Little is known about how daily life mood reactivity to minor stressors (stress reactivity) might change following major depressive disorder (MDD) treatment. We investigate whether (i) mood states and appraisals of daily stressors change after treatment; (ii) stress reactivity to event, activity, or social stress differs; (iii) stress reactivity depends on severity of residual depressive symptoms; and (iv) stress reactivity in individuals with remitted or non-remitted depression differ from that of never-depressed individuals.

Thirty depressed individuals participated in an experience sampling study before and after a treatment period of 18 months; 39 healthy individuals formed a comparison group. Reactivity of positive affect (PA) and negative affect (NA) to daily stressors were measured.

More residual symptoms were associated with larger NA responses to stress. Compared to healthy controls, participants with non-remitted MDD showed higher NA-reactivity to all stressors. In contrast, stress reactivity to event and activity stressors was normalized in remitted patients. However, they still showed heightened NA-reactivity to social stress.

Greater stress reactivity to event and activity stress appears to be state-dependent. The heightened social stress reactivity in remitted patients suggests that sensitivity to social stress may reflect an underlying vulnerability in MDD.

One influential view is that vulnerability to major depressive disorder (MDD) is associated with a proneness to experience negative emotions in general. In contrast, blame attribution theories emphasise the importance of blaming oneself rather than others for negative events. Our previous exploratory study provided support for the attributional hypothesis that patients with remitted MDD show no overall bias towards negative emotions, but a selective bias towards emotions entailing self-blame relative to emotions that entail blaming others. More specifically, we found a decreased proneness for contempt/disgust towards others relative to oneself (i.e. self-contempt bias). Here, we report a definitive test of the competing general negative versus specific attributional bias theories of MDD.

We compared a medication-free remitted MDD (n = 101) and a control group (n = 70) with no family or personal history of MDD on a previously validated experimental test of moral emotions. The task measures proneness to specific emotions associated with different types of self-blame (guilt, shame, self-contempt/disgust, self-indignation/anger) and blame of others (other-indignation/anger, other-contempt/disgust) whilst controlling for the intensity of unpleasantness.

We confirmed the hypothesis that patients with MDD exhibit an increased self-contempt bias with a reduction in contempt/disgust towards others. Furthermore, they also showed a decreased proneness for indignation/anger towards others.

This corroborates the prediction that vulnerability to MDD is associated with an imbalance of specific self- and other-blaming emotions rather than a general increase in negative emotions. This has important implications for neurocognitive models and calls for novel focussed interventions to rebalance blame in MDD.

Joint hypermobility syndrome (JHS) has repeatedly been associated with anxiety and anxiety disorders, fibromyalgia, irritable bowel syndrome and temporomandibular joint disorder. However, the neural underpinnings of these associations still remain unclear. This study explored brain responses to facial visual stimuli with emotional cues using fMRI techniques in general population with different ranges of hypermobility.

Fifty-one non-clinical volunteers (33 women) completed state and trait anxiety questionnaire measures, were assessed with a clinical examination for hypermobility (Beighton system) and performed an emotional face processing paradigm during functional neuroimaging.

Trait anxiety scores did significantly correlate with both state anxiety and hypermobility scores. BOLD signals of the hippocampus did positively correlate with hypermobility scores for the crying faces versus neutral faces contrast in ROI analyses. No results were found for any of the other studied ROIs. Additionally, hypermobility scores were also associated with other key affective processing areas (i.e. the middle and anterior cingulate gyrus, fusiform gyrus, parahippocampal region, orbitofrontal cortex and cerebellum) in the whole brain analysis.

Hypermobility scores are associated with trait anxiety and higher brain responses to emotional faces in emotion processing brain areas (including hippocampus) described to be linked to anxiety and somatic symptoms. These findings increase our understanding of emotion processing in people bearing this heritable variant of collagen and the mechanisms through which vulnerability to anxiety and somatic symptoms arises in this population.

Alcohol dependence (AD) is associated with an increase in physical comorbidities. The effects of these diseases on general hospital-based mortality are unclear. Consequently, we conducted a mortality study in which we investigated if the burden of physical comorbidities and their relevance on general hospital-based mortality differs between individuals with and without AD during a 12.5-year observation period in general hospital admissions.

During 1 January 2000 and 30 June 2012, 23,371 individuals with AD were admitted at least once to seven General Manchester Hospitals. Their physical comorbidities with a prevalence ≥ 1% were compared to those of 233,710 randomly selected hospital controls, group-matched for age and gender (regardless of primary admission diagnosis or specialized treatments). Physical comorbidities that increased the risk of hospital-based mortality (but not outside of the hospital) during the observation period were identified using multiple logistic regression analyses.

Hospital-based mortality rates were 20.4% in the AD sample and 8.3% in the control sample. Individuals with AD compared to controls had a higher burden of physical comorbidities, i.e. alcoholic liver and pancreatic diseases, diseases of the conducting airways, neurological and circulatory diseases, diseases of the upper gastrointestinal tract, renal diseases, cellulitis, iron deficiency anemia, fracture neck of femur, and peripheral vascular disease. In contrast, coronary heart related diseases, risk factors of cardiovascular disease, diverticular disease and cataracts were less frequent in individuals with AD than in controls. Thirty-two individual physical comorbidities contributed to the prediction of hospital-based mortality in univariate analyses in the AD sample; alcoholic liver disease (33.7%), hypertension (16.9%), chronic obstructive pulmonary disease (14.1%), and pneumonia (13.3%) were the most frequent diagnoses in deceased individuals with AD. Multiple forward logistic regression analysis, accounting for possible associations of diseases, identified twenty-three physical comorbidities contributing to hospital-based mortality in individuals with AD. However, all these comorbidities had an equal or even lower impact on hospital-based mortality than in the comparison sample.

The excess of in-hospital deaths in general hospitals in individuals with AD is due to an increase of multiple physical comorbidities, even though individual diseases have an equal or even reduced impact on general hospital-based mortality in individuals with AD compared to controls.

In this work we consider Cloninger's psychobiological model, which measures two dimensions of personality: character and temperament. Temperament refers to the biological basis of personality and its characteristics, while character refers to an individual's attitudes towards own self, towards humanity and as part of the universe.

The Temperament and Character Inventory-Revised-140 (TCI-R-140) was administered to 3 divergent samples: a general population sample, a sample of male conscripts and a sample of individuals attending a substance abuse rehabilitation programme. Score differences among the three samples were assessed controlling for age and gender and reliability coefficients are reported. The latent structure was studied in all samples, using exploratory and confirmatory factor analysis methods (EFA and CFA respectively).

The proposed structure was partially replicated via EFA. CFA however indicated less than satisfactory fit, as in previously reported results. To improve the fit, the path diagram was augmented to account for multiple factor complexity, as suggested by the EFA results in all samples. While retaining the original seven-factor structure, the augmented model provided adequate fit. The consistency of the inventory was satisfactory in all samples. Evidence for the construct validity was found in relation to aggression.

This is the first study to conclude in adequate fit, after allowing for the indicators to load on more than one factor within each dimension. While cross-national differences apply, our results were similar (when comparable) with previously reported ones in the literature.

Ethnic minority groups show elevated suicide attempt rates across Europe. Evidence suggests a similar trend for women of Turkish origin in Germany, yet data on suicidal behaviour in minorities in Germany is scarce. The objective was to examine rates of suicidal behaviour, underlying motives, and to explore the effectiveness of an intervention program.

From 05/2009–09/2011, data on all suicide attempts among women of Turkish origin who presented at a hospital-based emergency unit in Berlin, Germany, were collected. A multi-modal intervention was conducted in 2010 and the effects of age, generation and the intervention on suicide attempt rates were examined.

At the start, the highest rate was found in women aged 18–24 years with 225.4 (95% CI = 208.8–242.0)/100,000. Adjustment disorder was the most prevalent diagnosis with 49.7% (n = 79), being more common in second-generation women (P = .004). Further analyses suggested an effect of the intervention in the youngest age group (trend change of ß = –1.25; P = .017).

Our findings suggest a particularly high rate of suicide attempts by 18–24-year-old, second-generation women of Turkish origin in Berlin. Furthermore, our results suggest a trend change in suicide attempts in women aged 18–24 years related to a population-based intervention program.

Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence. These findings suggest that DNTBP1 may be involved in pathways that lead to multiple psychiatric phenotypes. In this study, we explored the association between DTNBP1 SNPs (single nucleotide polymorphisms) and multiple psychiatric phenotypes included in the Diagnostic Interview of Psychosis (DIP).

Five DTNBP1 SNPs, rs17470454, rs1997679, rs4236167, rs9370822 and rs9370823, were genotyped in 235 schizophrenia subjects screened for various phenotypes in the domains of depression, mania, hallucinations, delusions, subjective thought disorder, behaviour and affect, and speech disorder. SNP-phenotype association was determined with ANOVA under general, dominant/recessive and over-dominance models.

Post hoc tests determined that SNP rs1997679 was associated with visual hallucination; SNP rs4236167 was associated with general auditory hallucination as well as specific features including non-verbal, abusive and third-person form auditory hallucinations; and SNP rs9370822 was associated with visual and olfactory hallucinations. SNPs that survived correction for multiple testing were rs4236167 for third-person and abusive form auditory hallucinations; and rs9370822 for olfactory hallucinations.

These data suggest that DTNBP1 is likely to play a role in development of auditory related, visual and olfactory hallucinations which is consistent with evidence of DTNBP1 activity in the auditory processing regions, in visual processing and in the regulation of glutamate and dopamine activity.

The CACNA1C rs1006737 risk A allele has been associated with affective psychoses and functional studies indicate that it is associated with increased hippocampal/amygdala activity during emotional face-processing. Here we studied the impact of the risk A allele on affective startle modulation.

Hundred and ninety-four healthy males stratified for their CACNA1C rs1006737 genotype (GG:111, GA:67, AA:16) were presented with 18 pleasant, 18 unpleasant and 18 neutral pictures with acoustic probes (104 dB) occurring during 12 pictures in each affective category. Baseline startle was assessed during blank screens. State mood was self-rated on arrival, pre- and post-test and the emotional valence and arousal of affective pictures at post-test.

Relative to the other genotypes, risk A allele homozygotes presented with higher anxiety/negative affect at pre-test, reduced and exaggerated physiological responses to the pleasant and negative pictures respectively, negative affect with reduced arousal at post-test and rated the affective pictures as less arousing and inconsistently to their physiological responses (all P < 0.05). Sustained contextual negative mood predicted reduced baseline and affective startle reactivity in the AA group.

Healthy homozygous males for the risk A allele appear to have marked contextual sensitivity, affective reactivity akin to anxiety and depression and inefficient emotional appraisal. Our findings provide phenotypic detail of the CACNA1C AA genotype in non-symptomatic individuals, which suggest primary effects in emotional circuitry, consistent with previously documented alterations in hippocampal/amygdala processing.

Interpersonal violence and suicide are among the main causes of mortality and morbidity around the world. In several developing countries, such as Colombia, they are among the first five entities of public health concern. Aggressiveness is an important endophenotype for aggression and suicidal behavior, having a heritability of around 50%. Exploration of classical candidate genes, involved in serotoninergic and dopaminergic neurotransmission, has identified few consistent risk factors for aggressiveness. miRNAs are a novel class of molecules with a growing role in normal neural function and neuropsychiatric disorders; of special interest, miR-124 is a brain-specific miRNA that is key for neuronal plasticity. We evaluated the hypothesis that a functional polymorphism in MIR124-1 gene might be associated with aggressiveness in a Colombian sample.

The Spanish adaptation of the refined version of the Aggression Questionnaire and the abbreviated Barratt Impulsiveness Scale were applied to 170 young subjects. The functional SNP in MIR124-1 (rs531564) was genotyped by a TaqMan assay.

We found a significant association between the MIR124-1 and aggressiveness in our sample, with G/G carriers having lower scores (P = 0.01). This association seemed to be specific for aggressiveness, as it was not significant for impulsiveness.

We showed for the first time the association of a functional polymorphism in MIR124-1 and aggressiveness. Known targets of miR-124 (such as BDNF and DRD4 genes) could explain the effect of this miRNA on behavior. A future analysis of additional novel functional polymorphisms in other brain expressed miRNAs could be useful for a deeper understanding of aggression in humans.

To investigate the effects of atomoxetine on emotional control in adults with ADHD.

We performed an integrated analysis using individual patient data pooled from three Eli Lilly-sponsored studies. An integrated analysis can be viewed as a meta-analysis of individual patient-level data, rather than study-level summary data.

Two populations were identified: a large sample of patients with pre-treatment baseline data (the “overall population”; n = 2846); and a subset of these patients with placebo-controlled efficacy data from baseline to 10 or 12 weeks after initiating treatment (the “placebo-controlled population”; n = 829). At baseline, in the overall population, ∼50% of ADHD patients had BRIEF-AS (Behavior Rating Inventory of Executive Function-Adult Version Self-Report) Emotional control subscores between 21 and 30, compared with ∼10% of normative subjects in the BRIEF-A manual. At endpoint, in the placebo-controlled population, atomoxetine led to a small (effect size 0.19) but significant (P = 0.013) treatment effect for emotional control. The effect size was 0.32 in patients with BRIEF-AS Emotional control scores > 20 at baseline. Improvements in emotional control correlated with improvements in the core ADHD symptoms and quality-of-life.

As deficient emotional control is associated with impaired social, educational and occupational functioning over and above that explained by core ADHD symptoms alone, improvements in emotional control may be clinically relevant.

At baseline, adults with ADHD were more likely to have impaired emotional control than normative subjects. In the adult ADHD patients, atomoxetine treatment was associated with improvements in emotional control, as well as in core ADHD symptoms and quality-of-life.

There are few approved therapies for adults with attention-deficit/hyperactivity disorder (ADHD) in Europe. Lisdexamfetamine (LDX) is an effective treatment for ADHD; however, no clinical trials examining the efficacy of LDX specifically in European adults have been conducted. Therefore, to estimate the efficacy of LDX in European adults we performed a meta-regression of existing clinical data.

A systematic review identified US- and Europe-based randomized efficacy trials of LDX, atomoxetine (ATX), or osmotic-release oral system methylphenidate (OROS-MPH) in children/adolescents and adults. A meta-regression model was then fitted to the published/calculated effect sizes (Cohen's d) using medication, geographical location, and age group as predictors. The LDX effect size in European adults was extrapolated from the fitted model. Sensitivity analyses performed included using adult-only studies and adding studies with placebo designs other than a standard pill-placebo design.

Twenty-two of 2832 identified articles met inclusion criteria. The model-estimated effect size of LDX for European adults was 1.070 (95% confidence interval: 0.738, 1.401), larger than the 0.8 threshold for large effect sizes. The overall model fit was adequate (80%) and stable in the sensitivity analyses.

This model predicts that LDX may have a large treatment effect size in European adults with ADHD.

Asenapine is the most recent compound that has been FDA- and EMA-approved for treatment of mania. Its efficacy and safety have been assessed in placebo-controlled trials, but little is known about its performance in routine clinical conditions. In this study, we compared features of patients treated with adjunctive asenapine or other adjunctive antipsychotics and the costs of the treatment.

A combined prospective and retrospective data collection and analysis was conducted from January 2011 to December 2013 following a clinical interview and assessment of manic and depressive symptoms (YMRS, HDRS-17), clinical state (CGI-BP-M), psychosocial functioning (FAST), sexual dysfunction (PRSexDQ) and health resource costs associated with treatment with adjunctive asenapine versus other adjunctive antipsychotics.

Hundred and fifty-two patients from different university hospitals were included. Fifty-three patients received adjunctive asenapine and 99 received other adjunctive antipsychotics concomitantly to mood stabilizers. Considering inpatients, those treated with adjunctive asenapine presented a significantly less severe manic episode (P = 0.001), less psychotic symptoms (P = 0.030) and more comorbid personality disorder (P = 0.002). Regarding outpatients, those treated with adjunctive asenapine showed significantly less severe manic episode (P = 0.046), more previous mixed episodes (P = 0.013) and more sexual dysfunction at baseline (P = 0.036). No significant differences were found in mean total costs per day.

Clinicians tended to use adjunctive asenapine in patients with less severe manic symptoms but more complex clinical profile, including more mixed episodes in the past, concomitant personality disorder, and sexual problems. Treatment with adjunctive asenapine was not associated with higher costs when compared to other options.