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Acta Psychiatrica Scandinavica Mar 2021To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic mental disorders in adulthood.
METHODS
Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, longitudinal cohort studies in the English language examining child or adolescent exposure to trauma, and adult-diagnosed depression, anxiety, psychotic disorder or bipolar disorder. A total of 23 manuscripts were retained.
RESULTS
Results revealed a significant association between the following childhood exposures and adult mental disorder: bullying (victimhood, perpetration and frequency); emotional abuse; physical neglect; parental loss; and general maltreatment (unspecified and/or multiple trauma exposure). There was some evidence of a dose-response relationship with those exposed to multiple forms of maltreatment having more than three times the odds of developing a mental disorder (Odds ratio = 3.11, 95% CI = 1.36-7.14). There was no significant association found between physical or sexual abuse and adult mental disorder; however, this is likely an artefact of how these adversities were assessed.
CONCLUSION
There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for later mental illness, and an important period in which to focus intervention strategies.
Topics: Adolescent; Adult; Adult Survivors of Child Abuse; Anxiety Disorders; Child; Child Abuse; Cohort Studies; Humans; Longitudinal Studies; Psychotic Disorders
PubMed: 33315268
DOI: 10.1111/acps.13268 -
European Neuropsychopharmacology : the... Apr 2019Long-Acting Injectable Antipsychotics (LAIs) are used to overcome non-compliance in psychoses, mainly schizophrenia spectrum disorders. We aimed to summarize available... (Review)
Review
Long-Acting Injectable Antipsychotics (LAIs) are used to overcome non-compliance in psychoses, mainly schizophrenia spectrum disorders. We aimed to summarize available evidence of studies comparing the efficacy of LAIs to placebo or oral medications for Bipolar Disorder (BD) and/or Schizoaffective Disorder (SAD). We searched six databases from inception to 28-March-2018, using the strategy: long-acting antipsychotics AND (bipolar disorder OR schizoaffective disorder OR mania OR manic OR bipolar depression). We included peer-reviewed double-blind comparisons of LAIs for any clinical outcome occurrence in BD, or open mirror studies with same prospective as retrospective assessment periods. We excluded studies reporting on mixed schizophrenia/SAD populations without reporting results separately. The pooled records amounted to 642. After duplicate removal and inclusion/exclusion criteria application, we included 15 studies, 6 double-blind and 9 open, 13 assessing BD and 2 SAD. Depot neuroleptics prevented manic, but not depressive recurrences and may worsen depressive symptoms. Risperidone long-acting injectable was found to be effective in protecting from any mood/manic symptom compared to placebo, but not from depressive recurrences. Add-on or monotherapy paliperidone palmitate in SAD patients protected from psychotic, depressive, and manic symptoms. In patients with BD-I with a manic episode at study enrolment, aripiprazole monohydrate significantly delayed time to recurrence of manic episodes without inducing depressive episodes. LAIs are effective and well-tolerated maintenance treatments for BD and SAD. They showed better efficacy in preventing mania than depression. LAIs may be first-line for BD-I and SAD patients with a manic predominant polarity and with non-adherence problems.
Topics: Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Humans; Injections, Intramuscular; Psychotic Disorders; Recurrence
PubMed: 30770235
DOI: 10.1016/j.euroneuro.2019.02.003 -
Acta Psychiatrica Scandinavica Jul 2021Narcolepsy is a rare sleep disorder in which psychotic-like symptoms can present diagnostic and therapeutic challenges. We aimed to review the association between, and... (Review)
Review
OBJECTIVE
Narcolepsy is a rare sleep disorder in which psychotic-like symptoms can present diagnostic and therapeutic challenges. We aimed to review the association between, and medical management of, narcolepsy and psychosis in children and adults.
METHODS
We reviewed the full text of 100 papers from 187 identified by a PubMed search on narcolepsy plus any of these keywords: psychosis, schizophrenia, delusion, side effects, safety, and bipolar disorder.
RESULTS
Three relevant groups are described. (i) In typical narcolepsy, psychotic-like symptoms include predominantly visual hallucinations at the sleep-wake transition (experienced as "not real") and dissociation because of intrusion of rapid eye movement (REM) sleep phenomena into wakefulness. (ii) Atypical patients ("the psychotic form of narcolepsy") experience more severe and vivid, apparently REM-related hallucinations or dream/reality confusions, which patients may rationalize in a delusion-like way. (iii) Some patients have a comorbid schizophrenia spectrum disorder with psychotic symptoms unrelated to sleep. Psychostimulants used to treat narcolepsy may trigger psychotic symptoms in all three groups. We analyzed 58 published cases from groups 2 and 3 (n = 17 and 41). Features that were reported significantly more frequently in atypical patients include visual and multimodal hallucinations, sexual and mystical delusions, and false memories. Dual diagnosis patients had more disorganized symptoms and earlier onset of narcolepsy.
CONCLUSION
Epidemiological studies tentatively suggest a possible association between narcolepsy and schizophrenia only for very early-onset cases, which could be related to the partially overlapping neurodevelopmental changes observed in these disorders. We propose a clinical algorithm for the management of cases with psychotic-like or psychotic features.
Topics: Adult; Child; Hallucinations; Humans; Narcolepsy; Psychotic Disorders; Schizophrenia; Sleep, REM
PubMed: 33779983
DOI: 10.1111/acps.13300 -
International Journal of Molecular... Dec 2017In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow... (Review)
Review
In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far.
Topics: Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; Psychotic Disorders
PubMed: 29207548
DOI: 10.3390/ijms18122608 -
The Cochrane Database of Systematic... Jul 2022Schizophrenia is a disabling psychotic disorder characterised by positive symptoms of delusions, hallucinations, disorganised speech and behaviour; and negative symptoms... (Review)
Review
BACKGROUND
Schizophrenia is a disabling psychotic disorder characterised by positive symptoms of delusions, hallucinations, disorganised speech and behaviour; and negative symptoms such as affective flattening and lack of motivation. Cognitive behavioural therapy (CBT) is a psychological intervention that aims to change the way in which a person interprets and evaluates their experiences, helping them to identify and link feelings and patterns of thinking that underpin distress. CBT models targeting symptoms of psychosis (CBTp) have been developed for many mental health conditions including schizophrenia. CBTp has been suggested as a useful add-on therapy to medication for people with schizophrenia. While CBT for people with schizophrenia was mainly developed as an individual treatment, it is expensive and a group approach may be more cost-effective. Group CBTp can be defined as a group intervention targeting psychotic symptoms, based on the cognitive behavioural model. In group CBTp, people work collaboratively on coping with distressing hallucinations, analysing evidence for their delusions, and developing problem-solving and social skills. However, the evidence for effectiveness is far from conclusive.
OBJECTIVES
To investigate efficacy and acceptability of group CBT applied to psychosis compared with standard care or other psychosocial interventions, for people with schizophrenia or schizoaffective disorder.
SEARCH METHODS
On 10 February 2021, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, four other databases and two trials registries. We handsearched the reference lists of relevant papers and previous systematic reviews and contacted experts in the field for supplemental data.
SELECTION CRITERIA
We selected randomised controlled trials allocating adults with schizophrenia to receive either group CBT for schizophrenia, compared with standard care, or any other psychosocial intervention (group or individual).
DATA COLLECTION AND ANALYSIS
We complied with Cochrane recommended standard of conduct for data screening and collection. Where possible, we calculated risk ratio (RR) and 95% confidence interval (CI) for binary data and mean difference (MD) and 95% CI for continuous data. We used a random-effects model for analyses. We assessed risk of bias for included studies and created a summary of findings table using GRADE.
MAIN RESULTS
The review includes 24 studies (1900 participants). All studies compared group CBTp with treatments that a person with schizophrenia would normally receive in a standard mental health service (standard care) or any other psychosocial intervention (group or individual). None of the studies compared group CBTp with individual CBTp. Overall risk of bias within the trials was moderate to low. We found no studies reporting data for our primary outcome of clinically important change. With regard to numbers of participants leaving the study early, group CBTp has little or no effect compared to standard care or other psychosocial interventions (RR 1.22, 95% CI 0.94 to 1.59; studies = 13, participants = 1267; I = 9%; low-certainty evidence). Group CBTp may have some advantage over standard care or other psychosocial interventions for overall mental state at the end of treatment for endpoint scores on the Positive and Negative Syndrome Scale (PANSS) total (MD -3.73, 95% CI -4.63 to -2.83; studies = 12, participants = 1036; I = 5%; low-certainty evidence). Group CBTp seems to have little or no effect on PANSS positive symptoms (MD -0.45, 95% CI -1.30 to 0.40; studies =8, participants = 539; I = 0%) and on PANSS negative symptoms scores at the end of treatment (MD -0.73, 95% CI -1.68 to 0.21; studies = 9, participants = 768; I = 65%). Group CBTp seems to have an advantage over standard care or other psychosocial interventions on global functioning measured by Global Assessment of Functioning (GAF; MD -3.61, 95% CI -6.37 to -0.84; studies = 5, participants = 254; I = 0%; moderate-certainty evidence), Personal and Social Performance Scale (PSP; MD 3.30, 95% CI 2.00 to 4.60; studies = 1, participants = 100), and Social Disability Screening Schedule (SDSS; MD -1.27, 95% CI -2.46 to -0.08; studies = 1, participants = 116). Service use data were equivocal with no real differences between treatment groups for number of participants hospitalised (RR 0.78, 95% CI 0.38 to 1.60; studies = 3, participants = 235; I = 34%). There was no clear difference between group CBTp and standard care or other psychosocial interventions endpoint scores on depression and quality of life outcomes, except for quality of life measured by World Health Organization Quality of Life Assessment Instrument (WHOQOL-BREF) Psychological domain subscale (MD -4.64, 95% CI -9.04 to -0.24; studies = 2, participants = 132; I = 77%). The studies did not report relapse or adverse effects.
AUTHORS' CONCLUSIONS
Group CBTp appears to be no better or worse than standard care or other psychosocial interventions for people with schizophrenia in terms of leaving the study early, service use and general quality of life. Group CBTp seems to be more effective than standard care or other psychosocial interventions on overall mental state and global functioning scores. These results may not be widely applicable as each study had a low sample size. Therefore, no firm conclusions concerning the efficacy of group CBTp for people with schizophrenia can currently be made. More high-quality research, reporting useable and relevant data is needed.
Topics: Adult; Cognitive Behavioral Therapy; Hallucinations; Humans; Psychotic Disorders; Quality of Life; Schizophrenia
PubMed: 35866377
DOI: 10.1002/14651858.CD009608.pub2 -
European Archives of Psychiatry and... Jun 2020We conducted a systematic review of meta-analyses and systematic reviews to evaluate the impact of cannabis use on the onset and course of psychoses. Following a... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review of meta-analyses and systematic reviews to evaluate the impact of cannabis use on the onset and course of psychoses. Following a systematic literature search of five data bases (2005-2016) and consecutive structured evaluation, we were able to include 26 systematic reviews and meta-analyses. The methodological quality of the included publications were in the range of high and poor. The scientific literature indicates that psychotic illness arises more frequently in cannabis users compared to non-users, cannabis use is associated with a dose-dependent risk of developing psychotic illness, and cannabis users have an earlier onset of psychotic illness compared to non-users. Cannabis use was also associated with increased relapse rates, more hospitalizations and pronounced positive symptoms in psychotic patients. We make recommendations about the type of research that is required to better characterize the relationship between cannabis use and the development and outcomes of psychosis.
Topics: Humans; Marijuana Use; Psychotic Disorders
PubMed: 31563981
DOI: 10.1007/s00406-019-01068-z -
The Cochrane Database of Systematic... Jan 2015Early and accurate diagnosis and treatment of schizophrenia may have long-term advantages for the patient; the longer psychosis goes untreated the more severe the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Early and accurate diagnosis and treatment of schizophrenia may have long-term advantages for the patient; the longer psychosis goes untreated the more severe the repercussions for relapse and recovery. If the correct diagnosis is not schizophrenia, but another psychotic disorder with some symptoms similar to schizophrenia, appropriate treatment might be delayed, with possible severe repercussions for the person involved and their family. There is widespread uncertainty about the diagnostic accuracy of First Rank Symptoms (FRS); we examined whether they are a useful diagnostic tool to differentiate schizophrenia from other psychotic disorders.
OBJECTIVES
To determine the diagnostic accuracy of one or multiple FRS for diagnosing schizophrenia, verified by clinical history and examination by a qualified professional (e.g. psychiatrists, nurses, social workers), with or without the use of operational criteria and checklists, in people thought to have non-organic psychotic symptoms.
SEARCH METHODS
We conducted searches in MEDLINE, EMBASE, and PsycInfo using OvidSP in April, June, July 2011 and December 2012. We also searched MEDION in December 2013.
SELECTION CRITERIA
We selected studies that consecutively enrolled or randomly selected adults and adolescents with symptoms of psychosis, and assessed the diagnostic accuracy of FRS for schizophrenia compared to history and clinical examination performed by a qualified professional, which may or may not involve the use of symptom checklists or based on operational criteria such as ICD and DSM.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened all references for inclusion. Risk of bias in included studies were assessed using the QUADAS-2 instrument. We recorded the number of true positives (TP), true negatives (TN), false positives (FP), and false negatives (FN) for constructing a 2 x 2 table for each study or derived 2 x 2 data from reported summary statistics such as sensitivity, specificity, and/or likelihood ratios.
MAIN RESULTS
We included 21 studies with a total of 6253 participants (5515 were included in the analysis). Studies were conducted from 1974 to 2011, with 80% of the studies conducted in the 1970's, 1980's or 1990's. Most studies did not report study methods sufficiently and many had high applicability concerns. In 20 studies, FRS differentiated schizophrenia from all other diagnoses with a sensitivity of 57% (50.4% to 63.3%), and a specificity of 81.4% (74% to 87.1%) In seven studies, FRS differentiated schizophrenia from non-psychotic mental health disorders with a sensitivity of 61.8% (51.7% to 71%) and a specificity of 94.1% (88% to 97.2%). In sixteen studies, FRS differentiated schizophrenia from other types of psychosis with a sensitivity of 58% (50.3% to 65.3%) and a specificity of 74.7% (65.2% to 82.3%).
AUTHORS' CONCLUSIONS
The synthesis of old studies of limited quality in this review indicates that FRS correctly identifies people with schizophrenia 75% to 95% of the time. The use of FRS to diagnose schizophrenia in triage will incorrectly diagnose around five to 19 people in every 100 who have FRS as having schizophrenia and specialists will not agree with this diagnosis. These people will still merit specialist assessment and help due to the severity of disturbance in their behaviour and mental state. Again, with a sensitivity of FRS of 60%, reliance on FRS to diagnose schizophrenia in triage will not correctly diagnose around 40% of people that specialists will consider to have schizophrenia. Some of these people may experience a delay in getting appropriate treatment. Others, whom specialists will consider to have schizophrenia, could be prematurely discharged from care, if triage relies on the presence of FRS to diagnose schizophrenia. Empathetic, considerate use of FRS as a diagnostic aid - with known limitations - should avoid a good proportion of these errors.We hope that newer tests - to be included in future Cochrane reviews - will show better results. However, symptoms of first rank can still be helpful where newer tests are not available - a situation which applies to the initial screening of most people with suspected schizophrenia. FRS remain a simple, quick and useful clinical indicator for an illness of enormous clinical variability.
Topics: Adolescent; Adult; Diagnosis, Differential; Early Diagnosis; Humans; Mental Disorders; Prospective Studies; Psychotic Disorders; Retrospective Studies; Schizophrenia; Sensitivity and Specificity; Symptom Assessment
PubMed: 25879096
DOI: 10.1002/14651858.CD010653.pub2 -
Neuropsychobiology 2020Schizophrenia spectrum disorders (SSD) represent a cluster of severe mental illnesses. Diet has been identified as a modifiable risk factor and opportunity for...
INTRODUCTION
Schizophrenia spectrum disorders (SSD) represent a cluster of severe mental illnesses. Diet has been identified as a modifiable risk factor and opportunity for intervention in many physical illnesses and more recently in mental illnesses such as unipolar depression; however, no dietary guidelines exist for patients with SSD.
OBJECTIVE
This review sought to systematically scope the existing literature in order to identify nutritional interventions for the prevention or treatment of mental health symptoms in SSD as well as gaps and opportunities for further research.
METHODS
This review followed established methodological approaches for scoping reviews including an extensive a priori search strategy and duplicate screening. Because of the large volume of results, an online program (Abstrackr) was used for screening and tagging. Data were extracted based on the dietary constituents and analyzed.
RESULTS
Of 55,330 results identified by the search, 822 studies met the criteria for inclusion. Observational evidence shows a connection between the presence of psychotic disorders and poorer quality dietary patterns, higher intake of refined carbohydrates and total fat, and lower intake or levels of fibre, ω-3 and ω-6 fatty acids, vegetables, fruit, and certain vitamins and minerals (vitamin B12 and B6, folate, vitamin C, zinc, and selenium). Evidence illustrates a role of food allergy and sensitivity as well as microbiome composition and specific phytonutrients (such as L-theanine, sulforaphane, and resveratrol). Experimental studies have demonstrated benefit using healthy diet patterns and specific vitamins and minerals (vitamin B12 and B6, folate, and zinc) and amino acids (serine, lysine, glycine, and tryptophan).
DISCUSSION
Overall, these findings were consistent with many other bodies of knowledge about healthy dietary patterns. Many limitations exist related to the design of the individual studies and the ability to extrapolate the results of studies using dietary supplements to dietary interventions (food). Dietary recommendations are presented as well as recommendations for further research including more prospective observational studies and intervention studies that modify diet constituents or entire dietary patterns with statistical power to detect mental health outcomes.
Topics: Diet; Humans; Nutritional Physiological Phenomena; Psychotic Disorders; Schizophrenia
PubMed: 30359969
DOI: 10.1159/000493399 -
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 -
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