Studying secular trends in the exposure to risk and protective factors of depression and whether these trends are associated with secular trends in the prevalence of depression is important to estimate future healthcare demands and to identify targets for prevention.

Three birth cohorts of 55–64-year olds from the population-based Longitudinal Aging Study Amsterdam were examined using identical methods in 1992 (n = 944), 2002 (n = 964) and 2012 (n = 957). A two-stage screening design was used to identify subthreshold depression (SUBD) and major depressive disorder (MDD). Multinomial logistic regression analyses were used to identify secular trends in depression prevalence and to identify factors from the biopsychosocial domains of functioning that were associated with these trends.

Compared with 1992, MDD became more prevalent in 2002 (OR 1.90, 95% CI 1.10–3.28, p = 0.022) and 2012 (OR 1.80, 95% CI 1.03–3.14, p = 0.039). This was largely attributable to an increase in the prevalence of chronic diseases and functional limitations. Socioeconomic and psychosocial improvements, including an increase in labor market participation, social support and mastery, hampered MDD rates to rise more and were also associated with a 32% decline of SUBD-rates in 2012 as compared with 2002 (OR 0.68, 95% CI 0.48–0.96, p = 0.03).

Among late middle-aged adults, there is a substantial net increase of MDD, which is associated with deteriorating physical health. If morbidity and disability continue to increase, a further expansion of MDD rates may be expected. Improving socioeconomic and psychosocial conditions may benefit public health, as these factors were protective against a higher prevalence of both MDD and SUBD.

Network analysis (NA) conceptualizes psychiatric disorders as complex dynamic systems of mutually interacting symptoms. Major depressive disorder (MDD) is a heterogeneous clinical condition, and very few studies to date have assessed putative changes in its psychopathological network structure in response to antidepressant (AD) treatment.

In this randomized trial with adult depressed outpatients (n = 151), we estimated Gaussian graphical models among nine core MDD symptom-domains before and after 8 weeks of treatment with either escitalopram or desvenlafaxine. Networks were examined with the measures of cross-sectional and longitudinal structure and connectivity, centrality and predictability as well as stability and accuracy.

At baseline, the most connected MDD symptom-domains were fatigue–cognitive disturbance, whereas at week 8 they were depressed mood–suicidality. Overall, the most central MDD symptom-domains at baseline and week 8 were, respectively, fatigue and depressed mood; in contrast, the most peripheral symptom-domain across both timepoints was appetite/weight disturbance. Furthermore, the psychopathological network at week 8 was significantly more interconnected than at baseline, and they were also structurally dissimilar.

Our findings highlight the utility of focusing on the dynamic interaction between depressive symptoms to better understand how the treatment with ADs unfolds over time. In addition, depressed mood, fatigue, and cognitive/psychomotor disturbance seem to be central MDD symptoms that may be viable targets for novel, focused therapeutic interventions.

There are currently no neuroanatomical biomarkers of anorexia nervosa (AN) available to make clinical inferences at an individual subject level. We present results of a multivariate machine learning (ML) approach utilizing structural neuroanatomical scan data to differentiate AN patients from matched healthy controls at an individual subject level.

Structural neuroimaging scans were acquired from 15 female patients with AN (age = 20, s.d. = 4 years) and 15 demographically matched female controls (age = 22, s.d. = 3 years). Neuroanatomical volumes were extracted using the FreeSurfer software and input into the Least Absolute Shrinkage and Selection Operator (LASSO) multivariate ML algorithm. LASSO was ‘trained’ to identify ‘novel’ individual subjects as either AN patients or healthy controls. Furthermore, the model estimated the probability that an individual subject belonged to the AN group based on an individual scan.

The model correctly predicted 25 out of 30 subjects, translating into 83.3% accuracy (sensitivity 86.7%, specificity 80.0%) (p < 0.001; χ2 test). Six neuroanatomical regions (cerebellum white matter, choroid plexus, putamen, accumbens, the diencephalon and the third ventricle) were found to be relevant in distinguishing individual AN patients from healthy controls. The predicted probabilities showed a linear relationship with drive for thinness clinical scores (r = 0.52, p < 0.005) and with body mass index (BMI) (r = −0.45, p = 0.01).

The model achieved a good predictive accuracy and drive for thinness showed a strong neuroanatomical signature. These results indicate that neuroimaging scans coupled with ML techniques have the potential to provide information at an individual subject level that might be relevant to clinical outcomes.

Impairments in the attribution of salience are thought to be fundamental to the development of psychotic symptoms and the onset of psychotic disorders. The aim of the present study was to explore longitudinal alterations in salience processing in ultra-high-risk subjects for psychosis.

A total of 23 ultra-high-risk subjects and 13 healthy controls underwent functional magnetic resonance imaging at two time points (mean interval of 17 months) while performing the Salience Attribution Test to assess neural responses to task-relevant (adaptive salience) and task-irrelevant (aberrant salience) stimulus features.

At presentation, high-risk subjects were less likely than controls to attribute salience to relevant features, and more likely to attribute salience to irrelevant stimulus features. These behavioural differences were no longer evident at follow-up. When attributing salience to relevant cue features, ultra-high-risk subjects showed less activation than controls in the ventral striatum at both baseline and follow-up. Within the high-risk sample, amelioration of abnormal beliefs over the follow-up period was correlated with an increase in right ventral striatum activation during the attribution of salience to relevant cue features.

These findings confirm that salience processing is perturbed in ultra-high-risk subjects for psychosis, that this is linked to alterations in ventral striatum function, and that clinical outcomes are related to longitudinal changes in ventral striatum function during salience processing.

Poor educational achievement is associated with a range of psychiatric disorders. Several studies suggest that this underperformance is due to cognitive deficits that commence before disease onset and reflect a genetic risk for this disorder. However, the specificity and the familial contribution of this cognitive deficit are not clear. We analysed lifetime educational achievement of psychiatric patients diagnosed with schizophrenia, bipolar or depressive disorder and their unaffected siblings.

In a register-based case-control study, 1561 patients with schizophrenia, 813 patients with bipolar disorder, 8112 patients with depression, and their siblings were each matched with eight population controls. Patients, siblings and controls were compared on the highest educational stream they completed.

Lower educational achievement was present in schizophrenia patients from primary school onwards [completing primary school: odds ratio (OR) 0.69; completing secondary school: OR 0.69; completing academic education: OR 0.46], compared to patients with bipolar disorder or depression. Siblings of schizophrenia, bipolar or depressed patients showed no underachievement at primary or secondary school, but siblings of schizophrenia patients as well as siblings of depressed patients were less successful in their educational achievement after secondary school (completing academic education, schizophrenia siblings: OR 0.90; depressive disorder siblings: OR 0.91).

Educational underachievement from primary school onwards is specifically related to schizophrenia and not to bipolar disorder or depression. Moreover, it appears to be a harbinger of the illness, since it is not found in their siblings. These results add to evidence that early cognitive deficits are a distinct feature of the schizophrenia phenotype.

There is uncertainty about the incidence of breakthrough psychosis in treatment adherent patients, and the role that factors, such as cumulative antipsychotic exposure, play in this phenomenon.

In a nationwide cohort of individuals treated for schizophrenia-spectrum disorders in Finland between 1 January 1996 and 31 December 2015, ‘Breakthrough Psychosis on Antipsychotic Maintenance Medication’ (BAMM) was defined as hospitalization for psychosis despite ongoing continuous treatment with long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs) for ⩾8 weeks. Incidence rates, survival curves, and risk factors were presented.

In a cohort of 16 031 continuous LAI treatment episodes with virtually assured adherence [median duration = 441 days, interquartile range (IQR) = 155–1277], BAMM incidence was 31.5%. For 42 867 OAPs treatment episodes (median duration = 483 days, IQR = 167–1491), for whom adherence was modeled by the PRE2DUP method, BAMM incidence was 31.1%. Factors related to illness instability at treatment onset were associated with BAMM, although median time to BAMM was 291 days (IQR = 121–876) for LAIs and 344 days (IQR = 142–989) for OAPs, and 27.4% (N = 1386) of the BAMM events in the LAI, and 32.9% (N = 4378) in the OAP group occurred despite >1 year since last hospitalization at treatment onset. Cumulative antipsychotic exposure was not a consistent risk factor.

BAMM was relatively common even when adherence was confirmed with LAIs. Illness instability at treatment onset accounted for most cases, but relapse after years of continuous treatment was still prevalent. There was insufficient evidence to support causality between cumulative antipsychotic exposure and BAMM. Future research needs to address the role of symptom severity and neurobiology in BAMM.

Depression following myocardial infarction (MI) independently increases risk for early cardiac morbidity and mortality. Studies suggest that somatic, but not cognitive, depressive symptoms are responsible for the increased risk. However, the effects of somatic depressive symptoms at follow-up, after sufficient time has elapsed to allow for physical recovery from the initial infarction, are not known. Our aim was to examine the relationship between cognitive and somatic depressive symptom dimensions at baseline and 12 months post-MI and subsequent mortality and cardiovascular morbidity.

Patients were 2442 depressed and/or socially isolated men and women with acute MI included in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial. We used principal components analysis (PCA) of the Beck Depression Inventory (BDI) items to derive subscales measuring cognitive and somatic depressive symptom dimensions, and Cox regression with Bonferroni correction for multiple testing to examine the contribution of these dimensions to all-cause mortality, cardiovascular mortality, and first recurrent non-fatal MI.

After adjusting for medical co-morbidity and Bonferroni correction, the somatic depressive symptom dimension assessed proximately following MI did not significantly predict any endpoints. At 12 months post-MI, however, this dimension independently predicted subsequent all-cause [hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.13–1.81] and cardiovascular mortality (HR 1.60, 95% CI 1.17–2.18). No significant associations were found between the cognitive depressive symptom dimension and any endpoints after Bonferroni correction.

Somatic symptoms of depression at 12 months post-MI in patients at increased psychosocial risk predicted subsequent mortality. Psychosocial interventions aimed at improving cardiac prognosis may be enhanced by targeting somatic depressive symptoms, with particular attention to somatic symptom severity at 12 months post-MI.

Minimal efficacy differences have been found between cognitive behavioral therapy (CBT) and psychodynamic therapies for depression, but little is known about patient characteristics that might moderate differential treatment effects. We aimed to generate hypotheses regarding such potential prescriptive factors.

We conducted post-hoc model-based recursive partitioning analyses alongside a randomized clinical trial comparing the efficacy of CBT and short-term psychodynamic supportive psychotherapy (SPSP). Severely depressed patients received additional antidepressant medication. We included 233 adults seeking treatment for a major depressive episode in psychiatric outpatient clinics, who completed post-treatment assessment. Post-treatment mean Hamilton Depression Rating Scale scores constituted the main outcome measure.

While treatment differences (CBT v. SPSP) were minimal in the total sample of patients (d = 0.04), model-based recursive partitioning indicated differential treatment efficacy in certain subgroups of patients. SPSP was found more efficacious among moderately depressed patients receiving psychotherapy only who showed low baseline co-morbid anxiety levels (d = −0.40) and among severely depressed patients receiving psychotherapy and antidepressant medication who reported a duration of the depressive episode of ⩾1 year (d = −0.31), while CBT was found more efficacious for such patients reporting a duration <1 year (d = 0.83).

Our findings are observational and need validation before they can be used to guide treatment selection, but suggest that knowledge of prescriptive factors can help improve the efficacy of psychotherapy for depression. Depressive episode duration and co-morbid anxiety level should be included as stratification variables in future randomized clinical trials comparing CBT and psychodynamic therapy.

The aim of this study was to investigate the functioning of patients with borderline personality disorder (BPD) compared to healthy controls on five neuropsychological domains, with regard to the possible effect of differences in IQ.

Out-patients and in-patients with BPD (n=35) and healthy comparison subjects (n=35) were tested with an extensive neuropsychological battery, where most cognitive domains were covered by several tests.

When controlling for the effect of IQ, patients were found to have reduced executive functioning as compared to healthy controls. With regard to the other neuropsychological domains (working memory, attention, long-term verbal memory, and long-term non-verbal memory), no differences were found between the two groups. Within-subject analyses also identified executive functioning as a selective deficit among patients whereas long-term verbal memory was identified as a relative strength. An association was identified between the covariate general intellectual functioning and every neuropsychological domain. No statistically significant differences were found between the subgroups of patients with and without co-morbid post-traumatic stress disorder (PTSD) or between those with and without co-morbid major depression, or between the medicated and unmedicated subgroups on any of the neuropsychological domains.

Patients with BPD demonstrate a selective deficit in executive functioning. This corroborates studies that have identified frontal regions as potential neurobiological substrates of the BPD syndrome. The relative strength of the verbal long-term memory function raises pertinent questions regarding the presumed importance of hippocampal structures.

Multiple studies have found Conscientiousness to be protective against dementia. The purpose of this study is to identify which specific aspects, or facets, of Conscientiousness are most protective against cognitive impairment and whether these associations are moderated by demographic factors and/or genetic risk.

Health and Retirement Study participants were selected for analysis if they completed the facets of Conscientiousness measure, scored in the range of normal cognitive functioning at the baseline personality assessment, and had at least one follow-up assessment of cognition over the up to 6-year follow-up (N = 11 181). Cox regression was used to test for risk of incident dementia and risk of incident cognitive impairment not dementia (CIND).

Over the follow-up, 278 participants developed dementia and 2186 participants developed CIND. The facet of responsibility had the strongest and most consistent association with dementia risk: every standard deviation increase in this facet was associated with a nearly 35% decreased risk of dementia; self-control and industriousness were also protective. Associations were generally similar when controlling for clinical, behavioral, and genetic risk factors. These three facets were also independent predictors of decreased risk of CIND.

The present research indicates that individuals who see themselves as responsible, able to control their behavior, and hard workers are less likely to develop CIND or dementia and that these associations persist after accounting for some common clinical, behavioral, and genetic risk factors.

Assessment of eating disorders at the symptom level can facilitate the refinement of phenotypes. We examined genetic and environmental contributions to liability to anorexia nervosa (AN) symptoms in a population-based twin sample using a genetic common pathway model.

Participants were from the Norwegian Institute of Public Health Twin Panel (NIPHTP) and included all female monozygotic (MZ; 448 complete pairs and four singletons) and dizygotic (DZ; 263 complete pairs and four singletons) twins who completed the Composite International Diagnostic Interview (CIDI) assessing DSM-IV Axis I and ICD-10 criteria. Responses to items assessing AN symptoms were included in a model fitted using the marginal maximum likelihood (MML) approach.

Heritability of the overall AN diagnosis was moderate [a2=0.22, 95% confidence interval (CI) 0.0–0.50] whereas heritabilities of the specific items varied. Heritability estimates for weight loss items were moderate (a2=0.31–0.34) and items assessing weight concern when at a low weight were smaller (0.18–0.29). Additive genetic factors contributed little to the variance of amenorrhea, which was most strongly influenced by unshared environment (a2=0.16, e2=0.71).

AN symptoms are differentially heritable. Specific criteria such as those related to body weight and weight loss history represent more biologically driven potential endophenotypes or liability indices. The results regarding weight concern differ somewhat from those of previous studies, highlighting the importance of assessing genetic and environmental influences on variance of traits within specific subgroups of interest.