Genetic Variation and Autism: A Field Synopsis and Systematic Meta-Analysis.

This study aimed to verify noteworthy findings between genetic risk factors and autism spectrum disorder (ASD) by employing the false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP). PubMed and the Genome-Wide Association Studies (GWAS) catalog were searched from inception to 1 August, 2019. We included meta-analyses on genetic factors of ASD of any study design. Overall, twenty-seven meta-analyses articles from literature searches, and four manually added articles from the GWAS catalog were re-analyzed. This showed that five of 31 comparisons for meta-analyses of observational studies, 40 out of 203 comparisons for the GWAS meta-analyses, and 18 out of 20 comparisons for the GWAS catalog, respectively, had noteworthy estimations under both Bayesian approaches. In this study, we found noteworthy genetic comparisons highly related to an increased risk of ASD. Multiple genetic comparisons were shown to be associated with ASD risk; however, genuine associations should be carefully verified and understood.

Environmental risk factors, protective factors, and peripheral biomarkers for ADHD: an umbrella review.

BACKGROUND: Many potential environmental risk factors, environmental protective factors, and peripheral biomarkers for ADHD have been investigated, but the consistency and magnitude of their effects are unclear. We aimed to systematically appraise the published evidence of association between potential risk factors, protective factors, or peripheral biomarkers, and ADHD. METHODS: In this umbrella review of meta-analyses, we searched PubMed including MEDLINE, Embase, and the Cochrane Database of Systematic Reviews, from database inception to Oct 31, 2019, and screened the references of relevant articles. We included systematic reviews that provided meta-analyses of observational studies that examined associations of potential environmental risk factors, environmental protective factors, or peripheral biomarkers with diagnosis of ADHD. We included meta-analyses that used categorical ADHD diagnosis criteria according to DSM, hyperkinetic disorder according to ICD, or criteria that were less rigorous than DSM or ICD, such as self-report. We excluded articles that did not examine environmental risk factors, environmental protective factors, or peripheral biomarkers of ADHD; articles that did not include a meta-analysis; and articles that did not present enough data for re-analysis. We excluded non-human studies, primary studies, genetic studies, and conference abstracts. We calculated summary effect estimates (odds ratio [OR], relative risk [RR], weighted mean difference [WMD], Cohen's d, and Hedges' g), 95% CI, heterogeneity I2 statistic, 95% prediction interval, small study effects, and excess significance biases. We did analyses under credibility ceilings, and assessed the quality of the meta-analyses with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). This study is registered with PROSPERO, number CRD42019145032. FINDINGS: We identified 1839 articles, of which 35 were eligible for inclusion. These 35 articles yielded 63 meta-analyses encompassing 40 environmental risk factors and environmental protective factors (median cases 16 850, median population 91 954) and 23 peripheral biomarkers (median cases 175, median controls 187). Evidence of association was convincing (class I) for maternal pre-pregnancy obesity (OR 1·63, 95% CI 1·49 to 1·77), childhood eczema (1·31, 1·20 to 1·44), hypertensive disorders during pregnancy (1·29, 1·22 to 1·36), pre-eclampsia (1·28, 1·21 to 1·35), and maternal acetaminophen exposure during pregnancy (RR 1·25, 95% CI 1·17 to 1·34). Evidence of association was highly suggestive (class II) for maternal smoking during pregnancy (OR 1·6, 95% CI 1·45 to 1·76), childhood asthma (1·51, 1·4 to 1·63), maternal pre-pregnancy overweight (1·28, 1·21 to 1·35), and serum vitamin D (WMD -6·93, 95% CI -9·34 to -4·51). INTERPRETATION: Maternal pre-pregnancy obesity and overweight; pre-eclampsia, hypertension, acetaminophen exposure, and smoking during pregnancy; and childhood atopic diseases were strongly associated with ADHD. Previous familial studies suggest that maternal pre-pregnancy obesity, overweight, and smoking during pregnancy are confounded by familial or genetic factors, and further high-quality studies are therefore required to establish causality. FUNDING: None.

Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence.

BACKGROUND: Numerous studies have identified potential risk factors and biomarkers for autism spectrum disorder. We aimed to study the strength and validity of the suggested environmental risk factors or biomarkers of autism spectrum disorder. METHODS: We did an umbrella review and systematically appraised the relevant meta-analyses of observational studies. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for papers published between database inception and Oct 17, 2018, and screened the reference list of relevant articles. We obtained the summary effect, 95% CI, heterogeneity, and 95% prediction intervals. We examined small study effects and excess significance. We did analyses under credibility ceilings. This review is registered with PROSPERO, number CRD42018091704. FINDINGS: 46 eligible articles yielded data on 67 environmental risk factors (544 212 cases, 81 708 787 individuals) and 52 biomarkers (15 614 cases, 15 433 controls). Evidence of association was convincing for maternal age of 35 years or over (relative risk [RR] 1·31, 95% CI 1·18-1·45), maternal chronic hypertension (odds ratio [OR] 1·48, 1·29-1·70), maternal gestational hypertension (OR 1·37, 1·21-1·54), maternal overweight before or during pregnancy (RR 1·28, 1·19-1·36), pre-eclampsia (RR 1·32, 1·20-1·45), prepregnancy maternal antidepressant use (RR 1·48, 1·29-1·71), and maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy (OR 1·84, 1·60-2·11). Only two associations, maternal overweight before or during pregnancy and SSRI use during pregnancy, retained their high level of evidence under subset sensitivity analyses. Evidence from biomarkers was scarce, being supported by p values close to the significance threshold and too few cases. INTERPRETATION: Convincing evidence suggests that maternal factors, such as age and features of metabolic syndrome, are associated with risk of autism spectrum disorder. Although SSRI use during pregnancy was also associated with such risk when exposed and non-exposed groups were compared, this association could be affected by other confounding factors, considering that prepregnancy maternal antidepressant use was also convincingly associated with higher risk of autism spectrum disorder. Findings from previous studies suggest that one possible confounding factor is underlying maternal psychiatric disorders. FUNDING: None.

A Look at Genetic Linkage between Clozapine-induced Agranulocytosis, Malignant Hyperthermia, Neuroleptic Malignant Syndrome, and Statin-induced Myopathy.

Clozapine-induced agranulocytosis, malignant hyperthermia (MH), statin-induced myopathy, and neuroleptic malignant syndrome (NMS) are all serious drug reactions with significant overlap in terms of clinical symptomatology. The use of clozapine can lead to neutropenia, as well as the development of NMS; thus, it seemed logical to explore a possible common genetic background for the development of these two adverse effects. Furthermore, due to the overwhelming clinical resemblance between NMS, MH, and statin-induced myopathy, we decided specifically to search for a common genetic background in the development of these conditions. Methods: We searched the PubMed, OMIM, WikiGenes, Medline, and Google Scholar databases to identify articles pertinent to our subject published over the last 30 years. Articles were reviewed according to our inclusion/exclusion criteria, and irrelevant articles were excluded. Results and Conclusions: In our exploration for a common genetic background between clozapine-induced agranulocytosis, MH, NMS, and statin-induced myopathy, we identified the SLCO1B1 gene, which was common to three of these four conditions (MH, statin-induced myopathy, and clozapine-induced agranulocytosis). Although we did not find a gene common among NMS and the other conditions, the overlap of clinical symptoms between NMS, MH, and statin-induced myopathy did not allow us to rule out the possibility of a common factor, in terms of genetic predisposition, between these conditions. Future studies can aid to fill in the gaps of knowledge in terms of any genetic linkage between these three conditions and the mechanism of their associations.

Association Between Antidepressants Use During Pregnancy and Autistic Spectrum Disorders: A Meta-analysis.

OBJECTIVE: Antidepressants have been reported in several studies in the literature to be associated with the development of autistic disorder symptoms in children exposed to them during the time of their mothers' pregnancies. There have also been reports of neurodevelopment delays associated with exposure to antidepressants in the same conditions. DESIGN: We searched the PUBMED, MEDLINE, PsycARTICLES, and ERIC for original articles published between January 1983 and May 2013 to identify studies on the association between autistic spectrum disorders (ASD) and neurodevelopment delays in children and exposure to antidepressants during pregnancy. CONCLUSION: At the end of our preliminary work, we retained only three articles that were pertinent to the purpose of our study. We extracted the available data in Excel files and then did a meta-analysis. The final results showed a positive association between the exposure to antidepressants in utero and autistic spectrum disorders.

Adderall-induced Trichotillomania: A Case Report.

Adderall (dextroamphet-amine/amphetamine) is a psychostimulant medication approved by the United States Food and Drug Administration for the treatment of attention deficit hyperactivity disorder. This medication is usually well tolerated with minimal side effects. We report a case of a 12-year-old girl who was prescribed Adderall by her primary care physician to treat her attention deficit hyperactivity disorder and who subsequently developed trichotillomania. A short time following the initiation of the medication, the patient's family members noticed the patient displaying unusual hair-pulling behavior. The patient was referred to a psychiatrist for an evaluation of trichotillomania. Following a thorough evaluation, the decision was made to discontinue the Adderall and switch the patient to guanfacine. The urge to pull her hair along with her anxiety dissipated following this change. Close follow-up was maintained for over a year with both the psychiatrist and the primary care physician, and during this time the patient did not display any unusual hair pulling behaviors. This case appears to display a very unusual side effect of Adderall.

Use of intramuscular ziprasidone for the control of acute psychosis or agitation in an inpatient geriatric population: an open-label study.

Objective. This open-label study examined the safety and efficacy of ziprasidone intramuscular with geriatric patients experiencing psychosis or agitation.Design. During an inpatient stay, consenting subjects who became acutely psychotic or agitated received ziprasidone intramuscular 10mg q 6 to 8 hours, up to a maximum dose of 20mg/24 hours. A within-group repeated measures design was employed to study whether the use of ziprasidone over the 24-hour observation period contributed to decreased agitation or to extrapyramidal side effects. The data were analyzed using an Analysis of Variance with trend analysis.Setting. The study was conducted on the geriatric psychiatry inpatient unit at the University of Toledo Medical Center, Toledo, Ohio.Participants. Fourteen patients, six men and eight women with mean age 77+/-8 years, participated in this study. Each patient had a diagnosis of dementia, co-occurring with one of the following: delirium, major depressive disorder with psychotic features, schizophrenia, bipolar disorder, or schizoaffective disorder.Measurements. The Brief Psychiatric Rating Scale, Delirium Rating Scale, and the Behavioral Activity Rating Scale were obtained at baseline and at 0.5, 2, and 24 hours after the first dose of ziprasidone intramuscular.Results. Overall, physiologic measures that would indicate undesirable side effects, including QTc intervals, remained unchanged pre- and post-study. However, there were significant improvements in scores on a variety of measures assessing agitation or psychosis.Conclusion. This study suggests that ziprasidone intramuscular may be a safe and effective short-term treatment for agitated or psychotic geriatric patients, and, therefore, additional studies should be conducted to confirm these findings.