Generalizability of antidepressant efficacy trials (AETs) to daily practice is questioned because of their very stringent patient selection. This study aims to determine eligibility for AETs of out-patients suffering from major depression in a routine out-patient setting and investigates influence of eligibility on treatment outcome.

Data collection (n=1653) was performed through routine outcome monitoring by independent trained research nurses. The Mini-International Neuropsychiatric Interview Plus and the Dimensional Assessment of Personality Pathology, short Dutch version were used for diagnostic assessment and personality pathology screening. The Montgomery–Asberg Depression Rating Scale (MADRS) was used for assessment of baseline severity and treatment outcome. Eligibility was assessed by stepwise application of commonly used exclusion criteria. Influence of eligibility on treatment outcome was investigated in a subsample of the 1653 patients who had at least one follow-up assessment (n=626). Eligible and non-eligible patients were compared on proportion of response (50% reduction) and remission on MADRS (MADRS⩽10).

Altogether, 17–25% of the patients were eligible for AETs. The most common reasons for exclusion would be ‘not meeting minimum baseline severity’ and ‘presence of co-morbid Axis I disorder’. Eligible and non-eligible patients did not differ in treatment outcome. Only ‘meeting the minimum baseline severity’ is associated with remission.

The majority of ‘real life’ out-patients are not eligible for AETs. However, the influence of eligibility on treatment outcome seems to be small. This suggests that stringent patient selection by eligibility criteria is not the major reason for lack of generalizability of AETs. Exclusion of less severely depressed patients from the analyses resulted in better treatment outcome. Milder depression is highly prevalent in daily practice and more research into treatment effectiveness in milder depression is warranted.

The prevalence of psychological distress and common mental disorders has been shown to peak in midlife but analyses have ignored the association of poor material circumstances with prevalence. This study aimed to test the hypothesis that the midlife prevalence peak occurs only in lower-income households.

Pooled data were used from the annual Health Survey for England, a nationally representative cross-sectional study, on community-dwelling individuals aged ⩾16 years from years 1997 to 2006 (n=100 457). 12-item General Health Questionnaire scores, reported mental illness diagnoses and receipt of relevant medication were assessed in relation to household income and age. Analyses were separated by gender and adjusted for age, ethnicity, smoking, social class, education and co-morbidities.

Prevalence of psychological distress, diagnoses and treatments rose with age until early middle age and declined subsequently. In analyses conducted separately by income categories, this pattern was marked in low-income groups but absent in high-income groups. Income-related inequalities in the prevalence of psychological distress were greatest in midlife; for example, in men aged 45–54 years the odds ratio of receiving psychiatric medication in the lowest income group compared with the highest was 7.50 [95% confidence interval (CI) 4.24–13.27] and in women aged 45–54 years the odds ratio of reporting mental illness was 10.25 (95% CI 6.16–17.05).

An increased prevalence of psychological distress, common mental disorder diagnoses and treatment in midlife is not a universal phenomenon but is found only in those in low-income households. This implies the phenomenon is not inevitable but is potentially manageable or preventable.

The clinical benefit for depression of an interactive computer-assisted cognitive-behavioral program on CD-ROM, the Wellness Workshop (WW), was evaluated in a randomized controlled trial.

A total of 191 individuals referred by primary-care physicians were randomly assigned to a control group, where physician-directed treatment as usual (TAU) was provided, or to a treatment group, where TAU was supplemented with the WW CD-ROM, delivered by mail (WW+TAU). Data were collected at baseline, at 6 weeks' post-intervention, and at a 6-month follow-up assessment. Participants were given a strong incentive by a reimbursement of $75 for completion of each assessment. Measures included symptom ratings obtained via structured clinical diagnostic interviews, as well as a battery of self-report questionnaires on symptoms specifically targeted by the intervention.

Analysis of results demonstrated evidence for skill acquisition for improving dysfunctional thinking and reducing anxiety. Among those who met diagnostic criteria for depression, WW+TAU participants were three times more likely to remit at 6 weeks' post-test than TAU participants.

The evidence supports the conclusion that the WW intervention added benefit to traditional care for depression. No placebo comparison group was included and the WW+TAU participants received slightly more attention (a supportive telephone contact, ⩽5 min from a psychologist 2 weeks after receiving the program). Overall, the findings add support to the accumulating evidence for the potential clinical benefit of computer-assisted behavioral health interventions.

Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations.

A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds.

In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20–1.93] and conduct disorder (CD; HR 2.27, CI 1.31–3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00–1.94). Logistic regression analysis suggested that the parental depression–offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63–3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95–6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses.

The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.

Depressed individuals demonstrate a poorer ability to recognize the emotions of others, which could contribute to difficulties in interpersonal behaviour. This emotion recognition deficit appears related to the depressive state and is particularly pronounced when emotions are labelled semantically. Here, we investigated its neural basis by comparing emotion recognition processing between depressed, recovered and healthy individuals.

Medication-naive patients with a first major depressive episode, medication-free patients who had recovered from a first episode, and a group of matched healthy individuals participated. They were requested to identify the emotion of angry and fearful face stimuli, either by matching them to other emotional faces on a perceptual basis or by matching them to a semantic label, while their brain activity was measured with functional magnetic resonance imaging.

The depressed individuals performed worse than recovered and healthy individuals on the emotion-labelling but not the emotion-matching task. The labelling deficit was related to increased recruitment of the right amygdala, left inferior frontal gyrus and anterior cingulate cortex.

Deficits in semantic labelling of negative emotions are related to increased activation in specific brain regions and these abnormalities are mood state-dependent. These results indicate that accessing semantic knowledge about negative information triggers increased amygdala and left inferior frontal gyrus processing, which subsequently impairs task-relevant behaviour. We propose that this may reflect the activation of negative schemas.

Pre-adult onset of major depressive disorder (MDD) may predict a more severe phenotype of depression. As data from naturalistic psychiatric specialty care settings are scarce, we examined phenotypic differences between pre-adult and adult onset MDD in a large sample of consecutive out-patients.

Altogether, 1552 out-patients, mean age 39.2±11.6 years, were diagnosed with current MDD on the Mini-International Neuropsychiatric Interview Plus diagnostic interview as part of the usual diagnostic procedure. A total of 1105 patients (71.2%) had complete data on all variables of interest. Pre-adult onset of MDD was defined as having experienced the signs and symptoms of a first major depressive episode before the age of 18 years. Patients were stratified according to the age at interview (20–40/40–65 years). Correlates of pre-adult onset were analysed using logistic regression models adjusted for age, age squared and gender.

Univariate analyses showed that pre-adult onset of MDD had a distinct set of demographic (e.g. less frequently living alone) and clinical correlates (more co-morbid DSM-IV – Text Revision diagnoses, more social phobia, more suicidality). In the multivariate model, we found an independent association only for a history of suicide attempts [odds ratio (OR) 3.15, 95% confidence intervals (CI) 1.97–5.05] and current suicidal thoughts (OR 1.81, 95% CI 1.26–2.60) in patients with pre-adult versus adult onset MDD.

Pre-adult onset of MDD is associated with more suicidality than adult onset MDD. Age of onset of depression is an easy to ascertain characteristic that may help clinicians in weighing suicide risk.

Depression increases the risk of subsequent vascular events in both cardiac and non-cardiac patients. Atherosclerosis, the underlying process leading to vascular events, has been associated with depression. This association, however, may be confounded by the somatic-affective symptoms being a consequence of cardiovascular disease. While taking into account the differentiation between somatic-affective and cognitive-affective symptoms of depression, we examined the association between depression and atherosclerosis in a community-based sample.

In 1261 participants of the Nijmegen Biomedical Study (NBS), aged 50–70 years and free of stroke and dementia, we measured the intima–media thickness (IMT) of the carotid artery as a measure of atherosclerosis and we assessed depressive symptoms using the Beck Depression Inventory (BDI). Principal components analysis (PCA) of the BDI items yielded two factors, representing a cognitive-affective and a somatic-affective symptom cluster. While correcting for confounders, we used separate multiple regression analyses to test the BDI sum score and both depression symptom clusters.

We found a significant correlation between the BDI sum score and the IMT. Cognitive-affective, but not somatic-affective, symptoms were also associated with the IMT. When we stratified for coronary artery disease (CAD), the somatic-affective symptom cluster correlated significantly with depression in both patients with and patients without CAD.

The association between depressive symptoms and atherosclerosis is explained by the somatic-affective symptom cluster of depression. Subclinical vascular disease thus may inflate depressive symptom scores and may explain why treatment of depression in cardiac patients hardly affects vascular outcome.

Depression and anxiety are common after diagnosis of breast cancer. We examined to what extent these are recurrences of previous disorder and, controlling for this, whether shame, self-blame and low social support after diagnosis predicted onset of depression and anxiety subsequently.

Women with primary breast cancer who had been treated surgically self-reported shame, self-blame, social support and emotional distress post-operatively. Psychiatric interview 12 months later identified those with adult lifetime episodes of major depression (MD) or generalized anxiety disorder (GAD) before diagnosis and onset over the subsequent year. Statistical analysis examined predictors of each disorder in that year.

Of the patients, two-thirds with episodes of MD and 40% with episodes of GAD during the year after diagnosis were experiencing recurrence of previous disorder. Although low social support, self-blame and shame were each associated with both MD and GAD after diagnosis, they did not mediate the relationship of disorder after diagnosis with previous disorder. Low social support, but not shame or self-blame, predicted recurrence after controlling for previous disorder.

Anxiety and depression during the first year after diagnosis of breast cancer are often the recurrence of previous disorder. In predicting disorder following diagnosis, self-blame and shame are merely markers of previous disorder. Low social support is an independent predictor and therefore may have a causal role.

The anxiety disorders are robust correlates/predictors of suicidal ideation, but it is unclear whether (a) the anxiety disorders are specifically associated with suicidal ideation or (b) the association is due to co-morbidity with depression and other disorders. One means of modeling co-morbidity is through the personality traits neuroticism/negative emotionality (N/NE) and extraversion/positive emotionality (E/PE), which account for substantial shared variance among the internalizing disorders. The current study examines the association between the internalizing disorders and suicidal ideation, after controlling for co-morbidity via N/NE and E/PE.

The sample consisted of 327 psychiatric out-patients. Multiple self-report and interview measures were collected for internalizing disorders [depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), social anxiety, panic and specific phobia] and suicidal ideation, as well as self-report measures for N/NE and E/PE. A model was hypothesized in which each disorder and suicidal ideation was regressed on N/NE, and depression and social anxiety were regressed on E/PE. Structural equation modeling (SEM) was used to examine the unique association of suicidality with each disorder, beyond shared variance with N/NE and E/PE.

The hypothesized model was an acceptable fit to the data. Although zero-order analyses indicated that suicidal ideation was moderately to strongly correlated with all of the disorders, only depression and PTSD remained significantly associated with suicidal ideation in the SEM analyses.

In a latent variable model that accounts for measurement error and a broad source of co-morbidity, only depression and PTSD were uniquely associated with suicidal ideation; panic, GAD, social anxiety and specific phobia were not.

The thickness of the cortical mantle is a sensitive measure for identifying alterations in cortical structure. We aimed to explore whether first episode schizophrenia patients already show a significant cortical thinning and whether cortical thickness anomalies may significantly influence clinical and cognitive features.

We investigated regional changes in cortical thickness in a large and heterogeneous sample of schizophrenia spectrum patients (n=142) at their first break of the illness and healthy controls (n=83). Magnetic resonance imaging brain scans (1.5 T) were obtained and images were analyzed by using brains2. The contribution of sociodemographic, cognitive and clinical characterictics was investigated.

Patients showed a significant total cortical thinning (F=17.55, d=−0.62, p<0.001) and there was a diffuse pattern of reduced thickness (encompassing frontal, temporal and parietal cortices) (all p's<0.001, d's>0.53). No significant group×gender interactions were observed (all p's>0.15). There were no significant associations between the clinical and pre-morbid variables and cortical thickness measurements (all r's<0.12). A weak significant negative correlation between attention and total (r=−0.24, p=0.021) and parietal cortical thickness (r=−0.27, p=0.009) was found in patients (thicker cortex was associated with lower attention). Our data revealed a similar pattern of cortical thickness changes related to age in patients and controls.

Cortical thinning is independent of gender, age, age of onset and duration of the illness and does not seem to significantly influence clinical and functional symptomatology. These findings support a primary neurodevelopment disorder affecting the normal cerebral cortex development in schizophrenia.

During the last decades we have seen a new focus on early treatment of psychosis. Several reviews have shown that duration of untreated psychosis (DUP) is correlated to better outcome. However, it is still unknown whether early treatment will lead to a better long-term outcome. This study reports the effects of reducing DUP on 5-year course and outcome.

During 1997–2000 a total of 281 consecutive patients aged >17 years with first episode non-affective psychosis were recruited, of which 192 participated in the 5-year follow-up. A comprehensive early detection (ED) programme with public information campaigns and low-threshold psychosis detection teams was established in one healthcare area (ED-area), but not in a comparable area (no-ED area). Both areas ran equivalent treatment programmes during the first 2 years and need-adapted treatment thereafter.

At the start of treatment, ED-patients had shorter DUP and less symptoms than no-ED-patients. There were no significant differences in treatment (psychotherapy and medication) for the 5 years. Mixed-effects modelling showed better scores for the ED group on the Positive and Negative Syndrome Scale negative, depressive and cognitive factors and for global assessment of functioning for social functioning at 5-year follow-up. The ED group also had more contacts with friends. Regression analysis did not find that these differences could be explained by confounders.

Early treatment had positive effects on clinical and functional status at 5-year follow-up in first episode psychosis.

We were interested in examining the relationship between socially relevant stimuli and decision processes in patients with schizophrenia.

We tested patients with schizophrenia and healthy controls on a stochastically rewarded associative learning task. Participants had to determine, through trial and error, which of two faces was associated with a higher chance of reward: one face was angry, the other happy.

Both patients and healthy controls were able to perform the task at above-chance accuracy, and there was no significant difference in overall accuracy between the groups. Both groups also reliably preferred the happy face, such that they selected it more often than the angry face on the basis of the same amount of positive versus negative feedback. However, patients were significantly more averse to the angry face, such that they chose it less often than control participants when the reward feedback strongly supported the angry face as the best choice.

Patients show an increased aversion to angry faces, in a task in which they must learn to associate rewards with expressions.

It is generally accepted that antipsychotics are more effective than placebo. However, it remains unclear whether antipsychotics induce a pattern or trajectory of response that is distinct from placebo. We used a data-driven technique, called growth mixture modelling (GMM), to identify the different patterns of response observed in antipsychotic trials and to determine whether drug-treated and placebo-treated subjects show similar or distinct patterns of response.

We examined data on 420 patients with schizophrenia treated for 6 weeks in two double-blind placebo-controlled trials using haloperidol and olanzapine. We used GMM to identify the optimal number of response trajectories; to compare the trajectories in drug-treated versus placebo-treated patients; and to determine whether the trajectories for the different dimensions (positive versus negative symptoms) were identical or different.

Positive symptoms were found to respond along four distinct trajectories, with the two most common trajectories (‘Partial responder’ and ‘Responder’) accounting for 70% of the patients and seen proportionally in both drug- and placebo-treated. The most striking drug–placebo difference was in the ‘Dramatic responders’, seen only among the drug-treated. The response of negative symptoms was more modest and did not show such distinct trajectories.

Trajectory models of response, rather than the simple responder/non-responder dichotomy, provide a better statistical account of how antipsychotics work. The ‘Dramatic responders’ (those showing >70% response) were seen only among the drug-treated and make a significant contribution to the overall drug–placebo difference. Identifying and studying this subset may provide specific insight into antipsychotic action.

Schizophrenia patients demonstrate impairment on visual backward masking, a measure of early visual processing. Most visual masking paradigms involve two distinct processes, an early fast-acting component associated with object formation and a later component that acts through object substitution. So far, masking paradigms used in schizophrenia research have been unable to separate these two processes.

We administered three visual processing paradigms (location masking with forward and backward masking, four-dot backward masking and a cuing task) to 136 patients with schizophrenia or schizoaffective disorder and 79 healthy controls. A psychophysical procedure was used to match subjects on identification of an unmasked target prior to location masking. Location masking interrupts object formation, four-dot masking task works through masking by object substitution and the cuing task measures iconic decay.

Patients showed impairment on location masking after being matched for input threshold, similar to previous reports. After correcting for age, patients showed lower performance on four-dot masking than controls, but the groups did not differ on the cuing task.

Patients with schizophrenia showed lower performance when masking was specific to object substitution. The difference in object substitution masking was not due to a difference in rate of iconic decay, which was comparable in the two groups. These results suggest that, despite normal iconic decay rates, individuals with schizophrenia show impairment in a paradigm of masking by object substitution that did not also involve disruption of object formation.

The few genetically informative studies to examine post-traumatic stress disorder (PTSD) and alcohol dependence (AD), all of which are based on a male veteran sample, suggest that the co-morbidity between PTSD and AD may be attributable in part to overlapping genetic influences, but this issue has yet to be addressed in females.

Data were derived from an all-female twin sample (n=3768) ranging in age from 18 to 29 years. A trivariate genetic model that included trauma exposure as a separate phenotype was fitted to estimate genetic and environmental contributions to PTSD and the degree to which they overlap with those that contribute to AD, after accounting for potential confounding effects of heritable influences on trauma exposure.

Additive genetic influences (A) accounted for 72% of the variance in PTSD; individual-specific environmental (E) factors accounted for the remainder. An AE model also provided the best fit for AD, for which heritability was estimated to be 71%. The genetic correlation between PTSD and AD was 0.54.

The heritability estimate for PTSD in our sample is higher than estimates reported in earlier studies based almost exclusively on an all-male sample in which combat exposure was the precipitating traumatic event. However, our findings are consistent with the absence of evidence for shared environmental influences on PTSD and, most importantly, the substantial overlap in genetic influences on PTSD and AD reported in these investigations. Additional research addressing potential distinctions by gender in the relative contributions of genetic and environmental influences on PTSD is merited.

Alcohol consumption is influenced by specific genetic risk factors for alcohol use disorders (AUDs), non-specific genetic risk factors for externalizing behaviors and various environmental experiences. We have limited knowledge of how these risk factors inter-relate through development.

Retrospective assessments in 1796 adult male twins using a life history calendar of key environmental exposures and alcohol consumption from early adolescence to mid-adulthood. Analysis by linear mixed models.

The importance of non-specific genetic risk factors on maximal alcohol consumption rose rapidly in early to mid-adolescence, peaked at ages 15–17 years and then declined slowly. Alcohol-specific genetic risk factors increased slowly in influence through mid-adulthood. We detected robust evidence for environmental moderation of genetic effects on alcohol consumption that was more pronounced in early and mid-adolescence than in later periods. Alcohol availability, peer deviance and low prosocial behaviors showing the strongest moderation effects. More interactions with environmental risk factors were seen for the non-specific externalizing disorder risk than for specific genetic risk for AUDs.

The impact of specific and non-specific genetic influences on alcohol consumption have different development trajectories. Genetic effects on alcohol use are more pronounced when social constraints are minimized (e.g. low prosocial behaviors or parental monitoring) or when the environment permits easy access to alcohol and/or encourages its use (e.g. high alcohol availability or peer deviance). Gene–environment interactions influencing alcohol intake may be more robust at younger ages, indicating greater plasticity of genetic influences early in the development of drinking patterns.

Obesity is characterized by chronic low-grade inflammation that may lead to emotional distress and behavioural symptoms. This study assessed the relationship between adiposity, low-grade inflammation, eating behaviour and emotional status in obese women awaiting gastric surgery and investigated the effects of surgery-induced weight loss on this relationship.

A total of 101 women with severe or morbid obesity awaiting gastric surgery were recruited. Assessments were performed before and at 1 year post-surgery and included the measurement of neuroticism and extraversion using the revised Neuroticism–Extraversion–Openness personality inventory (NEO-PI-R) and eating behaviour using the Three-Factor Eating Questionnaire (TFEQ). Blood samples were collected for the measurement of serum inflammatory markers [interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP)] and adipokines (leptin, adiponectin).

At baseline, body mass index (BMI) was positively correlated with inflammatory markers and adipokines. Regression analyses adjusting for age and diabetes revealed that baseline concentrations of IL-6 and hsCRP were associated with the depression and anxiety facets of neuroticism, with higher inflammation predicting higher anxiety and depression. This association remained significant after adjusting for BMI. Gastric surgery induced significant weight loss, which correlated with reduced inflammation. After controlling for BMI variations, decreases in inflammatory markers, notably hsCRP, were associated with reduced anxiety and TFEQ-cognitive restraint scores.

These findings indicate strong associations between adiposity, inflammation and affectivity in obese subjects and show that surgery-induced weight loss is associated concomitantly with reduced inflammation and adipokines and with significant improvement in emotional status and eating behaviour. Inflammatory status appears to represent an important mediator of emotional distress and psychological characteristics of obese individuals.

The P300 (P3) event-related potential (ERP) component, a possible endophenotype for attention deficit hyperactivity disorder (ADHD), has been widely examined in children, but received little attention in adults. Our objective was to conduct a meta-analysis of P3 studies in adults with ADHD.

We searched the Medline and PsycINFO databases for controlled studies examining both adult ADHD and matched healthy controls. Six relevant publications were identified for the meta-analysis, which had comparable data across studies with regard to the amplitude of ERP components related to target detection (P3, P3b). Pooled effect size (ES) for P3 amplitude as well as the association of the ES with age and gender were investigated using meta-regression.

Comparing the ADHD group versus controls, the pooled effect size for a decrease in P3 amplitude was in the medium range (Cohen's d=−0.55, p=0.0006). Additionally, meta-regression revealed that decrease in P3 amplitude significantly varied with the mean age of ADHD patients (p=0.0087), with a gradual increasing of the difference at higher ages. Results also showed a significant association between the ES and gender, indicating a more pronounced reduction of P3 amplitude in the ADHD group versus controls when females were predominantly represented in the sample.

To our knowledge, this is the first meta-analysis of P3 characteristics in adults with ADHD. It reveals a significantly decreased P3 amplitude during target detection. Our result that the reduction in P3 amplitude increases with age is interpreted in a neurodevelopmental context.