Ketamine is a rapidly-acting antidepressant treatment with robust response rates. Previous studies have reported that serial ketamine therapy modulates resting state functional connectivity in several large-scale networks, though it remains unknown whether variations in brain structure, function, and connectivity impact subsequent treatment success. We used a data-driven approach to determine whether pretreatment multimodal neuroimaging measures predict changes along symptom dimensions of depression following serial ketamine infusion.

Patients with depression (n = 60) received structural, resting state functional, and diffusion MRI scans before treatment. Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17), the Inventory of Depressive Symptomatology (IDS-C), and the Rumination Response Scale (RRS) before and 24 h after patients received four (0.5 mg/kg) infusions of racemic ketamine over 2 weeks. Nineteen unaffected controls were assessed at similar timepoints. Random forest regression models predicted symptom changes using pretreatment multimodal neuroimaging and demographic measures.

Two HDRS-17 subscales, the HDRS-6 and core mood and anhedonia (CMA) symptoms, and the RRS: reflection (RRSR) scale were predicted significantly with 19, 27, and 1% variance explained, respectively. Increased right medial prefrontal cortex/anterior cingulate and posterior insula (PoI) and lower kurtosis of the superior longitudinal fasciculus predicted reduced HDRS-6 and CMA symptoms following treatment. RRSR change was predicted by global connectivity of the left posterior cingulate, left insula, and right superior parietal lobule.

Our findings support that connectivity of the anterior default mode network and PoI may serve as potential biomarkers of antidepressant outcomes for core depressive symptoms.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Improvement in symptoms of depression is typically delayed with antidepressant treatment. Pipamperone (PIP) at low doses acts as a highly selective 5HT2A/D4 receptor antagonist. The purpose of this study was to investigate whether the addition of PIP to the SSRI citalopram (CIT) would increase the rate of resolution of depressive symptoms.

This was an 8-week, double-blind, parallel-group, single-dummy study in patients with MDD who received either CIT 40 mg daily or PIP 5 mg bid plus CIT 40 mg daily (PIPCIT).

The mean total MADRS score (±SD) of the 165 patients (81% women; mean age, 40 y) was 32.6±5.5. More CIT than PIPCIT patients discontinued treatment in the first 4 weeks [15 (18%) vs 3 (4%); P=0.003]. Reductions in mean total MADRS scores were significantly (ITT LOCF) larger in patients receiving PIPCIT after 1 week [-6.42±6.18 vs -3.99±5.15; P=0.007] and 4 weeks [-15.06±8.48 vs - 12.11±8.30; P=0.025] compared with those receiving CIT alone. Significant differences in favor of PIPCIT were observed in MADRS items “reduced sleep,” “reduced appetite,” “concentration difficulties,” and “pessimistic thoughts.” Mean CGI-I scores were also improved after 1 week of PIPCIT [3.09±0.85 vs. 3.47±0.72; P=0.002]. There were no significant differences observed at 8 weeks. No additional, clinically significant adverse events were noted in the PIPCIT group.

A low dose of PIP added to CIT provided superior antidepressant effects and less discontinuations compared with CIT alone during the first 4 weeks of treatment, and especially in the first week, at apparently no tolerability/safety cost.

Prior studies have demonstrated an inter-relationship between the diagnosis of diabetes, obesity and depression. Our data has demonstrated that baseline body mass index (BMI) was not predictive for clinical outcomes (remission at six months).

Our hypothesis was that obesity (BMI ≥30) and the diagnosis of diabetes in depressed primary patients would have no effect on depression remission rates six months after diagnosis.

This study was retrospective analysis of 1, 894 primary care patients diagnosed with Major Depressive Disorder or Dysthymia with a PHQ-9 score of 10 or greater.

1. ▪ Outcome variable was clinical remission (PHQ-9 < 5) at six months.

2. ▪ Logistic regression modeling included the demographic variables of age, gender, marital status, the clinical variables of BMI, baseline PHQ-9 score, diagnosis of diabetes (yes/no) and clinical diagnosis (recurrent or first episode of depression, or dysthymia).

Figure 1

Odds ratio for clinical remission (PHQ-9<5) at six months in depressed primary care patients, by variable (N=1,894).

Controlling for age, gender, marital status, race, clinical diagnosis and clinical site with logistic regression modeling.

1. ▪ Baseline obesity was not an independent predictor for depression outcome at six months.

2. ▪ Diagnosis of diabetes was not an independent predictor for depression outcome at six months.

This data suggests that obesity and diabetes were not associated with worsening clinical outcomes in depression management.

With one in ten young people being affected by ill mental health and stigma regularly cited as a factor affecting access to early intervention services, focussing resources on school based stigma reduction strategies seems prudent. ‘Headucate’, a student society, designed a 50 minute workshop which aims to increase mental health literacy and decrease stigma.

Repeated, cross sectional surveys were carried out at three time points; 1) immediately before (n=77), 2) Immediately after (n=81) and 3) three months post workshop (n=73). The surveys were paper based versions of the Reported Intended Behaviours Score (RIBS) and Mental Health Knowledge Scale (MAKS) utilising a social distance scale.

Four year 10 classed (pupils aged 14-15) were recruited. Post hoc t-tests were carried out when one-way ANOVAS were significant.

Disorder knowledge (from MAKS) and intended contact (from RIBS) significantly increased between time points one and two (p<0.01 and <0.004 respectively) but then decreased.

Analysis of the question pertaining to knowing where to access help showed a statistically significant increase (p<0.001) between time points one and two and then a decrease at time three, albeit to a higher value than at time point one (3.45 compared to 3.13, P=0.088).

Headucate workshops offer a low resource option which is well accepted by students. Like other school based stigma reduction strategies, a dramatic increase was seen between immediately before and after indicating that the workshop resonates with the pupils, but there was little sustained change in attitudes.

Against a backdrop of poor mental health education in UK schools a group of students from Norwich Medical School have formed a student society called ‘Headucate’ in order to create, deliver and evaluate an educational intervention for adolescents, initially to be delivered in Norfolk schools.

To create an educational intervention that:

• Is the length of a standard lesson

• Is age appropriate and acceptable

• Contains appropriate signposting

• Contains content that challenges common myths and replaces them with knowledge

• Contains content that encourages empathy and understanding towards those with mental illnesses

• Is easily delivered in the same way each time so that its effectiveness can be evaluated

To create an intervention effective at tackling stigma and empowering adolescents to recognise signs of poor mental health and access services appropriately.

Lesson plan created after consultation with psychiatrists, a psychologist, a GP, a university outreach professional, a teacher and secondary school age children, then trialled and revised.

Interactive workshop produced with 5 sections.

1. 1) Myth vs Fact activity that dispels prevalent myths

2. 2) Scenario based activity to demonstrate that mental health is a spectrum

3. 3) An interactive presentation covering the most common mental illnesses and their symptoms

4. 4) An activity focusing on talking to those with mental illnesses, furthering the scenario from the previous activity

5. 5) A question and answer session. Every student leaves with a leaflet containing appropriate signposting.

We have created an educational intervention ready to be delivered and evaluated.

Prior studies have demonstrated an inter-relationship between the diagnosis of diabetes, obesity and depression. Our prior studies have shown that the diagnosis of diabetes or baseline body mass index (BMI) did not impact six month depression remission rates.

Our hypothesis was that level of control of diabetes (hemoglobulin A1c < 8.0%) in depressed diabetic patients would have no effect on depression remission rates six months after diagnosis.

This study was retrospective analysis of 451 diabetic primary care patients diagnosed with Major Depressive Disorder or Dysthymia with a PHQ-9 score of 10 or greater.

1. ▪ Outcome variable was clinical remission (PHQ-9 < 5) at six months.

2. ▪ Logistic regression modeling included the demographic variables of age, gender, marital status, the clinical variables of BMI, baseline PHQ-9 score, hemoglobin A1c level (at date of diagnosis of depression) and clinical diagnosis (recurrent or first episode of depression, or dysthymia).

78.5% (354) of depressed diabetics were in good control of diabetes (hemoglobin A1c< 8%) at enrollment. Obesity (BMI≥ 30) at baseline was not different between the controlled and uncontrolled diabetic patients at baseline (approximately 70%), p=0.36.

Figure 1

Odds ratio for clinical remission (PHQ-9<5) at six months in diabetic primary care patients, by variable (N=451).

Controlling for age, gender, marital status, race, clinical diagnosis and clinical site.

1. ▪ Baseline control of diabetes was not an independent predictor for depression outcome at six months.

This data suggests that poor diabetic control was not associated worsening clinical outcomes in depression management.

Mental health education is not compulsory in the UK therefore adolescents have very varied experiences despite half of people with mental health illnesses reporting having experienced symptoms by 14 years old. University students are ideal for delivering a relaxed, educational intervention aimed at this age group, providing an opportunity to for them to learn necessary tools for recognising signs of poor mental health and tackle associated stigma.

To expand Headucate's membership, including other disciplines within the University of East Anglia (UEA) and provide core training enabling members to deliver a school-based educational intervention

Recruitment of members has been a multifaceted approach utilising social media sites such as Facebook and the Headucate website, and oncampus events and ‘awareness campaigns’ including several successful evening talks and lectures.

Three training sessions, which include ‘Introduction to Mental Health’, ‘Workshop run-through’ and ‘Child Protection’, have been developed for all members wishing to partake in the delivery of workshops.

We have recruited approximately 300 members since summer 2012; 70 fully paid members in 2012/13 academic year and currently 45 paid members for 2013/14.

A total of 18 members are fully trained and ready to deliver workshops within schools and 17 other members have just one training session remaining.

We are looking forward to delivering our first workshops in October and building on a successful first year. We are confident we can provide workshops for approximately 600 children per year.

The symptoms of many mental illnesses often begin during high school. Interventions to improve mental health awareness amongst adolescents may lead to improved outcomes. in the UK unfortunately many schools do not fulfil this need and mental health education is not a compulsory part of the curriculum.

To develop and measure the effectiveness of and educational intervention designed to raise awareness and empower adolescents to recognise signs of poor mental health and access services appropriately.

Evaluate the effectiveness of the intervention through baseline and follow up surveys.

Students at Norwich Medical School collaborated with teachers, psychiatrists and general practitioners to design an educational intervention that aims to tackle stigma and raise awareness of mental health conditions among 13-14 year olds in the hope that they can access services when needed, support those around them and look after their mental health. To evaluate effectiveness of the intervention, a knowledge, attitudes and practices survey that utilises a social distance scale that has been adapted for this age group and will be used to gather baseline and follow up data after six months.

We have developed a one-hour educational intervention delivered by medical students, that uses a variety of teaching techniques to raise awareness of mental health issues. We will start implementation in January 2013 so will have baseline effectiveness results shortly after.

Headucate has the potential to fill an important gap in effectively raising awareness of mental health issues in schools.

Perfectionism is a transdiagnostic risk factor across psychopathology. The Clinical Perfectionism Questionnaire (CPQ) was developed to assess change in order to provide clinical utility, but currently the psychometric properties of the CPQ with adolescents is unknown.

To assess the factor structure and construct validity of the CPQ in female adolescents.

The CPQ was administered to 267 females aged 14–19 years of age. Confirmatory factor analysis (CFA) was used to examine the validity of the two-factor model and a second-order factor model. Pearson correlations were used to evaluate the relationships between the CPQ and a wide range of measures of perfectionism, psychopathology and personality traits.

The study demonstrated internal consistency, construct validity and incremental validity of the CPQ in a sample of female adolescents. The CFA in the present study confirmed the two-factor model of the CPQ with Factor 1 relating to perfectionistic strivings and Factor 2 representing perfectionistic concerns. The second-order two factor model indicated no deterioration in fit.

The two-factor model of the CPQ fits with the theoretical definition of clinical perfectionism where the over-dependence of self-worth on achievement and concern over mistakes are key elements. The CPQ is suitable for use with female adolescents in future research that seeks to better understand the role of perfectionism in the range of mental illnesses that impact youth.