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.

Studies on the transmission of suicide risk have focused on parental history of suicide attempts (SAs), overlooking when the attempt happened. This study examined how the offspring's risk of attempting or dying by suicide varied by the timing of a first parental SA and the sex of the parent who attempted suicide.

Participants were 59 469 members of the 1987 Finnish Birth Cohort. The Finnish Hospital Discharge and Cause of Death Registers were the sources for parental and offspring SAs and offspring suicide. Timing of parental SA was coded as before (pre-pregnancy and pregnancy) and after the child's birth [infant/toddler years (0–2 years), childhood (3–11 years), adolescence (12–17 years), and young adulthood (18–26 years)].

In the multivariate models, having a parent who attempted suicide increased the offspring's risk of attempting suicide (odds ratio (OR) = 1.77, 95% confidence interval (CI) 1.39–2.25), but not of dying by suicide. Compared to unexposed offspring, those exposed after child's birth were at higher risk of attempting suicide (OR = 1.90, 95% CI 1.46–2.47), specifically when the parent attempted during offspring's childhood, adolescence, and young adulthood. A first maternal SA increased offspring's risk of attempting suicide regardless of the timing.

The impact of a parental SA on offspring's risk of attempting suicide differed depending on the timing and sex of the parent who attempted suicide, suggesting that the transmission of suicide risk may occur through genetic as well as environmental factors. Our findings call for an intergenerational approach in suicide risk assessment.

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.

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.

Lemborexant has demonstrated statistically significant improvements in sleep onset and sleep maintenance compared with placebo and zolpidem tartrate extended release, measured both objectively using polysomnography and subjectively using sleep diaries, in the phase 3 clinical trial SUNRISE 1. This study evaluated the cost-effectiveness of lemborexant compared with suvorexant, zolpidem immediate release (IR), and untreated insomnia.

A decision-tree model was developed for falls, motor vehicle collisions, and workplace accidents associated with insomnia and insomnia treatments from a Japanese healthcare perspective and with a 6-month time horizon. The model extracted subjective sleep onset latency treatment responses and disutility values for non-responders from SUNRISE 1. Cost-effectiveness was assessed using incremental cost per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were conducted to evaluate the impact of parameter uncertainty on the results.

In the base-case analysis, the mean estimated QALYs for lemborexant, suvorexant, zolpidem-IR, and untreated insomnia were 0.4220, 0.4204, 0.4113, and 0.4163, and expected medical costs were JPY 34 034, JPY 38 371, JPY 38 139, and JPY 15 383, respectively. Lemborexant saved JPY 4337 and JPY 4105 compared with suvorexant or zolpidem-IR, respectively, while conferring QALY benefits. The incremental cost-effectiveness ratio (ICER) of lemborexant compared with that of untreated insomnia was JPY 3 220 975 /QALY. Lemborexant was dominant over suvorexant and zolpidem-IR and was cost-effective when compared with untreated insomnia. Sensitivity analyses supported the results' robustness.

In a Japanese clinical practice setting, lemborexant may represent a better investment for treating insomnia in the healthcare system in Japan.

Research on biased processing of aversive stimuli in posttraumatic stress disorder (PTSD) has produced inconsistent results between response time (RT) and eye-tracking studies. Recent RT-based results of dot-probe studies showed no attentional bias (AB) for threat while eye-tracking research suggested heightened sustained attention for this information. Here, we used both RT-based and eye-tracking measures to explore the dynamics of AB to negative stimuli in PTSD.

Twenty-three individuals diagnosed with PTSD, 23 trauma-exposed healthy controls, and 23 healthy controls performed an emotional dot-probe task with pairs of negative and neutral scenes presented for either 1 or 2 s. Analyses included eye movements during the presentation of the scenes and RT associated with target localization.

There was no evidence for an AB toward negative stimuli in PTSD from RT measures. However, the main eye-tracking results revealed that all three groups showed longer dwell times on negative pictures than neutral pictures at 1 s and that this AB was stronger for individuals with PTSD. Moreover, although AB disappeared for the two groups of healthy controls with prolonged exposure, it persisted for individuals with PTSD.

PTSD is associated with an AB toward negative stimuli, characterized by heightened sustained attention toward negative scenes once detected. This study sheds light on the dynamics of AB to negative stimuli in PTSD and encourages us to consider optimized therapeutic interventions targeting abnormal AB patterns.

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.

Violence perpetrated by psychiatric inpatients is associated with modifiable factors. Current structured approaches to assess inpatient violence risk lack predictive validity and linkage to interventions.

Adult psychiatric inpatients on forensic and general wards in three psychiatric hospitals were recruited and followed up prospectively for 6 months. Information on modifiable (dynamic) risk factors were collected every 1–4 weeks, and baseline background factors. Data were transferred to a web-based monitoring system (FOxWeb) to calculate a total dynamic risk score. Outcomes were extracted from an incident-reporting system recording aggression and interpersonal violence. The association between total dynamic score and violent incidents was assessed by multilevel logistic regression and compared with dynamic score excluded.

We recruited 89 patients and conducted 624 separate assessments (median 5/patient). Mean age was 39 (s.d. 12.5) years with 20% (n = 18) female. Common diagnoses were schizophrenia-spectrum disorders (70%, n = 62) and personality disorders (20%, n = 18). There were 93 violent incidents. Factors contributing to violence risk were a total dynamic score of ⩾1 (OR 3.39, 95% CI 1.25–9.20), 10-year increase in age (OR 0.67, 0.47–0.96), and female sex (OR 2.78, 1.04–7.40). Non-significant associations with schizophrenia-spectrum disorder were found (OR 0.50, 0.20–1.21). In a fixed-effect model using all covariates, AUC was 0.77 (0.72–0.82) and 0.75 (0.70–0.80) when the dynamic score was excluded.

In predicting violence risk in individuals with psychiatric disorders, modifiable factors added little incremental value beyond static ones in a psychiatric inpatient setting. Future work should make a clear distinction between risk factors that assist in prediction and those linked to needs.

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.

De novo interictal psychosis, albeit uncommon, can develop in patients following temporal lobe surgery for epilepsy. Pathological alterations of the dentate gyrus, including cytoarchitectural changes, immaturity and axonal reorganization that occur in epilepsy, may also underpin co-morbid psychiatric disorders. Our aim was to study candidate pathways that may be associated with the development of interictal psychosis post-operatively in patients with hippocampal sclerosis (HS).

A total of 11 patients with HS who developed interictal psychosis (HS-P) post-operatively were compared with a matched surgical HS group without psychosis (HS-NP). Resected tissues were investigated for the extent of granule cell dispersion, mossy fibre sprouting and calbindin expression in the granule cells. We quantified doublecortin, mini-chromosome maintenance protein 2 (MCM2) and reelin-expressing neuronal populations in the dentate gyrus as well as the distribution of cannabinoid type 1 receptor (CBR1).

The patterns of neuronal loss and gliosis were similar in both groups. HS-P patients demonstrated less mossy fibre sprouting and granule cell dispersion (p < 0.01) and more frequent reduction in calbindin expression in granule cells. There were no group differences in the densities of immature MCM2, doublecortin and reelin-positive cells. CBR1 labelling was significantly lower in Cornu ammonis area CA4 relative to other subfields (p < 0.01); although reduced staining in all hippocampal regions was noted in HS-P compared with HS-NP patients, the differences were not statistically significant.

The alterations in dentate gyrus pathology found in HS-P patients could indicate underlying differences in the cellular response to seizures. These mechanisms may predispose to the development of psychosis in epilepsy and warrant further investigation.