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.

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.

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.

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.

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.

Few studies have examined whether attributional style (an individual's explanation of why events happen) is a genetically influenced vulnerability factor for depression.

To investigate whether attributional style is an enduring vulnerability trait for recurrent depression.

As part of the Cardiff Depression Study, we interviewed 108 people with depression and their siblings, and a control group of 105 healthy individuals and their siblings, using the Schedules for Clinical Assessment in Neuropsychiatry and the Life Events and Difficulties Schedule. Participants also completed the Attributional Style Questionnaire.

Regression analyses showed that attributional style results from mood state and is not a familial risk factor for depression. However, the tendency to internalise negative events was related to having had a prior episode of depression, suggesting a ‘scarring’ effect. Also, non-severe events were associated with one subset of optimistic attributions.

Attributional style mainly measures current mood and does not reflect a familial risk factor for depression.

Schneider's first-rank symptoms are given particular weight when making a diagnosis of schizophrenia, but the nuclear syndrome, characterised by one or more first-rank symptoms, has been found previously to have no heritability.

To estimate the heritability of the nuclear syndrome.

A total of 224 twin pairs (106 monozygotic, 118 same-gender dizygotic) were ascertained from the Maudsley Twin Register in London via probands with any psychosis. Lifetime-ever first-rank symptoms were rated using the OPCRIT checklist. Probandwise concordance rates were calculated for the nuclear syndrome and a heritability estimate was derived from biometric model fitting.

Probandwise concordance rates were 13/49 (26.5%) for monozygotic and 0/45 to 2/46 (0.0–4.3%) for dizygotic pairs. The heritability estimate for the best-fitting model was 71% (95% CI 57–82).

These results indicate that the nuclear syndrome shows substantial heritability, although this is slightly lower than that for schizophrenia as defined by the DSM and ICD systems.

OPCRIT (a suite of computer programs that allow data entry and generate diagnoses according to 12 operational diagnostic systems) is used in a wide range of psychiatric research including both European Science Foundation and NIMH research initiatives in the molecular genetics of mental disorders. We examined its concurrent validity in 100 subjects collected for linkage studies of Bipolar Disorder and Schizophrenia.

We compared diagnoses generated by OPCRIT from data rated by two trained clinicians with diagnoses made according to consensus, best-estimate, lifetime procedures by the same two raters according to DSM–III–R and RDC classifications.

Good to excellent agreement was achieved between OPCRIT diagnoses and those made by consensus best-estimate procedures.

OPCRIT provides a convenient, reliable, rapid and valid approach to polydiagnostic assessment that can be used as an adjunct to conventional (but time consuming) best-estimate consensus diagnostic procedures.