Personality traits may predict antidepressant discontinuation and response. However, previous studies were rather small, only explored a few personality traits and did not include adverse drug effects nor the interdependency between antidepressant discontinuation patterns and response.

GENDEP included 589 patients with unipolar moderate-severe depression treated with escitalopram or nortriptyline for 12 weeks. Seven personality dimensions were measured using the self-reported 240-item Temperament and Character Inventory-Revised (TCI-R). We applied Cox proportional models to study discontinuation patterns, logistic and linear regression to investigate response and remission after 8 and 12 weeks, and mixed-effects linear models regarding time-varying treatment response and adverse drug reactions.

Low harm avoidance, low cooperativeness, high self-transcendence and high novelty seeking were associated with higher risks for antidepressant discontinuation, independent of depressed mood, adverse drug reactions, drug, sex and age. Regression analyses showed that higher novelty seeking and cooperativeness scores were associated with a greater likelihood of response and remission after 8 and 12 weeks, respectively, but we found no correlations with response in the mixed-effects models. Only high harm avoidance was associated with more self-reported adverse effects.

This study, representing the largest investigation between several personality traits and response to two different antidepressants, suggests that correlations between personality traits and antidepressant treatment response may be confounded by differential rates of discontinuation. Future trials on personality in the treatment of depression need to consider this interdependency and study whether interventions aiming at improving compliance for some personality types may improve response to antidepressants.

For patients with major depressive disorder (MDD) experiencing side-effects or non-response to their first antidepressant, little is known regarding the effect of switching between a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI).

To compare the switch between the TCA nortriptyline and the SSRI escitalopram.

Among 811 adults with MDD treated with nortriptyline or escitalopram for up to 12 weeks, 108 individuals switched from nortriptyline to escitalopram or vice versa because of side-effects or non-response (trial registration: EudraCT No.2004-001723-38 (https://eudract.ema.europa.eu/) and ISRCTN No.03693000 (http://www.controlled-trials.com)). Patients were followed for up to 26 weeks after switching and response was measured with the Montgomery–Åsberg Depression Rating scale (MADRS). We performed adjusted mixed-effects linear regression models with full information maximum likelihood estimation reporting β-coefficients with 95% CIs.

Switching antidepressants resulted in a significant decrease in MADRS scores. This was present for switchers from escitalopram to nortriptyline (n = 36, β = −0.38, 95% CI −0.51 to −0.25, P<0.001) and from nortriptyline to escitalopram (n = 72, β = −0.34, 95% CI −0.41 to −0.26, P<0.001). Both switching options resulted in significant improvement among individuals who switched because of non-response or side-effects. The results were supported by analyses on other rating scales and symptom dimensions.

These results suggest that switching from a TCA to an SSRI or vice versa after non-response or side-effects to the first antidepressant may be a viable approach to achieve response among patients with MDD.

K.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. K.J.A. has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. D.S. has served on advisory boards for, and received unrestricted grants from, Lundbeck and AstraZeneca. A.F. and P.M. have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline.

Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.

To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.

The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.

In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.

This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.

Recent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.

To systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).

Analysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD–ASD (n = 16) and healthy controls (n = 78).

Weighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures.

Our results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors.

In recent years, the Kraepelinian dichotomy has been challenged in light of evidence on shared genetic and environmental factors for schizophrenia and bipolar disorder, but empirical efforts to identify a transdiagnostic phenotype of psychosis remain remarkably limited.

To investigate whether schizophrenia spectrum and bipolar disorder lie on a transdiagnostic spectrum with overlapping non-affective and affective psychotic symptoms.

Multidimensional item-response modelling was conducted on symptom ratings of the OPerational CRITeria (OPCRIT) system in 1168 patients with schizophrenia spectrum and bipolar disorder.

A bifactor model with one general, transdiagnostic psychosis dimension underlying affective and non-affective psychotic symptoms and five specific dimensions of positive, negative, disorganised, manic and depressive symptoms provided the best model fit and diagnostic utility for categorical classification.

Our findings provide support for including dimensional approaches into classification systems and a directly measurable clinical phenotype for cross-disorder investigations into shared genetic and environmental factors of psychosis.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism contributes to the development of depression (major depressive disorder, MDD), but it is unclear whether neural effects observed in healthy individuals are sustained in MDD.

To investigate BDNF Val66Met effects on key regions in MDD neurocircuitry: amygdala, anterior cingulate, middle frontal and orbitofrontal regions.

Magnetic resonance imaging scans were acquired in 79 persons with MDD (mean age 49 years) and 74 healthy volunteers (mean age 50 years). Effects on surface area and cortical thickness were examined with multiple comparison correction.

People who were Met allele carriers showed reduced caudal middle frontal thickness in both study groups. Significant interaction effects were found in the anterior cingulate and rostral middle frontal regions, in which participants in the MDD group who were Met carriers showed the greatest reduction in surface area.

Modulatory effects of the BDNF Val66Met polymorphism on distinct subregions in the prefrontal cortex in MDD support the neurotrophin model of depression.

Individuals with a mental health disorder appear to be at increased risk of medical illness.

To examine rates of medical illnesses in patients with bipolar disorder (n = 1720) and to examine the clinical course of the bipolar illness according to lifetime medical illness burden.

Participants recruited within the UK were asked about the lifetime occurrence of 20 medical illnesses, interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and diagnosed according to DSM-IV criteria.

We found significantly increased rates of several medical illnesses in our bipolar sample. A high medical illness burden was associated with a history of anxiety disorder, rapid cycling mood episodes, suicide attempts and mood episodes with a typically acute onset.

Bipolar disorder is associated with high rates of medical illness. This comorbidity needs to be taken into account by services in order to improve outcomes for patients with bipolar disorder and also in research investigating the aetiology of affective disorder where shared biological pathways may play a role.

None.

Most studies of post-traumatic stress disorder (PTSD) in low- and middle-income countries (LMICs) have focused on ‘high-risk’ populations defined by exposure to trauma.

To estimate the prevalence of post-traumatic stress disorder (PTSD) in a LMIC, the conditional probability of PTSD given a traumatic event and the strength of associations between traumatic events and other psychiatric disorders.

Our sample contained a mix of 3995 twins and 2019 non-twins. We asked participants about nine different traumatic exposures, including the category ‘other’, but excluding sexual trauma.

Traumatic events were reported by 36.3% of participants and lifetime PTSD was present in 2.0%. Prevalence of non-PTSD lifetime diagnosis was 19.1%. Of people who had experienced three or more traumatic events, 13.3% had lifetime PTSD and 40.4% had a non-PTSD psychiatric diagnosis.

Despite high rates of exposure to trauma, this population had lower rates of PTSD than high-income populations, although the prevalence might have been slightly affected by the exclusion of sexual trauma. There are high rates of non-PTSD diagnoses associated with trauma exposure that could be considered in interventions for trauma-exposed populations. Our findings suggest that there is no unique relationship between traumatic experiences and the specific symptomatology of PTSD.

© Royal College of Psychiatrists 2014. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence.

Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue.

To investigate whether higher BMI increases the risk of major depression.

Two instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case–control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI.

Linear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient −0.03, 95% CI −0.18 to 0.13, P = 0.73; GRS: coefficient −0.02, 95% CI −0.11 to 0.07, P = 0.62).

Our instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.

Little is known about the impact of different types of stressful events (for example divorce v. bereavement) on unipolar depression compared with bipolar disorder. Inconsistencies exist concerning the association between independent events (beyond an individual's control, such as bereavement) and bipolar disorder.

To examine the role of specific, independent and dependent events in mood disorders.

Life-event information was collected from 512 people with bipolar disorder, 1448 people with unipolar depression and over 600 controls.

Various events were associated with unipolar depression and bipolar disorder, but some event specificity was detected. For example, financial crisis was more strongly related to bipolar disorder rather than unipolar depression. Independent events were only related to unipolar depression and not bipolar disorder.

The events that were linked to bipolar disorder and unipolar depression were similar. Independent events were not associated with bipolar episodes, suggesting that life stress may be a consequence of, rather than a trigger for, bipolar episodes.

White matter abnormalities have been implicated in the aetiology of major depressive disorder; however, the relationship between the severity of symptoms and white matter integrity is currently unclear.

To investigate white matter integrity in people with major depression and healthy controls, and to assess its relationship with depressive symptom severity.

Diffusion tensor imaging data were acquired from 66 patients with recurrent major depression and a control group of 66 healthy individuals matched for age, gender and IQ score, and analysed with tract-based spatial statistics. The relationship between white matter integrity and severity of depression as measured by the Beck Depression Inventory was examined.

Depressive illness was associated with widespread regions of decreased white matter integrity, including regions in the corpus callosum, superior longitudinal fasciculus and anterior corona radiata, compared with the control group. Increasing symptom severity was negatively correlated with white matter integrity, predominantly in the corpus callosum.

Widespread alterations in white matter integrity are evident in major depressive disorder. These abnormalities are heightened with increasing severity of depressive symptoms.

The increasingly large sample size requirements of modern adult mental health research suggests the need for a data collection and diagnostic application that can be used across a broad range of clinical and research populations.

To develop a data collection and diagnostic application that can be used across a broad range of clinical and research settings.

We expanded and redeveloped the OPCRIT system into a broadly applicable diagnostic and data-collection package and carried out an interrater reliability study of this new tool.

OPCRIT+ performed well in an interrater reliability study with relatively inexperienced clinicians, giving a combined, weighted kappa of 0.70 for diagnostic reliability.

OPCRIT+ showed good overall interrater reliability scores for diagnoses. It is now incorporated in the electronic patient record of the Maudsley and associated hospitals. OPCRIT+ can be downloaded free of charge at http://sgdp.iop.kcl.ac.uk/opcritplus.