An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders.

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted an umbrella review (protocol  link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders.

Editorial Perspective: COVID-19-related publications on young people's mental health - what have been the key trends so far and what should come next?

In this Editorial Perspective, we take a systematic look at the overall nature of the Covid-19 related research on mental health in children and young people, to gain insight into the major trends in this area of research and inform future lines of investigation, clinical practices, and policies. By means of state-of-the-art scientometric approaches, we identified 3,692 relevant research outputs, mainly clustering around the following themes: (a) mental health consequences of the Covid-19 pandemic in children and young people; (b) impact of the pandemic on pre-existing psychiatric disorders; (c) family outcomes (i.e., family violence and parental mental health); and (d) link between physical and mental conditions. Only 23% of the retrieved publications reported new data, the remaining ones being reviews, editorials, opinion papers, and other nonempirical reports. The majority of the empirical studies used a cross-sectional design. We suggest that future research efforts should prioritise: (a) longitudinal follow-up of existing cohorts; (b) quasi-experimental studies to gain insight into causal mechanisms underlying pandemic-related psychopathology in children and young people; (c) pragmatic randomised controlled trials (RCTs) to test evidence-based intervention strategies; and (d) evidence-based guidelines for clinicians and policymakers.

Psychotic symptoms prior or concomitant to diagnosis of multiple sclerosis: a systematic review of case reports and case series.

OBJECTIVE: We aimed to examine the clinical features of psychotic symptoms preceding or concomitant to multiple sclerosis (MS) diagnosis. METHOD: From the 1st to 10th of January 2020 a systematic review was conducted through an electronic search of different databases. Results were limited to English, French, German, Italian and Spanish language articles. RESULTS: We identified 599 titles, and included 32 cases from case-report and case series. One case report from our department was added. The mean age of first psychiatric symptoms was 25.8 ± 10.2 years, the mean age of MS diagnosis was 31.2 ± 10.7 years and the mean delay until MS diagnosis was 2.7 ± 3 years. Most reported symptoms were delusions (81%), auditory hallucinations (59%) and visual hallucinations (50%). Upon the MS diagnosis, immunosuppressive therapy was significantly more effective for psychotic symptoms than antipsychotics (OR = 9.0; 95%CI: 2.15-37; p = 0.002). Diffuse periventricular lesions were found in 95.6% of cases, with mostly temporal or frontal predominant lesions. In cases affected by predominant temporal lesions, 83% of cases presented visual hallucinations (p < 0.05). CONCLUSION: Poor response or resistance to antipsychotics treatment should alert clinicians on the need to consider a differential diagnosis. Considering the impact of delay in MS diagnosis further research regarding this subject is warranted.KEY POINTSInsight into the occurrence of psychotic symptoms in multiple sclerosis (MS) is mainly limited to case reports and case series.Delay in MS management between initial psychotic symptoms and the MS diagnosis is 2.73 ± 3 years and 0.8 ± 1.2 years for patients presenting a first episode of psychosis.The resistance and poor response to antipsychotics found in most cases (75%) were associated with an excellent improvement (95%) of both psychiatric and neurologic symptoms with corticosteroids.Prospective studies are needed to investigate the spectrum of psychosis in MS.

Intranasal Oxytocin for Negative Symptoms of Schizophrenia: Systematic Review, Meta-Analysis, and Dose-Response Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Negative symptoms are a core aspect of psychopathology in schizophrenia. Currently available pharmacological agents have proven minimally efficacious for remediating negative symptoms. A promising treatment avenue is the intranasal administration of the neuropeptide oxytocin. However, there have been inconsistencies in effects of oxytocin on negative symptoms throughout the literature, and factors leading to inconsistent effects are unclear. METHODS: We conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect. Random effects meta-analyses and dose-response meta-analysis were performed on mean changes in negative symptoms. RESULTS: In an initial analysis of all 9 identified randomized clinical trials, intranasal oxytocin showed no significant effect on negative symptoms. For higher doses (>40-80 IU), a beneficial effect on negative symptoms was found with a moderate effect size, but this effect disappeared after exclusion of 1 outlier study. The dose-response meta-analysis predicted that higher doses of oxytocin may be more efficacious for negative symptoms. For positive symptoms, no beneficial effect of oxytocin was found in the main meta-analysis, but the dose-response meta-analysis suggested a potential advantage of higher doses. CONCLUSIONS: The present results show no consistent beneficial effect of intranasal oxytocin for the treatment of negative and positive symptoms. The dose-response meta-analysis does not allow drawing any firm conclusions but suggests that high doses of intranasal oxytocin may be more efficacious. If future studies are conducted, an effort to reach adequate CNS concentrations for a sufficient duration is required.

Prodopaminergic Drugs for Treating the Negative Symptoms of Schizophrenia: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The negative symptoms of schizophrenia pose a heavy burden on patients and relatives and represent an unmet therapeutic need. The observed association of negative symptoms with impaired reward system function has stimulated research on prodopaminergic agents as potential adjunctive treatments. METHODS: We conducted a systematic review and meta-analysis of published randomized controlled trials of amphetamine, methylphenidate, modafinil, armodafinil, lisdexamphetamine, L-dopa, levodopa, bromocriptine, cabergoline, quinagolide, lisuride, pergolide, apomorphine, ropinirole, pramipexole, piribedil, and rotigotine augmentation in schizophrenia and schizoaffective disorder.Medline, EMBASE, and several other databases as well as trial registries were searched for placebo-controlled trials. RESULTS: Ten randomized controlled trials were included in the meta-analysis, 6 trials on modafinil, 2 on armodafinil, 1 on L-dopa, and 1 on pramipexole. Overall, prodopaminergic agents did not significantly reduce negative symptoms. Restricting the analysis to studies requiring a minimum threshold for negative symptom severity, modafinil/armodafinil showed a significant but small effect on negative symptoms. A subset of studies allowed for calculating specific effects for the negative symptom dimensions diminished expression and amotivation, but no significant effect was found. Prodopaminergic agents did not increase positive symptom scores. CONCLUSIONS: The currently available evidence does not allow for formulating recommendations for the use of prodopaminergic agents for the treatment of negative symptoms. Nevertheless, the observed improvement in studies defining a minimum threshold for negative symptom severity in the absence of an increase in positive symptoms clearly supports further research on these agents.

Sexual Identity Disorder and Psychosis in Klinefelter Syndrome: A Synthesis of Literature and a Case Report.

Klinefelter syndrome (KS) 47, XXY is the most frequent chromosomal abnormality causing hypogonadism in humans. This chromosomal abnormality of number in its classical form called homogeneous (supernumerary X) is generally the result of a meiosis accident. Several studies have suggested that individuals with KS are at greater risk of developing various psychiatric disorders, including depression and schizophrenia. The diagnosis is made based on subnormal testosterone with high pituitary gonadotropins and confirmed by determining the karyotype on a blood simple. We did a literature review using an electronic search in three databases: Pubmed/MEDLINE, Google Scholar, and PsychInfo. We found that since 1989, seven case reports with KS and mental disorders with similar and different characteristics of our case illustration of a patient with KS and psychosis were published.

[Sequential grafts of cutaneous cells: First results of a new procedure and review of the literature]. / GREFFES SÉQUENTIELLES DE CELLULES CUTANÉES PREMIERS RÉSULTATS D'UN NOUVEAU PROCÉDÉ ET REVUE DE LA LITTÉRATURE.

OBJECTIVE: A new choice for major burn wounds is presented. An alternative method for skin grafting and cutaneous substitute for bum victims and chronic non healing wounds. The new method of skin grafting is applied repetitively and non-invasively until healing is achieved. PATIENTS AND PROCEDURE: 39 patients including 33 burns victims and six with chronic wounds were treated between February and September 2012. One to four square centimeters of autologous skin graft were transformed with biodegradation of cellular peptic bonds with the goal of obtaining a rich solution of cutaneous cells (1.5 million skin cells/cm2). The process duration averaged 100 minutes. Part of the solution was sprayed immediately on the recipient skin zones. The remaining solution was divided up and kept in cryotubes inside a container of liquid nitrogen. Successive sprays were performed at each dressing. RESULTS: Good esthetic results on the whole as well as functional for patients with deep 2nd degree burns; healing was achieved in 10-12 days. Third degree burns and chronic wounds showed encouraging results for small surfaces. DISCUSSION: We present a new original technique without prior in vitro culture that gives autologous cellular grafts, including epidermal, junctional and stem cells that are necessary for skin regeneration. The contraindications to the technique are infected, oozing, hemorrhagic or granulomatous wounds. CONCLUSION: This is a technique that deserves to be practiced and should have its place in the therapeutic arsenal of burns and chronic wounds.

Psychiatric manifestations in moyamoya disease: more than a puff of smoke? a systematic review and a case-reports meta-analysis.

Introduction: Moyamoya disease (MMD) is a life-threatening condition characterized by stenosis of intracranial arteries. Despite the frequency and the impact of psychiatric symptoms on the long-term prognosis and quality of life of MMD patients, no systematic review on this topic exists. Methods: This systematic review and meta-analysis included 41 studies (29 being case reports), from PubMed, Scopus, Embase until 27/3/2023, on MMD patients exhibiting psychiatric symptoms. Results: Despite a fair average quality of the articles, quantitative synthesis through logistic regression was possible only for case reports, due to heterogeneity between the other studies. Psychosis, the most frequent psychiatric symptom reported in case reports, was more frequent in MMD patients with left hemisphere involvement. Neurological symptoms occurrence increased the odds of MMD diagnosis preceding psychiatric symptoms. Psychiatric symptoms are highly prevalent in MMD patients and are relatively often the only presenting symptoms. Discussion: We discuss the diagnostic, therapeutic, and prognostic implications of recognizing and characterizing specific psychiatric symptoms in MMD, outlining preliminary guidelines for targeted pharmacological and psychotherapeutic interventions. Lastly, we outline future research and clinical perspectives, striving to enhance the oft-overlooked psychiatric care for MMD patients and to ameliorate their long-term outcome. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023406303.

Positive and negative symptoms in methamphetamine-induced psychosis compared to schizophrenia: A systematic review and meta-analysis.

BACKGROUND: The clinical profiles of methamphetamine-induced psychosis (MIP) and schizophrenia are largely overlapping making differentiation challenging. In this systematic review and meta-analysis, we aim to compare the positive and negative symptoms of MIP and schizophrenia to better understand the differences between them. STUDY DESIGN: In accordance with our pre-registered protocol (CRD42021286619), we conducted a search of English-language studies up to December 16th, 2022, in PubMed, EMBASE, and PsycINFO, including stable outpatients with MIP and schizophrenia. We used the Newcastle-Ottawa Scale to measure the quality of cross-sectional, case-control, and cohort studies. STUDY RESULTS: Of the 2052 articles retrieved, we included 12 studies (6 cross-sectional, 3 case-control, and 2 cohort studies) in our meta-analysis, involving 624 individuals with MIP and 524 individuals with schizophrenia. Our analysis found no significant difference in positive symptoms between the two groups (SMD, -0.01; 95%CI, -0.13 to +0.11; p = 1). However, individuals with MIP showed significantly less negative symptoms compared to those with schizophrenia (SMD, -0.35; 95CI%, -0.54 to -0.16; p = 0.01; I2 = 54 %). Our sensitivity analysis, which included only studies with a low risk of bias, did not change the results. However, our meta-analysis is limited by its cross-sectional approach, which limits the interpretation of causal associations. Furthermore, differences in population, inclusion criteria, methodology, and drug exposure impact our findings. CONCLUSIONS: Negative symptoms are less prominent in individuals with MIP. While both groups do not differ regarding positive symptoms, raises the possibility of shared and partly different underlying neurobiological mechanisms related to MIP and schizophrenia.

Targeted psychological and psychosocial interventions for auditory hallucinations in persons with psychotic disorders: Protocol for a systematic review and meta-analysis.

BACKGROUND: In recent years, a growing body of evidence has demonstrated the efficacy of non-pharmacological interventions for schizophrenia spectrum disorders (SSD) including positive symptoms such as auditory hallucinations (AH). However, clinical trials predominantly examine general treatment effects for positive symptoms. Therefore, previous research is lacking in comprehensive and clear evidence about psychological and psychosocial approaches that are primarily tailored to treat AH. To overcome this knowledge gap in the current literature, we will conduct a systematic review and meta-analysis to assess the efficacy of clearly targeted psychological and psychosocial interventions for AH in persons with SSD. METHODS AND ANALYSIS: This study protocol has been developed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We will include all randomized controlled trials analyzing the efficacy of targeted psychological and psychosocial interventions especially aimed at treating AH in SSD. We will include studies on adult patients with SSD experiencing AH. The primary outcome will be the change on a published rating scale measuring AH. Secondary outcomes will be delusions, overall symptoms, negative symptoms, depression, social functioning, quality of life, and acceptability (drop-out). We will search relevant databases and the reference lists of included literature. The study selection process will be conducted by two independent reviewers. We will conduct a random-effect meta-analysis to consider heterogeneity across studies. Analyses will be carried out by software packages in R. The risk of bias in each study will be evaluated using the Cochrane Risk of Bias tool. Assessment of heterogeneity and sensitivity analysis will be conducted. DISCUSSION: The proposed study will augment the existing evidence by providing an overview of effective treatment approaches and their overall efficacy at treating AH in SSD. These findings will complement existing evidence that may impact future treatment implementations in clinical practice by addressing effective strategies to treat AH and therefore improve outcomes for the addressed population. ETHICS AND DISSEMINATION: No ethical issues are foreseen. We will publish the results from this study in peer-reviewed journals and at relevant scientific conferences. TRIAL REGISTRATION: PROSPERO registration number: CRD42023475704.

Mindfulness-based interventions for patients with schizophrenia spectrum disorders: A systematic review of the literature.

BACKGROUND: Mindfulness-based interventions (MBIs) have emerged as secular practices, including elements of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT). While MBIs have been widely adopted for physical and mental illness, only a few available programs are explicitly adapted for psychosis. However, previous reviews have reported the vital heterogeneity regarding treatment program structure. Therefore, this review aims to compare the structure of different mindfulness protocols applied to patients with schizophrenia spectrum disorder (SSD). METHODS: A systematic search was conducted up to March 2023 in PubMed, Embase and PsycInfo. Following our protocol (CRD 42023253356), we followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. RESULTS: We included 22 randomized controlled trials (RCTs) involving 1500 patients SSD. All programs varied in structure, session components, duration, and instructor experience. While MBSR-like programs focused on stress reactivity, MBCT-like programs addressed primary symptoms of psychosis and relapse prevention. Despite the heterogeneity of programs, some common mechanisms emerged, including attention training, emotion and stress regulation, decentering, self-compassion, and cognitive restructuring. CONCLUSIONS: The critical heterogeneity found limits the interpretation of results. However, most recent trials present fewer risks of bias and more homogenous programs. Findings suggested potential benefits, such as reduced negative symptoms, increased well-being, and decreased hospitalization rates. For future studies, authors should align on more congruent MBIs programs for patients with SSD. Further research is needed to identify optimal mindfulness teaching approaches for patients with psychosis and investigate specific mechanisms of action, relevant processes, and optimal doses in varying settings.

Half a Century of Research on Posttraumatic Stress Disorder: A Scientometric Analysis.

We conducted a scientometric analysis to outline clinical research on posttraumatic stress disorder (PTSD). Our primary objective was to perform a broad-ranging scientometric analysis to evaluate key themes and trends over the past decades. Our secondary objective was to measure research network performance. We conducted a systematic search in the Web of Science Core Collection up to 15 August 2022 for publications on PTSD. We identified 42,170 publications published between 1945 and 2022. We used CiteSpace to retrieve the co-cited reference network (1978-2022) that presented significant modularity and mean silhouette scores, indicating highly credible clusters (Q = 0.915, S = 0.795). Four major trends of research were identified: 'war veterans and refugees', 'treatment of PTSD/neuroimaging', 'evidence syntheses', and 'somatic symptoms of PTSD'. The largest cluster of research concerned evidence synthesis for genetic predisposition and environmental exposures leading to PTSD occurrence. Research on war-related trauma has shifted from battlefield-related in-person exposure trauma to drone operator trauma and is being out published by civilian-related trauma research, such as the 'COVID-19' pandemic impact, 'postpartum', and 'grief disorder'. The focus on the most recent trends in the research revealed a burst in the 'treatment of PTSD' with the development of Mhealth, virtual reality, and psychedelic drugs. The collaboration networks reveal a central place for the USA research network, and although relatively isolated, a recent surge of publications from China was found. Compared to other psychiatric disorders, we found a lack of high-quality randomized controlled trials for pharmacological and nonpharmacological treatments. These results can inform funding agencies and future research.

Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders: A Systematic Review and Dose-Response Meta-Analysis.

Importance: Noninvasive brain stimulation (NIBS) interventions have been shown to be efficacious in several mental disorders, but the optimal dose stimulation parameters for each disorder are unknown. Objective: To define NIBS dose stimulation parameters associated with the greatest efficacy in symptom improvement across mental disorders. Data Sources: Studies were drawn from an updated (to April 30, 2023) previous systematic review based on a search of PubMed, OVID, and Web of Knowledge. Study Selection: Randomized clinical trials were selected that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for any mental disorder in adults aged 18 years or older. Data Extraction and Synthesis: Two authors independently extracted the data. A 1-stage dose-response meta-analysis using a random-effects model was performed. Sensitivity analyses were conducted to test robustness of the findings. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The main outcome was the near-maximal effective doses of total pulses received for TMS and total current dose in coulombs for tDCS. Results: A total of 110 studies with 4820 participants (2659 men [61.4%]; mean [SD] age, 42.3 [8.8] years) were included. The following significant dose-response associations emerged with bell-shaped curves: (1) in schizophrenia, high-frequency (HF) TMS on the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (χ2 = 9.35; df = 2; P = .009) and TMS on the left temporoparietal junction for resistant hallucinations (χ2 = 36.52; df = 2; P < .001); (2) in depression, HF-DLPFC TMS (χ2 = 14.49; df = 2; P < .001); (3) in treatment-resistant depression, LDLPFC tDCS (χ2 = 14.56; df = 2; P < .001); and (4) in substance use disorder, LDLPFC tDCS (χ2 = 33.63; df = 2; P < .001). The following significant dose-response associations emerged with plateaued or ascending curves: (1) in depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (χ2 = 25.67; df = 2; P = .001); (2) for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (χ2 = 5.86; df = 2; P = .004); (3) in obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (χ2 = 20.65; df = 2; P < .001) and LF TMS on the orbitofrontal cortex with a plateaued curve (χ2 = 15.19; df = 2; P < .001); and (4) in posttraumatic stress disorder, LF-RDLPFC TMS with ascending curve (χ2 = 54.15; df = 2; P < .001). Sensitivity analyses confirmed the main findings. Conclusions and Relevance: The study findings suggest that NIBS yields specific outcomes based on dose parameters across various mental disorders and brain regions. Clinicians should consider these dose parameters when prescribing NIBS. Additional research is needed to prospectively validate the findings in randomized, sham-controlled trials and explore how other parameters contribute to the observed dose-response association.

The Italian contribution to pediatric sleep medicine: A scientometric analysis.

We conducted the first scientometric analysis to quantitatively assess the scientific contribution of researchers from Italian institutions in the field of pediatric sleep medicine. We searched Science Citation Index Expanded from Web of Science (WOS) Science Citation up to November 3rd, 2022. Bibliometrix R packages (3.1.4) and CiteSpace (6.0.R2) were used to extract and analyze co-citation reference networks, co-occurring keyword networks, co-authorship network, co-cited institutions, and co-cited journals. We retrieved a total of 2499 documents, published between 1975 and 2022. Co-cited reference networks showed four main clusters of highly cited topics: evidence synthesis of publications on sleep disorders in children and adolescents, sleep and neurological disorders, non-pharmacological treatments of sleep disturbances, and sleep and Covid-19 in youth. Co-occurring keyword networks showed an earlier focus on the neurophysiology of sleep/neurological disorders, followed by a trend on the association of sleep disturbances to neurodevelopmental disorders and behavioral aspects. Co-authorship network showed that Italian researchers in the field of pediatric sleep medicine tend to be highly collaborative internationally. Overall, Italian researchers have provided a crucial contribution to pediatric sleep medicine across a number of specific topics, spanning from neurophysiology to treatment, and from neurological to behavioral/psychopathological aspects.

Neuropsychiatric disturbances in mild cognitive impairment: A scientometric analysis.

Behavioral and psychological symptoms of dementia (BPSD) have been extensively studied in dementia than its prodromal stage, known as mild cognitive impairment (MCI). A scientometric study on BPSD in MCI would be valuable in synthesizing the existing body of research and providing insights into the trends, networks, and influencers within this area. We searched for related literature in the Web of Science database and extracted complete text and citation records of each publication. The primary objective was to map the research evolution of BPSD in MCI and highlight dominant research themes. The secondary objective was to identify research network characteristics (authors, journals, countries, and institutions) and abundances. A total of 12,369 studies published between 1980 and 2022 were included in the analysis. We found 51 distinct clusters from the co-cited reference network that were highly credible with significant modularity (Q = 0.856) and silhouette scores (S = 0.932). Five major research domains were identified: symptoms, diagnosis, brain substrates, biochemical pathways, and interventions. In recent years, the research focus in this area has been on gut microbiota, e-health, COVID-19, cognition, and delirium. Collectively, findings from this scientometric analysis can help clarify the scope and direction of future research and clinical practices.

Comparative Effects of 11 Antipsychotics on Weight Gain and Metabolic Function in Patients With Acute Schizophrenia: A Dose-Response Meta-Analysis.

Objective: To investigate the association of metabolic side effects with antipsychotic dose, we conducted a dose-response meta-analysis of randomized controlled trials (RCTs) in which antipsychotics were administered to people with schizophrenia. The primary outcome was mean change in weight. The secondary outcomes were the mean changes in metabolic parameters.Data Sources: MEDLINE, Embase, PubMed, PsyARTICLES, PsycINFO, Cochrane Database of Systematic Reviews, and different trial registries were searched for articles published in English until February 2021.Study Selection: We identified fixed-dose RCTs with first- or second-generation antipsychotics. The quality of RCTs was measured with Cochrane's Risk of Bias tool.Data Extraction: We performed a dose-response meta-analysis.Results: We retained 52 RCTs including 22,588 participants. With the exception of aripiprazole long-acting injectable (LAI), all investigated antipsychotics presented significant dose-response associations with weight, from lurasidone with a quasi-parabolic shaped curve (9 studies, estimation of 95% effective dose [ED95; 59.93 mg/d] = 0.53 kg/6 wk) to olanzapine LAI with a curve that continued to increase with the dose (1 study, ED95 [15.05 mg/d] = 4.29 kg/8 wk). All curves could be ordered in 3 different classes of shapes-quasi-parabolic, plateau, and ascending.Conclusions: We found significant dose-response associations for weight and metabolic variables, with a unique signature for each antipsychotic. Weight gain can occur at a relatively low median effective dose, and increasing doses can be associated with greater weight gain for some drugs. Despite several limitations, including the limited number of available studies, our results may provide useful information for preventing weight gain and metabolic disturbance by adapting antipsychotic doses.Registration: PROSPERO ID number CRD42021176569.

Pharmaco-EEG of antipsychotic treatment response: a systematic review.

Response to antipsychotic medications (AP) is subjected to a wide and unpredictable variability and efforts were directed to discover predictive biomarkers to personalize treatment. Electroencephalography abnormalities in subjects with schizophrenia are well established, as well as a pattern of EEG changes induced by APs. The aim of this review is to provide a synthesis of the EEG features that are related to AP efficacy, including both pre-treatment signatures and changes induced by APs during treatment. A systematic review of English articles using PubMed, PsychINFO and the Cochrane database of systematic reviews was undertaken until july 2023. Additional studies were added by hand search. Studies having as an endpoint the relationship between AP-related clinical improvement and electroencephalographic features were included. Heterogeneity prevented a quantitative synthesis. Out of 1232 records screened, 22 studies were included in a final qualitative synthesis. Included studies evaluated resting-state and task-related power spectra, functional connectivity, microstates and epileptic abnormalities. At pre-treatment resting-state EEG, the most relevant predictors of a poor response were a change in theta power compared to healthy control, a high alpha power and connectivity, and diminished beta power. Considering EEG during treatment, an increased theta power, a reduced beta-band activity, an increased alpha activity, a decreased coherence in theta, alpha and beta-band were related to a favorable outcome. EEG is promising as a method to create a predictive biomarker for response to APs; further investigations are warranted to harmonize and generalize the contradictory results of reviewed studies.

Thirty years of research on negative symptoms of schizophrenia: A scientometric analysis of hotspots, bursts, and research trends.

Research on negative symptoms of schizophrenia has received renewed interest since the 1980s. A scientometric analysis that objectively maps scientific knowledge, with changes in recent trends, is currently lacking. We searched the Web of Science Core Collection (WOSCC) on December 17, 2021 using relevant keywords. R-bibliometrix and CiteSpace were used to perform the analysis. We retrieved 27,568 references published between 1966 and 2022. An exponential rise in scientific interest was observed, with an average annual growth rate in publications of 16.56% from 1990 to 2010. The co-cited reference network that was retrieved presented 24 different clusters with a well-structured network (Q=0.7921; S=0.9016). Two distinct major research trends were identified: research on the conceptualization and treatment of negative symptoms. The latest trends in research on negative symptoms include evidence synthesis, nonpharmacological treatments, and computational psychiatry. Scientometric analyses provide a useful summary of changes in negative symptom research across time by identifying intellectual turning point papers and emerging trends. These results will be informative for systematic reviews, meta-analyses, and generating novel hypotheses.

A century of research on neuromodulation interventions: A scientometric analysis of trends and knowledge maps.

Interest in neurostimulation interventions has significantly grown in recent decades, yet a scientometric analysis objectively mapping scientific knowledge and recent trends remains unpublished. Using relevant keywords, we conducted a search in the Web of Science Core Collection on September 23, 2022, retrieving a total of 47,681 documents with 987,979 references. We identified two prominent research trends: 'noninvasive brain stimulation' and 'invasive brain stimulation.' These methods have interconnected over time, forming a cluster focused on evidence synthesis. Noteworthy emerging research trends encompassed 'transcutaneous auricular vagus nerve stimulation,' 'DBS/epilepsy in the pediatric population,' 'spinal cord stimulation,' and 'brain-machine interface.' While progress has been made for various neurostimulation interventions, their approval as adjuvant treatments remains limited, and optimal stimulation parameters lack consensus. Enhancing communication between experts of both neurostimulation types and encouraging novel translational research could foster further development. These findings offer valuable insights for funding agencies and research groups, guiding future directions in the field.

Psilocybin-assisted therapy for depression: A systematic review and dose-response meta-analysis of human studies.

Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a dose-response meta-analysis to find the optimal dosage of psilocybin to reduce depression scores. Following our protocol (CRD 42022220190) multiple electronic databases were searched from their inception until February 2023, to identify double-blind randomized placebo-controlled (RCTs) fixed-dose trials evaluating the use of psilocybin for adult patients with primary or secondary depression. A one-stage dose-response meta-analysis with restricted cubic splines was used. Cochrane risk of bias was used to assess risk of bias. Our analysis included seven studies with a total of 489 participants. Among these, four studies focused on primary depression (N = 366), including one study with patients suffering from treatment-resistant depression. The remaining three studies examined secondary depression (N = 123). The determined 95% effective doses per day (ED95) were 8.92, 24.68, and 36.08 mg/70 kg for patients with secondary depression, primary depression, and both subgroups, respectively. We observed significant dose-response associations for all curves, each plateauing at different levels, except for the bell-shaped curve observed in the case of secondary depression. Additionally, we found significant dose-response associations for various side effects, including physical discomfort, blood pressure increase, nausea/vomiting, headache/migraine, and the risk of prolonged psychosis. In conclusion, we discovered specific ED95 values for different populations, indicating higher ED95 values for treatment-resistant depression, primary depression, and secondary depression groups. Further RCTs are necessary for each population to determine the optimal dosage, allowing for maximum efficacy while minimizing side effects.