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Bipolar Disorders Mar 2022The association between impaired social cognition and bipolar disorder (BD) is well established. However, to our knowledge, there has not been a recent systematic review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between impaired social cognition and bipolar disorder (BD) is well established. However, to our knowledge, there has not been a recent systematic review that characterizes disparate dimensions of social cognition in BD. Herein, this systematic review and meta-analysis aimed to synthesize the literature on core aspects of social cognition (i.e., Theory of Mind, emotion recognition, and social judgment) to identify potential areas of impairment.
METHODS
Online databases (i.e., PubMed, Cochrane Libraries, PsycINFO) and Google Scholar were searched from inception to May 2021. Studies with populations ages ≥16 with DSM-IV or DSM-5 defined BD (I or II) either in a euthymic or symptomatic state were included. The risk of bias was measured using the ROBINS-1 tool, and the quality of the sources was evaluated using GRADE criteria. The results of the studies were quantitatively measured by synthesizing Hedge's g effect sizes through a random effects meta-analytic approach.
RESULTS
A total of 29 studies were included in the final review (i.e., 12 studies on the Theory of Mind, 11 on emotion recognition, and 6 on social judgment). Overall, results demonstrated social cognition to be moderately impaired in individuals with BD (d = 0.59). The individual domains ranged in effect size (0.38 < d < 0.70), providing evidence for variation in impairment within social cognition.
DISCUSSION
Individuals with BD exhibit clinically significant deficits in social cognition during euthymic and symptomatic states. Social cognition impairments in individuals with BD are an important therapeutic target for treatment discovery and development.
Topics: Bipolar Disorder; Cognition; Cognitive Dysfunction; Cyclothymic Disorder; Humans; Social Cognition; Theory of Mind
PubMed: 34825440
DOI: 10.1111/bdi.13163 -
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 -
Psychiatry Research Jan 2021Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present... (Meta-Analysis)
Meta-Analysis
Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present an update of our previously published algorithms for the use of psychopharmacologic agents in these patients taking into account more recent studies and findings in meta-analyses, reviews, and other published algorithms. We propose three algorithms: BPSD in an emergent, urgent, and non-urgent setting. In the emergent setting when intramuscular (IM) administration is necessary, the first-line recommendation is for olanzapine (since IM aripiprazole, previously favored, is no longer available) and haloperidol injection is the second choice, followed by possible consideration of an IM benzodiazepine. In the urgent setting, the first line would be oral second-generation antipsychotics (SGAs) aripiprazole and risperidone. Perhaps next could be then prazosin, and lastly electroconvulsive therapy is a consideration. There are risks associated with these agents, and adverse effects can be severe. Dosing strategies, discontinuation considerations, and side effects are discussed. In the non-emergent setting, medications are proposed for use in the following order: trazodone, donepezil and memantine, antidepressants such as escitalopram and sertraline, SGAs, prazosin, and carbamazepine. Other options with less support but potential future promise are discussed.
Topics: Academic Medical Centers; Aged; Algorithms; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Citalopram; Dementia; Electroconvulsive Therapy; Haloperidol; Humans; Olanzapine; Psychopharmacology; Risperidone
PubMed: 33340800
DOI: 10.1016/j.psychres.2020.113641 -
Scientific Reports Aug 2018We carried out systematic review and meta-analysis to evaluate whether peripheral levels of pro-inflammatory markers including Interleukin-1 beta (IL-1β), Interleukin-6... (Meta-Analysis)
Meta-Analysis Review
We carried out systematic review and meta-analysis to evaluate whether peripheral levels of pro-inflammatory markers including Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF- α) and C-Reactive Protein (CRP) are significantly higher in elderly with depression and Alzheimer's disease. We searched Pubmed, PsycINFO and Embase, and thirty-four relevant studies (2609 with Depression, 1645 with Alzheimer's disease and 14363 Controls) were included. Compared with controls, IL-1β (pooled standardized mean difference [SMD]: 0.642; 95% confidence interval [CI]: 0.078-1.206; significant heterogeneity: I = 86.28%) and IL-6 (pooled SMD: 0.377; 95% CI: 0.156-0.598; significant heterogeneity: I = 88.75%) were significantly elevated in depression. There was no difference in TNF-α (p = 0.351) and CRP (p = 0.05) between those with depression and controls. Compared with controls, IL-1β (pooled SMD: 1.37, 95% CI: 0.06-2.68, significant heterogeneity: I = 96.01%) was significantly elevated in Alzheimer's disease. There were no differences in IL-6 (p = 0.138), TNF-α (p = 0.451) and CRP (p = 0.07) between elderly with Alzheimer's disease and controls. After Bonferroni adjustment, only IL-6 remained significantly higher in depression. Elderly with depression have higher IL-6 than controls, while those with Alzheimer's disease did not have higher peripheral inflammatory markers.
Topics: Adaptor Proteins, Signal Transducing; Aged; Alzheimer Disease; C-Reactive Protein; Depression; Depressive Disorder; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Middle Aged; Proteins
PubMed: 30104698
DOI: 10.1038/s41598-018-30487-6 -
JAMA Network Open Nov 2022Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety.
OBJECTIVE
To provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs).
DATA SOURCES
PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022.
STUDY SELECTION
Observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD.
DATA EXTRACTION AND SYNTHESIS
Independent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline.
MAIN OUTCOMES AND MEASURES
The outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest.
RESULTS
Nineteen studies (with 3 931 532 participants including children, adolescents, and adults; 60.9% male), of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years (median, 1.5 years). Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents (RR, 1.18; 95% CI, 0.91-1.53), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or older adults (RR, 1.59; 95% CI, 0.62-4.05). No significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97) were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72), cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), or myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65). There was no associations with any CVD in female patients (RR, 1.88; 95% CI, 0.43-8.24) and in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases.
CONCLUSIONS AND RELEVANCE
This meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use.
Topics: Adolescent; Child; Middle Aged; Humans; Female; Male; Aged; Cardiovascular Diseases; Attention Deficit Disorder with Hyperactivity; Heart Disease Risk Factors; Central Nervous System Stimulants; Heart Arrest; Observational Studies as Topic
PubMed: 36416824
DOI: 10.1001/jamanetworkopen.2022.43597 -
JAMA Psychiatry Jun 2023The relative efficacy of ketamine and electroconvulsive therapy (ECT) in adults with major depressive episode (MDE) needs clarification. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The relative efficacy of ketamine and electroconvulsive therapy (ECT) in adults with major depressive episode (MDE) needs clarification.
OBJECTIVE
To compare depression rating outcomes with ketamine vs ECT in adults with MDE and to compare response and remission rates, number of sessions to response and remission, and adverse effects.
DATA SOURCES
Two investigators independently systematically searched MEDLINE, ScienceDirect, and Google Scholar databases using a combination of relevant Medical Subject Headings terms and free-text keywords from database inception through May 15, 2022, to identify relevant English-language trials.
STUDY SELECTION
Parallel-group randomized clinical trials (RCTs).
DATA EXTRACTION AND SYNTHESIS
Two investigators independently extracted data and assessed risk of bias. One-week posttreatment outcomes were pooled as standardized mean difference (SMD; Hedges g) for continuous outcomes and risk ratio (RR) for categorical outcomes in random-effects meta-analyses.
MAIN OUTCOMES AND MEASURES
Efficacy outcomes were 1-week (or nearest) posttreatment depression ratings, 1-week (or nearest) study-defined response and remission rates, and number of sessions to treatment response and remission. Safety outcomes were reported adverse effects.
RESULTS
Five trials (ketamine group: n = 141; ECT group: n = 137) were meta-analyzed. The overall pooled SMD for posttreatment depression ratings was -0.39 (95% CI, -0.81 to 0.02; I2 = 45%; 5 RCTs). For this efficacy outcome, in a sensitivity analysis of methodologically stronger trials, ECT was superior to ketamine (SMD, -0.45; 95% CI, -0.75 to -0.14; I2 = 6%; 2 RCTs). ECT was also superior to ketamine for study-defined response (RR, 1.27; 95% CI, 1.06-1.53; I2 = 0%; 3 RCTs) and remission (RR, 1.43; 95% CI, 1.12-1.82; I2 = 0%; 2 RCTs) rates. No significant differences were noted between groups for number of sessions to response and remission and for cognitive outcomes. Key limitations were small number of studies, limited sample size, and high risk of bias in all trials.
CONCLUSION AND RELEVANCE
The findings of this systematic review and meta-analysis suggest an efficacy advantage for ECT over ketamine in adults with MDE. These conclusions are tempered by the small number and size of existing trials.
Topics: Adult; Humans; Ketamine; Electroconvulsive Therapy; Depressive Disorder, Major
PubMed: 37043224
DOI: 10.1001/jamapsychiatry.2023.0562 -
Frontiers in Psychiatry 2021Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce...
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies ( = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.
PubMed: 34566723
DOI: 10.3389/fpsyt.2021.724606 -
BJPsych Open Apr 2023There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders. (Review)
Review
BACKGROUND
There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders.
AIMS
To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders.
METHOD
MEDLINE, Embase, PsycINFO and Cochrane databases were systematically searched for articles from inception to 6 September 2022. Studies that included adults with any mood or anxiety disorder treated with a low carbohydrate or ketogenic intervention, reporting effects on mood or anxiety symptoms were eligible for inclusion. PROSPERO registration CRD42019116367.
RESULTS
The search yielded 1377 articles, of which 48 were assessed for full-text eligibility. Twelve heterogeneous studies (stated as ketogenic interventions, albeit with incomplete carbohydrate reporting and measurements of ketosis; diet duration: 2 weeks to 3 years; = 389; age range 19 to 75 years) were included in the final analysis. This included nine case reports, two cohort studies and one observational study. Data quality was variable, with no high-quality evidence identified. Efficacy, adverse effects and discontinuation rates were not systematically reported. There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety. Relapse after discontinuation of the diet was reported in some individuals.
CONCLUSIONS
Although there is no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, several uncontrolled studies suggest possible beneficial effects. Robust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit and whether a ketogenic diet (beyond low carbohydrate) is required and to characterise adverse effects and the risk of relapse after diet discontinuation.
PubMed: 37066662
DOI: 10.1192/bjo.2023.36 -
Psychopharmacology Jan 2022Terminally ill patients may experience existential distress, depression, or anxiety, limiting quality of life in the final stage. Existing psychotherapeutic or... (Review)
Review
BACKGROUND
Terminally ill patients may experience existential distress, depression, or anxiety, limiting quality of life in the final stage. Existing psychotherapeutic or pharmacological interventions have (time) limited efficacy. Psychedelic treatment may be a safe and effective alternative treatment option.
AIM
Systematically review studies on psychedelic treatment with and without psychotherapy for existential distress, depression, and anxiety in terminally ill patients.
METHODS
Medline, PsycINFO, and Embase were searched for original-data studies on the treatment of depression, anxiety, and existential distress with classical or a-typical psychedelics in patients with a terminal illness, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
A total of 1850 records were screened, and 33 articles were included in this review: 14 studies on classical psychedelics (DPT, LSD, and psilocybin) and 19 studies on atypical psychedelics (MDMA and ketamine). Results of early pre-post studies are promising but have serious methodological flaws. Recent (controlled) trials with LSD, psilocybin, ketamine, and MDMA are of higher methodological quality and indicate positive effects on existential and spiritual well-being, quality of life, acceptance, and reduction of anxiety and depression with few adverse and no serious adverse effects.
CONCLUSIONS
Both classical and a-typical psychedelics are promising treatment options in patients with terminal illness. To draw final conclusions on effectiveness and safety of psychedelics, we need larger high-quality studies for classical psychedelics and MDMA. Ketamine studies should pay more attention to existential dimensions of well-being and the psychotherapeutic context of the treatment.
Topics: Anxiety; Depression; Hallucinogens; Humans; Psilocybin; Quality of Life
PubMed: 34812901
DOI: 10.1007/s00213-021-06027-y -
Journal of the American Academy of... Feb 2023Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-analysis: Efficacy of Pharmacological Interventions for Irritability and Emotional Dysregulation in Autism Spectrum Disorder and Predictors of Response.
OBJECTIVE
Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a broad range of pharmacological interventions for emotional dysregulation and irritability in ASD and predictors of response.
METHOD
Following a preregistered protocol (PROSPERO: CRD42021235779), we systematically searched multiple databases until January 1, 2021. We included placebo-controlled randomized controlled trials (RCTs) and evaluated the efficacy of pharmacological interventions and predictors of response for emotional dysregulation and irritability. We assessed heterogeneity using Q statistics and publication bias. We conducted subanalyses and meta-regressions to identify predictors of response. The primary effect size was the standardized mean difference. Quality of studies was assessed using the Cochrane Risk of Bias Tool (RoB2).
RESULTS
A total of 2,856 individuals with ASD in 45 studies were included, among which 26.7% of RCTs had a high risk of bias. Compared to placebo, antipsychotics (standardized mean difference = 1.028, 95% CI = 0.824-1.232) and medications used to treat attention-deficit/hyperactivity disorder (ADHD) (0.471, 0.061-0.881) were significantly better than placebo in improving emotional dysregulation and irritability, whereas evidence of efficacy was not found for other drug classes (p > .05). Within individual medications, evidence of efficacy was found for aripiprazole (1.179, 0.838-1.520) and risperidone (1.074, 0.818-1.331). Increased rates of comorbid epilepsy (β = -0.049, p = .026) were associated with a lower efficacy.
CONCLUSION
Some pharmacological interventions (particularly risperidone and aripiprazole) have proved efficacy for short-term treatment of emotional dysregulation and irritability in ASD and should be considered within a multimodal treatment plan, taking into account also the tolerability profile and families' preferences.
Topics: Humans; Risperidone; Aripiprazole; Antipsychotic Agents; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity
PubMed: 35470032
DOI: 10.1016/j.jaac.2022.03.033