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Psychopharmacology May 2016Psychosocial stressors are a well-documented risk factor for mental illness. Neuroinflammation, in particular elevated microglial activity, has been proposed to mediate... (Review)
Review
RATIONALE
Psychosocial stressors are a well-documented risk factor for mental illness. Neuroinflammation, in particular elevated microglial activity, has been proposed to mediate this association. A number of preclinical studies have investigated the effect of stress on microglial activity. However, these have not been systematically reviewed before.
OBJECTIVES
This study aims to systematically review the effects of stress on microglia, as indexed by the histological microglial marker ionised calcium binding adaptor molecule 1 (Iba-1), and consider the implications of these for the role of stress in the development of mental disorders.
METHODS
A systematic review was undertaken using pre-defined search criteria on PubMed and EMBASE. Inclusion and data extraction was agreed by two independent researchers after review of abstracts and full text.
RESULTS
Eighteen studies met the inclusion criteria. These used seven different psychosocial stressors, including chronic restraint, social isolation and repeated social defeat in gerbils, mice and/or rats. The hippocampus (11/18 studies) and prefrontal cortex (13/18 studies) were the most frequently studied areas. Within the hippocampus, increased Iba-1 levels of between 20 and 200 % were reported by all 11 studies; however, one study found this to be a duration-dependent effect. Of those examining the prefrontal cortex, ∼75 % found psychosocial stress resulted in elevated Iba-1 activity. Elevations were also consistently seen in the nucleus accumbens, and under some stress conditions in the amygdala and paraventricular nucleus.
CONCLUSIONS
There is consistent evidence that a range of psychosocial stressors lead to elevated microglial activity in the hippocampus and good evidence that this is also the case in other brain regions. These effects were seen with early-life/prenatal stress, as well as stressors in adulthood. We consider these findings in terms of the two-hit hypothesis, which proposes that early-life stress primes microglia, leading to a potentiated response to subsequent stress. The implications for understanding the pathoaetiology of mental disorders and the development of new treatments are also considered.
Topics: Animals; Humans; Inflammation; Mental Disorders; Microglia; Psychoneuroimmunology; Psychotic Disorders; Stress, Psychological
PubMed: 26847047
DOI: 10.1007/s00213-016-4218-9 -
The Cochrane Database of Systematic... Dec 2021Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an... (Review)
Review
BACKGROUND
Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an antipsychotic, another treatment (e.g. mifepristone), or combination of an antidepressant plus an antipsychotic. This is an update of a review first published in 2005 and last updated in 2015.
OBJECTIVES
1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, mifepristone monotherapy, and the combination of an antidepressant plus an antipsychotic versus placebo and/or each other. 2. To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment.
SEARCH METHODS
A search of the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR); Ovid MEDLINE (1950-); Embase (1974-); and PsycINFO (1960-) was conducted on 21 February 2020. Reference lists of all included studies and related reviews were screened and key study authors contacted.
SELECTION CRITERIA
All randomised controlled trials (RCTs) that included participants with acute major depression with psychotic features, as well as RCTs consisting of participants with acute major depression with or without psychotic features, that reported separately on the subgroup of participants with psychotic features.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias in the included studies, according to criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used intention-to-treat data. Primary outcomes were clinical response for efficacy and overall dropout rate for harm/tolerance. Secondary outcome were remission of depression, change from baseline severity score, quality of life, and dropout rate due to adverse effects. For dichotomous efficacy outcomes (i.e. response and overall dropout), risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Regarding the primary outcome of harm, only overall dropout rates were available for all studies. If the study did not report any of the response criteria as defined above, remission as defined here could be used as an alternative. For continuously distributed outcomes, it was not possible to extract data from the RCTs. MAIN RESULTS: The search identified 3947 abstracts, but only 12 RCTs with a total of 929 participants could be included in the review. Because of clinical heterogeneity, few meta-analyses were possible. The main outcome was reduction in severity (response) of depression, not of psychosis. For depression response, we found no evidence of a difference between antidepressant and placebo (RR 8.40, 95% CI 0.50 to 142.27; participants = 27, studies = 1; very low-certainty evidence) or between antipsychotic and placebo (RR 1.13, 95% CI 0.74 to 1.73; participants = 201, studies = 2; very low-certainty evidence). Furthermore, we found no evidence of a difference in overall dropouts with antidepressant (RR 1.24, 95% CI 0.34 to 4.51; participants = 27, studies = 1; very low-certainty evidence) or antipsychotic monotherapy (RR 0.79, 95% CI 0.57 to 1.08; participants = 201, studies = 2; very low-certainty evidence). No evidence suggests a difference in depression response (RR 2.09, 95% CI 0.64 to 6.82; participants = 36, studies = 1; very low-certainty evidence) or overall dropouts (RR 1.79, 95% CI 0.18 to 18.02; participants = 36, studies = 1; very low-certainty evidence) between antidepressant and antipsychotic. For depression response, low- to very low-certainty evidence suggests that the combination of an antidepressant plus an antipsychotic may be more effective than antipsychotic monotherapy (RR 1.83, 95% CI 1.40 to 2.38; participants = 447, studies = 4), more effective than antidepressant monotherapy (RR 1.42, 95% CI 1.11 to 1.80; participants = 245, studies = 5), and more effective than placebo (RR 1.86, 95% CI 1.23 to 2.82; participants = 148, studies = 2). Very low-certainty evidence suggests no difference in overall dropouts between the combination of an antidepressant plus an antipsychotic versus antipsychotic monotherapy (RR 0.79, 95% CI 0.63 to 1.01; participants = 447, studies = 4), antidepressant monotherapy (RR 0.91, 95% CI 0.55 to 1.50; participants = 245, studies = 5), or placebo alone (RR 0.75, 95% CI 0.48 to 1.18; participants = 148, studies = 2). No study measured change in depression severity from baseline, quality of life, or dropouts due to adverse events. We found no RCTs with mifepristone that fulfilled our inclusion criteria. Risk of bias is considerable: we noted differences between studies with regards to diagnosis, uncertainties around randomisation and allocation concealment, treatment interventions (pharmacological differences between various antidepressants and antipsychotics), and outcome criteria.
AUTHORS' CONCLUSIONS
Psychotic depression is heavily under-studied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone. Evidence for efficacy of mifepristone is lacking.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Major; Humans; Psychotic Disorders; Systematic Reviews as Topic
PubMed: 34875106
DOI: 10.1002/14651858.CD004044.pub5 -
Social Psychiatry and Psychiatric... Apr 2022This systematic review summarizes and presents the current state of research quantifying the relationship between mental disorder and overdose for people who use opioids. (Review)
Review
PURPOSE
This systematic review summarizes and presents the current state of research quantifying the relationship between mental disorder and overdose for people who use opioids.
METHODS
The protocol was published in Open Science Framework. We used the PECOS framework to frame the review question. Studies published between January 1, 2000, and January 4, 2021, from North America, Europe, the United Kingdom, Australia, and New Zealand were systematically identified and screened through searching electronic databases, citations, and by contacting experts. Risk of bias assessments were performed. Data were synthesized using the lumping technique.
RESULTS
Overall, 6512 records were screened and 38 were selected for inclusion. 37 of the 38 studies included in this review show a connection between at least one aspect of mental disorder and opioid overdose. The largest body of evidence exists for internalizing disorders generally and mood disorders specifically, followed by anxiety disorders, although there is also moderate evidence to support the relationship between thought disorders (e.g., schizophrenia, bipolar disorder) and opioid overdose. Moderate evidence also was found for the association between any disorder and overdose.
CONCLUSION
Nearly all reviewed studies found a connection between mental disorder and overdose, and the evidence suggests that having mental disorder is associated with experiencing fatal and non-fatal opioid overdose, but causal direction remains unclear.
Topics: Analgesics, Opioid; Drug Overdose; Europe; Humans; Opiate Overdose; Psychotic Disorders
PubMed: 34796369
DOI: 10.1007/s00127-021-02199-2 -
Schizophrenia Research Dec 2022The aim was to examine the general outcome of schizophrenia after 20 years or more. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim was to examine the general outcome of schizophrenia after 20 years or more.
METHODS
Using the PRISMA guidelines, we conducted a systematic review and meta-analysis with meta-regression on long-term follow-up studies of schizophrenia up until April 21, 2021. We included prospective studies with at least 20 years of follow-up on patients with a diagnosis of schizophrenia, and the studies had to include face-to-face clinical evaluation. We examined outcome in three nested groups: 'recovery', 'good or better' (including also 'recovery'), and 'moderate or better' (including also 'recovery' and 'good or better'). We used random-effects meta-analysis and meta-regression to examine mean estimates and possible moderators.
RESULTS
We identified 1089 records, which were screened by two independent researchers. 14 prospective studies (1991 patients) published between 1978 and 2020 were found eligible. The studies used a range of different scales and definitions for outcome, and some used the same definitions for different outcomes. To compare outcome across studies, we designed and applied a unified template for outcome definitions and cutoffs, based on earlier studies' recommendations. Our meta-analysis found that 24.2 % had 'recovered' (n = 246, CI: 20.3-28.0 %), 35.5 % had a 'good or better' outcome (n = 766, CI: 26.0-45.0%), and 59.7% had 'moderate or better' outcome (n = 1139, CI: 49.3-70.1 %).
CONCLUSIONS
The results contribute to debunk the myth that schizophrenia inevitably has a deteriorating course. Recovery is certainly possible. Schizophrenia remains, however, a severe and complex mental disorder, exhibiting a limited change in prognosis despite >100 years of research and efforts to improve treatment.
Topics: Humans; Schizophrenia; Follow-Up Studies; Prospective Studies; Psychotic Disorders; Prognosis
PubMed: 36417817
DOI: 10.1016/j.schres.2022.11.010 -
BioMed Research International 2015Behavioral and psychological symptoms of dementia (BPSD) are defined as a group of symptoms of disturbed perceptive thought content, mood, or behavior that include... (Review)
Review
INTRODUCTION
Behavioral and psychological symptoms of dementia (BPSD) are defined as a group of symptoms of disturbed perceptive thought content, mood, or behavior that include agitation, depression, apathy, repetitive questioning, psychosis, aggression, sleep problems, and wandering. Care of patients with BPSD involves pharmacological and nonpharmacological interventions. We reviewed studies of nonpharmacological interventions published in the last 10 years.
METHODS
We performed a systematic review in Medline and Embase databases, in the last 10 years, until June 2015. Key words used were (1) non-pharmacological interventions, (2) behavioral symptoms, (3) psychological symptoms, and (4) dementia.
RESULTS
We included 20 studies published in this period. Among these studies, program activities were more frequent (five studies) and the symptoms more responsive to the interventions were agitation.
DISCUSSION
Studies are heterogeneous in many aspects, including size sample, intervention, and instruments of measures.
CONCLUSION
Nonpharmacological interventions are able to provide positive results in reducing symptoms of BPSD. Most studies have shown that these interventions have important and significant efficacy.
Topics: Aggression; Dementia; Depression; Humans; Musculoskeletal Manipulations; Psychomotor Agitation; Psychotic Disorders
PubMed: 26693477
DOI: 10.1155/2015/218980 -
JAMA Psychiatry Jul 2020Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry.
IMPORTANCE
Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry.
OBJECTIVE
To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations.
EVIDENCE REVIEW
Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes.
FINDINGS
In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohen d = 0.57) or educational functioning (Cohen d = 0.21), social functioning (Cohen d = 1.25), and quality of life (Cohen d = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohen d = 0.35) and negative symptoms (Cohen d = 0.39) as well as low functioning (Cohen d = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered.
CONCLUSIONS AND RELEVANCE
This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.
Topics: Adolescent; Adult; Female; Humans; Male; Meta-Analysis as Topic; Psychotic Disorders; Young Adult
PubMed: 32159746
DOI: 10.1001/jamapsychiatry.2019.4779 -
Early Intervention in Psychiatry Feb 2016Psychotic-like experiences (PLEs) or subclinical psychotic experiences have received increased attention as some studies have suggested continuity between PLEs and... (Review)
Review
AIMS
Psychotic-like experiences (PLEs) or subclinical psychotic experiences have received increased attention as some studies have suggested continuity between PLEs and psychotic disorders. However, epidemiological and correlational studies of PLEs showed mixed findings - it is observed that different studies use a wide variety of definitions of PLEs, as well as different assessment tools that are designed to capture such described experiences. The differences in definitions and assessment tools adopted could contribute to the discrepancy of findings. The current review aims to examine the definitions and assessment tools adopted in the studies of PLEs.
METHODS
Literature search was conducted between October 2013 and February 2014 using three search engines: Medline, Web of Science and PubMed.
RESULTS
A total of 76 papers met the selection criteria and were included in the current review. It is found that the majority of papers reviewed defined PLEs quantitatively using assessment tools and do not have a specific phenomenological definition, whereas assessment tools adopted have a wide variety. Furthermore, phenomenological studies of PLEs were rare.
CONCLUSIONS
The variations in definitions and assessment tools of PLEs might contribute to mixed findings in researches. Reaching to a consensus through the study of phenomenology of PLEs is essential to further advancement of the research in this area.
Topics: Humans; Prodromal Symptoms; Psychiatric Status Rating Scales; Psychotic Disorders; Terminology as Topic
PubMed: 25772746
DOI: 10.1111/eip.12228 -
Acta Psychiatrica Scandinavica Aug 2023Genetic studies of bipolar disorder (BD) have shown varied results, which is in part because of the heterogeneity of the disorder. Identifying clinical phenotypes of BD... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genetic studies of bipolar disorder (BD) have shown varied results, which is in part because of the heterogeneity of the disorder. Identifying clinical phenotypes of BD could reduce variability and benefit research. Since BD has a robust genetic component, studies can investigate clinical traits that cluster in families to identify phenotypes with a probable genetic basis.
METHODS
We conducted a systematic review of the current literature on familial clinical traits of BD. Text screening and data extraction were performed independently by two reviewers, and random effects meta-analysis was used.
RESULTS
Of 1117 unique records, 16 studies met inclusion criteria. These studies indicated 14 potentially familial traits of BD: age of onset (OR: 4.50; 95% CI: [3.25, 6.22]), bipolar type (OR: 2.05 [1.50, 2.79]), lithium response (OR: 3.71 [1.28, 10.82]), polarity at onset (OR: 1.17 [1.03, 1.34]), psychotic features (OR: 2.20 [1.51, 3.20]), mood-incongruent psychosis (OR: 2.52 [1.66, 3.83]), puerperal psychosis (OR: 6.54 [2.55, 16.77]), rapid cycling (OR: 4.95 [0.96, 25.40]), suicide attempt (OR: 1.04 [0.65, 1.67]), alcoholism (OR: 1.53 [1.09, 2.16]), obsessive-compulsive disorder (OR: 3.10 [1.31; 7.09]), panic disorder (OR: 2.69 [1.12; 6.48]), social anxiety disorder (OR: 1.00 [0.39, 2.55]), and specific phobia (OR: 1.94 [0.95; 3.96]). For most traits, tests of heterogeneity were significant and publication bias was likely.
CONCLUSION
The results of our review and meta-analysis highlight the lack of studies investigating familial clinical traits of BD, despite the need to address heterogeneity. The large degree of variability between studies must be reduced for future research.
Topics: Humans; Bipolar Disorder; Phenotype; Psychotic Disorders; Obsessive-Compulsive Disorder; Panic Disorder
PubMed: 37190775
DOI: 10.1111/acps.13569 -
Substance use and psychotic-like experiences in young people: a systematic review and meta-analysis.Psychological Medicine Jan 2023This study aimed to systematically review and synthesise the available evidence on the prevalence and associations between psychotic-like experiences (PLEs) and... (Meta-Analysis)
Meta-Analysis Review
This study aimed to systematically review and synthesise the available evidence on the prevalence and associations between psychotic-like experiences (PLEs) and substance use in children and adolescents aged ⩽17 years, prior to the typical age of development of prodromal symptoms of psychosis. As substance use has been associated with earlier age of psychosis onset and more severe illness, identifying risk processes in the premorbid phase of the illness may offer opportunities to prevent the development of prodromal symptoms and psychotic illness. MEDLINE, PsycINFO, and CINAHL databases were searched for chart review, case-control, cohort, twin, and cross-sectional studies. Study reporting was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist, and pooled evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Searches identified 55 studies that met inclusion criteria. Around two-in-five substance users reported PLEs [rate = 0.41, 95% confidence interval (CI) 0.32-0.51; low quality evidence], and one-in-five with PLEs reported using substances (rate = 0.19, 95% CI 0.12-0.28; moderate-to-high quality evidence). Substance users were nearly twice as likely to report PLEs than non-users [odds ratio (OR) 1.77, 95% CI 1.55-2.02; moderate quality evidence], and those with PLEs were twice as likely to use substances than those not reporting PLEs (OR 1.93, 95% CI 1.55-2.41; very low quality evidence). Younger age was associated with greater odds of PLEs in substance users compared to non-users. Young substance users may represent a subclinical at-risk group for psychosis. Developing early detection and intervention for both substance use and PLEs may reduce long-term adverse outcomes.
Topics: Child; Adolescent; Humans; Aged; Cross-Sectional Studies; Prodromal Symptoms; Psychotic Disorders; Substance-Related Disorders; Risk Factors
PubMed: 36377500
DOI: 10.1017/S0033291722003440 -
Molecular Psychiatry Aug 2022In psychotic and mood disorders, immune alterations are hypothesized to underlie cognitive symptoms, as they have been associated with elevated blood levels of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In psychotic and mood disorders, immune alterations are hypothesized to underlie cognitive symptoms, as they have been associated with elevated blood levels of inflammatory cytokines, kynurenine metabolites, and markers of microglial activation. The current meta-analysis synthesizes all available clinical evidence on the associations between immunomarkers (IMs) and cognition in these psychiatric illnesses.
METHODS
Pubmed, Web of Science, and Psycinfo were searched for peer-reviewed studies on schizophrenia spectrum disorder (SZ), bipolar disorder (BD), or major depressive disorder (MDD) including an association analysis between at least one baseline neuropsychological outcome measure (NP) and one IM (PROSPERO ID:CRD42021278371). Quality assessment was performed using BIOCROSS. Correlation meta-analyses, and random effect models, were conducted in Comprehensive Meta-Analysis version 3 investigating the association between eight cognitive domains and pro-inflammatory and anti-inflammatory indices (PII and AII) as well as individual IM.
RESULTS
Seventy-five studies (n = 29,104) revealed global cognitive performance (GCP) to be very weakly associated to PII (r = -0.076; p = 0.003; I = 77.4) or AII (r = 0.067; p = 0.334; I = 38.0) in the combined patient sample. Very weak associations between blood-based immune markers and global or domain-specific GCP were found, either combined or stratified by diagnostic subgroup (GCP x PII: SZ: r = -0.036, p = 0.370, I = 70.4; BD: r = -0.095, p = 0.013, I = 44.0; MDD: r = -0.133, p = 0.040, I = 83.5). We found evidence of publication bias.
DISCUSSION
There is evidence of only a weak association between blood-based immune markers and cognition in mood and psychotic disorders. Significant publication and reporting biases were observed and most likely underlie the inflation of such associations in individual studies.
Topics: Humans; Depressive Disorder, Major; Psychotic Disorders; Bipolar Disorder; Cognitive Dysfunction; Biomarkers
PubMed: 35484245
DOI: 10.1038/s41380-022-01582-y