Emotional disorders are highly prevalent in primary care. We aimed to determine whether a transdiagnostic psychological therapy plus treatment-as-usual (TAU) is more efficacious than TAU alone in primary care adult patients.

A randomized, two-arm, single-blind clinical trial was conducted in 22 primary care centres in Spain. A total of 1061 adult patients with emotional disorders were enrolled. The transdiagnostic protocol (n = 527) consisted of seven 90-min sessions (8–10 patients) delivered over a 12–14-week period. TAU (n = 534) consisted of regular consultations with a general practitioner. Primary outcome measures were self-reported symptoms of anxiety, depression, and somatizations. Secondary outcome measures were functioning and quality of life. Patients were assessed at baseline, post-treatment, and at 3, 6, and 12 months. Intention-to-treat and per-protocol analyses were performed.

Post-treatment primary outcomes were significantly better in the transdiagnostic group compared to TAU (anxiety: p < 0.001; Morris's d = −0.65; depression: p < 0.001; d = −0.58, and somatic symptoms: p < 0.001; d = −0.40). These effects were sustained at the 12-month follow-up (anxiety: p < 0.001; d = −0.44; depression: p < 0.001; d = −0.36 and somatic symptoms: p < 0.001; d = −0.32). The transdiagnostic group also had significantly better outcomes on functioning (d = 0.16–0.33) and quality of life domains (d = 0.24–0.42), with sustained improvement at the 12-month follow-up in functioning (d = 0.25–0.39) and quality of life (d = 0.58–0.72). Reliable recovery rates showed large between-group effect sizes (d > 0.80) in favour of the transdiagnostic group after treatment and at the 12-month follow-up.

Adding a brief transdiagnostic psychological intervention to TAU may significantly improve outcomes in emotional disorders treated in primary care.

isrctn.org identifier: ISRCTN58437086

The coronavirus disease 2019 (COVID-19) pandemic had brought negative consequences and new stressors to mothers. The current study aims to compare factors predicting maternal mental health during the COVID-19 lockdown in China, Italy, and the Netherlands.

The sample consisted of 900 Dutch, 641 Italian, and 922 Chinese mothers (age M = 36.74, s.d. = 5.58) who completed an online questionnaire during the lockdown. Ten-fold cross-validation models were applied to explore the predictive performance of related factors for maternal mental health, and also to test similarities and differences between the countries.

COVID-19-related stress and family conflict are risk factors and resilience is a protective factor in association with maternal mental health in each country. Despite these shared factors, unique best models were identified for each of the three countries. In Italy, maternal age and poor physical health were related to more mental health symptoms, while in the Netherlands maternal high education and unemployment were associated with mental health symptoms. In China, having more than one child, being married, and grandparental support for mothers were important protective factors lowering the risk for mental health symptoms. Moreover, high SES (mother's high education, high family income) and poor physical health were found to relate to high levels of mental health symptoms among Chinese mothers.

These findings are important for the identification of at-risk mothers and the development of mental health promotion programs during COVID-19 and future pandemics.

Individuals with attention-deficit hyperactivity disorder (ADHD) often display over-response to stimuli that are irrelevant to the ongoing task, and their attentional abilities disproportionately worsen in the presence of competing stimuli. Auditory event-related potentials (ERPs) such as mismatch negativity (MMN) and P3a using the passive oddball paradigm have been studied in children and adolescents with ADHD. Still, there is no such data for adults with ADHD. This study aimed to compare the MMN and P3a and their clinical and neurocognitive correlations between drug-naive adults with ADHD and control adults.

We recruited 52 adults with ADHD (26.5 ± 6.2 years), and 62 age-matched controls (25.6 ± 5.6 years). They received the psychiatric interviews, auditory ERP, the Conners' continuous performance test (CCPT), and the Cambridge gambling test (CGT). They also completed the questionnaires about ADHD symptoms and real-world executive functions. MMN and P3a were assessed during a passive duration-deviant auditory oddball paradigm from the midline electrodes Cz.

Adults with ADHD demonstrated smaller Cz MMN amplitude, more severe ADHD symptoms, poorer attention profiles (CCPT), and a wide range of executive dysfunctions than controls. As for the correlates, Cz peak amplitude of MMN correlated with inattention symptoms, executive dysfunctions, attentional vigilance (CCPT), and decision-making (CGT) in ADHD adults but only with decision-making in controls.

Our findings that smaller amplitude of MMN and its differential associated pattern with inattention, real-world executive dysfunction, and decision-making, in drug-naive adults with ADHD from adult controls, provide evidence to support the potential electrophysiological biomarker for adult ADHD.

There is growing interest in using composite individualized treatment rules (ITRs) to guide depression treatment selection, but best approaches for doing this are not widely known. We develop an ITR for depression remission based on secondary analysis of a recently published trial for second-line antidepression medication selection using a cutting-edge ensemble machine learning method.

Data come from the SUN(^_^)D trial, an open-label, assessor blinded pragmatic trial of previously-untreated patients with major depressive disorder from 48 clinics in Japan. Initial clinic-level randomization assigned patients to 50 or 100 mg/day sertraline. We focus on the 1549 patients who failed to remit within 3 weeks and were then rerandomized at the individual-level to continuation with sertraline, switching to mirtazapine, or combining mirtazapine with sertraline. The outcome was remission 9 weeks post-baseline. Predictors included socio-demographics, clinical characteristics, baseline symptoms, changes in symptoms between baseline and week 3, and week 3 side effects.

Optimized treatment was associated with significantly increased cross-validated week 9 remission rates in both samples [5.3% (2.4%), p = 0.016 50 mg/day sample; 5.1% (2.7%), p = 0.031 100 mg/day sample] compared to randomization (30.1–30.8%). Optimization was also associated with significantly increased remission in both samples compared to continuation [24.7% in both: 11.2% (3.8%), p = 0.002 50 mg/day sample; 11.7% (3.9%), p = 0.001 100 mg/day sample]. Non-significant gains were found for optimization compared to switching or combining.

An ITR can be developed to improve second-line antidepressant selection, but replication in a larger study with more comprehensive baseline predictors might produce stronger and more stable results.

The coronavirus disease 2019 (COVID-19) pandemic led to measures that reduced social contact and support. We explored whether UK residents with more frequent or supportive social contact had fewer depressive symptoms during March−August 2020, and potential factors moderating the relationship.

A convenience sample of UK dwelling participants aged ⩾18 in the internet-based longitudinal COVID-19 Social Study completed up to 22 weekly questionnaires about face-to-face and phone/video social contact frequency, perceived social support, and depressive symptoms using the PHQ-9. Mixed linear models examined associations between social contact and support, and depressive symptoms. We examined for interaction by empathic concern, perspective taking and pre-COVID social contact frequency.

In 71 117 people with mean age 49 years (standard deviation 15), those with high perceived social support scored 1.836 (1.801–1.871) points lower on PHQ-9 than those with low support. Daily face-to-face or phone/video contact was associated with lower depressive symptoms (0.258 (95% confidence interval 0.225–0.290) and 0.117 (0.080–0.154), respectively) compared to no contact. The negative association between social relationships and depressive symptoms was stronger for those with high empathic concern, perspective taking and usual sociability.

We found during lockdown that those with higher quality or more face-to-face or phone/video contact had fewer depressive symptoms. Contact quality was more strongly associated than quantity. People who were usually more sociable or had higher empathy had more depressive symptoms during enforced reduced contact. The results have implications for COVID-19 and potential future pandemic management, and for understanding the relationship between social factors and mental health.

Self-harm is a major health concern, not only as a signal of distress but also as a strong predictor of later suicide. Self-harm can be further refined into suicidal self-harm (SSH, i.e. suicide attempt) and non-suicidal self-harm (NSSH). Understanding the aetiologies of NSSH and SSH can help inform suicide prevention strategies. Using a twin design, we investigated the phenotypic and aetiological relationships between NSSH and SSH, and their aetiological overlap with mental health problems.

We analysed data from the Twins Early Development Study using structural equation modelling. At age 21 years, 9063 twins (62.4% female) answered questions related to self-harm. At age 16 years, 19 self- or parent-reported mental health measures were administered, including measures of internalising and externalising problems, psychotic-like experiences and substance abuse.

Prevalences for NSSH and SSH were 21.9% and 10.5%, respectively. Additive genetic factors explained half of the variance in NSSH (55%) and SSH (50%), with the rest explained by non-shared environmental factors. Phenotypically, NSSH and SSH were strongly correlated (r = 0.87) with their correlation explained by genetic (57%) and non-shared environmental (43%) factors. We found no evidence that NSSH and SSH differed in their phenotypic and aetiological relationships with mental health measures.

Our findings suggest no aetiological difference between NSSH and SSH. NSSH and SSH should be regarded as two different ends of a continuum, rather than as two distinct categories.

Evidence on inequalities in mental health in lesbian, gay, and bisexual people arises primarily from non-random samples.

To use a probability sample to study change in mental health inequalities between two survey points, 7 years apart; the contribution of minority stress; and whether associations vary by age, gender, childhood sexual abuse, and religious identification.

We analysed data from 10 443 people, in two English population-based surveys (2007 and 2014), on common mental disorder (CMD), hazardous alcohol use, and illicit drug use. Multivariable models were adjusted for age, gender, and economic factors, adding interaction terms for survey year, age, gender, childhood sexual abuse, and religious identification. We explored bullying and discrimination as mediators.

Inequalities in risks of CMD or substance misuse were unchanged between 2007 and 2014. Compared to heterosexuals, bisexual, and lesbian/gay people were more likely to have CMD, particularly bisexual people [adjusted odds ratio (AOR) = 2.86; 95% CI 1.83–4.46], and to report alcohol misuse and illicit drug use. When adjusted for bullying, odds of CMD remained elevated only for bisexual people (AOR = 3.21; 95% CI 1.64–6.30), whilst odds of alcohol and drug misuse were unchanged. When adjusted for discrimination, odds of CMD and alcohol misuse remained elevated only for bisexual people (AOR = 2.91; 95% CI 1.80–4.72; and AOR = 1.63; 95% CI 1.03–2.57 respectively), whilst odds of illicit drug use remained unchanged. There were no interactions with age, gender, childhood sexual abuse, or religious identification.

Mental health inequalities in non-heterosexuals have not narrowed, despite increasing societal acceptance. Bullying and discrimination may help explain the elevated rate of CMD in lesbian women and gay men but not in bisexual people.

Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics.

Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher).

In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment.

Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use.

Mass shootings account for a small fraction of annual worldwide murders, yet disproportionately affect society and influence policy. Evidence suggesting a link between mass shootings and severe mental illness (i.e. involving psychosis) is often misrepresented, generating stigma. Thus, the actual prevalence constitutes a key public health concern.

We examined global personal-cause mass murders from 1900 to 2019, amassed by review of 14 785 murders publicly described in English in print or online, and collected information regarding perpetrator, demographics, legal history, drug use and alcohol misuse, and history of symptoms of psychiatric or neurologic illness using standardized methods. We distinguished whether firearms were or were not used, and, if so, the type (non-automatic v. semi- or fully-automatic).

We identified 1315 mass murders, 65% of which involved firearms. Lifetime psychotic symptoms were noted among 11% of perpetrators, consistent with previous reports, including 18% of mass murderers who did not use firearms and 8% of those who did (χ2 = 28.0, p < 0.01). US-based mass shooters were more likely to have legal histories, use recreational drugs or misuse alcohol, or have histories of non-psychotic psychiatric or neurologic symptoms. US-based mass shooters with symptoms of any psychiatric or neurologic illness more frequently used semi-or fully-automatic firearms.

These results suggest that policies aimed at preventing mass shootings by focusing on serious mental illness, characterized by psychotic symptoms, may have limited impact. Policies such as those targeting firearm access, recreational drug use and alcohol misuse, legal history, and non-psychotic psychopathology might yield more substantial results.

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.

Depression is a well-known risk factor for recurrent cardiac events (RCEs) but findings are less consistent for anxiety, not previously reported on using a time-dependent approach. We aimed to study the prognostic effect of anxiety and depression symptom levels on RCEs.

Data (N = 595) were drawn from the UPBEAT-UK heart disease patient cohort with 6-monthly follow-ups over 3 years. Hospital Anxiety and Depression Scale symptoms were grouped into: agitation (three items), anxiety (four items), and depression (seven items) subscales. We performed two types of multivariate analyses using Cox proportional hazard models with delayed entry: with baseline variables (long-term analysis), and with variables measured 12-to-18 months prior to the event (short-term time-dependent analysis), as RCE risk factors.

In the baseline analysis, both anxiety and depression, but not agitation, were separate RCE risk factors, with a moderating effect when considered jointly. In the short-term time-dependent analysis, elevated scores on the anxiety subscale were associated with increased RCE risk even when adjusted for depression [hazard ratio (95% confidence interval) 1.22 (1.05–1.41), p = 0.009]. Depression was no longer a significant predictor when adjusted for anxiety [1.05 (0.87–1.27), p = 0.61]. For anxiety, individual items associated with RCEs differed between the two approaches: item 5 ‘worrying thoughts’ was the most significant long-term risk factor [1.52 (1.21–1.91), p = 0.0004] whereas item 13 ‘feelings of panic’ was the most significant time-dependent short-term risk factor [1.52 (1.18–1.95), p = 0.001].

Anxiety is an important short-term preventable and potentially causal risk factor for RCEs, to be targeted in secondary cardiac disease prevention programmes.

Impulsivity is a central symptom of borderline personality disorder (BPD) and its neural basis may be instantiated in a frontoparietal network involved in response inhibition. However, research has yet to determine whether neural activation differences in BPD associated with response inhibition are attributed to attentional saliency, which is subserved by a partially overlapping network of brain regions.

Patients with BPD (n = 45) and 29 healthy controls (HCs; n = 29) underwent functional magnetic resonance imaging while completing a novel go/no-go task with infrequent odd-ball trials to control for attentional saliency. Contrasts reflecting a combination of response inhibition and attentional saliency (no-go > go), saliency processing alone (oddball > go), and response inhibition controlling for attentional saliency (no-go > oddball) were compared between BPD and HC.

Compared to HC, BPD showed less activation in the combined no-go > go contrast in the right posterior inferior and middle-frontal gyri, and less activation for oddball > go in left-hemispheric inferior frontal junction, frontal pole, superior parietal lobe, and supramarginal gyri. Crucially, BPD and HC showed no activation differences for the no-go > oddball contrast. In BPD, higher vlPFC activation for no-go > go was correlated with greater self-rated BPD symptoms, whereas lower vlPFC activation for oddball > go was associated with greater self-rated attentional impulsivity.

Patients with BPD show frontoparietal disruptions related to the combination of response inhibition and attentional saliency or saliency alone, but no specific response inhibition neural activation difference when attentional saliency is controlled. The findings suggest a neural dysfunction in BPD underlying attention to salient or infrequent stimuli, which is supported by a negative correlation with self-rated impulsiveness.

Psychosocial factors may influence mortality and morbidity after coronary bypass surgery (CABG), but it is unclear when, post-surgery, they best predict the outcome, if they interact, or whether results differ for men and women.

This prospective, observational study assessed depression symptoms, social support, marital status, household responsibility, functional impairment, mortality and need for further coronary procedures over 14 years of follow-up. Data were collected in-hospital post-CABG and at home 1-year later. Mortality and subsequent cardiac procedure data were extracted from a Cardiac Registry.

Of 296 baseline participants, 78% (43% were women) completed data at 1-year post-CABG. Long-term survival was shorter with 1-year depression and lower household responsibility but that was not true for the measures taken at baseline [HR for depression = 1.27; 95% CI 1.02–1.59 v. 0.99 (0.78–1.25), and HR = 0.71; 95% CI 0.52–0.97 v. 0.97 (0.80–1.16)] for household responsibility. An interaction between depression symptoms and social support at year 1 [χ2 (11) = 111.05, p < 0.001] revealed a greater hazard of mortality d with increased depression only at mean (HR = 1.67; 95% CI 1.21–2.26) and high social support (HR = 2.23; 95% CI 1.46–3.40). Depression also accounted for increased event recurrence. There were no significant interactions of sex with medical long-term outcomes.

In a sex-balanced sample, depression and household responsibility measured at 1-year post-CABG were associated with significant variance in unadjusted and adjusted predictor models of long-term mortality whereas the same indices determined right after the procedure were not significant predictors.

Previous research on the depression scale of the Patient Health Questionnaire (PHQ-9) has found that different latent factor models have maximized empirical measures of goodness-of-fit. The clinical relevance of these differences is unclear. We aimed to investigate whether depression screening accuracy may be improved by employing latent factor model-based scoring rather than sum scores.

We used an individual participant data meta-analysis (IPDMA) database compiled to assess the screening accuracy of the PHQ-9. We included studies that used the Structured Clinical Interview for DSM (SCID) as a reference standard and split those into calibration and validation datasets. In the calibration dataset, we estimated unidimensional, two-dimensional (separating cognitive/affective and somatic symptoms of depression), and bi-factor models, and the respective cut-offs to maximize combined sensitivity and specificity. In the validation dataset, we assessed the differences in (combined) sensitivity and specificity between the latent variable approaches and the optimal sum score (⩾10), using bootstrapping to estimate 95% confidence intervals for the differences.

The calibration dataset included 24 studies (4378 participants, 652 major depression cases); the validation dataset 17 studies (4252 participants, 568 cases). In the validation dataset, optimal cut-offs of the unidimensional, two-dimensional, and bi-factor models had higher sensitivity (by 0.036, 0.050, 0.049 points, respectively) but lower specificity (0.017, 0.026, 0.019, respectively) compared to the sum score cut-off of ⩾10.

In a comprehensive dataset of diagnostic studies, scoring using complex latent variable models do not improve screening accuracy of the PHQ-9 meaningfully as compared to the simple sum score approach.

Expressive writing about a traumatic event is promising in treating posttraumatic stress disorder (PTSD) symptoms in adult trauma survivors. To date, the comparative efficacy and acceptability of this approach is uncertain. Therefore, we aimed to examine the comparative efficacy and acceptability of expressive writing treatments.

We included 44 RCTs with 7724 participants contributing 54 direct comparisons between expressive writing (EW), enhanced writing (i.e. including additional therapist contact or individualized writing assignments; EW+), PTSD psychotherapies (PT), neutral writing (NW), and waiting-list control (WL).

EW, EW+, PT, and NW were statistically significantly more efficacious than WL at the longest available follow-up, with SMDs (95% CI) of −0.78 (−1.10 to −0.46) for PT, −0.81 (−1.02 to −0.61) for EW+ , −0.43 (−0.65 to −0.21) for EW, and −0.37 (−0.61 to −0.14) for NW. We found small to moderate differences between the active treatments. At baseline mean PTSD severity was significantly lower in EW+ compared with WL. We found considerable heterogeneity and inconsistency and we found elevated risk of bias in at least one of the bias dimensions in all studies. When EW+-WL comparisons were excluded from the analyses EW+ was no longer superior compared with EW.

The summarized evidence confirms that writing treatments may contribute to improving PTSD symptoms in medium to long-term. Methodological issues in the available evidence hamper definite conclusions regarding the comparative efficacy and acceptability of writing treatments. Adequately sized comparative randomized controlled trials preferably including all four active treatment approaches, reporting long-term data, and including researchers with balanced preferences are needed.

Altered expression of the complement component C4A gene is a known risk factor for schizophrenia. Further, predicted brain C4A expression has also been associated with memory function highlighting that altered C4A expression in the brain may be relevant for cognitive and behavioral traits.

We obtained genetic information and performance measures on seven cognitive tasks for up to 329 773 individuals from the UK Biobank, as well as brain imaging data for a subset of 33 003 participants. Direct genotypes for variants (n = 3213) within the major histocompatibility complex region were used to impute C4 structural variation, from which predicted expression of the C4A and C4B genes in human brain tissue were predicted. We investigated if predicted brain C4A or C4B expression were associated with cognitive performance and brain imaging measures using linear regression analyses.

We identified significant negative associations between predicted C4A expression and performance on select cognitive tests, and significant associations with MRI-based cortical thickness and surface area in select regions. Finally, we observed significant inconsistent partial mediation of the effects of predicted C4A expression on cognitive performance, by specific brain structure measures.

These results demonstrate that the C4 risk locus is associated with the central endophenotypes of cognitive performance and brain morphology, even when considered independently of other genetic risk factors and in individuals without mental or neurological disorders.

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.