ORCID Profile
0000-0002-9463-7808
Current Organisation
University of Brescia
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Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.EURONEURO.2021.12.005
Abstract: Variation in the expression level and activity of genes involved in drug disposition and action in tissues of pharmacological importance have been increasingly investigated in patients treated with psychotropic drugs. Findings are promising, but reliable predictive biomarkers of response have yet to be identified. Here we conducted a PRISMA-compliant systematic search of PubMed, Scopus and PsycInfo up to 12 September 2020 for studies investigating RNA expression levels in cells or biofluids from patients with major depressive disorder, schizophrenia or bipolar disorder characterized for response to psychotropic drugs (antidepressants, antipsychotics or mood stabilizers) or adverse effects. Among 5497 retrieved studies, 123 (63 on antidepressants, 33 on antipsychotics and 27 on mood stabilizers) met inclusion criteria. Studies were either focused on mRNAs (n = 96), microRNAs (n = 19) or long non-coding RNAs (n = 1), with only a minority investigating both mRNAs and microRNAs levels (n = 7). The most replicated results include genes playing a role in inflammation (antidepressants), neurotransmission (antidepressants and antipsychotics) or mitochondrial function (mood stabilizers). Compared to those investigating response to antidepressants, studies focused on antipsychotics or mood stabilizers more often showed lower s le size and lacked replication. Strengths and limitations of available studies are presented and discussed in light of the specific designs, methodology and clinical characterization of included patients for transcriptomic compared to DNA-based studies. Finally, future directions of transcriptomics of psychopharmacological interventions in psychiatric disorders are discussed.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
DOI: 10.1038/TP.2015.180
Abstract: Several studies have demonstrated that allelic variants related to inflammation and the immune system may increase the risk for major depressive disorder (MDD) and reduce patient responsiveness to antidepressant treatment. Proteasomes are fundamental complexes that contribute to the regulation of T-cell function. Only one study has shown a putative role of proteasomal PSMA7 , PSMD9 and PSMD13 genes in the susceptibility to an antidepressant response, and sparse data are available regarding the potential alterations in proteasome expression in psychiatric disorders such as MDD. The aim of this study was to clarify the role of these genes in the mechanisms underlying the response/resistance to MDD treatment. We performed a case-control association study on 621 MDD patients, of whom 390 were classified as treatment-resistant depression (TRD), and we collected peripheral blood cells and fibroblasts for mRNA expression analyses. The analyses showed that subjects carrying the homozygous GG genotype of PSMD13 rs3817629 had a twofold greater risk of developing TRD and exhibited a lower PSMD13 mRNA level in fibroblasts than subjects carrying the A allele. In addition, we found a positive association between PSMD9 rs1043307 and the presence of anxiety disorders in comorbidity with MDD, although this result was not significant following correction for multiple comparisons. In conclusion, by confirming the involvement of PSMD13 in the MDD treatment response, our data corroborate the hypothesis that the dysregulation of the complex responsible for the degradation of intracellular proteins and potentially controlling autoimmunity- and immune tolerance–related processes may be involved in several phenotypes, including the TRD.
Publisher: Cold Spring Harbor Laboratory
Date: 28-08-2023
DOI: 10.1101/2023.08.26.23294659
Abstract: A significant proportion of patients with major depressive disorder (MDD) do not experience remission after one or more pharmacological treatments. Research has explored brain structural measures, particularly the hippoc us, as potential predictors of treatment response in MDD, as well as genetic factors. This study investigated the association of polygenic scores (PGSs) for seven subcortical brain volumes (including the hippoc us, nucleus accumbens, amygdala, and caudate nucleus) with treatment non-response and non-remission in MDD. Patients with MDD were recruited in the context of five clinical studies, including a total of 3,637 in iduals. PGSs were estimated using a Bayesian framework and continuous shrinkage priors (PRS-CS-auto) after standard genotype quality control and imputation. Logistic regressions were performed between PGSs and non-response or non-remission in each s le, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across s les, using a random-effect model. Caudate volume PGS was nominally associated with non-remission (OR=1.09, 95% CI=1.01–1.19, p=0.036). Leave-one-out sensitivity analyses suggested a possible association with the amygdala and thalamus PGSs. However, no association was significant after multiple testing correction. These results, although preliminary, suggest a possible link between caudate volume PGS and lack of symptom remission. Methodological improvements in PGSs estimation and statistical power may enhance their predictive performance and provide a contribution to precision psychiatry.
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.EURONEURO.2022.04.007
Abstract: Several data indicate that the success of pharmacological treatment in major depressive disorder (MDD) is still unsatisfactory. The reasons for the low response and remission rates are multiple and depend on environmental and biological factors intrinsic to the disease and drug treatments. Pharmacogenetic (PG) tests have the potential to increase efficacy predicting outcome and to reduce antidepressant discontinuation due to side effects. Several studies investigated the utility of PG tests for antidepressants in MDD with interesting but contrasting results. To date most of them are observational studies with no comparator group, and few are randomized controlled trials (RCTs). The aim of this review is to provide an evaluation of the state of art on clinical methodologic features of RCTs with PG tests for antidepressant drugs in MDD, offering suggestions and favoring new insights that could be useful in the implementation of future trials. Several limitations concerning study design, generalization of results, duration of trials, patients group studied, and cost-effectiveness ratio were found, and a number of barriers have been noted in the adoption of PG tests into clinical practice. Despite some preliminary positive results, there is the need for larger and longer-term RCT studies, with the goal to capture the real impact of PG tests, also with stratified analysis concerning MDD features in terms of severity and antidepressant treatment failures in different ethnicity cohorts.
Location: Germany
Location: Italy
No related grants have been discovered for Alessandra Minelli.