C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.

To explore CRP in MDD and its phenotypic associations.

We recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers. High-sensitivity CRP in peripheral venous blood, body mass index (BMI) and questionnaire assessments of depression, anxiety and childhood trauma were measured. Group differences in CRP were estimated, and partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes.

Compared with healthy volunteers, BMI-corrected CRP was significantly elevated in the treatment-resistant group (P = 0.007; Cohen's d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two-factor solution that accounted for 34.7% of variation in clinical measures and for 36.0% of variation in CRP. Clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were vegetative depressive symptoms, BMI, state anxiety and feeling unloved as a child or wishing for a different childhood.

CRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.

S.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research & Development, LLC., of Johnson & Johnson, and hold stock in Johnson & Johnson. The other authors report no financial disclosures or potential conflicts of interest.

Ketamine has been demonstrated to improve depressive symptoms.

Evaluation of efficacy, safety and feasibility of repeated oral ketamine for out-patients with treatment-resistant depression (TRD).

In a randomised, double-blind, placebo-controlled, proof-of-concept trial, 41 participants received either 1 mg/kg oral ketamine or placebo thrice weekly for 21 days (ClinicalTrials.gov Identifier: NCT02037503). Evaluation was performed at baseline, 40 and 240 min post administration and on days 3, 7, 14 and 21. The main outcome measure was change in Montgomery–Åsberg Depression Rating Scale (MADRS).

Twenty-two participants were randomised to the ketamine group, and 19 to the control, with 82.5% (n = 33) completing the study. In the ketamine group, a decrease in depressive symptoms was evident at all time points, whereas in the control group a decrease was evident only 40 min post administration. The reduction in MADRS score on day 21 was 12.75 in the ketamine group versus 2.49 points with placebo (P < 0.001). Six participants in the ketamine group (27.3%) achieved remission compared with none of the controls (P < 0.05). The number needed to treat for remission was 3.7. Side-effects were mild and transient.

Repeated oral ketamine produced rapid and persistent amelioration of depressive symptoms in out-patients with TRD, and was well tolerated. These results suggest that add-on oral ketamine may hold significant promise in the care of patients suffering from TRD in the community.

None.

Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.

We conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD.

Participants with TRD (defined as insufficient response to at least two antidepressants) were randomised to at least one augmentation treatment in the trial. Pre-post analysis assessed treatment effectiveness, providing an effect size (ES) independent of comparator interventions.

Of 28 trials, 3 investigated psychological treatments and 25 examined pharmacological interventions. Pre-post analyses demonstrated N-methyl-d-aspartate-targeting drugs to have the highest ES (ES = 1.48, 95% CI 1.25–1.71). Other than aripiprazole (four studies, ES = 1.33, 95% CI 1.23–1.44) and lithium (three studies, ES = 1.00, 95% CI 0.81–1.20), treatments were each investigated in less than three studies. Overall, pharmacological (ES = 1.19, 95% CI 1.08–1.30) and psychological (ES = 1.43, 95% CI 0.50–2.36) therapies yielded higher ESs than pill placebo (ES = 0.78, 95% CI 0.66–0.91) and psychological control (ES = 0.94, 95% CI 0.36–1.52).

Despite being used widely in clinical practice, the evidence for augmentation treatments in TRD is sparse. Although pre-post meta-analyses are limited by the absence of direct comparison, this work finds promising evidence across treatment modalities.

In the past 3 years, A.H.Y. received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion and Janssen; and research grant support from Janssen. In the past 3 years, A.J.C. received honoraria for speaking from AstraZeneca and Lundbeck; honoraria for consulting with Allergan, Janssen, Livanova, Lundbeck and Sandoz; support for conference attendance from Janssen; and research grant support from Lundbeck. B.B. has recently been (soon to be) on the speakers/advisory board for Hexal, Lilly, Lundbeck, Mundipharma, Pfizer, and Servier. No other conflicts of interest.

Depression is a leading cause of disability, with older people particularly susceptible to poor outcomes.

To investigate whether the prevalence of depression and antidepressant use have changed across two decades in older people.

The Cognitive Function and Ageing Studies (CFAS I and CFAS II) are two English population-based cohort studies of older people aged ≥65 years, with baseline measurements for each cohort conducted two decades apart (between 1990 and 1993 and between 2008 and 2011). Depression was assessed by the Geriatric Mental State examination and diagnosed with the Automated Geriatric Examination for Computer-Assisted Taxonomy algorithm.

In CFAS I, 7635 people aged ≥65 years were interviewed, of whom 1457 were diagnostically assessed. In CFAS II, 7762 people were interviewed and diagnostically assessed. Age-standardised depression prevalence in CFAS II was 6.8% (95% CI 6.3–7.5%), representing a non-significant decline from CFAS I (risk ratio 0.82, 95% CI 0.64–1.07, P = 0.14). At the time of CFAS II, 10.7% of the population (95% CI 10.0–11.5%) were taking antidepressant medication, more than twice that of CFAS I (risk ratio 2.79, 95% CI 1.96–3.97, P < 0.0001). Among care home residents, depression prevalence was unchanged, but the use of antidepressants increased from 7.4% (95% CI 3.8–13.8%) to 29.2% (95% CI 22.6–36.7%).

A substantial increase in the proportion of the population reporting taking antidepressant medication is seen across two decades for people aged ≥65 years. However there was no evidence for a change in age-specific prevalence of depression.

There is limited evidence on the prevalence and identification of antenatal mental disorders.

To investigate the prevalence of mental disorders in early pregnancy and the diagnostic accuracy of depression-screening (Whooley) questions compared with the Edinburgh Postnatal Depression Scale (EPDS), against the Structured Clinical Interview DSM-IV-TR.

Cross-sectional survey of women responding to Whooley questions asked at their first antenatal appointment. Women responding positively and a random sample of women responding negatively were invited to participate.

Population prevalence was 27% (95% CI 22–32): 11% (95% CI 8–14) depression; 15% (95% CI 11–19) anxiety disorders; 2% (95% CI 1–4) obsessive–compulsive disorder; 0.8% (95% CI 0–1) post-traumatic stress disorder; 2% (95% CI 0.4–3) eating disorders; 0.3% (95% CI 0.1–1) bipolar disorder I, 0.3% (95% CI 0.1–1%) bipolar disorder II; 0.7% (95% CI 0–1) borderline personality disorder. For identification of depression, likelihood ratios were 8.2 (Whooley) and 9.8 (EPDS). Diagnostic accuracy was similar in identifying any disorder (likelihood ratios 5.8 and 6).

Endorsement of Whooley questions in pregnancy indicates the need for a clinical assessment of diagnosis and could be implemented when maternity professionals have been appropriately trained on how to ask the questions sensitively, in settings where a clear referral and care pathway is available.

L.M.H. chaired the National Institute for Health and Care Excellence CG192 guidelines development group on antenatal and postnatal mental health in 2012–2014.

Electroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates.

To investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression.

A meta-analysis was conducted according to the PRISMA statement. A literature search identified recent studies that reported on at least one of the potential predictors.

Of the 2193 articles screened, 34 have been included for meta-analysis. Presence of psychotic features is a predictor of ECT remission (odds ratio (OR) = 1.47, P = 0.001) and response (OR = 1.69, P < 0.001), as is older age (standardised mean difference (SMD) = 0.26 for remission and 0.35 for response (P < 0.001)). The severity of depression predicts response (SMD = 0.19, P = 0.001), but not remission. Data on melancholic symptoms were inconclusive.

ECT is particularly effective in patients with depression with psychotic features and in elderly people with depression. More research on both biological and clinical predictors is needed to further evaluate the position of ECT in treatment protocols for major depression.

None.

Many studies have reported associations between prenatal stress and the development of psychotic, anxiety and depressive disorders; however, to date no studies have investigated potential associations with personality disorders.

This study investigated potential associations between exposure to prenatal stress and personality disorder in offspring.

In a subsample (N = 3626) of a large Finnish birth cohort, we used logistic regression models to examine associations between self-reported maternal stress during pregnancy, collected monthly during antenatal clinic appointments, and personality disorder in offspring. Familial and outcome information were obtained by linking data from the Finnish Hospital Discharge Register and the Finnish Population Register.

Compared with those unexposed, children exposed to any maternal stress during gestation had three times the odds of developing a personality disorder (odds ratio 2.76, 95% CI 1.59–4.80, P = 0.000). Those exposed to moderate stress had three times the odds (odds ratio 3.13, 95% CI 1.42–6.88, P = 0.005) and those exposed to severe stress had seven times the odds (odds ratio 7.06, 95% CI 2.10–23.81, P = 0.002) of developing a personality disorder. These associations remained after adjusting for parental psychiatric history, comorbid psychiatric diagnoses, prenatal smoking and antenatal depression.*

Exposure to stress during gestation increases the odds of personality disorder in offspring, independent of other psychiatric disorders. These results suggest the assessment of maternal stress and well-being during pregnancy may be useful in identifying those at greatest risk of developing personality disorder, and highlight the importance of prenatal care for good maternal mental health during pregnancy.

Diagnosing eating disorders can be difficult and few people with the disorder receive specialist services despite the associated high morbidity and mortality.

To examine the burden of eating disorders in the population in terms of incidence, comorbidities and survival.

We used linked electronic health records from general practitioner and hospital admissions in Wales, UK within the Secure Anonymised Information Linkage (SAIL) databank to investigate the incidence of new eating disorder diagnoses. We examined the frequency of comorbid diagnoses and prescribed medications in cases and controls in the 2 years before and 3 years after diagnosis, and performed a survival analysis.

A total of 15 558 people were diagnosed with eating disorders between 1990 and 2017. The incidence peaked at 24 per 100 000 people in 2003/04. People with eating disorders showed higher levels of other mental disorders (odds ratio 4.32, 95% CI 4.01–4.66) and external causes of morbidity and mortality (odds ratio 2.92, 95% CI 2.44–3.50). They had greater prescription of central nervous system drugs (odds ratio 3.15, 95% CI 2.97–3.33), gastrointestinal drugs (odds ratio 2.61, 95% CI 2.45–2.79) and dietetic drugs (odds ratio 2.42, 95% CI 2.24–2.62) before diagnosis. These excess diagnoses and prescriptions remained 3 years after diagnosis. Mortality was raised compared with controls for some eating disorders, particularly in females with anorexia nervosa.

Incidence of diagnosed eating disorders is relatively low in the population but there is a major longer term burden in morbidity and mortality to the individual.

There is strong public belief that polyunsaturated fats protect against and ameliorate depression and anxiety.

To assess effects of increasing omega-3, omega-6 or total polyunsaturated fat on prevention and treatment of depression and anxiety symptoms.

We searched widely (Central, Medline and EMBASE to April 2017, trial registers to September 2016, ongoing trials updated to August 2019), including trials of adults with or without depression or anxiety, randomised to increased omega-3, omega-6 or total polyunsaturated fat for ≥24 weeks, excluding multifactorial interventions. Inclusion, data extraction and risk of bias were assessed independently in duplicate, and authors contacted for further data. We used random-effects meta-analysis, sensitivity analyses, subgrouping and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment.

We included 31 trials assessing effects of long-chain omega-3 (n = 41 470), one of alpha-linolenic acid (n = 4837), one of total polyunsaturated fat (n = 4997) and none of omega-6. Meta-analysis suggested that increasing long-chain omega-3 probably has little or no effect on risk of depression symptoms (risk ratio 1.01, 95% CI 0.92–1.10, I2 = 0%, median dose 0.95 g/d, duration 12 months) or anxiety symptoms (standardised mean difference 0.15, 95% CI 0.05–0.26, I2 = 0%, median dose 1.1 g/d, duration 6 months; both moderate-quality evidence). Evidence of effects on depression severity and remission in existing depression were unclear (very-low-quality evidence). Results did not differ by risk of bias, omega-3 dose, duration or nutrients replaced. Increasing alpha-linolenic acid by 2 g/d may increase risk of depression symptoms very slightly over 40 months (number needed to harm, 1000).

Long-chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symptoms.

L.H. and A.A. were funded to attend the World Health Organization Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health meetings and present review results. The authors report no other conflicts of interest.

Many studies have documented robust relationships between depression and hopelessness and subsequent suicidal thoughts and behaviours; however, much weaker and non-significant effects have also been reported. These inconsistencies raise questions about whether and to what degree these factors confer risk for suicidal thoughts and behaviours.

This study aimed to evaluate the magnitude and clinical utility of depression and hopelessness as risk factors for suicide ideation, attempts and death.

We conducted a meta-analysis of published studies from 1971 to 31 December 2014 that included at least one longitudinal analysis predicting suicide ideation, attempt or death using any depression or hopelessness variable.

Overall prediction was weaker than anticipated, with weighted mean odds ratios of 1.96 (1.81–2.13) for ideation, 1.63 (1.55–1.72) for attempt and 1.33 (1.18–1.49) for death. Adjusting for publication bias further reduced estimates. Effects generally persisted regardless of sample severity, sample age or follow-up length.

Several methodological constraints were prominent across studies; addressing these issues would likely be fruitful moving forward.

None.

Mental illnesses may explain vulnerability to develop extremist beliefs that can lead to violent protest and terrorism. Yet there is little evidence.

To investigate the relationship between mental illnesses and extremist beliefs.

Population survey of 618 White British and Pakistani people in England. Extremism was assessed by an established measure of sympathies for violent protest and terrorism (SVPT). Respondents with any positive scores (showing sympathies) were compared with those with all negative scores. We calculated associations between extremist sympathies and ICD-10 diagnoses of depression and dysthymia, and symptoms of anxiety, personality difficulties, autism and post-traumatic stress. Also considered were demographics, life events, social assets, political engagement and criminal convictions.

SVPT were more common in those with major depression with dysthymia (risk ratio 4.07, 95% CI 1.37–12.05, P = 0.01), symptoms of anxiety (risk ratio 1.09, 95% CI 1.03–1.15, P = 0.002) or post-traumatic stress (risk ratio 1.03, 95% CI 1.01–1.05, P = 0.003). At greater risk of SVPT were: young adults (<21 versus ≥21: risk ratio 3.05, 95% CI 1.31–7.06, P = 0.01), White British people (versus Pakistani people: risk ratio 2.24, 95% CI 1.25–4.02, P = 0.007) and those with criminal convictions (risk ratio 2.23, 95% CI 1.01–4.95, P = 0.048). No associations were found with life events, social assets and political engagement.

Depression, dysthymia and symptoms of anxiety and post-traumatic stress are associated with extremist sympathies.

Internationally, intimate partner violence (IPV) cohorts have demonstrated associations with depression and anxiety. However, this association has not yet been described in a UK population, nor has the association with serious mental illness (SMI).

To explore the relationship between IPV exposure and mental illness in a UK population.

We designed a retrospective cohort study whereby we matched 18 547 women exposed to IPV to 74 188 unexposed women. Outcomes of interest (anxiety, depression and SMI) were identified through clinical codes.

At baseline, 9174 (49.5%) women in the exposed group had some form of mental illness compared with 17 768 (24.0%) in the unexposed group, described as an adjusted odds ratio of 2.62 (95% CI 2.52–2.72). Excluding those with mental illness at baseline, 1254 exposed women (incidence rate 46.62 per 1000 person-years) went on to present with any type of mental illness compared with 3119 unexposed women (incidence rate 14.93 per 1000 person-years), with an aIRR of 2.77 (95% CI 2.58–2.97). Anxiety (aIRR 1.99, 95% CI 1.80–2.20), depression (aIRR 3.05, 95% CI 2.81–3.31) and SMI (aIRR 3.08, 95% CI 2.19–4.32) were all associated with exposure to IPV.

IPV remains a significant public health issue in the UK. We have demonstrated the significant recorded mental health burden associated with IPV in primary care, at both baseline and following exposure. Clinicians must be aware of this association to reduce mental illness diagnostic delay and improve management of psychological outcomes in this group of patients.

None.

Previous research has documented marked occupational differences in suicide risk, but these estimates are 10 years old and based on potentially biased risk assessments.

To investigate occupation-specific suicide mortality in England, 2011–2015.

Estimation of indirectly standardised mortality rates for occupations/occupational groups based on national data.

Among males the highest risks were seen in low-skilled occupations, particularly construction workers (standardised mortality ratio [SMR] 369, 95% CI 333–409); low-skilled workers comprised 17% (1784/10 688) of all male suicides (SMR 144, 95% CI 137–151). High risks were also seen among skilled trade occupations (SMR 135 95% CI 130–139; 29% of male suicides). There was no evidence of increased risk among some occupations previously causing concern: male healthcare professionals and farmers. Among females the highest risks were seen in artists (SMR 399, 95% CI 244–616) and bar staff (SMR 182, 95% CI 123–260); nurses also had an increased risk (SMR 123, 95% CI 104–145). People in creative occupations and the entertainment industry – artists (both genders), musicians (males) and actors (males) – were at increased risk, although the absolute numbers of deaths in these occupations were low. In males (SMR 192, 95% CI 165–221) and females (SMR 170, 95% CI 149–194), care workers were at increased risk and had a considerable number of suicide deaths.

Specific contributors to suicide in high-risk occupations should be identified and measures – such as workplace-based interventions – put in place to mitigate this risk. The construction industry seems to be an important target for preventive interventions.

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.