New research is dramatically altering our understanding of the molecular mechanisms underlying neuronal communication.

To elucidate the molecular mechanisms underlying the therapeutic effects of mood stabilisers.

Results from integrated clinical and laboratory studies are reviewed.

Chronic administration of lithium and valproate produced a striking reduction in protein kinase C (PKC) isozymes in rat frontal cortex and hippocampus. In a small study, tamoxifen (also a PKC inhibitor) had marked antimanic efficacy. Both lithium and valproate regulate the DNA binding activity of the activator protein 1 family of transcription factors. Using mRNA differential display, it was also shown that chronic administration of lithium and valproate modulates expression of several genes. An exciting finding is that of a robust elevation in the levels of the cytoprotective protein, bcl-2.

The results suggest that regulation of signalling pathways may play a major part in the long-term actions of mood stabilisers. Additionally, mood stabilisers may exert underappreciated neuroprotective effects.

Psychological interventions may be beneficial in bipolar disorder.

To evaluate the efficacy of psychological interventions for adults with bipolar disorder.

A systematic review of randomised controlled trials was conducted. Outcomes were meta-analysed using RevMan and confidence assessed using the GRADE method.

We included 55 trials with 6010 participants. Moderate-quality evidence associated individual psychological interventions with reduced relapses at post-treatment (risk ratio (RR) = 0.66, 95% CI 0.48–0.92) and follow-up (RR = 0.74, 95% CI 0.63–0.87), and collaborative care with a reduction in hospital admissions (RR =0.68, 95% CI 0.49–0.94). Low-quality evidence associated group interventions with fewer depression relapses at post-treatment and follow-up, and family psychoeducation with reduced symptoms of depression and mania.

There is evidence that psychological interventions are effective for people with bipolar disorder. Much of the evidence was of low or very low quality thereby limiting our conclusions. Further research should identify the most effective (and cost-effective) interventions for each phase of this disorder.

There have been changes to the criteria for diagnosing post-traumatic stress disorder (PTSD) in DSM-5 and changes are proposed for ICD-11.

To investigate the impact of the changes to diagnostic criteria for PTSD in DSM-5 and the proposed changes in ICD-11 using a large multisite trauma-exposed sample and structured clinical interviews.

Randomly selected injury patients admitted to four hospitals were assessed 72 months post trauma (n = 510). Structured clinical interviews for PTSD and major depressive episode, as well as self-report measures of disability and quality of life were administered.

Current prevalence of PTSD under DSM-5 scoring was not significantly different from DSM-IV (6.7% v. 5.9%, z = 0.53, P = 0.59). However, the ICD-11 prevalence was significantly lower than ICD-10 (3.3% v. 9.0%, z =–3.8, P<0.001). The PTSD current prevalence was significantly higher for DSM-5 than ICD-11 (6.7% v. 3.3%, z = 2.5, P = 0.01). Using ICD-11 tended to show lower rates of comorbidity with depression and a slightly lower association with disability.

The diagnostic systems performed in different ways in terms of current prevalence rates and levels of comorbidity with depression, but on other broad key indicators they were relatively similar. There was overlap between those with PTSD diagnosed by ICD-11 and DSM-5 but a substantial portion met one but not the other set of criteria. This represents a challenge for research because the phenotype that is studied may be markedly different according to the diagnostic system used.

Wartime traumatic events are related to subsequent psychological and physical health, but quantifying the association is problematic. Memory changes over time and is influenced by psychological status.

To use a large, two-stage cohort study of members of the UK armed forces to study changes in recall of both traumatic and ‘toxic’ hazards.

A questionnaire-based follow-up study assessed 2370 UK military personnel, repeating earlier questions about exposure to military hazards.

The κ statistics for reporting of hazards were good for some exposures, but very low for others. Gulf veterans reported more exposures over time (no significant rise in the Bosnia cohort). In the Gulf cohort only, reporting new exposures was associated with worsening health perception, and forgetting previously reported exposures with improved perception. We found no association between physical health, psychological morbidity or post-traumatic stress disorder symptoms and endorsement or non-endorsement of exposures.

Reporting of military hazards after a conflict is not static, and is associated with current self-rated perception of health. Self-report of exposures associated with media publicity needs to be treated with caution.

Health of the Nation Outcome Scales (HoNOS) have been developed to measure outcomes in people with mental health problems.

The particular physical and cognitive problems affecting older people requires a specific scale for their measurement. We describe the development of such a scale, named HoNOS 65+.

Pilot, validity and reliability studies were carried out on an amended scale. Validity was assessed by comparison with existing scales reflecting depression, cognitive function, psychiatric symptomatology, activities of daily living and functional abilities. Reliability was measured in two centres.

HoNOS 65+ was successfully amended to include specific aspects of mental health problems in older people including the phenomenology of depression, delusions occurring in the presence of dementia, incontinence and agitation/restlessness. HoNOS 65+ was able to discriminate between people suffering from organic and functional illnesses. Correlations with other scales indicated reasonable validity. Reliability was satisfactory.

Aversion of HoNOS 65+ is presented (see pp. 435–438, this issue) which is appropriate for use in elderly people with mental health problems.

Citalopram is a serotonin reuptake inhibitor which has been demonstrated to be highly selective and with a superior tolerability profile to the classical tricyclic antidepressants. This study was designed to test whether there was any difference in eff icacy in the management of panic disorder (PD) between Citalopram and placebo.

This was a double-blind, placebo and clomipramine controlled, parallel group eight-week study. A total of 475 patients with PD, with or without agoraphobia, were randomised to treatment with either placebo, clomipramine 60 or 90 mg/day, or Citalopram 10 or 15 mg/day, 20 or 30 mg/day, or 40 or 60 mg/day. Doses were increased over the first three weeks, stabilised during the fourth week and fixed between weeks five and eight.

Treatment with Citalopram at 20 or 30 mg, 40 or 60 mg and clomipramine were significantly superior to placebo, judged by the number of patients free of panic attacks in the week prior to the final assessment. All rating scales examined suggested that Citalopram 20 or 30 mg was more effective than Citalopram 40 or 60 mg.

The most advantageous benefit/risk ratio for the treatment of PD was associated with citalopram 20 or 30 mg/day.

Long-acting injections (LAIs) of antipsychotic drugs were developed over 40 years ago in an attempt to improve the long-term treatment of schizophrenia.

To review existing guidelines concerning antipsychotic use generally, and LAIs in particular, and how patients might be identified as potential candidates for LAI treatment.

Literature review.

Currently several first-generation and one second-generation antipsychotic LAIs are available, with others under development. Although the use of LAIs is widespread around the world, patterns of use vary widely. Important considerations regarding the use of LAIs include the indications for long-term pharmacotherapy in schizophrenia in general, the indications for LAIs, the risks associated with LAIs, the need to update guidelines and the issue of cost.

The use of these injections in first-episode psychosis and treatment-refractory schizophrenia is not currently a focus of recommendations, but should be considered. Long-acting injections remain an underutilised option in many countries despite frequent non-adherence with oral medication and subsequent relapse.

Reducing the global treatment gap for mental disorders requires treatments that are economical, effective and culturally appropriate.

To describe a systematic approach to the development of a brief psychological treatment for patients with severe depression delivered by lay counsellors in primary healthcare.

The treatment was developed in three stages using a variety of methods: (a) identifying potential strategies; (b) developing a theoretical framework; and (c) evaluating the acceptability, feasibility and effectiveness of the psychological treatment.

The Healthy Activity Program (HAP) is delivered over 6–8 sessions and consists of behavioral activation as the core psychological framework with added emphasis on strategies such as problem-solving and activation of social networks. Key elements to improve acceptability and feasibility are also included. In an intention-to-treat analysis of a pilot randomised controlled trial (55 participants), the prevalence of depression (Beck Depression Inventory II ⩾19) after 2 months was lower in the HAP than the control arm (adjusted risk ratio = 0.55, 95% CI 0.32–0.94, P = 0.01).

Our systematic approach to the development of psychological treatments could be extended to other mental disorders. HAP is an acceptable and effective brief psychological treatment for severe depression delivered by lay counsellors in primary care.

England's Time To Change (TTC) social marketing campaign emphasised social contact between people with and without mental health problems to reduce stigma and discrimination.

We aimed to assess the effectiveness of the mass media component and also that of the mass social contact events.

Online interviews were performed before and after each burst of mass media social marketing to evaluate changes in knowledge, attitudes and behaviour and associations between campaign awareness and outcomes. Participants at social contact events were asked about the occurrence and quality of contact, attitudes, readiness to discuss mental health and intended behaviour towards people with mental health problems.

Prompted campaign awareness was 38-64%. A longitudinal improvement was noted for one intended behaviour item but not for knowledge or attitudes. Campaign awareness was positively associated with greater knowledge (β = 0.80, 95% CI 0.52-1.08) and more favourable attitudes (commonality OR 1.37, 95% CI 1.10-1.70; dangerousness OR 1.41, 95% CI 1.22-1.63) and intended behaviour (β = 0.75, 95% CI 0.53-0.96). Social contact at events demonstrated a positive impact (M=2.68) v. no contact (M = 2.42) on perceived attitude change; t(211)= 3.30, P=0.001. Contact quality predicted more positive attitude change (r=0.33, P<0.01) and greater confidence to challenge stigma (r=0.38, P<0.01).

The favourable short-term consequences of the social marketing campaign suggest that social contact can be used by anti-stigma programmes to reduce stigma.

Daily-life stress sensitivity is associated with depression, but prospective data are lacking.

To examine associations between baseline ecological daily-life stress sensitivity and later depression, and to identify genetic and non-genetic factors moderating the transition from stress sensitivity to depression.

Daily-life stress sensitivity was assessed at baseline in twins (n = 502). One baseline and four follow-up measurements of depressive symptoms and negative life events were collected, as well as interview-based diagnoses at baseline and last follow-up. Hypothesised genetic markers were determined.

Baseline stress sensitivity was associated with increased depressive symptoms at follow-up and risk of major depressive disorder. Both genetic liability and major life events moderated the probability of transition from stress sensitivity to depression.

Onset of depression is attributable to pre-onset ecological measurements of stress sensitivity, particularly where genetic liability is high and individuals have reached a stage where the influence of competing environmental causes is low.

Promising evidence has emerged of clinical gains using guided self-help cognitive–behavioural therapy (CBT) for child anxiety and by involving parents in treatment; however, the efficacy of guided parent-delivered CBT has not been systematically evaluated in UK primary and secondary settings.

To evaluate the efficacy of low-intensity guided parent-delivered CBT treatments for children with anxiety disorders.

A total of 194 children presenting with a current anxiety disorder, whose primary carer did not meet criteria for a current anxiety disorder, were randomly allocated to full guided parent-delivered CBT (four face-to-face and four telephone sessions) or brief guided parent-delivered CBT (two face-to-face and two telephone sessions), or a wait-list control group (trial registration: ISRCTN92977593). Presence and severity of child primary anxiety disorder (Anxiety Disorders Interview Schedule for DSM-IV, child/parent versions), improvement in child presentation of anxiety (Clinical Global Impression –Improvement scale), and change in child anxiety symptoms (Spence Children's Anxiety Scale, child/parent version and Child Anxiety Impact scale, parent version) were assessed at post-treatment and for those in the two active treatment groups, 6 months post-treatment.

Full guided parent-delivered CBT produced superior diagnostic outcomes compared with wait-list at post-treatment, whereas brief guided parent-delivered CBT did not: at post-treatment, 25 (50%) of those in the full guided CBT group had recovered from their primary diagnosis, compared with 16 (25%) of those on the wait-list (relative risk (RR) 1.85, 95% CI 1.14–2.99); and in the brief guided CBT group, 18 participants (39%) had recovered from their primary diagnosis post-treatment (RR = 1.56, 95% CI 0.89–2.74). Level of therapist training and experience was unrelated to child outcome.

Full guided parent-delivered CBT is an effective and inexpensive first-line treatment for child anxiety.

It is reported that people with mild learning disability have a higher point prevalence of schizophrenia than the normal population, the reasons for which are unclear.

Thirty-nine subjects with mild learning disability and schizophrenia, 34 control subjects with schizophrenia and 28 control subjects with mild learning disability were seen. Interviews with relatives and carers were also conducted. Assessments were made of clinical variables, psychopathology, neurological ‘soft'signs, IQ, memory and family history. Blood was taken for karyotypic analysis from comorbid subjects.

The comorbid group had more negative symptoms, episodic memory deficits, soft neurological signs, epilepsy and receive more community supports than control subjects with schizophrenia. Comorbid subjects had a tendency to belong to multiply affected families and show high rates of chromosomal variants on routine karyotypic testing.

Future work on the generality of schizophrenia should include people with premorbid learning disability, as a discrete subtype from whom valuable genetic aetiological clues may be obtained.

The neurocognitive basis of auditory verbal hallucinations is unclear.

To investigate whether people with a history of such hallucinations would misattribute their own speech as external and show differential activation in brain areas implicated in hallucinations compared with people without such hallucinations.

Participants underwent functional magnetic resonance imaging (fMRI) while listening to pre-recorded words. The source (self/non-self) and acoustic quality (undistorted/distorted) were varied across trials. Participants indicated whether the speech they heard was their own or that of another person. Twenty people with schizophrenia (auditory verbal hallucinations n=10, no hallucinations n=10) and healthy controls (n=11) were tested.

The hallucinator group made more external misattributions and showed altered activation in the superior temporal gyrus and anterior cingulate compared with both other groups.

The misidentification of self-generated speech in patients with auditory verbal hallucinations is associated with functional abnormalities in the anterior cingulate and left temporal cortex. This may be related to impairment in the explicit evaluation of ambiguous auditory verbal stimuli.