A reliable biomarker signature for bipolar disorder sensitive to illness phase would be of considerable clinical benefit. Among circulating blood-derived markers there has been a significant amount of research into inflammatory markers, neurotrophins and oxidative stress markers.

To synthesise and interpret existing evidence of inflammatory markers, neurotrophins and oxidative stress markers in bipolar disorder focusing on the mood phase of illness.

Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a systematic review was conducted for studies investigating peripheral biomarkers in bipolar disorder compared with healthy controls. We searched Medline, Embase, PsycINFO, SciELO and Web of Science, and separated studies by bipolar mood phase (mania, depression and euthymia). Extracted data on each biomarker in separate mood phases were synthesised using random-effects model meta-analyses.

In total, 53 studies were included, comprising 2467 cases and 2360 controls. Fourteen biomarkers were identified from meta-analyses of three or more studies. No biomarker differentiated mood phase in bipolar disorder individually. Biomarker meta-analyses suggest a combination of high-sensitivity C-reactive protein/interleukin-6, brain derived neurotrophic factor/tumour necrosis factor (TNF)-α and soluble TNF-α receptor 1 can differentiate specific mood phase in bipolar disorder. Several other biomarkers of interest were identified.

Combining biomarker results could differentiate individuals with bipolar disorder from healthy controls and indicate a specific mood-phase signature. Future research should seek to test these combinations of biomarkers in longitudinal studies.

None.

Collaborative care can support the treatment of depression in people with long-term conditions, but long-term benefits and costs are unknown.

To explore the long-term (24-month) effectiveness and cost-effectiveness of collaborative care in people with mental-physical multimorbidity.

A cluster randomised trial compared collaborative care (integrated physical and mental healthcare) with usual care for depression alongside diabetes and/or coronary heart disease. Depression symptoms were measured by the symptom checklist-depression scale (SCL-D13). The economic evaluation was from the perspective of the English National Health Service.

191 participants were allocated to collaborative care and 196 to usual care. At 24 months, the mean SCL-D13 score was 0.27 (95% CI, −0.48 to −0.06) lower in the collaborative care group alongside a gain of 0.14 (95% CI, 0.06-0.21) quality-adjusted life-years (QALYs). The cost per QALY gained was £13 069.

In the long term, collaborative care reduces depression and is potentially cost-effective at internationally accepted willingness-to-pay thresholds.

None.

Single patient or ‘n-of-1’ trials are a pragmatic method to achieve optimal, evidence-based treatments for individual patients. Such trials could be particularly valuable in chronic, heterogeneous, difficult to treat illnesses such as schizophrenia.

To identify how often, and in what way, n-of-1 trials have been used in schizophrenia.

We performed a systematic search in the major electronic databases for studies adopting n-of-1 methodology in schizophrenia, published in English from the start of records until the end of January 2017.

We identified six studies meeting inclusion criteria. There was wide variability in study methodology and analysis. Each trial reported positive outcomes for their respective intervention, but all studies were at high risk of bias.

In conclusion, n-of-1 trials are currently underutilised in schizophrenia. Existing trials suggest the method is well tolerated and potentially effective in achieving optimal treatments for patients, but more standardised methods of design, execution and analysis are required in future trials.

S.M.L. has received grants and personal fees from Janssen, and personal fees from Otsuka and Sunovion, in the past 3 years, outside the submitted work.

None.

Attention-deficit hyperactivity disorder (ADHD) is associated with mental health problems and functional impairment across many domains. However, how the longitudinal course of ADHD affects later functioning remains unclear.

We aimed to disentangle how ADHD developmental patterns are associated with young adult functioning.

The Environmental Risk (E-Risk) Longitudinal Twin Study is a population-based cohort of 2232 twins born in England and Wales in 1994–1995. We assessed ADHD in childhood at ages 5, 7, 10 and 12 years and in young adulthood at age 18 years. We examined three developmental patterns of ADHD from childhood to young adulthood – remitted, persistent and late-onset ADHD – and compared these groups with one another and with non-ADHD controls on functioning at age 18 years. We additionally tested whether group differences were attributable to childhood IQ, childhood conduct disorder or familial factors shared between twins.

Compared with individuals without ADHD, those with remitted ADHD showed poorer physical health and socioeconomic outcomes in young adulthood. Individuals with persistent or late-onset ADHD showed poorer functioning across all domains, including mental health, substance misuse, psychosocial, physical health and socioeconomic outcomes. Overall, these associations were not explained by childhood IQ, childhood conduct disorder or shared familial factors.

Long-term associations of childhood ADHD with adverse physical health and socioeconomic outcomes underscore the need for early intervention. Young adult ADHD showed stronger associations with poorer mental health, substance misuse and psychosocial outcomes, emphasising the importance of identifying and treating adults with ADHD.

None.

Major depressive disorder (MDD) is underdiagnosed and undertreated in schizophrenia, and has been strongly associated with impaired quality of life.

To determine the prevalence and associated factors of MDD and unremitted MDD in schizophrenia, to compare treated and non-treated MDD.

Participants were included in the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment. MDD was defined by a Calgary score ≥6. Non-remitted MDD was defined by current antidepressant treatment (unchanged for >8 weeks) and current Calgary score ≥6.

613 patients were included and 175 (28.5%) were identified with current MDD. MDD has been significantly associated with respectively paranoid delusion (odds ratio 1.8; P = 0.01), avolition (odds ratio 1.8; P = 0.02), blunted affect (odds ratio 1.7; P = 0.04) and benzodiazepine consumption (odds ratio 1.8; P = 0.02). Antidepressants were associated with lower depressive symptoms score (5.4 v. 9.5; P < 0.0001); however, 44.1% of treated patients remained in non-remittance MDD. Nonremitters were found to have more paranoid delusion (odds ratio 2.3; P = 0.009) and more current alcohol misuse disorder (odds ratio 4.8; P = 0.04). No antidepressant class or specific antipsychotic were associated with higher or lower response to antidepressant treatment. MDD was associated with Metabolic syndrome (31.4 v. 20.2%; P = 0.006) but not with increased C-reactive protein.

Antidepressant administration is associated with lower depressive symptom level in patients with schizophrenia and MDD. Paranoid delusions and alcohol misuse disorder should be specifically explored and treated in cases of non-remission under treatment. MetS may play a role in MDD onset and/or maintenance in patients with schizophrenia.

None.

Little is known about the effect of persistent depressive symptoms on the trajectory of cognitive decline.

We aimed to investigate the longitudinal association between the duration of depressive symptoms and subsequent cognitive decline over a 10-year follow-up period.

The English Longitudinal Study of Ageing cohort is a prospective and nationally representative cohort of men and women living in England aged ≥50 years. We examined 7610 participants with two assessments of depressive symptoms at wave 1 (2002–2003) and wave 2 (2004–2005), cognitive data at wave 2 and at least one reassessment of cognitive function (wave 3 to wave 7, 2006–2007 to 2014–2015).

The mean age of the 7610 participants was 65.2 ± 10.1 years, and 57.0% were women. Of these, 1157 (15.2%) participants had episodic depressive symptoms and 525 participants (6.9%) had persistent depressive symptoms. Compared with participants without depressive symptoms at wave 1 and wave 2, the multivariable-adjusted rates of global cognitive decline associated with episodic depressive symptoms and persistent depressive symptoms were faster by –0.065 points/year (95% CI –0.129 to –0.000) and –0.141 points/year (95% CI –0.236 to –0.046), respectively (P for trend < 0.001). Similarly, memory, executive and orientation function also declined faster with increasing duration of depressive symptoms (all P for trend < 0.05).

Our results demonstrated that depressive symptoms were significantly associated with subsequent cognitive decline over a 10-year follow-up period. Cumulative exposure of long-term depressive symptoms in elderly individuals could predict accelerated subsequent cognitive decline in a dose-response pattern.

None.

Little is known about the prevalence of mental health outcomes in UK personnel at the end of the British involvement in the Iraq and Afghanistan conflicts.

We examined the prevalence of mental disorders and alcohol misuse, whether this differed between serving and ex-serving regular personnel and by deployment status.

This is the third phase of a military cohort study (2014–2016; n = 8093). The sample was based on participants from previous phases (2004–2006 and 2007–2009) and a new randomly selected sample of those who had joined the UK armed forces since 2009.

The prevalence was 6.2% for probable post-traumatic stress disorder, 21.9% for common mental disorders and 10.0% for alcohol misuse. Deployment to Iraq or Afghanistan and a combat role during deployment were associated with significantly worse mental health outcomes and alcohol misuse in ex-serving regular personnel but not in currently serving regular personnel.

The findings highlight an increasing prevalence of post-traumatic stress disorder and a lowering prevalence of alcohol misuse compared with our previous findings and stresses the importance of continued surveillance during service and beyond.

All authors are based at King's College London which, for the purpose of this study and other military-related studies, receives funding from the UK Ministry of Defence (MoD). S.A.M.S., M.J., L.H., D.P., S.M. and R.J.R. salaries were totally or partially paid by the UK MoD. The UK MoD provides support to the Academic Department of Military Mental Health, and the salaries of N.J., N.G. and N.T.F. are covered totally or partly by this contribution. D.Mu. is employed by Combat Stress, a national UK charity that provides clinical mental health services to veterans. D.MacM. is the lead consultant for an NHS Veteran Mental Health Service. N.G. is the Royal College of Psychiatrists’ Lead for Military and Veterans’ Health, a trustee of Walking with the Wounded, and an independent director at the Forces in Mind Trust; however, he was not directed by these organisations in any way in relation to his contribution to this paper. N.J. is a full-time member of the armed forces seconded to King's College London. N.T.F. reports grants from the US Department of Defense and the UK MoD, is a trustee (unpaid) of The Warrior Programme and an independent advisor to the Independent Group Advising on the Release of Data (IGARD). S.W. is a trustee (unpaid) of Combat Stress and Honorary Civilian Consultant Advisor in Psychiatry for the British Army (unpaid). S.W. is affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's College London in partnership with Public Health England, in collaboration with the University of East Anglia and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, the Department of Health, Public Health England or the UK MoD.

Stress-related illnesses are a major threat to public health, and there is increasing demand for validated treatments.

To test the efficacy of nature-based therapy (NBT) for patients with stress-related illnesses.

Randomised controlled trial (ClinicalTrials.gov ID NCT01849718) comparing Nacadia® NBT (NNBT) with the cognitive–behavioural therapy known as Specialised Treatment for Severe Bodily Distress Syndromes (STreSS). In total, 84 participants were randomly allocated to one of the two treatments. The primary outcome measure was the mean aggregate score on the Psychological General Well-Being Index (PGWBI).

Both treatments resulted in a significant increase in the PGWBI (primary outcome) and a decrease in burnout (the Shirom–Melamed Burnout Questionnaire, secondary outcome), which were both sustained 12 months later. No significant difference in efficacy was found between NNBT and STreSS for primary outcome and secondary outcomes.

The study showed no statistical evidence of a difference between NNBT and STreSS for treating patients with stress-related illnesses.

None.

Empirical evidence on the effectiveness of evidence-based treatments for adolescents with post-traumatic stress disorder (PTSD) in low-resource settings is needed.

To evaluate the comparative effectiveness of prolonged exposure and supportive counselling in adolescents with PTSD.

Sixty-three adolescents (13–18 years) with PTSD were randomly assigned to receive either of the interventions comprising 7–14 sessions of treatment (trial registration in the Pan African Clinical Trials Registry: PACTR201511001345372). The primary outcome measure was PTSD symptom severity, as independently assessed on the Child PTSD Symptom Scale at pre-treatment, post-treatment, and at 3- and 6-month follow-up.

Participants receiving prolonged exposure experienced greater improvement on the PTSD symptom severity scale than those receiving supportive counselling (between group differences at post-intervention, mean 12.49, 95% CI 6.82–18.17, P<0.001; d = 1.22). A similar effect size was maintained at 3-month (d = 0.85) and 6-month (d = 1.02) follow-up assessments.

Adolescents with PTSD experienced greater benefit from prolonged exposure treatment when provided by non-specialist health workers (nurses) in a community setting.

None.

Early life maltreatment (ELM), borderline personality disorder (BPD) and major depressive disorder (MDD) have been shown to increase the potential of abuse. Emotion regulation is an identified mediator for the association of ELM and BPD with abuse potential. Until now, there has been no study to account for the co-occurrence of these risk factors in one analysis, although BPD and MDD are known as common sequelae of ELM. This is paired with a lack of studies investigating the effects of abuse potential on child well-being.

Our study aims at (a) disentangling the effects of maternal ELM, MDD and BPD on abuse potential; (b) exploring the role of emotion regulation as a mediator; and (c) testing for intergenerational effects of abuse potential on child psychopathology.

The research design included 114 mothers with/without ELM, BPD and MDD in remission and their children, all of which were between 5 and 12 years of age. A path analysis was conducted to investigate the multiple associations between our variables.

ELM, MDD and BPD were all associated with abuse potential, with emotion regulation acting as a mediator for BPD and MDD. Furthermore, an elevated abuse potential was related to higher psychopathology in the child.

History of ELM as well as the common sequelae, BPD and MDD, pose risks for child abuse. Our findings suggest improvement of emotion regulation as a potential target for intervention programs. These programs should also aim at non-substantiated cases because even an elevated abuse potential affected child mental health.

None.

There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.

To investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls.

Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls.

Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest.

Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.

R.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.

Potentially modifiable risk factors for developing dementia have been identified. However, risk factors for increased mortality in patients with diagnosed dementia are not well understood. Identifying factors that influence prognosis would help clinicians plan care and address unmet needs.

To investigate diagnosed depression and sociodemographic factors as predictors of mortality in patients with dementia in UK secondary clinical care services.

We conducted a cohort study of patients with a dementia diagnosis in an electronic health records database in a UK National Health Service mental health trust.

In 3374 patients with 10 856 person-years of follow-up, comorbid depression was not associated with mortality (adjusted hazard ratio 0.94; 95% CI 0.71–1.24). Single patients had higher mortality than those who were married (adjusted hazard ratio 1.25; 95% CI 1.03–1.50). Patients of Asian ethnicity had lower mortality rates than White British patients (adjusted hazard ratio 0.50; 95% CI 0.34–0.73).

Clinically diagnosed depression does not increase mortality in patients with dementia. Patients who are single are a potential high-mortality risk group. Lower mortality rates in Asian patients with dementia that have been reported in the USA also apply in the UK.

None.

Concerns have been raised about the increase in the use of involuntary detentions under the Mental Health Act in England over a number of years, and whether this merits consideration of legislative change.

To investigate changes in the rate of detentions under Part II (civil) and Part III (forensic) sections of the Mental Health Act in England between 1984 and 2016.

Retrospective analysis of data on involuntary detentions from the National Archives and NHS Digital. Rates per 100 000 population were calculated with percentage changes. The odds of being formally admitted to a National Health Service hospital compared with a private hospital were calculated for each year.

Rates of detention have at least trebled since the 1980s and doubled since the 1990s. This has been because of a rise in Part II (civil) sections. Although the overall rate of detentions under Part III (forensic) sections did not rise, transfers from prison increased and detentions by the courts reduced. The odds of being detained in a private hospital increased fivefold.

The move to community-based mental health services in England has paradoxically led to an increase in the number of people being detained in hospital each year, and in particular an inexorable rise in involuntary admissions. This is likely to be partly because of improved case finding with an increased focus on treatment and risk management, and partly because of changes in legislation. An increasing proportion of this government-funded care is being provided by private hospitals.

None.

Retrospective studies have shown a high association between child abuse and subsequent psychiatric morbidity. Prospective studies are rarer.

To examine, using a prospective record-linkage analysis, whether substantiated child maltreatment is associated with adverse psychological outcomes in early adulthood.

The participants were 3778 mother and child pairs enrolled in a population-based birth cohort study in Brisbane, Australia. Exposure to suspected child maltreatment was measured by linkage with state child protection agency data. The primary outcomes were the internalising and externalising scales of the Youth Self-Report and the Centre for Epidemiological Studies-Depression scales (CES-D) at approximately 21 years of age. A subset completed the Composite International Diagnostic Interview-Auto version (CIDI-Auto).

In total, 171 (4.5%) participants had a history of substantiated child maltreatment, most commonly emotional abuse (n = 91), followed by physical abuse (n = 78), neglect (n = 73) and sexual abuse (n = 54). After adjustment for potential confounders, depressive symptoms on the CES-D, as well as internalising and externalising behaviours were strongly associated with substantiated abuse in all forms, except sexual abuse. The results for the subset of the sample who completed the CIDI-Auto were less clear. Anxiety, especially post-traumatic stress disorder, showed the strongest association whereas the findings for depressive disorder were equivocal. However, across all diagnostic categories, emotional abuse and neglect, as well as multiple forms of abuse, showed a consistent association.

Child maltreatment, particularly neglect and emotional abuse, has serious adverse effects on early adult mental health. These two warrant the attention given to other forms of child maltreatment. Children experiencing more than one type of maltreatment are at particular risk.

None.

The medical burden in mood disorders is high; various factors are thought to drive this pattern. Little research has examined the role of childhood maltreatment and its effects on medical morbidity in adulthood among people with unipolar depression and bipolar disorder.

This is the first study to explore the association between childhood maltreatment and medical morbidity in bipolar disorder and in unipolar depression, and examine whether the impact of abuse and neglect are distinct or combined.

The participants consisted of 354 psychiatrically healthy controls, 248 participants with recurrent unipolar depression and 72 with bipolar disorder. Participants completed the Childhood Trauma Questionnaire and received a validated medical history interview.

Any type of childhood maltreatment, child abuse and child neglect were significantly associated with the medical burden in bipolar disorder, but not unipolar depression or for controls. These associations worked in a dose–response fashion where participants with bipolar disorder with a history of two or more types of childhood maltreatment had the highest odds of having a medical illness relative to those without such history or those who reported one form. No such significant dose–response patterns were detected for participants with unipolar depression or controls.

These findings suggest that childhood maltreatment may play a stronger role in the development of medical illnesses in individuals with bipolar disorder relative to those with unipolar depression. Individuals who had been maltreated with a mood disorder, especially bipolar disorder may benefit most from prevention and intervention efforts surrounding physical health.

None.

The aetiology of dementia is not yet fully understood. Stress can have a damaging effect on brain health. The prognostic effect of anxiety is still unclear regarding Alzheimer's disease as well as vascular dementia.

To explore the association between anxiety and future dementia.

Medline, PsycINFO, CINAHL, Web of Science and ALOIS were searched for publications up to 12 January 2018. Longitudinal studies with a follow-up of at least 2 years were included, if the trait or state anxiety had been assessed at baseline. Studies with cognitive impairment at baseline were not included. We used a random effects model to calculate the pooled time to Alzheimer's disease and incidence of vascular dementia.

Anxiety predicts risk of Alzheimer's disease (n = 26 193 out of seven studies, hazard ratio1.53, 95% CI 1.16–2.01, P < 0.01) and vascular dementia (n = 4916 out of two studies, odds ratio1.88, 95% CI 1.05–3.36, P < 0.01). The pooled hazard ratio regarding risk of Alzheimer's disease was still significant when excluding studies with critical risk of bias (n = 14 110 out of six studies, hazard ratio 1.35, 95% CI 1.08–1.70, P < 0.01).

Anxiety is a risk factor for both types of dementia. The temporal and functional relation between anxiety and dementia needs investigation in future studies. The protective value of treating anxiety should be explored further.

None.

Pay-for-performance policies aim to improve population health by incentivising improvements in quality of care.

To assess the relationship between general practice performance on severe mental illness (SMI) and depression indicators under a national incentivisation scheme and suicide risk in England for the period 2006–2014.

Longitudinal spatial analysis for 32 844 small-area geographical units (lower super output areas, LSOAs), using population-structure adjusted numbers of suicide as the outcome variable. Negative binomial models were fitted to investigate the relationship between spatially estimated recorded quality of care and suicide risk at the LSOA level. Incidence rate ratios (IRRs) were adjusted for deprivation, social fragmentation, prevalence of depression and SMI as well as other 2011 Census variables.

No association was found between practice performance on the mental health indicators and suicide incidence in practice localities (IRR=1.000, 95% CI 0.998–1.002). IRRs indicated elevated suicide risks linked with area-level social fragmentation (1.030; 95% CI 1.027–1.034), deprivation (1.013, 95% CI 1.012–1.014) and rurality (1.059, 95% CI 1.027–1.092).

Primary care has an important role to play in suicide prevention, but we did not observe a link between practices' higher reported quality of care on incentivised mental health activities and lower suicide rates in the local population. It is likely that effective suicide prevention needs a more concerted, multiagency approach. Better training in suicide prevention for general practitioners is also essential. These findings pertain to the UK but have relevance to other countries considering similar programmes.

None.

Little is known about the relationship between adolescent affective problems (anxiety and depression) and mortality.

To examine whether adolescent affective symptoms are associated with premature mortality, and to assess whether this relationship is independent of other developmental factors.

Data (n = 3884) was from Britain's oldest birth cohort study – the National Survey of Health and Development. Adolescent affective symptoms were rated by teachers at ages 13 and 15 years: scores were summed and classified into three categories: mild or no, moderate and severe symptoms (1st–50th, 51st–90th and 91st–100th percentiles, respectively). Mortality data were obtained from national registry data up to age 68 years. Potential confounders were parental social class, childhood cognition and illness, and adolescent externalising behaviour.

Over the 53-year follow-up period, 12.2% (n = 472) of study members died. Severe adolescent affective symptoms were associated with an increased rate of mortality compared with those with mild or no symptoms (gender adjusted hazard ratio 1.76, 95% CI 1.33–2.33). This association was only partially attenuated after adjustment for potential confounders (fully adjusted hazard ratio 1.61, 95% CI 1.20–2.15). There was suggestive evidence of an association across multiple causes of death. Moderate symptoms were not associated with mortality.

Severe adolescent affective symptoms are associated with an increased rate of premature mortality over a 53-year follow-up period, independent of potential confounders. These findings underscore the importance of early mental health interventions.

None.

Better indicators of prognosis are needed to personalise post-traumatic stress disorder (PTSD) treatments.

We aimed to evaluate early symptom reduction as a predictor of better outcome and examine predictors of early response.

Patients with PTSD (N = 134) received sertraline or prolonged exposure in a randomised trial. Early response was defined as 20% PTSD symptom reduction by session two and good end-state functioning defined as non-clinical levels of PTSD, depression and anxiety.

Early response rates were similar in prolonged exposure and sertraline (40 and 42%), but in sertraline only, early responders were four times more likely to achieve good end-state functioning at post-treatment (Number Needed to Treat = 1.8, 95% CI 1.28–3.00) and final follow-up (Number Needed to Treat = 3.1, 95% CI 1.68–16.71). Better outcome expectations of sertraline also predicted higher likelihood of early response.

Higher expectancy of sertraline coupled with early response may produce a cascade-like effect for optimal conditions for long-term symptom reduction. Therefore, assessing expectations and providing clear treatment rationales may optimise sertraline effects.

None.