scholarly journals Neurological disorder-associated genetic variants in individuals with psychogenic nonepileptic seizures

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Costin Leu ◽  
Jocelyn F. Bautista ◽  
Monica Sudarsanam ◽  
Lisa-Marie Niestroj ◽  
Arthur Stefanski ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Large Scale ◽  
Genetic Factors ◽  
Tertiary Care ◽  
Genetic Research ◽  
Genetic Investigation ◽  
Psychogenic Nonepileptic Seizures ◽  
Whole Exome ◽  
Nonepileptic Seizures

Abstract Psychogenic nonepileptic seizures (PNES) are diagnosed in approximately 30% of patients referred to tertiary care epilepsy centers. Little is known about the molecular pathology of PNES, much less about possible underlying genetic factors. We generated whole-exome sequencing and whole-genome genotyping data to identify rare, pathogenic (P) or likely pathogenic (LP) variants in 102 individuals with PNES and 448 individuals with focal (FE) or generalized (GE) epilepsy. Variants were classified for all individuals based on the ACMG-AMP 2015 guidelines. For research purposes only, we considered genes associated with neurological or psychiatric disorders as candidate genes for PNES. We observe in this first genetic investigation of PNES that six (5.88%) individuals with PNES without coexistent epilepsy carry P/LP variants (deletions at 10q11.22-q11.23, 10q23.1-q23.2, distal 16p11.2, and 17p13.3, and nonsynonymous variants in NSD1 and GABRA5). Notably, the burden of P/LP variants among the individuals with PNES was similar and not significantly different to the burden observed in the individuals with FE (3.05%) or GE (1.82%) (PNES vs. FE vs. GE (3 × 2 χ2), P = 0.30; PNES vs. epilepsy (2 × 2 χ2), P = 0.14). The presence of variants in genes associated with monogenic forms of neurological and psychiatric disorders in individuals with PNES shows that genetic factors are likely to play a role in PNES or its comorbidities in a subset of individuals. Future large-scale genetic research studies are needed to further corroborate these interesting findings in PNES.

Psychogenic Nonepileptic Seizures in Women

2017 ◽  
Vol 37 (06) ◽  
pp. 624-631 ◽  
Author(s):  
Gaston Baslet ◽  
Barbara Dworetzky
Keyword(s):  
Risk Factors ◽  
Tertiary Care ◽  
Traumatic Experiences ◽  
Clinical Approach ◽  
Evidence Based ◽  
Accurate Identification ◽  
Psychogenic Nonepileptic Seizures ◽  
Evidence Based Treatments ◽  
Nonepileptic Seizures ◽  
The Difference

AbstractPsychogenic nonepileptic seizures (PNES) are the most common type of functional neurological symptom disorders and are frequently diagnosed in tertiary care epilepsy monitoring units. These are associated with significant decline in social functioning and quality of life. The majority of patients with PNES are women, outnumbering men by a ratio of 3:1. Female sex preponderance occurs after puberty and usually before the age of 55 years. Many of the psychiatric risk factors in PNES (depression, anxiety, history of traumatic experiences, other somatic symptom disorders) are more common in women and may partially account for the difference in sex prevalence. Neurobiological and neurohumoral mechanisms may also play a role, but our understanding is limited at this point. In this review, we present information on epidemiology and risk factors, neurobiological and psychological mechanisms, clinical approach to diagnosis, evidence-based treatment, and long-term outcomes. We highlight findings related to differences between women and men in PNES. Most of these data are not decisive and require further corroboration. While the disorder may be more frequently suspected in women, all patients with suspected PNES deserve an objective and thorough investigation of their symptoms. Early and accurate identification of this disorder should be a priority, especially as evidence-based treatments, which may lead to improved outcomes, are increasingly available.

Psychiatric disorders in patients with psychogenic nonepileptic seizures and drug-resistant epilepsy: A study of an Argentine population

2013 ◽  
Vol 29 (1) ◽  
pp. 155-160 ◽  
Author(s):  
Laura Scévola ◽  
Julia Teitelbaum ◽  
Silvia Oddo ◽  
Estela Centurión ◽  
César Fabián Loidl ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Drug Resistant ◽  
Psychogenic Nonepileptic Seizures ◽  
Nonepileptic Seizures ◽  
Drug Resistant Epilepsy

Genetic correlations between subcortical brain volumes and psychiatric disorders

2020 ◽  
Vol 216 (5) ◽  
pp. 280-283
Author(s):  
Kazutaka Ohi ◽  
Takamitsu Shimada ◽  
Yuzuru Kataoka ◽  
Toshiki Yasuyama ◽  
Yasuhiro Kawasaki ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Large Scale ◽  
Association Studies ◽  
Genetic Correlations ◽  
Intracranial Volume ◽  
Genome Wide Association Studies ◽  
Brain Volumes ◽  
Subcortical Brain ◽  
Genome Wide

SummaryPsychiatric disorders as well as subcortical brain volumes are highly heritable. Large-scale genome-wide association studies (GWASs) for these traits have been performed. We investigated the genetic correlations between five psychiatric disorders and the seven subcortical brain volumes and the intracranial volume from large-scale GWASs by linkage disequilibrium score regression. We revealed weak overlaps between the genetic variants associated with psychiatric disorders and subcortical brain and intracranial volumes, such as in schizophrenia and the hippocampus and bipolar disorder and the accumbens. We confirmed shared aetiology and polygenic architecture across the psychiatric disorders and the specific subcortical brain and intracranial volume.

scholarly journals Role of Biomarkers in Differentiating New-onset Seizures from Psychogenic Nonepileptic Seizures

2017 ◽  
Vol 08 (04) ◽  
pp. 581-584 ◽  
Author(s):  
Mahendra Javali ◽  
Purushottam Acharya ◽  
Shripal Shah ◽  
Rohan Mahale ◽  
Pushparaja Shetty ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Serum Prolactin ◽  
Review Of Literature ◽  
Partial Seizures ◽  
Psychogenic Nonepileptic Seizures ◽  
Nonepileptic Seizures ◽  
Clonic Seizures ◽  
The Mean ◽  
New Onset

ABSTRACT Introduction: Review of literature revealed very limited studies considering a combination of serum prolactin (PRL) and serum creatine kinase (CK) as markers for differentiating epileptic and psychogenic nonepileptic seizures (PNES). Therefore, in the present study, we analyzed the role of serum PRL and serum CK, individually and in combination. Methodology: This prospective study was conducted in a tertiary care medical teaching hospital over a period of 18 months. Patients aged over 15 years suspected to have new-onset seizures presenting within 5 h of ictus were included in this study. CK, serum PRL was measured at 0–1, 1–3, and 3–5 h after seizures. Results: Hundred subjects were studied for the role of serum PRL and serum CK in differentiating epileptic and PNES. The mean age was 42.24 years with a male:female ratio of 1.27:1. All patients of generalized tonic–clonic seizures (GTCS), who presented within 1 h, had elevated PRL, whereas 75% of patients with partial seizures had elevated PRL within 1 h of presentation. Nearly 91.66% of patients with GTCS who presented within 1 h had elevated CPK, whereas 70% of patients with partial seizures had elevated CPK. None of the patients diagnosed with PNES showed rise in either of the markers. Conclusion: In the present study, none of the patients with PNES showed raise in either serum PRL or CK. However, there was no correlation between the types of seizure and PRL or serum CK levels.

scholarly journals Whole Exome Sequencing Identifies genetic variants in Chinese Han pregnant women with Venous thromboembolism-a case control study

2020 ◽  
Author(s):  
Yupei Shen ◽  
Yan Zhang ◽  
Ying Xiong ◽  
Zhiping Zhang ◽  
Baohua Zhang ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Pregnant Women ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Large Scale ◽  
Single Nucleotide Variants ◽  
Chinese Han ◽  
Whole Exome ◽  
Increased Risk

Abstract Background: Venous thromboembolism (VTE) is a common health problem, causing considerable morbidity and mortality. The incidence of VTE is higher in pregnant women than in those who are not pregnant. However, genetic factors for VTE in pregnant women are largely unknown.Methods: We performed a large-scale prospective cohort study of 65138 pregnancies. Pregnant patients with VTE and pregnant women without VTE were enrolled in the study and sequenced by whole exome sequencing. Functional and enrichment analyses were performed using the DAVID online database. The protein-protein interaction network was constructed using the STRING database. Results: 5810 significant variants were associated with pregnant patients with VTE, including 4874 single nucleotide variants and 936 short deletions which were annotated in 3417 genes (P < 0.05). Fifty-six variants annotated in 46 genes (P < 0.001) and the top 3 variants, including rs2706258 (RNA LOC102724050, p = 1.25 × 10-6), rs17057520 (SCARA3, p = 4.64 × 10-5), and rs3739550 (CAAP1, p = 4.64 × 10-5), were identified. Fourteen low frequency variants had a minor allele frequency (MAF) of less than 1%. Logistic analysis revealed that rs7099478 (GRK5), rs8041208 (WDR72), rs17215792 (KLF7), rs13035688 (KLF7), rs6725221 (KLF7), and rs3214417 (KLF7) were associated with an increased risk of developing VTE (P < 0.05, OR > 1). In addition, combined pathway and PPI analyses revealed that CDC7 and MCM6 involved with DNA replication were associated with VTE in pregnant individuals.Conclusion: The study identified a series of variants and genes that may contribute to VTE in the Chinese pregnant population. Several genes may be risk factors for VTE including KLF7, GRK5, and WDR72. CDC7 and MCM6 may be related to the potential functions of VTE in pregnant women. Notably, the KLF7 gene had 4 genetic variants that were found to be associated with lipid metabolism and cardiovascular diseases. Therefore, further validation is required to reveal the KLF7 mechanism in pregnant women with VTE.

scholarly journals VEP-G2P: A Tool for Efficient, Flexible and Scalable Diagnostic Filtering of Genomic Variants

2018 ◽  
Author(s):  
Anja Thormann ◽  
Mihail Halachev ◽  
William McLaren ◽  
David J Moore ◽  
Victoria Svinti ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Large Scale ◽  
De Novo ◽  
Genetic Research ◽  
Evidence Based ◽  
Large Numbers ◽  
Whole Exome ◽  
Variant Filtering ◽  
And Control ◽  
Exome Sequence

AbstractPurposeWe aimed to develop an efficient, flexible, scalable and evidence-based approach to sequence-based diagnostic analysis/re-analysis of conditions with very large numbers of different causative genes. We then wished to define the expected rate of plausibly causative variants coming through strict filtering in control in comparison to disease populations to quantify background diagnostic “noise”.MethodsWe developed G2P (www.ebi.ac.uk/gene2phenotype) as an online system to facilitate the development, validation, curation and distribution of large-scale, evidence-based datasets for use in diagnostic variant filtering. Each locus-genotype-mechanism-disease-evidence thread (LGMDET) associates an allelic requirement and a mutational consequence at a defined locus with a disease entity and a confidence level and evidence links. We then developed an extension to Ensembl Variant Effect Predictor (VEP), VEP-G2P, which can filter based on G2P other widely used gene panel curation systems. We compared the output of disease-associated and control whole exome sequence (WES) using Developmental Disorders G2P (G2PDD; 2044 LGMDETs) and constitutional cancer predisposition G2P (G2PCancer; 128 LGMDETs).ResultsWe have shown a sensitivity/precision of 97.3%/33% and 81.6%/22.7% for causative de novo and inherited variants respectively using VEP-G2PDD in DDD study probands WES. Many of the apparently diagnostic genotypes “missed” are likely false-positive reports with lower minor allele frequencies and more severe predicted consequences being diagnostically-discriminative features.ConclusionCase:control comparisons using VEP-G2PDD established an observed:expected ratio of 1:30,000 plausibly causative variants in proband WES to ~1:40,000 reportable but presumed-benign variants in controls. At least half the filtered variants in probands represent background “noise”. Supporting phenotypic evidence is, therefore, necessary in genetically-heterogeneous disorders. G2P and VEP-G2P provides a practical approach to optimize disease-specific filtering parameters in diagnostic genetic research.

Shared genetic etiology between anxiety disorders and psychiatric and related intermediate phenotypes

2019 ◽  
Vol 50 (4) ◽  
pp. 692-704 ◽  
Author(s):  
Kazutaka Ohi ◽  
Takeshi Otowa ◽  
Mihoko Shimada ◽  
Tsukasa Sasaki ◽  
Hisashi Tanii
Keyword(s):  
Anxiety Disorders ◽  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Large Scale ◽  
Genetic Correlations ◽  
Well Being ◽  
Subjective Well Being ◽  
Intermediate Phenotypes ◽  
Genome Wide ◽  
Common Genetic Variants

AbstractBackgroundPsychiatric disorders and related intermediate phenotypes are highly heritable and have a complex, overlapping polygenic architecture. A large-scale genome-wide association study (GWAS) of anxiety disorders identified genetic variants that are significant on a genome-wide. The current study investigated the genetic etiological overlaps between anxiety disorders and frequently cooccurring psychiatric disorders and intermediate phenotypes.MethodsUsing case–control and factor score models, we investigated the genetic correlations of anxiety disorders with eight psychiatric disorders and intermediate phenotypes [the volumes of seven subcortical brain regions, childhood cognition, general cognitive ability and personality traits (subjective well-being, loneliness, neuroticism and extraversion)] from large-scale GWASs (n= 7556–298 420) by linkage disequilibrium score regression.ResultsAmong psychiatric disorders, the risk of anxiety disorders was positively genetically correlated with the risks of major depressive disorder (MDD) (rg± standard error = 0.83 ± 0.16,p= 1.97 × 10−7), schizophrenia (SCZ) (0.28 ± 0.09,p= 1.10 × 10−3) and attention-deficit/hyperactivity disorder (ADHD) (0.34 ± 0.13,p= 8.40 × 10−3). Among intermediate phenotypes, significant genetic correlations existed between the risk of anxiety disorders and neuroticism (0.81 ± 0.17,p= 1.30 × 10−6), subjective well-being (−0.73 ± 0.18,p= 4.89 × 10−5), general cognitive ability (−0.23 ± 0.08,p= 4.70 × 10−3) and putamen volume (−0.50 ± 0.18,p= 5.00 × 10−3). No other significant genetic correlations between anxiety disorders and psychiatric or intermediate phenotypes were observed (p> 0.05). The case–control model yielded stronger genetic effect sizes than the factor score model.ConclusionsOur findings suggest that common genetic variants underlying the risk of anxiety disorders contribute to elevated risks of MDD, SCZ, ADHD and neuroticism and reduced quality of life, putamen volume and cognitive performance. We suggest that the comorbidity of anxiety disorders is partly explained by common genetic variants.

Eye movement desensitization and reprocessing treatment in functional neurological symptom disorder with psychogenic nonepileptic seizures: A study of two cases

2021 ◽  
pp. 135910452110372
Author(s):  
Onur O Demirci ◽  
Eser Sagaltici
Keyword(s):  
Psychiatric Disorders ◽  
Eye Movement ◽  
Neurological Symptom ◽  
Term Treatment ◽  
Post Traumatic Stress ◽  
Psychogenic Nonepileptic Seizures ◽  
Long Term Treatment ◽  
Scale Scores ◽  
Nonepileptic Seizures ◽  
Functional Neurological Symptom Disorder

Patients with functional neurological symptom disorder (FND) have many diverse symptoms including psychogenic nonepileptic seizures (PNES), positive movements such as tremor, dystonia, or gait abnormalities, loss of motor function such as leg or arm paresis, and loss of sensory functions, such as blindness, deafness, or loss of feeling in the limbs. Eye movement desensitization and reprocessing (EMDR) is a therapy method that includes some techniques arising from psychodynamic, cognitive, and behavioral approaches. EMDR is known as a proven psychotherapeutic approach in post-traumatic stress disorder, but there are also numerous studies reporting its efficacy in other psychiatric disorders and trauma-associated symptoms, in patients with comorbid psychiatric disorders. This article presents the outcome of EMDR treatment of two patients’ cases, a 13-year-old female and a 16-year-old male, who were diagnosed as FND with PNES, according to the DSM-5 diagnostic criteria. In both cases, there was a significant decrease in Adolescent Dissociative Experiences Scale scores and no pseudo seizures were found, even at the sixth-month follow-up visits. These case studies suggest that EMDR can be an effective method in the long-term treatment of FND with PNES and a useful alternative to other treatment methods.

Psychiatric Disorders in Children and Adolescents With Psychogenic Nonepileptic Seizures

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012270
Author(s):  
Anne Sofie Hansen ◽  
Charlotte Ulrikka Rask ◽  
Ann-Eva Christensen ◽  
Maria Rodrigo-Domingo ◽  
Jakob Christensen ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Psychiatric Disorders ◽  
Wide Spectrum ◽  
Psychiatric Evaluation ◽  
Healthy Controls ◽  
Psychogenic Nonepileptic Seizures ◽  
Relative Risks ◽  
Wide Range ◽  
Comparison Groups ◽  
Nonepileptic Seizures

Objective:Knowledge regarding psychiatric disorders in children and adolescents with psychogenic nonepileptic seizures (PNES) is limited. This study outlines the spectrum and risk of psychiatric disorders in childhood-onset PNES.Methods:A nationwide matched cohort study of children and adolescents with PNES aged 5-17 years at time of diagnosis between January 1, 1996 and December 31, 2014. Two matched comparison groups were included: children and adolescents with epilepsy (ES), and children and adolescents without PNES or epilepsy, termed healthy controls (HC). Outcomes were prevalent psychiatric disorders prior to index (i.e. date of diagnosis or corresponding date for HCs), and incident psychiatric disorders two years after index. Relative risks (RRs) were calculated and adjusted for potential confounders.Results:We included 384 children and adolescents with validated PNES, 1,152 with epilepsy, and 1,920 healthy controls. Among the PNES cases, 153 (39.8%) had prevalent psychiatric disorders and 150 (39.1%) incident psychiatric disorders. As compared to the epilepsy and healthy controls, children and adolescents with PNES had elevated risks of both prevalent psychiatric disorders (adjusted RRPNES/ES: 1.87, 95% CI: 1.59–2.21, adjusted RRPNES/HC: 5.54, 95% CI: 4.50–6.81), and incident psychiatric disorders (adjusted RRPNES/ES: 2.33, 95% CI: 1.92–2.83, adjusted RRPNES/HC: 8.37, 95% CI: 6.31–11.11). A wide spectrum of specific psychiatric disorders displayed elevated RRs.Conclusions:Children and adolescents with PNES are at higher risk of a wide range of psychiatric disorders as compared to children and adolescents with epilepsy and healthy controls. A careful psychiatric evaluation is warranted to optimize and individualize treatment.

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