The aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is still unknown. The identification of risk factors for CFS/ME is of great importance to practitioners.

A systematic scoping review was conducted to locate studies that analysed risk factors for CFS/ME using multiple predictors. We searched for published and unpublished literature in 11 electronic databases, reference lists of retrieved articles and guideline stakeholder submissions in conjunction with the development of a forthcoming national UK guideline. Risk factors and findings were extracted in a concise tabular overview and studies synthesized narratively.

Eleven studies were identified that met inclusion criteria: two case-control studies, four cohort studies, three studies combining a cohort with a case-control study design, one case-control and twin study and one cross-sectional survey. The studies looked at a variety of demographic, medical, psychological, social and environmental factors to predict the development of CFS/ME. The existing body of evidence is characterized by factors that were analysed in several studies but without replication of a significant association in more than two studies, and by studies demonstrating significant associations of specific factors that were not assessed in other studies. None of the identified factors appear suitable for the timely identification of patients at risk of developing CFS/ME within clinical practice.

Various potential risk factors for the development of CFS/ME have been assessed but definitive evidence that appears meaningful for clinicians is lacking.

Patients with borderline personality disorder (BPD) show negative and unstable self- and other-evaluations compared to healthy individuals. It is unclear, however, how they process self- and other-relevant social feedback. We have previously demonstrated a positive updating bias in healthy individuals: When receiving social feedback on character traits, healthy individuals integrate desirable more than undesirable feedback. Here, our aim was to test whether BPD patients exhibit a more negative pattern of social feedback processing.

We employed a character trait task in which BPD patients interacted with four healthy participants in a real-life social interaction. Afterwards, all participants rated themselves and one other participant on 80 character traits before and after receiving feedback from their interaction partners. We compared how participants updated their ratings after receiving desirable and undesirable feedback. Our analyses included 22 BPD patients and 81 healthy controls.

Healthy controls showed a positivity bias for self- and other-relevant feedback as previously demonstrated. Importantly, this pattern was altered in BPD patients: They integrated undesirable feedback for themselves to a greater degree than healthy controls did. Other-relevant feedback processing was unaltered in BPD patients.

Our study demonstrates an alteration in self-relevant feedback processing in BPD patients that might contribute to unstable and negative self-evaluations.

Psychotherapies for depression are equally effective on average, but individual responses vary widely. Outcomes can be improved by optimizing treatment selection using multivariate prediction models. A promising approach is the Personalized Advantage Index (PAI) that predicts the optimal treatment for a given individual and the magnitude of the advantage. The current study aimed to extend the PAI to long-term depression outcomes after acute-phase psychotherapy.

Data come from a randomized trial comparing cognitive therapy (CT, n = 76) and interpersonal psychotherapy (IPT, n = 75) for major depressive disorder (MDD). Primary outcome was depression severity, as assessed by the BDI-II, during 17-month follow-up. First, predictors and moderators were selected from 38 pre-treatment variables using a two-step machine learning approach. Second, predictors and moderators were combined into a final model, from which PAI predictions were computed with cross-validation. Long-term PAI predictions were then compared to actual follow-up outcomes and post-treatment PAI predictions.

One predictor (parental alcohol abuse) and two moderators (recent life events; childhood maltreatment) were identified. Individuals assigned to their PAI-indicated treatment had lower follow-up depression severity compared to those assigned to their PAI-non-indicated treatment. This difference was significant in two subsets of the overall sample: those whose PAI score was in the upper 60%, and those whose PAI indicated CT, irrespective of magnitude. Long-term predictions did not overlap substantially with predictions for acute benefit.

If replicated, long-term PAI predictions could enhance precision medicine by selecting the optimal treatment for a given depressed individual over the long term.

Despite its importance as a paradigmatic personality disorder, little is known about the measurement invariance of the DSM-IV borderline personality disorder (BPD) criteria; that is, whether the criteria assess the disorder equivalently across different groups.

BPD criteria were evaluated at interview in 2794 young adult Norwegian twins. Analyses, based on item-response modeling, were conducted to test for differential age and sex moderation of the individual BPD criteria characteristics given factor-level covariate effects.

Confirmatory factor analytic results supported a unidimensional structure for the nine BPD criteria. Compared to males, females had a higher BPD factor mean, larger factor variance and there was a significant age by sex interaction on the factor mean. Strong differential sex and age by sex interaction effects were found for the ‘impulsivity’ criterion factor loading and threshold. Impulsivity related to the BPD factor poorly in young females but improved significantly in older females. Males reported more impulsivity compared to females and this difference increased with age. The ‘affective instability’ threshold was also moderated, with males reporting less than expected.

The results suggest the DSM-IV BPD ‘impulsivity’ and ‘affective instability’ criteria function differentially with respect to age and sex, with impulsivity being especially problematic. If verified, these findings have important implications for the interpretation of prior research with these criteria. These non-invariant age and sex effects may be identifying criteria-level expression features relevant to BPD nosology and etiology. Criterion functioning assessed using modern psychometric methods should be considered in the development of DSM-V.

A significant number of patients with schizophrenia fail to respond to antipsychotic medication. Although several studies have investigated associated patient characteristics, the emerging findings from genetic studies offer further scope for study.

In 612 schizophrenia patients with detailed clinical information, common genetic variants indexed by polygenic risk scores, and rare variants indexed by deletion and duplication burden genomewide, we explored potential genetic predictors alongside other established risk factors for treatment resistance. Clinical outcomes of treatment resistance were also calculated using lifetime measures of positive, negative/disorganized and mood symptoms as well as number of hospitalizations and suicide attempts.

Logistic regression models identified a significant relationship between treatment resistance and total duplication burden genomewide, years of formal schooling and age at onset. Clinically, treatment-resistant patients were characterized by greater negative/disorganized and positive symptoms and greater number of hospitalizations.

Taken together, these findings suggest genetic information, specifically the genomewide burden of rare copy number variants, may increase our understanding and clinical management of patients with treatment-resistant schizophrenia.

Non-psychotic affective symptoms are important components of psychotic syndromes. They are frequent and are now thought to influence the emergence of paranoia and hallucinations. Evidence supporting this model of psychosis comes from recent cross-fertilising epidemiological and intervention studies. Epidemiological studies identify plausible targets for intervention but must be interpreted cautiously. Nevertheless, causal inference can be strengthened substantially using modern statistical methods.

Directed Acyclic Graphs were used in a dynamic Bayesian network approach to learn the overall dependence structure of chosen variables. DAG-based inference identifies the most likely directional links between multiple variables, thereby locating them in a putative causal cascade. We used initial and 18-month follow-up data from the 2000 British National Psychiatric Morbidity survey (N = 8580 and N = 2406).

We analysed persecutory ideation, hallucinations, a range of affective symptoms and the effects of cannabis and problematic alcohol use. Worry was central to the links between symptoms, with plausible direct effects on insomnia, depressed mood and generalised anxiety, and recent cannabis use. Worry linked the other affective phenomena with paranoia. Hallucinations were connected only to worry and persecutory ideation. General anxiety, worry, sleep problems, and persecutory ideation were strongly self-predicting. Worry and persecutory ideation were connected over the 18-month interval in an apparent feedback loop.

These results have implications for understanding dynamic processes in psychosis and for targeting psychological interventions. The reciprocal influence of worry and paranoia implies that treating either symptom is likely to ameliorate the other.

Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).

Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.

Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.

This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.

Panic disorder with agoraphobia is characterized by panic attacks and anxiety in situations where escape might be difficult. However, neuroimaging studies specifically focusing on agoraphobia are rare. Here we used functional magnetic resonance imaging (fMRI) with disorder-specific stimuli to investigate the neural substrates of agoraphobia.

We compared the neural activations of 72 patients suffering from panic disorder with agoraphobia with 72 matched healthy control subjects in a 3-T fMRI study. To isolate agoraphobia-specific alterations we tested the effects of the anticipation and perception of an agoraphobia-specific stimulus set. During fMRI, 48 agoraphobia-specific and 48 neutral pictures were randomly presented with and without anticipatory stimulus indicating the content of the subsequent pictures (Westphal paradigm).

During the anticipation of agoraphobia-specific pictures, stronger activations were found in the bilateral ventral striatum and left insula in patients compared with controls. There were no group differences during the perception phase of agoraphobia-specific pictures.

This study revealed stronger region-specific activations in patients suffering from panic disorder with agoraphobia in anticipation of agoraphobia-specific stimuli. Patients seem to process these stimuli more intensively based on individual salience. Hyperactivation of the ventral striatum and insula when anticipating agoraphobia-specific situations might be a central neurofunctional correlate of agoraphobia. Knowledge about the neural correlates of anticipatory and perceptual processes regarding agoraphobic situations will help to optimize and evaluate treatments, such as exposure therapy, in patients with panic disorder and agoraphobia.

Previous research suggests an increase in schizophrenia population attributable risk fraction (PARF) for cannabis use disorder (CUD). However, sex and age variations in CUD and schizophrenia suggest the importance of examining differences in PARFs in sex and age subgroups.

We conducted a nationwide Danish register-based cohort study including all individuals aged 16–49 at some point during 1972–2021. CUD and schizophrenia status was obtained from the registers. Hazard ratios (HR), incidence risk ratios (IRR), and PARFs were estimated. Joinpoint analyses were applied to sex-specific PARFs.

We examined 6 907 859 individuals with 45 327 cases of incident schizophrenia during follow-up across 129 521 260 person-years. The overall adjusted HR (aHR) for CUD on schizophrenia was slightly higher among males (aHR = 2.42, 95% CI 2.33–2.52) than females (aHR = 2.02, 95% CI 1.89–2.17); however, among 16–20-year-olds, the adjusted IRR (aIRR) for males was more than twice that for females (males: aIRR = 3.84, 95% CI 3.43–4.29; females: aIRR = 1.81, 95% CI 1.53–2.15). During 1972–2021, the annual average percentage change in PARFs for CUD in schizophrenia incidence was 4.8 among males (95% CI 4.3–5.3; p < 0.0001) and 3.2 among females (95% CI 2.5–3.8; p < 0.0001). In 2021, among males, PARF was 15%; among females, it was around 4%.

Young males might be particularly susceptible to the effects of cannabis on schizophrenia. At a population level, assuming causality, one-fifth of cases of schizophrenia among young males might be prevented by averting CUD. Results highlight the importance of early detection and treatment of CUD and policy decisions regarding cannabis use and access, particularly for 16–25-year-olds.

Recently published diagnostic criteria for mild cognitive impairment with Lewy bodies (MCI-LB) include five neuropsychiatric supportive features (non-visual hallucinations, systematised delusions, apathy, anxiety and depression). We have previously demonstrated that the presence of two or more of these symptoms differentiates MCI-LB from MCI due to Alzheimer's disease (MCI-AD) with a likelihood ratio >4. The aim of this study was to replicate the findings in an independent cohort.

Participants ⩾60 years old with MCI were recruited. Each participant had a detailed clinical, cognitive and imaging assessment including FP-CIT SPECT and cardiac MIBG. The presence of neuropsychiatric supportive symptoms was determined using the Neuropsychiatric Inventory (NPI). Participants were classified as MCI-AD, possible MCI-LB and probable MCI-LB based on current diagnostic criteria. Participants with possible MCI-LB were excluded from further analysis.

Probable MCI-LB (n = 28) had higher NPI total and distress scores than MCI-AD (n = 30). In total, 59% of MCI-LB had two or more neuropsychiatric supportive symptoms compared with 9% of MCI-AD (likelihood ratio 6.5, p < 0.001). MCI-LB participants also had a significantly greater delayed recall and a lower Trails A:Trails B ratio than MCI-AD.

MCI-LB is associated with significantly greater neuropsychiatric symptoms than MCI-AD. The presence of two or more neuropsychiatric supportive symptoms as defined by MCI-LB diagnostic criteria is highly specific and moderately sensitive for a diagnosis of MCI-LB. The cognitive profile of MCI-LB differs from MCI-AD, with greater executive and lesser memory impairment, but these differences are not sufficient to differentiate MCI-LB from MCI-AD.

Health anxiety is common, disabling and costly due to patients’ extensive use of health care services. Internet-delivered treatment may overcome barriers of accessibility to specialized treatment. We aimed to evaluate the efficacy of internet-delivered acceptance and commitment therapy (iACT).

A randomized, controlled trial of iACT versus an internet-delivered discussion forum (iFORUM), performed in a Danish university hospital setting. Patients self-referred and underwent video-diagnostic assessment. Eligible patients (≥18 years) with health anxiety were randomized to 12 weeks of intervention. The randomization was blinded for the assessor. The primary outcome was between-group unadjusted mean differences in health anxiety symptoms measured by the Whiteley-7 Index (WI-7, range 0–100) from baseline to 6-month follow-up (6-MFU) using intention to treat and a linear mixed model. The study is registered at clinicaltrials.gov, number NCT02735434.

A total of 151 patients self-referred, and 101 patients were randomized to iACT (n = 53) or iFORUM (n = 48). A mean difference in change over time of 19.0 points [95% confidence interval (CI) 10.8–27.2, p < 0.001] was shown on the WI-7, and a large standardized effect size of d = 0.80 (95% CI 0.38–1.23) at 6-MFU. The number needed to treat was 2.8 (95% CI 1.8–6.1, p < 0.001), and twice as many patients in iACT were no longer clinical cases (35% v. 16%; risk ratio 2.17, 95% CI 1.00–4.70, p = 0.050). Adverse events were few and insignificant.

iACT for health anxiety led to sustained effects at 6-MFU. The study contributes to the development of easily accessible treatment options and deserves wider application.

Temperament and personality traits, including negative emotionality/neuroticism, may represent risk factors for eating disorders. Further, risk factors may differ by sex. We examined longitudinal temperament/personality pathways of risk for purging and binge eating in youth stratified by sex using data from a large-scale prospective study.

Temperament, borderline personality features, sensation seeking, ‘big five’ personality factors, and depressive symptoms were measured at five time points from early childhood to adolescence in 5812 adolescents (3215 females; 2597 males) in the Avon Longitudinal Study of Parents and Children. We conducted univariate analyses with these predictors of binge eating and purging at 14 and 16 years for total and sex-stratified samples. We used structural equation modeling (SEM) to fit data to a path analysis model of hypothesized associations.

Of the total sample, 12.54% engaged in binge eating and 7.05% in purging by 16 years. Prevalence was much greater and increased dramatically for females from 14 years (7.50% binge eating; 2.40% purging) to 16 years (15.80% binge eating; 9.50% purging). For both sexes, borderline personality, depressive symptoms and lower emotional stability predicted eating disorder behaviors; sensation seeking and conscientiousness were also significant predictors for females. SEM identified an ‘emotional instability’ pathway for females from early childhood into adolescence (RMSEA = 0.025, TLI = 0.937 and CFI = 0.970).

Binge eating and purging are common in female and male adolescents. Early temperament/personality factors related to difficulty regulating emotions were predictive of later adolescent eating disorder behaviors. Results have important clinical implications for eating disorder prevention and intervention.

Depression is a highly prevalent and heterogeneous disorder. This study aims to determine whether depression with atypical features shows different heritability and different degree of overlap with polygenic risk for psychiatric and immuno-metabolic traits than other depression subgroups.

Data included 30 069 European ancestry individuals from the UK Biobank who met criteria for lifetime major depression. Participants reporting both weight gain and hypersomnia were classified as ↑WS depression (N = 1854) and the others as non-↑WS depression (N = 28 215). Cases with non-↑WS depression were further classified as ↓WS depression (i.e. weight loss and insomnia; N = 10 142). Polygenic risk scores (PRS) for 22 traits were generated using genome-wide summary statistics (Bonferroni corrected p = 2.1 × 10−4). Single-nucleotide polymorphism (SNP)-based heritability of depression subgroups was estimated.

↑WS depression had a higher polygenic risk for BMI [OR = 1.20 (1.15–1.26), p = 2.37 × 10−14] and C-reactive protein [OR = 1.11 (1.06–1.17), p = 8.86 × 10−06] v. non-↑WS depression and ↓WS depression. Leptin PRS was close to the significance threshold (p = 2.99 × 10−04), but the effect disappeared when considering GWAS summary statistics of leptin adjusted for BMI. PRS for daily alcohol use was inversely associated with ↑WS depression [OR = 0.88 (0.83–0.93), p = 1.04 × 10−05] v. non-↑WS depression. SNP-based heritability was not significantly different between ↑WS depression and ↓WS depression (14.3% and 12.2%, respectively).

↑WS depression shows evidence of distinct genetic predisposition to immune-metabolic traits and alcohol consumption. These genetic signals suggest that biological targets including immune-cardio-metabolic pathways may be relevant to therapies in individuals with ↑WS depression.