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Brain Sciences Nov 2023Pharmacological antipsychotic drug interventions represent the cornerstone of the management of patients with schizophrenia and other psychotic spectrum disorders. The... (Review)
Review
Pharmacological antipsychotic drug interventions represent the cornerstone of the management of patients with schizophrenia and other psychotic spectrum disorders. The choice of the "best" treatment should be made on the basis of several clinical domains. However, despite available treatments, the quality of life reported by patients with schizophrenia taking antipsychotics is still very poor, and this outcome is rarely taken into account in trials assessing the efficacy and effectiveness of antipsychotic treatments. Therefore, we performed a systematic review in order to assess the impact of antipsychotic treatment on patients' quality of life. In particular, we aimed to identify any differences in the improvement in quality of life according to the (a) type of formulation of antipsychotic drugs (i.e., oral vs. depot vs. long-acting injectable); (b) type of the drug (first vs. second vs. third generation); and (c) patients' clinical characteristics. One hundred and eleven papers were included in the review. The main findings were as follows: (1) quality of life is usually considered a secondary outcome in trials on the efficacy and effectiveness of drugs; (2) second-generation antipsychotics have a more positive effect on quality of life; and (3) long-acting injectable antipsychotics are associated with a more stable improvement in quality of life and with a good safety and tolerability profile. Our systematic review confirms that quality of life represents a central element for selecting the appropriate treatment for people with schizophrenia. In particular, the availability of new treatments with a better tolerability profile, a proven effectiveness on patients' cognitive and social functioning, and with a more stable blood concentration might represent the appropriate strategy for improving the quality of life of people with schizophrenia.
PubMed: 38002537
DOI: 10.3390/brainsci13111577 -
BMC Pregnancy and Childbirth Aug 2023Bipolar disorder (BD) is a mental disorder characterized by mood shifts from severe depression to mania. Pregnant women with BD may experience manic or depressive...
BACKGROUND
Bipolar disorder (BD) is a mental disorder characterized by mood shifts from severe depression to mania. Pregnant women with BD may experience manic or depressive episodes, so they are usually concerned about the effects of BD on their pregnancy. The aim of this systematic review is to determine the effects of BD on maternal health and fetal health, weight, and development. It also addresses how BD affects the probability of incidence of pregnancy complications in women with bipolar compared with healthy controls.
METHODS
Seven electronic databases (Ovid MEDLINE, Embase, MIDRIS, APA PsychINFO, Scopus, Web of Science, and ScienceOpen) were searched, and 1728 eligible studies were identified. After deduplication, screening, and manual search processes, we included only 15 studies. Descriptive analysis, and calculation of the probability of incidence for each pregnancy outcome were used to analyze the results.
RESULTS
The findings of the included studies suggest that BD during pregnancy may affect both fetal growth and maternal health by increasing the risk of giving birth to an infant with some birth defects such as microcephaly, CNS problems, small for gestational age, and other congenital anomalies, in addition to causing some obstetric complications such as gestational hypertension, preterm labor, need for assisted delivery, hospital readmission, and others.
CONCLUSION
Bipolar disorder during pregnancy negatively affects mothers and their fetuses and increases the probability of incidence of obstetrics complications.
Topics: Infant; Infant, Newborn; Female; Pregnancy; Humans; Bipolar Disorder; Prenatal Care; Fetus; Psychotic Disorders; Parturition
PubMed: 37641006
DOI: 10.1186/s12884-023-05924-8 -
Molecular Psychiatry Aug 2023Psychotic disorders are characterized by structural and functional abnormalities in brain networks. Neuroimaging techniques map and characterize such abnormalities using... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psychotic disorders are characterized by structural and functional abnormalities in brain networks. Neuroimaging techniques map and characterize such abnormalities using unique features (e.g., structural integrity, coactivation). However, it is unclear if a specific method, or a combination of modalities, is particularly effective in identifying differences in brain networks of someone with a psychotic disorder.
METHODS
A systematic meta-analysis evaluated machine learning classification of schizophrenia spectrum disorders in comparison to healthy control participants using various neuroimaging modalities (i.e., T1-weighted imaging (T1), diffusion tensor imaging (DTI), resting state functional connectivity (rs-FC), or some combination (multimodal)). Criteria for manuscript inclusion included whole-brain analyses and cross-validation to provide a complete picture regarding the predictive ability of large-scale brain systems in psychosis. For this meta-analysis, we searched Ovid MEDLINE, PubMed, PsychInfo, Google Scholar, and Web of Science published between inception and March 13th 2023. Prediction results were averaged for studies using the same dataset, but parallel analyses were run that included studies with pooled sample across many datasets. We assessed bias through funnel plot asymmetry. A bivariate regression model determined whether differences in imaging modality, demographics, and preprocessing methods moderated classification. Separate models were run for studies with internal prediction (via cross-validation) and external prediction.
RESULTS
93 studies were identified for quantitative review (30 T1, 9 DTI, 40 rs-FC, and 14 multimodal). As a whole, all modalities reliably differentiated those with schizophrenia spectrum disorders from controls (OR = 2.64 (95%CI = 2.33 to 2.95)). However, classification was relatively similar across modalities: no differences were seen across modalities in the classification of independent internal data, and a small advantage was seen for rs-FC studies relative to T1 studies in classification in external datasets. We found large amounts of heterogeneity across results resulting in significant signs of bias in funnel plots and Egger's tests. Results remained similar, however, when studies were restricted to those with less heterogeneity, with continued small advantages for rs-FC relative to structural measures. Notably, in all cases, no significant differences were seen between multimodal and unimodal approaches, with rs-FC and unimodal studies reporting largely overlapping classification performance. Differences in demographics and analysis or denoising were not associated with changes in classification scores.
CONCLUSIONS
The results of this study suggest that neuroimaging approaches have promise in the classification of psychosis. Interestingly, at present most modalities perform similarly in the classification of psychosis, with slight advantages for rs-FC relative to structural modalities in some specific cases. Notably, results differed substantially across studies, with suggestions of biased effect sizes, particularly highlighting the need for more studies using external prediction and large sample sizes. Adopting more rigorous and systematized standards will add significant value toward understanding and treating this critical population.
Topics: Humans; Diffusion Tensor Imaging; Neuroimaging; Psychotic Disorders; Brain; Schizophrenia; Magnetic Resonance Imaging
PubMed: 37563277
DOI: 10.1038/s41380-023-02195-9 -
Frontiers in Psychiatry 2023While the molecular underpinnings of vascular dysfunction in psychosis are under active investigation, their implications remain unclear due to inconsistent and... (Review)
Review
BACKGROUND
While the molecular underpinnings of vascular dysfunction in psychosis are under active investigation, their implications remain unclear due to inconsistent and sometimes sparse observations. We conducted a comprehensive meta-analysis to critically assess the alterations of vascular-related molecules in the cerebrospinal fluid (CSF) and blood of patients with psychotic disorders compared with healthy individuals.
METHODS
Databases were searched from inception to February 23, 2023. Meta-analyses were performed using a random-effects model. Meta-regression and subgroup analyses were conducted to assess the effects of clinical correlates.
RESULTS
We identified 93 eligible studies with 30 biomarkers investigated in the CSF and/or blood. Among the biomarkers examined, psychotic disorders were associated with elevated CSF-to-serum albumin ratio (standardized mean difference [SMD], 0.69; 95% confidence interval [CI], 0.35-1.02); blood S100B (SMD, 0.88; 95% CI, 0.59-1.17), matrix metalloproteinase-9 (MMP-9; SMD, 0.66; 95% CI, 0.46-0.86), and zonulin (SMD, 1.17; 95% CI, 0.04-2.30). The blood levels of S100B, MMP-9, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion molecule 1 (VCAM-1) were altered in patient subgroups differing in demographic and clinical characteristics. Blood S100B level was positively correlated with age and duration of illness. Substantial between-study heterogeneity was observed in most molecules.
CONCLUSION
The alterations in certain vascular-related fluid markers in psychotic disorders suggest disturbances in normal vascular structures and functions. However, not all molecules examined displayed clear evidence of changes. While potential impacts of clinical factors, including the administered treatment, were identified, the exploration remained limited. Further studies are needed to investigate the diverse patterns of expression, and understand how these abnormalities reflect the pathophysiology of psychosis and the impact of clinical factors.
PubMed: 37692299
DOI: 10.3389/fpsyt.2023.1241422 -
Psychological Medicine Oct 2023Childhood maltreatment (CM) has been related to social functioning and social cognition impairment in people with psychotic disorders (PD); however, evidence across... (Meta-Analysis)
Meta-Analysis Review
Examining associations, moderators and mediators between childhood maltreatment, social functioning, and social cognition in psychotic disorders: a systematic review and meta-analysis.
Childhood maltreatment (CM) has been related to social functioning and social cognition impairment in people with psychotic disorders (PD); however, evidence across different CM subtypes and social domains remains less clear. We conducted a systematic review and meta-analysis to quantify associations between CM, overall and its different subtypes (physical/emotional/sexual abuse, physical/emotional neglect), and domains of social functioning and social cognition in adults with PD. We also examined moderators and mediators of these associations. A PRISMA-compliant systematic search was performed on 24 November 2022 (PROSPERO CRD42020175244). Fifty-three studies ( = 13 635 individuals with PD) were included in qualitative synthesis, of which 51 studies ( = 13 260) with 125 effects sizes were pooled in meta-analyses. We found that CM was negatively associated with global social functioning and interpersonal relations, and positively associated with aggressive behaviour, but unrelated to independent living or occupational functioning. There was no meta-analytic evidence of associations between CM and social cognition. Meta-regression analyses did not identify any consistent moderation pattern. Narrative synthesis identified sex and timing of CM as potential moderators, and depressive symptoms and maladaptive personality traits as possible mediators between CM and social outcomes. Associations were of small magnitude and limited number of studies assessing CM subtypes and social cognition are available. Nevertheless, adults with PD are at risk of social functioning problems after CM exposure, an effect observed across multiple CM subtypes, social domains, diagnoses and illness stages. Maltreated adults with PD may thus benefit from trauma-related and psychosocial interventions targeting social relationships and functioning.
Topics: Adult; Child; Humans; Child Abuse; Social Cognition; Social Interaction; Psychotic Disorders; Emotions
PubMed: 37458216
DOI: 10.1017/S0033291723001678 -
Psychiatry Research May 2024Traumatic events increase risk of mental illnesses, but childhood neglect prevalence in psychiatric disorders is understudied. This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Traumatic events increase risk of mental illnesses, but childhood neglect prevalence in psychiatric disorders is understudied. This systematic review and meta-analysis assessed neglect prevalence, including emotional neglect (EN) and physical neglect (PN), among adults with psychiatric disorders. We conducted a systematic search and meta-analysis in 122 studies assessing different psychiatric disorders. Prevalence was 46.6% (95%CI[34.5-59.0]) for unspecified neglect (Ne), 43.1% (95%CI[39.0-47.4]) for EN, and 34.8% (95%CI[30.6-39.2]) for PN. Although a moderating effect of the psychiatric diagnostic category was not confirmed, some clinical diagnoses had significantly lower prevalence rates than others. Patients with bipolar disorder and major depressive disorder showed lower prevalence rates of EN and PN, whereas lower prevalence was found in psychotic disorders and eating disorders for PN only. Neglect assessment was a significant moderator for Ne and PN. No moderating effect of age and sex on neglect prevalence was found. Heterogeneity levels within and between psychiatric diagnostic categories remained high. This is the first meta-analysis examining diverse types of neglect prevalence considering different psychiatric diagnoses. Our results explore the prevalence of childhood neglect and its subtypes among adults with psychiatric disorders, contributing to understanding the nuanced interplay between neglect and specific psychiatric conditions, and guiding interventions for affected individuals.
Topics: Adult; Child; Humans; Child Abuse; Depressive Disorder, Major; Prevalence; Bipolar Disorder; Feeding and Eating Disorders
PubMed: 38579459
DOI: 10.1016/j.psychres.2024.115881 -
BMJ Mental Health Oct 2023This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
QUESTION
This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
STUDY SELECTION AND ANALYSIS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed.
FINDINGS
Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio.
CONCLUSIONS
The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.
Topics: Humans; Acetylcysteine; Amino Acids; Anti-Inflammatory Agents; Antipsychotic Agents; Schizophrenia; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37852631
DOI: 10.1136/bmjment-2023-300771 -
JAMA Psychiatry May 2024Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated.
OBJECTIVE
To provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls.
DATA SOURCES
In this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022.
STUDY SELECTION
Original studies reporting data on cognitive function in antipsychotic drug-naive patients with first-episode psychosis (FEP) were included.
DATA EXTRACTION AND SYNTHESIS
Data were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias.
MAIN OUTCOMES AND MEASURES
The main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability.
RESULTS
Fifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = -1.16; 95% CI, -1.35 to -0.98; verbal learning: Hedges g = -1.08; 95% CI, -1.28 to -0.88; visual learning: Hedges g = -1.05; 95% CI, -1.27 to -0.82; working memory: Hedges g = -1.04; 95% CI, -1.35 to -0.73; attention: Hedges g = -1.03; 95% CI, -1.24 to -0.82; reasoning/problem solving: Hedges g = -0.90; 95% CI, -1.12 to -0.68; executive function: Hedges g = -0.88; 95% CI, -1.07 to -0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92).
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.
Topics: Humans; Psychotic Disorders; Cognitive Dysfunction; Executive Function; Cognition; Antipsychotic Agents; Schizophrenia
PubMed: 38416480
DOI: 10.1001/jamapsychiatry.2024.0016 -
Schizophrenia Research Apr 2024Schizophrenia is often associated with severe difficulties in social functioning, resulting in increased isolation and subsequent loneliness. Interpersonal distance -... (Review)
Review
BACKGROUND AND HYPOTHESIS
Schizophrenia is often associated with severe difficulties in social functioning, resulting in increased isolation and subsequent loneliness. Interpersonal distance - the amount of space around an individual's body during social interaction - can signal such difficulties. However, little is known about how individuals with schizophrenia regulate their interpersonal distance during social encounters. Summarizing the current empirical findings of interpersonal distance regulation in schizophrenia can bring novel perspectives for understanding interpersonal difficulties observed in this clinical population.
STUDY DESIGN
This systematic review examined empirical studies indexed in Web of Science and PubMed based on a-priori-defined criteria. 1164 studies were screened with the final review consisting of 14 studies. They together included 1145 adult participants, of whom 668 were diagnosed with schizophrenia or psychotic disorder.
STUDY RESULTS
The studies clearly showed that patients maintain greater interpersonal distances than do controls. Furthermore, a larger distance was linked to more severe positive and negative symptoms. More specifically, the link to symptoms was more pronounced when patients were being approached by someone else during interactions. On a neurobiological level, the increased activity and functional connectivity of the dorsal inferior parietal sulcus and increased subjective state-dependent stress are further indicated as being potentially related to increase interpersonal distancing in schizophrenia.
CONCLUSIONS
We provided information about the aberrant modulation of interpersonal distance in schizophrenia. Studies showed substantial heterogeneity in tasks used to measure interpersonal distance. Future studies should look at links to social functioning, underlying neurobiology, and neuroendocrinal regulation of interpersonal space in schizophrenia.
Topics: Adult; Humans; Interpersonal Relations; Schizophrenia; Psychotic Disorders; Loneliness; Social Interaction
PubMed: 38359513
DOI: 10.1016/j.schres.2024.02.006 -
Psychopharmacology Feb 2024Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce dopaminergic transmission but have limited activity at postsynaptic receptors and so may have antipsychotic activity with lower risk of tardive dyskinesia.
METHODS
We conducted a systematic database search from inception to September 2022 for articles describing the use of VMAT-2 inhibitors in psychosis. Inclusion criteria were as follows: Population: adults diagnosed with psychosis or schizophrenia; Intervention: treatment with tetrabenazine, deutetrabenazine or valbenazine; Comparison: comparison with placebo or/and antipsychotic drug; Outcomes: with efficacy outcomes (e.g. Brief Psychiatric Rating Scale (BPRS) change or clinician assessment) and adverse effects ratings (e.g. rating scale or clinician assessment or dropouts); and Studies: in randomised controlled trials and non-randomised studies.
RESULTS
We identified 4892 records relating to VMAT-2 inhibitor use of which 5 (173 participants) met our a priori meta-analysis inclusion criteria. VMAT-2 inhibitors were more effective than placebo for the outcome 'slight improvement' (risk ratio (RR) = 1.77 (95% CI 1.03, 3.04)) but not for 'moderate improvement' (RR 2.81 (95% CI 0.27, 29.17). VMAT-2 inhibitors were as effective as active comparators on both measures for-'slight improvement' (RR 1.05 (95% CI 0.6, 1.81)) and 'moderate improvement' (RR 1.11 (95% CI 0.51, 2.42). Antipsychotic efficacy was also suggested by a narrative review of 37 studies excluded from the meta-analysis.
CONCLUSIONS
VMAT-2 inhibitors may have antipsychotic activity and may offer promise for treatment of psychosis with the potential for a reduced risk of TD.
Topics: Adult; Humans; Antipsychotic Agents; Psychotic Disorders; Schizophrenia; Tardive Dyskinesia; Tetrabenazine; Vesicular Monoamine Transport Proteins
PubMed: 38238580
DOI: 10.1007/s00213-023-06488-3