Substantial healthcare resources are devoted to panic disorder (PD) and coronary heart disease (CHD); however, the association between these conditions remains controversial. Our objective was to conduct a systematic review of studies assessing the association between PD, related syndromes, and incident CHD.

Relevant studies were retrieved from Medline, EMBASE, SCOPUS and PsycINFO without restrictions from inception to January 2015 supplemented with hand-searching. We included studies that reported hazard ratios (HR) or sufficient data to calculate the risk ratio and 95% confidence interval (CI) which were pooled using a random-effects model. Studies utilizing self-reported CHD were ineligible. Twelve studies were included comprising 1 131 612 persons and 58 111 incident CHD cases.

PD was associated with the primary incident CHD endpoint [adjusted HR (aHR) 1.47, 95% CI 1.24–1.74, p < 0.00001] even after excluding angina (aHR 1.49, 95% CI 1.22–1.81, p < 0.00001). High to moderate quality evidence suggested an association with incident major adverse cardiac events (MACE; aHR 1.40, 95% CI 1.16–1.69, p = 0.0004) and myocardial infarction (aHR 1.36, 95% CI 1.12–1.66, p = 0.002). The risk for CHD was significant after excluding depression (aHR 1.64, 95% CI 1.45–1.85) and after depression adjustment (aHR 1.38, 95% CI 1.03–1.87). Age, sex, length of follow-up, socioeconomic status and diabetes were sources of heterogeneity in the primary endpoint.

Meta-analysis showed that PD was independently associated with incident CHD, myocardial infarction and MACE; however, reverse causality cannot be ruled out and there was evidence of heterogeneity.

Pediatric loss-of-control (LOC) eating is a robust behavioral precursor to binge-type eating disorders. Elucidating precursors to LOC eating and binge-type eating disorders may refine developmental risk models of eating disorders and inform interventions.

We review evidence within constructs of the Negative Valence Systems (NVS) domain, as specified by the Research Domain Criteria framework. Based on published studies, we propose an integrated NVS model of binge-type eating-disorder risk.

Data implicate altered corticolimbic functioning, neuroendocrine dysregulation, and self-reported negative affect as possible risk factors. However, neuroimaging and physiological data in children and adolescents are sparse, and most prospective studies are limited to self-report measures.

We discuss a broad NVS framework for conceptualizing early risk for binge-type eating disorders. Future neural and behavioral research on the developmental trajectory of LOC and binge-type eating disorders is required.

Despite the extensive literature assessing associations between religiosity/spirituality and health, few studies have investigated the clinical applicability of this evidence. The purpose of this paper was to assess the impact of religious/spiritual interventions (RSI) through randomized clinical trials (RCTs).

A systematic review was performed in the following databases: PubMed, Scopus, Web of Science, PsycINFO, Cochrane Collaboration, Embase and SciELO. Through the use of a Boolean expression, articles were included if they: (i) investigated mental health outcomes; (ii) had a design consistent with RCTs. We excluded protocols involving intercessory prayer or distance healing. The study was conducted in two phases by reading: (1) title and abstracts; (2) full papers and assessing their methodological quality. Then, a meta-analysis was carried out.

Through this method, 4751 papers were obtained, of which 23 remained included. The meta-analysis showed significant effects of RSI on anxiety general symptoms (p < 0.001) and in subgroups: meditation (p < 0.001); psychotherapy (p = 0.02); 1 month of follow-up (p < 0.001); and comparison groups with interventions (p < 0.001). Two significant differences were found in depressive symptoms: between 1 and 6 months and comparison groups with interventions (p = 0.05). In general, studies have shown that RSI decreased stress, alcoholism and depression.

RCTs on RSI showed additional benefits including reduction of clinical symptoms (mainly anxiety). The diversity of protocols and outcomes associated with a lack of standardization of interventions point to the need for further studies evaluating the use of religiosity/spirituality as a complementary treatment in health care.

Overvaluation of body shape/weight is thought to be the core psychopathology underlying eating disorders, which propels engagement in non-compensatory weight-control behaviors. In turn, these behaviors lead to binge eating and/or maintenance of low weight thereby reinforcing overvaluation. The present study investigated the reciprocal relationship between overvaluation and engagement in non-compensatory weight-control behaviors (defined in two ways: restrictive eating and compulsive exercise) among women diagnosed with anorexia nervosa or bulimia nervosa (N = 237).

Participants completed clinical interviews in which weekly eating disorder symptoms and behaviors were assessed over 2 years.

Overvaluation on a given week was associated with greater engagement in non-compensatory weight-control behaviors during the following week. Further, engagement in non-compensatory weight-control behaviors on a given week was associated with greater overvaluation during the following week. These findings held true regardless of participants’ shape/weight concerns (feelings of fatness and fat phobia), and eating disorder diagnosis.

Our data provide empirical support for key aspects of the transdiagnostic cognitive-behavioral model of eating disorders and suggest that targeting non-compensatory weight-control behaviors in treatment may help alleviate overvaluation and shape/weight concerns.

Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated.

The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7–26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood.

Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult.

Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged.

Telomere attrition might be one of the mechanisms through which psychosocial stress leads to somatic disease. To date it is unknown if exposure to adverse life events in adulthood is associated with telomere shortening prospectively. In the current study we investigated whether life events are associated with shortening of telomere length (TL).

Participants were 1094 adults (mean age 53.1, range 33–79 years) from the PREVEND cohort. Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Life events were assessed with an adjusted version of the List of Threatening Events (LTE). TL was measured by monochrome multiplex quantitative PCR at T1, T2, and T3. A linear mixed model was used to assess the effect of recent life events on TL prospectively. Multivariable regression analyses were performed to assess whether the lifetime life events score or the score of life events experienced before the age of 12 predicted TL cross-sectionally. All final models were adjusted for age, sex, body mass index, presence of chronic diseases, frequency of sports, smoking status, and level of education.

Recent life events significantly predicted telomere attrition prospectively (B = −0.031, p = 0.007). We were not able to demonstrate a significant cross-sectional relationship between the lifetime LTE score and TL. Nor did we find exposure to adverse life events before the age of 12 to be associated with TL in adulthood.

Exposure to recent adverse life events in adulthood is associated with telomere attrition prospectively.

Attentional impairment is a core cognitive feature of major depressive disorder (MDD) and bipolar disorder (BD). However, little is known of the characteristics of response time (RT) distributions from attentional tasks. This is crucial to furthering our understanding of the profile and extent of cognitive intra-individual variability (IIV) in mood disorders.

A computerized sustained attention task was administered to 138 healthy controls and 158 patients with a mood disorder: 86 euthymic BD, 33 depressed BD and 39 medication-free MDD patients. Measures of IIV, including individual standard deviation (iSD) and coefficient of variation (CoV), were derived for each participant. Ex-Gaussian (and Vincentile) analyses were used to characterize the RT distributions into three components: mu and sigma (mean and standard deviation of the Gaussian portion of the distribution) and tau (the ‘slow tail’ of the distribution).

Compared with healthy controls, iSD was increased significantly in all patient samples. Due to minimal changes in average RT, CoV was only increased significantly in BD depressed patients. Ex-Gaussian modelling indicated a significant increase in tau in euthymic BD [Cohen's d = 0.39, 95% confidence interval (CI) 0.09–0.69, p = 0.011], and both sigma (d = 0.57, 95% CI 0.07–1.05, p = 0.025) and tau (d = 1.14, 95% CI 0.60–1.64, p < 0.0001) in depressed BD. The mu parameter did not differ from controls.

Increased cognitive variability may be a core feature of mood disorders. This is the first demonstration of differences in attentional RT distribution parameters between MDD and BD, and BD depression and euthymia. These data highlight the utility of applying measures of IIV to characterize neurocognitive variability and the great potential for future application.

Rumination is an important cognitive risk factor for onset and relapse of depression. However, no studies have employed a dimensional approach in investigating the neural correlates of rumination and the relationship with depression.

Non-clinical healthy subjects (n = 306), who completed the classical rumination and depression scales, were studied using voxel-based morphometry and regional homogeneity (ReHo). Subsequently, mediation analysis was conducted to examine the influence of rumination on the relationship between brain structure and depression. Moreover, depressive patients (n = 60) and a control group (n = 63) of comparable age and education were studied with regions of interest that were identified in the healthy individuals.

For healthy individuals, regional grey-matter volume (rGMV) of dorsolateral prefrontal cortex (DLPFC) and parahippocampal gyrus (PHG) were positively correlated with rumination. In addition, rumination had a mediating effect on the relationship between the DLPFC and PHG and depression. Moreover, ReHo analysis showed that rumination had a significantly negative correlation with functional homogeneity of DLPFC. However, compared to the control group, depressed patients showed significant decrease of rGMV in the DLPFC and PHG and there was a significant negative correlation between DLPFC volume and depressive rumination.

Increased DLPFC volume (decreased ReHo) in healthy individuals while decreased in depression indicated the trend of DLPFC from inefficient inhibition (‘overload state’) to impaired regulatory mechanism (‘paralysis state’). This finding might elucidate when and why healthy individuals would develop sustained negative mood and depression eventually.

Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Additionally, environmental factors such as perinatal stress and early adversities contribute to the occurrence and severity of ADHD. Recently, DNA methylation has emerged as a mechanism that potentially mediates gene–environmental interaction effects in the aetiology and phenomenology of psychiatric disorders. Here, we investigated whether serotonin transporter gene (SLC6A4) methylation patterns were associated with clinical characteristics and regional cortical thickness in children with ADHD.

In 102 children with ADHD (age 6–15 years), the methylation status of the SLC6A4 promoter was measured. Brain magnetic resonance imaging was obtained and ADHD symptoms were evaluated.

A higher methylation status of the SLC6A4 promoter was significantly associated with worse clinical presentations (more hyperactive-impulsive symptoms and more commission errors). Additionally, a negative correlation was observed between SLC6A4 methylation levels and cortical thickness values in the right occipito-temproral regions.

Our results suggest that the SLC6A4 methylation status may be associated with certain symptoms of ADHD, such as behavioural disinhibition, and related brain changes. Future studies that use a larger sample size and a control group are required to corroborate these results.

The National Institute of Health and Care Excellence (NICE) in England and Wales recommends the combination of pharmacotherapy and psychotherapy for the treatment of moderate to severe depression. However, the cost-effectiveness analysis on which these recommendations are based has not included psychotherapy as monotherapy as a potential option. For this reason, we aimed to update, augment and refine the existing economic evaluation.

We constructed a decision analytic model with a 27-month time horizon. We compared pharmacotherapy with cognitive–behavioural therapy (CBT) and combination treatment for moderate to severe depression in secondary care from a healthcare service perspective. We reviewed the literature to identify relevant evidence and, where possible, synthesized evidence from clinical trials in a meta-analysis to inform model parameters.

The model suggested that CBT as monotherapy was most likely to be the most cost-effective treatment option above a threshold of £22 000 per quality-adjusted life year (QALY). It dominated combination treatment and had an incremental cost-effectiveness ratio of £20 039 per QALY compared with pharmacotherapy. There was significant decision uncertainty in the probabilistic and deterministic sensitivity analyses.

Contrary to previous NICE guidance, the results indicated that even for those patients for whom pharmacotherapy is acceptable, CBT as monotherapy may be a cost-effective treatment option. However, this conclusion was based on a limited evidence base, particularly for combination treatment. In addition, this evidence cannot easily be transferred to a primary care setting.

Callous-unemotional (CU) traits represent a significant risk factor for severe and persistent conduct problems in children and adolescents. Extensive neuroimaging research links CU traits to structural and functional abnormalities in the amygdala and ventromedial prefrontal cortex. In addition, adults with psychopathy (a disorder for which CU traits are a developmental precursor) exhibit reduced integrity in uncinate fasciculus, a white-matter (WM) tract that connects prefrontal and temporal regions. However, research in adolescents has not yet yielded similarly consistent findings.

We simultaneously modeled CU traits and externalizing behaviors as continuous traits, while controlling for age and IQ, in order to identify the unique relationship of each variable with WM microstructural integrity, assessed using diffusion tensor imaging. We used tract-based spatial statistics to evaluate fractional anisotropy, an index of WM integrity, in uncinate fasciculus and stria terminalis in 47 youths aged 10–17 years, of whom 26 exhibited conduct problems and varying levels of CU traits.

Whereas both CU traits and externalizing behaviors were negatively correlated with WM integrity in bilateral uncinate fasciculus and stria terminalis/fornix, simultaneously modeling both variables revealed that these effects were driven by CU traits; the severity of externalizing behavior was not related to WM integrity after controlling for CU traits.

These results indicate that WM abnormalities similar to those observed in adult populations with psychopathy may emerge in late childhood or early adolescence, and may be critical to understanding the social and affective deficits observed in this population.

Gender differences in the prevalence of alcohol use disorder (AUD) have motivated the separate study of its risk factors and consequences in men and women. However, leveraging gender as a third variable to help account for the association between risk factors and consequences for AUD could elucidate etiological mechanisms and clinical outcomes.

Using data from a large, community sample followed longitudinally from 17 to 29 years of age, we tested for gender differences in psychosocial risk factors and consequences in adolescence and adulthood after controlling for gender differences in the base rates of AUD and psychosocial factors. Psychosocial factors included alcohol use, other drug use, externalizing and internalizing symptoms, deviant peer affiliation, family adversity, academic problems, attitudes and use of substances by a romantic partner, and adult socio-economic status.

At both ages of 17 and 29 years, mean levels of psychosocial risks and consequences were higher in men and those with AUD. However, the amount of risk exposure in adolescence was more predictive of AUD in women than men. By adulthood, AUD consequences were larger in women than men and internalizing risk had a stronger relationship with AUD in women at both ages.

Despite higher mean levels of risk exposure in men overall, AUD appears to be a more severe disorder in women characterized by higher levels of adolescent risk factors and a greater magnitude of the AUD consequences among women than men. Furthermore, internalizing symptoms appear to be a gender-specific risk factor for AUD in women.

Impaired emotion regulation may underlie exaggerated emotional reactivity in patients with obsessive compulsive disorder (OCD), yet instructed emotion regulation has never been studied in the disorder.

This study aimed to assess the neural correlates of emotion processing and regulation in 43 medication-free OCD patients and 38 matched healthy controls, and additionally test if these can be modulated by stimulatory (patients) and inhibitory (controls) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (dlPFC). Participants performed an emotion regulation task during functional magnetic resonance imaging before and after a single session of randomly assigned real or sham rTMS. Effect of group and rTMS were assessed on self-reported distress ratings and brain activity in frontal-limbic regions of interest.

Patients had higher distress ratings than controls during emotion provocation, but similar rates of distress reduction after voluntary emotion regulation. OCD patients compared with controls showed altered amygdala responsiveness during symptom provocation and diminished left dlPFC activity and frontal-amygdala connectivity during emotion regulation. Real v. sham dlPFC stimulation differentially modulated frontal-amygdala connectivity during emotion regulation in OCD patients.

We propose that the increased emotional reactivity in OCD may be due to a deficit in emotion regulation caused by a failure of cognitive control exerted by the dorsal frontal cortex. Modulatory rTMS over the left dlPFC may influence automatic emotion regulation capabilities by influencing frontal-limbic connectivity.

Mixed anxiety–depression (MAD) has been under scrutiny to determine its potential place in psychiatric nosology. The current study sought to investigate its prevalence, clinical characteristics, course and potential validators.

Restricted latent-class analyses were fit to 12-month self-reports of depression and anxiety symptom criteria in a large population-based sample of twins. Classes were examined across an array of relevant indicators (demographics, co-morbidity, adverse life events, clinical significance and twin concordance). Longitudinal analyses investigated the stability of, and transitions between, these classes for two time periods approximately 1.5 years apart.

In all analyses, a class exhibiting levels of MAD symptomatology distinctly above the unaffected subjects yet having low prevalence of either major depression (MD) or generalized anxiety disorder (GAD) was identified. A restricted four-class model, constraining two classes to have no prior disorder history to distinguish residual or recurrent symptoms from new onsets in the last year, provided an interpretable classification: two groups with no prior history that were unaffected or had MAD and two with prior history having relatively low or high symptom levels. Prevalence of MAD was substantial (9–11%), and subjects with MAD differed quantitatively but not qualitatively from those with lifetime MD or GAD across the clinical validators examined.

Our findings suggest that MAD is a commonly occurring, identifiable syndromal subtype that warrants further study and consideration for inclusion in future nosologic systems.

Delusional disorder (DD) is thought to be distinct from schizophrenia (SZ). However, few systematic investigations have been conducted on DD because of the difficulty in ascertaining a representative sample size. Existing knowledge has been mostly generated from inpatient cohorts, which may be biased towards a more severe sample.

We compared the demographic, clinical and cognitive differences between 71 patients with first-episode DD and 71 age-matched patients with first-episode SZ. Participants were consecutively recruited from a population-based territory-wide study of early psychosis in Hong Kong targeting first-episode psychosis. Basic demographic information, premorbid functioning, duration of untreated psychosis, pathways to care, symptomatology, social, occupational, and cognitive functioning were comprehensively assessed using standardized measurements.

Patients with DD had less premorbid schizoid and schizotypal traits compared to patients with SZ. More patients with DD were married compared to patients with SZ. However, at first episode, there were no significant differences between the two groups in regards to the duration of untreated psychosis, pathways to care, symptom severity, neurocognitive performance, treatment, and functioning.

Our findings challenge previous thinking that patients with DD had better functioning than patients with SZ. This study not only provides an updated perspective into conceptualizing the clinical differences between DD and SZ, but also expands the descriptive account of the two disorders to include the neurocognitive dimension.

In cross-sectional studies, cocaine users generally display elevated levels of self-reported and cognitive impulsivity. To what extent these impairments are stable v. variable markers of cocaine use disorder, and, thus, are pre-existing or drug-induced, has not yet been systematically investigated.

We conducted a longitudinal study with cocaine users who changed or maintained their consumption intensity, measuring self-reported impulsivity with the Barratt Impulsiveness Scale (BIS-11), and cognitive impulsivity with the Rapid Visual Processing task (RVP), Iowa Gambling task (IGT), and Delay Discounting task (DD) at baseline and at 1-year follow-up. We assessed 48 psychostimulant-naive controls and 19 cocaine users with decreased, 19 users with increased, and 19 users with unchanged cocaine intake after 1 year as confirmed by hair analysis.

Results of linear multilevel modelling showed significant group × time interactions for the BIS-11 total score and the IGT total card ratio. Increasers showed a trend for elevated scores, whereas decreasers exhibited reduced self-reported impulsivity scores within 1 year. Surprisingly, increasers’ IGT performance was improved after 1 year, whereas decreasers’ performance deteriorated. By contrast, neither RVP response bias B″ nor DD total score showed substantial group × time interactions. Importantly, BIS-11 and DD revealed strong test–retest reliabilities.

Self-reported impulsivity (BIS-11) and decision-making impulsivity (IGT) covary with changing cocaine use, whereas response bias and delay discounting remain largely unaffected. Thus, self-reported impulsivity and gambling decision-making were strongly state-dependent in a stimulant-using population and may be suitable to monitor treatment success, whereas delay of gratification was confirmed as a potential endophenotype of stimulant addiction.

Executive processes consist of at least two sets of functions: one concerned with cognitive control and the other with reward-related decision making. Abnormal performance in both sets occurs in late-life depression. This study tested the hypothesis that only abnormal performance in cognitive control tasks predicts poor outcomes of late-life depression treated with escitalopram.

We studied older subjects with major depression (N = 53) and non-depressed subjects (N = 30). Executive functions were tested with the Iowa Gambling Test (IGT), Stroop Color-Word Test, Tower of London (ToL), and Dementia Rating Scale – Initiation/Perseveration domain (DRS-IP). After a 2-week placebo washout, depressed subjects received escitalopram (target daily dose: 20 mg) for 12 weeks.

There were no significant differences between depressed and non-depressed subjects on executive function tests. Hierarchical cluster analysis of depressed subjects identified a Cognitive Control cluster (abnormal Stroop, ToL, DRS-IP), a Reward-Related cluster (IGT), and an Executively Unimpaired cluster. Decline in depression was greater in the Executively Unimpaired (t = −2.09, df = 331, p = 0.0375) and the Reward-Related (t = −2.33, df = 331, p = 0.0202) clusters than the Cognitive Control cluster. The Executively Unimpaired cluster (t = 2.17, df = 331, p = 0.03) and the Reward-Related cluster (t = 2.03, df = 331, p = 0.0433) had a higher probability of remission than the Cognitive Control cluster.

Dysfunction of cognitive control functions, but not reward-related decision making, may influence the decline of symptoms and the probability of remission of late-life depression treated with escitalopram. If replicated, simple to administer cognitive control tests may be used to select depressed older patients at risk for poor outcomes to selective serotonin reuptake inhibitors who may require structured psychotherapy.

Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood.

DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria.

The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points.

ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD.