Studies have found associations between psychological distress (PD) and increased risk of myocardial infarction (MI). However, it is not clear whether the relationship reflects the subtle influence of pre-existing illness on both PD and MI. This study examines the association between PD and MI in a prospective epidemiological study of 1864 middle-aged men to examine if the association is explained by existing illness.

This study was a prospective cohort study modelling the association between PD, measured using the 30-item General Health Questionnaire (GHQ) and non-fatal myocardial infarction (NFMI) and fatal/non-fatal myocardial infarction (FNFMI).The relationship was modelled in a series of logistic regression models adjusted for age, then cigarette smoking, then social position, and finally for all sociodemographic characteristics, coronary heart disease (CHD) risk factors, and baseline CHD.

PD was associated with a 70% and 68% increased risk of NFMI and FNFMI in fully adjusted analysis. However, PD was not associated with an increased risk of NFMI and FNFMI in analyses excluding those with baseline CHD. Further, being psychologically distressed and physically ill was associated with a greater than twofold risk of NFMI and FNFMI, 2·37 (95% CI 1·33–4·20) and 2·33 (95% CI 1·32–4·12) respectively.

This study suggests that PD is a moderator of the increased risk of MI associated with existing physical illness. PD in men who are physically ill is a marker of an underlying chronic physical illness. The prospective association of PD with MI is not independent of baseline physical illness.

Reports of changes in patients’ social behavior during deep brain stimulation (DBS) raised the question whether DBS induces changes in personality. This study explored if (1) DBS is associated with changes in personality in patients suffering from treatment-resistant depression (TRD), (2) how personality dimensions and depression are associated, and (3) if TRD patients’ self-ratings of personality are valid.

TRD patients were assessed before DBS (n = 30), 6 months (t2, n = 21), 2 (t3, n = 17) and 5 years (t4, n = 11) after the initiation of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB-DBS). Personality was measured with the NEO-Five-Factor Inventory (NEO-FFI), depression severity with Hamilton (HDRS), and Montgomery–Åsberg Depression Rating Scale (MADRS).

Personality dimensions did not change with slMFB-DBS compared with baseline. Extraversion was negatively correlated with HDRS28 (r = −0.48, p < 0.05) and MADRS (r = −0.45, p < 0.05) at t2. Inter-rater reliability was high for the NEO-FFI at baseline (Cronbach's α = 0.74) and at t4 (α = 0.65). Extraversion [t(29) = −5.20; p < 0.001] and openness to experience [t(29) = −6.96; p < 0.001] differed statistically significant from the normative sample, and did not predict the antidepressant response.

slMFB-DBS was not associated with a change in personality. The severity of depression was associated with extraversion. Personality of TRD patients differed from the healthy population and did not change with response, indicating a possible scar effect. Self-ratings of personality seem valid to assess personality during TRD.

The DSM-5 alcohol use disorder (AUD) criteria proposal contains 11 criteria that include most of the DSM-IV abuse and dependence criteria plus craving. The aims of the current study in a large and international alcohol-consuming sample were to confirm the dimensionality of the DSM-5 AUD criteria and to differentiate grades of severity of DSM-5 AUD in subjects who pass the proposed DSM-5 diagnostic threshold of two criteria.

We used the World Health Organization (WHO)/International Society on Biomedical Research on Alcoholism (ISBRA) Study on State and Trait Markers of Alcohol Use and Dependence dataset. Subjects included in the analyses were aged ⩾18 years and were recruited in five countries: Australia, Brazil, Canada, Finland and Japan. Assessment of AUD and additional characteristics was conducted using an adapted version of the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS). Dimensionality of the DSM-5 criteria was evaluated using factor analysis and item response theory (IRT) models. The IRT results led to the classification of AUD patients into three severity groups. External validators were used to differentiate statistically across subgroups.

A total of 1424 currently drinking individuals were included in the analyses. Factor and IRT analyses confirmed the dimensional structure of DSM-5 AUD criteria. More than 99% of the subjects could be allocated to one of the suggested severity subgroups. The magnitude of the external validators differed significantly across the severity groups.

The results confirm the dimensional structure of the proposed DSM-5 AUD criteria. The suggested stages of severity (mild, moderate and severe) may be useful to clinicians by grouping individuals not only in the mild but also in the moderate to severe spectrum of DSM-5 AUD.

Persisting symptoms after treatment for major depressive disorder (MDD) contribute to ongoing impairment and relapse risk. Whether cognitive behavior therapy (CBT) or antidepressant medications result in different profiles of residual symptoms after treatment is largely unknown.

Three hundred fifteen adults with MDD randomized to treatment with either CBT or antidepressant medication in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study were analyzed for the frequency of residual symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) item scores at the end of the 12-week treatment period. Separate comparisons were made for treatment responders and non-responders.

Among treatment completers (n = 250) who responded to CBT or antidepressant medication, there were no significant differences in the persistence of residual MADRS symptoms. However, non-responders treated with medication were significantly less likely to endorse suicidal ideation (SI) at week 12 compared with those treated with CBT (non-responders to medication: 0/54, 0%, non-responders to CBT: 8/30, 26.7%; p = .001). Among patients who terminated the trial early (n = 65), residual MADRS item scores did not significantly differ between the CBT- and medication-treated groups.

Depressed adults who respond to CBT or antidepressant medication have similar residual symptom profiles. Antidepressant medications reduce SI, even among patients for whom the medication provides little overall benefit.

Anxiety symptoms gradually emerge during childhood and adolescence. Individual differences in behavioral inhibition (BI), an early-childhood temperament, may shape developmental paths through which these symptoms arise. Cross-sectional research suggests that level of early-childhood BI moderates associations between later anxiety symptoms and threat-related amygdala–prefrontal cortex (PFC) circuitry function. However, no study has characterized these associations longitudinally. Here, we tested whether level of early-childhood BI predicts distinct evolving associations between amygdala–PFC function and anxiety symptoms across development.

Eighty-seven children previously assessed for BI level in early childhood provided data at ages 10 and/or 13 years, consisting of assessments of anxiety and an fMRI-based dot-probe task (including threat, happy, and neutral stimuli). Using linear-mixed-effects models, we investigated longitudinal changes in associations between anxiety symptoms and threat-related amygdala–PFC connectivity, as a function of early-childhood BI.

In children with a history of high early-childhood BI, anxiety symptoms became, with age, more negatively associated with right amygdala–left dorsolateral-PFC connectivity when attention was to be maintained on threat. In contrast, with age, low-BI children showed an increasingly positive anxiety–connectivity association during the same task condition. Behaviorally, at age 10, anxiety symptoms did not relate to fluctuations in attention bias (attention bias variability, ABV) in either group; by age 13, low-BI children showed a negative anxiety–ABV association, whereas high-BI children showed a positive anxiety–ABV association.

Early-childhood BI levels predict distinct neurodevelopmental pathways to pediatric anxiety symptoms. These pathways involve distinct relations among brain function, behavior, and anxiety symptoms, which may inform diagnosis and treatment.

Offspring of parents with mental disorder are at risk of a range of adverse outcomes. We sought to establish whether such risks extend to offending by examining rates of criminal conviction, including conviction for violent and sexual offences, among offspring of parents with mental disorder compared to offspring without parental disorder.

From a random sample of the Danish population, a cohort aged ⩽15 years (n=412 117) was followed for the occurrence of conviction between January 1981 and December 2006. Incidence rate ratios (IRRs) and cumulative incidences for offspring conviction by parental mental disorder status were calculated using a Cox regression model. Analyses were repeated for conviction for a serious first offence.

Offspring with history of parental mental disorder had higher rates of conviction than those without parental disorder; rates were highest for those with two affected parents [IRR 3.39, 95% confidence interval (CI) 3.08–3.73]. The association persisted when parental gender, offspring gender and the nature of parental disorder were considered. Absolute rates were lower but relative rates higher for female offspring (IRR 3.26 for males with two affected parents, 4.52 for females). Similar patterns were seen for conviction for serious offences. Associations were attenuated after adjustment was made for family socio-economic position (SEP) and parental criminality.

Offspring of parents with mental disorder represent a group at elevated risk of criminality. This raises the possibility of shared familial vulnerability for mental disorder and criminal behaviour, and highlights the need to consider early identification and intervention in this group.

Recent theories suggest that poor working memory (WM) may be the cognitive underpinning of negative symptoms in people with schizophrenia. In this study, we first explore the effect of cognitive remediation (CR) on two clusters of negative symptoms (i.e. expressive and social amotivation), and then assess the relevance of WM gains as a possible mediator of symptom improvement.

Data were accessed for 309 people with schizophrenia from the NIMH Database of Cognitive Training and Remediation Studies and a separate study. Approximately half the participants received CR and the rest were allocated to a control condition. All participants were assessed before and after therapy and at follow-up. Expressive negative symptoms and social amotivation symptoms scores were calculated from the Positive and Negative Syndrome Scale. WM was assessed with digit span and letter-number span tests.

Participants who received CR had a significant improvement in WM scores (d = 0.27) compared with those in the control condition. Improvements in social amotivation levels approached statistical significance (d = −0.19), but change in expressive negative symptoms did not differ between groups. WM change did not mediate the effect of CR on social amotivation.

The results suggest that a course of CR may benefit behavioural negative symptoms. Despite hypotheses linking memory problems with negative symptoms, the current findings do not support the role of this cognitive domain as a significant mediator. The results indicate that WM improves independently from negative symptoms reduction.

The neurodevelopmental and trauma theories are two widely cited models of psychosis. A third – the developmental risk factor model (DRFM) – recognises the combined role of neurodevelopmental risks and trauma. Our objective was to test these theories using preterm populations as a natural experiment, given the high prevalence of neurodevelopmental deficits and exposure to trauma.

Two population-based preterm birth cohorts, the Bavarian Longitudinal Study (BLS; N = 399) and EPICure Study (N = 184), were included with term-born controls. Peer victimisation in childhood was assessed by parent and child report and psychotic experiences (PE) were assessed in early adulthood. Different models of psychosis were tested using regression and mediation analyses.

There was support for the trauma and DRFM in the BLS. Peer victimisation increased the risk of PE for preterm and term-born participants equally [odds ratio = 4.87, 95% confidence interval (CI) 1.96–12.08]. There was an indirect effect where preterm children were more likely to be victimised, which subsequently increased risk of PE [β = 1.12 (s.e. = 0.61), 95% CI 0.11–2.48]. The results were replicated in EPICure.

Exposure to trauma which is experienced more often by neurodevelopmental risk children rather than neurodevelopmental risk per se increases the risk of PE. The findings are consistent with the trauma model and DRFM. Interventions focused on reducing trauma may reduce the development of PE.

The gene encoding the regulator of G-protein signaling subtype 4 (RGS4), located on chromosome 1q23-3, has been proposed as a possible susceptibility gene for schizophrenia and has been specifically linked to prefrontal cortical structural and functional integrity.

The effects of four core single nucleotide polymorphisms (SNPs) within the RGS4 gene on oculomotor parameters in a battery of oculomotor tasks (saccade, antisaccade, smooth eye pursuit, fixation) were investigated in a sample of 2243 young male military conscripts.

The risk allele of RGS4SNP18 was found to be associated with two variables of antisaccade performance, increased error rate and variation in the correct antisaccade latency. By contrast, the same allele and also the risk allele of RGS4SNP4 led to an improvement in smooth eye pursuit performance (increased gain). Structural equation modeling confirmed that the combined gene variation of RGS4SNP4 and RGS4SNP18 was a significant predictor of antisaccade but not smooth eye pursuit performance.

These results provide evidence for a specific effect of schizophrenia-related RGS4 genotype variations to prefrontal dysfunction measured by oculomotor indices of performance in normal individuals, further validating the hypothesis that RGS4 is related to prefrontal dysfunction in schizophrenia.

Neuroimaging studies on major depressive disorder (MDD) have identified an extensive range of brain structural abnormalities, but the exact neural mechanisms associated with MDD remain elusive. Most previous studies were performed with voxel- or surface-based morphometry which were univariate methods without considering spatial information across voxels/vertices.

Brain morphology was investigated using voxel-based morphometry (VBM) and source-based morphometry (SBM) in 1082 MDD patients and 990 healthy controls (HCs) from the REST-meta-MDD Consortium. We first examined group differences in regional grey matter (GM) volumes and structural covariance networks between patients and HCs. We then compared first-episode, drug-naïve (FEDN) patients, and recurrent patients. Additionally, we assessed the effects of symptom severity and illness duration on brain alterations.

VBM showed decreased GM volume in various regions in MDD patients including the superior temporal cortex, anterior and middle cingulate cortex, inferior frontal cortex, and precuneus. SBM returned differences only in the prefrontal network. Comparisons between FEDN and recurrent MDD patients showed no significant differences by VBM, but SBM showed greater decreases in prefrontal, basal ganglia, visual, and cerebellar networks in the recurrent group. Moreover, depression severity was associated with volumes in the inferior frontal gyrus and precuneus, as well as the prefrontal network.

Simultaneous application of VBM and SBM methods revealed brain alterations in MDD patients and specified differences between recurrent and FEDN patients, which tentatively provide an effective multivariate method to identify potential neurobiological markers for depression.

Depression is characterised by a heightened self-focus, which is believed to be associated with differences in emotion and reward processing. However, the precise relationship between these cognitive domains is not well understood. We examined the role of self-reference in emotion and reward processing, separately and in combination, in relation to depression.

Adults experiencing varying levels of depression (n = 144) completed self-report depression measures (PHQ-9, BDI-II). We measured self, emotion and reward processing, separately and in combination, using three cognitive tasks.

When self-processing was measured independently of emotion and reward, in a simple associative learning task, there was little association with depression. However, when self and emotion processing occurred in combination in a self-esteem go/no-go task, depression was associated with an increased positive other bias [b = 3.51, 95% confidence interval (CI) 1.24–5.79]. When the self was processed in relation to emotion and reward, in a social evaluation learning task, depression was associated with reduced positive self-biases (b = 0.11, 95% CI 0.05–0.17).

Depression was associated with enhanced positive implicit associations with others, and reduced positive learning about the self, culminating in reduced self-favouring biases. However, when self, emotion and reward processing occurred independently there was little evidence of an association with depression. Treatments targeting reduced positive self-biases may provide more sensitive targets for therapeutic intervention and potential biomarkers of treatment responses, allowing the development of more effective interventions.

Family-based treatment (FBT) is the first-line treatment for adolescent anorexia nervosa (AN). Yet, remission is not achieved for about half of adolescents with AN receiving FBT. Understanding patient- and parent-level factors that predict FBT response may inform treatment development and improve outcomes.

Network analysis was used to identify the most central symptoms of AN in adolescents who completed the Eating Disorder Examination (EDE) prior to FBT (N = 409). Bridge pathways between adolescent AN and parental self-efficacy in facilitating their child's recovery from AN were identified in a subset of participants (n = 184). Central and bridge symptoms were tested as predictors of early response (⩾2.4 kg weight gain by the fourth session of FBT) and end-of-treatment weight restoration [⩾95% expected body weight (EBW)] and full remission (⩾95% EBW and EDE score within 1 standard deviation of norms).

The most central symptoms of adolescent AN included desiring weight loss, dietary restraint, and feeling fat. These symptoms predicted early response, but not end-of-treatment outcomes. Bridge symptoms were parental beliefs about their responsibility to renourish their child, adolescent discomfort eating in front of others, and adolescent dietary restraint. Bridge symptoms predicted end-of-treatment weight restoration, but not early response nor full remission.

Findings highlight the prognostic utility of core symptoms of adolescent AN. Parent beliefs about their responsibility to renourish their child may maintain associations between parental self-efficacy and AN psychopathology. These findings could inform strategies to adapt FBT and improve outcomes.

The pathophysiology of obsessive-compulsive disorder (OCD) remains unclear despite extensive neuroimaging work on the disorder. Exposure to medication and comorbid mental disorders can confound the results of OCD studies. The goal of this study was to explore differences in brain functional connectivity (FC) within the cortico-striato-thalamo-cortical (CSTC) loop of drug-naïve and drug-free OCD patients and healthy controls (HCs).

A total of 29 drug-naïve OCD patients, 22 drug-free OCD patients, and 25 HCs matched on age, gender and education level underwent functional magnetic resonance imaging scanning at resting state. Seed-based connectivity analyses were conducted among the three groups. The Yale Brown Obsessive Compulsive Scale and clinical inventories were used to assess the clinical symptoms.

Compared with HCs, the drug-naïve OCD patients had reduced FC within the limbic CSTC loop. In the drug-naïve OCD participants, we also found hyperconnectivity between the supplementary motor area and ventral and dorsal putamen (p < 0.05, corrected for multiple comparisons).

Exposure to antidepressants such as selective serotonin reuptake inhibitors may affect the function of some brain regions. Future longitudinal studies could help to reveal the pharmacotherapeutic mechanisms in these loops.