Improvement in depression within the first 2 weeks of antidepressant treatment predicts good outcomes, but non-improvers can still respond or remit, whereas improvers often do not.

We aimed to investigate whether early improvement of individual depressive symptoms better predicts response or remission.

We obtained individual patient data of 30 trials comprising 2184 placebo-treated and 6058 antidepressant-treated participants. Primary outcome was week 6 response; secondary outcomes were week 6 remission and week 12 response and remission. We compared models that only included improvement in total score by week 2 (total improvement model) with models that also included improvement in individual symptoms.

For week 6 response, the area under the receiver operating characteristic curve and negative and positive predictive values of the total improvement model were 0.73, 0.67 and 0.74 compared with 0.77, 0.70 and 0.71 for the item improvement model. Model performance decreased for week 12 outcomes. Of predicted non-responders, 29% actually did respond by week 6 and 43% by week 12, which was decreased from the baseline (overall) probabilities of 51% by week 6 and 69% by week 12. In post hoc analyses with continuous rather than dichotomous early improvement, including individual items did not enhance model performance.

Examining individual symptoms adds little to the predictive ability of early improvement. Additionally, early non-improvement does not rule out response or remission, particularly after 12 rather than 6 weeks. Therefore, our findings suggest that routinely adapting pharmacological treatment because of limited early improvement would often be premature.

None.

The effectiveness of Early Intervention in Psychosis (EIP) services for individuals with a first episode of psychosis (FEP) could be thwarted by high rates of early disengagement.

To investigate which factors predict disengagement with EIP services.

Using data from a naturalistic cohort of 786 EIP clients in East Anglia (UK), we investigated the association between sociodemographic and clinical predictors and disengagement using univariable and multivariable Cox proportional hazards models.

Over half (54.3%) of our sample were discharged before receiving 3 years of EIP care, with 92 (11.7%) participants discharged due to disengagement. Milder negative symptoms, more severe hallucinations, not receiving an FEP diagnosis, polysubstance use and being employed were associated with greater disengagement.

Our findings highlight heterogeneous reasons for disengagement with EIP services. For some patients, early disengagement may hinder efforts to sustain positive long-term EIP outcomes. Efforts to identify true FEP cases and target patients with substance use problems and more severe positive symptoms may increase engagement.

None.

Fractional anisotropy in the uncinate fasciculus and the cingulum may be biomarkers for bipolar disorder and may even be distinctly affected in different subtypes of bipolar disorder, an area in need of further research.

This study aims to establish if fractional anisotropy in the uncinate fasciculus and cingulum shows differences between healthy controls, patients with bipolar disorder type I (BD-I) and type II (BD-II), and their unaffected siblings.

Fractional anisotropy measures from the uncinate fasciculus, cingulum body and parahippocampal cingulum were compared with tractography methods in 40 healthy controls, 32 patients with BD-I, 34 patients with BD-II, 17 siblings of patients with BD-I and 14 siblings of patients with BD-II.

The main effects were found in both the right and left uncinate fasciculus, with patients with BD-I showing significantly lower fractional anisotropy than both patients with BD-II and healthy controls. Participants with BD-II did not differ from healthy controls. Siblings showed similar effects in the left uncinate fasciculus. In a subsequent complementary analysis, we investigated the association between fractional anisotropy in the uncinate fasciculus and polygenic risk for bipolar disorder and psychosis in a large cohort (n = 570) of healthy participants. However, we found no significant association.

Fractional anisotropy in the uncinate fasciculus differs significantly between patients with BD-I and patients with BD-II and healthy controls. This supports the hypothesis of differences in the physiological sub-tract between bipolar disorder subtypes. Similar results were found in unaffected siblings, suggesting the potential for this biomarker to represent an endophenotype for BD-I. However, fractional anisotropy in the uncinate fasciculus seems unrelated to polygenic risk for bipolar disorder or psychosis.

None.

Pregnancy and childbirth are a period of high risk for women with bipolar disorder and involve difficult decisions particularly about continuing or stopping medications.

To explore what clinical predictors may help to individualise the risk of perinatal recurrence in women with bipolar disorder.

Information was gathered retrospectively by semi-structured interview, questionnaires and case-note review from 887 women with bipolar disorder who have had children. Clinical predictors were selected using backwards stepwise logistic regression, conditional permutation random forests and reinforcement learning trees.

Previous perinatal history of affective psychosis or depression was the most significant predictor of a perinatal recurrence (odds ratio (OR) = 8.5, 95% CI 5.04–14.82 and OR = 3.6, 95% CI 2.55–5.07 respectively) but even parous women with bipolar disorder without a previous perinatal mood episode were at risk following a subsequent pregnancy, with 7% developing postpartum psychosis.

Previous perinatal history of affective psychosis or depression is the most important predictor of perinatal recurrence in women with bipolar disorder and can be used to individualise risk assessments.

None.

Consent to research with decision-making capacity for research (DMC-R) is normally a requirement for study participation. Although the symptoms of schizophrenia and related psychoses are known to affect decision-making capacity for treatment (DMC-T), we know little about their effect on DMC-R.

We aimed to determine if DMC-R differs from DMC-T in proportion and associated symptoms in an in-patient sample of people with schizophrenia and related psychoses.

Cross-sectional study of psychiatric in-patients admitted for assessment and/or treatment of schizophrenia and related psychoses. We measured DMC-R and DMC-T using ‘expert judgement’ clinical assessment guided by the MacArthur Competence Assessment Tool for Clinical Research, the MacArthur Competence Assessment Tool for Treatment and the legal framework of the Mental Capacity Act (2005), in addition to symptoms of psychosis.

There were 84 participants in the study. Half the participants had DMC-R (51%, 95% CI 40–62%) and a third had DMC-T (31%, 95% CI 21–43%) and this difference was statistically significant (P < 0.01). Thought disorder was most associated with lacking DMC-R (odds ratio 5.72, 95% CI 2.01–16.31, P = 0.001), whereas lack of insight was most associated with lacking DMC-T (odds ratio 26.34, 95% CI 3.60–192.66, P = 0.001). With the exception of improved education status and better DMC-R, there was no effect of sociodemographic variables on either DMC-R or DMC-T.

We have shown that even when severely unwell, people with schizophrenia and related psychoses in in-patient settings commonly retain DMC-R despite lacking DMC-T. Furthermore, different symptoms have different effects on decision-making abilities for different decisions. We should not view in-patient psychiatric settings as a research ‘no-go area’ and, where appropriate, should recruit in these settings.

None.

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.

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.

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.

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.

Copy number variants (CNVs) are established risk factors for neurodevelopmental disorders. To date the study of CNVs in psychiatric illness has focused on single disorder populations. The role of CNVs in individuals with intellectual disabilities and psychiatric comorbidities are less well characterised.

To determine the type and frequency of CNVs in adults with intellectual disabilities and comorbid psychiatric disorders.

A chromosomal microarray analysis of 599 adults recruited from intellectual disabilities psychiatry services at three European sites.

The yield of pathogenic CNVs was high – 13%. Focusing on established neurodevelopmental disorder risk loci we find a significantly higher frequency in individuals with intellectual disabilities and comorbid psychiatric disorder (10%) compared with healthy controls (1.2%, P<0.0001), schizophrenia (3.1%, P<0.0001) and intellectual disability/autism spectrum disorder (6.5%, P < 0.00084) populations.

In the largest sample of adults with intellectual disabilities and comorbid psychiatric disorders to date, we find a high rate of pathogenic CNVs. This has clinical implications for the use of genetic investigations in intellectual disability psychiatry.

None.

Connectedness is a central dimension of personal recovery from severe mental illness (SMI). Research reports that people with SMI have lower social capital and poorer-quality social networks compared to the general population.

To identify personal well-being network (PWN) types and explore additional insights from mapping connections to places and activities alongside social ties.

We carried out 150 interviews with individuals with SMI and mapped social ties, places and activities and their impact on well-being. PWN types were developed using social network analysis and hierarchical k-means clustering of this data.

Three PWN types were identified: formal and sparse; family and stable; and diverse and active. Well-being and social capital varied within and among types. Place and activity data indicated important contextual differences within social connections that were not found by mapping social networks alone.

Place locations and meaningful activities are important aspects of people's social worlds. Mapped alongside social networks, PWNs have important implications for person-centred recovery approaches through providing a broader understanding of individual's lives and resources.

None.

Non-suicidal self-injury (NSSI) is highly prevalent in adolescents and may be a behavioural marker for emergent mental illnesses.

To determine whether sporadic or recurrent NSSI up to the age of 14 years predicted increased risk of new onset of psychiatric disorder in the subsequent 3 years, independent of psychiatric symptoms and social risk factors.

In total, 945 individuals aged 14 years with no past/present history of mental illness completed a clinical interview and completed a questionnaire about NSSI at the ages of 14 and 17 years.

Recurrent NSSI at baseline predicted total disorders, depression and eating disorders. Sporadic baseline NSSI predicted new onset of anxiety disorders only.

NSSI (especially recurrent NSSI) in the early-adolescent years is a behavioural marker of newly emerging mental illnesses. Professionals should treat both recurrent and sporadic NSSI as important risk factors, and prevention strategies could be targeted at this vulnerable group.

None.

Mental disorders in children and adolescents have an impact on educational attainment.

To examine the temporal association between attainment in education and subsequent diagnosis of depression or self-harm in the teenage years.

General practitioner, hospital and education records of young people in Wales between 1999 and 2014 were linked and analysed using Cox regression.

Linked records were available for 652 903 young people and of these 33 498 (5.1%) developed depression and 15 946 (2.4%) self-harmed after the age of 12 but before the age of 20. Young people who developed depression over the study period were more likely to have achieved key stage 1 (age 7 years) but not key stage 2 (age 11) (hazard ratio (HR) = 0.79, 95% CI 0.74–0.84) milestones, indicating that they were declining in academic attainment during primary school. Conversely, those who self-harmed were achieving as well as those who did not self-harm in primary school, but showed a severe decline in their attainment during secondary school (HR = 0.72, 95% CI 0.68–0.78).

Long-term declining educational attainment in primary and secondary school was associated with development of depression in the teenage years. Self-harm was associated with declining educational attainment during secondary school only. Incorporating information on academic decline with other known risk factors for depression/self-harm (for example stressful life events, parental mental health problems) may improve risk profiling methods.

None.

Outcome measures for mental health services need to adopt a service-user recovery focus.

To develop and validate a 10- and 20-item self-report recovery-focused quality of life outcome measure named Recovering Quality of Life (ReQoL).

Qualitative methods for item development and initial testing, and quantitative methods for item reduction and scale construction were used. Data from >6500 service users were factor analysed and item response theory models employed to inform item selection. The measures were tested for reliability, validity and responsiveness.

ReQoL-10 and ReQoL-20 contain positively and negatively worded items covering seven themes: activity, hope, belonging and relationships, self-perception, well-being, autonomy, and physical health. Both versions achieved acceptable internal consistency, test–retest reliability (>0.85), known-group differences, convergence with related measures, and were responsive over time (standardised response mean (SRM) > 0.4). They performed marginally better than the Short Warwick-Edinburgh Mental Well-being Scale and markedly better than the EQ-5D.

Both versions are appropriate for measuring service-user recovery-focused quality of life outcomes.

M.B. and J.Co. were members of the research group that developed the Clinical Outcomes in Routine Evaluation (CORE) outcome measures.

22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of neurodevelopmental disorder, however, the links between developmental coordination disorder (DCD), intellectual function and psychiatric disorder remain unexplored.

To establish the prevalence of indicative DCD in children with 22q11.2DS and examine associations with IQ, neurocognition and psychopathology.

Neurocognitive assessments and psychiatric interviews of 70 children with 22q11.2DS (mean age 11.2, s.d. = 2.2) and 32 control siblings (mean age 11.5, s.d. = 2.1) were carried out in their homes. Nine children with 22q11.2DS and indicative DCD were subsequently assessed in an occupational therapy clinic.

Indicative DCD was found in 57 (81.4%) children with 22q11.2DS compared with 2 (6.3%) control siblings (odds ratio (OR) = 36.7, P < 0.001). Eight of nine (89%) children with indicative DCD met DSM-5 criteria for DCD. Poorer coordination was associated with increased numbers of anxiety, (P < 0.001), attention-deficit hyperactivity disorder (ADHD) (P < 0.001) and autism-spectrum disorder (ASD) symptoms (P < 0.001) in children with 22q11.2DS. Furthermore, 100% of children with 22q11.2DS and ADHD had indicative DCD (20 of 20), as did 90% of children with anxiety disorder (17 of 19) and 96% of children who screened positive for ASD (22 of 23). The Developmental Coordination Disorder Questionnaire score was related to sustained attention (P = 0.006), even after history of epileptic fits (P = 0.006) and heart problems (P = 0.009) was taken into account.

Clinicians should be aware of the high risk of coordination difficulties in children with 22q11.2DS and its association with risk of mental disorder and specific neurocognitive deficits.

None.

Comorbid post-traumatic stress disorder (PTSD) is associated with poorer outcomes of other disorders, but is treatable.

To estimate the frequency of clinically undetected PTSD in secondary care.

A systematic review of studies that screened for PTSD and reported on PTSD documentation in clinical records. Frequency of undetected PTSD was estimated, and reasons for heterogeneity explored.

The median proportion of participants with undetected PTSD (29 studies) was 28.6% (interquartile range 18.2–38.6%). There was substantial heterogeneity, with studies conducted in the USA and those with the highest proportions of in-patients and patients with psychotic disorder reporting higher frequencies of undetected PTSD.

Undetected PTSD is common in secondary care, even if the true value is at the lower limit of the estimates reported here. Trials examining the impact of routine screening for PTSD are required to determine whether such programmes should be standard procedure for all mental health services.

None.

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.

Evaluations of primary healthcare co-located welfare advice services have been methodologically limited.

To examine the impact and cost-consequences of co-located benefits and debt advice on mental health and service use.

Prospective, controlled quasi-experimental study in eight intervention and nine comparator sites across North Thames. Changes in the proportion meeting criteria for common mental disorder (CMD, 12-item General Health Questionnaire); well-being scores (Shortened Warwick and Edinburgh Mental Well-being Scale), 3-month GP consultation rate and financial strain were measured alongside funding costs and financial gains.

Relative to controls, CMD reduced among women (ratio of odds ratios (rOR) = 0.37, 95% CI 0.20–0.70) and Black advice recipients (rOR=0.09, 95% CI 0.03–0.28). Individuals whose advice resulted in positive outcomes demonstrated improved well-being scores (β coefficient 1.29, 95% CI 0.25–2.32). Reductions in financial strain (rOR=042, 95% CI 0.23–0.77) but no changes in 3-month consultation rate were found. Per capita, advice recipients received £15 per £1 of funder investment.

Co-located welfare advice improves short-term mental health and well-being, reduces financial strain and generates considerable financial returns.