The popularity of cognitive remediation (CR) interventions for individuals with psychosis is in part based on the well-established link between cognition and functioning and the assumption that by targeting cognition, function can improve. While numerous trials have reported CR's efficacy, it is still not considered an evidence-based treatment. Importantly, little is known about the mechanisms through which it may affect functioning.

In this study, we evaluated CR's proximal and distal effects, and examined potential mechanisms. A total of 75 individuals with psychotic disorders were randomized to a combination of strategy-based and drill-and-practice CR or wait-list control, with assessments of training task performance, neurocognition, functional capacity, symptoms and functioning conducted at baseline, end of the 2-month intervention, and 2-month follow-up.

Compared with treatment as usual, CR was associated with large post-training improvements on training tasks targeting attention, visuospatial memory, and verbal learning and memory, with persisting group differences at the 2-month follow-up. These generalized to mostly large improvements on neuropsychological measures targeting visuospatial memory, verbal learning and memory, delayed verbal memory and verbal working memory. While there were no CR-associated improvements on measures of functional capacity, symptoms, or a self-report measure of independent living skills, there was an effect on an interviewer-rated measure of functioning (Quality of Life Scale), which appeared primarily driven by the Intrapsychic Foundations subscale. Finally, for those randomized to CR, there were significant, medium-sized correlations between training task improvement, neuropsychological improvement and functioning measures.

This suggests a complex, multifactorial relationship between CR, and cognitive and functional change.

Anorexia nervosa (AN) is a serious illness leading to substantial morbidity and mortality. The treatment of AN very often is protracted; repeated hospitalizations and lost productivity generate substantial economic costs in the health care system. Therefore, this study aimed to determine the differential cost-effectiveness of out-patient focal psychodynamic psychotherapy (FPT), enhanced cognitive–behavioural therapy (CBT-E), and optimized treatment as usual (TAU-O) in the treatment of adult women with AN.

The analysis was conducted alongside the randomized controlled Anorexia Nervosa Treatment of OutPatients (ANTOP) study. Cost-effectiveness was determined using direct costs per recovery at 22 months post-randomization (n = 156). Unadjusted incremental cost-effectiveness ratios (ICERs) were calculated. To derive cost-effectiveness acceptability curves (CEACs) adjusted net-benefit regressions were applied assuming different values for the maximum willingness to pay (WTP) per additional recovery. Cost–utility and assumptions underlying the base case were investigated in exploratory analyses.

Costs of in-patient treatment and the percentage of patients who required in-patient treatment were considerably lower in both intervention groups. The unadjusted ICERs indicated FPT and CBT-E to be dominant compared with TAU-O. Moreover, FPT was dominant compared with CBT-E. CEACs showed that the probability for cost-effectiveness of FTP compared with TAU-O and CBT-E was ⩾95% if the WTP per recovery was ⩾€9825 and ⩾€24 550, respectively. Comparing CBT-E with TAU-O, the probability of being cost-effective remained <90% for all WTPs. The exploratory analyses showed similar but less pronounced trends.

Depending on the WTP, FPT proved cost-effective in the treatment of adult AN.

Autoimmune encephalitis associated with anti-neuronal antibodies may be challenging to distinguish from primary psychiatric disorders. The significance of anti-neuronal antibodies in psychiatric patients without clear evidence of autoimmune encephalitis is unknown. We investigated the serum prevalence of six anti-neuronal autoantibodies in a cohort of unselected patients admitted to acute psychiatric care.

Serum was drawn from 925 patients admitted to acute psychiatric in-patient care. Psychiatric diagnoses were set according to International Classification of Diseases (ICD)-10 criteria. Antibody analysis was performed with an indirect immunofluorescence test for N-methyl d-aspartate receptor (NMDAR) antibodies and five other anti-neuronal autoantibodies of the immunoglobulin (Ig) classes IgA, IgG and IgM isotype.

Anti-neuronal autoantibodies were found in 11.6% of patients: NMDAR antibodies in 7.6%, contactin-associated protein-like 2 (CASPR2) antibodies in 2.5%, glutamic acid decarboxylase-65 (GAD65) antibodies in 1.9%, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antibodies in 0.1%. Leucine-rich glioma-inactivated protein-1 (LGI1) and γ-aminobutyric acid B (GABAB) receptor antibodies were not detected. NMDAR antibodies of class IgG were present in five patients only (0.5%). NMDAR antibodies of all Ig classes were equally prevalent in patients with and without psychosis. There were no significant differences in antibody prevalence in the different diagnostic categories, except for a higher odds ratio of being NMDAR antibody positive for patients without a specific psychiatric diagnosis.

NMDAR IgG autoantibodies, which are known to be strongly associated with anti-NMDAR encephalitis, were rarely found. CASPR2 and GAD65 antibodies were more frequently encountered in the present study than previously reported. Further research on the clinical significance of anti-neuronal autoantibodies in patients with acute psychiatric symptoms is needed.

Concerns relating to increased use of psychotropic medication contrast with those of under-treatment and under-recognition of common mental disorders in children and young people (CYP) across developed countries. Little is known about the indications recorded for antidepressant prescribing in primary care in CYP.

This was an electronic cohort study of routinely collected primary-care data from a population of 1.9 million, Wales, UK. Poisson regression was undertaken to model adjusted counts of recorded depression symptoms, diagnoses and antidepressant prescriptions. Associated indications were explored.

3 58 383 registered patients aged 6–18 years between 1 January 2003 and 31 December 2013 provided a total of 19 20 338 person-years of follow-up. The adjusted incidence of antidepressant prescribing increased significantly [incidence rate ratio (IRR) for 2013 = 1.28], mainly in older adolescents. The majority of new antidepressant prescriptions were for citalopram. Recorded depression diagnoses showed a steady decline (IRR = 0.72) while depression symptoms (IRR = 2.41) increased. Just over half of new antidepressant prescriptions were associated with depression (diagnosis or symptoms). Other antidepressant prescribing, largely unlicensed, was associated with diagnoses such as anxiety and pain.

Antidepressant prescribing is increasing in CYP while recorded depression diagnoses decline. Unlicensed citalopram prescribing occurs outside current guidelines, despite its known toxicity in overdose. Unlicensed antidepressant prescribing is associated with a wide range of diagnoses, and while accepted practice, is often not supported by safety and efficacy studies. New strategies to implement current guidance for the management of depression in CYP are required.

Using a large Canadian population-based sample, this study aimed to verify whether televiewing in toddlerhood is prospectively associated with self-reported social impairment in middle school.

Participants are from a prospective–longitudinal birth cohort of 991 girls and 1006 boys from the Quebec Longitudinal Study of Child Development. Child self-reported ratings of relational difficulties at age 13 years were linearly regressed on parent-reported televiewing at age 2 years while adjusting for potential confounders.

Every additional 1 h of early childhood television exposure corresponded to an 11% s.d. unit increase in self-reported peer victimization [unstandardized β = 0.03, 95% confidence interval (CI) 0.02–0.04], a 10% s.d. unit increase in self-reported social isolation (unstandardized β = 0.04, 95% CI 0.03–0.05), a 9% s.d. unit increase in self-reported proactive aggression (unstandardized β = 0.02, 95% CI 0.01–0.03) and a 6% s.d. unit increase in self-reported antisocial behavior (unstandardized β = 0.01, 95% CI 0.01–0.01) at age 13 years. These results are above and beyond pre-existing individual and family factors.

Televiewing in toddlerhood was prospectively associated with experiencing victimization and social withdrawal from fellow students and engaging in antisocial behavior and proactive aggression toward fellow students at age 13 years. Adolescents who experience relational difficulties are at risk of long-term health problems (like depression and cardiometabolic disease) and socio-economic problems (like underachievement and unemployment). These relationships, observed more than a decade later, and independent of key potential confounders, suggest a need for better parental awareness of how young children invest their limited waking hours.

Childhood trauma is associated with higher risk for mental disorders, including psychosis. Heightened sensitivity to social stress may be a mechanism. This virtual reality study tested the effect of childhood trauma on level of paranoid ideations and distress in response to social stress, in interaction with psychosis liability and level of social stress exposure.

Seventy-five individuals with higher psychosis liability (55 with recent onset psychotic disorder and 20 at ultra-high risk for psychosis) and 95 individuals with lower psychosis liability (42 siblings and 53 controls) were exposed to a virtual café in five experiments with 0–3 social stressors (crowded, other ethnicity and hostility). Paranoid ideation was measured after each experiment. Subjective distress was self-rated before and after experiments. Multilevel random regression analyses were used to test main effects of childhood trauma and interaction effects.

Childhood trauma was more prevalent in individuals with higher psychosis liability, and was associated with higher level of (subclinical) psychotic and affective symptoms. Individuals with a history of childhood trauma responded with more subjective distress to virtual social stress exposures. The effects of childhood trauma on paranoia and subjective distress were significantly stronger when the number of virtual environmental stressors increased. Higher psychosis liability increased the effect of childhood trauma on peak subjective distress and stress reactivity during experiments.

Childhood trauma is associated with heightened social stress sensitivity and may contribute to psychotic and affective dysregulation later in life, through a sensitized paranoid and stress response to social stressors.

When sober, problematic drinkers display exaggerated reactivity to threats that are uncertain (U-threat). Since this aversive affective state can be alleviated via acute alcohol intoxication, it has been posited that individuals who exhibit heightened reactivity to U-threat at baseline are motivated to use alcohol as a means of avoidance-based coping, setting the stage for excessive drinking. To date, however, no study has attempted to characterize the dispositional nature of exaggerated reactivity to U-threat and test whether it is a vulnerability factor or exclusively a disease marker of problematic alcohol use.

The current investigation utilized a family study design to address these gaps by examining whether (1) reactivity to U-threat is associated with risk for problematic alcohol use, defined by family history of alcohol use disorder (AUD) and (2) reactivity to U-threat is correlated amongst adult biological siblings. A total of 157 families, and 458 individuals, participated in the study and two biological siblings completed a threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Startle potentiation was collected as an index of aversive responding.

Within biological siblings, startle potentiation to U-threat [intraclass correlation (ICC) = 0.35] and P-threat (ICC = 0.63) was significantly correlated. In addition, independent of an individuals’ own AUD status, startle potentiation to U-threat, but not P-threat, was positively associated with risk for AUD (i.e. AUD family history).

This suggests that heightened reactivity to U-threat may be a familial vulnerability factor for problematic drinking and a novel prevention target for AUD.

Researchers have studied psychological disorders extensively from a common cause perspective, in which symptoms are treated as independent indicators of an underlying disease. In contrast, the causal systems perspective seeks to understand the importance of individual symptoms and symptom-to-symptom relationships. In the current study, we used network analysis to examine the relationships between and among depression and anxiety symptoms from the causal systems perspective.

We utilized data from a large psychiatric sample at admission and discharge from a partial hospital program (N = 1029, mean treatment duration = 8 days). We investigated features of the depression/anxiety network including topology, network centrality, stability of the network at admission and discharge, as well as change in the network over the course of treatment.

Individual symptoms of depression and anxiety were more related to other symptoms within each disorder than to symptoms between disorders. Sad mood and worry were among the most central symptoms in the network. The network structure was stable both at admission and between admission and discharge, although the overall strength of symptom relationships increased as symptom severity decreased over the course of treatment.

Examining depression and anxiety symptoms as dynamic systems may provide novel insights into the maintenance of these mental health problems.

In search of empirical classifications of depression and anxiety, most subtyping studies focus solely on symptoms and do so within a single disorder. This study aimed to identify and validate cross-diagnostic subtypes by simultaneously considering symptoms of depression and anxiety, and disability measures.

A large cohort of adults (Lifelines, n = 73 403) had a full assessment of 16 symptoms of mood and anxiety disorders, and measurement of physical, social and occupational disability. The best-fitting subtyping model was identified by comparing different hybrid mixture models with and without disability covariates on fit criteria in an independent test sample. The best model's classes were compared across a range of external variables.

The best-fitting Mixed Measurement Item Response Theory model with disability covariates identified five classes. Accounting for disability improved differentiation between people reporting isolated non-specific symptoms [‘Somatic’ (13.0%), and ‘Worried’ (14.0%)] and psychopathological symptoms [‘Subclinical’ (8.8%), and ‘Clinical’ (3.3%)]. Classes showed distinct associations with clinically relevant external variables [e.g. somatization: odds ratio (OR) 8.1–12.3, and chronic stress: OR 3.7–4.4]. The Subclinical class reported symptomatology at subthreshold levels while experiencing disability. No pure depression or anxiety, but only mixed classes were found.

An empirical classification model, incorporating both symptoms and disability identified clearly distinct cross-diagnostic subtypes, indicating that diagnostic nets should be cast wider than current phenomenology-based categorical systems.

Cannabis is a widely used drug associated with increased risk for psychosis. The dopamine hypothesis of psychosis postulates that altered salience processing leads to psychosis. We therefore tested the hypothesis that cannabis users exhibit aberrant salience and explored the relationship between aberrant salience and dopamine synthesis capacity.

We tested 17 cannabis users and 17 age- and sex-matched non-user controls using the Salience Attribution Test, a probabilistic reward-learning task. Within users, cannabis-induced psychotic symptoms were measured with the Psychotomimetic States Inventory. Dopamine synthesis capacity, indexed as the influx rate constant Kicer, was measured in 10 users and six controls with 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine positron emission tomography.

There was no significant difference in aberrant salience between the groups [F1,32 = 1.12, p = 0.30 (implicit); F1,32 = 1.09, p = 0.30 (explicit)]. Within users there was a significant positive relationship between cannabis-induced psychotic symptom severity and explicit aberrant salience scores (r = 0.61, p = 0.04) and there was a significant association between cannabis dependency/abuse status and high implicit aberrant salience scores (F1,15 = 5.8, p = 0.03). Within controls, implicit aberrant salience was inversely correlated with whole striatal dopamine synthesis capacity (r = −0.91, p = 0.01), whereas this relationship was non-significant within users (difference between correlations: Z = −2.05, p = 0.04).

Aberrant salience is positively associated with cannabis-induced psychotic symptom severity, but is not seen in cannabis users overall. This is consistent with the hypothesis that the link between cannabis use and psychosis involves alterations in salience processing. Longitudinal studies are needed to determine whether these cognitive abnormalities are pre-existing or caused by long-term cannabis use.

Self-harm among young adults is a common and increasing phenomenon in many parts of the world. The long-term prognosis after self-harm at young age is inadequately known. We aimed to estimate the risk of mental illness and suicide in adult life after self-harm in young adulthood and to identify prognostic factors for adverse outcome.

We conducted a national population-based matched case-cohort study. Patients aged 18-24 years (n = 13 731) hospitalized after self-harm between 1990 and 2003 and unexposed individuals of the same age (n = 137 310 ) were followed until December 2009. Outcomes were suicide, psychiatric hospitalization and psychotropic medication in short-term (1-5 years) and long-term (>5 years) follow-up.

Self-harm implied an increased relative risk of suicide during follow-up [hazard ratio (HR) 16.4, 95% confidence interval (CI) 12.9–20.9). At long-term follow-up, 20.3% had psychiatric hospitalizations and 51.1% psychotropic medications, most commonly antidepressants and anxiolytics. There was a six-fold risk of psychiatric hospitalization (HR 6.3, 95% CI 5.8–6.8) and almost three-fold risk of psychotropic medication (HR 2.8, 95% CI 2.7–3.0) in long-term follow-up. Mental disorder at baseline, especially a psychotic disorder, and a family history of suicide were associated with adverse outcome among self-harm patients.

We found highly increased risks of future mental illness and suicide among young adults after self-harm. A history of a mental disorder was an important indicator of long-term adverse outcome. Clinicians should consider the substantially increased risk of suicide among self-harm patients with psychotic disorders.

Little is known about the precursors of suicide risk among primary-care patients. This study aimed to examine suicide risk in relation to patterns of clinical consultation, psychotropic drug prescribing, and psychiatric diagnoses.

Nested case-control study in the Clinical Practice Research Datalink (CPRD), England. Patients aged ⩾16 years who died by suicide during 2002–2011 (N = 2384) were matched on gender, age and practice with up to 20 living control patients (N = 46 899).

Risk was raised among non-consulting patients, and increased sharply with rising number of consultations in the preceding year [⩾12 consultations v. 1: unadjusted odds ratio (OR) 6.0, 95% confidence interval (CI) 4.9–7.3]. Markedly elevated risk was also associated with the prescribing of multiple psychotropic medication types (⩾5 types v. 0: OR 62.6, CI 44.3–88.4) and with having several psychiatric diagnoses (⩾4 diagnoses v. 0: OR 31.1, CI 19.3–50.1). Risk was also raised among patients living in more socially deprived localities. The confounding effect of multiple psychotropic drug types largely accounted for the rising risk gradient observed with increasing consultation frequency.

A greater proportion of patients with several psychiatric diagnoses, those prescribed multiple psychotropic medication types, and those who consult at very high frequency might be considered for referral to mental health services by their general practitioners. Non-consulters are also at increased risk, which suggests that conventional models of primary care may not be effective in meeting the needs of all people in the community experiencing major psychosocial difficulties.

Psychosocial therapy after deliberate self-harm might be associated with reduced risk of specific causes of death.

In this matched cohort study, we included patients, who after an episode of deliberate self-harm received psychosocial therapy at a Suicide Prevention Clinic in Denmark between 1992 and 2010. We used propensity score matching in a 1:3 ratio to select a comparison group from 59 046 individuals who received standard care. National Danish registers supplied data on specific causes of death over a 20-year follow-up period.

At the end of follow-up, 391 (6.9%) of 5678 patients in the psychosocial therapy group had died, compared with 1736 (10.2%) of 17 034 patients in the matched comparison group. Lower odds ratios of dying by mental or behavioural disorders [0.54, 95% confidence interval (CI) 0.37–0.79], alcohol-related causes (0.63, 95% CI 0.50–0.80) and other diseases and medical conditions (0.61, 95% CI 0.49–0.77) were noted in the psychosocial therapy group. Also, we found a reduced risk of dying by suicide as well as other external causes, however, not by neoplasms and circulatory system diseases. Numbers needed to treat were 212.9 (95% CI 139.5–448.4) for mental or behavioural disorders as a cause of death, 111.1 (95% CI 79.2–210.5) for alcohol-related causes and 96.8 (95% CI 69.1–161.8) for other diseases and medical conditions.

Our findings indicate that psychosocial therapy after deliberate self-harm might reduce long-term risk of death from select medical conditions and external causes. These promising results should be tested in a randomized design.

Suicide message boards have been at the core of debates about negative influences of the Internet on suicidality. Nothing is currently known about communication styles that may help users to psychologically improve in these settings.

In all, 1182 archival threads with 20 499 individual postings from seven non-professional suicide message boards supporting an ‘against-suicide’, ‘neutral’ or ‘pro-suicide’ attitude were randomly selected and subject to content analysis. Initial needs of primary posters (i.e. individual who open a thread), their psychological improvement by the end of the thread, their responses received and indicators of suicidality were coded. Differences between ‘pro-suicide’, ‘neutral’ and ‘against suicide’ boards, and correlations between primary posters and respondents in terms of suicidality were assessed. Logistic regression was used to test associations with psychological improvement.

‘Pro-suicide’ boards (n = 4) differed from ‘neutral’ (n = 1) and ‘against-suicide’ (n = 2) boards in terms of communicated contents. Indicators of suicidality correlated moderately to strongly between primary posters and respondents on ‘pro-suicide’ message boards, but less on other boards. Several communicative strategies were associated with psychological improvement in primary posters, including the provision of constructive advice [adjusted odds ratio (aOR) 4.10, 95% confidence interval (CI) 2.40–7.03], active listening (aOR 1.60, 95% CI 1.12–2.27), sympathy towards the poster (aOR 2.22, 95% CI 1.68–2.95) and provision of alternatives to suicide (aOR 2.30, 95% CI 1.67–3.18).

Respondents resemble primary posters with regard to suicidality in ‘pro-suicide’ boards, which may hinder psychological improvement. Still, opportunities to intervene in these settings using simple communication techniques exist and need to be taken and evaluated.

Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms in patients with schizophrenia. This has the potential to revolutionize treatment for schizophrenia. In this study, we tested the hypothesis that SNP leads to a reduction in psychotic symptoms and an improvement in spatial working memory (SWM) performance in patients with schizophrenia.

This was a single-centre, randomized, double-blind, placebo-controlled trial performed from 27 August 2014 to 10 February 2016 (clinicaltrials.gov identifier: NCT02176044). Twenty patients with schizophrenia aged 18–60 years with a diagnosis of schizophrenia or schizoaffective disorder were recruited from psychiatric outpatient clinics in the South London and Maudsley NHS Trust, London, UK. Baseline symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18), and SWM was assessed using the CANTAB computerized test. Participants received either an infusion of SNP (0.5 μg/kg per min for 4 h) or placebo and were re-assessed for symptoms and SWM performance immediately after the infusion, and 4 weeks later.

SNP did not lead to any reduction in psychotic symptoms or improvement in SWM performance compared to placebo.

Although this study was negative, it is possible that the beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms.

The effects of cognitive behavioural therapy of anxiety disorders on depression has been examined in previous meta-analyses, suggesting that these treatments have considerable effects on depression. In the current meta-analysis we examined whether the effects of treatments of anxiety disorders on depression differ across generalized anxiety disorder (GAD), social anxiety disorder (SAD) and panic disorder (PD). We also compared the effects of these treatments with the effects of cognitive and behavioural therapies of major depression (MDD).

We searched PubMed, PsycINFO, EMBASE and the Cochrane database, and included 47 trials on anxiety disorders and 34 trials on MDD.

Baseline depression severity was somewhat lower in anxiety disorders than in MDD, but still mild to moderate in most studies. Baseline severity differed across the three anxiety disorders. The effect sizes found for treatment of the anxiety disorders ranged from g = 0.47 for PD, g = 0.68 for GAD and g = 0.69 for SAD. Differences between these effect sizes and those found in the treatment of MDD (g = 0.81) were not significant in most analyses and we found few indications that the effects differed across anxiety disorders. We did find that within-group effect sizes resulted in significantly (p < 0.001) larger effect sizes for depression (g = 1.50) than anxiety disorders (g = 0.73–0.91). Risk of bias was considerable in the majority of studies.

Patients participating in trials of cognitive behavioural therapy for anxiety disorders have high levels of depression. These treatments have considerable effects on depression, and these effects are comparable to those of treatment of primary MDD.