Depressed mood following an acute coronary syndrome (ACS) is a risk factor for future cardiac morbidity. Hypothalamic–pituitary–adrenal (HPA) axis dysregulation is associated with depression, and may be a process through which depressive symptoms influence later cardiac health. Additionally, a history of depression predicts depressive symptoms in the weeks following ACS. The purpose of this study was to determine whether a history of depression and/or current depression are associated with the HPA axis dysregulation following ACS.

A total of 152 cardiac patients completed a structured diagnostic interview, a standardized depression questionnaire and a cortisol profile over the day, 3 weeks after an ACS. Cortisol was analysed using: the cortisol awakening response (CAR), total cortisol output estimated using the area under the curve method, and the slope of cortisol decline over the day.

Total cortisol output was positively associated with history of depression, after adjustment for age, gender, marital status, ethnicity, smoking status, body mass index (BMI), Global Registry of Acute Cardiac Events (GRACE) risk score, days in hospital, medication with statins and antiplatelet compounds, and current depression score. Men with clinically diagnosed depression after ACS showed a blunted CAR, but the CAR was not related to a history of depression.

Patients with a history of depression showed increased total cortisol output, but this is unlikely to be responsible for associations between depression after ACS and later cardiac morbidity. However, the blunted CAR in patients with severe depression following ACS indicates that HPA dysregulation is present.

The trajectories of psychological distress differ between individuals, but these differences can be difficult to understand because the measures contain both consistent and situational features; however, in longitudinal studies these sources of information can be disentangled. In addition to occasion-specific features, interindividual differences can be decomposed into two sources of information: trait and carry-over effects between neighboring occasions that are not related to the trait (i.e. accumulated situational effects).

To disentangle these three sources of variance throughout adulthood, the consistency (trait and accumulated situational effects) and occasion specificity of nine indicators of psychological distress from the Malaise Inventory were examined in two birth cohorts, the 1958 National Child Development Study (NCDS58), and the 1970 British Cohort Study (BCS70).

The scale was administered at ages 23, 33, 42, and 50 in NCDS58 (n = 7147), and at ages 26, 30, 34, and 42 in BCS70 (n = 6859). For each psychological symptom, more variance was consistent than occasion-specific. The majority of the consistency was due to trait variance as opposed to accumulated situational effects, indicating that an individual predisposed to be distressed at the beginning of the study remained more likely to be distressed over the whole period. Symptoms of rage were notably more consistent among males than females in both cohorts (78.1% and 81.3% variance explained by trait in NCDS58 and BCS70, respectively), and among females in the NCDS58 (69%).

Symptoms of psychological distress exhibited high stability throughout adulthood, especially among men, due mostly to interindividual trait differences.

UK veterans suffering from a psychological or psychiatric illness as a consequence of service in the Second World War were entitled to a war pension. Their case files, which include regular medical assessments, are a valuable resource to investigate the nature, distribution and duration of symptoms.

A standardised form was used to collect data from pension records of a random sample of 500 UK army veterans from the first presentation in the 1940s until 1980. Data were also gathered from 50 civilians and 54 emergency responders with a pension for post-traumatic illness following air-raids.

The 10 most common symptoms reported by veterans were anxiety, depression, sleep problems, headache, irritability/anger, tremor/shaking, difficulty completing tasks, poor concentration, repeated fears and avoidance of social contact. Nine of the 10 were widely distributed across the veteran population when symptoms were ranked by the number of subjects who reported them. Nine symptoms persisted significantly longer in the veteran sample than in emergency responders. These included seven of the most common symptoms, together with two others: muscle pain and restlessness. The persistence of these symptoms in the veteran group suggests a post-traumatic illness linked to lengthy overseas service in combat units.

The nature and duration of symptoms exhibited by veterans may be associated with their experience of heightened risks. Exposure to severe or prolonged trauma seems to be associated with chronic multi-symptom illness, symptoms of post-traumatic stress and somatic expressions of pain that may delay or complicate the recovery process.

Foetal nutrition and growth seem to affect the risk of developing schizophrenia. Exposure to famine during foetal development and low birthweight increase the risk. However, few studies have investigated the association between schizophrenia and adult height and weight or patterns of growth.

The study population consisted of two subpopulations: families with at least one member with schizophrenia, and families of offspring of mothers with psychotic disorder, and controls. Using a seven-parameter model of height growth curves, we compared the parameters of persons who later developed schizophrenia and their unaffected siblings from the same families. We also studied how growth curve parameters differed in children with genetic risk for schizophrenia and controls, and whether weight, height and body mass index (BMI) at different ages predicted later development of schizophrenia.

The predicted growth curves based on a parametric model were nearly identical for persons with schizophrenia and their unaffected siblings. Adult height of daughters of mothers with psychoses was borderline significantly (p=0.0536) lower compared to controls, while no difference was detected among sons (p=0.3283).

No association between growth characteristics and schizophrenia in families with at least one member with schizophrenia was found. Family-related factors should be taken into account as possible confounders in future studies on growth and schizophrenia.

Altered expression of the complement component C4A gene is a known risk factor for schizophrenia. Further, predicted brain C4A expression has also been associated with memory function highlighting that altered C4A expression in the brain may be relevant for cognitive and behavioral traits.

We obtained genetic information and performance measures on seven cognitive tasks for up to 329 773 individuals from the UK Biobank, as well as brain imaging data for a subset of 33 003 participants. Direct genotypes for variants (n = 3213) within the major histocompatibility complex region were used to impute C4 structural variation, from which predicted expression of the C4A and C4B genes in human brain tissue were predicted. We investigated if predicted brain C4A or C4B expression were associated with cognitive performance and brain imaging measures using linear regression analyses.

We identified significant negative associations between predicted C4A expression and performance on select cognitive tests, and significant associations with MRI-based cortical thickness and surface area in select regions. Finally, we observed significant inconsistent partial mediation of the effects of predicted C4A expression on cognitive performance, by specific brain structure measures.

These results demonstrate that the C4 risk locus is associated with the central endophenotypes of cognitive performance and brain morphology, even when considered independently of other genetic risk factors and in individuals without mental or neurological disorders.

Two types of mentalization-based treatment (MBT), day hospital MBT (MBT-DH) and intensive outpatient MBT (MBT-IOP), have been shown to be effective in treating patients with borderline personality disorder (BPD). This study evaluated trajectories of change in a multi-site trial of MBT-DH and MBT-IOP at 36 months after the start of treatment.

All 114 patients (MBT-DH n = 70, MBT-IOP n = 44) from the original multicentre trial were assessed at 24, 30 and 36 months after the start of treatment. The primary outcome was symptom severity measured with the Brief Symptom Inventory. Secondary outcome measures included borderline symptomatology, personality and interpersonal functioning, quality of life and self-harm. Data were analysed using multilevel modelling and the intention-to-treat principle.

Patients in both MBT-DH and MBT-IOP maintained the substantial improvements made during the intensive treatment phase and showed further gains during follow-up. Across both conditions, 83% of patients improved in terms of symptom severity, and 97% improved on borderline symptomatology. No significant differences were found between MBT-DH and MBT-IOP at 36 months after the start of treatment. However, trajectories of change were different. Whereas patients in MBT-DH showed greater improvement during the intensive treatment phase, patients in MBT-IOP showed greater continuing improvement during follow-up.

Patients in both conditions showed similar large improvements over the course of 36 months, despite large differences in treatment intensity. MBT-DH and MBT-IOP were associated with different trajectories of change. Cost-effectiveness considerations and predictors of differential treatment outcome may further inform optimal treatment selection.

The impact of initial treatment outcome on long-term healthcare costs in depression remains to be determined. We aimed to identify demographic and clinical characteristics associated with initial treatment outcomes and to test whether and how these outcomes influence total healthcare costs over the subsequent 3 years.

In this secondary analysis of a large healthcare database, a national cohort of adult patients (n = 126 471) who received antidepressant treatment for depression was identified and factors associated with initial outcomes were examined. Potential predictors of total healthcare costs in the subsequent years were assessed using generalized linear modeling, with a particular focus on initial outcome status after antidepressant treatment and co-morbidities.

Depression type and co-morbid painful physical symptoms (PPS) or mental illnesses were found to be associated with initial outcome status. Having sustained treatment-free status after initial treatment was shown to be associated with a 22–33% reduction in total healthcare costs in the second and third years (compared to those with late recontacts). Although the presence of co-morbid PPS was associated with higher healthcare costs, having certain co-morbid anxiety disorders was associated with lower costs over the 3 years.

Initial outcome status after antidepressant treatment has a sustained impact on individuals' total healthcare costs over the following 3 years. Future efforts to improve initial treatment outcome of depression are warranted.

Accelerated cellular ageing, which can be examined by telomere length (TL), may be an overarching mechanism underlying the association between personality and adverse health outcomes. This 6-year longitudinal study examined the relation between personality and leukocyte telomere length (LTL) across time among adults with a wide age-range.

Data from the Netherlands Study of Depression and Anxiety were used and included patients with a depression and/or anxiety disorder and healthy controls. Overall, 2936 persons (18–65 years, 66% female) had data on LTL at baseline and 1883 persons had LTL at 6-year follow-up. The Big Five personality traits (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) and Type D personality were assessed.

Neuroticism was negatively (B = −2.11, p = 0.03) and agreeableness was positively (B = 3.84, p = 0.03) related to LTL measured across two time points, which became just non-significant after adjusting for somatic health, lifestyle factors, and recent life stress (B = −1.99, p = 0.06; and B = 3.01, p = 0.10). Type D personality was negatively (B = −50.16, p < 0.01) related to LTL across two time points, which still remained statistically significant after full adjustment (B = −47.37, p = 0.01). Associations did not differ by age, gender, and current psychiatric status.

The Big Five traits high neuroticism and low agreeableness, and Type D personality were associated with shorter LTL measured across a 6-year period. Associations with the Big Five traits became non-significant after controlling for somatic health, lifestyle factors, and recent life stress, yet similar trends were observed. Type D personality remained independently associated with shorter LTL after full adjustment.

Early neurodevelopmental deviations, such as abnormal cortical folding patterns, are candidate biomarkers of major depressive disorder (MDD). We aimed to investigate the association of MDD with the local gyrification index (LGI) in each cortical region at the whole-brain level, and the association of the LGI with clinical characteristics of MDD.

We obtained T1-weighted images from 234 patients with MDD and 215 healthy controls (HCs). The LGI values from 66 cortical regions in the bilateral hemispheres were automatically calculated according to the Desikan–Killiany atlas. We compared the LGI values between the MDD and HC groups using analysis of covariance, including age, sex, and years of education as covariates. The association between the clinical characteristics and LGI values was investigated in the MDD group.

Compared with HCs, patients with MDD showed significantly decreased LGI values in the cortical regions, including the bilateral ventrolateral and dorsolateral prefrontal cortices, medial and lateral orbitofrontal cortices, insula, right rostral anterior cingulate cortex, and several temporal and parietal regions, with the largest effect size in the left pars triangularis (Cohen's f2 = 0.361; p = 1.78 × 10−13). Regarding the association of clinical characteristics with LGIs within the MDD group, recurrence and longer illness duration were associated with increased gyrification in several occipital and temporal regions, which showed no significant difference in LGIs between the MDD and HC groups.

These findings suggest that the LGI may be a relatively stable neuroimaging marker associated with MDD predisposition.

One hypothesis proposed to underlie formal thought disorder (FTD), the incoherent speech is seen in some patients with schizophrenia, is that it reflects impairment in frontal/executive function. While this proposal has received support in neuropsychological studies, it has been relatively little tested using functional imaging. This study aimed to examine brain activations associated with FTD, and its two main factor-analytically derived subsyndromes, during the performance of a working memory task.

Seventy patients with schizophrenia showing a full range of FTD scores and 70 matched healthy controls underwent fMRI during the performance of the 2-back version of the n-back task. Whole-brain corrected, voxel-based correlations with FTD scores were examined in the patient group.

During 2-back performance the patients showed clusters of significant inverse correlation with FTD scores in the inferior frontal cortex and dorsolateral prefrontal cortex bilaterally, the left temporal cortex and subcortically in the basal ganglia and thalamus. Further analysis revealed that these correlations reflected an association only with ‘alogia’ (poverty of speech, poverty of content of speech and perseveration) and not with the ‘fluent disorganization’ component of FTD.

This study provides functional imaging support for the view that FTD in schizophrenia may involve impaired executive/frontal function. However, the relationship appears to be exclusively with alogia and not with the variables contributing to fluent disorganization.

Childhood abuse and neglect often occurs within families and can have a large influence on mental well-being across the lifespan. However, the sibling concordance of emotional abuse and neglect (i.e. together referred to as emotional maltreatment; EM), physical abuse (PA) and sexual abuse (SA) and the long-term impact on the context of siblings' maltreatment experiences are unclear. To examine the influence of EM, PA and SA on adult depressive symptoms within the family framework we differentiate between (a) the family-wide (mean level of all siblings) effects and (b) the individual deviation from the mean family level of maltreatment.

The sample (N = 636) consists of 256 families, including at least one lifetime depressed or anxious individual and their siblings. Multilevel modeling was used to examine the family-wide and relative individual effects of childhood maltreatment (CM).

(a) Siblings showed most similarity in their reports of EM followed by PA. SA was mostly reported by one person within a family. In line with these observations, the mean family levels of EM and PA, but not SA, were associated with more depressive symptoms. In addition, (b) depression levels were more elevated in individuals reporting more EM than the family mean.

Particularly in the case of more visible forms of CM, siblings' experiences of EM and PA are associated with the elevated levels of adult depressive symptoms. Findings implicate that in addition to individual maltreatment experiences, the context of siblings' experiences is another crucial risk factor for an individuals' adult depressive symptomatology.

Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. Compared to ECT, repetitive transcranial magnetic stimulation (rTMS) is less effective at treating severe depression, but has the advantage of being quick, easy to use, and producing almost no side effects. In this study, our objective was to assess the priming effect of rTMS sessions before ECT on clinical response in patients with TRD.

In this multicenter, randomized, double-blind, sham-controlled trial, 56 patients with TRD were assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham neuronavigated rTMS were administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Any relative improvements were then compared between both groups after five ECT sessions, in order to assess the early response to treatment.

After ECT, the active rTMS group exhibited a significantly greater relative improvement than the sham group [43.4% (28.6%) v. 25.4% (17.2%)]. The responder rate in the active group was at least three times higher. Cognitive complaints, which were assessed using the Cognitive Failures Questionnaire, were higher in the sham rTMS group compared to the active rTMS group, but this difference was not corroborated by cognitive tests.

rTMS could be used to enhance the efficacy of ECT in patients with TRD. ClinicalTrials.gov: NCT02830399.

Abnormal auditory processing of deviant stimuli, as reflected by mismatch negativity (MMN), is often reported in schizophrenia (SCZ). At present, it is still under debate whether this dysfunctional response is specific to the full-blown SCZ diagnosis or rather a marker of psychosis in general. The present study tested MMN in patients with SCZ, bipolar disorder (BD), first episode of psychosis (FEP), and in people at clinical high risk for psychosis (CHR).

Source-based MEG activity evoked during a passive auditory oddball task was recorded from 135 patients grouped according to diagnosis (SCZ, BD, FEP, and CHR) and 135 healthy controls also divided into four subgroups, age- and gender-matched with diagnostic subgroups. The magnetic MMN (mMMN) was analyzed as event-related field (ERF), Theta power, and Theta inter-trial phase coherence (ITPC).

The clinical group as a whole showed reduced mMMN ERF amplitude, Theta power, and Theta ITPC, without any statistically significant interaction between diagnosis and mMMN reductions. The mMMN subgroup contrasts showed lower ERF amplitude in all the diagnostic subgroups. In the analysis of Theta frequency, SCZ showed significant power and ITPC reductions, while only indications of diminished ITPC were observed in CHR, but no significant decreases characterized BD and FEP.

Significant mMMN alterations in people experiencing psychosis, also for diagnoses other than SCZ, suggest that this neurophysiological response may be a feature shared across psychotic disorders. Additionally, reduced Theta ITPC may be associated with risk for psychosis.