The long-term outcome of first-episode schizophrenia needs improvement. Here, we evaluate the effectiveness of 5 years sustained specialist treatment (ST), ST including Parent groups (ST + P) or treatment as usual (TAU) on psychotic relapse and social functioning.

A three condition randomized, parallel assigned, single-blind efficacy trial, in which 198 first-episode psychosis (FEP) patients aged 15–28 years were included. The effect on time to first relapse, first relapse rates, mean number of relapses per patient, and time to the improvement of social functioning were analyzed using Cox regression or ANOVA.

We found no significant differences between treatment conditions in the ITT analysis concerning time to first relapse, nor first relapse rate. Mean number of relapses per patient differed at a trend level between ST, ST + P or TAU conditions, respectively: 0.72; 0.62 or 1.02 (p = 0.069). No evidence was found for differential effect of treatment conditions on social functioning.

Five years sustained ST of FEP nor addition of parent groups increased time to first relapse or reduced first relapse rate, compared to sustained TAU. Indications for favorable effects of parent groups were found on relapses per patient.

Nicotine dependence has been shown to represent a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder though only a limited number of the findings have been replicated.

In the present study, a genome-wide linkage scan for nicotine dependence was conducted in a community sample of 950 probands and 1204 relatives recruited through the University of California, San Francisco (UCSF) Family Alcoholism Study. A modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) with additional questions that probe nicotine use was used to derive DSM-IV nicotine dependence diagnoses.

A locus on chromosome 2q31.1 at 184 centiMorgans nearest to marker D2S2188 yielded a logarithm (base 10) of odds (LOD) score of 3.54 (point-wise empirical p=0.000012). Additional peaks of interest were identified on chromosomes 2q13, 4p15.33-31, 11q25 and 12p11.23-21. Follow-up analyses were conducted examining the contributions of individual nicotine dependence symptoms to the chromosome 2q31.1 linkage peak as well as examining the relationship of this chromosomal region to alcohol dependence.

The present report suggests that chromosome 2q31.1 confers risk to the development of nicotine dependence and that this region influences a broad range of nicotine dependence symptoms rather than a specific facet of the disorder. Further, the results show that this region is not linked to alcohol dependence in this population, and thus may influence nicotine dependence specifically.

Medical patients are often screened for distress in the clinic using a questionnaire such as the Hospital Anxiety and Depression Scale (HADS) while awaiting their consultation. However, might the context of the clinic artificially inflate the distress score? To address this question we aimed to determine whether those who scored high on the HADS in the clinic remained high scorers when reassessed later at home.

We analysed data collected by a distress and depression screening service for cancer out-patients. All patients had completed the HADS in the clinic (on computer or on paper) prior to their consultation. For a period, patients with a high score (total of ⩾15) also completed the HADS again at home (over the telephone) 1 week later. We used these data to determine what proportion remained high scorers and the mean change in their scores. We estimated the effect of ‘regression to the mean’ on the observed change.

Of the 218 high scorers in the clinic, most [158 (72.5%), 95% confidence interval (CI) 66.6–78.4] scored high at reassessment. The mean fall in the HADS total score was 1.74 (95% CI 1.09–2.39), much of which could be attributed to the estimated change over time (regression to the mean) rather than the context.

Pre-consultation distress screening in clinic is widely used. Reassuringly, it only modestly overestimates distress measured later at home and consequently would result in a small proportion of unnecessary further assessments. We conclude it is a reasonable and convenient strategy.

The mechanisms underlying the antipsychotic potential of cannabidiol (CBD) remain unclear but growing evidence indicates that dysfunction in the insula, a key brain region involved in the processing of motivationally salient stimuli, may have a role in the pathophysiology of psychosis. Here, we investigate whether the antipsychotic mechanisms of CBD are underpinned by their effects on insular activation, known to be involved in salience processing.

A within-subject, crossover, double-blind, placebo-controlled investigation of 19 healthy controls and 15 participants with early psychosis was conducted. Administration of a single dose of CBD was compared with placebo in psychosis participants while performing the monetary incentive delay task, an fMRI paradigm. Anticipation of reward and loss were used to contrast motivationally salient stimuli against a neutral control condition.

No group differences in brain activation between psychosis patients compared with healthy controls were observed. Attenuation of insula activation was observed following CBD, compared to placebo. Sensitivity analyses controlling for current cannabis use history did not affect the main results.

Our findings are in accordance with existing evidence suggesting that CBD modulates brain regions involved in salience processing. Whether such effects underlie the putative antipsychotic effects of CBD remains to be investigated.

Reported associations between depression and myocardial infarction in some studies might be explained by use of psychotropic drugs, residual confounding, and/or reverse causation (whereby heart disease precedes depression). We investigated these hypotheses in a large prospective study of UK women with no previous vascular disease.

At baseline in median year 2001 (IQR 2001–2003), Million Women Study participants reported whether or not they were currently being treated for depression or anxiety, their self-rated health, and medication use during the previous 4 weeks. Follow-up was through linkage to national hospital admission and mortality databases. Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the first myocardial infarction event in those reporting treatment for depression or anxiety (subdivided by whether or not the treatment was with psychotropic drugs) v. not, and stratified by self-reported health and length of follow-up.

During mean follow-up of 13.9 years of 690 335 women (mean age 59.8 years) with no prior heart disease, stroke, transient ischaemic attack, or cancer, 12 819 had a first hospital admission or death from myocardial infarction. The aHRs for those reporting treatment for depression or anxiety with, and without, regular use of psychotropic drugs were 0.96 (95% CI 0.89–1.03) and 0.99 (0.89–1.11), respectively. No associations were found separately in women who reported being in good/excellent or poor/fair health or by length of follow-up.

The null findings in this large prospective study are consistent with depression not being an independent risk factor for myocardial infarction.

Comprehensive Behavioral Intervention for Tics (CBIT) is recommended as a first-line treatment for Tourette syndrome in children and adults. While there is strong evidence proving its efficacy, the mechanisms of reduction in tic severity during CBIT are still poorly understood. In a recent study, our group identified a functional brain network involved in tic suppression in children with TS. We reasoned that voluntary tic suppression and CBIT may share some mechanisms and thus we wanted to assess whether functional connectivity during tic suppression was associated with CBIT outcome.

Thirty-two children with TS, aged 8 to 13 years old, participated in a randomized controlled trial of CBIT v. a treatment-as-usual control condition. EEG was recorded during tic suppression in all participants at baseline and endpoint. We used a source-reconstructed EEG connectivity pipeline to assess functional connectivity during tic suppression.

Functional connectivity during tic suppression did not change from baseline to endpoint. However, baseline tic suppression-related functional connectivity specifically predicted the decrease in vocal tic severity from baseline to endpoint in the CBIT group. Supplementary analyses revealed that the functional connectivity between the right superior frontal gyrus and the right angular gyrus was mainly driving this effect.

This study revealed that functional connectivity during tic suppression at baseline predicted reduction in vocal tic severity. These results suggest probable overlap between the mechanisms of voluntary tic suppression and those of behavior therapy for tics.

Certain ways of responding to psychotic experiences (PEs) appear more commonly associated with clinical distress (e.g. avoidance) and other ways with benign or positive outcomes (e.g. reappraisal and acceptance). Past research has largely been limited to retrospective self-report. We aimed to compare clinical and non-clinical individuals on experimental analogues of anomalous experiences.

Response styles of two groups with persistent PEs (clinical n = 84; non-clinical n = 92) and a control group without PEs (n = 83) were compared following experimental analogues of thought interference (Cards Task, Telepath) and hearing voices (Virtual Acoustic Space Paradigm).

The non-clinical group with PEs were less likely to endorse unhelpful response styles, such as passive responding or attempts to avoid, suppress, worry about or control mental experiences, compared with the clinical group on all three tasks. The clinical group were more likely to endorse unhelpful response styles compared with controls on two out of three tasks (Cards Task and Telepath). The non-clinical group performed similarly to controls on unhelpful responding across all tasks. There were no group differences for helpful response styles, such as cognitive reappraisal or mindful acceptance of experiences.

In line with cognitive models of psychosis, the findings suggest that the way in which individuals respond to unusual experiences may be an important factor in understanding clinical distress, supporting the therapeutic rationale of targeting potentially unhelpful patterns of response.

Psychotic-like experiences (PLEs) are risk factors for the development of psychiatric conditions like schizophrenia, particularly if associated with distress. As PLEs have been related to alterations in both white matter and cognition, we investigated whether cognition (g-factor and processing speed) mediates the relationship between white matter and PLEs.

We investigated two independent samples (6170 and 19 891) from the UK Biobank, through path analysis. For both samples, measures of whole-brain fractional anisotropy (gFA) and mean diffusivity (gMD), as indications of white matter microstructure, were derived from probabilistic tractography. For the smaller sample, variables whole-brain white matter network efficiency and microstructure were also derived from structural connectome data.

The mediation of cognition on the relationships between white matter properties and PLEs was non-significant. However, lower gFA was associated with having PLEs in combination with distress in the full available sample (standardized β = −0.053, p = 0.011). Additionally, lower gFA/higher gMD was associated with lower g-factor (standardized β = 0.049, p < 0.001; standardized β = −0.027, p = 0.003), and partially mediated by processing speed with a proportion mediated of 7% (p = < 0.001) for gFA and 11% (p < 0.001) for gMD.

We show that lower global white matter microstructure is associated with having PLEs in combination with distress, which suggests a direction of future research that could help clarify how and why individuals progress from subclinical to clinical psychotic symptoms. Furthermore, we replicated that processing speed mediates the relationship between white matter microstructure and g-factor.

Anorexia nervosa (AN) is characterized by severe emaciation and drastic reductions of brain mass, but the underlying mechanisms remain unclear. The present study investigated the putative association between the serum-based protein markers of brain damage neurofilament light (NF-L), tau protein, and glial fibrillary acidic protein (GFAP) and cortical thinning in acute AN.

Blood samples and magnetic resonance imaging scans were obtained from 52 predominantly adolescent, female patients with AN before and after partial weight restoration (increase in body mass index >14%). The effect of marker levels before weight gain and change in marker levels on cortical thickness (CT) was modeled at each vertex of the cortical surface using linear mixed-effect models. To test whether the observed effects were specific to AN, follow-up analyses exploring a potential general association of marker levels with CT were conducted in a female healthy control (HC) sample (n = 147).

In AN, higher baseline levels of NF-L, an established marker of axonal damage, were associated with lower CT in several regions, with the most prominent clusters located in bilateral temporal lobes. Tau protein and GFAP were not associated with CT. In HC, no associations between damage marker levels and CT were detected.

A speculative interpretation would be that cortical thinning in acute AN might be at least partially a result of axonal damage processes. Further studies should thus test the potential of serum NF-L to become a reliable, low-cost and minimally invasive marker of structural brain alterations in AN.

Experiences of felt presence (FP) are well documented in neurology, neuropsychology and bereavement research, but systematic research in relation to psychopathology is limited. FP is a feature of sensorimotor disruption in psychosis, hypnagogic experiences, solo pursuits and spiritual encounters, but research comparing these phenomena remains rare. A comparative approach to the phenomenology of FP has the potential to identify shared and unique processes underlying the experience across these contexts, with implications for clinical understanding and intervention.

We present a mixed-methods analysis from three online surveys comparing FP across three diverse contexts: a population sample which included people with experience of psychosis and voice-hearing (study 1, N = 75), people with spiritual and spiritualist beliefs (study 2, N = 47) and practitioners of endurance/solo pursuits (study 3, N = 84). Participants were asked to provide descriptions of their FP experiences and completed questionnaires on FP frequency, hallucinatory experiences, dissociation, paranoia, social inner speech and sleep. Data and code for the study are available via OSF.

Hierarchical linear regression analysis indicated that FP frequency was predicted by a general tendency to experience hallucinations in all three studies, although paranoia and gender (female > male) were also significant predictors in sample 1. Qualitative analysis highlighted shared and diverging phenomenology of FP experiences across the three studies, including a role for immersive states in FP.

These data combine to provide the first picture of the potential shared mechanisms underlying different accounts of FP, supporting a unitary model of the experience.

There is growing evidence that gray matter atrophy is constrained by normal brain network (or connectome) architecture in neuropsychiatric disorders. However, whether this finding holds true in individuals with depression remains unknown. In this study, we aimed to investigate the association between gray matter atrophy and normal connectome architecture at individual level in depression.

In this study, 297 patients with depression and 256 healthy controls (HCs) from two independent Chinese dataset were included: a discovery dataset (105 never-treated first-episode patients and matched 130 HCs) and a replication dataset (106 patients and matched 126 HCs). For each patient, individualized regional atrophy was assessed using normative model and brain regions whose structural connectome profiles in HCs most resembled the atrophy patterns were identified as putative epicenters using a backfoward stepwise regression analysis.

In general, the structural connectome architecture of the identified disease epicenters significantly explained 44% (±16%) variance of gray matter atrophy. While patients with depression demonstrated tremendous interindividual variations in the number and distribution of disease epicenters, several disease epicenters with higher participation coefficient than randomly selected regions, including the hippocampus, thalamus, and medial frontal gyrus were significantly shared by depression. Other brain regions with strong structural connections to the disease epicenters exhibited greater vulnerability. In addition, the association between connectome and gray matter atrophy uncovered two distinct subgroups with different ages of onset.

These results suggest that gray matter atrophy is constrained by structural brain connectome and elucidate the possible pathological progression in depression.