveness of putamen and ventral striatum).

We acquired resting-state functional magnetic resonance images from 21 patients with schizophrenia in a psychotic episode and 42 controls.

Patients had decreased functional connectivity: the putamen with right anterior insula and dorsal prefrontal cortex, the ventral striatum with left anterior insula. Decreased functional connectivity between putamen and right anterior insula was specifically associated with patients' hallucinations. Functional connectivity distinctiveness was impaired only for the putamen.

Results indicate aberrant extra-striatal connectivity during psychosis and a relationship between reduced putamen–right anterior insula connectivity and hallucinations. Data suggest that altered intrinsic connectivity links striatal and insular pathophysiology in psychosis.