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Systematic review and critical appraisal of child abuse measurement instruments

Saini SM, Hoffmann CR, Pantelis C, Everall IP, Bousman CA

Psychiatry Res, 2019 02;272:106-113.
PMID: 30580133 DOI: 10.1016/j.psychres.2018.12.068

Child abuse is a major public health concern and a strong predictor of adult psychopathology. However, a consensus on how best to measure child abuse is not evident. This review aimed to critically appraise the methodological quality and measurement properties of published child abuse measures, examined the strength of evidence of these instruments for research use using the COnsensus-based Standards for the selection of health Measurement InstrumeNts (COSMIN) checklist and determined which measures were capable of providing information on the developmental timing of abuse. Systematic search of electronic databases identified 52 eligible instruments from 2095 studies. Only 15% (n = 8) of the instruments had strong to moderate levels of evidence for three or more of the nine COSMIN criteria. No instrument had adequate levels of evidence for all criteria, and no criteria were met by all instruments. Our results indicate there is no single instrument that is superior to all others across settings and populations. The availability of measures capable of capturing the effects of child abuse on brain development and associated behavioral phenotypes are limited. Refined instruments with a focus on capturing abuse events during development are warranted in addition to further evaluation of the psychometric properties of these instruments.
Beneficial effects of natural products on female sexual dysfunction: A systematic review and meta-analysis

Sha'ari N, Woon LS, Sidi H, Das S, Bousman CA, Mohamed Saini S

Phytomedicine, 2021 Dec;93:153760.
PMID: 34638031 DOI: 10.1016/j.phymed.2021.153760

BACKGROUND: Female sexual dysfunction (FSD) includes female orgasmic disorder, female sexual interest or arousal disorder, and genito-pelvic pain or penetration disorder. FSD affects 40% of women worldwide, but it is understudied and likely undertreated. Natural products are frequently used by women to treat FSD, but scientific evidence of their efficacy is lacking.
OBJECTIVE: This systematic review and meta-analysis focused on the study of the efficacy of natural products on FSD.
STUDY DESIGN: Systematic review and meta-analysis of existing studies on natural products in the treatment of FSD.
METHODS: The literature search included MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trial databases for studies published from January 2000 to February 2020. The quality and the level of evidence of the studies were assessed. The association between natural products and FSD was summarized using standardized mean differences (SMD) with a 95% confidence interval (CI).
RESULTS: A total of 536 studies were identified, with 20 of them meeting the criteria. According to this meta-analysis, Tribulus terrestris showed a significant positive effect in improving overall female sexual function (SMD = 1.12, 95% CI = 0.46 - 1.79, p = 0.001) and individual sexual arousal (SMD = 1.03, 95% CI = 0.22 - 1.84, p = 0.013), sexual desire (SMD = 1.08, 95% CI = 0.52 - 1.63, p ≤ 0.001) and sexual orgasm (SMD = 0.51, 95% CI = 0.02 - 1.00, p = 0.040) domains compared to placebo. Panax ginseng was found to be effective in treating sexual arousal (SMD = 0.54, 95% CI = 0.11 - 0.97, p = 0.014) and sexual desire (SMD = 0.59, 95% CI = 0.27 - 0.90, p < 0.001) compared to placebo. Meanwhile, other natural products reviewed in this study, such as Trifolium pretense, did not differ significantly from placebo in terms of improving FSD.
CONCLUSION: Preliminary evidence suggests that Tribulus terrestris and Panax ginseng may be effective as alternative treatments for FSD in a clinical setting.
Fulltext Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk

Saini SM, Mancuso SG, Mostaid MS, Liu C, Pantelis C, Everall IP, et al.

Transl Psychiatry, 2017 Aug 08;7(8):e1196.
PMID: 28786982 DOI: 10.1038/tp.2017.172

Genome-wide association study (GWAS) evidence has identified the metabotropic glutamate receptor 3 (GRM3) gene as a potential harbor for schizophrenia risk variants. However, previous meta-analyses have refuted the association between GRM3 single-nucleotide polymorphisms (SNPs) and schizophrenia risk. To reconcile these conflicting findings, we conducted the largest and most comprehensive meta-analysis of 14 SNPs in GRM3 from a total of 11 318 schizophrenia cases, 13 820 controls and 486 parent-proband trios. We found significant associations for three SNPs (rs2237562: odds ratio (OR)=1.06, 95% confidence interval (CI)=1.02-1.11, P=0.017; rs13242038: OR=0.90, 95% CI=0.85-0.96, P=0.016 and rs917071: OR=0.94, 95% CI=0.91-0.97, P=0.003). Two of these SNPs (rs2237562, rs917071) were in strong-to-moderate linkage disequilibrium with the top GRM3 GWAS significant SNP (rs12704290) reported by the Schizophrenia Working Group of the Psychiatric Genomics Consortium. We also found evidence for population stratification related to rs2237562 in that the 'risk' allele was dependent on the population under study. Our findings support the GWAS-implicated link between GRM3 genetic variation and schizophrenia risk as well as the notion that alleles conferring this risk may be population specific.
Genetic variation in glutamatergic genes moderates the effects of childhood adversity on brain volume and IQ in treatment-resistant schizophrenia

Mohamed Saini S, Bousman CA, Mancuso SG, Cropley V, Van Rheenen TE, Lenroot RK, et al.

Schizophrenia (Heidelb), 2023 Sep 14;9(1):59.
PMID: 37709784 DOI: 10.1038/s41537-023-00381-w
An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

de Leon J, Schoretsanitis G, Smith RL, Molden E, Solismaa A, Seppälä N, et al.

Pharmacopsychiatry, 2021 Dec 15.
PMID: 34911124 DOI: 10.1055/a-1625-6388

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
Correction: An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

de Leon J, Schoretsanitis G, Smith RL, Molden E, Solismaa A, Seppälä N, et al.

Pharmacopsychiatry, 2022 Jan 20.
PMID: 35052001 DOI: 10.1055/a-1737-1527