Internalizing and externalizing psychopathology factors explain much of the covariance among psychiatric conditions, especially at the level of genetic risk. However, few studies have examined internalizing and externalizing factors in middle-aged samples, especially their ability to predict later symptoms across midlife. The goals of the current study were (i) to quantify the genetic and environmental influences on internalizing and externalizing psychopathology in individuals in their early 40s, and (ii) examine the extent to which these genetic and environmental influences predict self-reported measures of internalizing and externalizing symptoms 15–20 years later.

1484 male twins completed diagnostic interviews of psychopathology at mean age 41 and self-reported measures of anxiety, depression, substance use, and related variables at up to two time-points in late middle age (mean ages 56 and 62).

Structural equation modeling of the diagnostic interviews confirmed that internalizing and externalizing factors accounted for most of the genetic variance in individual disorders, with substantial genetic (ra = 0.70) and environmental (re = 0.77) correlations between the factors. Internalizing psychopathology at age 41 was correlated with latent factors capturing anxiety, depression, and/or post-traumatic stress symptoms at ages 56 (r = 0.51) and 62 (r = 0.43). Externalizing psychopathology at age 41 was correlated r = 0.67 with a latent factor capturing aggression, tobacco use, and alcohol use at age 56. Stability of both factors was driven by genetic influences.

These findings demonstrate the considerable stability of internalizing and externalizing psychopathology symptoms across middle age, especially their genetic influences. Diagnostic interviews effectively predict self-reported symptoms and behaviors 15–20 years later.

Psilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.

In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up.

PT was associated with decreases in neuroticism (B = −0.63), introversion (B = −0.38), disagreeableness (B = −0.47), impulsivity (B = −0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = −0.47) and disagreeableness (B = −0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = −0.38), disagreeableness (B = −0.26), impulsivity (B = −0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = −0.46) remaining decreased at month 6. No significant between-condition differences were observed.

Personality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.

Numerous theories posit different core features to borderline personality disorder (BPD). Recent advances in network analysis provide a method of examining the relative centrality of BPD symptoms, as well as examine the replicability of findings across samples. Additionally, despite the increase in research supporting the validity of BPD in adolescents, clinicians are reluctant to diagnose BPD in adolescents. Establishing the replicability of the syndrome across adolescents and adults informs clinical practice and research. This study examined the stability of BPD symptom networks and centrality of symptoms across samples varying in age and clinical characteristics.

Cross-sectional analyses of BPD symptoms from semi-structured diagnostic interviews from the Collaborative Longitudinal Study of Personality Disorders (CLPS), the Methods to Improve Diagnostic Assessment and Service (MIDAS) study, and an adolescent clinical sample. Network attributes, including edge (partial association) strength and node (symptom) expected influence, were compared.

The three networks were largely similar and strongly correlated. Affective instability and identity disturbance emerged as relatively central symptoms across the three samples, and relationship difficulties across adult networks. Differences in network attributes were more evident between networks varying both in age and in BPD symptom severity level.

Findings highlight the relative importance of affective, identity, and relationship symptoms, consistent with several leading theories of BPD. The network structure of BPD symptoms appears generally replicable across multiple large samples including adolescents and adults, providing further support for the validity of the diagnosis across these developmental phases.

It has not yet been determined if the commonly reported cannabis–psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders.

We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort.

PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects.

These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis–psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.

This study aimed to identify perinatal and early-life factors associated with trajectories of psychopathic traits across childhood.

Participants were 1631 children (51.5% girls) from the Quebec Longitudinal Study of Child Development. A wide range of perinatal and early-life factors were assessed from pregnancy to age 2.5 years using medical files and mothers’ reports. Psychopathic traits were assessed via teachers’ reports at ages 6, 7, 8, 10, and 12 years. Latent class growth analyses and multinomial logistic regressions controlling for child sex were conducted. Two-way interaction effects between perinatal/early-life factors and child sex were explored.

Four trajectories of psychopathic traits were identified: High-stable (4.48%), Increasing (8.77%), Decreasing (11.46%), and Low-stable (75.29%). A few perinatal factors and most child-level and family-level early-life factors significantly increased the odds of following the High-stable v. the Low-stable trajectory. Higher levels of psychotropic exposures during pregnancy, socioeconomic adversity, child's physical aggression, child's opposition, mother's depressive symptoms, and hostile parenting increased the likelihood of following the Increasing instead of the Low-stable trajectory. Higher socioeconomic adversity, mother's depressive symptoms, and inconsistent parenting were associated with membership to the High-stable instead of the Decreasing trajectory. Most associations were not moderated by child sex.

These results shed light on the perinatal and early-life factors that are associated with specific pathways of psychopathic traits during childhood and suggest that different factors could be targeted to prevent the exacerbation (v. low and stable levels) or the stability at high levels (v. attenuation) of these traits.

Antidepressants are frequently prescribed but results regarding their efficacy have been equivocal for different spectra of the severity continuum and their side-effects are often burdensome. Non-adherence is a likely consequence. The objective was therefore to examine patients’ trade-offs between the efficacy, side-effects and other drawbacks of antidepressants and whether these trade-offs predicted non-adherence.

Trade-offs from 225 antidepressant users, recruited through community pharmacies, were assessed with an Adaptive Conjoint Analysis (ACA) choice task that was customized to each individual patient. From the estimated utilities, relative importance scores of treatment properties were calculated. Non-adherence was measured through self-report and pharmacy refill data.

Relapse prevention and symptom relief were on average equally important. Side-effects were as important and the side-effect stomach and intestine complaints was on average even slightly more important than relapse prevention and symptom relief. Additional treatment with psychotherapy was preferred by 61% of the patients. A benefit/drawback ratio revealed that 18% of the patients did not consider the efficacy to outweigh the drawbacks. A higher benefit/drawback ratio was associated with a decreased odds of intentional non-adherence [odds ratio (OR) 0.2, 95% confidence interval (CI) 0.07–0.7, Wald = 6.7, p = 0.01).

For nearly one in five patients, the efficacy of antidepressants does not outweigh their drawbacks. Knowing patients’ trade-offs is likely to aid both physicians and patients to identify important treatment preferences, to improve adherence and to make more deliberate decisions on whether or not to continue treatment.

Cannabis is the most widely used illicit drug in the United States and is often associated with changes in attention function, which may ultimately impact numerous other cognitive faculties (e.g. memory, executive function). Importantly, despite the increasing rates of cannabis use and widespread legalization in the United States, the neural mechanisms underlying attentional dysfunction in chronic users are poorly understood.

We used magnetoencephalography (MEG) and a modified Posner cueing task in 21 regular cannabis users and 32 demographically matched non-user controls. MEG data were imaged in the time−frequency domain using a beamformer and peak voxel time series were extracted to quantify the oscillatory dynamics underlying use-related aberrations in attentional reorienting, as well as the impact on spontaneous neural activity immediately preceding stimulus onset.

Behavioral performance on the task (e.g. reaction time) was similar between regular cannabis users and non-user controls. However, the neural data indicated robust theta-band synchronizations across a distributed network during attentional reorienting, with activity in the bilateral inferior frontal gyri being markedly stronger in users relative to controls (p's < 0.036). Additionally, we observed significantly reduced spontaneous theta activity across this distributed network during the pre-stimulus baseline in cannabis users relative to controls (p's < 0.020).

Despite similar performance on the task, we observed specific alterations in the neural dynamics serving attentional reorienting in regular cannabis users compared to controls. These data suggest that regular cannabis users may employ compensatory processing in the prefrontal cortices to efficiently reorient their attention relative to non-user controls.

Inflammation might play a role in bipolar disorder (BD), but it remains unclear the relationship between inflammation and brain structural and functional abnormalities in patients with BD. In this study, we focused on the alterations of functional connectivity (FC), peripheral pro-inflammatory cytokines and their correlations to investigate the role of inflammation in FC in BD depression.

In this study, 42 unmedicated patients with BD II depression and 62 healthy controls (HCs) were enrolled. Resting-state-functional magnetic resonance imaging was performed in all participants and independent component analysis was used. Serum levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were measured in all participants. Correlation between FC values and IL-6 and IL-8 levels in BD was calculated.

Compared with the HCs, BD II patients showed decreased FC in the left orbitofrontal cortex (OFC) implicating the limbic network and the right precentral gyrus implicating the somatomotor network. BD II showed increased IL-6 (p = 0.039), IL-8 (p = 0.002) levels. Moreover, abnormal FC in the right precentral gyrus were inversely correlated with the IL-8 (r = −0.458, p = 0.004) levels in BD II. No significant correlation was found between FC in the left OFC and cytokines levels.

Our findings that serum IL-8 levels are associated with impaired FC in the right precentral gyrus in BD II patients suggest that inflammation might play a crucial role in brain functional abnormalities in BD.

A transdiagnostic and contextual framework of ‘clinical characterization’, combining clinical, psychopathological, sociodemographic, etiological, and other personal contextual data, may add clinical value over and above categorical algorithm-based diagnosis.

Prediction of need for care and health care outcomes was examined prospectively as a function of the contextual clinical characterization diagnostic framework in a prospective general population cohort (n = 6646 at baseline), interviewed four times between 2007 and 2018 (NEMESIS-2). Measures of need, service use, and use of medication were predicted as a function of any of 13 DSM-IV diagnoses, both separately and in combination with clinical characterization across multiple domains: social circumstances/demographics, symptom dimensions, physical health, clinical/etiological factors, staging, and polygenic risk scores (PRS). Effect sizes were expressed as population attributable fractions.

Any prediction of DSM-diagnosis in relation to need and outcome in separate models was entirely reducible to components of contextual clinical characterization in joint models, particularly the component of transdiagnostic symptom dimensions (a simple score of the number of anxiety, depression, mania, and psychosis symptoms) and staging (subthreshold, incidence, persistence), and to a lesser degree clinical factors (early adversity, family history, suicidality, slowness at interview, neuroticism, and extraversion), and sociodemographic factors. Clinical characterization components in combination predicted more than any component in isolation. PRS did not meaningfully contribute to any clinical characterization model.

A transdiagnostic framework of contextual clinical characterization is of more value to patients than a categorical system of algorithmic ordering of psychopathology.

Externalizing traits or behaviors are typically assessed by self-report scales or criminal records. Few genetically informative studies have used both methods to determine whether they assess the same genetic or environmental risk factors.

We examined 442 male Swedish twin pairs with self-reported externalizing behaviors at age 16–17 years [externalizing traits (EXT), self-reported delinquency (SRD), impulsivity (IMP), grandiosity (GRD) and callousness (CLS)] and criminal behavior (CB) from the National Suspect Registry from age 13 to 25 years. Multivariate structural equation modeling was conducted with Mx.

The best-fit model contained one genetic, one shared environmental and two non-shared environmental common factors, and variable specific genetic and non-shared environmental factors. The risk for CB was influenced substantially by both genetic (a2 = 0.48) and familial–environmental factors (c2 = 0.22). About one-third of the genetic risk for CB but all of the shared environmental risk was indexed by the self-report measures. The degree to which the individual measures reflected genetic versus familial–environmental risks for CB varied widely. GRD and CLS were correlated with CB mainly through common genetic risk factors. SRD and CB covaried largely because of shared familial–environmental factors. For EXT and IMP, observed correlations with CB resulted in about equal parts from shared genetic and shared familial–environmental factors.

In adolescence, measures of grandiose and callous temperament best tap the genetic liability to CB. Measures of antisocial behaviors better index familial–environmental risks for CB. A substantial proportion of the genetic risk to CB was not well reflected in any of the self-report measures.

In older populations disturbed 24-h activity rhythms, poor sleep, and depressive symptoms are often lingering and co-morbid, making treatment difficult. To improve insights into these commonly co-occurring problems, we assessed the bidirectional association of sleep and 24-h activity rhythms with depressive symptoms in middle-aged and elderly persons.

In 1734 participants (mean age: 62.3 ± 9.3 years, 55% women) from the prospective Rotterdam Study, 24-h activity rhythms and sleep were estimated with actigraphy (mean duration: 146 ± 19.6 h), sleep quality with the Pittsburgh Sleep Quality Index, and depressive symptoms with the Center for Epidemiological Studies Depression scale. Repeated measures were available for 947 participants (54%) over a median follow-up of 6 years (interquartile range = 5.6–6.3). Linear-mixed models were used to assess temporal associations of 24-h activity rhythms and sleep with depressive symptoms in both directions.

High 24-h activity rhythm fragmentation (IV) (B = 1.002, 95% confidence interval (CI) = 0.641–1.363), long time in bed (TIB) (B = 0.111, 95% CI = 0.053–0.169), low sleep efficiency (SE) (B = −0.015, 95% CI = −0.020 to −0.009), long sleep onset latency (SOL) (B = 0.009, 95% CI = 0.006–0.012), and low self-rated sleep quality (B = 0.112, 95% CI = 0.0992–0.124) at baseline were associated with increasing depressive symptoms over time. Conversely, more depressive symptoms at baseline were associated with an increasing 24-h activity rhythm fragmentation (B = 0.002, 95% CI = 0.001–0.003) and TIB (B = 0.009, 95% CI = 0.004–0.015), and a decreasing SE (B = −0.140, 95% CI = −0.196 to −0.084), SOL (B = 0.013, 95% CI = 0.008–0.018), and self-rated sleep quality (B = 0.193, 95% CI = 0.171–0.215) over time.

This study demonstrates a bidirectional association of 24-h activity rhythms, actigraphy-estimated sleep, and self-rated sleep quality with depressive symptoms over a time frame of multiple years in middle-aged and elderly persons.

Previous studies on reporting bias generally examined whether trials were published in stand-alone publications. In this study, we investigated whether pooled-trials publications constitute a specific form of reporting bias. We assessed whether negative trials were more likely to be exclusively published in pooled-trials publications than positive trials and examined the research questions, individual trial results, and conclusions presented in these articles.

Data from a cohort of 105 randomized controlled trials of 16 antidepressants were extracted from earlier publications and the corresponding Food and Drug Administration (FDA) reviews. A systematic literature search was conducted to identify pooled-trials publications.

We found 107 pooled-trials publications that reported results of 23 (72%) of 32 trials not published in stand-alone publications. Only two (3.8%) of 54 positive trials were published exclusively in pooled-trials publications, compared with 21 (41.1%) of 51 negative trials (p < 0.001). Thirteen (12%) of 107 publications had as primary aim to present data on the trial's primary research question (drug efficacy compared with placebo). Only four of these publications, reporting on five (22%) trials, presented individual efficacy data for the primary research question. Additionally, only five (5%) of 107 pooled-trials publications had a negative conclusion.

Compared with positive trials, negative trials of antidepressants for depression were much more likely to be reported exclusively in pooled-trials publications. Pooled-trials publications flood the evidence base with often-redundant articles that, instead of addressing the original primary research question, present (positive) results on secondary questions. Therefore, pooled-trials publications distort the apparent risk–benefit profile of antidepressants.