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Neuroscience and Biobehavioral Reviews Jan 2022Although schizophrenia is associated with increased presynaptic dopamine function in the striatum, it remains unclear if neuromelanin levels, which are thought to serve... (Meta-Analysis)
Meta-Analysis Review
Although schizophrenia is associated with increased presynaptic dopamine function in the striatum, it remains unclear if neuromelanin levels, which are thought to serve as a biomarker for midbrain dopamine neuron function, are increased in patients with schizophrenia. We conducted a systematic review and meta-analysis of magnetic resonance imaging (MRI) and postmortem studies comparing neuromelanin (NM) levels between patients with schizophrenia and healthy controls (HCs). Standard mean differences were calculated to assess group differences in NM accumulation levels between patients with schizophrenia and HCs. This study included 7 articles in total. Five studies employed NM-sensitive MRI (NM-MRI) and two were postmortem brain studies. The patient group (n = 163) showed higher NM levels in the substantia nigra (SN) than HCs (n = 228) in both the analysis of the seven studies and the subgroup analysis of the 5 NM-MRI studies. This analysis suggest increased NM levels in the SN may be a potential biomarker for stratifying schizophrenia, warranting further research that accounts for the heterogeneity of this disorder.
Topics: Humans; Magnetic Resonance Imaging; Melanins; Schizophrenia; Substantia Nigra
PubMed: 34718049
DOI: 10.1016/j.neubiorev.2021.10.028 -
JAMA Network Open May 2024Noninvasive brain stimulation (NIBS) interventions have been shown to be efficacious in several mental disorders, but the optimal dose stimulation parameters for each... (Meta-Analysis)
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.
Topics: Humans; Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation; Mental Disorders; Adult; Male; Female; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 38776083
DOI: 10.1001/jamanetworkopen.2024.12616 -
Journal of Psychiatric Research Jun 2024Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and... (Review)
Review
Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and risperidone are two commonly prescribed antipsychotics, metabolized primarily through CYP2D6. Here, we aimed to provide an overview of the effect of CYP2C19 and CYP2D6 on side-effects of aripiprazole and risperidone, and expand on existing literature by critically examining methodological issues associated with pharmacogenetic studies. A PRISMA compliant search of six electronic databases (Pubmed, PsychInfo, Embase, Central, Web of Science, and Google Scholar) identified pharmacogenetic studies on aripiprazole and risperidone. 2007 publications were first identified, of which 34 were included. Quality of literature was estimated using Newcastle-Ottowa Quality Assessment Scale (NOS) and revised Cochrane Risk of Bias tool. The average NOS score was 5.8 (range: 3-8) for risperidone literature and 5 for aripiprazole (range: 4-6). All RCTs on aripiprazole were rated as high risk of bias, and four out of six for risperidone literature. Study populations ranged from healthy volunteers to inpatient individuals in psychiatric units and included adult and pediatric samples. All n = 34 studies examined CYP2D6. Only one study genotyped for CYP2C19 and found a positive association with neurological side-effects of risperidone. Most studies did not report any relationship between CYP2D6 and any side-effect outcome. Heterogeneity between and within studies limited the ability to synthesize data and draw definitive conclusions. Studies lacked statistical power due to small sample size, selective genotyping methods, and study design. Large-scale randomized trials with multiple measurements, providing robust evidence on this topic, are suggested.
Topics: Humans; Aripiprazole; Cytochrome P-450 CYP2D6; Risperidone; Cytochrome P-450 CYP2C19; Antipsychotic Agents
PubMed: 38631139
DOI: 10.1016/j.jpsychires.2024.04.001 -
BMJ Open Mar 2021To examine the literature on how recovery of people with severe mental illness (SMI) is conceptualised in low/middle-income countries (LMICs), and in particular what... (Review)
Review
OBJECTIVE
To examine the literature on how recovery of people with severe mental illness (SMI) is conceptualised in low/middle-income countries (LMICs), and in particular what factors are thought to facilitate recovery.
DESIGN
Scoping review.
DATA SOURCES AND ELIGIBILITY
We searched 14 electronic databases, hand searched citations and consulted with experts during the period May-December 2019. Eligible studies were independently screened for inclusion and exclusion by two reviewers. Unresolved discrepancies were referred to a third reviewer.
DATA EXTRACTION AND SYNTHESIS
All bibliographical data and study characteristics were extracted using a data charting form. Selected studies were analysed through a thematic analysis emerging from extracted data.
RESULTS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram offers a summary of the results: 4201 titles, 1530 abstracts and 109 full-text articles were screened. Ten articles were selected for inclusion: two from Turkey, two from India, and one each from China, Swaziland, Indonesia, Egypt, South Africa and Vietnam. Although most studies used qualitative methods, data collection and sampling methods were heterogeneous. One study reported on service provider perspectives while the rest provided perspectives from a combination of service users and caregivers. Three themes emerged from the data analysis. First, studies frame recovery as a personal journey occurring along a continuum. Second, there was an emphasis on social relationships as a facilitator of recovery. Third, spirituality emerged as both a facilitator and an indicator of recovery. These themes were not mutually exclusive and some overlap exists.
CONCLUSION
Although there were commonalities with how high-income countries describe recovery, we also found differences in conceptualisation. These differences in how recovery was understood reflect the importance of framing the personal recovery concept in relation to local needs and contextual issues found in LMICs. This review highlighted the current sparse evidence base and the need to better understand recovery from SMI in LMICs.
Topics: China; Developing Countries; Egypt; Eswatini; Humans; India; Indonesia; Mental Disorders; South Africa; Turkey; Vietnam
PubMed: 33762242
DOI: 10.1136/bmjopen-2020-045005 -
Annals of Medicine Dec 2023The aim of this systematic review and meta-analysis was to identify, evaluate, and synthesize the evidence from studies that have investigated the treatment effect... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review and meta-analysis was to identify, evaluate, and synthesize the evidence from studies that have investigated the treatment effect telemedicine interventions on depressive symptoms, quality of life, and work and social functioning in patients with depression. Six electronic databases (MEDLINE [1916-2021], PubMED [1950-2021], PsycINFO [1971-2021], Scopus [2004-2021], Embase [1972-2021], and CINAHL [1937-2021]) were systematically searched in March 2021. Reference lists of identified articles were hand searched. Randomized controlled trials were included if they investigated the treatment effects telemedicine interventions in patients who had a depression diagnosis. Quality assessment was evaluated using the critical appraisal checklists developed by the Joanna Briggs Institute. Seventeen (17) trials ( = 2,394) met eligibility criteria and were included in the analysis. Eleven (11) randomized controlled trials shared common outcome measures, allowing meta-analysis. The results provided evidence that treatment telemedicine interventions were beneficial for depressive symptoms (standardized mean difference= -0.44; 95% CI= -0.64 to -0.25; < .001) and quality of life (standardized mean difference= 0.25, 95% CI -0.01 to 0.49, = .04) in patients of depression. There were insufficient data for meta-analysis of work and social functioning. This study showed the positive effects of treatment telemedicine interventions on depressive symptoms and quality of life in patients with depression and supported the idea for clinical practice to establish a well-organized telepsychiatry system.KEY MESSAGESTelemedicine is effective at reducing symptoms of depression.Telemedicine can improve quality of life in persons with depression.
Topics: Humans; Depression; Quality of Life; Psychiatry; Telemedicine
PubMed: 36920229
DOI: 10.1080/07853890.2023.2187078 -
Progress in Neuro-psychopharmacology &... Jun 2022Next-generation sequencing now enables the rapid and affordable production of reliable biological data at multiple molecular levels, collectively referred to as "omics".... (Review)
Review
Next-generation sequencing now enables the rapid and affordable production of reliable biological data at multiple molecular levels, collectively referred to as "omics". To maximize the potential for discovery, computational biologists have created and adapted integrative multi-omic analytical methods. When applied to diseases with traceable pathophysiology such as cancer, these new algorithms and statistical approaches have enabled the discovery of clinically relevant molecular mechanisms and biomarkers. In contrast, these methods have been much less applied to the field of molecular psychiatry, although diagnostic and prognostic biomarkers are similarly needed. In the present review, we first briefly summarize main findings from two decades of studies that investigated single molecular processes in relation to mood disorders. Then, we conduct a systematic review of multi-omic strategies that have been proposed and used more recently. We also list databases and types of data available to researchers for future work. Finally, we present the newest methodologies that have been employed for multi-omics integration in other medical fields, and discuss their potential for molecular psychiatry studies.
Topics: Biomarkers; Genomics; Humans; Mood Disorders
PubMed: 35104608
DOI: 10.1016/j.pnpbp.2022.110520 -
Psychiatry Research Nov 2023Assessing and managing suicide behaviors is highly relevant to individuals with schizophrenia spectrum disorders. Our study aims to assess the association between... (Meta-Analysis)
Meta-Analysis Review
Assessing and managing suicide behaviors is highly relevant to individuals with schizophrenia spectrum disorders. Our study aims to assess the association between adverse childhood experiences and suicidal behaviors in individuals with schizophrenia spectrum disorders. We included observational studies comparing the probability of suicide behaviors in adults with schizophrenia spectrum disorders exposed and unexposed to adverse childhood experiences. Odds ratio estimates were obtained by pooling data using a random-effects pairwise meta-analysis. Standardized criteria were used to assess the strength of the association of the pooled estimate. We found 21 eligible studies reporting outcomes for 6257 individuals from 11 countries. The primary outcome revealed an association between any suicidal behavior and adverse childhood experiences, which resulted "highly suggestive" according to validated Umbrella Criteria. Similarly, a positive association was confirmed for suicidal ideation and suicide attempt and for any subtype of adverse childhood experience. This meta-analysis showed that exposure to adverse childhood experiences strongly increases the probability of suicide behaviors in people with schizophrenia spectrum disorders.
Topics: Adult; Humans; Suicidal Ideation; Schizophrenia; Adverse Childhood Experiences; Suicide, Attempted; Probability
PubMed: 37769371
DOI: 10.1016/j.psychres.2023.115488 -
European Psychiatry : the Journal of... Nov 2021To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP).
METHODS
A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies.
RESULTS
One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49-58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27-36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found.
CONCLUSIONS
Half of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years.
Topics: Databases, Factual; Employment; Humans; Psychotic Disorders; Registries
PubMed: 34730080
DOI: 10.1192/j.eurpsy.2021.2246 -
Bipolar Disorders Jun 2022Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in... (Review)
Review
Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force.
BACKGROUND
Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations.
METHODS
The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials.
RESULTS
We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking.
CONCLUSIONS
Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.
Topics: Bipolar Disorder; Cognition; Cognitive Dysfunction; Humans; Lurasidone Hydrochloride; Mood Disorders
PubMed: 35174594
DOI: 10.1111/bdi.13193 -
Journal of Affective Disorders May 2020Maternal use of benzodiazepines during pregnancy is common and has increased over the last decades. In this systematic review and meta-analysis, we studied the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Maternal use of benzodiazepines during pregnancy is common and has increased over the last decades. In this systematic review and meta-analysis, we studied the literature to estimate the worldwide use of benzodiazepines before, during and after pregnancy, which could help to estimate benzodiazepine exposure and to prioritize and guide future investigations.
METHODS
We systematically searched Embase, Medline Ovid, Web of Science and Cochrane Central up until July 2019 for studies reporting on benzodiazepine use before (12 months), during and after pregnancy (12 months). Random effects meta-analysis was conducted to calculate pooled prevalence estimates, as well as stratified according to substantive variables.
RESULTS
We identified 32 studies reporting on 28 countries, together reporting on 7,343,571 pregnancies. The worldwide prevalence of benzodiazepine use/prescriptions during pregnancy was 1.9% (95%CI 1.6%-2.2%; I 97.48%). Highest prevalence was found in the third trimester (3.1%; 95%CI 1.8%-4.5%; I 99.83%). Lorazepam was the most frequently used/prescribed benzodiazepine (1.5%; 95%CI 0.5%-2.5%; I 99.87%). Highest prevalence was found in Eastern Europe (14.0%; 95%CI 12.1%-15.9%; I 0.00%).
LIMITATIONS
All analyses revealed considerable heterogeneity.
CONCLUSIONS
Our meta-analysis confirmed that benzodiazepine use before, during and after pregnancy is prevalent. The relatively common use of benzodiazepines with possible risks for both mother and (unborn) child is worrying and calls for prescription guidelines for women, starting in the preconception period. Given the substantial proportion of children exposed to benzodiazepines in utero, future research should continue to study the short- and long-term safety of maternal benzodiazepine use during pregnancy and to explore non-pharmacological alternative treatments.
Topics: Anxiety; Benzodiazepines; Child; Female; Humans; Hypnotics and Sedatives; Pharmaceutical Preparations; Pregnancy; Prevalence
PubMed: 32217339
DOI: 10.1016/j.jad.2020.03.014