ORCID Profile
0000-0002-8855-7393
Current Organisation
Vanderbilt University Medical Center
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Publisher: Wiley
Date: 15-07-2022
DOI: 10.1002/AJMG.B.32911
Abstract: Testing the association between genetic scores for Attention Deficit Hyperactivity Disorder (ADHD) and health conditions, can help us better understand its complex etiology. Electronic health records linked to genetic data provide an opportunity to test whether genetic scores for ADHD correlate with ADHD and additional health outcomes in a health care context across different age groups. We generated polygenic scores (ADHD‐PGS) trained on summary statistics from the latest genome‐wide association study of ADHD ( N = 55,374) and applied them to genome‐wide data from 12,383 unrelated in iduals of African‐American ancestry and 66,378 unrelated in iduals of European ancestry from the Vanderbilt Biobank. Overall, only Tobacco use disorder (TUD) was associated with ADHD‐PGS in the African‐American ancestry group (Odds ratio [95% confidence intervals] = 1.23[1.16–1.31], p = 9.3 × 10 −09 ). Eighty‐six phenotypes were associated with ADHD‐PGS in the European ancestry in iduals, including ADHD (OR[95%CIs] = 1.22[1.16–1.29], p = 3.6 × 10 −10 ), and TUD (OR[95%CIs] = 1.22[1.19–1.25], p = 2.8 × 10 −46 ). We then stratified outcomes by age (ages 0–11, 12–18, 19–25, 26–40, 41–60, and 61–100). Our results suggest that ADHD polygenic scores are associated with ADHD diagnoses early in life and with an increasing number of health conditions throughout the lifespan (even in the absence of ADHD diagnosis). This study reinforces the utility of applying trait‐specific PGSs to biobank data, and performing exploratory sensitivity analyses, to probe relationships among clinical conditions.
Publisher: American Psychiatric Association Publishing
Date: 06-2014
Publisher: Elsevier BV
Date: 03-2013
Publisher: Cold Spring Harbor Laboratory
Date: 09-11-2019
DOI: 10.1101/836197
Abstract: Moving in synchrony to the beat is a fundamental component of musicality. Here, we conducted a genome-wide association study (GWAS) to identify common genetic variants associated with beat synchronization in 606,825 in iduals. Beat synchronization exhibited a highly polygenic architecture, with sixty-nine loci reaching genome-wide significance (p ×10 −8 ) and SNP-based heritability (on the liability scale) of 13%-16%. Heritability was enriched for genes expressed in brain tissues, and for fetal and adult brain-specific gene regulatory elements, underscoring the role of central nervous system-expressed genes linked to the genetic basis of the trait. We performed validations of the self-report phenotype (through internet-based experiments) and of the GWAS (polygenic scores for beat synchronization were associated with patients algorithmically classified as musicians in medical records of a separate biobank). Genetic correlations with breathing function, motor function, processing speed, and chronotype suggest shared genetic architecture with beat synchronization and provide avenues for new phenotypic and genetic explorations.
Publisher: BMJ
Date: 29-11-2022
Abstract: Caring for children with pathogenic neurodevelopmental Copy Number Variants (CNVs) (ie, deletions and duplications of genetic material) can place a considerable burden on parents and their quality of life. Our study is the first to examine the frequency of psychiatric diagnoses in mothers of children with CNVs compared with the frequency of psychiatric problems in age-matched mothers from a large community study. Case–control study. 268 mothers of children with a CNV diagnosed in a medical genetics clinic and 2680 age-matched mothers taking part in the Avon Longitudinal Study of Parents and Children study. Mothers of children with CNVs reported higher frequency of depression, anorexia, bulimia, alcohol abuse and drug addiction problems compared with the age-matched mothers from the community s le. Focusing on psychiatric problems arising immediately after the birth of the index child, we found that the levels of depression symptoms were similar between the two groups (48% in mothers of children with CNVs vs 44% in mothers of the community s le, p=0.43), but mothers of children with CNVs had higher frequency of anxiety symptoms (55%) compared with mothers from the community s le (30%, p=0.03). Our study highlights the need for healthcare providers to devise treatment plans that not only focus on meeting the child’s needs but also assess and, if needed, address the mental health needs of the parent.
Publisher: Royal College of Psychiatrists
Date: 2014
DOI: 10.1192/BJP.BP.113.132324
Abstract: Children with 22q11.2 deletion syndrome (22q11.2DS) have been reported to have high rates of cognitive and psychiatric problems. To establish the nature and prevalence of psychiatric disorder and neurocognitive impairment in children with 22q11.2DS and test whether risk of psychopathology is mediated by the children's intellectual impairment. Neurocognition and psychopathology were assessed in 80 children with 22q11.2DS (mean age 10.2 years, s.d. = 2.1) and 39 sibling controls (mean age 10.9 years, s.d. = 2.0). More than half (54%) of children with 22q11.2DS met diagnostic criteria for one or more DSM-IV-TR psychiatric disorder. These children had lower IQ (mean 76.8, s.d. = 13.0) than controls (mean 108.6, s.d. = 15.2) ( P .001) and showed a range of neurocognitive impairments. Increased risk of psychopathology was not mediated by intellectual impairment. 22q11.2DS is not related to a specific psychiatric phenotype in children. Moreover, the deletion has largely independent effects on IQ and risk of psychopathology, indicating that psychopathology in 22q11.2DS is not a non-specific consequence of generalised cognitive impairment.
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.SCHRES.2014.01.020
Abstract: 22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of psychotic disorder, particularly schizophrenia. The deletion is considered to be a biological model for understanding this debilitating psychiatric disorder. It is unclear whether the psychotic manifestations in 22q11.2DS are similar to those in schizophrenia patients without the deletion. Catechol-O-methyltransferase (COMT), a positional candidate gene for schizophrenia, resides within the 22q11.2 region. It remains unknown whether hemizygosity for this gene is associated with risk of psychotic disorder. This study includes 83 adults with 22q11.2DS, 90 non-deleted in iduals with schizophrenia, and 316 normal controls. Psychopathology was assessed using the Schedules for Clinical Assessment in Neuropsychiatry, the Schedules for the Assessment of Positive and Negative Symptoms and the Global Assessment Scale. Schizotypy was assessed with the Kings Schizotypy Questionnaire and Oxford Liverpool Inventory of Feelings and Emotions. IQ estimates were also obtained. Adults with 22q11.2DS were genotyped for a number of COMT polymorphisms as well as the Ashkenazi risk haplotype. This study confirms high rates of psychotic disorder (29%) in in iduals with 22q11.2DS of which the majority had schizophrenia (22%). There does not appear to be a differential expression of schizophrenic symptom clusters in 22q11.2DS in relation to sporadic schizophrenia, though schizophrenia in 22q11.2DS seems to be less severe in terms of global assessment scores. Psychosis proneness seems to be of genetic origin in 22q11.2DS as in iduals with 22q11.2DS without schizophrenia had higher schizotypy scores than normal controls. Finally, COMT was not associated with schizophrenia status or schizotypy.
Publisher: Wiley
Date: 27-02-2023
DOI: 10.1111/NYAS.14972
Abstract: New interdisciplinary research into genetic influences on musicality raises a number of ethical and social issues for future avenues of research and public engagement. The historical intersection of music cognition and eugenics heightens the need to vigilantly weigh the potential risks and benefits of these studies and the use of their outcomes. Here, we bring together erse disciplinary expertise (complex trait genetics, music cognition, musicology, bioethics, developmental psychology, and neuroscience) to interpret and guide the ethical use of findings from recent and future studies. We discuss a framework for incorporating principles of ethically and socially responsible conduct of musicality genetics research into each stage of the research lifecycle: study design, study implementation, potential applications, and communication.
Publisher: Wiley
Date: 10-2018
DOI: 10.1002/AJMG.A.40359
Publisher: Elsevier BV
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 28-09-2022
Publisher: Elsevier BV
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 16-06-2022
DOI: 10.1038/S41562-022-01359-X
Abstract: Moving in synchrony to the beat is a fundamental component of musicality. Here we conducted a genome-wide association study to identify common genetic variants associated with beat synchronization in 606,825 in iduals. Beat synchronization exhibited a highly polygenic architecture, with 69 loci reaching genome-wide significance ( P 5 × 10 −8 ) and single-nucleotide-polymorphism-based heritability (on the liability scale) of 13%–16%. Heritability was enriched for genes expressed in brain tissues and for fetal and adult brain-specific gene regulatory elements, underscoring the role of central-nervous-system-expressed genes linked to the genetic basis of the trait. We performed validations of the self-report phenotype (through separate experiments) and of the genome-wide association study (polygenic scores for beat synchronization were associated with patients algorithmically classified as musicians in medical records of a separate biobank). Genetic correlations with breathing function, motor function, processing speed and chronotype suggest shared genetic architecture with beat synchronization and provide avenues for new phenotypic and genetic explorations.
Publisher: Springer Science and Business Media LLC
Date: 23-05-2015
DOI: 10.1007/S00127-015-1072-8
Abstract: The purpose of this study is to highlight the Avon Longitudinal Study of Parents and Children (ALSPAC) as a resource to study psychopathology. To demonstrate this, we review the studies related to depression and psychosis in childhood and adolescence and discuss the results in relation to the aetiology of depression and psychotic experiences (PEs) and possible underlying mechanisms. We examined the list of publications from ALSPAC and then classified them as examining (a) the course and risk factors of maternal and paternal depression, (b) the effects of maternal and paternal depression on child development, (c) risk factors for depression in childhood and adolescence, (d) the frequency, clinical relevance and risk factors of PEs, and (e) shared risk factors for depression and PEs. There was evidence that environmental stressors and the way these are interpreted contribute to risk of depression and evidence that biological factors related to puberty are also likely to play a role. With regards to PEs, the findings further support the existence of 'a continuum of psychosis' while they also suggest that PEs might be of limited clinical utility in predicting psychotic disorder during adolescence and early adulthood. Finally, most risk factors examined were found to be shared between depression and PEs. The ALSPAC birth cohort has provided important insights for our understanding of the aetiological mechanisms underlying depression and PEs. Future research could aim to incorporate measures of automatic psychological mechanisms to provide insights into the brain mechanisms that underlie these clinical phenomena.
Publisher: Springer Science and Business Media LLC
Date: 16-01-2019
DOI: 10.1038/S41398-018-0339-8
Abstract: Deletion and duplication of 16p11.2 (BP4–BP5) have been associated with an increased risk of intellectual disability and psychiatric disorder. This is the first study to compare the frequency of a broad spectrum of psychiatric disorders in children with 16p11.2 deletion and duplication. We aimed to evaluate (1) the nature and prevalence of psychopathology associated with copy number variation (CNV) in children with 16p11.2 by comparing deletion and duplication carriers with family controls (2) whether deletion and duplication carriers differ in frequency of psychopathology. 217 deletion carriers, 77 deletion family controls, 114 duplication carriers, and 32 duplication family controls participated in the study. Measures included standardized research diagnostic instruments. Deletion carriers had a higher frequency of any psychiatric disorder (OR = 8.9, p 0.001), attention deficit hyperactivity disorder (ADHD) (OR = 4.0, p = 0.01), and autism spectrum disorder (ASD) (OR = 39.9, p = 0.01) than controls. Duplication carriers had a higher frequency of any psychiatric diagnosis (OR = 5.3, p = 0.01) and ADHD (OR = 7.0, p = 0.02) than controls. The prevalence of ASD in child carriers of deletions and duplications was similar (22% versus 26%). Comparison of the two CNV groups indicated a higher frequency of ADHD in children with the duplication than deletion (OR = 2.7, p = 0.04) as well as a higher frequency of overall psychiatric disorders (OR = 2.8, p = 0.02) and psychotic symptoms (OR = 4.7, p = 0.02). However, no differences between deletion and duplications carriers in the prevalence of ASD were found. Both deletion and duplication are associated with an increased risk of psychiatric disorder, supporting the importance of early recognition, diagnosis, and intervention in these groups.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JPSYCHIRES.2017.04.006
Abstract: 22q11.2 Deletion Syndrome (22q11.2DS) is one of the strongest known genetic risk factors for developing schizophrenia. In iduals with 22q11.2DS have high rates of neurodevelopmental disorders in childhood, while in adulthood ∼25% develop schizophrenia. Similar to the general population, high rates of comorbidity are common in 22q11.2DS. Employing a dimensional approach where psychopathology is examined at the symptom-level as complementary to diagnostic categories in a population at such high genetic risk for schizophrenia can help gain a better understanding of how psychopathology is structured as well as its genetic underpinnings. This is the first study to examine the dimensional structure of a wide spectrum of psychopathology in the context of a homogeneous genetic etiology like 22q11.2DS. We evaluated 331 in iduals with 22q11.2DS, mean age (SD) = 16.9(8.7) 51% males, who underwent prospective comprehensive phenotyping. We sought to replicate previous findings by examining a bi-factor model that derives a general factor of psychopathology in addition to more specific dimensions of psychopathology (i.e., internalizing, externalizing and thought disorder). Psychopathology in 22q11.2DS was ided into one 'general psychopathology' factor and four specific dimensions (i.e., 'anxiety', 'mood', 'ADHD' and 'psychosis'). The 'psychosis' symptoms loaded strongly on the 'general psychopathology' factor. The similarity of the symptom structure of psychopathology between 22q11.2DS and community and clinical populations without the deletion indicate that 22q11.2DS can provide a model to explore alternative approaches to our current nosology. Our findings add to a growing literature indicating the need to reorganize current diagnostic classification systems.
Publisher: Oxford University Press (OUP)
Date: 10-10-2017
Publisher: Springer Science and Business Media LLC
Date: 16-06-2023
DOI: 10.1186/S11689-023-09485-X
Abstract: Although polygenic scores (PGS) for autism have been related to various psychiatric and medical conditions, most studies to date have been conducted in research ascertained populations. We aimed to identify the psychiatric and physical conditions associated with autism PGS in a health care setting. We computed PGS for 12,383 unrelated participants of African genetic ancestry (AF) and 65,363 unrelated participants of European genetic ancestry (EU) from Vanderbilt’s de-identified biobank. Next, we performed phenome wide association studies of the autism PGS within these two genetic ancestries. Seven associations surpassed the Bonferroni adjusted threshold for statistical significance ( p = 0.05/1374 = 3.6 × 10 −5 ) in the EU participants, including mood disorders (OR (95%CI) = 1.08(1.05 to 1.10), p = 1.0 × 10 −10 ), autism (OR (95%CI) = 1.34(1.24 to 1.43), p = 1.2 × 10 –9 ), and breast cancer (OR (95%CI) = 1.09(1.05 to 1.14), 2.6 × 10 −5 ). There was no statistical evidence for PGS-phenotype associations in the AF participants. Conditioning on the diagnosis of autism or on median body mass index (BMI) did not impact the strength of the reported associations. Although we observed some sex differences in the pattern of associations, there was no significant interaction between sex and autism PGS. Finally, the associations between autism PGS and autism diagnosis were stronger in childhood and adolescence, while the associations with mood disorders and breast cancer were stronger in adulthood. Our findings indicate that autism PGS is not only related to autism diagnosis but may also be related to adult-onset conditions, including mood disorders and some cancers. Our study raises the hypothesis that genes associated with autism may also increase the risk for cancers later in life. Future studies are necessary to replicate and extend our findings.
Publisher: The Royal Society
Date: 23-08-2021
Abstract: The development of rhythmicity is foundational to communicative and social behaviours in humans and many other species, and mechanisms of synchrony could be conserved across species. The goal of the current paper is to explore evolutionary hypotheses linking vocal learning and beat synchronization through genomic approaches, testing the prediction that genetic underpinnings of birdsong also contribute to the aetiology of human interactions with musical beat structure. We combined state-of-the-art-genomic datasets that account for underlying polygenicity of these traits: birdsong genome-wide transcriptomics linked to singing in zebra finches, and a human genome-wide association study of beat synchronization. Results of competitive gene set analysis revealed that the genetic architecture of human beat synchronization is significantly enriched for birdsong genes expressed in songbird Area X (a key nucleus for vocal learning, and homologous to human basal ganglia). These findings complement ethological and neural evidence of the relationship between vocal learning and beat synchronization, supporting a framework of some degree of common genomic substrates underlying rhythm-related behaviours in two clades, humans and songbirds (the largest evolutionary radiation of vocal learners). Future cross-species approaches investigating the genetic underpinnings of beat synchronization in a broad evolutionary context are discussed. This article is part of the theme issue ‘Synchrony and rhythm interaction: from the brain to behavioural ecology’.
Publisher: Wiley
Date: 27-05-2014
DOI: 10.1002/AJMG.B.32245
Abstract: Children reporting psychotic experiences (PEs) are at increased risk of developing psychosis in adulthood. Cognitive deficits and anxiety disorders often precede psychotic disorders and are associated with higher risk of PEs. While the high activity alleles of variants within COMT have been associated with cognitive deficits, and the low activity alleles with higher risk of anxiety disorders, no associations of COMT with PEs have been found. One possible explanation is that the association between COMT and PEs is indirect, through cognitive function and anxiety disorders. We examined whether the association between PEs and COMT (four single nucleotide polymorphisms and three haplotypes) is indirect, through cognition or anxiety disorders. 6,784 in iduals from the Avon Longitudinal Study of Parents and Children (ALSPAC) were genotyped and completed neurocognitive assessments at ages 8 and 11, as well as semi-structured interviews for anxiety disorders and PEs at ages 10 and 12, respectively. Alleles rs2097603 and rs4680, and two COMT haplotypes, all indexing high activity, were indirectly associated with higher risk of PEs through impaired processing speed, IQ and attention. There was no evidence of a total effect of COMT on PEs, nor for an indirect effect through anxiety disorders. This is the first study to examine indirect effects of COMT on PEs. Evidence of an indirect association suggests a complex developmental pathway underlies the emergence of PEs in children, with possible implications for prevention/intervention strategies. Our findings provide additional support for processing speed and attention as endophenotypes in psychotic disorders.
Publisher: Wiley
Date: 24-09-2015
DOI: 10.1002/AJMG.B.32378
Publisher: Royal College of Psychiatrists
Date: 10-2017
DOI: 10.1192/BJP.BP.116.195651
Abstract: 22q11.2 deletion syndrome (22q11.2DS) is associated with a high risk of childhood as well as adult psychiatric disorders, in particular schizophrenia. Childhood cognitive deterioration in 22q11.2DS has previously been reported, but only in studies lacking a control s le. To compare cognitive trajectories in children with 22q11.2DS and unaffected control siblings. A longitudinal study of neurocognitive functioning (IQ, executive function, processing speed and attention) was conducted in children with 22q11.2DS ( n = 75, mean age time 1 ( T 1 ) 9.9, time 2 ( T 2 ) 12.5) and control siblings ( n = 33, mean age T 1 10.6, T 2 134). Children with 22q11.2DS exhibited deficits in all cognitive domains. However, mean scores did not indicate deterioration. When in idual trajectories were examined, some participants showed significant decline over time, but the prevalence was similar for 22q11.2DS and control siblings. Findings are more likely to reflect normal developmental fluctuation than a 22q11.2DS-specific abnormality. Childhood cognitive deterioration is not associated with 22q11.2DS. Contrary to previous suggestions, we believe it is premature to recommend repeated monitoring of cognitive function to identifying in idual children with 22q11.2DS at high risk of developing schizophrenia.
Publisher: American Psychiatric Association Publishing
Date: 05-2013
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Maria Niarchou.