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- Sangchooli, Arshiya, et al.
(author)
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Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity
- 2024
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In: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X.
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Research review (peer-reviewed)abstract
- Importance In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.
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- Di Feo, Maria Francesca, et al.
(author)
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Inferring disease course from differential exon usage in the wide titinopathy spectrum
- 2024
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In: Annals of Clinical and Translational Neurology. - : John Wiley and Sons Inc. - 2328-9503.
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Journal article (peer-reviewed)abstract
- Objective: Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult-onset limb-girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging. Methods: In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023. TTN mutations were detected through exome or genome sequencing. Information about familial and personal clinical history was collected in a standardized form. RNA-sequencing and analysis of TTN exon usage were performed on an internal sample cohort including postnatal skeletal muscles, fetal skeletal muscles, postnatal heart muscles, and fetal heart muscles. In addition, publicly available RNA-sequencing data was retrieved from ENCODE. Results: We generated new RNA-seq data on TTN exons and identified genotype–phenotype correlations with prognostic implications for each titinopathy patient (whether worsening or improving in prenatal and postnatal life) using percentage spliced in (PSI) data for the involved exons. Interestingly, thanks to exon usage, we were also able to rule out a titinopathy diagnosis in one prenatal case. Interpretation: This study demonstrates that exon usage provides valuable insights for a more exhaustive clinical interpretation of TTNtv; additionally, it may serve as a model for implementing personalized medicine in many other genetic diseases, since most genes undergo alternative splicing.
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- Farrahi, Hassan, et al.
(author)
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Psychometric properties of the Persian version of the overall anxiety severity and impairment scale (OASIS)
- 2020
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In: Iranian Journal of Psychiatry and Behavioral Sciences. - : Kowsar Medical Publishing Company. - 1735-8639. ; 14:4
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Journal article (peer-reviewed)abstract
- Objectives: This study was conducted to assess the psychometric properties of the Persian version of the overall anxiety severity and impairment scale (OASIS), a measure designed to evaluate the severity and functional impairments associated with clinical and subsyndromal anxiety.Methods: Using a descriptive-analytic framework, first, the OASIS was translated into Persian according to the forward-backward translation guidelines. Then, a total of 463 students of Guilan University of Medical Sciences in the academic year 2017 - 18 were selected using the convenience sampling method. Participants completed seven measures (i.e., OASIS, anxiety and stress subscales of depression anxiety stress scales-21, Beck anxiety inventory, openness subscale of NEO five-factor inventory, positive affect and negative affect scales, Connor-Davidson resilience scale, and state subscale of state-trait anxiety inventory), and the data were analyzed by SPSS V. 20.0 for windows and Lisrel V. 8.80.Results: Internal consistency reliability of the OASIS was acceptable (Cronbach’s α = 0.877). The exploratory factor analysis indicated that all items were loaded on a single factor (loadings = 0.799 - 0.849). The confirmatory factor analysis revealed that the single-factor model has resulted in an adequate model fit. The OASIS was positively correlated with the anxiety- and negative affect-related scales, whereas it was negatively correlated with the resilience- and positive affect-related scales. Correlations with the openness subscale were not significant.Conclusions: In line with previous studies, the findings showed that the psychometric properties of the Persian version of the OASIS are acceptable. Therefore, it seems that the measure can be used in clinical practices and research studies in Iran.
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- van der Kolk, Birgitta W., et al.
(author)
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Molecular pathways behind acquired obesity : Adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI
- 2021
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In: Cell Reports Medicine. - : Elsevier BV. - 2666-3791. ; 2:4, s. 100226-
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Journal article (peer-reviewed)abstract
- Tissue-specific mechanisms prompting obesity-related development complications in humans remain unclear. We apply multiomics analyses of subcutaneous adipose tissue and skeletal muscle to examine the effects of acquired obesity among 49 BMI-discordant monozygotic twin pairs. Overall, adipose tissue appears to be more affected by excess body weight than skeletal muscle. In heavier co-twins, we observe a transcriptional pattern of downregulated mitochondrial pathways in both tissues and upregulated inflammatory pathways in adipose tissue. In adipose tissue, heavier co-twins exhibit lower creatine levels; in skeletal muscle, glycolysis- and redox stress-related protein and metabolite levels remain higher. Furthermore, metabolomics analyses in both tissues reveal that several proinflammatory lipids are higher and six of the same lipid derivatives are lower in acquired obesity. Finally, in adipose tissue, but not in skeletal muscle, mitochondrial downregulation and upregulated inflammation are associated with a fatty liver, insulin resistance, and dyslipidemia, suggesting that adipose tissue dominates in acquired obesity.
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