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.

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.

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.

Leading theories suggest that borderline personality disorder (BPD) is an emotion dysregulation disorder involving lower basal vagal tone, higher baseline emotion, heightened emotional reactivity, delayed emotional recovery, and emotion regulation deficits. However, the literature to date lacks a unifying paradigm that tests all of the main emotion dysregulation components and comprehensively examines whether BPD is an emotion dysregulation disorder and, if so, in what ways. This study addresses the empirical gaps with a unified paradigm that assessed whether BPD is characterized by five leading emotion dysregulation components compared to generalized anxiety disorder (GAD) and healthy control (HC) groups.

Emotion was assessed across self-report, sympathetic, and parasympathetic indices. Participants with BPD, GAD, and HCs (N = 120) first underwent baseline periods assessing basal vagal tone and baseline emotional intensity, followed by rejection-themed stressors assessing emotional reactivity. Participants then either reacted normally to assess emotional recovery or attempted to decrease emotion using mindfulness or distraction to assess emotion regulation implementation deficits.

Individuals with BPD and GAD exhibited higher self-reported and sympathetic baseline emotion compared to HCs. The BPD group also exhibited self-reported emotion regulation deficits using distraction only compared to the GAD group.

There is minimal support for several emotion dysregulation components in BPD, and some components that are present appear to be pervasive across high emotion dysregulation groups rather than specific to BPD. However, BPD may be characterized by problems disengaging from emotion using distraction.

Previous studies have found that stressful life events (SLEs) are associated with an increased risk of adult depression. However, many studies are observational in nature and limited by methodological issues, such as potential confounding by genetic factors. Genetically informative research, such as the co-twin control design, can strengthen causal inference in observational studies. Discrete-time survival analysis has several benefits and multilevel survival analysis can incorporate frailty terms (random effects) to estimate the components of the biometric model. In the current study, we investigated associations between SLEs and depression risk in a population-based twin sample (N = 2299).

A co-twin control design was used to investigate the influence of the occurrence of SLEs on depression risk. The co-twin control design involves comparing patterns of associations in the full sample and within dizygotic (DZ) and monozygotic twins (MZ). Associations were modelled using discrete-time survival analysis with biometric frailty terms. Data from two time points were used in the analyses. Mean age at Wave 1 was 28 years and mean age at Wave 2 was 38 years.

SLE occurrence was associated with increased depression risk. Co-twin control analyses indicated that this association was at least in part due to the causal influence of SLE exposure on depression risk for event occurrence across all SLEs and for violent SLEs. A minor proportion of the total genetic risk of depression reflected genetic effects related to SLEs.

The results support previous research in implicating SLEs as important risk factors with probable causal influence on depression risk.

Cannabis use and cannabis use disorder (CUD) is increased in patients with schizophrenia. It is important to establish if this is explained by non-causal factors, such as shared genetic vulnerability. We aimed to investigate whether the polygenic risk scores (PRS) for schizophrenia and other psychiatric disorders would predict CUD in controls, patients with schizophrenia, and patients with other psychiatric disorders.

We linked nationwide Danish registers and genetic information obtained from dried neonatal bloodspots in an observational analysis. We included people with schizophrenia, other psychiatric disorders, and controls. The exposures of interest were the PRS for schizophrenia, attention-deficit hyperactivity disorder (ADHD) autism spectrum disorder, and anorexia nervosa. The main outcome of interest was the diagnosis of CUD.

The study included 88 637 individuals. PRS for schizophrenia did not predict CUD in controls [hazard ratio (HR) = 1.16, 95% CI 0.95–1.43 per standard-deviation increase in PRS, or HR = 1.47, 95% CI 0.72–3.00 comparing highest v. remaining decile], but PRS for ADHD did (HR = 1.27, 95% CI 1.08–1.50 per standard-deviation increase, or HR = 2.02, 95% CI 1.27–3.22 for the highest decile of PRS). Among cases with schizophrenia, the PRS for schizophrenia was associated with CUD. While CUD was a strong predictor of schizophrenia (HR = 4.91, 95% CI 4.36–5.53), the inclusion of various PRS did not appreciably alter this association.

The PRS for schizophrenia was not associated with CUD in controls or patients with other psychiatric disorders than schizophrenia. This speaks against the hypothesis that shared genetic vulnerability would explain the association between cannabis and schizophrenia.

Subclinical adolescent alcohol use is highly prevalent and may have deleterious effects on important psychosocial and brain outcomes. Prior research has focused on identifying endophenotypes of pathological drinking, and the predictors of normative drinking remain understudied. This study investigated the incremental predictive value of two potential psychophysiological endophenotypes, P3 amplitude (an index of decision making) and midfrontal theta power (a correlate of attentional control), for prospectively predicting the expression and initiation of alcohol use emerging in adolescence.

A large (N = 594) epidemiological sample was prospectively assessed at ages 11/14/17. Alcohol/substance use was assessed at all ages via a computerized self-report inventory. EEG was recorded at age-14 during a visual oddball task to elicit P3 and theta.

Reduced target-related P3 and theta at age-14 prospectively predicted drinking at age-17 independent of one another. Among alcohol-naive individuals at age-14, attenuated P3 and theta increased the odds of new-onset alcohol behaviors 3 years later. Importantly, the endophenotypes provided significant incremental predictive power of future non-clinical alcohol use beyond relevant risk factors (prior alcohol use; tobacco/illicit drug initiation; parental alcohol use disorder).

The current report is the first of our knowledge to demonstrate that deviations in parietal P3 and midfrontal theta prospectively predict the emergence of normative/non-pathological drinking. P3 and theta provide modest yet significant explanatory variance beyond prominent self-report and familial risk measures. Findings offer strong evidence supporting the predictive utility of P3 and theta as candidate endophenotypes for adolescent drinking.

Despite a large body of research on planning performance in adult schizophrenia patients, results of individual studies are equivocal, suggesting either no, moderate or severe planning deficits. This meta-analysis therefore aimed to quantify planning deficits in schizophrenia and to examine potential sources of the heterogeneity seen in the literature.

The meta-analysis comprised outcomes of planning accuracy of 1377 schizophrenia patients and 1477 healthy controls from 31 different studies which assessed planning performance using tower tasks such as the Tower of London, the Tower of Hanoi and the Stockings of Cambridge. A meta-regression analysis was applied to assess the influence of potential moderator variables (i.e. sociodemographic and clinical variables as well as task difficulty).

The findings indeed demonstrated a planning deficit in schizophrenia patients (mean effect size: $\hat \mu \; = 0.67$; 95% confidence interval 0.56–0.78) that was moderated by task difficulty in terms of the minimum number of moves required for a solution. The results did not reveal any significant relationship between the extent of planning deficits and sociodemographic or clinical variables.

The current results provide first meta-analytic evidence for the commonly assumed impairments of planning performance in schizophrenia. Deficits are more likely to become manifest in problem items with higher demands on planning ahead, which may at least partly explain the heterogeneity of previous findings. As only a small fraction of studies reported coherent information on sample characteristics, future meta-analyses would benefit from more systematic reports on those variables.

Adolescent suicide is a global public health concern and the second leading cause of adolescent death worldwide. This study aimed to estimate the burden of adolescent suicidal behaviours and its association with violence and unintentional injury, psychosocial, protective, lifestyle and food security-related factors amongst school-based adolescents across 77 countries in the six World Health Organization (WHO) regions.

This study comprised a sample of 251 763 adolescents drawn from the latest Global School-based Student Health Survey of school-based adolescents, aged 11–17 years, across 77 countries. Logistic regression analyses were employed to estimate the adjusted effect of independent factors on adolescent suicidal behaviours.

The population-weighted 12-month prevalence of suicidal ideation (SI), suicidal planning (SP) and suicidal attempts (SA) amongst school-based adolescents was 18, 18 and 16%, respectively. Adolescent suicidal behaviours (i.e. SI, SP and SA) were respectively associated with being physically attacked, physical fighting, high levels of anxiety, feeling lonely, being bullied, lack of parental support, poor peer support, not having close friends and high levels of sedentary behaviours. Overall, these associations also extended to the context of food insecurity across regions and country income groups, where the magnitude of association slightly varied from odds ratios of 1.25 times to 3.13.

The burden of school-going adolescent suicidal thoughts, suicide planning and suicide attempts is of particular concern in low-resource countries. Comprehensive suicide prevention programmes for school-going adolescents in LMICs are needed that address socio-cultural inequities related to violence and unintentional injury, social support and psychological factors, protective, and lifestyle-related factors.

There is demand for new, effective and scalable treatments for depression, and development of new forms of cognitive bias modification (CBM) of negative emotional processing biases has been suggested as possible interventions to meet this need.

We report two double blind RCTs, in which volunteers with high levels of depressive symptoms (Beck Depression Inventory ii (BDI-ii) > 14) completed a brief course of emotion recognition training (a novel form of CBM using faces) or sham training. In Study 1 (N = 36), participants completed a post-training emotion recognition task whilst undergoing functional magnetic resonance imaging to investigate neural correlates of CBM. In Study 2 (N = 190), measures of mood were assessed post-training, and at 2-week and 6-week follow-up.

In both studies, CBM resulted in an initial change in emotion recognition bias, which (in Study 2) persisted for 6 weeks after the end of training. In Study 1, CBM resulted in increases neural activation to happy faces, with this effect driven by an increase in neural activity in the medial prefrontal cortex and bilateral amygdala. In Study 2, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias at either 2 or 6-week follow-ups.

CBM of emotion recognition has effects on neural activity that are similar in some respects to those induced by Selective Serotonin Reuptake Inhibitors (SSRI) administration (Study 1), but we find no evidence that this had any later effect on self-reported mood in an analogue sample of non-clinical volunteers with low mood (Study 2).

Glyco-metabolic deteriorations are the most limiting adverse reactions to antipsychotics in the long term. They have been incompletely investigated and the properties of antipsychotics that determine their magnitude are not clarified.

To rank antipsychotics by the magnitude of glyco-metabolic alterations and to associate it to their pharmacological and chemical properties, we conducted a network meta-analysis.

We searched PubMed, Embase, and Psycinfo on 10 September 2020. We selected studies containing the endpoint-baseline difference or the distinct values of at least one outcome among glucose, HbA1c, insulin, HOMA-IR, triglycerides, total/HDL/LDL cholesterols. Of 2094 articles, 46 were included in network meta-analysis. Study quality was assessed by the RoB 2 and ROBINS-I tools. Mean differences (MD) were obtained by random-effects network meta-analysis; relations between MD and antipsychotic properties were analyzed by linear regressions. Antipsychotic properties investigated were acidic and basic pKa, polar surface area, polarizability, and occupancies of D2, H1, M1, M3, α1A, α2A, 5-HT1A, 5-HT2A, 5-HT2C receptors.

We meta-analyzed 46 studies (11 464 patients); on average, studies lasted 15.47 weeks, patients had between 17.68 and 61.06 years of mean age and 61.64% were males. Olanzapine and clozapine associated with greater deteriorations, aripiprazole and ziprasidone with smaller deteriorations. Higher polarizability and 5-HT1A receptor occupancy were associated with smaller deteriorations, H1, M1, and M3 receptor occupancies with larger deteriorations.

Drug rankings may guide antipsychotic switching toward metabolically safer drugs. Mechanistic insights may suggest improvements for combination therapies and drug development. More data are required regarding newer antipsychotics.

Previous research has suggested an association between depression and subsequent acute stroke incidence, but few studies have examined any effect modification by sociodemographic factors. In addition, no studies have investigated this association among primary care recipients with hypertension.

We examined the anonymized records of all public general outpatient visits by patients aged 45+ during January 2007–December 2010 in Hong Kong to extract primary care patients with hypertension for analysis. We took the last consultation date as the baseline and followed them up for 4 years (until 2011–2014) to observe any subsequent acute hospitalization due to stroke. Mixed-effects Cox models (random intercept across 74 included clinics) were implemented to examine the association between depression (ICPC diagnosis or anti-depressant prescription) at baseline and the hazard of acute stroke (ICD-9: 430–437.9). Effect modification by age, sex, and recipient status of social security assistance was examined in extended models with respective interaction terms specified.

In total, 396 858 eligible patients were included, with 9099 (2.3%) having depression, and 10 851 (2.7%) eventually hospitalized for stroke. From the adjusted analysis, baseline depression was associated with a 17% increased hazard of acute stroke hospitalization [95% confidence interval (CI) 1.03–1.32]. This association was suggested to be even stronger among men than among women (hazard ratio = 1.29, 95% CI 1.00–1.67).

Depression is more strongly associated with acute stroke incidence among male than female primary care patients with hypertension. More integrated services are warranted to address their needs.