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  1. Article ; Online: An interview with Dr Chiara Fabbri: pharmacogenomics and drug repurposing for treatment-resistant depression.

    Fabbri, Chiara

    Pharmacogenomics

    2021  

    Language English
    Publishing date 2021-11-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2019513-8
    ISSN 1744-8042 ; 1462-2416
    ISSN (online) 1744-8042
    ISSN 1462-2416
    DOI 10.2217/pgs-2021-0134
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  2. Article: The Role of Genetics in Bipolar Disorder.

    Fabbri, Chiara

    Current topics in behavioral neurosciences

    2020  Volume 48, Page(s) 41–60

    Abstract: Bipolar disorder (BP) is a highly heritable disease, with heritability estimated between 60 and 85% by twin studies. The underlying genetic architecture was poorly understood for years since the available technology was limited to the candidate gene ... ...

    Abstract Bipolar disorder (BP) is a highly heritable disease, with heritability estimated between 60 and 85% by twin studies. The underlying genetic architecture was poorly understood for years since the available technology was limited to the candidate gene approach that did not allow to explore the contribution of multiple loci throughout the genome. BP is a complex disorder, which pathogenesis is influenced by a number of genetic variants, each with small effect size, and environmental exposures. Genome-wide association studies (GWAS) provided meaningful insights into the genetics of BP, including replicated genetic variants, and allowed the development of novel multi-marker methods for gene/pathway analysis and for estimating the genetic overlap between BP and other traits. However, the existing GWAS had also relevant limitations. Notably insufficient statistical power and lack of consideration of rare variants, which may be responsible for the relatively low heritability explained (~20% in the largest GWAS) compared to twin studies. The availability of data from large biobanks and automated phenotyping from electronic health records or digital phenotyping represent key steps for providing samples with adequate power for genetic analysis. Next-generation sequencing is becoming more and more feasible in terms of costs, leading to the rapid growth in the number of samples with whole-genome or whole-exome sequence data. These recent and unprecedented resources are of key importance for a more comprehensive understanding of the specific genetic factors involved in BP and their mechanistic action in determining disease onset and prognosis.
    MeSH term(s) Bipolar Disorder/genetics ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Humans ; Phenotype
    Language English
    Publishing date 2020-08-07
    Publishing country Germany
    Document type Journal Article
    ISSN 1866-3370
    ISSN 1866-3370
    DOI 10.1007/7854_2020_153
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  3. Article ; Online: Polygenic risk scores for mood and related disorders and environmental factors: Interaction effects on wellbeing in the UK biobank.

    Fabbri, Chiara / Lewis, Cathryn M / Serretti, Alessandro

    Progress in neuro-psychopharmacology & biological psychiatry

    2024  Volume 132, Page(s) 110972

    Abstract: Mood disorders have a genetic and environmental component and interactions (GxE) on the risk of psychiatric diseases have been investigated. The same GxE interactions may affect wellbeing measures, which go beyond categorical diagnoses and reflect the ... ...

    Abstract Mood disorders have a genetic and environmental component and interactions (GxE) on the risk of psychiatric diseases have been investigated. The same GxE interactions may affect wellbeing measures, which go beyond categorical diagnoses and reflect the health-disease continuum. We evaluated GxE effects in the UK Biobank, considering as outcomes subjective wellbeing (feeling good and functioning well) and objective measures (education and income). We estimated the polygenic risk scores (PRSs) of major depressive disorder, bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. Stressful/traumatic events during adulthood or childhood were considered as E variables, as well as social support. The addition of the PRSxE interaction to PRS and E variables was tested in linear or multinomial regression models, adjusting for confounders. We included 33 k-380 k participants, depending on the variables considered. Most PRSs and E factors showed additive effects on outcomes, with effect sizes generally 3-5 times larger for E variables than PRSs. We found some interaction effects, particularly when considering recent stress, history of a long illness/disability/infirmity, and social support. Higher PRSs increased the negative effects of stress on wellbeing, but they also increased the positive effects of social support, with interaction effects particularly for the outcomes health satisfaction, loneliness, and income (p < Bonferroni corrected threshold of 1.92e-4). PRSxE terms usually added ∼0.01-0.02% variance explained to the corresponding additive model. PRSxE effects on wellbeing involve both positive and negative E factors. Despite small variance explained at the population level, preventive/therapeutic interventions that modify E factors could be beneficial at the individual level.
    MeSH term(s) Humans ; Adult ; Child ; Depressive Disorder, Major/genetics ; Genetic Risk Score ; Biological Specimen Banks ; UK Biobank ; Multifactorial Inheritance/genetics ; Risk Factors
    Language English
    Publishing date 2024-02-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 781181-0
    ISSN 1878-4216 ; 0278-5846
    ISSN (online) 1878-4216
    ISSN 0278-5846
    DOI 10.1016/j.pnpbp.2024.110972
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  4. Article ; Online: Efficacy of Brexpiprazole Combination Therapy on Anhedonia in a Case of Treatment Resistant Bipolar II Depression.

    Scala, Mauro / Biondi, Laura / Fabbri, Chiara / Serretti, Alessandro

    Journal of clinical psychopharmacology

    2023  Volume 43, Issue 5, Page(s) 453–455

    MeSH term(s) Humans ; Anhedonia ; Depression ; Bipolar Disorder/drug therapy ; Quinolones/pharmacology ; Treatment Outcome
    Chemical Substances brexpiprazole (2J3YBM1K8C) ; Quinolones
    Language English
    Publishing date 2023-07-14
    Publishing country United States
    Document type Case Reports ; Letter
    ZDB-ID 604631-9
    ISSN 1533-712X ; 0271-0749
    ISSN (online) 1533-712X
    ISSN 0271-0749
    DOI 10.1097/JCP.0000000000001732
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  5. Article ; Online: Is a polygenic predictor of antidepressant response a possibility?

    Fabbri, Chiara

    Pharmacogenomics

    2017  Volume 18, Issue 8, Page(s) 749–752

    MeSH term(s) Antidepressive Agents/therapeutic use ; Genome/genetics ; Genome-Wide Association Study/methods ; Humans ; Multifactorial Inheritance/genetics ; Pharmacogenetics/methods
    Chemical Substances Antidepressive Agents
    Language English
    Publishing date 2017
    Publishing country England
    Document type Journal Article
    ZDB-ID 2019513-8
    ISSN 1744-8042 ; 1462-2416
    ISSN (online) 1744-8042
    ISSN 1462-2416
    DOI 10.2217/pgs-2017-0056
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  6. Article ; Online: Obsessive-Compulsive, Psychotic, and Autism Dimensions Overlap in Real World: A Case Report.

    Scala, Mauro / Biondi, Laura / Serretti, Alessandro / Fabbri, Chiara

    Clinical neuropharmacology

    2023  

    Abstract: Background: Obsessions, compulsions, and stereotypes are common psychopathological manifestations of obsessive-compulsive, psychotic, and autism spectrum disorders (ASDs). These nosological entities may be present in comorbidity, with relevant clinical ... ...

    Abstract Background: Obsessions, compulsions, and stereotypes are common psychopathological manifestations of obsessive-compulsive, psychotic, and autism spectrum disorders (ASDs). These nosological entities may be present in comorbidity, with relevant clinical difficulties in the differential diagnosis process. Moreover, ASDs are a complex group of disorders, with a childhood onset, which also persist into adulthood and present heterogeneous symptom patterns that could be confused with psychotic disorders.
    Methods and results: We report a case of a 21-year-old man characterized by sexual and doubt obsessions; disorganized, bizarre, and stereotyped behaviors and compulsions; and social withdrawal, inadequate social skills, visual dispersions, and hypersensitivity to light stimuli. Obsessive and compulsive features were initially included within the differential diagnosis of psychotic and obsessive-compulsive spectrum disorders. However, aforementioned psychopathological elements did not improve when multiple antipsychotic drugs (olanzapine, haloperidol, and lurasidone) were administered in the hypothesis of schizophrenia and even worsened with clozapine therapy at a dose of 100 mg/d. Obsessions and compulsions progressively reduced during the fluvoxamine 14-week treatment paradigm at a dose of 200 mg/d. Considering the persistent deficits in social communication and interactions as well as the restricted interests pattern, a differential diagnostic hypothesis of ASD was formulated, and it was then confirmed at the final evaluation at a third-level health care center.
    Conclusions: We discuss similarities and differences in the psychopathology of obsessions, compulsions, and stereotypes in the previously mentioned disorders, to underline factors that can help in the differential diagnosis of similar cases, and consequently in the appropriateness of treatment choice.
    Language English
    Publishing date 2023-06-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 199293-4
    ISSN 1537-162X ; 0362-5664
    ISSN (online) 1537-162X
    ISSN 0362-5664
    DOI 10.1097/WNF.0000000000000561
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  7. Article ; Online: Clinical insights into the cross-link between mood disorders and type 2 diabetes: A review of longitudinal studies and Mendelian randomisation analyses.

    Possidente, Chiara / Fanelli, Giuseppe / Serretti, Alessandro / Fabbri, Chiara

    Neuroscience and biobehavioral reviews

    2023  Volume 152, Page(s) 105298

    Abstract: Mood disorders and type 2 diabetes mellitus (T2DM) are prevalent conditions that often co-occur. We reviewed the available evidence from longitudinal and Mendelian randomisation (MR) studies on the relationship between major depressive disorder (MDD), ... ...

    Abstract Mood disorders and type 2 diabetes mellitus (T2DM) are prevalent conditions that often co-occur. We reviewed the available evidence from longitudinal and Mendelian randomisation (MR) studies on the relationship between major depressive disorder (MDD), bipolar disorder and T2DM. The clinical implications of this comorbidity on the course of either condition and the impact of antidepressants, mood stabilisers, and antidiabetic drugs were examined. Consistent evidence indicates a bidirectional association between mood disorders and T2DM. T2DM leads to more severe depression, whereas depression is associated with more complications and higher mortality in T2DM. MR studies demonstrated a causal effect of MDD on T2DM in Europeans, while a suggestive causal association in the opposite direction was found in East Asians. Antidepressants, but not lithium, were associated with a higher T2DM risk in the long-term, but confounders cannot be excluded. Some oral antidiabetics, such as pioglitazone and liraglutide, may be effective on depressive and cognitive symptoms. Studies in multi-ethnic populations, with a more careful assessment of confounders and appropriate power, would be important.
    MeSH term(s) Humans ; Diabetes Mellitus, Type 2/complications ; Mood Disorders/drug therapy ; Mood Disorders/complications ; Depressive Disorder, Major/drug therapy ; Hypoglycemic Agents/therapeutic use ; Pioglitazone
    Chemical Substances Hypoglycemic Agents ; Pioglitazone (X4OV71U42S)
    Language English
    Publishing date 2023-06-28
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 282464-4
    ISSN 1873-7528 ; 0149-7634
    ISSN (online) 1873-7528
    ISSN 0149-7634
    DOI 10.1016/j.neubiorev.2023.105298
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  8. Article ; Online: Genetic and Environmental Contribution to Major Depressive Disorder and Self-declared Depression.

    Fabbri, Chiara

    EBioMedicine

    2016  Volume 14, Page(s) 7–8

    MeSH term(s) Depression/etiology ; Depressive Disorder, Major/etiology ; Environment ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Genetic Variation ; Humans ; Self Report
    Language English
    Publishing date 2016-12
    Publishing country Netherlands
    Document type Letter
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2016.11.030
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  9. Article ; Online: COVID-19 hospitalization rates in individuals with substance or alcohol use disorders.

    Pavarin, Raimondo Maria / Fabbri, Chiara / De Ronchi, Diana

    Psychiatry research

    2022  Volume 311, Page(s) 114521

    Abstract: People with Substance or Alcohol Use Disorders (SUDs/AUDs) are likely to be more vulnerable to COVID-19 infection than the general population. We performed a cross-sectional study to compare the hospitalization rate (CHR) for COVID-19 in 2020 in patients ...

    Abstract People with Substance or Alcohol Use Disorders (SUDs/AUDs) are likely to be more vulnerable to COVID-19 infection than the general population. We performed a cross-sectional study to compare the hospitalization rate (CHR) for COVID-19 in 2020 in patients diagnosed with SUDs or AUDs in the previous 10 years vs the population without these disorders (NAS). We included individuals who were resident in the Metropolitan Area of Bologna (Northern Italy). People with SUDs or AUDs have a greater probability of being hospitalized for COVID-19 infection compared to the general population NAS, suggesting that they suffer from worse physical symptoms/conditions than the general population. Furthermore, we found higher mortality rates during hospitalization for COVID-19 in patients with AUDs or SUDs than the general population NAS. These findings highlight the importance of a careful monitoring and early intervention measures in these patients.
    MeSH term(s) Alcoholism/epidemiology ; COVID-19 ; Cross-Sectional Studies ; Hospitalization ; Humans ; Substance-Related Disorders/diagnosis ; Substance-Related Disorders/epidemiology
    Language English
    Publishing date 2022-03-20
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 445361-x
    ISSN 1872-7123 ; 1872-7506 ; 0925-4927 ; 0165-1781
    ISSN (online) 1872-7123 ; 1872-7506
    ISSN 0925-4927 ; 0165-1781
    DOI 10.1016/j.psychres.2022.114521
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  10. Article ; Online: The search for personalized antidepressant treatments: what have we learned and where are we going.

    Serretti, Alessandro / Fabbri, Chiara

    Pharmacogenomics

    2020  Volume 21, Issue 15, Page(s) 1095–1100

    Abstract: Over 20 years after the initial report of gene variants within the central nervous system modulating antidepressant response, we are now facing for the first time routine clinical pharmacogenetic applications. The scientific community is divided between ... ...

    Abstract Over 20 years after the initial report of gene variants within the central nervous system modulating antidepressant response, we are now facing for the first time routine clinical pharmacogenetic applications. The scientific community is divided between enthusiasm and skepticism. It seems clear that the benefit of existing tools is not huge, at least for the central nervous system gene variants, while it is generally accepted for the metabolic gene variants. Findings from large international consortia suggest for the first time in psychiatric genetic research history that cumulative scores comprising many variants across the whole genome may reliably constitute liability factors for psychiatric disorders, this approach will most likely improve also present pharmacogenetic tools. A composite genetic score complemented with clinical risk factors for each patient is the most promising approach for a more effective method of targeted treatment for patients with depression.
    MeSH term(s) Antidepressive Agents/adverse effects ; Antidepressive Agents/therapeutic use ; Genetic Variation/genetics ; Humans ; Mental Disorders/drug therapy ; Mental Disorders/genetics ; Pharmacogenetics/methods ; Pharmacogenetics/trends ; Precision Medicine/methods ; Precision Medicine/trends ; Serotonin Plasma Membrane Transport Proteins/genetics
    Chemical Substances Antidepressive Agents ; SLC6A4 protein, human ; Serotonin Plasma Membrane Transport Proteins
    Language English
    Publishing date 2020-10-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2019513-8
    ISSN 1744-8042 ; 1462-2416
    ISSN (online) 1744-8042
    ISSN 1462-2416
    DOI 10.2217/pgs-2019-0086
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