Few studies have examined the concurrent effects of physical disease and systemic inflammation on suicide risk in patients with depression. The authors investigated the independent contributions of chronic physical disease and systemic inflammation as indexed by C-reactive protein (CRP), on risk of suicide attempt.

In this case–control study, 1468 cases of suicide attempters and 14 373 controls, both aged 18–65 years with a diagnosis of depression during 2011–2015, were identified from the hospital-wide database. Regression models were implemented to identify separate effects of physical diseases and systemic inflammation indexed by CRP, on risk of suicide attempt.

Compared with having no physical disease, having one, two, and three or more physical diseases was associated with a 3.6-, 6.4-, and 14.9-fold increase in odds of making a suicide attempt, respectively, after adjusting for age, sex, and race/ethnicity. In a sub-sample of cases and controls with available CRP values, patients with high CRP (>3 mg/L) had 1.9 times the odds of suicide attempt compared with patients with low CRP (<1 mg/L). This association was no longer significant when controlling for the effect of physical disease.

The presence of physical disease is an important risk factor for suicide attempt among patients with depression. Systemic inflammation is likewise associated with increased risk for suicide attempt, however, this association appears to be accounted for by the presence of physical disease among patients receiving care in a medical center setting. Healthcare providers should consider the risk of suicide attempt in depressed patients burdened with multiple comorbidities.

Psychotic symptoms have been linked to salience abnormalities in the brain reward system, perhaps caused by a dysfunction of the dopamine neurotransmission in striatal regions. Blocking dopamine D2 receptors dampens psychotic symptoms and normalises reward disturbances, but a direct relationship between D2 receptor blockade, normalisation of reward processing and symptom improvement has not yet been demonstrated. The current study examined the association between blockade of D2 receptors in the caudate nucleus, alterations in reward processing and the psychopathology in a longitudinal study of antipsychotic-naïve first-episode schizophrenia patients.

Twenty-two antipsychotic-naïve first-episode schizophrenia patients (10 males, mean age 23.3) and 23 healthy controls (12 males, mean age 23.5) were examined with single-photon emission computed tomography using 123I-labelled iodobenzamide. Reward disturbances were measured with functional magnetic resonance imaging (fMRI) using a modified version of the monetary-incentive-delay task. Patients were assessed before and after 6 weeks of treatment with amisulpride.

In line with previous results, patients had a lower fMRI response at baseline (0.2 ± 0.5 v. 0.7 ± 0.6; p = 0.008), but not at follow-up (0.5 ± 0.6 v. 0.6 ± 0.7), and a change in the fMRI signal correlated with improvement in Positive and Negative Syndrome Scale positive symptoms (ρ = −0.435, p = 0.049). In patients responding to treatment, a correlation between improvement in the fMRI signal and receptor occupancy was found (ρ = 0.588; p = 0.035).

The results indicate that salience abnormalities play a role in the reward system in schizophrenia. In patients responding to a treatment-induced blockade of dopamine D2 receptors, the psychotic symptoms may be ameliorated by normalising salience abnormalities in the reward system.

Establishing neurobiological markers of posttraumatic stress disorder (PTSD) is essential to aid in diagnosis and treatment development. Fear processing deficits are central to PTSD, and their neural signatures may be used as such markers.

Here, we conducted a meta-analysis of seven Pavlovian fear conditioning fMRI studies comparing 156 patients with PTSD and 148 trauma-exposed healthy controls (TEHC) using seed-based d-mapping, to contrast neural correlates of experimental phases, namely conditioning, extinction learning, and extinction recall.

Patients with PTSD, as compared to TEHCs, exhibited increased activation in the anterior hippocampus (extending to the amygdala) and medial prefrontal cortex during conditioning; in the anterior hippocampus-amygdala regions during extinction learning; and in the anterior hippocampus-amygdala and medial prefrontal areas during extinction recall. Yet, patients with PTSD have shown an overall decreased activation in the thalamus during all phases in this meta-analysis.

Findings from this metanalysis suggest that PTSD is characterized by increased activation in areas related to salience and threat, and lower activation in the thalamus, a key relay hub between subcortical areas. If replicated, these fear network alterations may serve as objective diagnostic markers for PTSD, and potential targets for novel treatment development, including pharmacological and brain stimulation interventions. Future longitudinal studies are needed to examine whether these observed network alteration in PTSD are the cause or the consequence of PTSD.

Combat exposure is associated with elevated risk for post-traumatic stress disorder (PTSD). Despite considerable research on PTSD symptom clustering, it remains unknown how symptoms of PTSD re-organize following combat. Network analysis provides a powerful tool to examine such changes.

A network analysis approach was taken to examine how symptom networks change from pre- to post-combat using longitudinal prospective data from a cohort of infantry male soldiers (Mage = 18.8 years). PTSD symptoms measured using the PTSD Checklist (PCL) were assessed after 6 months of combat training but before deployment and again after 6 months of combat (Ns = 910 and 725 at pre-deployment and post-combat, respectively)

Stronger connectivity between PTSD symptoms was observed post-combat relative to pre-deployment (global strength values of the networks were 7.54 pre v. 7.92 post; S = .38, p < 0.05). Both the re-experiencing symptoms cluster (1.92 v. 2.12; S = .20, p < 0.03) and the avoidance symptoms cluster (2.61 v. 2.96; S = .35, p < 0.005) became more strongly inter-correlated post-combat. Centrality estimation analyses revealed that psychological reaction to triggers was central and linked the intrusion and avoidance sub-clusters at post-combat. The strength of associations between the arousal and reactivity symptoms cluster remained stable over time (1.85 v. 1.83; S = .02, p = .92).

Following combat, PTSD symptoms and particularly the re-experiencing and avoidance clusters become more strongly inter-correlated, indicating high centrality of trigger-reactivity symptoms.

Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia, but they can also appear in otherwise healthy individuals. Imaging studies implicate language networks in the generation of AVH; however, it remains unclear if alterations reflect biologic substrates of AVH, irrespective of diagnostic status, age, or illness-related factors. We applied multimodal imaging to identify AVH-specific pathology, evidenced by overlapping gray or white matter deficits between schizophrenia patients and healthy voice-hearers.

Diffusion-weighted and T1-weighted magnetic resonance images were acquired in 35 schizophrenia patients with AVH (SCZ-AVH), 32 healthy voice-hearers (H-AVH), and 40 age- and sex-matched controls without AVH. White matter fractional anisotropy (FA) and gray matter thickness (GMT) were computed for each region comprising ICBM-DTI and Desikan–Killiany atlases, respectively. Regions were tested for significant alterations affecting both SCZ-AVH and H-AVH groups, relative to controls.

Compared with controls, the SCZ-AVH showed widespread FA and GMT reductions; but no significant differences emerged between H-AVH and control groups. While no overlapping pathology appeared in the overall study groups, younger (<40 years) H-AVH and SCZ-AVH subjects displayed overlapping FA deficits across four regions (p < 0.05): the genu and splenium of the corpus callosum, as well as the anterior limbs of the internal capsule. Analyzing these regions with free-water imaging ascribed overlapping FA abnormalities to tissue-specific anisotropy changes.

We identified white matter pathology associated with the presence of AVH, independent of diagnostic status. However, commonalities were constrained to younger and more homogenous groups, after reducing pathologic variance associated with advancing age and chronicity effects.

Bipolar disorder I (BD-I) is defined by episodes of mania, depression and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood.

We first assessed the severity of NS in 25 euthymic BD-I patients compared with 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral (VS) and dorsal striatal (DS) activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS.

In BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant VS and DS activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole-brain analyses revealed reduced extra-striatal activation in BD-I patients compared with HC and an association between reduced activation of the inferior frontal gyrus and apathy.

This study found that in BD-I patients apathy is present to an extent comparable to SZ, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

Family education programs (FEPs) target caregiving-related psychological distress for carers of relatives/friends diagnosed with serious mental health conditions. While FEPs are efficacious in reducing distress, the mechanisms are not fully known. Peer group support and greater mental health knowledge are proposed to reduce carers' psychological distress by reducing stigmatising attitudes and self-blame, and strengthening carers' relationship with their relative.

Adult carers (n = 1016) who participated in Wellways Australia's FEP from 2009 to 2016 completed self-report questionnaires at the core program's start and end, during the consolidation period, and at a 6-month follow-up. Those who enrolled early completed questionnaires prior to a wait-list period. We used linear mixed-effects modelling to assess the program's effectiveness using a naturalistic wait-list control longitudinal design, and multivariate latent growth modelling to test a theory-based process change model.

While there was no significant change over the wait-list period, psychological distress, self-blame and stigmatising attitudes significantly decreased, and communication and relationship quality/feelings increased from the core program's start to its end. Changes were maintained throughout the consolidation period and follow-up. Peer group support significantly predicted the declining trajectory of distress. Peer group support and greater knowledge significantly predicted declining levels of self-blame and stigmatising attitudes, and increasing levels of communication.

This is the first study to quantitatively validate the mechanisms underlying the effect of FEPs on carers' psychological distress. Peer group support is key in modifying carers' appraisals of their friend/relatives' condition. Continued implementation of FEPs within mental health service systems is warranted.

Previous research has shown an association between subjective wellbeing and incident diabetes. Less is known about the role of wellbeing for subclinical disease trajectories as captured via glycated hemoglobin (HbA1c). We aimed to explore the association between subjective wellbeing and future HbA1c levels, and the role of sociodemographic, behavioral and clinical factors in this association.

We used data from the English Longitudinal Study of Ageing for this study (N = 2161). Subjective wellbeing (CASP-19) was measured at wave 2 and HbA1c was measured 8 years later at wave 6. Participants were free from diabetes at baseline. We conducted a series of analyses to examine the extent to which the association was accounted for by a range of sociodemographic, behavioral and clinical factors in linear regression models.

Models showed that subjective wellbeing (CASP-19 total score) was inversely associated with HbA1c 8 years later after controlling for depressive symptoms, age, sex, and baseline HbA1c (B = −0.035, 95% CI −0.060 to –0.011, p = 0.005). Inclusion of sociodemographic variables and behavioral factors in models accounted for a large proportion (17.0% and 24.5%, respectively) of the relationship between wellbeing and later HbA1c; clinical risk factors explained a smaller proportion of the relationship (3.4%).

Poorer subjective wellbeing is associated with greater HbA1c over 8 years of follow-up and this relationship can in part be explained by sociodemographic, behavioral and clinical factors among older adults.

Euthanasia or assisted suicide (EAS) for psychiatric disorders, legal in some countries, remains controversial. Personality disorders are common in psychiatric EAS. They often cause a sense of irremediable suffering and engender complex patient–clinician interactions, both of which could complicate EAS evaluations.

We conducted a directed-content analysis of all psychiatric EAS cases involving personality and related disorders published by the Dutch regional euthanasia review committees (N = 74, from 2011 to October 2017).

Most patients were women (76%, n = 52), often with long, complex clinical histories: 62% had physical comorbidities, 97% had at least one, and 70% had two or more psychiatric comorbidities. They often had a history of suicide attempts (47%), self-harming behavior (27%), and trauma (36%). In 46%, a previous EAS request had been refused. Past psychiatric treatments varied: e.g. hospitalization and psychotherapy were not tried in 27% and 28%, respectively. In 50%, the physician managing their EAS were new to them, a third (36%) did not have a treating psychiatrist at the time of EAS request, and most physicians performing EAS were non-psychiatrists (70%) relying on cross-sectional psychiatric evaluations focusing on EAS eligibility, not treatment. Physicians evaluating such patients appear to be especially emotionally affected compared with when personality disorders are not present.

The EAS evaluation of persons with personality disorders may be challenging and emotionally complex for their evaluators who are often non-psychiatrists. These factors could influence the interpretation of EAS requirements of irremediability, raising issues that merit further discussion and research.

A dominant idea is that impaired capacities for theory of mind (ToM) are the reasons for impairments in social functioning in several conditions, including autism and schizophrenia. In this paper, we present empirical evidence that challenges this influential assumption.

We conducted three studies examining the association between ToM and social functioning in participants diagnosed with a non-affective psychotic disorder and healthy individuals. We used both the experience sampling method, a structured diary technique collecting information in daily-life, and a standardised questionnaire to assess social functioning. Analysed data are part of Wave 1 and Wave 3 of the Genetic Risk and Outcome of Psychosis (GROUP) study.

Results were highly consistent across studies and showed no significant association between the two constructs.

These findings question the leading assumption that social cognition is a prerequisite for social functioning, but rather suggest that social cognition is possibly a result of basic social interactive capacities.

To determine the baseline individual characteristics that predicted symptom recovery and functional recovery at 10-years following the first episode of psychosis.

AESOP-10 is a 10-year follow up of an epidemiological, naturalistic population-based cohort of individuals recruited at the time of their first episode of psychosis in two areas in the UK (South East London and Nottingham). Detailed information on demographic, clinical, and social factors was examined to identify which factors predicted symptom and functional remission and recovery over 10-year follow-up. The study included 557 individuals with a first episode psychosis. The main study outcomes were symptom recovery and functional recovery at 10-year follow-up.

At 10 years, 46.2% (n = 140 of 303) of patients achieved symptom recovery and 40.9% (n = 117) achieved functional recovery. The strongest predictor of symptom recovery at 10 years was symptom remission at 12 weeks (adj OR 4.47; CI 2.60–7.67); followed by a diagnosis of depression with psychotic symptoms (adj OR 2.68; CI 1.02–7.05). Symptom remission at 12 weeks was also a strong predictor of functional recovery at 10 years (adj OR 2.75; CI 1.23–6.11), together with being from Nottingham study centre (adj OR 3.23; CI 1.25–8.30) and having a diagnosis of mania (adj OR 8.17; CI 1.61–41.42).

Symptom remission at 12 weeks is an important predictor of both symptom and functional recovery at 10 years, with implications for illness management. The concepts of clinical and functional recovery overlap but should be considered separately.

Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial.

In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS).

MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance.

Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.

Posttraumatic stress disorder (PTSD) is associated with higher risk of incident hypertension, but it is unclear whether specific aspects of PTSD are particularly cardiotoxic. PTSD is a heterogeneous disorder, comprising dimensions of fear and dysphoria. Because elevated fear after trauma may promote autonomic nervous system dysregulation, we hypothesized fear would predict hypertension onset, and associations with hypertension would be stronger with fear than dysphoria.

We examined fear and dysphoria symptom dimensions in relation to incident hypertension over 24 years in 2709 trauma-exposed women in the Nurses’ Health Study II. Posttraumatic fear and dysphoria symptom scores were derived from a PTSD diagnostic interview. We used proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for each symptom dimension (quintiles) with new-onset hypertension events (N = 925), using separate models. We also considered lower-order symptom dimensions of fear and dysphoria.

Higher levels of fear (P-trend = 0.02), but not dysphoria (P-trend = 0.22), symptoms were significantly associated with increased hypertension risk after adjusting for socio-demographics and family history of hypertension. Women in the highest v. lowest fear quintile had a 26% higher rate of developing hypertension [HR = 1.26 (95% CI 1.02–1.57)]; the increased incidence associated with greater fear was similar when further adjusted for biomedical and health behavior covariates (P-trend = 0.04) and dysphoria symptoms (P-trend = 0.04). Lower-order symptom dimension analyses provided preliminary evidence that the re-experiencing and avoidance components of fear were particularly associated with hypertension.

Fear symptoms associated with PTSD may be a critical driver of elevated cardiovascular risk in trauma-exposed individuals.

Preterm birth is associated with an increased risk for cognitive-neurophysiological impairments and attention-deficit/hyperactivity disorder (ADHD). Whether the associations are due to the preterm birth insult per se, or due to other risk factors that characterise families with preterm-born children, is largely unknown.

We employed a within-sibling comparison design, using cognitive-performance and event-related potential (ERP) measures from 104 preterm-born adolescents and 104 of their term-born siblings. Analyses focused on ADHD symptoms and cognitive and ERP measures from a cued continuous performance test, an arrow flanker task and a reaction time task.

Within-sibling analyses showed that preterm birth was significantly associated with increased ADHD symptoms (β = 0.32, p = 0.01, 95% CI 0.05 to 0.58) and specific cognitive-ERP impairments, such as IQ (β = −0.20, p = 0.02, 95% CI −0.40 to −0.01), preparation-vigilance measures and measures of error processing (ranging from β = 0.71, −0.35). There was a negligible within-sibling association between preterm birth with executive control measures of inhibition (NoGo-P3, β = −0.07, p = 0.45, 95% CI −0.33 to 0.15) or verbal working memory (digit span backward, β = −0.05, p = 0.63, 95% CI −0.30 to 0.18).

Our results suggest that the relationship between preterm birth with ADHD symptoms and specific cognitive-neurophysiological impairments (IQ, preparation-vigilance and error processing) is independent of family-level risk and consistent with a causal inference. In contrast, our results suggest that previously observed associations between preterm birth with executive control processes of inhibition and working memory are instead linked to background characteristics of families with a preterm-born child rather than preterm birth insult per se. These findings suggest that interventions need to target both preterm-birth specific and family-level risk factors.

Social anxiety lies on a continuum, and young adults with elevated symptoms are at risk for developing a range of psychiatric disorders. Yet relatively little is known about the factors that govern the hour-by-hour experience and expression of social anxiety in the real world.

Here we used smartphone-based ecological momentary assessment (EMA) to intensively sample emotional experience across different social contexts in the daily lives of 228 young adults selectively recruited to represent a broad spectrum of social anxiety symptoms.

Leveraging data from over 11 000 real-world assessments, our results highlight the central role of close friends, family members, and romantic partners. The presence of such close companions was associated with enhanced mood, yet socially anxious individuals had fewer confidants and spent less time with the close companions that they do have. Although higher levels of social anxiety were associated with a general worsening of mood, socially anxious individuals appear to derive larger benefits – lower levels of negative affect, anxiety, and depression – from their close companions. In contrast, variation in social anxiety was unrelated to the amount of time spent with strangers, co-workers, and acquaintances; and we uncovered no evidence of emotional hypersensitivity to these less-familiar individuals.

These findings provide a framework for understanding the deleterious consequences of social anxiety in emerging adulthood and set the stage for developing improved intervention strategies.

Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.

We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.

We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.

Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.

Computerized cognitive remediation therapy (CCRT) is generally effective for the cognitive deficits of schizophrenia. However, there is much uncertainty about what factors mediate or moderate effectiveness and are therefore important to personalize treatment and boost its effects.

In total, 311 Chinese inpatients with Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia were randomized to receive CCRT or Active control for 12 weeks with four to five sessions per week. All participants were assessed at baseline, post-treatment and 3-month follow-up. The outcomes were cognition, clinical symptoms and functional outcomes.

There was a significant benefit in the MATRICS Consensus Cognitive Battery (MCCB) total score for CCRT (F1,258 = 5.62; p = 0.02; effect size was 0.27, 95% confidence interval 0.04–0.49). There were no specific moderators of CCRT improvements. However, across both groups, Wisconsin Card Sort Test improvement mediated a positive effect on functional capacity and Digit Span benefit mediated decreases in positive symptoms. In exploratory analyses younger and older participants showed cognitive improvements but on different tests (younger on Symbol Coding Test, while older on the Spatial Span Test). Only the older age group showed MSCEIT benefits at post-treatment. In addition, cognition at baseline negatively correlated with cognitive improvement and those whose MCCB baseline total score was around 31 seem to derive the most benefit.

CCRT can improve the cognitive function of patients with schizophrenia. Changes in cognitive outcomes also contributed to improvements in functional outcomes either directly or solely in the context of CCRT. Age and the basic cognitive level of the participants seem to affect the cognitive benefits from CCRT.

The aetiology of nausea and vomiting during pregnancy (NVP) is multifactorial, but the relative contribution of biological and psychological determinants is insufficiently understood. We examined the association of human chorionic gonadotropin (hCG), thyroid hormones (thyroid-stimulating hormone and thyroxin) and psychological factors with NVP.

Blood chemistry and psychological measures were obtained in 1682 pregnant women participating in the Holistic Approach to Pregnancy and the first Postpartum Year (HAPPY) study between 12 and 14 weeks of gestation. The presence of NVP was measured using the Pregnancy-Unique Quantification of Emesis scale. Depressive symptoms were assessed using the Edinburgh Depression Scale. Multivariable logistic regression analyses were used to investigate the independent role of hCG, thyroid hormones and depression as related to NVP, adjusting for age, body mass index, education, parity, smoking status, unplanned pregnancy and history of depression.

Elevated levels of NVP were observed in 318 (18.9%) participants. High hCG levels [odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.11–1.95], elevated depressive symptoms in the first trimester (OR = 1.67, 95% CI = 1.15–2.43) and a history of depression (OR = 1.53, 95% CI = 1.11–2.11) were independently related to high NVP. Multiparity (OR = 1.47, 95% CI = 1.12–1.92) and younger age (OR = 0.91, 95% CI = 0.87–0.94) were also associated with high NVP, whereas (sub)clinical hyperthyroidism was not related to high NVP.

The current study is the first to demonstrate that a combination of hCG hormone and psychological factors are independently related to nausea and vomiting during early pregnancy.