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Broadening prediction efforts from imminent psychotic symptoms to neurodevelopmental vulnerabilities can enhance the accuracy of diagnosing severe mental disorders. Early interventions, especially during adolescence, are vital as these disorders often follow a long prodromal phase of neurodevelopmental disturbances. Child and adolescent mental health services should lead a developmentally-sensitive model for timely, effective detection and intervention.
Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics and to antidepressants in individuals at clinical high-risk for psychosis (CHR-P) have opposite prognostic effects as regards imminent transition to psychosis, with antipsychotics associated with higher risk and antidepressants associated with a lower risk in comparison to not-exposed individuals. Despite their common use, baseline exposure to benzodiazepines (BDZ) in CHR-P has surprisingly received poor attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap.
Methods
Systematic scrutiny of Medline and Cochrane library, performed up to 31 December 2022, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on BDZ baseline exposure in relation to such outcome.
Results
Of 1893 identified records, five studies were included in the systematic review and meta-analysis. The proportion of participants with exposure to BDZ at baseline ranged from 5.5% (one study) to 46.2%, with an average of 16.8%. At the end of the period of observation, i.e., the follow-up as reported in the study, 28.4% [95% confidence interval (CI) 19.7–39.1%] participants developed psychosis among the BDZ-exposed against 9.3% (7.3 to 11.9%) among the controls. CHR-P participants who were already under BDZ treatment at baseline had more than double chance of transition to psychosis than CHR-P participants who were BDZ-naïve. The risk ratio (RR) was 2.42 (95% CI 1.38–4.23) in the common effects model (z = 3.09; p = 0.002), and 2.40 (1.53 to 3.77) in the random-effects model (z = 5.40; p = 0.006; tau-squared = 0.0). There was no relevant heterogeneity: Cochran's Q = 1.49; df = 4; p = 0.828; I2 = 0.0% (95% CI 0.0–79%). Quality was good in four studies.
Conclusions
Ongoing BDZ exposure at inception in CHR-P is associated with a higher risk of transition to psychosis at follow up. This meta-analytic association, which echoes a similar effect of baseline antipsychotic exposure, plausibly indicates that the clinicians' prescription of pharmacological intervention captures some form of prognostically-relevant information (e.g. an anxiety permeated mental state requiring BDZ prescription) that are not adequately encompassed by current CHR-P categorical criteria.
Currently there is no first-line treatment recommended for the negative symptoms of schizophrenia. Psychosocial and behavioural interventions are widely used to reduce the burden of negative symptoms. Meta-analytic studies have summarised the evidence for specific approaches but not compared evidence quality and benefit.
Aim
To review and evaluate the evidence from meta-analytic studies of psychosocial and behavioural interventions for the negative symptoms of schizophrenia.
Method
A systematic literature search was undertaken to identify all meta-analyses evaluating psychosocial and behavioural interventions reporting on negative symptom outcomes in people with schizophrenia. Data on intervention, study characteristics, acceptability and outcome were extracted. Risk of bias was evaluated. Results were summarised descriptively, and evidence ranked on methodological quality.
Results
In total, 31 systematic reviews met the inclusion criteria evaluating the efficacy of negative symptom interventions on 33 141 participants. Exercise interventions showed effect sizes (reduction in negative symptoms) ranging from −0.59 to −0.24 and psychological interventions ranging from −0.65 to −0.04. Attrition ranged between 12% to 32%. Across the studies considered heterogeneity varied substantially (range 0–100). Most of the reviews were of very low to low methodological quality. Methodological quality ranking suggested that the effect size for cognitive remediation and exercise therapy may be more robust compared with other approaches.
Conclusions
Most of the interventions considered had a small-to-moderate effect size, good acceptability levels but very few had negative symptoms as the primary intervention target. To improve the confidence of these effect sizes being replicated in clinical settings future studies should minimise risk of bias.
Cognitive impairment is a core feature of schizophrenia, associated with poor functional outcomes. The course of cognitive function in the years following illness onset has remained a subject of debate, with a previous analysis finding no worsening, providing support for the neurodevelopmental model of schizophrenia. Since then, many more studies have reported on longitudinal cognitive performance in early psychosis, with some indicating deterioration, which does not align with this view.
Aims
This study aims to quantitatively review the literature on the longitudinal trajectory of cognitive deficits in the years following psychosis onset, in comparison with healthy controls. It is the first to also synthesise longitudinal data on social cognition.
Method
Electronic databases (‘PubMed’, ‘PsycInfo’ and ‘Scopus’) were searched (to end September 2021). Meta-analyses of 25 longitudinal studies of cognition in early psychosis were conducted (1480 patients, 789 health controls). Unlike previous analyses, randomised controlled trials and those with multiple cognitive testing periods within the first year were excluded to minimise bias (PROSPERO, ID: CRD42021241525).
Results
Small improvements were observed for global cognition (g = 0.25, 95% CI 0.17–0.33) and individual cognitive domains, but these were comparable with healthy controls and likely an artefact of practice effects.
Conclusions
There is no evidence of continued cognitive decline or improvement in the early years following psychosis onset, with a need for more studies over longer follow-up periods. Practice effects highlight the importance of including control samples in longitudinal and intervention studies. Further data are needed to evaluate the course of social cognition subdomains.
Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics in individuals at clinical high-risk for psychosis (CHR-P) is associated with a higher risk of an imminent transition to psychosis. Despite their tolerability profile and potential beneficial effects, baseline exposure to antidepressants (AD) in CHR-P has surprisingly received far less attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap.
Methods
Systematic scrutiny of Medline and Cochrane library, performed up to 1 August 2021, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on AD baseline exposure in relation to such outcome.
Results
Of 1942 identified records, 16 studies were included in the systematic review and meta-analysis. 26% of the participants were already exposed to AD at baseline; at the end of the follow-up 13.5% (95% CI 10.2–17.1%) of them (n = 448) transitioned to psychosis against 21.0% (18.9 to 23.3%) of non-AD exposed CHR-P (n = 1371). CHR-P participants who were already under AD treatment at baseline had a lower risk of transition than non-AD exposed CHR-P. The RR was 0.71 (95% CI 0.56–0.90) in the fixed-effects model (z = −2.79; p = 0.005), and 0.78 (0.58–1.05) in the random-effects model (z = −1.77; p = 0.096; tau-squared = 0.059). There was no relevant heterogeneity (Cochran's Q = 18.45; df = 15; p = 0.239; I2 = 18.7%).
Conclusions
Ongoing AD exposure at inception in CHR-P is associated to a reduced risk of transition to psychosis at follow up.
The clinical high-risk (CHR) for psychosis paradigm is changing psychiatric practice. However, a widespread confounder, i.e. baseline exposure to antipsychotics (AP) in CHR samples, is systematically overlooked. Such exposure might mitigate the initial clinical presentation, increase the heterogeneity within CHR populations, and confound the evaluation of transition to psychosis at follow-up. This is the first meta-analysis examining the prevalence and the prognostic impact on transition to psychosis of ongoing AP treatment at baseline in CHR cohorts.
Methods
Major databases were searched for articles published until 20 April 2020. The variance-stabilizing Freeman-Tukey double arcsine transformation was used to estimate prevalence. The binary outcome of transition to psychosis by group was estimated with risk ratio (RR) and the inverse variance method was used for pooling.
Results
Fourteen studies were eligible for qualitative synthesis, including 1588 CHR individuals. Out of the pooled CHR sample, 370 individuals (i.e. 23.3%) were already exposed to AP at the time of CHR status ascription. Transition toward full-blown psychosis at follow-up intervened in 112 (29%; 95% CI 24–34%) of the AP-exposed CHR as compared to 235 (16%; 14–19%) of the AP-naïve CHR participants. AP-exposed CHR had higher RR of transition to psychosis (RR = 1.47; 95% CI 1.18–1.83; z = 3.48; p = 0.0005), without influence by age, gender ratio, overall sample size, duration of the follow-up, or quality of the studies.
Conclusions
Baseline AP exposure in CHR samples is substantial and is associated with a higher imminent risk of transition to psychosis. Therefore, such exposure should be regarded as a non-negligible red flag for clinical risk management.
Depression is considered to be the most difficult to treat phase of bipolar disorder as patients experience residual symptoms causing long-term disability. This work aims to explore the role of add-on stimulant and stimulant-like medication in resistant bipolar depression patients.
Methods
Systematic review of add-on stimulants and stimulant-like drugs in resistant bipolar depression by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analysis was performed using the random-effects models. Heterogeneity was evaluated with Cochran’s Q and I2 statistics.
Results
Six randomized controlled trials of add-on modafinil, armodafinil, and lisdexamphetamine (LDX) (n = 813) vs placebo (n = 815) in the treatment of resistant bipolar depression were included. These drugs were more likely to induce remission from an episode of resistant bipolar depression (relative risk [RR] = 1.37; 95% confidence interval [CI]: 1.06-1.77; number needed to treat for an additional beneficial outcome = 16). Moreover, they did not induce more dropouts than placebo (RR = 1.04; 95% CI: 0.91-1.18), nor did they increase the risk of adverse effects (53/772 vs 41/771) at the end of treatment (RR = 1.30; 95% CI: 0.81-2.10; number needed to treat for an additional harmful outcome = 62). Suicidality and manic switch were not affected by active treatment. Heterogeneity was low (Cochran’s Q: P > .05), but sometimes with a large CI.
Conclusions
LDX, modafinil, and armodafinil seem to offer a reasonably well-tolerated and safe treatment in resistant bipolar depression. Treatment guidelines should, therefore, be revised to include these medications earlier in the therapeutic algorithm for resistant acute bipolar depression. Further research is, however, necessary for the elucidation of the clinical usefulness of these and other similar compounds.
Cognitive difficulties are common in people with psychosis and associated with considerable disability. Cognitive remediation (CR) can reduce the burden of cognitive difficulties and improve functioning. While mental health care has predominantly shifted to the community, people with greater illness severity and complexity, and those with poor response to treatment and concomitant greater cognitive difficulties, continue to receive inpatient care. The aim of this study is to review and evaluate the acceptability and efficacy of CR for inpatients with psychosis. A systematic search was used to identify randomized controlled trials of CR for inpatients with psychosis. Demographic and clinical information was extracted by independent raters together with therapy outcomes. Study quality was assessed using the Cochrane Collaboration Risk of Bias Assessment tool. Standardized mean change for cognitive and functional outcomes was calculated using Hedges's g and used to infer therapy effects with meta-analysis. Twenty studies were identified considering 1509 participants. Results from random-effect models suggested that CR was effective in improving processing speed (g = 0.48), memory (g = 0.48) and working memory (g = 0.56). While there was an indication of improvements in the levels of vocational, social and global functioning, these were less reliable. On average, 7% of participants dropped-out of treatment. Studies methodological quality was moderate. CR is an acceptable intervention for inpatients with psychosis and can lead to significant cognitive improvements. Evidence for improvement in functioning requires more robust and converging evidence. Future research should extend the evaluation of inpatient CR to subsequent post-discharge community functioning and further need for care.
We present the factor structure and psychometric properties of the Italian version of the SCL-90-R based on a large sample of the Italian population. The sample (N = 3631) included high-school and university students and adults from the community (age range=13–70 yrs; 39.2% males). Principal component analysis (PCA) supported by parallel analysis, yielded eight components, partially overlapping those in the original version; no evidence of Psychoticism and Paranoid Ideation as separate subscales emerged. Twenty-one items were consecutively deleted, leading to a 69-item version of the scale. Internal coherence was good for all subscales (α values between 0.70 and 0.96). However, the eight-factor solution did not prove consistent when analyses were replicated after dividing the sample in subgroups according to gender and age. A second-order PCA yielded a single factor, supporting the adoption of the GSI as an index of general distress. A 69-item brief version of the scale has been empirically derived in this study, and can possibly be adopted as a screening measure for general distress in Italian adults and adolescents; however, caution should be exercised when interpreting the clinical profile due to the instability of factor structure.
Social desirability can be conceived as a proxy for self-deception, as it involves a positive attribution side and a denial side. People with mental disorders have lower scores on measures of social desirability, which could depend on cognitive load caused by symptoms. This suggests that self-deception is an active strategy and not merely a faulty cognitive process.
Little is known about the cross-national population prevalence or
correlates of personality disorders.
Aims
To estimate prevalence and correlates of DSM–IV personality disorder
clusters in the World Health Organization World Mental Health (WMH)
Surveys.
Method
International Personality Disorder Examination (IPDE) screening questions
in 13 countries (n = 21 162) were calibrated to masked
IPDE clinical diagnoses. Prevalence and correlates were estimated using
multiple imputation.
Results
Prevalence estimates are 6.1% (s.e. = 0.3) for any personality disorder
and 3.6% (s.e. = 0.3), 1.5% (s.e. = 0.1) and 2.7% (s.e. = 0.2) for
Clusters A, B and C respectively. Personality disorders are significantly
elevated among males, the previously married (Cluster C), unemployed
(Cluster C), the young (Clusters A and B) and the poorly educated.
Personality disorders are highly comorbid with Axis I disorders.
Impairments associated with personality disorders are only partially
explained by comorbidity.
Conclusions
Personality disorders are relatively common disorders that often co-occur
with Axis I disorders and are associated with significant role
impairments beyond those due to comorbidity.
Grouping severe mental disorders into a global category is likely to lead to a “theory of everything” which forcefully explains everything and nothing. Speculation even at the phenotypic level of the single disorder cannot be fruitful, unless specific and testable models are proposed. Inclusive fitness must be incorporated in such models.