Bipolar disorder (BD) is an overarching diagnostic class defined by the presence of at least one prior manic episode (BD I) or both a prior hypomanic episode and a prior depressive episode (BD II). Traditionally, BD II has been conceptualized as a less severe presentation of BD I, however, extant literature to investigate this claim has been mixed.

We apply genomic structural equation modeling (Genomic SEM) to investigate divergent genetic pathways across BD's two major subtypes using the most recent GWAS summary statistics from the PGC. We begin by identifying divergences in genetic correlations across 98 external traits using a Bonferroni-corrected threshold. We also use a theoretically informed follow-up model to examine the extent to which the genetic variance in each subtype is explained by schizophrenia and major depression. Lastly, transcriptome-wide SEM (T-SEM) was used to identify neuronal gene expression patterns associated with BD subtypes.

BD II was characterized by significantly larger genetic overlap across non-psychiatric medical and internalizing traits (e.g. heart disease, neuroticism, insomnia), while stronger associations for BD I were absent. Consistent with these findings, follow-up modeling revealed a substantial major depression component for BD II. T-SEM results revealed 35 unique genes associated with shared risk across BD subtypes.

Divergent patterns of genetic relationships across external traits provide support for the distinction of the bipolar subtypes. However, our results also challenge the illness severity conceptualization of BD given stronger genetic overlap across BD II and a range of clinically relevant traits and disorders.

Trauma is prevalent amongst early psychosis patients and associated with adverse outcomes. Past trials of trauma-focused therapy have focused on chronic patients with psychosis/schizophrenia and comorbid Post-Traumatic Stress Disorder (PTSD). We aimed to determine the feasibility of a large-scale randomized controlled trial (RCT) of an Eye Movement Desensitization and Reprocessing for psychosis (EMDRp) intervention for early psychosis service users.

A single-blind RCT comparing 16 sessions of EMDRp + TAU v. TAU only was conducted. Participants completed baseline, 6-month and 12-month post-randomization assessments. EMDRp and trial assessments were delivered both in-person and remotely due to COVID-19 restrictions. Feasibility outcomes were recruitment and retention, therapy attendance/engagement, adherence to EMDRp treatment protocol, and the ‘promise of efficacy’ of EMDRp on relevant clinical outcomes.

Sixty participants (100% of the recruitment target) received TAU or EMDR + TAU. 83% completed at least one follow-up assessment, with 74% at 6-month and 70% at 12-month. 74% of EMDRp + TAU participants received at least eight therapy sessions and 97% rated therapy sessions demonstrated good treatment fidelity. At 6-month, there were signals of promise of efficacy of EMDRp + TAU v. TAU for total psychotic symptoms (PANSS), subjective recovery from psychosis, PTSD symptoms, depression, anxiety, and general health status. Signals of efficacy at 12-month were less pronounced but remained robust for PTSD symptoms and general health status.

The trial feasibility criteria were fully met, and EMDRp was associated with promising signals of efficacy on a range of valuable clinical outcomes. A larger-scale, multi-center trial of EMDRp is feasible and warranted.

People with borderline intellectual functioning (BIF) encounter greater social adversities than the general population and have an increased prevalence of mental illness. However, little is known about the socio-demographic characteristics and mental health of parents with BIF.

A secondary data analysis of the Adult Psychiatric Morbidity Survey 2014 was conducted. Logistic regression models were fitted to compare differences in socio-demographic, mental health and service-use characteristics between parents and non-parents with and without BIF, and to investigate if the relationship between parent status and mental health outcomes was modified by BIF status, sex, and employment.

Data from 6872 participants was analyzed; 69.1% were parents. BIF parents had higher odds of common mental disorder, severe mental illness, post-traumatic stress disorder, self-harm/suicide and were more likely to see their General Practitioner (GP) and to receive mental health treatment than non-BIF parents. BIF parents did not have a higher prevalence of mental health problems than BIF non-parents. Being a parent, after adjusting for BIF status and other confounders, was associated with increased odds of having a common mental disorder, visits to see a GP and treatment for mental health. Female parents had higher odds of treatment for mental health problems.

Being a parent is associated with elevated rates of common mental disorders. There is a higher burden of mental health problems and service use in people with BIF. A greater provision of specialist support services including ascertainment is indicated for this group.

Previous research has proposed that there may be potential synergies between psychedelic and meditation interventions, but there are still knowledge gaps that merit further investigation.

Using a longitudinal observational research design with samples representative of the US and UK adult population with regard to sex, age, and ethnicity (N = 9732), we investigated potential associations between self-reported psychedelic use and meditation practice.

The follow-up survey was completed by 7667 respondents (79% retention rate), with 100 respondents reporting psychedelic use during the 2-month study period (1.3% of follow-up respondents). In covariate-adjusted regression models, psychedelic use during the study period was associated with greater increases in the number of days of mindfulness meditation practice in the past week (B = 0.40, p = 0.004). Among those who reported psychedelic use during the study period, covariate-adjusted regression models revealed that the subjective experience of insight during respondents' most intense psychedelic experience in that period was also associated with greater increases in the number of days of mindfulness and loving-kindness or compassion meditation practice in the past week (B = 0.42, p = 0.021; B = 0.38, p = 0.017). Notably, more days of loving-kindness or compassion meditation practice in the past week at baseline was associated with less severe subjective feelings of death or dying during respondents' most intense psychedelic experience in the study period (B = −0.29, p = 0.037).

Psychedelic use might lead to greater engagement with meditation practices such as mindfulness meditation, while meditation practices such as loving-kindness or compassion medication might buffer against certain challenging experiences associated with psychedelic use.

To test for publication bias with alprazolam, the most widely prescribed benzodiazepine, by comparing its efficacy for panic disorder using trial results from (1) the published literature and (2) the US Food and Drug Administration (FDA).

From FDA reviews, we included data from all phase 2/3 efficacy trials of alprazolam extended-release (Xanax XR) for the treatment of panic disorder. A search for matching publications was performed using PubMed and Google Scholar. Publication bias was examined by comparing: (1) overall trial results (positive or not) according to the FDA v. corresponding publications; (2) effect size (Hedges's g) based on FDA data v. published data.

The FDA review showed that five trials were conducted, only one of which (20%) was positive. Of the four not-positive trials, two were published conveying a positive outcome; the other two were not published. Thus, according to the published literature, three trials were conducted and all (100%) were positive. Alprazolam's effect size calculated using FDA data was 0.33 (CI95% 0.07–0.60) v. 0.47 (CI95% 0.30–0.65) using published data, an increase of 0.14, or 42%.

Publication bias substantially inflates the apparent efficacy of alprazolam XR.

Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown.

Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. CBD) and linear between-group relationships, such that placebo > CBD > controls or controls > CBD > placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses.

Placebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo.

These findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.

The post-COVID-19 condition describes the persistence or onset of somatic symptoms (e.g. fatigue) after acute COVID-19. Based on an existing cognitive-behavioral treatment protocol, we developed a specialized group intervention for individuals with post-COVID-19 condition. The present study examines the feasibility, acceptance, and effectiveness of the program for inpatients in a neurological rehabilitation setting.

The treatment program comprises eight sessions and includes psychoeducational and experience-based interventions on common psychophysiological mechanisms of persistent somatic symptoms. A feasibility trial was conducted using a one-group design in a naturalistic setting. N = 64 inpatients with a history of mild COVID-19 that fulfilled WHO criteria for post-COVID-19 condition were enrolled. After each session, evaluation forms were completed and psychometric questionnaires on somatic and psychopathological symptom burden were collected pre- and post-intervention.

The treatment program was well received by participants and therapists. Each session was rated as comprehensible and overall satisfaction with the sessions was high. Pre-post effect sizes (of standard rehabilitation incl. new treatment program; intention-to-treat) showed significantly reduced subjective fatigue (p < 0.05, dav = 0.33) and improved disease coping (ps < 0.05, dav = 0.33–0.49).

Our results support the feasibility and acceptance of the newly developed cognitive-behavioral group intervention for individuals with post-COVID-19 condition. Yet, findings have to be interpreted cautiously due to the lack of a control group and follow-up measurement, the small sample size, and a relatively high drop-out rate.

Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory.

One hundred and twenty-six persons aged 18–85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics.

Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model.

Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.

Childhood trauma (CT) may increase vulnerability to psychopathology through affective dysregulation (greater variability, autocorrelation, and instability of emotional symptoms). However, CT associations with dynamic affect fluctuations while considering differences in mean affect levels across CT status have been understudied.

346 adults (age = 49.25 ± 12.55, 67.0% female) from the Netherlands Study of Depression and Anxiety participated in ecological momentary assessment. Positive and negative affect (PA, NA) were measured five times per day for two weeks by electronic diaries. Retrospectively-reported CT included emotional neglect and emotional/physical/sexual abuse. Linear regressions determined associations between CT and affect fluctuations, controlling for age, sex, education, and mean affect levels.

Compared to those without CT, individuals with CT reported significantly lower mean PA levels (Cohen's d = −0.620) and higher mean NA levels (d = 0.556) throughout the two weeks. CT was linked to significantly greater PA variability (d = 0.336), NA variability (d = 0.353), and NA autocorrelation (d = 0.308), with strongest effects for individuals reporting higher CT scores. However, these effects were entirely explained by differences in mean affect levels between the CT groups. Findings suggested consistency of results in adults with and without lifetime depressive/anxiety disorders and across CT types, with sexual abuse showing the smallest effects.

Individuals with CT show greater affective dysregulation during the two-week monitoring of emotional symptoms, likely due to their consistently lower PA and higher NA levels. It is essential to consider mean affect level when interpreting the impact of CT on affect dynamics.

Laboratory paradigms are widely used to study fear learning in posttraumatic stress disorder (PTSD). Recent basic science models demonstrate that, during fear learning, patterns of activity in large neuronal ensembles for the conditioned stimuli (CS) begin to reinstate neural activity patterns for the unconditioned stimuli (US), suggesting a direct way of quantifying fear memory strength for the CS. Here, we translate this concept to human neuroimaging and test the impact of post-learning dopaminergic neurotransmission on fear memory strength during fear acquisition, extinction, and recall among women with PTSD in a re-analysis of previously reported data.

Participants (N = 79) completed a context-dependent fear acquisition and extinction task on day 1 and extinction recall tests 24 h later. We decoded activity patterns in large-scale functional networks for the US, then applied this decoder to activity patterns toward the CS on day 1 and day 2.

US decoder output for the CS+ increased during acquisition and decreased during extinction in networks traditionally implicated in human fear learning. The strength of US neural reactivation also predicted individuals skin conductance responses. Participants randomized to receive L-DOPA (n = 43) following extinction on day 1 demonstrated less US neural reactivation on day 2 relative to the placebo group (n = 28).

These results support neural reactivation as a measure of memory strength between competing memories of threat and safety and further demonstrate the role of dopaminergic neurotransmission in the consolidation of fear extinction memories.

Restriction of food intake is a central pathological feature of anorexia nervosa (AN). Maladaptive eating behavior and, specifically, limited intake of calorie-dense foods are resistant to change and contribute to poor long-term outcomes. This study is a preliminary examination of whether change in food choices during inpatient treatment is related to longer-term clinical course.

Individuals with AN completed a computerized Food Choice Task at the beginning and end of inpatient treatment to determine changes in high-fat and self-controlled food choices. Linear regression and longitudinal analyses tested whether change in task behavior predicted short-term outcome (body mass index [BMI] at discharge) and longer-term outcome (BMI and eating disorder psychopathology).

Among 88 patients with AN, BMI improved significantly with hospital treatment (p < 0.001), but Food Choice Task outcomes did not change significantly. Change in high-fat and self-controlled choices was not associated with BMI at discharge (r = 0.13, p = 0.22 and r = 0.10, p = 0.39, respectively). An increase in the proportion of high-fat foods selected (β = 0.91, p = 0.02) and a decrease in the use of self-control (β = −1.50, p = 0.001) predicted less decline in BMI over 3 years after discharge.

Short-term treatment is associated with improvement in BMI but with no significant change, on average, in choices made in a task known to predict actual eating. However, the degree to which individuals increased high-fat choices during treatment and decreased the use of self-control over food choice were associated with reduced weight loss over the following 3 years, underscoring the need to focus on changing eating behavior in treatment of AN.

Inducing hallucinations under controlled experimental conditions in non-hallucinating individuals represents a novel research avenue oriented toward understanding complex hallucinatory phenomena, avoiding confounds observed in patients. Auditory-verbal hallucinations (AVH) are one of the most common and distressing psychotic symptoms, whose etiology remains largely unknown. Two prominent accounts portray AVH either as a deficit in auditory-verbal self-monitoring, or as a result of overly strong perceptual priors.

In order to test both theoretical models and evaluate their potential integration, we developed a robotic procedure able to induce self-monitoring perturbations (consisting of sensorimotor conflicts between poking movements and corresponding tactile feedback) and a perceptual prior associated with otherness sensations (i.e. feeling the presence of a non-existing another person).

Here, in two independent studies, we show that this robotic procedure led to AVH-like phenomena in healthy individuals, quantified as an increase in false alarm rate in a voice detection task. Robotically-induced AVH-like sensations were further associated with delusional ideation and to both AVH accounts. Specifically, a condition with stronger sensorimotor conflicts induced more AVH-like sensations (self-monitoring), while, in the otherness-related experimental condition, there were more AVH-like sensations when participants were detecting other-voice stimuli, compared to detecting self-voice stimuli (strong-priors).

By demonstrating an experimental procedure able to induce AVH-like sensations in non-hallucinating individuals, we shed new light on AVH phenomenology, thereby integrating self-monitoring and strong-priors accounts.

Perinatal maternal depression may affect fetal neurodevelopment directly or indirectly via exposures such as smoking, alcohol, or antidepressant use. The relative contribution of these risk factors on child executive function (EF) has not been explored systematically.

A prospective pregnancy cohort of 197 women and their children was studied to determine whether maternal depression diagnosis and the trajectory of maternal depressive symptoms (MDSs) from early pregnancy to 12 months postpartum predicts child EF at age 4 (measured using the preschool age psychiatric assessment, NEPSY-II, and Shape School task) using latent growth curve modeling. Indirect effects of smoking, alcohol, and antidepressant use were also formally tested.

Increasing maternal perinatal depressive symptoms over time predicted more inattentive symptoms, poorer switching, and motor inhibition, but not cognitive inhibition. When adjusted for multiple comparison, and after accounting for maternal cognition and education, the association with child inattentive symptoms remained significant. However, diagnosed depression did not predict child EF outcomes. Prenatal exposure to smoking, alcohol, and antidepressants also did not mediate pathways from depressive symptoms to EF outcomes. Our findings were limited by sample size and statistical power to detect outcome effects of smaller effect size.

This study suggests that increasing MDSs over the perinatal period is associated with poorer EF outcomes in children at age 4 – independent of prenatal smoking, drinking, or antidepressant use. Depressive chronicity, severity, and postpartum influences may play crucial roles in determining childhood outcomes of EF.

Identifying adolescents at risk of internalizing problems is a key priority. However, studies have tended to consider such problems in simple ways using diagnoses, or item summaries. Network theory and methods instead allow for more complex interaction between symptoms. Two key hypotheses predict differences in global network properties for those at risk: altered structure and increased connectivity.

The current study evaluated these hypotheses for nine risk factors (e.g. income deprivation and low parent/carer support) individually and cumulatively in a large sample of 12–15 year-olds (N = 34 564). Recursive partitioning and bootstrapped networks were used to evaluate structural and connectivity differences.

The pattern of network interactions was shown to be significantly different via recursive partitioning for all comparisons across risk-present/absent groups and levels of cumulative risk, except for income deprivation. However, the magnitude of differences appeared small. Most individual risk factors also showed relatively small effects for connectivity. Exceptions were noted for gender and sexual minority risk groups, as well as low parent/carer support, where larger effects were evident. A strong linear trend was observed between increasing cumulative risk exposure and connectivity.

A robust approach to considering the effect of risk exposure on global network properties was demonstrated. Results are consistent with the ideas that pathological states are associated with higher connectivity, and that the number of risks, regardless of their nature, is important. Gender/sexual minority status and low parent/carer support had the biggest individual impacts on connectivity, suggesting these are particularly important for identification and prevention.

Psychosis is one of the most disabling psychiatric disorders. Pediatric traumatic brain injury (pTBI) has been cited as a developmental risk factor for psychosis, however this association has never been assessed meta-analytically.

A systematic review and meta-analysis of the association between pTBI and subsequent psychotic disorders/symptoms was performed. The study was pre-registered (CRD42022360772) adopting a random-effects model to estimate meta-analytic odds ratio (OR) and 95% confidence interval (CI) using the Paule–Mandel estimator. Subgroup (study location, study design, psychotic disorder v. subthreshold symptoms, assessment type, and adult v. adolescent onset) and meta-regression (quality of evidence) analyses were also performed. The robustness of findings was assessed through sensitivity analyses. The meta-analysis is available online as a computational notebook with an open dataset.

We identified 10 relevant studies and eight were included in the meta-analysis. Based on a pooled sample size of 479686, the pooled OR for the association between pTBI and psychosis outcomes was 1.80 (95% CI 1.11–2.95). There were no subgroup effects and no outliers. Both psychotic disorder and subthreshold symptoms were associated with pTBI. The overall association remained robust after removal of low-quality studies, however the OR reduced to 1.43 (95% CI 1.04–1.98). A leave-one-out sensitivity analysis showed the association was robust to removal of all but one study which changed the estimate to marginally non-significant.

We report cautious meta-analytic evidence for a positive association between pTBI and future psychosis. New evidence will be key in determining long-term reliability of this finding.

Individuals with schizophrenia spectrum and related psychotic disorders (SSD) experience significant impairments in social cognition that impede functioning. Social cognition is a multidimensional construct consisting of four domains: 1. theory of mind, 2. emotion processing, 3. attributional style and 4. social perception. Metacognitive training (MCT) is an intervention designed to target cognitive biases in psychosis containing two modules addressing social cognition.

A systematic review and meta-analysis was conducted to investigate the effects of MCT on social cognition and two of its domains: theory of mind and emotion processing. Ten electronic databases were scoured from 2007 to 1 February 2022 for MCT studies reporting social cognition outcomes for people with SSD (1050 identified, 282 assessed). Effect sizes were calculated using Cohen's d in R.

Nine studies were included in the meta-analysis (nMCT = 212, ncontrol = 194). MCT had a small but positive effect on global social cognition (d = 0.28 [95% CI 0.07–0.49]) and theory of mind (d = 0.27 [95% CI 0.01–0.52]). MCT showed no evidence of an effect on emotion processing (d = 0.03 [95% CI –0.26 to 0.32]).

MCT has a small but significant effect on social cognition for people with SSD. Our results add to other recent meta-analyses showing significant effects of MCT on clinically relevant outcomes such as positive symptoms, cognitive biases and cognitive insight. We recommend that future studies on MCT report outcomes on all four domains of social cognition.

PROSPERO (in the process of registration) available at https://www.crd.york.ac.uk/prospero/#recordDetails